FMP2-Summary of All Notes 1

00 FMP 08 Week 8 Intro Pages
Sunday, February 10, 2008

7:19 PM
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01 SCHAFFER 2008 Diagnosis and Etiology of Depression 2x3
7:18 PM
• Sadness = healthy, normal condition that everyone feels

• Depression = medical condition
Briefly describe how

sadness is different
from depression?
List 5 signs that
indicate the presence
of depression?(7)
ie. The thoughts that one has affects one's mood and • Have to differentiate sadness from depression
• Remember that depression lasts for weeks or months
thereby makes one depressed
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In order to diagnose
someone with a major
depressive episode (MDE),
there are 3 major diagnostic
criteria according to DSM IV;
what are they?
In order to diagnose
someone with a major
depressive episode (MDE),
there they must have 5 or
more of which symptoms
during a 2 week period? (list
5, there's a total of 9)
Dysthymia is a mood disorder that falls within the depression spectrum. Not considered to be as severe as major depression, dysthymic disorder is generally
List 4 diagnoses that are
thought to be a chronic depression. According to the APA, DSM-IV (2000), two or more of six possible symptoms must be present for a diagnosis of dysthymia. associated with MDE's(6)?
These symptoms include poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or difficulty making
decisions, and feelings of hopelessness [Hersen, M., Turner, S. M., & Beidel, D. C. (Eds.). (2007). Pasted from <http://en.wikipedia.org/wiki/Dysthymia>
List 3 medical conditions

that can lead to a mood
disorder due to a general
medical condition?(5)
Name 2 vitamin
deficiencies that can cause
a mood disorder?
• All the following have

established links with
depression
What is substance-induced
MDE?
List 2 ways you can be
Eg. Of having melanoma vs. brain tumor and cancer secondary to latter but can't more assured of a
really justify it being secondary to the former (skin cancer) since not directly linked substance-induced MDE
diagnosis; ie. There are 3
criteria that must be met
to confirm substance-
induced MDE, list 2?
Give examples of 3
substances that can
lead to substance-
induced MDE?(4)
T/F: Adjustment Disorder

with Depressed Mood is
diagnosed in patients with a
mental illness/disorder?
• Eg. If someone loses a job, excessive if spend next week in bed What is Adjustment
Disorder with depressed
mood?
How many months within
the onset of a stressful
event must depression occur
and after how many months
must it resolve in order to
be diagnosed with
Adjustment Disorder with
Depresed Mood?
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List 4 diagnostic
criteria for
Dysthymia?(5)
How is major depressive

disorder diagnosed?
In diagnosing dysthymia,
the patient should
"never be without
symptoms for…" what
period of time?
T/F: Major depressive

disorder occurs more
frequently in the elderly (+60
years old) than in those less
than 60 years old?
Within the course of Major
Depressive Disorder, what is
the mean duration of an
untreated Major Depressive
Episode?
The mean number of lifetime
episodes for someone who
suffers from Major
Depressive Disorder is __ to
__?
T/F: According to the
• Population was randomly sampled
Canadian Community Health
○ Women experience depression more frequently than men
Survey, women over 64 are
○ Highest in youngest age group of 15-24
significantly more likely to
○ No significant gender differences found in geriatric populations suffer from depression than
men over 64?
Depression CAN be a Canadian Community Health
Survey, the highest rate of
chronic condition! Major Depressive Disorder
was amongst the 15-24 year
old age group?
Canadian Community Health
Survey, women are overall
more likely to suffer from
depression compared to
men?
50% of those with Major
Depressive Disorder have
onset before the age of ___?
• 50% of time patients have low grade depressive symptoms T/F: True depression is NOT a
• Followed depressive patients for 12 years chronic condition but is by
• What they did: each week over 12 years classified the intensity definition acute episodes of
depressive symptoms?
of the depressive symptoms (as colored above)
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How much of the variance
1 in the incidence of
(prior to age 11)
depression is accounted
for by life events?
(higher in women)
List 6 risk factors for

depression?(8)
• So if you go through large groups of patients histories, only

10% is actually associated with stressors; most people are not
experiencing a period of depression after stressful events
• So if any one of us developed dpression in the next month, • If a child experiences loss of parent especially before age of 11,
we'd be able to go back and identify some stressor that we then increased risk for depression
could link with that depression; so there's stress but also
vulnerability for people to develop depression
List 3 neurotransmitters
involved in depression?(3)
Biochemically, what is the
response to anti -depressants
that target norepinephrine?
How are serotonin levels
linked to precipitating the
symptoms of depression?
Do antidepressants increase
or decrease dopamine levels?
Do antidepressants work by
upregulating or
downregulating beta-
adrenergic receptors (thereby
influencing norepineprhine)?
What is the effect of untreated

depression on hippocampal
volume?
What happens to blood flow to
the attention/cognition areas of
the brain in depression versus
blood flow to the vegetative-
autonomic areas of the brain?
• On y axis: total hipp vol.; x axis days of untreated • Looking at blood flow in the brain; work done at UofT; found
depression that the blue, the upper part was dec. blood flow and the lower
• Showed that longer pts untreated for, part was inc. blood flow
• If looked at as a mean, patients who were depressed had
smaller the hipp'l vol was decreased blood flow and believed to be associated with some
• So some neurotoxicity associated with depression cognitive difficulties
• One of the other features of the anti -depressants is that • Increased blood flow in the limbic system (ie. Amygdala,
they increase Brain Derived Neurotropic Factor (BDNF) associated with anxiety and fear)
and regeneration of hippocampus (in animal models) • Patients with depression also had lower hippocampal volume
• brain derived neurotropic factor
○ Now looking for stem cells that will increase
proliferation of stem cells in the hippocampus
Week8 Page 9
What did the Dunedin
Multidisciplinary Health and
Development Study reveal
regarding genetics and depression
in S/S genotyped individuals?
• Found that treatment reveresed the blood flow; top is

areas in which blood flow increased in brain and bottom
areas that
• Looking at dorsolateral prefrontal cortex
Probability
experiencing
MDE (major
depressive
episode)
increased in S/S
• Dunedin study: looked at serotonin system

At 2,3,4 stressful
○ S= short allele
life events, begin
○ L=long allele
to see separation
What did the Dunedin

Multidisciplinary Health
and Development Study
reveal regarding
maltreatment, serotonin
transporter gene
promoter region
genotypes, and
propensity to experience
depression?
• In same group looked at maltreatment during childhood

• If you look at the genotype, those who had the L/L, even if
they experienced trauma as a child, much less likely to
experience depression
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Brain derived neurotrophic factor
Tuesday, February 12, 2008
8:53 AM
Brain-derived neurotrophic factor

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found in the brain and the periphery. It is a
protein that acts on certain neurons of the central nervous system and the peripheral nervous system that helps to
support the survival of existing neurons and encourage the growth and differentiation of new neurons and
synapses. In the brain, it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning,
memory, and higher thinking. BDNF was the second neurotrophic factor to be characterized after nerve growth
factor (NGF).
Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain
retain the ability to grow new neurons from neural stem cells in a process known as neurogenesis. Neurotrophins
are chemicals that help to stimulate and control neurogenesis, BDNF being one of the most active. Mice born
without the ability to make BDNF suffer developmental defects in the brain and sensory nervous system, and
usually die soon after birth, suggesting that BDNF plays an important role in normal neural development.
Despite its name, BDNF is actually found in a range of tissue and cell types, not just in the brain. It is also expressed
in the retina, the CNS, motor neurons, the kidneys, and the prostate.
Contents
[hide]
• 1 Effects of stress and BDNF's link in depression
• 2 Mechanism of action for BDNF
• 3 Other diseases associated with low BDNF levels
• 4 High BDNF levels
• 5 Epilepsy
• 6 References
• 7 External links
• 8 Further reading
[edit] Effects of stress and BDNF's link in depression

Exposure to stress and the stress hormone corticosterone has been shown to decrease the expression of BDNF in
rats, and leads to an eventual atrophy of the hippocampus if exposure is persistent. Similar atrophy has been
shown to take place in humans suffering from chronic depression. In addition, rats bred to be heterozygous for
BDNF, therefore reducing its expression, have been observed to exhibit similar hippocampal atrophy, suggesting
that an etiological link between the development of depressive illness and regulation of BDNF exists. On the other
hand, the excitatory neurotransmitter glutamate, voluntary exercise, caloric restriction, intellectual stimulation,
and various treatments for depression (such as antidepressants and electroconvulsive therapy) strongly increase
expression of BDNF in the brain, and have been shown to protect against this atrophy. [citation needed]
[edit] Mechanism of action for BDNF

BDNF binds at least two receptors on the surface of cells which are capable of responding to this growth factor,
TrkB (pronounced "Track B") and the LNGFR (for "low affinity nerve growth factor receptor", also known as p75).
TrkB is a receptor tyrosine kinase (meaning it mediates its actions by causing the addition of phosphate molecules
on certain tyrosines in the cell, activating cellular signaling). There are other related Trk receptors, TrkA and TrkC.
Also, there are other neurotrophic factors structurally related to BDNF: NGF (for Nerve Growth Factor), NT-3 (for
Neurotrophin-3) and NT-4 (for Neurotrophin-4). While TrkB mediates the effects of BDNF and NT-4,TrkA binds and
is activated by NGF, and TrkC binds and is activated by NT-3. NT-3 binds to TrkA and TrkB as well, but with less
affinity.
The other BDNF receptor, the LNGFR, plays a somewhat less clear role. Some researchers have shown the LNGFR
binds and serves as a "sink" for neurotrophins. Cells which express both the LNGFR and the Trk receptors might
therefore have a greater activity - since they have a higher "microconcentration" of the neurotrophin. It has also
been shown, however, that the LNGFR may signal a cell to die via apoptosis - so therefore cells expressing the
LNGFR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.
[edit] Other diseases associated with low BDNF levels

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[edit] Other diseases associated with low BDNF levels
Various studies have shown possible links between low levels of BDNF and conditions such as depression,
schizophrenia, Obsessive-compulsive disorder, Alzheimer's disease, Huntington's disease, Rett syndrome, and
dementia, though it is still not known whether these levels represent a cause or a symptom. [citation needed]
[edit] High BDNF levels

High levels of BDNF and Substance P have been found associated with increased itching in eczema [1].
[edit] Epilepsy
Epilepsy has also been linked with polymorphisms in BDNF. Given BDNF's vital role in the development of the
landscape of the brain, there is quite a lot of room for influence on the development of neuropathologies from
BDNF.
Levels of both BDNF mRNA and BDNF protein are known to be up-regulated in epilepsy (Gall C, et.al. 1991). BDNF
modulates excitatory and inhibitory synaptic transmission by inhibiting GABAA-receptor mediated post-synaptic
currents. This provides a potential reason for the observed up-regulation.
[edit] References
1. ^ 'Blood chemicals link' to eczema [1]
[edit] External links

• BDNF and Alzheimer's Disease- What's the Connection?
• New Clue to Huntington's May Lead to Treatment
• New Findings May Support Soy-Dementia in Men
• Low BDNF activity promotes resilience
[edit] Further reading

• Gall C, Lauterborn J, Bundman M, Murray K, Isackson P (1991). "Seizures and the regulation of neurotrophic
factor and neuropeptide gene expression in brain". Epilepsy Res. Suppl. 4: 225-45. PMID 1815605.
• Jones KR, Fariñas I, Backus C, Reichardt LF (1994). "Targeted disruption of the BDNF gene perturbs brain and
sensory neuron development but not motor neuron development". Cell 76 (6): 989-99. PMID 8137432.
• Arévalo JC, Waite J, Rajagopal R, et al (2006). "Cell survival through Trk neurotrophin receptors is
differentially regulated by ubiquitination". Neuron 50 (4): 549-59. doi:10.1016/j.neuron.2006.03.044. PMID
16701206.
• Yamada K, Nabeshima T (2004). "Brain-derived neurotrophic factor/TrkB signaling in memory processes.". J.
Pharmacol. Sci. 91 (4): 267-70. PMID 12719654.
• Pang PT, Lu B (2005). "Regulation of late-phase LTP and long-term memory in normal and aging
hippocampus: role of secreted proteins tPA and BDNF.". Ageing Res. Rev. 3 (4): 407-30.
doi:10.1016/j.arr.2004.07.002. PMID 15541709.
• Hashimoto K, Koizumi H, Nakazato M, et al. (2005). "Role of brain-derived neurotrophic factor in eating
disorders: recent findings and its pathophysiological implications.". Prog. Neuropsychopharmacol. Biol.
Psychiatry 29 (4): 499-504. doi:10.1016/j.pnpbp.2005.01.007. PMID 15866349.
• Tsai SJ (2007). "Increased central brain-derived neurotrophic factor activity could be a risk factor for
substance abuse: Implications for treatment.". Med. Hypotheses 68 (2): 410-4.
doi:10.1016/j.mehy.2006.05.035. PMID 16824691.
• Bath KG, Lee FS (2006). "Variant BDNF (Val66Met) impact on brain structure and function.". Cognitive,
affective & behavioral neuroscience 6 (1): 79-85. PMID 16869232.
• Nair A, Vaidya VA (2006). "Cyclic AMP response element binding protein and brain-derived neurotrophic
factor: molecules that modulate our mood?". J. Biosci. 31 (3): 423-34. PMID 17006024.
Pasted from <http://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor>
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Food and Your Moods
8:52 AM
by Julia Ross, author of The Diet Cure

Are you an emotional basket case who can't get by without comfort food? If you had more strength, could
you power through your problems without overeating? Should you feel ashamed of yourself for needing
emotional sustenance from foods? No! I hope to help you understand why you are using food as self-
medication. It's not because you are weak willed, it's because you're low in certain brain chemicals. You
don't have enough of the brain chemicals that should naturally be making you emotionally strong and
complete.
HealthyPlace.com Video
Eating Behavior Modification Strategies for Overweight Adults and Children
Medical Approaches to Weight Loss

These brain chemicals are thousands of times stronger than street drugs like heroin. And your body has
to have them. If not, it sends out a command that is stronger than anyone's willpower: "Find a druglike
food or a drug, or some alcohol, to substitute for our missing brain chemicals. We cannot function without
them!" Your depression, tension, irritability, anxiety, and cravings are all symptoms of a brain that is
deficient in its essential calming, stimulating, and mood-enhancing chemicals.
Why Are Your Natural Mood-Enhancing Chemicals Sometimes Deficient?
Something has interfered with your body's ability to produce its own natural brain drugs. What is it? It's
obviously not too unusual, or there wouldn't be so many people using food to feel better, or taking Prozac
for depression relief. Actually, there are several common problems that can result in your becoming
depleted in your feel-good brain chemicals, and none of them is your fault!
You may have inherited deficiencies. We are learning more all the time about the genes that determine
our moods and other personality traits. Some genes program our brains to produce certain amounts of
mood-enhancing chemicals. But some of us inherited genes that undersupply some of these vital mood
chemicals. That is why some of us are not emotionally well balanced and why the same emotional traits
seem to run in families. If your mother always seemed to be on edge, and had a secret stash of chocolate
for herself, it should come as no surprise that you, too, need foods like candy or cookies to calm yourself.
Parents who have low supplies of naturally stimulating and sedating brain chemicals often produce
depressed or anxious children who use food, alcohol, or drugs as substitutes for the brain chemicals they
desperately need.
Prolonged stress "uses up" your natural sedatives, stimulants, and pain relievers. This is particularly true
if you have inherited marginal amounts to begin with. The emergency stores of precious brain chemicals
can get used up if you continually need to use them to calm yourself over and over again. Eventually your
brain can't keep up with the demand. That's why you start to "help" your brain by eating foods that have
druglike effects on it.
Regular use of druglike foods such as refined sugars and flours, and regular use of alcohol or drugs
(including some medicines), can inhibit the production of any of your brain's natural pleasure chemicals.
All of these substances can plug into your brain and actually fill up the empty places called receptors,
where your natural brain drugs - the neurotransmitters - should be plugging in. Your brain senses that the
receptors are already full, so it further reduces the amounts of neurotransmitters that it produces. As the
amounts of these natural brain chemicals drop (remember, they can be thousands of times stronger than
the hardest street drugs), more and more alcohol, drugs, or druglike foods are needed to fill newly
emptied brain slots. This vicious circle ends when these substances you ingest are unable to "fill the bill"
any longer. Now your brain's natural mood resources, never fully functional, are now more depleted than
they ever were, and you still crave your mood-enhancing drugs - whether it's sugar or alcohol and
cocaine.
You may be eating too little protein. In fact, you almost certainly are if you've been dieting or avoiding fatty
foods, many of which are high in protein, too. Your brain relies on protein - the only food source of amino
acids - to make all of its mood-enhancing chemicals. If you are not getting enough protein, you won't be
able to manufacture those crucial chemicals. A little later in this chapter and in chapter 18, you'll learn
about complete and incomplete proteins, and what is "enough" protein for you. Simply put, eating the
equivalent of three eggs, a chicken breast, or a fish or tofu steak at every meal might get you enough
protein to keep your brain in repair.
The Physical Cause of Emotional Eating
In the late 1970s, I was the supervisor of a large San Francisco alcoholism treatment program. Our clients
were very serious about getting sober, and we gave them the most intensive treatment available
anywhere. Yet they could not stop drinking. Eighty to ninety percent relapse rates were standard then,
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anywhere. Yet they could not stop drinking. Eighty to ninety percent relapse rates were standard then,
and still are, in the alcohol and drug addiction fields.
As I studied these heartbreaking relapses, I began to see a pattern. Our clients had stopped drinking, but
they had quickly developed a heavy addiction to sweets. Sugar is almost identical to alcohol
biochemically. Both are highly refined, simple carbohydrates that are instantly absorbed, not needing
digestion (complex carbs, like whole grains, need time to be digested). Both sugar and alcohol instantly
skyrocket blood sugar levels and temporarily raise levels of at least two potent mood chemicals in the
brain. This high would be followed by a low, of course. So, just as when they were using alcohol, our
clients who had switched to eating large amounts of sugar were moody, unstable, and full of cravings.
Since alcohol usually works even faster than sugar does, at some point, caught in a particularly low
mood, they would break down and have a drink to get some relief. One drink would become a full-blown
relapse.
In 1980, when I became the director of the program, I began hiring nutritionists to help solve this
disturbing relapse problem. They suggested to our clients that they quit eating sweetened foods, foods
made from refined (white) flour, and caffeine, and that they eat more whole grains and vegetables.
Unfortunately, these nutritional efforts didn't pay off. For reasons that we understood only later, our clients
just couldn't stop eating the sweets and starches that eventually led them back to alcohol. For six years
we struggled for a solution, then, in 1986, we found one.
The solution came from Dr. Joan Mathews Larson, the director of a nutritionally oriented alcoholism -
treatment center in Minneapolis, Minnesota. This brilliant pioneer, the author of Seven Weeks to Sobriety,
introduced me to a technique that was quickly eliminating her alcoholic clients' cravings and raising her
center's long-term success rate from 20 percent to 80 percent! The technique involved the use of specific
amino acids that could rapidly feed the addicted brain exactly the type of protein that it needed to
naturally fill up its empty mood-chemical sites. The results were spectacular. No longer did alcoholic
clients need sweets or alcohol to feel good! Amino acid therapy revolutionized the work at our clinic, too,
dramatically raising our success rates with alcohol and drug-addicted clients. Moreover, we were able to
successfully treat clients with other addictions as well. In fact, our most spectacular successes were with
food-addicted clients. Ninety percent of the compulsive overeaters we have treated with amino acid
therapy have been freed from their food cravings within forty-eight hours.
Using Amino Acids to End Emotional Eating
When psychological help does not clear up emotional eating, we need to look at the four brain
chemicals - neurotransmitters - that create our moods. They are:
1. dopamine/norepinephrine, our natural energizer and mental focuser
2. GABA (gamma amino butyric acid), our natural sedative
3. endorphin, our natural painkiller
4. serotonin, our natural mood stabilizer and sleep promoter
If we have enough of all four, our emotions are stable. When they are depleted, or out of balance, what
we call "pseudo-emotions" can result. These false moods can be every bit as distressing as those
triggered by abuse, loss or trauma. They can drive us to relentless overeating.
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For some of us, certain foods, particularly ones that are sweet and starchy, can have a druglike effect,
altering our brains' mood chemistry and fooling us into a false calm, or a temporary energy surge. We can
eventually become dependent on these druglike foods for continued mood lifts. The more we use them,
the more depleted our natural mood-enhancing chemistry becomes. Substituting amino acid supplements
for these drug foods can have immediate and dramatic effects.
Toni, a 26-year-old Native American, was referred to our clinic because she was exhausted, profoundly
depressed, anxious and suffering lifelong trauma from the physical and emotional violence of her family.
Toni drank alcohol and ate sweets to cope. She went regularly to her scheduled counseling sessions but
was unable to rouse herself to communicate with her counselor. She had volunteered to come to
Recovery Systems, hoping that a new approach would help. Toni had already been through three long-
term treatment programs for alcohol addiction. Clearly, she was motivated to solve her problem.
When we saw Toni's condition, the nutritionist and I conferred and decided to give her amino acids on the
spot. I asked her to tell me one thing: What was the worst thing she was experiencing at that moment?
She said "I'm sooooo tired." Her slumped body and still, dull eyes confirmed this.
Our goal? To treat her lack of energy and depression by raising her levels of the neurotransmitter
norepinephrine, the body's natural energizer. We gave her our smallest dose - 500 milligrams of L-
tyrosine. While we waited and hoped for an effect, I spoke about how and why amino acids can be
helpful.
After about ten minutes, Toni said, "I'm not tired anymore."
"Great!" I said. And then I asked my next question: "What is the worse thing you are experiencing, now
that your energy is better?"
She answered by bending over and grasping herself around the stomach. "I'm really uptight."
We then gave Toni the smallest dose of GABA - 100 milligrams - a natural Valium-like chemical along
with 300 milligrams of L-taurine. We suspected that together these supplements would help relieve her
tension and allow her to relax - and they did. She stretched her legs out in front of her and then stood up,
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tension and allow her to relax - and they did. She stretched her legs out in front of her and then stood up,
got a glass of water, and went to the bathroom. While she was gone, her counselor came in and
happened to tell me that Toni was in a lot of emotional pain because of the chronic alcoholic violence in
her family. When her family members drank alcohol, they all became different people, vicious and cruel.
And they had never been able to stay away from alcohol.
When Toni returned, I asked her, "Can we give you something to help you endure the emotional pain that
you are in?" She said yes, so I gave her a supplement containing 300 milligrams DL-phenylalanine and
150 milligrams L-glutamine. (DL-phenylalanine is the amino acid used to alleviate emotional pain.)
In ten minutes I asked Toni how she was feeling, and she smiled and said, "Just right."
I was incredulous. How could these small amounts really be helping her? Our European American clients
usually need two to four times as much of each type of amino acid to get such dramatic effects.
I asked if she would like any more of any of the aminos I had already given her for energy, relaxation, or
pain relief. Her answer: "Just right," and a shake of her head.
By this time Toni's eyes were sparkling. Weeks later her counselor reported that by continuing with the
amino acids she had first used in our office, Toni was actually talking for the first time in their counseling
sessions, and was being praised at work, was being noticed for the first time by men, and was staying
sober and sugar-free.
Mood Foods: How Amino Acids Feed Your Brain
The four key mood chemicals (neurotransmitters) are made of amino acids. There are at least twenty -two
amino acids contained in protein foods. High-protein foods, such as fish, eggs, chicken, and beef, contain
all twenty-two, including the nine amino acids that are considered essential for humans. Other foods,
such as grains and beans, have some but not all of the essential nine aminos, so they need to be
carefully combined to provide a complete protein (for example, rice and beans, or corn and nuts).
If you are eating three meals a day, each meal including plenty of protein (most people with eating and
weight problems are doing neither), your positive moods and freedom from cravings can be maintained.
But most people need to kick-start the brain's repair job, using certain key amino acids. This will allow you
to actually enjoy eating protein and vegetables instead of cookies and ice cream. After a few months, you
will be getting all the aminos you need from your food alone and won't need to take amino acids as
supplements any longer.
Restoring depleted brain chemistry sounds like a big job - but it isn't. Three of the four neurotransmitters
that color all your moods are made from just a single amino acid each! Because biochemists have
isolated the key amino acids, you can easily add the specific ones that may be deficient. These "free
form" amino acids are instantly bioavailable (in other words they are predigested), unlike protein powders
from soy or milk, which can be hard to absorb. Hundreds of research studies at Harvard, MIT, and
elsewhere (some of which date back to the early part of this century) have confirmed the effectiveness of
using just a few targeted amino acid "precursors" to increase the key neurotransmitters, thereby
eliminating depression, anxiety, and cravings for food, alcohol and drugs.
Stopping Carbohydrate Cravings
It may sound impossible, but you can stop your food cravings almost instantly with just one amino acid
supplement. Any absence of fuel for your brain's functions is perceived correctly by your body as a code -
red emergency. Powerful biochemical messages then order you to immediately eat refined carbohydrates
to quickly fuel your brain. There are only two fuels that the brain can readily use:
1. glucose, which is blood sugar made from sweets, starches, or alcohol
2. L-glutamine, an amino acid available in protein foods (or as a supplement, carried in all health food
stores). L-glutamine reaches the starving brain within minutes and can often immediately put a stop
to even the most powerful sweet and starch cravings. The brain is fueled by L-glutamine when
glucose levels drop too low. Don't be intimidated by the strong effects of supplementation. L-
glutamine is a natural food substance; in fact, it's the most abundant amino acid in our bodies. It
serves many critical purposes: stabilizing our mental functioning, keeping us calm yet alert, and
promoting good digestion.
Restoring Energy and Focus
When your brain is adequately fueled with its back-up emergency supplies of L-glutamine, you are ready
to rebuild your four key neurotransmitters, starting with dopamine/norepinephrine, your natural caffeine.
Without this natural brain stimulant, you can be slow and tired and have a hard time concentrating. You
don't sparkle and can't stay on track mentally. It's hard to get things done and you can feel dull and
sometimes just want to stay in bed. Your physical as well as your mental energy drops without adequate
norepinephrine. The amino acid that provides this jet-fuel is the nutritional powerhouse L-tyrosine. L-
tyrosine produces thyroid hormones and adrenaline as well as well as norepinephrine. Like L-glutamine,
L-tyrosine goes to work in minutes to perk you up.
Enhancing Your Ability to Relax
The next key mood-enhancing chemical is GABA (gamma amino butyric acid), our natural Valium. GABA
acts like a sponge, soaking up excess adrenaline and other by -products of stress and leaving us relaxed.
It seems to drain the tension and stiffness right out of knotted muscles. GABA can even smooth out
seizure activity in the brain. My colleague, Elliot Wagner, a specialist in drug detox, taught me that GABA
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can even give relief to heroin addicts going through the severe anxiety of early withdrawal. Think what it
can do for garden variety stress and uptightness!
When Food is Comfort
More Info
You May Be Depressed! What Do You Do Now?
Food and Your Moods
Recovering from Compulsive Overeating - Binge Eating
Chocolate is My Kryptonite: Feeding Your Feelings
For many people, overeating helps compensate for a depletion of the natural pain relievers, the
endorphins. Life's pain can be unendurable without adequate amounts of these buffer chemicals. Some of
us (for example, those of us from alcoholic families) may be born with too little natural pain tolerance. We
are overly sensitive to emotional (and sometimes physical) pain. We cry easily. Like our alcoholic parents,
we need something to help us endure our daily lives, which seem so painful. Others of us use up too
much endorphin through trauma and stress. We just run out, especially if we were born short on
endorphins to begin with. When our comfort chemicals run low, many of use turn to comfort foods.
If you need food as a reward and a treat, or to numb your feelings, your natural pleasure enhancers, the
pain-killing endorphins, are probably in short supply. Foods that elevate your endorphin activity can easily
become addictive. If you "love" certain foods, those foods are firing a temporary surge of endorphins.
Euphoria, joy, the "runner's high" - these are all feelings produced by endorphins. Some people have so
much natural endorphins that they smile all the time and get great pleasure from everyday life. Of course,
we all endure suffering and loss. But, with enough endorphins, we can bounce back.
For anorectics and bulimics, the trauma of starving and vomiting can trigger an addictive endorphin high,
because trauma of any kind can set off an automatic burst of soothing endorphins. You may know of
people who felt no pain for hours after a terrible physical injury. Runners don't get their big endorphin high
until they have run past "the wall of pain." At that point, they have run too far!
Raising Serotonin, Our Natural Prozac
Low serotonin can be the easiest deficiency of all to develop. Very few foods are high in the amino acid
tryptophan, which is the only nutrient that the body can use to make serotonin. According to a 1997
Lancet study, tryptophan is one of the first nutrients to be depleted by weight -loss dieting. If, in addition to
dieting, you inherited low serotonin levels and experience a lot of stress, your levels can fall low enough
to set off a major eating disorder or serious emotional disturbances.
Restoring your serotonin levels can be a life-or-death matter. Suicides and violent crimes are closely
associated with deficiencies of serotonin. The sometimes fatal obsessions and self-hate of bulimics and
anorectics are clearly linked to low serotonin levels as well.
Do you have any obsessions that might be caused by low serotonin levels? The women I have worked
with who report obsessive behavior tend to be "neat-niks" and suffer from negative obsessing about their
physical appearance, while the men are often "neat-freaks," although they also complain about troubling
sexual fantasies they can't stop. As we all know, anorectics (who are low in serotonin) are driven to
obsessive control of their food intake. Obsessive fears and phobias are common among people with low
serotonin levels.
It may be a difficult adjustment for you to begin to see symptoms like control, fear, and low self-esteem as
biochemical problems, not just psychological ones. But the success of drugs like Prozac has already
alerted us to the biochemical nature of many symptoms that don't respond to psychological help alone.
Drugs like Prozac are called serotonin reuptake inhibitors (SSRIs) because they keep whatever serotonin
we have active. But they do not actually provide additional serotonin. For this reason, most people using
SSRIs often continue to have some low-serotonin symptoms. Before there were SSRIs, the
pharmaceutical compound L-tryptophan was commonly used to increase serotonin levels. For more than
twenty years, psychiatrists and health food stores enthusiastically recommended it for relieving
depression and food cravings and normalizing sleep without side effects. Many people found that their
symptoms were eliminated permanently after only a few months of L-tryptophan use.
In 1989, a series of bad batches of L-tryptophan, which filled forty people and made many more very sick,
prompted the Food and Drug Administration (FDA) to stop all U.S. sales. One Japanese company,
Showa Denko, had produced all of these batches, which, it was found, were contaminated because they
had eliminated three filter systems that they'd been using for years - just why they chose to take away
these safety filters is a question that remains unanswered. Showa Denko has never made tryptophan
again. Despite evidence that no other manufacturer has ever made a problem batch, the FDA
recommended for years that L-tryptophan not be used as a supplement. (Interestingly, they have made
no effort to stop the sale of infant formulas, most of which contain added L-tryptophan.)
With L-tryptophan unavailable, drugs like Prozac, Zoloft, and Redux have become our primary tools for
combating the crippling symptoms of low serotonin. Unfortunately, these drugs provide only temporary
and incomplete benefits, and often have uncomfortable or dangerous side effects. Fortunately, in 1996,
many compounding pharmacies began providing L-tryptophan again, by physician prescription, and a
new version of tryptophan called 5HTP (5-hydroxytryptophan) became available over the counter in 1998
without FDA opposition. In 2000, Lidtke Technologies Corporation of Phoenix, Arizona, made L-
tryptophan available through health professionals without prescription. Look for other supplement
suppliers to follow suit, as the FDA has never formally banned the sale of this essential amino acid.
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suppliers to follow suit, as the FDA has never formally banned the sale of this essential amino acid.
Whatever mood-enhancing brain chemicals you have in short supply, they can be replenished quickly,
easily, and safely.
Tryptophan Depletion: The Path to Depression, Low Self-esteem, Obsession and
Eating Disorders
Serotonin, perhaps the most well known of the brain's four key mood regulators, is made from the amino
acid L-tryptophan. Because few foods contain high amounts of tryptophan, it is one of the first nutrients
that you can lose when you start dieting. A new study shows that serotonin levels can drop too low within
seven hours of tryptophan depletion. Let's follow this single essential protein (there are nine altogether)
as it becomes more and more deeply depleted by dieting. To see how decreased levels of even one brain
nutrient might turn you toward depression, compulsive eating, bulimia, or anorexia.
In his best seller, Listening to Prozac, Peter Kramer, M.D., explains that when our serotonin levels drop,
so do our feelings of self-esteem, regardless of our actual circumstances or accomplishments. These
feelings can easily be the result of not eating the protein foods that keep serotonin levels high. As their
serotonin-dependent self-esteem drops, girls tend to diet even more vigorously. "If I get thin enough, I'll
feel good about myself again!" Tragically, they don't know that they will never be thin enough to satisfy
their starving minds. Extreme dieting is actually the worst way to try to raise self-esteem because the
brain can only deteriorate further and become more self-critical as it starves. More and more dieters
worldwide are experiencing this miserable side effect of weight reduction on the brain.
When tryptophan deficiency causes serotonin levels to drop, you may become obsessed by thoughts you
can't turn off or behaviors you can't stop. Once this rigid behavior pattern emerges in the course of
dieting, the predisposition to eating disorders is complete. Just as some low-serotonin obsessive-
compulsives wash their hands fifty times a day, some young dieters may begin to practice a constant,
involuntary vigilance regarding food and the perfect body. They become obsessed with calorie counting,
with how ugly they are, and on how to eat less and less. As they eat less, their serotonin levels fall
farther, increasing dieters' obsession with undereating. As their zinc and B vitamin levels drop low as well,
their appetite is lost. This can be the perfect biochemical setup for anorexia.
What so many therapists and others have observed as the central issue of "control" in anorexia often
comes down to this: just as vitamin C deficiency (scurvy) results in an outbreak of red spots, do does
tryptophan (and serotonin) deficiency result in an outbreak of the obsessive-compulsive behavior that we
call "control." There may be psychological elements in the picture, too, but a low-serotonin brain is ill
equipped to resolve them.
Source: excerpted with permission from The Diet Cure: The 8-Step Program to Rebalance Your Body
Chemistry and End Food Cravings, Weight Problems, and Mood Swings-Now, by Julia Ross.
Read this transcript with Dr. Kathleen DesMaisons, author of "Potatoes Not Prozac". She discusses how
sugar addiction can affect your mood.
RELATED LINKS AND INFO
Triumphant Journey: A Cyberguide To Stop Overeating
Compulsive Overeating: Dealing With The Feelings and How To Treat It
Starting an Exercise Program: The Right Time Is Now
Mind/Body Medicine for Treating Depression
Prayer May Heal Depression
What Dr. Andrew Weil Recommends for Treating Depression Symptoms
Depression Treatment Overview
depression treatments: alternative ~ antidepressants ~ ect
emdr ~ therapy ~ self-help ~ transcranial magnetic stimulation
vagus nerve stimulation
Pasted from <http://www.healthyplace.com/Communities/Depression/treatment/alternative/food_moods.asp>
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01 SCHAFFER 2008 Diagnosis and Etiology of Depression
7:16 PM
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02 SCHAFFER 2008 Biological Treatment of Depression 2x3
7:19 PM
How did trends in the

