The kidney (Pseudo) Practical questions… for questions… Ella ([email protected]) • The kidneys are all about keeping the body’s homeostasis Ingestion Product of metabolism H2O Ca++ K+ Na+ H2O ClH2O Mg++ Excretion metabolism ∑ 1 Ingested + Product of metabolism =∑ Excreted + Metabolized 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: Urine creatinine: Plasma potassium: Urine potassium: 0.03 mg/ml 0.3 mg/ml 0.005 mmol/ml mmol/ml 0.01 mmol/ml mmol/ml What is this man’ man’s GFR? Plasma creatinine: Urine creatinine: Plasma potassium: Urine potassium: 0.03 mg/ml 0.3 mg/ml 0.005 mmol/ml mmol/ml 0.01 mmol/ml mmol/ml Cs = Us V Ps Us V Ps = the substance’s concentration in the urine = the volume of urine collected per time unit = the substance’s concentration in the plasma Ccr = (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: Urine creatinine: Plasma potassium: Urine potassium: 0.03 mg/ml 0.3 mg/ml 0.005 mmol/ml mmol/ml 0.01 mmol/ml mmol/ml • What is the Renal clearance of K? • CK = (0.01 mmol/ml * 4320 ml/day) 0.005 mmol/ml = 8640 ml/day = 6 ml/min • As CK < 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: Urine creatinine: Plasma potassium: Urine potassium: 0.03 mg/ml 0.3 mg/ml 0.005 mmol/ml mmol/ml 0.01 mmol/ml mmol/ml • Assuming that K is freely filtered, it would be filtered at a rate of GFR * plasma concentration (this is the Filtered load) • FLK = GFR x PK = 30 ml/min * 0.005 mmol/ml = 0.15 mmol/min • the difference, or reabsorption rate, is therefore: FLK – UKV = 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=7.4 pH pH [H+] [H+] Acidosis Alkalosis Carbonic anhydrase Lung regulation CO2 + H2O H2CO3 Carbonic acid H+ + HCO3- Kidney regulation Bicoarbonate • The clinical laboratory returns the following arterial blood values for a patient: pH: 7.31 (normal - pH 7. 36-7.44) plasma HCO3- : 32 mmol/L (normal - 24-32 mmol/L) plasma PCO2 : 65 mmHg (normal - 35-45 mmHg) what is this patient’s acid-base disorder? acidosis/alkalosis? respiratory or metabolic based? 6 pH: 7.31 (normal - pH 7. 3636-7.44) plasma HCO3- : 32 mmole/L mmole/L (normal - 2424-32 mmol/L) mmol/L) plasma PCO2 : 65 mmHg (normal - 3535-45 mmHg) • pH is lower than normal, therefore: Acidosis • What is the origin of the acidosis? • Increased PCO2 implies that it is respiratory based (not clearing out enough CO2) • How do the kidneys compensate for acidosis? Carbonic anhydrase CO2 + H2O H2CO3 Carbonic acid HCO3- + H+ Bicoarbonate Bicarbonate “reabsorption” H+ ATPase pumps Na+/H+ countertransporters Carbonic anhydrase CO2 + H2O 7 H2CO3 Carbonic acid HCO3- + H+ Bicoarbonate Bicarbonate creation Carbonic anhydrase CO2 + H2O H2CO3 Carbonic acid HCO3- + H+ Bicoarbonate Bicarbonate creation NH3 + H+ -> NH4+ Carbonic anhydrase CO2 + H2O 8 H2CO3 Carbonic acid HCO3- + H+ Bicoarbonate pH: 7.31 (normal - pH 7. 3636-7.44) plasma HCO3- : 32 mmole/L mmole/L (normal - 2424-32 mmol/L) mmol/L) plasma PCO2 : 65 mmHg (normal - 3535-45 mmHg) • Therefore we expect to find in this patient with respiratory acidosis: • Higher plasma HCO3- (we don’t see it! Perhaps the kidneys are not handling this acidosis well) • elevated urine NH4+ • lowered urine pH • reduced urine excretion of HCO3- 9
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