Metabolics

Question 1

What lipid modification therapy should be initiated in patients who have had an acute coronary syndrome (ACS)?

Answer 1

Atorvastatin 80mg on

Patients with established cardiovascular disease (e.g. IHD, stroke, PVD) should take high-intensity statin therapy (e.g. atorvastatin 80mg) regardless of baseline lipid profile

Question 2

hypocalcaemia. On investigating the patient what may you elicit?

Answer 2

Chvostek’s sign: percussion over the facial nerve

Trousseau sign (carpopedal spasm on inflation of a blood pressure cuff) is also seen in hypocalcaemia.

Hypocalcaemia causes a prolonged QT interval whereas hypercalcaemia causes shortening of the QT interval.

Again, it is hypercalcaemia that causes marked dehydration, hyporeflexia and muscle weakness. Whereas hypocalcaemia causes hyperactive reflexes and muscle spasms

Question 3

features if deficient thiamine

Answer 3

Wernicke-Korsakoff syndrome

Question 4

features if deficient Folic acid

Answer 4

Neural tube defects

Question 5

features if deficient Vitamin K

Answer 5

Haemorrhagic disease of the newborn

Question 6

When interpreting the blood tests which one of the following would not normally be raised in response to an acute infection?

Answer 6

Albumin
Albumin is a protein made by the liver and its levels in the blood are often used as an indicator of nutritional status and liver function. In acute inflammation or infection, albumin levels may actually decrease due to increased capillary permeability, leading to leakage of albumin into the interstitial space. Additionally, there may be reduced synthesis as the liver diverts resources towards producing acute phase proteins. Therefore, unlike other markers of inflammation or infection, albumin would not normally be raised.

Question 7

A 65-year-old gentleman with known multiple myeloma presents with abdominal pain, polydipsia and confusion. Some blood results are shown below.

Na+ 145 mmol/l
K+ 4.1 mmol/l
Albumin 35 g/l
Calcium 3.55 mmol/l
Alkaline phosphatase 120 iu/l
Urea 7.2mmol/l
Creatinine 130µmol/l

Answer 7

IV 0.9% saline

IV fluid therapy is the first-line management in patients with hypercalcaemia

This patient is presenting with hypercalcaemia, which is a common complication of multiple myeloma. The most common symptom of hypercalcaemia is confusion, as seen in this patient. The initial management for severe symptomatic hypercalcemia should be rehydration with intravenous (IV) normal saline to increase renal calcium excretion. According to the UK guidelines, bisphosphonates like pamidronate should only be considered after initial rehydration.

Question 8

high-intensity statin and should be started as primary prevention against cardiovascular disease?

Answer 8

Atorvastatin 20mg

Atorvastatin 80mg is used in secondary prevention.

Question 9

A 68-year-old man is brought to the emergency department with a 10-day history of muscle cramping and fatigue. Blood tests are taken and an ECG is performed.

Blood tests:

Na+ 140 mmol/L (135 - 145)
K+ 3.7 mmol/L (3.5 - 5.0)
Bicarbonate 28 mmol/L (22 - 29)
Urea 6.2 mmol/L (2.0 - 7.0)
Creatinine 95 µmol/L (55 - 120)
Calcium 1.7 mmol/L (2.1-2.6)
Phosphate 1.3 mmol/L (0.8-1.4)
Magnesium 0.62 mmol/L (0.7-1.0)

The ECG demonstrates a regular sinus rhythm at a rate of 72 BPM. The QTc is calculated as 480ms.

What is the next best management step?

Answer 9

Intravenous calcium gluconate
Hypocalcaemia: prolonged QT interval is an indication for urgent IV calcium gluconate

This scenario describes a 68-year-old man who has presented with hypocalcaemia causing a prolonged QT interval. It is important to note that the definition of a prolonged QT interval varies across the literature, but some sources define it as >450ms in adult males and >460ms in adult females.

A prolonged QT interval in hypocalcemia is an indication for urgent intravenous calcium gluconate. This urgent therapy is indicated in severe hypocalcaemia which can present with hand & foot spasming, tetany, seizures, and prolonged QT interval. A prolonged QT interval is of high importance as it can predispose the individual to develop cardiac arrhythmias, including Torsades de pointes.

