Chem Path EMQs

Question 1

Sodium handlingA EthanolB SIADHC FrusemideD Chronic kidney diseaseE Conn’s syndromeF DiarrhoeaG Congestive cardiac failureH Addison’s diseaseI HyperlipidaemiaA 50-year-old woman with known diabetes has a routine blood test whichdemonstrates 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 HyperlipidaemiaPseudo-hyponatraemia can occur in patients with hyperlipidaemia(I) or hyperproteinaemia. In such states, lipids and proteins willoccupy a high proportion of the total serum volume. Although thesodium concentrationin serum water is in fact normal, a lowersodium concentrationwill be detected due to dilution by increasedlipids and protein molecules. As a consequence, there is an apparenthyponatraemia.A spurious result due to the sample being taken fromthe drip arm can also cause pseudo-hyponatraemia.

Question 2

Sodium handlingA EthanolB SIADHC FrusemideD Chronic kidney diseaseE Conn’s syndromeF DiarrhoeaG Congestive cardiac failureH Addison’s diseaseI HyperlipidaemiaA 45-year-old man is seen by his specialist. His last blood and urine testsdemonstrated 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 diseaseA true hyponatraemic state occurs when the osmolality is simultaneouslylow. Chronic kidney disease (CKD; D) results in urinary proteinloss and hence oedema. A reduced circulating volume causes activationof the renin–angiotensin system, thereby raising blood sodium levels.This in turn causes release of antidiuretic hormone (ADH) from theposterior pituitary leading to water retention and hypervolaemichyponatraemia. Water reabsorption in the renal tubules increases urineosmolality (>20 mmol/L indicates a renal cause of hyponatraemia). CKDis also associated with hyperkalaemia and azotaemia.

Question 3

Sodium handlingA EthanolB SIADHC FrusemideD Chronic kidney diseaseE Conn’s syndromeF DiarrhoeaG Congestive cardiac failureH Addison’s diseaseI HyperlipidaemiaA 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 diseaseAddison’s disease (H) is also known as primary adrenal insufficiency(reduced aldosterone and cortisol); consequently there is a rise in theproduction of adrenocorticotropic hormone (ACTH). An impaired synthesisof aldosterone reduces reabsorption of sodium and increasesexcretion of potassium in the distal convoluted tubule and collectingducts of the kidney; this leads to a simultaneous hyponatraemia andhyperkalaemia. Reduced cortisol production causes hypoglycaemia dueto impaired gluconeogenesis. Clinical features of Addison’s diseaseinclude hyperpigmentation, postural hypotension and weight loss.

Question 4

Sodium handlingA EthanolB SIADHC FrusemideD Chronic kidney diseaseE Conn’s syndromeF DiarrhoeaG Congestive cardiac failureH Addison’s diseaseI HyperlipidaemiaA 30-year old woman is seen by her GP after a 5-day episode of productivecough and lethargy. The GP notes dullness on percussion of the patient’s leftlower 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 SIADHThe syndrome of inappropriate ADH secretion (B; SIADH) results fromthe excess release of ADH. In this case the clinical features suggestpneumonia is the cause, but the aetiologies of SIADH are numerous,including malignancy, meningitis and drugs (carbamazepine). Criteriato diagnose SIADH include the following:• Hyponatraemia 100 mmol/L• High urine sodium >20 mmol/L• Euvolaemia• No adrenal, renal or thyroid dysfunctionCharacteristically the urine osmolality is inappropriately high; in normalcircumstances if the plasma osmolality is low, the urine osmolalitywill stop rising as reduced ADH secretion prevents water retention. Asa rule of thumb in SIADH, urine osmolality is greater than plasmaosmolality.

Question 5

Sodium handlingA EthanolB SIADHC FrusemideD Chronic kidney diseaseE Conn’s syndromeF DiarrhoeaG Congestive cardiac failureH Addison’s diseaseI HyperlipidaemiaA 63-year-old man with chronic obstructive pulmonary disease (COPD) sees hisGP 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 failureCongestive cardiac failure (G) may present with shortness of breath, pittingperipheral oedema and/or raised jugular venous pulse (JVP). In thisscenario, shortness of breath may be masked by the patient’s COPD.The clinical picture together with the blood result demonstrating a lowsodium and low osmolality suggest a hypervolaemic hyponatraemia.This scenario can be differentiated from hypervolaemia as a result ofCKD (D) by the urine osmolality, which is less than 20 mmol/L in thisinstance, thereby suggesting a non-renal cause for the hyponatraemiaEthanol (A) may cause hyponatraemia in the context of a raised plasmaosmolality (>295 mmol/L). Other low molecular weight solutes that cancause hyponatraemia (when osmolality is raised) include mannitol andglucose.Frusemide (C) and other diuretics cause a hypovolaemic hyponatraemia.As well as a low plasma sodium and osmolality, the urine osmolality willbe greater than 20 mmol/L, signifying a renal cause of hyponatraemia.Conn’s syndrome (E), also known as primary aldosteronism, resultsfrom 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 osmolalitywill be lower than 20 mmol/L indicating an extra-renal cause ofhyponatraemia.

