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Path Guide 2022/23 > Chemical Pathology > Flashcards

Chemical Pathology Flashcards

1
Q

What percentage of total body weight is water, intracellular and extracellular?

A

60-40-20 rule:
60% total body weight = water
40% of body weight = intracellular
20% of body weight = extracellular

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2
Q

What volume/percentage of compartment is intracellular?

A

28L/60-65%

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3
Q

What volume/percentage of compartment is intracellular?

A

14L/35-40%
Interstitial (between cells) = 10L/24%
Intravascular = 3L (5%)
Transcellular (within epithelial lines spaces, e.g. CSF, joint fluid, bladder urine, aqueous humour) = 1L/3%

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4
Q

Which gender has more water per unit weight?

A

Males (higher fat content in females)

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5
Q

What ions are higher/lower in ECF than ICF?

A

Cells used to live in sea, therefore the require salty water to survive.
ECF is higher in sodium and chloride, and lower in potassium than the intracellular fluid

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6
Q

Osmolality definition and units

A

Total number of particles in solution - measured with an osmometer, units = mmol/kg

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7
Q

Osmolarity definition and units. Whats the equation used?

A

Calculated number of particles in solution, mmol/L
Osmolarity = 2(Na+ & K+) + urea + glucose

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8
Q

What is the difference between osmolality and osmolarity?

A

Osmolar gap. Useful in metabolic acidosis. There must be extra solutes dissolved in serum if its large.

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9
Q

What is the normal range of serum osmolality and what diagnostic criteria is this useful for?

A

275 - 295 mmol/kg, useful for SIADH

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10
Q

What is the normal range for sodium? How is sodium pumped into ECF?

A

135-145. Na+/K+ ATPase (ECF volume directly dependent on Na+)

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11
Q

How do you manage hyponatraemia?

A

Mild hyponatraemia (130-135) is common in hospital. Treat underlying cause, unless severe (<125) and symptomatic. Hyponatraemia that is compensated (usually chronic) is rarely emergency. More dangerous to correct them too fast than leave them.

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12
Q

What is seen in symptomatic hyponatraemia?

A

N&V (<134)
Confusion (<131)
Seizures, non-cardiogenic pulmonary oedema (<125)
Coma (<117) and death

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13
Q

What are the causes of hyponatraemia with high, normal and low osmolality? What is the mechanism of pseudohyponatraemia?

A

High - glucose/mannitol/infusion
Normal - spurious, drip arm sample, pseudohyponatraemia (hyperlipidaemia/paraproteinaemia)
Low - true hyponatraemia
Normal is pseudohyponatraemia. This is since increased protein/lipid volume is sensed by analyser in lab to be water, so sodium appears diluted and osmolality will be normal.
High is also pseudohyponatraemia. There is an excess of osmotically active solutes in plasma (often glucose in HHS, but can also be mannitol). Water drawn into the plasma, which dilutes the sodium. It is still true hyponatraemia, but due to another chemical

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14
Q

What are the causes of hyponatraemia with high, normal and low osmolality?

A

High - glucose/mannitol/infusion
Normal - spurious, drip arm sample, pseudohyponatraemia (hyperlipidaemia/paraproteinaemia)
Low - true hyponatraemia
Normal is pseudohyponatraemia. This is since increased protein/lipid volume is sensed by analyser in lab to be water, so sodium appears diluted and osmolality will be normal.
High is also pseudohyponatraemia. There is an excess of osmotically active solutes in plasma (often glucose in HHS, but can also be mannitol). Water drawn into the plasma, which dilutes the sodium. It is still true hyponatraemia, but due to another chemical.

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15
Q

What is the mechanism of pseudohyponatraemia?

A

Normal is pseudohyponatraemia. This is since increased protein/lipid volume is sensed by analyser in lab to be water, so sodium appears diluted and osmolality will be normal.
High is also pseudohyponatraemia. There is an excess of osmotically active solutes in plasma (often glucose in HHS, but can also be mannitol). Water drawn into the plasma, which dilutes the sodium. It is still true hyponatraemia, but due to another chemical.

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16
Q

What is TURP syndrome?

A

Hyponatraemia from irrigation absorbed through damaged prostate
TURP irrigation done by 1.5% glycine
Metabolism of glycine and hyponatraemia -> dilution -> clinical presentation

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17
Q

What are the causes the management of hypovolaemic hyponatraemia?

A

Urine Na <20 = D&V, skin loss (sweat, burns)
Urine Na >20 = adrenocortical deficiency, renal failure/disease, diuretics, cerebral salt wasting
(Stop diuretics before measuring urine Na)
Fluid replacement with 0.9% NaCl (isotonic saline)

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18
Q

What is the management of euvolaemic hyponatraemia?

A

Treat underlying cause
Osmolality <100 = acute water load, psychogenic polydipsia, tea and toast/beer diets
Osmolality >100 = SIADH, glucocorticoid deficiency (hydrocortisone +/- fludrocortisone), chronic hypothyroidism (levothyroxine), acute water load

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19
Q

What is the management of hypervolaemic hyponatraemia?

A

Fluid restriction +/- diuresis and correct the cause
Urine Na >20 = renal failure
Urine Na <20 = heart failure, cirrhosis, nephrotic syndrome, primary polydipsia

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20
Q

How do cirrhosis and HF cause hyponatraemia?

