Chem Path

Question 1

A 29 year old man presents with eruptive xanthomas and a yellow discolouration to the palm. Blood tests reveal high total cholesterol and triglyceride levels. Genetic studies reveal ApoE2. What is the diagnosis?

Answer 1

Type 3 hyperlipoproteinemia

Human apolipoprotein E (ApoE) plays a crucial role in cholesterol and lipid metabolism. There are three major isoforms of ApoE: ApoE2, ApoE3, and ApoE4.

ApoE3 is the most common isoform found in the majority of the population.

ApoE4 is found with increased prevalence amongst those with Alzheimer’s disease and is thought to confer increased risk of the condition, whereas ApoE2 is thought to provide some protection against Alzheimer’s disease.

ApoE2 is also the cause of Type 3 hyperlipoproteinemia (Familial dysbetalipoproteinaemia), a condition characterised by increased total cholesterol and triglycerides.

Question 2

Which term describes the total number of particles per Kilogram of solution and is measured with an osmometer?

Answer 2

Osmolality

OsmolaLity is a measure of all the particles in a solution and is measured in mmol/kg.

OsmolaRity is an alternative measure of the particles in solution and has the units mmol/L. OsmolaRity is calculated using the formula below:

Osmolarity = 2(Na + K ) + urea + glucose

You may notice we do not need to know the concentration of negative ions in order to calculate osmolarity. The concentration of negative ions should equal the concentration of positive ions. Therefore we simply multiply the positive ions by 2.

OsmolaLity and OsmolaRity should roughly equal. If they do not this is called the Osmolar gap.

You may ask why we have two different but similar terms. OsmolaRity can be easily calculated from the concentration of electrolytes, however, because it is measured per 1 Litre of solvent it can vary with temperature. OsmolaLity requires measuring in a lab using an osmometer, but does not vary with temperature as it is measured per 1 Kilogram of solvent, and is therefore the preferred term for biological systems.

Question 3

In a patient with pseudopseudohypoparathyroidism, what would you expect the serum calcium level to be?

Answer 3

Normal

Pseudopseudohypoparathyroidism presents with the phenotypic appearances of Albright hereditary osteodystrophy but with normal biochemical findings and without resistance to parathyroid hormone (PTH).

Question 4

Name a drug used in the treatment of non-acute gout to reduce urate levels by increasing the fractional excretion of uric acid?

Answer 4

Probenecid

The aim of treatment in an acute flare up of gout is to reduce inflammation. First line is NSAIDs (eg. Diclofenac). Colchicine is also useful in reducing inflammation and acts by inhibiting polymerisation of tubulin to reduce migration of neutrophils. Glucocorticoids can be injected or given orally.

During the intervals between acute gout, the aim is to reduce urate levels. Patients should be advised to drink plenty of water and avoid dietary sources high in purines such as port wine and organ meats. Medications should also be reviewed and diuretics stopped. Allopurinol inhibits the enzyme xanthine oxidase to reduce urate synthesis, and Probenecid increases fractional excretion of uric acid.

Question 5

Which protein, found in blood plasma, exchanges triglycerides and cholesterol esters between lipoproteins?

Answer 5

Cholesteryl ester transfer protein (CETP)

Cholesteryl ester transfer protein (CETP) mediates the movement of cholesteryl ester from HDL into VLDL/LDL, and the movement of triglyceride from VLDL/LDL into HDL.

A defect in this protein is a cause of hyperalphalipoproteinemia 1 (HALP1) where there are raised levels of HDL-cholesterol.

Question 6

Lomitapide is a low density lipoprotein lowering drug.

What protein does Lomitapide inhibit?

Answer 6

Microsomal triglyceride transfer protein

Lomitapide is a lipid lowering medication used in the treatment of Familial Hypercholesterolemia.

Lomitapide acts by inhibiting Microsomal triglyceride transfer protein (MTP), thereby blocking the release of VLDL from the liver.

This in turn leads to reduced LDL levels.

Question 7

A 15 year old girl has a panic attack and is brought into A&E.

What acid base disturbance would you expect this patient to have?

Answer 7

Respiratory alkalosis

When interpreting blood gases always look at the pH first. Low pH indicates acidosis whereas high pH indicates alkalosis.

Next look at the CO2 and HCO3- to see if the change in pH has a metabolic or respiratory cause. There may be a mixed picture.

Respiratory compensation for a metabolic disturbance can occur quickly, however, metabolic compensation for respiratory pathology may take several days.

This allows you to distinguish between acute and chronic respiratory pathology.

Question 8

An asymptomatic 50 year old man attends his GP for a routine check-up. His fasting plasma glucose is measured as 6.7 mmol/L. What is the diagnosis?

Answer 8

Impaired fasting glucose

Impaired fasting glucose and impaired glucose tolerance describe the early metabolic abnormalities that precede diabetes but do not quite reach the cut-off for a diagnosis of diabetes.

Impaired fasting glucose and impaired glucose tolerance are both risk factors for future type 2 diabetes mellitus.

Impaired fasting glucose is defined as fasting plasma glucose between 6.1 - 6.9 mmol/L.

Impaired glucose tolerance is defined as 2 hour oral glucose tolerance test plasma glucose 7.8 - 11.0 mmol/L.

These patients are at high risk of developing future diabetes without lifestyle modification.

Question 9

An alcoholic is admitted for treatment of alcohol withdrawal. He is started on chlordiazepoxide and vitamin supplementation. The patient is found to have a low serum sodium and so the F1 starts him on IV fluids and his serum sodium rises rapidly. Over the next few days he becomes progressively lethargic, has trouble speaking, swallowing and walking.

What is the most likely diagnosis?

Answer 9

Central pontine myelinolysis

Central pontine myelinolysis is most commonly associated with rapid corrections of hyponatraemia. Quadraparesis and pseudobulbar palsy are characteristic and result from involvement of the corticospinal tracts in the pons and midbrain. Delirium tremens as a result of alcohol withdrawal or Wernicke’s encephalopathy from chronic malnutrition may have contributed to the patient’s symptoms. However, the question states he was started on Chlordiazepoxide and vitamin supplementation. Therefore this is less likely and would not explain all his symptoms. The rapid rise in serum sodium was the clue to this question.

Question 10

A 14 month old boy presents showing signs of delayed motor development and self-mutilation of the lips and fingers. He is found to have hyperuricaemia.

What enzyme is deficient in this condition?

Answer 10

HGPRT (Hypoxanthine-guanine phosphoribosyltransferase)

A young boy with developmental delay and self-mutilation of the lips and digits is characteristic of Lesch Nyhan syndrome. The X-linked disorder results from an absolute deficiency of HGPRT (or HPRT), the key enzyme in the salvage pathway of purine metabolism. This results in hyperuricaemia causing juvenile gout.

Question 11

ApoE4 classically gives an increased risk of developing which neurodegenerative condition?

Answer 11

Alzheimer’s disease

Human apolipoprotein E (ApoE) plays a crucial role in cholesterol and lipid metabolism. There are three major isoforms of ApoE: ApoE2, ApoE3, and ApoE4.

ApoE3 is the most common isoform found in the majority of the population.

ApoE4 is found with increased prevalence amongst those with Alzheimer’s disease and is thought to confer increased risk of the condition, whereas ApoE2 is thought to provide some protection against Alzheimer’s disease.

ApoE2 is also the cause of Type 3 hyperlipoproteinemia (Familial dysbetalipoproteinaemia), a condition characterised by increased total cholesterol and triglycerides.

Question 12

A patient with Bipolar Affective Disorder complains of excessive thirst and says they have been drinking more than usual and passing urine more frequently for some time now. Urine osmolality is low. Blood glucose is 5.1 mmol/L. You decide to do a water deprivation test. At the start of the test urine osmolality is 196 mOsmol/kg and after 4 hours urine osmolality remains low. After a subcutaneous injection of Desmopressin is given urine osmolality is 204 mOsmol/kg.

