Chemical Pathology Flashcards

1
Q

What is the formula for osmolarity of serum?

A

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

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2
Q

What is the normal range for serum osmolality?

A

A. 275-295 mmol/kg

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3
Q

What is the osmolar gap and why is it important?

A

A. The osmolar gap is the difference between serum osmolality and osmolarity (which should roughly equate).

If the osmolarity is lower, it means that there are extra unmeasured solutes e.g. glucose, ethanol, mannitol in the serum, which is important in some pathology

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4
Q

What are the symptoms of hyponatraemia? (Normal range (135-145 mmol/l) )

A

A.

  • Nausea and vomiting
  • Confusion
  • Seizures, non-cardiogenic pulmonary oedema
  • Coma and death
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5
Q

Define true hyponatraemia and list 4 causes of a false reading

A

A. True hyponatreamia is low sodium with low serum osmolality

  1. Glucose/mannitol infusion (high osmolality)
  2. Spurious sample
  3. Drip arm sample
  4. Pseudohyponatraemia (high lipids or proteins)
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6
Q

Give three causes each for hypervolaemic, euvolaemic and hypovolaemic hyponatraemia

A

A. Hyper - heart, renal and liver failure (cirrhosis)
Eu - hypothyroidism, glucocorticoid insufficiency, SIADH (all endocrine)
Hypo - diarhhoea, vomiting, diuretics, salt losing nephropathy

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7
Q

What is the purpose of measuring urinary sodium in patients with true hyponatraemia?

A

A. To distinguish between renal (>20 mmol/l) and non-renal causes.

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8
Q

What is a risk of rapid correction of serum sodium?

A

A. Central pontine myelinosis (pseudobulbar palsy, paraparesis, locked-in syndrome) therefore aim to increase sodium by 1mmol/l per hour. Increased risk in malnourished alcoholics.

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9
Q

What is the diagnosis given the following?

  • Sodium 127 mmol/l
  • Well hydrated patient with no oedema
  • Urinary sodium 25 mmol/l
  • Normal 9am cortisol and TFTs
A

A. SIADH (diagnosis of exclusion)

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10
Q

Give four causes of SIADH

A

A.

  1. Malignancy - SCLC, pancreas, prostate, lymphoma
  2. CNS disorder
  3. Chest - TB, pneumonia, abscess
  4. Drugs - opiates, SSRIs, carbamazepine, PPIs
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11
Q

What are the symptoms of hypernatraemia?

A

A.

  • Thirst
  • Confusion
  • Seizures + ataxia
  • Coma
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12
Q

Give three causes of hypernatraemia

A

A.

  1. Hypovolaemic - fluid losses (renal, GI, skin)
  2. Euvolaemic - Diabetes insipidus
  3. Hypervolaemic - Conn’s
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13
Q

How do you diagnose nephrogenic diabetes insipidus?

A

A. Clincal features include symptoms of or measured hypernatraemia with euvolaemic status. Urine remains dilute despite an 8 hour fluid deprivation test and administration of desmopressin.

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14
Q

How is nephrogenic diabetes treated?

A

A. Thiazide diuretics

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15
Q

Give four causes of hypokalaemia (normal range 3.5-5.5 mmol/l)

A

A.

  1. GI loss
  2. Renal loss - hyperaldosteronism, thiazide and loop diuretics, osmotic diuresis
  3. Redistribution - insulin, beta-agonists, metabolic alkalosis
  4. Renal tubular acidosis type 1 and 2
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16
Q

What is the management approach for the hypokalaemic patient?

A

A. Oral SandoK and monitor potassium. If lower than 3.0, consider IV KCl (no greater than 10mM/hr). High aldosterone renin ratio implies Conn’s.

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17
Q

Give three causes of hyperkalaemia (normal range 3.5-5.5 mmol/l)

A

A.

  1. Excessive intake - almost always iatrogenic
  2. Transcellular movement (ICF>ECF) - acidosis, DKA, rhabdo
  3. Decreased excretion - acute/chronic renal failure, Spironolactone, Addison’s, NSAIDs, ACEi, ARBs
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18
Q

How is hyperkalaemia treated?

A

A. 10mls 10% calcium gluconate, 100mls 20% dextrose, and 10 units insulin +/- salbutamol.
Treat underlying cause.

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19
Q

Give three causes each of metabolic acidosis and alkalosis

A

A. Acidosis - DKA, renal tubular acidosis, intestinal fistla
Alkalosis - Pyloric stenosis, hypokalaemia, bicarbonate ingestion

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20
Q

Give two causes each of respiratory acidosis and alkalosis

A

A. Acidosis - lung injury, decreased ventilation

Alkalosis - mechanical ventilation, panic

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21
Q

What is the anion gap and how is it calculated?

A

A. Difference between concentration of total principal cations and anions, giving the concentration of unmeasured anions in plasma.

(Na + K) - (Cl - HCO3).