A

In liver failure, poor breakdown of vasodilators like NO, these cause low BP. Subsequent ADH release causes water retention, dilutes Na+.
Low cardiac output causes ADH release. BNP/ANP are natriuretic and though to worsen hyponatraemia too.

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21
Q

In what case is hypertonic (3%) saline used?

A

Patient who is in status epilepticus secondary to hyponatraemia, only done in ITU under advice of specialist

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22
Q

What is the consequence of rapid correction of Na?

A

Central pontine myelinolysis (pseudobulbar palsy, paraparesis, locked-in syndrome, worse in malnourished alcoholics)
Aim to increased Na+ by no more than 8-10 mmol/L per 24 hours

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23
Q

Why can you get hyponatraemia post-surgery?

A

Overhydration with hypotonic IV fluids
Transient rise in ADH due to stress of surgery

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24
Q

What is the diagnostic criteria for SIADH?

A

Dx of exclusion
True hyponatraemia (<135) + low plasma/serum Osm (<270) + high urine sodium (>20) + high urine Osm (>100) + no adrenal/thyroid/renal dysfunction
Increased ADH -> increased water reabsorption -> low plasma Osm (due to dilution) -> less water excreted in urine -> urine Osm is high

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25
Q

How do you confirm the Dx of SIADH?

A

Normal 9am cortisol and normal TFTs

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26
Q

What are the causes of SIADH?

A

Malignancy - SCLC (most common), pancreas, prostate, lymphoma (ectopic secretion)
CNS disorders- meningoencephalitis, haemorrhage, abscess
Chest - TB, pneumonia, abscess
Drugs - opiates, SSRIs, TCAs, carbamazepine, PPIs

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27
Q

Mx of SIADH?

A

Fluid restriction and treat the cause
Demeclocycline (increased ADH resistance) and tolvaptan
Severe = slow IV hypertonic 3% saline

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28
Q

How do you investigate hypernatraemia?

A

Raised urea, albumin, PCV (plasma cell volume)

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29
Q

What is the normal cause of hypernatraemia in hospital?

A

Iatrogenic, common problem in ITU patients
Ask why pt is unable to drink water (pts should be able to self-correct sodium unless they’re unwell)

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30
Q

What are the symptoms of hypernatraemia?

A

Thirst -> confusion -> seizures + ataxia -> coma

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31
Q

What is the consequence of rapid correction of hypernatraemia?

A

Cerebral oedema

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32
Q

What are the causes of hypovolaemic hypernatraemia?

A

Water is lost more than sodium - most common form of hypernatraemia
Low urinary Na+ - D&V, excessive sweating, burns
High urinary Na+ - renal losses, loop diuretics, osmotic diuresis (uncontrolled DM, glucose, mannitol following initial hyponatraemia), DI, renal disease (can’t concentrate)

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33
Q

What are the causes of euvolaemic hypernatraemia?

A

Respiratory (tachypnoea), skin (sweating, fever), DI

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34
Q

What are the causes of hypervolaemic hypernatraemia?

A

Mineralocorticoid excess (Conn’s syndrome), inappropriate saline

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35
Q

What is the Mx of hypernatraemia?

A

Generally, slow fluids
Speed>fluid choice, can even use normal saline (albeit slower than dextrose/Hartmann’s, causes initial rise in Na, then fall)
Slow and steady, encourage PO fluids so body can regulate own fluids

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36
Q

What are the features/Sx of DI?

A

Hypernatraemia (lethargy, thirst, irritability, confusion, coma, fits), euvolaemic, polyuria, polydipsia, urine:plasma osmolality<2 (dilute urine despite concentrated plasma)

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37
Q

What are the causes and Mx of cranial DI?

A

Causes: surgery, trauma, tumours (craniopharyngioma), AI hypophysitis (from CTLA-4 iplimumab) - no ADH production
Mx: desmopressin

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38
Q

What are the causes and Mx of nephrogenic DI?

A

Receptor defect - insensitivity to ADH
Causes - inherited channelopathies, drugs (lithium, demeclocycline), electrolyte disturbances (hypokalaemia, hypercalcaemia)
Mx: thiazide diuretics (bizarre!)

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39
Q

What are the Ix for suspected DI?

A

Serum glucose (to exclude DM)
Serum K+ (exclude hypokalaemia)
Serum Ca (exclude hypercalcaemia)
Plasma and urine osmolality
8-hour water deprivation test
Significant DI is excluded is urine:plasma Osm ration > 2:1, provided plasma osmolality >295

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40
Q

How do you differentiated between normal, primary polydipsia, cranial DI and nephrogenic DI in 8 hour water deprivation test?

A

Normal: urine Osm > 600, U:P >2 (normal concentrating ability)
Primary polydipsia: urine concentrates, but less than normal (>400-600)
Cranial DI: urine Osm increases to >600, only after desmopressin
Nephrogenic DI: no increased in urine Osm even after desmopressin

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41
Q

What is the normal range of K+?

A

3.5 - 5.5 mmol/L
Predominant intracellular cation, into ICP by Na+/K+ ATPase

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42
Q

What are the causes of hypokalaemia?

