Past Years (2006 & 2007) Questions And Answers Compilation.

2006 Q1. A 70 year old womans blood pressure is found to be elevated on two
separate occasions (180/105). Describe the mechanisms of action and the possible
adverse effects of two drug classes that you would consider using to lower blood
pressure in this woman.
Antihypertensive Drugs: ABCD AVAC
ACE-Inhibitors
Beta-blockers
Calcium-channel blockers
Diuretics
Angiotensin II antagonists
Alpha-blockers
Vasodilators
Central sympathophlegics
ThiazideDiuretics
Ex.Hydrochlorthiazide
MOA:.Inhibition of NaCl reabsorption in early distal tubule of renal nephron, decrease water
reabsorption, decrease in blood volume.
S.E.s Fatigue
Hypokalaemia
Impotance
Glucose intolerance
Dyslipidaemia
Hyperuricaemia
Beta-blockers
Examples
Non-selective; Propranolol,
1 selective; Atenolol
With vasodilatation; Pindolol(1 selective antagonist and partial agonist at B2 adrenoceptors)
Carvidalol (non-selective -blocker but also 1 blocker)
Nebivolol (releases NO)
Mechanisms of action: decrease HR, and decrease CO
Inhibition of rennin secretion
- S.Es:
Bronchospasm(non-selective)
Worsening of peripheral vascular disease (non-selective)
Glucose intolerance
Dyslipidaemia
Negative inotrophy
Impotance
Fatigue CNS effects, nightmares
Q2. A 10 year old girl with asthma is still suffering recurrent moderately severe attacks of
asthma despite treatment with an inhaled beta-2 adrenoceptor agonist. Discuss the
mechanisms of action and side effects of two classes of drugs you would consider adding to
her treatment regimen, so as to reduce frequency and severity of attacks.

Bronchodilators
B2 adrenoreceptor agonists
Muscarinic (M3) antagonists
Xanthines
Anti-inflammatory Drugs
Glucocorticoids
Cromones
Leukotriene synthesis inhibitors & receptor antagonists

1. MUSCARINIC ANTAGONISTS
Ipratropium Bromide - derivative of N-isopropylatropine
Tiotropium bromide - Newer long-acting :
Administration
Given by inhalation
not well absorbed -little systemic effects.
Mechanism of action
Inhibition of the action of acetyl choline at M1, M2,
and M3 muscarinic receptors. thus producing
bronchodilation and reducing mucous secretion.
Slower acting than B2 agonists.

2. XANTHINES
Caffeine
Theophylline
Oral.
Short T1/2.
Sustained release preparations available
Aminophylline
IV.

MOA: Relax bronchial smooth muscle (bronchodilation)

by inhibiting phosphodiesterase resulting in increased
cAMP and cGMP.
Also anti-inflammatory actions (inhibit the late phase)
? inhibition of phosphodiesterase present in
inflammatory cells.
Selective PD4 inhibitors (Roflumilast, Cilomilast)
may be particularly beneficial in COAD)

Side Effects
Narrow therapeutic range (27-80mmol/l)
Side effects likely with concentrations >110mmol/l
gastrointestinal: nausea / anorexia
cardiovascular: arrhythmias can be fatal
CNS: nervousness, tremor, seizures
Pharmacokinetics
Metabolised in the liver
T1/2 increased by liver disease, heart failure and decreased by
smoking and heavy drinking
NB Drug interactions
Pharmacokinetic Drug Interactions occur with Theophylline because of extensive
Metabolism by Cytochrome P450 Enzymes
Cytochrome P450 1A2 is the main isoform responsible for the metabolism of theophylline
Erythromicin and Cimetidine are also metabolised by this isoform hence competitive
inhibition can occur when co-administered
Enzyme inducers such as; Phenytoin, Carbamazepine, Rifampicin, Barbiturates, Alcohol
result in reduced plasma concentrations and decreased effects of drugs (such as
theophylline) which are extensively metabolised by Cytochrome P450 enzymes
Note: Delayed onset (2-3 weeks) as enzyme induction requires synthesis of new protein.
Note: Pharmacokinetic drug interactions are most important for drugs, such as
theophilline, that have a low therapeutic index

Q3. Describe the treatment of arrhythmias, giving special attention to the Vaughan
Class IV
( Ca channel
blockers)

Verapmil

-Reduce cardia
Block the L-type of Ca channel.
contractility.
Shorten phase 2 (plateau)
Diltaizem
Reduce contractility of heart.
-Bradycardia
Act on AV node
Treat SVT
Class V
Digoxin
-Hypokalaemia
Increases vagal activity via its central
action on the central nervous system.
(Digitalis)
-Nausea &
Thus, decreasing the conduction of
electrical impulses through the AV node. vomiting.
Positive inotropic effect
Williams classification and side effects of two classes of anti-arrhythmic drugs.

There are five main classes in the Vaughan Williams

classification of antiarrhythmic agents:

Class I agents interfere with the sodium (Na+) channel.

Class II agents are anti-sympathetic nervous system agents. All agents in this class
are beta blockers.
Class III agents affect potassium (K+) efflux.
Class IV agents affect the AV node.
Class V agents work by other or unknown mechanisms.

Q4. The levels of plasma lipoproteins in human subjects are used diagnostically to
evaluate cardiovascular risk. Name the two lipoproteins mainly responsible for
cholesterol transport and state FOUR of the properties by which these two may be
distinguished.

Low density lipoprotein (LDL)

Lower density, larger
Contain a larger proportion of cholesterol than HDL
Move cholesterol around to/from liver and peripheral tissues in the circulatory
system
As a result, cholesterol may be deposited in the walls of blood vessels and cause
cardiovascular diseases such as atherosclerosis
High density lipoprotein (HDL)
Higher density, smaller
Carry least amount of cholesterol
Carry cholesterol back to liver for elimination from body

As a result, accelerate the removal of cholesterol from blood, reducing the likelihood
of cholesterol becoming deposited in arterial walls provide protection from
cardiovascular diseases

Q5. A family travel to Australia to visit their relations. On arrival in Sydney, the
mother experiences chest pain and is admitted to hospital. She is found to have a
pulmonary embolus. Describe how a pulmonary embolus interferes with respiratory
function.

Pulmonary embolus blockage of pulmonary artery by matters such as fat, tumour

or a clot from vein
Decrease perfusion / underperfusion
Larger ventilation/perfusion (V/Q) ratio
Increased physiological dead space, wasted ventilation
Increases PO2 and decreases PCO2
Alveoli contract, pulmonary artery relax
Symptoms: dyspnoea, tachypnoea, pleuritic pain, cough, haemoptysis

Q6. Describe the intrinsic ability of the heart to adapt to changes in venous return.
Illustrate your answer with a diagram.
Venous return: The rate of blood flow back to the heart is the venous return. It normally
limits cardiac output. VR at RA determines amount of blood flowing thru pulmonary circ
(L.Atrium) and hence through systemic circ (at L.Ventricle)
Cardiac output is affected by preload (: is the pressure stretching the ventricle of the heart,
after passive filling and atrial contraction / LVEDP: L.ventricle end diastolic pressure)
Preload affected by...VENOUS RETURN:
Left ventricle (LV) function curve, or Frank - Starling curve (1914):
Normal range of the LVEDP, 5-6 mmHg
Optimal initial preload, 15-20 mmHg (at optimal length of Sarcomere, 2.0
2.2 m)
When the LVEDP > 20 mmHg, LV work is maintained at almost the same level, does
not change with the increase of LVEDP
What affects LVEDP??
Period of the ventricle diastole (filling) heart rate
Speed of the venous return (difference between the venous pressure and
atrial pressure)

Mechanism: VR increase, LV work inc, smooth muscle stretching inc, LVEDP

increase, more blood pumped out of heart, vice versa

Basically, heart gives away all that it receives.

Concept of heterometric regulation: regulation depending upon change in size (i.e. LVP)
Q7. In a group on a hiking tour to the historic site of Machu Picchu in the Peruvian
Andes, some develop acute mountain sickness but others acclimatise normally to the
high altitude. Describe the cardiovascular and respiratory changes that occur during
acclimatisation.

Physiological effects of altitude are due to decrease in barometric pressure

Air composition stays the same but PO2 in the air falls PAO2 and PaO2 fall
Lower amount of oxygen available to inhale (hypoxia), less oxygen reaches the
blood (hypoxemia)
Cardiovascular: pulmonary hypertension, increased HR and CO
Respiratory: ventilation increases by 65% to bring in more oxygen at rapid rate
PACO2 and PaCO2 decrease (hypocaptic)
Q8. On suddenly standing upright, you may feel dizzy and faint. Describe the reflex
physiological response which normally counteracts postural hypotension.

Drop in bp sensed by baroreceptor increase firing rate to medulla activate

sympathetic increase hr increase co increase bp

Q9. Describe the changes in left ventricular pressure occurring during the cardiac
cycle. Illustrate your answer with a diagram giving absolute values of pressure.

Q10. Prior to elective surgery for a hip replacement, a patient is found to have
haemoglobin of 8g/dl. Discuss the balance between oxygen availability and demand
in this situation.

1.

2.

3.

4.

