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S.P.-SBA-1-85 1. You review a 39-year-old sportsman who complains of knee pain. Arthroscopy reveals damage to the cartilage. Which of the following stems best describes a property of hyaline cartilage?

It has a blood supply from small arterioles

It is rich in type 1 collagen

Chondrocytes secrete collagen only

It is avascular Correct answer

Pressure from normal joint loading accelerates damage to cartilage

Hyaline cartilage forms the articular surface and is avascular, relying on diffusion from synovial fluid for nutrients. It is rich in type II collagen and forms a meshwork containing proteoglycan molecules that retain water. Intermittent pressure from joint loading is essential to maintain normal cartilage function. Chondrocytes secrete proteoglycans and collagen and are embedded in the cartilage. They migrate to the joint surface along with the matrix that they produce. 2. A 54-year-old woman has undergone some blood tests as part of an employment health screen. She reports she is in good health and, being very health conscious, takes regular vitamin and mineral supplements. She is taking bendrofluazide 2.5 mg for hypertension and her blood pressure is 132/82 mmHg. The only abnormality is a serum calcium concentration of 2.94 mmol/l. Which of the following is the most likely cause?

Diuretic treatment

High dietary calcium intake

High dietary vitamin D intake

Occult malignancy

Primary hyperparathyroidism Correct answer

Thiazides can cause hypercalcaemia but it is usually only mild. Vitamin D itself is physiologically inactive and, whereas 1-hydroxylated derivatives can be a cause of hypercalcaemia, vitamin D – which has to be metabolised to activate it – is less commonly so. Intestinal absorption of calcium is subject to tight control, and a high intake does not cause hypercalcaemia. The two most common causes of hypercalcaemia are primary hyperparathyroidism and malignancy. In an asymptomatic individual, primary hyperparathyroidism is the more likely cause. 3. A 24-year-old woman undergoes resection of the terminal ileum with fashioning of an ileostomy for Crohn’s disease. Some 2 weeks after surgery, she is making a good recovery, and is eating a high-energy, low-residue diet, but has a high ileostomy volume, necessitating intravenous fluid replacement. Her serum calcium concentration is 1.82 mmol/l, phosphate 1.28 mmol/l, alkaline phosphatase 82 U/l (normal < 150), albumin 30 g/l, creatinine 80 m mol/l. Prior to surgery, her serum calcium concentration was 2.18 mmol/l, albumin 36 g/l. What is the most likely cause of her hypocalcaemia?

Formation of insoluble calcium salts in the intestine

Hypoalbuminaemia

Hypomagnesaemia Correct answer

Malabsorption of calcium

Malabsorption of vitamin D

Impaired fat absorption can lead to the formation of insoluble calcium salts in the gut. Fat and calcium are absorbed in the proximal small intestine, so, too, is vitamin D. Although bile salts are absorbed distally, and impaired absorption can lead to a secondary decrease in proximal fat absorption, this is unlikely to be responsible for hypocalcaemia developing so quickly. The normal alkaline phosphatase level also mitigates against vitamin D deficiency. Hypocalcaemia would normally be expected to stimulate parathyroid hormone secretion and cause the plasma phosphate concentration to fall (PTH is phosphaturic). Patients with ileostomies can lose large amounts of magnesium through their stomas; hypomagnesaemia impairs PTH secretion and can cause hypocalcaemia that is resistant to an increased provision of calcium. 4. A patient receives too many infusions after an operation resulting in a 20% increase in his blood volume.

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What is the physiological process that is most likely to correct this abnormality?

Reduced activity of arterial pressure sensors

Increased activity of renal sympathetic nerves

Aldosterone release

Atrial natriuretic peptide (ANP) release Correct answer

Venous dilatation

The atria contain granulated cells that release peptides, atrial natriuretic peptide (ANP), in response to stretch. This natriuretic agent also relaxes the peripheral vasculature and thereby opposes the actions of the sympathetic and renin–angiotensin systems. 5. In metabolic alkalosis associated with prolonged nasogastric aspiration in postoperative ileus, what is the most important cause of the acid–base disturbance?

Hypoventilation

Increased renal bicarbonate reabsorption

Loss of gastric acid Correct answer

Potassium depletion

Secondary aldosteronism

Loss of unbuffered gastric acid is the cause of the metabolic alkalosis seen under these circumstances if there is inadequate replacement of the fluid lost with intravenous physiological saline. Increased renal bicarbonate reabsorption (needed to allow adequate renal sodium reabsorption in the presence of hypochloraemia), potassium depletion (gastric secretions contain about 10 mmol/l of potassium) and secondary aldosteronism (a result of extracellular fluid loss) all help to maintain the alkalosis, but they do not cause it. Hypoventilation is a compensatory change: on its own, hypoventilation causes carbon dioxide retention and a respiratory acidosis. 6. An overweight 32-year-old woman presents with a short history of painless jaundice. There is no previous history of illness and, apart from the jaundice, she has no signs of chronic liver disease. Initial investigations reveal a haemoglobin of 12.7 g/dl, MCV 105 fl, serum bilirubin 162 mmol/l, AST 145 U/l, alkaline phosphatase 224 U/l, gamma-glutamyltransferase 200 U/l. Which of the following is the most likely diagnosis?

Alcoholic liver disease Correct answer

Autoimmune chronic hepatitis

Carcinoma of the head of the pancreas

Cholecystitis

Hepatitis A infection

Jaundice with an elevation of both AST and alkaline phosphatase suggests mixed hepatocellular damage and cholestatic liver disease, typical of acute alcoholic hepatitis on a background of chronic liver disease (and is not excluded by the lack of physical signs). The high gamma-glutamyltransferase lends support to this (although it may be increased in liver disease of any cause). Macrocytosis is typical of chronic excessive alcohol intake and is not a feature of the other conditions; although were it not present, autoimmune liver disease would need to be considered.

In hepatitis A, AST is typically higher than alkaline phosphatase, while the reverse is true of pancreatic carcinoma. Chronic cholecystitis can cause jaundice but it would be unusual for there to be no history of acute episodes.

7. A 75-year-old woman is being followed by her GP for suspected developing primary hypothyroidism. Which of the following biochemical changes would you most expect to occur first?

Fall in serum free thyroxine

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Fall in serum thyroxine-binding globulin

Fall in serum free triiodothyronine

Fall in serum total triiodothyronine

Increase in serum TSH Correct answer

Hypothyroidism develops gradually, often over many months or even years. In the early stages, free thyroxine concentrations are maintained in the normal range by the increased secretion of TSH. Patients with a slightly elevated TSH and low–normal thyroxine are said to have ‘compensated’ or ‘borderline’ hypothyroidism. In some individuals, it appears that this state can be maintained without progression to frank hypothyroidism. Triiodothyronine concentrations tend to fall later than thyroxine concentrations in hypothyroidism; the concentration of thyroxine-binding globulin does not change significantly. 8. A 52-year-old woman undergoes investigation for jaundice. She first noticed this symptom 2 months ago, but for 4 months prior to that, she had been experiencing generalised pruritus. The results of liver function tests are as follows: serum bilirubin 325 mmol/l, aspartate aminotransaminase 55 U/l (15–42), alkaline phosphatase 436 U/l (80–150), gamma-glutamyltransferase 82 U/l (11–51), albumin 36 g/l, total protein 82 g/l. Which of the following is the most likely diagnosis?

Alcoholic cirrhosis

Carcinoma of the head of the pancreas

Cholangiocarcinoma

Primary biliary cirrhosis Correct answer

Primary sclerosing cholangitis

The high alkaline phosphatase concentration suggests cholestatic jaundice. Alcoholic cirrhosis is common but is unlikely (though not excluded) by the only slightly elevated g-glutamyltransferase. Cholangiocarcinoma is a rare tumour. Carcinoma of the head of the pancreas frequently presents in this manner (though weight loss is often present also), but the slight elevation in total protein with low–normal albumin suggests a high globulin concentration, which suggests autoimmune liver disease. Primary sclerosing cholangitis is a possibility but is commoner in men than women (3:1), and in 75% of cases is associated with inflammatory bowel disease. Primary biliary cirrhosis is more common in women. 9. A 21-year-old male medical student who has been feeling non-specifically unwell for several days is noticed to have slightly icteric sclerae by his girlfriend and has liver function tests performed. The results of these are normal apart from a serum bilirubin concentration of 44 mmol/l (3–17). His urine does not contain bilirubin. Which of the following is the most likely diagnosis?

Dubin–Johnson syndrome

Gilbert’s syndrome Correct answer

Hereditary spherocytosis

Infectious mononucleosis

Rotor syndrome

Dubin–Johnson, Rotor and Gilbert’s syndromes are all inherited disorders of bilirubin metabolism. However, in the first two, there is a defect in the secretion of bilirubin from the liver and the bilirubin that accumulates in the plasma is conjugated, water-soluble and thus is excreted in the urine.

Infectious mononucleosis can cause hepatitis and jaundice but an elevated transaminase activity would be expected. Hereditary spherocytosis is a chronic haemolytic disorder due to a defect in the red cell membrane (most frequently in spectrin, a structural protein). It can present with a wide range of severity, from jaundice at birth to asymptomatic anaemia or jaundice in adults, but is much less common (approximately 1:5000 in Northern Europeans) than Gilbert’s syndrome (approximately 1:20).