A

GI loss: D&V
Renal loss: hyperaldosteronism (high BP, low K+), iatrogenic excess cortisol
Increased sodium to distal nephron (thiazide and loop diuretics)
Osmotic diuresis
Redistribution into cells: insulin, beta-agonists, metabolic alkalosis, refeeding syndrome
Rare tubular acidosis type 1&2, hypomagnesaemia

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43
Q

What are the types of renal tubular acidosis?

A

Type 1: most severe, distal failure of H+ excretion, subsequent acidosis and hypokalaemia (failed H+-K+ pumping)
Type 2: milder, proximal failure to reabsorb bicarb, leads to acidosis and hypokalaemia
Type 4: aldosterone deficiency/resistance (acidosis and hyperkalaemia)
Type 3 is rarely relevant

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44
Q

What are the clinical features of hypokalaemia?

A

Muscle weakness, cardiac arrhythmias, polyuria, polydipsia (nephrogenic DI)

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45
Q

What is the treatment of hypokalaemia?

A

3-3.5 = Oral KCl (2 SandoK tablets TDS for 2 days), recheck serum K+
<3 = (risk of cardiac arrest), IV KCl (10mmol/h, otherwise of arrhythmia, insert central line if higher)

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46
Q

What are the Ix for hypokalaemia?

A

Aldosterone: renin ratio (high=Conn’s due to high aldosterone, switches off renin due to -ve feedback)

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47
Q

What are the causes of hyperkalaemia?

A

Excessive intake - oral (fasting), parenteral, stored blood transfusion
Transcellular movement (ICF>ECF) - acidosis, insulin shortage (DKA), tissue damage/catabolic state (rhabdomyolysis)
Decreased excretion - acute renal failure (oliguric phase), CRF (late), drugs (K+ sparing diuretics e.g. spironolactone), NSAIDs, ACEi, ARBs, mineralocorticoid deficiency (Addison’s), Type 4 RTA

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48
Q

What are the ECG changes in hyperkalaemia?

A

Loss of p waves, tall tented T waves, widened QRS
Sine wave (ECG is ‘pulled apart) if severe and untreated

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49
Q

Which patient are the most important to give intervention to in hyperkalaemia?

A

Potassium > 5.5 with ECG changes or
Potassium > 6.5. regardless of ECG changes

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50
Q

What is the treatment pathway for hyperkalaemia?

A

10 ml 10% calcium gluconate (purely cardioprotective)
100ml 20% dextrose, 10 units short-acting insulin (e.g. Actrapid - drives K+ back into cells, dextrose prevents hypoglycaemia)
Nebulised salbutamol as adjunct
Sometimes: calcium resonium 15g PO or 30g PR (binds K+ in gut)
Always treat cause
Pts on digoxin - take care with IV Ca, can lead to arrhythmias, cardiac monitoring)
N.B. H+ and K+ are linked, as one moves into cells, one moves out (H+-K+ co-transporter) - understand mechanism!

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51
Q

What are the causes of metabolism acidosis (based on anion gap) and how does the body compensate?

A

Anion gap (AG) = Na + K - Cl -HCO3
High AG = ketones, lactate (shock, ischaemia, sepsis), EtOH, aspirin, biguanides (metformin), ethylene glycol, uraemia
Normal AG = diarrhoea (small intestine GI loss of HCO3), actazolamide (CA inhibitor), high output stoma, pancreatic fistula (loss of HCO3), Addison’s, RTA, ammonium chloride ingestion
Hyperventilation to compensate

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52
Q

What are the causes of metabolic alkalosis and how does the body compensate?

A

Vomiting (H+ loss, bulimia), loop diuretics (K+ depletion), hypokalaemia, Conn’s (K+ loss), antacid use, burns
Hypoventilation to compensate

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53
Q

What are the causes of respiratory acidosis and how does the body compensate?

A

Hypoventilation (T2 resp failure): acute/chronic lung disease (commonest=COPD), opioids, sedatives, neuromuscular weakness
Normal/high PaCO2 is worrying - ITU RV/vent support (exhaustion)
Increased renal HCO3 reabsorption to compensate (delayed)

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54
Q

What are the causes of respiratory alkalosis and how does the body compensate?

A

Hyperventilation: stroke, SAH, meningitis, asthma, anxiety, PE, pregnancy, altitude (hypoxaemia), salicylates (early - brainstem stimulation)
Decreased renal HCO3 reabsorption to compensate (delayed)

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55
Q

What is the definition of anion gap, normal range and equation?

A

Difference between total concetration of principal cations and principal anions (concentration of unmeasured anions in plasma)
Usually all albumin (beware in hypoalbuminaemia)
Normal range = 14-18mmol/L
Na + K - Cl - HCO3

56
Q

What are the causes of elevated anion gap metabolic acidosis?

A

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

57
Q

What is the osmolar gap and normal range?

A

Measured osmolality - calculated osmolarity
Normal = <10

58
Q

What is the indication for raised osmolar gap?

A

Indirect evidence for the presence of abnormal solute
Increased by extra solutes in plasma (e.g. alcohols, mannitol, ketones, lactate)
Can be raised in advanced CKD, due to retained small solutes
Helpful in differentiating cause of elevated anion gap metabolic acidosis

59
Q

What are the markers of liver cell damage?