Things need to know

o Source of oxygen
o How body respond if
Demand increase
Demand decrease
o Effect to pO2 & pCO2
o Example for each situation
o Regulator
Source of oxygen
o From ventilation process
o Diffuse to blood
o Pump by heart
If demand increase
o Example exercise
o Effect pO2 low, pCO2 high
o How body respond
Ventilation increase (accessory muscle)
Blood flow increase to muscle (higher c. output, heart rate )
If demand decrease
o Example sleeping
o How body respond
Ventilation normal (not involve accessory muscle)
Blood flow not focus to muscle
Regulator

o Detector chemoreceptor (central, peripheral)

o Central controller medulla, respiratory centre
o Effector respiratory muscle
Q11. A young man is brought to the Accident and Emergency Department following a
stab wound to the 4th right intercostal space and has developed a pneumothorax. List
the layers of the chest wall that the knife has passed through. Where does the
neurovascular bundle lie in the intercostal space and what does it contain? What are
the surface markings of the pleural cavities? Answers.
Layers of the chest wall that the knife has passed through:
- Skin
- Fat
- External intercostal muscle
- Internal intercostal muscle
- Innermost intercostal muscle
- Endothoracic fascia
- Parietal pleura
- Pleural cavity
- Visceral pleura
Neurovascular bundle:
Lies within the costal groove (upper part of the intercostal space)
The contains, from top to the bottom, are intercostal vein, intercostal artery, and
intercostal nerve.
The surface marking of the pleural cavity:
-

About 2 cm above the clavicle

At 4th costal cartilage, the left pleural line pass laterally, while the right line
continues down
- The lines pass obliquely laterally across the 6th costal cartilage
- In the midclavicular line, the lines across the 8th rib
- In the midaxillary line, they cross the 10th rib
- In the midscapular line, they cross the 12th rib
Q12. During a routine physical examination, you auscultate your patients chest.
Describe or draw the surface markings of the heart and the heart valves. Indicate
where you would place a stethoscope to listen to each valve.
-

Heart border: upper left end: 2nd left CC, upper right end: 3rd right CC, lower right end: 6th
CC, lower left end: 5th intercostal space, midclavicular line. Surface marking of the heart
valves: retrosternal.
Valve

Surface marking

Auscultation

Pulmonary

3rd CC, left sternal border

2nd cc, left sternal border

Aortic

3rd ICS, right sternal border

2nd cc, right sternal border

Mitral

4th CC, left sternal border

5th ICS, midclavicular line

Tricuspid

4td ICS, right sternal border

Left lower sternal border

1. Aortic region (between the 2nd and 3rd intercostal spaces at the right sternal
border) (RUSB right upper sternal border).
2. Pulmonic region (between the 2nd and 3rd intercostal spaces at the left sternal
border) (LUSB left upper sternal border).
3. Tricuspid region (between the 3rd, 4th, 5th, and 6th intercostal spaces at the left
sternal border) (LLSB left lower sternal border).
4. Mitral region (near the apex of the heard between the 5th and 6th intercostal spaces
in the mid-clavicular line) (apex of the heart).
Q13. Describe the diaphragm, with reference to its attachments and nerve supply.
List the openings that exist to allow passage of structures between the thoracic
and abdominal cavities; include the vertebral levels of these openings and name
the structures which pass through them.
Diaphragm is a sheet of muscle across the bottom of the ribcage, separating thoracic cavity and
abdominal cavity.
Attachment:
1. sternal origin- xiphoid
2. 6 costal origin
a. 6 costal cartilages (7-12)
3. crura
a. right crura T3/T4
b. left crura T2/T3
4. arcuate ligaments
- median : across aorta
- medial : across psoas minor
- lateral : across psoas major
Nerve supply:
Phrenic nerve (C 3,4,5 keeps the diaphragm alive)
1. Right phrenic nerve descend to diaphragm near orifice of IVC T8.
2. Left phrenic nerve descend to diaphragm near cardiac apex (left, muscular portion)
(motor- entire diaphragm, sensory- central tendon, sensory to the peripheral is by local
intercostal nerves)

Openings:
T8 IVC, right phrenic nerve (at central tendon)
T10 oesophagus, R&L vagus nerve (and esophageal branches of left gastric
arteries&veins)
T12 aorta, azygos vein, thoracic duct
Q14. A 29 year old man develops shoulder pains following a tennis match. Explain
with reference to their attachments, how the muscles of the shoulder girdle control
rotation of the scapula when reaching out and opening a door.
1. flexion of the shoulder when reaching out
a. anterior part of deltoid- attached from spine of scapula, acromium process,
lateral 1/3 clavicle to humerus
b. pectoralis major (clavicular part)- attached from clavicle, sternum and costal
cartilages
c. coracobrachialis
d. biceps
2. extension of shoulder when opening a door
a. latissimus dorsi (assist by teres major) attached from spinous process (T6T12), sacrum, iliac crest and ribs (10-12) to humerus (floor of the bicipital
groove)
b. posterior part of deltoid attached from spine of scapula, acromium
process, lateral 1/3 clavicle to humerus (deltoid tuberosity)
c. teres major attached from inferior angle of scapula to intertubercular
sulcus of the humerus (medial lip)
d. triceps attached from:
i. long head: inferior glenoid tubercle of the scapula
ii. lateral head: posterior humerus, above spiral grioove
iii. medial head: posterior humerus, below the spiral groove
to olecranon process of ulna
10

3. Abduction of Shoulder joint when reaching out

Supraspinatus
Supraspinatus fossa of scapula

Greater tubercle

Up to 90

Deltoid

Spine of scapula, acromium

process, lateral 1/3 clavicle

Deltoid tuberosity

Rotation of
scapula,
allows
another 60
abduction

Serratus anterior

Upper 8 ribs

Medial border of scapula

Trapezoid

Occipital protuberance

Origin of deltoid:

Ligamentum nuchae

Spine of scapula, acromium

process, lateral 1/3 clavicle

Spinous process of C1-T7

Q15. A 29 year old man accidentally puts his hand through a sheet of glass, causing a
laceration of his thenar eminence. Describe the movements of the thumb. Indicate the
muscles involved and their innervation.
Finger and Thumb Movements
Flexion
Thumb bends medially along the palm
Fingers bend anteriorly
Extension
Thumb points laterally
Fingers move posteriorly
Abduction/Adduction
Movement of thumb forward (anteriorly) is abduction and Movement of thumb forward
(anteriorly) is adduction
The thenar eminence (ball of the thumb)has a flexor pollicis brevis, an abductor pollicis brevis,
and an opponens pollicis. Each of the muscles is supplied by T1 from median nerve.
Flexion

bends medially along the palm

Extension

points laterally

Abduction

Movement of thumb forward (anteriorly)

Adduction

Movement of thumb backward (posteriorly)

FPL
FPB
EPL
EPB
APL
APB
AP

Median
Median
Radial
Radial
Median
Radial
Ulnar

2006 (repeat)
Q1. A young women presents to the Accident & Emergency Department with
dysphagia (difficulty swallowing), after swallowing a large piece of biscuit. Describe
the structure, course and relations of the thoracic oesophagus. Describe the points at
which the oesophagus is narrowed.

Q2. A young child is brought to the Accident and Emergency Department after
inhaling a peanut. Describe the trachea and bronchial tree within the thorax,
including their structure, position and relations. Into which segmental bronchus is an
inhaled foreign body most likely to lodge if a patient is standing upright? Or lying
down?

The right main bronchus is wider, shorter, and more

vertical than the left main bronchus.

The cartilage and mucous membrane of the primary

bronchi are similar to that in the trachea.

As the branching continues through the bronchial tree,

the amount of hyaline cartilage in the walls decreases
until it is absent in the smallest bronchioles. As the
cartilage decreases, the amount of smooth muscle
increases. The mucous membrane also undergoes a
transition from ciliated pseudostratified columnar
epithelium to simple cuboidal epithelium to simple
squamous epithelium.

Standing upright? Or lying down? (probably standing up,

because the trachea is straight vertically in this
positionprobably.)

Q3. A patient presents to her GP with a mass in the lateral breast and fullness in her
axilla. Describe the structure of the female breast, including relations blood supply
and lymphatic drainage. What structures in the axilla might be damaged during
surgery?

What structures in the axilla

might be damaged during
surgery?
It could be the brachial plexus,
axillary art and vein. The lymph
nodes can be removed surgically.

Q4. A footballer dislocates his shoulder during a match, damaging the axillary nerve.
Describe this nerve, including its origin, course and distribution (motor and
cutaneous). What is its root value? How would you test for its function clinically?

Comes off the posterior cord of the brachial plexus at the level of the axilla (armpit) and
carries nerve fibers from C5 and C6. The axillary nerve travels through the
quadrangular space with the posterior circumflex humeral artery and vein.
It supplies two muscles, deltoid (a muscle of the shoulder), and teres minor (one of the
rotator cuff muscles).
Sensory information from the shoulder joint, as well as the skin covering the inferior
region of the deltoid muscle, regimental patch (Superior Lateral Cutaneous Nerve
branch).

It lies at first behind the axillary artery, and in front of the Subscapularis, and passes
downward to the lower border of that muscle. It then winds backward, in company with
the posterior humeral circumflex artery, through a quadrilateral space bounded above
by the Teres Minor, below by the Teres major, medially by the long head of the Triceps
brachii, and laterally by the surgical neck of the humerus, and divides into an anterior
and a posterior branch.

