Unit. 11.2w.pdf

Functional organization of the kidney: the nephron. Glomerular function. Renal Blood flow and its control Unit 11.2 Second Medicine  Renal blood flow control Kidneys are involved in long-term regulation of arterial pressure by excreting variable amounts...

Functional organization of the kidney: the nephron. Glomerular function. Renal Blood flow and its control Unit 11.2 Second Medicine  Renal blood flow control Kidneys are involved in long-term regulation of arterial pressure by excreting variable amounts of sodium and water, and they also contribute to short-term arterial pressure regulation by secreting hormones and vasoactive factors as renin that lead to the formation of vasoactive products as angiotensin II. Kidneys oxygen’s consumption is twice the one of brain with 7 times the blood flow of the brain. The oxygen in the kidneys exceeds their metabolic needs, and the arterial- venous extraction of oxygen is low compared with that of most other tissues.  Renal blood flow control O2 consumed by the kidneys is proportional to the high rate of active sodium reabsorption by the renal tubules. If renal blood flow and Glomerular Flow Rate (GFR) are reduced and sodium is not filtered, renal oxygen consumption reduces 3/4. The remaining ¼ reflects the basic metabolic needs of the renal cells. The renal blood flow is determine by: Renal blood flow control  Renal blood flow control Renal artery pressure is the one of the systemic arterial pressure, and renal vein pressure averages about 3 to 4 mm Hg under most conditions. The total vascular resistance in the kidneys is determined by the sum of the resistances in the individual vasculature segments. Most of the renal vascular resistance resides in: interlobular arteries, afferent arterioles, and efferent arterioles, which is controlled by the sympathetic nervous system, various hormones, and local internal renal control mechanisms.  Renal blood flow control An increment of the vascular resistance of the kidneys reduces the renal blood flow, whereas a decrease in vascular resistance increases renal blood flow. The kidneys have effective mechanisms for maintaining renal blood flow and GFR relatively constant over an arterial pressure range between 80 and 170 mm Hg, a process called autoregulation. The renal cortex receives more than 95% of the kidney’s blood flow, with only 2% of blood flow in the renal medulla, through the vasa recta, parallel with the loops of Henle.  Renal blood flow control The GFR is determined by many variable included the glomerular hydrostatic pressure and the glomerular capillary colloid osmotic pressure. These variables are influenced by the sympathetic nervous system, hormones and autacoids (vasoactive substances released by the kidneys with local action), and other feedback controls that are intrinsic to the kidneys.  Sympathetic nervous system All the blood vessels of the kidneys are innervated by sympathetic nerve fibers. A big activation of the renal sympathetic nerves constricts the renal arterioles and decrease renal blood flow and GFR, but smaller sympathetic stimulation has little influence on renal blood flow and GFR. Its effect is more important after injuries than in the healthy resting person.  Hormonal and autacoids control of renal circulation Vasoconstriction hormones (NA and epinephrine) only cause reductions in GFR and renal blood flow under extreme conditions, such as severe hemorrhage. Endothelin, a peptide released by damaged vascular endothelial cells of the kidneys, may contribute to homeostasis when a blood vessel is damaged, and contribute to renal vasoconstriction and decreased GFR.  Hormonal and autacoids control of renal circulation Angiotensin II is formed in the kidneys and in the systemic circulation and there are receptors in all blood vessels of the kidneys, except the afferent arterioles, due to the local release of vasodilators, as nitric oxide and prostaglandins. The efferent arterioles are highly sensitive to angiotensin II, because angiotensin II formation occurs with decreased arterial pressure or volume depletion.  Hormonal and autacoids control of renal circulation An autacoid that decreases renal vascular resistance, released by the vascular endothelium is endothelial-derived nitric oxide, which basal level production’s maintains vasodilation of the kidneys. The administration of drugs that inhibit formation of nitric oxide increases renal vascular resistance and decreases GFR and urinary sodium excretion, causing high blood pressure.  Hormonal and autacoids control of renal circulation Prostaglandins (PGE2 and PGI2) and bradykinin cause vasodilation and increased renal blood flow and GFR, in illness with vasoconstrictor effects of the sympathetic nerves or angiotensin II, especially in the afferent arterioles. Prostaglandins help prevent excessive reductions in GFR and renal blood flow. control of renal circulation  Autorregulation of renal circulation The autoregulation in the kidneys maintains a constant GFR and controls renal excretion of water and solutes, but the blood flow in the kidneys is much higher than that required for these functions. The GFR remains almost constant in spite of the arterial pressure fluctuations, barely changing around a 10% due to its auto regulation, specially: (1) renal auto regulation prevents large changes in GFR, and (2) there are additional adaptive mechanisms in the renal tubules that cause them to increase their reabsorption rate when GFR rises which is called glomerulotubular balance  Autorregulation of renal circulation But, still changes in arterial pressure have significant effects on renal excretion of water and sodium: the pressure diuresis or pressure natriuresis, and it is crucial in the regulation of body fluid volumes and arterial pressure  Myogenic mechanism of renal circulation Myogenic mechanism is the ability of blood vessels to resist stretching during increased arterial pressure. This mechanism prevents excessive increases in renal blood flow and GFR when arterial pressure increases and protects the kidney from hypertension-induced injury.  