major surgery:
A. Insulin
B. Cortisol
C. Renin
E. Prolactin
Endocrine parameters reduced in
stress response:
Insulin
Testosterone
Oestrogen
Antidiuretic hormone
Glucagon
Pituitary gland
Cortisol
Growth hormone
Alpha Endorphin
Increased
Antidiuretic hormone
Insulin
Carbohydrate metabolism
Protein metabolism
Initially there is inhibition of protein anabolism, followed later, if the stress
response is severe, by enhanced catabolism
The amount of protein degradation is influenced by the type of surgery and
also by the nutritional status of the patient
Mainly skeletal muscle protein is affected
The amino acids released form acute phase proteins (fibrinogen, C reactive
protein, complement proteins, a2-macroglobulin, amyloid A and
ceruloplasmin) and are used for gluconeogenesis
Nutritional support has little effect on preventing catabolism
Lipid metabolism
Increased catecholamine, cortisol and glucagon secretion, and insulin deficiency,
promotes lipolysis and ketone body production.
ADH causes water retention, concentrated urine, and potassium loss and may
continue for 3 to 5 days after surgery
Renin causes sodium and water retention
Cytokines
Glycoproteins
Interleukins (IL) 1 to 17, interferons, and tumour necrosis factor
Synthesized by activated macrophages, fibroblasts, endothelial and glial cells
in response to tissue injury from surgery or trauma
IL-6 main cytokine associated with surgery. Peak 12 to 24 h after surgery and
increase by the degree of tissue damage Other effects of cytokines include
fever, granulocytosis, haemostasis, tissue damage limitation and promotion of
healing.
C. The activation of factor 8 is the point when the intrinsic and the
extrinsic pathways meet
The extrinsic pathway is the main path of coagulation. Heparin inhibits the activation
of factors 2,9,10,11. The activation of factor 10 is when both pathways meet.
Thrombin converts fibrinogen to fibrin. During fibrinolysis plasminogen is converted
to plasmin to break down fibrin.
Coagulation cascade
Tissue damage
Factor 7 binds to Tissue factor
This complex activates Factor 9
Activated Factor 9 works with Factor 8 to activate Factor 10
Common pathway
Fibrinolysis
Plasminogen is converted to plasmin to facilitate clot resorption
A. Hydrochloric acid
B. Mucus
C. Magnesium
D. Intrinsic factor
E. Calcium
Chief of Pepsi cola = Chief cells
secrete PEPSInogen
Gastric secretions
Gastric acid
The diagram below illustrates some of the factors involved in regulating gastric acid
secretion and the relevant associated pharmacology
A 45 year old male is diagnosed with carcinoma of the head of the pancreas. He
reports that his stool sticks to the commode and will not flush away. Loss of which of
the following enzymes is most likely to be responsible for this problem?
A. Lipase
B. Amylase
C. Trypsin
D. Elastase
Pancreatic cancer
Adenocarcinoma
Risk factors: Smoking, diabetes, Adenoma, Familial adenomatous polyposis
Mainly occur in the head of the pancreas (70%)
Spread locally and metastasizes to the liver
Carcinoma of the pancreas should be differentiated from other periampullary
tumours with better prognosis
Clinical features
Weight loss
Painless jaundice
Epigastric discomfort (pain usually due to invasion of the coeliac plexus is a
late feature)
Pancreatitis
Trousseau's sign: migratory superficial thrombophlebitis
Investigations
Management
A. Vitamin c
B. Zinc
C. Vitamin B12
D. Copper
E. Molybdenum
Rapid emptying food from stomach into the duodenum: diarrhoea, abdominal pain,
hypoglycaemia
Complications: Vitamin B12 and iron malabsorption, osteoporosis
Treatment: High protein, low carbohydrate diet. Replace B12/Fe/Ca
Gastric emptying
The stomach serves both a mechanical and immunological function. Solid and
liquid are retained in the stomach during which time repeated peristaltic
activity against a closed pyloric sphincter will cause fragmentation of food
bolus material. Contact with gastric acid will help to neutralise any pathogens
present.
Controlling factors
Neuronal stimulation of the stomach is mediated via the vagus and the
parasympathetic nervous system will tend to favor an increase in gastric motility. It is
for this reason that individuals who have undergone truncal vagotomy will tend to
routinely require either a pyloroplasty or gastro-enterostomy as they would otherwise
have delayed gastric emptying.
Iatrogenic
Gastric surgery can have profound effects on gastric emptying. As stated above any
procedure that disrupts the vagus can cause delayed emptying. Whilst this is
particularly true of Vagotomy this operation is now rarely performed. Surgeons are
divided on the importance of vagal disruption that occurs during an oesophagectomy
and some will routinely perform a pyloroplasty and other will not.
When a distal gastrectomy is performed the type of anastomosis performed will
impact on emptying. When a gastro-enterostomy is constructed, a posterior, retrocolic
gastroenterostomy will empty better than an anterior one.
Diabetic gastroparesis
This is predominantly due to neuropathy affecting the vagus nerve. The stomach
empties poorly and patients may have episodes of repeated and protracted vomiting.
Diagnosis is made by upper GI endoscopy and contrast studies, in some cases a radio
nucleotide scan is needed to demonstrate the abnormality more clearly. In treating
these conditions drugs such as metoclopramide will be less effective as they exert
their effect via the vagus nerve. One of the few prokinetic drugs that do not work in
this way is the antibiotic erythromycin.
Malignancies
Obviously a distal gastric cancer may obstruct the pylorus and delay emptying. In
addition malignancies of the pancreas may cause extrinsic compression of the
duodenum and delay emptying. Treatment in these cases is by gastric decompression
using a wide bore nasogastric tube and insertion of a stent or if that is not possible by
a surgical gastroenterostomy. As a general rule gastroenterostomies constructed for
bypass of malignancy are usually placed on the anterior wall of the stomach (in spite
of the fact that they empty less well). A Roux en Y bypass may also be undertaken but
the increased number of anastomoses for this in malignant disease that is being
palliated is probably not justified.
A. Vitamin A
B. Vitamin B
C. Vitamin C
D. Vitamin D
E. Vitamin E
Collagen Diseases
Osteogenesis imperfecta
Ehlers Danlos
Osteogenesis imperfecta:
-8 Subtypes
-Defect of type I collagen
-In type I the collagen is normal quality but insufficient quantity
-Type II- poor quantity and quality
-Type III- Collagen poorly formed, normal quantity
-Type IV- Sufficient quantity but poor quality
Patients have bones which fracture easily, loose joint and multiple other defects
depending upon which sub type they suffer from
Ehlers Danlos:
-Multiple sub types
-Abnormality of types 1 and 3 collagen
-Patients have features of hypermobility.
-Individuals are prone to joint dislocations and pelvic organ prolapse. In addition to
many other diseases related to connective tissue defects
A 56 year old man has long standing chronic pancreatitis and develops pancreatic
insufficiency. Which of the following will be absorbed normally?
A. Fat
B. Protein
C. Folic acid
D. Vitamin B12
Pancreatic juice
Alkaline solution pH 8
1500ml/day
Composition: acinar secretion (ENZYMES: trypsinogen, procarboxylase,
amylase, lecithin) and ductile secretion (HCO, Na+, water)
Pancreatic juice action: Trypsinogen is converted via enterokinase to active
trypsin in the duodenum. Trypsin then activates the other inactive enzymes.
A 56 year old male presents to the acute surgical take with severe abdominal pain. He
is normally fit and well. He has no malignancy. The biochemistry laboratory contacts
the ward urgently, his corrected calcium result is 3.6 mmol/l. What is the medication
of choice to treat this abnormality?
A. IV Pamidronate
B. Oral Alendronate
C. Dexamethasone
D. Calcitonin
E. IV Zoledronate
IV Pamidronate is the drug of choice as it most effective and has long lasting effects.
Calcitonin would need to be given with another agent, to ensure that the
hypercalcaemia is treated once its short term effects wear off. IV zoledronate is
preferred in scenarios associated with malignancy.
Management of hypercalcaemia
Management:
Bisphosphonates
Analogues of pryrophosphate
Prevent osteoclast attachment to bone matrix and interfere with osteoclast
activity.
Inhibit bone resorption.
Agents
Calcitonin
Prenisolone
n over enthusiastic medical student decides to ask you questions about ECGs. Rather
than admitting your dwindling knowledge on this topic, you bravely attempt to
answer her questions! One question is what segment of the ECG represents
ventricular repolarization?
A. QRS complex
B. Q-T interval
C. P wave
D. T wave
E. S-T segment
P wave
Time from the onset of the P wave to the beginning of the QRS complex
Ranges from 0.12 to 0.20 seconds in duration
Represents the time between the onset of atrial depolarization and the onset of
ventricular depolarization
QRS complex
ST segment
T wave
Q-T interval
A. Hypothermia
B. Respiratory alkalosis
C. Low altitude
C O2
A cidosis
2,3-DPG
E xercise
T emperature
The curve is shifted to the right when there is an increased oxygen requirement by the
tissue. This includes:
Increased temperature
Acidosis
Increased DPG:
Oxygen Transport
Oxygen transport
Almost all oxygen is transported within erythrocytes. It has limited solubility and only
1% is carried as solution. Therefore the amount of oxygen transported will depend
upon haemoglobin concentration and its degree of saturation.
Haemoglobin
Globular protein composed of 4 subunits. Haem consists of a protoporphyrin ring
surrounding an iron atom in its ferrous state. The iron can form two additional bonds;
one with oxygen and the other with a polypeptide chain. There are two alpha and two
beta subunits to this polypeptide chain in an adult and together these form globin.
Globin cannot bind oxygen but is able to bind to carbon dioxide and hydrogen ions,
the beta chains are able to bind to 2,3 diphosphoglycerate. The oxygenation of
haemoglobin is a reversible reaction. The molecular shape of haemoglobin is such
that binding of one oxygen molecule facilitates the binding of subsequent molecules.
Oxygen dissociation curve
Bohr effect
*2,3-diphosphoglycerate
A 73 year old lady is admitted for a laparoscopic cholecystectomy. During her pre-
operative assessment it is noted that she is receiving furosemide for the treatment of
hypertension. Where is the site of action of this diuretic?
E. Collecting ducts
Action of furosemide = ascending
limb of the loop of Henle
Furosemide and bumetanide are loop diuretics that act by inhibiting the Na-K-Cl
cotransporter in the thick ascending limb of the loop of Henle, reducing the absorption
of NaCl.
Diuretic agents
The diuretic drugs are divided into three major classes, which are distinguished
according to the site at which they impair sodium reabsorption: loop diuretics in the
thick ascending loop of Henle, thiazide type diuretics in the distal tubule and
connecting segment; and potassium sparing diuretics in the aldosterone - sensitive
principal cells in the cortical collecting tubule.
In the kidney, sodium is reabsorbed through Na+/ K+ ATPase pumps located on the
basolateral membrane. These pumps return reabsorbed sodium to the circulation and
maintain low intracellular sodium levels. This latter effect ensures a constant
concentration gradient.
A. Spironolactone
B. Carbimazole
C. Chlorpromazine
D. Cimetidine
E. Methyldopa
Mnemonic for drugs causing
gynaecomastia: DISCO
D igitalis
I soniazid
S pironolactone
C imentidine
O estrogen
M etoclopramide
E ctopic oestrogen
T rauma skull/tumour breast, testes
O rchitis
C imetidine, Cushings
L iver cirrhosis
O besity
P araplegia
RA
A cromegaly
M ethyldopa
I soniazid
D igoxin
E thionamide
Gynaecomastia
tricyclics
isoniazid
calcium channel blockers
heroin
busulfan
methyldopa
43 year old lady is recovering on the intensive care unit following a Whipples
procedure. She has a central venous line in situ. Which of the following will lead to
the "y" descent on the waveform trace?
A. Ventricular contraction
E. Cardiac tamponade
JVP
3 Upward deflections and 2 downward
deflections
Upward deflections
Downward deflections
The 'y' descent represents the emptying of the atrium and the filling of the right
ventricle.
Cardiac physiology
The heart has four chambers ejecting blood into both low pressure and high
pressure systems.
The pumps generate pressures of between 0-25mmHg on the right side and 0-
120 mmHg on the left.
At rest diastole comprises 2/3 of the cardiac cycle.
The product of the frequency of heart rate and stroke volume combine to give
the cardiac output which is typically 5-6L per minute.
Detailed descriptions of the various waveforms are often not a feature of MRCS A
(although they are on the syllabus). However, they are a very popular topic for
surgical physiology vivas in the oral examination.
Electrical properties
Intrinsic myogenic rhythm within cardiac myocytes means that even the
denervated heart is capable of contraction.
In the normal situation the cardiac impulse is generated in the sino atrial node
in the right atrium and conveyed to the ventricles via the atrioventricular node.
The sino atrial node is also capable of spontaneous discharge and in the
absence of background vagal tone will typically discharge around 100x per
minute. Hence the higher resting heart rate found in cardiac transplant cases.
In the SA and AV nodes the resting membrane potential is lower than in
surrounding cardiac cells and will slowly depolarise from -70mV to around -
50mV at which point an action potential is generated.
Differences in the depolarisation slopes between SA and AV nodes help to
explain why the SA node will depolarise first. The cells have a refractory
period during which they cannot be re-stimulated and this period allows for
adequate ventricular filling. In pathological tachycardic states this time period
is overridden and inadequate ventricular filling may then occur, cardiac output
falls and syncope may ensue.
Parasympathetic fibres project to the heart via the vagus and will release
acetylcholine. Sympathetic fibres release nor adrenaline and circulating adrenaline
comes from the adrenal medulla. Noradrenaline binds to β 1 receptors in the SA node
and increases the rate of pacemaker potential depolarisation.
Cardiac cycle
Mid diastole: AV valves open. Ventricles hold 80% of final volume. Outflow
valves shut. Aortic pressure is high.
The negative atrial pressures are of clinical importance as they can allow air
embolization to occur if the neck veins are exposed to air. This patient positioning is
important in head and neck surgery to avoid this occurrence if veins are inadvertently
cut, or during CVP line insertion.
Mechanical properties
It states that for hollow organs with a circular cross section, the total
circumferential wall tension depends upon the circumference of the wall,
multiplied by the thickness of the wall and on the wall tension.
The total luminal pressure depends upon the cross sectional area of the lumen
and the transmural pressure. Transmural pressure is the internal pressure
minus external pressure and at equilibrium the total pressure must
counterbalance each other.
In terms of cardiac physiology the law explains that the rise in ventricular
pressure that occurs during the ejection phase is due to physical change in
heart size. It also explains why a dilated diseased heart will have impaired
systolic function.
Starlings law
Baroreceptor reflexes
Which of the following are not characteristic features of central chemoreceptors in the
control of ventilation?
They are stimulated by arterial carbon dioxide. It takes longer to equilibrate than the
peripheral chemoreceptors located in the carotid. They are less sensitive to acidity due
to the blood brain barrier.
Control of ventilation
Respiratory centres
Inspiratory and expiratory neurones. Has ventral group which controls forced
voluntary expiration and the dorsal group controls inspiration. Depressed by opiates.
Apneustic centre:
Lower pons
Stimulates inspiration - activates and prolongs inhalation
Overridden by pneumotaxic control to end inspiration
Pneumotaxic centre:
Upper pons, inhibits inspiration at a certain point. Fine tunes the respiratory rate.
A 32 year old man has a glomerular filtration rate of 110ml / minute at a systolic
blood pressure of 120/80. If his blood pressure were to fall to 100/70 what would
glomerular filtration rate be?
A. 110ml / minute
B. 100ml/ minute
C. 55ml/ minute
D. 25ml/ minute
E. 75ml/ minute
The proposed drop in blood pressure falls within the range within which the kidney
autoregulates its blood supply. GFR will therefore remain unchanged.
Renal Physiology
Overview
Each nephron is supplied with blood from an afferent arteriole that opens onto
the glomerular capillary bed.
Blood then flows to an efferent arteriole, supplying the peritubular capillaries
and medullary vasa recta.
The kidney receives up to 25% of resting cardiac output.
The kidney is able to autoregulate its blood flow between systolic pressures of
80- 180mmHg so there is little variation in renal blood flow.
This is achieved by myogenic control of arteriolar tone, both sympathetic
input and hormonal signals (e.g. renin) are responsible.
Glomerular filtration rate = Total volume of plasma per unit time leaving the
capillaries and entering the bowman's capsule
1. Inert
2. Free filtration from the plasma at the glomerulus (not protein bound)
3. Not absorbed or secreted at the tubules
4. Plasma concentration constant during urine collection
The clearance of a substance is dependent not only on its diffusivity across the
basement membrane but also subsequent tubular secretion and / or
reabsorption.
So glucose which is freely filtered across the basement membrane is usually
reabsorbed from tubules giving a clearance of zero.
Tubular function
Loop of Henle
A. Gastrin
B. Atenolol
C. Protein
D. Secretin
Glucose
Amino acid
Vagal cholinergic
Secretin/Gastrin/CCK
Fatty acids
Beta adrenergic drugs
Insulin
Anabolic hormone
Structure
Synthesis
Function
A 63 year old female is referred to the surgical clinic with an iron deficiency anaemia.
Her past medical history includes a left hemi colectomy but no other co-morbidities.
At what site is most dietery iron absorbed?
A. Stomach
B. Duodenum
C. Proximal ileum
D. Distal ileum
E. Colon
Iron is best absorbed from the proximal small bowel (duodenum and jejunum) in the
Fe 2+ state. Iron is transported across the small bowel mucosa by a divalent membrane
transporter protein (hence the improved absorption of F2 2+. The intestinal cells
typically store the bound iron as ferritin. Cells requiring iron will typically then
absorb the complex as needed.
Iron metabolism
Distribution in body
Total body iron 4g
Haemoglobin 70%
Ferritin and haemosiderin 25%
4%
Myoglobin
Plasma iron 0.1%
Which of the following drugs increases the rate of gastric emptying in the
vagotomised stomach?
A. Ondansetron
B. Metoclopramide
C. Cyclizine
D. Erythromycin
E. Chloramphenicol
Vagotomy seriously compromises gastric emptying which is why either a
pyloroplasty or gastro-enterostomy is routinely performed at the same time.
The stomach serves both a mechanical and immunological function. Solid and
liquid are retained in the stomach during which time repeated peristaltic
activity against a closed pyloric sphincter will cause fragmentation of food
bolus material. Contact with gastric acid will help to neutralise any pathogens
present.
Controlling factors
Neuronal stimulation of the stomach is mediated via the vagus and the
parasympathetic nervous system will tend to favor an increase in gastric motility. It is
for this reason that individuals who have undergone truncal vagotomy will tend to
routinely require either a pyloroplasty or gastro-enterostomy as they would otherwise
have delayed gastric emptying.
Iatrogenic
Gastric surgery can have profound effects on gastric emptying. As stated above any
procedure that disrupts the vagus can cause delayed emptying. Whilst this is
particularly true of Vagotomy this operation is now rarely performed. Surgeons are
divided on the importance of vagal disruption that occurs during an oesophagectomy
and some will routinely perform a pyloroplasty and other will not.
Malignancies
Obviously a distal gastric cancer may obstruct the pylorus and delay emptying. In
addition malignancies of the pancreas may cause extrinsic compression of the
duodenum and delay emptying. Treatment in these cases is by gastric decompression
using a wide bore nasogastric tube and insertion of a stent or if that is not possible by
a surgical gastroenterostomy. As a general rule gastroenterostomies constructed for
bypass of malignancy are usually placed on the anterior wall of the stomach (in spite
of the fact that they empty less well). A Roux en Y bypass may also be undertaken but
the increased number of anastomoses for this in malignant disease that is being
palliated is probably not justified.
