Table of Contents
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Lecture 1 (1/24) (Collins)
2
Boundary layers form around you, with layers of heat
gradually going from body heat to ambient.
Forced convection disrupts the boundary layers. Ex. fan.
o Evaporation Liquids absorb heat from skin and become vapor,
thereby cooling the animal. Ex. Sweating, panting.
o Radiation just letting off heat through skin. Absorbing heat
due to environment/sunlight.
Counter current heat exchange - When you 2 fluids
flowing in different directions (ex. Veins and arteries
that touch), very efficient heat exchange will occur.
o This is used by mammals and birds to prevent heat
loss in the extremities.
3
o Isoenzymes isoforms of enzymes. Only one can be produced at a
time. They have different optimal temps and MRs.
Heterotherms- Animals capable of varying degrees of heat production.
o Temporal Heterotherms - Tb (hibernation, day/night fluctuations)
Hibernation regulate Tb, but at much lower level).
Torpor (birds, small mammals suspend thermoregulation and
let Tb get very low.
o Regional Heterotherms different temps at a different parts
Ex. Testes in mammals.
Thermogenesis Converting chemical energy into heat
o Shivering thermogenesis muscle contractions make heat
o Non-shivering thermogenesis metabolizing fat to make heat
Brown adipose tissue (BAT) is a specialized fat for this.
Its found in neck/shoulders in mammals. It heats up
quickly and is highly vascularized.
Temperature is regulated using 3 components. (negative feedback)
o Sensor measures level.
In humans, this is in preoptic area/anterior hypothalamus
o Integrator compares level to set point and controls effector.
Set point the temperature its supposed to be at.
In humans, this is in the same area as the sensor.
o Effector Regulates everything so it returns to the set point.
In humans, effectors are shivering, BAT, etc.
Pyrogens are fever producing substances
o Exogenous pyrogens are very potent and produced by gram negative
bacteria.
o Endogenous pyrogens are produced by the body itself (like from
White blood cells)
They can also be released due to exogenous pyrogens.
6
o Colloids- large negatively charged proteins.
Major Cations (positive ions): Na+, K+, Ca2+.
o In Plasma Na+ high
o In ICF- K+ high. Ca2+ very low.
Major Anions (negative ions): Cl-, bicarbonate Hco3-, Phosphate ions.
o In plasma: Cl- and bicarbonate.
o In ICF: phosphate
Balance of charge the number of charges has to be identical (11+,
11- ) but the actual number of ions doesnt have to be equal.
Electrical disequilibrium
o Potential difference of about -70mv on the cell membrane
This is the resting membrane potential
This is the difference in potential between the ICF and ECF
Negative inside cell, positive outside.
Membrane potential has many causes
o Separation of the electrolytes between compartments is one.
Permeability of membrane drives the electrolytic imbalance.
Not really the actual change in conc. Of ions!!!
More channels, more permeability.
o Potential can pull ions in as well. called the electrical force
This will lead to the electro-chemical gradient.
Equilibrium potential is the voltage generated in the membrane for a
single ion that the membrane is permeable to.
Equilibrium potential can be calculated using the Nernst equation.
o Nernst potential = equilibrium potential. (units are millivolts)
o It only applies to one ion at a time!
61 []
o 61 is a gas constant and all = ( ) (10 ([] ))
o Z = valence electrons.
so for ex. +1 for K+; -1 for Cl-; +2 for Ca2+
Goldman-Hodgkin-Katz equation
o Predicts the resting membrane potential for several permeable
ions
[ + ] + [+ ]
o 61 is a gas constant and all = 61 ( [ + ] + [+ ]
)
o P is the permeability of the specific ion
Permeability are relative
o K really dominates the equation... Pk is almost 40x Pna
o If you are adding other ions to the equation, remember that for
negative ions the concentrations must be flipped (in/out)
Conceptualizing the Goldman equation:
7
o THINK PERMEABILITY, NOT ION CONCENTRATION
Assume that all concentrations are the same. Only
permeability changes.
o When things are logged, log (1) = 0. All logs over 1 get more
positive as you increase value. All logs under 1 get smaller
when you decrease value
o What this means is that as the numerator of the fraction
increases, the voltage increases.
o When the denominator decreases, the voltage increases.
o Ex. K is more on the inside than out. So it looks like (5/150)
When you increase the permeability, the denominator will
increase more than the numerator. This means voltage
decrease.
Carrier proteins move ions and substances across the membrane.
o There are 3 types:
Uniport only transports 1 molecule in one direction
Antiport pumps 2 things in different directions.
Symport secondary transport move 2 molecules in 1 way.
o They are never open to both the ECF and ICF at the same time
o Some use ATP, others are facilitated diffusion.
o Some pumps are electrogenic pumps they help maintain the
electrochemical gradient in the membrane.
o Ex. Na/K pump pumps out Na, and pumps in K.
Channel proteins form either open channels or gated channel
o They form a pore continuity between ECF and ICF.
o Open channels dont open/close. They stay open. Ex. aquaporins.
o Gated channels are very important. 3 types:
Mechanically gated channels
Voltage gated channels (Gated by Na, K, Ca, etc.)
Chemically gated channels (ligand gated channel)
CFTR (cystic fibrosis transmembrane regulator)
o A chemically/ligand gated channel. Its a Cl- channel.
o cystic fibrosis is a disease when CFTR isnt able to be inserted
Disease caused by mucous becoming thick and sticky
o CFTR is regulated by the level of ATP inside the cell.
o In normal conditions cl- and na+ flow in, H20 cant go through
membrane, so the conc. of water outside increases dilutes
sweat.
o If Cl- cant go into cell (disease) the sweat is really salty.
o In resp. tract, Cl- leaves cell and brings water with it...
This makes a saline layer that forms under the mucous.
Without saline layer, Mucous will clog up the bronchi
and kill you.
8
Lecture 7 (2/14) (Cabot)
10
o In the node of Ranvier are where the voltage gated channels are.
o The myelin helps to speed up the reaction because instead of
having the action potential generated every mm, they are only
generated at the nodes of Ranvier, allowing the signal to leap
down the axon, instead of say, crawling.
This is called saltatory conduction.
o Myelination allows very fast speed of propagation.
During an action potential, there is a time interval, called the
absolute refractory period.
o During this, its impossible for the membrane to fire another
action potential.
This is due to closed inactivation gates on the Na+
channel.
o This prevents the signal from going back up the way it came.
o The period occurs on the upstroke and repolarization phases, as
they are above the threshold.
The relative refractory period occurs during the hyperpolarization of
the cell
o This is when some of the inactivation gates have opened, but not
all.
o During this, you need more than the threshold to fire another
potential.
The extra power needed lowers as you get close to normal.
Know the difference between Graded and Action Potentials!
11
There are 2 types of physiological communication between cells:
o Electrical communication is not receptor-mediated
o Chemical communication requires receptor mediation
Gap junctions are a form of electrical communication.
o 2 connexin proteins on each membrane join together to form a
pore.
o Syncytium when cells are so tightly connected to each other
that they act like a single massive cell.
Chemical communication is done through the use of many signal
molecules
o A Ligand is a primary (first) chemical messenger.
o The ligand can go to any cells in the body.
However, it can only invoke a response in a cell with the
receptor for that specific ligand.
o Many different types of cells can have different reactions to
the same ligand.
This is due to the receptor and how it recognizes the
ligand.
3 types of chemical communication:
o Contact dependent signaling one membrane has specific
carbohydrates or proteins that match a receptor on the other
cells membrane. Ex. antigens in immune system.
o Local signaling: a cell releases the ligand for use in the local
environment.
Autocrine the messenger released by the cell also binds
to its own membrane, thereby causing changes on itself.
Paracrine the ligand affects neighboring cells.
Synaptic transmission is a specialized form of
paracrine signaling in the nervous system.
o Endocrine system Endocrine cells release hormones into the
blood stream. This allows for widespread signal transduction.
Receptors on target cells are required for the hormone to
have an effect.
Neuralhormone neurons can insert special hormones into
the blood stream.
Steps of the simple chemical signaling pathway
o A ligand binds to a valid receptor.
o The receptor, changes the conformation. And opens an ion channel
o The ion channel will lead to a cell response.
Some pathways have many relay molecules in a signal transduction
pathway
o The receptor activates relay molecules.
Typically the first one is a G protein.
12
Substance A will activate substance B, which will activate
Substance C
Substance C will then send out a secondary messenger, like
Ca2+.
o All of these leads to signal amplification and major changes.
o This pathway is the most common.
There are 4 types of receptors. We only need to know 3 of them:
o Ligand gated channels
o G protein coupled receptor
o Receptor enzyme system.
Ligand gated channel
o Binding of the ligand leads to an ion channel opening. Generates
voltage change cell response.
o Example : ACh (acetylcholine) at neuromuscular junction
ACh is a neurotransmitter that binds to the nicotinic ACh
Called this because nicotine can also bind to this
receptor and produce the same response.
