Renal 11-12 Flashcards
What is the formula/definition of pH?
pH is a measure of the log of the H+ concentration (use the log because the actual concentrations vary in such a wide range)
pH = -log [H+]
Concentration in physiological solution ranges from 0.13 M in gastric juice → 3x10^-8 M in pancreatic juice
Why is it important for the kidney to excrete protons?
Metabolic reactions generate acid (H+) → have to excrete to maintain pH ~ 7.4 and extracellular bicarbonate ~ 22-26 mEq/L
Which metabolic reactions give rise to endogenous acids?
- Oxidation of organic sulphur to SO4 (2-) → 2H+
- Conversion of neutral foodstuffs to organic acids:
- Glucose
- Triglyceride
- Nucleoprotein - Hydrolysis of phosphoesters
*Ends up in the plasma an consumes HCO3-
What is the difference between Acidosis and Acidemia and between Alkalosis and Alkalemia?
Acidosis and Alkalosis are processes (of generating acid or losing acid/base)
Acidemia and Alkalemia are states of high/low acid
What is the Henderson-Hasselbalch equation?
pH = pK + log [HCO3-]/sP CO2
sP CO2 → solubility of CO2 (depends on T˚)
[HCO3-] → plasma concentration of HCO3-
Knowing CO2 and pH, can calculate HCO3- and inversly
*Helps determine if metabolic or respiratory acidosis (depending on levels of bicarbonate)
Equation starts from [H+][HCO3-]/[H2CO3]=k’ and [H+][HCO3-]/[CO2]=k
What is the Isohydric principle?
It accounts for the effect of multiple H+ buffers in the blood with which H+ is in equilibrium (extension of Henderson-Hasselbalch equation)
pH = pK1 + log [HCO3-]/sPCO2 = pK2 + log [HPO4 (2-)]/[H2PO4-] = pK3 + log sPNH3/[NH4+]
All buffers equilibrate according to they respective pK values. Bicarbonate being the predominant buffer, other buffers become more important in distal nephron after most bicarbonate is reabsorbed
What is the anion gap?
It is the difference between the concentration of Na+ and the concentraton of the major anions (bicarbonate and Cl) → Accounts for presence of other anions that make plasma neutral (= Na+)
Plasma anion gap = [Na+] - ([HCO3-] + [Cl-]) in mEq/L
normal range: 8-14 mEq/L
- Anionic proteins
- Phosphate
- Sulfate
- Organic anions
*In fasting, with baking down of fatty acid → larger anion gap
What are 2 strategies for acid-base ahndling utilizing bicarbonate?
- Recapturing bicarbonate from the ultrafiltrate
- Synthesizing new bicarbonate
What are the major molecular mechanisms of Bicarbonate reabsorption?
Proximal tubule:
Through acid secretion → HCO3- + H+ → CO2 reabsorbed passively
- H+ ATPase or NHE3 (Na+/H+ antiporter) secretes H+
Collecting duct → 2 types of intercalated cells:
1. H+ secreting intercalated cells → A-type (Acid secreting)
- K+/H+ ATPase (antiport)
- H+ ATPase pump
- HCO3- + H+ → CO2 + H2O → CO2 diffuse back in the cells → C.A. → HCO3- + H+ → H+ pumped back out and HCO3- antiporter out of the cell on basolateral membrane side by HCO3-/Cl- antiporter
(Cl- is recycled back out of the cell by channel)
- HCO3- secreting intercalated cells → B-type (Base secreting)
- CO2 diffuses inside the cells from the blood → C.A
- HCO3-/Cl- antiporter on apical membrane and H+ ATPase on basolateral side
(Cl- transporter also on basolateral membrane)
What are the major sites of bicarbonate reabsorption?
~ 80% in PT, 10% in TAL, 6% DT, 4% CCD, ~0% excreted
What mechanisms enhances the efficiency of renal acid excretion through de novo bicarbonate synthesis?
- Titratable acid excretion:
H+ secreted by H+ ATP pump → interact with buffer → H-buffer → driving force for H+ doesn’t go down
*Rate of secretion != rate of excretion
(titratable acids are filtered in their base form and secreted protonated)
- NH4+ excretion:
In proximal tubule → S1 and S2 segments synthesize NH4+ from glutamine
- NH4+ antiporter with Na+ (Na/H transporters)
- NH3 free diffusion + H+/Na+ antiport (reassemble in the lumen)
In collecting duct → NH4+ entry by Na/K+ ATPase (basolateral membrane) then apical NH3 efflux (free diffusion) + H+ transporter (V ATPase) export → reassemble to form NH4+ in the lumen
Which one is ammonia vs ammonium?
Ammonia = NH3
Ammonium = NH4+
What is the rhesus protein RhCG?
Ammonia (NH3) transporter specific to the Collecting duct → On bothbasolateral and apical membrane
Increases efficiency of diffusion
How does the interstitial ammonia concentration change in the kidney?
Increase concentration of interstitial ammonia from the cortex to the medulla to the papillae
*In the bottom of the loop of Henle → medullary accumulation loop
Recylcing of ammonia in the loop of henle TAL → thin descending limb and in from the TAL → collecting duct
*Highest lumenal concentration in the bottom of the loop of Henle
What is the equation for the Net acid excretion?
What is the equation for the Total acid secretion?
What is the paradox?
Net acid excretion = urine NH4+ + titratable acidity - urine HCO3-
Total acid secretion = HCO3- reabsorbed + urine NH4+ + titratable acidity
*Urine NH4+ carries ou a proton
*titratable acidity → buffer capacity of urine
Paradox:
Net acid excretion increases in response to metabolic acidosis, but total acid secretion may decrease → because not as much secretion in the PT to not recover it
What effect does metabolic acidosis have on plasma CO2, H+ and HCO3- (both sides of the equilibrium equation), on respiratory compensation and on renal compensation?
Metabolic acidosis:
Initial disturbance = Increase in H+
- Decrease in CO2 + H2O side
- decrease in HCO3-
- Respiratory compensation → Hyperventilation
- Renal compensation → increase H+ excretion + increase HCO3- reabsorption
*Metabolic → arrows from H+ are in opposit direction than other arrows of the equation
What effect does metabolic alkalosis have on plasma CO2, H+ and HCO3- (both sides of the equilibrium equation), on respiratory compensation and on renal compensation?
Metabolic alkalosis:
Initial disturbance = Decrease in H+
- Increase in CO2 + H2O side
- Increase in HCO3-
- Respiratory compensation → Hypoventilation
- Renal compensation → Increase HCO3- excretion
*Metabolic → arrows from H+ are in opposit direction than other arrows of the equation