Hypovolaemic shock:
blood volume depletion
e.g. haemorrhage, vomiting, diarrhoea, dehydration, third-space losses during major
operations
increased SVR
increased HR
decreased cardiac output
decreased blood pressure
Septic shock:
occurs when the peripheral vascular dilatation causes a fall in SVR
similar response may occur in anaphylactic shock, neurogenic shock
reduced SVR
increased HR
normal/increased cardiac output
decreased blood pressure
Shock
Septic shock
Septic shock is a major problem and those patients with severe sepsis have a mortality
rate in excess of 40%. In those who are admitted to intensive care mortality ranges
from 6% with no organ failure to 65% in those with 4 organ failure.
Patients with infections and two or more elements of SIRS meet the diagnostic criteria
for sepsis. Those with organ failure have severe sepsis and those with refractory
hypotension -septic shock.
During the septic process there is marked activation of the immune system with
extensive cytokine release. This may be coupled with or triggered by systemic
circulation of bacterial toxins. These all cause endothelial cell damage and neutrophil
adhesion. The overall hallmarks are thus those of excessive inflammation,
coagulation and fibrinolytic suppression.
The surviving sepsis campaign highlights the following key areas for attention:
In surgical patients, the main groups with septic shock include those with anastomotic
leaks, abscesses and extensive superficial infections such as necrotising fasciitis.
When performing surgery the aim should be to undertake the minimum necessary to
restore physiology. These patients do not fare well with prolonged surgery. Definitive
surgery can be more safely undertaken when physiology is restored and clotting in
particular has been normalised.
Haemorrhagic shock
The average adult blood volume comprises 7% of body weight. Thus in the 70 Kg
adult this will equate to 5 litres. This changes in children (8-9% body weight) and is
slightly lower in the elderly.
The table below outlines the 4 major classes of haemorrhagic shock and their
associated physiological sequelae:
In patients suffering from trauma the most likely cause of shock is haemorrhage.
However, the following may also be the cause or occur concomitantly:
Tension pneumothorax
Spinal cord injury
Myocardial contusion
Cardiac tamponade
Neurogenic shock
This occurs most often following a spinal cord transection, usually at a high level.
There is resultant interruption of the autonomic nervous system. The result is either
decreased sympathetic tone or increased parasympathetic tone, the effect of
which is a decrease in peripheral vascular resistance mediated by marked
vasodilation.
This results in decreased preload and thus decreased cardiac output (Starlings law).
There is decreased peripheral tissue perfusion and shock is thus produced. In contrast
with many other types of shock peripheral vasoconstrictors are used to return vascular
tone to normal.
Cardiogenic shock
In medical patients the main cause is ischaemic heart disease. In the traumatic
setting direct myocardial trauma or contusion is more likely. Evidence of ECG
changes and overlying sternal fractures or contusions should raise the suspicion of
injury. Treatment is largely supportive and transthoracic echocardiography should be
used to determine evidence of pericardial fluid or direct myocardial injury. The
measurement of troponin levels in trauma patients may be undertaken but they are
less useful in delineating the extent of myocardial trauma than following MI.
When cardiac injury is of a blunt nature and is associated with cardiogenic shock the
right side of the heart is the most likely site of injury with chamber and or valve
rupture. These patients require surgery to repair these defects and will require
cardiopulmonary bypass to achieve this. Some may require intra aortic balloon pump
as a bridge to surgery.
Anaphylactic shock
Anaphylaxis may be defined as a severe, life-threatening, generalised or systemic
hypersensitivity reaction.
Anaphylaxis is one of the few times when you would not have time to look up the
dose of a medication. The Resuscitation Council guidelines on anaphylaxis have
recently been updated. Adrenaline is by far the most important drug in anaphylaxis
and should be given as soon as possible. The recommended doses for adrenaline,
hydrocortisone and chlorphenamine are as follows:
Adrenaline can be repeated every 5 minutes if necessary. The best site for IM
injection is the anterolateral aspect of the middle third of the thigh.
B. Vital capacity
C. Inspiratory capacity
E. Tidal volume
Lung volumes
Definitions
Tidal volume (TV) Is the volume of air inspired and expired during each
ventilatory cycle at rest.
It is normally 500mls in males and 340mls in
females.
Residual volume (RV) Is that volume of air remaining in the lungs after a
maximal expiration.
RV = FRC - ERV. 1500mls.
Functional residual Is the volume of air remaining in the lungs at the end
capacity (FRC) of a normal expiration.
FRC = RV + ERV. 2500mls.
Vital capacity (VC) Is the maximal volume of air that can be forcibly
exhaled after a maximal inspiration.
VC = TV + IRV + ERV. 4500mls in males, 3500mls
in females.
Total lung capacity Is the volume of air in the lungs at the end of a
(TLC) maximal inspiration.
TLC = FRC + TV + IRV = VC + RV. 5500-6000mls.
Forced vital capacity The volume of air that can be maximally forcefully
(FVC)
exhaled.
Which of the following does not decrease the functional residual capacity?
A. Obesity
B. Pulmonary fibrosis
C. Muscle relaxants
D. Laparoscopic surgery
E. Upright position
Increased FRC:
Erect position
Emphysema
Asthma
Decreased FRC:
Pulmonary fibrosis
Laparoscopic surgery
Obesity
Abdominal swelling
Muscle relaxants
When the patient is upright the diaphragm and abdominal organs put less pressure on
the lung bases, allowing for an increase in the functional residual capacity (FRC).
Other causes of increased FRC include:
Emphysema
Asthma
Abdominal swelling
Pulmonary oedema
Reduced muscle tone of the diaphragm
Age
Lung volumes
Definitions
Tidal volume (TV) Is the volume of air inspired and expired during each
ventilatory cycle at rest.
It is normally 500mls in males and 340mls in
females.
Residual volume (RV) Is that volume of air remaining in the lungs after a
maximal expiration.
RV = FRC - ERV. 1500mls.
Functional residual Is the volume of air remaining in the lungs at the end
capacity (FRC) of a normal expiration.
FRC = RV + ERV. 2500mls.
Vital capacity (VC) Is the maximal volume of air that can be forcibly
exhaled after a maximal inspiration.
VC = TV + IRV + ERV. 4500mls in males, 3500mls
in females.
Total lung capacity Is the volume of air in the lungs at the end of a
(TLC) maximal inspiration.
TLC = FRC + TV + IRV = VC + RV. 5500-6000mls.
Forced vital capacity The volume of air that can be maximally forcefully
(FVC) exhaled.
A. Posterior pituitary
DHEA possesses some androgenic activity and is almost exclusively released from
the adrenal gland.
Renin-angiotensin-aldosterone system
Renin
Low BP
Hyponatraemia
Sympathetic nerve stimulation
Catecholamines
Erect posture
Angiotensin
Aldosterone
A. Rectum
B. Small bowel
C. Gallbladder
D. Pancreas
E. Stomach
The rectum has the potential to generate secretions rich in potassium. This is
the rationale behind administration of resins for hyperkalaemia and the
development of hypokalaemia in patients with villous adenoma of the rectum.
Potassium secretion -GI tract
Potassium secretions
Salivary glands Variable may be up to 60mmol/L
Stomach 10 mmol/L
Bile 5 mmol/L
Pancreas 4-5 mmol/L
Small bowel 10 mmol/L
Rectum 30 mmol/L
The above table provides average figures only and the exact composition
varies depending upon the existence of disease, serum aldosterone levels and
serum pH.
A key point to remember for the exam is that gastric potassium secretions are
low. Hypokalaemia may occur in vomiting, usually as a result of renal wasting
of potassium, not because of potassium loss in vomit.
What is the typical stroke volume in a resting 70 Kg man?
A. 10ml
B. 150ml
C. 125ml
D. 45ml
E. 70ml
The stroke volume equates to the volume of blood ejected from the ventricle during
each cycle of cardiac contraction. The volumes for both ventricles are typically equal
and equate roughly to 70ml for a 70Kg man. It is calculated by subtracting the end
systolic volume from the end diastolic volume.
Cardiac size
Contractility
Preload
Afterload
A patient loses 1.6L fresh blood from their abdominal drain. Which of the following
will not decrease?
A. Cardiac output
B. Renin secretion
E. Blood pressure
Renin secretion will increase as systemic hypotension will cause impairment of renal
blood flow. Although the kidney can autoregulate its own blood flow over a range of
systemic blood pressures a loss of 1.6 L will usually produce an increase in renin
secretion.
Shock
Septic shock
Septic shock is a major problem and those patients with severe sepsis have a mortality
rate in excess of 40%. In those who are admitted to intensive care mortality ranges
from 6% with no organ failure to 65% in those with 4 organ failure.
Patients with infections and two or more elements of SIRS meet the diagnostic criteria
for sepsis. Those with organ failure have severe sepsis and those with refractory
hypotension -septic shock.
During the septic process there is marked activation of the immune system with
extensive cytokine release. This may be coupled with or triggered by systemic
circulation of bacterial toxins. These all cause endothelial cell damage and neutrophil
adhesion. The overall hallmarks are thus those of excessive inflammation,
coagulation and fibrinolytic suppression.
The surviving sepsis campaign highlights the following key areas for attention:
Haemorrhagic shock
The average adult blood volume comprises 7% of body weight. Thus in the 70 Kg
adult this will equate to 5 litres. This changes in children (8-9% body weight) and is
slightly lower in the elderly.
The table below outlines the 4 major classes of haemorrhagic shock and their
associated physiological sequelae:
In patients suffering from trauma the most likely cause of shock is haemorrhage.
However, the following may also be the cause or occur concomitantly:
Tension pneumothorax
Spinal cord injury
Myocardial contusion
Cardiac tamponade
Neurogenic shock
This occurs most often following a spinal cord transection, usually at a high level.
There is resultant interruption of the autonomic nervous system. The result is either
decreased sympathetic tone or increased parasympathetic tone, the effect of
which is a decrease in peripheral vascular resistance mediated by marked
vasodilation.
This results in decreased preload and thus decreased cardiac output (Starlings law).
There is decreased peripheral tissue perfusion and shock is thus produced. In contrast
with many other types of shock peripheral vasoconstrictors are used to return vascular
tone to normal.
Cardiogenic shock
In medical patients the main cause is ischaemic heart disease. In the traumatic
setting direct myocardial trauma or contusion is more likely. Evidence of ECG
changes and overlying sternal fractures or contusions should raise the suspicion of
injury. Treatment is largely supportive and transthoracic echocardiography should be
used to determine evidence of pericardial fluid or direct myocardial injury. The
measurement of troponin levels in trauma patients may be undertaken but they are
less useful in delineating the extent of myocardial trauma than following MI.
When cardiac injury is of a blunt nature and is associated with cardiogenic shock the
right side of the heart is the most likely site of injury with chamber and or valve
rupture. These patients require surgery to repair these defects and will require
cardiopulmonary bypass to achieve this. Some may require intra aortic balloon pump
as a bridge to surgery.
Anaphylactic shock
Anaphylaxis may be defined as a severe, life-threatening, generalised or systemic
hypersensitivity reaction.
Anaphylaxis is one of the few times when you would not have time to look up the
dose of a medication. The Resuscitation Council guidelines on anaphylaxis have
recently been updated. Adrenaline is by far the most important drug in anaphylaxis
and should be given as soon as possible. The recommended doses for adrenaline,
hydrocortisone and chlorphenamine are as follows:
Release of vasopressin from the pituitary will result in which of the following?
Renal Physiology
Overview
Each nephron is supplied with blood from an afferent arteriole that opens onto
the glomerular capillary bed.
Blood then flows to an efferent arteriole, supplying the peritubular capillaries
and medullary vasa recta.
The kidney receives up to 25% of resting cardiac output.
The kidney is able to autoregulate its blood flow between systolic pressures of
80- 180mmHg so there is little variation in renal blood flow.
This is achieved by myogenic control of arteriolar tone, both sympathetic
input and hormonal signals (e.g. renin) are responsible.
Glomerular filtration rate = Total volume of plasma per unit time leaving the
capillaries and entering the bowman's capsule
1. Inert
2. Free filtration from the plasma at the glomerulus (not protein bound)
3. Not absorbed or secreted at the tubules
4. Plasma concentration constant during urine collection
The clearance of a substance is dependent not only on its diffusivity across the
basement membrane but also subsequent tubular secretion and / or
reabsorption.
So glucose which is freely filtered across the basement membrane is usually
reabsorbed from tubules giving a clearance of zero.
Tubular function
Loop of Henle
A. Vasopressin
B. Angiotensin I
C. Aldosterone
D. Somatostatin
E. Cholecystokinin
A. 50%
B. 5%
C. 35%
D. 65%
E. 25%
70 Kg male = 42 L water (60%
of total body weight)
Fluid compartment physiology
A. A α fibres
B. A β fibres
C. B fibres
D. C fibres
Somatic pain
B. 200ml
C. 500ml
D. 1500ml
E. 3000ml
Pancreatic juice
Alkaline solution pH 8
1500ml/day
Composition: acinar secretion (ENZYMES: trypsinogen, procarboxylase,
amylase, lecithin) and ductile secretion (HCO, Na+, water)
Pancreatic juice action: Trypsinogen is converted via enterokinase to active
trypsin in the duodenum. Trypsin then activates the other inactive enzymes.
D. Direct laryngoscopy
Exploration of the parathyroid glands may result in impairment of the blood supply.
Serum PTH levels can fall quickly and features of hypocalcaemia may ensue, these
include neuromuscular irritability and laryngospasm. Prompt administration of
intravenous calcium gluconate can be lifesaving. The absence of any neck swelling
and no blood in the drain would go against a contained haematoma in the neck (which
should be managed by removal of skin closure).
Calcium homeostasis
Calcium ions are linked to a wide range of physiological processes. The largest store
of bodily calcium is contained within the skeleton. Calcium levels are primarily
controlled by parathyroid hormone, vitamin D and calcitonin.
Both growth hormone and thyroxine also play a small role in calcium metabolism.
Theme: Interpretation of aterial blood gas results
Which of the following arterial blood gases fit with the description below?
pH 7.19, pCO2 10.2, pO2 16 (FiO2 85%), Bicarbonate 23.8, Base excess -
2.2 mmol
pH 7.32, PCO2 3.8, PaO2 22.2 (FiO2 40%), Bicarbonate 19.1, Base excess
-7.9
pH 7.36, PaCO2 7.3, PO2 8.9 (FiO2 40%), Bicarbonate 30.2, Base excess
5.3
In advanced life support training, a 5 step approach to arterial blood gas interpretation
is advocated.
D. Adrenal medulla
Hydrocortisone = 1
Prednisolone = 4
Dexamethasone = 25
Cortisol
Glucocorticoid
Released by zona fasiculata of the adrenal gland
90% protein bound; 10% active
Circadian rhythm: High in the mornings
Negative feedback via ACTH
Actions
Glycogenolysis
Glucaneogenesis
Protein catabolism
Lipolysis
Stress response
Anti-inflammatory
Decrease protein in bones
Increase gastric acid
Increases neutrophils/platelets/red blood cells
Inhibits fibroblastic activity
Which of the following is not an intravenous colloid?
A. Gelofusine
B. Dextran 40
D. Hydroxyethyl starch
E. Bicarbonate 8.4%
Bicarbonate is a crystalloid
Please select the most likely reason for hyponatraemia for each scenario given. Each
option may be used once, more than once or not at all.
38. A 73 year old man presents to pre operative clinic for an elective total hip
replacement. He is on frusemide for hypertension. He is found to have the
following blood results:
Na 120
Urine Na 10 (low)
Serum osmolality 280 (normal)
The blood results reflect extra-renal sodium loss. The body is trying to
preserve the sodium by not allowing any sodium into the urine (hence the low
Na in the urine). Note with renal sodium loss the Urinary sodium is high.
39. A 67 year old man presents to pre operative clinic for an elective hernia
repair. He is on frusemide for heart failure. He is found to have the following
blood results:
Na 120
Urine Na 35 (high)
Urine osmolality 520 (high)
Serum osmolality 265 (low)
40. A 77 year old man presents to pre operative clinic for a total knee
replacement. He is on frusemide for hypertension. He is known to have
multiple myeloma. He is found to have the following blood results:
Na 120
Serum osmolality 280 (normal)
Urine osmolallity normal
Urine Na normal
Pseudohyponatraemia
SIADH:
Hyponatraemia
Hyponatraemia
This is commonly tested in the MRCS (despite most surgeons automatically seeking
medical advice if this occurs!). The most common cause in surgery is the over
administration of 5% dextrose.
Classification
Urinary sodium > 20 Sodium depletion, renal loss Mnemonic: Syndrome
mmol/l of INAPPropriate Anti-
Patient often Diuretic Hormone:
hypovolaemic In creased
Diuretics (thiazides) Na (sodium)
Addison's PP (urine)
Diuretic stage of renal
failure
SIADH (serum osmolality
low, urine osmolality
high, urine Na high)
Patient often euvolaemic
Management
Symptomatic Hyponatremia :
Disorders of acid- base balance are often covered in the MRCS part A, both in the
SBA and EMQ sections.
The acid-base normogram below shows how the various disorders may be
categorised
Metabolic acidosis
Metabolic acidosis secondary to high lactate levels may be subdivided into two types:
Metabolic alkalosis
Causes
Respiratory acidosis
Causes
COPD
Decompensation in other respiratory conditions e.g. Life-threatening asthma /
pulmonary oedema
Sedative drugs: benzodiazepines, opiate overdose
Respiratory alkalosis
Causes
A. Cerebral vasoconstriction
B. Cerebral vasodilation
Applied neurophysiology
A. 4 mmol/L
B. 14 mmol/L
C. 20 mmol/L
D. 21 mmol/L
E. 23 mmol/L
Anion gap
Lignocaine blocks sodium channels. They will typically be activated first, hence the
pain some patients experience on administration.
Lidocaine
An amide
Local anaesthetic and a less commonly used antiarrhythmic (affects Na
channels in the axon)
Hepatic metabolism, protein bound, renally excreted
Toxicity: due to IV or excess administration. Increased risk if liver
dysfunction or low protein states. Note acidosis causes lidocaine to detach
from protein binding.
Drug interactions: Beta blockers, ciprofloxacin, phenytoin
Features of toxicity: Initial CNS over activity then depression as lidocaine
initially blocks inhibitory pathways then blocks both inhibitory and activating
pathways. Cardiac arrhythmias.
Increased doses may be used when combined with adrenaline to limit systemic
absorption.
Cocaine
Bupivicaine
Prilocaine
All local anaesthetic agents dissociate in tissues and this contributes to their
therapeutic effect. The dissociation constant shifts in tissues that are acidic e.g. where
an abscess is present and this reduce the efficacy.
References
An excellent review is provided by:
French J and Sharp L. Local Anaesthetics. Ann R Coll Surg Engl 2012; 94: 76-80.
A 22 year old man suffers a blunt head injury. He is drowsy and has a GCS of 7 on
admission. Which of the following is the major determinant of cerebral blood flow in
this situation?
D. Hypoxaemia
E. Acidosis
Hypoxaemia and acidosis may both affect cerebral blood flow. However, in the
traumatic situation increases in intracranial pressure are far more likely to occur
especially when GCS is low. This will adversely affect cerebral blood flow.
Cerebral blood flow
A. α-1
B. α-2
C. ß-1
D. ß-2
E. D-1
Dobutamine is a sympathomimetic with both alpha- and beta-agonist
properties; it displays a considerable selectivity for beta1-cardiac receptors.
Inotropes and cardiovascular receptors
Inotrope Cardiovascular receptor action
Adrenaline α-1, α-2, β-1, β-2
Noradrenaline α-1,( α-2), (β-1), (β-2)
Dobutamine β-1, (β 2)
Dopamine (α-1), (α-2), (β-1), D-1,D-2
Minor receptor effects in brackets
B. Anterior pituitary
C. Thyroid gland
D. Posterior pituitary
E. Adrenal glands
Calcitonin has the opposite effect of PTH and is release from the thyroid gland.