The anterior branch (upper branch) winds around the surgical neck of the humerus,
beneath the Deltoideus, with the posterior humeral circumflex vessels, as far as the
anterior border of that muscle, supplying it, and giving off a few small cutaneous
branches, which pierce the muscle and ramify in the skin covering its lower part.
The posterior branch (lower branch) supplies the Teres minor and the posterior part of
the Deltoideus; upon the branch to the Teres minor an oval enlargement
(pseudoganglion) usually exists. The posterior branch then pierces the deep fascia and
is continued as the lateral brachial cutaneous nerve, which sweeps around the posterior
border of the Deltoideus and supplies the skin over the lower two-thirds of the
posterior part of this muscle, as well as that covering the long head of the Triceps
brachii.
The trunk of the axillary nerve gives off an articular filament which enters the shoulderjoint below the Subscapularis.
The axillary nerve may be injured in anterior dislocations of the shoulder joint,
compression of the axilla with a crutch or fracture of the surgical neck of the humerus.
Clinical test includes
o Abduction of shoulder >10. Paralysis of the teres minor and deltoid muscles.
o Sensory of regimental patch

Q5. When putting up a shelf, you use a screwdriver to attach it to the wall. Define the
movements of pronation and supination of the upper limb. Name and briefly describe
the joints involved in pronation and supination. Name two pronators and two
supinators.
Pronation : Rotation of forearm to bring the palm facing backward.

Supination : Rotation of forearm to bring the palm facing forward (supine position).
Joint involved : Proximal & distal radioulnar joints (Where the radius and ulnar articulate,
and both are synovial joints)
Pronators : Pronator Teres & Pronator Quadratus

 Supinators : Supinator (Synergist) & Biceps Brachii (Main)

Q6. In the human lung, the alveolar surface is composed of two main cell types.
Compare briefly the metabolic functions and capabilities of type I and type II
pneumocytes.
Type I Pneumocyte
Type II Pneumocyte
Flat, small cells (Squamous)
Large cells (Cuboidal)
Unable to repair or regenerate (Because it
Able to repair and regenerate
cannot replicate)
Responsible for gas exchange in the alveolus
Produce surfactant which helps to reduce
(Because its oxygen consumption is nearly
surface tension of the alveolus
zero)
Q7. Draw and label a myocardial pacemaker potential. Relate each phase to the
corresponding change in ion conductance.

SA node is the cardiac pacemaker

Resting potential : About -55mV (Since the fast Na+ channel only active at around 60mV, therefore it is inactivated in SA node)
Na+ slowly gets into the fibre, thus depolarising it towards the threshold which is -40mV
Once it achieves the threshold, slow Ca2+/Na+ channel opens, leading to action potential
of SA node
After about 200msec, Ca2+/Na+ channel closes and K+ leak channel opens
K+ leaves the cell and leading to repolarisation of SA node to its resting potential (55mV)
Q8. Describe the cardiac actions of the neurotransmitters noradrenaline and acetylcholine.
Noradrenalin (NA)
Comparison
Acetylcholine (ACh)
Adrenergic (Beta 1 receptor)
Receptor
Cholinergic (M2 receptor)
Adenylate cyclise (Increase
Adenylate cyclise (Decrease
2 messenger
cAMP production)
cAMP production)
Sympathetic
Type of ANS
Parasympathetic
Increase heart rate
Effect on SA node
Reduce heart rate
Open Ca2+/Na+ channels
Open K+ channels
Ca2+/Na+ enters
K+ leaves cardiac cells
Depolarise
Hyperpolarise
Bring the base (-55mV)
Bring the base further away

closer to threshold (-40mV),

thus making SA node faster
to be depolarized
Increase contractility
Increase permeability of
cardiac cells to Ca2+
Increase Ca2+ influx

Effect on Atria

from the threshold, thus

making SA node harder to
be depolarized
Reduce contractility
Reduce the cAMP
production

Q9. Compare and contrast the pressure differences in the systemic and pulmonary
circulations, accompanied by numerical values.
SYSTEMIC CIRCULATION: circulation of oxygenated blood from the left ventricle of the
heart to the various tissues and of venous blood back to the right atrium of the heart, is high
pressure circulation
PRESSURES INVOLVED:
SYSTEMIC PRESSURES

SYSTOLIC/DIASTOLIC

NOTES

Systemic blood pressure

aorta

120/80mmHg

SBP mainly determined

by CO
DBP mainly determined
by Total Peripheral
Resistance

Pulse pressure (PP)

40mmHg

SBP-DBP

Mean Arterial Pressure

(MAP)

93mmHg

=DBP + 1/3PP

Pressure in capillary beds

17mmHg

Right Atrial Pressure

(RAP) and vena cava

0mmHg (range= 04mmHg)

RAP~JVP~CVP

So people measure JVP

height to reflect venous
return/ hydration state
(i.e. as blood volume also
affects v.return) and
assess cardiac function
Raised JVP>2cm = right
side HF

PULMONARY CIRCULATION: Flow of blood from the right ventricle of the heart through the
blood vessels of the lungs and back to the left ventricle of the heart, is low pressure
circulation
PRESSURES INVOLVED:

PULMONARY PRESSURES

SYSTOLIC/DIASTOLIC

NOTES

Pulmonary Artery

25/10mmHg

Pulse pressure

15mmHg

SBP-DBP

Mean pulmonary artery P

15 mmHg

DBP + 1/3 PP

Pulmonary capillaries

~7 mm Hg

Pulmonary venous P

~ 2 mm Hg (2-6)

Left atrial pressure

~2-6mmHg

Falls to ~0 in cardiac cycle

Raised in Left Heart Failure

Pulmonary Capillary wedge

pressure (PWP)

~7 mmHg
A lil above LAP

-pressure measured in a
pulmonary artery after
occlusion of that artery.
-provides an indirect
measure of the left atrial
pressure.
- measured by a catheter
wedged into the distal
pulmonary artery
-usually real LAP<PWP

Q10. In a group on a hiking tour to the historic site of Machu Picchu in the Peruvian
Andes, some develop acute mountain sickness but others acclimatize normally to the
high altitude. Describe the cardiovascular and respiratory changes that occur during
acclimatization.

Physiological effects of altitude are due to decrease in barometric pressure

Air composition stays the same but PO2 in the air falls PAO2 and PaO2 fall
Lower amount of oxygen available to inhale (hypoxia), less oxygen reaches the
blood (hypoxemia)
Cardiovascular: pulmonary hypertension, increased HR and CO
Respiratory: ventilation increases by 65% to bring in more oxygen at rapid rate
PACO2 and PaCO2 decrease (hypocaptic)

Q11. A 25 year old man was admitted through A & E with carbon monoxide poisoning.
How does carbon monoxide affect the carriage of oxygen and the oxygen dissociation
curve?
Hb binds CO 240X more avidly than O2 forming carboxyHb which does not bind O2,
this will persist for 4-6 hours
Therefore, less Hb is available for O2 binding
CarboxyHb reduces the O2-binding capacity of Hb
CarboxyHb shifts the O2 dissociation curve to the left


Blood O2 content is actually increased but none are being delivered to the tissues
Q12. Describe the effects of different levels of exercise on heart rate, stroke volume
and cardiac output quoting approximate values.
Sympathetic cholinergic nerves are activated even before the exercise begins
Lets say initial HR=70bts/min, SV= 70mL/beat, so CO= 4.9L/min
When the exercise begins, sympathetic cholinergic nerves are activated by psychic
stimuli, central command, muscle ergoreceptor, joint receptor
These increases HR=200bts/min, SV=150mL/beat, so CO=30L/min
As exercise intensity raises eg by training, HR maintains at 200bts/min, CO and SV
varies at values that agrees with CO=HR X SV
In moderate exercise, HR increase by 200% (140 bts/min), SV increase by 120%
(85mL/beat), CO increase by 240% (12L/min)
In severe exercise, HR increases by 300% (200bts/min), SV increases by 175%
(125mL/beat), CO increases by 500% (25L/ min)
In athletes, max CO=35L/min, max HR 200bts/min, SV=175mL/beat
Training does not affect:
- maximum heart rate
- diffusion capacity
- hemoglobin content
- resting CO
- VO2 at rest
Training causes:
- reduced heart rate training bradychardia
- increased resting stroke volume
- increased SV, CO, VO2 max, VE max
- increased O2 debt, anaerobic threshold
- increased oxidative and glycolytic capacity
- increased capillary density
- increased muscle fibre length type 1 2 transition
Q13. Explain why the combination of nitrates and beta blockers may be more
effective than either alone in treating a patient with angina.
Continuous exposure to high doses of nitrates can cause tolerance and marked
reduction in pharmacological effect, therefore need nitrate free period every
24hours
Nitrates causes extreme hypotension with phosphodiesterase-5 inhibitor such as
Sildenafil
Most beta blockers are cardioselective but not cardioselective at high doses
Both drugs treat angina using different mechanism nitrates work by increasing
blood supply to myocardium by causing vasodilatation of large coronary arteries,
while betablockers work by decreasing myocardial O2 demand by decreasing heart
rate, blood pressure and contractility
Q14. Describe the difference between the two types of blockers of the rennin
angiotensin system with reference to:
a) Mechanism of action
b) Efficacy in treating blood pressure.

c) Production of dry cough

Angiotensin Converting
Angiotensin II antagonist
Enzyme (ACE) inhibitor
a Inhibits ACE, hence blocks the conversion
of Angiotensin I to Angiotensin II,
therefore:
- reduces circulating AT II levels. This
causes a decrease in peripheral vascular
resistance, decreasing afterload.
- prevents release of aldosterone , hence
sodium and water retention, decreasing
preload
- decreases SNS activity (blocks release of
Noradrenaline)

It blocks the angiotensin II receptors:

- AT1A receptor (at the blood receptors)
causes vasodilation, decreasing afterload.
- AT1B receptor (at the adrenal cortex and
pituitary gland) causes reduced secretion of
aldosterone and vasopressin, reducing
preload.

