Chemical Pathology EMQs

Question 1

Sodium handling

A Ethanol

B SIADH

C Frusemide

D Chronic kidney disease

E Conn’s syndrome

F Diarrhoea

G Congestive cardiac failure

H Addison’s disease

I Hyperlipidaemia

A 50-year-old woman with known diabetes has a routine blood test which
demonstrates the following:
Na 130 (135–145 mmol/L)
K 4.1 (3.5–5.0 mmol/L)
Urea 4.2 (3.0–7.0 mmol/L)
Glucose 3.1 (2.2–5.5 mmol/L)
Osmolality 283 (275–295 mOsm/kg)

Answer 1

I Hyperlipidaemia

Pseudo-hyponatraemia can occur in patients with hyperlipidaemia
(I) or hyperproteinaemia. In such states, lipids and proteins will
occupy a high proportion of the total serum volume. Although the
sodium concentration
in serum water is in fact normal, a lower
sodium concentration
will be detected due to dilution by increased
lipids and protein molecules. As a consequence, there is an apparent
hyponatraemia.
A spurious result due to the sample being taken from
the drip arm can also cause pseudo-hyponatraemia.

Question 2

Sodium handling

A Ethanol

B SIADH

C Frusemide

D Chronic kidney disease

E Conn’s syndrome

F Diarrhoea

G Congestive cardiac failure

H Addison’s disease

I Hyperlipidaemia

A 45-year-old man is seen by his specialist. His last blood and urine tests
demonstrated the following:
Na 129 (135–145 mmol/L)
K 5.5 (3.5–5.0 mmol/L)
Urea 8.2 (3.0–7.0 mmol/L)
Glucose 4.2 (2.2–5.5 mmol/L)
Osmolality 265 (275–295 mOsm/kg)
Urine osmolality 26 mOsm/kg

Answer 2

D Chronic kidney disease

A true hyponatraemic state occurs when the osmolality is simultaneously
low. Chronic kidney disease (CKD; D) results in urinary protein
loss and hence oedema. A reduced circulating volume causes activation
of the renin–angiotensin system, thereby raising blood sodium levels.
This in turn causes release of antidiuretic hormone (ADH) from the
posterior pituitary leading to water retention and hypervolaemic
hyponatraemia. Water reabsorption in the renal tubules increases urine
osmolality (>20 mmol/L indicates a renal cause of hyponatraemia). CKD
is also associated with hyperkalaemia and azotaemia.

Question 3

Sodium handling

A Ethanol

B SIADH

C Frusemide

D Chronic kidney disease

E Conn’s syndrome

F Diarrhoea

G Congestive cardiac failure

H Addison’s disease

I Hyperlipidaemia

A 30-year-old woman visits her GP due to pigmentation of her palmar creases.
Two weeks later the following blood and urine tests are received:
Na 128 (135–145 mmol/L)
K 5.9 (3.5–5.0 mmol/L)
Urea 5.2 (3.0–7.0 mmol/L)
Glucose 1.8 (2.2–5.5 mmol/L)
Osmolality 264 (275–295 mOsm/kg)
Urine osmolality 24 mOsm/kg

Answer 3

H Addison’s disease

Addison’s disease (H) is also known as primary adrenal insufficiency
(reduced aldosterone and cortisol); consequently there is a rise in the
production of adrenocorticotropic hormone (ACTH). An impaired synthesis
of aldosterone reduces reabsorption of sodium and increases
excretion of potassium in the distal convoluted tubule and collecting
ducts of the kidney; this leads to a simultaneous hyponatraemia and
hyperkalaemia. Reduced cortisol production causes hypoglycaemia due
to impaired gluconeogenesis. Clinical features of Addison’s disease
include hyperpigmentation, postural hypotension and weight loss.

Question 4

Sodium handling

A Ethanol

B SIADH

C Frusemide

D Chronic kidney disease

E Conn’s syndrome

F Diarrhoea

G Congestive cardiac failure

H Addison’s disease

I Hyperlipidaemia

A 30-year old woman is seen by her GP after a 5-day episode of productive
cough and lethargy. The GP notes dullness on percussion of the patient’s left
lower lung. Blood and urine tests reveal the following:
Na 128 (135–145 mmol/L)
K 4.1 (3.5–5.0 mmol/L)
Urea 3.5 (3.0–7.0 mmol/L)
Glucose 3.2 (2.2–5.5 mmol/L)
Osmolality 265 (275–295 mOsm/kg)
Urine osmolality 285 mOsm/kg

Answer 4

B SIADH

The syndrome of inappropriate ADH secretion (B; SIADH) results from
the excess release of ADH. In this case the clinical features suggest
pneumonia is the cause, but the aetiologies of SIADH are numerous,
including malignancy, meningitis and drugs (carbamazepine). Criteria
to diagnose SIADH include the following:
• Hyponatraemia 100 mmol/L
• High urine sodium >20 mmol/L
• Euvolaemia
• No adrenal, renal or thyroid dysfunction

Characteristically the urine osmolality is inappropriately high; in normal
circumstances if the plasma osmolality is low, the urine osmolality
will stop rising as reduced ADH secretion prevents water retention. As
a rule of thumb in SIADH, urine osmolality is greater than plasma
osmolality.

Question 5

Sodium handling

A Ethanol

B SIADH

C Frusemide

D Chronic kidney disease

E Conn’s syndrome

F Diarrhoea

G Congestive cardiac failure

H Addison’s disease

I Hyperlipidaemia

A 63-year-old man with chronic obstructive pulmonary disease (COPD) sees his
GP due to oedematous ankles. His blood and urine tests show the following:
Na 130 (135–145 mmol/L)
K 4.4 (3.5–5.0 mmol/L)
Urea 4.2 (3.0–7.0 mmol/L)
Glucose 3.1 (2.2–5.5 mmol/L)
Osmolality 268 (275–295 mOsm/kg)
Urine osmolality 16–mmol/LmOsm/kg

Answer 5

G Congestive cardiac failure

Congestive cardiac failure (G) may present with shortness of breath, pitting
peripheral oedema and/or raised jugular venous pulse (JVP). In this
scenario, shortness of breath may be masked by the patient’s COPD.
The clinical picture together with the blood result demonstrating a low
sodium and low osmolality suggest a hypervolaemic hyponatraemia.
This scenario can be differentiated from hypervolaemia as a result of
CKD (D) by the urine osmolality, which is less than 20 mmol/L in this
instance, thereby suggesting a non-renal cause for the hyponatraemia

Ethanol (A) may cause hyponatraemia in the context of a raised plasma
osmolality (>295 mmol/L). Other low molecular weight solutes that can
cause hyponatraemia (when osmolality is raised) include mannitol and
glucose.
Frusemide (C) and other diuretics cause a hypovolaemic hyponatraemia.
As well as a low plasma sodium and osmolality, the urine osmolality will
be greater than 20 mmol/L, signifying a renal cause of hyponatraemia.
Conn’s syndrome (E), also known as primary aldosteronism, results
from an aldosterone-producing adenoma producing excess aldosterone.
Biochemical (and concurrent clinical) features include hypernatraemia
(hypertension) and hypokalaemia (paraesthesia, tetany and weakness).
Diarrhoea (F) leads to a hypovolaemic hyponatraemia (as does vomiting).
Plasma sodium and osmolality will be low and urine osmolality
will be lower than 20 mmol/L indicating an extra-renal cause of
hyponatraemia.