10. A 20-year-old man presents with mild jaundice following a flu-like illness. Following review by a gastroenterologist, he has been told that a diagnosis of Gilbert’s syndrome is probable. Which laboratory test is most likely to confirm this diagnosis?

Absence of bilirubin in the urine Correct answer

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Decreased serum haptoglobin concentration

Elevated serum aspartate aminotransferase (transaminase, AST) activity

Increased reticulocyte count

Increased urinary urobilinogen excretion

In Gilbert’s syndrome, the excess bilirubin is unconjugated, and does not appear in the urine. The same is true for jaundice secondary to haemolysis. However, in haemolytic jaundice, urinary urobilinogen is increased (increased production of bilirubin, and hence of urobilinogen), the reticulocyte count may be elevated and serum haptoglobin concentration decreased. Haemolysis may also cause a slight increase in serum aminotransferase (transaminase) activity. 11. Phase 0 of the cardiac action potential relates to a:

Rapid efflux of calcium

Rapid influx of calcium

Rapid influx of potassium

Rapid influx of sodium Correct answer

None of the above

Phase 0 rapid sodium influx

Phase 1 efflux of potassium

Phase 2 slow influx of calcium

Phase 3 efflux of potassium

Phase 4 sodium/calcium efflux, potassium influx

12. A 42-year-old man is put on a proton-pump inhibitor to suppress symptoms of oesophagitis. The cell and membrane biology of the gastric acid pump has which of the following features?

Histamine-stimulated acid production is independent of the proton pump

The proton is exchanged with magnesium ions

Acetylcholine-stimulated acid production is independent of the proton pump

The proton pump spans the apical membrane of the gastric parietal cell Correct answer

The proton pump spans the basolateral membrane of the gastric parietal cell

The H+–K+-ATPase is embedded in the apical membrane. The channel is susceptible to agents that bind to cysteine residues (particularly 813 and 822). The proton pump is the final common pathway of histamine and acetylcholine-stimulated production, and particularly explains the enhanced efficacy of proton-pump inhibitors in comparison to H2 antagonists or acetylcholine antagonists (eg pirenzepine). 13. A patient undergoes respiratory function tests. Which of the following are normal readings for a 70-kg man?

Peak expiratory flow of 376 l/min

Total lung capacity of 3.5 litres

Functional residual capacity of 3.5 litres

Tidal volume of 250 ml

Inspiratory reserve volume of 2 litres Correct answer

Normal readings for such a patient would be:

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peak expiratory flow 520–700 l/min

total lung capacity 5–6.5 litres

functional residual capacity 2–3 litres

tidal volume 500–700 ml

14. Which of the following respiratory physiology tests would be consistent with a diagnosis of moderately established cryptogenic fibrosing alveolitis?

Diffusion capacity decreased, FEV1/FVC normal, total lung capacity reduced Correct answer

Diffusion capacity increased, FEV1/FVC normal, total lung capacity increased

Diffusion capacity normal, FEV1/FVC reduced, total lung capacity reduced

Diffusion capacity decreased, FEV1/FVC normal, total lung capacity n ormal

Diffusion capacity decreased, FEV1/FVC increased, total lung capacity increased

Diffusion capacity is characteristically decreased in restrictive lung disorders. FEV1/FVC reduced would be seen in obstructive airways disease, which would be reversible in asthma and irreversible in COPD. In restrictive conditions FEV1/FVC ratio is normal or increased. Total lung capacity is reduced in restrictive lung disease, whilst it is normal or increased in obstructive airways disease. 15. Which of the following takes place during inspiration?

The diaphragm drops by 10 cm during normal breathing

A negative pressure of 1–3 mmHg is created Correct answer

The rib cage recoils

Abdominal muscles contract

Accessory muscles relax

During normal breathing the diaphragm may drop 1 cm, creating a pressure drop of 1–3 mmHg and an air intake of 500 ml. During strenuous exercise the diaphragm may drop 10 cm, producing a pressure drop of 100 mmHg and an air intake of 3000 ml. During passive expiration the rib cage recoils, the abdominal muscles contract and the accessory muscles relax. 16. Regarding the clinical physiology of the adrenal gland in Cushing’s disease, which of the following pertains?

The zona glomerulosa of the cortex is predominantly responsible for sex steroid production

The zona fasciculata is predominantly controlled by ACTH and is often hypertrophied Correct answer

The zona reticularis is predominantly responsible for mineralocorticoid production

About 15% of glucocorticoid production takes place in the adrenal medulla

The zona fasciculata is primarily responsible for mineralocorticoid production

The zona glomerulosa of the cortex is predominantly responsible for mineralocorticoid production, the zona fasciculata for glucocorticoid production and the zona reticularis for sex corticoid production. The adrenal medulla originates from the neural crest and hence there is almost complete demarcation of function, with the medulla being responsible for the production of catecholamine-related compounds. 17. Which of the following physiological characteristics relates to the lining of the respiratory tract?

About 1 litre of mucus is produced every day

The cilia are under the control of a physiological motor, dynein Correct answer

The mucociliary escalator moves at 0.2 cm/minute

The bronchioles have cartilage in their wall

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The bronchioles have diameters up to 5 mm

About 100 ml of mucus is produced every day. The cilia are under the control of a physiological motor, dynein (which is absent in Kartagener’s syndrome). The mucociliary escalator moves at 2 cm/minute. The bronchioles do not have cartilage in their wall (which distinguishes them from bronchi). The bronchioles can be up to 1 mm in diameter. 18. Pulmonary gas exchange occurs under which of the following physiological principles?

Gas exchange can occur in the final seven branches of the bronchoalveolar tree Correct answer

The first 12 branches of the bronchial tree are collectively known as the conducting zone

The equilibration of gases takes about 2.5 s in the resting lung

Only about 0.15% of oxygen is carried in solution in the plasma

Carbon dioxide is less water-soluble than oxygen

Gas exchange can occur in the final seven branches of the bronchoalveolar tree (the respiratory zone). The first 16 branches of the bronchial tree are collectively known as the conducting zone. The equilibration of gases takes about 0.25 s in the resting lung. Only about 1.5% of oxygen is carried in solution in the plasma. Carbon dioxide is more water-soluble than oxygen, between 5 and 10% of and this is the predominant method of carriage of CO2 is carried in dissolved form. 19. Which one of the following is MOST likely to increase during exercise?

Peripheral vascular resistance

Pulmonary vascular resistance

Stroke volume Correct answer

Diastolic pressure

Venous compliance

During exercise, increased oxygen consumption and increased venous return to the heart result in an increase in cardiac output and an increase in blood flow to both skeletal muscle and coronary circulation, when oxygen utilization is greatest. The increase in cardiac output is due to an increase in both heart rate and stroke volume. Syst 20. Which one of the following is higher at the apex of the lung than at the base when a person is standing?

V/Q ratio Correct answer

Ventilation

PaCO2

Compliance

Blood flow

The alveoli at the apex of the lung are larger than those at the base so their compliance is less. Because of the reduced compliance, less inspired gas goes to the apex than to the base. Also, because the apex is above the heart level, less blood flows through the apex than through the base. However, the reduction in air flow is less than the reduction in blood flow, so that the V/Q ratio at the top of the lung is greater than it is at the bottom. The increased V/Q ratio at the apex makes PaCO2 lower and PaO2 higher at the apex than they are at the base 21. A 56-year-old woman sustains a myocardial infarction. ST elevation and Q waves are present in leads V4–V6, I and AVL. Which of the following aspects of the heart is most likely to have been involved in the infarct?

Anterior

Anterolateral Correct answer

Anteroseptal

Inferior

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Lateral

This combination suggests an anterolateral infarct. Purely anterior infarcts tend to involve the chest leads only (typically V2–V5), anteroseptal V1–V3, lateral infarcts chest leads only (I, II, AVL) and inferior infarcts II, III and AVF. 22. High titres of antithyroid microsomal and antithyroglobulin antibodies would suggest which of the following diagnoses in a patient presenting with a complaint of tiredness? Single best answer - choose ONE true option only

Hashimoto’s thyroiditis Correct answer

Reidel’s thyroiditis

Graves disease

Hypoparathyroidism

Idiopathic hypothyroidism

This finding in Hashimoto’s thyroiditis is characteristic, but lower titres can occur in Reidel’s thyroiditis and Graves disease. High titres of these antibodies in euthyroid individuals indicate the possibility of future thyroid failure, but this may be many years away; hence the need for thyroid function tests every 1–2 years in such individuals. 23. An elderly man with a history of prostatism presents with acute retention of urine. His serum creatinine concentration is 520 mmol/l. Which of the following additional abnormal serum biochemistry test results is most suggestive of a chronic component to his renal failure? Single best answer - choose ONE true option only

Hyperkalaemia

Hyperuricaemia

Hypocalcaemia Correct answer

Hyponatraemia

Low serum bicarbonate concentration

Hyperkalaemia and hyperuricaemia (due to decreased excretion), hyponatraemia (due mainly to continued water intake with decreased ability to excrete it) and metabolic acidosis occur in both acute and chronic renal failure. The presence of hypocalcaemia in renal failure suggests that this is, at least in part, of longstanding, and is due to decreased renal synthesis of calcitriol (1,25-dihydroxycholecalciferol). 24. A 71-year-old man with known chronic obstructive pulmonary disease is admitted to A&E with severe shortness of breath. Blood gas analysis shows: arterial [H+] 55 nmol/l (pH 7.26), p(CO2) 9.4 kPa, p(O2) 9.1 kPa, derived [HCO3

–] 31 mmol/l. Which of the following types of acid–base disturbance is most likely?