outpatient treamtent of
depression change
between 1987 and 1997
in the US?
• Data coming from canadian community health survey; what's • So in 1987, if they did go to family physician/psyhciatrist then What is the difference
the chance in the last 12 months that you actually saw only 35% chance would be given meds between the goals of
someone with that condition • Now closer to 80%! acute, continuation, and
• So only about a third of the people with one of these • So there's been a shift to more medical treatment maintenance treatment
conditions got any help with these symtpoms with respect to treating
○ General rule is family practitioners: they go to their depression?
family doctor most frequently to report psychiatric
conditions
○ Next up the list is psychiatrists but only 12% chance;
most are family physicians
• Acute treatment aims to remove all signs and symptoms of the current episode of depression and to
restore psychosocial and occupational functioning (a remission). A remission (absence of symptoms) may occur either
spontaneously or with treatment. If the patient improves significantly, but does not fully remit with treatment, a response i s declared. If the
symptoms return and are severe enough to meet syndromal criteria within 6 months following remission, a relapse (return of sy mptoms of the
current episode) is declared.
• Continuation treatment is intended to prevent this relapse. Once the patient has been asymptomatic for at least 4
to 9 months following an episode, recovery from the episode is declared. At recovery, continuation treatment may be stopped. For those with
recurrent depressions, however, a new episode (recurrence) may occur months or years later.
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recurrent depressions, however, a new episode (recurrence) may occur months or years later.
• Maintenance treatment is aimed at preventing a new episode of depression and may be prescribed
for 1 year to a lifetime, depending on the likelihood of recurrences.
Pasted from <http://www.mentalhealth.com/bookah/p44-d2a.html>
How long does the acute
phase of antidepressant
treatment last?
How long does the
maintenance phase of
antidepressant treatment
last?
How long does the
continuation phase of
last?
Every patient treated for
depression needs to go
through at least which 2
phases of treatment?
Give 3 examples of TCA

antidepressants?
How do TCA antidepressants
work?
• 3 stages when prescribing Why are SSRI's more sought
○ Acute: treat depression quickly after than TCAs?
○ Continuation: treatment to prevent relapse List 2 common side effects of
 Every patient treated for depression needs to TCAs?
have the acute and continuation Give 2 examples of SNRIs?
○ Maintenance: only required for some patients Give 2 examples of SSRIs?
What is the generic name of
Celexa?
Prozac?
Effexor?
Zoloft?
Paxil?
How do SSRIs work?
How do SNRIs work?
Which is the MOST toxic in
overdose: SSRIs, TCAs, SNRIs?
SNRIs: Allow for more
noradrenaline in the synaptic cleft
• Older TCA's; came out in 60's no brand names because came out in 60's; so all
generic; used in areas not just related to psychiatry or depression
• Patients can take lots of ssri's but not have anything happen • Amitriptyline used for chronic pain; high doses good anti-depressive effects
to them
How does
Buproprione
(Wellbutrin) work?
Buproprion (Wellbutrin),
at high doses, has which
common side-effect?
What is the generic

name for Remeron?
How do MAOI
antidepressants work?
List 2 common side
effects of MAOIs?(3)
What is the
mechanism of action
of Mirtazapine?
List 2 common side-effects

of Mirtazapine
(Remeron)?(3)
• Eg. Tyramine: precursor for dopamine; found in many List 2 common side-effects
foods including tofu and cheese of Buproprion (Wellbutrin)?
○ If you're on a MAOI antidpressant and not able to Give an example of a
break doewn the dopamine, get all sorts of side reversible MAOI
effects in peripehery leading to hypertension and antidepressant and another
headaches secondary to HTN example of an irreversible
• Lots of mao-a and mao-b in the gut MAOI antidepressant?
• Drug-drug interactions: many other meds will also Tyramine ingestion while
increase levels serotonin and NE: eg. Migraine meds taking MAOIs can cause
(triptans) ___?
• Get serotonin syndrome with increasing serotonin levels Why should tripants (used
• Any kind of aged foods, meat, fish, fermented projets in the treatment of
• Wellbutrin: inhibits reuptake of dopamine; issues: migraines) not be taken
increased risk of seizures especially at higher doses with MAOI
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increased risk of seizures especially at higher doses
• Mirtazapine (remeron): alpha -2 adrenergic receptors: antidepressants?
sit presynaptically Tyramine is the precursor
for ___?
Which type of anti -
Foods to be restricted or avoided because of a 'tyramine' reaction (high BP)
1. Cheeses. Some have very high levels of tyramine, especially ‘mature’ cheese types like Stilton, Brie and depressant class has a high
Camembert, Mozzarella; the 'smellier' it is the more tyramine it contains. A tw enty gram serving of a rate of drug-
strong cheese could possibly raise the BP to a measurable extent (but not to a dangerous extent). drug and drug-food
Larger quantities become progressively more risky. Most modern supermarket processed cheese has
low (to the extent of being completely safe) levels of tyramine; how ever tyramine levels are interactions?
unpredictable, so it is risky to experiment because the w orst possible outcome, even if that is remote, is
a ‘stroke’. We can say that 'ricotta' and 'cottage' cheese types are alw ays safe to eat.
2. Extracts such as ‘Vegemite’, ‘Promite’, 'Marmite', ‘Bovril’ must be avoided.Foods like soy sauce,
'tofu' and 'miso' are made in a similar w ay; ie by 'fermentation' of brew s containing proteins, so only
small amounts can be safely eaten. Because the BP goes up in proportion to the amount of tyramine
that is eaten, it is OK to have small quantities (see below for what 'small' really means).
3. Meat products are safe, but if they are not fresh, ie if they have been subject to decomposition by • Basically, avoid any
m icro-organisms, then they may be risky; eg liver pate (and similar meat or fish pastes) are perfectly foods that have been
safe if freshly made and properly refrigerated. But after a couple days left out at room temperature they acted on siginficantly
could be risky. Similarly 'salami' and 'pepperoni' sausages, and dried meats, are usually OK but caution by microorganisms,
is w arranted. Liver that is near its' 'use by' date w hen purchased, and is then kept in a domestic fridge as these may contain
that is not cold enough, may possibly be risky. dangerously high
4. Alcoholic drinks in true m oderation(two drinks in any six hour period) is very likely to be safe. tyramine levels
Modern hygienic production methods w ill make excessive tyramine levels rare. Badly made or stored
drinks may be risky, so avoid ‘home made’ w ines or beers. Bottled beer is almost certain to be safe; but
avoid ‘live’ beers w hich may be available from 'boutique' producers. They can be distinguished by the
sediment (of dead yeast) in the bottom and they are cloudy if shaken. Also ‘keg’ or 'tap' beers may
sometimes have significant tyramine levels and are best avoided.
5. Sauerkraut can sometimes contain sufficient tyramine levelsto w arrant restriction (see below) and
broad (fava) beans are OK but the bean pods should not be eaten.
Other non-serious interactions that are not dangerous
Many plant derived substances, eg 'herbs' and 'foods' like chocolate, coffee, and tea contain chemical
compounds that act as 'drugs', eg stimulants like caffeine. These effect everyone but may have an exaggerated
effect in those taking various sorts of antidepressant drugs, including MAOIs; they should be taken in
moderation and avoided if they precipitate symptoms such as anxiety, jitteriness, agitation, poor sleep etc
Pasted from <http://www.psychotropical.com/MAOIs_Information_full.shtml >
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List 4 factors that
should influence your
choice of which
antidepressant to
prescribe?
What are two specific
side effects of most
antidepressants that
you should warn
patients about?
The precursor for

dopamine, _____, is found
in many foods, including
Many patients with depression also have anxiety cheese and tofu?
1. Patients with anxiety respond well to serotnonin and those that increase dopamine and NE, then worsen these
symtpoms; so anxiety: go to SSRI meds
2. Avoid specific side effects: eg. Sexual side effects, major issue with SSRI's: want to avoid anti -dpresnts that
increase serotonin levels; another eg: weigth gain
3. Comorbid conditions: eg. Anxiety: another: chronic pain: TCA's: also used for pain: so use TCA to kill two birds
with one stone
4. Previous lack of response: if they've been on 5 SSRI's, and haven't tried a different class, then use another class!
What percentage,
approximately, of
patients will RESPOND
to treatment with a
first line
antidepressant? (nb.
Asking for response,
Most remission occurs NOT remission)
between 4 to 10 weeks
What is the difference
between response and
remission?
MOST remissions from
antidepressant use
Difference between response vs. remission occur between ___
• So weeks 4,6,8,10 will start to see remission
• Response: at least 50% improvement in depressive symptoms to___ weeks of use?
• @ 10 weeks effect begins to taper off
• Remission is the absence of depressive symptoms; about half
to two thirds will have good response to first antidprsnt that
go on but the remission, ony about 37% will actually remit;
after the 4th trial, about two-thirds
• Idea of these mediations is to get you back to who you are 4 possibilities to if meds not working:
• Common question: Aren't these meds addictive? 1. Review diagnosis/investigations; if still want to treat:
a. Combine
b. Increase dose or duration: so if someone comes in 4 weeks
later, then we suggest continue on antidepressant for
longer time
c. Switch
d. Add a second
List 4 strategies one
should follow if the
medications prescribed
for anti-depression
aren't helping?
What does it mean to
'augment' anti-
depressant medication
with other medications?
In using a 2nd
medication for
depression treatment,
what is the principle
that should be
followed?
• Investigations: TSH, b12, blood count, tox screen, drug screen • Lithium: augment
• Augmentation: meds that are not themselves antidpresents • T3: when added to antid. Can boost effectiveness; lots of other examples
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c. Switch
d. Add a second
List 4 strategies one
should follow if the
medications prescribed
for anti-depression
aren't helping?
What does it mean to
'augment' anti-
depressant medication
with other medications?
In using a 2nd
medication for
depression treatment,
what is the principle
that should be
followed?
• Investigations: TSH, b12, blood count, tox screen, drug screen • Lithium: augment
• Augmentation: meds that are not themselves antidpresents • T3: when added to antid. Can boost effectiveness; lots of other examples
but if you add them to antid. Have antid. Effects (examples that can be added;
later, eg. lithium) • on the right are combinations we sometimes use; want to use anti -d that
• Combination: 2 actual genuine antid. meds have complimentary mechanisms of action; DON'T WANT TO COMBINE
TWO OF THE SAME MEDS THAT HAVE THE SAME MECH OF ACTION
List 3 categories of
patients who would
require maintenance
treatment?(4)
• Remember 3rd phase of treatment: maintenance

• Recurrent: i f keep getting depressed, when not on meds, then have to start
• Gold standard treatment: combinations of antidepressent and preventing by keeping on meds
psychotherapy • Never been s hown to be a ny l ong term morbidity associated with maintenance
• Ra mi fications of relapse too high: single mother husband left marriage; caring for
two s mall children: CAS i nvolved; i f s he's the s ole provider then v. di fficult
Which other form of

treatment should be
added to antidepressant
therapy to achieve an
even better outcome?
How are number of
episodes of
correlated with length of
antidepressant
treatment?
T/F: A MINORITY of
patients achieve
remission from
depression with FIRST line
medication?
T/F: Most medication
choices have similar
efficacy?
A majority of depression
patients achieve
remission after how many
medication trials?
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T/F: A MAJORITY of
patients achieve
remission from
depression after
TWO OR MORE
medications?
• Phototherapy: for seasonal depression • Bilateral ECT: v. cotnroversial; been around for long time
○ UV-free • All major hospitlas with psych depts have ECT
○ Has biological antidepressant effects • Can be life-saving
• Changed lots since 1920's 30's as see in moveies
Apart from
pharmaceutical
therapy, list 2
other biological
treatments for
depression?(4)
• Repetitive transcranial: coil over left prefrontal cortex: • Margaret trudeau: came out with struggles with depression
magnetic field that stimultes activity in cortex underneath
• Deep brain stimulation: used in neurology and being tried in
psych: anterior cingulate hpyeractive in depression; prove
dampens activity in anterior cingulate; not in family docs ofice
but cutting edge in biological treatments
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02 SCHAFFER 2008 Biological Treatment of Depression
7:19 PM
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03 ZARETSKY 2008 Cognitive Therapy for Depression 2x3
7:52 PM
Take home messages:
○ Cbt is an active, structured form of psychot. That is empirically validated and broad spectrum
○ CBT is as effective as meds for mild to moderate

depression and more effective in reducing relapse
○ Cbt for depression ultiilizes behavioural activation and congitive restructuring techniques
• Like meds, psychotherapy can be said to have a mechanism of

• CBT: consdiered be gold standard for psychotherapy
action and this can be specific or non-specific
List 3 non-specific
mechanisms of
action of
psychotherapy?
List 3 specific
mechanisms of
action of
psychotherapy?
List 2 different
forms of
psychotherapy?(3)
• Se slide (new slide, not in these lectures)

• Forms of Psychotherapy:
○ Psychodynamic therapy: focus on past and
relationships
○ Interpersonal therapy: manualized supportive
therapy - focuses on interpersonal problems of patient
○ Cognitive thereapy/CBT/behaviour therapy
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The cognitive model
states that one's
core beliefs in a
situation influence
which 3 factors?
• Cognitive model has a myriad of applications

Eg. Of a thought: "I'm not a good lecturer"
Cognitive therapy is
generally time limited
to how many months
(for uncomplicated
depression or anxiety)?
T/F: Cognitive therapy
can be done
individually but should
not be done in groups?
• So what is COGNITIVE therapy? Distilled to its essence: 2 premises:

1. It's the thought that counts: it's your thinking that explains why
you do certain things
2. Don't believe everything you think! Vis -a-vis dysfunctional
thoughts
• Goal of therapy: teach the patient to become their own therapist: we
don't like patients to be in treatment for 40 years: not a good
outcome to be in psychotherapy; that's why v. popular with patients;
very empowering; structured and goal oriented; in every session
actually have an agenda try to address the patients needs nad bigger
goals of treatment
• For uncomplicated depression or anxiety, over in 4 to 6 months
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What are the stages in the Cognitive
Model of Depression?(hint: 5 linear
steps before get to symptoms of
depression)?
Different types
of adversity
that lead to...
NB: all of us have negative core beliefs

but not all of us get depressed; therefore
have to also have biology
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Give examples of
how CBT is a
structured therapy?
• At the end of every session actually ask patient: what did you take
from this session; actually want feedback about the session; very
empowering for patient
• Eg. Self help exercises: manual: mind over mood; self help mood;
from greenberger and deretsky; taking patient through CBT step
by step
What are the 6

steps in cognitive
restructuring?
List 5 cognitive
distortions?(10)
Eg. Cognitive distortions: all or nothing thinking: you're either

comptent or a failure
• Cognitive therapy more than just being supportive
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Which of the following is an
example of Socratic
questioning, in response to
a student saying "I'm a
complete failure" (there
may be more than one right
answer): 1. What makes
you think you are a
complete failure?; 2. Why
are you being so hard on
yourself?; 3. What would a
good student do?; 4. Would
a complete failure be able
to get 75% on an exam?; 5.
On a scale of 0-100%,
where do you fall? Where
do other people fall?
In a typical course of CBT

for depression, organize
the following session
goals from earliest to
latest: Goal setting,
relapse prevention and
termination, assessment
and suitability,
behavioural activation,
use of an automatic
thought record?
Typical course:
Assessment --> goal setting --> behavioral activaiton --> ATR --> deeper core beliefs --> relapse prevention
T/F: CBT is as effective as

medication for chronic
depression?
Give a few examples of
comorbidities of depression?
List 4 psychiatric conditions
in which CBT is the gold
standard?
T/F: If you wish to start a
patient on CBT, this SHOULD
NOT be started mid-way
through their medication
course because of the
inability to discern which is
• CBT focuses on skill deficits having a positive effect?
• Patient came in for presentation; came to cbt after 4 -5 years of psychotherapy T/F: CBT is NOT as effective
as medication for more
severe non-psychotic
depression?
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Give an example
of how CBT can
be used to
maintain patients
in remission
more effectively
than clinical case
management?
Therefore a much higher

proportion (close to 75%) of
those who achieved remission
REMAINED IN REMISSION
using CBT as opposed to only
approximately 15% with
clinical case management.
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T/F: For chronic
depression, there is no
difference between
using CBT alone versus
using medication
alone?
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Apart from
depression, list 2
other common
medical problems
which CBT be used
for?(5)
CBT and SRI

treatment
responsive OCD
patients show
similar decreased
activitiy in which
brain structure?
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T/F: CBT is as effective
as medication for mild
to moderate
depression?
T/F: CBT is MORE
effective than
medication in reducing
relapses?
• SEE SLIDES MISSED IN HANDOUT LECTURE9
Take home messages:

○ Cbt is an active, structured form of psychot. That is empirically validated and broad spectrum
○ Is as effective as meds for mild to moderate

depression and more effective in reducing relapse
○ Cbt for depression ultiilizes behavioural activation and congitive restructuring techniques
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04 SCHAFFER 2008 Introduction to Bipolar Disorder 2x3
7:21 PM
What are the 2

criteria used to
define bipolar
disorder?
In diagnosing a manic
episode, what are the
4 general categories?
In diagnosing a manic
episode, patients
must experience 3 or
more of which 7
symptoms?(just
name 5)
• Eg. Patient had stopped a way for hurricanes to happen; Are depressive episodes
put up wall! necessary for the
• Most specific symptom of mania: decreased sleep need, diagnosis of bipolar
genuine; don't feel tired when wake up; just sleeping 2 disorder?
hours
• Increase in goal directed activity: washing dishes and
renovating house at night
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A genuine manic
episode generally lasts
for at least how long?
What is Bipolar
Disorder Type II?
According to the mood
spectrum, what's the
difference between
bipolar type I and type
II?
List 3 criteria for

hypomanic episodes?(6)
• Hypomani: 4 days Hypomania +

• Mania: at least 1 week Depression = ___?
List 3 symptoms
that overlap
between mania
and
depression?(6)
What are the 3 diagnostic

criteria for a mixed
episode?
In diagnosing a mixed
episode, criteria for BOTH
a manic episode AND
major depressive episode
should be met for what
minimum period of time?
What percentage of
bipolar patients have
recurrence?
What are the two most
common conditions
that are comorbid with
bipolar disorder?
Week8 Page 94
What is the most common
age for the onset of
bipolar disorder in males
and females?
The presence of mania, in
Canada, is highest in
which age group: 15-24,
25-64, or over 64?
The leading cause of

mortality in patients
with BD is due to ___?
T/F: Bipolar disorder is

NOT caused by parents
but CAN be reversed by
will power?
T/F: Bipolar disorder MAY

run in families?
T/F: Patients with bipolar
disorder do not actually
have morphological
abnormalities but they do
have second messenger
and mitochondrial
dysfunction?
Week8 Page 95
BIPLOR DISORDER IS OFTEN MISDIAGNOSED!
Approximately
___% of
depressed
patients have
bipolar disorder?
List 3 populations
that are
particularly at
risk for bipolar
disorder?(6)
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List 2 psychiatric
disorders for which
mood stabilizers are
indicated for?
T/F: Mood stabilizers

DO NOT worsen
mania or
depression?
Apart from mood
stabilizers and
antidepressants
what are some other
treatments for
bipolar disorder?
With respect to
lithium levels, the
treatment of mania
or depression has a
higher target blood
level?
With respect to lithium

administration, what is
the range of dosages
used to treat bipolar
disorder?
Would a higher target
blood level of lithium
be sought to treat
acute mania or acute
depression?
Would a higher target
blood level of lithium
be sought to treat
acute depression or for
maintenance
treatment of bipolar
disorder?
The administration of
which anticonvulsant
has a 1:1000 risk of
___ Syndrome?
Divalproex and
lamotrigine are both
___?
Both anticonvulsants
What is the generic

name for Divalproex?
What is Lamotrigine?
Lamotrigine is primarily
used for the treatment
o f …?
T/F: Valproic acid is
primarily used to treat
bipolar depression?
The administration of
which bipolar
medication has a
1:1000 risk of Stevens-
Johnson Syndrome?
What does CANMAT
stand for?
Week8 Page 97
Give 2 examples of atypical
antipsychotics?(4)
Atypical antipsychotics
were originally introduced
for the treatment of ___?
Atypical antipsychotics are
used more for the
treatment of mania or
bipolar depression?
Would lithium,
olanzapine, and
divalproex be
appropriate
combination therapy
for the treatment of
acute bipolar mania?
The main side effects
of the atypical
antipsychotics are ___
risks, such as …(name
2)?(3)
Monotherapy for
treatment of bipolar
depression includes
which 2 medications?
List 2 popular
combination therapies
bipolar depression?(3)
List a popular
combination
therapy for the
treatment of
acute bipolar
mania?
T/F: Lamotrigine and

Divalproex are indicated
as combination therapy
bipolar depression?
Which category of long-
term mood stabilizers
has the highest risk of
causing dyslipidemia?
causing teratogenicity?
causing sexual
dysfuntion?
For the pharmacological management of acute bipolar mania, which medications are commonly used for monotherapy? Which category of long-
Long term lithium use has potential complications for which organ? term mood stabilizers
Which of the following lead to weight gain (may be more than one right answer): atypical antipsychotics, anticonvulsants, has the highest risk of
lithium? causing liver problems?
Which of the following are potential complications of long-term mood stabilizer use: teratogenicity, glucose dysregulation, Which category of long-
renal effects, liver problems, sexual dysfunction, dyslipidemia, weight gain? term mood stabilizers
Sexual dysfunction is a prominent side effect of long-term use of which mood stabilizer? has the highest risk of
Which of the following are side effects of anticonvulsants: teratogenicity, glucose dysregulation, renal effects, liver probl ems, causing glucose
sexual dysfunction, dyslipidemia, weight gain? dysregulation?
List 3 potential complications of long term mood stabilizer use?(7)
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List 2 different
psychosocial
interventions for
the maintenance
phase of bipolar
disorder?(4)
Olanzapine,
risperidone,
clozapine, and
quetiapine are all
examples of
which class of
medications?
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04 SCHAFFER 2008 Introduction to Bipolar Disorder
7:22 PM
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05 KAHAN 2008 Substance Abuse Key Concepts 2x3
7:53 PM
List 3 factors that are

correlated with the
addictive potential of
drugs?(5)
List 3 ways in which you
could make a drug less
addictive?(5)
What is the primary

difference between the
reward pathway of cocaine
compared to alcohol,
nicotine and opioids?
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What are the 4 C's of
addiction?
Week8 Page 139

The ____ and NMDA ____ are
inhibited by alcohol?
Symptoms of alcohol
withdrawal typically start
how many hours after the
last drink?
Does tolerance to alcohol
develop quickly or slowly?
Alcohol inhibits which system
in the brain?
Tachycardia and vomiting are
examples of complicated or
uncomplicated signs of
alcohol withdrawal?
Alcohol suppresses ___ and

enhances ___ (both
neurotransmitters)?
Cessation of alcohol use
leads to unopposed activity
of which neurotransmitter?
How are the symptoms of

uncomplicated alcohol
withdrawal different from
those of complicated alcohol
withdrawal?
Alcohol enhances ___, which
is an inhibitory
neurotransmitter and
suppreses ___ which is a
neuroexcitatory
neurotransmitter?
Week8 Page 140

What are the
psychiatric chronic
effects of alcohol
consumption?
What are the CNS
chronic effects of
alcohol consumption?
What are the hepatic
chronic effects of
What are the GI chronic
effects of alcohol
consumption?
What are the
cardiovascular chronic
effects of alcohol
consumption?
According to the Low-

risk Drinking
Guidelines, how many
drinks are low risk for
the general population
to have per day?
risk Drinking
women to drink per
week?
risk Drinking
men to drink per
week?
What is a standard
drink for beer, wine,
liquor (give
quantities)?
As a laboratory marker for

alcohol consumption, is MCV
found to be depressed or
elevated?
What is the CAGE
questionnaire?
T/F: BOTH GGT and MCV are
poor screening methods for
excess alcohol use since both
Pasted from <http://images.google.com/images?um=1&hl=en&rls=com.microsoft%3Aen-us&q=acamprosate> have low sensitivity AND
specificity values?
Week8 Page 141

between the condition that
Naltrexone is used to treat
vs. Naloxone?
List 2 medications that

can be used to reduce
• Naloxone is a drug used to counter the effects of opioid overdose, for example heroin or drinking?
morphine overdose. Naloxone is specifically used to counteract life -threatening
depression of the central nervous system and respiratory system. Pasted from
What is the mechanism
<http://en.wikipedia.org/wiki/Naloxone> of action of Naltrexone?
Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol What is the mechanism
dependence and opioid dependence. Pasted from <http://en.wikipedia.org/wiki/Naltrexone>
of action of
Acamprosate?
T/F: Nicotine can be both a

relaxant AND a stimulant?
veranacline?
Severe withdrawal from
nicotine lasts approximately
how many days?
Week8 Page 142

T/F: Nicotine
replacement therapy
is far SAFER than
cigarette smoking?
What is the
mechanism of action
of Champix?
Approximately how
long does it take for
Buproprion to work?
Opioids act on
which receptors?
Another name
for endorphin
receptors is ___
receptors?
Week8 Page 143

Physical symptoms of
opioid withdrawal
include … (name 2)?
Are opioids safe in
pregnancy (if not, why;
what may they cause)?
Are opioids effective for

acute pain only, chronic
pain only, or both?
List 2 psychological
symptoms of opioid
withdrawal?(3)
In using opioids, what's the
difference in the rate of
development of tolerance
to psychoactive vs.
analgesic effects?
Does methadone
administration induce
sedation?
Another name for
Suboxone is ___?
Why can you not overdose
on Buprenophine
(Suboxone)?
T/F: Buprenorphine is AS
EFFECTIVE as methadone
at 60-80 mg?
What is the mechanism of
action of buprenophine?
Week8 Page 144

Which of the following is
a complication of
cannabis use (may be
more than one): poor
social functioning, mania,
delerium tremens, drug
induced psychosis,
cravings, fatigue and
irritability, mood
disorders?
Cocaine blocks the
presynaptic uptake of
which 3
neurotransmitters?
Usually a cocaine high is
20 minutes but with
repeated use the
euphoria only lasts for
___, followed by ___?
Another name for MDMA is

___?
Give 2 examples of
hallucinogens?(3)
What are the withdrawal
symptoms seen in
withdrawal from
hallucinogens?
Which of the following is a
complication of hallucinogen
use (may be more than one):
poor social functioning,
mania, delerium tremens,
drug induced psychosis,
cravings, fatigue and
irritability, mood disorders?
Another name for ecstasy is

___?
T/F: MDMA use may acutely

lead to serotonergic
syndrome?
Which important
neurotransmitter does
MDMA (ecstasy) stimulate
the release of?
What are the components of
serotonergic syndrome?
T/F: The effects of MDMA
may be temporarily
decreased by treating with
an SSRI?
GHB stands for ___?
GHB is a metabolite of ___?
GHB use leads to ___
• Myoclonus: brief, involuntary twitching effects, like ___?
Treatment for GHB use is
of a muscle or a group of muscles
___?
T/F: The withdrawal
symptoms experienced in
GHB withdrawal are similar
to those experienced by
withdrawal from
hallucinogens?
What are the withdrawal
symtpoms in GHB
withdrawal?
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06 RICHTER 2008 Anxiety Disorders 2x3
7:54 PM
How is anxiety
differentiated from fear?
• Anxiety has physiological, cognitive, and behavioural components
What is the approximate

lifetime prevalence of
anxiety disorders?
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List 2 core features of
anxiety disorders?
T/F: In chronic
anxiety, patients'
anxiety levels will dip
to normal for a few
days at most but will
be above normal at a
constant level most of
the time?
List the 3 phases

to a panic attack?
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(LECTURING ABOUT EACH OF THESE BELOW)
List 6 anxiety
disorders?(11)
In diagnosing a
panic attack,
patients must
experience 4 or
more of the
following (list
5)?(13)
PANIC DISORDER
What are the three
related diagnoses for
anxiety disorder?(ie. Panic
disorder with…, etc.)
In order to be diagnosed
with panic disorder, a
patient must have both
recurrent panics and one
or more of which three
symptoms?
For the diagnosis of panic
disorder patients must
have symptoms for more
than how long (ie. How
many weeks or months)?
AGORAPHOBIA
List typical situations in
patients would
experience agoraphobia?
In agoraphobia, situations
are ___, ___, or require
the presence of ___?
List 3 examples of
agoraphobic situtations?
Agoraphobia is an anxiety disorder, often precipitated by

the fear of having a panic attack in a setting from which there is
no easy means of escape. As a result, sufferers of agoraphobia may avoid
public and/or unfamiliar places. In severe cases, the sufferer may become
confined to their home, experiencing difficulty traveling from this "safe place."
Week8 Page 151

SPECIFIC PHOBIAS
Are males or females

more prone to panic
disorders?
What are the 4 major
types of phobias?
What is the gold
standard treatment for
phobias?
The two major classes of
pharmacotherapy for
the treatment of
phobias are ___ and
___?
SOCIAL ANXIETY DISORDER (SAD)

What is social anxiety
disorder?
The single most common

mental disorder is ___?
List three subtypes of

specific phobias?
between generalized
and non-generalized
social anxiety disorder?
List 3 physical
symptoms of social
anxiety?(9)
Types of anxiolytics
Anxiolytics are generally divided into two groups of medication, benzodiazepines and non-benzodiazepines.
• Benzodiazepines
• Main article: Benzodiazepine
Benzodiazepines are prescribed for short-term relief of severe and disabling anxiety. Common medications arelorazepam (Ativan), clonazepam
(Klonopin), alprazolam (Xanax), and diazepam (Valium). Benzodiazepines may also be indicated to cover the latent periods associated with the
medications prescribed to treat an underlying anxiety disorder. They are used to treat a wide variety of conditions and symptoms and are usually a
first choice when short-term CNS sedation is needed. Longer term uses include treatment for severe anxiety and psychosis. There is a risk of
withdrawal symptoms and rebound syndrome after continuous usage past two weeks. There is also the added problem of the accumulation of drug
metabolites and adverse effects.
• Non-benzodiazepines
See also: Nonbenzodiazepine
Buspirone (BuSpar) is a serotonin 1A agonist. It lacks the sedation and the dependence associated with benzodiazepines and causes much less
cognitive impairment. It may be less effective than benzodiazepines in patients who have been previously treated with benzodia zepines as the
medication does not provide the sedation that these patients may expect or equate with anxiety relief.
• Barbiturates
Barbiturates and meprobamate exert an anxiolytic effect linked to the sedation they cause. The risk of abuse and addiction is high. Many experts
consider these drugs as obsolete for treating anxiety, although they may be valuable for the short term treatment of severe insomnia.
Week8 Page 152

• Herbal treatments
Certain herbs, such as valerian, kava (Kava Kava), chamomile, Kratom, Blue Lotus extracts, Sceletium tortuosum (kanna) and bacopa monniera are
reputed to have anxiolytic properties. With the exception of kava kava, only limited evidence exists for their efficacy.[1][2]
Use of marijuana as an anxiolytic has seen promising results in regions where its practical study is possible, but its statusas a controlled substance in
many countries make its study as such difficult. However a team from Brazil found cannabidiol to be an effective anti-psychotic and anxiolytic [3] 'CBD
induced a clear anxiolytic effect and a patternof cerebral activity compatible with ananxiolytic activity (27). Therefore, similar to the data obtained in
animal models, results from studies on healthy volunteers have strongly suggested an anxiolytic-like effect of CBD'.
Pasted from <http://en.wikipedia.org/wiki/Anxiolytic>
For the diagnsosis of

Social Anxiety Disorder,
individuals older than 18
years must have SAD for a
duration greater than ___
months?
In diagnosing social
anxiety disorder, it must
not be related to any
general medical condition,
such as ___?
Which two classes of
meds are frequently used
to treat performance
anxiety?
OCD

between obsessions
and compulsions?
List a few obsessions

related to OCD?
List a few
compulsions related
to OCD?
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What are the 2
DSM-IV criteria for
the diagnosis of
OCD?
T/F: Insight is
usually absent in
patients with OCD?
OCD is frequently
comorbid with
other ___
disorders and ___?
PTSD
GENERALIZED ANXIETY DISORDER (GAD)

For Generalized Anxiety
Disorder to be diagnosed,
worry must be present most
days for greater than or
equal to ___ months?
between acute stress
disorder and PTSD?
Pharmacologic treatment of
Generalized Anxiety
Disorder (GAD) may involve
the use of which class of
psychiatric medications?
EMDR (eye movement
desensitization and
reprocessing) is indicated
for the treatment of which
disorder?
For Generalized Anxiety
Disorder to be diagnosed,
there must be 3 or more of
the following symptoms (list
4)?
Buspirone is an anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione
class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an
efficacy comparable to diazepam in treating generalized anxiety disorder.[1][2]
Pasted from <http://en.wikipedia.org/wiki/Buspirone>
ANXIETY DUE TO A GENERAL

MEDICAL CONDITION
Pharmacologic treatment for
generalized anxiety disorder
(GAD) may involve the use of
which drugs (list 3)?
Is generalized anxiety
disorder more prevalent in
Week8 Page 154

ANXIETY DUE TO A GENERAL
MEDICAL CONDITION
Pharmacologic treatment for
generalized anxiety disorder
(GAD) may involve the use of
which drugs (list 3)?
Is generalized anxiety
disorder more prevalent in
males or females?
Buspirone is a benzo or
non-benzo?
SUBSTANCE-INDUCED
ANXIETY DISORDER
List 3 substances whos
use can lead to
substance-induced
anxiety disorder?(4)
Substance-Induced
anxiety disorder may be
associated with
withdrawal from (which
drugs) ___ or ___?
In Mowrer's two stage

model of anxiety, which
type of conditioning is
required for the
development of fear
and which for the
maintenance of fear?
Week8 Page 155

List the 3 major
categories of
neurotransmitters
related to biogenic
amines?
GABA and glutamate are
both examples of
neurotransmitters that
are biogenic amines,
amino acids, or peptides?
The neurobiology of
anxiety involves which 3
major types of
neurotransmitters?
Cell bodies secreting
majority of
norepinephrine are
located in the ___?
Stimulation of the locus
ceruleus leads ...?
Which are the two major

nuclei on which serotonin
has it's effects?
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GABA is the major
(inhibitory/stimulatory)
neurotransmitter?
BZDP (benzo's),
barbiturates, and alcohol all
bind to which receptor of a
major class of
neurotransmitters?
A high density of GABA-
BZDP receptors are found in
the ___, ___ an doccipital
/frontal cortex?
GABAA has allosteric binding
sites for which major drugs
(name 3)?
In the neuroanatomical
model of anxiety, panic is
thought to originate in the
___ and conditioned and
unconditioned fear in the
___ and the ___?
model of anxiety,
unconditioned fear is
thought to originate in the
___ and conditioned fear
in the ___?
model of anxiety, the
limbic lobe is responsible
for which type of anxiety?
model of anxiety,
avoidance is mediated by
which brain region?
The major brain
structures involved in OCD
are the ___ and the ___?
T/F: Anxiety is CLEARLY

genetic but it's also likely
to be multifactorial?
T/F: GABA has been
implicated in both panic
and ___?
HPA axis dysfunction is
prominently involved in
which disorder?
• Neurotransmitters and Anxiety:

Neurotransmitter Anxiety Condition
NE Panic
GABA Panic, GAD
Serotonin All anxiety disorders, especially OCD
Adrenergic, HPA axis PTSD
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T/F: CBT is the FIRST-LINE
treatment for ALL anxiety
disorders?
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Give examples of
introceptive expsoures?
• Imipramine, TCA (Imip)

• Placebo (PBO)
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First-line treatment for
GAD and SAD is ___?
For all anxiety disorders
EXCEPT GAD and SAD, ___
are indicated as first-line
treatment?
T/F: In the treatment of

BENZODIAZEPINES: anxiety disorders, benzo's
NEVER 1st OR 2nd are never first line
LINE TREATMENT FOR treatment but they may be
ANXIETY! second line treatment?
In the treatment of anxiety,
when can you prescribe
benzo's PRN?
There's generally a ___ to