What is the most likely underlying diagnosis?

Answer 12

Nephrogenic Diabetes Insipidus

A thorough history is key in the diagnosis and management of a patient with Diabetes Insipidus (DI). A history of surgery or traumatic brain injury may indicate Cranial DI whereas Nephrogenic DI is commonly associated with long-term lithium therapy, for example in those with Bipolar Affective Disorder.

Blood glucose or urine dip is important to exclude Diabetes Mellitus and a fluid deprivation test can rule out Primary Polydipsia and help differentiate Nephrogenic and Cranial DI. Nephrogenic DI results from a resistance to ADH (Vasopressin) in the renal collecting duct causing reduced reabsorption of water. This leads to inappropriately dilute urine with low urine osmolality. In this question the water deprivation test confirms the DI is Nephrogenic in origin as the urine osmolality remains low after administration of Desmopressin, a Vasopressin analogue. In Cranial DI the urine osmolality would be expected to rise to >600 mOsmol/kg but smaller rises are sometimes seen in partial defects.

Question 13

Levels of what enzyme must be checked before starting azathioprine?

Answer 13

Thiopurine methyltransferase

Biochemical theory

Azathioprine is a powerful immunosuppressant drug used in the treatment of inflammatory bowel disease and other conditions.

TPMT deficiency is a congenital deficiency in an enzyme used to convert 6-mercaptopurine, a breakdown product of azathioprine, into less toxic, excretable metabolites. Approximately 1 in 300 people are deficient.

There are only two ways the body can clear 6-mercaptopurine: TPMT and the Xanthine Oxidase pathway.

If a patient is on both azathioprine and allopurinol AND they have TPMT deficiency - this leads to a buildup of toxic metabolites that may lead to profound leukopenia and death.

Clinical relevance:

All patients starting azathioprine need TPMT levels checked

Be cautious about patients on both allopurinol + azathioprine - have their TPMT levels been checked?

Question 14

Phytosterolemia (Sitosterolemia) is a disorder characterised by raised levels of plant sterol in the blood.

Name a gene which undergoes a mutation causing this disorder?

Answer 14

ABCG5

ABCG5 and ABCG8 are genes encoding transporter proteins sterolin-1 and -2 respectively. These proteins are involved in regulating the absorption and excretion of cholesterol and non-cholesterol sterols.

Non-cholesterol sterols, for examples plant sterols, are mostly excreted and are not retained. However, mutations of ABCG5 and ABCG8 cause more non-cholesterol sterols to be retained causing the autosomal recessive disorder Phytosterolemia (Sitosterolemia). The raised levels of non-cholesterol sterols presents with premature atherosclerosis and tendon xanthomas.

Question 15

The van den Bergh reaction is used to measure serum bilirubin via fractionation. What kind of bilirubin is measured with the direct reaction?

Answer 15

Conjugated

The van den Bergh reaction is used to measure serum bilirubin via fractionation.

The direct reaction measures conjugated bilirubin whereas a complete reaction measures total bilirubin.

The indirect reaction refers to the difference between these two and measures unconjugated bilirubin.

Question 16

What is the most common joint to be affected in acute gout?

Answer 16

1st metatarsophalangeal

Gout is a crystal arthropathy caused by the deposition of monosodium urate crystals in the synovium of joints. In chronic gout (tophaceous) there may also be deposition of crystals (tophi) around joints and at other locations such as the ear lobes. Acute gout (podagra) presents as a rapid build-up of severe pain in a red and swollen joint. The most common joint to be affected is the 1st metatarsophalangeal joint and it is more common in men.

Monosodium urate crystals are negatively birefringent which means under polarised light they appear orange when parallel to a red light filter and blue when perpendicular. This allows them to be differentiated from calcium pyrophosphate crystals of pseudogout which show positive birefringence.

Question 17

What enzyme would you classically expect to be raised in Paget’s disease of bone?

Answer 17

Alkaline Phosphatase

Paget’s disease of bone is a focal disorder of bone remodelling with increased bone turnover. This leads to localised areas of poorly organised bone overgrowth causing fractures and deformities. The only biochemical abnormality detected is a raised Alkaline Phosphatase (ALP) due to the increased action of osteoblasts. Patients may present with localised pain and warmth, loss of hearing and bowing of the legs.

Question 18

A 35 year old type 2 diabetic complains of skin changes around the back of her neck and in her armpits. On examination the skin appears dark and velvety. What is the most likely diagnosis?

Answer 18

Acanthosis nigricans

Acanthosis nigricans is a skin condition typically associated with insulin resistance, for example in those with diabetes, obesity and other endocrinopathies. Rarely, it can be due to a malignancy.

The affected skin is typically described as dark and velvety and is usually found in areas of skin folds and creases such as the armpits, groin and neck.

Question 19

A 24 year old gentleman is brought into hospital by ambulance. He was recovered by firefighters from a house fire. He has a reduced GCS (M6 V4 E4) and is confused. He has no visible burns and there is no obvious airway oedema. However, he has a cough productive of black sputum.

He is complaining about a severe headache and a bitter almond taste in his mouth.

Observations reveal he is tachycardic and hypertensive. An ECG shows first degree AV block.

What chemical compound is responsible for his symptoms?

Answer 19

Cyanide

Question 20

Cholestyramine is a cholesterol lowering drug. What does Cholestyramine bind to in the gut in order to cause the liver to break down more cholesterol?

Answer 20

Bile acids

Most bile acids are reabsorbed from the gut in the ileum and are then recycled back to the liver for secretion into the biliary system again. This enterohepatic circulation of bile acids minimises the conversion of cholesterol into new bile acids.

Cholestyramine binds to bile acids in the gut stopping them from being reabsorbed. The liver then has to convert greater amounts of cholesterol into bile acids in order to maintain adequate secretion of bile acids into the biliary system. Cholestyramine therefore acts as a cholesterol lowering drug.

Question 21

In familial hypocalciuric hypercalcaemia (FHH), which receptor has suffered a mutation?

Answer 21

Calcium Sensing Receptor

The calcium sensing receptor on the parathyroid glands regulates release of PTH. In FHH a mutation of this receptor causes it to be relatively insensitive to calcium. This results in a greater release of PTH in response to a normal calcium level. The mutation also causes reduced calcium loss in the urine (hypocalciuria). These two mechanisms together result in hypercalcaemia. FHH is also known as Familial Benign Hypercalcaemia as it is often asymptomatic and does not require treatment. FHH must be differentiated from primary hyperparathyroidism causing hypercalcaemia. A calcium/creatinine clearance ratio measured from a 24 hour urine collection tends to be lower in FHH than in primary hyperparathyroidism. Diagnosis of FHH can be confirmed with genetic testing of the CASR gene.

Question 22

A 24 year old lady is referred to a cardiologist. She has irregular yellow growths on her hands and one on her achilles tendon. The cardiologist informs her she has premature atherosclerosis. Blood tests show grossly raised levels of plant sterol in her blood. Which autosomal recessive disorder does she most likely have?

Answer 22

Phytosterolemia
ABCG5 and ABCG8 are genes encoding transporter proteins sterolin-1 and -2 respectively. These proteins are involved in regulating the absorption and excretion of cholesterol and non-cholesterol sterols.

Non-cholesterol sterols, for examples plant sterols, are mostly excreted and are not retained. However, mutations of ABCG5 and ABCG8 cause more non-cholesterol sterols to be retained causing the autosomal recessive disorder Phytosterolemia (Sitosterolemia). The raised levels of non-cholesterol sterols presents with premature atherosclerosis and tendon xanthomas.

Question 23

What protein is commonly measured clinically as a marker of liver synthetic function?

Answer 23

Albumin

Prothrombin time, bilirubin and albumin are all measures of liver function.

AST and ALT, classically part of LFTs (liver function tests) are in fact enzymes released when the liver is damaged and so are not technically measures of liver function.