Question 6

Potassium handling

A Spurious sample

B Anorexia

C Diarrhoea

D Renal tubular acidosis

E Insulin overdose

F Bartter syndrome

G Frusemide

H Renal failure

I ACE inhibitors

A 15-year-old boy presents to accident and emergency with loss of
consciousness. His blood sugars are found to be extremely low. Blood tests
demonstrate the following:
Na 138 (135–145 mmol/L)
K 3.0 (3.5–5.0 mmol/L)
Urea 4.2 (3.0–7.0 mmol/L)
Creatinine 74 (60–120 mmol/L)
pH 7.48 (7.35–7.45)
HCO3 31 (22–28 mmol/L)

Answer 6

E Insulin overdose

Insulin overdose (E) in a diabetic patient will cause a redistributive
hypokalaemia and concurrent metabolic alkalosis. Insulin causes a shift
of potassium ions from the extracellular space to the intracellular space,
thereby lowering blood potassium levels. Metabolic alkalosis can also
cause a redistributive hypokalaemia; a reduced hydrogen ion concentration
in the blood causes increased intracellular hydrogen ion loss to increase
extracellular levels via Na+/H+ ATPase; potassium ions therefore diffuse
intracellularly to maintain the electrochemical potential. Adrenaline and
re-feeding syndrome also cause redistributive hypokalaemia.

Question 7

Potassium handling

A Spurious sample

B Anorexia

C Diarrhoea

D Renal tubular acidosis

E Insulin overdose

F Bartter syndrome

G Frusemide

H Renal failure

I ACE inhibitors

A 64-year-old man who is an inpatient on the Care of the Elderly ward is found
to have the following blood results:
Na 136 (135–145 mmol/L)
K 5.5 (3.5–5.0 mmol/L)
Urea 14.4 (3.0–7.0 mmol/L)
Creatinine 165 (60–120 mmol/L)
pH 7.44 (7.35–7.45)
HCO3 27 (22–28 mmol/L)

Answer 7

H Renal failure

Renal failure (H) can lead to hyperkalaemia secondary to reduced
distal
renal delivery of sodium ions. As a consequence, there is
reduced exchange of potassium ions via the Na/K ATPase pump in
the collecting
duct, which thereby leads to accumulation of potassium
ions in the blood and hence hyperkalaemia. An increase in aldosterone
release will initially cause a compensatory loss of potassium ions;
as renal failure progresses, this homeostatic mechanism will become
decompensated and hyperkalaemia will result. Renal failure will also
be reflected in the deranged urea and creatinine levels due to reduced
excretion.

Question 8

Potassium handling

A Spurious sample

B Anorexia

C Diarrhoea

D Renal tubular acidosis

E Insulin overdose

F Bartter syndrome

G Frusemide

H Renal failure

I ACE inhibitors

A 16-day-old baby girl is found to have low blood pressure. Urinary calcium
levels are found to be elevated. Blood tests demonstrate the following results:
Na 138 (135–145 mmol/L)
K 2.8 (3.5–5.0 mmol/L)
Urea 3.4 (3.0–7.0 mmol/L)
Creatinine 62 (60–120 mmol/L)
pH 7.51 (7.35–7.45)
HCO3 33 (22–28mmol/L)

Answer 8

F Bartter syndrome

Bartter syndrome (F) is an autosomal recessive condition due to a defect
in the thick ascending limb of the loop of Henle. It is characterized by
hypokalaemia, alkalosis and hypotension. The condition may also lead
to increased calcium loss via the urine (hypercalcuria) and the kidneys
(nephrocalcinosis). Various genetic defects have been discovered; neonatal
Bartter syndrome is due to mutations in either the NKCC2 or ROMK
genes. In the associated milder Gitelman syndrome, the potassium transporting
defect is in the distal convoluted tubule of the kidney.

Question 9

Potassium handling

A Spurious sample

B Anorexia

C Diarrhoea

D Renal tubular acidosis

E Insulin overdose

F Bartter syndrome

G Frusemide

H Renal failure

I ACE inhibitors

A 32-year-old man presents to his GP for a check-up. His serum aldosterone is
found to be low. Blood tests reveal the following:
Na 140 (135–145 mmol/L)
K 5.6 (3.5–5.0 mmol/L)
Urea 5.3 (3.0–7.0 mmol/L)
Creatinine 92 (60–120 mmol/L)
pH 7.38 (7.35–7.45)
HCO3 24 (22–28 mmol/L)

Answer 9

I ACE inhibitors

ACE inhibitors (I) will lead to hyperkalaemia due to reduced potassium
excretion. ACE inhibitors antagonize the effect of angiotensin converting
enzyme, the enzyme which catalyzes the production of angiotensin
II from angiotensin I. A decreased level of angiotensin II reduces the
production of aldosterone in the adrenal glands, a key hormone causing
the excretion of potassium. Other causes of reduced excretion of potassium
include Addison’s disease, renal failure and potassium sparing
diuretics.

Question 10

Potassium handling

A Spurious sample

B Anorexia

C Diarrhoea

D Renal tubular acidosis

E Insulin overdose

F Bartter syndrome

G Frusemide

H Renal failure

I ACE inhibitors
A 68-year-old woman on the Care of the Elderly ward is found to have the
following blood results:
Na 138 (135–145 mmol/L)
K 3.0 (3.5–5.0 mmol/L)
Urea 4.2 (3.0–7.0 mmol/L)
Creatinine 74 (60–120 mmol/L)
pH 7.31 (7.35–7.45)
HCO3 28 (22–28 mmol/L)

Answer 10

D Renal tubular acidosis

Renal tubular acidosis (D) occurs when there is a defect in hydrogen
ion secretion into the renal tubules. Potassium secretion into the renal
tubules therefore increases to balance sodium reabsorption. This results
in hypokalaemia with acidosis. Renal tubular acidosis is classified
according to the location of the defect: type 1 (distal tubule), type 2
(proximal tubule), type 3 (both distal and proximal tubules). Type 4
results from a defect in the adrenal glands and is included in the classification
as it results in a metabolic acidosis and hyperkalaemia.

