CPATH

Question 1

Give one endocrine cause of atrial fibrillation, and indicate how it can be diagnosed biochemically (2)

Answer 1

Hyperthyroidism, elevated thyroxine and/or suppressed TSH

Question 2

Explain why atrial fibrillation increases the risk of cerebrovascular accident (particularly following its correction by cardioversion) (2)

Answer 2

Failure of atria to empty promotes thrombus formation (particularly in the atrial fimbriae) which then dislodge once fibrillation is corrected and embolize to the brain.

Question 3

Describe a strategy that can be employed to minimize this risk (1)

Answer 3

anti-coagulation therapy with warfarin, a vitamin K antagonist.

Question 4

Explain the mode of action of such a strategy (1)

Answer 4

Interferes with clotting factor synthesis by the liver.

Question 5

Define “apparent” mineralocorticoid excess (3)

Answer 5

The presence of hypertension, Na, K, HCO3, suppressed renin but with low plasma aldosterone levels

Question 6

List two (2) causes of apparent mineralocorticoid excess (1)

Answer 6

Cushing’s syndrome
Excessive liquorice ingestion
Liddle’s syndrome (overactive ENaC channel)
11β-hydroxysteroid dehydrogenase type II (11HSD type II) defect

Question 7

List three (3) causes for apparent mineralocorticoid excess (1x½ = 1½)

Answer 7

Liqourice/ 11β-hydroxysteroid dehydrogenase type II deficiency
Cushing syndrome
Liddle’s syndrome (overactive epithelial sodium channel)

Question 8

List three (3) tests used to screen for Cushing’s Syndrome (3x½ = 1½)

Answer 8

Midnight cortisol (serum/saliva)
24 hour urine cortisol
Low dose dexamethasone suppression test
Loss of diurnal rhythm

Question 9

Explain the mechanism whereby Cushing’s Syndrome can cause secondary hypertension (4)

Answer 9

Capacity of the enzyme 11-β hydroxysteroid dehydrogense to convert cortisol to inactive cortisone is overwhelmed by excessive cortisol production [2].

Cortisol is able to bind to and activate the mineralocorticoid receptor [1].

Mineralocorticoid receptor stimulates excessive uptake of sodium and therefore water leading to hypertension [1].

Question 10

List four (4) biochemical features of primary hyperaldosteronism (4)

Answer 10

Hypokalaemia, Metabolic alkalosis, Aldosterone, Renin, Mild hypernatreamia, Urine potassium > 30 mmol/day

Question 11

State which single biochemical test is most useful for distinguishing primary hyperaldosteronism from apparent mineralocorticoid excess (1)

Answer 11

Plasma aldosterone

Question 12

List five (5) biochemical analytes (in blood) that would support this diagnosis. For each analayte, state the direction of change (5x½ = 2½)

Answer 12

Aldosterone, Renin, Hypokalaemia, Hypernatraemia, Metabolic alkalosis (high pH, low [H+], high [HCO3-])

Question 13

State the two (2) analytes that would differentiate between a renin producing tumour and primary hyperaldosterone according to their direction of change. For each, state the direction of change in the case of a renin producing tumour (4x½ = 2)

Answer 13

Renin increased/normal, Sodium normal

Question 14

List the biochemical changes in blood typically present in this condition: (3x½ = 1½)

Answer 14

Hypernatraemia, Hypokalaemia, Metabolic alkalosis

Question 15

List five (5) biochemical markers in blood and/or urine that will support this diagnosis and state whether each of these markers will be increased, decreased or normal (5)

Answer 15

Blood potassium, Urine potassium, Mildly Blood sodium
Blood: metabolic alkalosis
Blood renin, Blood aldosterone

Question 16

State whether renin will be increased, decreased or unchanged in this condition (½)

Answer 16

Decreased

Question 17

In unilateral renal artery stenosis, state the direction of change of renin (½)

Answer 17

Increased

Question 18

State the reason for the direction of change (1)

Answer 18

Decreased renal perfusion (on the side of the occlusion) leads increased renin secretion.

Question 19

Post surgery, the patient developed the syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH).

List the biochemical findings in serum and urine which would support this diagnosis (4x½ = 2)

Answer 19

Hyponatraemia, low plasma osmolality. Inappropriately high urine sodium and osmolality

Question 20

List two (2) conditions that must be excluded before the diagnosis of SIADH can be made (2x½ = 1)

Answer 20

Hypothyroidism; decreased cortisol; renal dysfunction

Question 21

After being treated for his meningitis, patient was found to have persistently elevated BP. Blood tests reveal hypokalemia.

Using the algorithm below, fill in the possible causes (a – f) for a patient presenting with hypertension plus hypokalaemia (6x1 = 6)

Answer 21

a) Hypertension plus extra-renal loss of potassium (extra-renal or GIT or burns)
b) Renin-producing tumour
c) Renal artery stenosis
d) Liddle’s / 11 beta hydroxyl steroid dehydrogenase deficiency/licourice excess
e) Cushing’s
f) Conn’s or Primary hyperaldosteronism

Question 22

State the expected acid base disturbance present in Clinton (1)

Answer 22

Metabolic alkalosis

Question 23

Briefly outline the mechanism for the hypokalaemia in a patient with condition (f) in question 1 (3)

Answer 23

Excess aldosterone leads to excessive stimulation of mineralocorticoid receptor [1], which in turn causes increased expression of the ENaC channel[1], increased uptake of sodium[1] with accompanying loss of potassium renally.

Question 24

List four (4) clinical findings that would support a diagnosis of phaeochromocytoma (4x½ = 2)

Answer 24

The hypertension was severe, Episodic in nature, Tachycardia, Anxiety, Hyperglycaemia, Sweating, Palpitations, Tremor,Headache

Question 25

Name one biochemical test that could be used to confirm your diagnosis (½)

Answer 25

Any one of the following: Adrenaline/noradrenaline/metanephrine/normetanephrine/chromogranin A

Question 26

High levels of homocystine have been implicated in cerebral thrombosis.

State three (3) dietary components that are important for controlling plasma homocystine levels, and indicate for each how they reduce homocystine (3)

Answer 26

Vitamins B6 (pyridoxine), folic acid and vitamin B12. B6 is required for the first step of homocystine catabolism, and folate and B12 are required to recycle homocystine to methionine.

Question 27

A rare but treatable cause of hypertension is Conn’s syndrome. Explain what causes Conn’s syndrome and indicate five (5) abnormal plasma findings in this condition (3½)

Answer 27

An aldosterone-producing tumour of the adrenal (usually benign); findings: ↑Na, ↓K, ↑HCO3, ↓renin, ↑aldosterone

Question 28

Explain what is meant by a ‘phaeochromocytoma’ (1)

Answer 28

A tumour of sympathetic nervous system (typically located in the adrenal medulla) secreting adrenalin and or noradrenalin.

Question 29

Describe the unique clinical features of the hypertension associated with phaeochromocytoma (2)

Answer 29

hypertension is sporadic and associated with adrenergic symptoms (sweating, pallor, tachycardia, anxiety),

Question 30

State how it can be diagnosed biochemically (1)

Answer 30

Measurement of urinary catecholamine metabolites like metadrenalin and VMA

Question 31

Explain the dangers associated with its surgical Rx (2)

Answer 31

Release of adrenalin during tumour handling causing acute hypertension, post-operative hypotension from acute catecholamine withdrawal in a patient with depleted intravascular volume.