Ach causes the ion channel to open. This channel allows Na+
to come in, and K+ to leave the cell. Cell depolarizes.
A depolarizing graded potential is generated.
Antagonist venom from the snake called a krait will block
the receptor, and cause paralysis leading to death.
G Protein coupled receptor, opens ion channel (simple)
o A ligand binds to the receptor it changes the G protein thats
attached to the receptor G protein separates into 3 parts
the 3 parts go and make things happen.
o Example: ACh binding to a G protein, opening an ion channel.
ACh binds to the muscarinic receptor
Called this because muscarine is a toxin from a
poisonous mushroom that activates the receptor too.
G protein separates into the subunit and a / subunit.
The / subunit opens a K+ ion channel. Cell hyperpolarizes
Antagonist drugs that block this receptor lead to pupil
dilation and increased heart rate.
G proteins can generate a secondary messenger instead. (complex)
o Ligand binds to receptor, G protein activates, and separates
either the subunit or the / subunit activate an amplifier
enzyme this enzyme converts an inactive secondary messenger to
an active one Secondary messenger causes cell response.
o Example: G protein-coupled adenylate cyclase-cAMP system
Ligand binds to receptor and G protein splits
13
Active subunit activates the membrane protein adenylate
cyclase.
Adenylate cyclase takes ATP and generates cAMP
cAMP activates PKA, which goes around phosphorylating all
kinds of different proteins.
o Example: G protein coupled phospholipase C system
Ligand binds and G protein splits
Active subunit activates the protein phospholipase C
Phospholipase C breaks up membrane phospholipids called
PIP2 into IP3.
IP3 binds to a receptor on the Ca2+ ion channel of the
endoplasmic reticulum (stores Ca2+)
Ca2+ leads to smooth muscle contraction.
Different receptors have different responses
o Epinephrine will cause dilation in bronchi
It uses an adenylate cyclase system for this.
The Ca2+ secondary messenger causes contraction.
o Epinephrine will cause dilation in arteries
It uses a adenylate cyclase pathway instead
This leads to relaxation.
Tyrosine-kinase receptors
o When ligands bind, the two proteins of the receptor come
together and activate They become phosphorylated and can
activate up to 6 relay proteins
o Example: Insulins (hormone) mechanism of action
Insulin is released due to high glucose levels in the blood
It binds to the receptor, activating lots of reaction
There are transporters that are waiting in vesicles to be
added to the membrane
The activated receptor helps the vesicles attach to the
receptor, which allows more glucose to come into the cell.
There is only pathway that doesnt use the cell membrane
o Special ligands can pass through the membrane and bind to
enzymes inside the cytoplasm or in the nucleus.
The ligand must be hydrophobic, lipophilic, and small.
Steroid hormones bind to cytosolic receptors
Thyroid hormones bind to nuclear receptors.
The receptor determines the response, not the ligand!
Synaptic transmission: transmission from a neuron to other cells.
o Action potential reaches the terminal of the synapse.
o Voltage gated Ca2+ channels open, and Ca2+ flows in.
o Ca2+ causes the exocytosis of neurotransmitter.
14
It binds to the vesicles and causes them to fuse with the
membrane and dump the load.
Synaptic transmissions must be stopped once theyre done
o Glial cells can absorb the neurotransmitter.
o You can have the neurotransmitter enter the blood stream
o You can chop up the neurotransmitter with an enzyme
This is the case of ACh.
AChE degrades Ach into 2 parts acetyl and choline
The choline goes back into the cell to be reused
15
------------------------- Begin Midterm 2 Material -----------------------
Muscle Terminology
19
Myofibrils do the
contracting.
Excitation
Somatic neurons send a
single through the
nerve and synapse on
the neuromuscular
synapse.
Motor unit a motor
neuron and all of the
muscle fibers that it
innervates.
o Each muscle fiber
is only
innervated by one
motor neuron.
The motor end plate
(where the axon meets the muscle fiber) and the sarcolemma are very
different from each other.
What happens at the junction:
o The action potential arrives at the axon terminal, and ACh is
released.
o ACh binds to the nicotinic ion-gated channel. Both Na & K can
flow. The motor end plate depolarizes a lot. It sends a graded
potential outward.
To stop the signal, AChE chops up ACh at the motor plate.
20
o The sarcolemma membrane picks up the graded potential and turns
it into an action potential that propagates along the sarcolemma
and down the T-tubules.
o As soon as the action potential reaches the T-tubules, it opens
a Ca2+ port in the SR.
o The Ca2+ leads to the contraction of the sarcomeres.
Properties of the neuromuscular junction
o Specialized synaptic junction between an motoneuron axon
terminal and a skeletal muscle fiber
o The motor end plate potential generated by the synaptic release
of ACh is always a graded, depolarizing potential.
o The amplitude of the end-plate potential is always above the
threshold for action potential generation, and the subsequent
conduction of the action potential into the t-tubules
o When a motor neuron axon terminal depolarizes, and releases ACh,
the underlying muscle fiber contracts.
Skeletal and cardiac muscles are called striated muscle due to the
sarcomeres.
Myofibril structure
o Thin filament
Actin
Tropomyosin (regulatory proteins)
Troponin (regulator proteins)
Tropomyosin runs through the actin. Troponin ____
o Thick Filament
Myosin has 2 globular heads. Each head has 2 binding
sides.
1 binding site is for the actin
The other binding site is for ATP
o There are 2 proteins that help give structure
Titin holds the myosin thick filaments.
the longest protein in the body
Nebulin holds the actin thin
filaments.
Sarcomere goes from Z disc to Z disc.
A band is where all of the myosin is.
The H zone is where you have no overlap of
actin and myosin filaments.
M line (center) is where all of the tails of
the myosin are.
I band is where theres no myosin, only actin
o Center of I band is the Z line/disc.
21
When a sarcomere moves the actin filaments slide over the myosin
filaments
o I band and H zone get smaller.
How sarcomeres contract
o At rest, Tropomyosin is like a string that rests on top of the
active sites of the actin.
o Troponin is a calcium binding molecule. It is attached along the
Tropomyosin.
o Calcium binds to troponin, while causes the Tropomyosin to
uncover the active sites of the actin.
o The energized myosin head binds to the exposed active sides and
forms a crossbridge.
o When ADP and Phosphate released from the myosin head, the power
stroke happens the myosin head pivots, moving the actin
filament back (causing contraction)
o ATP binds, and is used to release the myosin from the actin.
o Myosin head returns to original position with high energy and an
ADP and Phosphate molecule.
o Calcium unbinds from the troponin and calcium pumps use energy
to bring the calcium back into the SR.
Rigor mortis a few hours after death, the body stiffens up, because
the myosin molecule cannot dissociate from actin due to lack of ATP.
Roles of Ca2+
o It causes release of ACh at the junction
o The resulting action potential down the T-tubule triggers the
DHP receptor (DHPR). DHPR opens a significant ion channel.
Theres a mechanical foot protein that connects the DHPR to the
ryanodine receptor (RyR). The RyR is a Ca2+ channel in the SR
cistern. When DHPR is triggered, the RyR opens, and Ca2+ comes
out. RyR is really what causes the main Ca2+ release, not DHPR.
24
The AV node helps delay the ventricular contraction so it
happens after the atrial contractions.
Also ensures that the heart contracts from the apex, and
not the base.
Cardiac muscles arent innervated with nerves. Only electrical
signals control them.
o Membrane potentials flow thorough the gap junctions of cardiac
cells called intercalated discs.
o The cells are so interconnected that the cells act as a single
fiber.
o They also dont have neuromuscular junctions.
SA Node cells are autorhythmic They generate own cells.
o They are 3 types of voltage ages ion channels: Na, K, and Ca2+.
o Na+ channel is very different its called an HCN Channel.
It has no inactivation and activation gates.
It opens to both Na+ and K+. its non-specific
F-type (Funny) voltage-gated channel.
The repolarizing of the membrane causes the opening of the
channel.
3 phases of the action potentials:
o Pacemaker Potential: due to the opening of funny channel.
o Depolarization
o Repolarization.
Action potential at SA Node:
o When Na+ gate opens, the depolarization of the membrane opens
the voltage gated Ca2+ gate at a threshold. This causes the rise
of AP.
o This process takes a long time 250-300 ms (2-3 ms normal)
o Regular K+ channel ends the AP.
Action potential at muscle: google
o The opening of the gated channels led to a movement of ions
through the gap junctions into the next cell.
o Muscle cells have almost no permeability to the Na+ ions.
o During repolarizing of the membrane, voltage gated Ca2+ ions
come in.
Slows down the repolarizing and leads to the really long
action potential.
Cardiac muscle respond to action potentials a little differently:
o In skeletal muscles, the opening of the DHPR calcium channel was
insignificant.
The foot protein would open the RyR channel in SR.
o In cardiac muscles, there are no foot proteins; everything is
dependent on the DHPR calcium.
