Chemical Pathology Fluid Balance - ⅔ INTRACELLULAR - ⅓ EXTRACELLULAR Electrolytes Cations Intracellular = K+ (3.5 - 5) Extracellular = Na+ (135 - 145) Anions Intracellular = protein and phosphate Extracellular = Cl- and HCO3- (22 -26) Osmolality “Total number of solute particles in solvent” (280-295 mosmol/l) Calculated Plasma osmolality = 2([Na+] +[K+]) + urea +glucose Osmolar Gap (<10) = Measured osmolality – calculated osmolality Anion Gap (~ 18 mmol) = Na + K - Cl - Bicarbonate Key controllers of ECF Extra-renal System Stimulated by: Osmoreceptors Baroreceptors (low volume) Action by: Thirst Anti-diuretic hormone from posterior pituitary ANF (reduced sensitivity of osmoreceptors, RAA antagonism) Intra-renal System Stimulated by: Reduced renal perfusion Action by: Renin-angiotensin-aldosterone system (positive) ANF (negative) Too much fluid Increased intake (rarely a problem) Increased/inappropriate sodium reabsorption Cardiac failure Nephrotic syndrome Reduced excretion Renal failure Nephritic syndrome Too little fluid Inadequate intake (during illness) Distribution problem Sepsis 3rd spacing Excess loss Fluids (gut, kidneys, skin, respiratory) Blood (internal vs. external)
Uric acid metabolism Plasma concentrations. Men 0.12 – 0.42 mmol/l 0.12 – 0.36 mmol/l Gout Monosodium crystals Men>women Clinical features Exquisite pain Red, hot and swollen joint 1st MTP is classical Diagnosis Negatively birefringent crystals Treatment NSAIDS are the first line treatment acutely Colchicine lowers levels Allopurinol for chronic episodes Pseudogout Pyrophosphate crystals Self limiting 1 – 3 weeks Positively brefringent crystals Endocrine Investigations Condition Causes Diagnosis Cushing’s Syndrome (↑Cortisol) Pituitary (Micro/macroadenoma) Adrenals (Adenoma/carcinoma) Malignancy Exogenous steroids Midnight plasma cortisol Low dose DEXA test Salivary cortisol Urinary free cortisol Conn’s Syndrome (↑Aldosterone) “Hyperfunction of aldosterone secreting cells” Adenoma, carcinoma, hyperplasia Plasma aldosterone ↑ Plasma ↓ Addison’s Disease (↓Cortisol) Synacthen test Thyroid Disease TSH T3 +/- thyroid autoantibodies Protein Markers Protein Function Information CRP Acute phase protein Peaks at 48h α-1 anti-trypsin Prevents neutrophil elastase activation ↓ in emphesema & cirrhosis Transferrin Plasma Fe Transport Caeruloplasmin Contains Cu Mops-up superoxide radicals Deficiency in Wilson’s disease Ferritin ↓ in IDA, ↑ in Fe overload & inflammation Haptoglobin ↓ in haemolysis β2-microglobulin MHC Class I component
Carbohydrate disorders Alteration of carbohydrate cycling in the cell Lactose intolerance Gycogen storage disorders Hypoglycaemia Lactic acidosis Cataract formation problems Peroxisomal disease Disorders of lipid metabolism where there are empty cell persoxisomes Zellweger syndrome Hypotonia Seizures Mitochondrial disease Mutations in mitochondrial DNA. Most serious when affects muscle, brain. Mitocondrial myopathies e.g. diabetes mellitus and deafness, Leber’s hereditary optic neuropathy Lots Lysosomal storage disorders Various defects in lysosomal function that lead to accumulation of toxic substances Gauncher’s disease Niemann-Pick disease Tay-Sachs disease Present late (adulthood)