Path - Chemical Pathology Flashcards
What is the general underlying pathogenesis of hyponatraemia?
A. Deficiency in salts B. Excess extracellular salts C. Deficiency in water D. Excess extracellular water E. Acid-base imbalance
D. Excess extracellular water
Which of the following is not a function of ADH?
A. Regulation of calcium exchange between cells and serum
B. Re-absorption of sodium in the Loop of Henle
C. Aquaporin insertion into the apical membrane of collecting duct cells
D. Vasoconstriction
E. Stimulation of thirst
(remember ADH actions on V1, V2, V3 (ACTH from pit gland release) functions
A. Regulation of calcium exchange between cells and serum
Which option is a cause of hyponatraemia in a hypervolemic patient?
A. Diarrhoea B. Hypothyroidism C. SIADH D. Vomiting E. Cirrhosis
E. Cirrhosis
Hypovolemic hyponatraemia (losses): Diarrhoea Vomiting Diuretics Salt-losing nephropathy
Euvolemic hyponatraemia (endocrine abnormalities):
Hypothyroidism
Adrenal insufficiency
SIADH (key! - euvolaemic, remember 2ndary natriuretic responses causing Na+ and water loss)
Hypervolemic hyponatraemia (organ failures- think of fluid overload):
Cardiac failure
Cirrhosis
Nephrotic syndrome
Which of the following is true of SIADH?
A. It is only caused by cranial pathology SIADH
B. It affects 5-10% of hospitalised patients
C. It is the most common cause of hyponatraemia
D. It causes a hypovolemic hyponatraemia
E. It is associated with lithium use
C. It is the most common cause of hyponatraemia
The causes of SIADH are implausibly varied: pathologies of most types and organs can cause it, but there are a few causes you should be familiar with because Amir Sam always mentions them.
Various CNS pathologies can cause SIADH (subdural haematoma, subarachnoid haemorrhage, trauma, cavernous sinus thrombosis).
The other frequently mentioned causes of SIADH are lung pathology (generally cancer or infection), a wide range of tumours, a wide range of drugs (SSRIs, PPIs, opiates, TCAs, sodium valproate, carbemazepine), and surgery (ADH rises post-op).
What is the key concern about quickly raising a patient’s sodium (by more than 8-10 mmol/ hour)?
A. Hypernatraemia B. Dehydration C. Renal failure D. Cell lysis E. Central pontine myelinolysis
E. Central pontine myelinolysis
Rapidly elevating serum sodium may, in the worst case, lead to damage to the cells in the Pons of the brain stem, causing central pontine myelinolysis. It is characterised by acute paralysis, dysphagia, dysarthria, and other neurological deficits, and is thought to occur because rapidly rising sodium levels drive water out of cells into the blood, causing damage.
What are the two main stimuli for ADH secretion?
A. Reduced blood volume and reduced serum osmolality
B. Increased blood volume and increased serum osmolality
C. Increased blood volume and reduced serum osmolality
D. Reduced blood volume and increased serum osmolality
D. Reduced blood volume and increased serum osmolality
(remember hypothalamic osmoreceptors detecting osmolality of blood- main stimulation)
Which of the following is not a cause of hyperkalaemia?
A. Renal impairment B. ACE inhibitors C. Addison's disease D. Cushing's syndrome E. Acidosis
D. Cushing’s syndrome
Aldosterone is the key hormone regulating sodium excretion and potassium retention (aldosterone causes hyperNa+ and hypoK+). However mineralocorticoid receptors (e.g. for aldosterone) are non-specific, and are stimulated by cortisol. Hence, Cushing’s patients have high sodium and low potassium.
Renal impairment will impair the secretion of potassium, causing it to rise.
ACE inhibitors prevent the production of angiotensin II from angiotensin I. Angiotensin II stimulates release of aldosterone, hence ACE inhibitors can lead to hyperkalaemia.
Acidosis leads to hyperkalaemia through the body’s attempt to maintain the pH balance of the blood: H+ ions are transported into cells to lower the pH, but this uses a co-transporter which moves potassium into the blood, resulting in hyperkalaemia. REMEMBER acidosis goes the same way as kalaemia (both hyper together or both hypo)
A 90 year-old woman is found on her bathroom floor having fallen and been unable to get up again. She has been on the floor for two days and is delirious. She is taken to hospital where examination confirms she is acutely confused with virtually no urine output. Blood tests show elevated urea and creatine kinase. She is given an I.V. fluid challenge and shows marked improvement. She begins to pass urine but it is tea-coloured. Shortly afterwards she is noticed to be breathing rapidly and reports having palpitations; her ECG shows bradycardia, tented T waves, and a prolonged P-R interval. A rapidly taken VBG shows the following:
pH: 7.22 Bicarbonate: 15 O2 Sat: 76% PaO2: 5.0 kPa PaCO2: 5.5 kPa Na+: 141 K+: 6.8 Glucose: 5mmol/L
What is the most appropriate next step in the patient’s management?
A. Administer another I.V. fluid challenge and monitor urine output. Regularly auscultate the lungs to check for pulmonary oedema, and refer the patient to a specialist renal unit.
B. Continue to rehydrate the patient with I.V. saline, and monitor their potassium regularly for at least 6 hours.
C. Give 50ml 50% saline, beta blockers, and begin a bicarbonate infusion. Refer the patient to a cardiologist.
D. Give 10ml 10% calcium chloride, 10 units soluble insulin in 25g glucose, and nebulised salbutamol
E. Urgently refer the patient to ICU for intensive support and haemofiltration
D. Give 10ml 10% calcium chloride, 10 units soluble insulin in 25g glucose, and nebulised salbutamol
This patient has developed hyperkalaemia, which has affected her heart’s rhythm and carries a significant risk of causing cardiac arrest. Her hyperkalaemia could be caused either by the toxic cell products released during rhabdomyolysis from her fall and extended down time, or by the AKI resulting from her extreme dehydration from not drinking for two days. Either way, she has an acute kidney injury which leaves her unable to excrete potassium.
The most important goal in this scenario is to manage the patient’s hyperkalaemia and prevent cardiac arrest. Calcium chloride is given to stabilise the heart’s rhythm; calcium gluconate can be given, but contains less calcium, and more frequently needs repeat doses to elicit an adequate response. 10 units of insulin dissolved in 25g glucose is given to open cell membrane channels that allow potassium to move out of the blood and into cells (drives K+ into cells). Nebulised salbutamol has a similar effect, and helps shift potassium out of the blood.
Once the acute emergency has been managed, then the patient’s AKI can be addressed, but if the hyperkalaemia is not made a priority, they will arrest.
NB:
Modern blood gas analysers can interpret the blood levels of electrolytes, which is much faster than sending samples to the lab. This is especially useful in emergency cases such as this one. VBGs cannot be used to assess oxygen or carbon dioxide content of arterial blood, but they give an accurate measure of electrolytes and pH (which differs by a mean of 0.03).
The European Resuscitation Council classifies hyperkalaemia as:
mild: 5.5 - 5.9 mmol/L
moderate: 6.0 - 6.4 mmol/L
severe: ≥ 6.5 mmol/L
(3.5 - 5 is normal!)
Which of the following features the lowest serum calcium?
A. Primary hyperparathyroidism B. Secondary hyperparathyroidism C. Osteoporosis D. Paget's disease of the bone E. Breast cancer
B. Secondary hyperparathyroidism
Secondary hyperparathyridism refers to PTH that is elevated in response to hypocalcaemia, so calcium must, by definition, be low. Calcium is normal in both Paget’s and osetoeporosis, and high in primary hyperparathyroidism. Breast cancer may feature elevated calcium levels, as cancer cells may release un-regulated PTHrp which has the same effect as PTH and raises serum calcium.
NB: The majority of cases of secondary hyperparathyroidism are caused by chronic kidney disease. The diseased kidneys fail to hydroxylate enough vitamin D to stimulate sufficient calcium absorption form the gut. Furthermore, the kidneys fail to excrete phosphate, which reacts with calcium in the blood to form a complex which is then excreted, further lowering calcium.