A

ALT, AST, ALP, GGT, bilirubin

60
Q

What are the markers of synthetic function of the liver?

A

Clotting (INR), albumin, glucose

61
Q

What is the best marker of liver function in acute liver injury?

A

Prothrombin time

62
Q

What is the indication if transaminitis is in the 1000s

A

Acute viral hepatitis, toxins (e.g. paracetamol), ischaemic hit

63
Q

What are the indications if AST and ALT are raised

A

AST and ALT found in liver, cardiac and skeletal muscle, kidney, brain
Hepatitis/transaminitis
ALT>AST: chronic liver disease (inc. NASH), chronic hep C, hepatic obstruction, advanced fibrosis/cirrhosis - AST:ALT>0.8 in absence of EtOH)
AST:ALT 2:1 - EtOH liver disease (Stella)
AST:ALT 1:1: - viral hepatitis (viraL)

64
Q

Indications of raised GGT and ALP

A

GGT found in hepatocytes and biliary cells, kidney and pancreas
Cholestatic/obstructive picture
GGT raised in chronic EtOH use, bile duct disease and mets - used to confirm hepatic source of raised ALP

65
Q

Indications of isolated raised ALP

A

ALP high conc. in liver, bone (osteoblastic activity), intestine and placenta
1) Physiological: Pregnancy (3T), childhood (growth spurt)
2) Pathological: >5x ULN = bone (Paget’s disease - osteoblasts), osteomalacia, liver (cholestatis, cirrhosis)
<5x ULN = bone (primary tumours e.g. sarcoma, fractures, osteomyelitis), liver (infiltrative disease, hepatitis), renal osteodystrophy
Plasma cells suppress osteoblasts, therefore ALP is normal in myeloma!

66
Q

Indications of low albumin (hypoalbuminaemia)

A

200 mg/kg a day, binds to hormones, calcium and other metabolites
Liver synthetic function
Chronic liver disease, malnutrition, protein-losing enteropathy, nephrotic syndrome, sepsis (3rd spacing)
Common in hospital pts as acute illness/systemic inflammation and malnutrition contribute to low albumin
Low albumin in critically ill patient is poor prognostic factor

67
Q

Indications of low urea

A

Severe liver disease (synthesised in liver), malnutrition, pregnancy

68
Q

Indications of raised urea (x10 ULN)

A

1) Upper Gi bleed (or large protein meal)
2) Dehydration/AKI (urea excreted renally)

69
Q

Indication of deranged clotting factors

A

Liver synthesises Factor 5, 7, 9, 10, 12, 13, fibrinogen and prothrombin
INR is prothrombin time standardised for age and population expressed as a ratio of ‘norma’
Deranged clotting alone not diagnostic of hepatocellular dysfunction
Other causes = iatrogenic (therapeutic warfarinisation), hereditary thrombophilia, acquired consumption (DIC)

70
Q

Describe the metabolism and excretion of bilirubin

A

Breakdown product of heme, majority is produced by breakdown of haemoglobin
Conjugates in hepatocytes, subsequent secretion into bile ducts and GIT
Conjugated bilirubin metabolised further in GIT to urobilinogen
Urobilinogen partially reabsorbed and excreted in kidneys are urobilin
Rest of urobilinogen converted to stercobilin (brown pigment in faces)

71
Q

Causes of prehepatic jaundice and how to tell clinically/by bloods

A

1) Haemolytic anaemia (raised LDH and reduced haptoglobin)
2) Ineffective erythropoiesis e.g. thalassaemia
3) Congestive cardiac failure
Increased unconjugated BR/urobilinogen. Splenomegaly. No urine bilirubin/conjugated BR in urine since unconjugated BR tightly bound to albumin, cannot pass through glomerulus

72
Q

Causes of hepatic jaundice and how to tell clinically/by bloods

A

1) Hepatocellular dysfunction (viral, alcoholic dysfunction)
2) Impaired conjugation/BR excretion/BR uptake
Raised conjugated BR, unconjugated BR, urobilinogen, present urine bilirubin and conjugated BR in urine
Dark urine (urobilinogen + conjugated BR), normal/pale stool
Raised AST/ALT/ALP. Splenomegaly.

73
Q

Causes of post-hepatic jaundice and how to tell clinically/by bloods

A

Obstruction of biliary tree:
1) Intraluminal (stones, strictures)
2) Luminal (mass/neoplasm, inflammation, e.g. PBC, PSC)
3) Extra-luminal (Ca pancreas, cholangio Ca)
Raised conjugated BR, normal unconjugated BR, decreased/absent urobilinogen. Present urine bilirubin/conjugated BR in urine
Dark urine (conjugated BR leaks out of hepatocytes, absorbed by blood), pale stools (low stercobilinogen)
Raised ALP, AST, ALT. No splenomegaly

74
Q

Causes of hepatomegaly, differentiated by smooth margin and craggy border

A

Smooth margin: viral hepatitis, biliary tract obstruction, hepatic congestion secondary to HF, Budd Chiari
Craggy border: hepatic metastatic disease, polycystic disease, cirrhosis (will shrink)

75
Q

Define porphyrias

A

7 disorders caused by enzyme deficiencies, involved in haem biosynthesis, leading to build up of toxic haem precursors

76
Q

How do you differentiated between the acute porphyrias?