Normal range is 14-18 mmol/l

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22
Q

Give four causes of elevated anion gap metabolic acidosis

A

Ketoacidosis (DKA, alcohol, starvation)
Uraemia (renal failure)
Lactic acidosis
Toxins (ethylene glycol, methanol, paraldehyde, salicylate)

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23
Q

Which LFTs are markers of synthetic function?

A

A. Clotting (INR)
Albumin
Glucose

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24
Q

What are the normal ranges of aminotransferases (AST/ALT), ALP and GGT?

A

A. AST/ALT - <40iu/L
ALP - 30-150 iu/L
GGT - 30-150 iu/L

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25
Which of the following is not true of acute intermittent porphyria (AIP)? 1. Autosomal dominant inheritance 2. HMB synthase deficiency 3. Neurovisceral and cutaneous manifestations 4. Diagnosed by ALA + PBG in urine ("Port wine urine") 5. Treated by avoiding precipitating factors, analgesia and IV carbohydrate/ haem arginate
A. 3. There are NO cutaneous manifestations of AIP due to absence of porphyrinogens. Neurovisceral symptoms include GIT symptoms, psych disturbances, seizures, sensory loss, and muscle weakness Precipitating factors include ALA synthase inducers (steroid, ethanol), stress, and reduced caloric intake
26
Which of the porphyrias are acute and have skin lesions?
A. Heriditary coproporphyria (HCP) and variegate porphyria (VP). They're both autosomal dominant.
27
Which of the porphyrias are non-acute and have only skin lesions?
A. Congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT).
28
Which porphyria has symptoms of photosensitivity, burning and itching oedema following sun exposure?
A. Erythropoietic protoporphyria (EPP)
29
Which of the following is not true of porphyria cutanea tarda (PCT)? 1. HMB synthase deficiency 2. Sun exposure leads to vesicle formation 3. Diagnosed via raised urinary uroporphyrins, coproporphyrins and ferritin 4. Treated via avoiding precipitants and phlebotomy 5. Precipitants include alcohol and hepatic compromise
A. 1. PCT is caused by uroporphyrinogen decarboxylase deficiency.
30
What are contraindications to the combined pituitary function test?
A. Ischaemic heart disease, epilepsy and untreated hypothyroidism (impairs GH and cortisol response)
31
How do you conduct a combined pituitary function test, and which side effects should you watch out for?
A. Procedure: administration of GnRH, TRH and insulin. Measure pituitary hormones at 0 and every 30 minutes for two hours. Side effects include sweating, palpitations, LOC, convulsions (hypoglycaemia), metallic taste, flushing, nausea.
32
What is a normal response to the combined pituitary function test?
A. Rise in pituitary hormones: Insulin tolerance test: cortisol and GH rise TRH test: TSH rises GNRH test: LH and FSH rise
33
Give three causes of excess ADH
1. Lung pathology - paraneoplasiaes e.g. pneumonia or SCLC 2. Brain pathology - TBI, meningitis, tumour 3. Iatrogenic - SSRIs, amitryptilline, carbamazepine, PPIs
34
Give three causes of nephrogenic diabetes insipidus
1. Iatrogenic - lithium 2. Hypercalcaemia 3. Renal failure
35
What is dipsogenic diabetes insipidus?
A. Failure or damage to the hypothalamus leading to loss of thirst drive and hypernatraemia.
36
Which of the following (may be one or more) have high uptake on an isotope scan? 1. Subacute De Quervains thyroiditis 2. Primary atrophic hypothyroidism 3. Toxic multinodular goitre 4. Graves disease 5. Toxic adenoma
A. 3, 4, and 5. 1. Is a low uptake cause of hyperT and is a self limiting, post viral and has a painful goitre. 2. Is an autoimmune cause of hypoT with diffuse lymphocytic infiltration and atrophy 3. Causes 30-50% of hyperT 4. Causes 40-60% of hyperT. Autoimmune, mostly in women. 5. Causes 5% of hyper T. One area of uptake "hot nodule" on scan.
37
Give three non-immune causes of hypoT
1. Iodine deficiency 2. Post thyroidectomy/radioiodine 3. Drug induced - anithyroid, lithium, amiodarone
38
Which type of thryroid neoplasia produces calcitonin? 1. Papillary 2. Medullary 3. Follicular 4. Lymphoma 5. Anaplastic
A. 2, Medullary neoplasias originate in parafollicular C cells, are linked with MEN2 and produce calcitonin. 1. Papillary neoplasias represent over 60% of all cases, peak at 30-40 years. Psammoma bodies are seen on histology. Treatment is with surgery +/- radioiodine. 3. Follicular neoplasia accounts for 25% of all cases, is well differentiated but spreads early. 4. Thryoid lymphoma originates in MALT tissue may be caused by chronic Hashimotos. 5. Anaplastic neoplasias mostly occur in the elderly and respond poorly to treatment.