What is the storage form of vitamin D prior to activation?
A. Cholecalciferol B. 25 hydroxyvitamin D C. Alfacalcidol D. 1, 25 hydroxyvitamin D E. Ergocalciferol
B. 25 hydroxyvitamin D
Vitamin D synthesis begins with 7-dehydrocholesterol, which is converted to cholecalciferol in the skin using UV light. Cholecalciferol is then hydroxylated in the liver to form 25-hydroxycholecalciferol, which is also stored in the liver. The active metabolite of vitamin D is produced in the kidney by 1-hydroxylase which produces 1, 25-dihydroxycholecalciferol.
Which of the following DEXA scan results would indicate osteopenia?
A. -2.8 B. -1.0 C. -0.8 D. -1.8 E. 0.3
D. -1.8
Dual energy x-ray absroptiometry (DEXA) is used to evaluate bone density. A score of -1 to -2.5 indicates osteopenia, whereas a score of -2.5 indicates osteoporosis.
Which of the following is the most sensitive measure of acute liver fuction impairment?
A. AST B. ALT C. ALP D INR E. Albumin
D. INR
Liver function tests are poorly named as they do not reflect liver function, instead they should be considered markers of liver cell damage. Albumin and INR are both measures of liver function (i.e. synthetic function), but albumin usually only drops in chronic liver disease (also in inflammation), whereas INR is a good indicator of acute impairment. This is because the half-life of clotting factors is a few hours, so INR (or PT time) will begin to change very quickly after synthetic function is impaired, whereas the half-life of albumin is 3 weeks.
A patient’s set of LFTs read as follows:
Bilirubin - 15 (<17) AST - 250 (<40 U/L) ALT - 75 (<40 IU/L) ALP - 80 (35-51 U/L) GGT - 120 (11-42 U/L)
What is the most likely diagnosis?
A. Viral hepatitis B. Alcoholic liver disease C. Ischaemic hepatitis D. Hepatocellular carcinoma E. Gallstones
B. Alcoholic liver disease
If both AST and ALT are elevated, the ratio between them is important. A ratio of AST:ALT >2 is classically associated with alcoholic liver disease
HCC marker is a-FP (AFP) not ALP
A patient’s set of LFTs read as follows:
Bilirubin - 236 (<17) AST - 55 (<40 U/L) ALT - 65 (<40 IU/L) ALP - 1024 (35-51 U/L) GGT - 59 (11-42 U/L)
What is the most likely diagnosis?
A. Viral hepatitis B. Alcoholic liver disease C. Ischaemic hepatitis D. Hepatocellular carcinoma E. Gallstones
E. Gallstones
The very high ALP in conjunction with other raised markers of liver damage imply a cholestatic picture (note that isolated raised ALP does not suggest cholestasis). This points to gallstones blocking the bile duct.
A patient’s set of LFTs read as follows:
Bilirubin - 168 (<17) AST - 2380 (<40 U/L) ALT - 2500 (<40 IU/L) ALP - 190 (35-51 U/L) GGT - 39 (11-42 U/L)
Toxin screens are negative, as is hepatitis serology
What is the most likely diagnosis?
A. Autoimmune hepatitis B. Alcoholic liver disease C. Ischaemic hepatitis D. Hepatocellular carcinoma E. Gallstones
C. Ischaemic hepatitis
There are three things that can elevate AST and ALT into the thousands and they are: toxic hepatitis, ischaemic damage (rare as liver blood supply is v good), and viral hepatitis.
Which of the following is not a sign of liver failure?
A. Spider naevi B. Dupuytren's contracture C. Palmar erythema D. Kolionychia E. Gynaecomastia
D. Kolionychia
(side note- remember difference between compensated and decompensated cirrhosis and their signs. decompensated when liver can’t copy anymore- jaundice, ascites, encephalopathy, peripheral oedema, variceal bleeding. Spider naevi, gynaecomastia, dupuytren’s etc. all compensated).
Blood tests provide the following results: Na: 145 K 5.0 Urea: 10 pH: 6.85 Glucose: 25
What is this patient’s osmolality?
335 osm/L
Osmolality = 2(Na + K) + U + G Osmolality = 2(145 + 5) + 10 + 25 Osmolality = 335 osm/L
Blood tests provide the following results: Na: 145 K 5.0 Urea: 10 pH: 6.85 Glucose: 25 Chloride: 102 HCO3: 24
What is the anion gap?
24 mM
Anion Gap = Na + K - Cl - HCO3
Anion Gap = 145 + 5 - 102 - 24
Anion Gap = 24mM
The normal range for an anion gap varies depending on how it is measured, but with modern selective electrode measuring is 3/4-11/12mmol/L
Blood tests provide the following results: Na: 160 K: 6.0 Urea: 50 pH: 7.30 Glucose: 60
What is the osmolality?
442 osm/L
Osmolality = 2(Na + K) + Urea + Glucose Osmolality = 2(160 + 6) + 50 + 60 Osmolality = 442 osm/L
normal is 275-295 mOsm/kg
(osmolarity /L, osmolality/kg)
Blood tests provide the following results: Na: 140 K: 4.0 Urea: 4.0 pH: 7.10 Glucose: 4.0
What is the osmolality?
296 osm/L
Osmolality = 2(Na + K) + Urea + Glucose Osmolality = 2(140 + 4) + 4 + 4 Osmolality = 296
Blood tests provide the following results: Na: 140 K: 4.0 Urea: 4.0 pH: 7.10 Glucose: 4.0 Chloride: 90 HCO3: 4.0
What is the anion gap?
50 mM
Anion Gap = Na + K - Cl - HCO3
Anion Gap = 140 + 4 - 90 - 4
Anion Gap = 50mM
The normal range for an anion gap varies depending on how it is measured, but with modern selective electrode measuring is 3/4-11/12mmol/L
A patient presents with the following blood test results:
Na: 125 K: 6.5 U: 10 Glucose: 2.9 FT4: <5 TSH: >50
What is the most likely diagnosis?
A. Grave's disease B. A toxic thyroid nodule C. Schmidt's syndrome D. Primary hypothyroidism E. Addison's disease
C. Schmidt’s syndrome
Schmidt’s syndrome refers to occurrence of primary hypothyroidism along with Addison’s disease, as they occur together more often than they should by sheer chance.
schmidt’s syndrome also known as a autoimmune polyglandular syndrome- are endocrine disorder defined by the combined occurrence of primary adrenal insufficiency with autoimmune thyroid disease and/or type 1 diabetes (also autoimmune)
A 33 year-old with previously recorded hypertension has the following blood test results:
Na: 147 K: 2.8 U: 4.0 Glucose: 4.0 Plasma aldosterone high Plasma renin low
What is the most likely diagnosis?
A. Essential hypertension B. Conn's syndrome C. Phaeochromocytoma D. Cushing's syndrome E. Cushing's disease
B. Conn’s syndrome
Conn’s syndrome is caused by excess aldosterone secretion from the adrenal glands, due to hyperplasia or tumours. This causes suppression of renin release from the juxtaglomerular apparatus.
(also pt is young for HTN- think phaeo, Conn’s)
A 33 year-old with previously recorded hypertension has the following blood test results:
Na: 146 K: 2.9 U: 4.0 Glucose: 14.0 Plasma aldosterone low Plasma renin low High dose dexamethasone test fails to suppress cortisol
What is the most likely diagnosis?
A. Essential hypertension B. Conn's syndrome C. Phaeochromocytoma D. Cushing's syndrome E. Cushing's disease
Which test has superseded the high-dose dexamethasone suppression test?
D. Cushing’s syndrome
Cushing’s syndrome refers to excess cortisol release, whereas Cushing’s disease specifically refers to high cortisol as a result of an ACTH-releasing pituitary adenoma.
Inferior petrosal sinus sampling has superseded high-dose dexamethasone tests as it is more reliable, though the technology to perform sampling is not always available.
Which of the following is not a direct effect of PTH?