Calcium homeostasis
Calcium ions are linked to a wide range of physiological processes. The largest store
of bodily calcium is contained within the skeleton. Calcium levels are primarily
controlled by parathyroid hormone, vitamin D and calcitonin.
Both growth hormone and thyroxine also play a small role in calcium metabolism.
What is the half life of insulin in the circulation of a normal healthy adult?
E. Over 6 hours
Insulin is degraded by enzymes in the circulation. It typically has a half life of less
than 30 minutes. Abnormalities of the clearance of insulin may occur in type 2
diabetes.
Insulin
Anabolic hormone
Structure
Synthesis
Function
Although aprotinin reduces fibrinolysis and thus bleeding, it is associated with increased risk
of death and was withdrawn in 2007. Protein C is dependent upon vitamin K and this may
paradoxically increase the risk of thrombosis during the early phases of warfarin treatment.
Coagulation cascade
Tissue damage
Factor 7 binds to Tissue factor
This complex activates Factor 9
Activated Factor 9 works with Factor 8 to activate Factor 10
Common pathway
Activated Factor 10 causes the conversion of prothrombin to thrombin
Thrombin hydrolyses fibrinogen peptide bonds to form fibrin and also activates
factor 8 to form links between fibrin molecules
Fibrinolysis
Plasminogen is converted to plasmin to facilitate clot resorption
A. Ondansetron
B. Metoclopramide
C. Cyclizine
D. Erythromycin
E. Cisapride
F. Haloperidol
Please select the most appropriate drug for the given scenario. Each option may be
used once, more than once or not at all.
3. A 78 year old manwith diabetes develops autonomic gastropathy and persistant
a troublesome vomiting.
4. A drug which blocks the chemoreceptor trigger zone in the area postrema.
5 HT3 blockers are most effective for many types of nausea for this reason.
5. A 48 year old man with oesphageal varices has a profuse haemorrhage on the
ward.
Metoclopramide
Vomiting
The vomiting centre is in part of the medulla oblongata and is triggered by receptors
in several locations:
A. Macrophages
B. Fibroblasts
C. Myofibroblasts
D. Endothelial cells
E. Neutrophils
The blood - brain barrier is not highly permeable to which of the following?
A. Carbon dioxide
B. Barbituates
C. Glucose
D. Oxygen
E. Hydrogen ions
Cerebrospinal fluid
The CSF fills the space between the arachnoid mater and pia mater (covering surface
of the brain). The total volume of CSF in the brain is approximately 150ml.
Approximately 500 ml is produced by the ependymal cells in the choroid plexus
(70%), or blood vessels (30%). It is reabsorbed via the arachnoid granulations which
project into the venous sinuses.
Circulation
1. Lateral ventricles (via foramen Munro)
2. 3rd ventricle
3. Cerebral aqueduct (aqueduct Sylvius)
4. 4th ventricle (via foramina of Magendie and Luschka)
5. Subarachnoid space
6. Reabsorbed into venous system via arachnoid granulations in superior sagittal sinus
Composition
Glucose: 50-80mg/dl
Protein: 15-40 mg/dl
Red blood cells: Nil
White blood cells: 0-3 cells/ mm3
A 43 year old presents to the urology clinic complaining of impotence. Which of the
following will occur in response to increased penile parasympathetic stimulation?
A. Detumescence
B. Ejaculation
C. Erection
Penile erection
Physiology of erection
Autonomic Sympathetic nerves originate from T11-L2 and parasympathetic
nerves from S2-4 join to form pelvic plexus.
Parasympathetic discharge causes erection, sympathetic
discharge causes ejaculation and detumescence.
Somatic Supplied by dorsal penile and pudendal nerves. Efferent signals are
nerves relayed from Onufs nucleus (S2-4) to innervate ischiocavernosus and
bulbocavernosus muscles.
Autonomic discharge to the penis will trigger the veno-occlusive mechanism which
triggers the flow of arterial blood into the penile sinusoidal spaces. As the inflow
increases the increased volume in this space will secondarily lead to compression of
the subtunical venous plexus with reduced venous return. During the detumesence
phase the arteriolar constriction will reduce arterial inflow and thereby allow venous
return to normalise.
Priapism
Prolonged unwanted erection, in the absence of sexual desire, lasting more than 4
hours.
Classification of priaprism
Low flow Due to veno-occlusion (high intracavernosal pressures).
priaprism
Most common type
Often painful
Often low cavernosal flow
If present for >4 hours requires emergency treatment
Causes
Tests
Management
n class II haemorrhagic shock in a 70Kg male, one would not expect to find?
B. Tachycardia
Urine output in class II shock (assuming 70Kg adult) is typically between 20 and
30ml.
Shock
Septic shock
Septic shock is a major problem and those patients with severe sepsis have a mortality
rate in excess of 40%. In those who are admitted to intensive care mortality ranges
from 6% with no organ failure to 65% in those with 4 organ failure.
Patients with infections and two or more elements of SIRS meet the diagnostic criteria
for sepsis. Those with organ failure have severe sepsis and those with refractory
hypotension -septic shock.
During the septic process there is marked activation of the immune system with
extensive cytokine release. This may be coupled with or triggered by systemic
circulation of bacterial toxins. These all cause endothelial cell damage and neutrophil
adhesion. The overall hallmarks are thus those of excessive inflammation,
coagulation and fibrinolytic suppression.
The surviving sepsis campaign highlights the following key areas for attention:
Haemorrhagic shock
The average adult blood volume comprises 7% of body weight. Thus in the 70 Kg
adult this will equate to 5 litres. This changes in children (8-9% body weight) and is
slightly lower in the elderly.
The table below outlines the 4 major classes of haemorrhagic shock and their
associated physiological sequelae:
In patients suffering from trauma the most likely cause of shock is haemorrhage.
However, the following may also be the cause or occur concomitantly:
Tension pneumothorax
Spinal cord injury
Myocardial contusion
Cardiac tamponade
Neurogenic shock
This occurs most often following a spinal cord transection, usually at a high level.
There is resultant interruption of the autonomic nervous system. The result is either
decreased sympathetic tone or increased parasympathetic tone, the effect of
which is a decrease in peripheral vascular resistance mediated by marked
vasodilation.
This results in decreased preload and thus decreased cardiac output (Starlings law).
There is decreased peripheral tissue perfusion and shock is thus produced. In contrast
with many other types of shock peripheral vasoconstrictors are used to return vascular
tone to normal.
Cardiogenic shock
In medical patients the main cause is ischaemic heart disease. In the traumatic
setting direct myocardial trauma or contusion is more likely. Evidence of ECG
changes and overlying sternal fractures or contusions should raise the suspicion of
injury. Treatment is largely supportive and transthoracic echocardiography should be
used to determine evidence of pericardial fluid or direct myocardial injury. The
measurement of troponin levels in trauma patients may be undertaken but they are
less useful in delineating the extent of myocardial trauma than following MI.
When cardiac injury is of a blunt nature and is associated with cardiogenic shock the
right side of the heart is the most likely site of injury with chamber and or valve
rupture. These patients require surgery to repair these defects and will require
cardiopulmonary bypass to achieve this. Some may require intra aortic balloon pump
as a bridge to surgery.
Anaphylactic shock
Anaphylaxis may be defined as a severe, life-threatening, generalised or systemic
hypersensitivity reaction.
Anaphylaxis is one of the few times when you would not have time to look up the
dose of a medication. The Resuscitation Council guidelines on anaphylaxis have
recently been updated. Adrenaline is by far the most important drug in anaphylaxis
and should be given as soon as possible. The recommended doses for adrenaline,
hydrocortisone and chlorphenamine are as follows:
Please match the diagnosis with the arterial blood gas result. Each option may be used once,
more than once or not at all.
11. Ureterosigmoidostomy
There is acidosis. To compensate the patient will attempt to reduce the pH level in
the blood by hyperventilating, hence the low CO2 level .
Disorders of acid- base balance are often covered in the MRCS part A, both in the SBA and
EMQ sections.
The acid-base normogram below shows how the various disorders may be categorised
Metabolic acidosis
Metabolic acidosis secondary to high lactate levels may be subdivided into two types:
Metabolic alkalosis
Causes
Respiratory acidosis
Causes
COPD
Decompensation in other respiratory conditions e.g. Life-threatening asthma /
pulmonary oedema
Sedative drugs: benzodiazepines, opiate overdose
Respiratory alkalosis
Causes
Parathyroid hormone
Parathyroid hormone is secreted by the chief cells of the parathyroid glands. It acts to
increase serum calcium concentration by stimulation of the PTH receptors in the
kidney and bone. PTH has a plasma half life of 4 minutes.
Effects of PTH
Bone Binds to osteoblasts which signal to osteoclasts to cause resorption of
bone and release calcium
Kidney Active reabsorption of calcium and magnesium from the distal
convoluted tubule. Decreases reabsorption of phosphate.
Intestine via Increases intestinal calcium absorption by increasing activated
kidney vitamin D. Activated vitamin D increases calcium absorption.
Which of the following drugs does not cause syndrome of inappropriate anti diuretic
hormone release?
A. Haloperidol
B. Carbamazepine
C. Amitriptylline
D. Cyclophosphamide
E. Methotrexate
Drugs causing SIADH: ABCD
Hyponatraemia
Hyponatraemia
This is commonly tested in the MRCS (despite most surgeons automatically seeking
medical advice if this occurs!). The most common cause in surgery is the over
administration of 5% dextrose.
Classification
Urinary sodium > 20 Sodium depletion, renal loss Mnemonic: Syndrome
mmol/l of INAPPropriate Anti-
Patient often Diuretic Hormone:
hypovolaemic In creased
Diuretics (thiazides) Na (sodium)
Addison's PP (urine)
Diuretic stage of renal
failure
SIADH (serum osmolality
low, urine osmolality
high, urine Na high)
Patient often euvolaemic
Management
Symptomatic Hyponatremia :
A. Rising haematocrit
C. Metabolic acidosis
E. Hypernatraemia
Hypernatraemia
Rising haematocrit
Metabolic acidosis
Rising lactate
Increased serum urea to creatinine ratio
Urinary sodium <20 mmol/litre
Urine osmolality approaching 1200mosmol/kg
Pre operative fluid management
Warfarin
Liver disease
P450 enzyme inhibitors, e.g.: amiodarone, ciprofloxacin
Cranberry juice
Drugs which displace warfarin from plasma albumin, e.g. NSAIDs
Inhibit platelet function: NSAIDs
Side-effects
Haemorrhage
Teratogenic
Skin necrosis: when warfarin is first started biosynthesis of protein C is
reduced. This results in a temporary procoagulant state after initially starting
warfarin, normally avoided by concurrent heparin administration. Thrombosis
may occur in venules leading to skin necrosis.
Which of the following does not cause an increased anion gap acidosis?
A. Uraemia
B. Paraldehyde
C. Diabetic ketoacidosis
D. Ethylene glycol
E. Acetazolamide
M - Methanol
U - Uraemia
D - DKA/AKA
P - Paraldehyde/phenformin
I - Iron/INH
L - Lactic acidosis
E - Ethylene glycol
S - Salicylates
Disorders of acid- base balance are often covered in the MRCS part A, both in the SBA and
EMQ sections.
The acid-base normogram below shows how the various disorders may be categorised
Image sourced from Wikipedia
Metabolic acidosis
Metabolic acidosis secondary to high lactate levels may be subdivided into two types:
Metabolic alkalosis
Causes
Respiratory acidosis
Rise in carbon dioxide levels usually as a result of alveolar hypoventilation
Renal compensation may occur leading to Compensated respiratory acidosis
Causes
COPD
Decompensation in other respiratory conditions e.g. Life-threatening asthma /
pulmonary oedema
Sedative drugs: benzodiazepines, opiate overdose
Respiratory alkalosis
Causes
*Salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early
stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct
acid effects of salicylates (combined with acute renal failure) may lead to an acidosis
Which one of the following is least associated with thrombocytopenia?
A. Heparin therapy
B. Rheumatoid arthritis
C. Infectious mononucleosis
D. Liver disease
E. Pregnancy
Thrombocytopenia
ITP
DIC
TTP
haematological malignancy
hich of the following will increase the volume of pancreatic exocrine secretions?
A. Octreotide
B. Cholecystokinin
C. Aldosterone
D. Adrenaline
Pancreatic juice
Alkaline solution pH 8
1500ml/day
Composition: acinar secretion (ENZYMES: trypsinogen, procarboxylase,
amylase, lecithin) and ductile secretion (HCO, Na+, water)
Pancreatic juice action: Trypsinogen is converted via enterokinase to active
trypsin in the duodenum. Trypsin then activates the other inactive enzymes.
A. Bone
B. Haemoglobin
D. Myoglobin
E. Plasma iron
Iron metabolism
Distribution in body
Total body iron 4g
Haemoglobin 70%
Ferritin and haemosiderin 25%
4%
Myoglobin
Plasma iron 0.1%
A 44 year old man recieves a large volume transfusion of whole blood. The whole blood is
two weeks old. Which of the following best describes its handling of oxygen?
A. It will have a low affinity for oxygen
Stored blood has less 2,3 DPG and therefore has a higher affinity for oxygen, this reduces its
ability to release it at metabolising tissues.
Oxygen Transport
Oxygen transport
Almost all oxygen is transported within erythrocytes. It has limited solubility and only 1% is
carried as solution. Therefore the amount of oxygen transported will depend upon
haemoglobin concentration and its degree of saturation.
Haemoglobin
Globular protein composed of 4 subunits. Haem consists of a protoporphyrin ring
surrounding an iron atom in its ferrous state. The iron can form two additional bonds; one
with oxygen and the other with a polypeptide chain. There are two alpha and two beta
subunits to this polypeptide chain in an adult and together these form globin. Globin cannot
bind oxygen but is able to bind to carbon dioxide and hydrogen ions, the beta chains are
able to bind to 2,3 diphosphoglycerate. The oxygenation of haemoglobin is a reversible
reaction. The molecular shape of haemoglobin is such that binding of one oxygen molecule
facilitates the binding of subsequent molecules.
The oxygen dissociation curve describes the relationship between the percentage of
saturated haemoglobin and partial pressure of oxygen in the blood. It is not affected
by haemoglobin concentration.
Chronic anaemia causes 2, 3 DPG levels to increase, hence shifting the curve to the
right
Bohr effect
Shifts to left = for given oxygen tension there is increased saturation of Hb with
oxygen i.e. Decreased oxygen delivery to tissues
Shifts to right = for given oxygen tension there is reduced saturation of Hb with
oxygen i.e. Enhanced oxygen delivery to tissues
*2,3-diphosphoglycerate
Which of the following does not occur during the physiological response to surgery?
A. Glycogenolysis
D. Bronchoconstriction
Response to surgery
Endocrine response
Vascular endothelium
The Bainbridge reflex is the increase in heart rate mediated via atrial stretch receptors that
occurs following a rapid infusion of blood.
Cardiac physiology
The heart has four chambers ejecting blood into both low pressure and high
pressure systems.
The pumps generate pressures of between 0-25mmHg on the right side and 0-120
mmHg on the left.
At rest diastole comprises 2/3 of the cardiac cycle.
The product of the frequency of heart rate and stroke volume combine to give the
cardiac output which is typically 5-6L per minute.
Detailed descriptions of the various waveforms are often not a feature of MRCS A (although
they are on the syllabus). However, they are a very popular topic for surgical physiology
vivas in the oral examination.
Electrical properties
Intrinsic myogenic rhythm within cardiac myocytes means that even the denervated
heart is capable of contraction.
In the normal situation the cardiac impulse is generated in the sino atrial node in the
right atrium and conveyed to the ventricles via the atrioventricular node.
The sino atrial node is also capable of spontaneous discharge and in the absence of
background vagal tone will typically discharge around 100x per minute. Hence the
higher resting heart rate found in cardiac transplant cases. In the SA and AV nodes
the resting membrane potential is lower than in surrounding cardiac cells and will
slowly depolarise from -70mV to around -50mV at which point an action potential is
generated.
Differences in the depolarisation slopes between SA and AV nodes help to explain
why the SA node will depolarise first. The cells have a refractory period during which
they cannot be re-stimulated and this period allows for adequate ventricular filling.
In pathological tachycardic states this time period is overridden and inadequate
ventricular filling may then occur, cardiac output falls and syncope may ensue.
Parasympathetic fibres project to the heart via the vagus and will release acetylcholine.
Sympathetic fibres release nor adrenaline and circulating adrenaline comes from the adrenal
medulla. Noradrenaline binds to β 1 receptors in the SA node and increases the rate of
pacemaker potential depolarisation.
Cardiac cycle
Mid diastole: AV valves open. Ventricles hold 80% of final volume. Outflow valves
shut. Aortic pressure is high.
Late diastole: Atria contract. Ventricles receive 20% to complete filling. Typical end
diastolic volume 130-160ml.
Early systole: AV valves shut. Ventricular pressure rises. Isovolumetric ventricular
contraction. AV Valves bulge into atria (c-wave). Aortic and pulmonary pressure
exceeded- blood is ejected. Shortening of ventricles pulls atria downwards and
drops intra atrial pressure (x-descent).
Late systole: Ventricular muscles relax and ventricular pressures drop. Although
ventricular pressure drops the aortic pressure remains constant owing to peripheral
vascular resistance and elastic property of the aorta. Brief period of retrograde flow
that occurs in aortic recoil shuts the aortic valve. Ventricles will contain 60ml end
systolic volume. The average stroke volume is 70ml (i.e. Volume ejected).
Early diastole: All valves are closed. Isovolumetric ventricular relaxation occurs.
Pressure wave associated with closure of the aortic valve increases aortic pressure.
The pressure dip before this rise can be seen on arterial waveforms and is called the
incisura. During systole the atrial pressure increases such that it is now above zero
(v- wave). Eventually atrial pressure exceed ventricular pressure and AV valves open
- atria empty passively into ventricles and atrial pressure falls (y -descent )
The negative atrial pressures are of clinical importance as they can allow air embolization to
occur if the neck veins are exposed to air. This patient positioning is important in head and
neck surgery to avoid this occurrence if veins are inadvertently cut, or during CVP line
insertion.
Mechanical properties
It states that for hollow organs with a circular cross section, the total circumferential
wall tension depends upon the circumference of the wall, multiplied by the
thickness of the wall and on the wall tension.
The total luminal pressure depends upon the cross sectional area of the lumen and
the transmural pressure. Transmural pressure is the internal pressure minus
external pressure and at equilibrium the total pressure must counterbalance each
other.
In terms of cardiac physiology the law explains that the rise in ventricular pressure
that occurs during the ejection phase is due to physical change in heart size. It also
explains why a dilated diseased heart will have impaired systolic function.
Starlings law
Increase in end diastolic volume will produce larger stroke volume.
This occurs up to a point beyond which cardiac fibres are excessively stretched and
stroke volume will fall once more. It is important for the regulation of cardiac output
in cardiac transplant patients who need to increase their cardiac output.
Baroreceptor reflexes
Hyperkalaemia
Causes of hyperkalaemia
*beta-blockers interfere with potassium transport into cells and can potentially cause
hyperkalaemia in renal failure patients - remember beta-agonists, e.g. Salbutamol, are
sometimes used as emergency treatment
A. 10%
B. 70%
C. 40%
D. 90%
E. 20%
Although they are small, the submandibular glands provide the bulk of salivary
secretions and contribute 70%, the sublingual glands provide 5% and the remainder
from the parotid.