Question 24

A 27 year old lady presents regularly to A&E with hypoglycaemia of an unknown cause. She lives with her partner who has type 1 diabetes.

Her serum insulin levels are measured as high.

The consultant is unsure whether this is factitious hypoglycaemia from taking her partner’s insulin, or whether there is an endogenous cause of excessive insulin.

Measurement of what molecule would confirm whether the excessive insulin is exogenous or endogenous?

Answer 24

C-peptide

C-peptide is a short chain of amino acids cleaved in the conversion of proinsulin to insulin. It is created in equimolar amounts to insulin making it useful in the investigation of hypoglycaemia.

Hypoglycaemia with high insulin and low C-peptide suggests an exogenous source of insulin. This may be in a type 1 diabetic or from surreptitious use of insulin.

Hypoglycaemia with high insulin and high C-peptide suggests an endogenous source of insulin. Causes include insulinoma and inborn errors of metabolism. Sulfonylureas, used to lower blood sugar in type 2 diabetes, may also cause hypoglycaemia with high C-peptide due to increased release of endogenously produced insulin.

Factitious hypoglycaemia may be caused by surreptitious use of insulin or sulfonylureas. A Sulfonylurea screen is useful in distinguishing an insulin-secreting tumour from surreptitious sulfonylurea ingestion.

Question 25

A patient with chronic kidney disease (CKD) has low calcium and raised phosphate. PTH levels are found to be high. What kind of hyperparathyroidism does this patient have?

Answer 25

Secondary Secondary hyperparathyroidism can be caused by any disorder that results in hypocalcaemia, with chronic kidney disease being a common example. CKD results in reduced vitamin D activation (due to reduced renal 1-alpha hydroxylation) and also reduced phosphate excretion. This in turn leads to hypocalcaemia and secondary hyperparathyroidism as a response.

Question 26

A patient with acute gout undergoes arthrocentesis of the affected joint. What kind of birefringence is shown by a monosodium urate crystal under polarised light?

Answer 26

Negative Gout is a crystal arthropathy caused by the deposition of monosodium urate crystals in the synovium of joints. In chronic gout (tophaceous) there may also be deposition of crystals (tophi) around joints and at other locations such as the ear lobes. Acute gout (podagra) presents as a rapid build-up of severe pain in a red and swollen joint. The most common joint to be affected is the 1st metatarsophalangeal joint and it is more common in men. Monosodium urate crystals are negatively birefringent which means under polarised light they appear orange when parallel to a red light filter and blue when perpendicular. This allows them to be differentiated from calcium pyrophosphate crystals of pseudogout which show positive birefringence.

Question 27

Which enzyme has reduced activity in Gilbert’s syndrome and is responsible for the elevated unconjugated billirubin levels?

Answer 27

UDP glucuronyl transferase Gilbert’s syndrome is an inherited metabolic disorder and common cause of isolated unconjugated hyperbilirubinaemia. It is caused by defective conjugation of bilirubin in the liver but liver function is otherwise unaffected. Jaundice is often precipitated by fasting or periods of physiological stress. Haemolysis may also cause raised unconjugated bilirubin, and this must be excluded before a diagnosis of Gilbert’s can be made.

Question 28

Which enzyme forms the rate limiting step in de novo purine synthesis?

Answer 28

PAT Phosphoribosyl pyrophosphate amidotransferase (PAT) is the enzyme responsible for the conversion of PRPP into PRA. This is the rate limiting step in the de novo synthesis of purines. Guanylic acid (GMP) and adenylic acid (AMP) exert negative feedback on PAT.

Question 29

A patient is hypocalcaemic, has an elevated serum phosphate and has an elevated parathyroid hormone (PTH). Upon examination you notice they have short 4th and 5th metacarpals. What is the most likely diagnosis?

Answer 29

Pseudohypoparathyroidism The endocrinologist Fuller Albright was first to suggest pseudohypoparathyroidism results from an inherited resistance to PTH. He also identified the characteristic phenotypic appearance amongst these patients which includes short 4th and 5th metacarpals, obesity and rounded facies. This syndrome is now known as Albright hereditary osteodystrophy.

Question 30

A patient presents to A&E with a red swollen joint at the base of their big toe. They say it is exquisitely painful. Following arthrocentesis, microscopy shows needle shaped crystals. Under polarised light, what colour would you expect these needle shaped crystals to appear when parallel to a red filter?

Answer 30

Orange Gout is a crystal arthropathy caused by the deposition of monosodium urate crystals in the synovium of joints. In chronic gout (tophaceous) there may also be deposition of crystals (tophi) around joints and at other locations such as the ear lobes. Acute gout (podagra) presents as a rapid build-up of severe pain in a red and swollen joint. The most common joint to be affected is the 1st metatarsophalangeal joint and it is more common in men. Monosodium urate crystals are negatively birefringent which means under polarised light they appear orange when parallel to a red light filter and blue when perpendicular. This allows them to be differentiated from calcium pyrophosphate crystals of pseudogout which show positive birefringence.

Question 31

In the liver which cytochrome P450 enzyme catalyses the first step in the formation of bile acids via the classical pathway?

Answer 31

Cholesterol 7 alpha-hydroxylase Bile acid synthesis from cholesterol occurs in the liver via two different pathways; the classical pathway and alternative pathway. The classical pathway begins with the conversion of cholesterol into 7-alpha-hydroxycholesterol. This is the first and rate limiting step in the classical pathway and is catalysed by the cytochrome P450 enzyme cholesterol 7 alpha-hydroxylase (CYP7A1).

Question 32

A patient presents with hyperkalaemia and changes are detected on his ECG. What should be given intravenously as a cardioprotective measure?

Answer 32

Calcium Gluconate Severe hyperkalaemia with ECG changes requires urgent administration of calcium gluconate to reduce myocardial excitability. This is only temporary and does not lower serum potassium levels. To lower the potassium level, an intravenous injection of insulin with dextrose is given. This acts to drive potassium into cells. Salbutamol can act to reduce potassium in a similar way. These are also only temporary. The cause of the hyperkalaemia must also be addressed along with any underlying acidosis.

Question 33

What is the name of the cholesterol transport channel targeted by the drug Ezetimibe?

Answer 33

NPC 1L1 NPC1L1 (Niemann-Pick C1-like 1) transporter is found on epithelial cells of the GI tract and hepatocytes and is involved in the absorption of cholesterol from the gut. Ezetimibe is a sterol absorption inhibitor which targets the NPC1L1 transporter. Ezetimibe results in lower blood cholesterol and can be prescribed alongside a statin.

Question 34

A 16 year old presents to A&E following an overdose of medications from the family medicine cabinet 4 hours ago. His mother says he took 20 of her antidepressant tablets. Observations show he is tachycardic and hypotensive with a GCS of 14. He has dilated pupils, an ataxic gait and has very flushed hands and feet. He says he feels very thirsty and has a dry mouth. An ECG shows first degree heart block with tachycardia. What class of medication is he likely to have overdosed on?

Answer 34

Tricyclic Antidepressants

Question 35

Looser’s zones are a pathognomonic X-ray finding of which condition?

Answer 35

Osteomalacia Looser’s zones, also known as milkman fractures, are pseudofractures lying perpendicular to the surface of the bone. They are seen in osteomalacia as a result of defective bone mineralisation and are often bilateral and symmetrical.

Question 36

What class of drug must not be co-administered with azathioprine in individuals with TPMT deficiency, else a potentially fatal buildup of toxic metabolites may occur?