Myogenic mechanism of renal circulation Small arterioles respond to increased wall tension or wall stretch by contraction of the vascular smooth muscle, which allows increased movement of calcium ions from the extracellular fluid into the cells, causing contraction, that prevents excessive stretch of the vessel which rise vascular resistance.  Glomerular filtrate Urine formation begins with filtration of fluid through the glomerular capillaries into Bowman’s capsule. Those capillaries are relatively impermeable to proteins, so the glomerular filtrate has almost none protein nor cells. Other constituents of the glomerular filtrate has almost the concentrations in the plasma, except for a few low molecular-weight substances (Ca, fatty acids, etc) that are not filtered because they are bound to the plasma proteins.  Glomerular filtration In kidneys, as in other capillaries glomerular filtration (GFR) represents 20% of the renal plasma flow and it 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.  Glomerular filtration The glomerular capillaries have a much higher rate of filtration than most other capillaries because of a high glomerular hydrostatic pressure and a large Kf. In the average adult human, the GFR is about 125 ml/min, or 180 L/day.  Glomerular filtration 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.  Glomerular filtration rate It is the best test to messure the kidney function, stimating how much blood passes through the glomeruli each minute. It is determine by the net filtration pressure and a glomerular capillary filtration coefficient. The net filtration pressure is the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration across the glomerular capillaries.  Glomerular filtration rate The net filtration pressure include: (1) hydrostatic pressure inside the glomerular capillaries, which promotes filtration; (2) the hydrostatic pressure in Bowman’s capsule outside the capillaries, which opposes filtration; (3) the colloid osmotic pressure of the glomerular capillary plasma proteins which opposes filtration; (4) the colloid osmotic pressure of the proteins in Bowman’s capsule which is normally so low that it is considered zero.  Glomerular capillary filtration coefficient This value cannot be determined directly, but it is estimated dividing the rate of glomerular filtration by net filtration pressure. The GFR of both kidneys is estimated to be 125 ml/min and the net filtration pressure is around 10 mmHg, the value assumed is 12,5 ml/min/mm Hg. This value is about 400 folds as high as the capillary filtration coefficient (Kf) of most other capillary systems of the body, which helps to their rapid rate of fluid filtration.  Glomerular capillary filtration coefficient If the Kf increases, the GFR will raise and if Kf reduces the GFR will drop, which means that Kf does not regulate the normal GFR. But in some renal diseases the number of functional glomerular capillaries it is reduced or the thickness of the glomerular capillary membrane augmented (as in chronic hypertension, or diabetes mellitus) reducing its hydraulic conductivity and there is loss of capillary function.  Bowman’s capsule hydrostatic pressure Measurements of hydrostatic pressure in Bowman’s capsule gives a pressure in humans of around 18 mm Hg under normal conditions. The increment of the hydrostatic pressure in Bowman’s capsule reduces GFR, whereas decreasing this pressure raises GFR, but this is not a mechanism of GFR regulation.  Bowman’s capsule hydrostatic pressure In certain illness where there is an obstruction of the urinary tract, Bowman’s capsule pressure can increase reducing GFR, as the presence of “stones” in the ureter. This reduction of GFR can cause hydronephrosis (distention and dilation of the renal pelvis and calyces) that damage the kidney. Hydronephrosis  Glomerular capillary colloid osmotic pressure While blood passes from the afferent arteriole through the glomerular capillaries to the efferent arterioles, the plasma protein concentration increases a 25 %. This happen because one fifth of the fluid in the capillaries filters into Bowman’s capsule, and concentrates the not filtered glomerular plasma proteins. Since the normal colloid osmotic pressure of plasma is 28 mm Hg, this value usually rises to 36 mm Hg in the efferent end of the capillaries. The average colloid osmotic pressure of the glomerular capillary plasma proteins is 32 mm Hg.  Glomerular capillary colloid osmotic pressure There are two factors that influence the glomerular capillary colloid osmotic pressure: (1) the arterial plasma colloid osmotic pressure (2) the fraction of plasma filtered by those capillaries. The increment of the arterial plasma colloid osmotic pressure raises the glomerular capillary colloid osmotic pressure, which decreases GFR.  