A

Skin lesions - present in HCP (hereditary coprophyria) and VP (variegate porphyria) but not acute intermittent porphyria (AIP)
Urine and faeces for porphyrins - raised in HCP and VP, but not AIP
Urine PBG - raised in all 3 (send urine sample protected from light)

77
Q

What inheritance pattern is acute porphyria, what deficiency is it and how does it present?

A

Autosomal dominant
HMB (Hydroxymethylbilane) synthase deficiency
Neurovisceral only (Painful abdomen, seizures, Peripheral neuropathy, Psychosis, Port urine, muscle weakness, constipation, urinary incontinence)
No porphyrinogens, therefore no cutaneous manifestations
Hyponatraemia + AIP = SIADH
Urine colour change + abdo pain = AIP

78
Q

How do you diagnose acute intermittent porphyria? What are its precipitating factors and Mx?

A

2nd commonest
Dx: increased urinary porphobilinogen and aminoevulinic acid
Precipitating factors: ALA synthase inducers (steroids, ethanol, barbituates), stress (infection, surgery), reduced caloric intake and endocrine factors (e.g. premenstrual)
Mx: avoid precipitating factors, adequate nutrition and analgesia
Mx of underlying infection/illness, IV carbohydrate, IV haem arginate

79
Q

Which acute porphyrias have skin symptoms, what is their inheritance pattern, how do they present, what is the Ix:

A

HCP + VP (i.e. neurovisceral + skin), skin lesion fragility
Both autosomal dominant
Skin lesions on back of hands -> blistering under Sun
Ix: stool sample for coproporphyrinogen III

80
Q

What are the cutaenous types of porphyria and how does it present? What are the Ix and Mx?

A

Non-acute
1) Porphyria Cutanea Tarda (PCT) - most common
Uroporphyrinogen decarboxylase deficiency
Photosensitivity, facial hyperpigmentation, hypertrichosis, blistering, milia, scarring, exacerbated by EtOH
Increased urinary uroporphyrins and coproporphyrins (pink red fluorescence with Wood’s lamp) often increased ferritin, abnormal LFTs
Mx: avoid sun, precipitants (EtOH, Hep C, HIV), chloroquine)

2) Erythropoietic protoporphyria (EPP) - found in children, cutaenous erythema without blisters/bullae (blistering found in congenital erythropoietic porphyria), cannot use urine is protoporphyrin is lipophilic
Ix: RBC protoporphyrin

3) Congenital erythropoeitic porphyria (CEP)

81
Q

What are the hypothalamic hormones and their action on pituitary hormones?

A

GHRH - stimulates GH
GnRH - stimulates LH/FSH
TRH - stimulates TSH and prolactin
Dopamine - inhibits prolactin
(Prolactin has inhibitory effect on LH/FSH)
CRH - stimulates ACTH

82
Q

What are the indications and contraindications for combined pituitary function test?

A

Indications: assessment of all components of anterior pituitary function used particularly in pituitary tumours or following tumour treatment
Contraindications: IHD, epilepsy, untreated hypothyroidism (impairs the GH and cortisol response)

83
Q

What are the side effects of the combined pituitary function test?

A

Adrenergic effects of hypoglycaemia - sweating, palpitations, LOC
Rarely - convulsions with hypoglycaemia
TRH infection - transient Sx of metallic taste in mouth, flushing, nausea

84
Q

Give a summary of the hormones given and measured in the combined pituitary function test

A

Administer LHRH (GnRH), TRH and insulin
Insulin induces hypoglycaemic state, minics stress, should increased GH and cortisol
Measured glucose to make sure that stress is induced, <2.2 mM
TRH increases TSH and prolactin
GnRH increases LH and FSH
Measure 0, 30, 60, 90, 120 minute levels of pituitary hormones

85
Q

What is the procedure for the CPFT?

A

1) Fast patient overnight, ensure good IV access, weigh patient
2) Mix into 5ml syrine: insulin dose (0.15 units/kg), TRH 200mcg, LHRH 100 mcg -> give IV
3) Bloods: basal thyroxine plus glucose, cortisol, GH, LH, FSH, TSH, prolactin every 30 min for 1 hour
Glucose, cortisol, GH up to 2 hours
Replacements: urgent hydrocortisone, T4, oestrogen, GH

86
Q

Explain the insulin tolerance test aspect of the CPFT

A

Hypoglycaemia <2.2 mmol/L
Increases ACTH and GH
Cortisol = increase of >170 to above 500 nmol/l
GH = increase greater than 6 mcg/L

87
Q

Explain the thyrotrophin releasing hormone test aspect of the CPFT

A

Increased TSH and prolactin (high prolactin can lead to hypothyroidism)
Normal = TSH rise to >5 mU/l, 30 min value >60 min value
Hyperthyroid: TSH remains suppressed
Hypothyroid: exaggerated response
Don’t need this test for Dx of hyperthyroid, TSH assay basal levels are sensitive enough

