Acid/Base Homeostasis

Question 1

What is the normal pH of blood?

Answer 1

7.4

Question 2

Isohydric Principle

Answer 2

• The ratio of dissociated/un-dissociated buffer pairs is dep on pH and pKa of buffer pair
• AND all body buffers are in equilibrium
• SO change in ratio of any 1 buffer pair is reflected in all pairs

Buffers in body: Bicarb/carbonic acid, albumin, hemoglobin, phos compounds, bone

Question 3

How is bicarb/carbonic acid an “open” buffer system? (what 2 components contribute to this ability?)

Answer 3

-Concentrations can change to maintain stable pH

1-Lung Homeostasis = CO2 - transported to lungs by blood (diffuse into RBC –> carbonic acid and H+ taken up by hemoglobin –> back to CO2 in pulmonary caps)
“can blow off CO2 in response to inc acid in blood”

2- Renal Homeostasis = alter amount of bicarb

Question 4

How are acids produced in body? (2) How are bases produced in body? (2)

Answer 4

• Acid Production
  1- Volatile - CO2 (oxidative metabolism of carbs, fats, protein); THIS IS MOST ACID PROD
  2- Fixed/Non-volatile - H2SO4, H3PO4, organic acids; all excreted by kidneys; THIS IS SMALL AMOUNT OF ACID PROD
• Base Production
  1- Make bicarb from aspartate and glutamate metabolism
  2- Organic anions consume H+ –> bicarb

Question 5

In general, how is acid/base homeostasis maintained in kidney?

Answer 5

• Bicarb freely filtered in glomerulus so must be reclaimed (90% reclamation in proximal tubule)
• Distal tubules secrete non-volatile acids
• Ammonium is generated in proximal tubule –> shunted into medullary interstitium –> trapped in CD –> excretion

Question 6

How is bicarb reclaimed in proximal tubule?

Answer 6

• Carbonic anhydrase converts carbonic acid to CO2 + H2O which diffuse across apical membrane where another carbonic anhydrase converts it back to carbonic acid –> HCO3- and H+
• H+ then recycled back across apical membrane via Na-H exchanger while HCO3- reabsorbed by Na-3HCO3- transporter (this transporter is driven by electrochemical gradient created by Na-K pump)
• There is a tubular reabsorption threshold (26-28 mmol/L); once above this point the rest of the bicarb is excreted

Question 7

What 5 things stimulate inc bicarb reclamation? What 4 things inhibit it?

Answer 7

Stimulated By:
1- Volume depletion (anything that inc Na reabsorption will inc bicarb reabsorption)
2- Chloride depletion (less Cl to co-transport w/ Na then use bicarb instead)
3- Inc intracellular H+ (inc gradient for H+ secretion which is coupled w/ bicarb reabsorption)
4- Dec intracellular K+ (hypokalemia –> K+ leaves cell –> H+ replaces K+ in cell –> higher gradient for H+ secretion and thus bicarb reabsorption)
5- Inc PCO2 (also makes intracellular pH lower –> favors H+ secretion and bicarb reabsorption)

Inhibited By:
1- Volume expansion         
2- Alkalemia
3- Inc intracellular K+
4- Dec PCO2

Question 8

How are non-volatile acids secreted in distal tubule?

Answer 8

• By type A intercalated cells
• Mechanism: carbonic anhydrase inside intercalated cells –> HCO3- and H+; H+ recycled across apical via H+ ATPase or H+, K+ ATPase while bicarb is transported across basolateral via bicarb/Cl- exchanger
• Principal cells maintain an electrochemical gradient that powers this process
• Must have buffers in urine to accommodate for this acid load in urine from H+ being pumped out
  - Titratable acids (H2SO4, H3PO4, organic acids)
  - Leftover bicarb (the 10% not reabsorbed in prox)
  - Ammonium

Question 9

What 4 things stimulate non-volatile acid secretion? What 4 things inhibit it?

Answer 9

Stimulated By: (anything that inc Na delivery to distal tubule –> inc Na reabsorption there –> more neg gradient from P cells –> more H+ secretion)

1- Inc Na delivery
2- Inc Na reabsorption thru ENaC
3- Inc in poorly reabsorbed non-Cl- anion
4- Aldosterone (mineralocoticoid) excess (indirectly by enhancing Na reabsorption here and direct stimulation of H+ secretion)

Inhibited By:
1- Dec Na delivery
2 - Inhibition of ENaC
3- Mineralocorticoid deficiency
4 - Urinary buffer deficiency

Question 10

3 Steps of Ammonium Generation and Secretion

Answer 10

1-Made in proximal tubule: glutamine is deaminated –> 2NH4+ which crosses apical and alpha-ketoglutarate which is broken down into CO2 (CO2 + H2O –> bicarb) and bicarb exits basolateral membrane

2- This NH4+ is now in Loop of Henle and gets shunted into the medullary interstitium: NH4+ is transferred in place of K+ on the Na-K-2Cl transporter –> medullary interstitium

3-Then trapped in CD: CD is impermeable to NH4+ so it diffuses across CD apical membrane as NH3 and H+ then reforms NH4+ in CD (b/c such low pH in CD that it stays in this form) –> trapped b/c impermeable to this NH4+ form

Question 11

What stimulates Ammonium Generation?

Answer 11

-low pH in cell (want to get rid of H+ in urine)

Question 12

What is the role of type B intercalated cells? How?

Answer 12

• Provide a mechanism to combat aklalemia (ex - high alkaline diet)
• Via pendrin - transported on apical membrane of Type B intercalated cells that transports Cl- in/ bicarb out