Submandibular gland
Innervation
Arterial supply
Branch of the Facial artery. The facial artery passes through the gland to groove its
deep surface. It then emerges onto the face by passing between the gland and the
mandible.
Venous drainage
Anterior Facial vein (lies deep to the Marginal Mandibular nerve)
Lymphatic drainage
Deep cervical and jugular chains of nodes
Which is not a cause of hyperuricaemia?
A. Severe psoriasis
B. Lesch-Nyhan syndrome
C. Hyperthyroidism
D. Diabetic ketoacidosis
E. Alcohol
Mnemonic of the drugs causing hyperuricaemia as a result of reduced excretion of
urate
'Can't leap'
C iclosporin
A lcohol
N icotinic acid
T hiazides
L oop diuretics
E thambutol
A spirin
P yrazinamide
Hyperuricaemia
Increased levels of uric acid may be seen secondary to either increased cell
turnover or reduced renal excretion of uric acid. Hyperuricaemia may be found
in asymptomatic patients who have not experienced attacks of gout
Lesch-Nyhan disease
Myeloproliferative disorders
Diet rich in purines
Exercise
Psoriasis
Cytotoxics
Decreased excretion
A 20 year old man is hit in the face and occludes his airway. Which of the following
stimuli and receptor groups would the most potently activated as a result?
The carotid bodies are the most vascular site and hypercapnia the most potent
stimulus.
Control of ventilation
Respiratory centres
Medullary respiratory centre:
Inspiratory and expiratory neurones. Has ventral group which controls forced
voluntary expiration and the dorsal group controls inspiration. Depressed by opiates.
Apneustic centre:
Lower pons
Stimulates inspiration - activates and prolongs inhalation
Overridden by pneumotaxic control to end inspiration
Pneumotaxic centre:
Upper pons, inhibits inspiration at a certain point. Fine tunes the respiratory rate.
Which of the following statements relating to low molecular weight heparins is false?
Heparin
Better bioavailability
Lower risk of bleeding
Longer half life
Little effect on APTT at prophylactic dosages
Less risk of HIT
Complications
Bleeding
Osteoporosis
Heparin induced thrombocytopenia (HIT): occurs 5-14 days after 1st exposure
Anaphylaxis
A. Medulla oblongata
Onufs nucleus is located in the anterior horn of S2 and is the origin of neurones to the
external urethral sphincter.
Urinary incontinence
Urinary incontinence
Involuntary passage of urine. Most cases are female (80%). It has a prevalence of
11% in those aged greater than 65 years. The commonest variants include:
Males
Males may also suffer from incontinence although it is a much rarer condition in men.
A number of anatomical factors contribute to this. Males have 2 powerful sphincters;
one at the bladder neck and the other in the urethra. Damage to the bladder neck
mechanism is a factor in causing retrograde ejaculation following prostatectomy. The
short segment of urethra passing through the urogenital diaphragm consists of striated
muscle fibres (the external urethral sphincter) and smooth muscle capable of more
sustained contraction. It is the latter mechanism that maintains continence following
prostatectomy.
Females
The sphincter complex at the level of bladder neck is poorly developed in females. As
a result the external sphincter complex is functionally more important, its composition
being similar to that of males. Innervation is via the pudendal nerve and the
neuropathy that may accompany obstetric events may compromise this and lead to
stress urinary incontinence.
Innervation
Somatic innervation to the bladder is via the pudendal, hypogastric and pelvic nerves.
Autonomic nerves travel in these nerve fibres too. Bladder filling leads to detrusor
relaxation (sympathetic) coupled with sphincter contraction. The parasympathetic
system causes detrusor contraction and sphincter relaxation. Overall control of
micturition is centrally mediated via centres in the Pons.
Urethral mobility:
Pressure not transmitted appropriately to the urethra resulting in involuntary passage
of urine during episodes of raised intra-abdominal pressure.
Sphincter dysfunction:
Sphincter fails to adapt to compress urethra resulting in involuntary passage of urine.
When the sphincter completely fails there is often to continuous passage of urine.
Urge incontinence
In these patients there is sense of urgency followed by incontinence. The detrusor
muscle in these patients is unstable and urodynamic investigation will demonstrate
overactivity of the detrusor muscle at inappropriate times (e.g. Bladder filling).
Urgency may be seen in patients with overt neurological disorders and those without.
The pathophysiology is not well understood but poor central and peripheral co-
ordination of the events surrounding bladder filling are the main processes.
Assessment
Careful history and examination including vaginal examination for cystocele.
Bladder diary for at least 3 days
Consider flow cystometry if unclear symptomatology or surgery considered and
diagnosis is unclear.
Exclusion of other organic disease (e.g. Stones, UTI, Cancer)
Management
Conservative measures should be tried first; Stress urinary incontinence or mixed
symptoms should undergo 3 months of pelvic floor exercise. Over active bladder
should have 6 weeks of bladder retraining.
Drug therapy for women with overactive bladder should be offered with oxybutynin if
conservative measures fail.
In women with detrusor instability who fail non operative therapy a trial of sacral
neuromodulation may be considered, with conversion to permanent implant if good
response. Augmentation cystoplasty is an alternative but will involve long term
intermittent self catheterisation.
In women with stress urinary incontinence a urethral sling type procedure may be
undertaken. Where cystocele is present in association with incontinence it should be
repaired particularly if it lies at the introitus.
NICE guidelines
A 43 year old lady presents with urinary incontinence. At which of the following
locations is Onufs nucleus likely to be found?
A. Medulla oblongata
B. Anterior horn of L5 nerve roots
Onufs nucleus is located in the anterior horn of S2 and is the origin of neurones to the
external urethral sphincter.
Urinary incontinence
Urinary incontinence
Involuntary passage of urine. Most cases are female (80%). It has a prevalence of
11% in those aged greater than 65 years. The commonest variants include:
Males
Males may also suffer from incontinence although it is a much rarer condition in men.
A number of anatomical factors contribute to this. Males have 2 powerful sphincters;
one at the bladder neck and the other in the urethra. Damage to the bladder neck
mechanism is a factor in causing retrograde ejaculation following prostatectomy. The
short segment of urethra passing through the urogenital diaphragm consists of striated
muscle fibres (the external urethral sphincter) and smooth muscle capable of more
sustained contraction. It is the latter mechanism that maintains continence following
prostatectomy.
Females
The sphincter complex at the level of bladder neck is poorly developed in females. As
a result the external sphincter complex is functionally more important, its composition
being similar to that of males. Innervation is via the pudendal nerve and the
neuropathy that may accompany obstetric events may compromise this and lead to
stress urinary incontinence.
Innervation
Somatic innervation to the bladder is via the pudendal, hypogastric and pelvic nerves.
Autonomic nerves travel in these nerve fibres too. Bladder filling leads to detrusor
relaxation (sympathetic) coupled with sphincter contraction. The parasympathetic
system causes detrusor contraction and sphincter relaxation. Overall control of
micturition is centrally mediated via centres in the Pons.
Urethral mobility:
Pressure not transmitted appropriately to the urethra resulting in involuntary passage
of urine during episodes of raised intra-abdominal pressure.
Sphincter dysfunction:
Sphincter fails to adapt to compress urethra resulting in involuntary passage of urine.
When the sphincter completely fails there is often to continuous passage of urine.
Urge incontinence
In these patients there is sense of urgency followed by incontinence. The detrusor
muscle in these patients is unstable and urodynamic investigation will demonstrate
overactivity of the detrusor muscle at inappropriate times (e.g. Bladder filling).
Urgency may be seen in patients with overt neurological disorders and those without.
The pathophysiology is not well understood but poor central and peripheral co-
ordination of the events surrounding bladder filling are the main processes.
Assessment
Careful history and examination including vaginal examination for cystocele.
Bladder diary for at least 3 days
Consider flow cystometry if unclear symptomatology or surgery considered and
diagnosis is unclear.
Exclusion of other organic disease (e.g. Stones, UTI, Cancer)
Management
Conservative measures should be tried first; Stress urinary incontinence or mixed
symptoms should undergo 3 months of pelvic floor exercise. Over active bladder
should have 6 weeks of bladder retraining.
Drug therapy for women with overactive bladder should be offered with oxybutynin if
conservative measures fail.
In women with detrusor instability who fail non operative therapy a trial of sacral
neuromodulation may be considered, with conversion to permanent implant if good
response. Augmentation cystoplasty is an alternative but will involve long term
intermittent self catheterisation.
In women with stress urinary incontinence a urethral sling type procedure may be
undertaken. Where cystocele is present in association with incontinence it should be
repaired particularly if it lies at the introitus.
NICE guidelines
A. Older age
Lung compliance is a measure of the ease of expansion of the lungs and thorax, determined
by pulmonary volume and elasticity. A high degree of compliance indicates a loss of elastic
recoil of the lungs, as in old age or emphysema. This increased lung compliance is due to loss
of supportive tissue around the airways. While a normal lung has a high passive elastic
recoil, the sick lung has a decreased elasticity (i.e. decreased transpulmonary pressure)
which leads to increased lung compliance.
Decreased compliance means that a greater change in pressure is needed for a given change
in volume, as in atelectasis, pulmonary fibrosis, pneumonia, or lack of surfactant.
Lung volumes
Definitions
Tidal volume (TV) Is the volume of air inspired and expired during each
ventilatory cycle at rest.
It is normally 500mls in males and 340mls in females.
Inspiratory reserve Is the maximum volume of air that can be forcibly inhaled
volume (IRV) following a normal inspiration. 3000mls.
Expiratory reserve Is the maximum volume of air that can be forcibly exhaled
volume (ERV) following a normal expiration. 1000mls.
Residual volume (RV) Is that volume of air remaining in the lungs after a maximal
expiration.
RV = FRC - ERV. 1500mls.
Functional residual Is the volume of air remaining in the lungs at the end of a
capacity (FRC) normal expiration.
FRC = RV + ERV. 2500mls.
Vital capacity (VC) Is the maximal volume of air that can be forcibly exhaled
after a maximal inspiration.
VC = TV + IRV + ERV. 4500mls in males, 3500mls in females.
Total lung capacity Is the volume of air in the lungs at the end of a maximal
(TLC) inspiration.
TLC = FRC + TV + IRV = VC + RV. 5500-6000mls.
Forced vital capacity The volume of air that can be maximally forcefully exhaled.
(FVC)
Which of the following statements relating to alveolar ventilation is untrue?
A patient inhales 100% oxygen to empty the conducting zone gases of nitrogen and
then exhales through a mouthpiece which analyses the nitrogen concentration at the
mouth. Initially the exhaled gases contain no nitrogen as this is dead space gas; the
nitrogen concentration will increase
as the alveolar gases are exhaled. Nitrogen which is measured following the breath of
100% oxygen must then have come only from gas exchanging areas of the lung and
not dead space.
Alveolar ventilation
Dead space ventilation describes the volume of gas not involved in exchange
in the blood.
Volume of gas in the alveoli and anatomical dead space not involved in
gaseous exchange.
Alveolar ventilation is the volume of fresh air entering the alveoli per minute.
A. mu
B. alpha
C. sigma
D. beta
E. kappa
Opioids
- Combine to specific opiate receptors in the CNS (periaqueductal grey matter, limbic
system, substantia gelatinosa)
A. Adrenaline
B. Glucagon
C. Gastrin
D. Arginine
Insulin
Anabolic hormone
Structure
Synthesis
Function
A. Creatinine
C. Inulin
D. Glucose
E. Protein
Renal plasma flow = (amount of PAH in urine per unit time) / (difference in PAH
concentration in the renal artery or vein)
Renal Physiology
Overview
Each nephron is supplied with blood from an afferent arteriole that opens onto
the glomerular capillary bed.
Blood then flows to an efferent arteriole, supplying the peritubular capillaries
and medullary vasa recta.
The kidney receives up to 25% of resting cardiac output.
The kidney is able to autoregulate its blood flow between systolic pressures of
80- 180mmHg so there is little variation in renal blood flow.
This is achieved by myogenic control of arteriolar tone, both sympathetic
input and hormonal signals (e.g. renin) are responsible.
Glomerular filtration rate = Total volume of plasma per unit time leaving the
capillaries and entering the bowman's capsule
The clearance of a substance is dependent not only on its diffusivity across the
basement membrane but also subsequent tubular secretion and / or
reabsorption.
So glucose which is freely filtered across the basement membrane is usually
reabsorbed from tubules giving a clearance of zero.
Tubular function
Loop of Henle
A. Creatinine
C. Inulin
D. Glucose
E. Protein
Renal plasma flow = (amount of PAH in urine per unit time) / (difference in PAH
concentration in the renal artery or vein)
Renal Physiology
Overview
Each nephron is supplied with blood from an afferent arteriole that opens onto
the glomerular capillary bed.
Blood then flows to an efferent arteriole, supplying the peritubular capillaries
and medullary vasa recta.
The kidney receives up to 25% of resting cardiac output.
The kidney is able to autoregulate its blood flow between systolic pressures of
80- 180mmHg so there is little variation in renal blood flow.
This is achieved by myogenic control of arteriolar tone, both sympathetic
input and hormonal signals (e.g. renin) are responsible.
Glomerular filtration rate = Total volume of plasma per unit time leaving the
capillaries and entering the bowman's capsule
1. Inert
2. Free filtration from the plasma at the glomerulus (not protein bound)
3. Not absorbed or secreted at the tubules
4. Plasma concentration constant during urine collection
The clearance of a substance is dependent not only on its diffusivity across the
basement membrane but also subsequent tubular secretion and / or
reabsorption.
So glucose which is freely filtered across the basement membrane is usually
reabsorbed from tubules giving a clearance of zero.
Tubular function
Loop of Henle
A. Thiazides
B. Antacids
C. Coeliac disease
D. Sarcoidosis
E. Zolinger-Ellison syndrome
Mnemonic for the causes of
hypercalcaemia:
CHIMPANZEES
C alcium supplementation
H yperparathyroidism
I atrogentic (Drugs: Thiazides)
M ilk Alkali syndrome
P aget disease of the bone
A cromegaly and Addison's
Disease
N eoplasia
Z olinger-Ellison Syndrome
(MEN Type I)
E xcessive Vitamin D
E xcessive Vitamin A
S arcoidosis
Hypercalcaemia
Main causes
Malignancy
Primary hyperparathyroidism
Less common
Clinical features
A. Distal gastrectomy
B. Cholecystectomy
Calcium is mainly absorbed from the small bowel and this will have a direct long
term impact on calcium metabolism and increase the risk of osteoporosis. Gastric
banding and distal gastrectomy may affect a patients dietary choices but any potential
deleterious nutritional intake may be counteracted by administration of calcium
supplements orally. Only 10% of calcium is absorbed from the colon so that a sub
total colectomy will only have a negligible effect.
Calcium homeostasis
Calcium ions are linked to a wide range of physiological processes. The largest store
of bodily calcium is contained within the skeleton. Calcium levels are primarily
controlled by parathyroid hormone, vitamin D and calcitonin.
Hb 10.7 g/dl
MCV 121 fl
Plt 177 * 10^9/l
WBC 5.4 * 10^9/l
B. Vitamin C deficiency
E. Vitamin E deficiency
Vitamin B12 is mainly used in the body for red blood cell development and also
maintenance of the nervous system. It is absorbed after binding to intrinsic factor
(secreted from parietal cells in the stomach) and is actively absorbed in the terminal
ileum. A small amount of vitamin B12 is passively absorbed without being bound to
intrinsic factor.
pernicious anaemia
post gastrectomy
poor diet
disorders of terminal ileum (site of absorption): Crohn's, blind-loop etc
macrocytic anaemia
sore tongue and mouth
neurological symptoms: e.g. Ataxia
neuropsychiatric symptoms: e.g. Mood disturbances
Management
A 43 year old lady is diagnosed with primary hyperparathyroidism. Her serum PTH
levels are elevated. An endocrine surgeon performs a parathyroidectomy. How long
will it take for the serum PTH levels to fall if the functioning adenoma has been
successfully removed?
A. 6 hours
B. 24 hours
C. 2 hours
D. 1 hour
E. 10 minutes
PTH has a very short half life usually less than 10 minutes. Therefore a demonstrable
drop in serum PTH should be identified within 10 minutes of removing the adenoma.
This is useful clinically since it is possible to check the serum PTH intraoperatively
prior to skin closure and explore the other glands if levels fail to fall.
Calcium homeostasis
Calcium ions are linked to a wide range of physiological processes. The largest store
of bodily calcium is contained within the skeleton. Calcium levels are primarily
controlled by parathyroid hormone, vitamin D and calcitonin.
Both growth hormone and thyroxine also play a small role in calcium metabolism.
Which of the following statements relating to abnormal coagulation is false?
In haemophilia A the APTT is prolonged and there is reduced levels of factor 8:C.
The bleeding time and PT are normal. Cholestatic jaundice prevents the absorption of
the fat soluble vitamin K. Massive transfusion (>10u blood or equivalent to the blood
volume of a person) puts the patient at risk of thrombocytopaenia, factor 5 and 8
deficiency.
Abnormal coagulation
Work of breathing is decreased which is one reasons it is popular option for weaning
ventilated patients. Humdified air in this setting helps to reduce the viscosity of
mucous that forms.
Trachea
Trachea
Location C6 vertebra to the upper border of T5 vertebra
(bifurcation)
Arterial and venous Inferior thyroid arteries and the thyroid venous plexus.
supply
Nerve Branches of vagus, sympathetic and the recurrent nerves
Anterior
Manubrium sterni, the remains of the thymus, the aortic arch, left common
carotid arteries, and the deep cardiac plexus
Lateral
In the superior mediastinum, on the right side is the pleura and right vagus; on
its left side are the left recurrent nerve, the aortic arch, and the left common
carotid and subclavian arteries.
A 34 year old man presents with a peptic ulcer. Which of the following is responsible for the
release of gastric acid?
A. Chief cells
B. Parietal cells
C. Brunners Glands
D. G Cells
Parietal cells are responsible for the release of gastric acid. Brunners glands are found in the
duodenum.
Gastric secretions
A working knowledge of gastric secretions is important for surgery because peptic ulcers are
common, surgeons frequently prescribe anti secretory drugs and because there are still
patients around who will have undergone acid lowering procedures (Vagotomy) in the past.
Gastric acid
The diagram below illustrates some of the factors involved in regulating gastric acid
secretion and the relevant associated pharmacology
Image sourced from Wikipedia
A 34 year old man presents with a peptic ulcer. Which of the following is responsible for the
release of gastric acid?
A. Chief cells
B. Parietal cells
C. Brunners Glands
D. G Cells
Parietal cells are responsible for the release of gastric acid. Brunners glands are found in the
duodenum.
Gastric secretions
A working knowledge of gastric secretions is important for surgery because peptic ulcers are
common, surgeons frequently prescribe anti secretory drugs and because there are still
patients around who will have undergone acid lowering procedures (Vagotomy) in the past.
Gastric acid
The diagram below illustrates some of the factors involved in regulating gastric acid
secretion and the relevant associated pharmacology
Somatostatin D cells in the Fat, bile salts and Decreases acid and pepsin secretion,
pancreas and glucose in the decreases gastrin secretion, decreases
stomach intestinal lumen pancreatic enzyme secretion, decreases
insulin and glucagon secretion
inhibits trophic effects of gastrin, stimulates
gastric mucous production
Which of the following does not lead to relaxation of the lower oesophageal
sphincter?
A. Metoclopramide
C. Nicotine
D. Alcohol
E. Theophylline
Metoclopramide acts directly on the smooth muscle of the LOS to cause it to contract.
Theophylline is a phosphodiesterase inhibitor (mimics action of prostaglandin E1)
which causes relaxation of the LOS.