88
Q

Explain the GnRH aspect of the CPFT

A

Increase in LH and FSH, normal peaks either at 30 or 60 minutes
LH should >10, FSH should >2 U/l
Inadequate response = possible hypopituitarusm
Gonadotrophin deficiency now based on basal levels
M = low testosterone in the absence of raised basal gonadotrophins
F = low oestradiol without elevated basal gonadotrophins and no response to clomiphene (induces ovulation)
Pre-pubertal children should have no response, if present (i.e. precicious puberty), pituitary will be primed and respond to LHRH. Priming with steroids must NOT occur before test

89
Q

Give the 2 types of pituitary tumour and how to differentiate between them on bloods and clinically

A

Microadenoma < 10 mm, usually benign
Macroadenoma >10 mm, aggressive. Press on optic chiasm = bitemporal hemianopia.
Non-functioning macroadenoma may crush stable, less blood flow, less dopamine inhibition, increased prolactin (relatively small)

90
Q

Give the causes of prolactinaemia, classified by elevation level

A

Mild elevation (<1000) = stress, recent breast examination, vaginal examination, hypothyroid, PCOS
Moderate elevation (1000-5000) = hypothalamic tumour, non-functioning pituitary tumour compress hypothalamus, microprolactinoma, PCOS, drugs e.g. domperidone, phenothiazines
Extreme elevation (>5000) = macroprolactinoma

91
Q

What are the findings and Mx in prolactinoma?

A

Prolactin > 6000, no rise in GH (>10) and cortisol (>550)
1st line Mx: replacements (hydrocortisone, T4, oestrogen, GH), DA antagonists (cabergoline, bromocriptine)
2nd line Mx: transphenoidal surgery (if visual/pressure Sx not responding to drugs)n

92
Q

What are the findings and Mx in non-functioning pituitary adenoma?

A

Increased prolactin (1000-5000)
Mx: cabergoline/bromocriptine, watch and wait if asymptomatic
No Mx of no Sx

93
Q

What are the findings, Ix and Mx of acromegaly?

A

Increase GH (even before baseline), increase in prolactin, but not in cortisol
Ix: OGTT (gold standard), IGF-1 for follow up after Dx
High glucose, Ca, PO4
Mx: transsphenoidal surgery, pituitary radiotherapy if fails, cabergoline, octreotide (somatostatin analogue, expensive, cannot stop once started), GH antagonist (pegvisomant)
F/U: yearly GH, IGF1 +/- OGTT, visual fields, vascular assessment, BMI, photos

94
Q

What are the posterior hormones?

A

ADH and oxytocin

95
Q

What can cause excess ADH? And what does it cause?

A

Lung - lung paraneoplasia (SCLC, pneumonia)
Brain - TBI, meningitis, primary or secondary tumours
Iatrogenic - SSRIs, amitryptilline, carbamazepine, PPIs
Effect - SIADH - Euvolaemic hyponatraemia

96
Q

What are causes of ADH failure?

A

DI - neurogenic (50% idiopathic), nephrogenic (lithium, hypercalcaemia, renal failure)
Dipsogenic - failure/damage to hypothalamus and thirst drive, hypernatraemia without increased thirst response

97
Q

What are the reference ranges for TSH, free T4 and T3

A

TSH: 0.33 - 4.5 mu/L
Free T4: 10.2 - 22 pmol/L
Free T3: 3.2 - 6.5 pmol/L

98
Q

Causes of increased TSH and low T4

A

Hypothyroidism: atrophic, Hashimotos, subacute (De Quervain’s), postpartum, Riedel thyroiditis

99
Q

Causes of increased TSH and normal T4

A

Treated hypothyroidism or subclinical hypothyroidism (look for assos high cholesterol)

100
Q

Causes of low TSH, raised T4/T3

A

Hyperthyroidism: Grave’s, toxic multinodular goitre (Plummer’s), toxic adenoma, drugs (thyroxine, amiodarone), ectopic (trophoblastic tumour, struma ovarii)

101
Q

Causes of low TSH, normal T3 and T4

A

Subclinical hyperthyroidism. Can progress to primary hypothyroidism, esp if patient is anti-TPO antibody positive

102
Q

Causes of low TSH and T4

A

Secondary hypothyroid (hypothalamic/pituitary disorder)

103
Q

Causes of high, then low TSH, low T3/T4

A

Sick euthyroid (any severe illness). Body tries to shut down metabolism as thyroid gland has reduced output

104
Q

Causes of normal TSH, abnormal T4

A

? assay interference, changes in TBG, amiodarone

105
Q

Mx of hyperthyroid

A

Medical - symptoms relief with beta blockers, topical steroids (dermopathy), eye drops (Graves)
Carbimazole - 2 approaches, titrate to normal T3 or block and replace (cause hypothyroidism, then give levothyroxine, uncommon as high risk of side effects, agranulocytosis and rashes)
Radioiodine - good for primary treatment, can lead to permanent hypothyroid, CI in pregnancy and lactating women
Surgical hemi/total thyroidectomy indications:
Women intending to become pregnant in the next 6/12
Local compression secondary to thyroid goitre (oesophageal/tracheal)
Cosmetic
Suspected cancer
Co-existing hyperparathyroidism
Refractory to medical therapy
MUST be euthyroid before surgery, need thyroid replacement after

106
Q

What is thyroid storm and how do you treat?