Question 11

Acid–base balance
A Metabolic acidosis
B Metabolic acidosis with
respiratory compensation
C Metabolic alkalosis
D Metabolic alkalosis with
respiratory compensation
E Respiratory acidosis
F Respiratory acidosis with
metabolic compensation
G Respiratory alkalosis
H Respiratory alkalosis with
metabolic compensation
I Mixed metabolic and respiratory
acidosis

pH 7.31 (7.35–7.45)
pO2 7.6 (10.6–13 kPa)
pCO2 8.2 (4.7–6.0 kPa)
HCO3 26 (22–28 mmol/L)

Answer 11

E Respiratory acidosis

Respiratory acidosis (E) is defined by a low pH (acidosis) together with
a high pCO2, due to carbon dioxide retention secondary to a pulmonary,
neuromuscular or physical causes. There is no metabolic compensation
in this case, suggesting this is an acute pathology; a compensatory
metabolic rise in HCO3 from the kidneys can take hours or days.
This patient is also hypoxic with a low pO2. Causes of an acute respiratory
acidosis include an acute exacerbation of asthma, foreign body
obstruction and cardiac arrest.

Question 12

Acid–base balance
A Metabolic acidosis
B Metabolic acidosis with
respiratory compensation
C Metabolic alkalosis
D Metabolic alkalosis with
respiratory compensation
E Respiratory acidosis
F Respiratory acidosis with
metabolic compensation
G Respiratory alkalosis
H Respiratory alkalosis with
metabolic compensation
I Mixed metabolic and respiratory
acidosis

pH 7.36 (7.35–7.45)
pO2 14.2 (10.6–13 kPa)
pCO2 4.1 (4.7–6.0 kPa)
HCO3 14 (22–28 mmol/L)

Answer 12

B Metabolic acidosis with
respiratory compensation

Metabolic acidosis with respiratory compensation (B) occurs when pH
is low (acidosis) and HCO3 is low with concurrent respiratory compensation
by decreasing pCO2. The anion gap can differentiate between
causes of metabolic acidosis (anion gap = [Na++ K+] – [Cl−+ HCO3
−];
normal range between 10 and 18 mmol/L). Causes of a raised anion gap
can be remembered by the mnemonic MUDPILES: methanol/metformin,
uraemia, diabetic ketoacidosis, paraldehyde, iron, lactate, ethanol and
salicylates. Causes of a normal anion gap include diarrhoea, Addison’s
disease and renal tubular acidosis.

Question 13

Acid–base balance
A Metabolic acidosis
B Metabolic acidosis with
respiratory compensation
C Metabolic alkalosis
D Metabolic alkalosis with
respiratory compensation
E Respiratory acidosis
F Respiratory acidosis with
metabolic compensation
G Respiratory alkalosis
H Respiratory alkalosis with
metabolic compensation
I Mixed metabolic and respiratory
acidosis

pH 7.45 (7.35–7.45)
pO2 10.2 (10.6–13 kPa)
pCO2 7.2 (4.7–6.0 kPa)
HCO3 32 (22–28 mmol/L)

Answer 13

D Metabolic alkalosis with
respiratory compensation

Metabolic alkalosis with respiratory compensation (D) occurs when pH is
high (alkalosis) and HCO3 is high with a compensatory reduction in respiratory
effort that increases pCO2. As respiratory effort is reduced there
is the possibility of the patient becoming hypoxic. Causes of metabolic
alkalosis include vomiting, potassium depletion secondary to diuretic
use, burns and sodium bicarbonate ingestion. Respiratory compensation
increase serum CO2 concentration, which reduces pH back towards normal.

Question 14

Acid–base balance
A Metabolic acidosis
B Metabolic acidosis with
respiratory compensation
C Metabolic alkalosis
D Metabolic alkalosis with
respiratory compensation
E Respiratory acidosis
F Respiratory acidosis with
metabolic compensation
G Respiratory alkalosis
H Respiratory alkalosis with
metabolic compensation
I Mixed metabolic and respiratory
acidosis

pH 7.30 (7.35–7.45)
pO2 8.2 (10.6–13 kPa)
pCO2 7.2 (4.7–6.0 kPa)
HCO3 19 (22–28 mmol/L)

Answer 14

I Mixed metabolic and respiratory
acidosis

Mixed metabolic and respiratory acidosis (I) occurs when there is a
low pH and a simultaneous high pCO2 and low HCO3. In the case of a
mixed metabolic and respiratory acidosis, the metabolic acidosis component
may be due to conditions such as uraemia, ketones produced as
a result of diabetes mellitus or renal tubular acidosis. The respiratory
acidosis component may be due to any cause of respiratory failure.
Hence, this mixed picture may occur in a COPD patient with concurrent
diabetes mellitus.

Question 15

Acid–base balance
A Metabolic acidosis
B Metabolic acidosis with
respiratory compensation
C Metabolic alkalosis
D Metabolic alkalosis with
respiratory compensation
E Respiratory acidosis
F Respiratory acidosis with
metabolic compensation
G Respiratory alkalosis
H Respiratory alkalosis with
metabolic compensation
I Mixed metabolic and respiratory
acidosis

pH 7.49 (7.35–7.45)
pO2 13.6 (10.6–13 kPa)
pCO2 4.1 (4.7–6.0 kPa)
HCO3 23 (22–28 mmol/L)

Answer 15

G Respiratory alkalosis

Respiratory alkalosis (G) is biochemically defined by a raised pH (alkalosis)
and reduced pCO2. As previously mentioned, metabolic compensation
can take hours or days to occur. The primary pathology causing
respiratory alkalosis is hyperventilation which causes increased CO2 to be lost via the lungs. Causes of hyperventilation may be due to central
nervous system disease, for example stroke. Other causes of hyperventilation
include anxiety (panic attack), pulmonary embolism and drugs
(salicylates).

Question 16

Liver function tests
A Alcohol abuse
B Gilbert’s syndrome
C Gallstones
D Dublin–Johnson syndrome
E Non-alcoholic fatty liver disease
F Crigler–Najjar syndrome
G Alcoholic liver disease
H Paracetamol poisoning
I Hepatocellular carcinoma

AST 65 (3–35 IU/L)
ALT 72 (3–35 IU/L)
GGT 82 (11–51 IU/L)
ALP 829 (35–51 IU/L)
Total bilirubin 234 (3–17 μmol/L)
Conjugated bilirubin 63 (1.0–5.1 μmol/L)

Answer 16

C Gallstones

Gallstones (C) may be composed of cholesterol, bilirubin or mixed in
nature. The major complication of gallstones is cholestasis, whereby
the flow of bile is blocked from the liver to the duodenum. This results
in right upper quadrant abdominal pain, nausea and vomiting. Other
causes of cholestasis include primary biliary cirrhosis, primary sclerosing
cholangitis and abdominal masses compressing the biliary tree.
Biochemically, cholestasis is defined by rises in GGT and ALP (obstructive
picture) that are greater than the rises in AST and ALT.