Acute respiratory acidosis

Chronic, compensated respiratory acidosis

Exacerbation of chronic respiratory acidosis Correct answer

Mixed respiratory acidosis and metabolic alkalosis

Severe metabolic acidosis

The patient is acidotic but the elevated bicarbonate concentration is incompatible with a metabolic acidosis. The high p(CO2) indicates that there is a respiratory acidosis. Were this to be acute, the bicarbonate concentration would be normal or only marginally elevated and a higher hydrogen-ion concentration would be expected (hydrogen-ion concentration increases by approximately 5.5 nmol/l for each increase in p(CO2) by 1 kPa in an acute disturbance.) Were compensation to be complete, it would be expected that the patient would be less acidotic, and the bicarbonate concentration higher.

The data are compatible with both an acute exacerbation of a chronic respiratory acidosis and a mixed respiratory acidosis and metabolic alkalosis, but the clinical setting makes the former the more likely.

25. Which of the following cells secretes intrinsic factor?

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Goblet cells

Kupffer cells

Peptic cells

Chief cells

Parietal cells Correct answer

Goblet cells are mucus-secreting cells, widely distributed throughout epithelial surfaces, but especially dense in the gastrointestinal and respiratory tracts. Kupffer cells have phagocytic properties and are found in the liver. They participate in the removal of ageing erythrocytes and other particulate debris. The gastric mucosa contains many cell subtypes, including acid-secreting cells (also known as parietal or oxyntic cells), pepsin secreting cells (also known as peptic, chief or zymogenic cells) and G-cells (gastrin-secreting cells). Peptic cells synthesise and secrete the proteolytic enzyme, pepsin. Parietal cells actively secrete hydrochloric acid into the gastric lumen, accounting for the acidic environment encountered in the stomach. However parietal cells are also involved in the secretion of the glycoprotein, intrinsic factor. Intrinsic factor plays a pivotal role in the absorption of vitamin B12 from the terminal ileum. Autoimmune damage to parietal cells leads to a lack of intrinsic factor and hydrochloric acid, leading to vitamin B12 deficiency and achlorhydria. This is known as pernicious anaemia. Pernicious anaemia is associated with a 3-fold increase in gastric cancer risk. 26. Splenectomy increases susceptibility to which of the following organisms?

Streptococcus pyogenes

Schistosoma haematobium

Bacteroides fragilis

Neisseria meningitidis Correct answer

Staphylococcus aureus

The spleen plays an important role in the removal of dead and dying erythrocytes and in the defence against microbes. Removal of the spleen (splenectomy) leaves the host susceptible to a wide array of pathogens, but especially to encapsulated organisms. Certain bacteria have evolved ways of evading the human immune system. One way is through the production of a ‘slimy’ capsule on the outside of the bacterial cell wall. Such a capsule resists phagocytosis and ingestion by macrophages and neutrophils. This allows them not only to escape direct destruction by phagocytes, but also to avoid stimulating T-cell responses through the presentation of bacterial peptides by macrophages. The only way that such organisms can be defeated is by making them more ‘palatable’ by coating their capsular polysaccharide surfaces in opsonising antibody. The production of antibody against capsular polysaccharide primarily occurs through T-cell independent mechanisms. The spleen plays a central role in both the initiation of the antibody response and the phagocytosis of opsonised encapsulated bacteria from the bloodstream. This helps to explain why the asplenic individuals are most susceptible to infection from encapsulated organisms, notably Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus) and Haemophilus influenzae. The risk of acquiring such infections is reduced by immunising individuals against such organisms and by placing patients on prophylactic penicillin, in most cases for the rest of their lives. In addition, asplenic individuals should be advised to wear a MedicAlert bracelet to warn other health care professionals of their condition. 27. Cardiac output is decreased:

During stimulation of sympathetic nerves to the heart

On cutting the vagus nerves to the heart

By increasing the end diastolic volume of the heart

As a result of decreased pressure within the carotid sinus

Upon assuming the upright position Correct answer

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Stimulation of the sympathetic nervous system results in a rise in heart rate and stroke volume and therefore cardiac output increases. Cutting the vagus nerves to the heart results in an increase in heart rate because of the abolition of vagal tone and therefore cardiac output increases. If the end diastolic volume of the heart (pre-load) is increased, under normal physiological circumstances, cardiac output is increased by the Frank-Starling mechanism. The exception is in the failing heart where the Law of LaPlace becomes more important and cardiac output actually falls. Arterial blood pressure is homeostatically regulated through the action of baroreceptors, principally located in the carotid sinus and the wall of the aortic arch. If the carotid sinus pressure is reduced, the baroreceptors become inactive and lose their inhibitory effect on the vasomotor centre in the brainstem. The result is activation of the sympathetic nervous system. This produces a rise in heart rate, stroke volume, mean systemic filling pressure and venous return, leading to an increase in cardiac output and return of the mean arterial blood pressure to its original value. Cardiac output falls when one stands up due to the pooling of blood on the venous side of the circulation, which has a large capacitance. Stepping out of a hot bath exacerbates this pooling effect because superficial cutaneous veins dilate in response to heat, increasing their capacitance even further. Under normal circumstances, activation of the baroreceptor reflex compensates to some degree, preventing syncope. However, in the elderly, or in patients on anti-hypertensives, inadequate compensation from the baroreceptor reflex may result in a vasovogal syncope, or othostatic hypotension. 28. Flow through a vessel or lumen is:

Is inversely proportional to the pressure head of flow

Is inversely proportional to the radius

Is directly proportional to the length of the tube

Is directly proportional to the viscosity of blood passing through it

Is directly proportional to the fourth power of radius Correct answer

The Hagen-Poiseuille law states that the flow through a vessel is:

Directly proportional to the pressure head of flow

Directly proportional to the fourth power of radius

Inversely proportional to the viscosity

Inversely proportional to the length of the tube

The radius of the tube is therefore the most important determinant of flow through a blood vessel. Thus, doubling the radius of the tube will lead to a 16-fold increase in flow at a constant pressure gradient. The implications of this are several fold. First, owing to the fourth power effect on resistance and flow, active changes in radius constitute an extremely powerful mechanism for regulating both the local blood flow to a tissue and central arterial pressure. The arterioles are the main resistance vessels of the circulation and their radius can be actively controlled by the tension of smooth muscle within its wall. Second, in terms of intravenous fluid replacement in hospital, flow is greater through a peripheral cannula than through central lines. The reason is that peripheral lines are short and wide (and therefore of lower resistance and higher flow) compared to central lines, which are long and possess a narrow lumen. A peripheral line is therefore preferential to a central line when urgent fluid resuscitation, or blood, is required. 29. In a lung function test, the functional residual capacity:

Is the sum of the tidal volume and residual volume

Is the sum of the inspiratory reserve volume, the expiratory reserve volume and the tidal volume

Can be measured directly by spirometry

Is equal to the sum of the residual volume and the expiratory reserve volume Correct answer

Is that volume of air that remains in the lung after forced expiration

Spirometry traces are easy to understand if you remember the following two rules: 1. There are 4 lung volumes and 5 capacities that you need to remember. 2. A capacity is made up of 2 or more lung volumes The 4 lung volumes are: Tidal volume = volume of air inspired or expired with each normal breath in quiet breathing; approximately 500mls. Residual volume = that volume of air that remains in the lung after forced expiration. Inspiratory reserve volume = extra volume of air that can be inspired over and above the normal tidal volume. Expiratory reserve volume = extra volume of air that can be expired by forceful expiration after the end of a normal tidal expiration. The 5 lung capacities are:

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Functional residual capacity = that volume of air that remains in the lung at the end of quiet expiration. Equal to the sum of the residual volume and the expiratory reserve volume. Inspiratory capacity = inspiratory reserve volume + tidal volume Expiratory capacity = expiratory reserve volume + tidal volume Vital capacity = inspiratory reserve volume + tidal volume + expiratory reserve volume (or total lung capacity – residual volume) Total lung capacity = vital capacity + residual volume The residual volume (and therefore functional residual capacity and total lung capacity) cannot be measured directly by spirometry. They are measured by either whole body plethysmography, or by using the helium dilution or nitrogen washout techniques. 30. Lung compliance:

Is defined as the change in pressure per unit volume

Is synonymous with elastance

Is increased in emphysema Correct answer

Is equal in inflation and deflation

Is reduced by the presence of surfactant

Compliance is expressed as volume change per unit change in pressure. Elastance is the reciprocal of compliance. The pressure-volume curve of the lung is non-linear with the lungs becoming stiffer at high volumes. The curves which the lung follows in inflation and deflation are different. This behaviour is known as hysteresis. The lung volume at any given pressure during deflation is larger than during inflation. This behaviour depends on structural proteins (collagen, elastin), surface tension and the properties of surfactant. Surfactant is formed in and secreted by type II pneumocytes. The active ingredient is dipalmitoyl phosphatidylcholine. It helps prevent alveolar collapse by lowering the surface tension between water molecules in the surface layer. In this way it helps to reduce the work of breathing (makes the lungs more compliant) and permits the lung to be more easily inflated. Various disease states are associated with either a decrease or increase in the lung compliance. Fibrosis, atelectasis and pulmonary oedema all result in a decrease in lung compliance (stiffer lungs). An increased lung compliance occurs in emphysema where an alteration is elastic tissue is probably responsible (secondary to the long term effects of smoking). The lung effectively behaves like a “soggy bag” so that a given pressure change results in a large change in volume (i.e. the lungs are more compliant). However, during expiration the airways are less readily supported and collapse at higher lung volumes resulting in gas trapping and hyperinflation. 31. Which one of the following hormones is secreted by the anterior pituitary?

