BIOL 2402 Renal Function

Transcription

1 BIOL 2402 Renal Function Dr. Chris Doumen Collin County Community College 1 Renal Clearance and GFR Refers to the volume of blood plasma from which a component is completely removed in one minute by all the nephrons. Clearance thus compares the rate at which the glomeruli filter a substance (H 2 O) or solute) with the rate that the kidneys excrete it into the urine. If we measure difference in amount of substance filtered and excreted, we can estimate the net amount reabsorbed or secreted by renal tubules. Gives us information about the 3 basic functions of the kidneys: Glomerular filtration Tubular reabsorption Tubular secretion 2 1

2 Renal Clearance and GFR Amount excreted in Urine = Glomerular Filtration - amount reabsorbed + amount secreted 3 Renal Clearance and GFR Amount excreted in Urine = Glomerular Filtration - amount reabsorbed + amount secreted Thus, if the component is freely filtered, and is neither secreted nor reabsorbed, one obtains an excretion rate which then equals the glomerular filtration rate. In addition, this component has to be metabolically inert ( not metabolized anywhere in the body) INULIN is such a component ( = plant polysaccharide, extracted from the Jerusalem Artichoke) 4 2

3 Renal Clearance and GFR The following relationship holds true when considering what is present in the blood and what ends up in the urine : The concentration of a substance X in the blood multiplied by the amount removed by the kidneys per time unit has to be equal to the concentration in the urine of substance X times the volume of urine formed per time unit. Conc. of X in systemic blood plasma P x x Conc. of X in urine C x = U x x V Volume of urine formed in given time Clearance 5 Renal Body Clearance Water Content and GFR By re-arranging we obtain : Clearance Conc. of X in urine C x = U x x V P x Volume of urine formed in given time Conc. of X in systemic blood plasma 6 3

4 Renal Clearance and GFR Example calculation for Inulin Plasma conc. : 0.3 mg/ml Urine conc. : 30 mg/ml Urine rate : 1.25 ml/min Inulin Clearance = (U in x V) / P in = (30 mg/ml x 1.25 ml/min) / 0.3 mg/ml = 125 ml inulin cleared from plasma/min = GFR 7 Drawbacks of INULIN Most reliable method of measuring GFR, not useful clinically. Inulin must be administered by IV to get relatively constant plasma levels. Chemical analysis of inulin in plasma and urine is technically demanding. Problems of IV infusion of GFR marker avoided by using an endogenous substance with inulin-like properties CREATININE. 8 4

5 CREATININE Creatinine is a by product of muscle metabolism ( not to be confused with creatine). The use of creatinine avoids IV infusion; just requires venous blood and urine samples. It is easily measured by colorimetric spectroscopic means: thus cheap, easy, and fairly reliable. C Cr = U Cr x V P Cr 9 CREATININE Problems with use of creatinine : Creatinine itself is secreted by tubules, so might overestimate GFR by 20% in humans. However, colorimetry methods used to measure creatinine overestimate creatinine concentrations. Luckily, these 2 errors cancel each other out, and calculated creatinine clearance inulin clearance. Must remember to take into account if person has muscle disease/damage, or has had large quantities of meat to eat. Usually measure over 24 hr period to get reliable results and take samples before breakfast. 10 5

6 RENAL PLASMA FLOW Most substances are NOT cleared completely on 1 st pass through the kidney some amount goes out in venous blood. Theoretically, if a substance is complete cleared from the plasma in one pass, the clearance of that substance is equal to the total renal plasma flow In such case, renal clearance of X = arterial renal plasma flow. PAH (p-aminohippurate ) is such a substance Delivery for filtration to kidney RPF PAH x P PAH = U PAH x V Conc. of PAH in systemic blood plasma 11 RENAL PLASMA FLOW PAH is an organic acid that is not usually present in the body, so it is given by IV infusion. It is both filtered and secreted so that almost none is left in the renal vein. P PAH = 0.1 mg/ml U PAH = 6 mg/ml V = 1 mg/ml RPF = 600 ml/min 12 6

7 RENAL PLASMA FLOW In reality, clearance of PAH is not 100 % but 90 % To correct for this we calculate a normal RPF and then divide by 0.9 Thus for the previous example : RPF = 600 ml/min Corrected = 600/0.9 Real RFP = 666 ml/min 13 Filtration Fraction Filtration Fraction is defined as follows : FF = Glomerular Filtration Rate Renal Plasma Flow Thus for the previous example : FF = (125 ml/min) / (666 ml/min) = or close to 20 % Thus ~ 20 % of the plasma that enters the glomeruli is typically filtered 14 7

8 GFR and CLEARANCE VALUES Measuring clearance means you measure OVERALL nephron function i.e. all ~2 million nephrons in both kidneys. This gives the SUM of ALL transport processes occurring along nephrons. So, no information about precise sites and mechanisms of transport. But each individual solute has its own Clearance and this provides information on how the nephrons handle each component. 15 GFR and CLEARANCE VALUES Recall this relationship : Amount excreted in Urine = Renal (Plasma ) Clearance = Glomerular Filtration - amount reabsorbed + amount secreted What additional information does this give us about a solute? If the plasma clearance = GFR, then that substance is neither reabsorbed nor secreted. If the plasma clearance > GFR, than it indicates that the solute is filtered and secreted. If the plasma clearance < GFR, it indicates that the solute is filtered and reabsorbed. 16 8

