GLOMERULAR FILTRATION RATE AND RENAL CONTROL ACID-BASE BALANCE
1. Glomerular Filtration Rate
a. Composition of the Glomerular Filtrate The filtered fluid (called the glomerular filtrate) is essentially protein free and devoid of cellular elements, including red blood cells. most salts and organic molecules, are similar to the concentrations in the plasma. Exceptions to this generalization include a few low-molecular-weight substances, such as calcium and fatty acids, that are not freely filtered because they are partially bound to the plasma proteins. b. GFR Is About 20 Percent of the Renal Plasma Flow the GFR is determined by: 1. the balance of hydrostatic and colloid osmotic forces acting across the capillary membrane 2. the capillary filtration coefficient (Kf), the product of the permeability and filtering surface area of the capillaries. The fraction of the renal plasma flow that is filtered (the filtration fraction) averages about 0.2; this means that about 20 percent of the plasma flowing through the kidney is filtered through the glomerular capillaries The filtration fraction is calculated as follows: Glomerular Capillary Membrane - The high filtration rate across the glomerular capillary membrane is due partly to its special characteristics: *The capillary endothelium is perforated by thousands of small holes called fenestrae. Although the fenestrations are relatively large, endothelial cells are richly endowed with fixed negative charges that hinder the passage of plasma proteins. *the basement membrane, which consists of a meshwork of collagen and proteoglycan fibrillae that have large spaces through which large amounts of water and small solutes can filter. The basement membrane effectively prevents filtration of plasma proteins, in part because of strong negative electrical charges associated with the proteoglycans. *The epithelial cells, which also have negative charges, provide additional restriction to filtration of plasma proteins. Thus, all layers of the glomerular capillary wall provide a barrier to filtration of plasma proteins. Filterability of Solutes Is Inversely Related to Their Size - - Negatively Charged Large Molecules Are Filtered Less Easily Than Positively Charged Molecules of Equal Molecular Size c. Determinants of the GFR - GFR=Kf x Net Filtration Pressure - The GFR is determined by: o the sum of the hydrostatic and colloid osmotic forces across the glomerular membrane, which gives the net filtration pressure o the glomerular capillary filtration coefficient, Kf. - The net filtration pressure represents the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration across the glomerular capillaries: - These forces include (1) hydrostatic pressure inside the glomerular capillaries (glomerular hydrostatic pressure, PG), which promotes filtration; (2) the hydrostatic pressure in Bowman's capsule (P B) outside the capillaries, which opposes filtration; (3) the colloid osmotic pressure of the glomerular capillary plasma proteins (G), which opposes filtration; and (4) the colloid osmotic pressure of the proteins in Bowman's capsule ( B), which promotes filtration. (Under normal conditions, the concentration of protein in the glomerular filtrate is so low that the colloid osmotic pressure of the Bowman's capsule fluid is considered to be zero.)
- Increased Glomerular Capillary Filtration Coefficient Increases GFR
- Increased Bowman's Capsule Hydrostatic Pressure Decreases GFR - Increased Glomerular Capillary Colloid Osmotic Pressure Decreases GFR - Increased Glomerular Capillary Hydrostatic Pressure Increases GFR Glomerular hydrostatic pressure is determined by three variables, each of which is under physiologic control: (1) arterial pressure, (2) afferent arteriolar resistance, and (3) efferent arteriolar resistance d. Physiologic Control of Glomerular Filtration and Renal Blood Flow 1. Sympathetic Nervous System Activation Decreases GFR Strong activation of the renal sympathetic nerves can constrict the renal arterioles and decrease renal blood flow and GFR. Moderate or mild sympathetic stimulation has little influence on renal blood flow and GFR. 2. Hormonal and Autacoid Control of Renal Circulation
and Increases GFR 4. Prostaglandins and Bradykinin Tend to Increase GFR
2. Renal Control Acid-Base Balance
The kidneys control acid-base balance by excreting either acidic or basic urine The overall mechanism by which the kidneys excrete acidic or basic urine is as follows: Large numbers of HCO3- are filtered continuously into the tubules, and if they are excreted into the urine this removes base from the blood. Large numbers of H+ are also secreted into the tubular lumen by the tubular epithelial cells, thus removing acid from the blood. If more H + is secreted than HCO3- is filtered, there will be a net loss of acid from the extracellular fluid. Conversely, if more HCO 3- is filtered than H+ is secreted, there will be a net loss of base When there is a reduction in the extracellular fluid H + concentration (alkalosis), the kidneys fail to reabsorb all the filtered HCO 3- thereby increasing the excretion of HCO3-. Because HCO3- normally buffers H+ in the extracellular fluid, this loss of HCO3- is the same as adding an H+ to the extracellular fluid. Therefore, in alkalosis, the removal of HCO 3- raises the extracellular fluid H+ concentration back toward normal. In acidosis, the kidneys do not excrete HCO 3- into the urine but reabsorb all the filtered HCO3- and produce new HCO3- , which is added back to the extracellular fluid. This reduces the extracellular fluid H + concentration back toward normal. Thus, the kidneys regulate extracellular fluid H + concentration through three fundamental mechanisms: (1) secretion of H +, (2) reabsorption of filtered HCO3- , and (3) production of new HCO3- .