25
Cardiac cells get Ca2+ from the ECF due to the DHPR.
o The calcium released from the DHPR channel opens the Ca2+ RyR
channel in the SR. (Calcium induced calcium release)
o Cardiac cells must use a passive protein pump to pump out the
Ca2+ back out to the ECF using the inward flow of Na+ to power
the pump.
Cardiac action potential has a huge refractory period for almost 250
ms. This prevents the contractions from summating and reaching a
tetanus state (max tension.. fully contracted, and not relaxing)
o Autorhythmic cells have no refractory period.
26
o QRS complex ventricular depolarization
Q contraction of interventricular septum (separates left
and right ventricles)
R contraction of the ventricles from the apex starts.
S completion of the contraction.
Contraction of the ventricles starts at the top of the R
phase.
o T Wave.
Repolarization of the ventricular muscle.
Ventricular fibrillation ventricles are contracting all out of
whack.
o Damage to ventricular muscle resulting in uncoordinated
contraction. This can be lethal.
A defibrillator works by depolarizing the heart, which stops all of
the activity. As the heart repolarizes, the SA node will start
sending action potentials again. This resets the system.
Blood pressure
o Systolic pressure maximum pressure exerted by the blood
against the artery walls.
Results from ventricular systole
Normally around 120 mmhg.
o Diastolic pressure lowest pressure in the artery
Results from ventricular diastole
Happens right before ventricular systole.
Usually around 80 mmhg.
o Pulse pressure difference between systolic and diastolic
pressure.
Blood pressure measurements
o Pump up the blood pressure cuff and collapse the artery
There will be no sound b/c theres no flow.
o Once you start to lower the pressure, youll hear sounds
The pressure when you hear the sounds is the systolic.
The noise is due to turbulent flow through the constricted
the artery. (Period of turbulent flow)
o Once the sounds stop, you reach the diastolic pressure.
Once the pressure releases, the artery goes back to normal
and the turbulent flow stops. (Period of laminar flow)
MAP is the pressure in the aorta.
Its assumed that when vena cava enters the atrium, their
pressure is 0.
o Mean arterial pressure (MAP)= Diastolic pressure + 1/3 pulse
pressure
27
Rough estimate.
o MAP = Cardiac output (CO) X Resistance to blood flow (R)
MAP is a dependent variable; CO & R are independent
variables.
CO (L/min) = Heart rate (beats/min) X stroke volume (L/beat)
Heart rate is regulated using SA node pacemaker cells (~ 100 bpm)
o Unregulated (denervated) heart rate = 100 beats/min
o But a normal resting heart rate is 72-80 bpm.
ACh activation of muscarinic receptors in SA nodal cells decrease
heart rate (parasympathetic nervous system cardiac innervation)
o Parasympathetic simulation hyperpolarizes the cells. This causes
the action potential to be generated slower.
NE,E activation of the -adrenergic receptions in the nodal cells
causes increases in heart rate.(sympathetic system innervation)
o This depolarizes the cells, and increases the slope of the
action potential, causing the potentials to be faster.
Increasing the heart rate 3 ways to do it
o Increase the -adrenergic stimulation from the sympathetic
system.
o Withdraw the Muscarinic stimulation from the parasympathetic
system.
o Hormonal control of heart rate add more plasma epinephrine.
Decrease the heart rate
o Increase the muscarinic stimulation from the parasympathetic
system. (most effective way to do it)
o Withdraw the -adrenergic stimulation from the sympathetic
system.
o Decrease levels of plasma epinephrine.
Stroke volume the amount of blood pumped by each ventricle each
heartbeat. The average is around 70 ml per beat.
o It represents the difference between the EDV(max amount of blood
in the ventricle) and the ESV (blood left over in the ventricle)
o As you increase the EDV, the stroke volume will increase.
Very unique property of
the heart there is a
range where the heart
muscle can match the
increased volume put
into the ventricle with
output.
Frank-starling curve.
28
This is important for when venous return increases
The venous system can hold blood it holds up to 61% of blood.
o Squeezing the veins will pump a lot more venous blood into the
heart.
The heart will have to compensate for this by increasing
the stroke volume.
Venous return must equal cardiac output.
Cardiac muscle can also change stroke volume and tension development
by altering contractility.
o Contractility an increase in
developed tension without a
change in the resting length.
o For any given EDV, if you
increase contractility, you
increase the stroke volume.
o This allows increased CO while
increasing rate.
o Sympathetic system also innervates ventricular muscles cells.
It causes an increase in contractility.
Recap:
Cant be tetanized.
Over a large range of
initial muscle lengths,
increasing muscle length
increases force development
(frank-sterling law of the
heart)
Can increase contracility
increase tension developed
without changing muscle
length.
29
o Its composed of Smooth muscle with layer of epithelium and its
under control of sympathetic system. It also responds to
hormones.
o It also responds to paracrine messengers
Blood pressure decreases as it flows through the system, starting
very high at the aorta, and near 0 at the venae cave.
o This is because there is a decrease in flow resistance (R in MAP
= CO X R). (CO constant) High resistance High MAP.
Resistance to blood flow in the system is influenced by:
o Blood flow is opposed by friction.
o Length of vascular system
o Blood vessel radius
o Viscosity of blood (hematocrit)
o Increasing/decreasing resistance manually.
R= (8L)/( r4)
o 8 and pi are constants so they arent important
o L = Length of vascular system. This is constant unless you are
obese (fat tissue is highly vascularized)
o = viscosity of blood. Constant unless at high altitudes.
o R = radii of arterioles. This is important since it is raised to
the 4th power. Very small changes have very large impacts.
Very small decreases lead to very large increase in MAP.
During normal activity, the sympathetic system makes sure the
arterioles are always contracted at rest. (called vasomotor tone)
NE attaches to receptors that cause vasoconstriction
Withdrawing the NE will cause vasodilation.
Hormones such as epinephrine, angiotensin and vasopressin cause
vasoconstriction. Epinephrine can cause dilation on -receptors too.
Local tissue can cause vasodilation due to paracrine resources such
as oxygen
Nitric oxide (EDRF+) also causes vasodilation (Viagra)
Histamine will also cause vasodilation.
Changes in MAP due to peripheral resistance (CO Constant!)
o Will increase if blood vessel length increases (morbid obesity)
o Will increase is hematocrit increases (high altitude)
o Will increase if there is systemic vasoconstriction (decrease in
arteriolar radius)
o Will decrease if there is systematic vasodilation happens.
Capillaries are the exchange vessels. They do metabolic exchange.
o They deliver all kinds of products O2, CO2, glucose, etc.
o They do primary and secondary active transport.
30
o Transcytosis movement of very large molecules (endo &
exocytosis)
Bulk flow is important.
o Mass movement of water and dissolved solutes between blood and
interstitial fluid.
o Function isnt exchange of nutrients, electrolytes, etc but
rather the distribution of extracellular fluid (ECF)
o Capillary wall is highly permeable to water and all solutes, but
not large proteins.
Proteins give the compartments different osmotic pressures.
This helps maintain water distribution.
ECF distribution is a balance between capillary blood
pressure and the protein-induced osmotic pressure.
o Filtration direction of movement is out of the capillary into
the interstitial space into the capillary
o Absorption - direction of movement is into of the capillary into
the interstitial space into the capillary
o At the arterial end of the capillary, the blood pressure is
greater than osmotic pressure, and fluid flows out of the
capillary. (Filtration)
o At the venule end of the capillary, the blood pressure is lower
than the osmotic pressure, and fluid flows into the capillary.
o More filtration happens than absorption though. (~20L/day
filtrated, 17L/day absorption)
Because you have more filtration than absorption, the lymph system
absorbs the remaining 2-3 L/day and returns it back to the blood.
If you have more absorption than filtration, it leads to interesting
consequences.
o If you bleed, the body can do this to get more fluid into the
blood.
Baroreceptors are nerve fibers that lie in the blood vessel and sense
the blood pressure in both the aorta and the carotid artery.
o Increasing the MAP increases the frequency of firing action
potential of these nerves. And Vice versa.
o The Medulla will interpret the information and generate an
appropriate action. It fixes what needs to be done.
It can change the SA node frequency using the
parasympathetic system. (Heart Rate)
It can use the sympathetic system, it can make the
ventricles contract with more force. (Stroke Volume)
It can also use sympathetic system for changing radius of
arterioles and veins. (resistance of the arterioles)
31
Orthostasis Going from a laying down position to a standing up
position. I stood up too fast; I feel lightheaded
o Blood rushes out of the brain suddenly
o Decrease in venous return leads to EDV and stroke volume
decrease. This leads to a decrease in CO and MAP.
o Baroreceptors drop in activity and the brain responds by
increasing sympathetic cardiac and peripheral nerve activity.
You also drop the parasympathetic cardiac nerve activity
(most effective way)
o All of this results in increase heart rate, stroke volume and
resistance. This in effect increases MAP.
Hypertension chronically increases MAP, BP greater than 140/90.
o Associated with chronically increased total peripheral
resistance, due to decreased arteriolar radius.
o Baroreceptors reset to a new set blood pressure.
o Renal dysfunction can be the cause of hypertension.
o Its important to treat because the heart is the most affected
organ
Heart has to work harder.
