Exam 2: Renal acid / base regulation and disorders I

Question 1

šDefine acid, base, strong acid, strong base

Answer 1

• Acid
  
  • molecules containing hydrogen atoms that can release H⁺ in solutions
• Base
  
  • ion or molecule that can accept an H⁺
• Strong acid
  
  • rapidly dissociates and releases large amounts of H⁺ in solution
• Strong base
  
  • reacts rapidly and strongly with H⁺ to form water

Question 2

šDefine the normal plasma H⁺ levels

Answer 2

š

• Normal H⁺ concentration is 40nM

Question 3

Describe factors that alter H⁺ plasma levels

Answer 3

š

• Factors that alter H+ plasma levels:
  
  • Metabolism of ingested food
  • Secretions of the GI tract
  • De novo generation of acids and bases from metabolism of stored fat and glycogen
  • Changes in the production of CO2

Question 4

šDescribe 3 systems that regulate H⁺ concentration

Answer 4

• Buffer system; prevent changes in H⁺ concentration
  
  • Acts within seconds
• Respiratory center; regulates removal of CO₂ and therefore H₂CO₃
  
  • Acts within minutes
• Kidneys; excrete either acid or alkaline urine and readjust the extracellular H⁺ fluid concentration
  
  • Acts within hours to days

Question 5

Know the buffer systems and where they are located

Answer 5

• Bicarbonate buffer system
  
  • šmajor extracellular HCO₃^-
• Phosphate buffer system
  
  • šimportant urinary buffer and intracellular buffer
• Proteins and organic phosphates
  
  • šintracellular buffers

Question 6

Respiratory Regulation of Acid-Base

Answer 6

• Control of extracellular CO₂ concentration
• Increase ventilation
  
  • decreases CO₂ concentration
  • reduces H⁺ concentration
• Decreased ventilation
  
  • increases CO₂
  • increases H⁺ concentration

Question 7

Renal transport of acids and bases:

3 main mechanisms of regulation

Answer 7

1. Regulate secretion of H+
2. Regulate reabsorption of filtered HCO₃^-
3. Regulate production of new HCO₃^-

• H⁺ secretion and HCO₃^- reabsorption
  
  • Most occur** in the **proximal tubule
  • occur in all parts except** the descending and ascending **thin limbs of the loop of Henle

Question 8

šExplain how the kidneys secretes H^{+<span> </span>}:

Sites?

Mechanisms?

Answer 8

1) Proximal tubule, Thick ascending loop, Early distal tubule

• Mechanism: Sodium hydrogen counter-transport

2) Late distal tubule, Collecting tubules

• Mechanism: Hydrogen ATPase

Question 9

šExplain how the kidneys secretes H^{+<span> </span>}:

In the Proximal tubule, Thick ascending loop, Early distal tubule

Answer 9

Proximal tubule, Thick ascending loop, Early distal tubule

• Mechanism: Sodium hydrogen counter-transport
  
  • Begins with CO₂
    
    • CO₂ either diffuses into the tubular cells or is formed by cellular metabolism
  • CO₂ + H₂O (carbonic anhydrase) form H₂CO₃ that dissociates into HCO₃^- and H⁺
  • H+ secreted by the Na-hydrogen exchanger
    
    • Allows bicarb in lumen to come back into cells
    • Does not require energy and takes no ATP
  • Sodium gradient into the cell drives H+ against its gradient
    
    • The sodium gradient is established by the Na-K pump in the basolateral membrane
  • Does NOT establish a high H+ concentration in the tubular fluid (not very acidic)
    
    • Only becomes acidic in the collecting tubules and collecting duct

Question 10

šExplain how the kidneys secretes H^{+<span> </span>}:

Late distal tubule, Collecting tubules

Answer 10

Late distal tubule, Collecting tubules

• Mechanism: Hydrogen ATPase
  
  • For each H⁺ secreted
    
    • a HCO₃^- reabsorbed via Cl^- / HCO₃^- exchange
  • H⁺ secretion is achieved via primary active transport in intercalated cells
• ššH⁺ is titrated with HCO₃^- which leads to reabsorption of one HCO₃^- for each H⁺ secreted
  
  • šWhen H⁺ is secreted in excess of the HCO₃^-
    
    • šKidneys will reabsorb all filtered HCO₃^-
    • šH⁺ will combine with buffers in the tubular fluid
      
      • Phosphate buffer, Ammonia buffer, Urate and citate (weak buffer system)
    • The excess H⁺ that combines with buffers other than HCO₃^- will generate new HCO₃^-
• Secretion of H⁺ results in a huge effect on H⁺ concentration and pH
  
  • Tubular fluid can decrease to a pH of approximately 4.5
  • The secretion of H⁺ in the late distal tubules and collecting tubules is important in forming acidic urine

Question 11

šExplain how the kidneys reabsorbs HCO₃^{-<span> </span>}:

Sites?