___ week lag in benefits
from antidepressants and
antianxiety medications?
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In the treatment of panic
disorder, what are the
indicated first and second
line treatments?
In the treatment of panic
disorder, what are the
indicated third line and
third line/adjunctive
treatments?
T/F: MAOIs are indicated
as second line treatment in
the treatment of panic
disorder?
T/F: in addiiton to SSRIs,
Venlafaxine is indicated as
FIRST LINE treatment for
panic disorder BUT NOT
for social phobia?
• phenelzine sulfate: a monoamine oxidase inhibitor

used as an antidepressant and in the prophylaxis of
migraine; administered orally.
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• venlafaxine (Effexor) hydrochloride: an inhibitor of
serotonin and norepinephrine reuptake, unrelated chemically to any other Buspirone is indicated as
antidepressants, that potentiates neurotransmitter activity in the central nervous
first line treatment for ___?
system; used as an antidepressant and antianxiety agent, administered orally.
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• CBT: FIRST LINE!
• Generally treat anxiety disorders with SSRIs, benzo's
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06 RICHTER 2008 Anxiety Disorders
7:58 PM
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07 FMP 08 Week 8 Substance Abuse SEMINAR NOTES
7:55 PM
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• Atenolol: a cardioselective
1-adrenergic blocking agent
used in the treatment of
hypertension and chronic
angina pectoris and the
prophylaxis and treatment of
myocardial infarctionand
cardiac arrhythmias;
administered orally or
intravenously.
• Prazosin
hydrochloride: a
quinazoline derivative with
vasodilator properties, used
as an oral antihypertensive.
• Hydrochlorothiazide:
a thiazide diuretic, used for
treatment of hypertension
and edema; administered
orally. It is often used in
combination with a
potassium-sparing diuretic.
• Enalapril: an angiotensin-
converting enzyme inhibitor
with antihypertensive and
vasodilator actions. See also
enalaprilat.
• 5oz of wine one standard drink

• 12oz for beer
• So ask him about maximum amount; what's the most you would've had to drink in the last week or month?
Week8 Page 251

CAGE questionnaire is not a diagnostic test; just screening!
T/F: The CAGE questionnaire is a

good diagnostic test for diagnosing
someone with alcoholism ONLY if
males score 2/4 or higher and
females score 1/4 or higher?
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Tolerance/withdrawal - physical depenence critera
Psych dependence
○ Increased time spent using the substance getting using recovering from it
○ Using more than originally intended
○ Neglect of or giving up responsibilities related to home work social
○ Multiple unsuccessful attemps to cutdown
○ Contiiued use despite consequences secondary to the substance
• How do you treat severe alcohol withdrawal; use valium

○ Use diazepam loading protocol; one of the receptors that alcohol uses is the gabaergic receptors; when
Week8 Page 253

○ Contiiued use despite consequences secondary to the substance
• How do you treat severe alcohol withdrawal; use valium

○ Use diazepam loading protocol; one of the receptors that alcohol uses is the gabaergic receptors; when
someone chornically drinking or alcohol dependent, then the immediate removal of all that alcohol will
caause rebound excitatory consetllation of symptoms (sweating, seizures, etc.) so diazepam replaces alchool
so that whatever left of gaabaergic symptoms prevents the onset of
○ Alcohol and diazepam crossreact; wait until they go into alcohol withdrawal; and then do CIWA based
diazepam loading protocol; withdrawal symptoms scored out of 7 if score more than 10 then
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• Acetaminophen: the
amide of acetic acid and p-
aminophenol, having analgesic
and antipyretic effects similar
to aspirin but only weak
antiinflammatory effects.
Administered orally and
rectally. Called also
paracetamol.
• Cocaine: a crystalline
alkaloid, obtained from leaves
of Erythroxylon coca (coca
leaves) and other Erythroxylon
species, or by synthesis from
ecgonine or its derivatives;
used as a local anesthetic and
vasoconstrictor applied
topically to mucous
membranes. Abuse of cocaine
or its salts leads to
dependence.
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Trazedone: when used in antidepressant doses makes people very sedated
○ Second generation antipsychotics also commonly used off label to help people sleep
Week8 Page 256

• Zyban (buproprion, or wellbutrin) also used
to quit smoking; nicotine replacement
therapy
• Pharm'l and non-pharm'l therapy
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Week8 Page 258
Seminar: Substance Abuse: A Case-Based Approach
Thursday, March 06, 2008
5:51 PM
List what a standard drink is in

terms of beer, wine, and liquor?
Week8 Page 259

In addition to asking how
much a patient drinks on
average per week and
defining the size of the
container of the type of
alcohol they drink, which
other important question
should be asked to quantify
alcohol consumption per
week?
A 750 cc bottle of wine

contains approximately how
many standard drinks?
An ounce contains
approximately ___ cc's and a
standard drink of wine
contains about ___ oz?
What are the low risk drinking

guidelines for men and
women (ie. Maximum ___
standard drinks per week, or
___ drinks on any one day for
men, … for women)?
T/F: Most of the cardiovascular

benefits of alcohol can be obtained
by drinking less than one drink per
day and these benefits of reducing
mortality from coronary artery
disease are seconary to inhibition
of platelet function and
improvement in the lipid profile?
The CAGE questionnaire is scored

as "positive" if men score higher
than ___ out of 4 and women
score higher than ___ out of 4?
T/F: Low Risk Drinking Guidelines

recommend 14 standard drinks per
week and three drinks MAXIMUM
per day for MEN and 9 standard
drinks per week and MAXIMUM 1
drink per day for WOMEN?
Week8 Page 260

If you suspect that a patient has an
alcohol problem, which other
questions, besides frequency and
quantity of drinks per week and
screening using the CAGE
questionnaire, would you ask?
T/F: Problem drinkers DO experience

alcohol withdrawal?
What is the definition of "alcohol

dependence" (hint: 4 criteria, one
of them being a type of
dependence)?
Week8 Page 261

STRATEGIES TO AVOID INTOXICATION (7)
If someone is a
problem drinker and
you'd like to encourage
them to recude their
rate of drinking, what
strategies can you
recommend to help
patients avoid
intoxication (list 5)?(7)
In tracking a problem
drinker's progress over
time, it may be helpful
to order GGT and ___
at baseline and follow-
up?
Week8 Page 262

What are the clinical
features of alcohol
dependence (list
3)?(5)
In treating alcohol withdrawal,

diazepam is a good choice
because it (list 3 reasons)?(5)
Week8 Page 263

Apart from an inpatient
program, list 2 effective
treatment plans that you can
use for treating problem
drinking?
T/F: There is NO evidence
that inpatient programs are
more effective than
outpatient in treating binge
drinking and alcohol
dependence?
T/F: Naltrexone is a
competitive beta-2 adrenergic
antantagonist, and has been
shown in several randomized
trials to decrease the intensity
and severity of binge drinking
in alcohol dependent patients
engaged in formal treatment
programs?
Another name for Naltrexone
is ___?
T/F: Naltrexone use reduces
alcohol cravings?
Why does Naltrexone use
make it easier for patients to
practise strategies learned in
counselling to control
excessive drinking habits?
action of Naltrexone (ReVia)
work?
___ is a clue that a patient

on treatment for alcohol
dependence may be
relapsing?(3)
Week8 Page 264

Percocet is a combination of
___ and ___?
What are the clinical

features of opioid
withdrawal (list 2 objective
signs and 2 subjective
symptoms)? (
What is the time course of
opioid withdrawal?
The most common
symptom of opioid
withdrawal is ___?
Insomnia and dysphoria
may still be experienced for
___ after opioid
withdrawal?
For a patient experiencing
alcohol withdrawal, which 3
other important questions
would you ask on history?
Week8 Page 265

action of methadone?
Methadone is an oral
opioid ___ with a half-life
of __ hours?
Methadone is used in the
treatment of patients who
are physically and
psychologically dependent
on ___, such as ___ or high
doses of other potent
opioids such as ___ (just an
example of one)?
T/F: even if titrated
carefully, methadone still
causes drowsiness but this
is a tolerated side-effect
since it DOES relieve
withdrawal and cravings,
enabling patients to escape
the biological compulsion
to continue drug use?
The 4 main components of
methadone treatment are:
(4)?
Week8 Page 266

What are the adverse
effects of benzo's in the
elderly?
There is evidence that
benzodiazepine use in the
elderly increases the risk
for … and the risk of …?
Give an example of a long
acting benzodiazepines
(which, as a group, have
been implicated in
increasing the risk of falls
and hip fractures in
seniors)?
Benzo's increase risk of (5):

1. Falls and hip fractures in seniors, especially long-acting ones like
diazepam and chlodiazepoxide
2. Confusion and impaired recall
3. MVA's
4. excerbate symptoms of depression
5. Potentially fatal hypoxia secondary to decreased respiratory drive in
patients with sleep apnea and COPD
Week8 Page 267

How long does buproprion take
to work?
How effective is smoking
cessation counselling?
If someone has had a coronary
event, how long should they
wait before using a nicotine
patch and gum?
Week8 Page 268

GHB is a structural analogue and metabolite of ___?
__ and ___ characterize mild intoxication with GHB?
What is the difference in symptoms experienced between mild intoxication with GHB and intoxication at higher
doses?
GHB can cause severe withdrawal syndrome similar to ___ withdrawal?
GHB overdose is treated with Phenobarbital?
GHB overdose at higher doses is characterized by which symptoms (name 3)?
An 18 year old patient was brought in by ambulance to the emerg after his friends foundhim unresponsive in an
after-hours night club. In the ambulance they gave him O2 and naloxone, to which he didn't respond. In the ER he
was unresponsive to deep pain and was noted to have myoclonus and bradycardia and his O2 saturation was 80.
After several hours he abruptly woke up, confused but otherwise well. What drug did he overdose on?
Week8 Page 269

Week 8 Review Questions
5:59 PM
FMP 2007 – 2008 Week 8 Review Questions
Depression
1. What are the two “core” symptoms of a major depressive episode?
2. What are the other symptoms of depression? Classify them into two major categories.
3. What are the varieties of conditions associated with major depressive episodes?
4. What “general medical conditions” can cause depression?
5. What etiologic factors contribute to depression?
6. What brain anatomical changes are seen in some patients with depression?
7. What is the natural history of major depressive disorder?
8. What treatments in are available for depression?
9. What is psychotherapy?
10. What are the essential elements of cognitive behavioural therapy?
11. What kind of evidence supports the use of CBT?
12. What classes of medications are available to treat depression?
13. What are principles of the use of anti-depressants:
a) How long to treat?
b) Who needs maintenance treatment?
c) How to treat refractory depression?
14. What neurotransmitter systems do these anti-depressants alter?
15. What are the major side effects of these anti-depressants?
16. What is the virtue of adding psychotherapy to anti-depressants?
Bipolar disorder
17. What are the major features of a manic episode?
18. What is an expansive mood?
19. What is the natural history of bipolar disorder?
20. What is the difference between bipolar I and bipolar II?
21. What three medications or classes of medications are available for the treatment of mania?
22. What are the major side effects of each of these treatments?
Substance abuse - general

23. What is meant by each of the following terms?
a) Addiction
b) Tolerance
c) Withdrawal
d) Physical dependence
24. What are the major drugs of abuse?
25. What is the meaning of the following terms:
a) Dependence
b) Withdrawal
c) Tolerance
d) Addiction
Substance abuse - Ethanol
26. What are manifestations of alcohol withdrawal?
27. How should alcohol withdrawal be treated?
28. What are chronic effects of excessive alcohol use?
29. What are safe drinking limits for men, women and pregnant women?
30. What is a standard drink?
31. What is the meaning of the following strategies used in treatment of drug abuse, and give examples of each:
a) Aversive therapy
b) Agonist substitution
c) Anti-craving therapy
32. What laboratory tests can be used to help indicate if someone is using ethanol to excess?
33. What is the CAGE questionnaire, and how should answers to it be interpreted?
Substance abuse - Nicotine

34. What is the meaning of referring to nicotine as a chameleon drug?
35. What are features of nicotine withdrawal?
36. What three classes of drug are available to treat nicotine withdrawal?
Substance abuse - Other

37. What are clinical features of opioid abuse?
Week8 Page 270

37. What are clinical features of opioid abuse?
38. What happens as a consequence of opioid withdrawal?
39. How does methadone work to assist with opioid addiction management?
40. What is buprenorphine?
41. What are consequences of the abuse of each of the following:
a) cocaine
b) cannabis
c) Gamma-hydroxy-butyrate
d) Ecstasy
e) Hallucinogens
Anxiety disorders
42. What are the diagnostic criteria for each of the following:
a) Post-traumatic stress disorder
b) Panic disorder
c) Agarophobia
d) Social anxiety disorder
e) Generalized anxiety disorder
f) Obsessive-compulsive disorder
43. What is a panic attack?
44. What general medical conditions can cause anxiety?
45. What is the preferred treatment for all anxiety disorders?
46. What medications are available for anxiety disorders? Which are first line? What is the role of benzodiazepines?
Pasted from <https://portal.utoronto.ca/courses/1/Fall-2007-FMP211Y1-Y-LEC0101/content/_913877_1/FMP%202008%20week%2008%20review%20questions.doc?

bsession=11327372&bsession_str=session_id=11327372,user_id_pk1=501825,user_id_sos_id_pk2=1,one_time_token=>
Week8 Page 271

Dr. Schreiber Review Lecture Tuesday, February 19, 2008
11:16 AM
What are the 4 C's of addiction?
1. What are the 4 C's of addiction?

a. Consequences
i. Person knows it's bad for them but they keep doing it anyway
b. Control
i. Loss of control
c. Cravings!
d. Compulsive use (over and over again)
2. What is the difference between tolerance and withdrawal and dependence? What is the difference
a. Tolerance: between tolerance and
i. Increased dose for same effect dependence?
1) need more of drug to get same effect
b. Withdrawal
i. Drug opposite effects without the drug
c. Dependence
i. In absence of continued substance use, get withdrawal symptoms
ii. NB: addiction and dependence are not the same thing; we use lots of opiods in management of
chronic cancer pain; average patient is dependetn on opiods with chronic cancer pain;
1) Addict means loss of control and cravings…
3. Alcohol Withdrawal
a. What is uncomplicated alcohol withdrawal?
i. Autonomic "stuff"- Sweating, palpitations, ↑HR, ↑palpitations, ↑sweat, ↑tremor, anxiety You see someone who
b. Moderate withdrawal - usually happens less than 48 hours you suspect has alcohol
i. Hallucinations withdrawal. He reports
1) Classic: pink elephants that he had a seizure
2) Often visual hallucinations; patients with schiz. Typically get auditory hallucinations that started with the
ii. Generalized tonic clonic seizures arm then the whole
1) Eg. Question: see someone evidently alcohol withdrawal; says he had a seizure; started with body started to shake.
arm, then whole body started shaking; THIS IS NOT AN ALCOHOL WITHDRAWAL SEIZURE; Is this evidence of
should have no focal point if it's alcohol withdrawal seizure! alcohol withdrawal?
c. Severe - within 3-5 days go completely nuts - quite high rate of mortality
i. Delirium Tremens
ii. Tachycardic, fever, severely impaired
4. What is the Treatment of choice for alcohol withdrawal?
a. Benzo's - replace the sedating effect of the ethanol; want to use a drug that has a much longer half-life than
alcohol -
i. Typically use Diazepam - (Valium) - longer halflife, about 36 hours In choosing a drug to treat alcohol
5. Standard drink: 13 grams of alcohol withdrawal, the principle that you use is to
a. 12 oz beer select one which has a much (longer/shorter)
b. 5 oz wine half-life than alcohol?
c. 1.5 oz liquer What does the CAGE questionnaire stand
for?
What is the treatment for choice for alcohol
Safe drinking limits:
withdrawal?
• Female: 2/day, 9 per week (smaller, less body water)
Patient with moderate alcohol withdrawal
• Male: 2 per day; 14 per week
often have (auditory OR visual)
• Pregnant Woman: 0
hallucinations?
The half-life of diazepam is much longer than
Men: 8 drinks per day for 10 years: 20% chance of cirrhosis
alcohol, at around approximately ___ hours?
• CAGE questionnaire
○ Cutdown?
○ Annoyed?
○ Guilty?
○ Eye-opener?
Suggest two lab tests for measuring
baseline and follow up alcohol intake?
• Two or more for men; one or more for women suggests drinking problem; just suggests you should explore further
A standar drink is approximately how
many grams of alcohol?
• 2 lab tests linked to alcohol intake:
○ GGT
○ ↑MCV
• 3 DRUGS SHOULD DEFINITELY KNOW:

○ Disulfiram: PAVLOVIAN! inhibits alcohol dehydrogenase; when acetaldehyde accumulates, it causes Does MCV rise or fall with increased
flushing, nausea; if person drinks then they'll get flushed and vomiting and start to associate with alcohol alcohol intake?
intake Disulfiram inhibits which enzyme?
○ Naltrexone - reduces cravings What is the mechanism of action of
○ Acamprosate - resduces withdrwal symptoms Disulfiram?
Acamprosate, also known by the brand name Campral®, is a drug used for treating alcohol What is disulfiram used for the
dependence. treatment of?
Acamprosate is thought to stabilize the chemical balance in the brain that would otherwise be Acamprosate reduces cravings OR
disrupted by alcoholism, possibly by blocking glutaminergic N-methyl-D-aspartate receptors, while withdrawal symptoms?
gamma-aminobutyric acid (GABA) type A receptors are activated.[3] Reports indicate that Naltrexone reduces cravings OR
acamprosate only works with a combination of attending support groups and abstinence from withdrawal symptoms?
alcohol.[4] Certain serious side effects include allergic reactions, irregular heartbeats, and low or high
blood pressure, while less serious side effects include headaches, insomnia, and impotence.[5]
Acamprosate should not be taken by people with kidney problems or allergies to the drug.[6]
Pasted from <http://en.wikipedia.org/wiki/Acamprosate>
Week8 Page 272

Pasted from <http://en.wikipedia.org/wiki/Acamprosate>
SMOKING
1. Nicotine replacement therapy - people relapse though; so may need to use Buproprion
○ Treatment: patch, gum, inhale When used for depression, buproprion
2. Buproprion is called ___ whereas when it's used
a. Wen used for depression called Wellbutrin for smoking cessation, it's called ___?
b. When for smoking: Zyban ___ is probably the most effective
3. Champix (Varenicline) smoking cessation therapy available
a. Probably the most effective today?
Another name for Varenicline is ___?
Opioids:
○ Signs of overuse of opioids on physical exam include:
 ↓HR
 ↓RR
Withdrawl from opioids results in "drug
 ↓pupils
opposite effects", which include … (list
 ↓BP
3)?(6)
 ↓LoC (level of consciousness)
What is the antidote to opioid
○ Withdrawal (remember: drug opposite effects)
withdrawal?
 Anxious, sweating, can't sleep, vomiting, diarrhea, muscle pain
○ How does methadone work?
 LONG HALF-LIFE!
○ What is the antidote to opioid withdrawal?
 Naloxone! - one of the few drugs useful to memorize dose
□ Brand name is Narcan
an opioid antagonist structurally related to oxymorphone, used in the diagnosis and treatment
of opioid toxicity, to reverse opioid-induced respiratory depression, and as an adjunct in the
treatment of hypotension associated with septic shock; administered parenterally.
○ Cocaine
 What are the medical consequences of cocaine use? List 3 medical
1) Stroke consequences of cocaine
2) Intracerebral hemorrhage use?(7)
3) Seizures Chronic complications of
4) Severe HTN alcohol use include …(list
5) MI 1 per: liver, GI, CVS,
6) Arrhythmias (sympathetic agonist) CNS, )?(4)
7) Rhabdomyolysis
 Acute renal failure
○ Chronic Alcohol Use - Chronic complications
 Liver
1) Fatty Liver
2) Alcoholic hepatitis List 2 CNS
3) Cirrhosis consequences of
4) Hepatocellular Carcinoma - any cause of cirrhosis can lead to hepatocellular carcinoma chronic alcohol
 GI consumption?(4)
1) Pancreatitis
 Acute or chronic - BOTH can be triggered by alcohol
 CVS
1) (contributes to) High blood pressure
2) Cardiomyopathy
3) Atrial fib
 CNS
1) Dementia
2) Cerebellar atrophy
3) Ataxia
4) Neuropathy
List the 3 major neurotransmitters

• 3 neurotransmitters messed up in people with major depression: which have been shown to be out of
1. Serotonin balance in people with depression?
2. Dopamine
3. Norepinephrine
• Hippocampus: shown to expand in people treated for depression The hippocampus of patients TREATED
for depression was shown to expand OR
Criteria for major depressive episode: contract?
Have to have one or other of these two:
 Depressed mood
 Anhedonia
□ Lack of interest/lack of pleasure
 4 other symptoms that can be divided into 2 groups:
□ Mental
 Suicidal ideation
 Decreased ability concentrate
 Feeling worthless
□ Physical
 ∆ Sleep
 ∆ Appetite/Weight
 ∆ Psychomotor retardation
 Fatigue
• Almost every psychological diagnosis involves impairment in social or cognitive functioning
Week8 Page 273

• Almost every psychological diagnosis involves impairment in social or cognitive functioning
DRUGS FOR DEPRESSION!

○ SSRIs List 3 SSRIs? (below is just a partial list of
i. Prozac 5)
□ Fluoxetine Another name for Zoloft is __?
ii. Citalopram Another name for Citalopram is __?
□ Celexa Another name for Citraline is __?
iii. Paroxetine Another name for Fluvoxamine is __?
□ Paxil Another name for Paroxetine is __?
iv. Citraline Is Venlafaxine an SSRI or an SNRI?
□ Zoloft Another name for Venlafaxine is ___?
v. Fluvoxamine What is the difference in the mechanism
□ Luvox of action of Venlafaxine vs. Fluvoxamine?
○ SNRIs
 Venlafaxine
□ Effexor - contributes to ↑HTN
○ Buproprion (DA)
○ Mirtazapine - works as an alpha 2 agonist, serotonin reuptake inhibitors
 Mirtazapine: an antidepressant compound unrelated to any of the classes of antidepressants;
administered orally.
 What is the mechanism of action of
○ MAOI - monoamine oxidase inhibitors Mirtazapine?
 What every doctor should know: interacts with certain foods, decongestants, meds, CAN TRIGGER What is Mirtazapine used for?
HYPERTENSIVE CRISIS! So may cause ↑↑BP
○ TCA - 2 different names, same class
 -ipramines
 -
MANIA!
○ CORE SYMPTOM: Elevated euphoric or irritable mood that lasts for at least a week
○ Sleep deprivation without fatigue
○ ↑ speed of speech
○ ↑speed thought
○ ↑ pleasurable activities
○ ↑ goal directed activity
Bipolar 2:
○ Not full extent of mania
• List 3 types of mood stabilizers? List 3 categories of mood

1. Lithium stabilizers?
i. Causes impairment of renal water conservation and may contribute to renal failure Risperidone and olanazapine are
2. Anticonvulsants both ___?
i. Carbamazepine An important side effect of
ii. Valproate lithium consumption is that it
iii. Lamotragine causes …?
3. Antipsychotics List 2 anticonvulsants that are
i. Atypical (risperidone, olanzapine) used as mood stabilizers?(3)
□ Worst side effect: Leukopenia ↓WBC
Week8 Page 274

Summary Week 8 Questions
01 SCHAFFER 2008 Diagnosis and Etiology of Depression 2x3

50% of those with Major Depressive Disorder have onset before the age of ___?
Biochemically, what is the response to anti-depressants that target norepinephrine?
Briefly describe how sadness is different from depression?
Do antidepressants increase or decrease dopamine levels?
Do antidepressants work by upregulating or downregulating beta-adrenergic receptors (thereby
influencing norepineprhine)?
Give examples of 3 substances that can lead to substance-induced MDE?(4)
How are serotonin levels linked to precipitating the symptoms of depression?
How is major depressive disorder diagnosed?
How many months within the onset of a stressful event must depression occur and after how many
months must it resolve in order to be diagnosed with Adjustment Disorder with Depresed Mood?
How much of the variance in the incidence of depression is accounted for by life events?
In diagnosing dysthymia, the patient should "never be without symptoms for…" what period of time?
In order to diagnose someone with a major depressive episode (MDE), there are 3 major diagnostic
criteria according to DSM IV; what are they?
In order to diagnose someone with a major depressive episode (MDE), there they must have 5 or more
of which symptoms during a 2 week period? (list 5, there's a total of 9)
List 2 ways you can be more assured of a substance-induced MDE diagnosis; ie. There are 3 criteria that
must be met to confirm substance-induced MDE, list 2?
List 3 medical conditions that can lead to a mood disorder due to a general medical condition?(5)
List 3 neurotransmitters involved in depression?(3)
List 4 diagnoses that are associated with MDE's(6)?
List 4 diagnostic criteria for Dysthymia?(5)
List 5 signs that indicate the presence of depression?(7)
List 6 risk factors for depression?(8)
Name 2 vitamin deficiencies that can cause a mood disorder?
T/F: According to the Canadian Community Health Survey, the highest rate of Major Depressive
Disorder was amongst the 15-24 year old age group?
T/F: According to the Canadian Community Health Survey, women are overall more likely to suffer from
depression compared to men?
T/F: According to the Canadian Community Health Survey, women over 64 are significantly more likely
to suffer from depression than men over 64?
T/F: Adjustment Disorder with Depressed Mood is diagnosed in patients with a mental illness/disorder?
T/F: Major depressive disorder occurs more frequently in the elderly (+60 years old) than in those less
than 60 years old?
T/F: True depression is NOT a chronic condition but is by definition acute episodes of depressive
symptoms?
The mean number of lifetime episodes for someone who suffers from Major Depressive Disorder is __
to __?
What did the Dunedin Multidisciplinary Health and Development Study reveal regarding genetics and
depression in S/S genotyped individuals?
What did the Dunedin Multidisciplinary Health and Development Study reveal regarding maltreatment,
serotonin transporter gene promoter region genotypes, and propensity to experience depression?
What happens to blood flow to the attention/cognition areas of the brain in depression versus blood
flow to the vegetative-autonomic areas of the brain?
What is Adjustment Disorder with depressed mood?
What is substance-induced MDE?
What is the effect of untreated depression on hippocampal volume?
Within the course of Major Depressive Disorder, what is the mean duration of an untreated Major
Depressive Episode?
Week8 Page 275

02 SCHAFFER 2008 Biological Treatment of Depression 2x3
A majority of depression patients achieve remission after how many medication trials?
Apart from pharmaceutical therapy, list 2 other biological treatments for depression?(4)
Buproprion (Wellbutrin), at high doses, has which common side-effect?
Every patient treated for depression needs to go through at least which 2 phases of treatment?
Give 2 examples of SNRIs?
Give 2 examples of SSRIs?
Give 3 examples of TCA antidepressants?
Give an example of a reversible MAOI antidepressant and another example of an irreversible MAOI
antidepressant?
How are number of episodes of antidepressant treatment correlated with length of antidepressant
treatment?
How did trends in the outpatient treamtent of depression change between 1987 and 1997 in the US?
How do MAOI antidepressants work?
How do SNRIs work?
How do SSRIs work?
How do TCA antidepressants work?
How does Buproprione (Wellbutrin) work?
How long does the acute phase of antidepressant treatment last?
How long does the continuation phase of antidepressant treatment last?
How long does the maintenance phase of antidepressant treatment last?
In using a 2nd medication for depression treatment, what is the principle that should be followed?
List 2 common side effects of MAOIs?(3)
List 2 common side effects of TCAs?
List 2 common side-effects of Buproprion (Wellbutrin)?
List 2 common side-effects of Mirtazapine (Remeron)?(3)
List 3 categories of patients who would require maintenance treatment?(4)
List 4 factors that should influence your choice of which antidepressant to prescribe?
List 4 strategies one should follow if the medications prescribed for anti-depression aren't helping?
MOST remissions from antidepressant use occur between ___ to___ weeks of use?
T/F: A MAJORITY of patients achieve remission from depression after TWO OR MORE medications?
T/F: A MINORITY of patients achieve remission from depression with FIRST line medication?
T/F: Most medication choices have similar efficacy?
The precursor for dopamine, _____, is found in many foods, including cheese and tofu?
Tyramine ingestion while taking MAOIs can cause ___?
Tyramine is the precursor for ___?
What are two specific side effects of most antidepressants that you should warn patients about?
What does it mean to 'augment' anti-depressant medication with other medications?
What is the difference between response and remission?
What is the difference between the goals of acute, continuation, and maintenance treatment with
respect to treating depression?
What is the generic name for Remeron?
What is the generic name of Celexa?
What is the generic name of Effexor?
What is the generic name of Paxil?
What is the generic name of Prozac?
What is the generic name of Zoloft?
What is the mechanism of action of Mirtazapine?
What percentage, approximately, of patients will RESPOND to treatment with a first line
antidepressant? (nb. Asking for response, NOT remission)
Which is the MOST toxic in overdose: SSRIs, TCAs, SNRIs?
Which other form of treatment should be added to antidepressant therapy to achieve an even better
outcome?
Which type of anti-depressant class has a high rate of drug-drug and drug-food interactions?
Why are SSRI's more sought after than TCAs?
Week8 Page 276

Why are SSRI's more sought after than TCAs?
Why should tripants (used in the treatment of migraines) not be taken with MAOI antidepressants?
03 ZARETSKY 2008 Cognitive Therapy for Depression 2x3

Apart from depression, list 2 other common medical problems which CBT be used for?(5)
CBT and SRI treatment responsive OCD patients show similar decreased activitiy in which brain
structure?
Cognitive therapy is generally time limited to how many months (for uncomplicated depression or
anxiety)?
Give a few examples of comorbidities of depression?
Give an example of how CBT can be used to maintain patients in remission more effectively than clinical
case management?
Give examples of how CBT is a structured therapy?
In a typical course of CBT for depression, organize the following session goals from earliest to latest:
Goal setting, relapse prevention and termination, assessment and suitability, behavioural activation,
use of an automatic thought record?
List 2 different forms of psychotherapy?(3)
List 3 non-specific mechanisms of action of psychotherapy?
List 3 specific mechanisms of action of psychotherapy?
List 4 psychiatric conditions in which CBT is the gold standard?
List 5 cognitive distortions?(10)
T/F: CBT is as effective as medication for chronic depression?
T/F: CBT is as effective as medication for mild to moderate depression?
T/F: CBT is MORE effective than medication in reducing relapses?
T/F: CBT is NOT as effective as medication for more severe non-psychotic depression?
T/F: Cognitive therapy can be done individually but should not be done in groups?
T/F: For chronic depression, there is no difference between using CBT alone versus using medication
alone?
T/F: If you wish to start a patient on CBT, this SHOULD NOT be started mid-way through their
medication course because of the inability to discern which is having a positive effect?
The cognitive model states that one's core beliefs in a situation influence which 3 factors?
What are the 6 steps in cognitive restructuring?
What are the stages in the Cognitive Model of Depression?(hint: 5 linear steps before get to symptoms
of depression)?
Which of the following is an example of Socratic questioning, in response to a student saying "I'm a
complete failure" (there may be more than one right answer): 1. What makes you think you are a
complete failure?; 2. Why are you being so hard on yourself?; 3. What would a good student do?; 4.
Would a complete failure be able to get 75% on an exam?; 5. On a scale of 0-100%, where do you fall?
Where do other people fall?
04 SCHAFFER 2008 Introduction to Bipolar Disorder 2x3

A genuine manic episode generally lasts for at least how long?
According to the mood spectrum, what's the difference between bipolar type I and type II?
Apart from mood stabilizers and antidepressants what are some other treatments for bipolar disorder?
Approximately ___% of depressed patients have bipolar disorder?
Are depressive episodes necessary for the diagnosis of bipolar disorder?
Atypical antipsychotics are used more for the treatment of mania or bipolar depression?
Atypical antipsychotics were originally introduced for the treatment of ___?
Divalproex and lamotrigine are both ___?
For the pharmacological management of acute bipolar mania, which medications are commonly used
for monotherapy?
Give 2 examples of atypical antipsychotics?(4)
Hypomania + Depression = ___?
In diagnosing a manic episode, patients must experience 3 or more of which 7 symptoms?(just name 5)
In diagnosing a manic episode, what are the 4 general categories?
In diagnosing a mixed episode, criteria for BOTH a manic episode AND major depressive episode should
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be met for what minimum period of time?
Lamotrigine is primarily used for the treatment o f …?
List 2 different psychosocial interventions for the maintenance phase of bipolar disorder?(4)
List 2 popular combination therapies for the treatment of bipolar depression?(3)
List 2 psychiatric disorders for which mood stabilizers are indicated for?
List 3 criteria for hypomanic episodes?(6)
List 3 populations that are particularly at risk for bipolar disorder?(6)
List 3 potential complications of long term mood stabilizer use?(7)
List 3 symptoms that overlap between mania and depression?(6)
List a popular combination therapy for the treatment of acute bipolar mania?
Long term lithium use has potential complications for which organ?
Monotherapy for treatment of bipolar depression includes which 2 medications?
Olanzapine, risperidone, clozapine, and quetiapine are all examples of which class of medications?
Sexual dysfunction is a prominent side effect of long-term use of which mood stabilizer?
T/F: Bipolar disorder is NOT caused by parents but CAN be reversed by will power?
T/F: Bipolar disorder MAY run in families?
T/F: Lamotrigine and Divalproex are indicated as combination therapy for the treatment of bipolar
depression?
T/F: Mood stabilizers DO NOT worsen mania or depression?
T/F: Patients with bipolar disorder do not actually have morphological abnormalities but they do have
second messenger and mitochondrial dysfunction?
T/F: Valproic acid is primarily used to treat bipolar depression?
The administration of which anticonvulsant has a 1:1000 risk of ___ Syndrome?
The administration of which bipolar medication has a 1:1000 risk of Stevens-Johnson Syndrome?
The leading cause of mortality in patients with BD is due to ___?
The main side effects of the atypical antipsychotics are ___ risks, such as …(name 2)?(3)
The presence of mania, in Canada, is highest in which age group: 15-24, 25-64, or over 64?
What are the 2 criteria used to define bipolar disorder?
What are the 3 diagnostic criteria for a mixed episode?
What are the two most common conditions that are comorbid with bipolar disorder?
What does CANMAT stand for?
What is Bipolar Disorder Type II?
What is Lamotrigine?
What is the generic name for Divalproex?
What is the most common age for the onset of bipolar disorder in males and females?
What percentage of bipolar patients have recurrence?
Which category of long-term mood stabilizers has the highest risk of causing dyslipidemia?
Which category of long-term mood stabilizers has the highest risk of causing glucose dysregulation?
Which category of long-term mood stabilizers has the highest risk of causing liver problems?
Which category of long-term mood stabilizers has the highest risk of causing sexual dysfuntion?
Which category of long-term mood stabilizers has the highest risk of causing teratogenicity?
Which of the following are potential complications of long-term mood stabilizer use: teratogenicity,
glucose dysregulation, renal effects, liver problems, sexual dysfunction, dyslipidemia, weight gain?
Which of the following are side effects of anticonvulsants: teratogenicity, glucose dysregulation, renal
effects, liver problems, sexual dysfunction, dyslipidemia, weight gain?
Which of the following lead to weight gain (may be more than one right answer): atypical
antipsychotics, anticonvulsants, lithium?
With respect to lithium administration, what is the range of dosages used to treat bipolar disorder?
With respect to lithium levels, the treatment of mania or depression has a higher target blood level?
Would a higher target blood level of lithium be sought to treat acute depression or for maintenance
treatment of bipolar disorder?
Would a higher target blood level of lithium be sought to treat acute mania or acute depression?
Would lithium, olanzapine, and divalproex be appropriate combination therapy for the treatment of
acute bipolar mania?
05 KAHAN 2008 Substance Abuse Key Concepts 2x3