Testosterone

Oxytocin

TSH Correct answer

CRH

ADH

The pituitary gland (hypophysis) is the conductor of the endocrine orchestra. It is divided into both an anterior part and posterior part. The anterior pituitary (adenohypophysis or pars distalis) secretes 6 hormones namely: FSH/LH: Reproduction ACTH: Stress response TSH: Basal metabolic rate GH: Growth Prolactin: Lactation The posterior pituitary (neurohypophysis or pars nervosa) secretes only 2 hormones: ADH (vasopressin): Osmotic regulation Oxytocin: Milk ejection and labour Testosterone is produced from Leydig cells in the testis and from the adrenal glands. CRH is produced by the median eminence of the hypothalamus. 32. The Haemoglobin Oxygen-Dissociation Curve is shifted to the left by:

An increase in pCO2

A fall in pH

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A rise in temperature

An increase in 2,3-DPG

Fetal haemoglobin Correct answer

The haemoglobin oxygen dissociation curve is sigmoidal in shape which reflects the underlying biochemical properties of haemoglobin. The significance of the sigmoidal curve is that haemoglobin becomes highly saturated at high oxygen partial pressures (and is therefore highly efficient at collecting oxygen), and releases a significant amount of oxygen at pressures which are fairly low, but not extremely so (with the result that haemoglobin is highly effective at supplying oxygen where it is needed). The effect of things that shift the curve to the right (raised CO2, lowered pH, increased temperature, increase in 2,3-DPG) is to increase oxygen availability in the tissues. The effect of CO2/H+ on O2 carriage is known as the Bohr shift or effect. This is exactly what is needed in metabolising tissues; release of acids or CO2 thus liberates O2 to fulfil the metabolic needs of the tissue. Do not confuse this with the effect of changes in O2 on CO2 carriage which is called the Haldane effect. A shift of the oxygen dissociation curve to the left is characteristic of fetal haemoglobin. When compared with adult haemoglobin, it is composed of 2 alpha and 2 gamma chains, instead of the usual 2 alpha and 2 beta chains of adult haemoglobin. This arrangement assists in the transfer of oxygen across the placenta from the maternal to the fetal circulation. The corollary of this is that fetal tissue oxygen levels have to be low to permit the release of oxygen from the haemoglobin. 33. Which of the following cells is cytotoxic?

CD4 T-cells

CD8 T-cells Correct answer

B cells

TH1 cells

TH2 cells

Lymphocytes can be divided into two main subtypes – T cells and B cells. B cells (or plasma cells) secrete antibodies. T cells can be divided into two further subtypes – CD4 T-cells and CD8 T-cells. CD4 (helper) T-cells can recognise antigen only in the context of MHC Class II, whereas CD8 (cytotoxic) T-cells recognise cell-bound antigens only in association with Class I MHC. This is known as MHC restriction. CD4 and CD8 T-cells perform distinct but somewhat overlapping functions. The CD4 helper T-cell can be viewed as a master regulator. By secreting cytokines (soluble factors that mediate communication between cells), CD4 helper T-cells influence the function of virtually all other cells of the immune system including other T-cells, B-cells, macrophages and natural killer cells. The central role of CD4 cells is tragically illustrated by the HIV virus which cripples the immune system by selective destruction of this T-cell subset. In recent years two functionally different populations of CD4 helper T-cells have been recognised – TH1 cells and TH2 cells, each characterised by the cytokines that they produce. In general, TH1 cells facilitate cell-mediated immunity, whereas TH2 cells promote humoral-mediated immunity. CD8 cytotoxic T-cells mediate their functions primarily by acting as cytotoxic cells (i.e. they are T-cells that kill other cells). They are important in the host defence against cytosolic pathogens. Two principal mechanisms of cytotoxicity have been discovered – perforin-granzyme-dependent killing and Fas-Fas ligand dependent killing. 34. A 3-week-old baby exhibits projectile vomiting shortly after feeding and failure to thrive. On examination an olive-shaped mass is palpable in the right upper quadrant of the abdomen. A clinical diagnosis of pyloric stenosis is made. What biochemical laboratory features would support the diagnosis?

Hypokalaemia, metabolic alkalosis, low urinary pH Correct answer

Hyperkalaemia, metabolic acidosis, high urinary pH

Hypokalaemia, metabolic acidosis, high urinary pH

Hyperkalaemia, metabolic alkalosis, low urinary pH

Hypokalaemia, metabolic alkalosis, high urinary pH

Following a diagnosis of pyloric stenosis, the first concern is to correct the metabolic abnormalities that invariably coexist with the condition. The serum electrolytes and capillary gases should be measured and corrected prior to surgery. With prolonged vomiting, the infant becomes dehydrated, with a hypochloraemic metabolic alkalosis. The alkalosis is a result of loss of unbuffered hydrogen ions in gastric juice with concomitant retention of bicarbonate.

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Fluid loss stimulates renal sodium reabsorption, but sodium can only be reabsorbed either with chloride, or in exchange for hydrogen and potassium ions (to maintain electroneutrality). Gastric juice has a high concentration of chloride and patients losing gastric secretions become hypochloraemic. This means that less sodium than normal can be reabsorbed with chloride. However, it appears that the defence of extracellular fluid volume takes precedence over acid-base homeostasis and further sodium reabsorption occurs in exchange for hydrogen ions (perpetuating the alkalosis) and potassium ions (leading to potassium depletion). This explains the apparently paradoxical finding of acidic urine in patients with pyloric stenosis. Potassium is also lost in the gastric juice and thus patients frequently become potassium-depleted and yet are losing potassium in their urine. 35. Normal Cerebrospinal fluid (CSF):

Is produced within arachnoid granulations

Has an identical composition to that of plasma

Has a protein content that is 0.5% that of plasma Correct answer

Has a higher potassium content than that of plasma

pH is heavily buffered

Most of the CSF is produced by the choroid plexus, which is situated in the lateral, 3rd and 4th ventricles. CSF is absorbed directly into the cerebral venous sinuses through the arachnoid villi, or granulations, by a process known as mass or bulk flow. The composition of CSF is different to plasma. Of importance to mention are the concentrations of K+, Ca2+, bicarbonate and protein which are lower in CSF than in plasma. This is to prevent high concentrations of these electrolytes inadvertently exciting neurones present within the brain substance. The potassium content of the CSF in this respect is particularly important. Further buffering of the K+ content of CSF takes place through astrocytes. Likewise, the low protein content of the CSF (the CSF protein content is 0.5% that of plasma) is deliberate to prevent some proteins and amino acids acting as “false neurotransmitters”. The CSF is more acidic than plasma because pH of the CSF plays a critical role in the regulation of pulmonary ventilation and cerebral blood flow. Another reason why the CSF protein is kept deliberately low is to prevent proteins buffering pH. The result is that the pH of the CSF accurately reflects carbon dioxide levels of the blood. In this way changes in pH act as a powerful regulator of the respiratory system (through the action of pH on central chemoreceptors) and on cerebral blood flow. 36. A patient on has chronic renal impairment, with a plasma creatinine of 225µmol/l and the glomerular filtration rate (GFR) of 25ml/min. Concerning renal function:

The GFR is the main factor determining the rate of urine production

GFR can be measured by para-aminohippuric acid (PAH)

The normal GFR is 50mls/min

Inulin clearance can be used to estimate GFR Correct answer

A normal plasma creatinine implies normal renal function

In the normal adult human the GFR (or normal renal clearance) averages 125ml/min, or 180 litres/day. The entire plasma volume (about 3 litres) can therefore be filtered and processed by the kidney approximately 60 times each day. The rate of urine production in humans is dominated by tubular function and not by GFR. The GFR remains relatively constant through autoregulation. After 35 years of age, GFR falls at about 1ml/min/year. By the age of 80, GFR has fallen to about 50% of its youthful level. GFR can decrease by as much as 50% before plasma creatinine rises beyond the normal range. Consequently, a normal creatinine does not necessarily imply normal renal function, although a raised creatinine does usually indicate impaired renal function. A substance used to measure the GFR must be freely filtered at the glomerulus, not be secreted by the tubules, not be reabsorbed, not be metabolised or synthesized in the body, not alter the renal function/GFR, be non-toxic and soluble in plasma. Such a substance is the polyfructose molecule, inulin. However, it is too cumbersome to use in routine clinical practice. Instead, GFR is more commonly quantified by measuring the 24-hour urinary creatinine excretion. Para-aminohippuric acid is used to measure renal blood flow and not GFR. 37. Gastric acid secretion is stimulated by:

Somatostatin

Gastrin Correct answer

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Secretin

The glossopharyngeal nerve

Cholecystokinin

Gastric acid is stimulated by 3 factors:

Acetylcholine: From parasympathetic neurones of the vagus nerve that innervate parietal cells directly.