Answer 36

Xanthine Oxidase inhibitors Biochemical theory Azathioprine is a powerful immunosuppressant drug used in the treatment of inflammatory bowel disease and other conditions. TPMT deficiency is a congenital deficiency in an enzyme used to convert 6-mercaptopurine, a breakdown product of azathioprine, into less toxic, excretable metabolites. Approximately 1 in 300 people are deficient. There are only two ways the body can clear 6-mercaptopurine: TPMT and the Xanthine Oxidase pathway. If a patient is on both azathioprine and allopurinol AND they have TPMT deficiency - this leads to a buildup of toxic metabolites that may lead to profound leukopenia and death. Clinical relevance: All patients starting azathioprine need TPMT levels checked Be cautious about patients on both allopurinol + azathioprine - have their TPMT levels been checked?

Question 37

A 9 year old boy presents to the GP with enlarged orange coloured tonsils. Examination elicits a peripheral neuropathy and blood tests show very low plasma HDL levels. What is the most likely diagnosis?

Answer 37

Tangier disease Tangier disease is an inherited disorder caused by mutations in the ABCA1 gene. This prevents the release of cholesterol and lipids from cells which results in them accumulating in certain organs. This may present as hepatomegaly, splenomegaly, or classically as enlarged orange tonsils in children. The condition is characterised by low HDL levels in the blood conferring an increased risk of cardiovascular disease.

Question 38

What kind of inheritance is shown by the Multiple Endocrine Neoplasia syndromes?

Answer 38

Autosomal Dominant he Multiple Endocrine Neoplasias (MEN) describe syndromes of associated neoplasias which are inherited in an autosomal dominant fashion. MEN 1 Pituitary adenoma Parathyroid hyperplasia Pancreatic tumours Think MEN 1 = PPP MEN 2A Parathyroid hyperplasia Medullary thyroid carcinoma Phaeochromocytoma Think all the Cs: Calcitonin (medullary thyroid cancer), Calcium (Parathyroid hyperplasia) and Catecholamines (Phaeo) MEN 2B Medullary thyroid carcinoma Phaeochromocytoma Marfanoid body habitus Mucosal neuromas Think B is for Big (marfanoid) and Belly problems (mucosal neuromas)

Question 39

What vitamin converts cyanide to a renally cleared, less toxic, metabolite and is the first line medication for cyanide poisoning?

Answer 39

Hydroxocobalamin

Question 40

A 43 year old lady with Type II Diabetes and previous suicidal ideation presents to A&E confused and drowsy. She is fluctuating in and out of consciousness. She appears sweaty and is shaking. Her blood sugar is 1.3 mmol/L. She has high levels of insulin and a high C-peptide level. What investigation should be performed to exclude a factitious hypoglycaemia?

Answer 40

Blood sulfonylurea levels C-peptide is a short chain of amino acids cleaved in the conversion of proinsulin to insulin. It is created in equimolar amounts to insulin making it useful in the investigation of hypoglycaemia. Hypoglycaemia with high insulin and low C-peptide suggests an exogenous source of insulin. This may be in a type 1 diabetic or from surreptitious use of insulin. Hypoglycaemia with high insulin and high C-peptide suggests an endogenous source of insulin. Causes include insulinoma and inborn errors of metabolism. Sulfonylureas, used to lower blood sugar in type 2 diabetes, may also cause hypoglycaemia with high C-peptide due to increased release of endogenously produced insulin. Factitious hypoglycaemia may be caused by surreptitious use of insulin or sulfonylureas. A Sulfonylurea screen is useful in distinguishing an insulin-secreting tumour from surreptitious sulfonylurea ingestion.

Question 41

A 26 year old man presents to his GP with a yellow nodule on his achilles tendon. You notice a bluey grey ring around his cornea and yellow irregularly shaped deposits around his eyelids. Low density lipoprotein (LDL) is raised whereas high density lipoprotein (HDL) and triglycerides are normal. Genetic studies reveal a LDL receptor mutation. What is the diagnosis?

Answer 41

Familial Hypercholesterolemia LDL receptor mutations are a common genetic defect underlying Familial hypercholesterolemia. The LDL receptor usually removes LDL from the circulation and so the disorder results in high levels of LDL predisposing to early atherosclerotic disease.

Question 42

A 15 year old is found unconscious next to an opened packet of pills by her friend. She is brought into the emergency department. Her breathing is shallow, she is tachycardic, tachypnoeic. Her GCS is 9. An airway adjunct is placed. On closer examination she has a fine tremor and is sweaty. Her friend said that she seemed drunk before she lost consciousness. What is the most important blood test in the assessment of an unconscious patient?

Answer 42

Blood glucose level In the management of an unwell patient - don't forget your A-E approach. Anyone who is unconscious and you don't know why should have their blood glucose checked. This may be either from a capilary blood glucose or from a ABG/VBG. In this example, the tablets were sulphonylureas (though you wouldn't know that from the question) and the overdose therefore has precipitated a hypogylcaemic episode.

Question 43

A 23 year old woman is admitted to Intensive Care with a BMI of 13.7 for treatment of her Anorexia Nervosa. She is started on a strict diet by the ICU team and is only allowed occasional visitors. After a few days she becomes increasingly confused and reports severe palpitations. Blood tests show low levels of potassium, phosphate and magnesium. What is the most likely diagnosis?

Answer 43

Refeeding syndrome Refeeding syndrome describes the physiological consequences of rapid reintroduction of nutrition to a chronically malnourished person. This causes fluid shifts which result in electrolyte abnormalities. Refeeding syndrome can lead to cardiac failure and is potentially fatal.

Question 44

A patient with small cell lung cancer is found to be hyponatraemic. They are clinically euvolaemic with low serum osmolality and high urine osmolality. 9am cortisol and TFTs are normal. What is the most likely underlying diagnosis?

Answer 44

Syndrome of Inappropriate Anti Diuretic Hormone SIADH is a diagnosis of exclusion. An inappropriately high level of ADH (Vasopressin) causes excessive activation of the V2 receptor in the collecting duct, resulting in water reabsorption. It can be caused by a range of underlying pathologies including malignancies, disorders of the central nervous system and certain drugs. Small cell lung cancer is a common malignant cause of SIADH. Management of SIADH is initially aimed at correcting the hyponatraemia and includes fluid restriction and treating the cause. Tolvaptan, a V2 receptor antagonist, has been shown to be effective in persistent SIADH resistant to fluid restriction but is expensive.

Question 45

A 50 year old obese Indian lady is concerned about diabetes which runs in her family. She complains of increased thirst and urinary frequency. Above or equal to what HbA1c value (mmol/mol) would confirm a diagnosis of diabetes?

Answer 45

48 HbA1c is a measure of glycated haemoglobin and gives an average of blood glucose over the past 3 months. HbA1c below 42 mmol/mol (6.0%) is considered normal, 48 mmol/mol (6.5%) or greater suggests diabetes. In symptomatic individuals, diabetes can be diagnosed from a single HbA1c or fasting plasma glucose, although a second test may be advisable. However in asymptomatic individuals, diabetes cannot be diagnosed from a single abnormal HbA1c or fasting plasma glucose.

Question 46

A 30 year old type 1 diabetic presents to A&E with vomiting and abdominal pain. Arterial blood gas shows: pH: 7.31 (NR: 7.35-7.45) PaO2: 13 (NR: 11-13 kPa on 21% FiO2) PaCO2: 4.9 kPa (NR: 4.7-6.0 kPa) HCO3-: 16 mmol/L (NR: 22-26 mEq/L) How would you describe this patient’s acid base disturbance?

Answer 46

Metabolic acidosis When interpreting blood gases always look at the pH first. Low pH indicates acidosis whereas high pH indicates alkalosis. Next look at the CO2 and HCO3- to see if the change in pH has a metabolic or respiratory cause. There may be a mixed picture. Respiratory compensation for a metabolic disturbance can occur quickly, however, metabolic compensation for respiratory pathology may take several days. This allows you to distinguish between acute and chronic respiratory pathology.

Question 47

Alendronate is an example of what kind of drug?