Combined effect of this causes reduction of

blood pressure

- potentiate effect of diuretics in heart

failure
ACE is one of the kinases that break down
bradykinin, inactivating it. Therefore, ACE
inhibitor activates bradykinin. Bradykinin
causes vasodilation, decreasing afterload.
b Presumably ACE inhibitor has greater efficacy in treating high blood pressure since it acts
on the earlier part of the RAA system, hence inhibiting much more downstream effects of
the system. In addition, it also acts on bradykinin in which Angiotensin II antagonist does
not act on.
c Bradykinin is also thought to be the cause
of the dry cough in some patients on
angiotensin converting enzyme (ACE)
inhibitor drugs. This refractory cough is a
common cause for stopping ACE inhibitor
therapy (wiki)

Presumably, it does not cause dry cough

since it does not any effect on bradykinin.

Q15. Explain the advantages of inhaled therapy over systemic therapy in the
management of asthma and chronic obstructive airways disease. COPD
Faster (in reaching the target site), hence
speed relief of symptoms.

Directly goes into the airway

Limits the numbers of area in the body

exposed to the medicine and. For example,
using inhaled B-blockers in asthma treatment
can avoid the B-receptors elsewhere e.g.: B-

Reduce the risk of systemic side effects

receptors in the cardiac muscle

Inhaled therapy does not require the patient
to swallow the medicine as how the systemic
therapy may be administered

This avoids minor stomach upset or heartburn

which can do long term damage.

Summer 2007
Q.1:

Give the surface markings of ALL of the following:

[a] the outline of the heart; (2 x 3 =6)

2nd intercostal space near left sternal edge
3rd intercostal space near the right stenal edge
6th intercostal space at the right sternal edge
5th intecostal space in MCL
[b] the formation of the brachiocephalic veins;
Immediately posterior to sternoclavicular joints,
Vertebral level T2
[c] the superficial palmar arterial arch;
Approximately level with the tip of a fully extended thumb
[d] the flexor retinaculum;
About 2cm square in the midline just distal to distal wrist crease (in the hand)
[e] the position of the base of the breast and nipple.
Base of breast = 6th rib (breast overlies ribs 2-6 vertically and sternal edge to midaxillary
line horizontally.
Nipple is at T4 in a lean man.
Vary in women, depends on the size of the breast.

Q.2: Describe the effects of gravity on the distribution of pulmonary blood flow.
Answer: (CVR 17)

Pulmonary circulation / Blood Flow:

transports deoxygenated blood from right ventricle to the alveolar
capillaries - returns oxygenated blood to the left atrium
low pressure system
Alveolar Capillaries
- lack a strong supporting structure
- distended by capillary blood pressure

-but
compressed
by
(PALV = atmospheric = 0mmHg)

alveolar

air

pressure

On Standing
The effect of gravity is it exerts hydrostatic pressure which influences
pulmonary blood flow within the alveolar capillaries
blood pressure is reduced above cardiac level (0.74mmHg per cm; lung
about 30cm high: so 22mmHg difference, base to apex)
Apex of lung is -14; base is +8 mmHg relative to cardiac level
This develops three possible zones in lung in relation to the blood flow in the
alveolar capillaries within lung at respective zones
Three Possible Zones in lungs
Zone 1 (at apex)
No flow
capillary systolic P less than alveolar.
but only under abnormal conditions, e.g. very low pulmonary
systolic pressure (e.g. due to blood loss) - no flow at apex.
Zone 2
intermittent flow
- capillary diastolic pressure less than alveolar
(at apex: 10-14= -4 mmHg)
Zone 3 (at base)
continuous flow
- capillary diastolic pressure more than alveolar (most of lung).
Q.3: A 30 year old is investigated following a mini-stroke and found to have a
patent foramen ovale on echocardiogram. Describe the right atrium, including the
main internal features. Add a note on the development of the interatrial septum.

Answer: (CVR 22)

Two parts
Anterior

Rough surface contributed owing to the Pectinate Muscle

Includes atrial apendage

Smooth

Posterior

The two parts are separated by Crista terminalis internally and sulcus terminalis
externally
Receives blood from SVC and IVC and coronary sinus
At the lower end of the crista terminalis, are two non functional valves of IVC and
coronary sinus which guard the orifices of these vessels
Valve of IVC is continuous with the limbus edge of fossa ovalis
Fossa ovalis= a cresentric ridge on atrial septum marking site of prenatal foramen
ovale (by which means blood pass from right to left atrium bypassing nonfunctional
lungs)
Outflow valve to right ventricle= tricuspid
Atrial septum

Thicker part of it is formed from embryological septum secundum and ends at the
limbus of fossa ovalis
while the thinner part in the floor of the fossa is formed by septum primum
two septa normally unite, crista terminalis marks the junction between the 2
embryological parts of RA.
Q.4: A patient is found to have a pulmonary embolus following a long-haul flight.
Describe anatomical and physiological dead space and explain how an embolus
affects the physiological dead space. Answer: (CVR 34&35)
Dead space:

dead space air is air that does not take part in exchange with the blood
of the 500 ml inspired with each breath, only 350 ml enters the alveoli for exchange
the rest (150 ml) occupies the dead space in the mouth, nose, pharynx, trachea etc
and does not exchange with the blood

anatomical dead space:

volume of the conducting airways,
decresed by a tracheostomy and increased by breathing through a tube
measured by Fowlers method
physiological dead space:

is this plus air in alveoli that does not exchange with blood
may increase in respiratory disease (e.g. obstructive/ interstitial lung disease).
measured by Bohrs method:
o VD is calculated by measuring the % CO2 in alveolar and expired air and
measuring the gradient
o all of the expired CO2 comes from the VA and none from the VD (which
contains atmospheric air which has no CO2)
o therefore VT X FE = VA x FA
o but VT = VA + VD so VA = VT - VD

o
o

so VT X FE = (VT - VD) x FA
so VD = VT X [(FA - FE)/ FA]

normally, the volumes are almost the same

and explain how an embolus affects the physiological dead space
During PE, embolised part of the lung ventilated but not perfused. So unperfused paart of
alveoli no longer able to expire CO2 to air.
i.e. increase in area of lung that gets air without air exchange occurring.
So physiological dead space increase in this case.
Extra: respiratory symptom of PE:Acute respiratory consequences of PE include increased
alveolar dead space, pneumoconstriction, hypoxemia, and hyperventilation. Later, 2 additional
consequences may occur: regional loss of surfactant and pulmonary infarction. Arterial
hypoxemia is a frequent but not universal finding in patients with acute embolism. The
mechanisms of hypoxemia include ventilation-perfusion mismatch, intrapulmonary shunts,
reduced cardiac output, and intracardiac shunt via patent foramen ovale. Pulmonary
infarction is an uncommon consequence because of the bronchial arterial collateral
circulation
Q.5: A thirty-five year old man with a history of myocardial infarction and severe
familial hypercholesterolaemia is started on Atorvastatin and Gemfibrozil. Write
short notes on the potential benefits and risks of this therapy. (CVR20)
Atorvastatin is an HMG CoA reductase inhibitors
Statins are the most effective and best tolerated agents for treating dyslipidemia
HMG CoA reductase inhibitors are the most potent drugs at reducing LDL
cholesterol (Strongly associated with atherosclerosis and CHD events)
Competitive inhibitors of HMG-CoA reductase, which catalyzes an early, ratelimiting step in cholesterol biosynthesis. So, inhibit the early and rate limiting step
in cholesterol biosynthesis, which results in increased expression of the LDL
receptor.
Multiple trials have shown reduction in fatal and non fatal CHD events
Other effects of Statins
Endothelial function
Plaque stability
Inflammation
Lipoprotein oxidation
Platelet aggregation
Generally well tolerated
Side effects: Hepatotoxicity and Myopathy

- Hepatitis

- Muscle aches

- Myositis

- Angio-oedema

- Sleep disturbance
Gemfibrozil is a fibrate

 Fibrates are most effective at lowering triglycerides

Mechanism of action unclear, involves interaction with the nuclear transcription
factor PPAR that regulates several genes involved in lipid metabolism
Increase activity of peripheral lipoprotein lipase
Reduce VLDL production, increase hepatic LDL uptake
Statin + gemfibrozil = increased mytotoxicity: Gemfibrozil, the drug most commonly
associated with statin induced myopathy (GI disturbance and increased liver
enzyme)
Other common side effects: nausea, skin rash, GIT disturbance, vommitting, diorrhea

Q.6: An individual has their blood pressure measured as 125/80 mmHg. Calculate
pulse pressure and estimate mean blood pressure and explain your reasoning. What
values would you estimate for left ventricular pressure in this individual
(systolic/diastolic).
blood pressure measured as 125/80 mmHg.
(Systolic BP determined by Cardiac output ,
Diastolic BP mainly by Total Peripheral Resistance)
Calculate pulse pressure :
(SBP DBP); 125 80 =45 mmHg
and estimate mean blood pressure :
diastolic + 1/3 pulse pressure = 80 + 15 = 95
What values would you estimate for left ventricular pressure in this individual
(systolic/diastolic). 125/0
Note in LVP (CVR 2):

Diastole
(i) falls to 0mmHg (diastolic recoil-enlarging the chamber - more than
counteracts filling from atrium
(ii) rises slowly as blood flows from atrium into ventricle (atrium has filled with
blood during ventricular systole)
(iii)
ventricular pressure rises as atrium contracts and expels blood into
ventricle (a)

Systole
Initially Isovolumetric Contraction of ventricle. Pressure rises rapidly - AV
valve closes (can't alter blood volume of ventricle until aortic valve opens) pressure rises until higher than aortic (~80mmHg) - aortic valve opens blood expelled.
Period of Ejection - until aortic valve closes.