Mechanisms?

Answer 11

Proximal tubule, Thick ascending loop, Early distal tubule

• Mechanism: Na^- / HCO₃^- co-transport
  
  • H⁺ combines with HCO₃^- in the lumen to form carbonic acid
  • Carbonic acid dissociates to form CO₂ and H₂O
  • CO₂ travels into the cell to combine with H₂O and eventually HCO₃^-
  • Moves downhill across the basolateral membrane into the interstitial fluid and capillary blood
  • For every H+ secreted into the tubular lumen, a HCO3- enters the blood

Question 12

Why such a convoluted way to reabsorb HCO3-?

Answer 12

Proximal tubule, Thick ascending loop, Early distal tubule

• Mechanism: Na^- / HCO₃^- co-transport
• Why such a convoluted way to reabsorb HCO3-?
  
  • Bicarbonate ions cannot permeate the renal tubular cells
  • Normal conditions:
    
    • 4400mEq/L H+ secreted
    • 4320mEq/l HCO3- filtered
    • Slight excess of H+ combines with urinary buffers to be excreted in the urine

Question 13

Metabolic Alkalosis

vs.

Metabolic Acidosis

Answer 13

• Metabolic Alkalosis
  
  • Excess HCO3- relative to H+
  • Excess of HCO3- is not reabsorbed
  • HCO3- excreted in the urine to correct metabolic alkalosis
• Metabolic Acidosis
  
  • Excess of H+ relative to HCO3-
  • Complete reabsorption of HCO3-
  • Excess H+ passes via urine

Question 14

šDescribe the phosphate buffer system.

Answer 14

• Composed of HPO₄^- and H₂PO₄^-
• As long as there is HCO₃^- in the tubular fluid, H⁺ will combine with HCO₃^-
• When all the HCO₃^- is reabsorbed and no longer available, excess H⁺ will combine with phosphate buffer to be excreted as a sodium salt
  
  • H⁺ combines with NaHPO₄^- to form NaH₂PO₄^-
• The combination of H+ with phosphate buffer results in net gain of HCO₃^- to the blood
  
  • NEW BICARB! (NOT REABSORBED BICARB!)

Question 15

šDescribe the ammonia buffer system.

Answer 15

• Two parts to the ammonia buffer system which involves NH₃ and NH₄⁺ (ion)
  
  • 1. Ammonium ion synthesized from glutamine makes 2 new HCO₃^-
       * Glutamine derived from metabolism of amino acids in the liver
       * Proximal tubules, thick ascending limb of the loop of Henle, and distal tubule
  • 2. NH₃ present in the lumen combines with secreted H⁺ to form NH₄⁺ and makes 1 new HCO₃^-
       * Collecting tubules
• Ammonia buffer system accounts for:
  
  • 50% of acid excretion
  • 50% of new HCO₃^- generation
• With chronic acidosis, the dominant mechanism by which acid is eliminated is excretion of NH₄⁺
• 2 new bicarbs from break down of glutamine plus another 1 new bicarb from the ammonia buffer in lumen
  
  • Vs. phosphate buffer which only creats 1 new bicarb

Question 16

Ammonia buffer system: Differentiate the mechanisms between the

Proximal tubular cells

from the

Collecting tubular cells

Answer 16

Ammonia buffer system

• mechanisms of proximal tubular cells
  
  • Glutamine metabolized in the cell yielding 2NH₄⁺ and 2HCO₃^-
  • NH₄⁺ secreted into the tubular lumen by the sodium-NH₄⁺ exchanger
  • HCO₃^- transported across the basolateral membrane along with reabsorbed sodium
  • Each molecule of glutamine metabolized, 2 NH₄⁺ secreted into urine and 2 HCO₃^- reabsorbed into the blood
• mechanisms of collecting tubular cells
  
  • Ammonia diffuses into the tubular lumen
  • Ammonia reacts with H⁺to form NH₄⁺ which is then excreted
  • For each NH₄⁺ excreted, 1 new HCO₃^- is formed and returned to the blood
• Nets 3 new bicarbs!