Which of the following is a complication of hallucinogen use (may be more than one): poor social
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Which of the following is a complication of hallucinogen use (may be more than one): poor social
functioning, mania, delerium tremens, drug induced psychosis, cravings, fatigue and irritability, mood
disorders?
According to the Low-risk Drinking Guidelines, how many drinks are low risk for men to drink per week?
According to the Low-risk Drinking Guidelines, how many drinks are low risk for the general population
to have per day?
According to the Low-risk Drinking Guidelines, how many drinks are low risk for women to drink per
week?
Alcohol enhances ___, which is an inhibitory neurotransmitter and suppreses ___ which is a
neuroexcitatory neurotransmitter?
Alcohol inhibits which system in the brain?
Alcohol suppresses ___ and enhances ___ (both neurotransmitters)?
Another name for ecstasy is ___?
Another name for endorphin receptors is ___ receptors?
Another name for MDMA is ___?
Another name for Suboxone is ___?
Approximately how long does it take for Buproprion to work?
Are opioids effective for acute pain only, chronic pain only, or both?
Are opioids safe in pregnancy (if not, why; what may they cause)?
As a laboratory marker for alcohol consumption, is MCV found to be depressed or elevated?
Cessation of alcohol use leads to unopposed activity of which neurotransmitter?
Cocaine blocks the presynaptic uptake of which 3 neurotransmitters?
Does methadone administration induce sedation?
Does tolerance to alcohol develop quickly or slowly?
GHB is a metabolite of ___?
GHB stands for ___?
GHB use leads to ___ effects, like ___?
Give 2 examples of hallucinogens?(3)
How are the symptoms of uncomplicated alcohol withdrawal different from those of complicated
alcohol withdrawal?
In using opioids, what's the difference in the rate of development of tolerance to psychoactive vs.
analgesic effects?
List 2 medications that can be used to reduce drinking?
List 2 psychological symptoms of opioid withdrawal?(3)
List 3 factors that are correlated with the addictive potential of drugs?(5)
List 3 ways in which you could make a drug less addictive?(5)
Opioids act on which receptors?
Physical symptoms of opioid withdrawal include … (name 2)?
Severe withdrawal from nicotine lasts approximately how many days?
Symptoms of alcohol withdrawal typically start how many hours after the last drink?
T/F: BOTH GGT and MCV are poor screening methods for excess alcohol use since both have low
sensitivity AND specificity values?
T/F: Buprenorphine is AS EFFECTIVE as methadone at 60-80 mg?
T/F: MDMA use may acutely lead to serotonergic syndrome?
T/F: Nicotine can be both a relaxant AND a stimulant?
T/F: Nicotine replacement therapy is far SAFER than cigarette smoking?
T/F: The effects of MDMA may be temporarily decreased by treating with an SSRI?
T/F: The withdrawal symptoms experienced in GHB withdrawal are similar to those experienced by
withdrawal from hallucinogens?
Tachycardia and vomiting are examples of complicated or uncomplicated signs of alcohol withdrawal?
The ____ and NMDA ____ are inhibited by alcohol?
Treatment for GHB use is ___?
Usually a cocaine high is 20 minutes but with repeated use the euphoria only lasts for ___, followed by
___?
What are the cardiovascular chronic effects of alcohol consumption?
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What are the cardiovascular chronic effects of alcohol consumption?
What are the CNS chronic effects of alcohol consumption?
What are the components of serotonergic syndrome?
What are the GI chronic effects of alcohol consumption?
What are the hepatic chronic effects of alcohol consumption?
What are the psychiatric chronic effects of alcohol consumption?
What are the withdrawal symptoms seen in withdrawal from hallucinogens?
What are the withdrawal symtpoms in GHB withdrawal?
What is a standard drink for beer, wine, liquor (give quantities)?
What is the CAGE questionnaire?
What is the difference between the condition that Naltrexone is used to treat vs. Naloxone?
What is the generic name of veranacline?
What is the mechanism of action of Acamprosate?
What is the mechanism of action of buprenophine?
What is the mechanism of action of Champix?
What is the mechanism of action of Naltrexone?
What is the primary difference between the reward pathway of cocaine compared to alcohol, nicotine
and opioids?
Which important neurotransmitter does MDMA (ecstasy) stimulate the release of?
Which of the following is a complication of cannabis use (may be more than one): poor social
functioning, mania, delerium tremens, drug induced psychosis, cravings, fatigue and irritability, mood
disorders?
Why can you not overdose on Buprenophine (Suboxone)?
06 RICHTER 2008 Anxiety Disorders 2x3

A high density of GABA-BZDP receptors are found in the ___, ___ an doccipital /frontal cortex?
Are males or females more prone to panic disorders?
Buspirone is a benzo or non-benzo?
Buspirone is indicated as first line treatment for ___?
BZDP (benzo's), barbiturates, and alcohol all bind to which receptor of a major class of
neurotransmitters?
Cell bodies secreting majority of norepinephrine are located in the ___?
EMDR (eye movement desensitization and reprocessing) is indicated for the treatment of which
disorder?
First-line treatment for GAD and SAD is ___?
For all anxiety disorders EXCEPT GAD and SAD, ___ are indicated as first-line treatment?
For Generalized Anxiety Disorder to be diagnosed, there must be 3 or more of the following symptoms
(list 4)?
For Generalized Anxiety Disorder to be diagnosed, worry must be present most days for greater than or
equal to ___ months?
For the diagnosis of panic disorder patients must have symptoms for more than how long (ie. How
many weeks or months)?
For the diagnsosis of Social Anxiety Disorder, individuals older than 18 years must have SAD for a
duration greater than ___ months?
GABA and glutamate are both examples of neurotransmitters that are biogenic amines, amino acids, or
peptides?
GABA is the major (inhibitory/stimulatory) neurotransmitter?
GABAA has allosteric binding sites for which major drugs (name 3)?
Give examples of introceptive expsoures?
How is anxiety differentiated from fear?
HPA axis dysfunction is prominently involved in which disorder?
In agoraphobia, situations are ___, ___, or require the presence of ___?
In diagnosing a panic attack, patients must experience 4 or more of the following (list 5)?(13)
In diagnosing social anxiety disorder, it must not be related to any general medical condition, such as
___?
In Mowrer's two stage model of anxiety, which type of conditioning is required for the development of
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fear and which for the maintenance of fear?
In order to be diagnosed with panic disorder, a patient must have both recurrent panics and one or
more of which three symptoms?
In the neuroanatomical model of anxiety, avoidance is mediated by which brain region?
In the neuroanatomical model of anxiety, panic is thought to originate in the ___ and conditioned and
unconditioned fear in the ___ and the ___?
In the neuroanatomical model of anxiety, the limbic lobe is responsible for which type of anxiety?
In the neuroanatomical model of anxiety, unconditioned fear is thought to originate in the ___ and
conditioned fear in the ___?
In the treatment of anxiety, when can you prescribe benzo's PRN?
In the treatment of panic disorder, what are the indicated first and second line treatments?
In the treatment of panic disorder, what are the indicated third line and third line/adjunctive
treatments?
Is generalized anxiety disorder more prevalent in males or females?
List 2 core features of anxiety disorders?
List 3 examples of agoraphobic situtations?
List 3 physical symptoms of social anxiety?(9)
List 3 substances whos use can lead to substance-induced anxiety disorder?(4)
List 6 anxiety disorders?(11)
List a few compulsions related to OCD?
List a few obsessions related to OCD?
List the 3 major categories of neurotransmitters related to biogenic amines?
List the 3 phases to a panic attack?
List three subtypes of specific phobias?
List typical situations in patients would experience agoraphobia?
OCD is frequently comorbid with other ___ disorders and ___?
Pharmacologic treatment for generalized anxiety disorder (GAD) may involve the use of which drugs
(list 3)?
Pharmacologic treatment of Generalized Anxiety Disorder (GAD) may involve the use of which class of
psychiatric medications?
Stimulation of the locus ceruleus leads ...?
Substance-Induced anxiety disorder may be associated with withdrawal from (which drugs) ___ or ___?
T/F: Anxiety is CLEARLY genetic but it's also likely to be multifactorial?
T/F: CBT is the FIRST-LINE treatment for ALL anxiety disorders?
T/F: GABA has been implicated in both panic and ___?
T/F: in addiiton to SSRIs, Venlafaxine is indicated as FIRST LINE treatment for panic disorder BUT NOT
for social phobia?
T/F: In chronic anxiety, patients' anxiety levels will dip to normal for a few days at most but will be
above normal at a constant level most of the time?
T/F: In the treatment of anxiety disorders, benzo's are never first line treatment but they may be second
line treatment?
T/F: Insight is usually absent in patients with OCD?
T/F: MAOIs are indicated as second line treatment in the treatment of panic disorder?
The major brain structures involved in OCD are the ___ and the ___?
The neurobiology of anxiety involves which 3 major types of neurotransmitters?
The single most common mental disorder is ___?
The two major classes of pharmacotherapy for the treatment of phobias are ___ and ___?
There's generally a ___ to ___ week lag in benefits from antidepressants and antianxiety medications?
What are the 2 DSM-IV criteria for the diagnosis of OCD?
What are the 4 major types of phobias?
What are the three related diagnoses for anxiety disorder?(ie. Panic disorder with…, etc.)
What is social anxiety disorder?
What is the approximate lifetime prevalence of anxiety disorders?
What is the difference between acute stress disorder and PTSD?
What is the difference between generalized and non-generalized social anxiety disorder?
What is the difference between obsessions and compulsions?
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What is the difference between obsessions and compulsions?
What is the gold standard treatment for phobias?
Which are the two major nuclei on which serotonin has it's effects?
Which two classes of meds are frequently used to treat performance anxiety?
07 FMP 08 Week 8 Substance Abuse SEMINAR NOTES

T/F: The CAGE questionnaire is a good diagnostic test for diagnosing someone with alcoholism ONLY if
males score 2/4 or higher and females score 1/4 or higher?
Dr. Schreiber Review Lecture Tuesday, February 19, 2008

___ is probably the most effective smoking cessation therapy available today?
A standar drink is approximately how many grams of alcohol?
Acamprosate reduces cravings OR withdrawal symptoms?
An important side effect of lithium consumption is that it causes …?
Another name for Citalopram is __?
Another name for Citraline is __?
Another name for Fluvoxamine is __?
Another name for Paroxetine is __?
Another name for Varenicline is ___?
Another name for Venlafaxine is ___?
Another name for Zoloft is __?
Chronic complications of alcohol use include …(list 1 per: liver, GI, CVS, CNS, )?(4)
Disulfiram inhibits which enzyme?
Does MCV rise or fall with increased alcohol intake?
In choosing a drug to treat alcohol withdrawal, the principle that you use is to select one which has a
much (longer/shorter) half-life than alcohol?
Is Venlafaxine an SSRI or an SNRI?
List 2 anticonvulsants that are used as mood stabilizers?(3)
List 2 CNS consequences of chronic alcohol consumption?(4)
List 3 categories of mood stabilizers?
List 3 medical consequences of cocaine use?(7)
List 3 SSRIs? (below is just a partial list of 5)
List the 3 major neurotransmitters which have been shown to be out of balance in people with
depression?
Naltrexone reduces cravings OR withdrawal symptoms?
Patient with moderate alcohol withdrawal often have (auditory OR visual) hallucinations?
Risperidone and olanazapine are both ___?
Signs of overuse of opioids on physical exam include:
↓HR
↓RR
↓pupils
↓BP
↓LoC (level of consciousness)
Suggest two lab tests for measuring baseline and follow up alcohol intake?
The half-life of diazepam is much longer than alcohol, at around approximately ___ hours?
The hippocampus of patients TREATED for depression was shown to expand OR contract?
What does the CAGE questionnaire stand for?
What is disulfiram used for the treatment of?
What is Mirtazapine used for?
What is the antidote to opioid withdrawal?
What is the difference between tolerance and dependence?
What is the difference in the mechanism of action of Venlafaxine vs. Fluvoxamine?
What is the mechanism of action of Disulfiram?
What is the mechanism of action of Mirtazapine?
What is uncomplicated alcohol withdrawal?
Autonomic "stuff"- Sweating, palpitations, ↑HR, ↑palpitations, ↑sweat, ↑tremor, anxiety
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Autonomic "stuff"- Sweating, palpitations, ↑HR, ↑palpitations, ↑sweat, ↑tremor, anxiety
When used for depression, buproprion is called ___ whereas when it's used for smoking cessation, it's
called ___?
Withdrawl from opioids results in "drug opposite effects", which include … (list 3)?(6)
You see someone who you suspect has alcohol withdrawal. He reports that he had a seizure that started
with the arm then the whole body started to shake. Is this evidence of alcohol withdrawal?
Seminar: Substance Abuse: A Case-Based Approach

__ and ___ characterize mild intoxication with GHB?
___ is a clue that a patient on treatment for alcohol dependence may be relapsing?(3)
A 750 cc bottle of wine contains approximately how many standard drinks?
An 18 year old patient was brought in by ambulance to the emerg after his friends foundhim
unresponsive in an after-hours night club. In the ambulance they gave him O2 and naloxone, to which
he didn't respond. In the ER he was unresponsive to deep pain and was noted to have myoclonus and
bradycardia and his O2 saturation was 80. After several hours he abruptly woke up, confused but
otherwise well. What drug did he overdose on?
An ounce contains approximately ___ cc's and a standard drink of wine contains about ___ oz?
Another name for Naltrexone is ___?
Apart from an inpatient program, list 2 effective treatment plans that you can use for treating problem
drinking?
For a patient experiencing alcohol withdrawal, which 3 other important questions would you ask on
history?
GHB can cause severe withdrawal syndrome similar to ___ withdrawal?
GHB is a structural analogue and metabolite of ___?
GHB overdose at higher doses is characterized by which symptoms (name 3)?
GHB overdose is treated with Phenobarbital?
Give an example of a long acting benzodiazepines (which, as a group, have been implicated in increasing
the risk of falls and hip fractures in seniors)?
How effective is smoking cessation counselling?
How long does buproprion take to work?
If someone has had a coronary event, how long should they wait before using a nicotine patch and
gum?
If someone is a problem drinker and you'd like to encourage them to recude their rate of drinking, what
strategies can you recommend to help patients avoid intoxication (list 5)?(7)
If you suspect that a patient has an alcohol problem, which other questions, besides frequency and
quantity of drinks per week and screening using the CAGE questionnaire, would you ask?
In addition to asking how much a patient drinks on average per week and defining the size of the
container of the type of alcohol they drink, which other important question should be asked to quantify
alcohol consumption per week?
In tracking a problem drinker's progress over time, it may be helpful to order GGT and ___ at baseline
and follow-up?
In treating alcohol withdrawal, diazepam is a good choice because it (list 3 reasons)?(5)
Insomnia and dysphoria may still be experienced for ___ after opioid withdrawal?
List what a standard drink is in terms of beer, wine, and liquor?
Methadone is an oral opioid ___ with a half-life of __ hours?
Methadone is used in the treatment of patients who are physically and psychologically dependent on
___, such as ___ or high doses of other potent opioids such as ___ (just an example of one)?
Percocet is a combination of ___ and ___?
T/F: even if titrated carefully, methadone still causes drowsiness but this is a tolerated side-effect since
it DOES relieve withdrawal and cravings, enabling patients to escape the biological compulsion to
continue drug use?
T/F: Low Risk Drinking Guidelines recommend 14 standard drinks per week and three drinks MAXIMUM
per day for MEN and 9 standard drinks per week and MAXIMUM 1 drink per day for WOMEN?
T/F: Most of the cardiovascular benefits of alcohol can be obtained by drinking less than one drink per
day and these benefits of reducing mortality from coronary artery disease are seconary to inhibition of
platelet function and improvement in the lipid profile?
T/F: Naltrexone is a competitive beta-2 adrenergic antantagonist, and has been shown in several
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T/F: Naltrexone is a competitive beta-2 adrenergic antantagonist, and has been shown in several
randomized trials to decrease the intensity and severity of binge drinking in alcohol dependent patients
engaged in formal treatment programs?
T/F: Naltrexone use reduces alcohol cravings?
T/F: Problem drinkers DO experience alcohol withdrawal?
T/F: There is NO evidence that inpatient programs are more effective than outpatient in treating binge
drinking and alcohol dependence?
The 4 main components of methadone treatment are: (4)?
The CAGE questionnaire is scored as "positive" if men score higher than ___ out of 4 and women score
higher than ___ out of 4?
The most common symptom of opioid withdrawal is ___?
There is evidence that benzodiazepine use in the elderly increases the risk for … and the risk of …?
What are the adverse effects of benzo's in the elderly?
What are the clinical features of alcohol dependence (list 3)?(5)
What are the clinical features of opioid withdrawal (list 2 objective signs and 2 subjective symptoms)?
What are the low risk drinking guidelines for men and women (ie. Maximum ___ standard drinks per
week, or ___ drinks on any one day for men, … for women)?
What is the definition of "alcohol dependence" (hint: 4 criteria, one of them being a type of
dependence)?
What is the difference in symptoms experienced between mild intoxication with GHB and intoxication
at higher doses?
What is the mechanism of action of methadone?
What is the mechanism of action of Naltrexone (ReVia) work?
What is the time course of opioid withdrawal?
Why does Naltrexone use make it easier for patients to practise strategies learned in counselling to
control excessive drinking habits?
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00 FMP 2008 Week 9 Intro Material
Friday, February 15, 2008
• Complete iterative testing for MCQ FMP2 online

• Answer all questions for week objectives 8 and 9
• Create flashcard questions for weeks 8 and 9 lectures and also all past fmp and pbd
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Week 9 Review Questions
5:59 PM
FMP 2008 week 09 review questions
Liver enzyme abnormalities

1. What are the different patterns of liver to injury?
2. What are the elements of “fibrotest”?
3. What are the tests that actually assess liver function?
4. How can liver fibrosis be diagnosed?
5. What liver enzymes can have their level elevated in the setting of hepatitis?
6. What are enzymes of cholestasis?
7. What causes “mild” hepatitis with ALT > AST? Of AST > ALT?
8. What are genetic causes of liver disease, what are the clinical features of each, and how can they be treated?
9. Which causes of viral hepatitis are vaccine-preventable?
10. Which causes of chronic viral hepatitis are treatable?
11. What is non-alcoholic fatty liver?
12. What are 36 drug causes of hepatitis? (just kidding)
13. What is autoimmune hepatitis?
14. What causes severe hepatitis? (What constitutes “severe” in this context?)
15. What causes cholestasis?
16. What is primary sclerosing cholangitis?
17. What is primary biliary cirrhosis?
Viral hepatitis
18. What are the 5 major types of viral hepatitis?
19. What are the clinical features and clinical course of hepatitis A?
20. How is hepatitis A transmitted?
21. How is hepatitis A managed?
22. Who should receive the hepatitis A vaccine?
23. How is hepatitis B transmitted?
24. What are clinical features of hepatitis B?
25. How is hepatitis B infection diagnosed? What is the relevance of tests for hepatitis B e antigen and antibody?
26. What are the serologic patterns of infection with hepatitis B that recovers, and that stays chronic?
27. Who should receive hepatitis B vaccine?
28. What are sequelae of chronic viral hepatitis?
29. What are the available treatments for chronic hepatitis B?
30. Who should receive treatment for chronic hepatitis B?
31. How is hepatitis C transmitted?
32. What is natural history of hepatitis C infection?
33. What is treatment of chronic hepatitis C?
34. What is hepatitis D?
35. What is hepatitis E?
36. What is hepatitis G?
Esophageal disorders
37. What is dysphagia?
38. What are the major causes of dysphagia?
39. What is a reasonable algorithm for the diagnosis of dysphagia?
40. What is odynophagia?
41. List three treatments for achalasia.
42. What is the mechanism of GE reflux in most cases?
43. How can the diagnosis of reflux be confirmed?
44. What are the major complications of GE reflux?
45. What is esophagitis?
46. What is Barrett’s esophagus?
47. What is the key element of treatment of GE reflux?
48. What is the mechanism of parietal cell acid secretion?
49. List 5 proton pump inhibitors.
Dyspepsia and peptic ulcer

50. What is dyspepsia?
51. What is the commonest cause of dyspepsia:
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51. What is the commonest cause of dyspepsia:
a. Overall
b. That has an organic basis
52. What are other important causes of dyspepsia?
53. What laboratory tests are appropriate for work-up of patients with dyspepsia?
54. What are the two major underlying causes of peptic ulcer disease?
55. What is Zollinger-Ellison syndrome?
56. What are complications of peptic ulcer disease?
57. What is H. Pylori?
58. What are complications of H. pylori?
59. How is H pylori treated?
60. What are the potential effects of NSAIDs on the GI tract?
61. Why do NSAIDs lead to peptic ulcer?
62. What is the best way to diagnose peptic ulcer disease?
63. List four categories of drugs that can heal a peptic ulcer without the use of antibiotics. What is the chief benefit of adding
antibiotics to this regimen?
Gastrointestinal bleeding
64. What are the major causes of upper GI bleeding?
65. What are three high risk unusual causes of upper GI bleeding?
66. What do the following terms mean?
a. Hematemesis
b. Melena
c. Hematochezia
67. What is the natural history of bleeding due to peptic ulcer disease?
68. What are the prognostic factors related to overall outcome in patients with upper GI bleeding?
69. What is the general mortality rate in patients with upper GI bleeding due to peptic ulcer?
70. What are endoscopic findings that predict an adverse outcome in patients with upper GI bleeding due to peptic ulcer?
71. What are general supportive measures related to management of patients with upper GI bleeding?
72. What are specific therapeutic measures for patients with upper GI bleed due to peptic ulcer?
73. What are indications for surgery in patients with upper GI bleeding?
74. What leads to esophageal varices?
75. What are risk factors for bleeding among patients with esophageal varices?
76. What are adverse prognostic factors for bleeding esophageal varices?
77. What specific therapeutic modalities are available for bleeding varices?
78. What is octreotide?
79. What is TIPS?
80. What are major causes of lower GI bleeding?
81. What are the major investigative modalities available for lower GI bleeding?
82. What is a Meckel’s diverticulum?
Acute pancreatitis
83. What are the two major causes of acute pancreatitis?
84. What are the additional important causes of acute pancreatitis?
85. What do patients with acute pancreatitis complain of?
86. What are the major physical findings in a patient with pancreatitis?
87. What laboratory tests are most helpful in the diagnosis of acute pancreatitis?
88. What are other causes of hyperamylasemia?
89. What imaging tests are helpful in diagnosis of acute pancreatitis and its complications?
90. What are the local complications of acute pancreatitis?
91. What are the major elements of treatment?
92. What is the role of endoscopy in the therapy of acute pancreatitis?
Diarrhea
93. What causes acute diarrhea?
94. What causes chronic diarrhea?
95. What are major causes of bloody diarrhea?
96. What tests are appropriate in a patient with chronic diarrhea?
Inflammatory bowel disease

97. What are the major differences in the histopathology of Crohn’s disease versus ulcerative colitis?
98. What are the locations of Crohn’s disease in the GI tract?
99. How does IBD present?
100. What are intestinal complications of IBD?
101. What are the extraintestinal manifestations of IBD?
102. What items are appropriate to consider in the differential diagnosis of the patient with suspected IBD?
103.
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103. What factors on history, physical exam and lab testing contribute to the assessment of disease severity in a patient with IBD?
104. What are the major treatment options for patients with Crohn’s and those with UC?
105. What is infliximab?
106. What is azathioprine?
107. What is 5-ASA?
108. What are adverse effects of corticosteroids?
109. What is cyclosporine?
110. What is budesonide?
111. What is methotrexate?
112. What are indications for surgery in patients with IBD?
113.
Liver failure
114. What are the pathologic features of cirrhosis?
115. What are the causes of cirrhosis?
116. What are the physical findings of cirrhosis?
117. What are the laboratory test abnormalities seen in patients with cirrhosis?
118. What are the elements of the Child-Pugh-Turcotte prognostic scale?
119. What are the major complications of cirrhosis?
120. What is the pathogenesis of cirrhotic ascites?
121. What are the elements of management of cirrhotic ascites?
122. What is a paracentesis?
123. What are the major indications for liver transplantation?
124. What is fulminant hepatic failure?
125. What are symptoms associated with jaundice, and how do they help to differentiate the causes?
126. What are major differences between Crohn’s disease and ulcerative colitis:
a. Pathologically
b. Clinically
c. In terms of treatment
127. What are the major complications of portal hypertension?
128. How is spontaneous bacterial peritonitis:
a. Diagnosed
b. Treated
129. What are the indications for liver transplantation?
130. What are the clinical features of sclerosing cholangitis?
131. What is the pathogenesis of cirrhotic ascites?
132. What is a TIPS procedure?
GI cancer screening
133. What is appropriate screening for:
a. Colon cancer
b. Esophageal cancer
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01 WONG 2008 Abnormal Liver Biochemistry and Function
Saturday, February 16, 2008
5:55 PM
In the progression of
fibrosis, does INR
increase first or does
Albumin drop first?
How do the following
factors rise and fall
and in which order in
the progression of
liver fibrosis: Albumin,
INR, Platelets,
Bilirubin?
When do you first
start to experience
symptoms from the
progression of fibrosis
(name after which of
the following factors
rises or falls): bilirubin,
platelets, INR,
albumin?
T/F: Cirrhosis begins
to occur soon after
the start of symptoms
secondary to the drop
in platelets?
It takes a long time to get to liver cirrhosis
Not until losing 50-60% of

liver that you start to get
clinical signs, first platelets,
then INR starts going up (by
this time start to get sick);
after that if ignore INR
going up, then albumin
drops, then finally at very
end, they turn yellow
(because of high bilirubin) -
THIS IS THE END STAGE OF
LIVER DISEASE!
• Liver is unique in that there's regeneration T/F: you can donate

• Everyone can donate the right lobe of your liver and within the right lobe of your
two weeks the right lobe will grow back! liver and within two
weeks, it will grow
back?
List 3
investigations
you could use to
diagnose fibrosis
of the liver?
• Liver biopsy is the gold standard in the diagnosis of fibrosis!

• Sound waves travel faster in a stiff liver than in a soft liver,
called the Fibroscan; THE THING IN Europe now; coming to
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called the Fibroscan; THE THING IN Europe now; coming to
Canada soon
What is the
gold standard
for the
Liver biopsy is the gold standard in the diagnosis of fibrosis! diagnosis of
fibrosis?
GGT
Bilirubin
Alpha2 macroglobulin
Apolipoprotein A1
Haptoblobulin
Fibrotest vs. Biopsy

While primarily about Hyperlipidemia, this article verifies that FibroTest has been validated in chronic Hepatitis c. So, why are doctors still
using biopsies???
Screening for Fibrosis with Non-invasive Biomarkers (Fibrotest) in Hyperlipidemic Patients
Insulin resistance is a cause of liver disease that can lead to cirrhosis. Hyperlipidemic patients (HP) have multiple insulinresistance factors
and frequent abnormal liver function tests. HP should be screened for significant liver fibrosis (bridging fibrosis: early F2, advanced F3,
cirrhosis F4) but biopsy is inappropriate because of the high number of patients at risk.
The aim of the current study was to use FibroTest, validated in chronic hepatitis C, B, alcoholic and non-alcoholic steatosis, to identify HP
with F2F3F4.
A consecutive cohort of HP, HCV-HBVneg, <50g alcohol/day, followed in a lipid center was analyzed. Fibrotest was retrospectively performed
on frozen fasting sera (–80 C); a control group of blood donors was prospectively included. Fibrotest was performed blinded with security
algorithms to identify high-risk of false negative/positive.
Results
Among 1,542 subjects, 40 (2.59%) were excluded using security algorithms, and 1,502 included: 50.3% female, median age 49yrs,957 HP and
545 controls.
Among HP, 83.4% had cholesterol >=200mg/dl, 93.6% LDL-C >=100mg/dl, 17.5% triglycerides >=200mg/dl, 35.9% BMI >=27, 33% arterial
hypertension, 31.8% insulinemia >=10mUI/ml and 13.7% glucose >=6mmol/L.
GGT or ALT were elevated (>=50 IU/L) in 215 HP (22.5%).
F2F3F4 were identified by Fibrotest in 25/957 (2.6%) HP, including 13 F2, 8 F3 and 4 F4 but in none (0%) of the 545 controls (P<0.0001).
Among 25 HP with fibrosis, 19 had normal ALT, 14 normal GGT, 12 normal ALT and GGT, 4 elevated ALT and GGT and 9 elevated ALT or GGT.
Factors associated (p<0.01) with fibrosis were higher age, BMI, triglycerides, uricemia, and insulinemia. In multivariate logistic regression,
including alcohol consumption, insulinemia (P=0.003) and triglycerides (P=0.008) were the most significant risk factors.
In HP with triglycerides >=200 mg/dl prevalence of fibrosis was 8.3% and 6.6% with insulinemia >=10mUI/ml.
Conclusions
Based on these results, the authors conclude, “Screening strategies for liver fibrosis are feasible with biomarkers in high-risk groups such as
HP.”
“Without such non-invasive strategies a liver biopsy would have been indicated in up to 22.5% of HP with elevated GGT or ALT and would
have probably missed half of HP with fibrosis, who had normal GGT and ALT.”
Biopredictive Department, Metabolism Unit, Biochemistry Department, Transfusion Unit, and Hepato-Gastroenterology Department,GHPS,
Paris, France.
05/02/05
Reference
M Munteanu and others. SCREENING FOR SIGNIFICANT FIBROSIS USING NON-INVASIVE BIOMARKERS (FIBROTEST) IN HYPERLIPIDEMIC
PATIENTS (HP). Abstract 689. 40th EASL. April 13-17, 2005. Paris, France.
Pasted from <http://www.hepatitis-central.com/mt/archives/2005/05/fibrotest_vs_bi.html>
Chronic liver diseases lead to fibrosis which can lead to the portal hypertension, changes in the liver architecture and may produce such an
irreversible rearrangement of the circulation as to cause cirrhosis. These liver diseases can cause necrosis, collapse and scar formation
which can also lead to fibrosis.
Cirrhosis is the end-stage progression of fibrosis, and is defined as characterized by

irreversible scarring of the liver and impaired liver function.
Pasted from <http://www.medhelp.org/posts/show/235680>
Week9 Page 10
What is the
difference
between fibrosis
and cirrhosis?
Why is ultrasound
not a good
method for
diagnosing mild
fibrosis of the
liver?
Compared to a
fibrotic liver, a
normal liver will
show increased or
decreased
echogenicity on
ultrasound
examination?
Fibroscan
A point system known as the Child’s-Pugh-Turcotte score (CPT score)

has been devised to determine the severity of the cirrhosis. Depending on
the total score, a patient is classified as Class A (early cirrhosis) through
Class C (advanced cirrhosis).
Child-Pugh-Turcotte Criteria
1 Point 2 Points 3 Points
1. Albumin >3.5 2.8-3.5 <2.8 A point system known as the
Child’s-Pugh-Turcotte score
(g/dl)
(CPT score) has been devised
2. Bilirubin (mg/dL) <2 2-3 >3 to determine the severity of
___?
3. Ascites None Minimal Moderate
4. Encephalo-pathy None Grade 1-2 Grade 3-4
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5. PT (sec <4 4-6 >6
prolonged) <1.7 <1.7-2.3 >2.3
INR
Class A: 5-6 points; Class B: 7-9 points; Class C: 10-15 points
Pasted from <http://www.hcvadvocate.org/hcsp/articles/Herrera.html>
What is the Child’s-Pugh-

Turcotte score used for?
http://www.hcvadvocate.org/hcsp/articles/Herrera.html That was end-stage liver disease; nowadays we can intervene! List 5 criteria measured
to calculate a Child-Pugh-
Turcotte score?
List 2 enzymes
which are released
when the liver is
damaged?
List 3 potential
complications of
cirrhosis?(4)
• Surgeons came up with a score; realized back in 1950 that when

• If patient has abnormal blood tests, want to know if have cirrhosis
you operate on someone with liver disease, they usually die on
you; came up with 1 to 3 (mildly to highly abnormal)
• Even if it wasn't a liver surgery, just the operation itself, with the Name 2 enzymes that
addition of them having a bad liver, put them in group C at 80% are released when
risk of death within 30 days post surgery hepatocytes are
ie. "How do we damaged, but which DO
NOT correlate with liver
recognize liver injury?"
function?
T/F: Though ALT and
AST are markers of liver
damage, they HAVE NO
correlation with liver
function?
What do ALT and AST

stand for?
What does SGOT stand
• Liver enzymes have NOTHING to do with liver function; tell
for?
you what's going on Which is less sensitive
• How know if one problem with liver? There are proteins that
as a marker of liver
are predominantly inside liver cells that only get released damage: AST or ALT?
when there's damage; eg. In times of Hepatitis Apart from being found
• Remember, if go out and play vigorous sports, ALT also found
in the liver, AST is also
in muscle; AST found in cardiac muscle, skeletal muscle, and found in …(name 3 )?
other tissues; EVEN LESS SENSTITIVE than ALT! Apart from being found
in the liver, ALT is also
found in ___?
ALT was formerly
known as ___?
List 2 enzymes
related to
cholestasis?
The upper limits of the 4

major liver enzymes, GTT,
ALP, AST, ALT, are all ___
except for ALP which has an
Basically, high levels of ALP correlated with growth upper limit of 105?
spurts; therefore: children/teens and pregnant women! AST was formerly known as
• All the liver enzymes, upper limits of normal are 40 except for ALP (@105) ___?
• List of diseases that can cause the enzymes of cholestasis to rise
• GGT NOT found in bone or placenta
○ GGT RARELY comes from kidney pancrease intestines prostate Most blood tests are pretty
• Most blood tests are pretty stable with age except for ALP stable with age except for
○ Eg. Teenagerhigh; when settle down and stop growing, lower levels, at around 100 which prominent enzyme
• Rememeber cholestasis is impaired bile flow related to cholestasis?
Cholestasis refers to …?
Medical Encyclopedia: ALP T/F: ALP levels are not stable
URL of this page: http://www.nlm.nih.gov/medlineplus/ency/article/003470.htm with age, meaning that a
Alternative names growing teenager will have
Alkaline phosphatase levels which will vary, and be
Definition lower than usual, compared to
Alkaline phosphatase (ALP) is a protein found in all body tissues. Tissues with particularly high amounts of ALP a non-growing adult?
List 2 populations in which
include the liver, bile ducts, and bone.
A blood test can be done to measure the level of ALP. high levels of ALP are seen?
See also: ALP isoenzyme test List 3 other places in the body,
How the test is performed apart from the liver, in which
Blood is drawn from a vein, usually from the inside of the elbow or the back of the hand. The site is cleaned with GGT is found?
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Blood is drawn from a vein, usually from the inside of the elbow or the back of the hand. The site is cleaned with GGT is found?
T/F: GGT is NOT found in
germ-killing medicine (antiseptic). The health care provider wraps an elastic band around your upper arm to
apply pressure to the area and make the vein swell with blood. bone?
Next, the health care provider gently inserts a needle into the vein. The blood collects into an airtight vial or tube ALP is also, in addition to being
attached to the needle. The elastic band is removed from your arm. found in the liver, is found in
Once the blood has been collected, the needle is removed, and the puncture site is covered to stop any bleeding. ___ and ___?
How to prepare for the test Out of the following enzyme
You should not to eat or drink anything for 6 hours before the test, unless otherwise instructed by your doctor. blood tests, which is the LEAST
Many drugs affect the level of alkaline phosphatase in the blood. Your health care provider may tell you to stop stable with age: AST, ALP, ALT,
GGT?
taking certain drugs before the test. Never stop taking any medicine without first talking to your doctor.
• Allopurinol
• Antibiotics
• Anti-inflammatory medicines
• Birth control pills
• Certain arthritis drugs
• Certain diabetes medicines
• Chlorpromazine
• Cortisone
• Male hormones
• Methyldopa
• Narcotic pain medicines
• Propranolol
• Tranquilizers
• Tricyclic antidepressants
Why the test is performed
This test is done to diagnose liver or bone disease, or to see if treatments for those diseases are working. It may
be included as part of a routine liver function test.
Normal Values
The normal range is 44 to 147 IU/L (international units per liter).
High
Normal values may vary slightly from laboratory to laboratory. They also can vary with age and gender.
levels of ALP are normally seen in children undergoing

growth spurts and in pregnant women.
What abnormal results mean
Higher-than-normal ALP levels may be due to:
• Anemia
• Biliary obstruction
• Bone disease
• Healing fracture
• Hepatitis
• Hyperparathyroidism
• Leukemia
• Liver disease
• Osteoblastic bone cancers
• Osteomalacia
• Paget's disease
• Rickets
Lower-than-normal ALP levels (hypophosphatasemia) may be due to:
• Malnutrition
• Protein deficiency
Additional conditions under which the test may be performed: A cholestatic pattern of
• Alcoholic liver disease (hepatitis/cirrhosis) liver enzyme
• Alcoholism abnormality refers
• Biliary stricture mainly to high levels of
• Giant cell (temporal, cranial) arteritis which two liver
• Multiple endocrine neoplasia (MEN) II enzymes?
• renal cell carcinoma The diagnosis of viral
Update Date: 5/17/2007 hepatitis can be made
Updated by: Benjamin W. Van Voorhees, MD, MPH, Assistant Professor of Medicine, Pediatrics and Psychiatry, via ___ and ___?
The University of Chicago, Chicago, IL. Review provided by VeriMed Healthcare Network. T/F: fulminant liver
failure is an
Pasted from <http://www.nlm.nih.gov/medlineplus/print/ency/article/003470.htm> unfortunate, common
event in viral hepatitis?
In mild hepatitis is ALT

higher than AST or the
other way around?
T/F: In mild hepatitis, ALT
may be up to ALMOST 5
TIMES higher than AST?
T/F: Non-alcoholic Fatty
Liver can NEVER cause
fulminant liver failure BUT it
CAN LEAD TO cirrhosis?
With which of the following
causes of liver disease is
fulminant liver failure
possible (may be more than
one): viral hepatitis, non-
alcoholic fatty liver,
ALP, AST, ALT, GGT: Liver Function Enzymes medications and toxins,
autoimmune hepatitis,
alpha-1-antitrypsin
deficiency?
Vaccines are present
against which hepatitis
viruses?
Week9 Page 13
viruses?
Do the majority or minority
of patients with viral
hepatitis experience
fulminant liver failure?
In hepatitis ___ and ___
there is no chronic
infection?
People diagnosed with
metabolic disorder should
also be suspected of having
which liver disease?
Parenteral: [para- + enteral] not through the alimentary • Infection of liver with a virus that leads to damage;
canal but rather by injection through some other route, such SOMETIMES can lead to cirrhosis
as subcutaneous, intramuscular, intraorbital, intracapsular, • Fulminant: [L. fulminare to flare up] sudden, severe;
intraspinal, intrasternal, or intravenous. occurring suddenly and with great intensity.
The first step in the treatment
of liver disease secondary to
medication use is to …?
Cirrhosis secondary to non-
alcoholic fatty liver disease
develops over: days, weeks,
months, years, decades?
Onset of liver disease
secondary to medications and
toxins usually takes ____
(weeks, months, years) but
can take up to ___ (weeks,
months, years)?
What does fulminant mean?
T/F: the biggest culprit of

