Chemical Pathology Flashcards
What percentage of total body weight is water, intracellular and extracellular?
60-40-20 rule:
60% total body weight = water
40% of body weight = intracellular
20% of body weight = extracellular
What volume/percentage of compartment is intracellular?
28L/60-65%
What volume/percentage of compartment is intracellular?
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%
Which gender has more water per unit weight?
Males (higher fat content in females)
What ions are higher/lower in ECF than ICF?
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
Osmolality definition and units
Total number of particles in solution - measured with an osmometer, units = mmol/kg
Osmolarity definition and units. Whats the equation used?
Calculated number of particles in solution, mmol/L
Osmolarity = 2(Na+ & K+) + urea + glucose
What is the difference between osmolality and osmolarity?
Osmolar gap. Useful in metabolic acidosis. There must be extra solutes dissolved in serum if its large.
What is the normal range of serum osmolality and what diagnostic criteria is this useful for?
275 - 295 mmol/kg, useful for SIADH
What is the normal range for sodium? How is sodium pumped into ECF?
135-145. Na+/K+ ATPase (ECF volume directly dependent on Na+)
How do you manage hyponatraemia?
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.
What is seen in symptomatic hyponatraemia?
N&V (<134)
Confusion (<131)
Seizures, non-cardiogenic pulmonary oedema (<125)
Coma (<117) and death
What are the causes of hyponatraemia with high, normal and low osmolality? What is the mechanism of pseudohyponatraemia?
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
What are the causes of hyponatraemia with high, normal and low osmolality?
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.
What is the mechanism of pseudohyponatraemia?
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.
What is TURP syndrome?
Hyponatraemia from irrigation absorbed through damaged prostate
TURP irrigation done by 1.5% glycine
Metabolism of glycine and hyponatraemia -> dilution -> clinical presentation
What are the causes the management of hypovolaemic hyponatraemia?
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)
What is the management of euvolaemic hyponatraemia?
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
What is the management of hypervolaemic hyponatraemia?
Fluid restriction +/- diuresis and correct the cause
Urine Na >20 = renal failure
Urine Na <20 = heart failure, cirrhosis, nephrotic syndrome, primary polydipsia
How do cirrhosis and HF cause hyponatraemia?
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.
In what case is hypertonic (3%) saline used?
Patient who is in status epilepticus secondary to hyponatraemia, only done in ITU under advice of specialist
What is the consequence of rapid correction of Na?
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
Why can you get hyponatraemia post-surgery?
Overhydration with hypotonic IV fluids
Transient rise in ADH due to stress of surgery
What is the diagnostic criteria for SIADH?
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
How do you confirm the Dx of SIADH?
Normal 9am cortisol and normal TFTs
What are the causes of SIADH?
Malignancy - SCLC (most common), pancreas, prostate, lymphoma (ectopic secretion)
CNS disorders- meningoencephalitis, haemorrhage, abscess
Chest - TB, pneumonia, abscess
Drugs - opiates, SSRIs, TCAs, carbamazepine, PPIs
Mx of SIADH?
Fluid restriction and treat the cause
Demeclocycline (increased ADH resistance) and tolvaptan
Severe = slow IV hypertonic 3% saline
How do you investigate hypernatraemia?
Raised urea, albumin, PCV (plasma cell volume)
What is the normal cause of hypernatraemia in hospital?
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)
What are the symptoms of hypernatraemia?
Thirst -> confusion -> seizures + ataxia -> coma
What is the consequence of rapid correction of hypernatraemia?
Cerebral oedema
What are the causes of hypovolaemic hypernatraemia?
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)
What are the causes of euvolaemic hypernatraemia?
Respiratory (tachypnoea), skin (sweating, fever), DI
What are the causes of hypervolaemic hypernatraemia?
Mineralocorticoid excess (Conn’s syndrome), inappropriate saline
What is the Mx of hypernatraemia?
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
What are the features/Sx of DI?
Hypernatraemia (lethargy, thirst, irritability, confusion, coma, fits), euvolaemic, polyuria, polydipsia, urine:plasma osmolality<2 (dilute urine despite concentrated plasma)
What are the causes and Mx of cranial DI?
Causes: surgery, trauma, tumours (craniopharyngioma), AI hypophysitis (from CTLA-4 iplimumab) - no ADH production
Mx: desmopressin
What are the causes and Mx of nephrogenic DI?
Receptor defect - insensitivity to ADH
Causes - inherited channelopathies, drugs (lithium, demeclocycline), electrolyte disturbances (hypokalaemia, hypercalcaemia)
Mx: thiazide diuretics (bizarre!)
What are the Ix for suspected DI?
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
How do you differentiated between normal, primary polydipsia, cranial DI and nephrogenic DI in 8 hour water deprivation test?
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
What is the normal range of K+?
3.5 - 5.5 mmol/L
Predominant intracellular cation, into ICP by Na+/K+ ATPase
What are the causes of hypokalaemia?
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
What are the types of renal tubular acidosis?
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
What are the clinical features of hypokalaemia?
Muscle weakness, cardiac arrhythmias, polyuria, polydipsia (nephrogenic DI)
What is the treatment of hypokalaemia?
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)
What are the Ix for hypokalaemia?
Aldosterone: renin ratio (high=Conn’s due to high aldosterone, switches off renin due to -ve feedback)
What are the causes of hyperkalaemia?
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
What are the ECG changes in hyperkalaemia?
Loss of p waves, tall tented T waves, widened QRS
Sine wave (ECG is ‘pulled apart) if severe and untreated
Which patient are the most important to give intervention to in hyperkalaemia?
Potassium > 5.5 with ECG changes or
Potassium > 6.5. regardless of ECG changes
What is the treatment pathway for hyperkalaemia?
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!
What are the causes of metabolism acidosis (based on anion gap) and how does the body compensate?
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
What are the causes of metabolic alkalosis and how does the body compensate?
Vomiting (H+ loss, bulimia), loop diuretics (K+ depletion), hypokalaemia, Conn’s (K+ loss), antacid use, burns
Hypoventilation to compensate
What are the causes of respiratory acidosis and how does the body compensate?
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)
What are the causes of respiratory alkalosis and how does the body compensate?
Hyperventilation: stroke, SAH, meningitis, asthma, anxiety, PE, pregnancy, altitude (hypoxaemia), salicylates (early - brainstem stimulation)
Decreased renal HCO3 reabsorption to compensate (delayed)