Question 10

You are reviewing a patient’s blood results:

K+ 6.2 mmol/l

Which one of the following medications is most likely to be responsible for this result?

Answer 10

Spironolactone

Spironolactone is a potassium-sparing diuretic, which means it prevents the kidneys from removing too much potassium. This can lead to hyperkalaemia, a condition characterised by elevated levels of potassium in the blood. The patient’s blood results show a high level of potassium (K+), which is suggestive of hyperkalaemia. Therefore, Spironolactone would be the most likely medication to cause this result.

Question 11

A 27-year-old woman presents to her GP with a 5-day history of widespread muscle cramps and numbness of her hands and feet. She also describes a tingling sensation around her mouth.

She was diagnosed with epilepsy 6 weeks ago and has been started on phenytoin.

Which of the following would most likely be seen in her blood results?

Answer 11

Corrected calcium of 1.5 mmol/L
Key features of hypocalcaemia - perioral paraesthesia, cramps, tetany and convulsions
This patient is describing features typically associated with hypocalcaemia. Hypocalcaemia is a known side effect of phenytoin use. Due to altered neuromuscular excitability, hypocalcaemia can lead to seizures if not promptly treated. Mild (1.9-2.2 mmol/L) asymptomatic hypocalcaemia is typically managed with oral supplementation whilst symptomatic or severe (<1.9 mmol/L) hypocalcaemia is likely to require IV replacement.

Hypokalaemia is often asymptomatic, but severe hypokalaemia (<2.5mmol/L) may be associated with ascending muscle weakness and cardiac arrhythmias including torsades de pointes. This does not fit with the clinical picture described above

Question 12

hypercalcaemia signs

Answer 12

remember; bones (bone pain), stones (renal calculi), groans (constipation), thrones (polyuria) and moans (fatigue, depression, confusion).

Question 13

Hypernatraemia signs

Answer 13

nausea and vomiting, headache and confusion which this patient is not experiencing.

Question 14

A 43-year-old man requests a ‘medical’ as he is concerned about his risk of heart disease. His father died at the age of 45-years following a myocardial infarction. His lipid profile is as follows:

HDL 1.4 mmol/l
LDL 5.7 mmol/l
Triglycerides 2.3 mmol/l
Total cholesterol 8.2 mmol/l

Clinical examination reveals tendon xanthomata around his ankles. What is the most likely diagnosis?

Answer 14

Familial hypercholesterolaemia

The presence of tendon xanthomata and cholesterol levels meet the diagnostic criteria for familial hypercholesterolaemia

Question 15

A 33-year-old woman who is known to have familial hypercholesterolaemia comes for review. She is planning to have children and asks for advice regarding medication as she currently takes atorvastatin 80mg on. What is the most appropriate advice?

Answer 15

Stop atorvastatin before trying to conceive

Statins should be discontinued in women 3 months before conception due to the risk of congenital defects

Question 16

Which one of the following is most associated with the syndrome of inappropriate ADH secretion?

Answer 16

Small cell lung cancer

A common endocrine complication of small cell lung cancer is SIADH

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is most commonly associated with small cell lung cancer. SIADH results from the excessive release of antidiuretic hormone (ADH), leading to water retention and hyponatremia. Small cell lung cancer, a neuroendocrine tumour, often produces and secretes ADH ectopically, leading to SIADH.

Question 17

Hyperkalaemia ecg changes

Answer 17

This ECG has a number of features consistent with severe hyperkalaemia. There is a near sinusoidal pattern, with very wide QRS complexes, bizarre deep T-waves in V1 and V2 and peaked T-waves in V4 and V5.

Question 18

You are asked to review a potassium result whilst on-call:

Na+ 141 mmol/l
K+ 6.4 mmol/l
Bicarbonate 16 mmol/l
Urea 13.1 mmol/l
Creatinine 195 µmol/l

You are unsure whether to give calcium gluconate so you contact your senior. She asks you to only give calcium gluconate if there are ECG changes. Which of the following ECG changes are most consistent with hyperkalaemia?