• Terrible disease; no way of making diagnosis short of a • Usually get abnormal liver enzymes 1 to 2 months later; some 1 medications causing liver
liver biopsy year later disease are dermatologic
• Non-Alcoholic Fatty Liver associated with metabolic • Dose related: isoniazid (INH) and TB medications?
syndrome (and high BMI) • Biggest culprits are derm medications
• NEVER causes fulminant liver failure but IT CAN cause • People tend to forget about antibiotics; have cold, take
cirrhosis penicillin or amoxicillin;
• CAN cause fulminant failure
• CAN cause cirrhosis but have to take drug for long time
Fulminant is any event or process which occurs suddenly, quickly and is intense and
severe to the point of lethality , i.e, it has an explosive character. The word comes from Latin fulmināre, to
strike with lightning. It is most used in medicine, and there are several diseases which have this adjective:
• Fulminant liver failure
• Fulminant colitis
• Fulminant pre-eclampsia
• Fulminant meningitis
• Fulminant hepatic venous thrombosis (Budd-Chiari syndrome)
Pasted from <http://en.wikipedia.org/wiki/Fulminant>
DON'T NEED TO Memorize THIS; JUST FYI

Does autoimmune
hepatitis have a male
or female
predominance?
What is the
difference between
type 1 and type 2
autoimmune
hepatitis?
What is a potential
treatment for
autoimmune
hepatitis that can
prevent increased
liver fibrosis?
In autoimmune
hepatitis, how long
does it take for liver
cirrhosis to develop?
Hereditary causes of
hepatitis tend to
present earlier or
later in life?
Which of the
following types of
Week9 Page 14
DON'T NEED TO Memorize THIS; JUST FYI
Does autoimmune
hepatitis have a male
or female
predominance?
What is the
difference between
type 1 and type 2
autoimmune
hepatitis?
What is a potential
treatment for
autoimmune
hepatitis that can
prevent increased
liver fibrosis?
In autoimmune
hepatitis, how long
does it take for liver
cirrhosis to develop?
Hereditary causes of
hepatitis tend to
present earlier or
later in life?
Which of the
following types of
hepatitis does not
have a specific
diagnostic test:
autoimmune
hepatitis, hereditary
hemochromatosis,
alpha1-antitrypsin
deficiency, viral
hepatitis?
CAN cause fulminant liver

failure and/or cirhosis
• No specific diagnostic tests for autoimmune hepatitis

• Why tell people about this?
• Next talking about hereditary (genetic) diseases that are NOT very
○ Not that uncommon
common but tend to present later in life; CAN'T cause fulminant
○ CANNOT prevent it because don't know what causes it;
liver failure but can cause cirrhosis; is age-related
probably molecular mimicry
• Treatable by getting rid of iron; blood loss! Phlebotomy!
What is the treatment

for hereditary
hemochromatosis?
Why?
Apart from cirrhosis,
symptoms of
hemochromatosis can
include…(list 3)? (hint:
heart, skin, joints)
• Commonest ones in northern europeans ("white"

population): hemochromatosis: these people keep on • Protein misfolded!
absorbing iron their entire lives • VERY RARE!
• Will cause cirrhosis with NORMAL liver enzymes
• MUTATION IS NECESSARY BUT NOT SUFFICIENT; if you have
the mutation, not necessarily have the disease; if have the
disease, ALMOST CERTAINLY HAVE THE DISEASE!
List 3 non-hepatic
sources of mild hepatitis
Wilson's Disease where ALT < AST?
Week9 Page 15
CAN cause fulminant liver
failure and/or cirhosis
• No specific diagnostic tests for autoimmune hepatitis

• Why tell people about this?
• Next talking about hereditary (genetic) diseases that are NOT very
○ Not that uncommon
common but tend to present later in life; CAN'T cause fulminant
○ CANNOT prevent it because don't know what causes it;
liver failure but can cause cirrhosis; is age-related
probably molecular mimicry
• Treatable by getting rid of iron; blood loss! Phlebotomy!

for hereditary
hemochromatosis?
Why?
Apart from cirrhosis,
symptoms of
hemochromatosis can
include…(list 3)? (hint:
heart, skin, joints)
• Commonest ones in northern europeans ("white"

population): hemochromatosis: these people keep on • Protein misfolded!
absorbing iron their entire lives • VERY RARE!
• Will cause cirrhosis with NORMAL liver enzymes
• MUTATION IS NECESSARY BUT NOT SUFFICIENT; if you have
the mutation, not necessarily have the disease; if have the
disease, ALMOST CERTAINLY HAVE THE DISEASE!
List 3 non-hepatic
sources of mild hepatitis
Wilson's Disease where ALT < AST?
Kayser-Flescher rings
occur where?
Kayser-Flescher rings are
pathognomonic of which
disease?
Tetrathiomolibdate,
Trientene, zinc, and
• KNOW THIS ONE! REALLY RARE but genetic condition of an ATP • IF AST higher than ALT, then indicates cirrhosis penicillamine are all
responsible for transporting copper from one compartment of • Someone with hemolysis, muscle breakdown (myopathy, potential treatments for
the cell to another MI, muslce disease, etc., AST will be high; very non-specific) which disease?
• CAN CAUSE A FORM OF FULMINANT LIVER FAILURE Since there is rapid
○ Tends to happen in young; late teenagers, early twenty • Kayser-Fleischer ring, a golden brown or green deompensation in young
year olds; NEED A TRANSPLANT RIGHT AWAY IF YOU discoloration at the level of Descemet's membrane in Wilson's disease patients
RECOGNIZE THIS; it is actually treatable the limbic region of the cornea, seen in Wilson's disease with cirrhosis, they
○ SERUM COPPER is high in this and other liver disorders. should get an immediate
○ Usual trick: it's in the young; they usually already have ___?
cirrhosis;
○ SO
 Hemolysis
 Liver disease
 Young
□ = liver disease (secondary to WILSON'S
DISEASE)
• ALCOHOL Kayser-Fleischer ring in Wilson's disease.

○ Diagnosis is tricky because people don't answer truthfully;
don't ask "do you drink" but rather "what do you drink"?!
○ How does it present?: urine eventually becomes very dark
colour; start looking jaundiced; cycle of bouts of alcoholic T/F: Alcoholic liver
hepatitis and jaundice and cold turkey, BUT THEY DON'T disease causes cirrhosis
GET BETTER; over the course of
weeks and months
instead of
years/decades?
Mild hepatitis refers to
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○ Diagnosis is tricky because people don't answer truthfully;
don't ask "do you drink" but rather "what do you drink"?!
○ How does it present?: urine eventually becomes very dark
colour; start looking jaundiced; cycle of bouts of alcoholic T/F: Alcoholic liver
hepatitis and jaundice and cold turkey, BUT THEY DON'T disease causes cirrhosis
GET BETTER; over the course of
weeks and months
instead of
years/decades?
Mild hepatitis refers to

ALT and/or AST being less
than ___ x the limit of
normal whereas severe
hepatitits is defined as
ALT and AST levels up to
___x the level of normal?
Eg. Case: Patient presents to emerg: List 6 causes of ACUTE,
 Drinker, repeated bouts of feeling unwell; when gets SEVERE hepatitis?
severe, RUQ pain, increase in neutrophils, WBC
□ Will go down when stop drinking
• Potentially treatable when sick; can give steroids
• Alcoholic liver disease: CAN cause cirrhosis
What is a potential
treatment for hepatitis
secondary to chronic
What may be the cause

of itchy skin in
cholestasis?
• Memorize causes in yellow: causes of acute severe hepatitis!

• Note alcohol NOT on the list; it's not the primary culprit if
enzymes are really high; something else going on! A patient's skin turns
JUST FYI; DON'T NEED TO MEMORIZE THIS yellow in times of
stress. The likely
diagnosis is ___?
Gilbert's syndrome is
due to not being able
to get rid of ___
efficiently?
Gilbert's syndrome is a
common cause of
(choose one): isolated
hyperbilirubinemia,
autoimmune hepatitis,
Kayser-Fleischer rings,
liver cirrhosis, OR
primary biliary
cirrhosis ?
• In general, if ALP up alone, not the liver, but if Gilbert's Sy ndrome: Jaundice typically appears during times of:
both up, then likely the liver! ex ertion, stress, not eating, and infection. List 3 common causes
Pasted from <http://health.nytimes.com/health/guides/disease/gilberts -disease/overview.html>
of cholestasis?
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List 3
hepatobiliary
causes of
elevated ALP?
What is primary
sclerosing
cholangitis?
Primary
sclerosing
cholangitisis
diagnosed
through ___?
(Remember ALP released
ma i nly 3rd tri mester placenta)
Primary Sclerosing Cholangitis (PSC)
Pasted from <http://www.clevelandclinic.org/health/health-info/docs/4100/4150.asp?index=13316&src=newsp>

In primary sclerosing cholangitis (PSC), the bile ducts inside and outside the liver become inflamed and scarred. As the
scarring increases, the ducts become blocked. The ducts are important because they carry bile out of the liver. Bile is a liquid that helps
break down fat in food. If the ducts are blocked, bile builds up in the liver and damages liver cells. Eventually, PSC can cause liver failure.
Researchers do not know what causes PSC. Among the theories under investigation are the possible role of bacteria, viruses, and immune
system problems. PSC appears to be associated with ulcerative colitis, a type of inflammatory bowel disease.
The disease usually begins between ages 30 and 60, but the disease can also arise during childhood. PSC is more common in men
than women. PSC progresses slowly, so a person can have the disease for years before symptoms develop. The
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than women. PSC progresses slowly, so a person can have the disease for years before symptoms develop. The
main symptoms are itching, fatigue, and jaundice, which causes yellowing of the eyes or skin. An infection in the bile ducts can cause chills
and fever.
PSC is diagnosed through cholangiography, which involves injecting dye into the bile ducts and taking an x ray. Cholangiography
can be performed as an endoscopic procedure (endoscopic retrograde cholangiopancreatography, ERCP), through radiology or surgery, or
with magnetic resonance imaging (MRI) scans. Treatment includes medication to relieve itching, antibiotics to treat infections, and vitamin
supplements, as people with PSC are often deficient in vitamins A, D, and K. In some cases, surgery to open major blockages in the common
bile duct is also necessary. Liver transplantation may be an option if the liver begins to fail.
Pasted from <http://digestive.niddk.nih.gov/ddiseases/pubs/primarysclerosingcholangitis/>
Primary biliary cirrhosis (PBC)
Primary biliary cirrhosis

causes inflammation
and scarring that
destroy the small
ducts within the liver,
slowing and sometimes
blocking the normal
flow of bile, which is
necessary for digestion.
Pasted from <http://www.mayoclinic.com/popupnowrap.cfm?objectid=A4E1A07F-2A5D-9994-E401906607352167&method=display_full>
Introduction
Primary biliary cirrhosis is a disease in which the bile ducts in your liver are slowly destroyed. In primary
biliary cirrhosis, the destruction of your bile ducts can cause harmful substances to build up in your liver
and sometimes lead to irreversible scarring of liver tissue (cirrhosis).
The cause of primary biliary cirrhosis remains unclear. Many experts consider primary biliary cirrhosis an
autoimmune disease in which the body turns against its own cells, although it's likely that genetic and
environmental factors also play a part. Primary biliary cirrhosis develops slowly. Medication can slow the
progression of the disease, especially if treatment begins early.
Signs and symptoms
Early-stage
Although some people with primary biliary cirrhosis remain symptom-free for years after they're diagnosed,
others experience fatigue, itching, dry eyes and dry mouth early in the disease:
• Fatigue. This is the most common symptom of primary biliary cirrhosis. In general, energy levels are
normal in the morning, but fall later in the day and don't improve with rest. Doctors haven't found any
correlation between the degree of exhaustion and the severity of the illness. This means that people
with mild primary biliary cirrhosis and those with more serious disease may be equally fatigued.
• Itching. Another common symptom, itching (pruritis), is often most bothersome over your legs, arms
and back. The severity of itching may change, often becoming worse at night and improving during
the day. Nighttime itching can disturb sleep, making fatigue worse and sometimes leading to
depression. The cause of this severe itching isn't clear.
• Dry eyes and mouth (sicca syndrome). Sicca syndrome often occurs in people with other
autoimmune disorders. It causes inflammation in the moisture-secreting glands of the eyes and
mouth, resulting in the decreased production of tears and saliva. This can lead to difficulty swallowing,
light sensitivity and corneal ulcers.
Later stage
As the destruction of bile duct and liver cells progresses, other signs and symptoms may develop, such as:
• Jaundice. A common sign of advanced liver disease, jaundice turns your skin and the whites of your
eyes yellow. The discoloration is due to high blood levels of bilirubin, a byproduct of the breakdown of
the hemoglobin from old or damaged red blood cells. Normally, bile carries bilirubin out of the liver so
that it can be excreted from your body. But as more bile ducts are destroyed and the flow of bile
slows, bilirubin begins to build up in the blood and eventually becomes visible in your skin and eyes.
• Hyperpigmentation. Inadequate bile flow increases the production of the skin pigment melanin. This
causes your skin to become darker, even in areas that aren't exposed to the sun. Sometimes the
deeper color isn't uniform, and your skin appears blotchy.
• Swollen feet (edema) and abdomen (ascites). As liver damage progresses, your body begins to
retain salt and fluids. At first, the excess water accumulates mainly in your feet and ankles, which
tend to become more swollen late in the day. In time, fluid can also collect in your abdomen.
• Cholesterol deposits (xanthomas). Your body uses bile as the main way of eliminating excess
cholesterol. When disease interferes with this process, the amount of cholesterol in the blood
increases. This can lead to the formation of fatty deposits in the skin around the eyes, the eyelids, or
in the creases in the palms, soles, elbows, knees or buttocks. These raised, waxy growths usually
don't appear until blood cholesterol reaches very high levels. Even then, not everyone with primary
biliary cirrhosis develops them.
• Digestive problems. Because bile is essential for the digestion and absorption of fats, primary biliary
cirrhosis can cause intestinal problems. These include diarrhea and steatorrhea — greasy, bad-
smelling stools that result from poor fat digestion.
Urinary tract infections. About one in five women with primary biliary cirrhosis experiences recurring
Week9 Page 19
smelling stools that result from poor fat digestion.
• Urinary tract infections. About one in five women with primary biliary cirrhosis experiences recurring
urinary tract infections. The relationship between these infections and bile duct destruction isn't well
understood. A few studies suggest that the same bacteria responsible for urinary tract infections may
play a role in some cases of primary biliary cirrhosis.
Causes
The exact cause of primary biliary cirrhosis isn't known, but it appears to be an immune system disorder
that slowly destroys the bile ducts in your liver. Genetics and the environment also may play a role in this
disease.
Risk factors
The following factors may increase the risk of primary biliary cirrhosis:
• Your sex. More than 90 percent of people with primary biliary cirrhosis are women. Immune system
disorders in general affect far more women than men, but the reason for this isn't known.
• Your age. Most people diagnosed with primary biliary cirrhosis are 35 to 60 years old. Although older
adults can develop the disease, it is rare in children.
• Family history. Primary biliary cirrhosis isn't hereditary, but having a family member with the disease
increases your risk.
Screening and diagnosis
Common tests
Many people with primary biliary cirrhosis have no symptoms of the disease when they're diagnosed.
Instead, doctors often become aware of a problem during routine blood tests or an evaluation for another
condition.
Several tests can help diagnose primary biliary cirrhosis, including:
• Liver function tests. These blood tests check the levels of enzymes that may indicate liver disease
in general and bile duct injury in particular. Certain liver enzymes are elevated in most people with
primary biliary cirrhosis, especially alkaline phosphatase, which is produced in the bile ducts.
• Ultrasound imaging. This noninvasive test uses high-frequency sound waves to create precise
images of structures within the body, including the bile ducts. It's sometimes used to rule out other
causes of bile flow blockage, such as gallstones or tumors.
• Anti-mitochondrial antibodies (AMAs). Found in every cell, mitochondria are the prime energy
producers of the body. Antibodies are proteins in the blood that help destroy bacteria and other
harmful pathogens. Most people with primary biliary cirrhosis have anti-mitochondrial antibodies —
antibodies that target enzymes in the mitochondria. These antibodies almost never occur in people
who don't have primary biliary cirrhosis, even if they have other liver disorders. For that reason, a
positive AMA test is considered a very reliable indicator of the disease. At the same time, a small
percentage of people with primary biliary cirrhosis don't have AMAs. False-positive tests, which
indicate a problem where none exists, also can occur. Because an AMA test isn't entirely foolproof,
doctors usually perform a liver biopsy, which can definitively confirm the presence or absence of the
disease.
• Liver biopsy. In this test, a small sample of liver tissue (biopsy) is removed and examined in a
laboratory, either to confirm the diagnosis or to determine the extent (stage) of the disease. Doctors
withdraw the tissue through a small incision using a thin needle. Doctors may take more liver biopsies
as time goes on to check the progression of the disease.
• Magnetic resonance elastography (MRE). This relatively new test can help your doctor diagnose
primary biliary cirrhosis and may help avoid the need for liver biopsy, which is more invasive. MRE
technology works by combining traditional magnetic resonance imaging (MRI) with low-frequency
sounds waves. The MRI component uses a magnetic field and radio waves to create clear and
detailed cross-sectional images of your body, which show size and structure of your tissues and
organs. The low-frequency sound waves then help reveal physical properties of those tissues and
organs — such as tissue stiffness. Stiffness of your liver may indicate cirrhosis.
Complications
As liver damage progresses, people with primary biliary cirrhosis may develop a number of serious
problems, including:
• Cirrhosis. The term "primary biliary cirrhosis" isn't entirely accurate because cirrhosis develops only
in the last stages of the disease — often many years after diagnosis. Yet when it does occur, cirrhosis
can be life-threatening because it interferes with the liver's ability to carry out essential functions.
Cases of primary biliary cirrhosis are divided into four stages. The first stage — inflammation of the
bile ducts — is the least serious, and stage 4 — cirrhosis — the most serious. Ongoing cirrhosis
can lead to liver failure, which occurs when the liver is no longer able to function.
• Increased pressure in the portal vein (portal hypertension). Blood from your intestine, spleen and
pancreas enters your liver through a large blood vessel called the portal vein. Under normal
circumstances, the pressure in this vein is considerably lower than the pressure in the arteries. But
when scar tissue blocks normal circulation through the liver, blood backs up, much like water behind a
dam, leading to increased pressure within the vein. And because blood doesn't flow normally through
the liver, hormones, drugs and other toxins aren't filtered properly before entering the bloodstream.
• Enlarged veins (varices). When circulation through the portal vein is slowed or blocked, blood may
back up into other veins — mainly those in your stomach and esophagus. Sometimes veins also form
around your navel and at the rectum. The blood vessels are thin walled, and increased pressure in
the veins can cause bleeding in the upper stomach or esophagus. This is a life-threatening
emergency that requires immediate medical care.
• Liver cancer. The destruction of healthy liver tissue that occurs in cirrhosis greatly increases the risk
of liver cancer, primarily hepatocellular carcinoma, which affects the hepatocytes, the main type of
liver cell.
• Weak bones (osteoporosis). Liver scarring interferes with the liver's ability to process vitamin D and
calcium, both of which are essential for bone growth and health. As a result, weak, brittle bones and
bone loss may be complications of late-stage primary biliary cirrhosis, and your doctor may order a
bone density test to look for osteoporosis.
• Vitamin deficiencies. A lack of bile affects the absorption of fats and of the fat-soluble vitamins A, D,
E and K. This sometimes leads to deficiencies of these vitamins in advanced cases of primary biliary
cirrhosis.
Other complications
In addition to bile duct and liver damage, people with primary biliary cirrhosis are likely to have other
metabolic or immune system disorders, including:
Week9 Page 20
• Thyroid disease. Thyroid problems not only are common in people with primary biliary cirrhosis, but
often appear long before the bile duct damage is diagnosed.
• CREST syndrome. This immune system disorder is a subset of scleroderma, a disease that leads to
thickening, tightening and hardening of connective tissue. CREST syndrome can affect many body
systems, including the blood vessels and esophagus, and sometimes the digestive tract, lungs and
heart. People with primary biliary cirrhosis are more likely to have some, rather than all, of the signs
and symptoms of CREST.
• Raynaud's phenomenon. One of the components of CREST, this disorder is common in people with
primary biliary cirrhosis. It occurs when small blood vessels (capillaries) spasm in response to cold or
emotional stress, blocking the flow of blood. Although not everyone with Raynaud's experiences the
same signs and symptoms during an attack, the areas of affected skin generally turn white before
becoming blue, cold and numb. When circulation improves, the skin usually reddens and may throb or
tingle. Attacks of Raynaud's may last from a few minutes to several hours and tend to become worse
over time.
• Rheumatoid arthritis. Some people with primary biliary cirrhosis have the aching joints that typify
rheumatoid arthritis, another autoimmune disorder. Other people may have markers for rheumatoid
arthritis in their blood but no signs or symptoms of the disease.
Pasted from <http://www.mayoclinic.com/print/primary-biliary-cirrhosis/DS00604/METHOD=print&DSECTION=all>
Amyloidosis
Introduction
Amyloidosis is a rare and potentially fatal disease that occurs when substances called amyloid proteins
build up in your organs. Amyloid is an abnormal protein usually produced by cells in your bone marrow that
can be deposited in any tissue or organ.
Amyloidosis can affect different organs in different people, and there are many types of amyloid.
Amyloidosis frequently affects the heart, kidneys, liver, spleen, nervous system and gastrointestinal tract.
The exact cause of amyloidosis is unknown, and there's no cure for amyloidosis. However, therapies are
available to help you manage your symptoms and limit the production of amyloid protein.
Signs and symptoms
Purpura Around The Eyes
Some people with amyloidosis experience purpura — a condition where small blood vessels leak into the
skin, causing purplish patches.
Enlarged Tongue
An enlarged tongue (macroglossia) can be a sign of amyloidosis.
Pasted from <http://www.mayoclinic.com/print/amyloidosis/DS00431/METHOD=print&DSECTION=all>
Cholecystitis and Cholangitis

• CHOLECYSTITIS: Infection or inflammation of the gallbladder, which collects and
concentrates bile from the liver (Cholecystitis).
• CHOLANGITIS: Infection or inflammation of the ducts that drain bile from the liver to the
gallbladder (cholangitis).
Pasted from <http://www.rxmed.com/b.main/b1.illness/b1.1.illnesses/cholecystitis_and_cholangitis.html>
Primary sclerosing
cholangitis has a
Week9 Page 21
cholangitis has a
(male/female)
predominance while
NEITHER PSC OR PBC lead to fulminant liver failure(also, both 10-20 year cirrhosis, neither prevenable) primary biliary cirrhosis has
a (male/female)
predominance?
Which has a predominantly
FEMALE predominance:
Primary Biliary Cirrhosis OR
Primary Sclerosing
Cholangitis?
Primary Sclerosing
ERCP and MRCP - When and Why Cholangitis is associated
with ___?
In both primary sclerosing

cholangitis AND primary
biliary cirrhosis, how long
does it take, approximately,
for liver cirrhosis to
• Just be aware meds can do this; JUST FOR • Not preventable because we have no idea what causes it!
develop?
REFERENCE!; don't have to memorize! Can EITHER primary
sclerosing cholangitis OR
primary biliary cirrhosis lead
to fulminant liver failure?
The progression of primary
biliary cirrhosis is retarded
through the use of ___?
Out of the four

enzymes below,
which 2 would you
KNOW CAUSES OF SEVERE HEPATITIS test to further
• BE AWARE of liver function tests: INR, Albumin, Bilirubin: DO NOT investigate hepatitis
tell you about the liver! and which two for
cholestasis: ALP, AST,
ALT, GGT?
Eg. Can have Hep C