Answer 47

Bisphosphonate Bisphosphonates reduce bone turnover and hence can prevent progression of osteoporosis. Examples include alendronate (alendronic acid). Bisphosphonates do not directly increase bone density. The only treatment that directly increases bone density in osteoporosis is denosumab.

Question 48

An elderly lady living in a care home has limited mobility and rarely leaves home. Blood tests find low vitamin D, calcium and phosphate with high PTH and ALP. What is the most likely diagnosis?

Answer 48

Osteomalacia Osteomalacia results from incomplete mineralisation of bone in adults. It is common in the elderly with vitamin D deficiency being the most common cause. Rickets also results from defective bone mineralisation but occurs in children prior to growth plate closure. Osteoporosis is caused by a loss of bone mass rather than mineralisation, and therefore the biochemistry is normal. Osteoporosis is an age related process that particularly affects women post-menopause. Those with early menopause or who suffered from childhood illness are at increased risk. It is asymptomatic and usually presents first as a fracture, typically of the neck of femur, vertebra or wrist.

Question 49

Anion gap is the difference between the principally measured cations and anions in the blood. Calculation of anion gap most often includes two cations and two anions. The two cations are Na+ and K+. The two anions are HCO3- and what other ion?

Answer 49

Chloride Anion gap is the difference between the principally measured cations and anions in the serum. It is measured by subtracting the chloride and bicarbonate concentrations from the sodium and potassium concentrations. Sometimes potassium is excluded. Normal range is typically 14-18 mmol/L but this may vary between labs. Anion gap = (Na+ + K+) - (Cl- + HCO3-) The total number of cations should equal the total number of anions in order for net charge to be 0. This makes anion gap useful in the investigation of acid base disorders and indicates whether there are changes in the unmeasured ions in the blood. A metabolic acidosis with high anion gap may be due to the presence of ketones in diabetic ketoacidosis. Bicarbonate acts as a buffer against the increased ketoacids. Consequently, reduced bicarbonate causes the anion gap to increase. Low anion gap is rarer but may be caused by hypoalbuminaemia. Albumin is an anion and so reduced levels cause other negatively charged ions to be retained contributing to a lower anion gap.

Question 50

Bilirubin is secreted into the gut via the biliary tree. What do bacteria in the gut convert bilirubin into which gives stool its characteristic brown colour?

Answer 50

Stercobilin Bilirubin metabolism begins with red blood cell breakdown releasing unconjugated bilirubin. Unconjugated bilirubin is not water soluble and so is difficult to excrete. The liver converts unconjugated bilirubin to conjugated bilirubin which is water soluble. Conjugated bilirubin is released into the gut via the biliary tree where gut organisms convert it into urobilinogen, stercobilinogen and eventually stercobilin. Stercobilin gives stool its brown colour. Urobilinogen may be reabsorbed from the gut and reaches the kidney where it is excreted in the urine.

Question 51

An ECG shows bradycardia, P wave depression and tall peaked T waves. What electrolyte abnormality is most likely responsible for these ECG changes?

Answer 51

Hyperkalaemia Hyperkalaemia is usually diagnosed from blood levels but it can also be suspected from ECG changes. Typical ECG changes in hyperkalaemia include tall peaked (tented) T waves, a shortened QT interval or loss of P waves. Eventually this may progress to a sinusoidal rhythm and death.

Question 52

What is the volume status of a patient with normal skin turgor, wet mucous membranes, capillary refill time of 2 seconds and a jugular venous pressure measured 7cm above the right atrium?

Answer 52

Euvolaemic

Question 53

In sarcoidosis, production of which enzyme by granulomatous tissue can lead to hypercalcaemia?

Answer 53

1 alpha hydroxylase The granulomatous tissue seen in sarcoidosis has been known to increase activation of vitamin D via production of the enzyme 1 alpha hydroxylase normally expressed in the kidney. The raised vitamin D leads to an increase in absorption of calcium from the gut causing hypercalcaemia. Production of PTH-related-peptide (PTHrP) is another mechanism by which the granulomatous tissue can cause hypercalcaemia.

Question 54

A 14 year old type 1 diabetic presents to A&E with abdominal pain and vomiting. He realises his insulin pump has stopped working and so he has not received any insulin for some time. How do you expect the anion gap to have changed in this patient, relative to the normal range?

Answer 54

Raised Anion gap is the difference between the principally measured cations and anions in the serum. It is measured by subtracting the chloride and bicarbonate concentrations from the sodium and potassium concentrations. Sometimes potassium is excluded. Normal range is typically 14-18 mmol/L but this may vary between labs. Anion gap = (Na+ + K+) - (Cl- + HCO3-) The total number of cations should equal the total number of anions in order for net charge to be 0. This makes anion gap useful in the investigation of acid base disorders and indicates whether there are changes in the unmeasured ions in the blood. A metabolic acidosis with high anion gap may be due to the presence of ketones in diabetic ketoacidosis. Bicarbonate acts as a buffer against the increased ketoacids. Consequently, reduced bicarbonate causes the anion gap to increase. Low anion gap is rarer but may be caused by hypoalbuminaemia. Albumin is an anion and so reduced levels cause other negatively charged ions to be retained contributing to a lower anion gap.

Question 55

A young man is brought to the emergency department confused. He is mumbling nonsensical phrases and hyperventilating. The paramedics state he was found next to a number of white, circular pills however they were unable to determine what these were. A panel of bloods reveals normal kidney function, but a low bicarbonate (17, NR 22-28) . A head CT was unremarkable. Urine Drug Screen negative. Blood Alcohol levels negative. An ABG reveals a pH of 7.5 (NR 7.35-7.45) What drug is the patient likely to have overdosed on?

Answer 55

Salicylates

Question 56

Which drug, used in the treatment of acute gout to reduce inflammation, acts by inhibiting polymerisation of tubulin to reduce motility of neutrophils?

Answer 56

Colchicine The aim of treatment in an acute flare up of gout is to reduce inflammation. First line is NSAIDs (eg. Diclofenac). Colchicine is also useful in reducing inflammation and acts by inhibiting polymerisation of tubulin to reduce migration of neutrophils. Glucocorticoids can be injected or given orally. During the intervals between acute gout, the aim is to reduce urate levels. Patients should be advised to drink plenty of water and avoid dietary sources high in purines such as port wine and organ meats. Medications should also be reviewed and diuretics stopped. Allopurinol inhibits the enzyme xanthine oxidase to reduce urate synthesis, and Probenecid increases fractional excretion of uric acid.

Question 57

A patient presents to GP complaining of muscle spasms and tingling in their hands and feet. The doctor suspects an electrolyte abnormality and tests for Trousseau's sign. After a few minutes the patient’s wrist and metacarpophalangeal joints flex. There is also extension of the interphalangeal joints and adduction of the thumb. What electrolyte abnormality, if any, are these results suggestive of?

Answer 57

Hypocalcaemia Calcium is important for nerve and muscle function. Very low serum calcium (<2.2) can result in neuromuscular excitability. Trousseau’s sign, where a blood pressure cuff is used to occlude the brachial artery for a few minutes, may demonstrate spasms of the muscles of the hand and forearm. Chvostek’s sign involves tapping the facial nerve just anterior to the external auditory meatus and will cause ipsilateral contraction of the facial muscles. This test is not diagnostic as it may be present in those without hypocalcaemia. Other symptoms of hypocalcaemia include muscle cramps and tingling sensations in extremities.

Question 58

A urine dipstick positive for blood but negative for erythrocytes on direct microscopy suggests the presence of what molecule?

Answer 58

Myoglobin Rhabdomyolysis describes necrosis of muscle and release of intracellular components. It may be caused by traumatic crush injuries. A serum creatine kinase measurement greater than 5 times the upper limit of normal is considered diagnostic. Myoglobin is a protein normally present in urine in small amounts. The muscle breakdown in rhabdomyolysis causes raised serum myoglobin which leads to myoglobinuria. The high levels of myoglobin in the urine are responsible for the dark brown colour. It may occur after vigorous exercise. A urine dipstick test measures the peroxidase activity of erythrocytes and therefore will be positive for blood if myoglobin is present.