Peristalsis
Circular smooth muscle contracts behind the food bolus and longitudinal
smooth muscle propels the food through the oesophagus
Primary peristalsis spontaneously moves the food from the oesophagus into
the stomach (9 seconds)
Secondary peristalsis occurs when food, which doesn't enter the stomach,
stimulates stretch receptors to cause peristalsis
In the small intestine each peristalsis waves slows to a few seconds and causes
mixture of chyme
In the colon three main types of peristaltic activity are recognised (see below)
Colonic peristalsis
Segmentation Localised contractions in which the bolus is subjected to
contractions local forces to maximise mucosal absorption
Antiperistaltic Localised reverse peristaltic waves to slow entry into
contractions towards colon and maximise absorption
ileum
Mass movements Waves migratory peristaltic waves along the entire colon
to empty the organ prior to the next ingestion of food
bolus
Which of the following is not released from the islets of Langerhans?
A. Pancreatic polypeptide
B. Glucagon
C. Secretin
D. Somatostatin
E. Insulin
Which of the following is not classically seen in coning resulting from raised intra
cranial pressure?
A. Coma
B. Hypotension
E. Bradycardia
Cushings triad
Coning
The cranial vault is a confined cavity apart from infants with a non fused
fontanelle.
Rises in ICP may be accommodated by shifts of CSF.
Once the CSF shifting has reached its capacity ICP will start to rise briskly.
The brain autoregulates its blood supply, as ICP rises the systemic circulation
will display changes to try and meet the perfusion needs of the brain. Usually
this will involve hypertension.
As CSF rises further, the brain will be compressed, cranial nerve palsies may
be seen and compression of essential centres in the brain stem will occur.
When the cardiac centre is involved bradycardia will often develop.
Control of ventilation
Respiratory centres
Inspiratory and expiratory neurones. Has ventral group which controls forced
voluntary expiration and the dorsal group controls inspiration. Depressed by opiates.
Apneustic centre:
Lower pons
Stimulates inspiration - activates and prolongs inhalation
Overridden by pneumotaxic control to end inspiration
Pneumotaxic centre:
Upper pons, inhibits inspiration at a certain point. Fine tunes the respiratory rate.
A 54 year old lady has her serum calcium measured. Assuming her renal function is
normal, what proportion of calcium filtered at the glomerulus will be reabsorbed by
the renal tubules?
A. 5%
B. 15%
C. 25%
D. 50%
E. 95%
Calcium homeostasis
Calcium ions are linked to a wide range of physiological processes. The largest store
of bodily calcium is contained within the skeleton. Calcium levels are primarily
controlled by parathyroid hormone, vitamin D and calcitonin.
Both growth hormone and thyroxine also play a small role in calcium metabolism.
Which of the following does not cause hyperkalaemia?
A. Haemolysis
B. Burns
E. Severe malnutrition
'Machine' - Causes of Increased
Serum K+
Familial periodic paralysis has subtypes associated with hyper and hypokalaemia.
Hyperkalaemia
Causes of hyperkalaemia
*beta-blockers interfere with potassium transport into cells and can potentially cause
hyperkalaemia in renal failure patients - remember beta-agonists, e.g. Salbutamol, are
sometimes used as emergency treatment
C. Inhibits gluconeogenesis
D. Produced in response to an increase of amino acids
Glucagon
Glucagon, the hormonal antagonist to insulin, is released from the alpha cells of the
Islets of Langerhans in the pancreas. It will result in an increased plasma glucose
level.
Stimulation Inhibition
Decreased plasma glucose Somatostatin
Increased catecholamines Insulin
Increased free fatty acids and keto acids
Increased plasma amino acids
Sympathetic nervous system Increased urea
Acetylcholine
Cholecystokinin
A. Isoniazid
B. Oranges
C. Flucloxacillin
D. Amiodarone
E. Beef
Carcinoid syndrome
Clinical features
- Onset: years
- Flushing face
- Palpitations
- Tricuspid stenosis causing dyspnoea
- Asthma
- Severe diarrhoea (secretory, persists despite fasting)
Investigation
- 5-HIAA in a 24-hour urine collection
- Scintigraphy
- CT scan
Treatment
Octreotide
Surgical removal
A 52 year old man develops septic shock following a Hartmans procedure for
perforated diverticular disease. He is started on an adrenaline infusion. Which of the
following is least likely to occur?
A. Peripheral vasoconstriction
C. Gluconeogenesis
D. Lipolysis
E. Tachycardia
Its cardiac effects are mediated via β 1 receptors. The coronary arteries which have β
2 receptors are unaffected.
Adrenaline
Actions
α adrenergic receptors:
β adrenergic receptors:
E. An adult
The Monroe-Kelly Doctrine assumes that the cranial cavity is a rigid box. In children
with non fused fontanells this is not the case.
Applied neurophysiology
Pressure within the cranium is governed by the Monroe-Kelly doctrine. This
considers the skull as a closed box. Increases in mass can be accommodated
by loss of CSF. Once a critical point is reached (usually 100- 120ml of CSF
lost) there can be no further compensation and ICP rises sharply. The next step
is that pressure will begin to equate with MAP and neuronal death will occur.
Herniation will also accompany this process.
The CNS can autoregulate its own blood supply. Vaso constriction and
dilatation of the cerebral blood vessels is the primary method by which this
occurs. Extremes of blood pressure can exceed this capacity resulting in risk
of stroke. Other metabolic factors such as hypercapnia will also cause
vasodilation, which is of importance in ventilating head injured patients.
The brain can only metabolise glucose, when glucose levels fall,
consciousness will be impaired.
A. Anti-inflammatory effects
B. Hypoglycaemia
D. Stimulation of lipolysis
E. Mineralocorticoid effects
Prolactin
Antidiuretic hormone
Glucagon
Pituitary gland
Cortisol
Alpha Endorphin
Increased
Antidiuretic hormone
Insulin
Carbohydrate metabolism
Protein metabolism
Lipid metabolism
Increased catecholamine, cortisol and glucagon secretion, and insulin deficiency,
promotes lipolysis and ketone body production.
ADH causes water retention, concentrated urine, and potassium loss and may
continue for 3 to 5 days after surgery
Renin causes sodium and water retention
Cytokines
Glycoproteins
Interleukins (IL) 1 to 17, interferons, and tumour necrosis factor
Synthesized by activated macrophages, fibroblasts, endothelial and glial cells
in response to tissue injury from surgery or trauma
IL-6 main cytokine associated with surgery. Peak 12 to 24 h after surgery and
increase by the degree of tissue damage Other effects of cytokines include
fever, granulocytosis, haemostasis, tissue damage limitation and promotion of
healing.
References
Deborah Burton, Grainne Nicholson, and George Hall
Endocrine and metabolic response to surgery .
B. Alcohol abuse
C. Thyrotoxicosis
D. Chemotherapy
E. Diuretics
Diuretics increase the risk of re-feeding syndrome through a process of increasing the
risk of depletion of key electrolytes.
Hypophosphataemia
Hypokalaemia
Hypomagnesaemia
Abnormal fluid balance
Re-feeding problems
If patient not eaten for > 5 days, aim to re-feed at < 50% energy and protein levels
Prescription
Which of the following statements relating to the regulation of renal blood flow is
untrue?
The kidney autoregulates its blood supply over a range of systolic blood pressures.
Drop in arterial pressure is sensed by the juxtaglomerular cells and renin is released
leading to the activation of the renin-angiontensin system. Mesangial cells are
contractile cells that are located in the tubule and have no direct endocrine function.
Renal Physiology
Overview
Each nephron is supplied with blood from an afferent arteriole that opens onto
the glomerular capillary bed.
Blood then flows to an efferent arteriole, supplying the peritubular capillaries
and medullary vasa recta.
The kidney receives up to 25% of resting cardiac output.
The kidney is able to autoregulate its blood flow between systolic pressures of
80- 180mmHg so there is little variation in renal blood flow.
This is achieved by myogenic control of arteriolar tone, both sympathetic
input and hormonal signals (e.g. renin) are responsible.
Glomerular filtration rate = Total volume of plasma per unit time leaving the
capillaries and entering the bowman's capsule
1. Inert
2. Free filtration from the plasma at the glomerulus (not protein bound)
3. Not absorbed or secreted at the tubules
4. Plasma concentration constant during urine collection
Examples: inulin, creatinine
The clearance of a substance is dependent not only on its diffusivity across the
basement membrane but also subsequent tubular secretion and / or
reabsorption.
So glucose which is freely filtered across the basement membrane is usually
reabsorbed from tubules giving a clearance of zero.
Tubular function
Loop of Henle
A. Angiotensinogen
B. Renin
C. Angiotensin I
D. Angiotensin II
E. Aldosterone
The decrease in blood pressure will be sensed by the juxtaglomerular cells in the
kidney. This will cause renin secretion.
Shock
Septic shock
Septic shock is a major problem and those patients with severe sepsis have a mortality
rate in excess of 40%. In those who are admitted to intensive care mortality ranges
from 6% with no organ failure to 65% in those with 4 organ failure.
Patients with infections and two or more elements of SIRS meet the diagnostic criteria
for sepsis. Those with organ failure have severe sepsis and those with refractory
hypotension -septic shock.
During the septic process there is marked activation of the immune system with
extensive cytokine release. This may be coupled with or triggered by systemic
circulation of bacterial toxins. These all cause endothelial cell damage and neutrophil
adhesion. The overall hallmarks are thus those of excessive inflammation,
coagulation and fibrinolytic suppression.
The surviving sepsis campaign highlights the following key areas for attention:
In surgical patients, the main groups with septic shock include those with anastomotic
leaks, abscesses and extensive superficial infections such as necrotising fasciitis.
When performing surgery the aim should be to undertake the minimum necessary to
restore physiology. These patients do not fare well with prolonged surgery. Definitive
surgery can be more safely undertaken when physiology is restored and clotting in
particular has been normalised.
Haemorrhagic shock
The average adult blood volume comprises 7% of body weight. Thus in the 70 Kg
adult this will equate to 5 litres. This changes in children (8-9% body weight) and is
slightly lower in the elderly.
The table below outlines the 4 major classes of haemorrhagic shock and their
associated physiological sequelae:
Tension pneumothorax
Spinal cord injury
Myocardial contusion
Cardiac tamponade
Neurogenic shock
This occurs most often following a spinal cord transection, usually at a high level.
There is resultant interruption of the autonomic nervous system. The result is either
decreased sympathetic tone or increased parasympathetic tone, the effect of
which is a decrease in peripheral vascular resistance mediated by marked
vasodilation.
This results in decreased preload and thus decreased cardiac output (Starlings law).
There is decreased peripheral tissue perfusion and shock is thus produced. In contrast
with many other types of shock peripheral vasoconstrictors are used to return vascular
tone to normal.
Cardiogenic shock
In medical patients the main cause is ischaemic heart disease. In the traumatic
setting direct myocardial trauma or contusion is more likely. Evidence of ECG
changes and overlying sternal fractures or contusions should raise the suspicion of
injury. Treatment is largely supportive and transthoracic echocardiography should be
used to determine evidence of pericardial fluid or direct myocardial injury. The
measurement of troponin levels in trauma patients may be undertaken but they are
less useful in delineating the extent of myocardial trauma than following MI.
When cardiac injury is of a blunt nature and is associated with cardiogenic shock the
right side of the heart is the most likely site of injury with chamber and or valve
rupture. These patients require surgery to repair these defects and will require
cardiopulmonary bypass to achieve this. Some may require intra aortic balloon pump
as a bridge to surgery.
Anaphylactic shock
Anaphylaxis may be defined as a severe, life-threatening, generalised or systemic
hypersensitivity reaction.
Anaphylaxis is one of the few times when you would not have time to look up the
dose of a medication. The Resuscitation Council guidelines on anaphylaxis have
recently been updated. Adrenaline is by far the most important drug in anaphylaxis
and should be given as soon as possible. The recommended doses for adrenaline,
hydrocortisone and chlorphenamine are as follows:
Adrenaline can be repeated every 5 minutes if necessary. The best site for IM
injection is the anterolateral aspect of the middle third of the thigh.
A. Heparin
B. Ciprofloxacin
C. Salbutamol
D. Levothyroxine
E. Codeine phosphate
Both unfractionated and low-molecular weight heparin can cause hyperkalaemia. This
is thought to be caused by inhibition of aldosterone secretion. Salbutamol is a
recognised treatment for hyperkalaemia.
Hyperkalaemia
Causes of hyperkalaemia
*beta-blockers interfere with potassium transport into cells and can potentially cause
hyperkalaemia in renal failure patients - remember beta-agonists, e.g. Salbutamol, are
sometimes used as emergency treatment
A. Leptin
B. Thyroxine
C. Adiponectin
D. Ghrelin
E. Serotonin
Obesity hormones
leptin decreases
appetite
ghrelin increases
appetite
Whilst thyroxine can increase appetite it does not fit with the clinical picture being
described.
Obesity: physiology
Leptin
Leptin is thought to play a key role in the regulation of body weight. It is produced by
adipose tissue and acts on satiety centres in the hypothalamus and decreases appetite.
More adipose tissue (e.g. in obesity) results in high leptin levels.
Ghrelin
Where as leptin induces satiety, ghrelin stimulates hunger. It is produced mainly by
the fundus of the stomach and the pancreas. Ghrelin levels increase before meals and
decrease after meals
Which of the following bony complications is not linked to excess glucocorticoids?
A. Avascular necrosis
This infection is not typical of steroid excess, although general increased susceptibilty
to infections is.
Cortisol
Glucocorticoid
Released by zona fasiculata of the adrenal gland
90% protein bound; 10% active
Circadian rhythm: High in the mornings
Negative feedback via ACTH
Actions
Glycogenolysis
Glucaneogenesis
Protein catabolism
Lipolysis
Stress response
Anti-inflammatory
Decrease protein in bones
Increase gastric acid
Increases neutrophils/platelets/red blood cells
Inhibits fibroblastic activity
Which one of the following factors is most likely to be responsible for this result?
B. Digoxin therapy
C. Diarrhoea
D. Hypothermia
E. Rhabdomyolysis
Hypomagnasaemia
Diuretics
Total parenteral nutrition
Diarrhoea
Alcohol
Hypokalaemia, hypocalcaemia
Features
Paraesthesia
Tetany
Seizures
Arrhythmias
Decreased PTH secretion --> hypocalcaemia
ECG features similar to those of hypokalaemia
Exacerbates digoxin toxicity
A 43 year old man has a nasogastric tube inserted. The nurse takes a small aspirate of the
fluid from the stomach and tests the pH of the aspirate. What is the normal intragastric pH?
A. 0.5
B. 2
C. 4
D. 5
E. 6
Gastric secretions
A working knowledge of gastric secretions is important for surgery because peptic ulcers are
common, surgeons frequently prescribe anti secretory drugs and because there are still
patients around who will have undergone acid lowering procedures (Vagotomy) in the past.
Gastric acid
The diagram below illustrates some of the factors involved in regulating gastric acid
secretion and the relevant associated pharmacology
Somatostatin D cells in the Fat, bile salts and Decreases acid and pepsin secretion,
pancreas and glucose in the decreases gastrin secretion, decreases
stomach intestinal lumen pancreatic enzyme secretion, decreases
insulin and glucagon secretion
inhibits trophic effects of gastrin, stimulates
gastric mucous production
B. Stroke volume
Cardiac physiology
The heart has four chambers ejecting blood into both low pressure and high
pressure systems.
The pumps generate pressures of between 0-25mmHg on the right side and 0-120
mmHg on the left.
At rest diastole comprises 2/3 of the cardiac cycle.
The product of the frequency of heart rate and stroke volume combine to give the
cardiac output which is typically 5-6L per minute.
Detailed descriptions of the various waveforms are often not a feature of MRCS A (although
they are on the syllabus). However, they are a very popular topic for surgical physiology
vivas in the oral examination.
Electrical properties
Intrinsic myogenic rhythm within cardiac myocytes means that even the denervated
heart is capable of contraction.
In the normal situation the cardiac impulse is generated in the sino atrial node in the
right atrium and conveyed to the ventricles via the atrioventricular node.
The sino atrial node is also capable of spontaneous discharge and in the absence of
background vagal tone will typically discharge around 100x per minute. Hence the
higher resting heart rate found in cardiac transplant cases. In the SA and AV nodes
the resting membrane potential is lower than in surrounding cardiac cells and will
slowly depolarise from -70mV to around -50mV at which point an action potential is
generated.
Differences in the depolarisation slopes between SA and AV nodes help to explain
why the SA node will depolarise first. The cells have a refractory period during which
they cannot be re-stimulated and this period allows for adequate ventricular filling.
In pathological tachycardic states this time period is overridden and inadequate
ventricular filling may then occur, cardiac output falls and syncope may ensue.
Parasympathetic fibres project to the heart via the vagus and will release acetylcholine.
Sympathetic fibres release nor adrenaline and circulating adrenaline comes from the adrenal
medulla. Noradrenaline binds to β 1 receptors in the SA node and increases the rate of
pacemaker potential depolarisation.
Cardiac cycle
Image sourced from Wikipedia
Mid diastole: AV valves open. Ventricles hold 80% of final volume. Outflow valves
shut. Aortic pressure is high.
Late diastole: Atria contract. Ventricles receive 20% to complete filling. Typical end
diastolic volume 130-160ml.
Late systole: Ventricular muscles relax and ventricular pressures drop. Although
ventricular pressure drops the aortic pressure remains constant owing to peripheral
vascular resistance and elastic property of the aorta. Brief period of retrograde flow
that occurs in aortic recoil shuts the aortic valve. Ventricles will contain 60ml end
systolic volume. The average stroke volume is 70ml (i.e. Volume ejected).
Early diastole: All valves are closed. Isovolumetric ventricular relaxation occurs.
Pressure wave associated with closure of the aortic valve increases aortic pressure.
The pressure dip before this rise can be seen on arterial waveforms and is called the
incisura. During systole the atrial pressure increases such that it is now above zero
(v- wave). Eventually atrial pressure exceed ventricular pressure and AV valves open
- atria empty passively into ventricles and atrial pressure falls (y -descent )
The negative atrial pressures are of clinical importance as they can allow air embolization to
occur if the neck veins are exposed to air. This patient positioning is important in head and
neck surgery to avoid this occurrence if veins are inadvertently cut, or during CVP line
insertion.
Mechanical properties
It states that for hollow organs with a circular cross section, the total circumferential
wall tension depends upon the circumference of the wall, multiplied by the
thickness of the wall and on the wall tension.
The total luminal pressure depends upon the cross sectional area of the lumen and
the transmural pressure. Transmural pressure is the internal pressure minus
external pressure and at equilibrium the total pressure must counterbalance each
other.
In terms of cardiac physiology the law explains that the rise in ventricular pressure
that occurs during the ejection phase is due to physical change in heart size. It also
explains why a dilated diseased heart will have impaired systolic function.
Starlings law
Baroreceptor reflexes
B. Colonic angiodysplasia
E. Endometrial adenocarcinoma
A locally perforated colonic tumour will typically cause an intense
inflammatory response and if peritonitis is not present clinically then at the
very least a localised abscess. This inflammatory process is the most likely
(from the list) to falsely raise the serum ferritin level. Angiodysplasia and
dieulafoy lesions are mucosal arteriovenous malformations and unlikely to
result in considerable inflammatory activity.
Ferritin
Ferritin is an intracellular protein that binds iron and stores it to be released in
a controlled fashion at sites where iron is required. Because iron and ferritin
are bound the total body ferritin levels may be decreased in cases of iron
deficiency anaemia. Measurement of serum ferritin levels can be useful in
determining whether an apparently low haemoglobin and microcytosis is truly
caused by an iron deficiency state.