Gastrin: produced by pyloric G-cells.

Histamine: Produced by mast cells. This stimulates the parietal cells directly and also potentiates parietal cell stimulation by gastrin and neuronal stimulation. H2 blockers such as ranitidine are therefore an effective way of reducing acid secretion.

Gastric acid is inhibited by 3 factors:

Somatostatin

Secretin

Cholecystokinin

There are 3 classic phases of gastric acid secretion:

Cephalic (preparatory) phase [significant]: Results in the production of gastric acid before food actually enters the stomach. Triggered by the sight, smell, thought and taste of food acting via the vagus nerve.

Gastric phase [most significant]: Initiated by the presence of food in the stomach, particularly protein rich food.

Intestinal phase [least significant]: The presence of amino acids and food in the duodenum stimulate acid production.

38. Carbon dioxide is principally transported in the blood in the form of:

CO2 physically dissolved in solution

Carboxyhaemoglobin

Bicarbonate Correct answer

Carbaminohaemoglobin

Carbonic anhydrase

Carbon dioxide is transported in the blood in the form of:

Bicarbonate accounts for about 80-90% of the total CO2 in the blood

As carbamino compounds (5-10%)

Physically dissolved in solution (only 5%)

Carbon dioxide is carried on the haemoglobin molecule as carbamino-haemoglobin; carboxyhaemoglobin is the combination of haemoglobin with carbon monoxide. Erythrocytes contain the enzyme carbonic anhydrase that catalyses the reaction CO2 + H2O = H+ + HCO3

- and requires zinc as a co-factor. This plays an important role in carbon dioxide transport and in the buffering of pH. 39. The plateau phase of the cardiac action potential is due to:

Magnesium influx

Potassium influx

Calcium influx Correct answer

Chloride efflux

Sodium influx

The most important source of activator calcium in cardiac muscle remains its release from the sarcoplasmic reticulum. Calcium however also enters from the extracellular space during the plateau phase of the action potential. This calcium entry provides the stimulus that induces calcium release from the sarcoplasmic reticulum (calcium induced calcium release). The result is that tension generated in cardiac, but not in skeletal, muscle is profoundly influenced both by extracellular calcium levels and factors that affect the magnitude of the inward calcium current. This is of practical value in two key clinical situations;

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in heart failure where digoxin is utilised to increase cardiac contractility (by increasing the intracellular calcium concentration) and in hyperkalaemia where calcium gluconate is used to stabilise the myocardium. The plateau phase of the action potential in cardiac muscle (principally due to calcium influx) maintains the membrane at a depolarised potential for as long as 500ms. The result is that the cell membrane is refractory throughout most of the mechanical response, largely due to the inactivation of fast sodium channels. This prevents tetany upon repetitive stimulation which would be detrimental to cardiac output. Furthermore, the prolonged refractory period in cardiac muscle allows the impulse that originates in the sino-atrial node to propagate throughout the entire myocardium just once, thereby preventing re-entry arrhythmias. 40. The ejection fraction is defined as:

The ratio of the end diastolic volume to stroke volume

The ratio of stroke volume to end diastolic volume Correct answer

End diastolic volume minus end systolic volume

End systolic volume divided by stroke volume

The ratio of stroke volume to end systolic volume

During diastole, filling of the ventricles normally increases the volume of each ventricle to about 120mls. This volume is known as the end diastolic volume. Then, as the ventricles empty in systole, the volume decreases about 70mls, which is known as the stroke volume. The remaining volume in each ventricle, about 50mls, is known as the end systolic volume and acts as a reserve which can be utilised to increase stroke volume in exercise. The fraction of end diastolic volume that is ejected is called the ejection fraction – usually equal to about 60%. The ejection fraction is often used clinically as an indirect index of contractility. It is a particularly useful in assessing the state of the myocardium prior to aortic aneurysm repair where cross-clamping of the aorta places particular stress on the myocardium. 41. Bile salt reuptake principally occurs in the:

Duodenum

Jejenum

Ileum Correct answer

Colon

Caecum

90-95% of the bile salts are absorbed from the small intestine and then excreted again from the liver; most are absorbed from the terminal ileum. This is known as the enterohepatic circulation. The entire pool recycles twice per meal and approximately 6-8x per day. Disruption of the enterohepatic circulation, either by terminal ileal resection or through a diseased terminal ileum (e.g. Crohn’s disease), results in decreased fat absorption and cholesterol gallstone formation. The latter is believed to result because bile salts normally make cholesterol more water-soluble through the formation of cholesterol micelles. Loss of reuptake also results in the presence of bile salts in colonic contents, which alters colonic bacterial growth and stool consistency. 42. The cardiovascular effects of raised intracranial pressure include:

decreased blood pressure, decreased heart rate, decreased cerebral perfusion pressure

decreased blood pressure, increased heart rate, decreased cerebral perfusion pressure

increased blood pressure, increased heart rate, decreased cerebral perfusion pressure

increased blood pressure, decreasd heart rate, decreased cerebral perfusion pressure Correct answer

decreased blood pressure, increased heart rate HR, increased cerebral perfusion pressure

The important relationship between the cerebral perfusion, mean arterial blood pressure and intracranial pressure is as follows: CPP = MABP – ICP, where CPP = cerebral perfusion pressure MABP = mean arterial blood pressure ICP = intracranial pressure

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It stems from the fact that the adult brain is enclosed in a rigid, incompressible box, with the result that the volume inside it must remain constant (Monroe-Kelly doctrine). A rise in intracranial pressure therefore decreases cerebral perfusion pressure (and hence cerebral blood flow). In raised intracranial pressure, as the brainstem becomes compressed, local neuronal activity causes a rise in sympathetic vasomotor drive and thus a rise in blood pressure. This is known as the Cushing’s reflex. This elevated blood pressure evokes a bradycardia via the baroreceptor reflex. The Cushing’s reflex helps to maintain cerebral blood flow and protect the vital centres of the brain from loss of nutrition if the intracranial pressure rises high enough to compress the cerebral arteries. 43. Aldosterone is secreted from the:

Liver

Zona glomerulosa of the adrenal cortex Correct answer

Juxtaglomerular apparatus

Adrenal medulla

Zona fasciculata of the adrenal cortex

The adrenal gland comprises an outer cortex and an inner medulla, which represent two developmentally and functionally independent endocrine glands within the same anatomical structure. The adrenal medulla secretes adrenaline (70%) and noradrenaline (30%). The adrenal cortex consists of 3 layers, or zones. The layers from the surface inwards may be remembered by the mnemonic GFR: G = Zona glomerulosa (secretes aldosterone) F = Zona fasciculata (secretes cortisol and sex steroids) R = Zona reticularis (secretes cortisol and sex steroids) Aldosterone is a steroid hormone that facilitates the reabsorption of sodium and water and the excretion of potassium and hydrogen ions from the distal convoluted tubule and collecting ducts. Conn’s syndrome is characterised by increased aldosterone secretion from the adrenal glands. 44. Which of the following gastrointestinal fluids is richest in potassium?

Salivary Correct answer

Pancreatic

Gastric

Bile

Small bowel

In man about 1-1.5 litres of saliva are secreted each day. Secretion is an active process. The two-stage hypothesis of salivation states that a primary secretion is first formed by secretory end-pieces (that resembles an ultrafiltrate of plasma), which is then modified as it flows along the duct system. Na+ and Cl- are absorbed and K+ and HCO3

- are secreted as saliva flows along the ductal system. In addition, the ducts have a low water permeability. The final saliva is hypotonic with respect to plasma and contains a higher potassium concentration than any other gastrointestinal secretion of the body. Any abnormal state in which saliva is lost to the exterior of the body for long periods can lead to a serious depletion of potassium, leading in occasional circumstances to serious hypokalaemia and paralysis. 45. In the respiratory system, physiological shunt?

Is greater than the anatomical shunt Correct answer

Is not present in healthy adult

Affects arterial carbon dioxide more than arterial oxygen tension

Has the same effect on respiratory gas exchange as does physiological dead space

Is abolished when the subject breathes pure oxygen

The physiological shunt is the sum of the anatomical shunt (blood passing from the right ventricle to the systemic circulation via normal anatomical pathways, e.g. the bronchial vessels, without passing through the pulmonary alveolar capillaries), and the

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element of pulmonary alveolar capillary blood that has passed through non or poorly aerated alveoli. Therefore physiological shunt is always at least as great as or greater than the anatomical shunt. There is always a normal anatomical shunt even in the young healthy adult. The difference in carbon dioxide tension between arterial and mixed venous blood is a little less than 1 kPa, and therefore even a 50% shunt only increases arterial carbon dioxide tension by about 0.5 kPa. A 50% shunt would reduce arterial oxygen tension from 13.5kPa to below 9 kPa. The physiological dead space results primarily in a failure to remove carbon dioxide from alveolar gas, i.e. a rise in arterial carbon dioxide tension if ventilation not increased. The breathing of pure oxygen cannot eliminate the anatomical right to left portion of the physiological shunt. 46. The action potential of skeletal muscle?

