Renal2 - Renal Physiology Lecture 2 Glomerular filtration...

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Unformatted text preview: Renal Physiology Lecture 2 Glomerular filtration Tubular reabsorption/secretion Concept of clearance Glomerular filtration - everything with a small molecule weight will be filtered freely e.g. water, sodium potassium - it is easier to think about what is not filtered, because everything else is - cells (RBC's, platelets) proteins are too large to be filtered - half the plasma calcium is filtered, the other is bound to albumin What is filtered by glomerular filtration? glomerular filtration barrier Plasma Water Filtrate Bowman's space Water Low-molecular weight substances Low-molecular weight substances Cells Proteins (albumin, globulins) Protein-bound substances (1/2 of calcium ion, fatty acids) afferent Forces involved in filtration - follows pressure gradient - Figure 14.08 efferent oncotic pressure in the Bowman's space is 0 - no plasma proteins in the ISF (oncotic pressure) Glomerular filtration rate Glomerular filtration rate (GFR): the volume of fluid filtered from the glomeruli into Bowman’s space per unit time GFR is regulated by net filtration pressure particularly, intercapillary pressure usually do not contribute to membrane permeability regulation of GFR under physiological conditions, but do surface area available for filtration play an important role in pathological conditions Normal GFR (70 kg person): 180 L/day (125 ml/min) N.B. plasma volume of this person: 3.5 L 180/3.5 = 51 Plasma is filtered 51 times a day at glomeruli Regulation of GFR glomerulus constriction of afferent arteriole decrease pressure in capillary lumen, decrease filtration bowman's space constriction of efferent arteriole increase pressure in capillary lumen, increase filtration dilation of efferent arteriole - decrease pressure in capillary lumen, decrease filtration dilation of afferent arteriole - increase pressure in capillary lumen, increase filtration Filtered load Filtered load: total amount of any freely filtered substance Filtered load = GFR x plasma concentration of the substance e.g. Filtered load of glucose = 180 L/day x 1 g/L = 180 g/day Filtered load > amount excreted in the urine: net reabsorption Filtered load < amount excreted in the urine: net secretion Division of labor in the tubules-1 In order to excrete waste products adequately, the GFR must be very large. Thus, the filtered volume of water and the filtered loads of all the nonwaste plasma solutes are also very large. Proximal tubule: reabsorbs most of this filtered water and solutes. It is also a major site of secretion for various solutes, except K+. Henle’s loop: also reabsorbs relatively large quantities of the major ions (less water) Division of labor in the tubules-2 DCT/CD: volume of water and masses of solutes reaching here are relatively small. Fine-tuning. Determines the final amounts excreted in the urine by adjusting the rates of reabsorption, and, in a few cases, secretion. Most homeostatic controls are exerted here. Reabsorption: tubular lumen to peritubular capillary two main paths of reabsorption: between cells through the tight junctions paracellular through the cells - transcellular Paracellular Transcellular Tubular reabsorption filtered load urine small losses of water and sodium keep our body in fluid balance large filtered load and amount excreted never 100% for waste products, reabsorption rates decrease Potassium, mEq 720 100 net 86.1 - K+ can be toxic in high concentration acts somewhere in between Na+ and urea - K+ is reabsorbed and secreted - 86.1% is net reabsorbed after secretion N.B. K+ is secreted, too Important facts about tubular reabsorption-1 1. Filtered loads are enormous, generally greater than the amounts of the substance in the body. 2. Reabsorption of waste products is relatively incomplete (e.g. urea). 