Isovolumetric Relaxation - as ventricle relaxes - pressure falls - aortic valve

closes (as blood in aortic pushes back) - pressure falls until AV valve opens fills with blood from atrium next cycle
Q.7: You are called to examine a gentleman with a respiratory tract infection in the
middle lobe of his right lung. What are the surface markings of the right lung
including the fissures? Where would you place your stethoscope to auscultate the
right middle lobe?

Lung apex and its pleura extend 2cm above clavicle into the neck and the lower border
varies during breathing.
In forced expiration: (T8 median and T9 lateral)
In forced inspiration (T9 median and T12 lateral)
Right lung has 3 lobes, upper middle and lower that are demarcated by fissures:

Oblique: spine of vertebra T2/T3 to 6th costal cartilage

Horizontal: level of 4th CC, sternal edge to the point where it meets the line of
oblique fissure.
Auscultate right middle lobe
On anterior chest wall, place stethoscope at the right side and in the axilla
Q.8: A 75 year old ladys blood pressure is found to be elevated on two separate
occasions (180/105 mmHg). Describe the mechanism of action of a drug class that
you would use as your first choice to lower her blood pressure. If her blood pressure
improved but did not reduce to optimal levels of <140/90 mmHg, what drug would
you add to your first choice and why?
ACE-Inhibitors
Reduction in formation of angiotensin II (that could cause vasoconstriction
and renal sodium and water retention which ultimately cause hypertension
Beta-blockers
Lowers heart rate and cardiac output through inhibition of renin secretion
Calcium-channel blockers
Block entry of calcium that is essential for excitation-contraction coupling in
smooth & cardiac muscle cells.
Involved in diastolic depolarization and rapid depolarisation of pacemaker
cells of sinoatrial & atrioventricular nodes
Diuretics
Angiotensin II antagonists
Inhibit the pathway of activating angiotensinogen to angiotensin II (that
could cause vasoconstriction and renal sodium and water retention which
ultimately cause hypertension
Alpha-blockers
Blockade of 1 adrenoceptors resulting in vasodilation
Vasodilators
Central sympathophlegics
To reduce to optimal levels of <140/90 mmHg,

Use drug combinations. Start from adding two at low dose, observing responses, before
adding up more.
Drug classes that are compatible for combination:

The preferred combinations in the general hypertensive population are represented as

thick lines.
The frames indicate classes of agents proven to be beneficial in controlled intervention
trials
Q.9: Flow-volume curves are very useful in the diagnosis of respiratory disease.
Draw and describe a normal flow-volume curve.
FVC:
Flow volume curve is a graphic plot that provides useful information about lung
functions and the relationship between lung volume and maximal rate of airflow.
This is achieved during inspiration and expiration using maximum effort against
relevant lung volumes.
A normal
flow-volume curve

Peak
Expi
rator
y
Flow Rate is the highest flow rate achieved
during a maximal expiration and occurs at the beginning of expiration near
Total lung Capacity
The flow-volume curve during a normal inspiration and expiration (tidal loop), and
subsequently recorded during forced in- en expirations serve to demonstrate the
considerable ventilatory reserves available to a healthy subject. Compared to resting
ventilation inspiratory and expiratory flows can still be considerably increased.
During exercise the level of ventilation can be increased by greater inspiratory and
expiratory flows, as well as by increasing tidal volume and respiratory rate. In

general in exercising healthy subjects the end-expiratory lung volume (FRC)

remains by and large the same.
Q.10: Describe the cause, effect and treatment of neonatal respiratory distress
syndrome. What is the significance of the lecithin/sphingomyelin ratio? (CVR 36:
biochem of lung)
Cause: Premature babies have immature lungs because they lack surfactant.
Effect:
In lack of surfactant,
o Alveolar patency is hard to maintain
o Hard to control alveolar surface tension and resistance
o Cause atelectasis : alveolar collapse
L/S = Lecithin / Sphingomyelin Ratio is used as a measure of diagnosis and risk of incidence
of Respiratory Distress Syndrome

L/S > 2.0 is critical as L/s ratio should be at /or > 2 for optimum Independent Pulmonary
Function and to avoid Hyalin Membrane Disease (aka RDS)
<1.9 > 1.5, risk is approx. 40%.
< 1.5, risk is approx 75%

Treatment: give cortisol to

induce L/S ratio as cortisol can induce the rate limiting step in surfactant (dipalmitoyl
lecithin) production i.e. phosphorylating phosphatidic acid tobecome diacylglycerol.

Note: the lines on the graph should be bent/curved, Im too lazy to change it

Q.11: What is heart block? Describe the various degrees of heart block.

Q.12: A 30 year old male is stabbed in his axilla; he is brought to the Accident &
Emergency Department with profuse bleeding and a rapidly falling blood pressure.
Describe the course of the axillary artery, including its parts, branches and relations
to the brachial plexus.
Axillary artery
Is a continuation from subclavian artery
Starts at lateral border of 1st rib until the lower border of teres major
is divided in to 3 parts by the pectoralis minor muscle
branch of 1st part (medial to pectoralis minor)supreme/highest thoracic
branch of 2nd part (behind pec minor)
thoracoacromial : supply upper chest and acromial region, breast
lateral thoracic : to breast and chest
branch of 3rd part (between pec minor and lateral border of teres major)
subscapular : to scapular muscles, scapular anastomosis
anterior circumflex humeral
posterior circumflex humeral
Axillary artery passes between the lateral and medial cords of the plexus. The medial root of
median nerve crosses the axillary artery to unite with the lateral root to form the median nerve
which is lateral and anterior to the axillary artery.

Q.13: Briefly describe the ventilatory responses to hypoxia and hypercapnia.

Hypoxia: PO2 less than normal
Hyeprcapnia: PCO2 greater than normal
These conditions will be detected by peripheral arterial receptors.
This stimulates the respiratory centre causing an increase in breathing hence increase PaO2
and decrease in PaCO2 (i.e. negative feedback control mechanism)
Central chemoreceptors are also triggered by increase in brain ECF PCO2 and H+ but not by
decrease in PO2.
This causes ventilator response to increase ventilation and remove more CO2.
Q.14: A man falls on his outstretched hand. Explain the likely consequences of this
injury. Describe the boundaries and contents of the anatomical snuff box.
Fall on outstretch hands:

Fractured clavicle
Colles fracture (of the distal radius)(presentation: dinner fork deformity)
Fractures scaphoidtenderness in anatomical snuffbox
Bennets fracture: fracture of first metacarpal (presentation: thumb is pronated
to bring it into opposition w/ non-displaced palmar fragment)
Dislocated lunatemedian nerve injurycannot abduct hands against resistance (abduct
the thumb at right angles to the palm with fingertips in contact and forming a pyramid.)
Mid-shaft humeral fracture : radial nerve damage (presentation: cannot extend radial
3.5 fingers , test: no sensation on skin over 1st dorsal interosseous muscle )

Anatomical snuffbox:
Boundaries: Ulnar: tendons of extensor pollicis longus
Radial: tendons of Extensor pollicis brevis
deep/ floor on the radial side: tendons of abductor pollicis longus
Contents: radial artery
Q.15: Beta-blockers are an important group of drugs that are widely used in clinical
practice.
[a] Briefly explain their classification based on their action on beta receptors
providing one example of a drug on each;
[b] List three clinical conditions in which the use of beta-blockers is indicated and
describe the mechanism of action of the drug in two of these three examples.
Non-selective; Propranolol, : binds on bot B1 and B2 receptors

1 selective; Atenolol :only bind to B1 receptor

With vasodilatation;
Pindolol (1 selective antagonist and partial agonist at B2 adrenoceptors)
Carvidalol (non-selective -blocker but also 1 blocker)
Nebivolol (releases NO)
CLINICAL USE:
Hypertension: it decrease heart rate and cardiac output so decrease BP. They also decrease
level o renin secretion
Angina:
Block action of adren/nor-adren on the beta adrenergic receptors
These drugs also reduce mortality and reinfarction in postmyocardial infarction patients.
They reduce the myocardial oxygen demand by:
1) Reducing the HR.
2) Decrease the blood pressure (afterload).
3) Decrease contractility
Heart failure
Beta1 receptor in the heart. Increased force and rate of
contraction. Increase conduction velocity.
Beta2 receptor in smooth muscle mediates relaxation.
Hyperthyroidism / Thyrotoxicosis
Symptom relief in Anxiety
Prophylaxis of Migraine
Glaucoma
Post-Myocardial Infarct cardiovascular protection
Supra-ventricular tachycardias

2007 ( repeat )
1. A 48 year old man complains of central chest pain. Describe or draw the arterial
blood supply of the heart, adding a note on its venous drainage. Add a brief note
on the embryology of the right atrium.
2. With the aid of a diagram, illustrate and explain the changes in left ventricular
pressure during the cardiac cycle. Also, indicate when the AV and aortic valves are
open.