but also
hemochromatosis
• When see hepatitis: Fatty liver, alcohol, fatty liver

from obese
Week9 Page 22
Name an uncommon cause
of liver disease which, if
caught, is very important to
treat right away as it may be
acutely fatal?
List 3 biochemical disorders
that are uncommon but
important to know about in
having a differential for liver
disease?
How do AST, ALT, and ALP
levels manifest in hepatitis?
levels manifest in hepatitis?
levels manifest in
cholestasis?
levels manifest in hepatitis
List 3 medication classes
that are associated with
cholestasis?(5)
• Fluphenazine: the 2-trifluromethyl derivative of perphenazine, the most potent of the phenothiazine antipsychotic agents.
• Imipramine: a tricyclic antidepressant of the dibenzazepine class, the first of the tricyclic antidepressants to be used.
Week9 Page 23
Alkaline Phosphatase and Gamma Glutamyltransferase
Monday, March 31, 2008
David H. Vroon
Zafar Israili
Alkaline Phosphatase
Definition
Alkaline phosphatase (ALP) refers to a group of phosphomonoesterases that hydrolyze
phosphate esters with optimum in vitro activity at a pH of 10. Enzyme activity is expressed in
international units (IU), the amount of enzyme that catalyzes the conversion of 1 μmole of
substrate per minute. Reference ranges vary widely with methodology; the most commonly
used method produces a reference range of 35 to 125 IU per liter in an adult population.
Intraindividual variation in ALP activity has been shown to vary considerably less than the
interindividual variation included in reference ranges. Therefore comparison with
preestablished values by the same method in an individual may be the most useful reference.
Technique
Numerous methods utilizing different substrates and reaction conditions have been applied to
measurement of ALP activity. The heterogeneity of methods presents problems with comparing
results from different laboratories and often compromises the current application of data
previously reported in the literature.
Recent methodologic changes have emphasized the need for standardization and optimization
of the assay. Readily hydrolyzed, self-indicating substrates that permit continuous monitoring
under optimized reaction conditions are now preferred. Earlier methods (Bodansky, King, and
Armstrong), which involved indirect quantitation of reaction products, are obsolete.
The most widely used reference method utilizes 4-nitro-phenyl phosphate, a readily hydrolyzed,
self-indicating ALP substrate introduced in 1946 by Bessey, Lowry, and Brock. The reaction rate
is enhanced by removal of inhibitory phosphate and optimizing divalent cation (magnesium and
zinc) concentrations.
Serum is the specimen of choice, although heparinized plasma can be used. Chelating
anticoagulants, which remove the activator magnesium, are unacceptable. Since hemoglobin
may interfere spectrophotometrically, in vitro hemolysis should be avoided. Assay within 4
hours of specimen colection is recommended; frozen specimens should be kept at room
temperature for 12 hours prior to assay to assure complete enzyme reactivation.
Basic Science
Most human tissues contain ALP; kidney, liver, bone, intestine, reticuloendothelial tissue, and
placenta are particularly rich sources. Enzymes derived from different tissues share catalytic
properties, but differ in their chemical and physical characteristics. Three genetically
determined forms have been described: intestinal, placental, and
liver/bone/kidney/reticuloendothelial. Different molecular properties within these isoenzyme
groups are probably the result of posttranslational modifications. Various methods have been
used to separate organ-specific isoforms. None are entirely satisfactory, particularly in
quantifying components of the liver/bone isoenzyme group.
ALP activity in normal adult serum is derived predominantly from hepatic, osseous, and
Week9 Page 24
ALP activity in normal adult serum is derived predominantly from hepatic, osseous, and
reticuloendothelial sources. Physiologic bone growth in children increases serum activity to 2 to
5 times the levels observed in adults. Placental ALP causes 2-to 3-fold elevations during the
second and third trimesters of normal pregnancy. Serum enrichment by intestinal isoenzyme
may cause postprandial elevation, particularly in individuals with blood groups B or O who are
also secretors of ABH blood group substance.
A number of functions have been proposed. The location of hepatic ALP on the sinusoid
membrane suggests involvement in transport function. Increased ALP synthesis is observed
during cholestasis with increased bile acid concentration caused by intrahepatic or extrahepatic
obstruction of the biliary tree. Bone ALP is probably involved with calcification, perhaps by
hydrolyzing pyrophosphate, which inhibits mineralization. In hypophosphatasia, an inherited
disorder with virtual absence of the bone ALP isoenzyme, there is histochemical evidence for
deficient bone calcification. The intestinal isoenzyme appears to function in the transport of
fatty acids, calcium, and phosphate.
Clinical Significance
The majority of sustained elevated ALP levels are associated with disorders of the liver or bone,
or both. Therefore, these organ systems are of prime consideration in the differential diagnosis.
A variety of primary and secondary hepatic conditions may be associated with elevated serum
ALP levels. Since production is increased in response to cholestasis, serum ALP activity provides
a sensitive indicator of obstructive and space-occupying lesions of the liver. The latter includes
neoplastic (primary or metastic) and infiltrative diseases (granulomatous hepatitis). Bilirubin
excretion is compromised only with extensive biliary obstruction or diffuse hepatic cell
disruption; therefore, differential elevation of ALP relative to serum bilirubin provides an early
indicator for obstructive or space-occupying conditions. Hepatic cell lesions are manifested by
hyperbilirubinemia and dominant serum elevation of parenchymal enzymes, such as
aminotransferases; ALP elevations may be only minimal.
Diseases of bone associated with increased serum ALP are restricted to the presence of
osteoblastic activity. Elevations are generally detectable prior to roentgenographic
abnormalities. Neoplasms involving bone may be associated with marked serum elevations
when lesions incite osteoblastic reaction, such as metastatic adenocarcinoma of the prostate.
Conversely, osteolytic lesions such as occur within multiple myeloma are not associated with
increased serum ALP activity. Metabolic bone diseases usually associated with serum
enrichment by the bone isoenzyme include rickets, osteomalacia, and Paget's disease. Levels
are usually normal in osteoporosis. Increased serum activity may be observed after bone
fractures, rising after 1 week and persisting for up to 3 months.
Elevated serum ALP occurring with neoplastic disease may be due to hepatic metastases, bone
metastases, or direct contribution by neoplastic cells. Isoenzymes with physicochemical
characteristics similar to the placental isoenzyme have been attributed to ectopic production by
a variety of neoplasms; this apparently represents derepression of normally repressed
fetoplacental genes.
Clinically obscure elevations of ALP are commonly observed when multitest biochemical panels
are performed on hospital populations. Because of the cellular distribution of ALP, increased
serum activity may be caused by a wide variety of disorders involving multiple organs. Attempts
to define organ source by isoenzyme study may be met with limited success because of
technical limitations; accurate measurement of different isoenzymes contributing to total
serum ALP activity is not currently possible. However, the presence of the intestinal or placental
isoenzyme may be revealed by selected methods. Evaluation of an unexpectedly increased ALP
should include the following:
1. Exclude physiologic causes. Is the patient pregnant or an actively growing child?
Week9 Page 25
1. Exclude physiologic causes. Is the patient pregnant or an actively growing child?
2. Observe for the presence of clinical or biochemical clues to the origin of increased enzyme
activity. Increased serum bilirubin or aminotransferase (either aspartate or alanine) activity
suggests hepatic rather than bone origin. Disproportionate elevation of lactic
dehydrogenase (LDH) relative to transaminase usually suggests nonhepatobiliary or
multiorgan system disease. The association of elevated LDH, hypercalcemia, and
hyperuricemia suggests metastastic neoplastic disease.
3. Is the elevation transient such as observed in various tissue reparative processes, healing
bone fractures, or passive congestion of the liver?
4. Measurement of other enzymes such as 5′-nucleotidase or gamma-glutamyltransferase
may assist with identifying the hepatobiliary system as a source of elevated ALP since these
enzymes are not significantly present in bone. 5′-Nucleotidase is a highly specific but less
sensitive indicator of hepatobiliary disease. Gamma glutamyltransferase is more sensitive;
however, with the exception of its absence in bone and placenta, it is a less specific
indicator of hepatobiliary disease than ALP.
Gamma Glutamyltransferase
Definition
Gamma glutamyltransferase (GGT) is one of a broad group of enzymes that catalyze the transfer
of amino acids from one peptide to another amino acid or peptide. This enzyme is sometimes
referred to as a "transpeptidase" but is more appropriately included in the amino acid
transferase group. Specifically it catalyzes the transfer of a gamma glutamyl group to another
acceptor. The reference range with most commonly used methods is 0 to 50 IU/L in males and 0
to 30 IU/L in females. Higher activity in males is probably caused by high enzyme concentration
in prostatic tissue.
Technique
Self-indicating substrates with continuous reaction monitoring are preferred. Most commonly
gamma-glutamyl-para-nitroanilide is used as substrate and glyclyglycine as acceptor. The
substrate residue, para-nitroaniline, is directly measured by absorbance at 405 nm. The recently
proposed reference method utilizes a carboxyl derivative of gamma-glutamyl-para-nitroanilide
to enhance substrate solubility; higher levels of activity are observed with this substrate
derivative. However, most laboratories use the unsubstituted substrate because of established
clinical and laboratory experience.
Serum is the specimen of choice; hemoglobin may interfere spectrophotometrically and
hemolysis should be avoided. EDTA plasma is acceptable; other anticoagulants such as heparin,
citrate, or oxalate may interfere with the reaction.
Basic Science
High concentrations of GGT are found in renal, prostatic, pancreatic, and hepatobiliary tissue;
smaller amounts are found in all other tissues except muscle. A number of physiologic functions
have been suggested. Involvement in amino acid transport and glutathione metabolism are
most strongly indicated. Enzyme activity observed in serum is electrophoretically
heterogeneous; however, true isoenzyme forms have not been defined, and fractionation has
no clinical significance.
Clinical Significance
Hepatobiliary disease is the predominant source of increased serum GGT activity. Increases are
associated with all forms of primary and secondary hepatobiliary disorders. Elevations are
Week9 Page 26
moderate (2 to 5 times reference) with diffuse hepatic cell injury due to toxic or infectious
hepatitis. Cholestasis due to intrahepatic or extrahepatic biliary obstruction causes higher
serum levels (5 to 30 times reference). Increases occur earlier and persist longer than ALP in
cholestatic disorders. Since skeletal disease is not associated with increased serum activity,
measurement of GGT is of clinical value in identifying the source of obscure ALP elevations.
Levels in children after age 1 year and healthy pregnant women are within the usual adult
reference range.
Elevated serum levels of GGT are also found in alcoholics and patients receiving certain drugs,
such as phenytoin or phenobarbital. This is probably the result of microsomal induction of
enzyme activity. Serum measurement can be used to monitor alcoholic patients during therapy;
abstinence from alcohol is associated with decrease in serum GGT activity. In addition, alcohol-
induced hepatic cell injury may cause significantly higher serum levels than other causes of
parenchymal disorders.
Elevated GGT activity also occurs in patients with acute and chronic pancreatitis. Prostatic
adenocarcinoma may be associated with increased serum levels. Therefore, although increases
are absent with skeletal diseases, GGT activity should not be considered a highly specific
indicator of hepatobiliary disease.
References
Kaplan MM. Alkaline phosphatase. Gastroenterology 1972; 62: 452-68. (PubMed)
Rosalki SB. Gamma-glutamyl transpeptidase. Adv Clin Chem 1975; 17: 53-107. (PubMed)
Wolf PL. Clinical significance of an increased or decreased serum alkaline phosphatase level.
Arch Pathol Lab Med 1978; 102: 497-501. (PubMed)
Pasted from <http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cm.chapter.3148 >
Week9 Page 27
GGT
1:35 PM
Gamma-glutamyl transpeptidase
Contents of this page:
• Alternative Names • Why the Test is Performed
• Definition • Normal Results
• How the Test is Performed • What Abnormal Results Mean
• How to Prepare for the Test • Risks
• How the Test Will Feel • Considerations
Alternative Names
Gamma-GT; GGTP; GGT
Definition Return to top
Gamma-glutamyl transpeptidase is a test to measure the amount of the enzyme GGT in the
blood.
How the Test is Performed Return to top
Blood is drawn from a vein on the inside of the elbow or the back of the hand. The puncture
site is cleaned with antiseptic, and an elastic band is placed around the upper arm to apply
pressure and restrict blood flow through the vein. This causes veins below the band to fill with
blood.
A needle is inserted into the vein, and the blood is collected in an air-tight vial or a syringe.
During the procedure, the band is removed to restore circulation (blood flow). Once the blood
has been collected, the needle is removed, and the puncture site is covered to stop any
bleeding.
For an infant or young child:
The area is cleansed with antiseptic and punctured with a sharp needle or a lancet. The blood
may be collected in a pipette (small glass tube), on a slide, onto a test strip, or into a small
container. Cotton or a bandage may be applied to the puncture site if there is any continued
bleeding.
How to Prepare for the Test Return to top
The health care provider may advise you to stop taking any drugs that can affect the test (see
Special Considerations).
For infants and children:
The preparation you can provide for this test depends on your child's age and experience. For
specific information regarding how you can prepare your child, see the following:
• Infant test or procedure preparation (birth to 1 year)
• Toddler test or procedure preparation (1 to 3 years)
• Preschooler test or procedure preparation (3 to 6 years)
• School age test or procedure preparation (6 to 12 years)
• Adolescent test or procedure preparation (12 to 18 years)
How the Test Will Feel Return to top
When the needle is inserted to draw blood, some people feel moderate pain, while others feel
only a prick or stinging sensation. Afterward, there may be some throbbing.
Why the Test is Performed Return to top
This test is used to detect diseases of the liver, bile ducts, and kidney. It is also used to
differentiate liver or bile duct disorders from bone disease.
GGT participates in the transfer of amino acids across the cell membrane, and in glutathione
(an anti-oxidant) metabolism. High concentrations of GGT are found in the liver, bile ducts,
and the kidney.
GGT is measured in combination with other tests. In particular, the enzyme ALP is increased
in liver and bile duct disease as well as in bone disease. GGT is elevated in liver and bile duct
Week9 Page 28
disease, but not in bone disease. So, a patient with an elevated ALP and a normal GGT
probably has bone disease, not liver or bile ducts disease.
Normal Results Return to top
The normal range is 0 to 51 IU/L.
Note: IU/L = international units per liter
What Abnormal Results Mean Return to top
Greater-than-normal levels of GGT may indicate:
• Congestive heart failure
• Cholestasis (congestion of the bile ducts)
• Cirrhosis
• Hepatitis
• Liver ischemia (blood flow deficiency)
• Liver necrosis
• Liver tumor
• Use of hepatotoxic drugs (drugs toxic to liver)
Risks Return to top
• Excessive bleeding
• Fainting or feeling light-headed
• Hematoma (bleeding under the skin)
• Infection (a slight risk any time the skin is broken)
• Multiple punctures to locate veins
Considerations Return to top
Drugs that can increase GGT levels include alcohol, phenytoin, and phenobarbital.
Drugs that can decrease GGT levels include clofibrate and oral contraceptives (birth control
pills).
Veins and arteries vary in size from one patient to another and from one side of the body to
the other. Obtaining a blood sample from some people may be more difficult than from others.
Update Date: 1/22/2007
Pasted from <http://www.nlm.nih.gov/medlineplus/ency/article/003458.htm >
Week9 Page 29
Bilirubin
1:41 PM
Bilirubin
Contents of this page:
• Illustrations • Why the Test is Performed
• Alternative Names • Normal Results
• Definition • What Abnormal Results Mean
• How the Test is Performed • Considerations
• How to Prepare for the Test
Illustrations
Blood test
Alternative Names Return to top
Total bilirubin; Unconjugated bilirubin; Indirect bilirubin; Conjugated bilirubin; Direct bilirubin
Definition Return to top
Bilirubin is a product that results from the breakdown of hemoglobin. Total and direct bilirubin are usually
measured to screen for or to monitor liver or gallbladder problems.
How the Test is Performed Return to top
Blood is drawn from a vein (venipuncture) or capillary. The laboratory technician spins the blood in a
centrifuge to separate the serum (liquid part) from the cells. The bilirubin test is done on the serum.
How to Prepare for the Test Return to top
Fast for at least 4 hours before the test. Your health care provider may instruct you to stop taking drugs that
affect the test.
Drugs that can increase bilirubin measurements include allopurinol, anabolic steroids, some antibiotics,
antimalaria medications, azathioprine, chlorpropamide, cholinergics, codeine, diuretics, epinephrine,
meperidine, methotrexate, methyldopa, MAO inhibitors, morphine, nicotinic acid, oral contraceptives,
phenothiazines, quinidine, rifampin, salicylates, steroids, sulfonamides, and theophylline.
Drugs that can decrease bilirubin measurements include barbiturates, caffeine, penicillin, and high-dose
salicylates.
Why the Test is Performed Return to top
This test is useful in determining if a patient has liver disease or a blocked bile duct.
Bilirubin metabolism begins with the breakdown of red blood cells. Red blood cells contain hemoglobin, which
is broken down to heme and globin. Heme is converted to bilirubin, which is then carried by albumin in the
blood to the liver.
In the liver, most of the bilirubin is chemically attached to another molecule before it is released in the bile.
This "conjugated" (attached) bilirubin is called direct bilirubin; unconjugated bilirubin is called indirect bilirubin.
Total serum bilirubin equals direct bilirubin plus indirect bilirubin.
Conjugated bilirubin is released into the bile by the liver and stored in the gallbladder, or transferred directly to
the small intestines. Bilirubin is further broken down by bacteria in the intestines, and those breakdown
products contribute to the color of the feces. A small percentage of these breakdown compounds are taken in
again by the body, and eventually appear in the urine.
Normal Results Return to top
• Direct bilirubin: 0 to 0.3 mg/dL
• Total bilirubin: 0.3 to 1.9 mg/dL
Note: mg/dL = milligrams per deciliter
Normal values may vary slightly from laboratory to laboratory.
What Abnormal Results Mean Return to top
Jaundice is the discoloration of skin and the sclera of the eye, which occurs when bilirubin accumulates in the
blood at a level greater than approximately 2.5 mg/dL. Jaundice occurs because red blood cells are being
broken down too fast for the liver to process. This might happen due to liver disease or bile duct blockage.
If the bile ducts are blocked, direct bilirubin will build up, escape from the liver, and end up in the blood. If the
levels are high enough, some of it will appear in the urine. Only direct bilirubin appears in the urine. Increased
direct bilirubin usually means that the biliary (liver secretion) ducts are obstructed.
Increased indirect or total bilirubin may indicate:
• Crigler-Najjar syndrome
•
Week9 Page 30
• Erythroblastosis fetalis
• Gilbert's disease
• Healing of a large hematoma (bleeding under the skin)
• Hemolytic anemia
• Hemolytic disease of the newborn
• Physiological jaundice (normal in newborns)
• Sickle cell anemia
• Transfusion reaction
• Pernicious anemia
Increased direct bilirubin may indicate:
• Bile duct obstruction
• Cirrhosis
• Dubin-Johnson syndrome (very rare)
• Hepatitis
• Intrahepatic cholestasis (buildup of bile in the liver) of many causes
Additional conditions under which the test may be performed:
• Biliary stricture
• Cholangiocarcinoma
• Cholangitis
• Choledocholithiasis
• Hemolytic anemia due to G6PD deficiency
• Hepatic Encephalopathy
• Idiopathic aplastic anemia
• Idiopathic autoimmune hemolytic anemia
• Immune hemolytic anemia (including drug-induced immune hemolytic anemia)
• Secondary aplastic anemia
• Thrombotic thrombocytopenic purpura
• Wilson's disease
Considerations Return to top
Factors that interfere with bilirubin testing are:
• Hemolysis (breakdown) of blood will falsely increase bilirubin levels
• Lipids in the blood will falsely decrease bilirubin levels
• Bilirubin is light-sensitive; it breaks down in light
Pasted from <http://www.nlm.nih.gov/medlineplus/ency/article/003479.htm >
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Alpha2 macroglobulin
1:35 PM
Alpha 2-macroglobulin
Alpha-2 macroglobulin (abbreviated α2M or A2M) is a large plasma protein found in the blood. It is produced by
the liver, and is a major component of the alpha-2 band in protein electrophoresis.
Contents
[hide]
• 1 Structure
• 2 Function
• 3 Disease
• 4 References
Pasted from <http://en.wikipedia.org/wiki/Image:Fibrinolysis.png>
[edit] Structure
Alpha-2 macroglobulin is compose of four identical subunits bound together by -S-S- bonds.
[edit] Function
Alpha-2 macroglobulin is able to inactivate an enormous variety of proteinases (including serine-, cysteine-,
aspartic- and metalloproteinases).
Alpha-2 macroglobulin has in its structure a 35 aminoacid "bait" region. Proteinases binding and cleaving the bait
region become bound to α2M. The proteinase-α2M complex is recognised by macrophage receptors and cleared
from the system.
It functions as an inhibitor of coagulation by inhibiting thrombin.[1]
It functions as an inhibitor of fibrinolysis by inhibiting plasmin:
Pasted from <http://en.wikipedia.org/wiki/Alpha_2-macroglobulin>
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Apolipoprotein A1
1:41 PM
Apolipoprotein A1
Apolipoprotein A-I (ApoA-I) is an apolipoprotein. It is the major protein component of high density lipoprotein (HDL)
in plasma. The protein promotes cholesterol efflux from tissues to the liver for excretion. It is a cofactor for lecithin
cholesterolacyltransferase (LCAT) which is responsible for the formation of most plasma cholesteryl esters. ApoA-I
was also isolated as a prostacyclin(PGI2) stabilizing factor, and thus may have an anticlotting effect. [1] Defects in the
gene encoding it are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic
amyloidosis.
Contents
[hide]
• 1 Activity associated with high HDL-C and protection from heart disease
• 2 Role in other diseases
• 3 Factors affecting ApoA-I activity
• 4 References
[edit] Activity associated with high HDL-C and protection from heart
disease
As a major component of the high density lipoprotein complex ("good cholesterol"), ApoA-I helps to clear cholesterol
from arteries. Five of nine men found to carry a mutation (E164X) who were at least 35 years of age had developed
premature coronary artery disease.[2] One of four mutants of ApoA-I is present in roughly 0.3% of the Japanese
population, but is found 6% of those with low HDL cholesterol levels.
ApoA-I Milano is a naturally occurring mutant of ApoA-I, found in a family descended from a single couple of the 18th
century. Described in 1980, it was the first known molecular abnormality of apolipoproteins.[3] Paradoxically, carriers
of this mutation have very low HDL cholesterol levels, but no increase in the risk of heart disease. Biochemically,
ApoA-I contains an extra cysteine bridge, causing it to exist as a homodimer or as a heterodimer with ApoA-II.
However, the enhanced cardioprotective activity of this mutant (which likely depends on cholesterol efflux) cannot
easily be replicated by other cysteine mutants. [4]
Recombinant Apo-I Milano dimers formulated into liposomes can reduce atheromas in animal models by up to 30%.[5]
ApoA-I Milano has also been shown in small clinical trials to have a statistically significant [6] effect in reducing
(reversing) plaque build-up on arterial walls. In human trials the reversal of plaque build-up was measured over the
course of five weeks.[6][7]
APP018 (formerly D-4F), an 18-amino acid peptide (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH2[8][9], using D-amino
acids) that can be taken orally, was developed by Bruin Pharmaceuticals (a little-known company founded by Dr. Alan
Fogelman, named after the UCLA Bruins [10][11]) and sold to Novartis for $200 million USD. The peptide and close
variations thereof such as D-5F have been shown to elevate HDL-C and reduce atherosclerotic build-up in early animal
data. The peptide has been tested with a variety of modifications, formulated with an excipient such as poly(lactide-
co-glycolide) (PLG), and formed into ProLease[12] drug-polymer microspheres. If all continues to go well it is expected
to reach the pharmacy shelf around 2013. [13]
• Apolipoprotein AI-CIII-AIV gene cluster
Lately, two novel susceptibility haplotypes i.e. P2-S2-X1 and P1-S2-X1 have been discovered in ApoAI-CIII-AIV gene
cluster on chromosme 11q23, who confer approximately threefold higher risk of coronary heart disease in normal [4]
as well as non-insulin diabetes mellitus[5].
[edit] Role in other diseases
A G/A polymorphism in the promoter of the ApoA-I gene has been associated with the age at which patients
presented with Alzheimer disease.[14] Protection from Alzheimer disease by ApoA1 may rely on a synergistic
interaction with alpha-tocopherol[15].
Amyloid deposited in the knee following surgery consists largely of ApoA-I secreted from chondrocytes (cartilage
cells).[16] A wide variety of amyloidosis symptoms are associated with rare ApoA-I mutants.
ApoA-I binds to lipopolysaccharide or endotoxin, and has a major role in the anti-endotoxin function of HDL.[17]
• Apolipoprotein AI-CIII-AIV gene cluster
Lately, two novel susceptibility haplotypes i.e. P2-S2-X1 and P1-S2-X1 have been discovered in ApoAI-CIII-AIV gene
cluster on chromosme 11q23, who confer approximately threefold higher risk of coronary heart disease in normal [6]
Week9 Page 33
In one study, a decrease in ApoA1 levels was detected in schizophrenia patients' CSF, brain and peripheral tissues.[18]
[edit] Factors affecting ApoA-I activity
ApoA-I production is decreased by Vitamin D, and increased by a drug that antagonizes it. [19]
Exercise or statin treatment may cause an increase in HDL-C levels by inducing ApoA-I production, but this depends on
the G/A promoter polymorphism.[20]
[edit] References
1. ^ Yui Y, Aoyama T, Morishita H, Takahashi M, Takatsu Y, Kawai C (1988). "Serum prostacyclin stabilizing factor is
identical to apolipoprotein A-I (Apo A-I). A novel function of Apo A-I". J. Clin. Invest. 82 (3): 803-7. PMID
3047170.
2. ^ Dastani Z, Dangoisse C, Boucher B, Desbiens K, Krimbou L, Dufour R, Hegele RA, Pajukanta P, Engert JC, Genest
J, Marcil M (2006). "A novel nonsense apolipoprotein A-I mutation (apoA-I(E136X)) causes low HDL cholesterol in
French Canadians". Atherosclerosis 185 (1): 127-36. PMID 16023124.
3. ^ Franceschini G, Sirtori M, Gianfranceschi G, Sirtori CR (1981). "Relation between the HDL apoproteins and AI
isoproteins in subjects with the AIMilano abnormality". Metab. Clin. Exp. 30 (5): 502-9. PMID 6785551.
4. ^ Zhu X, Wu G, Zeng W, Xue H, Chen B (2005). "Cysteine mutants of human apolipoprotein A -I: a study of
secondary structural and functional properties". J. Lipid Res. 46 (6): 1303-11. PMID 15805548.
5. ^ Chiesa G, Sirtori CR (2003). "Apolipoprotein A-I(Milano): current perspectives". Curr. Opin. Lipidol. 14 (2):
159-63. PMID 12642784.
6. ^ a b Apo A1-Milano Trial: Where are we now?. Cleveland Clinic. Retrieved on 2006-11-09.
7. ^ Cedars-Sinai Heart Center - Apo A-1 Milano. Cedars-Sinai Heart Center. Retrieved on 2006-11-09.
8. ^ Patent US 7,144,862 B2
9. ^ Patent WO2006 118805
10. ^ Matthew Herper, Forbes 07.11.05 "Novartis Enters 'Good Cholesterol' Battle."
11. ^ Fierce Biotech. "Bruin Pharmaceuticals."
12. ^ Bartus et al., 1998, Science 281:1161-2 [1]
13. ^ BioMarket Group AB, "Antidyslipidemics: market set for contraction as generics hit hard", October 4, 2006.
14. ^ Vollbach H, Heun R, Morris CM, Edwardson JA, McKeith IG, Jessen F, Schulz A, Maier W, Kölsch H (2005).
"APOA1 polymorphism influences risk for early-onset nonfamiliar AD". Ann. Neurol. 58 (3): 436-41. PMID
16130094.
15. ^ Maezawa I, Jin LW, Woltjer RL, Maeda N, Martin GM, Montine TJ, Montine KS (2004). "Apolipoprotein E
isoforms and apolipoprotein AI protect from amyloid precursor protein carboxy terminal fragment -associated
cytotoxicity". J. Neurochem. 91 (6): 1312-21. PMID 15584908.
16. ^ Solomon A, Murphy CL, Kestler D, Coriu D, Weiss DT, Makovitzky J, Westermark P (2006). "Amyloid contained
in the knee joint meniscus is formed from apolipoprotein A-I". Arthritis Rheum. 54 (11): 3545-50. PMID
17075859.
17. ^ Ma J, Liao XL, Lou B, Wu MP (2004). "Role of apolipoprotein A-I in protecting against endotoxin toxicity". Acta
Biochim. Biophys. Sin. (Shanghai) 36 (6): 419-24. PMID 15188057.
18. ^ Huang JT, Wang L, Prabakaran S, Wengenroth M, Lockstone HE, Koethe D, Gerth CW, Gross S, Schreiber D,
Lilley K, Wayland M, Oxley D, Leweke FM, Bahn S (2007). "Independent protein-profiling studies show a decrease
in apolipoprotein A1 levels in schizophrenia CSF, brain and peripheral tissues". Mol Psychiatry.
doi:10.1038/sj.mp.4002108. PMID 17938634.
19. ^ Wehmeier K, Beers A, Haas MJ, Wong NC, Steinmeyer A, Zugel U, Mooradian AD (2005). "Inhibition of
apolipoprotein AI gene expression by 1, 25-dihydroxyvitamin D3". Biochim. Biophys. Acta 1737 (1): 16-26. PMID
16236546.
20. ^ Lahoz C, Peña R, Mostaza JM, Jiménez J, Subirats E, Pintó X, Taboada M, López-Pastor A (2003). "Apo A-I
promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy".
Atherosclerosis 168 (2): 289-95. PMID 12801612.
Pasted from <http://en.wikipedia.org/wiki/Apolipoprotein_A1>
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Haptoblobulin
1:44 PM
Haptoglobin
Haptoglobin (abbreviated as Hp) is a protein in the blood plasma that binds free hemoglobin released from
erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then
be removed by the reticuloendothelial system (mostly the spleen). In clinical settings, the haptoglobin assay is used to
screen for and monitor hemolytic anemia
Contents
[hide]
• 1 Clinical significance
• 2 Test order protocol
• 3 Results interpretation
• 4 Structure
• 5 Miscellaneous Information
• 6 Further reading
[edit] Clinical significance
Since the reticuloendothelial system will remove the haptoglobin-hemoglobin complex from the body, haptoglobin
levels will be decreased in hemolytic anaemias. In the process of binding hemoglobin, haptoglobin sequesters the iron
within hemoglobin, preventing iron-utilizing bacteria from benefitting from hemolysis. It is theorized that because of
this, haptoglobin has evolved into an acute phase protein.
[edit] Test order protocol
Haptoglobin is ordered whenever a patient exhibits symptoms of anemia, such as pallor, weakness, orthostatic
hypotension (positional changes in blood pressure) or shortness of breath along with physical signs of hemolysis, such
as jaundice or dark-colored urine. The test is also commonly ordered as a hemolytic anemia battery which also includes
a reticulocyte count and a peripheral blood smear. It can also be ordered along with a Direct Antiglobulin Test when a
patient is suspected of having a transfusion reaction. Finally, it may be ordered in conjunction with a bilirubin.
[edit] Results interpretation
A decrease in haptoglobin can support a diagnosis of hemolytic anemia, especially when correlated with a decreased
RBC count, Hemoglobin, and Hematocrit, and also an increased reticulocyte count.
If the reticulocyte count is increased, but the haptoglobin level is normal, this may indicate that cellular destruction is
occurring in the spleen and liver, which may indicate a drug induced hemolysis, or a red cell dysplasia. The spleen and
liver recognize an error in the red cells (either Drug coating the red cell membrane, or a dysfunctional red cell
membrane), and destroy the cell. This type of destruction does not release hemoglobin into the peripheral blood, so the
haptoglobin cannot bind to it. Thus, the haptoglobin will stay normal.
If there are symptoms of anemia but both the reticulocyte count and the haptoglobin level are normal, the anemia is
most likely not due to hemolysis, but instead some other error in cellular production, such as aplastic anemia
Haptoglobin levels which are decreased but do not accompany signs of anemia may indicate liver damage, as the liver is
not producing enough haptoglobin to begin with.
As haptoglobin is indeed an acute phase protein, any inflammatory process (infection, extreme stress, burns, major
crush injury, allergy, etc) may increase the levels of plasma haptoglobin.
[edit] Structure
Haptoglobin is produced mostly by hepatocytes but also by other tissues: e.g. skin, lung, and kidney. Haptoglobin, in its
simplest form, consists of two α- and two β-chains, connected by disulfide bridges. The chains originate from a common
precursor protein which is proteolytically cleaved during protein synthesis.
Hp exists in two allelic forms in the human population, so called Hp1 and Hp2; the latter one having arisen due to the
partial duplication of Hp1 gene. Three phenotypes of Hp, therefore are found in humans: Hp1-1, Hp2-1, and Hp2-2. Hp
of different phenotypes have been shown to bind hemoglobin with different affinities, with Hp2-2 being the weakest
binder.
[edit] Miscellaneous Information
Hp has been found in all mammals studied so far, some birds e.g. cormorant and ostrich but also, in its simpler form, in
bony fish e.g. zebrafish. Interestingly, Hp is absent in at least some amphibians (Xenopus) and neognathous birds
(chicken and goose).
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Pasted from <http://en.wikipedia.org/wiki/Haptoglobin>
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Fibroscan
1:51 PM
1: Am J Gastroenterol. 2007 Nov;102(11):2589-600. Epub 2007 Sep 10.
Links
FibroTest and FibroScan for the prediction of hepatitis C-related

fibrosis: a systematic review of diagnostic test accuracy.
Shaheen AA, Wan AF, Myers RP.
Liver Unit, Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
BACKGROUND: The accurate diagnosis of hepatitis C virus (HCV)-related fibrosis is crucial for prognostication and treatment
decisions. Due to the limitations of biopsy, noninvasive alternatives including FibroTest and FibroScan have been developed.
Our objective was to systematically review studies describing the accuracy of these tests for predicting HCV-related fibrosis.
METHODS: Studies comparing FibroTest or FibroScan versus biopsy in HCV patients were identified via an electronic search.
Random effects meta-analyses and areas under summary receiver operating characteristics curves (AUC) were examined to
characterize test accuracy for significant fibrosis (F2-4) and cirrhosis. Heterogeneity was explored using meta-regression.
RESULTS: Twelve studies were identified, 9 for FibroTest (N = 1,679) and 4 for FibroScan (N = 546). In heterogeneous analyses
for significant fibrosis, the AUCs for FibroTest and FibroScan were 0.81 (95% CI 0.78-84) and 0.83 (0.03-1.00), respectively. At a
threshold of approximately 0.60, the sensitivity and specificity of the FibroTest were 47% (35-59%) and 90% (87-92%). For
FibroScan (threshold approximately 8 kPa), corresponding values were 64% (50-76%) and 87% (80-91%), respectively.
Methodological quality, the length of liver biopsy specimens, and inclusion of special populations did not explain the observed
heterogeneity. However, the diagnostic accuracy of both measures was associated with the prevalence of significant fibrosis
and cirrhosis in the study populations. For cirrhosis, the summary AUCs for FibroTest and FibroScan were 0.90 (95% CI not
calculable) and 0.95 (0.87-0.99), respectively. CONCLUSIONS: FibroTest and FibroScan have excellent utility for the
identification of HCV-related cirrhosis, but lesser accuracy for earlier stages. Refinements are necessary before these tests can
replace liver biopsy.
PMID: 17850410 [PubMed - indexed for MEDLINE]
Pasted from <http://www.ncbi.nlm.nih.gov/pubmed/17850410>
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ALP, AST, ALT, GGT: Liver Function Enzymes
2:14 PM
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Wilson's Disease
2:16 PM
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ERCP and MRCP - When and Why
2:20 PM
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02 WONG 2008 Viral Hepatitis From PBD:
Saturday, February 16, 2008 1- 09 02 Herpesviridae Mazzulli.pdf
5:56 PM 2- 09 02 Herpesviridae Mazzulli.pdf
02 WONG ...
Audio recording started: 9:06 AM Tuesday, February 19, 2008
Hepatitis A
Is Hep A an RNA or
DNA virus?
What' s the
Incubation
period (range
and average) of
Hep A?
In which of the
following age
categories is
jaundice
frequently seen
during a Hep A
infection and in
which is it a more
rare occurrence:
< 6 y.o., 6-14
y.o., > 14 years
old?
Case fatality of Hep
A is highest in
which age group?
Name a
complication of
Hep A infection?
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If you suspect acute
HAV infection, which
antibody titre should
you check and when?
List 3 ways in which

Hep A can be
transmitted?
T/F: Hep A infection

CAN BE transmitted
through blood
exposure (ie. Injection
drug use or
transfusion)?
Recovery from Hep

A infection in the
majority of cases
takes approximately
___ month(s)?
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Out of the following,
which would be the
most contagious (ie.
Contain the most
virions) in a Hepatitis A
infected person: Serum,
Stool/Feces, Saliva,
Urine?
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Hepatitis B
Which groups/
persons are at
increased risk for
infection by Hep A
(name 3)?(5)
What' sthe
Incubation period
(range and
average) of Hep B?
Is jaundice
secondary to Hep B
infection seen more
commonly in
children < 5 y.o
or >5 y.o.?
T/F: If a patient tests

positive for HBsAg,
they have a Hep B
infection?
positive for HBsAg,
they have a Hep B
infection?
positive for HBsAg,
they have a Hep B
infection?
positive for levels of
Less infectious
Total anti-HBc, then
Less infectious infectious
infectious you still CANNOT
distinguish between
whether the person
has an acute or
chronic Hep B
infection?
What is the
difference between
Weeks after exposure the levels of anti-HBs
Weeks after exposure in acute vs. chronic
• NB: Total anti-HBc is ALWAYS high, in both patients with Hep B infection?
acute, spontaneous recovery AND chronic infection What is the
• Also, in both, IgM anti-HBc goes down quickly difference between
• Difference is in HBsAg: stays high in chronic; quickly the temporal profile
decreases in acute of HBsAg levels in
acute vs. chronic Hep
B infection?
Symptoms of Hep B
MARKER USUAL SIGNIFICANCE
infection start
1. HBsAg • Virus is present approximately how
many weeks after
2. Anti-HBs (surface • Virus is usually cleared exposure?
antibody) • Patient immune
3. HBeAg* (except for pre- • Active viral replication
core mutant strains of • Ongoing liver disease
HBV) • Patient infectious
4. Anti-HBe* (except for • Viral replication reduced
pre-core mutant strains • Inactive liver disease (usually)
of HBV) • Less infectious
5. HBcAg • Never detectable in serum
6. Anti-HBc (core • Patient has come into contact with
antibody) hepatitis B and may or may not still
Week9 Page 68
•
antibody) hepatitis B and may or may not still
be infected with the virus
• Does not signify immunity
7. IgM anti-HBc • Signifies recent contact with
(by routine hepatitis B
commercially
available assays)
8. HBV-DNA • Active viral replication
(by routine commercially • Ongoing liver disease
available assays) • Patient infectious
Pasted from <http://www.comeunity.com/adoption/health/hepatitis/smith.html>
Glossary
Hepatitis B: Liver disease caused by the hepatitis B virus (HBV). HBV is found in the blood of infected persons
and is commonly transmitted through unprotected sex.
Hepatitis B Immune Globulin (HBIG): A product available for prophylaxis against hepatitis B virus infection.
HBIG is prepared from plasma containing high titers of anti -HBs and provides short-term protection (three to
six months).
a. Hepatitis B Core Ag (HBcAg): A core protein antigen of the hepatitis B virus not readily detectable in
serum. It is an indicator of replicating hepatitis B virus.
b. Hepatitis B Core Antibody (anti-HBc): Antibody to the hepatitis core antigen. Appears at the onset of
symptoms in acute hepatitis B and persists for life. The presence of anti-HBc indicates previous or
ongoing infection with HBV.
c. Hepatitis B e Ab (anti-HBe): Antibody to HBeAg that indicates good probability of long lasting viral
clearance.
d. Hepatitis B e Antigen (HBeAg): Secreted product of the nucleocapsid gene of HBV found in serum
during acute and chronic hepatitis B. Its presence indicates the virus is replicating and the infected
individual is potentially infectious.
e. Hepatitis B Surface Antibody (anti-HBs): The presence of anti-HBs is generally interpreted as
indicating recovery and immunity from HBV infection.
f. Hepatitis B Surface Antigen (HBsAg): A serologic marker on the surface of HBV. It can be detected in
high levels in serum during acute or chronic hepatitis.
Pasted from <http://www.hepatitisbhelp.com/hepatitis_b_glossary.html>
Week9 Page 69
• In the immune
tolerant state Th2
is most active; Th1
and CD8 are
minimal
• In the immune
clearance state, all
Th2, Th1, and CD8
are active
• In the inactive,
carrier state, Th2
response is
stronger
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List the 2 main
populations in
canada who are at
risk for Hep B
Almost 1/5th of
infection?
immigrants have Hep B!
T/F: Immigrants are

screened for HIV,
syphillis, and HBV BUT
NOT TB?
In which of the following
body fluids are Hep B
levels the highest (may be
more than one): Urine,
Vaginal Fluid, Serum,
Saliva, Wound exudate,
Saliva, Semen, Breast
milk, Tears, Blood, Sweat,
Feces?
Untreated, chronic
infection with HBV
typically leads to ___ OR
___?
Is there a higher level

of HBV via
percutaneous and
perinatal
transmission or
sexual transmission?
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List 4 drug classes
that are available
for the treamtent
of HBV?
How long should

interferon treatment
for Hep B be given?
List 4 group sof drugs
that may be used to
treat Hep B?
T/F: There is NO
CURE for Hep B
infection?
What is the primary
immune modulatory
treatment for Hep B
infection?
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Hepatitis C
Is it safe to
BREASTFEED if a
mother has an HCV
infection?
T/F: Perinatal
transmission of HCV
occurs less frequently
in infants delivered
vaginally (ie. NOT via
C-section)?
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Hepatitis D
What is the
treatment for
Hep C?
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Hepatitis D
What is the
treatment for
Hep C?
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List the two steps in
evaluating for HCV
infection?
In evaluating for
HCV infection, if the
patient has ALT and
AST levels > 30,
then …?
In evaluating for
HCV infection, if the
patient has ALT and
AST levels < 30,
then …?
IF ALT and AST are
both < 30 and HCV
PCR is negative,
then what should
be done in follow
up to confirm no
Classification HCV infection?