3. Reabsorption of most useful plasma components (e.g. water, inorganic ions, and organic nutrients) is relatively complete. Important facts about tubular reabsorption-2 4. Reabsorption of some substances are not regulated (e.g. glucose, amino acids), while others are highly regulated (water, inorganic ions). Two mechanisms of reabsorption: diffusion and mediated transport Reabsorption by diffusion: often across the tight junctions connecting the tubular epithelial cells. e.g. urea reabsorption in the proximal tubule Urea is freely filtered at glomerulus. -->In the proximal tubule, water reabsorption occurs. -->Urea concentration in the tubular fluid becomes higher. -->Urea diffuses into the interstitial fluid and peritubular capillaries. Two mechanisms of reabsorption: diffusion and mediated transport Reabsorption by mediated transport occurs across tubular cells (transcellular epithelial transport). Requires the participation of transport proteins in the plasma membrane of tubular cells. Usually coupled to the reabsorption of sodium. Mediated transport symporter, cotransporter carries glucose along with Na+ against the concentration gradient Proximal tubule Na glucose Na facilitated diffusion of glucose along the concentration gradient glucose Na amino acids Na+/K+ antiporter K ATPase amino acids cotransporter (symporter) Mechanisms of solute transport (different way to classify) Passive: spontaneous, down an electrochemical gradient (no energy required) * Diffusion * Facilitated diffusion Channels Uniport Coupled transport (antiport or symport) * Solvent drag Active: against an e-c gradient (requires input of energy) R Mechanisms of solute transport (different way to classify) Passive: spontaneous, down an electrochemical gradient (no energy required) * Diffusion * Facilitated diffusion Channels Mediated Uniport transport Coupled transport (antiport or symport) * Solvent drag Active: against an e-c gradient (requires input of energy) Transport maximum (Tm) When the membrane transport proteins become saturated, the tubule can not reabsorb the substance any more. This limit is called transport maximum (Tm) e.g. in people with uncontrolled diabetes mellitus, the plasma concentration of glucose can become very high and the filtered load of glucose exceeds the capacity of the tubules to reabsorb glucose (Tm is exceeded). As a result, glucose appears in the urine (glucosuria). Tubular secretion Tubular secretion moves substances from peritubular capillaries into the tubular lumen (opposite of reabsorption). Also mediated by the two mechanisms, i.e. diffusion are only and transcellular mediated transport. thereand K+ 2 major ions that are secreted - H+ Most important substances secreted by the tubules: hydrogen ion and potassium. Tubular secretion is usually coupled to the reabsorption of sodium. Concept of clearance Clearance: the volume of plasma from which that substance is completely removed (“cleared”) by the kidneys per unit time. Mass of S excreted per unit time Clearance of S (Cs) = Plasma concentration of S (Ps) Mass of S excreted per unit time = Urine concentration of S (Us) x Urine volume per unit time (V) ∴ UsV Cs = Ps S = glucose, ion etc. Inulin clearance not an endogenous product - it is intravenously administered Inulin (not insulin) is a polysaccharide that would be administered intravenously. It is freely filtered at glomerulus but is NOT reabsorbed, secreted, or metabolized by the tubule. Thus, the clearance of inulin (CIN) is equal to the volume of plasma originally filtered (GFR). - there is no modification in the plasma to IN CIN = GFR (most accurate marker of GFR) GFR ? assume that the IV is hooked up for 24h and the test is done over 24h Urine volume = 2.4 L/day Inulin concentration in the urine = 300 mg/L Amount of inulin excreted in the urine = 2.4 L/day x 300 mg/L =720 mg/day CIN = 720 mg/day ÷ 4 mg/L = 180 L/day ∴ GFR = CIN = 180 L/day Creatinine clearance Creatinine is a waste product produced by muscle. It is filtered freely at glomerulus and is NOT reabsorbed. It is secreted at the tubule but the amount is small. It is NOT metabolized by the tubule. Thus, creatinine clearance is used as a clinical marker for GFR. an endogenous product, it is already there achieving constant plasma concentration it is so small it is negligible Creatinine clearance Urine volume (V) Urine concentration of creatinine (Ucr) Plasma concentration of creatinine (Pcr) Creatinine clearance = UcrV ≅ GFR Pcr Creatinine clearance Urine volume: 2 L per day Urine concentration of creatinine: 9.6 mmol/L Plasma concentration of creatinine: 0.3 mmol/L Creatinine clearance = UcrV = 9.6 x 2 = 64 L/day Pcr 0.3 This person has lost ~2/3 of GFR. and of kidney function Clearance vs GFR Clearance of a substance > GFR It is secreted at the tubule. Clearance of a substance < GFR It is reabsorbed at the tubule. Clearance > GFR (secretion) e.g. para-amino-hippurate marker of renal plasma flow Clearance < GFR (reabsorption) ...
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