Renal - Hydrogen Ion Excretion - Lecture 10 Flashcards
How is both the reabsorption of the filtered HCO3- and the excretion of nonvolatile acids achieved?
Via secretion of H+ by nephrons
- secreted H+ serves to reabsorb the filtered load of HCO3-
- urine acidity is usually 50 to 100 mEq of H+ –> urine is slightly acidic
Because the kidneys cannot excrete urine more acidic than pH of 4 to 4.5, how is the secretion of H+ achieved?
To secrete sufficient acid, a buffer like phosphate is used
or even creatinine, which has a less important role than Pi
What are the various urinary buffers for H+ called?
Titratable Acids
- excretion of H+ as a titratable acid is INSUFFICIENT to balance the daily nonvolatile acid load
Because the excretion of H+ as a titratable acid is INSUFFICIENT to balance the daily nonvolatile acid load, what other important mechanism contributed to the maintenance of acid-base balance in the kidney?
Via synthesis and excretion of NH4+ (ammonium)
Is the majority of HCO3-
- Filtered
- Excreted
- Secreted
- Reabsorbed
Where?
REABSORBED!
- in the proximal tubule (80%)
What reaction predominates in the Proximal tubule? What enzyme is vital to this reaction?
CO2 HYDRATION REACTION:
[HCO3- + H+ –> H2CO3 –> (CA) –> H2O + CO2]
The presence of Carbonic Anhydrase in the brush border
Why is the net secretion of H+ in the PT very low?
net secretion of H+ is very low due to neutralization reaction of H+ with HCO3 - during bicarbonate ion “recycling” or reabsorption
What mechanisms facilitate reabsorption in the PT? (2 transporters)
- Apical H+ - ATPase (out)
- Apical Na/H (out) Antiporter
H+ moves out in both cases!
What reactions predominate in the Distal Tubule and Collecting Duct for H+?
Is the net secretion of H+ in this area high or low? How is this achieved?
- Phosphate and Ammonium ion reactions
- no Carbonic Anhydrase here
- low HCO3- - Net secretion of H+ is HIGH due to proton pumping, buffered by phosphate and ion trapping as ammonium
Describe what occurs in DISTAL Renal Tubular Acidosis (Type I-RTA)
2 reasons
- Failure of distal nephron to secrete H+ !!!! (H+ remains in the plasma)
- Increased Back leaking of H+ or H+ pump failure (decreased plasma pH)
Describe what occurs in PROXIMAL Renal Tubular Acidosis (Type II-RTA)
2 reasons
REMEMBER** proximal is type 2 even tho proximal tubule comes 1st
- Failure of proximal nephron to recycle H+ due to low CARBONIC ANHYDRASE
- Decreased HCO3- reabsorption (low plasma pH = acidic)
Why does 80% of Reabsorption of filtered bicarbonate occur in the PROXIMAL TUBULE? (3)
- High Carbonic Anhydrase Activity
- Apical H+ - ATPase
- Basolateral Cl- / HCO3- Antiporter (HCO3- pumped out into the blood, Cl- pumped into the cell)
Why does 20% of Reabsorption of filtered bicarbonate occur in the Distal Tubule and Cortical Collecting Duct? (4)
- Low Carbonic Anhydrase Concentration (bad)
- Apical H+-ATPase
- Apical K+/H - ATPase
- Basolateral Cl-/HCO3 - Antiporter
The plasma HCO3 - concentration is regulated near what value for HCO3-?
Renal Plasma Threshold!
- important in regulating plasma [HCO3-]
What cells secrete HCO3-?
When do they facilitate the secretion of HCO3- and what mechanisms due they utilize to achieve this?
Collecting Duct!
- Basolateral H+-ATPase that pushes H+ back into the blood
- Apical Cl/HCO3- antiporter (cl in, HCO3 out)
- BOTH ACTIVATED in states of metabolic alkalosis
What 7 factors regulate HCO3- reabsorption?
- GFR
- Na balance
- Systemic Acid-Base Balance
- Aldosterone
- Arterial [K+]
- Arterial [Cl-]
- Extracellular Fluid Volume
How does GFR regulate HCO3- reabsorption? Which mechanism is important for this?
- Reabsorption rate of HCO3- is matched to changes in filtered load of HCO3- by GT BALANCE!
How does Na Balance regulate HCO3- reabsorption?
What happens to HCO3- reabsorption when you retain Na?
Lose Na?
- Apical Na/H Antiporter is important for HCO3- reabsorption (Na into cell, H+ out into TF!! - binds to NH4+ in the Tubular Fluid)
- Retain Na –> volume expansion and positive Na balance –> HCO3- reabsorption goes down (antiproton functioning less)
- Lose Na –> volume contraction and negative Na balance –> HCO3- reabsorption goes up!
How does Systemic acid/base balance regulate HCO3- reabsorption?
