Kidneys & Acid-Base Balance

Question 1

Production of metabolic nonvolatile acid

Answer 1

• e.g. H₂SO₄ and H₃PO₄
• 70 kg person ==> 60 mmol of H⁺ added to ECF/day

Question 2

ECF buffers: bicarbonate buffer system

Answer 2

• bicarbonate = HCO₃^-
• H⁺ + HCO₃^- <=> H₂CO₃ <=> CO₂ + H₂O
  
  • converts to CO₂ = volatile (gaseous) form than can be eliminated

Question 3

Challenges of bicarbonate buffer system

Answer 3

• must eliminate acid anions that are the source of H⁺ ions (HSO₄^-, H₂PO₄^-)
  
  • filtered and excreted in urine
• elimination of H⁺ ==> sacrifice of HCO₃^- ==> bicarbonate must be replaced
  
  • ROLE OF KIDNEY = maintenance of ECF bicarbonate via reabsorption and synthesis

Question 4

Kidney reabsorption of bicarbonate

Answer 4

• bicarb = small mlq = easily filtered = must be reabsorbed
• primarily occurs @ proximal tubule: 85% of filtered load
• Na/H exchanger: secretes H⁺ into lumen
• H⁺combines w/bicarb ==> carbonic acid (H₂CO₃) ==> carbonic anhydrase converts to CO₂ + H₂O
• CO₂ diffuses into cell + H₂O ==> H₂CO₃==> H⁺ + HCO₃^-
• bicarb ion (HCO₃^-) transported across basolateral membrane via Na/HCO₃^- co-transporter
  
  • movement of Na helps acheive electroneutrality

Question 5

Mechanism of bicarbonate synthesis by kidney

Answer 5

• occurs @ intercalated cells @ distal segments
• CO₂ enters cells from serosal side
• CO₂ + H₂O => H₂CO₂ => H⁺ + HCO₃^-
• H⁺ and bicarb are physically seperated by transporters
  
  • H ATPase: H⁺ into lumen
  • HCO₃^-/Cl^- exchanger: HCO₃^- into serosal ECF/blood

Question 6

Mechanism of urinary buffering

Answer 6

• must buffer H⁺ ions secreted as result of HCO₃^- synthesis
• titratable acid: complexing of hydrogen ion to a filter acid anion (e.g. HPO₄^2-)
  
  • incidental buffering capacity
• ammonia trapping: tubular cells break down glutamine ==> ammonia (NH₃) diffuses into tubule + H⁺ ==> NH₄⁺ = impermeable and “trapped” ==> excreted

Question 7

Regulation of ECF/serum bicarbonate

Answer 7

• any cell w/apical H⁺ secretion and basolateral HCO₃^- extrusion mechanisms can reabsorb or sythesize bicarb
• no bicarbonate sythesis takes places until bicarbonate reabsorption is complete
  
  • acts as a buffer that competitively inhibits synthesis
• metabolic acidosis ==> excess bicarb synthesis
• metabolic alkalosis ==> bicarb secretion + hydrogen ion retention

Question 8

Important factors in rate of bicarb reabsorp/synthesis

Answer 8

• apical secretion + basolateral extrusion of bicarb = rate limiting step of bicarb homeostasis
• rates of apical hydrogen ion secretion and basolateral bicarbonate extrusion depend on ECF pH and CO₂ levels
  
  • membrane transporters regulated by these factors

Question 9

Renal response to metabolic acidosis

Answer 9

• metabolic acidosis => increased H⁺ produced => buffered by bicarb => increased CO₂ production => eliminated by lungs
• buffering => decreased bicarb/decreased filtered load of bicarb => increased H⁺ion secretion capacity = synthesis of bicarb

Question 10

Regulatory range of bicarb

Answer 10

• @ normal: all filtered bicarb (3800 mmol) must be reabsorped + 60 mmol/day synthesized to replaced bicarb lost in respiration

Question 11

Impacts of potassium imbalance on acid/base status

Answer 11

• primary hypokalemia ==> alkalosis
  
  • lowering ECF K⁺ = shift H⁺ into all cells including tubular cells
  • increased H⁺ secretion + excretion
• hyperkalemia tends to induce acidosis
  
  • reduce rate of H⁺ secretion/excretion
  • H⁺ retained in ECF => acidosis