Heart becomes pumped up with muscle and its irreversible.
This is called hypertrophy.
The ventricles get smaller and smaller, and the person will
die due to heart failure.
32
o Hypertension also increases the chances of stroke and
cardiovascular disease.
Exercising
o EDV, SV, Heart Rate, all go up, leading to a CO increase of 220%
o But the resistance drops, so that the MAP only rises 121%
This is so that more blood gets to the muscle
o Skeletal muscle gets almost 3 times the amount of blood
o The system gets the more blood needed from the veins.
Kidneys are connected to the ureters which empty into the bladder
Micturition The act of urinating.
o It is under voluntary and involuntary control.
o The outlet of the bladder is wrapped in skeletal muscles.
(volitional control)
o Smooth muscle is controlled by parasympathetic and sympathetic
nerves. It is involuntary.
During filling.
o The detrusor muscle(main muscle of bladder) is relaxed allows
the bladder to get bigger and bigger. Sympathetic innervation.
o Skeletal muscle keeps the bladder closed.
o After a threshold however, the brain causes a reflex and causes
micturition.
During micturition
o The skeletal muscle becomes inhibited.
o The detrusor muscle becomes stimulated and contracts.
Function of the mammalian Kidney
o Elimination of metabolic waste products
Urea protein catabolism
Uric acid - Nucleic acid catabolism
Creatinine - Muscle creatine catabolism
o Regulation of Water and inorganic electrolyte (Na+,etc.) & pH.
o Removal of foreign chemicals (drugs such as penicillin, food
coloring, pesticides, etc.)
o Gluconeogenesis Generating glucose (extreme fasting only)
o Section of hormones and an enzyme
Erythropoietin (Stimulates RBC production)
1,25-dihydroxyvitamin D3 (important for Ca2+ homeostasis)
33
Renin(enzyme)controls formation of
angiotensin II, which influences
blood pressure and Na+ synthesis)
A nephron is the function unit of the kidney.
They are 2 locations
Cortical nephron
Juxtamedullary nephron.
Not going to be discussed.
Nephron blood flow
o Glomerular capillaries are arranged in a
ball called a glomerulus. This is inside
a capsule called bowmans capsule (also
called corpuscle)
The space between capillaries in
the capsule is called the bowman
space.
o There is an incoming afferent arteriole, and then the efferent
arteriole leaves
There is no gas exchange here.
o The efferent arteriole
then branches out into
lots of capillary beds
that surround the
tubules all the way
down. (called
peritubular capillaries
in the cortex(top) part)
This is because 99%
of the stuff that
are filtered in the
corpuscle is reclaimed into the blood stream.
So you need lots of vascularization!
Nephron Tubules.
o From Bowmans capsule (space), everything flows into the
proximal convoluted tubule (PCT), which goes into the descending
Loop of Henle.
o The loop then ascends, and goes into the distal convoluted
tubule (DCT), which then empties into the collecting duct.
34
Juxtaglomerular apparatus (JGA) The
distal tubule becomes in close proximity
to the afferent/efferent arteries.
Composed of:
o Granular cells synthesis and store
the enzyme renin.
Innervated by sympathetic
nervous system.
o Macula Densa Cells in the tubules
that are close to the granular cells.
Renal processes
o Filtration - happens in the bowmans
capsule)
o Reabsorption happens in capillaries
o Secretion some solutes are removed
from the blood of the peritubular
arteries and secreted by the tubular
cells into the filtrate (tubes)
o Filtration amount reabsorbed +
amount secreted = amount excreted.
o Most substances are either reabsorbed or secreted, but not both.
Transport
o Proximal convoluted tubule (PCT)
H+ is secreted.
Bicarbonate, NaCl, Water, Glucose get reabsorbed
o Loop of Henle
H20 & NaCl is reabsorbed.
o Distal tubule - under physiological regulation
o Cortical/Medullar Duct-
K+ is secreted. H20 is reabsorbed.
Fluid in the system
o In Bowmans capsule and end proximal tubule about 70% of the
filtrate is reabsorbed. Osmolarity remains at plasma level (300)
o At the end of the loop of Henle, 90% is reabsorbed, osmolarity
is 100 mOsm.
o At the end of the collecting duct, osmolarity varies.
Physiological regulation
o Forces generating glomerular filtration
o Regulating of the filtration rate.
o Regulation of reabsorption
o Regulation of secretion.
There are many forces that affect filtration
o Glomerular hydrostatic pressure blood pressure ~60mmhg.
35
More than regular capillaries (~35 mmhg)
o Capsular hydrostatic pressure oppose filtration - ~15 mmhg
The capsule is full of water, so it has a pressure inside.
o Glomerular osmotic pressure opposites filtration - ~28 mmhg
Proteins arent being filtered. Therefore its making a
pressure. (see bulk flow)
o Net filtration pressure: ~17 mmhg. (can never be negative)
Glomerular filtration rate (GFR) rate at which kidney is filtering.
Dependent on the net filtration pressure. ~125 ml/min
o GFR is autoregulated by the kidney.
o The diameter of the afferent arteriole changes
It constricts and reduces GFR. And vice versa.
GFR can be regulated using 2 ways
o Myogenic autoregulation
Increased blood pressure increases the outward pressure
against the sidewall of the arteriole. This causes the
artery to contract more.
Its very effective, and maintains a normal GFR for all
blood pressures between 80 and 180 mmhg.
o Tubuloglomerular autoregulation
Increase in GFR is sensed by the macula densa cells in the
tubule.
The macula densa sends a paracrine signal to the afferent
arteriole to contract.
This causes decrease in GFR.
o Neural and hormonal control of the afferent arteriole.
For ex. epinephrine causes vasoconstriction.
Regulation of reabsorption in proximal tubules.
o Active transport: Na+ flows into the tubule. It is passively
transported into the epithelium cells in the tubule. Its then
pumped using the Na/K pump into the interstitial space. The bulk
flow causes Na+ to go into the peritubular capillary blood.
o Secondary Active Transport: Glucose enters through a Symport
with Na+ ions. Na+ gradient provides energy for the glucose to
be pushed into the cell. It then diffuses out of the cell on the
other side.
In normal conditions, all glucose that is filtered is
reabsorbed.
With high blood sugar, all glucose cant be reabsorbed
Glucosuria pissing out glucose.
o Diffusion
Urea can diffuse through membranes.
So a concentration gradient must be formed for it.
36
Active transport of NaCl from the filtrate into the
peritubular capillaries causes water to follow.
So the concentration of urea has gone up since water
concentration has gone down.
This way, urea goes back into the blood stream.
Secretion can be regulated as a renal process as well.
o Normally involves transport against a concentration gradient.
o It occurs in the PCT and the DCT
o It handles H+ and K+
Diabetes Mellitus type 1
o Commonly autoimmune disease destruction of 1 cells in pancreas
o Insulin hyposecretion or hypoactivity.
Person has to intake artificial insulin
o Hyperglycemia elevated levels of plasma glucose.
Leads to glucosuria
This leads to polyuria (osmotic diuresis) increases the
amount of urine produced
Polydipsia youre going to always really thirsty.
Polyphagia youre going to always be hungry.
Causes damage to blood vessels, eyes, kidneys, CNS, etc.
Type 2 Diabetes 97% of all diabetics.
o Insulin resistance inability to recognize proper levels of
glucose and get rid of it.
Skeletal muscles and all wont really get glucose.
o Glucose tolerance test can find if theyre diabetic or not, but
they cant differentiate between Type 1 and Type 2.
o Hyperglycemia high blood sugar.
o If untreated, people will get atherosclerosis, renal failure,
blindness, neurological damage, etc.
o About 70% of people die from a cardiovascular disease.
Water reabsorption
37
o Water moves down its concentration gradient due to Na+
generating the gradient. (Na+ leaving makes water leave)
Na+ Reabsorption and Water reabsorption are independently regulated.
Water movement -
o Can only occur if epithelial cell membranes are permeable.
o H2O reabsorption is high in the PCT.
H2O and Na+ are reabsorbed in constant amounts in PCT.
o H20 permeability in the collecting duct can be high or low and
is physiologically regulated.
Hormonal control of H2O reabsorption
o In the hypothalamus are sensors that sense the osmolarity of
blood.
o If theres an increase in osmolarity (decrease in water), urine
production is slowed.
AVP is released
It decreases the generation of urine by reabsorbing more
water.
AVP is (arginine vasopressin), also called ADH (anti-diarrheic
hormone) is a hormone released by the hypothalamus/pituitary gland.
o It stimulated by many things.
Changes in osmolarity, volume or pressure of blood
Also released due to angiotensin.
o It binds to the vasopressin receptors on the collecting tubule
cells.
Receptor is a G protein receptor that sends out a secondary
messenger, cAMP.
o cAMP facilitates the delivery of vesicles to the apical
membrane. The vesicles have aquaporin channels.
o Doing this increases the permeability of the membrane to water
More water will be reabsorbed.