Glomerular capillary colloid osmotic pressure Increasing the filtration fraction concentrates the plasma proteins and raises the glomerular colloid osmotic pressure. The filtration fraction (GFR/renal plasma flow) can be increased either by raising GFR or by reducing renal plasma flow. Changes in renal blood flow can influence GFR with no influence in glomerular hydrostatic pressure. Romancing the macula densa at UAB L GABRIEL NAVAR and P DARWIN BELL  Glomerular capillary colloid osmotic pressure If the renal blood flow increases, there is a lower fraction of the plasma filtered out of the glomerular capillaries. Thus the glomerular capillary colloid osmotic pressure has a smaller rise and produces a minor inhibitory effect on GFR. With a constant glomerular hydrostatic pressure, a greater rate of blood flow into the glomerulus increases GFR and a lower rate of blood flow into the glomerulus diminishes GFR.  Glomerular capillary hydrostatic pressure The glomerular capillary hydrostatic pressure is 60 mm Hg under normal conditions, its changes are the primary physiologic regulation of GFR. If increases the glomerular hydrostatic pressure GFR raises; if decreases the glomerular hydrostatic pressure GFR is reduced. Glomerular hydrostatic pressure is determined by: (1) arterial pressure, (2) afferent arteriolar resistance, (3) efferent arteriolar resistance.  Glomerular capillary hydrostatic pressure Higher arterial pressure increases glomerular hydrostatic pressure and GFR, but it is attenuated by the autoregulatory mechanisms that maintain a constant glomerular pressure. When the resistance of afferent arterioles grows there is a reduction of the glomerular hydrostatic pressure and GFR. And the vasodilation of the afferent arterioles increases both.  Glomerular capillary hydrostatic pressure Vasoconstriction of the efferent arterioles increases the resistance to outflow from the glomerular capillaries, which raises the glomerular hydrostatic pressure, and if the renal blood flow is not very reduced, GFR increases slightly.  Glomerular capillary hydrostatic pressure But efferent arteriolar constriction also reduces renal blood flow. If the renal blood flow drops, the filtration fraction and glomerular colloid osmotic pressure rises as efferent arteriolar resistance raises. Therefore, a constriction of efferent arterioles that is a threefold increase in efferent arteriolar resistance, the rise in colloid osmotic pressure exceeds the increase in glomerular capillary hydrostatic pressure and the net force for filtration decreases, reducing GFR.  Glomerular capillary hydrostatic pressure Thus, efferent arteriolar constriction at moderate levels causes a slight increase in GFR, but severe constriction, reduces GFR. As efferent constriction becomes severe and as plasma protein concentration increases, there is a rapid, nonlinear increase in colloid osmotic pressure caused by the higher protein’s concentration and by Na, K, and the other cations held in the plasma by the proteins. (Donnan effect)  Creatinine Creatinine is a byproduct of skeletal muscle creatine metabolism, and it can be used to measure GFR. Creatinine is freely filtered across the glomerulus into Bowman's space, and to a first approximation, it is not reabsorbed,secreted, or metabolized by the cells of the nephron. Creatinine  Creatinine Accordingly, the amount of creatinine excreted in urine per minute equals the amount of creatinine filtered at the glomerulus each minute However, creatinine is not a perfect substance for measuring GFR because it is secreted to a small extent by the organic cation secretory system in the proximal tubule, which induces an error of around 10%  Creatinine The amount of creatinine excreted in urine exceeds the amount expected from filtration alone by 10%. However, the method used to measure the plasma creatinine concentration underestimates the true value by 10%. Consequently, the two errors cancel, and in most clinical situations, creatinine clearance provides a reasonably accurate measure of GFR.  Other substance to measure GFR Creatinine is not the only substance that can be used to measure GFR. Any substance that: Be freely filtered across the glomerulus into Bowman's space Not be reabsorbed or secreted by the nephron Not be metabolized or produced by the kidney Not alter the GFR can serve as an appropriate marker for the measurement of GFR.  Other substance to measure GFR Not all of the creatinine that enters the kidney in renal arterial plasma is filtered at the glomerulus. Not all of the plasma coming into the kidneys is filtered. Although nearly all of the plasma that enters the kidneys in the renal artery passes through the glomerulus, approximately 10% does not. The portion of filtered plasma is termed the filtration fraction and under normal conditions this represents about 20% of the plasma volume passing through the kidneys or approximately 180 L /day  Renal clearance Renal clearance is the volume of plasma from which a substance is completely removed by the kidney in a given amount of time (usually a minute) If a substance, like glucose in normal conditions is completely reabsorbed, its clearance is cero. If a substance, is completely secreted, the clearance will mach with the flow of plasma in the kidney, around 625 ml. The substance, like inulin, that are not reabsorbed nor secreted has a normal clearance of 125 ml/min. And finally, there are substance as urea  Renal clearance of urea The urea clearance has been measured to be 65 ml/min Because urea is partially reabsorbed by the nephrons!!!  Renal clearance There is an equation for clearance that has the dimensions of volume/time, and it represents a volume of plasma from which all the substance has been removed and excreted into urine per unit time.  Filtration fraction equation The equation is the glomerular filtration rate divided by the renal plasma flow. The PAH (para-aminohippurate) is a substance completely filtered from the plasma 20-30% in the glomerulus, and the rest secreted by the renal tubulus.