Question 17

Liver function tests
A Alcohol abuse
B Gilbert’s syndrome
C Gallstones
D Dublin–Johnson syndrome
E Non-alcoholic fatty liver disease
F Crigler–Najjar syndrome
G Alcoholic liver disease
H Paracetamol poisoning
I Hepatocellular carcinoma

AST 32 (3–35 IU/L)
ALT 29 (3–35 IU/L)
GGT 34 (11–51 IU/L)
ALP 53 (35–51 IU/L)
Total bilirubin 36 (3–17 μmol/L)
Conjugated bilirubin 3.4 (1.0–5.1 μmol/L)

Answer 17

B Gilbert’s syndrome

Gilbert’s syndrome (B) is an autosomal dominant condition in which
there is a mutation in the enzyme UDP glucuronosyl transferase which
reduces conjugation of bilirubin in the liver. As a consequence patients
experience mild, intermittent jaundice. Jaundice in patients with
Gilbert’s syndrome may be precipitated by infection or starved states.
Biochemistry will reveal that all liver function tests are normal apart
from an isolated raised unconjugated bilirubin level, while conjugated
bilirubin is within the normal range.

Question 18

Liver function tests
A Alcohol abuse
B Gilbert’s syndrome
C Gallstones
D Dublin–Johnson syndrome
E Non-alcoholic fatty liver disease
F Crigler–Najjar syndrome
G Alcoholic liver disease
H Paracetamol poisoning
I Hepatocellular carcinoma

AST 1259 (3–35 IU/L)
ALT 1563 (3–35 IU/L)
GGT 73 (11–51 IU/L)
ALP 46 (35–51 IU/L)
Total bilirubin 15.2 (3–17 μmol/L)
Conjugated bilirubin 4.2 (1.0–5.1 μmol/L)

Answer 18

E Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD; E) is due to fatty deposits
in the liver (steatosis), but where the underlying cause is not due to
alcohol. In such circumstances, aetiological factors include obesity,
diabetes, parenteral feeding and inherited metabolic disorders (glycogen
storage disease type 1). NAFLD may present with right upper quadrant
pain or may be asymptomatic. Liver function tests will reveal raised
AST and ALT levels (AST:ALT ratio

Question 19

Liver function tests
A Alcohol abuse
B Gilbert’s syndrome
C Gallstones
D Dublin–Johnson syndrome
E Non-alcoholic fatty liver disease
F Crigler–Najjar syndrome
G Alcoholic liver disease
H Paracetamol poisoning
I Hepatocellular carcinoma

AST 2321 (3–35 IU/L)
ALT 2562 (3–35 IU/L)
GGT 62 (11–51 IU/L)
ALP 182 (35–51 IU/L)
Total bilirubin 14 (3–17 μmol/L)
Conjugated bilirubin 3.4 (1.0–5.1 μmol/L)

Answer 19

H Paracetamol poisoning

Paracetamol poisoning (H) is a common cause of acute liver failure. The
clinical features of acute liver failure reflect the diminished synthetic
and metabolic functioning of the liver. Characteristics include reduced
blood sugar level, metabolic acidosis, increased tendency to bleed and
hepatic encephalopathy. Biochemical tests will reveal AST and ALT levels
greater than 1000 IU/L. AST and ALT levels will be greater than GGT
and ALP levels, reflecting the hepatic rather than obstructive picture of
the pathology.

Question 20

Liver function tests
A Alcohol abuse
B Gilbert’s syndrome
C Gallstones
D Dublin–Johnson syndrome
E Non-alcoholic fatty liver disease
F Crigler–Najjar syndrome
G Alcoholic liver disease
H Paracetamol poisoning
I Hepatocellular carcinoma

AST 34 (3–35 IU/L)
ALT 32 (3–35 IU/L)
GGT 134 (11–51 IU/L)
ALP 123 (35–51 IU/L)
Total bilirubin (3–17 μmol/L)
Conjugated bilirubin (1.0–5.1 μmol/L)

Answer 20

A Alcohol abuse

Alcohol abuse (A) can lead to deranged liver function tests. In the
absence of underlying liver disease, biochemical investigation may
demonstrate an isolated rise in GGT. There may also be mild elevations
in AST and ALT, reflecting mild hepatic damage. Haematology results
will show a macrocytic picture due to toxic effects of alcohol on the
bone marrow. Isolated raised GGT levels may also occur due to the
consumption of enzyme-inducing drugs such as phenytoin, carbamazepine
and phenobarbitone.

Question 21

Endocrine chemical pathology
A Prolactinoma
B Grave’s disease
C Addison’s disease
D Schmidst’s syndrome
E Acromegaly
F Conn’s syndrome
G Kallman’s syndrome
H Secondary hypoaldosteronism
I De Quervain’s thyroiditis

A 38-year-old woman is referred by her GP to the Endocrine Clinic for further
tests after experiencing fatigue and orthostatic hypotension. After a positive
short synACTHen test, a long synACTHen test reveals a cortisol of 750 nmol/L
after 24 hours.

Answer 21

C Addison’s disease

Addison’s disease (C) is caused by primary adrenal insufficiency resulting
in a reduced production of cortisol and aldosterone. It is diagnosed
using the synACTHen test. In the short synACTHen test, baseline
plasma cortisol is measured at 0 minutes, the patient is given 250 μg of
synthetic ACTH at 30 minutes and plasma cortisol is rechecked at 60
minutes; if the final plasma cortisol is

Question 22

Endocrine chemical pathology
A Prolactinoma
B Grave’s disease
C Addison’s disease
D Schmidst’s syndrome
E Acromegaly
F Conn’s syndrome
G Kallman’s syndrome
H Secondary hypoaldosteronism
I De Quervain’s thyroiditis

A 48-year-old man visits his GP complaining of muscle pain and weakness.
He is found to have raised blood pressure. Blood tests reveal Na 149 (135–
145 mmol/L) and K 3.1 (3.5–5.0 mmol/L).

Answer 22

F Conn’s syndrome

Conn’s syndrome (F) is defined as primary hyperaldosteronism secondary
to an aldosterone-producing adrenal adenoma. As a result of the
high aldosterone levels produced there will be an increased excretion
of potassium and reabsorption of sodium, leading to hypokalaemia and
hypernatraemia. The increased delivery of sodium to the juxtaglomerular
apparatus causes renin levels to be reduced. Plasma aldosterone
will either be raised or inappropriately normal (as ACTH is suppressed,
aldosterone should physiologically be reduced).

Question 23

Endocrine chemical pathology
A Prolactinoma
B Grave’s disease
C Addison’s disease
D Schmidst’s syndrome
E Acromegaly
F Conn’s syndrome
G Kallman’s syndrome
H Secondary hypoaldosteronism
I De Quervain’s thyroiditis

A 39-year-old woman sees an endocrinologist due to recent onset
galactorrhoea. She denies recent child birth. Thyroid function tests are found to
be normal.

