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.