Answer 18

Widening of the QRS complex. Hyperkalaemia, defined as a serum potassium level greater than 5.5 mmol/L, can cause several ECG changes. The most consistent and life-threatening change is widening of the QRS complex. This represents delayed ventricular depolarisation due to impaired sodium conductance across cell membranes. If left untreated, this can progress to a sine wave pattern and eventually ventricular fibrillation or asystole.

Question 19

body mass index is 38 kg/m^2

Answer 19

Clinically obese (Obese II)
World Health Organization (WHO) classification, a body mass index (BMI) of 30-34.9 kg/m^2 is categorized as Obese Class I, a BMI of 35-39.9 kg/m^2 is categorized as Obese Class II or clinically obese, and a BMI of 40 kg/m^2 or more is categorized as Obese Class III or morbidly obese. Therefore, with a BMI of 38 kg/m^2, this patient falls into the category of clinical obesity or Obese II.

Question 20

Does not cause rise in alkaline phosphatase

Answer 20

Hypoparathyroidism

Question 21

A 49-year-old man comes into clinic. One of his friends has recently had a myocardial infarction and he is concerned about his own risk of coronary heart disease. He has no past medical history of note other than anxiety for which he is not currently taking any medication. He does however smoke around 20 cigarettes a day. Cardiovascular examination is unremarkable. His BMI is 26 kg/m² and blood pressure is 126/82 mmHg.

You strongly advise him to stop smoking. What is the most appropriate further course of action?

Answer 21

Arrange a lipid profile then calculate his QRISK2 score

If we feed his age, gender and smoking history into QRISK2 this gives a 10-year-risk of cardiovascular disease (CVD) of 13.9%. He is therefore an appropriate person to have a ‘formal’ assessment of CVD risk using a lipid profile to further inform the QRISK2 score.

Question 22

An 89-year-old man with known metastatic prostate cancer is brought to the emergency department confused. He is unable to give further history but feels generally unwell. On examination his chest is clear, heart sounds normal and his abdomen soft with no tenderness. His initial blood tests are shown below.

Na+ 134 mmol/l
K+ 4.7 mmol/l
Urea 7.8 mmol/l
Creatinine 104 µmol/l
Adjusted Ca2+ 3.5 mmol/l
Mg2+ 0.81 mmol/l

What is your first treatment?

Answer 22

IV fluid therapy is the first-line management in patients with hypercalcaemia

Although there may be several causes for his presentation the most likely is malignancy-induced hypercalcaemia.

The most common presenting features of which are dehydration, psychiatric manifestations and confusion, anorexia and constipation. Although hypercalcaemia can be secondary to hyperparathyroidism, sarcoidosis, hyperthyroidism, drugs (thiazide diuretics, vitamin D etc) or prolonged immobility etc, 90% of severe cases (>3.0 mmol/l) requiring admission are due to malignancy (as in this gentleman).

Treatment involves IV access and requesting appropriate biochemistry, as other electrolytes may be abnormal. Following this chest x-ray and ECG.

Fluids resuscitation to replace deficit and maintain hydration often requires large volumes (3-4 litres in the first 24 hours) and this must be the first intervention.

If this fails to resolve the hypercalcaemia IV bisphosphonates, such as zoledronate or pamidronate can be used.
Following this specific anticancer therapies can be considered.

Question 23

A 60-year-old male is admitted to the surgical ward for observation following a head injury. Lab results reveal the following:

Na+ 121 mmol/l
K+ 3.0 mmol/l
Urine osmolality 588 mOsmol/kg (50-1200mOsmol/kg)
Serum osmolality 240 mOsmol/kg (275-290mOsmol/kg)

On examination, he is well hydrated with moist mucus membranes. What is the most likely cause of hyponatraemia in this case?

Answer 23

Syndrome of inappropriate anti diuretic hormone (SIADH)

SIADH and cerebral salt wasting are differentiated by fluid status

Hypotonic hyponatraemia can can be caused by three scenarios:

The retention of pure water, as seen in SIADH. This causes euvolaemic hyponatraemia.

The retention of sodium, but accompanied by an even greater retention of water. This is caused by liver failure, heart failure and nephrotic syndrome. Fluid leaks out of the vascular space as a result of increased hydrostatic pressure (heart failure) or reduced osmotic pressure (liver failure, nephrotic syndrome). This causes a reduction in blood pressure and subsequent activation of the rennin-angiotensin-aldosterone system with retention of sodium and water. This is hypervolaemic hyponatraemia.