Ferritin is an acute phase protein and may be synthesised in increased
quantities in situations where inflammatory activity is ongoing. Falsely
elevated results may therefore be encountered clinically and need to be taken
in context of the clinical picture and full blood count results.
Which of the following is least likely to cause a prolonged prothrombin time?
A. Cholestatic jaundice
D. Liver disease
Circular smooth muscle contracts behind the food bolus and longitudinal
smooth muscle propels the food through the oesophagus
Primary peristalsis spontaneously moves the food from the oesophagus into
the stomach (9 seconds)
Secondary peristalsis occurs when food, which doesn't enter the stomach,
stimulates stretch receptors to cause peristalsis
In the small intestine each peristalsis waves slows to a few seconds and causes
mixture of chyme
In the colon three main types of peristaltic activity are recognised (see below)
Colonic peristalsis
Segmentation Localised contractions in which the bolus is subjected to
contractions local forces to maximise mucosal absorption
Antiperistaltic Localised reverse peristaltic waves to slow entry into
contractions towards colon and maximise absorption
ileum
Mass movements Waves migratory peristaltic waves along the entire colon
to empty the organ prior to the next ingestion of food
bolus
24 year old man is injured in a road traffic accident. He becomes oliguric and his
renal function deteriorates. Which of the options below would favor acute tubular
necrosis over pre renal uraemia?
Acute renal failure: Pre renal failure vs. acute tubular necrosis
Gastric secretions
A working knowledge of gastric secretions is important for surgery because peptic ulcers are
common, surgeons frequently prescribe anti secretory drugs and because there are still
patients around who will have undergone acid lowering procedures (Vagotomy) in the past.
Gastric acid
The diagram below illustrates some of the factors involved in regulating gastric acid
secretion and the relevant associated pharmacology
Image sourced from Wikipedia
Gastric secretions
A working knowledge of gastric secretions is important for surgery because peptic ulcers are
common, surgeons frequently prescribe anti secretory drugs and because there are still
patients around who will have undergone acid lowering procedures (Vagotomy) in the past.
Gastric acid
The diagram below illustrates some of the factors involved in regulating gastric acid
secretion and the relevant associated pharmacology
Somatostatin D cells in the Fat, bile salts and Decreases acid and pepsin secretion,
pancreas and glucose in the decreases gastrin secretion, decreases
stomach intestinal lumen pancreatic enzyme secretion, decreases
insulin and glucagon secretion
inhibits trophic effects of gastrin, stimulates
gastric mucous production
Which part of the jugular venous waveform is associated with the closure of the
tricuspid valve?
A. a wave
B. c wave
C. x descent
D. y descent
E. v wave
JVP: {C} wave - {c}losure of
the tricuspid valve
The c wave of the jugular venous waveform is associated with the closure of the
tricuspid valve.
As well as providing information on right atrial pressure, the jugular vein waveform
may provide clues to underlying valvular disease. A non-pulsatile JVP is seen in
superior vena caval obstruction. Kussmaul's sign describes a paradoxical rise in JVP
during inspiration seen in constrictive pericarditis
'c' wave
'v' wave
due to passive filling of blood into the atrium against a closed tricuspid valve
giant v waves in tricuspid regurgitation
A. a wave
B. c wave
C. x descent
D. y descent
E. v wave
JVP: {C} wave - {c}losure of
the tricuspid valve
The c wave of the jugular venous waveform is associated with the closure of the
tricuspid valve.
As well as providing information on right atrial pressure, the jugular vein waveform
may provide clues to underlying valvular disease. A non-pulsatile JVP is seen in
superior vena caval obstruction. Kussmaul's sign describes a paradoxical rise in JVP
during inspiration seen in constrictive pericarditis
'c' wave
'v' wave
due to passive filling of blood into the atrium against a closed tricuspid valve
giant v waves in tricuspid regurgitation
A. Transferrin
B. Transthyretin
C. Ferritin
D. Albumin
Ferritin can be markedly increased during acute illness. The other parameters tend to
decrease during an acute phase response.
CRP
procalcitonin
ferritin
fibrinogen
alpha-1 antitrypsin
caeruloplasmin
serum amyloid A
haptoglobin
complement
During the acute phase response the liver decreases the production of other proteins
(sometimes referred to as negative acute phase proteins). Examples include:
albumin
transthyretin (formerly known as prealbumin)
transferrin
retinol binding protein
cortisol binding protein
Theme: Critical care
A. Hypovolaemia
B. Normal
C. Cardiogenic shock
D. Septic shock
For each of the scenarios outlined in the tables below, please select the most
likely diagnosis from the list. Each option may be used once, more than once
or not at all.
17. A 45 year old man is admitted to the intensive care unit following a
laparotomy. He has a central line, pulmonary artery catheter and arterial lines
inserted. The following results are obtained:
Pulmonary artery occlusion Cardiac Systemic vascular
pressure output resistance
Low Low High
Hypovolaemia
18. A 75 year old man is admitted to the intensive care unit following a
laparotomy. He has a central line, pulmonary artery catheter and arterial lines
inserted. The following results are obtained:
Pulmonary artery occlusion Cardiac Systemic vascular
pressure output resistance
High Low High
Cardiogenic shock
In cardiogenic shock pulmonary pressures are often high. This is the basis for
the use of venodilators in the treatment of pulmonary oedema.
19. A 22 year old lady is admitted to the intensive care unit following a
laparotomy. She has a central line, pulmonary artery catheter and arterial lines
inserted. The following results are obtained:
Pulmonary artery occlusion Cardiac Systemic vascular
pressure output resistance
Low High Low
Septic shock
Pulmonary artery occlusion pressure monitoring
Interpretation of PAOP
PAOP mmHg Scenario
Normal 8-12
Low <5 Hypovolaemia
Low with pulmonary oedema <5 ARDS
High >18 Overload
When combined with measurements of systemic vascular resistance and
cardiac output it is possible to accurately classify patients.
A. Atrial repolarisation
C. Ventricular repolarisation
Cardiac physiology
The heart has four chambers ejecting blood into both low pressure and high
pressure systems.
The pumps generate pressures of between 0-25mmHg on the right side and 0-120
mmHg on the left.
At rest diastole comprises 2/3 of the cardiac cycle.
The product of the frequency of heart rate and stroke volume combine to give the
cardiac output which is typically 5-6L per minute.
Detailed descriptions of the various waveforms are often not a feature of MRCS A (although
they are on the syllabus). However, they are a very popular topic for surgical physiology
vivas in the oral examination.
Electrical properties
Intrinsic myogenic rhythm within cardiac myocytes means that even the denervated
heart is capable of contraction.
In the normal situation the cardiac impulse is generated in the sino atrial node in the
right atrium and conveyed to the ventricles via the atrioventricular node.
The sino atrial node is also capable of spontaneous discharge and in the absence of
background vagal tone will typically discharge around 100x per minute. Hence the
higher resting heart rate found in cardiac transplant cases. In the SA and AV nodes
the resting membrane potential is lower than in surrounding cardiac cells and will
slowly depolarise from -70mV to around -50mV at which point an action potential is
generated.
Differences in the depolarisation slopes between SA and AV nodes help to explain
why the SA node will depolarise first. The cells have a refractory period during which
they cannot be re-stimulated and this period allows for adequate ventricular filling.
In pathological tachycardic states this time period is overridden and inadequate
ventricular filling may then occur, cardiac output falls and syncope may ensue.
Parasympathetic fibres project to the heart via the vagus and will release acetylcholine.
Sympathetic fibres release nor adrenaline and circulating adrenaline comes from the adrenal
medulla. Noradrenaline binds to β 1 receptors in the SA node and increases the rate of
pacemaker potential depolarisation.
Cardiac cycle
Mid diastole: AV valves open. Ventricles hold 80% of final volume. Outflow valves
shut. Aortic pressure is high.
Late diastole: Atria contract. Ventricles receive 20% to complete filling. Typical end
diastolic volume 130-160ml.
Late systole: Ventricular muscles relax and ventricular pressures drop. Although
ventricular pressure drops the aortic pressure remains constant owing to peripheral
vascular resistance and elastic property of the aorta. Brief period of retrograde flow
that occurs in aortic recoil shuts the aortic valve. Ventricles will contain 60ml end
systolic volume. The average stroke volume is 70ml (i.e. Volume ejected).
Early diastole: All valves are closed. Isovolumetric ventricular relaxation occurs.
Pressure wave associated with closure of the aortic valve increases aortic pressure.
The pressure dip before this rise can be seen on arterial waveforms and is called the
incisura. During systole the atrial pressure increases such that it is now above zero
(v- wave). Eventually atrial pressure exceed ventricular pressure and AV valves open
- atria empty passively into ventricles and atrial pressure falls (y -descent )
The negative atrial pressures are of clinical importance as they can allow air embolization to
occur if the neck veins are exposed to air. This patient positioning is important in head and
neck surgery to avoid this occurrence if veins are inadvertently cut, or during CVP line
insertion.
Mechanical properties
It states that for hollow organs with a circular cross section, the total circumferential
wall tension depends upon the circumference of the wall, multiplied by the
thickness of the wall and on the wall tension.
The total luminal pressure depends upon the cross sectional area of the lumen and
the transmural pressure. Transmural pressure is the internal pressure minus
external pressure and at equilibrium the total pressure must counterbalance each
other.
In terms of cardiac physiology the law explains that the rise in ventricular pressure
that occurs during the ejection phase is due to physical change in heart size. It also
explains why a dilated diseased heart will have impaired systolic function.
Starlings law
Baroreceptor reflexes
A 72-year-old woman is admitted to the acute surgical unit with profuse vomiting.
Admission bloods show the following:
A. Short PR interval
B. Short QT interval
C. Flattened P waves
D. J waves
E. U waves
Hypokalaemia - U waves
on ECG
J waves are seen in hypothermia whilst delta waves are associated with Wolff
Parkinson White syndrome.
ECG features in hypokalemia
U waves
Small or absent T waves (occasionally inversion)
Prolonged PR interval
ST depression
Long QT interval
A. Bile
B. Small bowel
C. Pancreatic juice
D. Gastric juice
E. Saliva
Of the secretions shown above, saliva has the greatest composition of
potassium. The exact amount secreted will depend upon aldosterone levels.
Potassium composition of secretions
Saliva 20-60 mmol/L
Gastric juice 5-10 mmol/L
Bile 5-8 mmol/L
Pancreatic juice 4-5 mmol/L
Small bowel 4-10 mmol/L
The oxygen-haemoglobin dissociation curve is shifted to the left in:
B. Respiratory acidosis
C. High altitude
D. Pyrexia
E. Haemolytic anaemia
S shaped
curve
The curve is shifted to the left when there is a decreased oxygen requirement by the tissue.
This includes:
1. Hypothermia
2. Alkalosis
3. Reduced levels of DPG:
DPG is found in erythrocytes and is reduced in non exercising muscles, i.e. when
there is reduced glycolysis.
4. Polycythaemia
Oxygen Transport
Oxygen transport
Almost all oxygen is transported within erythrocytes. It has limited solubility and only 1% is
carried as solution. Therefore the amount of oxygen transported will depend upon
haemoglobin concentration and its degree of saturation.
Haemoglobin
Globular protein composed of 4 subunits. Haem consists of a protoporphyrin ring
surrounding an iron atom in its ferrous state. The iron can form two additional bonds; one
with oxygen and the other with a polypeptide chain. There are two alpha and two beta
subunits to this polypeptide chain in an adult and together these form globin. Globin cannot
bind oxygen but is able to bind to carbon dioxide and hydrogen ions, the beta chains are
able to bind to 2,3 diphosphoglycerate. The oxygenation of haemoglobin is a reversible
reaction. The molecular shape of haemoglobin is such that binding of one oxygen molecule
facilitates the binding of subsequent molecules.
The oxygen dissociation curve describes the relationship between the percentage of
saturated haemoglobin and partial pressure of oxygen in the blood. It is not affected
by haemoglobin concentration.
Chronic anaemia causes 2, 3 DPG levels to increase, hence shifting the curve to the
right
Bohr effect
Shifts to left = for given oxygen tension there is increased saturation of Hb with
oxygen i.e. Decreased oxygen delivery to tissues
Shifts to right = for given oxygen tension there is reduced saturation of Hb with
oxygen i.e. Enhanced oxygen delivery to tissues
*2,3-diphosphoglycerate
A homeless 42 year old male had an emergency inguinal hernia repair 24 hours
previously. He has a BMI of 15. He has been put on a feeding regime of 35
kcal/kg/day with no additional medications. The nursing staff contact you as he has
become confused and unsteady. On examination the patient is disorientated to place,
has diplopia and nystagmus. What is the most likely diagnosis?
A. Cerebellar stroke
C. Refeeding syndrome
D. Parkinsonism
E. Wernickes encephalopathy
Triad of Wernicke
encephalopathy:
Acute confusion
Ataxia
Opthalmoplegia
This patient has received a carbohydrate rich diet without any thiamine or vitamin B
co strong replacement. This has led to Wernickes encephalopathy, which classically
presents with confusion, ataxia and opthalmoplegia. Characteristically it is associated
with chronic alcoholism, however it is also known to occur post bariatric surgery.
Hypophosphataemia
Hypokalaemia
Hypomagnesaemia
Abnormal fluid balance
Re-feeding problems
If patient not eaten for > 5 days, aim to re-feed at < 50% energy and protein levels
Prescription
B. Adrenaline
C. Hyponatraemia
D. Hypotension
E. Beta-blockers
Renin
A. Leutinising hormone
B. Dopamine
D. Oestrogen
Potassium depletion occurs either through the gastrointestinal tract or the kidney.
Chronic vomiting in itself is less prone to induce potassium loss than diarrhoea as
gastric secretions contain less potassium than those in the lower GI tract. If vomiting
produces a metabolic alkalosis then renal potassium wasting may occur as potassium
is excreted in preference to hydrogen ions. The converse may occur in potassium
depletion resulting in acid urine.
Hypokalaemia
Vomiting
Diuretics
Cushing's syndrome
Conn's syndrome (primary hyperaldosteronism)
Diarrhoea
Renal tubular acidosis
Acetazolamide
Partially treated diabetic ketoacidosis
Theme: Vitamin deficiency
A. Vitamin A
B. Vitamin B1
C. Vitamin B12
D. Vitamin B3
E. Vitamin C
F. Vitamin K
G. Vitamin D
Please select the vitamin deficiency most closely associated with the situation
described. Each option may be used once, more than once or not at all.
Vitamin D
10. A 44 year old lady presents with jaundice. Following a minor ward based
surgical procedure she develops troublesome and persistent bleeding.
Vitamin K
11. A 69 year old man who has been living in sheleted accomodation for many
months, with inadequate nutrition notices that his night vision is becoming
impaired.
Vitamin A
Loss of vitamin A will result in impaire rhodopsin synthesis and poor night
vision.
Vitamin deficiency
A. During the cephalic phase 40% of the total gastric secretion occurs
Histamine is released from enterochromaffin cells in the stomach mucosa which stimulates
acid secretion.
Intrinsic factor combines with B12 to prevent acid digestion in the stomach.
G cells can be found in the duodenum and jejunum
Gastric secretions
A working knowledge of gastric secretions is important for surgery because peptic ulcers are
common, surgeons frequently prescribe anti secretory drugs and because there are still
patients around who will have undergone acid lowering procedures (Vagotomy) in the past.
Gastric acid
The diagram below illustrates some of the factors involved in regulating gastric acid
secretion and the relevant associated pharmacology
Image sourced from Wikipedia
A 55 year old man undergoes a laparotomy and repair of incisional hernia. Which of
the following hormones is least likely to be released in increased quantities following
the procedure?
A. Insulin
B. ACTH
C. Glucocorticoids
D. Aldosterone
E. Growth hormone
Insulin and thyroxine are often have reduced levels of secretion in the post operative
period. This, coupled with increased glucocorticoid release may cause difficulty in
management of diabetes in individuals with insulin resistance.
Prolactin
Antidiuretic hormone
Glucagon
Pituitary gland
Cortisol
Growth hormone
Increased secretion after surgery has a minor role
Most important for preventing muscle protein breakdown and promote tissue
repair by insulin growth factors
Alpha Endorphin
Increased
Antidiuretic hormone
Insulin
Carbohydrate metabolism
Protein metabolism
Initially there is inhibition of protein anabolism, followed later, if the stress
response is severe, by enhanced catabolism
The amount of protein degradation is influenced by the type of surgery and
also by the nutritional status of the patient
Mainly skeletal muscle protein is affected
The amino acids released form acute phase proteins (fibrinogen, C reactive
protein, complement proteins, a2-macroglobulin, amyloid A and
ceruloplasmin) and are used for gluconeogenesis
Nutritional support has little effect on preventing catabolism
Lipid metabolism
Increased catecholamine, cortisol and glucagon secretion, and insulin deficiency,
promotes lipolysis and ketone body production.
ADH causes water retention, concentrated urine, and potassium loss and may
continue for 3 to 5 days after surgery
Renin causes sodium and water retention
Cytokines
Glycoproteins
Interleukins (IL) 1 to 17, interferons, and tumour necrosis factor
Synthesized by activated macrophages, fibroblasts, endothelial and glial cells
in response to tissue injury from surgery or trauma
IL-6 main cytokine associated with surgery. Peak 12 to 24 h after surgery and
increase by the degree of tissue damage Other effects of cytokines include
fever, granulocytosis, haemostasis, tissue damage limitation and promotion of
healing.
A. Insulin
B. ACTH
C. Glucocorticoids
D. Aldosterone
E. Growth hormone
Insulin and thyroxine are often have reduced levels of secretion in the post operative
period. This, coupled with increased glucocorticoid release may cause difficulty in
management of diabetes in individuals with insulin resistance.
Prolactin
Antidiuretic hormone
Glucagon
Pituitary gland
Cortisol
Growth hormone
Increased secretion after surgery has a minor role
Most important for preventing muscle protein breakdown and promote tissue
repair by insulin growth factors
Alpha Endorphin
Increased
Antidiuretic hormone
Insulin
Carbohydrate metabolism
Protein metabolism
Initially there is inhibition of protein anabolism, followed later, if the stress
response is severe, by enhanced catabolism
The amount of protein degradation is influenced by the type of surgery and
also by the nutritional status of the patient
Mainly skeletal muscle protein is affected
The amino acids released form acute phase proteins (fibrinogen, C reactive
protein, complement proteins, a2-macroglobulin, amyloid A and
ceruloplasmin) and are used for gluconeogenesis
Nutritional support has little effect on preventing catabolism
Lipid metabolism
Increased catecholamine, cortisol and glucagon secretion, and insulin deficiency,
promotes lipolysis and ketone body production.
ADH causes water retention, concentrated urine, and potassium loss and may
continue for 3 to 5 days after surgery
Renin causes sodium and water retention
Cytokines
Glycoproteins
Interleukins (IL) 1 to 17, interferons, and tumour necrosis factor
Synthesized by activated macrophages, fibroblasts, endothelial and glial cells
in response to tissue injury from surgery or trauma
IL-6 main cytokine associated with surgery. Peak 12 to 24 h after surgery and
increase by the degree of tissue damage Other effects of cytokines include
fever, granulocytosis, haemostasis, tissue damage limitation and promotion of
healing.
A. Iron reutilisation
B. Storage of platelets
C. Storage of monocytes
The reservoir function of the spleen is less marked in humans than other animals (e.g.
pigs) and in normal individuals it can sequester between 5 and 10% of the red cell
mass. The other stated processes are major splenic functions and this accounts for the
answer provided.
Spleen
Relations
Superiorly- diaphragm
Anteriorly- gastric impression
Posteriorly- kidney
Inferiorly- colon
Hilum: tail of pancreas and splenic vessels (splenic artery divides here,
branches pass to the white pulp transporting plasma)
Forms apex of lesser sac (containing short gastric vessels)
Contents
- White pulp: immune function. Contains central trabecular artery. The germinal
centres are supplied by arterioles called penicilliary radicles.