Diabetes Insipidus Has nothing to do with the other diabetes!
o H2O Diuresis you piss out tons of water.(25L/day vs 1.8 L/day)
o Occurs When AVP secretion and/or receptors dont work.
Water cant flow through concentration gradient.
H20 diuresis is different from osmotic diuresis
o H2O diuresis is not due to excessive solute loss
o Osmotic diuresis is water loss due to excessive solute loss. .
Na+ reabsorption
38
The kidney can produce and store renin in the JG cells. It can also
release them at the right time.
RAAS Steps:
o Stimulus to generate renin release is severe drop in MAP.
o Decrease in MAP causes brain to try and increase MAP.
Renal sympathetic nerve synapses on the Granular (JG) cells
Cells will then release Renin
o The liver generates angiotensinogen all of the time..
Renin chops off a piece of the angiotensinogen and makes it
angiotensin I.
Angiotensin I is a biologically inactive peptide.
o Many epithelium cells in the body have ACE Angiotensin
converting Enzyme.
Its particularly high in the Lung capillaries (~40%)
It converts Angiotensin I to Angiotensin II
Angiotensin II is biologically active.
o Angiotensin II has 2 different effects
It has a powerful effect of vasoconstriction in the
cardiovascular system. Causes increase in MAP.
Will cause GFR to decrease due to afferent arteriole
constricting.
It causes the adrenal cortex to synthesize and release the
steroid hormone aldosterone.
Because steroid hormones cant be stored due to being
lipophilic, they have to be made on the spot. This
takes a few hours.
o Aldosterone causes Na+ ion and water retention.
It affects the hypothalamus and causes release of AVP.
Aldosterone pathway:
o Aldosterone flows through the membrane and binds to receptors
inside the cytoplasm.
o The receptor-aldosterone goes into the nucleus and causes
protein production.
o 2 interesting proteins that are generated:
Increases synthesis/insertion of Na+ channels on the apical
(facing tubule) membrane.
Increases the permeability of the Na+ so it can be
reabsorbed so much.
Na+/K+ pumps are made. Na+ reabsorption increases a lot.
Water flows with the Na+ out.
39
Renal Regulation of K+
o Most abundant intracellular ion. ECF conc. is regulated.
Its critical to our survival.
o Important for maintain membrane potentials.
Processing of K+
o Its filtered.
o Its passively reabsorbed in the PCT.
o Its regulated in the collecting duct.
Increases in plasma angiotensin & plasma potassium leads to more
aldosterone.
o Aldosterone makes Na/K pumps that cause K to be pumped into the
cell. It also increases K+ channels on the apical side.
Causes K+ to be excreted.
2 Conditions due to K+ concentrations:
o Hyperkalemia: too much K+ depolarizes cells, can lead to
cardiac arrhythmias.
Things that usually wont reach threshold end up reaching
it.
Lethal its whats used in lethal injections.
40
o Hypokalemia: too little K+ - hyperpolarizes cells, can lead to
failure of respiratory and cardiac cells.
Graded potentials cant reach the threshold due to
hyperpolarization.
Clearance A useful way to measure renal function
o Its a non-invasive way to measure GFR
o Its defined as the volume of plasma from which a substance has
been completely removed per unit of time (cleared/time)
o Its a rate.
o To measure GFR, you need a substance thats filtered, but not
reabsorbed or secreted.
So filtered = excreted.
Inulin is this substance.
Process of clearance-
o Give someone an IV with inulin and measure how much you give and
what concentration. (lets say the conc. Is 4 inulin per 100 ml)
o Inulin will get filtered at the GFR rate. (lets say rate is
100ml/Min)
o Then you collect urine and analyze the rate. (so lets say
theres 4 inulin molecules. Then you know that GFR is 100ml/min)
o GFR = clearance of inulin.
If the clearance of a substance X is greater than clearance
of inulin, then its filtered and secreted.
If the clearance of a substance X is less than clearance of
inulin, then its filtered and reabsorbed.
If the clearance of a substance X is equal to clearance of
inulin, then its filtered, not reabsorbed, and not
metabolized.
Creatinine is the closest naturally occurring substance
with clearance values near those of inulin.
42
Humoral stimulus pathway example:
o Rise in plasma glucose inhibits cells in the pancreas and
stimulates cells in the pancreas to release insulin.
o Increased levels of insulin affect the liver and other cells.
Liver cells get affected by insulin
Glycolysis, glycogenesis, and lipogenesis are
increased.
Muscles and adipose tissue increase glucose transport.
o All of this leads to decrease in plasma glucose.
About insulin
o Half-life of 5 minutes (very short)
o Factors affecting release: plasma glucose, GI hormones, nerves.
o Target cells: liver, muscle/adipose tissue,
Brain, kidney and intestines are not insulin-dependent.
They take up glucose without insulin. This means that
if you have too much insulin and not enough glucose in
the blood, the brain will be glucose deprived (faint).
o Target receptor: tyrosine-kinase receptor.
o Actions: Lower plasma glucose, by increasing transport and use.
Increases synthesis in the
cell.
Glucagon is a peptide hormone that
follows the same pathway.
o It is released when cells in
the pancreas are stimulated.
Happens when glucose levels
get too low.
Also, cells are inhibited
from releasing insulin.
o Liver will then generate glucose
Gluconeogenesis and
glycogenolysis.
o Plasma glucose increases and you
get back to normal.
About glucagon
o Has a short half-life. 4-6
minutes.
o Stimulated by low plasma levels.
o Targets liver.
o Receptor is G protein-coupled adenylate cyclase with cAMP.
o Actions: gluconeogenesis and glycogenolysis in liver.
Neural Stimuli. Example pathway autonomic, insulin.
43
o Autonomic system sends an impulse down to a parasympathetic
ganglion, where it synapses and continues to the pancreas. The
pancreas then releases insulin.
Adrenal medulla pathway (sympathetic neural stimuli)
o Preganglionic sympathetic neuron synapses in the adrenal
medullas Chromaffin cells (wannabe neurons).
They have nicotinic acetylcholine receptors.
Channels open and the Chromaffin cell depolarizes, causing
ca2+ channels to open.
Ca2+ causes exocytosis of vesicles containing epinephrine
and some norepinephrine.
NE is both a neurotransmitter and a hormone.
E/NE bind to arteriolar muscle contraction ( receptors)
and bronchiolar smooth muscle relaxation ( receptors).
Neural control of hormones that release hormones etc. hypothalamus.
o Hypothalamus and pituitary gland are connected by neurons and
vasculature via the
pituitary stalk (called
infundibulum)
Pituitary gland has 2 parts
o Posterior gland is neural
tissue.
o Anterior gland is true
endocrine tissue.
Posterior pituitary gland:
o Has 2 hormones that it
releases:
o Oxytocin and AVP/ADH(See
kidney).
Oxytocin is used for
uterine contraction.
o Hormone is made and package
in cell body of neuron in hypothalamus. (green neurons in pic)
o Vesicles containing hormone are stored in posterior pituitary.
When youre drunk, you have to take a long piss. This is cause
alcohol inhibits AVP release.
Neurotransmitter is short distance. Neuralhormone is long distance.
Hormonal Stimuli complex endocrine pathways. AKA Hormone-ception.
o Stimulus causes hypothalamus to secrete a hormone. The hormone
causes an endocrine gland to release another hormone, which then
does the work.
44
Hypothalamus releases a hormone (Called a releasing
hormone) into a capillary bed called the median eminence at
the base of the hypothalamus.
This then goes to capillary bed of the anterior pituitary.
Anterior pituitary then releases the main hormone.
Capillary bed to capillary bed is called portal
circulation (connected via portal vessels)
Then this hormone can cause a release of another
hormone
o There are 6 anterior pituitary hormones.
CRH(Corticotrophin releasing hormone) Pathway (AKA stress pathway) :
o Stress causes CRH to be released from the hypothalamus.
o CRH is released into the capillaries of the median eminence. It
then passes through the portal vessels into the capillaries of
the anterior pituitary.
o CRH will cause the Anterior Pituitary to release the peptide
hormone ACTH adrenocorticotropic hormone) into the blood.
o ACTH will then bind to receptors in the adrenal cortex. Adrenal
cortex increases production of the steroid cortisol, which takes
a while to happen.
o Cortisol will then enter the blood stream. It causes increase in
blood glucose.
Cortisol is a glucocorticoid.
It promotes gluconeogenesis
Leads to hyperglycemia
Protein catabolism
Increases energy metabolism by mobilizing fat stores.
Depresses inflammatory and immune responses.
Vasoconstriction.
o Regulation: (negative feedback)
Increased levels of cortisol lower production of CRH and
ACTH. (long loop feedback)
ACTH levels also regulate CRH levels too. (short loop)
About Cortisol
o Steroid that is made from cholesterol.