Question 6

Potassium handlingA Spurious sampleB AnorexiaC DiarrhoeaD Renal tubular acidosisE Insulin overdoseF Bartter syndromeG FrusemideH Renal failureI ACE inhibitorsA 15-year-old boy presents to accident and emergency with loss ofconsciousness. His blood sugars are found to be extremely low. Blood testsdemonstrate 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 overdoseInsulin overdose (E) in a diabetic patient will cause a redistributivehypokalaemia and concurrent metabolic alkalosis. Insulin causes a shiftof potassium ions from the extracellular space to the intracellular space,thereby lowering blood potassium levels. Metabolic alkalosis can alsocause a redistributive hypokalaemia; a reduced hydrogen ion concentrationin the blood causes increased intracellular hydrogen ion loss to increaseextracellular levels via Na+/H+ ATPase; potassium ions therefore diffuseintracellularly to maintain the electrochemical potential. Adrenaline andre-feeding syndrome also cause redistributive hypokalaemia.

Question 7

Potassium handlingA Spurious sampleB AnorexiaC DiarrhoeaD Renal tubular acidosisE Insulin overdoseF Bartter syndromeG FrusemideH Renal failureI ACE inhibitorsA 64-year-old man who is an inpatient on the Care of the Elderly ward is foundto 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 failureRenal failure (H) can lead to hyperkalaemia secondary to reduceddistalrenal delivery of sodium ions. As a consequence, there isreduced exchange of potassium ions via the Na/K ATPase pump inthe collectingduct, which thereby leads to accumulation of potassiumions in the blood and hence hyperkalaemia. An increase in aldosteronerelease will initially cause a compensatory loss of potassium ions;as renal failure progresses, this homeostatic mechanism will becomedecompensated and hyperkalaemia will result. Renal failure will alsobe reflected in the deranged urea and creatinine levels due to reducedexcretion.

Question 8

Potassium handlingA Spurious sampleB AnorexiaC DiarrhoeaD Renal tubular acidosisE Insulin overdoseF Bartter syndromeG FrusemideH Renal failureI ACE inhibitorsA 16-day-old baby girl is found to have low blood pressure. Urinary calciumlevels 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 syndromeBartter syndrome (F) is an autosomal recessive condition due to a defectin the thick ascending limb of the loop of Henle. It is characterized byhypokalaemia, alkalosis and hypotension. The condition may also leadto increased calcium loss via the urine (hypercalcuria) and the kidneys(nephrocalcinosis). Various genetic defects have been discovered; neonatalBartter syndrome is due to mutations in either the NKCC2 or ROMKgenes. In the associated milder Gitelman syndrome, the potassium transportingdefect is in the distal convoluted tubule of the kidney.

Question 9

Potassium handlingA Spurious sampleB AnorexiaC DiarrhoeaD Renal tubular acidosisE Insulin overdoseF Bartter syndromeG FrusemideH Renal failureI ACE inhibitorsA 32-year-old man presents to his GP for a check-up. His serum aldosterone isfound 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 inhibitorsACE inhibitors (I) will lead to hyperkalaemia due to reduced potassiumexcretion. ACE inhibitors antagonize the effect of angiotensin convertingenzyme, the enzyme which catalyzes the production of angiotensinII from angiotensin I. A decreased level of angiotensin II reduces theproduction of aldosterone in the adrenal glands, a key hormone causingthe excretion of potassium. Other causes of reduced excretion of potassiuminclude Addison’s disease, renal failure and potassium sparingdiuretics.

Question 10

Potassium handlingA Spurious sampleB AnorexiaC DiarrhoeaD Renal tubular acidosisE Insulin overdoseF Bartter syndromeG FrusemideH Renal failureI ACE inhibitorsA 68-year-old woman on the Care of the Elderly ward is found to have thefollowing 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 acidosisRenal tubular acidosis (D) occurs when there is a defect in hydrogenion secretion into the renal tubules. Potassium secretion into the renaltubules therefore increases to balance sodium reabsorption. This resultsin hypokalaemia with acidosis. Renal tubular acidosis is classifiedaccording to the location of the defect: type 1 (distal tubule), type 2(proximal tubule), type 3 (both distal and proximal tubules). Type 4results from a defect in the adrenal glands and is included in the classificationas it results in a metabolic acidosis and hyperkalaemia.

Question 11

Acid–base balanceA Metabolic acidosisB Metabolic acidosis withrespiratory compensationC Metabolic alkalosisD Metabolic alkalosis withrespiratory compensationE Respiratory acidosisF Respiratory acidosis withmetabolic compensationG Respiratory alkalosisH Respiratory alkalosis withmetabolic compensationI Mixed metabolic and respiratoryacidosispH 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 acidosisRespiratory acidosis (E) is defined by a low pH (acidosis) together witha high pCO2, due to carbon dioxide retention secondary to a pulmonary,neuromuscular or physical causes. There is no metabolic compensationin this case, suggesting this is an acute pathology; a compensatorymetabolic rise in HCO3 from the kidneys can take hours or days.This patient is also hypoxic with a low pO2. Causes of an acute respiratoryacidosis include an acute exacerbation of asthma, foreign bodyobstruction and cardiac arrest.