- Red pulp: filters abnormal red blood cells
Function
Myelofibrosis
Chronic myeloid leukaemia
Visceral leishmaniasis (kala-azar)
Malaria
Gaucher's syndrome
*the majority of adults patients with sickle-cell will have an atrophied spleen due to
repeated infarction
Which one of the following is associated with increased lung compliance?
A. Kyphosis
B. Pulmonary oedema
C. Emphysema
D. Pulmonary fibrosis
E. Pneumonectomy
Lung compliance is defined as change in lung volume per unit change in airway
pressure
age
emphysema - this is due to loss alveolar walls and associated elastic tissue
pulmonary oedema
pulmonary fibrosis
pneumonectomy
kyphosis
A. Hypothalamus
B. Anterior pituitary
C. Cerebellum
D. Brain stem
E. Temporal lobe
Thermoregulation
Which of the following drugs does not interfere with the measurement of cortisol
levels?
A. Dexamethasone
B. Prednisolone
C. Hydrocortisone IV
D. Hydrocortisone PO
E. Hydrocortisone IM
Cortisol
Glucocorticoid
Released by zona fasiculata of the adrenal gland
90% protein bound; 10% active
Circadian rhythm: High in the mornings
Negative feedback via ACTH
Actions
Glycogenolysis
Glucaneogenesis
Protein catabolism
Lipolysis
Stress response
Anti-inflammatory
Decrease protein in bones
Increase gastric acid
Increases neutrophils/platelets/red blood cells
Inhibits fibroblastic activity
An elderly lady who presented with weight loss and malabsorption was found
to have amyloid of the small bowel. On presentation she was found to have
osteomalacia and was hypocalcaemic. Over the past seven days she has
received total parenteral nutrition with adequate calcium replacement. Despite
this she remained hypocalcaemic. Deficiency of which of the following
electrolytes is most likely to account for this process?
A. Magnesium
B. Potassium
C. Sodium
D. Phosphate
Magnesium is the fourth most abundant cation in the body. The body contains
1000mmol, with half contained in bone and the remainder in muscle, soft
tissues and extracellular fluid. There is no one specific hormonal control of
magnesium and various hormones including PTH and aldosterone affect the
renal handling of magnesium.
Hypertension and bradycardia are seen prior to coning. The brain autoregulates its
blood supply by controlling systemic blood pressure.
Head injury
Features
Pathophysiology
Primary brain injury may be focal (contusion/ haematoma) or diffuse (diffuse
axonal injury)
Diffuse axonal injury occurs as a result of mechanical shearing following
deceleration, causing disruption and tearing of axons
Intra-cranial haematomas can be extradural, subdural or intracerebral, while
contusions may occur adjacent to (coup) or contralateral (contre-coup) to the
side of impact
Secondary brain injury occurs when cerebral oedema, ischaemia, infection,
tonsillar or tentorial herniation exacerbates the original injury. The normal
cerebral auto regulatory processes are disrupted following trauma rendering
the brain more susceptible to blood flow changes and hypoxia
The Cushings reflex (hypertension and bradycardia) often occurs late and is
usually a pre terminal event
Management
Where there is life threatening rising ICP such as in extra dural haematoma
and whilst theatre is prepared or transfer arranged use of IV mannitol/
frusemide may be required.
Diffuse cerebral oedema may require decompressive craniotomy
Exploratory Burr Holes have little management in modern practice except
where scanning may be unavailable and to thus facilitate creation of formal
craniotomy flap
Depressed skull fractures that are open require formal surgical reduction and
debridement, closed injuries may be managed non operatively if there is
minimal displacement.
ICP monitoring is appropriate in those who have GCS 3-8 and normal CT
scan.
ICP monitoring is mandatory in those who have GCS 3-8 and Abnormal CT
scan.
Hyponatraemia is most likely to be due to syndrome of inappropriate ADH
secretion.
Minimum of cerebral perfusion pressure of 70mmHg in adults.
Minimum cerebral perfusion pressure of between 40 and 70 mmHg in
children.
A. Rifampicin
B. Quinine
C. Noradrenaline
D. Levodopa
E. Phenytoin
Haematuria
Causes of haematuria
Infection Remember TB
Benign Exercise
Iatrogenic Catheterisation
Radiotherapy; cystitis, severe haemorrhage, bladder
necrosis
Pseudohaematuria
References
Http://bestpractice.bmj.com/best-practice/monograph/316/overview/aetiology.html
A 74-year-old woman with thyroid cancer is admitted due to shortness of breath.
What is the best investigation to assess for possible compression of the upper
airways?
C. Transfer factor
Flow volume loop is the investigation of choice for upper airway compression.
A normal flow volume loop is often described as a 'triangle on top of a semi circle'
Flow volume loops are the most suitable way of assessing compression of the upper
airway
Which of the following statements relating to cerebrospinal fluid is untrue?
E. The foramen of Luschka are paired and lie laterally in the fourth
ventricle
Cerebrospinal fluid
The CSF fills the space between the arachnoid mater and pia mater (covering surface
of the brain). The total volume of CSF in the brain is approximately 150ml.
Approximately 500 ml is produced by the ependymal cells in the choroid plexus
(70%), or blood vessels (30%). It is reabsorbed via the arachnoid granulations which
project into the venous sinuses.
Circulation
1. Lateral ventricles (via foramen Munro)
2. 3rd ventricle
3. Cerebral aqueduct (aqueduct Sylvius)
4. 4th ventricle (via foramina of Magendie and Luschka)
5. Subarachnoid space
6. Reabsorbed into venous system via arachnoid granulations in superior sagittal sinus
Composition
Glucose: 50-80mg/dl
Protein: 15-40 mg/dl
Red blood cells: Nil
White blood cells: 0-3 cells/ mm3
Which substance can be used to achieve the most accurate measurement of the
glomerular filtration rate?
A. Glucose
B. Protein
C. Inulin
D. Creatine
Creatinine declines with age due to decline in renal function and muscle mass.
Glucose, protein (amino acids) and PAH are reabsorbed by the kidney.
Renal Physiology
Overview
Each nephron is supplied with blood from an afferent arteriole that opens onto
the glomerular capillary bed.
Blood then flows to an efferent arteriole, supplying the peritubular capillaries
and medullary vasa recta.
The kidney receives up to 25% of resting cardiac output.
The kidney is able to autoregulate its blood flow between systolic pressures of
80- 180mmHg so there is little variation in renal blood flow.
This is achieved by myogenic control of arteriolar tone, both sympathetic
input and hormonal signals (e.g. renin) are responsible.
Glomerular filtration rate = Total volume of plasma per unit time leaving the
capillaries and entering the bowman's capsule
Renal clearance = volume plasma from which a substance is removed per
minute by the kidneys
1. Inert
2. Free filtration from the plasma at the glomerulus (not protein bound)
3. Not absorbed or secreted at the tubules
4. Plasma concentration constant during urine collection
The clearance of a substance is dependent not only on its diffusivity across the
basement membrane but also subsequent tubular secretion and / or
reabsorption.
So glucose which is freely filtered across the basement membrane is usually
reabsorbed from tubules giving a clearance of zero.
Tubular function
Loop of Henle
A 45 year old man sustains a closed head injury. He is initially alert, however, his
level of consciousness deteriorates on arrival at hospital. An intra cranial pressure
monitor is inserted. What is the normal intracranial pressure?
A. 35 - 45mm Hg
B. 45 - 55mm Hg
C. <15mm Hg
D. 25 - 35mm Hg
E. 25 - 30 mm Hg
The normal intracranial pressure is between 7 and 15 mm Hg. The brain can
accommodate increases up to 24 mm Hg, thereafter clinical features will become
evident.
Applied neurophysiology
A 55-year-old man with a history of type 2 diabetes mellitus, bipolar disorder and
chronic obstructive pulmonary disease has bloods taken during a pre operative
assessment of an inguinal hernia repair:
Due to his smoking history a chest x-ray is ordered which is reported as normal. The
Consultant asks you what is the most likely cause for the hyponatraemia?
A. Metformin
B. Lithium
C. Carbamazepine
D. Sodium valproate
E. Pioglitazone
SIADH - drug causes: carbamazepine,
sulfonylureas, SSRIs, tricyclics
Lithium can cause diabetes insipidus but this is generally associated with a high
sodium. Lithium only tends to cause raised antidiuretic hormone levels following a
severe overdosage.
Malignancy
Neurological
stroke
subarachnoid haemorrhage
subdural haemorrhage
meningitis/encephalitis/abscess
Infections
tuberculosis
pneumonia
Drugs
sulfonylureas
SSRIs, tricyclics
carbamazepine
vincristine
cyclophosphamide
Other causes
A. 500 mL
B. 50 mL
C. 100 mL
D. 2000 mL
E. 150 mL
Between 500 mL and 1.5 L of bile enters the small bowel daily. Most bile salts
are recycled by the enterohepatic circulation. When the gallbladder contracts
the lumenal pressure is approximately 25cm water, which is why biliary colic
may be so painful.
Bile
Bile is produced at a rate of between 500ml and 1500mL per day. Bile is
composed of bile salts, bicarbonate, cholesterol, steroids and water. There are
three main factors regulating bile flow; hepatic secretion, gall bladder
contraction and sphincter of oddi resistance. Bile salts are absorbed in the
terminal ileum (and recycled to the liver). Over 90% of all bile salts are
recycled in this way, such that the total pool of bile salts is recycled up to six
times a day.
Pathophysiology of gallstones
Bile salts have a detergent action. They aggregate to form micelles and these
have a lipid centre in which fats may be transported. Excessive quantities of
cholesterol cannot be transported in this way and will tend to precipitate,
resulting in the formation of cholesterol rich gallstones.
At which of the following sites is the most water absorbed?
A. Right colon
B. Left colon
C. Stomach
D. Jejunum
E. Duodenum
Water absorption in the gastrointestinal tract predominantly occurs in the
small bowel (jejunum and ileum). The colon is an important site of water
absorption, however, its overall contribution is relatively small. The
importance of the colonic component to water absorption may increase
following extensive small bowel resections.
Water absorption
During a 24 hours period the average person will ingest up to 2000ml of liquid
orally. In addition a further 8000ml of fluid will enter the small bowel as
gastrointestinal secretions. Intestinal water absorption is a passive process and
is related to solute load. In the jejunum the active absorption of glucose and
amino acids will create a concentration gradient that water will flow across. In
the ileum most water is absorbed by a process of facilitated diffusion (with
sodium).
Approximately 150ml of water enters the colon daily, most is absorbed, the
colon can adapt to, and increase this amount following resection.
Which of the following is not a characteristic of the proximal convoluted tubule in the
kidney?
A. Up to 95% of filtered amino acids will be reabsorbed at this site
Renal Physiology
Overview
Each nephron is supplied with blood from an afferent arteriole that opens onto
the glomerular capillary bed.
Blood then flows to an efferent arteriole, supplying the peritubular capillaries
and medullary vasa recta.
The kidney receives up to 25% of resting cardiac output.
The kidney is able to autoregulate its blood flow between systolic pressures of
80- 180mmHg so there is little variation in renal blood flow.
This is achieved by myogenic control of arteriolar tone, both sympathetic
input and hormonal signals (e.g. renin) are responsible.
Glomerular filtration rate = Total volume of plasma per unit time leaving the
capillaries and entering the bowman's capsule
1. Inert
2. Free filtration from the plasma at the glomerulus (not protein bound)
3. Not absorbed or secreted at the tubules
4. Plasma concentration constant during urine collection
The clearance of a substance is dependent not only on its diffusivity across the
basement membrane but also subsequent tubular secretion and / or
reabsorption.
So glucose which is freely filtered across the basement membrane is usually
reabsorbed from tubules giving a clearance of zero.
Tubular function
Loop of Henle
Which of the following does not cause a normal anion gap acidosis?
A. Pancreatic fistula
B. Acetazolamide
C. Uraemia
D. Ureteric diversion
H-
Hyperalimentation/hyperventilation
A - Acetazolamide
R - Renal tubular acidosis
D - Diarrhoea
U - Ureteral diversion
P - Pancreatic fistula/parenteral
saline
Uraemia will typically cause a high anion gap acidosis. It is one of the unmeasured anions.
Disorders of acid- base balance are often covered in the MRCS part A, both in the SBA and
EMQ sections.
The acid-base normogram below shows how the various disorders may be categorised
Metabolic acidosis
Metabolic acidosis secondary to high lactate levels may be subdivided into two types:
Metabolic alkalosis
Causes
Respiratory acidosis
Causes
COPD
Decompensation in other respiratory conditions e.g. Life-threatening asthma /
pulmonary oedema
Sedative drugs: benzodiazepines, opiate overdose
Respiratory alkalosis
Causes
*Salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early
stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct
acid effects of salicylates (combined with acute renal failure) may lead to an acidosis
Which one of the following would cause a rise in the carbon monoxide transfer factor
(TLCO)?
A. Emphysema
B. Pulmonary embolism
C. Pulmonary haemorrhage
D. Pneumonia
E. Pulmonary fibrosis
Transfer factor
Where alveolar haemorrhage occurs the TLCO tends to increase due to the enhanced
uptake of carbon monoxide by intra-alveolar haemoglobin.
Transfer factor
The transfer factor describes the rate at which a gas will diffuse from alveoli into
blood. Carbon monoxide is used to test the rate of diffusion. Results may be given as
the total gas transfer (TLCO) or that corrected for lung volume (transfer coefficient,
KCO)
KCO also tends to increase with age. Some conditions may cause an increased KCO
with a normal or reduced TLCO
pneumonectomy/lobectomy
scoliosis/kyphosis
neuromuscular weakness
ankylosis of costovertebral joints e.g. ankylosing spondylitis
Release of somatostatin from the pancreas will result in which of the
following?
A. Decrease in pancreatic exocrine secretions
Somatostatinomas are rare pancreatic endocrine tumours and will result in the
clinical manifestations of diabetes mellitus, gallstones and steatorrhoea.
A 34 year old lady develops septic shock and features of the systemic inflammatory
response syndrome as a complication of cholangitis. Which of the following is not a
typical feature of this condition?
Septic shock will typically result in end organ hypoperfusion and as a result lactate
levels will often be high. In the surviving sepsis campaign it is suggested that elevated
lactate levels are an independent indicator for vasopressor support in patient with
sepsis. The WCC may be paradoxically low in severe sepsis, although it is most often
elevated.
Shock
Septic shock
Septic shock is a major problem and those patients with severe sepsis have a mortality
rate in excess of 40%. In those who are admitted to intensive care mortality ranges
from 6% with no organ failure to 65% in those with 4 organ failure.
Patients with infections and two or more elements of SIRS meet the diagnostic criteria
for sepsis. Those with organ failure have severe sepsis and those with refractory
hypotension -septic shock.
During the septic process there is marked activation of the immune system with
extensive cytokine release. This may be coupled with or triggered by systemic
circulation of bacterial toxins. These all cause endothelial cell damage and neutrophil
adhesion. The overall hallmarks are thus those of excessive inflammation,
coagulation and fibrinolytic suppression.
The surviving sepsis campaign highlights the following key areas for attention:
In surgical patients, the main groups with septic shock include those with anastomotic
leaks, abscesses and extensive superficial infections such as necrotising fasciitis.
When performing surgery the aim should be to undertake the minimum necessary to
restore physiology. These patients do not fare well with prolonged surgery. Definitive
surgery can be more safely undertaken when physiology is restored and clotting in
particular has been normalised.
Haemorrhagic shock
The average adult blood volume comprises 7% of body weight. Thus in the 70 Kg
adult this will equate to 5 litres. This changes in children (8-9% body weight) and is
slightly lower in the elderly.
The table below outlines the 4 major classes of haemorrhagic shock and their
associated physiological sequelae:
In patients suffering from trauma the most likely cause of shock is haemorrhage.
However, the following may also be the cause or occur concomitantly:
Tension pneumothorax
Spinal cord injury
Myocardial contusion
Cardiac tamponade
Neurogenic shock
This occurs most often following a spinal cord transection, usually at a high level.
There is resultant interruption of the autonomic nervous system. The result is either
decreased sympathetic tone or increased parasympathetic tone, the effect of
which is a decrease in peripheral vascular resistance mediated by marked
vasodilation.
This results in decreased preload and thus decreased cardiac output (Starlings law).
There is decreased peripheral tissue perfusion and shock is thus produced. In contrast
with many other types of shock peripheral vasoconstrictors are used to return vascular
tone to normal.
Cardiogenic shock
In medical patients the main cause is ischaemic heart disease. In the traumatic
setting direct myocardial trauma or contusion is more likely. Evidence of ECG
changes and overlying sternal fractures or contusions should raise the suspicion of
injury. Treatment is largely supportive and transthoracic echocardiography should be
used to determine evidence of pericardial fluid or direct myocardial injury. The
measurement of troponin levels in trauma patients may be undertaken but they are
less useful in delineating the extent of myocardial trauma than following MI.
When cardiac injury is of a blunt nature and is associated with cardiogenic shock the
right side of the heart is the most likely site of injury with chamber and or valve
rupture. These patients require surgery to repair these defects and will require
cardiopulmonary bypass to achieve this. Some may require intra aortic balloon pump
as a bridge to surgery.
Anaphylactic shock
Anaphylaxis may be defined as a severe, life-threatening, generalised or systemic
hypersensitivity reaction.
Anaphylaxis is one of the few times when you would not have time to look up the
dose of a medication. The Resuscitation Council guidelines on anaphylaxis have
recently been updated. Adrenaline is by far the most important drug in anaphylaxis
and should be given as soon as possible. The recommended doses for adrenaline,
hydrocortisone and chlorphenamine are as follows:
Adrenaline can be repeated every 5 minutes if necessary. The best site for IM
injection is the anterolateral aspect of the middle third of the thigh.
Common identified causes of anaphylaxis
A. Cholecystokinin
C. Secretin
D. Histamine
E. Somatostatin
Secretin: From mucosal cells in the duodenum and jejunum: inhibits gastric acid,
stimulates bile and pancreatic juice production
Which of the following statements relating to gastric acid secretions are untrue?
The intestinal phase of gastric acid secretion accounts for only 10% of gastric acid produced.
Gastric secretions
A working knowledge of gastric secretions is important for surgery because peptic ulcers are
common, surgeons frequently prescribe anti secretory drugs and because there are still
patients around who will have undergone acid lowering procedures (Vagotomy) in the past.
Gastric acid
Is produced by the parietal cells in the stomach
pH of gastric acid is around 2 with acidity being maintained by the H+/K+ ATP ase
pump. As part of the process bicarbonate ions will be secreted into the surrounding
vessels.
Sodium and chloride ions are actively secreted from the parietal cell into the
canaliculus. This sets up a negative potential across the membrane and as a result
sodium and potassium ions diffuse across into the canaliculus.
Carbonic anhydrase forms carbonic acid which dissociates and the hydrogen ions
formed by dissociation leave the cell via the H+/K+ antiporter pump. At the same
time sodium ions are actively absorbed. This leaves hydrogen and chloride ions in
the canaliculus these mix and are secreted into the lumen of the oxyntic gland.
The diagram below illustrates some of the factors involved in regulating gastric acid
secretion and the relevant associated pharmacology
Image sourced from Wikipedia
Calcium homeostasis
Calcium ions are linked to a wide range of physiological processes. The largest store
of bodily calcium is contained within the skeleton. Calcium levels are primarily
controlled by parathyroid hormone, vitamin D and calcitonin.
Both growth hormone and thyroxine also play a small role in calcium metabolism.
Which of the following inhibits gastric acid secretion?