Has a prolonged plateau phase

Spread inwards to all parts of the muscle via the T tubes Correct answer

Causes immediate uptake of Ca into the sarcoplasmic reticulum

Is longer than the action potential of cardiac muscle

Is not essential for contraction

The action potential of the skeletal muscle spreads out from the motor end plate, through the T tube system this causes mobilization of Ca2+ from the sarcoplasmic reticulum to the cytoplasm and this action potential is essential for contraction. The action potential of cardiac muscle is longer than that of the skeletal muscle and has plateau phase. 47. The rate at which a liquid meal leaves the stomach is?

Greater in the upright than in the supine position

Proportional to the volume of stomach content Correct answer

Greater if the meal contains fat

Slower if the meal is 5% glucose than if it is 50% glucose

Slower if vagotomy and drainage procedure (such as gastroenterostomy or pyloroplasty) has been performed

Gastric emptying accelerates on lying down. The rate of gastric emptying at any moment is proportional to the volume present in the stomach at that moment When the fat reaches the duodenum it stimulates mixed hormonal and vagal mechanisms that slow the rate of stomach emptying. An isotonic meal will empty at maximal rate but osmotically stronger or weaker solutions will empty more slowly. Vagotomy may temporarily slow gastric emptying, but its long term effect is to increase the rate of gastric emptying or leave it un changed so if a drainage procedure is accompanied by vagotomy there will be a tendency towards accelerating gastric emptying. 48. Which of the following organs has the greatest blood flow per 100 g of tissue?

Brain

Heart

Skin

Liver

Kidneys Correct answer

Organ Blood flow in ml/100g/min

Kidneys 420.0

Heart 84.0

Liver 57.7

Brain 54.0

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Skin 12.8

49. Absorption of calcium from the digestive tract?

Takes place mostly in the proximal jejunum Correct answer

Is prevented by the presence of small amounts of phytic acid in the diet , even when an excess calcium is ingested

Is facilitated by the presence of fat in food

Can be reversed (calcium is secreted into bowel lumen) when plasma calcium concentration is raised by a calcium infusion

Is about as rapid as that of sodium

Phytic acid produces insoluble calcium phytate, when all phytic acid has been precipitated the excess calcium is absorbed. Fatty acids form insoluble calcium salts (soaps). The shift of calcium ions across the intestinal mucosa is virtually one way. Sodium is absorbed at a speed fifty times that for calcium absorption. 50. The acute blood loss of 1.5 liters leads to a decrease in?

The rate of oxygen extraction by the peripheral tissues

Renin secretion

Platelet count

The cardiac output Correct answer

Coronary and cerebral blood flow due to sympathetic overactivity

The rate of oxygen extraction by the peripheral tissues is increased in response to acute blood loss, renin secretion is also increased due to renal hypoperfusion. Platelet count is increased and cardiac output decreased as the stroke volume decreases. The blood flow to the brain and the heart remains unchanged. 51. Considering the ABO and rhesus (Rh) systems

If the patient blood group is AB, his serum will have anti A and anti B antibodies

Naturally occurring anti A and anti B antibodies are usually IgG

Red blood cells are the only carrier of the antigen A,B and H

The presence of the D antigen makes the subject rhesus positive Correct answer

Rhesus antibodies are naturally occurring antibodies

In AB blood group, the patient will have A & B antigen but not anti-A and anti-B antibodies. These antibodies are usually Ig M and are present on most of body cells. Rhesus antibodies do not occur naturally and are formed as immune antibodies upon exposure to antigen. 52. Spontaneous respiration ceases after?

Transection of the brain stem above the pons

Transection of the brain stem at the caudal end of the medulla Correct answer

Bilateral vagotomy

Bilateral vagotomy combined with transection of the brain stem at the superior border of pons

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Transection of the spinal cord at the level of first thoracic segment

Rhythmic discharge of neurons in the medulla and pons produces automatic respiration, and so transection of the brain stem below the medulla stops the respiration. The respiratory muscles are supplied by C3 – C5 segments (diaphragm) and thoracic segments for intercostal & flat muscles of the trunk. 53. The following metabolic changes occur in the ebb phase (first 24 hours) of response to injury?

Plasma pH increases

The plasma level of free fatty acids decreases

Hypoglycemia

The plasma level of non protein nitrogen decreases

Plasma glycerol increases Correct answer

There is usually acidosis (pH decreases). Lipolysis increases leading to increase in fatty acids and glycerol. There is hyperglycemia and an increased level of non protein nitrogen. 54. Vasopressin (ADH)

Is synthesised in the posterior pituitary gland

Deficiency leads to a risk of water intoxication

Excessive secretion usually results in diabetes insipidus

Increased plasma osmolarity is the primary physiological stimulus Correct answer

Acts on the proximal convoluted tubules of the kidney

Vasopressin is synthesised in the supraoptic nucleus of the hypothalamus and transported to the posterior pituitary via the axons. Excessive secretion is associated with the risk of impaired water excretion. Diabetes insipidus results from deficient secretion or action of this hormone leading to thirst and polyuria. It acts mainly on the distal convoluted tubules and the collecting ducts of the kidney. 55. The following factors stimulate renin release

Is decreased by isoflurane in general anaesthesia

Propranolol

Increase in plasma K+ concentration

Angiotensin II

Salt depletion Correct answer

A decrease in blood pressure and salt depletion stimulates renin release. -blockers and increased K+ levels inhibit renin release. Angiotensin II inhibits renin release through a negative feed back mechanism. 56. The cerebral blood flow (CBF)

Accounts for about 15% of the cardiac output Correct answer

Is decreased by hypercapnia

Is decreased by hypoxia

Is mainly controlled by sympathetic and parasympathetic activity

Is decreased by isoflurane in general anaesthesia

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Cerebral blood flow accounts for about 15% of the cardiac output. Hypoxia and hypercapnia increase the CBF. An autonomic mechanism seems to be unimportant. Isoflurane increases CBF. 57. With respect to vomiting which of the following statements is the best answer?

The main receptor in the chemoreceptor trigger zone (CTZ) is adrenergic

The CTZ is outside the blood brain barrier Correct answer

5HT3 agonists may be effective in controlling cisplatin induced vomiting

H2 receptors are abundant in the vomiting centre

The vomiting centre is present in the reticular formation of the mid brain

The vomiting centre is present in the reticular formation of the medulla, the CTZ is outside the blood brain barrier and the main receptors are dopaminergic D2 receptors. 5HT3 antagonist is effective in controlling vomiting. H1 receptors have been identified in the vomiting centre. 58. Which of the following hormones exerts the least effect on growth?

Growth hormone

Testosterone

T4

Insulin

Vasopressin Correct answer

Growth is stimulated by growth hormone which stimulates IGF-I secretion, androgens and estrogens initially stimulate the growth, they then ultimately terminate the growth by causing the epiphysis to fuse to the long bones. Thyroid hormones have a permissive effect to the action of growth hormone possibly via somatomedines. Insulin promotes growth as it has an anabolic effect on protein metabolism. Vasopressin has no effect on growth. 59. Nociception (pain)

Is transmitted faster through C fibers than through A delta fibers

Pain impulse received in the dorsal horn can be modulated by other descending spinal inputs Correct answer

Opioids act on µ receptors in the peripheral nerves

Side effects of opioids can be reversed by neostigmine

Glycine is excitatory pain neurotransmitter

Pain impulse received by dorsal horn can be modulated by other ascending and descending spinal inputs (Gate Theory). Pain is transmitted faster in myelinated A delta fibers, opioids act on µ and ? opioid receptors in the central nervous system and their effects can be reversed by naloxone. Glycine is an inhibitory neurotransmitter. 60. Hypothyroidism due to disease of the thyroid gland is associated with increased plasma level of?

Cholesterol Correct answer

Albumin

RT3

Iodide

Thyroid binding globulin (TBG)

Thyroid hormone lowers circulating cholesterol level. The plasma cholesterol level drops before the metabolic rate rises.

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61. The symptoms of dumping syndrome in patients with intestinal short circuits such as anastomosis of the jejunum to the stomach are caused by?

Increased blood pressure

Increase secretion of glucagons

Increased secretion of CCK

Hypoglycemia Correct answer

Hyperglycemia

There are two types of dumping syndromes resulting from rapid gastric emptying; Early dumping which manifests by dizziness, sweating and palpitations within 5-45 minutes after eating. Late dumping occurs 2-4 hours after eating and is due to rebound hypoglycemia, small meals and glucose help to improve symptoms 62. With regard to CO2 transported in the blood, most of the CO2 is

Dissolved in plasma

In the form of carbamino compounds formed from plasma proteins

In the form of carbamino compounds formed from haemoglobin

Bound to Chloride

In the form of HCO3-

Correct answer

Carbon dioxide is transported in three main ways: · Carbamino compounds between CO2 and proteins. Most of these reactions are with the globin portion of haemoglobin, accounting for 20-30% of the transported CO2. · Dissolved CO2 accounts for about 10% of the transported CO2. · HCO3

- accounts for about 60-70% of the transported CO2. 63. Pepsin is secreted from which cells of the stomach?