Question 12

Acid–base balanceA Metabolic acidosisB Metabolic acidosis withrespiratory compensationC Metabolic alkalosisD Metabolic alkalosis withrespiratory compensationE Respiratory acidosisF Respiratory acidosis withmetabolic compensationG Respiratory alkalosisH Respiratory alkalosis withmetabolic compensationI Mixed metabolic and respiratoryacidosispH 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 withrespiratory compensationMetabolic acidosis with respiratory compensation (B) occurs when pHis low (acidosis) and HCO3 is low with concurrent respiratory compensationby decreasing pCO2. The anion gap can differentiate betweencauses of metabolic acidosis (anion gap = [Na++ K+] – [Cl−+ HCO3−];normal range between 10 and 18 mmol/L). Causes of a raised anion gapcan be remembered by the mnemonic MUDPILES: methanol/metformin,uraemia, diabetic ketoacidosis, paraldehyde, iron, lactate, ethanol andsalicylates. Causes of a normal anion gap include diarrhoea, Addison’sdisease and renal tubular acidosis.

Question 13

Acid–base balanceA Metabolic acidosisB Metabolic acidosis withrespiratory compensationC Metabolic alkalosisD Metabolic alkalosis withrespiratory compensationE Respiratory acidosisF Respiratory acidosis withmetabolic compensationG Respiratory alkalosisH Respiratory alkalosis withmetabolic compensationI Mixed metabolic and respiratoryacidosispH 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 withrespiratory compensationMetabolic alkalosis with respiratory compensation (D) occurs when pH ishigh (alkalosis) and HCO3 is high with a compensatory reduction in respiratoryeffort that increases pCO2. As respiratory effort is reduced thereis the possibility of the patient becoming hypoxic. Causes of metabolicalkalosis include vomiting, potassium depletion secondary to diureticuse, burns and sodium bicarbonate ingestion. Respiratory compensationincrease serum CO2 concentration, which reduces pH back towards normal.

Question 14

Acid–base balanceA Metabolic acidosisB Metabolic acidosis withrespiratory compensationC Metabolic alkalosisD Metabolic alkalosis withrespiratory compensationE Respiratory acidosisF Respiratory acidosis withmetabolic compensationG Respiratory alkalosisH Respiratory alkalosis withmetabolic compensationI Mixed metabolic and respiratoryacidosispH 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 respiratoryacidosisMixed metabolic and respiratory acidosis (I) occurs when there is alow pH and a simultaneous high pCO2 and low HCO3. In the case of amixed metabolic and respiratory acidosis, the metabolic acidosis componentmay be due to conditions such as uraemia, ketones produced asa result of diabetes mellitus or renal tubular acidosis. The respiratoryacidosis component may be due to any cause of respiratory failure.Hence, this mixed picture may occur in a COPD patient with concurrentdiabetes mellitus.

Question 15

Acid–base balanceA Metabolic acidosisB Metabolic acidosis withrespiratory compensationC Metabolic alkalosisD Metabolic alkalosis withrespiratory compensationE Respiratory acidosisF Respiratory acidosis withmetabolic compensationG Respiratory alkalosisH Respiratory alkalosis withmetabolic compensationI Mixed metabolic and respiratoryacidosispH 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 alkalosisRespiratory alkalosis (G) is biochemically defined by a raised pH (alkalosis)and reduced pCO2. As previously mentioned, metabolic compensationcan take hours or days to occur. The primary pathology causingrespiratory alkalosis is hyperventilation which causes increased CO2 to be lost via the lungs. Causes of hyperventilation may be due to centralnervous system disease, for example stroke. Other causes of hyperventilationinclude anxiety (panic attack), pulmonary embolism and drugs(salicylates).

Question 16

Liver function testsA Alcohol abuseB Gilbert’s syndromeC GallstonesD Dublin–Johnson syndromeE Non-alcoholic fatty liver diseaseF Crigler–Najjar syndromeG Alcoholic liver diseaseH Paracetamol poisoningI Hepatocellular carcinomaAST 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 GallstonesGallstones (C) may be composed of cholesterol, bilirubin or mixed innature. The major complication of gallstones is cholestasis, wherebythe flow of bile is blocked from the liver to the duodenum. This resultsin right upper quadrant abdominal pain, nausea and vomiting. Othercauses of cholestasis include primary biliary cirrhosis, primary sclerosingcholangitis and abdominal masses compressing the biliary tree.Biochemically, cholestasis is defined by rises in GGT and ALP (obstructivepicture) that are greater than the rises in AST and ALT.