Must be transported on binding globulin protein in blood.
o Half-life is 60-90 mins.
o Target receptor is intracellular (because its a steroid)
Giving external steroids reduces production of cortisol
o If this is prolonged, the cells that produce CRH/ACTh/cortisol
producing cells die.
Cushings syndrome: when you have too much cortisol production.
45
o You get a moon face with red cheeks.
o A buffalo hump fat deposits on the shoulder.
o Hypertension due to vasoconstriction.
o Increased abdominal fat.
o Easy bruising and poor wound healing.
Physiological responses to stress:
o Rapid response (HypothalamusAnt. Pit. adrenal cortex E/NE)
Increased CO, redirect blood flow, maintains BP
Maximized breathing
Increased sweat production.
Mobilizes carb and fat stores.
Increases glucose production and inhibits insulin.
o Prolonged response (CRHACTHCortisol)
Glucocorticoid response (cortisol)
Immunosuppression.
Fat breakdown.
Mineralocorticoid response.
Retention of sodium and water by kidney
BP will increase due to AVP & Angiotensin II.
46
------------------------ Begin Midterm 3 Material ------------------------
47
Internal defenses:
o Natural killer (NK) cells kills virally infected or cancerous
cells.
o Inflammatory response
o Fever.
Phagocytes they carry out phagocytosis.
o Theyll recognize something on the surface of the bacteria, and
then swallow it (endocytosis), and then merge with a lysosome,
which kill and digests the bacteria.
o They recognize bacteria based on carbs and lipids on the cell
walls. Also, tagging by the use of opsonins also helps
recognize.
Antimicrobial proteins
o Complement a series of 30+ proteins activated in a sequence.
When they come in contact with the bacteria, they make
holes in the wall of the bacteria, causing water and ions
to flow in, thereby bursting the bacteria.
This is called the Membrane Attack Complex (MAC)
Opsonin chemical mediator that binds to and tags a
microbe to promote phagocytosis.
Antibodies
Complement proteins. (called C3b)
o C3b acts as a ligand and triggers receptor
mediated phagocytosis in macrophages.
o Interferons
Its a cytokine it affects the growth and activity of the
microbe
It prevents replication of viral cells when they take over
host cells.
Infected cells will generate these.
o Natural Killer Cells
Has surface receptors that bind directly (but
nonspecifically) to virus infected cells and cancer cells.
Releases chemicals that induce apoptosis (cell death)
Inflammatory response Happens when skin/barrier is broken
o 4 signs: Swelling , Heat, redness, pain.
o Damaged cells and responding cells release chemicals
o Leads to vasodilation and increased vascular permeability.
o Chemicals cause the neutrophils in the blood to bind to the
endothelial cells in the blood vessels.
o Diapedesis- the cell squeezes out of the vessel.
o Chemotaxis cells move towards the infected cells via chemicals
Fever
48
o Most pathogens dont replicate well in high temperatures
o It enhances phagocytosis and a bunch of other immune stuff.
49
o They act as opsonins, the constant part (bottom part) acts as a
receptor for macrophages. This leads to phagocytosis.
o Antibodies help initiate the complement process, which create
the MAC.
o Antibodies clump and immobilize the antigens
o They neutralize viruses by surrounding and attaching to it.
T Cell Activation
o T cell receptors are 2 chained proteins embedded in the membrane
Are very different from the B cell receptors .
o T cell receptors cannot combine with an antigen unless the
antigen is first tagged with some of the bodys own proteins.
o Major Histocompatibility complex (MHC) proteins are the proteins
that the cell expresses.
MHC class I proteins are on the surface of all cells.
Except RBCS
The MHC proteins hold a piece of cut up protein from the
cell.
o T cells are born in the bone marrow, mature in thymus, and then
chill in the secondary lymphoid organs.
Cytotoxic T cell (CD8) activation
o They wander through the ECF looking at the surfaces of cells
looking for the MHC and the attached antigens.
If they find an MHC protein with virus dna on it, theyll
respond.
CD8 is the protein on the T cell that recognizes the MHC I.
o The T cell will release 2 types of paracrine molecules
Perforins they punch holes in the membranes of the cell.
Enzymes they go inside the holes and activate apoptosis.
o The T cell also clones itself a bunch of times, and some go to
storage.
MHC II proteins are found only on the surface of macrophages, B
cells, and dendritic cells. These cells are called APC cells
(antigen-presenting cells)
o MHC II proteins will show the chopped up antigen peptides.
o But cytotoxic T cells wont respond. Helper T cells will instead
Helper T cells use CD4 to recognize MHC II.
o Helper T cells help facilitate the response to the antigens.
They outnumber cytotoxic T cells by more than 2:1.
Helper T cell activation
o APC cells and Helper T cells match up with both the MHC II
complex, and another non-antigenic receptor.
o When this happens, the APC releases paracrine signals.
50
o The Helper T cell becomes activated and goes around activating
other responses.
o Activated Helper T cells can activate and help B cells.
They are needed for B cells to function normally.
o Activated Helper T cells also stimulate/activate cytotoxic T
cells.
Innate and Acquired (humoral and cell mediated) act synergistically
together.
Immune system failures
Autoimmune diseases incorrect immune response
o Type 1 diabetes
o Myasthenia gravis
o Multiple sclerosis
o Lupus
o Rheumatoid arthritis.
Overactive responses
o Allergic reactions. Can be lethal.
Lack of response
o Immunodeficiency diseases Primary or acquired
o AIDS is an acquired immunodeficiency diseases.
HIV/AIDS.
o HIV is an asymptomatic infection
o AIDS is basically destruction of the immune
system.
o Routes of transmission
Transfer of contaminated blood
Unprotected sex
Contaminated needles
Mother to fetus/child (Placenta or
breast milk)
HIV is a retrovirus that has reverse
transcriptase.
Process-
o Virus fuses with the cell and the capsid
(outer shell) proteins are removed.
o Reverse transcriptase helps synthesize a
DNA strand thats got the viral RNA.
o Virus uses cell machinery to produce lots
of copies of itself, and then sends them
out to infect some more.
51
HIV/AIDS Timeline:
o Virus infects and enters the
body, but lays dormant for 6-
8 years.
o After 6-8 years, it comes
back and destroys the immune
system by infecting the
Helper T cells.
Less Helper T cells,
means less activation of
CD8 cells and B cells.
o This leads to AIDS.
o AIDS leads to infection by
other regular microbes.
o This leads to death.
AIDS treatment strategy
o Drugs that prevent fusing of
the HIV virus to the CD8
cells
o Block Reverse Transcriptase
from transcribing viral DNA.
o Block Integrase from chopping up the nuclear envelope and
allowing Viral DNA from being inserted inside.
o Block HIV Enzymes from reassembling and activating the viral
DNA.
HAART Highly active anti-retroviral therapy.
o Cocktails of all of the aforementioned drugs.
o It lets HIV infected individuals live a long time.
58
Capillaries at the blood-brain
barrier dont let anything that
has a charge or polarization to
go through.
o So H+ cant go through.
H+ is produced in the CSF due to
increase in CO2 that crosses
through the blood-brain barrier.
o H+ changes in the CSF can
change the pH dramatically
o Decrease in pH is sensed by
the medulla, and rate is
increased.
In order for O2 to cause
changes, the partial pressure of
O2 needs to be below 60 mmhg in
the aortic arch (normal is ~100)
o This is rare- respiratory
drive is primarily controlled by CO2 levels.
Shallow Water Blackout
o Medical symptoms - Sudden loss of consciousness, amnesia, and
happens without warning
o Strikes typically happen within 15 feet of the surface.
o Physiological mechanisms for
shallow water blackout
Hyperventilation blows
off CO2, increases pH of
CSF, and decreases
respiratory drive. O2
levels remain the same
O2 remains the same
because its based
on hemoglobin,
which is almost
always full anyway.
O2 isnt very soluble
in blood.
Hypoventilation leads to
O2 drop, and huge CO2
increase.
This increases the
respiratory drive.
59
This leads to the breath hold time to decrease.
o Hyperventilation makes it so that it takes CO2 longer to rise to
the point where it doesnt trigger the urge to breathe, prior to
the O2 level reaching the blackout zone.
o On ascent from free dive, lungs re-expand and O2 pressure in the
lungs decrease.
Near surface, the driving force for O2 exchange approaches
zero.
Physiology of diving mammals and birds
o Animals with lower rate of O2 use can dive for longer periods of
time (low metabolism)
Either having it low normally (turtles) or reducing it.
o Diving animals have significantly increased oxygen capacity
Difference is minimal with lung capacity. Most of the
storage is done in the blood and muscle the most.
o Diving reflex neurological response due to water splashing on
face
Vasoconstriction peripheral blood flow is restricted.
Redirects blood to brain and heart.
Bradycardia heart rate and cardiac output drops.
Lowers metabolism and O2 demand.
60
o Unsaturated fats arent straight, and cant pack together, and
therefore are liquid at room temperature.