Answer 23

A Prolactinoma

A prolactinoma (A) is a prolactin-producing tumour and is the most
prevalent pituitary tumour. Prolactinomas are classified according to
size: microprolactinoma 10 mm diameter. The clinical consequences of prolactinoma are divided
into, first, those that occur as a result of increased prolactin production
and, second, effects due to the mass effect of the tumour. Hormonal
effects of prolactin include amenorrhoea, galactorrhoea and gynaecomastia
in males. Mass effects of the tumour can lead to compression of
pituitary cells producing other hormones such as thyroid stimulating
hormone, growth hormone and ACTH.

Question 24

Endocrine chemical pathology
A Prolactinoma
B Grave’s disease
C Addison’s disease
D Schmidst’s syndrome
E Acromegaly
F Conn’s syndrome
G Kallman’s syndrome
H Secondary hypoaldosteronism
I De Quervain’s thyroiditis

A 46-year-old man is seen by his GP after experiencing tremors, heat
intolerance and weight loss. His wife complained that his eyes were bulging.
Blood tests reveal T3 (1.2–3.0 nmol/L), T4 (70–140 nmol/L), TSH (0.5–5.7 mIU/L).

Answer 24

B Grave’s disease

Grave’s disease (B) is an autoimmune condition resulting in the production
of TSH-receptor antibodies, leading to elevated levels of T3 and T4.
TSH levels will therefore be suppressed as a result of negative feedback.
Clinical features will include exophthalmos, pretibial myxoedema,
diffuse thyroid enlargement as well as other systemic features of hyperthyroiditis
(tremor, excess sweating, heat intolerance and unintentional
weight loss). There is a strong association with other autoimmune conditions
such as vitiligo and type 1 diabetes mellitus.

Question 25

``` Endocrine chemical pathology A Prolactinoma B Grave’s disease C Addison’s disease D Schmidst’s syndrome E Acromegaly F Conn’s syndrome G Kallman’s syndrome H Secondary hypoaldosteronism I De Quervain’s thyroiditis ``` A 45-year-old woman is referred to an endocrinologist due to the appearance of enlarged hands and feet as well as a protruding jaw. After conducting an oral glucose tolerance test, growth hormone levels are found to be 5 mU/L (

Answer 25

E Acromegaly Acromegaly (E) is caused by the increased secretion of growth hormone as a result of a pituitary adenoma (rarely there may be ectopic production). Serum growth hormone levels are not a useful marker of acromegaly due to its pulsatile release from the pituitary. The diagnostic test for acromegaly is the oral glucose tolerance test with synchronous growth hormone measurement: 75 mg of glucose is administered to the patient; if growth hormone levels are not suppressed to below 2 mU/L, a diagnosis of acromegaly is made.

Question 26

``` Calcium handling A Primary hyperparathyroidism B Secondary hyperparathyroidism C Tertiary hyperparathyroidism D Pseudohypoparathyroidism E Primary hypoparathyroidism F Osteoporosis G Osteomalacia H Paget’s disease I Familial benign hypercalcaemia ``` ``` Ca 2.4 (2.2–2.6 mmol/L) PTH 4.2 (0.8–8.5 pmol/L) ALP 250 (30–150 u/L) PO4 1.1 (0.8–1.2 mmol/L) Vitamin D 76 (60–105 nmol/L) ```

Answer 26

H Paget’s disease Paget’s disease (H) is a condition associated with impaired bone remodelling. New bone is larger but weak and prone to fracture. The pathogenesis has been postulated to be linked to paramyxovirus. All calcium blood studies will be normal apart from ALP, which will be raised. Paget’s disease is associated with extreme bone pain, bowing and chalk-stick fractures. Bossing of the skull may lead to an eighth cranial nerve palsy and hence hearing loss. X-ray findings include lytic and sclerotic lesions.

Question 27

``` Calcium handling A Primary hyperparathyroidism B Secondary hyperparathyroidism C Tertiary hyperparathyroidism D Pseudohypoparathyroidism E Primary hypoparathyroidism F Osteoporosis G Osteomalacia H Paget’s disease I Familial benign hypercalcaemia ``` ``` Ca 3.1 (2.2–2.6 mmol/L) PTH 10.5 (0.8–8.5 pmol/L) ALP 165 (30–150 u/L) PO4 0.6 (0.8–1.2 mmol/L) Vitamin D 78 (60–105 nmol/L) ```

Answer 27

A Primary hyperparathyroidism Primary hyperparathyroidism (A) is caused by a parathyroid adenoma or parathyroid chief cell hyperplasia that leads to increased PTH production. Primary hyperparathyroidism leads to hypercalcaemia due to a raised PTH level. PTH achieves this by activating osteoclastic bone resorption (increasing blood ALP), stimulating calcium reabsorption in the kidney (with concurrent excretion of phosphate) and potentiating the action of the enzyme 1α hydroxylase in the kidney. 1α Hydroxylase acts on 25-hydroxyvitamin D3 to produce 1,25-dihydroxyvitamin D3 (calcitriol), which increases gut absorption of calcium.

Question 28

``` Calcium handling A Primary hyperparathyroidism B Secondary hyperparathyroidism C Tertiary hyperparathyroidism D Pseudohypoparathyroidism E Primary hypoparathyroidism F Osteoporosis G Osteomalacia H Paget’s disease I Familial benign hypercalcaemia ``` ``` Ca 2.1 (2.2–2.6 mmol/L) PTH 10.4 (0.8–8.5 pmol/L) ALP 190 (30–150 u/L) PO4 0.69 (0.8–1.2 mmol/L) Vitamin D 41 (60–105 nmol/L) ```

Answer 28

G Osteomalacia Osteomalacia (G; rickets in children) results from insufficient bone mineralization, secondary to vitamin D or phosphate deficiency. Low vitamin D causes hypocalcaemia, due to reduced 1,25-dihydoxyvitamin D3 production, and hence reduced reabsorption of calcium from the gut. Low blood calcium levels cause an increase in production of PTH in an attempt to normalize calcium. Therefore, calcium levels will either be low or inappropriately normal. Increased bone resorption will cause ALP levels to rise.