What 5 tests can
HDV is the only virus in the genus, Deltaviridae. HDV is not classified into a viral family because it is a unique virus depe ndent on
you do to assess the
HBV. HDV is a co-infection of HBV. The envelope of HDV particles contains the Hepatitis B surface antigen (HBsAg). The production
and transmission of HDV is entirely dependent on HBV to provide HBsAg. Thus, HDV is considered a satellite virus of HBV. Unlike a
severity of HCV
classical satellite virus, however, HDV does not share sequence similarity with HBV, and it can replicate independently of HB V. infection?
Clinical Features
Symptoms and Incubation
Although variable, the clinical course of HDV is typically more severe than that of the other hepatitis viruses . After an
incubation period of 3-7 weeks, nonspecific clinical symptoms, including fatigue, lethargy, nausea, and anorexia, begin and last
for about 3-7 days. Viral replication is usually diminished during this phase. Jaundice occurs in the next phase of symptoms.
Fatigue and nausea usually continue, and the serum bilirubin level becomes abnormal. At the same time, the infected person
may have clay-colored stool and dark urine. This is evidence of the liver’s diminished ability to excrete bilirubin .
Diagnosis
Type D hepatitis should be considered in individuals who are HBsAg positive or who have evidence of recent HBV
infection. The diagnosis for Hepatitis D infection is made following serologic tests for the virus. Total anti -HDV antibodies are
detected by radioimmunoassay (RIA) or enzyme immunoassay (EIA) kits. To monitor ongoing HDV infection, reverse transcriptase -
polymerase chain reaction (RT-PCR) should be used. RT-PCR can detect 10 to 100 copies of the HDV genome in infected blood serum.
Each of the markers of HDV infection, including IgM and IgG antibodies, disappears within months after recovery. In chronic H epatitis
D infection, on the other hand, HDV RNA, HDAg, IgM anti-HD antibodies, and IgG anti-HD antibodies persist.
Outcomes
The outcome of disease depends on whether HDV is contracted as a co -infection or a superinfection.
Co-infection: Co-infection occurs when both HDV and HBV are contracted simultaneously. This results in acute HDV and
HBV infection. Depending on the relative amounts of HBV and HDV, one or two episodes of hepatitis occurs. Co -infections of HDV and
HBV are usually acute and self-limiting infections. HBV/HDV co -infections cause chronic HDV infections in less than 5% of co -infected
patients. Although clinical symptoms disappear, fatigue and lethargy may persist for weeks or months.
Picture from CDC Website
Superinfection: Superinfection occurs when chronic HBV carriers are infected with HDV . This leads to severe acute hepatitis
and chronic Hepatitis D infection in 80% of the cases. Superinfection is associated with the fulminant form of viral hepatitis.
Fulminant viral hepatitis, the most severe form of acute disease, is about ten times more common in HDV infections than in th e other
types. It is characterized by hepatic encephalopathy that is manifested by changes in personality, disturbances in sleep, confusion,
difficulty concentrating, and sometimes abnormal behavior and coma. The mortality rate of fulminant hepatitis is about 80%. C hronic
hepatitis D infection progresses to liver cirrhosis in about 60 -70% of patients. Cirrhosis takes about 5-10 years to develop, but can
appear two years after the onset of infection. Hepatocellular carcinoma occurs in chronically infected HDV patients with the same
Week9 Page 79
frequency as in patients with ordinary HBV. Overall, the mortality rate for HDV infections lies between 2% and 20%, values
ten times greater than the mortality rates for HBV.
Fulminant viral hepatitis,

the most severe form of
acute disease, is about
ten times more common
in HDV infections
than in the other types.
Picture from CDC Website
Prevention and Treatment

Prevention of Hepatitis Delta Virus infection is based on prevention of HBV, as HDV requires the surface antigen of HBV to cause
infection. There is no vaccine for HDV, but there is an effective vaccine for HBV. In order to prevent HDV -HBV co-infection, the HBV
vaccine or post exposure prophylaxis (Hepatitis B Immune Globulin) can be used to prevent infection. The only way to prevent HBV -
HDV superinfection is to educate chronic HBV carriers about transmission and risky behaviors. HDV can be transmitted via bloo d
exchange, sexual contact, sharing needles, and from mother -to-child.
There is no specific treatment for HDV infections. Im m unosuppressiv e therapy has no positiv e clinical effect. Antiviral drugs,
including Acyclovir, Ribavirin, Lamivudine, and synthetic analogs of thymosin have all proved ineffective. For infected patients,
massive doses of a-interferon have caused disease remission, but most patients remained positive for HDV RNA whether or not there
was improvement in disease conditions. The effect of interferon therapy seems to be indirect, perhaps via an effect on HBV or the
immune response to the infection. Orthotopic liver transplantation has proven useful for treating fulminant acute and advanced
chronic hepatitis D infections.
Pasted from <http://www.stanford.edu/group/virus/delta/2005/>
• Orthotopic liver transplantation refers to a procedure in which a failed liver is removed from the patient's body and a healthy donor liver is transplanted
into the same location. In this case, the liver donor is someone who has recently died. The procedure is the most common meth od used to transplant
livers.
Pasted from <http://www.emedicinehealth.com/liver_transplant/article_em.htm>
Week9 Page 80
How can Hep D
jaundice infection be
prevented?
for Hep D infection?
• Note how the titres of HDV RNA and HBsAg stay high,
and also that ALT levels never go back down but oscillate
at a higher level, indicative of liver compromise
Hepatitis E Is Hep E an RNA or

DNA virus?
Week9 Page 81
In Hep E infection, ALT
reaches its peak
approximately how
many weks after
exposure?
Approximately how
many week after Hep
E exposure does the
virus show up in
stool?
In Hep E infection,
levels of (ALT or AST
or ALP) reach their
peak at approximately
the same time as
levels of (IgM anti -HEV
or IgG anti-HEV) reach
their peak?
Hepatitis G T/F: Hepatitis G

infection is actually
NOT associated with
liver infection?
Hepatitis ___ and ___
are the major causes
of end-stage liver
disease and liver
cancer?
T/F: Hep G infection is
associated with
downregulation of
which chemokine
Parenteral: [para- + enteral] not through the alimentary receptor that plays an
canal but rather by injection through some other route, important role in
such as subcutaneous, intramuscular, intraorbital, determining the
intracapsular, intraspinal, intrasternal, or intravenous. progression of HIV
infection?
Effect of Hepatitis G Virus Infection on Progression of HIV Infection in Patients with Hemophilia In HBV-HBD
Anthony E.T. Yeo, MD, MPH, PhD; Akihiro Matsumoto, MD, PhD; Michie Hisada, MD, ScD; James W. Shih, PhD; Harvey J. Superinfection, there
Alter, MD; James J. Goedert, MD, for the Multicenter Hemophilia Cohort Study* is a high risk of ___?
20 June 2000 | Volume 132 Issue 12 | Pages 959-963 Which of the hepatitis
Background: Infection with hepatitis G virus (HGV), also known as GB virus C, is prevalent but is not known to be viruses IS NOT
associated with any chronic disease. Infection with HGV may affect the risk for AIDS in HIV-infected persons. associated with liver
Objective: To compare AIDS-free survival in patients with and those without HGV infection during 16 years of follow - disease?
up after HIV seroconversion. How is Hepatitis G
Design: Subanalysis of a prospective cohort study. acquired?
Setting: Comprehensive hemophilia treatment centers in the United States and Europe.
Patients: 131 patients with hemophilia who became HIV-positive between 1978 and 1985.
Measurements: Age, CCR5 genotype, HIV and HCV viral loads, CD4+ and CD8+ lymphocyte counts, and 12-year AIDS-free
survival by HGV positivity (viremia [RNA] or anti-E2 antibodies).
Results: Compared with HGV-negative patients, the 60 HGV-positive patients (46%), including 22 who were positive for HGV
RNA, had higher CD4+ lymphocyte counts (difference, 211 cells/mm 3 [95% CI, 88 to 333 cells/mm 3]) and 12-year AIDS-free
survival rates (68% compared with 40%; rate difference, 1.9 per 100 person-years [CI, –0.3 to 4.2 per 100 person-years]),
despite similar ages and HIV viral loads. In multivariate proportional hazards models, risk for AIDS was 40% lower for HGV-
positive patients independent of age, HIV and HCV viral loads, CD4 + and CD8+ lymphocyte counts, and CCR5 genotype.
Conclusions: Patients with past or current HGV infection have higher CD4+
lymphocyte counts and better AIDS-free survival rates. The mechanism of this
association is unknown.
Pasted from <http://www.annals.org/cgi/content/full/132/12/959>
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12:45 AM
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Testing review of lecture
9:41 PM
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Past Hepatitis Lectures/Mentions
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03 LILLY 2008 Liver Failure
Which is more
common: cirrhosis
or fulminant liver
failure?
End Stage Liver Disease is

marked by ___ and ___?
T/F: The lower

the Child-Pugh
Score, the
better?
Week9 Page 97
• Budd-Chiari syndrome is the clinical
picture caused by occlusion of the
hepatic vein or inferior vena cava . It
presents with the classical triad
of
- abdominal pain
- ascites
- hepatomegaly
• Examples of occlusion include
thrombosis of hepatic veins and
membranous webs in the inferior
vena cava. The syndrome can be
fulminant, acute, chronic, or
asymptomatic. It occurs in 1 out of
100,000 individuals and is more
common in females.
Pasted from
<http://en.wikipedia.org/wiki/Budd-
Chiari_syndrome>
Cirrhosis
Compensation implies cirrhosis without complications. The

Cirrhosis of the liver can be 'compensated' or 'decompensated'.
complications that may develop include bleeding from varices (abnormal veins that form in the gullet), ascites,
jaundice and encephalopathy (confusion, reduction in conscious level and coma).
Compensated cirrhosis may be managed with abstinence from alcohol and nutritional support as above.
Treatment of decompensated cirrhosis

In patients with decompensated cirrhosis, specific treatments may be required to deal with the complications of the disease:
Bleeding varices
Bleeding varices may need treatment by endoscope (a flexible camera which can be passed into the stomach) to destroy the abnormal veins in the
wall of the gullet. Long-term treatment with tablets such as beta-blockers (eg propranolol) may reduce the risks of further bleeding. Patients with
alcoholic cirrhosis often have a 'screening' endoscopy test to identify any varices before a bleed occurs. Where varices are found, treatment with
beta-blockers has been shown to reduce the risk of a first bleed.
Ascites
Ascites require a low salt diet, and reduction of fluid intake is often advised. Patients will usually be treated with diuretics (water tablets) and may
require intermittent drainage of the fluid with a catheter or plastic drainage tube being inserted into the abdomen (paracent esis). In some cases
these measures will be unsuccessful, and further interventions such as a liver transplant may be needed.
Encephalopathy
Usually linked to additional stress on the body. This may include the use of inappropriate sedating or painkilling medicines, bleeding from the gullet
or stomach, constipation, infections or abnormalities in the salts (electrolytes) in the blood. The main factor involved in c ausing the encephalopathy
is an increase in ammonia levels in the brain. The treatment involves correcting the underlying problem, and treatment with lactulose (a liquid
laxative). Lactulose decreases the production of ammonia in the gut and its absorption into the body. It lowers ammonia level s in the blood and
may need to be taken long term to prevent recurrence of the encephalopathy.
Liver transplantation
In some patients with cirrhosis, liver function continues to deteriorate despite abstinence from alcohol and they may be severely affected by
complications. These individuals may need a liver transplant. But for patients to be considered for transplantation, they mus t:
○ have been abstinent from alcohol for six months.
○ have advanced liver disease with complications.
○ have no other organ damage.
○ have good social or family support.
Approximately 85 per cent of appropriate patients reach the five-year survival rates following a transplant.
References
Living in Britain - the 2001 general Household Survey. Department of Health. http://www.doh.gov.uk/public/livinginbritainsurvey.htm
Last updated 14.04.2004
Week9 Page 98
Pasted from <http://www2.netdoctor.co.uk/diseases/facts/alcliver.htm>
List 4 prognostic
factors in cirrhosis?
What is the
difference between
compensated and
decompensated
(5) cirrhosis?
How is
1 decompensated
cirrhosis managed?
Do patients with a Child-

Pugh Score of A or C have
5 higher 1-year and 5-year
survivals?
List 3 signs of
decompensated
cirrhosis?(4)
A synonym for
decompensation, in
the context of liver
failure, is …?
HRS = Hepato-Renal Syndrome
Week9 Page 99
(5)
TIPS = Transjugular Intrahepatic Portosystemic Shunt.
List the 5 steps in

the stepwise
approach to the
management of
ascites?
The average western

diet has approximately
___ - ___ meq of Na
whereas a low salt diet
has about ___ meq of
Na?
fig 1: Portal hypertension before the TIPS

procedure is performed.
Portal hypertension causes blood flow to be forced
backward, causing veins to enlarge and varices to
develop across the esophagus and stomach from the
pressure in the portal vein. The backup of pressure also
causes the spleen to become enlarged.
Week9 Page 100

fig 2: After the TIPS procedure is performed.
A radiologist makes a tunnel through the liver with a
needle, connecting the portal vein (the vein that
carries blood from the digestive organs to the liver) to
one of the hepatic veins (the three veins that carry
blood from the liver). A metal stent is placed in this
tunnel to keep the track open.
The shunt allows the blood to flow normally through
the liver to the hepatic vein. This reduces portal
hypertension, and allows the veins to shrink to normal
size, helping to stop variceal bleeding.
Pasted from <http://www.clevelandclinic.org/health/health-info/docs/0200/0237.asp?index=4956&src=newsp>
Depicted is the procedure for performing TIPS. (a) A needle is passed under radiologic
guidance from a hepatic vein into a major portal venous branch, and a guide wire is
advanced through this needle. (b) A balloon is passed over the guide wire, creating a tract
in the hepatic parenchyma. (c) An expandable stent is placed though this tract. (d) The
effective result is a nonselective portosystemic shunt.
Pasted from <http://www.heart-intl.net/HEART/011507/PortalHypertension.htm>
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Do recurrent bleeds
occur in the majority
of patients who have
had at least one
index variceal bleed
secondary to
cirrhosis?
What is the
prevalence of
cirrhosis in Hep C
infection?
The typical
incubation
period for Hep C
is ___ to ___
weeks?
Is cirrhosis or
chronic infection
more common as
a clinical feature
in Hep C
infection?
Week9 Page 103

Week9 Page 104
T/F: THE
MAJORITY of
deaths in HCV
infection are
liver-related?
Week9 Page 105

The most
common adult
indication for
liver transplant is
___?
The top two
adult indications
for liver
transplantation
are ___, ___ and
___?
Week9 Page 106

What is the definition
of fulminant hepatic
failure (include
whether or not it's
reversible and when
the onset of
encephalopathy
should occur after
appearance of first
symptoms)?
T/F: In fulminant
hepatic failure,
encephalopathy
occurs 2 weeks after
the onset of
symptoms?
Week9 Page 107

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05 KANDEL 2008 Dyspepsia and Peptic Ulcer Disease
What is dyspepsia?
List 3 common
causes of dyspepsia?
List 3 uncommon
causes of dyspepsia?
List 3 rare causes of
dyspepsia?
Which 3 cancers are
most commonly
related to complaints
of dyspepsia?
Is cancer a common,
uncommon, or rare
cause of dyspepsia?
• See Giardia lamblia page, FMP Week 9, for an overview of

Giardia lamblia
Week9 Page 112

What is giardia?
What is a helpful
menomic in
eliciting a history
of pain?
Questions to ask: 3A + D
○ Acid regurg?
○ Age?
○ Associated Sympx?
○ Drugs (esp. NSAIDs)?
What are the 4 key

questions to ask
someone presenting with
dyspepsia?
Week9 Page 113

Questions to ask: 3A + D
○ Acid regurg?
○ Age?
○ Associated Sympx?
○ Drugs (esp. NSAIDs)?
What are the 4 key

questions to ask
someone presenting with
dyspepsia?
Out of the 4 questions
that one should ask a
patient with dyspepsia,
which one is the only one
which is correlated with
a diagnosis?
Most patients who have

dyspepsia should be
investigated via (general
tests/investigations) ___, ___,
and ____?
T/F: In trying to minimize the
wastage of resources, only
ONE blood test should be done
for dyspepsia and that is
Helicobacter serology?
Week9 Page 114

In ordering an ordinary
workup for dyspepsia, which 4
lab investigations would you
order?
In ordering a STELLAR
workup for dyspepsia,
which 5 lab
investigations would
you order in addition
to: liver enzymes, CBC,
creatinine, and
glucose?
List 2 complications
of peptic ulcer
disease?(3)
Patients with peptic

ulcer disease
commonly present
with ___ and ___?
Diagnosis of a peptic
ulcer is made by
___?
Week9 Page 115

What should you do when
presented with any gastric
ulcer in order to rule out
cancer?
List 2 common causes of

peptic ulcer?
List 3 RARE causes of peptic
ulcer?
Week9 Page 116

The ONLY place where H.
Pylori is found is in the ___
mucosa?
T/F: ALL persons with H.
pylori infection have
gastritis, but only a minority
will go on to develop a
peptic ulcer and even fewer
gastric cancer?
The three drug regimen for
the treatment of H. pylori
infections usually includes a
proton pump inhibitor plus
the following two
antibiotics: ___ AND (___ OR
___)?
Classes of Drugs used to Treat H. pylori

Drug Class Drugs in the Class
Antibiotics (+2) (usually amox. + clarith/metro) • Amoxicillin,
• Clarithromycin,
• Metronidazole,
• Tetracycline
H2-Blockers • Cimetidine (Tagamet),

• Famotidine (Pepcid),
• Nizatidine (Axid),
• Ranitidine (Zantac)
Proton Pump Inhibitors (PPIs) (-prazole's) • Esomeprazole (Nexium),

• Lansoprazole (Prevacid),
• Omeprazole (Prilosec),
• Pantoprazole (Protonix),
• Rabeprazole (Aciphex)
Cytoprotective Agents • Bismuth subsalicylate,

• Bismuth subcitrate potassium,
• Sucralfate
Combination Products • Helidac,

• Prevpac,
• Pylera
Week9 Page 117

• The primary goal of therapy for ulcers caused by H. pylori is to eradicate or destroy the bacteria.
• To date, the most effective therapy for H. pylori are the three-drug regimens and four-drug regimens--specifically those regimens
that contain a proton pump inhibitor (PPI) plus two antibiotics--since cure rates are typically higher with these therapies. Two -drug
regimens tend to have a lower cure rate and should not be used, and four -drug regimens, while very effective,can be more
complicated to take. Therefore, a three-drug regimen or possibly a pre-packaged, combination product is recommended as the most
effective means of treating ulcers caused by H. pylori.
• Combination products such as Helidac, Prevpac, and Pylera are effective in treating H. pylori-induced ulcers. Use of these products
may help improve compliance with the treatment regimens but they are also more expensive treatment options. Additionally, no
head-to-head trials have been performed between these comparative products to determine if one is superior to the other in terms
of improving compliance or in curing the H. pylori infection.
• Generally, you want to take a treatment regimen that provides at least an 80% cure rate (or eradication rate). The most effective
treatment regimen contains a proton pump inhibitor (PPI), plus clarithromycin and either amoxicillin or metronidazole.
• The duration of therapy needed is still controversial. Some doctors favor a 7 -day treatment regimen while others favor a 10 - to 14-
day treatment regimen. The shorter treatment duration may enhance compliance (which is important when treating a bacterial
infection), but the longer treatment duration may have greater success in curing the infection (especially in persons who are
compliant with taking their medications). If the first treatment attempt was not successful, a 14 -day treatment duration is needed.
The American College of Gastroenterology recommends a 14 -day treatment duration.
• The four-drug regimen consisting of a PPI, bismuth, metronidazole, and tetracycline (all taken for 2 weeks) is also highly effective .
Pasted from <http://www.drugdigest.org/DD/Comparison/NewComparison/0,10621,550540 -21,00.html>
Most useful diagnostics for

H. pylori infection are ___
and ___, though the most
accurate is ___?
T/F: Disease secondary to H.

pylori infection occurs years
after the initial exposure and
infection?
T/F: H. pylori infection can now

be effectively eliminated with
a single drug?
T/F: Pathogen isolation NOT
NECESSARY to diagnose
someone with an H. pylori
infection?
Is there a higher rate of

dyspepsia or ulcer
complications in patients
who have adverse reactions
to NSAIDs?
Week9 Page 118

Is there a higher rate of
dyspepsia as a complication of
NSAID use or ulcer formation?
Is dyspepsia a
reliable indicator
of an ulcer?
What is the effect of

inhibition of cyclo-
oxygenase by NSAIDS on
prostaglandins levels?
Do decreasing
prostaglandin levels lead
to increased or decreased
levels of joint
inflammatino and gastric
cytoprotection?
T/F: Regarding complications

of NSAID use, there is a 10x
higher likelihood of dyspepsia
complications compared to
ulcer complications?
How are arthritis and gastric
mucosal stability related?
Week9 Page 119

Suppressing gastric acid
prevents and heals peptic
ulcers BUT ONLY WHILE …?
Oxyntic glands in the body

and fundus of the stomach
contain which 3 types of cells?
List the 3 regions of the
stomach?
Pyloric glands in the antrum
contain which 2 types of cells?
Chief cells produce ___?
Chief cells are located in the
___?
Parietal cells produce ___ and
___?
Parietal cells are located in
the ___?
G cells produce ___?
G cells are located in the ___?
Pepsinogen is secreted by ___
cells whereas gastrin is
secreted by ___ cells?
The cells which secrete pepsin
are located in which region of
the stomach?
The cells which secrete gastrin
the stomach?
The cells which secrete HCL
the stomach?
Intrinsic factor is produced by
___ cells located in the ___
region of the somtach?
Name a proton pump
inhibitor?
Week9 Page 120

Intrinsic factor - lack of
Intrinsic factor is a natural substance normally present in the stomach. It is essential to the digestion of vitamin
B-12.
○ Lack of intrinsic factor leads to pernicious anemia and vitamin B-12 deficiency .
Babies that are born without intrinsic factor cannot properly absorb vitamin B-12 starting around 6 months of age.
The juvenile type of lack of intrinsic factor tends to manifest itself after the age of ten.
Pasted from <http://www.nlm.nih.gov/medlineplus/ency/article/001155.htm>
Week9 Page 121

Which is a more
common cause
of dyspepsia:
Crohn's disease
or pancreatitis?
What is the
commonest cause
of dyspepsia?
Week9 Page 122

What is functional
dyspepsia?
The workup for

dyspepsia includes
which 3 tests (hint: one
is a blood test)?
Diagnosis of peptic ulcer
is made by ___?
T/F: The commonest
cause of peptic ulcer
disease is functional
dyspepsia?
T/F: The commonest
cause of functional
dyspepsia is peptic ulcer
disease?
Week9 Page 123

Giardia lamblia
Giardia lamblia
From Wikipedia, the free encyclopedia
(Redirected from Giardia)
Jump to: navigation, search
Giardia lamblia
Giardia cell, SEM

Scientific classification
Domain: Eukaryota
Phylum: Metamonada
Order: Diplomonadida
Family: Hexamitidae
Genus: Giardia
Species: G. lamblia
Binomial name
Giardia lamblia
(Kunstler, 1882)
Parasite life cycle.

Giardia lamblia (synonymous with Lamblia intestinalis and Giardia duodenalis) is a flagellated protozoan parasite that colonises
and reproduces in the small intestine, causing giardiasis. The giardia parasite attaches to the epithelium by a ventral adhesive disc, and
reproduces via binary fission [1]. Giardiasis does not spread via the bloodstream, nor does it spread to other parts of the gastro -intestinal
tract, but remains confined to the lumen of the small intestine [2]. Giardia trophozoites absorb their nutrients from the lumen of
the small intestine, and are anaerobes.
Contents
[hide]
• 1 Hosts
Week9 Page 124

• 1 Hosts
• 2 Life cycle
• 3 Manifestation of infection
• 4 Backcountry Water Sources
• 5 Prevention and Treatment
• 6 Microscopy
• 7 Research
• 8 History
• 9 References
• 10 See also
[edit] Hosts
Giardia affects humans, but is also one of the most common parasites infecting cats, dogs and birds . Mammalian hosts also include
cows, beavers, deer, and sheep.
Life cycle
Giardia infection can occur through
1. ingestion of dormant cysts in contaminated water, or
2. by the fecal-oral route (through poor hygiene practices).
The Giardia cyst can survive for weeks to months in cold water [3], and therefore can be present in contaminated wells and water
systems, and even clean-looking mountain streams, as well as city reservoirs, as the Giardia cysts are resistant to conventional water
treatment methods, such as chlorination and ozonolysis. [3] Zoonotic transmission is also possible, and therefore Giardia infection is a
concern for people camping in the wilderness or swimming in contaminated streams or lakes, especially the artificial lakes formed by
beaver dams (hence the popular name for giardiasis, "Beaver Fever").
As well as water-borne sources, fecal -oral transmission can also occur, for example in day care centres, where children may have poorer
hygiene practices. Those who work with children are also at risk of being infected, as are family members of infected individ uals. Not all
Giardia infections are symptomatic, so some people can unknowingly serve as carriers of the parasite.
The life cycle begins with a noninfective cyst being excreted with faeces of an infected individual. Once out in the environm ent, the cyst
becomes infective. A distinguishing characteristic of the cyst is 4 nuclei and a retracted cytoplasm. Once ingested by a host , the
trophozoite emerges to an active state of feeding and motility. After the feeding stage, the trophozoite undergoes asexual re plication
through longitudinal binary fission. The resulting trophozoites and cysts then pass through the digestive system in the faece s. While the
trophozoites may be found in the faeces, only the cysts are capable of surviving outside of the host.
Distinguishing features of the trophozoites are large karyosomes and lack of peripheral chromatin, giving the two nuclei a ha lo
appearance. Cysts are distinguished by a retracted cytoplasm. This protozoa lacks mitochondria, although the discovery of the presence
of mitochodrial remnant organelles in one recent study "indicate that Giardia is not primitively amitochondrial and that it has retained a
functional organelle derived from the original mitochondrial endosymbiont" [4]
Manifestation of infection
Nomenclature for Giardia species are difficult, as humans and other animals appear to have morphologically identical parasite s.
Colonisation of the gut results in inflammation and villous atrophy, reducing the gut's absorptive capability. In humans, infection is
symptomatic only about 50% of the time, and protocol for treating asymptomatic individuals is controversial. [3]
Symptoms of infection include (in order of frequency) diarrhoea, malaise, excessive gas (often flatulence or a foul or sulphuric -
tasting belch, which has been known to be so nauseating in taste that it can cause the infected person to vomit), steatorrhoea (pale, foul
smelling, greasy stools), epigastric pain, bloating, nausea, diminished interest in food, possible (but rare) vomiting which is often
violent, and weight loss.[3] Pus, mucus and blood are not commonly present in the stool. In healthy individuals, the condition is usually
self-limiting, although the infection can be prolonged in patients who are immunocompromised, or who have decreased gastric acid
secretion.[3] People with recurring Giardia infections, particularly those with a lack of IgA, may develop chronic disease. Lactase
deficiency may develop in an infection with Giardia, however this usually does not persist for more than a few weeks, and a full recover y
is the norm[citation needed].
Cats can be cured easily, lambs usually simply lose weight, but in calves the parasites can be fatal and often are not respon sive to
antibiotics or electrolytes. Carriers among calves can also be asymptomatic. Dogs have a high infection rate, as 30% of the p opulation
under one year old are known to be infected in kennels. The infection is more prevalent in puppies than in adult dogs. This p arasite is
deadly for chinchillas, so extra care must be taken by providing them with safe water. Infected dogs can be isolated and trea ted, or the
entire pack at a kennel can be treated together regardless. Kennels should also be then cleaned with bleach or other cleaning
disinfectants. The grass areas used for exercise should be considered contaminated for at least one month after dogs show sig ns of
infection, as cysts can survive in the environment for long periods of time. Prevention can be achieved by quarantine of infe cted dogs for
at least 20 days and careful management and maintenance of a clean water supply.
Prevention and Treatment

Treatment of drinking water for Giardiais not ordinarily indicated in wilderness regions, including much of the Sierra Nevada and other
similar locations in North America.
In many other areas frequented by hikers and campers, as well as places where many residents rely on untreated surface water, reliable
prevention may involve filtration and/or chemical disinfection of available surface water, such as chlorination or ozonation.
Normal concentrations of chlorine and ozone used in mass water treatment for most urban areas of the United States may not be
adequate to kill all cysts. Giardia cysts are generally present in very small numbers in many such urban water supplies in th e United
States.
Yet typically these very common and very low concentrations in public water supplies are not a realistic health concern.
Scooping water from the top of a stream or river is not an effective way to avoid Giardia. Filtering (<1µm pore) or boiling is
Week9 Page 125

Scooping water from the top of a stream or river is not an effective way to avoid Giardia. Filtering (<1µm pore) or boiling is
recommended for purification of drinking water in wilderness conditions.
Giardia lamblia infection in humans is frequently misdiagnosed.
Accurate diagnosis requires an antigen test or, if that is unavailable, an ova and parasite examination of stool. Multiple st ool
examinations are recommended, since the cysts and trophozoites are not shed consistently.
Human infection is conventionally treated with metronidazole, tinidazole or nitazoxanide. Although Metronidazole is the current first-
line therapy, it is mutagenic in bacteria and carcinogenic in mice, so should be avoided during pregnancy. [3] One of the most common
alternative treatments is berberine sulfate (found in Oregon grape root, goldenseal , yellowroot, and various other plants). Berberine has
been shown to have an antimicrobial and an antipyretic effect. Berberine compounds cause uterine stimulation, and so should be
avoided in pregnancy. High doses of berberine can cause bradycardia and hypotension. [5]
Drug Treatment duration Possible Side Effects
Metronidazole 5-7 days Metallic taste; nausea; vomiting; dizziness; headache; disulfiram-like effect; neutropenia
Tinidazole Single dose Metallic taste; nausea; vomiting; belching; dizziness; headache; disulfiram-like effect
Nitazoxanide 3 days Abdominal pain; diarrhea; vomiting; headache; yellow-green discolouration of urine
Table adapted from Huang, White.. [3]
[edit] Microscopy
This picture shows multiple views of a single Giardia lamblia (intestinalis) cyst as imaged at different instrument settings by confocal
microscopy.Bar = 10 micrometres.
(A) is the cyst imaged by transmission (differential interference contrast), only.
(B) is the cyst wall selectively imaged through use of fluorescent -labelled (TRITC) antibody that is cyst wall specific.
(C) is the cyst imaged through use of carboxy fluorescein diacetate, a viability stain.
(D) is a composite image of (B) and (C).
(E) is a composite image of (A), (B), and (C).
Under a normal compound light microscope, Giardia often looks like a "clown face," with two nuclei outlined by adhesive discs above
dark median bodies that form the "mouth." Cysts are oval, have four nuclei, and have clearly visible axostyles.
[edit] Research
Giardia alternates between two different forms — a hardy, dormant cyst that contaminates water or food and an active, disease-causing
form that emerges after the parasite is ingested. National Institute of General Medical Sciences grantee Dr. Frances Gillin of the
University of California, San Diego and her colleagues cultivated the entire life cycle of this parasite in the laboratory, and identified
biochemical cues in the host's digestive system which trigger Giardia's life cycle transformations. [6][7] They also uncovered several ways in
which the parasite evades the defences of the infected organism. One of these is by altering the proteins on its surface, which confounds
the ability of the infected animal's immune system to detect and combat the parasite (called antigenic variation). Gillin's work reveals
why Giardia infections are extremely persistent and prone to recur. In addition, these insights into Giardias biology and survival
techniques may enable scientists to develop better strategies to understand, prevent, and treat giardia infections.
[edit] References
1. ^ Oxford textbook of Medicine, Fourth Edition, Volume 1. Oxford University Press pp759-760
2. ^ Harrison's Internal Medicine, Harrison's Online Chapter 199 Protozoal intestinal infections and trochomoniasis
3. ^ a b c d e f g Huang DB, White AC (2006). "An updated review on Cryptosporidium and Giardia". Gastroenterol. Clin. North Am. 35
(2): 291-314, viii. doi:10.1016/j.gtc.2006.03.006. PMID 16880067.
4. ^ Tovar J, León-Avila G, Sánchez LB, et al (2003). "Mitochondrial remnant organelles of Giardia function in iron -sulphur protein
maturation". Nature 426 (6963): 172-6. doi:10.1038/nature01945. PMID 14614504.
5. ^ UpToDate (Lexi -Comp, Inc.) retrieved 28 August 2007
6. ^ Hetsko ML, McCaffery JM, Svärd SG, Meng TC, Que X, Gillin FD (1998). "Cellular and transcriptional changes during excystation
of Giardia lamblia in vitro". Exp. Parasitol. 88 (3): 172-83. doi:10.1006/expr.1998.4246. PMID 9562420.
7. ^ Svärd SG, Meng TC, Hetsko ML, McCaffery JM, Gillin FD (1998). "Differentiation -associated surface antigen variation in the
ancient eukaryote Giardia lamblia". Mol. Microbiol. 30 (5): 979-89. PMID 9988475.
8. ^ Ford, BJ The discovery of Giardia The Microscope 2005;53(4):148-153.
[edit] See also

• 1998 Sydney water crisis
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• 1998 Sydney water crisis
[edit] External links

• GiardiaDB: The Giardia lamblia genome sequencing project
• Washington State Department of Health fact sheet on Giardia .
• Center for Disease Control fact sheet on Giardia
• Giardia article at MicrobeWiki
• Video of Giardia Life Cycle
• Giardia and the Sierra Nevada
• http://diarrhea.emedtv.com/giardia -lamblia/giardia-lambia.html
Pasted from <http://en.wikipedia.org/wiki/Giardia >
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Zollinger-Ellison syndrome
Monday, March 31, 2008
Zollinger-Ellison syndrome, a triad comprising

(1) intractable, sometimes fulminating, and in many ways atypical peptic ulcers ;
(2) extreme gastric hyperacidity; and
(3) gastrin-secreting, non-beta islet cell tumors of the pancreas, which may be single or multiple, small or large, benign or
malignant.
The gastrinoma sometimes occurs in sites (e.g., the duodenum) other than the pancreas. See also multiple endocrine
neoplasia, type I.
Pasted from <http://127.0.0.1:8080/rami?COMMAND=applyStylesheet(dor@doc.xsl,dor@s/12777451.pub)&sword=12785538 >
multiple endocrine neoplasia, type I, a variety that includes tumors of the anterior pituitary, parathyroid glands, and
pancreatic islet cells in association with a high incidence of peptic ulcers and sometimes the Zollinger-Ellison syndrome; it is
caused by a genetic abnormality on the long arm of chromosome 11. Called also Wermer's syndrome.
Pasted from <http://127.0.0.1:8080/rami?COMMAND=applyStylesheet(dor@doc.xsl,dor@n/12561343.pub)&sword=12561395 >
Background
non–beta islet cell, gastrin-secreting tumor of
Zollinger-Ellison syndrome (ZES) is caused by a
the pancreas that stimulates the acid-secreting cells of the stomach to maximal
activity, with consequent gastrointestinal mucosal ulceration. ZES may occur
sporadically or as part of an autosomal dominant familial syndrome called multiple endocrine neoplasia type 1
(MEN 1). The primary tumor is usually located in the duodenum, the pancreas, and abdominal lymph nodes, but
ectopic locations have also been described (eg, heart, ovary, gall bladder, liver, kidney).
Pathophysiology
The symptoms of ZES are secondary to hypergastrinemia, which causes hypertrophy of the gastric mucosa,
leading to increased numbers of parietal cells and increased maximal acid output. Gastrin by itself also stimulates
acid secretion, resulting in increased basal acid secretion. The large quantity of acid produced leads to
gastrointestinal mucosal ulceration. It also leads to diarrhea and malabsorption. Malabsorption in ZES usually is
multifactorial, being caused by direct mucosal damage by acid, inactivation of pancreatic enzymes, and
precipitation of bile salts. ZES is sporadic in 75% of patients, while in the other 25% it is associated with MEN 1,
an autosomal dominant condition characterized by hyperparathyroidism, pancreatic endocrine tumors, and
pituitary tumors.
Frequency
United States
ZES occurs in approximately 0.1-1% of all patients with duodenal ulcers . Its frequency of occurrence is
reported to be approximately the same as insulinoma, the most common functioning pancreatic endocrine tumor.
International
Incidence is 1-3 cases per million patients per year in Sweden, 0.5 cases per million patients per year in Ireland,
and 0.1-0.2 cases per million patients per year in Denmark.
Mortality/Morbidity
Currently, the morbidity and mortality of ZES is low because of improved medical and surgical management of
the disease. Fewer than 5% of patients develop a complication, such as abdominal perforation, gastric outlet
obstruction, or esophageal stricture.
Race
All races can be affected.
Sex
A slight male predominance exists, with a male-to-female ratio of 1.3:1.
Age
The mean age of onset of ZES is 43 years, with the patients with MEN 1/ZES presenting a decade earlier.
Generally, a 5- to 7-year delay in diagnosis occurs. In a recent prospective study, fewer than 3% of patients were
younger than 20 years, while 7% were older than 60 years at the time of disease onset.
CLINICAL
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CLINICAL
History
A high index of clinical awareness is needed to make a diagnosis of ZES.
• Abdominal pain is the most common symptom, present in 75% of patients.
Typically, it is located in the upper abdomen and mimics that of peptic ulcer
disease. This symptom is reported more frequently by men and patients with the sporadic form of ZES.
• Of patients with ZES, 73% have diarrhea, and this is the most common symptom in patients who have
MEN 1/ZES and in female patients.
• The combination of diarrhea and abdominal pain is present in more than half the patients.
• Heartburn is the third most common symptom, and this symptom mimics
gastroesophageal reflux disease (GERD).
• Other symptoms include nausea, vomiting, gastrointestinal bleeding, and weight loss. Gastrointestinal
bleeding frequently is due to ulceration in the duodenum and is the presenting symptom in 25% of patients.
• In patients in whom MEN 1/ZES is suspected, a history indicative of nephrolithiasis, hypercalcemia, and
pituitary disorders should be sought. A family history of nephrolithiasis, hyperparathyroidism, and
gastrinoma also may be present.
Physical
The findings of the physical examination may be normal.
• Patients may be pale if presenting with gastrointestinal bleeding.
• Jaundice may occur if the tumor compresses the common bile duct, although this presentation is very rare.
• Epigastric tenderness may be present.
• Dental erosions may be noted if symptoms consistent with GERD are present.
• The presence of hepatomegaly suggests liver metastasis.
Causes
• ZES is caused by a non–beta islet cell, gastrin-secreting tumor of the pancreas that stimulates the acid-
secreting cells of the stomach to maximal activity, with consequent gastrointestinal mucosal ulceration.
• ZES may occur sporadically or as part of MEN 1.
Pasted from <http://www.emedicine.com/med/TOPIC2437.HTM>
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06 KANDEL 2008 Dysphagia and Gastro-esophageal Reflux Disease
(5)
List 5 common
causes of
dyspepsia?
List the 3 most
common causes
of dyspepsia?
H. pylori
infection and
NSAIDs are the
two most
common causes
of ___?
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Which patients
benefit most
from proton
pump inhibitors
(list 4 types)?
There's a high
correlation between
helicobacter infection
and which type of
cancer?
Coagulopathy (aka.Bleeding disorders )