A. Excretion of phosphate in the kidney B. Activation of 1-alpha hydroxylase C. Resorption of calcium in the kidney D. Absorption of calcium in the gut E. Resorption of calcium from bone
D. Absorption of calcium in the gut
This is a tricky one, but PTH does not directly act on the gut, it exerts an effect by activating 1-alpha hydroxylase which increases 1,25-OH vitamin D levels, which acts on the gut.
PTH increases blood Ca2+ by any means
Which of the following is the inactive storage form of vitamin D, and is the form that is usually measured?
A. 1,25-dihydroxycholecalciferol B. 25-hydroxycholecalciferol C. Cholecalciferol D. 7-dehydrocholesterol E. Cholesterol
B. 25-hydroxycholecalciferol
In which organ is 25-hydroxylase found?
A. Liver B. Kidney C. Skin D. Parathyroid E. Bone
A. Liver
25 hydroxylase converts cholecalciferol into 25-hydroxycholecalciferol - the main storage form of vitamin D. It is this form that is measured by a vitamin D test.
Which of the following commonly presents with depression?
A. Hyperkalaemia B. Hypokalaemia C. Hypercalcaemia D. Hypocalcaemia E. Uraemia
C. Hypercalcaemia
‘Stones, abdominal moans, and psychic groans’ is the way to remember the effects of hypercalcaemia:
Stones - renal stones
Abdominal moans - constipation and abdominal pain
Psychic groans - depression
A 28 year-old woman presents to hospital with jaundice, pruritis, and dark urine. Her only PMHx is a visit to her GP for antibiotics to treat a UTI (Augmentin). Her LFTs reveal a cholestatic picture, but USS shows no bile duct obstruction.
What is the most likely diagnosis?
A. Cholestasis of pregnancy B. Gallstones C. Primary sclerosing cholangitis D. Drug-induced cholestasis E. Pancreatic cancer
D. Drug-induced cholestasis
Drug induced cholestasis may present as an acute illness that promptly subsides with the withdrawal of the offending agent. It may present with or without jaundice.
Some common drugs associated with cholestatic injury include chlorpromazine, ciprofloxacin, ofloxacin, cimetidine, phenytoin, naproxen, captopril, erythromycin, azithromycin, and dicloxacillin. Amoxicillin-clavulanic (augmentin) acid is also an important cause of cholestatic jaundice.
A 74 year-old retired publican with a significant alcohol history presents with a 3-week history of itchiness, pale stools, dark urine, and yellow sclera. He has experienced 7kg weight loss over the past month. O/E you note epigastric fullness but no tenderness.
What is the most likely diagnosis?
A. Liver cirrhosis B. Gallstones C. Pancreatic cancer D. Primary sclerosing cholangitis E. Hepatocellular carcinoma
C. Pancreatic cancer
Remember Courvoisier’s rule: jaundice with a painless palpable gallbladder is unlikely to be due to gallstones. The alcohol history (questions may just say they are a publican and let you connect the dots) particularly indicates pancreatic cancer, liver cancer, and cirrhosis. The weight loss and epigastric fullness most suggest pancreatic cancer, and the itchiness, pale stools, and dark urine imply an obstructive picture i.e. the tumour is obstructing the bile duct.
likely to be cancer of the head of the pancreas
What are the three main buffers in the body?
Extracellular fluid - Bicarbonate
Intracellular fluid - Phosphate
Red blood cells - Haemoglobin (Haldane effect)
ie acid/base buffers
Assess the nature of the acid-base disturbance described by this ABG: pH - 6.9 pCO2 - 3.0 pO2 - 24 Bicarbonate - 6
Severe metabolic acidosis
Respiratory acidosis is caused by retaining CO2, and respiratory alkalosis is caused by over-ventilation causing depletion of CO2. Whilst this is simple to remember, the causes of metabolic acidosis and alkalosis are far more diverse.
Raised anion gap acidosis:
M - methanol
U - uraemia (renal failure-retains H+, not the uraemia itself)
D - diabetic ketoacidosis
P - paracetamol
I - iron, isoniazid, inborn error of metabolism
L - lactic acidosis
E - ethylene glycol (antifreeze) (ethanol is also included, but only causes acidosis through increased lactic acid in the blood, as does metformin in overdose)
S - salicylatyes (aspirin)
side note- A key concept for the exam is to understand that salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis. In children metabolic acidosis tends to predominate. + tinnitus
Normal gap acidosis:USED CAR Park U - ureteric-intestinal diversion S - sigmoid fistula E - excess saline D - diarrhoea C - carbonic anhydrase inhibitors A - Addison's R - renal tubular acidosis P - pancreatic fistula
Assess the nature of the acid-base disturbance described by this ABG: pH - 7.55 pCO2 - 8.2 pO2 - 10.0 Bicarbonate - 51
***Metabolic alkalosis
NB: due to the equilibrium of the reactions involving carbonic acid and bicarbonate, CO2 and bicarbonate will usually mimic each other
The three main causes of metabolic aklaosis that are taught to us are:
H+ loss (e.g. vomiting)
Long-standing hypokalaemia: If K+ plasma concentration is low, then the Na+/K+ co-transporter can’t work to pump Na+ out of cells. Instead, the Na+/H+ co-transporter moves Na+ out of the cell, but moves H+ into the cell, lowering the plasma pH. This may be caused by long-term diuretic use (which causes hypokalaemia). Furthermore in hypokalaemia, H+ ions will be lost in the kidney as K+/H+ transporters attempt to retain potassium.
Excess bicarbonate intake
Thiazide diuretics reduce potassium concentration in blood through two indirect mechanisms: inhibition of sodium-chloride symporter at distal convoluted tubule of a nephron and stimulation of aldosterone that activates Na+/K+-ATPase at collecting duct. Inhibition of sodium-chloride symporter increases availability of sodium and chloride in urine. When the urine reaches the collecting duct, the increase in sodium and chloride availability activates Na+/K+-ATPase, which increases the absorption of sodium and excretion of potassium into the urine. Long term administration of thiazide diuretics reduces total body blood volume. This activates the renin–angiotensin system, stimulates the secretion of aldosterone, thus activating Na+/K+-ATPase. Often ACEis given alongside TDs to prevent hypoK+
Assess the nature of the acid-base disturbance described by this ABG: pH - 7.41 pCO2 - 10.4 pO2 - 7.8 Bicarbonate - 47
Either:
Mixed respiratory acidosis and metabolic alkalosis
Or a fully compensated respiratory acidosis/ metabolic alkalosis
This case was a 72 y/o man with COPD causing CO2 retention, but was also taking furosemide for heart failure, which had lead to hypokalaemia and metabolic alkalosis. However without the clinical background, it is equally plausible to say this could be a fully compensated abnormality rather then a mixed picture.
furosemide-Hypokalemia is caused by the increased distal delivery of potassium and secondary mineralocorticoid excess
A man is brought to hospital 8 hours after taking an aspirin overdose.
Assess the nature of the acid-base disturbance described by this ABG:
pH - 7.46
pCO2 - 2.0
pO2 - 17.8
Bicarbonate - 10
Mixed respiratory alkalosis and metabolic acidosis
This picture is classic of aspirin overdose which produces mixed acidosis and alkalosis. There is a suggestion that this could be a partially compensated respiratory alkalosis, however this is very unlikely because respiratory alkalosis is caused by hyperventilation. The kidneys take much longer to compensate than the lungs, and so this person would have to be hyperventilating for weeks to produce this picture.
initially salicylic acid OD- resp alkalosis (as stims resp centres- hyperventilation) then metabolic acidosis (as it’s an acid)- mixed picture- remember this by lungs change pH much faster than kidneys
Which of the following would confirm a diagnosis of diabetes mellitus type 2?
