Kidney Function Flashcards
Proximal Tubule
Reabsorbs solutes and water
66% Na+
• Via cotransport with HCO3-, glucose, aa’s, phosphate, lactate
• Via countertransport with H+ via Na+/H+ exchanger
• Na+ gradient maintained by Na/K ATPase on basolateral side
66% of K+
• 100% glucose and amino acids
• 90% phosphate
• Water passively follows solutes (via aquaporins) = reabsorbed
Result: isotonic solution leaving proximal tubule
Affected by Carbonic anhydrase inhibitors (ex: acetazolamide)
• Diuretic
• Inhibits HCO3- reabsorption
• Water not pulled into cell = excreted
Loop of Henle
o Starts as isotonic solution
Descending limb:
• Water moves without Na+
• Most hypertonic at tip
Ascending limb: • Transport of Na+ (25%) and Cl- • Na+/K+/2Cl- cotransporter in luminal membrane • 20% of K+ reabsorption • Impermeable to water • Dilution of filtrate
Result: Countercurrent Multiplication
Site of action for loop diuretics (ex: Furosemide)
Distal convoluted Tubule
o Further reabsorption of Na+ (5%) and dilution of ultrafiltrate
• Via Na+/Cl- cotransporter
o Depending on K+ content in diet = can reabsorb or secrete K+
o Site of action of thiazide diuretics (ex: HCTZ)
o Impermeable to water → dilutes tubular fluid
Collecting Duct
o Contains principal and alpha-intercalated cells
Cortical:
• Na+ reabsorption (3%)
• K+ excretion
Medullary:
• Reabsorption of water due to ADH
• If no ADH = impermeable to water
Site of action:
• Aldosterone = increases Na+ reabsorption, increases K+ secretion
• ADH = inserts water channels in luminal membrane → increases water permeability
• K+-sparing diuretics (ex: spironolactone) = decrease K+ secretion
Erythropoietin
o Produced by proximal tubular epithelial cells and cortical interstitial cells
o Stimulated by low oxygen levels in tissues
• Kidney produced Hypoxia Inducible Factors (HIF)
• Lead to increased EPO production
o Result: acts on bone marrow to increase RBC production, maturation, and lifespan
1,25-Dihydroxyvitamin D3 (Calcitriol)
o Active form of vitamin D
o Necessary for Ca2+ absorption
o Produced in kidney: conversion from 25-Vit D via alpha-1 hydroxylase
o Stimulated when low Ca2+ or low phosphorus
o Result: maintain Ca2+ levels, promotes healthy bone formation, inhibits PTH
Clearance
= volume of plasma of a substance that is completely removed over time
Clearance = (U x V)/ P
• U: urinary concentration of substance (mg/ml)
• V: urine flow rate (ml/min)
• P: plasma concentration of a substance (mg/ml)
Creatinine clearance
o Endogenous substance
o Produced form muscle creatine
o Can do a timed (24 hour) collection
Error:
• Minimal secreation
• Variation in level with low or high muscle mass
• Level influenced if low meat intake
Limitations to 24 hour collection:
• Not efficient
• Not accurate
• Cumbersome
Cockcroft-Gault equation
o Avoids the 24 hour collection
o Weight is surrogate for muscle mass
o Accounts for age and gender
o Good estimate with high level of function
Creatinine clearance (ml/min) = [(140-age) x wt (kg)] / (serum creatinine (mg/dL) x 72) • Multiply by 0.85 for females
Modification of Diet in Renal Disease (MDRD)
o More complex formula (includes factors for age, measured serum creatinine, gender, race)
o Underestimates high function
o More useful in CKD patients with stable creatinine
o Not useful in AKI
CKD- EPI
o Newest formula = better than MDRD at higher level function
o Recommended by governing bodies
o Not useful in AKI
Describe the distribution of water and electrolytes within the compartments of the body
• Total body water (TBW) = 50-60% of total body weight
Divided into: Intracellular Fluid (ICF) = 2/3 of TBW = 0.4 x wt Extracellular Fluid (ECF) = 1/3 of TBW = 0.2 x wt • Interstitial fluid = 3/4 ECF = 0.15 x wt • Plasma = ¼ ECF = 0.05 x wt
Compartments are separated by semi-permeable membrane
o Water moves freely between
o Solutes (Na+, K+, Cl-) are restricted in movement
• Effective osmolarity is the same in all compartments!
Osmolality vs. Tonicity
• Osmoles = number of moles of free solute particles in solution
o Osmolality = number of osmoles/kg water
o Osmolality = 2[Na+] + [glucose] + [BUN]
• Tonicity is determined clinically by [Na+] and glucose because they are effective osmoles (cause water to move)
o Tonicity = 2[Na+] + [glucose]
o Urea is usually an ineffective osmole → usually does not cause shifts in water
Identify the factors that affect the distribution of fluid among these compartments.
ICF
o Major solutes: K+, phosphates, proteins
o Like a measure of water balance = changes in water content of body always affect ICF
o Changes in ICF are created by changes in serum Na+ concentration (osmolality)
o If increase osmolality = ICF shrinks
ECF
o All fluids outside the cell
o Major solutes: Na+, Cl-, HCO3-
o A measure of Na+ balance = increases/decreases in ECF are governed by changed in sodium content (NOT concentration!)
o A tricky compartment to gauge accurately
• “Intravascular volume” status = plasma compartment
• “Extravascular volume” status = interstitial compartment
OVERALL:
• ECF and tonicity are independent
• ICF and tonicity are linked
Explain the mechanisms that lead to an imbalance in distribution or in the amount of fluid in a compartment.
Isotonic o Same tonicity as the body o About 300 o If add isotonic solution: • Raise volume but not change serum Na+ • Increase ECF
Hypotonic o Lower tonicity in comparison to ECF (like more water being given) o If add hypotonic solution: • Increase ECF and decrease serum Na+ • Increase ICF
Hypertonic o Higher tonicity in comparison to ECF (like the solution has less water being given than the serum) o If add hypertonic solution: • Increase ECF and increase serum Na+ • Decrease ICF