Parietal cells

Chief cells Correct answer

G cells

Mucous cells

IX

There are many types of cells located within the gastric glands; Parietal cells secrete HCl and intrinsic factor Chief cells secrete pepsinogen, the precursor of pepsin G cells secrete the hormone gastrin Mucous cells secrete mucous 64. Vitamin K is involved in carboxylation of glutamic acid residues of the following clotting factors EXCEPT for? Single best answer question – choose ONE correct option only

XI Correct answer

Prothrombin

VII

IX

X

21

Vitamin K is essential for activation of clotting factors II (prothrombin), VII, IX, X. 65. At a given pO2, haemoglobin gives up oxygen more readily in the following situation

Decreased pCO2

Decreased levels of 2,3 DPG

Presence of fetal haemoglobin

Increased pH

Increased temperature Correct answer

The oxygen dissociation curve is a sigmoid shape; a shift to the right enables haemoglobin to give up oxygen more readily at a given pO2. This occurs where temperature rises, PCO2 rises and pH falls. Levels of 2,3, DPG rise in conditions causing chronic hypoxia, such as airway obstruction or living at high altitude, and also cause a right shift of the curve – hence B is false. The increased affinity of fetal haemoglobin for oxygen (i.e. a left shift of the curve) facilitates oxygen transport across the placenta – hence C is false. 66. Concerning the salivary glands

They secrete around 150 ml of saliva per day

They secrete saliva with a pH of 4-5

They secrete saliva which is hypertonic

They are supplied by the parasympathetic nervous system Correct answer

They secrete saliva containing trypsinogen

Saliva is secreted from the acini, and transported via the salivary ducts to the oral cavity. The secretion from the sublingual gland is predominately mucous, the parotid serous and the submandibular mixed. The pH of saliva varies from 7-8, and around 1.5L is produced per day. As well as a-amylase, saliva contains lipase and glycoproteins to lubricate food and protect the oral mucosa. Lysozyme, IgA and lactoferrin act as bacteriostatic agents, and proteins protect the tooth enamel. The saliva is isotonic when it is excreted from the acini; Na+ and Cl- are exchanged for K+ and HC03- in the ducts, and the saliva becomes hypotonic by the time it reaches the mouth. 67. During digestion of a fatty meal, which hormone causes contraction of the gall bladder and relaxation of the sphincter of Oddi?

Cholecystokinin Correct answer

Gastrin

Insulin

Secretin

Somatostatin

Cholecystokinin secretion from the duodenal and jejunal mucosa is stimulated by the presence of fatty acids, amino acids and peptides in the lumen of the duodenum and jejunum. As well as causing contraction of the gall bladder and relaxation of the sphincter of Oddi, it stimulates release of pancreatic enzymes, and increases the secretin mediated secretion of HC03

- by pancreatic duct cells. Its release is inhibited by somatostatin. 68. Which of the following hormones is secreted by the kidney in response to sympathetic nervous stimulation?

Aldosterone

Angiotensin I

Angiotensin II

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Erythropoetin

Renin Correct answer

Renin is produced by the juxtaglomerular apparatus of the kidney in response to hypovolaemia, via 3 mechanisms: 1. increased catecholamine levels secondary to sympathetic stimulation from arterial receptors 2. direct effect of hyponatraemia on the juxtaglomerular apparatus 3. reduction of renal perfusion pressure via afferent arteriolar baroreceptors Renin acts to cleave angiotensin I from angiotensinogen produced in the liver. Angiotensin converting enzyme is present in many tissues, especially the lungs, and converts angiotensin I to angiotensin II. Angiotensin II is a powerful vasoconstrictor, causing vasoconstriction of renal arteries, as well as a positive inotropic effect on the heart. It also causes release of ADH and adrenaline. Along with aldosterone, whose release is also stimulated, Angiotensin II conserves Na+ and H2O in the gut. Aldosterone acts to conserve Na+ and H2O in the distal renal tubule and collecting ducts. These mechanisms combine to restore the plasma volume in hypovolaemia. Erythropoetin is released by the kidney in response to hypoxia and high levels of the products of red cell breakdown, and increases the rate of red cell production. 69. Aldosterone causes the following effect

Na+, H2O loss and K+ conservation in the distal tubule

Na+, H2O conservation and K+ loss in the distal tubule Correct answer

H+ loss in the distal tubule

Na+, H2O loss and K+ conservation in the ascending limb of the loop of Henle

Na+, H2O conservation and K+ loss in the ascending limb of the loop of Henle

Aldosterone is a steroid hormone produced by the zona glomerulosa of the adrenal cortex. Its release is stimulated mainly by the rennin/ angiotensin system. ACTH also causes aldosterone production, as do hyponatraemia, hyperkalaemia and hypovolaemia. It regulates Na+/ K+ and water balance, as well as playing a role acid base balance. At the distal tubule, it acts to increase the Na+/K+ permeability of the luminal surface of the cells, and causes resorption of Na+ and H2O in exchange for K+, which is excreted into the urine. It also acts in the collecting ducts to secrete H+ ions, thereby regulating plasma HCO3

- levels. 70. Consider the following data; paO2 7.6 KPa paCO2 3.2 KPa pH 7.45 HCO3- 24 mmol/ l This blood gas analysis is most consistent with:

Compensated metabolic acidosis

Normal blood gas analysis

Metabolic acidosis

Respiratory acidosis

Type 1 respiratory failure Correct answer

The blood gases show a picture of type 1 respiratory failure, with a low pa O2 and low pa CO2, possibly due to consolidation of lung with compensatory hyperventilation. This pattern may be seen in conditions producing a ventilation/perfusion mismatch, such as pneumonia or pulmonary embolism. If ventilation is able to increase enough to keep CO2 normal, then a respiratory acidosis will not develop. A metabolic acidosis would have a pH of less than 7.35 and low bicarbonate. A compensated metabolic acidosis would show decreased bicarbonate as well as a low CO2 – due to respiratory compensation. 71. Anatomical dead space is decreased by

Adrenaline

Tracheostomy Correct answer

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A subject standing as opposed to lying supine

Increasing size of a subject

Increasing lung volume

Anatomical dead space is the volume of conducting airways down to a level where rapid mixture of gas already in the lungs with inspired gases takes place. The gas in this part of the lung does not take part in gas exchange. Physiological dead space is the total lung volume not taking part in gas exchange, and is usually the same as or more than the anatomical dead space. It includes the anatomical dead space, plus alveolar dead space, so any alveoli that are ventilated but not perfused are included in the physiological but not the anatomical dead space. Factors increasing anatomical dead space are: a subject standing rather than sitting, increasing size of a subject, increasing lung volume (e.g. during inspiration), and bronchodilatation due to drugs or endogenous agents such as adrenaline. Because tracheostomy bypasses the upper respiratory tract, it decreases anatomical dead space. 72. In a breathless patient, a pleural effusion with less than 3g of protein per 100ml of fluid is most likely to be caused by

Bronchial carcinoma

Mitral regurgitation Correct answer

Pneumonia

Tuberculosis

Tricuspid regurgitation

An effusion with less than 3g of protein per 100ml is a transudate. Other biochemical characteristics of a transudate include LDH < 200 iU/l, WCC < 1000/ml, glucose <3 mmol/l. Transudative effusions are most commonly due to factors such as decompensated liver failure and left ventricular failure. Malignancy and infection are causes of an exudative pleural effusion. Pulmonary embolism can cause either an exudative or transudative effusion, although the former is more common. In this question, B is more likely than E to be associated with left ventricular failure, and therefore a pleural effusion. Tricuspid regurgitation is usually functional and secondary to an enlarged right ventricle in right ventricular failure, and causes a pulsatile liver, peripheral oedema and ascites. 73. A parathyroid adenoma will be most likely to cause

Decreased osteoclastic activity

Decreased urinary phosphate excretion

Hypocalcaemia

Increased osteoblastic activity

Increased osteoclastic activity Correct answer

The parathyroid glands produce parathyroid hormone (PTH) in response to serum calcium levels via a negative feedback mechanism. High levels of serum Ca2+ inhibit PTH secretion, and low levels stimulate PTH secretion. The response to Ca2+ levels is very rapid, so effects are seen very quickly after removal of the glands. PTH affects calcium levels by its action on the bone, kidney and gut. In bone, increased osteoclastic activity causes calcium levels to rise. This is due firstly to acid secretion onto the bone surface, and secondly to proteases dissolving the matrix. In the kidney, PTH controls the hydroxylation of 25,hydroxy cholecalciferol D to 1,25 hydroxy cholecalciferol. This has the indirect effect of increasing calcium uptake in the gut. In the proximal tubule, PTH increases the urinary excretion of phosphate, which in turn increases the ionisation of calcium. There is also an increase in Ca2+ reabsorption in the distal tubule. Bicarbonate resorption is inhibited in the kidney, causing a hyperchloraemic acidosis which increase calcium ionisation and resorption from bone. PTH excess therefore causes hypercalcaemia, hypophosphataemia and hyperchloraemia, as well as raised urinary phosphate. 74. ADH (Vasopressin) release in response to dehydration causes

Decreased permeability of the collecting ducts to water

Decreased urine osmolality

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Increased Na+ resorption in the ascending limb of the loop of Henle

Increased Na+ resorption in the descending limb of the loop of Henle

Increased permeability of the collecting ducts to water Correct answer

ADH is released by the posterior pituitary in response to dehydration, from stimulation of osmoreceptors adjacent to the supraoptic nucleus, as well as volume receptors in the aorta atria and great veins. Water absorption in the collecting ducts is independent of sodium concentration, and is under the control of ADH, which causes increased permeability of the ducts. Increased ADH levels will increase the osmolality of the urine via this method. In the descending limb of the loop of Henle, sodium and water are passively resorbed. The ascending limb is impermeable to water, with active sodium resorption, producing a concentration gradient in the renal medulla, which is essential for the maintenance of water balance. 75. Which of the following hormones is synthesised in the hypothalamus and secreted from the posterior pituitary?