Animals are unable to make unsaturated fatty acids.
o Animals can easily use cis fats, but not trans fats
Trans fats are synthesized in factories, cis by animals.
Carbohydrates
o Carbs are all composed of glucose molecules. They are linked
between the 1 group and 4 group, called a 1-4 linkage.
o There are 2 major forms of carbs starch and cellulose
o 1-4 linkages create starch. It can easily be digested by us.
The hydroxyl groups are all in the same plane.
Starches create helical structures.
Plant starch is very simple compared to animal starches.
o 1-4 linkages create cellulose. We cant digest it.
The hydroxyl groups alternate side to side.
The structure of cellulose is very linear, and it can band
together in large strands.
Its used for strength and structure. Ex. cell wall.
Proteins
o Amino acids join together to create a back bone composed of a
nitrogen and 2 carbons that have side groups hanging off.
o Structure
Primary string of amino acids
Secondary helix or pleated sheet
Tertiary 3d functional protein
Quaternary multiple protein subunits come together to
make one massive protein (ex. hemoglobin)
Organic precursors we need sources of carbon and nitrogen.
Essential nutrients things we cant make
o Some amino acids
There are 8 we cant make. (know them!)
Methionine
Valine
Threonine
Phenylalanine
Isoleucine
Tryptophan
Lysine
o Essential Fatty acids
Deficiencies are rare, but theres one we depend
Polyunsaturated fatty acids (PUFAs) needed to make
membrane phospholipids
61
Animals cannot make omega-3 and omega-6 PUFAs.
o Vitamins
Can be water soluble or water insoluble
Soluble vitamins can be ingested a lot, transported to
wherever it needs to go to the body, and then get pissed
out. For ex. Vitamin C
Know everything on the table!!
Fat soluble vitamins (A,D,E,K).
They enter the fat and stay in the fat for a long
amount of time.
Greater toxicity risk.
o Minerals
Inorganic nutrients
Metallic elements involved in protein structure
For ex. calcium, NA, K, CL, iron, and iodine.
Four stages of food processing
o Ingestion eating
62
o Digestion breaking food down into molecules small enough to be
absorbed
o Absorption cells take up small molecules
o Elimination removal of undigested material
Digestion occurs in specialized compartments
o Intracellular digestion
o Extracellular digestion
Gastrovascular cavities & alimentary canals
Intracellular digestion, Ex. Paramecium
o Specialized ingestion through oral groove via pinocytosis
o Food is immediately put in a vacuole
o Digestion and absorption happens in the vacuole
Digestive enzymes secreted in
o Exocytosis at the anal pore.
Gastrovascular cavities
o Allows for larger things to be ingested.
o Has a single opening to the outside
o Ingest food via mouth, and digest it inside the cavity.
o Absorption is also done in cavity, and then it is eliminated
through the mouth.
Alimentary Canal
o Tubes that extend between two
openings (e.g. mouth Anus)
o Food moves in one direction (few
exceptions)
o Specialized regions for digestion
and absorption in steps.
Most absorption is done in the small
intestine.
GI tract (The whole tube) is lined
with strong smooth muscles.
Stomach has very acidic secretions.
Intestines have very basic secretions.
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Lecture 23 (4/24) (Collins)
Know everything in
the picture
We start digesting
food both
mechanically and
chemically in the
oral cavity.
Tongue forms a ball
(bolus) and pushes
it back.
Saliva produced by
the salivary glands
begin starch
breakdown.
Pharynx/esophagus
conducts the food
to the stomach.
o There is
striated
muscle at the top of the esophagus (voluntary control)
o There is smooth muscle in the lower esophagus.
o Involuntary waves of contractions move food bolus to the stomach
Called Peristalsis.
Stomach is a large elastic organ
o Animals dont have to eat constantly thanks to stomach
o It does the initial digestion of protein
Hydrochloric acid and pepsin (stomach pH 2)
Mixture of these 2 is called gastric juice
o Mechanical churning of food.
o Lining of stomach has thousands of gastric pits that have cells
Mucus cells protects the epithelium cells.
Parietal cells secretes hydrochloric acid.
Chief Cells Produce pepsinogen.
o Pepsinogen is an inactive proenzyme
It is synthesized as an inactive enzyme.
It is converted to active form as needed.
When HCl meets the pepsinogen, it activates it into pepsin
Pepsin can also activate pepsinogen (positive feedback!)
o The acid in the stomach does a lot of things.
It disrupts the ECM that holds cells together
Denatures (unfolds) proteins
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Kills most bacteria and pathogens.
o Smooth muscles mix the bolus with the gastric juice, to create
whats called acid chyme.
o Contractions push the acid chyme through the pyloric sphincter
into the small intestine.
Small Intestine
o Longest part of the intestine. Approx. 6 meters long.
o Major organ of digestion and absorption
Major site for enzymatic hydrolysis and nutrient absorption
3 Major Parts: Duodenum, Jejenum, and Ileum
Duodenum
o Short first part of small intestine. (~25cm)
o Acid chyme mixes with digestive juices.
o Digestive Juices come from multiple sources
Pancreas, liver/gallbladder, and gland cells all meet in
the duodenum.
o Pancreatic Secretions
Bicarbonate
neutralize acid
chyme (increase pH
to 7-8)
Peptidases
Protein digestions
Nucleases -
hydrolyze DNA &
RNA
Amylases Carb
digestion
Lipase fat
digestion.
The pancreas is both exocrine and endocrine.
o Pancreatic peptidases go from inactive to active like pepsin.
Trypsinogen trypsin
Procarboxypeptidase carboxypeptidase
Chymotrypsinogen chymotrypsin
The duodenum has a membrane bound enteropeptidase
This is what activates trypsin
Trypsin activates the other two, as well as itself.
o Liver secretes Bile
Bile is made by the liver, but stored in the gallbladder.
Bile contains bile salts and bile pigments.
Bile salts are composed of cholesterol and amino acids.
The salts break up the fat globs into small pieces.
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This facilitates hydrolysis of fat by the enzyme lipase.
Jejunum & Ileum
o Jejunum is the major site of digestion and absorption.
o It has a very large surface area due to -
Large circular folds into the lumen.
Finger like projections called villi.
The epithelial cells on the villi have their own
projections, called microvilli. Microvilli = brush border.
o Nutrients are absorbed through the epithelial cells in the
villi.
The nutrients are then transferred to either the
circulatory and lymphatic systems.
Sugars and amino acids go to the circulatory system
o The circulatory veins go through the hepatic
portal vein to the liver before the heart.
Fats go to the lymphatic system via lacteals, and then
into the veins ultimately.
o Fatty acids and glycerol and cholesterol are
assembled in the epithelial cells to make
chylomicrons.
o The chylomicrons then go into the lacteal.
o The Ileum absorbs whatever the jejunum doesnt.
Regulation of digestion
o Stomach releases gastrin
Food in stomach or parasympathetic nerves stimulate release
Gastrin causes secretion of gastric juices.
Gastrin is inhibited if the pH becomes too low.
o Secretin secreted by cells in the wall of the duodenum
Secreted in response to low level of pH of acid chyme
It stimulates the release of bicarbonate from the pancreas.
o Cholecystokinin(CCK) also secreted by duodenum wall cells
Secreted in response to amino acids & fatty acids
Stimulates release of pancreatic enzymes.
Causes contraction of gallbladder (releases bile)
o Enterogastrone is also secreted by wall cells.
It inhibits stomach motility and gastic acid secretion in
response to fatty acids in the duodenum
It effectively tells the stomach to stop/slow down while
the duodenum takes care of the fatty acids.
Large Intestine
o Has a pouch called a cecum, to which the appendix is attached.
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o By the time things reach the large intestine, 99% of the
nutrients have been absorbed. So everything in there is waste +
water
o Main purpose of large
intestine is reabsorption
However, most of the
water occurs in the
small intestine.
Water Reabsorption
o Get to know the chart on
the right very well
Evolutionary Adaptations
o Vegetation is more
difficult to digest.
o Herbivores and omnivores
tend to have longer canals.
More time and surface
area for digestion.
o They have really big cecums
Fiber enters in the cecum, which is full of symbiotic
organisms that break down the cecums.
Symbiotic organisms microorganisms such protists and bacteria
thrive in fermentation chambers in herbivores
o They provide essential nutrients, digest cellulose, and can be a
direct food source as well.
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Squids, etc.
Locomotion on land
o Primary challenge is overcoming gravity.
o Overcoming resistance of air is a minor problem
o Strong muscles and skeleton more important than a streamlined
shape
Flying
o Its more efficient than ground locomotion.
o Overcoming gravity is the major problem
o The shape of wings provides lift.
Skeletons
o Functions support against gravity, maintain form and shape,
protection, and movement
o Three types of skeletons
Hydrostatic skeletons
Its fluid held under pressure in a closed compartment
Its well suited for aquatic animals and provides
support for crawling/burrowing in terrestrials.
Water is heavy however, and its not very protective.
Animals with this skeleton move by contraction of
muscles against a relatively non compressible fluid.
