The kidney (Pseudo) Practical questions for questions Ella (striemit@gmail.com) The kidneys are all about keeping the body s homeostasis Ingestion Product of metabolism H 2 O Ca ++ Cl - K + Na + H 2 O H 2 O Mg ++ Excretion metabolism = Ingested + Product of metabolism Excreted + Metabolized 1
Glomerular Filtration Rate (GFR) GFR is the volume of fluid filtered out of the plasma through glomerular capillary walls into Bowman's capsules per unit of time. GFR It is also the best estimate of kidney function for diagnosis of kidney disease. The normal range of GFR for males and females is: (depending on age, race, etc.) Males: 97 to 137 ml/min. (139 197 L/day!) Females: 88 to 128 ml/min. Kidney function assessment Assessing GFR? GFR is best assessed by computing the Renal clearance (C) Renal clearance - The volume of plasma completely cleared of a specific compound per unit time (units ml/min) Most accurate assessment is by computing Inulin clearance it is are freely filtered but not secreted or reabsorbed second most accurate is computing creatinine clearance 2
Kidney function assessment You wish to evaluate kidney function in a 65 year old male and ask him to collect his urine over a 24 hours period. He returns to you 4.32 L of urine, collected over the preceding 24 hours. The clinical lab returns the following results from analysis of his urine and plasma samples: Plasma creatinine: 0.03 mg/ml Urine creatinine: 0.3 mg/ml Plasma potassium: 0.005 mmol/ml Urine potassium: 0.01 mmol/ml What is this man s s GFR? Plasma creatinine: 0.03 mg/ml Urine creatinine: 0.3 mg/ml Plasma potassium: 0.005 mmol/ml Urine potassium: 0.01 mmol/ml Cs = Us V Ps U s V P s = the substance s concentration in the urine = the volume of urine collected per time unit = the substance s concentration in the plasma C cr = (0.3 mg/ml * 4320 ml/day) 0.03 mg/ml = 43200 ml/day = 30 ml/min So his GFR is lower than normal (97 to 137 ml/min) implying kidney disease 3
Plasma creatinine: 0.03 mg/ml Urine creatinine: 0.3 mg/ml Plasma potassium: 0.005 mmol/ml Urine potassium: 0.01 mmol/ml What is the Renal clearance of K? C K = (0.01 mmol/ml * 4320 ml/day) 0.005 mmol/ml = 8640 ml/day = 6 ml/min As C K < GFR, K is reabsorbed (NET reabsorbed!) What is the renal reabsorption rate of potassium (K) in this patient? K + excretion = K + filtered K + reabsorbed + K + secreted Computing the difference between how much is filtered and how much is excreted gives total reabsorption rate. Plasma creatinine: 0.03 mg/ml Urine creatinine: 0.3 mg/ml Plasma potassium: 0.005 mmol/ml Urine potassium: 0.01 mmol/ml Assuming that K is freely filtered, it would be filtered at a rate of GFR * plasma concentration (this is the Filtered load) FL K = GFR x P K = 30 ml/min * 0.005 mmol/ml = 0.15 mmol/min the difference, or reabsorption rate, is therefore: FL K U K V = 0.15 mmol/min 0.01 mmol/ml * 4320 ml/day = 0.15 mmol/min 0.01 mmol/ml * 3 ml/min = 0.12 mmol/min 4
Therefore most of the K is reabsorbed How is this achieved? K is freely filtered, it is mostly reabsorbed and later secreted. The regulation is only for secretion K + Reabsorption Not regulated! In the proximal tube and thick ascending limb of the loop of Henle Absorption of ~90% of K + K + Secretion Coupled to Na + reabsorption Regulation of K + secretion is by aldosterone that drive increased uptake by the Na + /K + ATPase 5
Hydrogen ion regulation ph PH=7.4 ph [H + ] Acidosis [H + ] Alkalosis Lung regulation CO 2 + H 2 O H 2 CO 3 H + + HCO - 3 Kidney regulation The clinical laboratory returns the following arterial blood values for a patient: ph: 7.31 (normal - ph 7. 36-7.44) plasma HCO 3- : 32 mmol/l (normal - 24-32 mmol/l) plasma PCO 2 : 65 mmhg (normal - 35-45 mmhg) what is this patient s -base disorder? osis/alkalosis? respiratory or metabolic based? 6
ph: 7.31 (normal - ph 7. 36-7.44) plasma HCO - 3 : 32 mmole/l (normal - 24-32 mmol/l) plasma PCO 2 : 65 mmhg (normal - 35-45 mmhg) ph is lower than normal, therefore: Acidosis What is the origin of the osis? Increased PCO 2 implies that it is respiratory based (not clearing out enough CO 2 ) How do the kidneys compensate for osis? CO + H 2 2 O H CO 2 3 HCO - 3 + H + Bicarbonate reabsorption H + ATPase pumps Na + /H + countertransporters CO + H 2 2 O H CO 2 3 HCO - 3 + H + 7
Bicarbonate creation CO + H 2 2 O H CO 2 3 HCO - 3 + H + Bicarbonate creation CO + H 2 2 O H CO 2 3 HCO - 3 + H + NH 3 + H + -> NH 4 + 8
ph: 7.31 (normal - ph 7. 36-7.44) plasma HCO - 3 : 32 mmole/l (normal - 24-32 mmol/l) plasma PCO 2 : 65 mmhg (normal - 35-45 mmhg) Therefore we expect to find in this patient with respiratory osis: Higher plasma HCO 3- (we don t see it! Perhaps the kidneys are not handling this osis well) elevated urine NH 4 + lowered urine ph reduced urine excretion of HCO 3-9