Question 59

What is the gold standard investigation for quantification of urinary protein loss, not typically performed in clinical practice?

Answer 59

24 Hour Urine Collection

Question 60

A 54 year old man with type 2 diabetes presents to A&E with low GCS. He has dry mucous membranes and decreased skin turgor. His wife says he has been going to the toilet more frequently and drinking more for the last few days. Blood tests show blood glucose 57 mmol/L, serum osmolality high and ketones negative. What is the diagnosis?

Answer 60

Hyperosmolar Hyperglycaemic State Hyperosmolar Hyperglycaemic State (HHS) is a complication of type 2 diabetes resulting from significantly raised blood glucose resulting in high serum osmolality and leading to severe dehydration. This occurs without significant ketoacidosis but still has a high mortality. Individuals may present unconscious explaining why HHS is also known as Hyperglycaemia Hyperosmolar Nonketotic Coma (HONK). HHS usually develops over a few days and may be precipitated by an infection. Treatment is aimed at rehydration and reducing blood glucose safely. Serum osmolality must be reduced slowly and monitored frequently to avoid causing cerebral oedema.

Question 61

An infant with dysmorphic facies and congenital heart disease and cleft palate is found to have hypocalcaemia. What is the most likely diagnosis?

Answer 61

DiGeorge syndrome DiGeorge syndrome results from a deletion of part of chromosome 22 (22q11.2) (Question feedback: you must be specific to what has happened to the chromosome, ie a deletion, not simply state the locus affected) This results in a number of abnormalities which can be remembered with the acronym CATCH 22 (with the 22 referring to the chromosomal deletion): ``` Cardiac anomalies Abnormal facies Thymic aplasia Cleft palate Hypoparathyroidism ``` Individuals with DiGeorge syndrome are born without the 3rd and 4th branchial arches and so do not have parathyroid glands.

Question 62

In bile acid synthesis Acyl-CoA cholesterol acyltransferase (ACAT) is the enzyme that converts cholesterol into what?

Answer 62

Cholesterol ester Acyl-CoA cholesterol acyltransferase (ACAT) is found in nearly all cells and catalyses the esterification of cholesterol. ACAT therefore plays an important role in bile acid synthesis and is also involved in the process of atherosclerosis.

Question 63

A 43 year old man presents to his GP complaining of very smelly stool that is difficult to flush. He has been taking a new medication supposed to help him lose weight prior to his bariatric surgery in a few months’ time. However, he continues to eat takeaways most days of the week. What medication is this patient most likely taking?

Answer 63

Orlistat Orlistat is a anti-obesity drug, which inhibits lipases from breaking down triglycerides into free fatty acids which can then be absorbed from the gut. A side effect of this is steatorrhoea and patients are advised to follow a low-fat diet to reduce this side effect.

Question 64

A 21 year old woman with Borderline Personality Disorder presents to A&E after taking an overdose of medication. Her blood gas shows a metabolic acidosis with respiratory alkalosis. She refuses to tell you what she has taken but does say she has ringing in her ears. What has she most likely overdosed on?

Answer 64

Salicylates Patients with Salicylate (Aspirin) poisoning typically experience nausea and vomiting, dizziness and ringing in the ears. Severe poisoning characteristically causes a respiratory alkalosis with metabolic acidosis. This is because salicylates stimulate the respiratory centre causing hyperventilation and inhibit the Krebs cycle resulting in anaerobic metabolism.

Question 65

A 76 year old man is admitted following an exacerbation of his COPD. Arterial blood gas shows: pH 7.30 (NR: 7.35-7.45) PaCO2 9 kPa (NR: 4.7-6.0 kPa) PaO2 10 kPa (NR: 11-13 kPa on 21% FiO2) HCO3- 38 mmol/L (NR: 22-26 mEq/L) How would you describe this patient’s acid base disturbance?

Answer 65

Chronic respiratory acidosis When interpreting blood gases always look at the pH first. Low pH indicates acidosis whereas high pH indicates alkalosis. Next look at the CO2 and HCO3- to see if the change in pH has a metabolic or respiratory cause. There may be a mixed picture. Respiratory compensation for a metabolic disturbance can occur quickly, however, metabolic compensation for respiratory pathology may take several days. This allows you to distinguish between acute and chronic respiratory pathology.

Question 66

In general, what pH imbalance is associated with hypokalaemia?

Answer 66

Alkalosis In general, low blood pH (acidaemia) is associated with increased plasma potassium concentration (hyperkalaemia), whereas high blood pH (alkalaemia) is associated with decreased plasma potassium concentration (hypokalaemia). The underlying mechanism for this is due to a hydrogen potassium transporter, which exchanges K+ ions for H+ ions on cell membranes. In hypokalaemia there is a low concentration of K+ ions in the blood. To compensate for the low K+, this transporter pumps K+ out of the cell into the blood in exchange for H+. The reduced H+ in the blood results in an alkalosis.

Question 67

Allopurinol is used in the treatment of non-acute gout. What enzyme does Allopurinol inhibit to reduce urate synthesis?

Answer 67

Xanthine oxidase The aim of treatment in an acute flare up of gout is to reduce inflammation. First line is NSAIDs (eg. Diclofenac). Colchicine is also useful in reducing inflammation and acts by inhibiting polymerisation of tubulin to reduce migration of neutrophils. Glucocorticoids can be injected or given orally. During the intervals between acute gout, the aim is to reduce urate levels. Patients should be advised to drink plenty of water and avoid dietary sources high in purines such as port wine and organ meats. Medications should also be reviewed and diuretics stopped. Allopurinol inhibits the enzyme xanthine oxidase to reduce urate synthesis, and Probenecid increases fractional excretion of uric acid.

Question 68

An Indian lady complains of chronic bone and muscle pain. She moved to the UK from India 6 years ago and lives a fairly sedentary lifestyle. Her GP does some blood tests which find she is vitamin D deficient with low calcium, low phosphate and raised ALP. She has no other medical history of note. What hormone would you expect to be raised in this lady?

Answer 68

Parathyroid hormone This lady is suffering from vitamin D deficiency (osteomalacia). Dark skin and lack of sunlight are risk factors and contribute to the large prevalence of vitamin D deficiency in the UK. The low vitamin D results in reduced absorption of calcium from the gut which in turn stimulates the parathyroid glands to release more PTH. The raised PTH compensates for the low calcium by causing increased reabsorption of calcium in the kidney and increased bone resorption.

Question 69

A 2 year old boy is brought to the GP because his mother thinks his legs look a funny shape. She is a strict vegan and so is her child. The GP suspects there may be some deformity and requests X rays of the wrists and legs. X ray shows widened epiphysis at the wrists and bowed legs. What condition are these X ray findings pathognomonic for?

Answer 69

Rickets This child is likely suffering from Vitamin D deficiency and has presented with signs of rickets. Widening of the bones at the wrist and knees (sites of rapid bone growth) and bowing of the legs are characteristic features. They may also complain of bone pain. Management of children with nutritional rickets involves correcting the vitamin D deficiency and ensuring adequate calcium intake.

Question 70

What family of enzymes in the gut does Orlistat inhibit?

Answer 70

Lipases Orlistat is a anti-obesity drug, which inhibits lipases from breaking down triglycerides into free fatty acids which can then be absorbed from the gut. A side effect of this is steatorrhoea and patients are advised to follow a low-fat diet to reduce this side effect.

Question 71

Where in the gut are bile acids reabsorbed?

Answer 71

Terminal ileum Most bile acids are reabsorbed from the gut in the ileum and are then recycled back to the liver for secretion into the biliary system again. This enterohepatic circulation of bile acids minimises the conversion of cholesterol into new bile acids. Cholestyramine binds to bile acids in the gut stopping them from being reabsorbed. The liver then has to convert greater amounts of cholesterol into bile acids in order to maintain adequate secretion of bile acids into the biliary system. Cholestyramine therefore acts as a cholesterol lowering drug.