A. Fasting plasma glucose over 6.5mM
B. A 2 hour plasma glucose in a GGT of 9.0nM
C. A 2 hour plasma glucose in a GGT of 10.0nM
D. A 2 hour plasma glucose in a GGT of 11.0nM
E. HbA1c > 6.5% (48mmol/mol)
E. HbA1c > 6.5% (48mmol/mol)
T2DM diagnosis used to require either a fasting plasma glucose measurement of 7.0mM or greater, or a 2h GGT plasma glucose of 11.1mM or greater. These are both still in use, but an additional criterion has been added: an HbA1c > 6.5% can be used to diagnose diabetes.
https://www.diabetes.org.uk/for-professionals/improving-care/clinical-recommendations-for-professionals/diagnosis-ongoing-management-monitoring/new_diagnostic_criteria_for_diabetes
Which of the following is a measure of glucose control over the last 3 weeks?
A. Fasting plasma glucose B. Random plasma glucose C. OGTT D. HbA1c E. Fructosamine
E. Fructosamine
HbA1c gives a picture of control over the last 3 months, and is used to monitor control in diabetics. However in cases where the doctor needs a snapshot of control over the last few weeks, fructosamine is useful.
A 30 year-old man complains of polydipsia and polyuria. His fasting blood glucose is 4.7mmol/L. Biochemical tests reveal: Na+ - 140 K+ - 4.2 Ca - 2.85 Phosphate - 0.4 (0.8-1.4) PTH - 4.2 (1.1-6.8)
What is the most likely diagnosis?
A. Addison's disease B. Primary hyperparathyroidsim C. T2DM D. Renal failure E. Hypercalcaemia of malignancy
B. Primary hyperparathyroidsim
Although the PTH is normal, it is inappropriate for it to be normal because the calcium is elevated (2.2-2.56 usually).
A 50 year-old Asian woman complains of tingling in her hands and feet. When checking her blood pressure, her hands begin to spasm. Her fasting blood glucose is 4.9mmol/L. Biochemical investigations reveal: Na+ - 141 K+ - 4.1 Ca - 1.85 Phosphate - 1.4 (0.8-1.4) PTH - 80 (1.1-6.8)
What is the most likely diagnosis?
A. Primary hyperparathyroidism B. Paget's disease C. Secondary hyperparathyroidism D. Rickets E. Osteoporosis
C. Secondary hyperparathyroidism
This is hyperparathyroidism secondary to low vitamin D (i.e. osteomalacia). If this was a child, then option D - rickets - would also be correct, as that is vitamin D deficiency in children.
NB: The majority of cases of secondary hyperparathyroidism are caused by chronic kidney disease. The diseased kidneys fail to hydroxylate enough vitamin D to stimulate sufficient calcium absorption form the gut. Furthermore, the kidneys fail to excrete phosphate, which reacts with calcium in the blood to form a complex which is then excreted, further lowering calcium.
For hypocalcaemia, the effects can be remembered using CATs go numb: paraesthesia, convulsions, arrhythmias, tetany, and numbness in the hands and feet and around the mouth.
The spasm of the hand noted when applying the blood pressure cuff is known as Trousseau’s sign, and reflects the increased excitability of muscles when calcium is low. You may also observe widespread exaggerated reflexes.
A 51 year-old Asian woman complains of nocturia and dizziness. Her fasting blood glucose is 3.9 mmol/L.
Biochemical investigations reveal:
Na+ - 131 K+ - 6.1 Ca - 2.75 Phosphate - 1.0 (0.8-1.4) PTH - 1.3 (1.1-6.8)
What is the most likely diagnosis?
A. T1DM B. T2DM C. Primary hyperparathyroidism D. Addison's disease E. Cushing's syndrome
D. Addison’s disease
A combination of high potassium and low sodium points to Addison’s disease (primary hypoadrenalism). Aldosterone and cortisol both activate mineralocorticoid receptors in the colecting ducts of the kidney. Activation results in sodium retention and potassium excretion, so low levels of adrenal steroid hormones results in low sodium and high potassium. This can progress to an emergency Addisonian crisis featuring vomiting/ diarrhoea, confusion and reduced consciousness, electrolyte derangement, abdominal/ lower back/ leg pain, and hypotension. The high calcium is a result of dehydration.
NB: Cortisol has a high affinity for mineralocorticoid receptors. It is prevented from constantly over-stimulating them through the action of 11 beta-dehydrogenase 2, which is expressed in tissues alongside the receptors and converts cortisol to its inactive form - cortisone.
A 60 year-old man complains of pain in his knee and examination reveals an effusion. Withdrawal of fluid and microscopy reveals crystals, which on viewing under polarised light are positively birefringent.
What is the most likely diagnosis?
A. Hyperphosphataemia B. Pseudogout C. Gout D. Septic arthritis E. Hypercalcaemia
B. Pseudogout
In pseudogout, you will see rhomboid positively birefringent crystals, whereas in true gout you will see negatively birefringent needles.
A 30 year-old man complains of polyuria and polydipsia. His fasting blood glucose is 4.7mmol/L. Biochemical tests reveal:
Na+ - 157 K+ - 4.2 Ca - 2.35 Phosphate - 1.2 PTH - 4.2
What is the most likely diagnosis?
A. SIADH B. T2DM C. Diabetes insipidus D. Addison's disease E. Conn's syndrome
C. Diabetes insipidus
Sodium derangement is often due to changes in hydration as it is an extracellular ion. In this case the high sodium reflects dehydration which, along with the history and normal glucose, potassium, and calcium, indicates diabetes insipidus.
Diabetes insipidus can be either cranial (failure to produce vasopressin) or nephrogenic (insensitivity to vasopressin). Nephrogenic diabetes insipidus is often caused by drugs, particularly by lithium.
Cranial DI may be caused by a number of things, though an important and relatively common differential in a new presentation is metastases within the brain compressing the pituitary. However DI may also be idiopathic, and can be the result of trauma or cranial surgery. Ultimately, cranial DI may be caused by anything that damages the pituitary (infiltrative disease, autoimmune, infections etc.).
Why are peripheral joints more often affected in gout?
Because the amount of urate dissolved in the blood at any one time is very close to its limit of solubility. This limit decreases at lower temperatures, and so urate is more likely to precipitate and cause problems in the peripheries as they are cooler.
Give the three main functions of purines
Energy source (ATP, GTP)
Secondary messenger in cell membrane signalling (cAMP, cGMP)
Components of DNA
pyrimidines have ‘Y’ in them + uracil
Which of the following is a crucial enzyme for the salvage pathway of purine manufacture
A. HGPRT B. PAT C. Xanthine oxidase D. PPRP E. GTPase
A. HGPRT
HGPRT (also known just as HPRT) salvages purine metabolites to regenerate purines. The salvage pathway is far more efficient and predominates over the de novo pathway in most tissues.
Absolute deficiency of HGPRT leads to Lesch-Nyan syndrome, which usually presents as developmental delay around the 6 month mark though they appear normal at birth. Patients will also feature gout, classic self-mutilating behaviour (biting lips and digits), mental retardation, spasticity, and choreiform movements.
PAT is the general rate-limiting enzyme for purine metabolism.
A sample of fluid from a joint tap is analysed using polarised microscopy. Which if the following appearances would be suggestive of gout?
A. Rhomboid crystals which appear blue when aligned with the axis of the filter
B. Rhomboid crystals which appear blue when perpendicular to the axis of the filter
C. Needle-shaped crystals which appear blue when aligned with the axis of the filter
D. Needle-shaped crystals which appear blue when perpendicular to the axis of the filter
E. Needle-shaped crystals that do no exhibit colour change
D. Needle-shaped crystals which appear blue when perpendicular to the axis of the filter
Birefringence is frequently mentioned, but the way to actually tell whether something is positively or negatively birefringent is by the colour it turns depending on the direction of the light filter. If a crystal turns blue when aligned with the filter, and yellow/whiteish when perpendicular, then it is positively birefringent. If the reverse is true, it is negatively birefringent.
pale when perpendicular = positively birefringent (Ps)
Other colour is Blue
Which of the following statements are correct?
A. Allopurinol should be used for acute episodes of gout
B. NSAIDs are the first-line treatment for acute episodes of gout
C. Colchicine lowers urate levels
D. Allopurinol lowers urate levels by inhibiting HPRT
E. Allopurinol inhibits conversion of guanine to xanthine
B. NSAIDs are the first-line treatment for acute episodes of gout
In acute episodes of gout, the goal is to reduce inflammation, NOT to reduce uric acid levels as this may paradoxically cause more urate crystals to precipitate.