39
A patient presents with centripetal weight gain, muscles weakness, new onset hypertension and diabetes, which investigation is most likely to aid in diagnosis?
A. Low dose dexamethasone (0.5mg) and high dose dexamethasone (2mg). Low dose will fail to supress cortisol, but high dose will succeed in pituitary Cushing's (Cushing's disease, 85%). Other causes are an adrenal tumour, ectopic tumour and iatrogenic.
40
A patient presents with raised serum potassium and low sodium, postural hypotension and lethargy. Which test will reveal the diagnosis?
A. SynACTHen test.
41
What are four causes of Addison's disease?
1. Autoimmune 2. Tumour mets 3. Adrenal haemorrhage 4. Amyoloidosis
42
What are the clinical features of Conn's syndrome?
A. Uncontrollable HTN, raised sodium and low potassium. Raised aldosterone:renin ratio. (Treated with aldosterone agonists/potassium sparing diuretics e.g. spironolactone)
43
Which of the following is associated with pituitary, pancreatic, and parathyroid cancers? 1. MEN1 2. MEN2a 3. MEN2b
A. MEN1 (3Ps) ``` MEN 2a (2Ps, 1M) - parathyroid, phaeo, medullary thyroid MEN2b - (1P, 2Ms) - phaeo, medullary, mucocutaneous neuromas (&marfanoid) ```
44
Which of the following is not a feature of pheochromocytoma? 1. Raised catecholamines 2. Leads to hypotension, arrhythmia and death if untreated 3. Treated with beta blockade, then alpha blockade, then surgery when BP is controlled 4. Caused by a tumour in the adrenal medulla 5. Diagnosis includes measurement of plasma metadrenaline
A. 3. Alpha blockade must be given first as unopposed beta blockade can lead to paroxysmal refractory HTN.
45
What are the signs of lithium toxicity? 1. Arrythmia, anxiety, tremor, convulsions 2. Ataxia and nystagmus 3. Arrythmia, heart block, xanthopsia (seeing yellow) 4. Tremor, lethargy, fits, arrythmia, renal failure 5. Tinnitus, deafness, nystagmus, renal failure
A 4. Mx may require dialysis if in renal failure. 1. Theophylline. Omit/reduce dose. 2. Phenytoin. Mx as above 3. Digoxin. Administer Digibind. 5. Gentamicin Omit/ reduce dose.
46
What are the actions of PTH?
A. - Increase tubular 1a hydroxylation of vitamin D (25(OH)D) - Mobilises calcium from bone - Increase renal calcium absorption - Increase renal phosphate excretion
47
What are the actions of calcitriol (1, 25 (OH) 2D)?
- Increase calcium and phosphate absorption from the gut | - Bone remodelling
48
What is the management approach for mild and severe symptomatic hypocalcaemia?
A. Mild - Give calcium Severe - 10% calcium gluconate IV (In CKD, alfacalcidiol)
49
List causes of euvolaemic hyponatraemia
Urine osmolality >500: SIADH | <500: water overload, severe hypothyroidism, glucocorticoid insufficiency
50
Mx of hyponatraemia
- Correct acute at 1mM/hr and chronic at 10mM/day - Fluid restrict if asymptomatic - Otherwise cautious rehydration with 0.9% saline - Consider hypertonic saline e.g. 1.8% in emergency
51
Mx of hypernatraemia
- Water PO if possible - Otherwise slow IV 5% dextrose - 0.9% NS if hypovolaemic
52
ECG changes in hypokalaemia
- Flattened/inverted T waves - ST depression - Long PR and QT
53
Mx of hypokalaemia
Mild: oral supplement Symptomatic or severe: IV KCl 10mmol/hr Empiric Mg replacement
54
ECG changes of hyperkalaemia
- Tall tented T waves - Flattened P waves - Increased PR and wide QRS - Sine wave to VF
55
Mx of hyperkalaemia
``` Non-urgent: Rx cause + calcium resonium Emergency: - 10ml 10% calcium gluconate - 100ml 20% glucose + 10u Actrapid - Salbutamol 5mg nebuliser - Haemofiltration - Calcium resonium 15g PO or 30g PR ```
56
Presentation of hypocalcaemia (SPASMODIC)
``` Spasms (carpopedal = Trousseau's) Perioral paraesthesia Anxious Seizures Muscle tone increased Orientation impaired (confusion) Dermatitis Impetigo herpetiformis Chovsteks ```
57
Mx of hypercalcaemia
- Rx underlying cause e.g. Ca or HPT - Fluids, fluids, fluids - Frusemide when euvolaemic - Alendoronate in Ca
58
Alternative treatments for osteoporosis
Raloxifene - SERM Teriparetide - PTH analogue Denosumab - anti-RANKL
59
Alternative treatments for hyperlipidaemia
Fibrates: PPARa antagonists Ezetimibe: inhibits cholesterol absorption Niacin: increases HDL:LDL ratio
60
Features of homocystinuria
- Marfanoid - Mental retardation - Recurrent thrombosis
61
Features of type 1 Gaucher's (lysosomal disorder)
- Gross HSM - Brown skin pigmentation - Pancytopaenia - Pathological fractures