3. A 23-year-old woman is using salbutamol inhaler for frequent attacks of asthma.

a). How does salbutamol provide relief in such attacks?
b) Suggest three side effects that may occur with the long-term use of
salbutamol.
c) If the patient is not well-controlled on salbutamol, name one drug that can be
co-administered.
4. Describe the boundaries and contents of the carpal tunnel. What is carpal tunnel
syndrome and what are the likely causes and consequences?

5. Heterozygosity for the condition of familial hypercholesterolaemia (FH) has a

frequency of about 1/600 in the general population. What is the molecular defect
underlying this condition. State whether you think it would be responsive to statin
therapy, giving reasons for your answer.
-rare genetic disorder characterised by very high LDL cholesterol and early cardiovascular
disease running in families.
-mutation in either the LDL receptor or the ApoB100 protein
-defects in the cell surface receptor that normally removes LDL particles from the blood
plasma.
-In heterozygous FH, only one of the two DNA copies (alleles) is damaged, and there will be
at least 50% of the normal LDL receptor activity
-Heterozygous FH can be treated effectively with statins. These are drugs that inhibit the
body's ability to produce cholesterol by blocking the
enzyme hydroxymethylglutaryl CoA reductase (HMG-CoA-reductase) in cholesterol
biosynthesis.
- Maximum doses are often necessary.
-Statins work by forcing the liver to produce more LDL receptor to increase clearance of
LDL
-therefore statin can reduce the bodys cholesterol level.
6. A young tall and thin male presents with sudden onset of unilateral chest pain and
progressively increasing breathlessness. Chest X-ray confirmed the diagnosis of
pneumothorax.
a) Describe the various pressures acting on the wall of the alveoli.
b) What is tension pneumothorax and what are its cardiovascular consequences?
tension pneumothorax is a worsening condition of a simple pneumothorax associated with
the fromation of a one-way valve at the rupture site. during inspiration, pressure in the
thorax decrease, and air is sucked into the pleural space htrough a one-way valve. however,
during expiration, the pressure created to force air out of the pleural cavity is insignificant.
over time, air accumulates in the pleural cavity, and this creates an increasing amount of
pressure in the thorax. subsequently, the pressure will compress the mediastinum and the
heart, reducing the amount of diastolic filling of the ventricles. as a result, cardiac output
will decrease.

7. A 45 year old lady is diagnosed with breast carcinoma. Describe the position,
blood supply and lymphatic drainage of the breast. What are the signs of breast
carcinoma?
-blood supply: internal thoracic artery
lateral thoracic artery(branches of axillary artery),
thoracoacromial artery,
and posterior intercostal arteries
-position:2nd rib to 6th rib, 2/3 lies on pect major and
1/3 on the serratus anterior, only lies in superficial
fascia
-lymphatic drainage: mainly to axillry lymph nodes,
some goes to parasternal nodes and along intercostal
artery vessels
sign of breast carsinoma: lump on the breast, dimpling sign, and swollen of the lymph nodes
at axillary region.
8. With the aid of a diagram, describe the changes in membrane potential occurring
in a
myocardial SA node pacemaker cell during a normal cardiac cycle, and the ion
channels involved.

SA nodal action potentials are divided into three phases. Phase 4 is the spontaneous
depolarization (pacemaker potential) that triggers the action potential once the membrane
potential reaches threshold between -40 and -30 mV). Phase 0 is the depolarization phase of the
action potential. This is followed by phase 3 repolarization. Once the cell is completely
repolarized at about -60 mV, the cycle is spontaneously repeated.

The changes in membrane potential during the different phases are brought about by changes in
the movement of ions (principally Ca++ and K+, and to a lesser extent Na+) across the membrane
through ion channels that open and close at different times during the action potential. When a
channel is opened, there is increased electrical conductance (g) of specific ions through that ion
channel. Closure of ion channels causes ion conductance to decrease. As ions flow through open
channels, they generate electrical currents (i or I) that change the membrane potential.
9. Briefly describe how the elastic properties of the lung and chest wall can
influence the effectiveness of ventilation and the efficiency with which ventilation is
performed.
10. A patient is suspected of having a right lung pulmonary embolism seven days
post- operatively. Describe or draw the structures in the hilum of the right lung,
including the arteries, veins and lymphatics. Which nerve travels anterior to the
hilum, and which nerve
travels posterior to the hilum?
-Hilum is where the root of the lung enter and leave the lung. It consists of pulmonary
artery, bronchial vessels, pulmonary vein, bronchus, lymphatics and nerve.

-In the right hilum, bronchus is situated posteriorly. Bronchus is cartilages. Bronchus of the
right side gives it branch of superior lobe branches in the root, unlike on the left which
branches within the lung itself.
-Pulmonary artery is superiorly at the hilum. Its is longer than the left. It carries
deoxygenated blood from right ventricle to the lung.
-pulmonary vein is anterior and inferiorly. It carries oxygenated blood to the left atria.
- lymphatics system in the lung is drained into tracheobronchial nodes around the root of
lobar and main bronchi and along the trachea. It is then drained into mediastinal nodes at
posterior mediastenum and to the thoracic duct.
- the nerve travel anteriorly to the hilum is the phrenic nerve.
-the nerve travel posteriorly to the hilum is the vagus nerve.
11. Two individuals plan to perform heavy exercise. Person A is a well-trained athlete
having a resting heart rate of 50 beat per minute. Person B does not perform
regular exercise and has a resting heart rate of 80 beat per minute.
A) Explain why it is advantageous for Person A to have a slower resting heart rate
than person B?
B) Discuss the cardiac adjustments that will occur as the two individuals perform
the planned heavy exercise.

A) - slower resting heart rate would meant less work for the heart to pump the same or
greater amount of blood for the tissue all over the body.

-Person A has larger cardiac output if compared with person B.

- The circulatory system is able to provide increase cardiac output for delivery of oxygen
and other nutrients to the muscles during exercises.
- Therefore it can give the strength for the muscles themselves in setting the limit for
continued muscle work.

B) The sympathetic effect and decrease in parasympathetic affect which results in

- increase heart rate and increase pumping to deliver blood.
-most of the arterioles of the peripheral circulation are highly contracted,
the arterioles in the active muscles. Its aim is to supply more oxygen to
active muscle.

except
the

-contraction of vein increases mean systemic filling pressure. It is then

promoting the increase in venous return in the blood to heart, therefore
increase cardiac ooutput.
All the effect eventually increase the arterial pressure from normal 100mmHg up to 130160 mmHg during exersice ,which means more force to pull the blood to the muscle tissue
during exercise.
Long term increase workload without excess load of the heart cause increases mass and
contractile strength for the heart. This result in cardiac muscle hypertrophy and therefore
increase cardiac output.
(guyton&hall chapter 21-total body circulatory readjustment during exercise)
12. A sixty year old male has had one episode of sudden cardiac death and a five year
history of heart failure secondary to ischaemic heart disease. Write short notes on
the
optimal pharmacological approach to treating this patient.
1st,ischeamic heart disease means heart does not get enough 02..so we
need to give 02 to heart
by...increase preload BUT decrease the contraction of heart musle( as
blood will go to coronary circ. when heart relax)
so, i suggest we give beta blockers(hydralazine,to reduce
contraction)... also give nitrate like Isosorbide dinitrate,because hydralazine work best with
nitrates...then we give LOOP DIURETICS( e.g furosemide) which has an effect at preload
furosemide will acutely increased

13. A footballer dislocates his shoulder during a football match. Describe the anatomy
of the shoulder joint, naming the structures which contribute to its stability. What
nerve may be damaged by a dislocated shoulder and what are the motor and sensory
tests for this nerve?
Shoulder joint (glenohumeral joint) -articulation btw scapula and humerus, sacrifices
stability for mobility
-unstable coz glenoid fossa is shallow
Structures contribute to stability:
- Rotator cuff muscles:
Teres minor (most posterior)
Infraspinatus
Supraspinatus
Subscapularis (most anterior)
1st 3 attach to greater tuberosity Humerus, Subscapularis on lesser tuberosity
- Glenohumeral ligaments
-Dislocated shoulder can damage Axillary nerve
-Tests:
- Motor: shoulder abd
14. A patient with chronic obstructive pulmonary disease (COPD) is given some
additional
oxygen to breathe to try and improve the arterial blood PO2. Suddenly,
the patient stops
breathing. Explain why.
COPD would give rise to asphyxia where pO2 of O2 is low and the pCO2 is high.
This is a type 2 respiratory failure which is hypoventilation.During asphyxia, ventilation is
adjusted accordingly to adapt to hypercapnia but it does not counter hypoxia. During
asphyxia, ventilation is dependent on hypoxic reflex from the peripheral receptors. By
giving oxygen, it eliminates this reflex action which causes apnoea. Hypercapnia also
inhibits the nervous system and induces coma. Over dosage of oxygen given to a type 2
respiratory failure would even cause CO2 retention.
15. Describe how coronary blood flow varies with the cardiac cycle. Illustrate your
answer with a diagram.