NSAIDs are given first line to reduce inflammation, but where they are contra-indicated (e.g. due to severe asthma or recurrent peptic ulcers) colchicine is given. Colchicine interferes with tubulin within microtubules, which impairs the motility of neutrophils, reducing their recruitment and so reducing inflammation. Glucocorticoids may also be given.
Once an acute bout is settled, medications can be given to reduce uric acid levels in the blood. Patients are advised to stay hydrated and remedy any factors increasing their uric acid levels (e.g. diet rich in wine and red meat, thiazide diuretics). Allopurinol is used and works to inhibit the canthine oxidase enzyme to reduce uric acid production. Probenecid can be used to increase renal excretion, but is not often used in the UK.
Match each term with its definition
A. Sensitivity
B. Specificity
C. Positive predictive value
D. Negative predictive value
- True positives/ total positive results
- True positives/ total disease present
- True negatives/ total negative results
- True negative/ total disease absent
A. Sensitivity - 2. True positives/ total disease present
B. Specificity - 4. True negative/ total disease absent
C. Positive predictive value - 1. True positives/ total positive results
D. Negative predictive value - 3. True negatives/ total negative results
Which of the following is not a flag for a urea cycle disorder?
A. Vomiting without diarrhoea
B. High anion gap metabolic acidosis not accounted for by lactate
C. Avoidance of particular foodstuffs (e.g. high protein items)
D. Hyperammonaemia
E. Neurological encephalopathy
B. High anion gap metabolic acidosis not accounted for by lactate
The metabolic acidosis described is more typical of organic acidurias e.g. isovaleric acidaemia.
Respiratory alkalosis is relatively uncommon and, along with hyperammonaemia, can be a sign of a urea cycle disorder.
Which of the following would hypoketotic hypoglyaemia suggest?
A. A urea cycle disorder B. An organic aciduria C. PKU D. Cystic fibrosis E. MCADD
E. MCADD
MCADD is deficiency of an enzyme that breaks down medium-chain fatty acids, releasing Acetyl CoA. When this enzyme is deficient, the patient is susceptible to hypoglycaemia, and ketones will not be produced.
PKU is caused by phenylalanine hydroxylase (which usually converts it to tyrosine) deficiency and results in a build-up of phenylalanine and its metabolites in the blood. These products are toxic to the CNS and quickly cause severe damage leading to mental retardation if not treated (remember pic from 1st year POM lecture) . There are some very expensive drugs that can be used to treat PKU, but dietary modification is the core staple of treatment.
The organic acidurias are a group of genetic conditions, one of the signs of which is hyperammonia with high anion gap metabolic acidosis. The most significant diseases involve metabolism of the branched amino acids (leucine, isoleucine, valine). Signs include a cheesy/ sweaty odour (caused by excretion of metabolites in sweat), hypocalcaemia, and pancytopaenia. In neonates it causes lethargy and feeding problems, along with a strange hypertonia in the trunk but hypotonia in the limbs. Reye syndrome (vomiting, confusion, seizures, decerebration, and respiratory arrest) can be precipitated in these patients by drugs (e.g. aspirin, valproate).
A woman with a suspected pituitary tumour undergoes a CT head which shows a pituitary mass. Blood tests reveal her prolactin is 7,000 but she has not had recent sexual intercourse and a beta-hCG test is negative.
What is the most likely diagnosis?
A. Cushing's disease B. Acromegaly C. Prolactinoma D. Non-functioning pituitary adenoma E. Conn's syndrome
C. Prolactinoma
As a general rule, a prolactin level over 6000 must be due to a prolactinoma. Non-functioning adenomas can cause high prolactin by choking off dopamine neurons projecting down from the hypothalamus (the tuberoinfundibular pathway) thereby removing suppression of prolactin. However, this is not sufficient to cause a prolactin level of 7,000.
A patient with pituitary failure is given a regimen of medications to restore normal endocrine function.
Which of the following is most important to give, and which is totally unnecessary?
A. Fludrocortisone B. Hydrocortisone C. Thyroxine D. Oestrogen E. Growth hormone
B. Hydrocortisone - most important to give or they will be vulnerable to hypoadrenalism and all its complications
A. Fludrocortisone - totally unnecessary as aldosterone production is normal in a patient with pituitary failure; the RAS functions independently from the pituitary
Which of the following is the best treatment for a prolactinoma?
A. Octreotide B. Radiotherapy C. Cabergoline D. Surgical resection E. Dexamethasone
C. Cabergoline (D2 receptor agonist)
Cabergoline is a better treatment than surgery - it will shrink the tumour and has none of the risks of invasive surgery.
octeotride = somatostatin analogue
A patient is under investigations for acromegaly. O/E he has a barrel chest, a protruding jaw, large hands and feet, and an enlarged tongue. A glucose tolerance test fails to suppress GH.
Which other test could be used to confirm the diagnosis, and what would be the ideal first line treatment?
IGF-1
Surgery. If surgery is not available, medical management with cabergoline or octreotide is indicated.
An obese 36 year-old patient undergoes a low dose dexamethasone suppression test. Her Monday 9 a.m. cortisol is 650nM, and after being given 0.5mg dexamethasone every 6 hours for 48 hours, her Wednesday 9 a.m. cortisol is 500nM, suggesting insufficient suppression.
What should be done next?
A. Pituitary MRI B. Adrenal CT C. CXR to look for ectopic source D. High dose dexamethasone suppression test E. IPSS
E. IPSS
In previous years, the high dose dexamethasone suppression test was used. However it is not particularly good at distinguishing Cushing’s syndrome from Cushing’s disease, and so has been superseded by inferior petrosal sinus sampling (IPSS). High dose testing is supposed to distinguish pituitary causes of Cushing’s syndrome, but was correct less than 85% of the time. Since 85% of cases of Cushing’s syndrome have a pituitary cause, this method was less accurate than just assuming a pituitary cause.
Why is it ideal to resect the entire thyroid in cases of thyroid cancer where surgery is indicated?
Because it allows thyroglobulin to be used as an indicator of disease. If the entire thyroid is removed, thyroglobulin should be 0. Therefore if thyroglobulin >0 is detected on screening, the clinician knows the cancer has recurred. However this is only possible if the entire thyroid is removed.
A patient presents to their GP with tiredness, their TFTs are as follows:
TSH: 8.4 (0.33-4.5)
Free T4: 11.7 (10.2-22)
Thyroid peroxidase antibodies positive
Which option are these results consistent with?
A. Clinical primary hypothyroidism
B. Euthyroid status in a patient complaining of tiredness
C. Pituitary driven thyrotoxicosis
D. Secondary or pituitary hypothyroidism.
E. Sub-clinical hypothyroidism with risk of later clinical hypothyroidism
F. Non-pituitary driven thyrotoxicosis
E. Sub-clinical hypothyroidism with risk of later clinical hypothyroidism
This is essentially compensated hypothyroidism: the TSH level is above normal, but T4 is normal. Though it is unlikely to cause symptoms, sub-clinical hypothyroidism is associated with hypercholesteraemia (as in clinical hypothyroidism) and the presence of thyroid peroxidase (TPO) antibodies is a predictor of later symptomatic disease. TPO antibodies are most strongly associated with Hashimoto’s thyroiditis, but are also strongly associated with Grave’s disease.
A patient presents to their GP with tiredness, their TFTs are as follows:
TSH: 1.4 (0.33-4.5)
Free T4: 12.1 (10.2-22)
Which option are these results consistent with?
A. Clinical primary hypothyroidism
B. Euthyroid status in a patient complaining of tiredness
C. Pituitary driven thyrotoxicosis
D. Secondary or pituitary hypothyroidism.
E. Sub-clinical hypothyroidism with risk of later clinical hypothyroidism
F. Non-pituitary driven thyrotoxicosis
B. Euthyroid status in a patient complaining of tiredness
A patient presents to their GP with tiredness, their TFTs are as follows:
TSH: 22.4 (0.33-4.5)
Free T4: 6.3 (10.2-22)
Which option are these results consistent with?