Anti diuretic hormone (ADH) Correct answer

Adrenocorticotrophic hormone (ACTH)

Corticotrophin releasing hormone (CRH)

Thyrotrophin releasing hormone (TRH)

Thyroid stimulating hormone (TSH)

Vasopressin (ADH) and oxytocin are synthesised in the hypothalamic nuclei and pass down axons to the posterior pituitary where they are secreted into the blood stream. In contrast, the trophic hormones such as CRH and TRH are secreted by the hypothalamus in response to neural stimuli, and drain into the hypothalamo–hypophyseal portal vessels to the anterior pituitary. There is then resultant stimulation of ACTH and TSH secretion. The other hormones produced by a similar mechanism by the anterior pituitary are growth hormone (GH), prolactin (PRL), lutenising hormone (LH) and follicle stimulating hormone (FSH). 76. The cardiac index is equal to

Blood pressure x heart rate

Cardiac output / body surface area Correct answer

Cardiac output / height

Cardiac output x peripheral resistance

Stroke volume x heart rate

The cardiac index is a measure that allows cardiac output to be compared between patients of differing size for direct comparison. It is measured in L/min/m2, and usually ranges from 2.5-3.5. Stroke volume x heart rate is equal to the cardiac output, and cardiac output x peripheral resistance equals the blood pressure. Cardiac output/ height and blood pressure x heart rate are not useful measurements. 77. Increased venous return to the heart is most likely to be caused by

Deep inspiration Correct answer

Forced expiration

Hypovolaemia

Positive pressure ventilation

Tension pneumothorax

Blood returns to the heart from the lower limbs via the action of the calf muscle pumps, valves in the veins of the leg, and the effect of negative intra-thoracic pressure generated during inspiration. Anything causing the intra thoracic pressure to become less negative will decrease the venous return to the right atrium. Tension pneumothorax, positive pressure ventilation and

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forced expiration all cause this effect, and therefore reduce the venous return. Although hypovolaemia may cause vasoconstriction in an attempt to increase venous return, it is unlikely to increase above normal levels. 78. The largest contribution to systemic vascular resistance (SVR) is made by the

Aortic valve

Great arteries

Arterioles Correct answer

Venules

Great veins

The capillaries and arterioles each account for around 25% of the SVR. The large surface area of the capillaries, as well as the low flow and pressure drop through the capillary beds is vital to their function in exchange of gases and nutrients. The arterioles have abundant smooth muscle in their walls, and flow is regulated to a large degree by the sympathetic nervous system. They therefore exert a great deal of control over the flow through the capillary beds, as well as which capillary beds are open at a given time. 79. What is the half life of free triiodothyronine (T3) in the blood?

1 minute

1 hour

1 day Correct answer

1 week

1 month

Most of the T3 and thyroxine (T4) are carried in plasma bound to thyroxine binding globulin, and are inactive in this state. Only 1% of T3 and 0.05% of T4 is free. T3is the active hormone, and is formed from the intracellular deiodination of T4 by type 2 deiodinase. The half life of T4 is 1 week, and of T3 1 day, suggesting that T4 acts as a source of T3, rather than an active hormone in its own right. 80. Which of the following metabolic effects is most likely to be caused by thyroid hormone?

Decreased glycogenolysis in the liver

Increased glucose absorption in the gut Correct answer

Decreased lipolysis

Decreased expression of β adrenergic receptors

Decreased oxygen uptake in the mitochondria

Thyroid hormone has widespread metabolic effects. Increased glycogenolysis in the liver, increased glucose absorption in the gut and increased insulin breakdown all tend to increase blood glucose. The glycogenolytic effects of catecholamines are also potentiated. These effects can make the diagnosis and management of diabetes in thyrotoxicosis difficult. There is an overall lipolytic effect, with decreased serum cholesterol seen in thyrotoxicosis, and an increase in hypothyroidism. There is an increased expression of -adrenergic receptors in many tissues including skeletal and cardiac muscle. There is a positive inotropic effect with increased cardiac output and heart rate. A raised metabolic rate and increased heat production are due to increased oxygen uptake and ATP production in the mitochondria. There are also effects on bone, with an overall breakdown of bone, sometimes leading to hypercalcaemia. Increased serum 2,3 DPG leads to a right shift of the haemoglobin dissociation curve. Thyroid hormones are also essential for fetal development, with deficiency leading to cretinism. The fetus produces its own hormone from 18 weeks of gestation. 81. Which of the following is the most important direct stimulus to respiration?

Increased pCO2 of the CSF

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Increased H+ concentration of the CSF Correct answer

Decreased arterial pO2

Decreased arterial pH

Decreased arterial pCO2

Chemoreceptors involved with the control of respiration are present in the central nervous system and peripherally. The central chemoreceptors are situated in the ventral medulla, and increase firing in response to the H+ concentration of the brain extra cellular fluid, which is directly related to the H+ concentration in the CSF. CO2 / HCO3 cannot cross the blood brain barrier, but CO2 does so readily. This frees H+ ions, causing a low CSF pH, increased firing of the central chemoreceptors and increased ventilation. Peripheral chemoreceptors are found in the carotid bodies and aortic arch, and increase their firing rate in response to decreased PaO2, decreased arterial pH and increased paCO2. These are much less important, however, in stimulating respiration than the central chemoreceptors. 82. Which of the following systemic effects are most likely to be caused by a space occupying lesion in the brain?

Bradycardia Correct answer

Hypotension

Tachycardia

Tachypnoea

Venous ulceration

The cranium is a fixed volume containing blood, CSF and brain tissue in equilibrium. Increases in one component can be compensated by a decrease in the other components without increasing intracranial pressure (the Monroe-Kellie doctrine). Beyond a certain point, this compensation is insufficient, and raised intracranial pressure results (greater than 10-15mmHg). The effects of raised intracranial pressure are hydrocephalus, cerebral ischaemia (due to decreased cerebral perfusion pressure) and systemic effects. The systemic effects include hypertension, bradycardia, slowed respiration and gastric ulceration (Cushing’s ulcer). These are thought to be due to autonomic dysregulation resulting from hypothalamic compression. 83. Insulin levels are not increased by which of the following? Single best answer question – choose ONE correct option only

Amino acids

β-adrenergic stimulation

Hypokalaemia Correct answer

Increased plasma glucose

Vagal nerve stimulation

Glucose is the most important stimulus to insulin, causing its release from secretory granules in the -cells of the pancreas, and release of newly synthesised insulin. As well as glucose, insulin release is stimulated by amino acids, some fatty acids, and the gut hormones secretin and cholecystokinin. -adrenergic and vagal stimulation also increase insulin levels. One of the effects of insulin other than decreasing blood glucose is to cause an intracellular shift of K+. This reduces serum levels of K+, but not total body K+. Hypokalaemia acts to inhibit insulin release. 84. Which is the correct calculation for normal lung volumes?

Vital capacity = expiratory capacity + inspiratory capacity

Vital capacity = expiratory capacity + inspiratory reserve volume Correct answer

Total lung capacity = vital capacity + functional reserve capacity

Total lung capacity = inspiratory capacity + residual volume

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Functional residual capacity = residual volume + tidal volume

Normal adult lung volumes: Tidal volume (TV) = 7ml/kg (400-500ml). Vital capacity (VC) = 4.5L = expiratory capacity + inspiratory reserve volume, i.e. the combined maximum expiration + the maximum inspiration. A is incorrect as both inspiratory and expiratory capacity include the tidal volume, whereas the inspiratory reserve volume is the maximum inspiration possible above the normal tidal volume. Total lung capacity (TLC) = 7.5L = VC + residual volume (RV). Functional residual capacity (FRC) = 2.8L = the amount of air in the lungs after a normal breath. 85. The electrocardiogram (ECG) strip of a patient shows sagging of the ST segment, depression of the T-wave and elevation of the U-wave. What is the most likely electrolyte abnormality responsible for these ECG findings?

Hyperkalaemia

Hypermagnesaemia

Hypocalcaemia

Hypokalaemia Correct answer

Hypomagnesaemia

Cardiac effects of hypokalaemia are usually minimal until plasma potassium levels are less than 3 mmol/l. Hypokalaemia leads to sagging of the ST segment, depression of the T-wave and elevation of the U-wave. With marked hypokalaemia, the T-wave become progressively smaller and the U-wave becomes increasingly larger. Sometimes, a flat or positive T-wave merges with a positive U-wave, which can be confused with qT prolongation. Hypokalemia can also cause premature ventricular and atrial contractions, ventricular and atrial tachyarrhythmias and second- or third-degree atrioventricular block. Such arrhythmias become more severe with increasingly severe hypokalaemia; eventually, ventricular fibrillation can occur. Patients with significant pre-existing heart disease and/or those receiving digoxin are at risk of cardiac conduction abnormalities, even with mild hypokalaemia.