Question 17

Liver function testsA Alcohol abuseB Gilbert’s syndromeC GallstonesD Dublin–Johnson syndromeE Non-alcoholic fatty liver diseaseF Crigler–Najjar syndromeG Alcoholic liver diseaseH Paracetamol poisoningI Hepatocellular carcinomaAST 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 syndromeGilbert’s syndrome (B) is an autosomal dominant condition in whichthere is a mutation in the enzyme UDP glucuronosyl transferase whichreduces conjugation of bilirubin in the liver. As a consequence patientsexperience mild, intermittent jaundice. Jaundice in patients withGilbert’s syndrome may be precipitated by infection or starved states.Biochemistry will reveal that all liver function tests are normal apartfrom an isolated raised unconjugated bilirubin level, while conjugatedbilirubin is within the normal range.

Question 18

Liver function testsA Alcohol abuseB Gilbert’s syndromeC GallstonesD Dublin–Johnson syndromeE Non-alcoholic fatty liver diseaseF Crigler–Najjar syndromeG Alcoholic liver diseaseH Paracetamol poisoningI Hepatocellular carcinomaAST 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 diseaseNon-alcoholic fatty liver disease (NAFLD; E) is due to fatty depositsin the liver (steatosis), but where the underlying cause is not due toalcohol. In such circumstances, aetiological factors include obesity,diabetes, parenteral feeding and inherited metabolic disorders (glycogenstorage disease type 1). NAFLD may present with right upper quadrantpain or may be asymptomatic. Liver function tests will reveal raisedAST and ALT levels (AST:ALT ratio

Question 19

Liver function testsA Alcohol abuseB Gilbert’s syndromeC GallstonesD Dublin–Johnson syndromeE Non-alcoholic fatty liver diseaseF Crigler–Najjar syndromeG Alcoholic liver diseaseH Paracetamol poisoningI Hepatocellular carcinomaAST 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 poisoningParacetamol poisoning (H) is a common cause of acute liver failure. Theclinical features of acute liver failure reflect the diminished syntheticand metabolic functioning of the liver. Characteristics include reducedblood sugar level, metabolic acidosis, increased tendency to bleed andhepatic encephalopathy. Biochemical tests will reveal AST and ALT levelsgreater than 1000 IU/L. AST and ALT levels will be greater than GGTand ALP levels, reflecting the hepatic rather than obstructive picture ofthe pathology.

Question 20

Liver function testsA Alcohol abuseB Gilbert’s syndromeC GallstonesD Dublin–Johnson syndromeE Non-alcoholic fatty liver diseaseF Crigler–Najjar syndromeG Alcoholic liver diseaseH Paracetamol poisoningI Hepatocellular carcinomaAST 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 abuseAlcohol abuse (A) can lead to deranged liver function tests. In theabsence of underlying liver disease, biochemical investigation maydemonstrate an isolated rise in GGT. There may also be mild elevationsin AST and ALT, reflecting mild hepatic damage. Haematology resultswill show a macrocytic picture due to toxic effects of alcohol on thebone marrow. Isolated raised GGT levels may also occur due to theconsumption of enzyme-inducing drugs such as phenytoin, carbamazepineand phenobarbitone.

Question 21

Endocrine chemical pathologyA ProlactinomaB Grave’s diseaseC Addison’s diseaseD Schmidst’s syndromeE AcromegalyF Conn’s syndromeG Kallman’s syndromeH Secondary hypoaldosteronismI De Quervain’s thyroiditisA 38-year-old woman is referred by her GP to the Endocrine Clinic for furthertests after experiencing fatigue and orthostatic hypotension. After a positiveshort synACTHen test, a long synACTHen test reveals a cortisol of 750 nmol/Lafter 24 hours.

Answer 21

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

Question 22

Endocrine chemical pathologyA ProlactinomaB Grave’s diseaseC Addison’s diseaseD Schmidst’s syndromeE AcromegalyF Conn’s syndromeG Kallman’s syndromeH Secondary hypoaldosteronismI De Quervain’s thyroiditisA 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 syndromeConn’s syndrome (F) is defined as primary hyperaldosteronism secondaryto an aldosterone-producing adrenal adenoma. As a result of thehigh aldosterone levels produced there will be an increased excretionof potassium and reabsorption of sodium, leading to hypokalaemia andhypernatraemia. The increased delivery of sodium to the juxtaglomerularapparatus causes renin levels to be reduced. Plasma aldosteronewill either be raised or inappropriately normal (as ACTH is suppressed,aldosterone should physiologically be reduced).

Question 23

Endocrine chemical pathologyA ProlactinomaB Grave’s diseaseC Addison’s diseaseD Schmidst’s syndromeE AcromegalyF Conn’s syndromeG Kallman’s syndromeH Secondary hypoaldosteronismI De Quervain’s thyroiditisA 39-year-old woman sees an endocrinologist due to recent onsetgalactorrhoea. She denies recent child birth. Thyroid function tests are found tobe normal.