A. Clinical primary hypothyroidism
B. Euthyroid status in a patient complaining of tiredness
C. Pituitary driven thyrotoxicosis
D. Secondary or pituitary hypothyroidism.
E. Sub-clinical hypothyroidism with risk of later clinical hypothyroidism
F. Non-pituitary driven thyrotoxicosis
A. Clinical primary hypothyroidism
A patient presents to their GP with tiredness, their TFTs are as follows:
TSH: <0.01 (0.33-4.5)
Free T3: 15.6 (3.2-6.5)
Free T4: 38.0 (10.2-22)
Which option are these results consistent with?
A. Clinical primary hypothyroidism
B. Euthyroid status in a patient complaining of tiredness
C. Pituitary driven thyrotoxicosis
D. Secondary or pituitary hypothyroidism.
E. Sub-clinical hypothyroidism with risk of later clinical hypothyroidism
F. Non-pituitary driven thyrotoxicosis
F. Non-pituitary driven thyrotoxicosis
Which of the following is true regarding urine dipstick testing?
A. If the dipstick is negative for blood, it reliably excludes haematuria
B. Haematuria is the only cause of a positive dipstick test for blood
C. You can reliably exclude bacturia is the urine dipstick is negative for nitrites
D. The urine dipstick detects Bence-Jones proteins
E. Glycosuria detected by the dipstick means the patient has diabetes
A. If the dipstick is negative for blood, it reliably excludes haematuria
A urine dipstick may return a false positive as it can detect haemoglobin (haemolysis) or myoglobin (rhabdomyolysis) in the urine, but it is unlikely to return a false negative.
Negative nitrites cannot reliably exclude bacturia because nitrites are only produced by Gram negative pathogens. Although the main pathogen causing UTIs is Gram negative (Escherichia coli), Gram positive organisms such as Staphylococcus saprophyticus and Enterococcus can also infect the urinary tract. Furthermore the production of nitrites is dependent on sufficient time in the bladder for their production, and sufficient nitrate content in the diet.
Though the urine dipstick does detect protein in the urine, it is not specific for any particular protein, and is more sensitive to albumin than Bence-Jones proteins.
Glycosuria is found in diabetes, but not all the time, and there are other causes.
A 50 year-old known alcoholic presents to A&E generally unwell and intoxicated with an AKI and a raised anion gap acidosis. Urine microscopy reveals calcium oxalate crystals.
What is the most likely diagnosis?
A. Hypercalcaemia B. Ethylene glycol poisoning C. Gout D. Salicylate poisoning E. Acute pancreatitis
B. Ethylene glycol poisoning
Ethylene glycol is metabolised to oxalic acid, which then reacts with calcium to form calcium oxalate crystals which can be found in the urine. This along with the acute kidney injury and raised anion gap acidosis point to ethylene glycol poisoning.
NB: Ethylene glycol is found in antifreeze
What are the 4 characteristics of an ideal agent for predicting GFR?
Freely filtered
Not secreted or reabsorbed by tubular cells
Not bound to plasma proteins
Not modified by renal tubule cells
Which of the following treatments for thyrotoxicosis can, rarely, cause agranulocytosis?
A. Radioiodide B. Propranolol C. Surgical resection of the thyroid D. Carbimazole E. Alpha blockers
D. Carmbimazole
Thionamides work by inhibiting iodination of the tyrosine residue on iodine molecules (by blocking TPO). This prevents them being joined to form thyroxine.
Radioiodide can rarely precipitate a thyroid storm.
Alpha blockers are used in treatment of phaeochromocytomas, but not generally hyperthyroidism.
Why does T4 rise and TSH fall during pregnancy?
hCG has a somewhat similar structure to TSH, and so activates TSH receptors (specifically the hCG alpha subunit). This causes a physiological rise in T4, and TSH is inhibited via negative feedback.
Which of the options describes the correct percentage of T4 free in the circulation and bound to TBG (thyroglobulin binding globulin)?
A. Free: 0.03%, TBG bound: 75% B. Free: 0.3%, TBG bound: 50% C. Free: 5%, TBG bound: 75% D. Free: 30%, TBG bound: 25% E. Free: 50%, TBG bound: 25%
A. Free: 0.03%, TBG bound: 75%
Some T4 is bound to albumin (5%) and some to TBPA (20%), but the majority is bound to TBG, with only a tiny fraction free in the blood at any one time.
What are the three most common causes of hypothyroidism in the developed world?
Hashimoto’s disease
Atrophic thyroid
Iatrogenic - post-treatment for hyperthyroidism (and less commonly cancer)
Which if the following drugs may cause an AKI by decreasing efferent arteriolar constriction?
A. NSAIDs B. Calcineurin inhibitors C. ACEi or ARBs D. Diuretics E. All of the above
C. ACEi or ARBs
NSAIDs - decrease afferent arteriolar dilatation
Calcineurin inhibitors - decrease afferent arteriolar dilatation
ACEi or ARBs - decrease efferent arteriolar constriction
Diuretics – affect tubular function, decrease preload
NSAIDs inhibit the synthesis of prostaglandins by inhibiting the enzyme cyclooxygenase (COX). Prostaglandins help maintain renal blood flow by dilating renal blood vessels (they also are directly nephrotoxic to tubules)
ACE blocked to less angiotensin II. Angiotensin II is a potent vasoconstrictor, and its effects include vasoconstriction of both the efferent and afferent arterioles in the kidney. So ACEis cause dilation.
A 70 year-old man is involved in a road-traffic accident and is brought in under blue lights to hospital for emergency surgery. The surgery is successful but whilst he is convalescing, his urine output decreases and his creatinine starts to rise. Urine microscopy reveals muddy brown casts.
What is the prognosis for this patient?
A. He will need dialysis and ultimately a transplant
B. Kidney function will respond rapidly to restoration of circulating volume
C. There is a small chance of him regaining kidney function
D. He will need dialysis, but probably only for 1-3 weeks
E. His kidney will require surgical repair
D. He will need dialysis, but probably only for 1-3 weeks
Acute tubular necrosis is generally caused either by ischaemia or toxins. In this case, the blood loss from the RTA has caused ischaemic necrosis of his tubules. Despite its dramatic name, the prognosis is quite good. This patient will need dialysis in the meantime, but he should regain kidney function in 1-3 weeks, assuming his circulating volume is restored.
NB: Casts in urine can be very helpful diagnostic aids. Muddy brown casts are pathognomic of acute tubular necrosis.
Which of the following is the most common cause of in-hospital AKI?
A. Radiographic contrast B. Decreased perfusion C. Medications D. Sepsis E. Post-operative
B. Decreased perfusion
It is worth knowing what actually causes AKI. The order in terms of frequency is: B. Decreased perfusion A. Radiographic contrast C. Medications E. Post-operative D. Sepsis
NB: AKIs are serious - there is a 20% mortality rate
AKI CI drugs are DAAAMN (mnemonic), aminoglycoside ABx as well (so DAAAMN)
A patient comes to the renal clinic for a check-up. Their eGFR is 34ml/min.
What stage of CKD does this patient have?
A. 1 - Kidney damage with normal GFR B. 2 - Mild decrease in GFR C. 3 - Moderate decrease in GFR D. 4 - Severe decrease in GFR E. 5 - End-stage kidney failure
C. 3 - Moderate decrease in GFR
Stage 1: >90ml/min Stage 2: 60-89ml/min Stage 3: 30-59ml/min Stage 4: 15-29 ml/min Stage 5: <15ml/min OR receiving dialysis
remember 3a (60-45), 3b (30-45)
Which of the following is not a consequence of CKD?