Question 24

A 51-year-old man undergoes a routine medical examination as part of a pre-employment check. He reports no symptoms and physical examination is normal. Blood tests are ordered and the results are all within normal range with the exception of the following:

Uric acid 0.66 mmol/l (0.18-0.48 mmol/l)

The patient has done some reading online and is worried about his risk of gout.

Which of the following treatments should be commenced in light of this result?

Answer 24

No treatment

Treatment of asymptomatic hyperuricaemia in an attempt to prevent gout is not recommended by NICE

Gout is associated with high levels of serum uric acid however it is possible to have hyperuricaemia with no noticeable effects. In such cases, NICE recommends against primary prevention of gout as it has been shown to be neither cost-effective nor beneficial to patients. Lifestyle changes (less red meat, alcohol and sugar) can reduce uric acid levels without drug treatment and so can be advised.

Question 25

Vitamin deficiency

Answer 25

Vitamin Chemical name Deficiency state

A Retinoids Night-blindness (nyctalopia)

B1 Thiamine Beriberi
polyneuropathy, Wernicke-Korsakoff syndrome
heart failure

B3 Niacin Pellagra
dermatitis
diarrhoea
dementia

B6 Pyridoxine Anaemia, irritability, seizures

B7 Biotin Dermatitis, seborrhoea

B9 Folic acid Megaloblastic anaemia, deficiency during pregnancy - neural tube defects

B12 Cyanocobalamin Megaloblastic anaemia, peripheral neuropathy

C Ascorbic acid Scurvy
gingivitis
bleeding

D Ergocalciferol, cholecalciferol Rickets, osteomalacia

E Tocopherol, tocotrienol Mild haemolytic anaemia in newborn infants, ataxia, peripheral neuropathy

K Naphthoquinone Haemorrhagic disease of the newborn, bleeding diathesis

Question 26

A 77-year-old man on the ward has only produced 120 mL of urine in the past 8 hours. Which metabolic abnormality is the most serious potential complication of his condition?

Answer 26

Hyperkalaemia is the most serious electrolyte abnormality that can complicate acute kidney injury. It can result in muscle weakness, paralysis, arrhythmias and cardiac arrest. ECG changes are a more accurate way of identifying cardiac toxicity than plasma potassium level. If characteristic ECG changes of hyperkalaemia are seen, then it is important to give the patient either calcium gluconate or calcium chloride, which acts as a cardiac membrane stabiliser, while potassium-lowering treatments are given.

Hyperphosphataemia and hypocalcaemia are both complications of chronic kidney disease.

Question 27

a 75-year-old male, attended his GP complaining of lethargy, back pain and feeling unwell for several months. His GP ordered blood tests including liver function tests (LFT’s).

Bilirubin 10 µmol/l
ALP 895 u/l
ALT 22 u/l
γGT 35 u/l
Albumin 45 g/l

Which of the following conditions could have caused the abnormality in these liver function tests?

Answer 27

Bone metastases
Raised ALP in the presence of normal LFT’s should raise suspicion of malignancy. Particularly bone cancer/ metastases

These LFT’s show an isolated rise in alkaline phosphatase (ALP). A raised ALP in the presence of otherwise normal LFT’s should make you consider bony malignancy in view of the history of lethargy, back pain and feeling unwell in an elderly patient. The back pain could potentially be due to bony metastases, this is common particularly in prostate cancer. Other causes of raised ALP include: Paget’s disease, osteomalacia, rickets, bone fractures, primary bone tumours, pregnancy (as it is released by the placenta). Other tests you may wish to consider include: PTH, calcium, PSA and a skeletal survey.

Question 28

Hyperkalaemia ECG changes

Answer 28

ECG changes seen in hyperkalaemia include tall-tented T waves, small P waves, widened QRS leading to a sinusoidal pattern and asystole

Question 29

Causes of hyperkalaemia:

Answer 29

acute kidney injury
drugs*: potassium sparing diuretics, ACE inhibitors, angiotensin 2 receptor blockers, spironolactone, ciclosporin, heparin**
metabolic acidosis
Addison’s disease
rhabdomyolysis
massive blood transfusion