A

An acute stage - present as shock, with pyrexia, confusion, vomiting
Mx: HDU/ITU support, usually requires colling, high dose anti-thyroid medications, corticosteroids, circulatory and resp support

107
Q

What are the 3 types of high uptake hyperthyroidism and how do you differentiate?

A

Graves: 40-60%, F>M (9:1), painless goitre, anti-TSH receptor Abs, high diffuse uptake on isotope can (with Tc99)
Toxic multinodular goitre (Plummers): 30-50%, high update hot nodules, painless, enlarged follicular cells distended with colloid + flattened epithelium
Toxic adenoma: 5%, solitary ‘hot nodule’ on isotope scan (1 area of uptake)

108
Q

What are the 3 types of low uptake hyperthyroidism and how do you differentiate?

A

Subacute De Quervain’s thyroiditis: self-limiting post viral painful goiter. Initially hyperthyroid, then hypothyroid
Postpartum thyroiditis (like viral but post-partum)
Ectopic: trophoblastic tumour, struma ovarii (excessive hCG)

109
Q

Give the types of autoimmune hypothyroidism

A

Primary atrophic hypoT: commonest cause in UK
Diffuse lymphocytic infiltration causing atrophy. No goitre, so small thyroid. No know Ab, but assos with pernicious anaemia/vitiligo/endocrinopathies
Hashimoto’s thyroiditis: plasma cell infiltration and goitre. Elderly females. May be initial ‘Hashitoxicosis’. Anti-TPO/TG titres, Hurthle cells, painless

110
Q

Give the other causes of hypothyroid (not AI)

A

Iodine deficiency (common worldwide)
Post thyroidectomy/radioiodine
Drug induced - anti-thyroid drugs, lithium, amiodarone
Riedel’s thyroiditis - dense fibrosis replacing normal parenchyma, painless, stony hard

111
Q

Who/what kind of thyroid is at higher risk of thyroid neoplasms?

A

Solitary, solid, young, male, cold nodules

112
Q

What are the 5 types of thyroid neoplasias (in order of prevalence)

A

Papillary
Follicular
Medullary
Anaplastic
Lymphoma

113
Q

What is the presentation, epidemiology, Ix and Mx of papillary neoplasia?

A

75 - 85%
Painless cervical lymphadenopathy, no obvious clinical abnormality of thyroid
20 - 40 year F, assos with irradiation
Tumour marker: Thyroglobulin
Spread: lymph nodes and lung
Histology: Psammoma bodies (foci of calcification), empty appearing nuclei with central clearing (Orphan Annie eyes)
Mx: surgery +/- radioiodine, thyroxine (to lower TSH)

114
Q

What is the epidemiology, histology, spread and Mx of follicular neoplasia?

A

10 - 20%
40 - 60 year old, well differentiated but spreads early
Tumour marker: thyroglobulin
Spread: blood&raquo_space; lungs, bone, liver, breast, adrenals
Histology: fairly uniform cells forming small follicles, reminiscent of normal thyroid
Mx: surgery, radioiodine, thyroxine

115
Q

Give the origin, epidemiology, tumour marker, histology and Mx of medullary neoplasia

A

Neuroendocrine neoplasm derived from parafollicular C cells secreting calcitonin
5%
50 - 60 yo, 80% sporadic, 20% familial MEN2
Tumour marker: CEA, calcitonin
Histology: sheets of dark cells, amyloid deposition within tumour (calcitonin broken down to amyloid)
Mx: screen for phaeo pre-op + surgery + node clearance

116
Q

Give the spread, epidemiology and histology of anaplastic neoplasia

A

Early and wide mets common
Spread -> v aggressive -> local, lymph nodes, blood
Elderly, rare, most die within 1 yr
Histology: undifferentiated follicular, large pleomorphic giant cells, spindle cells with sarcomatous appearance

117
Q

Give the RF and prognosis for thyroid lymphoma

A

MALToma
RF: chronic Hashimoto’s (lymphocyte proliferation)
Good prognosis

118
Q

What is MEN?

A

Multiple Endocrine Neoplasia
Group of 3 inherited disorders (autosomal dominant), whereby there is a predisposition to develop Ca of endocrine system

119
Q

What are the 3 types of MEN?

A

MEN1 (3Ps): pituitary, pancreatic (e.g. insulinoma), parathyroid (hyperparathyroidism)
MEN2a (2Ps, 1M): parathyroid, phaeochromocytoma, medullary thyroid
MEN2b (1P, 2Ms): phaechromocytoma, medullary thyroid, mucocutaenous neuromas (& Marfanoid)

120
Q

What are the causes, Sx, Ix and Mx of Addison’s?

A

Causes: autoimmune (1st Europe), TB (1st worldwide), tumour mets, adrenal haemorrhage (meningococcus), amyloidosis
Sx: Increased K, reduced Na and glucose, postural hypotension, skin pigmentation, lethargy, depression, can lead to Addisonian crisis
Ix: synACTHen test
Mx: hormone replacement - hydrocortisone/fludrocortisone if primary adrenal lesion

121
Q

What are the causes of Cushing’s syndrome?