A. Histamine
B. Nausea
C. Calcium
E. Gastrin
Nausea inhibits gastric secretion via higher cerebral activity and sympathetic innervation.
Gastric secretions
A working knowledge of gastric secretions is important for surgery because peptic ulcers are
common, surgeons frequently prescribe anti secretory drugs and because there are still
patients around who will have undergone acid lowering procedures (Vagotomy) in the past.
Gastric acid
The diagram below illustrates some of the factors involved in regulating gastric acid
secretion and the relevant associated pharmacology
Image sourced from Wikipedia
73 year old lady is diagnosed with hyperaldosteronism. From which of the following
structures is aldosterone released?
D. Adrenal medulla
Aldosterone
A. Bleeding time
B. Prothrombin time
C. APTT
D. Platelet count
E. Factor I levels
PT: Vitamin K dependent
factors 2, 7, 9, 10
APTT: Factors 8, 9, 11, 12
Jaundice will impair the production of vitamin K dependent clotting factors. This is
most accurately tested by measuring the prothrombin time. APTT can be affected by
vitamin K deficiency (due to factor 9 deficiency), however this occurs to a lesser
extent and is normally associated with severe liver disease. The bleeding time is a
measure of platelet function.
Abnormal coagulation
Which of the following mechanisms best accounts for the release of adrenaline?
B. Release from the zona fasiculata from the adrenal gland in response
to increased sympathetic discharge
Actions
α adrenergic receptors:
β adrenergic receptors:
A. Pyrexia
B. Decreased albumin
D. Increased transferrin
Prolactin
Antidiuretic hormone
Glucagon
Pituitary gland
Cortisol
Growth hormone
Alpha Endorphin
Increased
Antidiuretic hormone
Insulin
Carbohydrate metabolism
Protein metabolism
Lipid metabolism
Increased catecholamine, cortisol and glucagon secretion, and insulin deficiency,
promotes lipolysis and ketone body production.
ADH causes water retention, concentrated urine, and potassium loss and may
continue for 3 to 5 days after surgery
Renin causes sodium and water retention
Cytokines
Glycoproteins
Interleukins (IL) 1 to 17, interferons, and tumour necrosis factor
Synthesized by activated macrophages, fibroblasts, endothelial and glial cells
in response to tissue injury from surgery or trauma
IL-6 main cytokine associated with surgery. Peak 12 to 24 h after surgery and
increase by the degree of tissue damage Other effects of cytokines include
fever, granulocytosis, haemostasis, tissue damage limitation and promotion of
healing.
References
Deborah Burton, Grainne Nicholson, and George Hall
Endocrine and metabolic response to surgery .
Blood products
SAG-Mannitol Removal of all plasma from a blood unit and substitution with:
Blood
Sodium chloride
Adenine
Anhydrous glucose
Mannitol
Their main advantage is that they avoid the use of infusion of blood from donors into
patients and this may reduce risk of blood borne infection. It may be acceptable to
Jehovah's witnesses. It is contraindicated in malignant disease for risk of facilitating
disease dissemination.
1. Stop warfarin
References
1. Dentali, F., C. Marchesi, et al. (2011). "Safety of prothrombin complex
concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-
analysis." Thromb Haemost 106(3): 429-438.
2. http://www.transfusionguidelines.org/docs/pdfs/bbt-03warfarin-reversal-flowchart-
2006.pdf
Which of the following statements relating the fluid physiology of a physiologically
normal 70 Kg adult male is false?
A. Deficiency of copper
B. Deficiency of iron
D. Deficiency of phosphate
E. None of the above
Vitamin C is involved in the cross linkage of collagen and impaired wound healing is
well described in cases of vitamin C deficiency.
Collagen
Collagen Diseases
Osteogenesis imperfecta
Ehlers Danlos
Osteogenesis imperfecta:
-8 Subtypes
-Defect of type I collagen
-In type I the collagen is normal quality but insufficient quantity
-Type II- poor quantity and quality
-Type III- Collagen poorly formed, normal quantity
-Type IV- Sufficient quantity but poor quality
Patients have bones which fracture easily, loose joint and multiple other defects
depending upon which sub type they suffer from
Ehlers Danlos:
-Multiple sub types
-Abnormality of types 1 and 3 collagen
-Patients have features of hypermobility.
-Individuals are prone to joint dislocations and pelvic organ prolapse. In addition to
many other diseases related to connective tissue defects
A 45 year old man is undergoing a small bowel resection. The anaesthetist decides to
administer an intravenous fluid which is electrolyte rich. Which of the following most
closely matches this requirement?
A. Dextrose / Saline
B. Pentastarch
C. Gelofusine
D. Hartmans
Na K Cl Bicarbonate Lactate
Plasma 137-147 4-5.5 95-105 22-25 -
0.9% Saline 153 - 153 - -
Dextrose / saline 30.6 - 30.6 - -
Hartmans 130 4 110 - 28
References
British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical
Patients
GIFTASUP (2009) Revised May 2011.
A 45 year old man is undergoing a small bowel resection. The anaesthetist decides to
administer an intravenous fluid which is electrolyte rich. Which of the following most
closely matches this requirement?
A. Dextrose / Saline
B. Pentastarch
C. Gelofusine
D. Hartmans
E. 5% Dextrose with added potassium 20mmol/ L
Na K Cl Bicarbonate Lactate
Plasma 137-147 4-5.5 95-105 22-25 -
0.9% Saline 153 - 153 - -
Dextrose / saline 30.6 - 30.6 - -
Hartmans 130 4 110 - 28
References
British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical
Patients
GIFTASUP (2009) Revised May 2011.
A 16 year old girl develops pyelonephritis and is admitted in a state of septic shock.
Which of the following is not typically seen in this condition?
E. Tachycardia
Cardiogenic Shock:
e.g. MI, valve abnormality
Hypovolaemic shock:
blood volume depletion
e.g. haemorrhage, vomiting, diarrhoea, dehydration, third-space losses during major
operations
increased SVR
increased HR
decreased cardiac output
decreased blood pressure
Septic shock:
occurs when the peripheral vascular dilatation causes a fall in SVR
similar response may occur in anaphylactic shock, neurogenic shock
reduced SVR
increased HR
normal/increased cardiac output
decreased blood pressure
Shock
Septic shock
Septic shock is a major problem and those patients with severe sepsis have a mortality
rate in excess of 40%. In those who are admitted to intensive care mortality ranges
from 6% with no organ failure to 65% in those with 4 organ failure.
During the septic process there is marked activation of the immune system with
extensive cytokine release. This may be coupled with or triggered by systemic
circulation of bacterial toxins. These all cause endothelial cell damage and neutrophil
adhesion. The overall hallmarks are thus those of excessive inflammation,
coagulation and fibrinolytic suppression.
The surviving sepsis campaign highlights the following key areas for attention:
In surgical patients, the main groups with septic shock include those with anastomotic
leaks, abscesses and extensive superficial infections such as necrotising fasciitis.
When performing surgery the aim should be to undertake the minimum necessary to
restore physiology. These patients do not fare well with prolonged surgery. Definitive
surgery can be more safely undertaken when physiology is restored and clotting in
particular has been normalised.
Haemorrhagic shock
The average adult blood volume comprises 7% of body weight. Thus in the 70 Kg
adult this will equate to 5 litres. This changes in children (8-9% body weight) and is
slightly lower in the elderly.
The table below outlines the 4 major classes of haemorrhagic shock and their
associated physiological sequelae:
In patients suffering from trauma the most likely cause of shock is haemorrhage.
However, the following may also be the cause or occur concomitantly:
Tension pneumothorax
Spinal cord injury
Myocardial contusion
Cardiac tamponade
Neurogenic shock
This occurs most often following a spinal cord transection, usually at a high level.
There is resultant interruption of the autonomic nervous system. The result is either
decreased sympathetic tone or increased parasympathetic tone, the effect of
which is a decrease in peripheral vascular resistance mediated by marked
vasodilation.
This results in decreased preload and thus decreased cardiac output (Starlings law).
There is decreased peripheral tissue perfusion and shock is thus produced. In contrast
with many other types of shock peripheral vasoconstrictors are used to return vascular
tone to normal.
Cardiogenic shock
In medical patients the main cause is ischaemic heart disease. In the traumatic
setting direct myocardial trauma or contusion is more likely. Evidence of ECG
changes and overlying sternal fractures or contusions should raise the suspicion of
injury. Treatment is largely supportive and transthoracic echocardiography should be
used to determine evidence of pericardial fluid or direct myocardial injury. The
measurement of troponin levels in trauma patients may be undertaken but they are
less useful in delineating the extent of myocardial trauma than following MI.
When cardiac injury is of a blunt nature and is associated with cardiogenic shock the
right side of the heart is the most likely site of injury with chamber and or valve
rupture. These patients require surgery to repair these defects and will require
cardiopulmonary bypass to achieve this. Some may require intra aortic balloon pump
as a bridge to surgery.
Anaphylactic shock
Anaphylaxis may be defined as a severe, life-threatening, generalised or systemic
hypersensitivity reaction.
Anaphylaxis is one of the few times when you would not have time to look up the
dose of a medication. The Resuscitation Council guidelines on anaphylaxis have
recently been updated. Adrenaline is by far the most important drug in anaphylaxis
and should be given as soon as possible. The recommended doses for adrenaline,
hydrocortisone and chlorphenamine are as follows:
Adrenaline can be repeated every 5 minutes if necessary. The best site for IM
injection is the anterolateral aspect of the middle third of the thigh.
A man is admitted after a period of prolonged self, induced starvation. Naso gastric
feeding is planned. Which of the following is least likely to occur?
A. Hypokalaemia
D. Hypophosphataemia
The process of starvation may lower DPG levels, in practice this is unlikely to occur
early as it is generated during glycolysis. Altered metabolism in starvation may be
more acidotic and this would also tend to impair oxygen carriage.
Nutrition - Refeeding syndrome
Hypophosphataemia
Hypokalaemia
Hypomagnesaemia
Abnormal fluid balance
Re-feeding problems
If patient not eaten for > 5 days, aim to re-feed at < 50% energy and protein levels
Prescription
A. Glomerulus
{Amiloride} is a weak diuretic which blocks the epithelial sodium channel in the
distal convoluted tubule.
Indications
A. α 1 receptors
B. α 2 receptors
C. β 1 receptors
D. β 2 receptors
E. G receptors
Theme from 2009 Exam
Noradrenaline is the precursor of adrenaline. It is a powerful α 1 stimulant
(although it will increase myocardial contractility). Infusions will produce
vasoconstriction and an increase in total peripheral resistance. It is the inotrope
of choice in septic shock.
Inotropes and cardiovascular receptors
Inotrope Cardiovascular receptor action
Adrenaline α-1, α-2, β-1, β-2
Noradrenaline α-1,( α-2), (β-1), (β-2)
Dobutamine β-1, (β 2)
Dopamine (α-1), (α-2), (β-1), D-1,D-2
Minor receptor effects in brackets
A. Aspartime
B. Glutamine
C. Arginine
D. Tyrosine
E. Alanine
Adrenal physiology
Adrenal medulla
The chromaffin cells of the adrenal medulla secrete the catecholamines noradrenaline
and adrenaline. The medulla is innervated by the splanchnic nerves; the preganglionic
sympathetic fibres secrete acetylcholine causing the chromaffin cells to secrete their
contents by exocytosis.
Phaeochromocytomas are derived from these cells and will secrete both adrenaline
and nor adrenaline.
Adrenal cortex
Three histologically distinct zones are recognised:
The glucocorticoids and aldosterone are mostly bound to plasma proteins in the
circulation. Glucocorticoids are inactivated and excreted by the liver.
Where are the arterial baroreceptors located?
Cardiac physiology
The heart has four chambers ejecting blood into both low pressure and high
pressure systems.
The pumps generate pressures of between 0-25mmHg on the right side and 0-120
mmHg on the left.
At rest diastole comprises 2/3 of the cardiac cycle.
The product of the frequency of heart rate and stroke volume combine to give the
cardiac output which is typically 5-6L per minute.
Detailed descriptions of the various waveforms are often not a feature of MRCS A (although
they are on the syllabus). However, they are a very popular topic for surgical physiology
vivas in the oral examination.
Electrical properties
Intrinsic myogenic rhythm within cardiac myocytes means that even the denervated
heart is capable of contraction.
In the normal situation the cardiac impulse is generated in the sino atrial node in the
right atrium and conveyed to the ventricles via the atrioventricular node.
The sino atrial node is also capable of spontaneous discharge and in the absence of
background vagal tone will typically discharge around 100x per minute. Hence the
higher resting heart rate found in cardiac transplant cases. In the SA and AV nodes
the resting membrane potential is lower than in surrounding cardiac cells and will
slowly depolarise from -70mV to around -50mV at which point an action potential is
generated.
Differences in the depolarisation slopes between SA and AV nodes help to explain
why the SA node will depolarise first. The cells have a refractory period during which
they cannot be re-stimulated and this period allows for adequate ventricular filling.
In pathological tachycardic states this time period is overridden and inadequate
ventricular filling may then occur, cardiac output falls and syncope may ensue.
Parasympathetic fibres project to the heart via the vagus and will release acetylcholine.
Sympathetic fibres release nor adrenaline and circulating adrenaline comes from the adrenal
medulla. Noradrenaline binds to β 1 receptors in the SA node and increases the rate of
pacemaker potential depolarisation.
Cardiac cycle
Mid diastole: AV valves open. Ventricles hold 80% of final volume. Outflow valves
shut. Aortic pressure is high.
Late diastole: Atria contract. Ventricles receive 20% to complete filling. Typical end
diastolic volume 130-160ml.
Late systole: Ventricular muscles relax and ventricular pressures drop. Although
ventricular pressure drops the aortic pressure remains constant owing to peripheral
vascular resistance and elastic property of the aorta. Brief period of retrograde flow
that occurs in aortic recoil shuts the aortic valve. Ventricles will contain 60ml end
systolic volume. The average stroke volume is 70ml (i.e. Volume ejected).
Early diastole: All valves are closed. Isovolumetric ventricular relaxation occurs.
Pressure wave associated with closure of the aortic valve increases aortic pressure.
The pressure dip before this rise can be seen on arterial waveforms and is called the
incisura. During systole the atrial pressure increases such that it is now above zero
(v- wave). Eventually atrial pressure exceed ventricular pressure and AV valves open
- atria empty passively into ventricles and atrial pressure falls (y -descent )
The negative atrial pressures are of clinical importance as they can allow air embolization to
occur if the neck veins are exposed to air. This patient positioning is important in head and
neck surgery to avoid this occurrence if veins are inadvertently cut, or during CVP line
insertion.
Mechanical properties
It states that for hollow organs with a circular cross section, the total circumferential
wall tension depends upon the circumference of the wall, multiplied by the
thickness of the wall and on the wall tension.
The total luminal pressure depends upon the cross sectional area of the lumen and
the transmural pressure. Transmural pressure is the internal pressure minus
external pressure and at equilibrium the total pressure must counterbalance each
other.
In terms of cardiac physiology the law explains that the rise in ventricular pressure
that occurs during the ejection phase is due to physical change in heart size. It also
explains why a dilated diseased heart will have impaired systolic function.
Starlings law
Baroreceptor reflexes
Which one of the following cells secretes the majority of tumour necrosis factor in
humans?
A. Neutrophils
B. Macrophages
D. Killer-T cells
E. Helper-T cells
TNF is secreted mainly by macrophages and has a number of effects on the immune
system, acting mainly in a paracrine fashion:
TNF-alpha binds to both the p55 and p75 receptor. These receptors can induce
apoptosis. It also cause activation of NFkB
TNF promotes the proliferation of fibroblasts and their production of protease and
collagenase. It is thought fragments of receptors act as binding points in serum
Systemic effects include pyrexia, increased acute phase proteins and disordered
metabolism leading to cachexia
Which of the following is responsible for the rapid depolarisation phase of the
myocardial action potential?
D. Efflux of potassium
NB cardiac muscle remains contracted 10-15 times longer than skeletal muscle
Conduction velocity
Atrial Spreads along ordinary atrial myocardial fibres at 1 m/sec
conduction
AV node 0.05 m/sec
conduction
Ventricular Purkinje fibres are of large diameter and achieve velocities of 2-4
conduction m/sec (this allows a rapid and coordinated contraction of the
ventricles
Which of the following is not a feature of normal cerebrospinal fluid?
Cerebrospinal fluid
The CSF fills the space between the arachnoid mater and pia mater (covering surface
of the brain). The total volume of CSF in the brain is approximately 150ml.
Approximately 500 ml is produced by the ependymal cells in the choroid plexus
(70%), or blood vessels (30%). It is reabsorbed via the arachnoid granulations which
project into the venous sinuses.
Circulation
1. Lateral ventricles (via foramen Munro)
2. 3rd ventricle
3. Cerebral aqueduct (aqueduct Sylvius)
4. 4th ventricle (via foramina of Magendie and Luschka)
5. Subarachnoid space
6. Reabsorbed into venous system via arachnoid granulations in superior sagittal sinus
Composition
Glucose: 50-80mg/dl
Protein: 15-40 mg/dl
Red blood cells: Nil
White blood cells: 0-3 cells/ mm3
Gastric secretions
A working knowledge of gastric secretions is important for surgery because peptic ulcers are
common, surgeons frequently prescribe anti secretory drugs and because there are still
patients around who will have undergone acid lowering procedures (Vagotomy) in the past.
Gastric acid
The diagram below illustrates some of the factors involved in regulating gastric acid
secretion and the relevant associated pharmacology
Image sourced from Wikipedia
Which of the following is the least likely to increase acid secretion in the stomach?
A. Calcium
B. Alcohol
C. Caffeine
D. Pear
Gastric emptying
The stomach serves both a mechanical and immunological function. Solid and
liquid are retained in the stomach during which time repeated peristaltic
activity against a closed pyloric sphincter will cause fragmentation of food
bolus material. Contact with gastric acid will help to neutralise any pathogens
present.
Controlling factors
Neuronal stimulation of the stomach is mediated via the vagus and the
parasympathetic nervous system will tend to favor an increase in gastric motility. It is
for this reason that individuals who have undergone truncal vagotomy will tend to
routinely require either a pyloroplasty or gastro-enterostomy as they would otherwise
have delayed gastric emptying.
Iatrogenic
Gastric surgery can have profound effects on gastric emptying. As stated above any
procedure that disrupts the vagus can cause delayed emptying. Whilst this is
particularly true of Vagotomy this operation is now rarely performed. Surgeons are
divided on the importance of vagal disruption that occurs during an oesophagectomy
and some will routinely perform a pyloroplasty and other will not.
Diabetic gastroparesis
This is predominantly due to neuropathy affecting the vagus nerve. The stomach
empties poorly and patients may have episodes of repeated and protracted vomiting.
Diagnosis is made by upper GI endoscopy and contrast studies, in some cases a radio
nucleotide scan is needed to demonstrate the abnormality more clearly. In treating
these conditions drugs such as metoclopramide will be less effective as they exert
their effect via the vagus nerve. One of the few prokinetic drugs that do not work in
this way is the antibiotic erythromycin.
Malignancies
Obviously a distal gastric cancer may obstruct the pylorus and delay emptying. In
addition malignancies of the pancreas may cause extrinsic compression of the
duodenum and delay emptying. Treatment in these cases is by gastric decompression
using a wide bore nasogastric tube and insertion of a stent or if that is not possible by
a surgical gastroenterostomy. As a general rule gastroenterostomies constructed for
bypass of malignancy are usually placed on the anterior wall of the stomach (in spite
of the fact that they empty less well). A Roux en Y bypass may also be undertaken but
the increased number of anastomoses for this in malignant disease that is being
palliated is probably not justified.