JC1 examinations (January 2008) Question 4

What are the physiological mechanisms for generating the resting membrane potential in a
typical neurone?
A membrane potential is generated by separation of opposite charge across plasma membrane of
neurone
Main ions involved are K+, Na+ and large protein anions (A-)
Establishment of concentration gradients for K+ and Na+ are by sodium-potassium ATPase

(which moves 3Na out for 2K in). Leaves potassium concentration high intracellularly, sodium
high extracellularly and contributes a small part of negative potential.
There is selective permeability of plasma membrane to K+ ions, with the negative membrane
potential driven in large part by K+ ion movement out of cells at rest via leak channels, plus
presence of large protein anions (exclusively intracellular)
Resting membrane potential (approx. -70mV)
Top answers/extra credit: giving specific concentrations of Na+/K+ ions, mentioning Nernst
equation gives equilibrium potential for an ion, how membrane potential might be measured
experimentally
Question 7
A patient suffering from angina is given a calcium channel blocker to reduce heart muscle
contraction. Describe excitation-contraction coupling in heart muscle.
The action potential propagates along the T system which penetrates the cell at the Z lines.
The sarcoplasmic reticulum of heart muscle is less well developed than in skeletal muscle, having
diads instead of triads and with only one diad or triad per sarcomere.
The action potential involves calcium entry into the cell through the dihydropyridine receptor
which causes calcium release from the SR through the ryanodine receptor i.e. calcium-induced
calcium release.
The calcium is bound by troponin which results in conformational changes in the troponintropomyosin complex allowing cross-bridge formation between the myosin and actin.
The myosin head is in a high energy state which allows for the power stroke and the pulling of
the actin filament towards the centre of the sarcomere during which phosphate and ADP are
released.
The myosin head then binds ATP which causes release of the head, ATP hydrolysis and the
return of the head to the high energy state for further cycles.
Relaxation occurs due to pumping of calcium back into the SR and by sodium/calcium exchange
at the sarcolemma.

JC1 HIS module short-notes paper January 2008

Question 1
Mary is a 52 year old lady recently diagnosed with breast cancer. Her left upper limb has
become noticeably swollen in the last month. How might this be related to her breast
cancer? Add a note on the structure of a lymph node.
The breast drains to the axillary (armpit/upper arm) lymph nodes thus cancer cells may spread
here from the breast & cause enlargement of the nodes, blocking lymphatic drainage from the
arm.
Structure of lymph node:
A lymph node is surrounded by an outer capsule (collagen) septae (trabeculae) radiate into the
gland from this capsule. Multiple lymphatics may enter a gland, a single efferent lymphatic will
exit.
Within the gland, there is an outer cortex and an inner medulla.
The cortex contains B cells, while the underlying paracortical areas contain T cells.
Following stimulation, clusters of B cells (follicles) may have a germinal centre.
The medulla contains cords of tissue surrounding sinuses and is largely populated by plasma cells
(active B cells).

Question 2
Briefly describe the structural changes that occur in hemoglobin on oxygen binding. How
do these changes affect hemoglobins affinity for oxygen, and how does this relate to
hemoglobins physiological role?
Haemoglobin is a tetrameric molecule with 4 polypeptide chains, 2 alpha () chains and 2 beta ()
chains. Each chain carries one haem moiety and can bind one molecule of oxygen. The overall
structure can be thought of as a dimer of dimers of the form () , with strong non-covalent
2

bonds within the dimers, and weaker non-covalent bonds between them. It is primarily the bonds
between the dimers that are affected by oxygen binding. DeoxyHb has a taut structure with
relatively strong bonds between the dimers. When oxygen binds to deoxyHb a conformational
change occurs that breaks some of the ionic bonds between the dimers, resulting in a structurally
relaxed form of Hb. The conformational change occurs due to changes in the electronic
configuration of the haem iron, which causes the iron to move more into the plane of the haem
ring structure, moving the proximal histidine and helix F to which it is attached.
3 JC1 examinations (January 2008)

The relaxed form of Hb has a higher affinity for oxygen that the taut, deoxy- form. This change in
affinity on oxygen binding means that oxygen binding to Hb is cooperative, and results in a
sigmoid oxygen binding curve. This has the effect of allowing almost twice as much oxygen to be
delivered to the peripheral tissues than would be the case if oxygen binding was not cooperative.
The affinity of Hb for oxygen is also affected by other allosteric modulators, including CO2, pH
and 2,3-BPG, all of which enhance Hbs physiological role by increasing the amount of O

released at the peripheral tissues, while not compromising the ability of Hb to bind O 2 in the
lungs.
Question 4
Name 3 ways in which the intact endothelium of a blood vessel regulates thrombosis. For
one of these, describe how drugs are used to target this area.
In general the intact endothelium prevents unwanted thrombus formation. It does this in a number
of ways:
1. it synthesizes and secretes, in a tonic fashion , Nitric Oxide (NO); which inhibits platelet
activation by elevating intracellular cGMP levels
2. it synthesizes and secretes, in a tonic fashion , prostacyclin (PGI2); which inhibits platelet
activation by elevating intracellular cAMP levels.
3. Intact endothelial cells express heparan sulphate, a proteoglycan on their surface. This
inhibits any unwanted, or inappropriate, activation of thrombin and Factor Xa,
thereby preventing the formation of fibrin. In other words an intact endothelial cell
acts as an inhibitor of the coagulation cascade
4. Intact endothelial cells express tissue-Plasminogen-Activator (tPA) on their surface. This
degrades any unwanted, or inappropriate, fibrin clot that is formed. In other words
intact endothelial cells acts as an promotors of the fibrinolytic cascade.
5. Intact endothelial cells express Thrombomodulin on their surface. Thrombomodulin binds
to thrombin and inhibits its procoagulant effect. The TT-complex also stimulates
fibrinolysis.
6. intact endothelial cells produce and secrete Tissue factor pathway inhibitor (TFPI),
which inhibits the coagulation cascade. This prevents unwanted clot formation.
7. In addition, intact endothelial cells prevent exposure of subendothelail collagen or
figrinogen and thereby prevent platelet adhesion and thrombus formation.
8. it can also be considered that intact endothelia prevent release of Tissue factor.
Any one of these pathways could be elaborated on for the second half of the question. The two
that I most expect to see are :
tPA- recombinant tPA is used therapeutically to degrade thrombi. It works by activating
plasminogen, which degrades fibrin polymers.
Heparin, derived from beef lung or from porcine intestinal mucosa, is a therapeutic agent that
mimics the expression of heparan sulphate on the surface of intact endothelia. It is used to prevent
unwanted or inappropriate clotting in patients at risk of thrombosis or during thrombosis. These
include patients who are immobilized following surgery and patients with recent myocardial
infarcts. It acts by binding with plasma antithrombinIIII, increasing its capacity to inhibit
thrombin and the coagulation cascade.
Obviously drugs which target any of the other pathways identified above are also acceptable such
as NO-donors (inhibit platelet activation in addition to causing vessel dilation), Dipyridamole,
inhibits platelet activation by elevating intrcellular cAMP.
Antithrombin drugs in general would also be acceptable as these inhibit the coagulation cascade.
4 JC1 examinations (January 2008)

JC1 NE module short-notes paper January 2008

Question 5
Describe cell membrane proteins and outline how they are involved in moving molecules
back and forth across the cell membrane. Discuss the requirements of energy in these
processes.
Answer: There are a variety of proteins that are found in the cell membrane. There are anchoring
proteins which attach cell membranes to each other or to internal or external structures.
Recognition proteins also known as identifiers, identify the cell and prevent attack by immune
system. Enzymes found in the cell membrane catalyse either intracellular or extracellular
reactions. Specific ligands found in the extracellular matrix bind to receptor proteins on the
membrane surface and in doing so send signals into the cell. Leak Channels permit continuous
movement of water and ions while gated channels close or open to regulate ion movement. It is
the carrier proteins that are primarily involved in the movement of molecules across the
membrane and in doing so may require an energy source such as ATP. Transport of molecules
across a membrane requiring energy occurs against a concentration gradient. This form of
transport is known as active transport and there are 3 types: primary active transport, secondary
active transport and group translocation. An example of active transport is the Na+ K+ pump.
This pump uses 1 molecule of ATP to transport 3 Na+ ions from the inside of the cell to the
outside with the subsequent transport of 2 K+ ions from the outside of the cell to the inside. An
example of secondary active transport is the transport of glucose into the cell. Glucose can be
transported into the cell only after Na+ has bound to the transport protein. In 3 cycles, 3 glucose
molecules and 3 Na+ are pumped into the cell. The Na+ is then pumped out via the Na+/K+
pump with the expenditure of 1 ATP. In group translocation a sugar is phosphorylated as it is
transported across the membrane. An example of this is the phospho-transferase system (PTS),
where the source of energy is phosphoenolpyruvate.
Question 6
Hyperphenylalaninaemia (PKU) is one of the more common inborn errors of metabolism in
Ireland. What is PKU and how may it be diagnosed
What is PKU?
_Autosomal recessive inborn error of phenylalanine metabolism
_~ 97% of case in Ireland due to mutation in gene which code for
the enzyme Phenylalanine Hydroxylase (PAH) and ~ 3% due to Mark >1
defective synthesis of the PAH enzyme cofactor, tetrahydrobiopterin
_Clinical Phenotype and management depends of residual PAH enzyme activity
_Phenylketonuria (PKU)
phe>600mol/L
o PAH deficiency
o DHPTR deficiency
_Hyperphenylalaninaemia Not required by pass students
phe >180 mol/L <600mol/L
o PAH partial deficiency
_Overall Incidence in Ireland about 1 in 4,500
_Clinical presentation in infants and children not diagnosed during the newborn period include:
_irritability, vomiting, fits
_mental retardation by 4 - 6 months
_pale skin, fair hair, blue eyes

How may it be diagnosed?