Answer 23

A ProlactinomaA prolactinoma (A) is a prolactin-producing tumour and is the mostprevalent pituitary tumour. Prolactinomas are classified according tosize: microprolactinoma 10 mm diameter. The clinical consequences of prolactinoma are dividedinto, first, those that occur as a result of increased prolactin productionand, second, effects due to the mass effect of the tumour. Hormonaleffects of prolactin include amenorrhoea, galactorrhoea and gynaecomastiain males. Mass effects of the tumour can lead to compression ofpituitary cells producing other hormones such as thyroid stimulatinghormone, growth hormone and ACTH.

Question 24

Endocrine chemical pathologyA ProlactinomaB Grave’s diseaseC Addison’s diseaseD Schmidst’s syndromeE AcromegalyF Conn’s syndromeG Kallman’s syndromeH Secondary hypoaldosteronismI De Quervain’s thyroiditisA 46-year-old man is seen by his GP after experiencing tremors, heatintolerance 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 diseaseGrave’s disease (B) is an autoimmune condition resulting in the productionof 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 unintentionalweight loss). There is a strong association with other autoimmune conditionssuch as vitiligo and type 1 diabetes mellitus.

Question 25

Endocrine chemical pathologyA ProlactinomaB Grave’s diseaseC Addison’s diseaseD Schmidst’s syndromeE AcromegalyF Conn’s syndromeG Kallman’s syndromeH Secondary hypoaldosteronismI De Quervain’s thyroiditisA 45-year-old woman is referred to an endocrinologist due to the appearanceof enlarged hands and feet as well as a protruding jaw. After conducting an oralglucose tolerance test, growth hormone levels are found to be 5 mU/L (

Answer 25

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

Question 26

Calcium handlingA Primary hyperparathyroidismB Secondary hyperparathyroidismC Tertiary hyperparathyroidismD PseudohypoparathyroidismE Primary hypoparathyroidismF OsteoporosisG OsteomalaciaH Paget’s diseaseI Familial benign hypercalcaemiaCa 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 diseasePaget’s disease (H) is a condition associated with impaired bone remodelling.New bone is larger but weak and prone to fracture. The pathogenesishas been postulated to be linked to paramyxovirus. All calciumblood studies will be normal apart from ALP, which will be raised.Paget’s disease is associated with extreme bone pain, bowing andchalk-stick fractures. Bossing of the skull may lead to an eighth cranialnerve palsy and hence hearing loss. X-ray findings include lytic andsclerotic lesions.

Question 27

Calcium handlingA Primary hyperparathyroidismB Secondary hyperparathyroidismC Tertiary hyperparathyroidismD PseudohypoparathyroidismE Primary hypoparathyroidismF OsteoporosisG OsteomalaciaH Paget’s diseaseI Familial benign hypercalcaemiaCa 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 hyperparathyroidismPrimary hyperparathyroidism (A) is caused by a parathyroid adenomaor parathyroid chief cell hyperplasia that leads to increased PTH production.Primary hyperparathyroidism leads to hypercalcaemia due toa raised PTH level. PTH achieves this by activating osteoclastic boneresorption (increasing blood ALP), stimulating calcium reabsorptionin the kidney (with concurrent excretion of phosphate) and potentiatingthe action of the enzyme 1α hydroxylase in the kidney. 1αHydroxylase acts on 25-hydroxyvitamin D3 to produce 1,25-dihydroxyvitaminD3 (calcitriol), which increases gut absorption of calcium.

Question 28

Calcium handlingA Primary hyperparathyroidismB Secondary hyperparathyroidismC Tertiary hyperparathyroidismD PseudohypoparathyroidismE Primary hypoparathyroidismF OsteoporosisG OsteomalaciaH Paget’s diseaseI Familial benign hypercalcaemiaCa 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 OsteomalaciaOsteomalacia (G; rickets in children) results from insufficient bonemineralization, secondary to vitamin D or phosphate deficiency. Lowvitamin D causes hypocalcaemia, due to reduced 1,25-dihydoxyvitaminD3 production, and hence reduced reabsorption of calcium from the gut.Low blood calcium levels cause an increase in production of PTH inan attempt to normalize calcium. Therefore, calcium levels will eitherbe low or inappropriately normal. Increased bone resorption will causeALP levels to rise.

Question 29

Calcium handlingA Primary hyperparathyroidismB Secondary hyperparathyroidismC Tertiary hyperparathyroidismD PseudohypoparathyroidismE Primary hypoparathyroidismF OsteoporosisG OsteomalaciaH Paget’s diseaseI Familial benign hypercalcaemiaCa 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 hypercalcaemiaFamilial benign hypercalcaemia (I) is a genetic condition leading toraised blood calcium levels. The disease results from a mutation in thecalcium receptor located on the parathyroid glands and kidneys. Thisreceptor defect therefore leads to underestimation of calcium, causingan increased production of PTH, despite the raised calcium levels. It is important to distinguish these patients from hyperparathyroid patientsas the management of these conditions differs. Receptor failure in thekidneys reduces calcium excretion, leading to a hypocalcuric state.