Example earthworm
o Made up of repeating segments. Each segment is a
sack of coelomic fluid.
o Antagonistic circular and longitudinal muscles
are coordinated to move it. (peristalsis)
o
Exoskeletons
Hard encasement on the surface of an animal
2 major categories
o Mollusks such as clams
Calcium carbonate shell that keeps growing
o Arthropods such as lobsters
Jointed skeletons made up of chitin
Exoskeleton is shed and replaced.
Endoskeletons
Hard supporting elements buried inside soft tissue
Chordates cartilage and bones
Provides support and increase mobility, as well as
protection.
Muscle Movement
o Movement is based on contraction of muscles against skeleton
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Muscle movement is always to contract
Extension is passive.
o Muscles work in antagonist pairs they work against each other
in opposite directions to move body parts.
o Skeletal muscle fibers generate tension by shortening(sarcomere)
o Each action potential in the motor neuron produces a twitch
contraction in all of the muscle fibers innervated by that motor
neuron.
Muscle fibers are slaves to the neuron that controls it.
o The time source and amount of tension generated is determined by
the properties of the muscle fibers.
Muscle Tension
o There are two ways that tension generated can be varied
Temporal summation vary the tension generated by an
individual muscle fiber
This is done by changing the frequency of the signal
being sent.
Recruitment vary the number of motor units (muscle
fibers) that are activated.
o Fatigue some muscles can only maintain max tension for a short
amount of time, while other muscles are fatigue resistant.
Temporal Summation
o A second action potential before the muscle relaxes from the
first one will cause an addition to the tension of the muscle.
o Increasing the frequency of action potentials increases the
amount of summation and therefore tension of the muscle.
o Tetanus when you reach the maximum summated twitch due to high
frequency of action potentials.
Muscle fatigue inability to maintain tension during periods of
sustained, repetitive activation.
o Muscles that use anaerobic metabolism fatigue due to lactic acid
accumulation
o Muscles that use aerobic metabolism dont fatigue.
Motor unit recruitment
o The strength of contraction can be increased by activating
additional motor units
o A motor unit is
One motor neuron and its axon and
All of the muscle fibers that it innervates.
o Each muscle fiber is only innervated by a single motor neuron.
o Each motor neuron activates many multiple muscle fibers.
o Motor units vary in size (large size = large tension)
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Usually, small motor units get recruited first, and then
larger motor units are recruited.
Smaller motor units result in finer control (such as tongue
and finger muscles)
Muscles that need to produce lots of tension at once (like
biceps) have larger motor units.
o 3 Categories of Motor units
Type S (slow) motor units
Contain slow oxidative muscle fibers
They contract and relax slowly. Long term tension
These are used for maintaining posture and position.
Type FR (fast fatigue-resistant) motor units
Contain fast oxidative muscle fibers
Fast, strong contractions
Fatigue resistant
Used for routine movements (Walking etc)
Type FF (fast fatiguing)
Contain fast glycolytic muscle fibers
Fastest, strongest contractions
Rapidly fatigue
Fibers used to rapidly generate maximum force.
o S is recruited first, then FR, and then FF
FF is rarely used on a daily basis though.
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------------------------ Begin Final Exam Material -----------------------
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Internal fertilization sperm is deposited in the female, and
fertilization occurs in the mother.
o Usually produces a small number of offspring, and provide
protection.
Human Reproduction
Sexual differentiation
o Humans, have 23 pairs of chromosomes. 22 pairs of autosomes, and
1 pair of sex chromosome.
o X & Y 1 pair of sex.
o Males have 1 X & 1 Y chromosome. Females are 2 XX chromosomes.
o SRY gene, sex determining gene on the Y chromosome.
A functioning SRY gene will produce the SRY protein, which
will lead to the gonadal tissue to becoming a testes.
Without a SRY gene, youll have ovaries.
o The gonadal tissue, once differentiated, will them produce
different hormones and proteins, that will do everything else.
Around the gondal tissue, you have 2 systems of ducts the mullerian
duct, and the wolffian duct.
o The mullerian duct forms the utures, fallopian tubes and part of
the vagina
o The wolffian duct forms the prostate, and seminal vesicles, etc.
o The SRY protein affects the medulla of the gonadal tissue and
cause differention.
o Testes will produce anti-mullerian hormones, which will prevent
the mullerian duct from growing, and the duct will degenerate.
Testes will also produce testosterone, which will develop
the wolffian duct into everything.
o Absense of testosterone will mean that the wolffian duct will
degenerate.
o Absense of anti-mullerian hormones will lead to the mullerian
duct growing.
SRY does not differentiate gender. It differentiates gonadal tissue.
o Default form is female
DHT, produced by the testes, will cause the external anatomy to
become male parts. Lack of DHT will cause female parts.
Male Reproductive Anatomy
o External reproductive organs
Scrotum houses testes & vas deferens.
Penis
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o Internal reproductive organs
Testes
Accessory Glands
Ducts
Testes
o Leydig cells Synthesize and
secrete Androgens
(testosterone)
o They develop high in the
abdominal cavity, and descend
later. Lower temp outside the
body favors sperm production.
o Seminiferous tubules highly
coiled tubes where sperm
cells form
They start young, and become sperm
as they reach the lumen of the
tubule.
Each main germ cell (spermatocyte)
will produce 4 sperms.
o Sperm will mature in the epididymis.
Accessory Glands
o Seminal Vesicles 60% of volume of
semen.
Thick & Alkaline mucus, sugars,
enzymes, prostaglandins
Sperm need to be in an alkaline environment to thrive.
o Prostate Gland largest accessory gland
Secretes thin milky fluid into urethra
o Bulbourethral glands
Secretes clear mucus fluid before ejaculation
Neutralizes acidic urine.
Carries some sperm released before ejaculation.
Pathway for Sperm SEVEn UP
o Seminiferous tubules Epididymus vas deferens ejaculatory
duct urethra Penis
Erection
o Penis is composed of three spongy cylinders of erectile tissue
o During vasodilation, leads to erectile tissue, filling with
blood.
Increasing pressure cuts off the veins that drain the penis
Female Anatomy
o External structures clitoris, labia, vaginal opening.
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Clitoris gets erect
during arousal too.
o Internal structures
ovaries and ducts.
Ovaries are enclosed in tough
connective tissues
o They arent attached to
fallopian tubes.
Theyre attached by
ligaments to uterus
Ovaries Contains many follicles
o Each follicle contains 1 egg
surrounded by layers of
cells.
o Cells of the follicles produce estrogen.
o All 400,000 follicles are formed before birth
o After an egg is expelled from a follicle, the femaining tissue
forms a solid mass (Corpus luteum) that secretes estrogen and
progesterone.
o The primary cell (oocyte) form 2 forms 2 polar bodies and 1
ovum.
Pathway for Ovum
o Ovum is released into abdominal cavity near the fallopian tubes.
o The cilia on the will draw the ovum into the tube.
o Fertilization happens in the fallopian tubes.
o Ovum passes through the uterus. The endometrium (inside) of the
uterus gets very thick.
o If Ovum isnt fertilized, the endometrium degenerates, which
produces menstrual flow.
o Then the ovum + blood flow out of the vagina.
Reproductive Hormones
o Testosterone
o 17 -estradiol (form of estrogen)
o Progesterone
o Oxytocin
o Prolactin
Male hormonal control of reproduction
o Hypothalamus has anterior pituitary gland produce FSH & LH.
o FSH affects sertoli cells, which increase spermatogenesis
o LH affects leydig cells and have them make testosterone,
o Testosterone also stimulates spermatogenesis
o Testosterone serves as negative feedback to the brain.
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Hormonal Control of
reproduction for females
o Cyclic Behavior
o Menstrual cycle
endometrium enlarges
and then breaks down
o Ovarian Cycle
oogenesis leading to
ovulation
Cycle starts on Day 1
o Menstrual flow
o Low levels of
estrogen &
progesterone
o Hypothalamus causes
release of LH & FSH
o FSH starts oogenesis
of an oocyte
o This causes estrogen
synthesis by the
follicle
Estrogen increase causes
increase in the
endometrium.
o This starts shutting
the hypothalamus down
though (negative
feedback)
Very high estrogen levels
stimulates section from
hypothalamus positive feedback.
o Theres a surge of LH.
o This causes ovulation.
o This occurs during day 14.
Corpus luteum, the ruptured follicle, starts releasing estrogen and
progesterone.
o Progesterone shuts down the hypothalamus again. (negative
feedback)
o Progesterone stimulates endometrium build up.
If ovum isnt fertilized, the corpus luteum runs out of estrogen and
progesterone 12 days after ovulation. This leads to menstruation, and
a restart of the cycle.
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If fertilization happens, the embryo/placenta will produce HCG, which
supports the corpus luteum, and prevents the corpus luteum from
running out.
Your biology skill has now increased. You must now rest and meditate on
what youve learned.
Copyright 2012. No portion of this work may be sold for any sort of
profit what so ever without express written consent. Thanks.
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