Question 29

``` Calcium handling A Primary hyperparathyroidism B Secondary hyperparathyroidism C Tertiary hyperparathyroidism D Pseudohypoparathyroidism E Primary hypoparathyroidism F Osteoporosis G Osteomalacia H Paget’s disease I Familial benign hypercalcaemia ``` ``` Ca 1.8 (2.2–2.6 mmol/L) PTH 9.6 (0.8–8.5 pmol/L) ALP 50 (30–150 u/L) PO4 1.9 (0.8–1.2 mmol/L) Vitamin D 82 (60–105 nmol/L) ```

Answer 29

I Familial benign hypercalcaemia Familial benign hypercalcaemia (I) is a genetic condition leading to raised blood calcium levels. The disease results from a mutation in the calcium receptor located on the parathyroid glands and kidneys. This receptor defect therefore leads to underestimation of calcium, causing an increased production of PTH, despite the raised calcium levels. It is important to distinguish these patients from hyperparathyroid patients as the management of these conditions differs. Receptor failure in the kidneys reduces calcium excretion, leading to a hypocalcuric state.

Question 30

``` Calcium handling A Primary hyperparathyroidism B Secondary hyperparathyroidism C Tertiary hyperparathyroidism D Pseudohypoparathyroidism E Primary hypoparathyroidism F Osteoporosis G Osteomalacia H Paget’s disease I Familial benign hypercalcaemia ``` ``` Ca 1.8 (2.2–2.6 mmol/L) PTH 0.69 (0.8–8.5 pmol/L) ALP 89 (30–150 u/L) PO4 1.5 (0.8–1.2 mmol/L) Vitamin D 76 (60–105 nmol/L) ```

Answer 30

E Primary hypoparathyroidism Primary hypoparathyroidism (E) is defined as dysfunction of the parathyroid glands leading to reduced production of PTH. As a result, the actions of PTH are blunted leading to reduced bone resorption as well as renal and gut calcium reabsorption. As a consequence there is hypocalcaemia and hyperphosphataemia. Other causes of hypocalcaemia include pseudoparathyroidism, vitamin D deficiency, renal disease (unable to make 1,25-dihydroxyvitamin D3), magnesium deficiency (magnesium required for PTH rise) and post-surgical (neck surgery may damage parathyroid glands).

Question 31

``` Plasma proteins A Bence–Jones protein B Carcino-embryonic antigen C Caeruloplasmin D Fibrinogen E Amylase F Ferritin G α-Fetoprotein H Albumin I CA125 ``` A 13-year-old boy presents to his GP with parotitis with pain in his testes. His previous history reveals an incomplete childhood vaccination record

Answer 31

E Amylase Amylase (E) is an enzyme that breaks down starch into maltose. Serum amylase levels are often elevated during inflammation involving the parotid glands (parotitis) as occurs in mumps. Amylase is produced in the salivary glands, the parotid gland being the largest producer of the enzyme. Inflammation of the parotid glands cause a release of amylase into the blood stream, hence elevating levels. Raised serum amylase levels are also used in the diagnosis of pancreatitis; the pancreas is another amylase producing site.

Question 32

``` Plasma proteins A Bence–Jones protein B Carcino-embryonic antigen C Caeruloplasmin D Fibrinogen E Amylase F Ferritin G α-Fetoprotein H Albumin I CA125 ``` A 50-year-old patient who has a 4-week history of tiredness undergoes a colonoscopy. Bleeding is noted in the large intestine.

Answer 32

F Ferritin Ferritin (F) is an intracellular protein responsible for the safe storage of iron, as free iron can be toxic to cells. Gastrointestinal bleeding may cause iron deficiency anaemia (microcytic anaemia), characterized haematologically by a reduced serum iron, raised total iron binding capacity and reduced ferritin. Ferritin levels will distinguish between other causes of microcytic anaemia: anaemia of chronic disease (raised ferritin) and thalassaemia (normal ferritin). As ferritin is an acute-phase protein, it will also be raised secondary to inflammation.

Question 33

``` Plasma proteins A Bence–Jones protein B Carcino-embryonic antigen C Caeruloplasmin D Fibrinogen E Amylase F Ferritin G α-Fetoprotein H Albumin I CA125 ``` A 62-year-old smoker with a history of ulcerative colitis presents to his GP with weight loss and tiredness. The patient admits noticing fresh blood mixed in with the stool.

Answer 33

A Bence–Jones protein Bence–Jones proteins (A) are monoclonal globular proteins that are a diagnostic feature of multiple myeloma. Multiple myeloma is defined as the proliferation of plasma cells in the bone marrow and is commonly associated with the elderly population. Malignant plasma cells produce monoclonal antibodies and/or κ or λ light chains (paraproteins). The light chains appear in the urine and can be detected by electrophoresis of a urine sample as a monoclonal band. Bence–Jones proteins are also a feature of Waldenstrom’s macroglobulinaemia and amyloid light chain amyloidosis.

Question 34

``` Plasma proteins A Bence–Jones protein B Carcino-embryonic antigen C Caeruloplasmin D Fibrinogen E Amylase F Ferritin G α-Fetoprotein H Albumin I CA125 ``` A 42-year-old woman presents to her GP with weight loss and abdominal pain. Bimanual examination reveals a mass in the left adnexa.

Answer 34

I CA125 CA-125 (cancer antigen 125; I) is a protein encoded by the MUC16 gene that may suggest the presence of ovarian cancer. Its low sensitivity and specificity prevents it from being a diagnostic marker but it is useful when used in conjunction with imaging modalities for the diagnosis of ovarian cancer. Many ovarian cancers are coelomic epithelial carcinomas and hence will express CA-125, which is a coelomic epithelium-related glycoprotein. CA-125 may be associated with endometrial, pancreatic and breast carcinomas but plasma levels are most elevated in ovarian cancer.

Question 35

``` Plasma proteins A Bence–Jones protein B Carcino-embryonic antigen C Caeruloplasmin D Fibrinogen E Amylase F Ferritin G α-Fetoprotein H Albumin I CA125 ``` A 15-year-old boy is brought in by his mother who has noted a change in his behaviour as well as a tremor. On slit lamp examination, Keiser–Fleischer rings are noted around the iris.

Answer 35

C Caeruloplasmin Caeruloplasmin (C) is a copper carrying protein encoded by the CP gene. Low plasma caeruloplasmin levels are associated with Wilson’s disease, an autosomal recessive condition in which there is an accumulation of copper within organs due to a defect in the copper transporter ATP7B (linking copper to caeruloplasmin). As a result caeruloplasmin is degraded in the blood stream. Clinical manifestations include neurological and psychiatric symptoms, and copper accumulation within the iris of the eyes leading to Keiser–Fleischer rings is pathognomonic.

Question 36

``` Vitamin deficiencies A Vitamin A B Vitamin B1 C Vitamin B2 D Vitamin B6 E Vitamin B12 F Vitamin C G Vitamin D H Vitamin E I Vitamin K ``` A 40-year-old patient with a history of Graves’ disease presents with bilateral weakness of her legs. On examination she is Babinski sign positive and blood tests reveal a megaloblastic anaemia.