Question 30

Calcium handlingA Primary hyperparathyroidismB Secondary hyperparathyroidismC Tertiary hyperparathyroidismD PseudohypoparathyroidismE Primary hypoparathyroidismF OsteoporosisG OsteomalaciaH Paget’s diseaseI Familial benign hypercalcaemiaCa 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 hypoparathyroidismPrimary hypoparathyroidism (E) is defined as dysfunction of the parathyroidglands leading to reduced production of PTH. As a result,the actions of PTH are blunted leading to reduced bone resorption aswell as renal and gut calcium reabsorption. As a consequence there ishypocalcaemia and hyperphosphataemia. Other causes of hypocalcaemiainclude 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 maydamage parathyroid glands).

Question 31

Plasma proteinsA Bence–Jones proteinB Carcino-embryonic antigenC CaeruloplasminD FibrinogenE AmylaseF FerritinG α-FetoproteinH AlbuminI CA125A 13-year-old boy presents to his GP with parotitis with pain in his testes. Hisprevious history reveals an incomplete childhood vaccination record

Answer 31

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

Question 32

Plasma proteinsA Bence–Jones proteinB Carcino-embryonic antigenC CaeruloplasminD FibrinogenE AmylaseF FerritinG α-FetoproteinH AlbuminI CA125A 50-year-old patient who has a 4-week history of tiredness undergoes acolonoscopy. Bleeding is noted in the large intestine.

Answer 32

F FerritinFerritin (F) is an intracellular protein responsible for the safe storageof iron, as free iron can be toxic to cells. Gastrointestinal bleedingmay cause iron deficiency anaemia (microcytic anaemia), characterizedhaematologically by a reduced serum iron, raised total iron bindingcapacity and reduced ferritin. Ferritin levels will distinguish betweenother causes of microcytic anaemia: anaemia of chronic disease (raised ferritin) and thalassaemia (normal ferritin). As ferritin is an acute-phaseprotein, it will also be raised secondary to inflammation.

Question 33

Plasma proteinsA Bence–Jones proteinB Carcino-embryonic antigenC CaeruloplasminD FibrinogenE AmylaseF FerritinG α-FetoproteinH AlbuminI CA125A 42-year-old woman presents to her GP with weight loss and abdominal pain.Bimanual examination reveals a mass in the left adnexa.

Answer 33

I CA125CA-125 (cancer antigen 125; I) is a protein encoded by the MUC16gene that may suggest the presence of ovarian cancer. Its low sensitivityand specificity prevents it from being a diagnostic marker but it isuseful when used in conjunction with imaging modalities for the diagnosisof ovarian cancer. Many ovarian cancers are coelomic epithelialcarcinomas and hence will express CA-125, which is a coelomicepithelium-related glycoprotein. CA-125 may be associated with endometrial,pancreatic and breast carcinomas but plasma levels are mostelevated in ovarian cancer.

Question 34

Plasma proteinsA Bence–Jones proteinB Carcino-embryonic antigenC CaeruloplasminD FibrinogenE AmylaseF FerritinG α-FetoproteinH AlbuminI CA125A 15-year-old boy is brought in by his mother who has noted a change in hisbehaviour as well as a tremor. On slit lamp examination, Keiser–Fleischer ringsare noted around the iris.

Answer 34

C CaeruloplasminCaeruloplasmin (C) is a copper carrying protein encoded by the CPgene. Low plasma caeruloplasmin levels are associated with Wilson’sdisease, an autosomal recessive condition in which there is an accumulationof copper within organs due to a defect in the copper transporterATP7B (linking copper to caeruloplasmin). As a result caeruloplasminis degraded in the blood stream. Clinical manifestationsinclude neurological and psychiatric symptoms, and copper accumulationwithin the iris of the eyes leading to Keiser–Fleischer rings ispathognomonic.

Question 35

Vitamin deficienciesA Vitamin AB Vitamin B1C Vitamin B2D Vitamin B6E Vitamin B12F Vitamin CG Vitamin DH Vitamin EI Vitamin KA 40-year-old patient with a history of Graves’ disease presents with bilateralweakness of her legs. On examination she is Babinski sign positive and bloodtests reveal a megaloblastic anaemia.

Answer 35

E Vitamin B12Vitamin B12 (cobalamin; E) deficiency may result from pathologiesaffecting the stomach or ileum, as well as pernicious anaemia. In perniciousanaemia, autoantibodies exist against intrinsic factor. Perniciousanaemia is also commonly associated with other autoimmune conditions,such as Graves’ disease. Anaemia is a common manifestation ofvitamin B12 deficiency, with raised mean cell volume and hypersegmentedneutrophils evident. Subacute combined degeneration of thecord can also result, causing ataxia and progressive weakness in limbsand trunk; Babinski sign may be positive.