Question 72

A 16 year old presents to A&E following an overdose of medications from the family medicine cabinet 4 hours ago. She says she feels very unwell, nauseous and has vomited 4 times in the last 3 hours. She says the room is spinning and that she can hear a high pitched ringing in her ears. Observations show that she is tachypneic and is feverish at 38c. What medication is she likely to have overdosed on?

Answer 72

Salicylates

Question 73

An 11 year old boy is brought into A&E by his mother. He is complaining of abdominal pain and has vomited multiple times. He appears thin and is drowsy. On examination you find dry mucous membranes and a fruity odour on his breath. What is the likely diagnosis?

Answer 73

Diabetic ketoacidosis Diabetic ketoacidosis (DKA) is a metabolic acidosis characterised by the presence of ketones and is a life threatening complication of diabetes. It occurs when, due to insulin deficiency, cells do not receive enough glucose to meet their metabolic demands. Consequently, fatty acids are broken down into ketones as an alternative fuel source. These ketones can be detected on a urine dip and can give a fruity odour to one’s breath.

Question 74

In which organ does the enzyme 25 hydroxylase convert cholecalciferol to 25-hydroxycholecalciferol?

Answer 74

Liver Cholecalciferol (vitamin D3) is synthesised in the skin from exposure to sunlight. Cholecalciferol is then converted to 25-hydroxycholecalciferol in the liver. The rate-limiting enzyme 1-alpha-hydroxylase is then responsible for converting 25-hydroxycholecalciferol in the kidney to the biologically active 1,25-dihydroxycholecalciferol.

Question 75

A patient’s blood tests have returned and show they have a low serum sodium level. What investigation should be done to determine if this is a true hyponatraemia?

Answer 75

serum osmolality A low serum osmolality tells you this is a true hyponatraemia. A normal or high serum osmolality tells you this is a pseudohyponatraemia. For example, hyponatraemia with high serum osmolality could be caused by taking blood from an arm with a glucose infusion. The infusion dilutes the sodium in that vein while the glucose creates a high osmolality. Throughout the rest of the body the sodium is normal. Hyponatraemia with normal serum osmolality can occur when there is a greater level of lipids or proteins in the patient’s serum which causes an apparent decrease in serum sodium concentration. This is known as the electrolyte exclusion effect. Marking note: We don't allow simply writing "osmolality" as an acceptable answer. You must state the fluid that you wish to test for osmolality - serum, plasma, urine or other.

Question 76

Purines can be made via a de novo synthesis pathway. What is the name of the other pathway by which purines can be made?

Answer 76

Salvage pathway Purines can be synthesised via 2 different pathways, either de novo (from scratch) or through the salvage pathway. The salvage pathway involves recycling of purine bases from their respective nucleotides. This is more efficient and predominates in most tissues.

Question 77

A 14 year old type 1 diabetic has just got home after walking from school. He feels a little dizzy and a bit drowsy. He also notices he is shaking. He skipped lunch at school and is now feeling very hungry. What is causing his symptoms?

Answer 77

Hypoglycaemia Hypoglycaemia is a potentially serious complication of type 1 diabetes. The individual may become shaky, sweaty, dizzy, drowsy and if not treated may lose consciousness. Hypoglycaemia is more likely to occur if the individual has not eaten for some time or has recently exercised. Type 1 diabetics must regularly measure their blood glucose and carb count in order to calculate an appropriate insulin dose.

Question 78

In de novo purine synthesis, what kind of feedback do guanylic acid (GMP) and adenylic acid (AMP) have on the enzyme PAT?

Answer 78

Negative Phosphoribosyl pyrophosphate amidotransferase (PAT) is the enzyme responsible for the conversion of PRPP into PRA. This is the rate limiting step in the de novo synthesis of purines. Guanylic acid (GMP) and adenylic acid (AMP) exert negative feedback on PAT.

Question 79

A patient with low serum calcium is present on the ward. The consultant wants to demonstrate the neuromuscular excitability caused by hypocalcaemia to the medical student. With the patient’s consent, he taps the facial nerve in the region slightly anterior to the external auditory meatus. The patient’s nose and lips twitch. What is the name of this sign?

Answer 79

Chvostek’s sign Calcium is important for nerve and muscle function. Very low serum calcium (<2.2) can result in neuromuscular excitability. Trousseau’s sign, where a blood pressure cuff is used to occlude the brachial artery for a few minutes, may demonstrate spasms of the muscles of the hand and forearm. Chvostek’s sign involves tapping the facial nerve just anterior to the external auditory meatus and will cause ipsilateral contraction of the facial muscles. This test is not diagnostic as it may be present in those without hypocalcaemia. Other symptoms of hypocalcaemia include muscle cramps and tingling sensations in extremities.

Question 80

A 38 year old man with hypertension has high plasma sodium and low plasma potassium. He is diagnosed with Conn’s syndrome. What is the likely result of an Aldosterone:Renin ratio in this patient?

Answer 80

Elevated Conn’s syndrome is a common and treatable form of primary hyperaldosteronism, which leads to hypertension. Excess aldosterone results in increased sodium reabsorption, hypertension and suppression of the renin-angiotensin system. This gives rise to a high Aldosterone:Renin ratio. In severe cases, the patient may also present with hypokalaemia causing weakness and muscle cramps.

Question 81

A 1 week old male infant presents to paediatric A&E. His mother says he has been projectile vomiting after feeding. The vomit is milky and nonbilious. After feeding he is still hungry. On examination you notice a small mass in the epigastrium. Investigations show: pH: 7.51 (NR: 7.35-7.45) pCO2: 5.8 kPa (NR: 4.7-6.0 kPa) HCO3-: 35 mmol/L. (NR: 22-26 mEq/L) How would you describe this patient’s acid base disturbance?

Answer 81

Metabolic alkalosis When interpreting blood gases always look at the pH first. Low pH indicates acidosis whereas high pH indicates alkalosis. Next look at the CO2 and HCO3- to see if the change in pH has a metabolic or respiratory cause. There may be a mixed picture. Respiratory compensation for a metabolic disturbance can occur quickly, however, metabolic compensation for respiratory pathology may take several days. This allows you to distinguish between acute and chronic respiratory pathology.

Question 82

What score, derived from a DEXA scan, describes how a patient’s bone mass varies compared to an age matched control?

Answer 82

Z score A DEXA (Duel energy X-ray absorptiometry) scan is used to investigate osteoporosis. The scan produces two scores, a T and a Z score. The T score describes how bone density varies compared to that of a young healthy population. It is used to determine risk of fracture. A T score of less than -1 but greater than -2.5 suggests osteopenia and less than -2.5 suggests osteoporosis. The Z score which describes how the patient’s bone mass varies compared to an age matched control and is useful in identifying accelerated bone loss relative to age.

Question 83

A patient with chronic kidney disease had a renal transplant and recovered well. However, on follow-up they are found to have high calcium and a raised PTH. What is the most likely diagnosis?

Answer 83

Tertiary Hypocalcaemia on a background of untreated chronic kidney disease may result in secondary hyperparathyroidism with hyperplasia of the parathyroid glands. Renal transplantation can correct the underlying kidney disease causing the hypocalcaemia but the hyperplasia of the parathyroid glands may persist after transplant. This results in an inappropriately high level of PTH and subsequent hypercalcaemia. This is known as tertiary hyperparathyroidism.

Question 84

A 53 year old woman, returning from her holiday in Australia, experiences a sudden sharp chest pain. She refused to wear the compression stockings on the plane because she finds them uncomfortable. When she arrives in A&E her arterial blood gas shows: pH 7.49 (NR 7.35-7.45) PaO2 8.7 kPa (NR: 11-13 kPa on 21% FiO2) PaCO2 3.1 kPa (NR: 4.7-6.0 kPa) HCO3- 23 mmol/L (NR 22-26 mEq/L) How would you describe this patient’s acid base disturbance?