Answer 36

E Vitamin B12 Vitamin B12 (cobalamin; E) deficiency may result from pathologies affecting the stomach or ileum, as well as pernicious anaemia. In pernicious anaemia, autoantibodies exist against intrinsic factor. Pernicious anaemia is also commonly associated with other autoimmune conditions, such as Graves’ disease. Anaemia is a common manifestation of vitamin B12 deficiency, with raised mean cell volume and hypersegmented neutrophils evident. Subacute combined degeneration of the cord can also result, causing ataxia and progressive weakness in limbs and trunk; Babinski sign may be positive.

Question 37

``` Vitamin deficiencies A Vitamin A B Vitamin B1 C Vitamin B2 D Vitamin B6 E Vitamin B12 F Vitamin C G Vitamin D H Vitamin E I Vitamin K ``` A 26-year-old man presents to his GP with a 5-month history of bleeding gums. Petechiae are also observed on the patient’s feet. The man admits he has had to visit his dentist recently due to poor dentition

Answer 37

F Vitamin C ``` Vitamin C (F) is a water soluble vitamin, essential for the hydroxylation of collagen. When deficiency of vitamin C is present, collagen is unable to form a helical structure and hence cannot produce cross-links. As a consequence, damaged vessels and wounds are slow to heal. Vitamin C deficiency results in scurvy, which describes both bleeding (gums, skin and joints) and bone weakness (microfractures and brittle bones) tendencies. Gum disease is also a characteristic feature. ```

Question 38

``` Vitamin deficiencies A Vitamin A B Vitamin B1 C Vitamin B2 D Vitamin B6 E Vitamin B12 F Vitamin C G Vitamin D H Vitamin E I Vitamin K ``` A 5-year-old girl who is a known cystic fibrosis sufferer is noted by her mother to have developed poor coordination of her hands and on examination her reflexes are absent. Blood tests also reveal anaemia.

Answer 38

H Vitamin E Vitamin E (tocopherol; H) is an important anti-oxidant which acts to scavenge free radicals in the blood stream. Deficiency leads to haemolytic anaemia as red blood cells encounter oxidative damage and are consequently broken down in the spleen. Spino-cerebellar neuropathy is also a manifestation, which is characterized by ataxia and areflexia. Vitamin E deficiency has also been suggested to increase the risk of ischaemic heart disease in later life, as low-density lipoproteins become oxidized perpetuating the atherosclerotic process.

Question 39

``` Vitamin deficiencies A Vitamin A B Vitamin B1 C Vitamin B2 D Vitamin B6 E Vitamin B12 F Vitamin C G Vitamin D H Vitamin E I Vitamin K ``` A 35-year-old man who is being treated for tuberculosis develops a rash on his trunk. Blood tests also reveal anaemia.

Answer 39

D Vitamin B6 Vitamin B6 (pyridoxine; D) is an essential co-factor in a number of metabolic pathways including the synthesis of amino acids and neurotransmitters. Common causes of deficiency include reduced dietary intake and isoniazid use for the treatment of tuberculosis. Vitamin B6 deficiency causes blood and skin abnormalities. Haematologically, vitamin B6 deficiency causes sideroblastic anaemia; dermatologically seborrhoeic dermatitis can occur. Diagnosis is made by determining erythrocyte levels of aspartate aminotransferase.

Question 40

``` Vitamin deficiencies A Vitamin A B Vitamin B1 C Vitamin B2 D Vitamin B6 E Vitamin B12 F Vitamin C G Vitamin D H Vitamin E I Vitamin K ``` A 40-year-old known alcoholic develops confusion and an unsteady gait. On examination bilateral lateral rectus palsy is noted.

Answer 40

B Vitamin B1 Vitamin B1 (thiamine; B) deficiency most commonly occurs in cases of alcoholism. The acute presentation of vitamin B1 deficiency is Wernicke’s encephalopathy, characterized by the triad of confusion, ophthalmoplegia and ataxia. Chronic alcoholism can lead to Korsakoff’s syndrome (amnesia and confabulation) and peripheral neuropathy. Beriberi can also occur, classified into wet and dry beriberi. Wet beriberi presents in a similar manner to heart failure, with cardiomegaly, oedema and dyspnoea. Dry beriberi involves an ascending impairment of nervous function involving both sensory (paraesthesia) and motor (foot drop, wrist drop and paralysis) components.

Question 41

``` Inborn errors of metabolism A Phenylketonuria (PKU) B Peroxisomal disorders C Maple syrup urine disease D Short-chain acyl-coenzyme A dehydrogenase (SCAD) deficiency E Von Gierke’s disease F Fabry’s disease G Urea cycle disorder H Homocystinuria I Galactosaemia ``` An 18-month-old girl is seen by the GP. Her mother is concerned by the child’s brittle hair and inability to walk. The mother reports her daughter has had two previous convulsions

Answer 41

H Homocystinuria Homocystinuria (H) is an amino acid disorder in which there is a deficiency in the enzyme cystathionine synthetase. This metabolic disorder presents in childhood with characteristic features such as very fair skin and brittle hair. The condition will usually lead to developmental delay or progressive learning difficulties. Convulsions, skeletal abnormalities and thrombotic episodes have also been reported. Management options include supplementing with vitamin B6 (pyridoxine) or maintaining the child on a low-methionine diet.

Question 42

``` Inborn errors of metabolism A Phenylketonuria (PKU) B Peroxisomal disorders C Maple syrup urine disease D Short-chain acyl-coenzyme A dehydrogenase (SCAD) deficiency E Von Gierke’s disease F Fabry’s disease G Urea cycle disorder H Homocystinuria I Galactosaemia ``` A fair haired 8-month-old baby, born in Syria, is seen together with his mother in the paediatric outpatient clinic. He is found to have developmental delay and a musty smell is being given off by the baby.

Answer 42

A Phenylketonuria (PKU) Phenylketonuria (PKU; A) is also an amino acid disorder. Children classically lack the enzyme phenylalanine hydroxylase, but other co-factors may be aberrant. Since the 1960s PKU has been diagnosed at birth using the Guthrie test but in some countries the test may not be available. The child will be fair-haired and present with developmental delay between 6 and 12 months of age. Later in life, the child’s IQ will be severely impaired. Eczema and seizures have also been implicated in the disease process.

