BY3BC1- Medical Biochemistry Lecture 4 - Renal function test LO- - Familiarise ourselves with the S & F of the kidney - Importance of measuring glomerular filtration rate and plasma creatine as biomarkers of kidney dysfunction Structure of the glomerulus - Kidney function - Extracellular fluid volume - H+ homeostasis (also ph balance as increase in H+ ions causes acidic pH) - Excretion of urea - Erythropoietin production (increase to increase oxygen uptake) - Vitamin d metabolism (vitamin D deficiency can cause bone pain and oseto problems) a. Basement membrane (very thin allows passage) b. Capillary lumen (large which can filter stuff towards the tubules) c. Urinary space ( Mesangial cells - immune cells Aldosterone - (Collecting ducts have 2 cells principal cells and intercalated disc which determine acid/base balance) - Secreted from adrenal cortex (RAS- renin angiotensin aldosterone ) - Acts on principal(P) cells in distal tubule and collecting duct - Increases sodium reabsorption (water follows - this increases blood pressure) - Modifies sodium channels - Promotes expression of new channels and ATPases Vasopressin (ADH) - Released from posterior pituitary (portion of the brain) - Acts on collecting duct cells to promote insertion of auraporin-2 water channels into luminal membrane (aquaporin channels in the tubular lumen allow water to be reabsorbed ) - Increases water permeability
- Increased water reabsorption (and returns It to the circulation) - Drop in Bp then ADH is useful in restoring that Glomerular filtration rate (GFR) - Used to assess glomerular function. - Creatinine (waste product) formed from creatine in muscle - an end product of nitrogen metabolism. - Plasma concentration depends on muscle mass and therefore lower values may be found in wasting diseases and in children. - Decreased in pregnancy and mildly increased by high meat intake or vigorous exercise. - Units are (ml/min) Creatinine concentration in urine (umol/ml) x urine flow (ml/min) Creatinine concentration in plasma (umol/ml) - Urine collection - 8.00am empty bladder and void - Start collecting - 8.00am next day empty bladderff collect urine and stop - Patients can forget to collect a sampleff if they take alcohol can interfere - Incorrect performance a major source of error in GFR measurement - Creatinine concentration is relatively static over time - Not a great biomarker (function to human error ) GFR or plasma creatine? - GFR changes substantially before change in plasma creatinine is detectable - Therefor GFR is a more sensitive indicatory of potential renal damage - However: - Measurement of plasma creatinine concentration is more precise than of GFR - Plasma creatinine is easier to measure than the GFR - Plasma creatine is entirely satisfactory to follow the course of renal disease or to detect rejection after renal transplantation Causes of elevated creatinine in plasma - Impaired renal perfusion - Due to decreased blood pressureff reduced blood volume or narrowing of renal artery - Loss of functioning nephrons
- E.g. glomerulonephritis which is associated with antibody mediated damage or deposition of immune complexes in glomeruli (inflammation of