Question 36

Vitamin deficienciesA Vitamin AB Vitamin B1C Vitamin B2D Vitamin B6E Vitamin B12F Vitamin CG Vitamin DH Vitamin EI Vitamin KA 26-year-old man presents to his GP with a 5-month history of bleedinggums. Petechiae are also observed on the patient’s feet. The man admits he hashad to visit his dentist recently due to poor dentition

Answer 36

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

Question 37

Vitamin deficienciesA Vitamin AB Vitamin B1C Vitamin B2D Vitamin B6E Vitamin B12F Vitamin CG Vitamin DH Vitamin EI Vitamin KA 5-year-old girl who is a known cystic fibrosis sufferer is noted by her motherto have developed poor coordination of her hands and on examination herreflexes are absent. Blood tests also reveal anaemia.

Answer 37

H Vitamin EVitamin E (tocopherol; H) is an important anti-oxidant which acts toscavenge free radicals in the blood stream. Deficiency leads to haemolyticanaemia as red blood cells encounter oxidative damage and areconsequently broken down in the spleen. Spino-cerebellar neuropathyis also a manifestation, which is characterized by ataxia and areflexia.Vitamin E deficiency has also been suggested to increase the risk ofischaemic heart disease in later life, as low-density lipoproteins becomeoxidized perpetuating the atherosclerotic process.

Question 38

Vitamin deficienciesA Vitamin AB Vitamin B1C Vitamin B2D Vitamin B6E Vitamin B12F Vitamin CG Vitamin DH Vitamin EI Vitamin KA 35-year-old man who is being treated for tuberculosis develops a rash on histrunk. Blood tests also reveal anaemia.

Answer 38

D Vitamin B6Vitamin B6 (pyridoxine; D) is an essential co-factor in a number ofmetabolic pathways including the synthesis of amino acids and neurotransmitters.Common causes of deficiency include reduced dietaryintake and isoniazid use for the treatment of tuberculosis. Vitamin B6deficiency causes blood and skin abnormalities. Haematologically, vitaminB6 deficiency causes sideroblastic anaemia; dermatologically seborrhoeicdermatitis can occur. Diagnosis is made by determining erythrocytelevels of aspartate aminotransferase.

Question 39

Vitamin deficienciesA Vitamin AB Vitamin B1C Vitamin B2D Vitamin B6E Vitamin B12F Vitamin CG Vitamin DH Vitamin EI Vitamin KA 40-year-old known alcoholic develops confusion and an unsteady gait. Onexamination bilateral lateral rectus palsy is noted.

Answer 39

B Vitamin B1Vitamin B1 (thiamine; B) deficiency most commonly occurs in casesof alcoholism. The acute presentation of vitamin B1 deficiency isWernicke’s encephalopathy, characterized by the triad of confusion,ophthalmoplegia and ataxia. Chronic alcoholism can lead to Korsakoff’ssyndrome (amnesia and confabulation) and peripheral neuropathy.Beriberi can also occur, classified into wet and dry beriberi. Wet beriberipresents 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 40

Inborn errors of metabolismA Phenylketonuria (PKU)B Peroxisomal disordersC Maple syrup urine diseaseD Short-chain acyl-coenzyme Adehydrogenase (SCAD) deficiencyE Von Gierke’s diseaseF Fabry’s diseaseG Urea cycle disorderH HomocystinuriaI GalactosaemiaAn 18-month-old girl is seen by the GP. Her mother is concerned by the child’sbrittle hair and inability to walk. The mother reports her daughter has had twoprevious convulsions

Answer 40

H HomocystinuriaHomocystinuria (H) is an amino acid disorder in which there is a deficiencyin the enzyme cystathionine synthetase. This metabolic disorderpresents in childhood with characteristic features such as very fair skinand brittle hair. The condition will usually lead to developmental delayor progressive learning difficulties. Convulsions, skeletal abnormalitiesand thrombotic episodes have also been reported. Management optionsinclude supplementing with vitamin B6 (pyridoxine) or maintaining thechild on a low-methionine diet.

Question 41

Inborn errors of metabolismA Phenylketonuria (PKU)B Peroxisomal disordersC Maple syrup urine diseaseD Short-chain acyl-coenzyme Adehydrogenase (SCAD) deficiencyE Von Gierke’s diseaseF Fabry’s diseaseG Urea cycle disorderH HomocystinuriaI GalactosaemiaA fair haired 8-month-old baby, born in Syria, is seen together with his motherin the paediatric outpatient clinic. He is found to have developmental delay anda musty smell is being given off by the baby.

Answer 41

A Phenylketonuria (PKU)Phenylketonuria (PKU; A) is also an amino acid disorder. Children classicallylack the enzyme phenylalanine hydroxylase, but other co-factorsmay be aberrant. Since the 1960s PKU has been diagnosed at birth usingthe Guthrie test but in some countries the test may not be available. Thechild will be fair-haired and present with developmental delay between 6and 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 42

Inborn errors of metabolismA Phenylketonuria (PKU)B Peroxisomal disordersC Maple syrup urine diseaseD Short-chain acyl-coenzyme Adehydrogenase (SCAD) deficiencyE Von Gierke’s diseaseF Fabry’s diseaseG Urea cycle disorderH HomocystinuriaI GalactosaemiaA 9-month-old baby is seen in accident and emergency as her mother hasreported that she has become ‘floppy’. The baby is found to be hypoglycaemicand on examination an enlarged liver and kidneys are noted.