A. Acidosis B. Bone disease C. Cardiomyopathy D. Macrocytic anaemia E. Hyperkalaemia
D. Macrocytic anaemia
The main consequences of CKD can be split into:
Homeostatic: acidosis, hyperkalaemia
Hormonal: normocytic anaemia (as EPO deficient), bone disease (renal osteodystrophy)
CVS: vascular calcification, uraemic cardiomyopathy (as a consequence of fluid overload)
Which occurs first in response to hypoglycaemia?
A. Suppression of insulin
B. Release of glucagon
C. Release of adrenaline
D. Release of cortisol
B. Release of glucagon
Which of the following findings would imply an obstructive cause of jaundice?
A. INR > 2.0 B. Low albumin C. An AST:ALT ratio >2.0 D. Scleral icterus E. Low urobilinogen
E. Low urobilinogen
Bilirubin is secreted into the small bowel as bile, whereupon some is converted into urobilinogen by the bacteria of the gut flora. Around half of the urobilinogen produced is reabsorbed and secreted in urine. If urobilinogen in the urine is low in the context of jaundice, it implies that there is an obstruction preventing secreting of bilirubin into the bowel. However, there are other causes of low urobilinogen (e.g. broad-spectrum antibiotic use that destroys gut flora).
Urobilinogen is the same thing as stercobilinogen; it is colourless, but is converted into stercobilin which gives faeces its brown colour.
INR (or PT) is the best measure of acute liver function, whereas albumin is the best measure of chronic function. However, derangement of either would more strongly imply a hepatic, rather than post-hepatic, issue as synthetic function would be impaired.
Scleral icterus is jaundice visible in the whites of the eyes; it is one of the first signs of jaundice but is not specific to a cause. An AST:ALT ratio of >2.0 is indicative of alcoholic liver disease.
NB: the dark urine seen in obstructive jaundice is caused by urinary excretion of conjugated bilirubin
A 76 year old man with a history of T2DM and hypertension, who is poorly compliant with medication, presented feeling unwell and having not passed urine in the past 24 hours. An ABG showed the following: pH: 7.21 PaO2: 11.1 kPa PaCO2: 4.2 kPa HCO3-: 14 Lactate: 1.3 Na+: 140 K+: 5.9 Cl-: 112 Glucose: 12.1
What is the most likely diagnosis?
A. Hypoadrenalism B. Renal failure C. Aspirin overdose D. Diabetic ketoacidosis E. Hyperosmolar hyperglycaemic non-ketotic coma
B. Renal failure
The key features of this patient’s ABG and history are the hyperkalaemia and the failure to pass urine for 24 hours. These findings suggest renal failure, presumably resulting as a complication of the patient’s poorly controlled diabetes. The renal failure has in turn caused a raised anion gap acidosis, as the damaged kidney is unable to excrete H+ ions.
The lack of urine output effectively excludes DKA, as it would cause a significant diuresis. Critera for DKA diagnosis:
• capillary blood glucose above 11 mmol/L
• capillary ketones above 3 mmol/L or urine ketones ++ or more
• venous pH less than 7.3 and/or bicarbonate less than 15 mmol/L
(according to Joint British Diabetes Societies
Inpatient Care Group: https://www.diabetes.org.uk/resources-s3/2017-09/Management-of-DKA-241013.pdf)
A 64 year-old man is brought to hospital in an ambulance having had a seizure at home. His daughter accompanies him and gives you a collateral history. She says he has been drowsy, fatigued, and disorientated recently. He has mentioned constipation and increased urinary frequency recently, though he has not passed urine all day. He has been complaining of aches and pains at various sites and unintentional weight loss of 6kg over two months. His notes show he was admitted to hospital three months ago for renal stones. Blood tests reveal the following:
Ca: 3.6
PTH: 0.1
Urea: 12.5
Given the most likely diagnosis, how should this patient be managed?
A. X-ray the painful sites, analyse a urine sample for Bence-Jones proteins, and refer the patient to oncology
B. Start the patient on a regimen of oral bisphosphonates and advise them to increase their fluid intake
C. Perform a respiratory exam and CXR, and check serum ACE levels
D. Establish I.V. access and give saline and pamidronate
E. Refer the patient for radiotherapy to address the pain from their bone lesions
D. Establish I.V. access and give saline and pamidronate
According to the Society for Endocrinology, a calcium of over 3.5 needs urgently treating due to the risk of coma and cardiac arrythmia. Severe hypercalcaemia is an emergency, and the mainstay of treatment is I.V. saline to rehydrate the patient. Furosemide can be used to avoid fluid overload if needed. Pamidronate is a bisphosphonate: bisphosphonates are incorporated into mineral bone and cannot be broken down by osteoclasts. This prevents breakdown of bone, but also interferes with physiological remodelling. Therefore though bisphosphonates do reduce the fracture rate, and will prevent the bone breakdown leading to hypercalcaemia in this case, they can also cause atypical fractures. Bisphosphonates are useful for hypercalcaemia, but will take a few days to work, hence the main treatment is saline.
Bisphosphonates should be delayed in suspected hyperparathyroidism because it alters PTH and phosphate, which can make diagnosis tricky. In cases where there is an underlying cancer (most common cause of hypercalcaemia in hospital) bisphosphonates can be given immediately, and are effective at relieving bone pain. Radiotherapy is also useful for relieving bone pain.
This is a history of hypercalcaemia of malignancy, the aetiology of which is multifactorial: PTH-related peptide (PTHrp) may be released from some tumours, bony metastases may release osteoclast-activating factors, and tumours may produce 1,25-hydroxycholecalciferol.
Link to useful Society for Endocrinology guidelines:
https://www.rcem.ac.uk/docs/External%20Guidance/10R.%20Acute%20Hypercalcaemia%20-%20Emergency%20Guidance%20(Society%20for%20Endocrinology,%20Jan%202014).pdf
A 58 year old woman is brought to A&E having tripped and fallen onto her outstretched hand. Her wrist is swollen, and an x-ray shows a fracture with the radius displaced posteriorly from the wrist (Colles’ fracture). This is the second time she has been to hospital in the past year for a fracture, having fractured her scaphoid 6 months ago. On further questioning she admits constipation, polyuria, and polydipsia, and says she has been seeing her GP regarding her low mood; a parathyroid adenoma is suspected.
Which of the following findings would support a diagnosis of parathyroid adenoma?
A. A normal serum calcium but an elevated ALP
B. Decreased Vitamin D, pseudofractures visible on x-ray
C. Multinucleate giant cells in bone seen on histology, and radial aspect cystic changes of the hand seen on x-ray
D. PTH <1.1mmol with a calcium of 2.7mmol, and PTH related peptide detected in the blood
E. Looser’s zones, pepper pot skull appearance, and codfish vertebrae
C. Multinucleate giant cell lesions in bone seen on histology, and radial aspect cystic changes of the hand seen on x-ray
This is a history of hypercalcaemia, in this case caused by primary hyperparathyroidism, ~90% of cases of which are caused by an adenoma. The multinucleate giant cell lesions mentioned are Brown tumours - aggregations of osteoclasts that can be seen either on histology or as lucencies on x-ray. The radial aspect cystic changes of the hand are typical of long-term uncontrolled hyperparathyroidism.
The features mentioned in E are found in osteomalacia, hyperparathyroidism, and osteoporosis/ osteomalacia respectively.
In which of the following would you NOT expect to find a raised ALP?
A. A 13 year old boy in the midst of a growth spurt
B. An 80 year old woman with a history of fractures due to osteoporosis
C. A 30 week pregnant woman generally well but with recent onset itching of her palms and soles
D. A 35 week pregnant woman who has been suffering from back pain and increased urinary frequency
E. A 72 year old man with metastatic prostate cancer
B. An 80 year old woman with a history of fractures due to osteoporosis
Though thought of as an LFT, ALP can be made in multiple different organs, especially bone, liver, and placenta. Any cause of increased bone turnover or remodelling will elevate ALP, hence Paget’s disease, bone metastases (E), and a child’s growth spurt (A) can all feature raised ALP. ALP can be elevated in a patient recovering from a fracture, but is not raised in osteoporosis (B), despite a history of past fractures.