Question 43

``` Inborn errors of metabolism A Phenylketonuria (PKU) B Peroxisomal disorders C Maple syrup urine disease D Short-chain acyl-coenzyme A dehydrogenase (SCAD) deficiency E Von Gierke’s disease F Fabry’s disease G Urea cycle disorder H Homocystinuria I Galactosaemia ``` A 9-month-old baby is seen in accident and emergency as her mother has reported that she has become ‘floppy’. The baby is found to be hypoglycaemic and on examination an enlarged liver and kidneys are noted.

Answer 43

E Von Gierke’s disease Von Gierke’s disease (E) is one of nine glycogen storage disorders, in which a defect in the enzyme glucose-6-phosphate results in a failure of mobilization of glucose from glycogen. The metabolic disease presents in infancy with hypoglycaemia. The liver is usually significantly enlarged and kidney enlargement can also occur. Other glycogen storage disorders (and enzyme defects) include Pompe’s (lysosomal α-glucosidase), Cori’s (amylo-1,6-glucosidase) and McArdle’s (phosphorylase); each disorder presents with varying degrees of liver and muscle dysfunction.

Question 44

``` Inborn errors of metabolism A Phenylketonuria (PKU) B Peroxisomal disorders C Maple syrup urine disease D Short-chain acyl-coenzyme A dehydrogenase (SCAD) deficiency E Von Gierke’s disease F Fabry’s disease G Urea cycle disorder H Homocystinuria I Galactosaemia ``` A 14-day-old girl of Jewish descent presents with lethargy, poor feeding and hypotonia. The paediatrician examining the child also notices excessively sweaty feet.

Answer 44

C Maple syrup urine disease Maple syrup urine disease (C) is an organic aciduria, a group of disorders that represent impaired metabolism of leucine, isoleucine and valine. As a result, toxic compounds accumulate causing toxic encephalopathy which manifests as lethargy, poor feeding, hypotonia and/or seizures. Characteristic of maple syrup urine disease are a sweet odour and sweaty feet. The gold standard diagnostic test is gas chromatography with mass spectrometry. Management involves the avoidance of the causative amino acids.

Question 45

``` Inborn errors of metabolism A Phenylketonuria (PKU) B Peroxisomal disorders C Maple syrup urine disease D Short-chain acyl-coenzyme A dehydrogenase (SCAD) deficiency E Von Gierke’s disease F Fabry’s disease G Urea cycle disorder H Homocystinuria I Galactosaemia ``` A 5-month-old boy is seen by the community paediatrician due to concerns of developmental delay. On examination dysmorphic features are noted, as well as a ‘cherry-red spot’ on the baby’s trunk.

Answer 45

F Fabry’s disease Fabry’s disease (F) is a lysosomal storage disorder in which there is deficiency in α-galactosidase. Presentation is almost always a child with developmental delay together with dysmorphia. Other findings may involve movement abnormalities, seizures, deafness and/or blindness. On examination, hepatosplenomegaly, pulmonary and cardiac problems may be noted. The pathognomonic feature of lysosomal storage disorders is the presence of a ‘cherry-red spot’.

Question 46

``` Therapeutic drug monitoring A Procainamide B Lithium C Methotrexate D Theophylline E Gentamicin F Carbamazepine G Cyclosporine H Phenytoin I Digoxin ``` A 35-year-old man presents to accident and emergency with feelings of lightheadedness and slurred speech. His wife mentions that the patient has been walking around ‘like a drunk’. The man’s blood pressure is found to be low.

Answer 46

H Phenytoin Phenytoin (H) is a commonly used anti-epileptic agent. Serum levels of phenytoin must be monitored due to its narrow therapeutic range (10–20 μg/mL). Phenytoin also exhibits saturation kinetics; a small rise in dose may lead to saturation of metabolism by CYP enzymes in the liver, hence producing a large increase in drug concentration in the blood as well as associated toxic effects. Phenytoin toxicity can lead to hypotension, heart block, ventricular arrhythmias and ataxia.

Question 47

``` Therapeutic drug monitoring A Procainamide B Lithium C Methotrexate D Theophylline E Gentamicin F Carbamazepine G Cyclosporine H Phenytoin I Digoxin ``` A 45-year-old woman is told she may be demonstrating signs of toxicity, 12 hours after being given an initial dose of medication. She has a coarse tremor and complains of feeling nauseous.

Answer 47

B Lithium Lithium (B) is a therapeutic agent used in the treatment of bipolar disorder. Drug monitoring is essential (12 hours post dose) due to its low therapeutic index as well as the potential life-threatening effects of toxicity. Lithium is excreted via the kidneys and therefore serum drug levels may increase (with potential toxicity) in states of low glomerular filtration rate, sodium depletion and diuretic use. Features of lithium toxicity include diarrhoea, vomiting, dysarthria and coarse tremor. Severe toxicity may cause convulsions, renal failure and possibly death.

Question 48

``` Therapeutic drug monitoring A Procainamide B Lithium C Methotrexate D Theophylline E Gentamicin F Carbamazepine G Cyclosporine H Phenytoin I Digoxin ``` A 65-year-old man being treated as an inpatient develops sudden onset ‘ringing in his ears’ as well as difficulty hearing.

Answer 48

E Gentamicin Gentamicin (E) is an aminoglycoside antibiotic, particularly useful against Gram-negative bacteria. It exhibits a low therapeutic index. Factors that may potentiate toxicity include dosage, kidney function (gentamicin is excreted through the kidneys) and other medications such as vancomycin. Gentamicin is an ototoxic and nephrotoxic agent and hence toxicity can lead to deafness and renal failure. Toxic effects on the ear are not limited to hearing, as the vestibular system is also affected, which may cause problems with balance and vision.

Question 49

``` Therapeutic drug monitoring A Procainamide B Lithium C Methotrexate D Theophylline E Gentamicin F Carbamazepine G Cyclosporine H Phenytoin I Digoxin ``` A 45-year-old woman is seen by her GP for a routine medications review. The patient complains of recent onset abdominal pain and tiredness. An electrocardiogram (ECG) reveals prolonged PR interval.

Answer 49

I Digoxin Digoxin (I) is an anti-arrhythmic agent used in the treatment of atrial fibrillation and atrial flutter. Symptoms of under-treatment and toxicity are similar. Toxicity commonly arises due to the narrow therapeutic index of the agent. Non-specific symptoms of toxicity include tiredness, blurred vision, nausea, abdominal pain and confusion. ECG changes may include a prolonged PR interval and bradycardia. As digoxin is excreted via the kidneys, renal failure may cause accumulation of digoxin.

Question 50

``` Therapeutic drug monitoring A Procainamide B Lithium C Methotrexate D Theophylline E Gentamicin F Carbamazepine G Cyclosporine H Phenytoin I Digoxin ``` A 45-year-old man presents to his GP for a routine medications review. The patient complains of recent diarrhoea and headaches. The GP notes the patient was treated with erythromycin for a community acquired pneumonia 1 week previous to the consultation.

Answer 50

D Theophylline Theophylline (D) is a drug used in the treatment of asthma and COPD. A low therapeutic index and wide variation in metabolism between patients lead to requirement for drug monitoring. Toxicity may manifest in a number of ways including nausea, diarrhoea, tachycardia, arrhythmias and headaches. Severe toxicity may lead to seizures. The toxic effects of theophylline are potentiated by erythromycin and ciprofloxacin. Without monitoring, many patients would be under-treated.