- In metabolic/respiratory acidosis
- In metabolic/respiratory alkalosis
- senses decrease in pH
- respiratory acidosis = increase in PaCO2
- metabolic acidosis = decrease in plasma HCO3-
a) Increase acidification of ICF –> increased insertion of apical H-ATPase -> increased H+ secretion and increased HCO3- reabsorption
- Senses Increase in pH:
- respiratory alkalosis = decrease in PaCO2
- metabolic alkalosis = increase in plasma HCO3-
b) decreased acidification of ICF –> decreased insertion of apical H-ATPase -> decreased H+ secretion and decreased HCO3- reabsorption
How does Aldosterone regulate HCO3- reabsorption?
- 2 cases of increased aldosterone and its affect of H+ secretion (state where and which cells)
- One case of decreased aldosterone
- a) Increased aldosterone –> increased secretion of H+ in intercalated cells of CD
b) increased aldosterone –> increased Na reabsorption by principal cells of CD
- -> increased Negativity of LUMEN of Tubule
- -> increased H+ secretion (indirect affect of Na reabsorption)
- Decreased aldosterone –> decreased H+ secretion in intercalated cells of CD
How does Arterial [K+] regulate HCO3- reabsorption?
- Increased
- what is the pH of urine
- what is the pH of the extracellular fluid
- is this hyperkalemia or hypokalemia? - Decreased
- what is the pH of urine
- what is the pH of the extracellular fluid
- is this hyperkalemia or hypokalemia?
- Increased arterial K+ :
- increased basolateral K-H exchange (K into cell, H+ into the plasma)
- -> extracellular acidosis with an ALKALINE urine –> hyperkalemic metabolic acidosis - Decreased Arterial K+ :
- DECREASED basolateral K-H exchange (K into cell, H+ into the plasma)
( K remains in the plasma since concentration is low to begin with, H+ is not pumped out of the
- extracellular alkalosis with an ACIDIC urine
= hypokalemic metabolic ALKALOSIS
How does Arterial [Cl-] regulate HCO3- reabsorption?
- Increased [Cl-]
- Decreased [Cl-]
- Increased [Cl-]
- decreased HCO3- reabsorption - Decreased [Cl-]
- increased HCO3- reabsorption
- maintains plasma electroneutrality since both compete for the same cations in tubular fluid
- little change in anion gap
What is the equation for the anion gap?
[A-] = [Na+] - [HCO3-] - [Cl-]
How does changing the ECF affect HCO3-?
expansion of ECF inhibits HCO3- reabsorption due to dilution of plasma [HCO3-]
What is the urine pH for
- Vegetarian diets
- Sulfur containing amino Acid Diets
What is the minimal urinary pH?
What is the source of urinary free H+?
- pH= 8 or higher
- pH = 5-6 (forms H2SO4)
- minimal pH is about 4.4
- impressive ability of distal nephron to secrete H+ against a strong acid gradient before back leaking occurs - fixed acids
titratable acids
- NOT CARBONIC ACID!!
- fixed acids
Carbonic Acid is a source of urinary free H+. True or False? Why?
FALSE!
- it readily becomes CO2 and diffuses back into the blood
Because secreted H+ combines with HPO4- to form H2PO4-, how does this prevent back diffusion?
Negatively charged ion is LIPID INSOLUBLE therefor no back diffusion will occur
What types of acids are the following and which functions best as a Titratable acid. Why?
- H2SO4
- H2PO4-
- NH4+
- H2SO4 –> Sulfuric Acid is a strong acid
- H2PO4–> pH lies mostly within the urinary pH range (4-7)
- NH4+ –> ammonium is a weak acid
What is the pK of NH3/NH4+?
What is NH3 produced from?
- 3
- metabolism of amino acids
Of the two, which is freely permeable and which is impermeable and why?
- NH3
- NH4+
- NH3
- freely permeably - NH4+
- lipid impermeable because it is CHARGED
- formation of NH4+ keeps the concentration of NH3 LOW!
- When is the formation of NH4+ enhanced?
- What compound production is increased?
- What does this permit the secretion of into TUBULAR FLUID?
- Chronic Acidosis
- NH3 production increases
- Permits the secretion of additional H+ load into tubular fluid at ph levels equivalent to normal
Describe the steps of chronic acidosis.
- Increased production rate of renal NH3
2. Increased secretion of additional H+ into tubular fluid (adaptation_
For each molecule of NH4+ excreted into urine, what is reabsorbed to ECF?
HCO3-!
-“new”
Where is NH4+ first secreted?
Where is it reabsorbed?
Where is it secreted again?
- Secreted in the Proximal tubule, and HCO3- is reabsorbed into the blood
- Reabsorbed in the THICK ASCENDING LIMB of the Loop of Henle and accumulates in the medullary interstitial
- Secreted by COLLECTING duct via nonionic diffusion and diffusion trapping and NH4+ antiprotons
