LECTURE 25: FILTRATION AND CLEARANCE NEPHRON FILTRATION 1. Everything in the plasma is filtered except large proteins and red blood cells. The filtrate in Bowman s capsule is an isosmotic fluid that is at the same concentration as plasma 2. Reabsorption of specific molecules and water - 99% of the original filtrate is reabsorbed, with varying percentages for each molecule 3. Some secretion from the capillaries passes back into the lumen 4. Solutes are excreted from the body
GLOMERULUS - Blood enters from the afferent arteriole and divides into many glomerular capillary before exiting through the efferent arteriole o Division into glomerular capillaries generates a larger surface area for filtration to occur - Found between glomerular capillaries are mesangial cells that are capable of altering the diameter of individual capillaries affects hydrostatic pressure and filtration - Podocytes surround the outside of the capillaries and have foot processes which help create slits through which filtration can take place o Capillaries within the glomerulus are fenestrated (large pores)
GLOMERULAR FILTRATION RATE (GFR) GFR is the volume of plasma filtered by the glomerulus per unit time - ~125mL/min or 180L/day Filtration fraction is another term that describes the proportion of plasma filtered by the glomerulus - Of all the plasma that pass through a glomerulus, only ~20% of the plasma volume is filtered Within a glomerulus, the hydrostatic pressure from the capillary is the main driving force that pushes filtration into the Bowman s capsule. Oncotic pressure in the plasma draws water back and the opposing hydrostatic pressure within the Bowman s capsule also works to push fluid back into the capillaries.
ARTERIOLE RESISTANCE CHANGES - Constriction of afferent arterioles will reduce renal blood flow and GFR - Constriction of efferent arteriole will reduce renal blood flow but increase GFR When the kidney are not receiving any direct stimulation from the sympathetic system, the both arterioles will be slightly constricted. In the case of exercise, the sympathetic system will trigger the constriction of afferent arterioles in an effort to redirect blood flow to the required areas of the body. AUTOREGULATION Changes in MAP between 80 and 180 mm Hg will not see significant change in GFR, as changes in GFR will see changes in reabsorption and secretion. 1. Myogenic Response - Intrinsic ability of the smooth muscle to stretch and respond to pressure changes o Increase in blood pressure causes arteriole walls to stretch o Stretch sensitive ion channels open and cause muscle cells to depolarise and contract
2. Tubuloglomerular Feedback - The pathway in which fluid flows through the tubule influences GFR - The juxtaglomerular apparatus is the main site of regulation o Ascending limb of loop of Henle connects between the afferent and efferent arterioles o Cells in this location are called macula densa cells which release paracrines that cause constriction in the afferent arterioles
EXCRETION VS RENAL CLEARANCE Excretion: - does not provide an indication of how that substance was handled. That is, was it reabsorbed and or secreted. Renal clearance: - provides information on the rate of urinary excretion of a substance relative to its plasma concentration - indicates rate at which a solute disappears from a body o either by excretion or by metabolism - non-invasive way of measuring GFR - inulin can be injected into the body or creatinine can be used to measure GFR CALCULATION OF CLEARANCE Clearance of X represents the volume of plasma cleared of X per unit time. That is, how much plasma is passed per unit time when excreting X.
INULIN CLEARANCE In clinical settings creatinine is used in place of inulin. Creatinine is a breakdown of phosphocreatine, an energy-storage compound found primarily in muscles, and is excreted at a regular rate similar to that of inulin. Always being present in the blood as well, creatinine is regularly used to estimate GFR.
GLUCOSE CLEARANCE
PENICILLIN CLEARANCE SUMMARY: This table only provides us with a net indication of what has happened. That is, even though we see a net reabsorption some secretion may have also occurred as well.