Definition
Bleeding disorders are a group of conditions involving the body's blood clotting process. Such disorders can lead to heavy
and prolonged bleeding after an injury.
Causes
Normal blood clotting involves as many as 20 different plasma proteins, which are known as blood clotting or coagulation
factors. These factors act together with other chemicals to form a substance called fibrin that stops bleeding.
Problems can occur when certain coagulation factors are low or missing. Bleeding problems can range from mild to
severe.
Some bleeding disorders are present at birth and are passed through families (inherited). Others develop during certain
illnesses (such as vitamin K deficiency or severe liver disease), or treatments (such as the use of drugs to stop blood clots
(anticoagulants) or the long-term use of antibiotics ).
Bleeding disorders can also result from having poorly working or too few of the blood cells that promote blood clotting
(platelets). These disorders can also be either inherited or picked up (acquired). The side effects of certain drugs often
lead to the acquired forms.
Symptoms
• Abnormal menstrual bleeding
• Bleeding into joints!
• Excess bruising
• Heavy bleeding
• Nose bleeds
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DYSPHAGIA
What is
achalasia?
The diagnosis of
achalasia is
confirmed by a
____ test?
Is gastroscopy in a
patient with
achalasia found to be
normal or abnormal?
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Scleroderma is a
disease of abnormal
____ (HINT: a type of
protein)?
In Scleroderma, there is
abnormal esophageal
motility, namely,
ABSENCE OF … and
DECREASED …?
Dysphagia can be due
to a lower esophageal
____'s ring?
A Schatzki ring or Schatzki-Gary ring is a ring found in the lower part of the esophagus that can cause difficulty swallowing. The ring is made
up of mucosal tissue (which lines the esophagus) or muscular tissue. [1] Patients with Schatzki rings can develop intermittent dysphagia
(difficulty swallowing), or, more seriously, a completely blocked esophagus.
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Pasted from <http://en.wikipedia.org/wiki/Schatzki_ring>
CREST
Week9 Page 136

T/F: a diagnosis of dysphagia
can be made by history
alone?
How can you distinguish

between mechanical and
neuromuscular obstruction
based on the type of food that
causes dysphagia?
If someone is deemed to have
progressive mechanical
obstruction, the next level in
the diagnositic algorithm is to
determine …?
If someone is deemed to have
progressive neuromuscular
obstruction, the next level in
the diagnositic algorithm is to
determine …?
In the algorithmic
approach to
dysphagia, food that
stops or "sticks"
after being
swallowed is
suggestive of ___
dysphagia whereas
a person who has
difficulty initiating
swallow has a
condition suggestive
of ___ dysphagia?
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Esophageal Stricture (peptic stricture)
Article Last Updated: Jun 27, 2006
Background
Disease processes that can produce esophageal strictures can be grouped into 3 general categories:
(1) intrinsic diseases that narrow the esophageal lumen through inflammation, fibrosis, or neoplasia;
(2) extrinsic diseases that compromise the esophageal lumen by direct invasion or lymph node enlargement; and
(3) diseases that disrupt esophageal peristalsis and/or lower esophageal sphincter (LES) function
by their effects on esophageal smooth muscle and its innervation.
Many diseases can cause esophageal stricture formation. These include acid peptic, autoimmune, infectious, caustic,
congenital, iatrogenic, medication-induced, radiation-induced, malignant, and idiopathic disease processes.
The etiology of esophageal stricture can usually be identified using radiologic and endoscopic modalities and can be
confirmed by endoscopic visualization and tissue biopsy. Use of manometry can be diagnostic when dysmotility is
Week9 Page 139

confirmed by endoscopic visualization and tissue biopsy. Use of manometry can be diagnostic when dysmotility is
suspected as the primary process. CT scan and endoscopic ultrasound are valuable aids in the staging of malignant
stricture. Fortunately, most benign esophageal strictures are amenable to pharmacological, endoscopic, and/or surgical
interventions.
Because peptic strictures account for 70-80% of all cases of esophageal stricture, peptic stricture is the focus of this
article. A detailed discussion of possible benign and malignant processes associated with esophageal stricture and its
management is beyond the scope of this article.
Pathophysiology
Peptic strictures are sequelae of gastroesophageal reflux–induced esophagitis, and they usually originate from the
squamocolumnar junction and average 1-4 cm in length.
• Two major factors involved in the development of a peptic stricture are as follows:
○ Dysfunctional lower esophageal sphincter: Mean LES pressures are lower in patients with peptic strictures
compared with healthy controls or patients with milder degrees of reflux disease. A study by Ahtaridis et al
(1979) showed that patients with peptic strictures had a mean LES pressure of 4.9 mm Hg versus 20 mm Hg
in control patients. LES pressure of less than 8 mm Hg appeared to correlate significantly with the presence
of peptic esophageal stricture without any overlap in controls.
○ Disordered motility resulting in poor esophageal clearance: In the same study, Ahtaridis et al (1979)
demonstrated that 64% of patients with strictures had motility disorders compared with 32% of patients
without strictures.
• Other possible associated factors include the following:
○ Presence of a hiatal hernia: Hiatal hernias are found in 10-15% of the general population, 42% of patients
with reflux symptoms and no esophagitis, 63% of patients with esophagitis, and 85% of patients with peptic
strictures. This suggests that hiatal hernias may play a significant role.
○ Acid and pepsin secretion: This does not appear to be a major factor. Patients with peptic strictures have
been demonstrated to have the same acid and pepsin secretion rates as gender-matched and age-matched
controls with esophagitis but no stricture formation. In fact, some authors believe that alkaline reflux may play
an important role.
○ Gastric emptying: No good evidence suggests that delayed emptying plays a role.
Pasted from <http://www.emedicine.com/med/TOPIC744.HTM>
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GERD stands for?
Extra-esophageal symptoms
of GERD include … (list 4)?
Week9 Page 141

The most accurate test for
reflux is …?
24 hour esophageal
pH monitor is the
most accurate test
for ___?
(Non-esophagitis reflux disease)
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List 3 esophageal
complications of
esophageal
reflux?(5)
In barrett's esophagus
there is metaplasia of the
esophageal mucosa from
___ to ___?
In barrett's esophagus
there is increased risk of
___ of the lower
esophagus?
What is the suggested
investigation in barrett's
esophagus?
Week9 Page 143

In esophageal
reflux, If nocturnal
symptoms are
present, what is a
suggested non-
pharmacological
treatment that can
alleviate
• Therefore less acidic intragastric contents are

associated with better healing of esophagitis
Week9 Page 144

-prazole's:
What does NERD stand for?

The efficacy of using a proton
pump inhibitor is close to
___%?
Name 3 receptors on parietal

cells which play an important
role in gastric acid secretion?
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Stomach D cells make ___?
Somatostatin decreases both
___ cell secretion of acid AND
___ cell secretion of gastrin?
___ and ___ affect parietal
cells via ____ cells?
What are ECL cells?
Somatostatin is made by
stomach ___ cells?
Reflux is due to transient

relaxation of the …?
2 accurate indicators of
reflux are ___ and ___?
Apart from
prescription of proton
pump inhibitors and
elevating the head of
the bed, what is
another common non-
pharmacological
approach to treating
reflux?
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Why may patients with
pneumonia be more likely
to be taking a proton
pump inhibitor than a
control group?
Because
pneumonia is one
of the extra-
esophageal signs of
reflux disease (also
wheezing,
laryngitis, cough).
The PPI is therefore
perhaps secondary
to a diagnosis or
less commonly, a
prophylactic.
Week9 Page 148

2:58 AM
Medical Encyclopedia: Scleroderma
URL of this page: http://www.nlm.nih.gov/medlineplus/ency/article/000429.htm

Alternative names
CREST syndrome; Progressive systemic sclerosis; Systemic sclerosis
Definition
Scleroderma is a widespread connective tissue disease that involves changes in the skin, blood vessels,
muscles, and internal organs.
Causes, incidence, and risk factors
The cause of scleroderma is unknown. Persons with this condition have a build up of a substance called
collagen in the skin and other organs. This build up leads to the symptoms associated with the disease.
The disease usually affects people 30 to 50 years old. Women are affected more often than men. Risk factors
are occupational exposure to silica dust and polyvinyl chloride.
Symptoms
• Blanching, blueness, or redness of fingers and toes in response to heat and cold (Raynaud's
phenomenon)
• Pain, stiffness, and swelling of fingers and joints
• Skin thickening and shiny hands and forearm
• Skin is hard
• Tight and mask-like facial skin
• Ulcerations on fingertips or toes
• Esophageal reflux or heartburn
Week9 Page 149

• Esophageal reflux or heartburn
• Difficulty swallowing
• Bloating after meals
• Weight loss
• Diarrhea
• Constipation
• Shortness of breath
Additional symptoms that may be associated with this disease:
• Wrist pain
• Wheezing
• Skin, abnormally dark or light
• Joint pain
• Hair loss
• Eye burning, itching, and discharge
Signs and tests
Examination of the skin may show tightness, thickening, and hardening.
Tests may include:
• ESR
• Rheumatoid factor
• Antinuclear antibody
• Urinalysis
• Chest x-ray
• Pulmonary function studies
• Skin biopsy
Treatment
Drugs used to treat scleroderma include:
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids
Other treatments for specific symptoms may include:
• Antacids for heartburn
• Medications to treat Raynaud's phenomenon
• Blood pressure medications (particularly ACE inhibitors) for high blood pressure or kidney problems
• Medicines to improve breathing
Treatment usually includes a combination of physical therapy and skin and joint protection techniques (for
example, avoiding cold in the case of Raynaud's phenomenon).
Support Groups
See: Scleroderma - support group
Expectations (prognosis)
In most patients, the disease slowly gets worse. People who only have skin involvement have a better outlook.
Death may occur from gastrointestinal, cardiac, kidney, or pulmonary (lung) involvement.
Complications
• Heart failure
• Kidney failure
• Pulmonary fibrosis
• Pulmonary hypertension
• Malabsorption
Calling your health care provider
Call for an appointment with your health care provider if:
• You have symptoms of scleroderma
• You have scleroderma and symptoms become worse or new symptoms develop
Prevention
There is no known prevention. Minimize exposure to silica dust and polyvinyl chloride.
Updated by: Steve Lee, DO, Rheumatology Fellow, Loma Linda University Medical Center, Loma Linda, CA.
Review provided by VeriMed Healthcare Network.
Week9 Page 150

Pasted from <http://www.nlm.nih.gov/medlineplus/print/ency/article/000429.htm>
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Esophageal Manometry
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Hiatus Hernia
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07 STEINHART 2008 Inflammatory Bowel Disease
IBD: a chronic recurrent, nonspecific inflammation of the GI tract

• Have tendency go through relapses & remissions
• No known cause: toxic insults (NSAIDS), and not due to bacteria
What is ulcerative colitis?

What is crohn's disease?
• Exact cause of IBD not currently known

• Main differences between Crohn's disease and UC:
1. UC, as colitis implies, is limited to the colon: T/F: Crohn's disease
Inflammation in UC refers to colon can affect ANY part of
2. CD can affect any part of the GI tract from
the GI tract, from the
mouth to anus and inflammation may be mouth to the anus?
patchy; areas of inflammation may be
separated from each other by areas of bowel
Week9 Page 158

Theory:
IBD prone
patients have
failure to down-
regulate acute
inflammation
What is thought to
be the pathogenesis
of IBD?
Week9 Page 159

Muscularis of the
bowel wall is not
inflamed and
therefore no
thickening of the
bowel wall in UC
On Pseudopolyps
The repeated cycle of ulceration, alternating with the deposition of granulation tissue
during the healing phase, results in the development of raised areas of inflamed tissue
that resemble polyps.
Week9 Page 160

However, these lesions are not neoplastic (i.e., true polyps), but inflammatory tissue, and
are called pseudopolyps. They have no malignant potential.
Pasted from <http://www.endoatlas.com/ib_uc_03.html>
Is it in Crohn's disease
or Ucerative Colitis
that skip lesions are
found?
that non-caseating
granulomas are found?
that the small bowel is
involved?
where there is
superficial
inflammation?
• In UC there are NO skip lesions, meaning inflammation is continuous from the rectum where thereis
proximally transmural
• In CD because the inflammation extends transmurally to the bowel wall the ulcers that occur inflammation?
What are the top 3
will bleed and therefore and extend to adjacent bowel or skin and result in fistulas
locations for Crohn's
disease?
The maximum
incidence of UC and CD
occurs between ___
and ___ years of age?
The primary diagnostic
sign of ulcerative colitis
is ___?
Is it in CD or UC that an
abdominal mass MAY
be present?
Weight loss, signs of
malnurtrition, and
perianal disease are
ALL MORE COMMON
in ulcerative colitis or
crohn's disease?
T/F: The ONLY
histologic feature
that's histologic of
ulcerative colitis is
crypt distortion?
Which clinical feature(s)

are most diagnostic of CD?
Strictures, fistulas, and
sepsis, are all common in
UC or CD?
Is the risk of malignancy
increased in UC or CD?
Is the risk of massive
hemorrhage increased in
UC or CD?
T/F: perianal disease may
or may not be present in
UC but it is very commonly
seen in CD?
Week9 Page 161

T/F: Toxic
• Gross oversimplification of how patients can present
megacolon is a
very rare
complication of
Crohn's Disease?
• With UC, important to point out that the hallmark is RECTAL BLEEDING
• These are chronic disorders so often have relapses; • If someone says have UC but NEVER had blood in stool, have to
remission may be many months or many years; can also questions the Dx; may be CD
go into remission spontaneously • Patients with UC typically don't get perianal disease
• We don't know what the trigger(s) are for relapse or • With UC no thickened loop of bowel or abdominal mass can detect
remission • Abdominal pain inc. in CD may be secondary to obstruction, passage of
• Can also have chronic continuous contents through narrow area
• Perianal disease more in CD rather than UC
• 30% of patients with CD may have
Manifestations of IBD that occur outside the bowel
• Can ultimately lead to liver

damage and cirrhosis
List 4 extraintestinal
• Toxic Megacolon: acute, severe form of colitis
○ Bowel wall becomes very thin in this situation manifestations of IBD?
• Fortunately not seen very often any more
So how do we make a diagnosis of Crohn's disease?

What is the differential
diagnosis of suspected
jejunal + ileal inflammation,
apart from CD?
apart from CD?
apart from CD?
List 3 common intestinal
complications of CD?
Is Toxic Megacolon more
associated with CD or UC?
Erythema Nodosum
Background
Erythema nodosum (EN) is an acute, nodular, erythematous eruption that usually is
limited to the extensor aspects of the lower legs. Chronic or recurrent EN is rare but may occur.
EN is presumed to be a hypersensitivity reaction and may occur in association with several systemic diseases or drug
therapies, or it may be idiopathic. The inflammatory reaction occurs in the panniculus.
Pathophysiology
EN probably is a delayed hypersensitivity reaction to a variety of antigens; circulating immune complexes have not been
found in idiopathic or uncomplicated cases but may be demonstrated in patients with inflammatory bowel disease.
Pasted from <http://www.emedicine.com/derm/topic138.htm>
Pyoderma Gangrenosum
Background
Pyoderma gangrenosum (PG) is an uncommon ulcerative cutaneous condition of uncertain etiology. PG was first described
in 1930. It is associated with systemic diseases in at least 50% of patients who are affected. The diagnosis is made by
excluding other causes of similar appearing cutaneous ulcerations, including infection, malignancy, vasculitis, collagen
vascular diseases, diabetes, and trauma. Ulcerations of PG may occur after trauma or injury to the skin in 30% of patients;
this process is termed pathergy.
The 2 primary variants of PG are the classic ulcerative form, usually observed on the legs, and a more superficial variant
known as atypical PG that tends to occur on the hands. Patients with PG may have involvement of other organ systems that
Week9 Page 162

known as atypical PG that tends to occur on the hands. Patients with PG may have involvement of other organ systems that
manifests as sterile neutrophilic abscesses. Culture-negative pulmonary infiltrates are the most common extracutaneous
manifestation. Other organs systems that may be involved include the heart, the central nervous system, the GI tract, the
eyes, the liver, the spleen, bones, and lymph nodes. The prognosis of PG is generally good; however, recurrences may
occur and residual scarring is common. Therapy of PG involves the use of anti-inflammatory agents, such as corticosteroids,
and immunosuppressive agents.
Pathophysiology
The pathophysiology of PG is poorly understood, but dysregulation of the immune system, specifically altered neutrophil
chemotaxis, is believed to be involved.
Pasted from <http://www.emedicine.com/derm/topic367.htm>
Toxic Megacolon
Background
Toxic megacolon is the clinical term for an acute toxic colitis with dilatation of the colon. The dilatation can be
either total or segmental. A more contemporary term for toxic megacolon is simply toxic colitis, because patients may
develop toxicity without megacolon. For purposes of this article, the term toxic megacolon is used, but either toxicity or
megacolon can occur exclusively of each other.
The hallmarks of toxic megacolon, a potentially lethal condition, are nonobstructive colonic dilatation larger than 6 cm and
signs of systemic toxicity. Toxic megacolon was recognized in 1950 by Marschak et al. Jalan et al described the diagnostic
criteria.
1. The first criterion is radiographic evidence of colonic dilatation.
2. The second criterion is any 3 of the following: fever (>101.5°F), tachycardia (>120), leukocytosis (>10.5), or anemia.
3. The third criterion is any 1 of the following: dehydration, altered mental status, electrolyte abnormality, or hypotension.
Toxic megacolon was first thought to be a complication of ulcerative colitis. In fact, toxic megacolon may complicate any
number of colitides, including inflammatory, ischemic, infectious, radiation, and pseudomembranous. The incidence of toxic
megacolon is expected to increase due to the rising prevalence of pseudomembranous colitis. Colonic dilatation may be
present in other conditions, such as Hirschsprung disease, idiopathic megacolon/chronic constipation, and intestinal
pseudoobstruction (Ogilvie syndrome). However, these patients do not develop signs of systemic toxicity and, therefore, do
not fall into the category of having toxic megacolon.
Pathophysiology
Although the precise pathophysiology of toxic megacolon is unproven, several factors may contribute to its development and
precipitation. Signs and symptoms of acute colitis may be present for as long as a week before dilatation develops.
Often, triggering or predisposing factors can be identified. While the risk of toxic megacolon increases with the severity of
colitis, rapid tapering or abrupt discontinuation of medications such as steroids, sulfasalazine, and 5-aminosalicylic acid may
precipitate toxemia and dilatation. Medications that negatively impact bowel motility also are implicated in the development
of toxic megacolon. These include, but are not limited to, anticholinergics, antidepressants, loperamide, and opioids.
Procedures such as barium enema or colonoscopy may cause distension, may impair blood supply, or may exacerbate a
microperforation and cause subsequent toxemia.
In cases of uncomplicated colitis, the inflammatory response is confined to the mucosa. The microscopic hallmark of toxic
megacolon is inflammation extending beyond the mucosa into the smooth-muscle layers and serosa. Myenteric plexus
involvement is not consistent and probably does not contribute to dilatation.
As inflammation progresses into the smooth-muscle layers of the colon, nitric oxide appears to be involved in the
pathogenesis of toxic megacolon. Nitric oxide inhibits smooth-muscle tone and is generated by inflammatory cells such as
neutrophils and macrophages in the inflamed portions of the colon. Studies performed by Mourelle et al. have shown
increased amounts of inducible nitric oxide synthetase in the muscularis propria of patients with toxic megacolon.
Inflammation and up-regulated nitric oxide synthetase are thought to increase local nitric oxide, which inhibits colonic
smooth muscle and causes dilatation.
Pasted from <http://www.emedicine.com/MED/topic1418.htm>
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More limited cf. CD but again depends on site of occurence
• If only rectum and sigmoid colon involved, then

In Ulcerative Colitis, if
need consider venereal diseases
ONLY the rectum and
sigmoid colon are
involved, then you
(with some erythema or should consider which
redness of the mucosa) category of diseases?
List 4 signs/symptoms
you would investigate in
order to assess the
severity of Ulcerative
Colitis?(6)
you would investigate in
order to assess the
severity of Crohn's
Disease?(6)
-- Tachycardi
Which blood tests would
you do (name 4) to
conduct a disease severity
assessment in IBD?(6)
In the disease
severity
assessment of
IBD, which 2
neutrophil -
derived proteins
can be measured
in the feces
because they are
released by cells
in inflammatory
conditions?
Calprotectin and lactoferrin in the assessment of intestinal inflammation

and organic disease
Abstract
Calprotectin and lactoferrin are specific neutrophil-derived proteins, which can be
Background and aims
measured in the feces because they are released by cells in inflammatory conditions. We evaluated the
efficacy of calprotectin and lactoferrin in detecting organic disease as assessed by colonoscopy.
Methods The study comprised 144 patients undergoing colonoscopy for lower gastrointestinal symptoms (abdominal pain, altered
bowel habits, and bloody stools) (67), or inflammatory bowel disease activity, or surveillance for dysplasia (77). A single s tool sample was
assayed for calprotectin and lactoferrin. The proportion of patients correctly diagnosed with each test and the relationship with
endoscopic and histological findings were measured.
Results Fecal excretion of calprotectin significantly correlated with the finding of colonic inflammation at endoscopy, both in ulcer ative
colitis and in Crohn’s disease (p<0,001 and p<0,008, respectively), while lactoferrin excretion significantly correlated with histological
inflammation (p=0.001 and p=0.009 respectively). Recommended cut-off values need to be adjusted in the inflammatory bowel disease
group. Overall sensitivity, specificity, positive predictive value, and diagnostic efficacy were 78, 83, 86, and 80% for calp rotectin and 80,
85, 87, and 81% for lactoferrin, respectively.
Conclusions Fecal calprotectin and lactoferrin appear to be equally recommendable as inflammatory disease markers in patients with
lower gastrointestinal symptoms. Both tests are needed to accurately discriminate activity in inflammatory bowel disease pati ents.
Keywords Calprotectin - Colon cancer - Crohn’s disease - Lactoferrin - Ulcerative colitis
Pasted from <http://www.springerlink.com/content/r66601746q885863/>
Week9 Page 164

Pasted from <http://www.springerlink.com/content/r66601746q885863/>
T/F: Since therapy must

be individualized in IBD
treatment based upon
disease and patient
factors, in many specific
circumstances, there may
NOT be an 'evidence
base' available for
treatments?
For the induction and
maintenance of
treatment remission in
BOTH UC and CD, which 2
drugs can be used?
Corticosteroids and
immunosuppressive
agents can be used to
induce remission in (CD
or UC)?
Oldest drugs used Antibiotics, ___ and
for treatment; methotrexate can be
related to aspirin used to induce remission
in (CD or UC)?
Azathioprine,
methotrexate, and
infliximab can be used to
or UC)?
Corticosteroids and
immunosuppressive
agents can be used to
or UC)?
Which two drugs can be
used to BOTH induce
AND maintain remission
in CD?
Which drug, apart from
sulphasalazine and 5-
ASA, can be used to
maintain remission in
BOTH CD and UC?
List 3 drugs that can be
used to induce remission
in UC?(4)
used to induce remission
in CD?(6)
used to maintain
remission in CD?(5)
used to maintain
remission in UC?(4)
T/F: There is NO role for
antibiotics in Crohn's
disease?
Metronidazole can be
used in (UC or CD) as a
treatment option?
Week9 Page 165

Avascular necrosis (AVN) is defined as cellular death of bone components due to
interruption of the blood supply; the bone structures then collapse, resulting in bone destruction, pain, and loss of
joint function. AVN is associated with numerous conditions and usually involves the epiphysis of long bones, such as
the femoral and humeral heads and the femoral condyles, but small bones can also be affected. AVN of the jaw
associated with bisphosphonate use was recently described. In clinical practice, AVN is most commonly
encountered in the hip.
Pasted from <http://www.emedicine.com/Med/topic2924.htm>
Budesonide is used to treat symptoms of stuffiness and runny nose due to allergies.
Pasted from <http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601030.html>
Newer Corticosteroids
These newer corticosteroids are more rapidly metabolized than traditional corticosteroids, and they offer the promise
of efficacy with fewer systemic side effects. The packaging of these agents in a pH-sensitive coating (similar to that
used for 5-ASA preparations) offers the possibility of drug delivery to the small bowel and right colon with a
minimum of side effects.
Pasted from <http://www.aafp.org/afp/980101ap/botoman.html>
Week9 Page 166

5-ASA and
sulphapyridine are both
derivatives of ___?
The two most important
side-effects of
(8) corticosteroids to worry
about in patients with
1
IBD are ___ and ___?
Worry about the most!
What is budesonide?
Budenoside has a high
topical affinity for the ___
receptor?
What is the advantage of
using budenoside as
(ie. Broken down very quickly opposed to conventional
to inactive metabolites) steroids?
Azathioprine/6-
Mercaptopurine is indicated
for ___ dependent or
resistant disease (especially
in (CD or UC)?
In prescribing
azathioprine/6-
mercaptopruine, which 2
blood tests should you order
to monitor levels?
SKIPPED OVER; NOT USED VERY MUCH ANYMORE;

MORE FOR HISTORICAL INTEREST
Interferes with folic

acid metabolism
___ may reduce the

immunogenecity of
infliximab?
T/F: Cyclosporine is
sometimes used in
maintenance therapy for
UC?
Week9 Page 167

Methotrexate may reduce
the immunogenecity of ___?
Even though there is NO role
for cyclosporine in
maintenance therapy for UC,
there MAY be a role for it in
treating (which type of) CD or
pyoderma gangrenosum?
List two indications for the

use of infliximab in UC?
List 3 indications for the use
of infliximab in CD?(5)
List 3 potentially
adverse outcomes
• REMICABE given as 3 treatments over 2 weeks; only treatment relating to the use of
that's been shown to actually close these fistulas biologics in the
treatment of IBD?(4)
SURGERY FOR TREATMENT OF IBD

Indications Indications
List 3 indications for

surgery in CD?(8)
surgery in UC?(7)
• Surgery is curative for patients with UC • In CD, surgery also an option
○ Have to have an ileostomy or a pelvic ○ CD CAN come back in previously unaffected
pouch procedure (pouch fashioned out of segments; NOT a curative procedure then
remaining small intestine)
Week9 Page 168

09 ROSSOS 2008 Pancreatitis
Difference between acute

and chronic pancreatitis?
What are the endocrine

and exocrine functions of
the pancreas?
Week9 Page 169

Regarding the
etiology of acute
pancreatitis, the
TWO MAJOR causes
are ___ and ___?
Overall mortality for

acute pancreatitis is ___
to ___%?
List 3 miscellaneous
causes of acute
pancreatitis (ie. Not
alcohol, gallstones,
ERCP: Endoscopic Retrograde CholangioPancreatography idiopathic)?(5)
During an endoscopic retrograde cholangiopancreatography, a catheter is advanced through the

endoscope and inserted into the pancreatic or biliary ducts. A contrast agent is injected into
these ducts and X-rays are taken to evaluate their caliber, length and course.
Narrowing, stones, and tumors in the ducts can be identified in the X-rays.
Pasted from <http://www.nlm.nih.gov/medlineplus/ency/imagepages/19564.htm>
(7)
Week9 Page 170

List 2 drugs which
may cause drug-
induced
(early)
pancreatitis via
chronic
accumulation of
toxic
metabolites?(3)
(months)
List 2 antimicrobial agents

that may cause acute
pancreatitis?(5)
List 7 groups of drugs that

cause acute pancreatitis?
Week9 Page 171

What is the gold standard
for establishing or
excluding a CF diagnosis?
T/F: It IS NOT
recommended that CFTR
mutation screening be
regularly performed in
patients with pancreatitis?
Week9 Page 172

(7)
Release of lipase from the

pancreas leads to which
major systemic effect?
Release of Phospholipase A2
from the pancreas leads to
which major systemic effect?
Release of complement from
the pancreas leads to which
Release of thrombin from
Week9 Page 173

Release of elastase,
chymotrypsin, and kallikrein
from the pancreas leads to
which major systemic
effect(s)?
Fat necrosis secondary may
occur secondary to the
release of which major
pancreatic enzyme?
How can you clinically diagnose

acute pancreatitis…list 5
ways?(5)
(Physical examination)
In actue pancreatitis, over the course

of the first week of enzyme release,
levels of which pancreatic enzyme
are generally higher than amylase?
amylase lipase
Week9 Page 174

of the first week of enzyme release,
levels of which pancreatic enzyme
are generally higher than amylase?
amylase lipase
In which of the
following causes of
increased serum lipase
will serum lipase
actually be NORMAL (ie.
NOT be raised):
pancreastitis, parotitis,
biliary stone, intestinal
injury, tubo-ovarian
disease, renal failure,
macroamylasemia.
In which of the following

causes of increased levels
of BOTH serum lipase AND
amylase will levels of
amylase and lipase
actually be INCREASED:
• So amylase levels are NORMAL in tubo-ovarian disease,
a. Parotitis, renal failure,
macoamylasemia,
b. Tubo-ovarian disease, and
intestinal injury,
c. Macroamylasemia pancreatitis, parotitis,
biliary stone?
In renal failure levels of
serum amylase and lipase
may be as high as ___ X
normal?
Week9 Page 175

serum amylase and lipase
may be as high as ___ X
normal?
Prognostic
factors in acute
pancreatitis
include (name 2
general ones)?
Examples of local
complications
secondary to
acute
pancreatitis
include?
Overall mortality
due to acute
pancreatitis is about
___ to ___%?
How is BMI related to
Week9 Page 176

How is BMI related to
prognosis of AP?
ERCP: Endoscopic Retrograde CholangioPancreatography

early (48-72 hrs) ERCP
in acute pancreatitis?
During an endoscopic retrograde cholangiopancreatography, a catheter is advanced through the

endoscope and inserted into the pancreatic or biliary ducts. A contrast agent is injected into
these ducts and X-rays are taken to evaluate their caliber, length and course.
Narrowing, stones, and tumors in the ducts can be identified in the X-rays.
Pasted from <http://www.nlm.nih.gov/medlineplus/ency/imagepages/19564.htm>
Week9 Page 177

(5)
1
List 3 supportive
therapies that can
be offered in
5
acute
pancreatitis?(5)
Signs and symptoms of

(4)
Pancreatitis is often
1 caused by ___ or by
___?
Symptoms of acute
pancreatitis include
4 …(list 4)?(5)
When does acute
pancreatitis become
chronic?
of chronic
pancreatitis?(4)
Week9 Page 178

09 ROSSOS 2008 Pancreatitis
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11 FMP 2008 THURS GI MALIGNANCY Seminar
Week9 Page 195

Week9 Page 196
1. Think of ways to categorize it: anatomically, according to motor/neuro
a. Motor
○ Rings: shasky rings: fibrotic rings; usually in lower esophageal area; webs that are in esophagus that can
cause dysphagia
b. Neuro
○ Achalasia - when you swallow fluid, LES relaxes; so failure to relax the LES; often these people have a lack of
peristaltic waves in lower end of esophagus
○ Parkinson's disease, myasthenia gravis, GBS
○ If think of oropharyngeal transfer dysphagia, most commonly dysphagia in orpharyngeal area is due to
stroke, parkinson's ms, lou gherig's disease; can also get webs, zenker's diverticulum
In anatomy, Zenker's diverticulum, also pharyngoesophageal diverticulum, is a diverticulum of the mucosa of the
pharynx, just above the cricopharyngeal muscle (i.e. above the upper sphincter of the oesophagus).
Pasted from <http://en.wikipedia.org/wiki/Zenker's_diverticulum>
What is Zenker's
diverticulum?
Zenker's diverticulum
typically occurs above
which muscle?
Pasted from <http://www.mayoclinic.org/images/zenkers-diverticulum-lg-bdy.jpg>
Week9 Page 197

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Colorectal Cancer Screening in Elderly Patients
1:57 PM
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Esophageal Cancer
1:57 PM
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00 FMP 08 Week 8 Intro Pages

Sunday, February 10, 2008

• Sadness = healthy, normal condition that everyone feels

Briefly describe how

List 3 medical conditions

• All the following have

T/F: Adjustment Disorder

How is major depressive

T/F: Major depressive

List 6 risk factors for

• So if you go through large groups of patients histories, only

What is the effect of untreated

• Found that treatment reveresed the blood flow; top is

• Dunedin study: looked at serotonin system

What did the Dunedin

• In same group looked at maltreatment during childhood

Brain-derived neurotrophic factor

[edit] Effects of stress and BDNF's link in depression

[edit] Mechanism of action for BDNF

[edit] Other diseases associated with low BDNF levels

[edit] High BDNF levels

[edit] External links

[edit] Further reading

Pasted from <http://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor>

by Julia Ross, author of The Diet Cure

Eating Behavior Modification Strategies for Overweight Adults and Children

Medical Approaches to Weight Loss

Pasted from <http://www.healthyplace.com/Communities/Depression/treatment/alternative/food_moods.asp>

How did trends in the

Give 3 examples of TCA

What is the generic

List 2 common side-effects

Pasted from <http://www.psychotropical.com/MAOIs_Information_full.shtml >

The precursor for

• Remember 3rd phase of treatment: maintenance

Which other form of

○ CBT is as effective as meds for mild to moderate

• Like meds, psychotherapy can be said to have a mechanism of

• Se slide (new slide, not in these lectures)

• Cognitive model has a myriad of applications

• So what is COGNITIVE therapy? Distilled to its essence: 2 premises:

NB: all of us have negative core beliefs

What are the 6

Eg. Cognitive distortions: all or nothing thinking: you're either

• Cognitive therapy more than just being supportive

In a typical course of CBT

T/F: CBT is as effective as

Therefore a much higher

CBT and SRI

• SEE SLIDES MISSED IN HANDOUT LECTURE9

Take home messages:

○ Is as effective as meds for mild to moderate

What are the 2

List 3 criteria for

• Hypomani: 4 days Hypomania +

What are the 3 diagnostic

The leading cause of

T/F: Bipolar disorder is

T/F: Bipolar disorder MAY

T/F: Mood stabilizers

With respect to lithium

What is the generic