Glomerular Filtration and Renal Blood Flow

Glomerular Filtration and Renal Blood Flow Glomerular Filtration • The filtration of blood plasma by the kidney is the same as the filtration of blood plasma across capillaries in other vascular beds. - However, the rate of filtration in the glomerulus greatly exceeds that in all other capillaries combined because of the greater starling forces and higher capillary permeability. Criteria for a substance to be qualified for the use in measuring GFR. • • • • Must be freely filtered in the glomerulus. Must be neither absorbed nor secreted by the renal tubules. Must not be synthesis, broken down or accumulated in the kidney. Must ne physiological inert - Neither toxic nor influences renal function Creatinine for renal function • • The source of plasma creatinine is the normal metabolism of creatinine phosphate in the muscle. Clinicians use endogenous plasma concentration of creatinine of about 1mg/dL as an instant index of GFR. - This uses the inverse relation between plasma creatinine concentration and the creatinine clearance. Filtration Barrier • • It consists of: - Endothelial cells - GBM - Epithelial podocytes - GBM and the podocyte layer both have negative charge. Filtration of a substance or a molecule depends on: - Charge - Size/weight (less than 5500 Da) - Shape - Starling Forces • The rapid increase in the oncotic pressure of the capillary blood is the major reason why the forces favouring and opposing filtration may balance each other at a point distance before the end of the glomerular capillary. - The reason as to why oncotic capillary pressure is higher at the efferent end of the capillary is because the filtered fluid leaves behind proteins, and since there is a decrease in fluid at that point, the concentration of proteins will rise. This will cause the oncotic pressure to rise and it will eventually catch up with the hydrostatic pressure, and will balance out. This will dimmish the driving force for filtration and we call this the filtration equilibrium. This will occur at some point along the length of the glomerulus. - Beyond this point, PUF is zero, and the system is said to be in filtration equilibrium (i.e., no further filtration). Renal Plasma Flow • • • 1 L/min out the total cardiac output (20%) Hydrostatic pressure is the pressure made by fluids. - Affected by lumen of the vessel. Increased glomerular blood flow increases GFR. - At low glomerular plasma flow, the filtration equilibrium occurs halfway down the capillary. At a high glomerular plasma flow, the profile for net ultrafiltration forces along the glomerular capillary stretches out considerably to the right, so that the point of equilibrium will be reached at site beyond the end of the capillary. Note from this picture: but arterioles do have a smooth muscle layer. This diagram shows what a capillary has. - Lipid soluble stuff pass across membrane by simple diffusion Water soluble through the intercellular clefts Blood Flow • • The peritubular capillaries provide nutrients for tubules and retrieve fluid the tubules reabsorb. BF in the renal cortex exceeds that in the renal medulla. - 90% of the blood leaving the glomeruli in the efferent arterioles perfuses the cortex. - 10% the medulla, with only 1-2% reaching the papilla. This is because the long vasa recta have a very high resistance. - This is important for minimising washout of the hypertonic medullary interstium and thus for producing concentrated urine. Factors that affect RBP and GFR • • • • • • • • RAAS -> constriction SNS -> vasoconstriction, especially efferent AVP: increase vascular resistance and decrease BF to medulla to minimise washing out of hypertonicity. ANP: released in response to increased arterial blood pressure. Vasodilates both the afferent and efferent arterioles, which increase the cortical and medullary blood flow. At higher levels it can also increase capillary permeability. Epinephrine: same as norepinephrine. Dopamine: vasodilate -> oppose epinephrine and norepinephrine. Endothelin’s: strong vasoconstriction action but very short half-life. Prostaglandins: prevent excess vasoconstriction, specially during SNS and RAAS.