‘C’ is hinting at obstetric cholestasis, which causes build up of bile acids during pregnancy and typically presents as itching of the palms and soles. This most commonly presents at around 30 weeks gestation, but may occur from ~8 weeks onwards. Jaundice may well not be present, as bilirubin is usually below 17mcmol/L, but must be over 34-51mcmol/L to cause jaundice.
‘D’ is 35 weeks pregnant - this option is designed to remind that back pain and increased urinary frequency are normal at this stage
NB: Prostate cancer frequently metastasises to bone
osteoporosis = all parameters normal (think of pathology- lack of bone density)
A 65 year old man comes in to his GP practice to receive the results of a blood test taken as part of a standard health check. His PMHx includes a STEMI 6 months ago; since then he has been taking aspirin, sotalol, atorvastatin, and ramipril. An extensive panel of blood tests reveals an abnormality.
Which of the following enzymes is most likely to be elevated?
A. Amylase B. Troponin C. BNP D. Creatinine E. Creatine kinase
E. Creatine kinase
The STEMI 6 months ago is not particularly relevant as all biomarkers form that event will have subsided by now. This is a question about which of the drugs this patient takes are known to derange enzyme levels. This is hinting at statin-induced myopathy, which features raised creatine kinase. Whilst BNP is a specific (but not sensitive) marker of cardiac failure, there is no mention of symptoms in the question which would suggest that.
Why does hyperventilation cause paraesthesia?
Hyperventilation increases the pH of the blood, which increases the amount of calcium that binds to albumin in the serum. This essentially causes hypocalcaemia which causes paraesthesia.
What are the emergency indications for dialysis?
- Pulmonary oedema
- Refractory hyperkalaemia
- Metabolic acidosis
- Uraemic encephalopathy
- Also some drug toxicity (e.g. lithium)
AEIOU mnemonic, which stands for: acidosis, electrolyte imbalances, intoxication, overload (volume), and uremia.
Which of the following results would best support a diagnosis of SIADH?
A. A urine osmolality of 120 B. A plasma osmolality of 280 C. Hypernatraemia D. A raised blood pressure E. Elevated prolactin
A. A urine osmolality of 120
SIADH should feature concentrated urine, i.e. with osmolality >100
normal ranges-
Serum: 275 – 295 mOsmol/Kg
Urine: 50 – 1200 mOsmol/Kg
blood and urine should match as urine corrects blood (ie dehydrated then more conc urine)
How should hypovolemic hyponatraemia be managed?
Volume replacement with 0.9% saline
3% saline is reserved for severe hyponatraemia (seizures, reduced GCS)
Give 2 causes of each of the following types of hyponatraemia:
Hypovolemic
Euvolemic
Hypervolemic
Hypovolemic = losses: Salt-wasting nephropathy Diarrhoea Vomiting Diuretic use
Euvolemic = Endocrine
Hypothyroidism
SIADH
Addison’s (unless in a crisis)
Hypervolemic = Failures
Heart failure
Cirrhosis/ liver failure
Nephrotic syndrome
salt wasting nephropathy = gitelmann’s, Liddle syndrome (ENaC mutation), Bartter syndrome etc
What is the management of hypernatraemia?
Correct the water deficit (the cause of the hypernatraemia) with 5% dextrose
They may also need 0.9% saline if they are hypovolemic
Serial Na+ measurements each 4-6 hours
5% dextrose as sugar used up by body so just pure water being given really? (NaCl sodium causes some shifts)
Match each of the following conditions to the appropriate calcium biochemistry results:
A. Primary hyperparathyroidism
B. Osteoporosis
C. Paget’s disease
D. Renal osteodystrophy
Normal ranges: Ca: 2.2–2.6 mmol/L PTH: 0.8–8.5pmol/L ALP: 30–150u/L PO4: 0.8–1.2mmol/L Vitamin D: 60–105nmol/L
- Ca: 2.0, PTH: 12.4, ALP: 169, PO4: 1.5, Vitamin D: 71
- Ca: 2.4, PTH: 5.7, ALP: 563, PO4: 0.9, Vitamin D: 76
- Ca: 2.8, PTH: 7.9, ALP: 160, PO4: 0.6, Vitamin D: 67
- Ca: 2.3, PTH: 4.6, ALP: 80, PO4: 1.0, Vitamin D: 84
- Ca: 2.0, PTH: 12.4, ALP: 169, PO4: 1.5, Vitamin D: 71 - D. Renal osteodystrophy
- Ca: 2.4, PTH: 5.7, ALP: 563, PO4: 0.9, Vitamin D: 76 - C. Paget’s disease
- Ca: 2.8, PTH: 7.9, ALP: 160, PO4: 0.6, Vitamin D: 67 -A. Primary hyperparathyroidism
- Ca: 2.3, PTH: 4.6, ALP: 80, PO4: 1.0, Vitamin D: 84 - B. Osteoporosis
Renal osteodystrophy refers to bone damage due to chronic renal failure and subsequent failure to produce the active form of Vitamin D via 1-alpha hydroxylation. 25-hydroxycholecalciferol is the precursor form of Vitamin D and is the form we measure, so it will confusingly be normal even though this patient essentially has Vitamin D deficiency. Renal osteodystrophy patients will have the characteristic findings of osteomalacia/ secondary hyperparathyroidism, but phosphate will be high due to lack of renal excretion through the damaged kidneys, and Vitamin D will be normal.
What are the most common causes of primary and secondary hyperparathyroidism?
Primary: A parathyroid adenoma
Secondary: Chronic renal failure
Which test has superseded the high dose dexamethasone suppression test?
Inferior petrosal sinus sampling
Which test is used to test overall pituitary function?
The Combined Pituitary Function Test (CPFT) or ‘triple test’ as it is also known
It involves giving GnRH, TRH, and insulin to induce metabolic stress and stimulate anterior pituitary hormone production
Porphyria cutanea tarda and acute intermittent porphyria are the two most common porphyrias: which enzymes are deficient in each?
Porphyria cutanea tarda - Uroporphyrinogen decarboxylase
Acute intermittent porphyria - HMB synthase (a.k.a. Porphobilinogen deaminase)
remember HMB with AIP and A (AIP) then B (HMB)
Why can’t aspirin be used to treat attacks of Gout?
It competes with urate for excretion in the kidney, and so actually worsens the hyperuricaemia
A 70 year old woman is seen in A&E because of a fall after which she was unable to weight bear. An x-ray diagnoses a fractured neck of femur. She has otherwise been well and living independently. A set of blood tests taken 2 days after the break reveal: normal Calcium, PTH, Vitamin D, and Phosphate, but an ALP of 250 (>150 abnormal).
What is the most likely underlying disease?
A. Cushing's syndrome B. Primary hyperparathyroidism C. Osteomalacia D. Paget's disease E. Osteoporosis
E. Osteoporosis
Though the history may seem to indicate Paget’s disease because of the elevated ALP, it is normal to see elevated ALP after a fracture as osteoblasts begin to heal the bone. Osteoporosis is significantly more common than Paget’s disease, and other than the raised ALP, nothing in the history or biochemistry suggests any of the other options.
NB: This is modified from a question from ‘Single Best Answers and EMQs in Clinical Pathology’
Match each of the descriptions to the most likely underlying vitamin deficiency
A. May affect the peripheral nervous system, the CNS, or the CVS, and is tested for using RBC transketolase
B. Causes colour/ night blindness
C. Causes cognitive impairment, GI disturbance and a ‘necklace’ erythematous and pigmented rash
D. Causes peripheral neuropathy and dermatitis
- Pellagra
- Beri-beri
- B6 deficiency
- Vitamin A deficiency
- Pellagra - C. Causes cognitive impairment, GI disturbance and a ‘necklace’ erythematous and pigmented rash
- Beri-beri - A. May affect the peripheral nervous system, the CNS (dry beri beri), or the CVS (wet beri beri), and is tested for using RBC transketolase
- B6 deficiency - D. Causes peripheral neuropathy and dermatitis (think of isoniazide which causes B6 deficiency)
- Vitamin A deficiency - B. Causes colour/ night blindness