Answer 84

Respiratory alkalosis When interpreting blood gases always look at the pH first. Low pH indicates acidosis whereas high pH indicates alkalosis. Next look at the CO2 and HCO3- to see if the change in pH has a metabolic or respiratory cause. There may be a mixed picture. Respiratory compensation for a metabolic disturbance can occur quickly, however, metabolic compensation for respiratory pathology may take several days. This allows you to distinguish between acute and chronic respiratory pathology.

Question 85

Which plasma protein is important in the calculation of a corrected calcium level?

Answer 85

Albumin Approximately 40% of serum Ca2+ is bound to the circulating plasma protein albumin. 50% of serum Ca2+ is free (ionised) and this makes up the active component. The concentration of this active component is tightly controlled. If the plasma albumin concentration falls the total calcium level will appear low but the free calcium level will remain the same. Calculating a corrected calcium level allows us to check if the free calcium concentration is normal in the presence of an abnormal albumin level. Corrected Ca = serum Ca × 0.02 × (40 - serum albumin g/L)

Question 86

Which term is used to describe increased bone density?

Answer 86

Osteosclerosis Osteosclerosis describes areas of increased bone density. Osteosclerosis appears on X-ray as areas of brighter white bone compared to the surrounding bone. Excess Vitamin D, hypoparathyroidism or Paget's Disease of Bone may cause osteosclerosis.

Question 87

An asymptomatic 50 year old man undergoes a 2 hour oral glucose tolerance test. After the 2 hours his plasma glucose is 9.4 mmol/L. What is the diagnosis?

Answer 87

Impaired glucose tolerance Impaired fasting glucose and impaired glucose tolerance describe the early metabolic abnormalities that precede diabetes but do not quite reach the cut-off for a diagnosis of diabetes. Impaired fasting glucose and impaired glucose tolerance are both risk factors for future type 2 diabetes mellitus. Impaired fasting glucose is defined as fasting plasma glucose between 6.1 - 6.9 mmol/L. Impaired glucose tolerance is defined as 2 hour oral glucose tolerance test plasma glucose 7.8 - 11.0 mmol/L. These patients are at high risk of developing future diabetes without lifestyle modification.

Question 88

A middle aged man presents to A&E with an exquisitely painful left knee. He is carrying a half empty bottle and says it contains moonshine. Blood tests show hyperuricaemia and a low Hb. He is under investigation for a sideroblastic anaemia. Intoxication of what element is responsible for causing his condition?

Answer 88

Lead Saturnine gout presents similarly to primary gout but with acute attacks more common in the knee. It is caused by lead toxicity, often associated with drinking homemade alcohol. Lead toxicity reduces renal urate excretion leading to hyperuricaemia.

Question 89

A patient has the following electrolyte levels. Sodium 139 mmol/L. Potassium 4.1 mmol/L. Urea 3.8 mmol/L. The serum concentration of what other substance is required in order to calculate the serum osmolarity?

Answer 89

Glucose OsmolaLity is a measure of all the particles in a solution and is measured in mmol/kg. OsmolaRity is an alternative measure of the particles in solution and has the units mmol/L. OsmolaRity is calculated using the formula below: Osmolarity = 2(Na + K ) + urea + glucose You may notice we do not need to know the concentration of negative ions in order to calculate osmolarity. The concentration of negative ions should equal the concentration of positive ions. Therefore we simply multiply the positive ions by 2. OsmolaLity and OsmolaRity should roughly equal. If they do not this is called the Osmolar gap. You may ask why we have two different but similar terms. OsmolaRity can be easily calculated from the concentration of electrolytes, however, because it is measured per 1 Litre of solvent it can vary with temperature. OsmolaLity requires measuring in a lab using an osmometer, but does not vary with temperature as it is measured per 1 Kilogram of solvent, and is therefore the preferred term for biological systems.

Question 90

A DEXA (Dual Energy X-ray Absorptiometry) scan is often used in the investigation of osteoporosis. A negative T score below what value indicates osteoporosis?

Answer 90

-2.5 A DEXA (Duel energy X-ray absorptiometry) scan is used to investigate osteoporosis. The scan produces two scores, a T and a Z score. The T score describes how bone density varies compared to that of a young healthy population. It is used to determine risk of fracture. A T score of less than -1 but greater than -2.5 suggests osteopenia and less than -2.5 suggests osteoporosis. The Z score which describes how the patient’s bone mass varies compared to an age matched control and is useful in identifying accelerated bone loss relative to age.

Question 91

A 16 year old girl presents to A&E following an overdose of medications from the family medicine cabinet 24 hours ago. She vomited three times an hour after taking the tablets, then twice overnight. Today, at 10pm, she is vomiting heavily and has severe pain in the right upper quadrant of her abdomen. Urine dip is positive for blood and protein. What medication is she likely to have overdosed on?

Answer 91

Paracetamol

Question 92

The portal tract is made up of three different vessels. What is the name of the vein found in the portal tract?

Answer 92

Hepatic portal vein The portal tract contains three different vessels: the hepatic portal vein, the hepatic artery, and a bile duct. Blood is supplied to the liver via the hepatic artery and hepatic portal vein, before draining away in the hepatic vein. Bile flows in the opposite direction through the bile ducts.

Question 93

A 24 year old bodybuilder presents to A&E unconscious. He was found at home with low GCS and his flatmate reported he had been shaking and appeared sweaty and confused. He has no past medical history of note. Blood tests show his insulin level is high and C-peptide is low. What is the most likely cause of his symptoms?

Answer 93

Insulin overdose C-peptide is a short chain of amino acids cleaved in the conversion of proinsulin to insulin. It is created in equimolar amounts to insulin making it useful in the investigation of hypoglycaemia. Hypoglycaemia with high insulin and low C-peptide suggests an exogenous source of insulin. This may be in a type 1 diabetic or from surreptitious use of insulin. Hypoglycaemia with high insulin and high C-peptide suggests an endogenous source of insulin. Causes include insulinoma and inborn errors of metabolism. Sulfonylureas, used to lower blood sugar in type 2 diabetes, may also cause hypoglycaemia with high C-peptide due to increased release of endogenously produced insulin. Factitious hypoglycaemia may be caused by surreptitious use of insulin or sulfonylureas. A Sulfonylurea screen is useful in distinguishing an insulin-secreting tumour from surreptitious sulfonylurea ingestion.

Question 94

Which type of cell forms foam cells in the formation of atheromatous plaques?

Answer 94

Macrophage The physiology of atherosclerotic plaque formation is a chronic inflammatory process. Low-density lipoprotein (LDL) accumulates in the intima of arteries and is oxidised forming pro-inflammatory mediators. Monocytes are recruited to the site of the plaque and migrate into the subendothelial space. Here they become macrophages and take up the oxidised LDL to form foam cells. These cells form the lipid rich core of the plaque after undergoing apoptosis. The inflammatory process also stimulates vascular smooth muscle cells which contribute to the formation of a fibrous cap stabilising the plaque.

Question 95

What is the volume status of a patient with reduced skin turgor, dry mucous membranes, increased capillary refill time and a low jugular venous pressure?

Answer 95

Hypovolaemic

Question 96

What is the inheritance pattern of Gilbert’s syndrome?

Answer 96

Autosomal recessive Gilbert’s syndrome is an inherited metabolic disorder and common cause of isolated unconjugated hyperbilirubinaemia. It is caused by defective conjugation of bilirubin in the liver but liver function is otherwise unaffected. Jaundice is often precipitated by fasting or periods of physiological stress. Haemolysis may also cause raised unconjugated bilirubin, and this must be excluded before a diagnosis of Gilbert’s can be made.