A

ACTH dependent (high ACTH):
- Pituitary tumour (Cushing’s disease - 85%)
- Ectopic ACTH-producing tumour (5%- SCLC, carcinoid tumour)
ACTH-independent:
- Adrenal adenoma/cancer (10%), adrenal nodular hyperplasia, iatrogenic steroid use

122
Q

What are the Sx of Cushing’s?

A

Moon face, buffalo hump, central obesity, striae, acne, HTN, DM, muscle weakness (proximal myopathy), Hirsuitism, Bruising

123
Q

What is the Ix and Mx for Cushing’s?

A

1st line: overnight dexamethasone suppression test/24 hour urinary free cortisol, +ve = true Cushing’s syndrome
2nd line: low dose (0.5mg) or high dose (2mg) dex suppression test (no longer used, use inferior pituitary petrosal sinus sampling instead due to FP rate 20%
i.e. ectopic ACTH can be suppressed by high-dose dex
Low dose dex will fail to suppress cortisol in all of these, but high dose will success in pituitary cushings
3rd line: CT/PET to identify source of ectopic ACTH
Mx: treat underlying disease - surgical removal of lesion

124
Q

What are the causes, Sx, Ix and Mx for Conn’s syndrome?

A

Adrenal adenoma
Uncontrollable HTN, high Ha, low K
Raised aldosterone: renin ratio
Mx: aldosterone antagonists/K+ sparing diuretics- spironolactone, epierenone, amiloride. If >4cm consider surgical excision

125
Q

What is the causes, Sx, Ix and Mx for phaeo?

A

Adrenal medulla tumour = high adrenaline
Triad: headaches, HTN and hyperhidrosis, arrhythmias, death if untreated
Ix: plasma and 24 hr urinary metadrenaline measurement/catecholamines and VMA (vannilylmandelic acid)

126
Q

What are the signs of toxicity, signs under treatment, interactions and cautions and Mx of phenytoin?

A

Signs toxicity: ataxia and nystagmus
Signs under Tx: seizures
Interactions and cautions: at high levels liver becomes saturated -> surge in blood levels
Mx: mainly supportive

127
Q

What are the signs of toxicity, signs under treatment, interactions and cautions and Mx of digoxin?

A

Signs toxicity: arrhythmias, heart block, confusion, xanthopsia (seeing yellow-green)
Signs under Tx: arrthymias
Interactions and cautions: levels increased with hypokalaemia, redcue dose in renal failure and in elderly
Mx: digibind (digoxin immune Fab)

128
Q

What are the signs of toxicity, signs under treatment, interactions and cautions and Mx of lithium?

A

Signs toxicity: tremor (early), lethargy, fits, arrhythmia, renal failure
Signs under treatment: relapse of mania in BPAD
Interactions and cautions: excretion impared by hyponatraemia, decreased renal function and diuretics
Mx: supportive. Osmotmic or forced alkaline diuresis. If Li>3, haemodialysis may be used

129
Q

What are the signs of toxicity, signs under treatment, interactions and cautions and Mx of aminoglycosides e.g. gentamicin, vancomycin?

A

Signs toxicity: tinnitus, deafness, nystagmus, renal failure
Signs under treatment: uncontrolled infection
Interactions and cautions: mostly use single daily dosing. Monitor peak and trough before next dose
Mx: omit/reduce dose

130
Q

What are the signs of toxicity, signs under treatment, interactions and cautions and Mx of theophylline/aminophylline?

A

Signs toxicity: arrthymias, convulsions, anxiety, tremor
Signs under Tx: bronchial smooth muscle doesn’t relax - asthma/ COPD worsens/does not improve
Interactions and cautions: variation t1/2, e.g. 4 hrs for smokers, 8 hrs for non-smokers, 30 hrs for liver disease
Level increased by erythromycin, cimetidine and phenytoin
Mx: omit/reduce dose

131
Q

What is the normal range of calcium and what proportions are where in the body?

A

Normal plasma range: 2.2-2.6 mmol/l
45% ionised (free - biologically active form)
50% bound to albumin (therefore affected by albumin level - used corrected calcium)
Remaining 5% bound to globulins and other ions e.g. citrate and bicarbonate

132
Q

What 2 main hormones are involved in calcium metabolism and how do they work?

A

PTH:
Increase tubular 1a-hydroxylation of vit D (25(OH)D)
Mobilises calcium from bone through osteoclast activation
Increases renal calcium reabsorption and phosphate excretion

Calcitriol:
Increases calcium and phosphate absorption from the gut. Involved in bone remodelling

133
Q

What is the defect in primary hyperparathyroidism and whats shown in the bloods

A

Intrinsic problem with parathyroid gland causing increased PTH
high Ca
low PO4
high/N PTH
High/N ALP
N Vit D

134
Q

What is the defect in secondary hyperparathyroidism and whats shown in the bloods

A

Pathology outside parathyroid gland (eg CKD); stimulation of parathyroid gland to produce more PTH
low Ca
high PO4
high PTH
high ALP
low/N Vit D

135
Q

What is the defect in tertiary hyperparathyroidism and whats shown in the bloods

A

Autonomous PTH secretion
high/N Ca
high or low PO4
high PTH
high/N ALP
N vit D

136
Q

What is the defect in hypoparathyroidism and whats shown in the bloods

A

Low levels of PTH

Path Guide 2022/23 (1 decks)

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