L31: Adaptation Of Renal Mechanism To Whole Body Acid Base Balance

Question 1

Essential pH range

Answer 1

7.38-7.42

Question 2

Chemical buffering agents

Answer 2

1. Bind H+ when pH drops
2. Release H+ when pH rises

• Inactivate excess acids and bases MOMENTARILY

Question 3

Functions of lungs and kidneys

Answer 3

Lungs:
- only remove volatile acid
—> bind H+ with HCO3-
—> H2O + CO2 (excreted)

Kidneys:

• Reabsorb, excrete and regenerate HCO3-
• Excrete H+ from non-volatile acid directly

Question 4

***Reabsorption of HCO3 and excretion of H in proximal tubules

Answer 4

• 80% HCO3 reabsorbed in proximal tubule, remaining reabsorbed in distal tubule
• Reabsorption of HCO3 always accompanied by excretion of H

1. Basolateral:
   —> Na/HCO3 cotransporter (Na out, HCO3 out)
   —> Na/K-ATPase (Na out, K in)
2. Apical:
   —> Na/H exchanger (NHE) (Na in by concentration gradient created by Na/K-ATPase i.e. secondary active transport, H/NH4 out)
   —> H-ATPase (out)

• membrane bound CA-IV: H2CO3 —> H2O + CO2
• intracellular CA-II: H2O + CO2 —> H+ + HCO3- (H+ for excretion, HCO3- for reabsorption)

Question 5

***Generation of new HCO3 in proximal tubule

Answer 5

Ammonium synthesis / Ammoniagenesis:
Glutamine —> 2 HCO3 + 2 NH4

• HCO3 reabsorbed into bloodstream via Na/HCO3 cotransporter
• NH4 excreted into filtrate via NHE (Na in/NH4 out)

Glutamine from:

• reabsorption from filtrate (100% reabsorbed) via Apical Amino Acid Tranporter
• uptake from circulation via Basolateral Glutamine Transporter (SN1)

Question 6

***Acid base balance in collecting duct

Answer 6

Intercalated cell (principal cells only responsible for ADH reabsorption of H2O)

Type A (IC-A): Secrete H and NH3, react to acidosis

• Apical: H-ATPase + H/K-ATPase (H out, K in)
• Basolateral: anion exchange (AE1) (HCO3 out, Cl in)

Type B (IC-B): Secrete HCO3, react to alkalosis

• Apical: Cl/HCO3 exchanger (Pendrin) (Cl in, HCO3 out)
• Basolateral: H-ATPase (H out)
• (Pendrin driven by H-ATPase)
• Hypochloremia —> ↓ Cl in filtrate —> ↓ excretion of HCO3 —> alkalosis

Question 7

Comparison between H+ secretion in proximal tubule and collecting duct

Answer 7

H+ must be accompanied by NH3 secretion —> NH4+ in filtrate
1. Maintain low H in filtrate for further H secretion
2. Neutralise acidic urine
—> impairment in NH4 secretion —> impairment in H secretion —> acidosis

Proximal tubule:
- NHE (NH4 out, Na in) (NH4 from glutamine synthesis of HCO3)

Collecting duct:

• Rhesus glycoprotein Rhcg (NH3 out)
• diffuse across apical membrane (NH4 from Na/K-ATPase, substitute K with NH4)

Question 8

Dysregulation of acid base balance

Answer 8

Respiratory acidosis —> compensated by Renal ↑ of HCO3
Metabolic acidosis —> compensated by Respiratory Hyperventilation

Respiratory alkalosis —> compensated by Renal ↓ of HCO3
Metabolic alkalosis —> compensated by Respiratory Hypoventilation

Question 9

Causes of metabolic acidosis

Answer 9

Reduction in HCO3 concentration in blood

1. Diabetic Ketoacidosis
2. Lactic acidosis
3. Diarrhoea
4. Renal failure
5. Hyperkalaemia
   (6. Hyperchloraemia)

Symptoms:

• headache
• respiratory hyperventilation
• ↑ HR
• fruity breath (diabetic ketoacidosis)
• osteoporosis

Question 10

Causes of metabolic alkalosis

Answer 10

2 stages: generation (H/K-ATPase) + maintanance (Pendrin) of metabolic alkalosis

Increased in HCO3 concentration in blood

1. Renal failure
2. Vomiting (loss of H)
3. Hypokalaemia / Hyperaldosteronism (Too much K in filtrate —> H/K-ATPase pump H out trying to reabsorb K)
4. Hypochloremia (Pendrin cannot pump HCO3 out)

Symptoms:

• headache
• respiratory hypoventilation
• arrhythmia
• muscle weakness