9 Tubular Reabsorption Examples GFR = 125 ml/min Glucose : P G = 1 mg/ml V = 1 mg/ml U G = 0 mg/ml Glucose plasma Clearance = (U G x V )/ P G = 0 ml/min Glucose Filtered Load = GFR x P G = 125 mg/min Tubular Reabsorption = Filtered Load - Excreted Load = (GFR x P G ) - (U G x V ) = 125 mg/min 17 Tubular Reabsorption Examples All filtered glucose is reabsorbed at plasma concentrations below 250 mg/dl The reabsorptive mechanisms becomes saturated at concentrations above 350 mg/dl Glucose begins to appear in the urine at plasma conc. of 250 mg/dl Clearance of glucose is thus 0 when blood plasma conc. < 250 mg/dl Above that, Clearance of glucose increases because it becomes excreted and it begins to approach the clearance of inulin. 18 9

10 Tubular Reabsorption Examples GFR = 125 ml/min Sodium : P G = 140 microg/ml U G = 70 microg/ml V = 1 mg/ml Sodium plasma Clearance = (U G x V )/ P G = 0.5 ml/min Sodium Filtered Load = GFR x P G = ug/min Tubular Reabsorption = (GFR x P G ) - (U G x V ) = ug/min 19 Tubular Secretion Example GFR = 125 ml/min Creatinine : Creatinine plasma Clearance = (U C x V )/ P c = 140 ml/min Creatinine Filtered Load = GFR x P C Tubular Secretion = Excreted Load- Filtered Load = (U C x V )- (GFR x P C ) 20 10

11 Blood Urea Nitrogen Blood urea nitrogen (BUN) measures the amount of urea nitrogen, a waste product of protein metabolism, in the blood. Urea is formed by the liver and carried by the blood to the kidneys for excretion. Because urea is cleared from the bloodstream by the kidneys, a test measuring how much urea nitrogen remains in the blood can be used as a test of renal function. However, there are many factors besides renal disease that can cause BUN alterations, including protein breakdown, hydration status, and liver failure. 21 Blood Urea Nitrogen Increased BUN levels means more urea stays behind in the blood (less urea is cleared by the kidneys) and thus may indicate Impaired renal function Poor renal perfusion due to low cardiac Ouput An increase in the BUN level is known as azotemia. An elevated BUN may also be caused by: * Dehydration (lack of fluid to excrete urea with) * Shock * Hemorrhage into the gastrointestinal tract (digested blood is a source of urea) * Acute myocardial infarction * Stress * Excessive protein intake or protein catabolism 22 11

12 Blood Urea Nitrogen A decreased BUN may be seen in: * Liver failure * Malnutrition * Anabolic steroid use * Overhydration, Which can result from prolonged intravenous fluids * Pregnancy (due to increased plasma volume) * Impaired nutrient absorption An assessment of the BUN is used as a gross index of glomerular function. Normal values : Adult: 7-20 mg/100 ml; men may have slightly higher values than women Pregnancy: values decrease about 25% Because the BUN is affected by the patient's hydration status, it is a less sensitive indicator of declining renal function than a creatinine clearance test. A BUN of over 100 mg/dl is a panic value. 23 Blood Creatinine Levels Measuring serum creatinine is a useful and inexpensive method of evaluating renal dysfunction (used to measure GFR)! Remember that Creatinine is a non-protein waste product of creatine phosphate metabolism by skeletal muscle tissue. Creatinine production is continuous and is proportional to muscle mass. Creatinine is freely filtered and therefore the serum creatinine level depends on the Glomerular Filtration Rate (GFR). Renal dysfunction diminishes the ability to filter creatinine and the serum creatinine rises. If the serum creatinine level doubles, the GFR is considered to have been halved. A threefold increase is considered to reflect a 75% loss of kidney function

13 Blood Creatinine Levels Reference values for serum creatinine: Adult males: mg/dl: values are slightly higher in males due to larger muscle mass Adult females: mg/dl: creatinine clearance is increased in pregnancy, resulting in lower serum levels Children: mg/dl: slight increases with age because values are proportional to body mass A panic value for creatinine is 10 mg/dl in nondialysis patients. Increased serum creatinine levels are seen in: * Impaired renal function * Chronic nephritis * Urinary tract obstruction * Muscle diseases such as gigantism, acromegaly, and myasthenia gravis * Congestive heart failure 25 * Shock Blood Creatinine Levels Decreased creatinine levels may be seen in: the elderly, persons with small stature, decreased muscle mass, or inadequate dietary protein. Muscle atrophy can also result in decreased serum creatinine level. Unlike the BUN, the serum creatinine level is not affected by hepatic protein metabolism. The serum creatinine level does not rise until at least half of the kidney's nephrons are destroyed or damaged. Because creatinine levels rise and fall more slowly than BUN levels, creatinine levels are often preferred to monitor renal function on a long-term basis

14 Blood BUN: Creatinine Levels Serum creatinine and Blood Urea nitrogen (BUN) are often compared to evaluate renal function. While serum creatinine increases only with nephron damage, the BUN is affected by hydration, hepatic metabolism of protein and reduced GFR. The mean ratio of serum creatinine to the BUN should be approximately 10:1 Values over 20:1 indicate a pre-renal (before the glomeruli) disease Reduced flow causes elevated BUN reabsorption within kidney; Cr is not reabsorbed, therefore BUN:Cr ratio increases Values below 10:1 indicate intra-renal disease Renal damage causes reduced BUN re-absorption, therefore lowering Bun:Cr ratio 27 14