Newborn screen (Heel-prick / Guthrie) test and biochemical analysis of blood
phenylalanine levels
Question 8
Discuss the central role of the TCA cycle (Krebs cycle) in metabolism.
The TCA cycle is cyclical biochemical pathway which begins with the joining of oxaloacetate
and acetylCoA to form citric acid, cycles through various intermediates and regenerates
oxaloacetate by the dehydrogenation of malate. The cycle serves two main purposes in
metabolism:
[1] It provides most of the cells energy by extracting it from Acetyl CoA in the form of GTP and
NADH (which is fed into the electron transport chain and oxidative phosphorylation). The
oxidative extraction of energy using the krebs cycle and oxidative phosphorylation is far more
efficient than anaerobic glycolysis, yielding 38 molecules of ATP as opposed to 2 for glycolysis
alone. The acetylCoA entering the TCA may come from,for example, glycolysis, via pyruvate
dehydrogenase or from the beta-oxidation of fatty acids. Allosteric control of TCA enzymes is
also an important factor in the overall control of energy metabolism
[2] It provides intermediate molecules which are converted into a number of other important
molecules for the cell. For example alpha-ketoglutarate is converted via transamination to the
amino acid glutamate, which further yields proline and glutamine; oxaloacetate is likewise
converted to aspartate which further yields asparagine. In addition, the breakdown products of
many compounds enter energy metabolism via the TCA, notably the carbon skeletons of many
amino acids. This is a very important process in prolonged starvation where body protein is
utilized to provide glucose via gluconeogenesis.
If students want to include the complete details of the TCA cycle reactions that is worthwhile, but
it should also show something of how the cycle is interconnected with other parts of metabolism.

A1 ANATOMY
1. Describe or draw a labelled diagram of the arterial blood supply of the hand.
Add a note on points of clinical significance.
2. Describe the attachments, actions, and nerve supply of triceps surae
(gastrocnemius/ soleus). Add a note on clinical conditions that commonly affect
these muscles.
3. Describe the ulnar nerve and its branches.
Explain the condition claw hand.
4. A Outline the structures contributing to the stability of the hip joint. Add a note on
points of clinical significance.
OR
B Outline the structures contributing to the stability of the ankle joint. Add a note
on points of clinical significance.
A2 PHYSIOLOGY
5. In 3 sentences of less, describe the function of the following molecules:
(i) Erythropoietin
(ii) Haemoglobin
(iii) Thrombopoietin
(iv) Thrombin
(v) Albumins
6. Describe the structural and functional differences between intra- and extrafusal

muscle fibers.
7. Draw a fully labelled diagram of an excitatory postsynaptic potential (EPSP)
evoked at an excitatory synapse in the central nervous system. Name the
commonest excitatory neurotransmitter in the central nervous system, and name
two sub-types of receptors for this neurotransmitter.
8. Name the two organs of balance in the ear. What movement of the head
stimulates each type of balance sense organ? Draw a fully labelled diagram of a
sensory hair cell located in such balance organs.
9. List (i) the three types of simple surface epithelium; (ii) the three types of cell
membrane specialisations of epithelial cells and (iii) the four types of epithelial
cell intercellular junctions.
A3 INTEGRATED
10. Describe the anatomy of muscle spindles and explain their physiological role in
muscle contraction.
January 2009
Q4. Draw a sketch of the neuromuscular junction (NMJ) and include a detailed
description of the normal sequence of events following the arrival of an action
potential.
Q5. What are the clinical uses and side effects of 1 adrenoreceptor antagonists?
Q6. Compare and contrast the effects and mechanisms of sympathetic and
parasympathetic control of the heart.
Q7. Bed rest causes atrophy of muscle fibres, especially type IIb fibres. Describe the
differences between type I and type IIb fibres.
2010
Q1. Neuromuscular Module (NM)
Give the surface markings of ALL of the following:
(a)
(b)
(c)
(d)
(e)

the great (long) saphenous vein

the dorsalis pedis pulse
the femoral pulse
the posterior tibial pulse
the common peroneal nerve

Answer:
(a) anterior to the medial malleolus, handsbreath behind the medial border of the patella, 1.5
inches below and lateral to the pubic tubercle
(b) lateral to the EHL tendon, 1/3 of the way down a line drawn between the anterior tibial
pulse (halfway between the 2 malleoli) and the first web space
(c) 2cm below the midinguinal point (which is half way between the ASIS and pubic
symphysis)
(d) halfway between the medial malleolus and the calcaneus
(e) behind head of fibula and then winds laterally around the neck of fibula
Marking scheme: 1 mark for 2 parts correct 2 marks for 3 parts correct 3 marks for 4 parts
correct
4 marks for all correct
Q2. Neuromuscular Module (NM)

Neuromuscular blocking drugs are used as an adjunct to anesthesia. Discuss why such
drugs are used. Which drugs are best suited to this task and describe their mechanism of
action.
Q3. Neuromuscular Module (NM)
Hypertension is treated with drugs that relax arteriolar smooth muscle, a type of
visceral smooth muscle. Describe the differences between visceral and multi unit smooth
muscle.

2008/2009
Question 4
What are the physiological mechanisms for generating the resting membrane potential in a
typical neurone?
A membrane potential is generated by separation of opposite charge across plasma membrane of
neurone
Main ions involved are K+, Na+ and large protein anions (A-)
Establishment of concentration gradients for K+ and Na+ are by sodium-potassium ATPase
(which moves 3Na out for 2K in). Leaves potassium concentration high intracellularly, sodium
high extracellularly and contributes a small part of negative potential.
There is selective permeability of plasma membrane to K+ ions, with the negative membrane
potential driven in large part by K+ ion movement out of cells at rest via leak channels, plus
presence of large protein anions (exclusively intracellular)
Resting membrane potential (approx. -70mV)
Top answers/extra credit: giving specific concentrations of Na+/K+ ions, mentioning Nernst
equation gives equilibrium potential for an ion, how membrane potential might be measured
experimentally
Question 7
A patient suffering from angina is given a calcium channel blocker to reduce heart muscle
contraction. Describe excitation-contraction coupling in heart muscle.
The action potential propagates along the T system which penetrates the cell at the Z lines.
The sarcoplasmic reticulum of heart muscle is less well developed than in skeletal muscle, having
diads instead of triads and with only one diad or triad per sarcomere.
The action potential involves calcium entry into the cell through the dihydropyridine receptor
which causes calcium release from the SR through the ryanodine receptor i.e. calcium-induced
calcium release.
The calcium is bound by troponin which results in conformational changes in the troponintropomyosin complex allowing cross-bridge formation between the myosin and actin.
The myosin head is in a high energy state which allows for the power stroke and the pulling of
the actin filament towards the centre of the sarcomere during which phosphate and ADP are
released.
The myosin head then binds ATP which causes release of the head, ATP hydrolysis and the
return of the head to the high energy state for further cycles.
Relaxation occurs due to pumping of calcium back into the SR and by sodium/calcium exchange
at the sarcolemma.

NM Question
There are three types of muscle, skeletal, cardiac, and smooth in the
human body. There are many diseases associated with each of these
muscle types.
a. Describe and differentiate between excitation-contraction coupling
in smooth and skeletal muscle. (2 marks)
b. Describe the distinguishing features between multiunit and singleunit smooth muscle. (2 marks)
Model Answer
a. The two things they have in common are that they contain actin and
myosin and that they use ATP as an energy source. The differences in
the excitation is that the skeletal muscle is excited by an impulse
traveling down a neuron which transmits an action potential into the T
tubules of the skeletal muscle which then opens voltage-sensitive
channels called dihydropyridine receptors that undergo a
conformational change allowing the ryanodine receptors to release
calcium from the sarcoplasmic reticulum. So it can be described as a
structural change in order to bring about the contraction in skeletal
muscle. Smooth muscle can be excited in a variety of ways including a
nerve impulse, temperature, stretch, chemicals such as hormones or
they can be self-excitatory an example would be Interstitial cells of Cajal.
Then the excitation and coupling also involves a rise in calcium but this
time the calcium comes from the extracellular fluid as well as the
sarcoplasmic reticulum. The calcium and an intracellular calcium binding
protein called calmodulin complex and activate the myosin light chain
kinase and this goes onto phosphorylate the myosin light chain and this
leads to a chemical change allowing the phosphorylated myosin filament
to combine with the actin filament and the muscle contracts.
b. Multiunit smooth muscle is controlled by nerve input and is well
innervated. It has well developed neuromuscular junctions and hence is
stimulated through a full action potential which goes onto to ensure a
muscle contraction. Hence, there is no spontaneous activity and there is
an absence of gap junctions in this type of smooth muscle.

Single-unit smooth muscle is self-excitable, so it does not require

nervous stimulation for contraction so there is sparse innervation of the
tissue. The self-excitable cells of the single-unit smooth muscle do not
maintain a constant resting potential. Instead their membrane potential
inherently fluctuates without any influences by factors external to the
cell. Two major types of spontaneous depolarisation displayed by selfexcitable cells are pacemaker potential is pacemaker cells and slow
wave potential in interstitial cells of Cajal. Such independent contractile
activity initiated by the muscle itself is termed as myogenic activity in
contrast to the neurogenic activity of the skeletal and multiunit smooth
muscles. The contraction is potentiated by the presence of gap junctions
and is often described as a functional syncytium. This type of muscle is
able to contract as a single-unit.