Answer 42

E Von Gierke’s diseaseVon Gierke’s disease (E) is one of nine glycogen storage disorders, inwhich a defect in the enzyme glucose-6-phosphate results in a failureof mobilization of glucose from glycogen. The metabolic diseasepresents in infancy with hypoglycaemia. The liver is usually significantlyenlarged and kidney enlargement can also occur. Other glycogenstorage disorders (and enzyme defects) include Pompe’s (lysosomalα-glucosidase), Cori’s (amylo-1,6-glucosidase) and McArdle’s (phosphorylase);each disorder presents with varying degrees of liver andmuscle dysfunction.

Question 43

Inborn errors of metabolismA Phenylketonuria (PKU)B Peroxisomal disordersC Maple syrup urine diseaseD Short-chain acyl-coenzyme Adehydrogenase (SCAD) deficiencyE Von Gierke’s diseaseF Fabry’s diseaseG Urea cycle disorderH HomocystinuriaI GalactosaemiaA 14-day-old girl of Jewish descent presents with lethargy, poor feeding andhypotonia. The paediatrician examining the child also notices excessively sweatyfeet.

Answer 43

C Maple syrup urine diseaseMaple syrup urine disease (C) is an organic aciduria, a group of disordersthat represent impaired metabolism of leucine, isoleucine andvaline. As a result, toxic compounds accumulate causing toxic encephalopathywhich manifests as lethargy, poor feeding, hypotonia and/orseizures. Characteristic of maple syrup urine disease are a sweet odourand sweaty feet. The gold standard diagnostic test is gas chromatographywith mass spectrometry. Management involves the avoidance ofthe causative amino acids.

Question 44

Inborn errors of metabolismA Phenylketonuria (PKU)B Peroxisomal disordersC Maple syrup urine diseaseD Short-chain acyl-coenzyme Adehydrogenase (SCAD) deficiencyE Von Gierke’s diseaseF Fabry’s diseaseG Urea cycle disorderH HomocystinuriaI GalactosaemiaA 5-month-old boy is seen by the community paediatrician due to concerns ofdevelopmental delay. On examination dysmorphic features are noted, as well asa ‘cherry-red spot’ on the baby’s trunk.

Answer 44

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

Question 45

Therapeutic drug monitoringA ProcainamideB LithiumC MethotrexateD TheophyllineE GentamicinF CarbamazepineG CyclosporineH PhenytoinI DigoxinA 35-year-old man presents to accident and emergency with feelings oflightheadedness and slurred speech. His wife mentions that the patient hasbeen walking around ‘like a drunk’. The man’s blood pressure is found to be low.

Answer 45

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

Question 46

Therapeutic drug monitoringA ProcainamideB LithiumC MethotrexateD TheophyllineE GentamicinF CarbamazepineG CyclosporineH PhenytoinI DigoxinA 45-year-old woman is told she may be demonstrating signs of toxicity, 12hours after being given an initial dose of medication. She has a coarse tremorand complains of feeling nauseous.

Answer 46

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

Question 47

Therapeutic drug monitoringA ProcainamideB LithiumC MethotrexateD TheophyllineE GentamicinF CarbamazepineG CyclosporineH PhenytoinI DigoxinA 65-year-old man being treated as an inpatient develops sudden onset‘ringing in his ears’ as well as difficulty hearing.

Answer 47

E GentamicinGentamicin (E) is an aminoglycoside antibiotic, particularly usefulagainst 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 medicationssuch as vancomycin. Gentamicin is an ototoxic and nephrotoxic agentand hence toxicity can lead to deafness and renal failure. Toxic effectson the ear are not limited to hearing, as the vestibular system is alsoaffected, which may cause problems with balance and vision.

Question 48

Therapeutic drug monitoringA ProcainamideB LithiumC MethotrexateD TheophyllineE GentamicinF CarbamazepineG CyclosporineH PhenytoinI DigoxinA 45-year-old woman is seen by her GP for a routine medications review.The patient complains of recent onset abdominal pain and tiredness. Anelectrocardiogram (ECG) reveals prolonged PR interval.

Answer 48

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

Question 49

Therapeutic drug monitoringA ProcainamideB LithiumC MethotrexateD TheophyllineE GentamicinF CarbamazepineG CyclosporineH PhenytoinI DigoxinA 45-year-old man presents to his GP for a routine medications review. Thepatient complains of recent diarrhoea and headaches. The GP notes the patientwas treated with erythromycin for a community acquired pneumonia 1 weekprevious to the consultation.

Answer 49

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