Renal Handling of Chloride and Calcium - Hausmann

Question 1

What is the concentration of protons in the blood?

How many protons are free in the body?

What is daily acid production?

Answer 1

[H+] = 40nmol (compare to 140mmol, difference of 10^-6)

Total amount of protons free in plasma/body fluid is 0.002mEq (not concentration, absolute).
Daily acid production /day = 22,000meq/day from carbohydrates and another 50-100mEq/day from NA and AA

Question 2

What is the pathophysiology of renal tubular acidosis type II?

Answer 2

Decreased reabsorption of bicarbonate into the proximal tubule. This can be caused by mutated Na+/H+ antiporter, Na+/HCO3- cotransporter or cytosolic carbonic anhydrase.

If there is too much bicarbonate excreted there will be too much H+ in the body.

Question 3

What is the F-/Cl- antiporter

Answer 3

H+/Na+ antiporter balanced by F- (formate ion pumped out)/Cl- (in) antiporter
Formate ion binds with hydrogen to form formic acid which can diffuse into cell as formic acid and then diffuses into formate and hydrogen ions which are then reused in their respective transporters. Results in NaCl on the inside. Reabsorbs NaCl instead of NaHCO3.
Compensates for the loss of bicarbonate in order to absorb sodium. Parallel to high Na conc is a high Cl concentration = hyperchloremic acidosis.
If not enough HCO3- reabsorbed you get hypochloremic acidosis

Question 4

Pathophysiology of Renal Tubular Acidosis Type I

Answer 4

AKA Distal Renal Tubular Acidosis

Inability of the distal tubule to acidify the urine d/t abnormalities in luminal H-ATPase, basolateral Cl-/HCO3- exchanger.

Associated with autoimmune diseases and hypokalemia (due to increased distal K+ secretion in lieu of H+ secretion in exchange for Na+)

Question 5

What is the pathogenesis of Renal Tubular acidosis type IV?

Answer 5

Hyporeninemic hypoaldosteronism (hypo/hypo)

Complication of diabetes (usually)

Leads to hyperkalemia

Question 6

Action of ammonia/ammonium in the tubule

Answer 6

In interstitium of corticocollecting duct. Able to take a proton to produce ammonium (NH4+). It is able to pass freely through membranes. Sits and waits for protons. Where does it come from?
Ammoniakinesis
Glutamine
Metabolized in the prox epith tub cell to glutamate + NH4+. Further metabolized into NH4 + alphaketoglutarate. Alphaketoglutarate becomes 2 bicarbonate molecules that are transported out of the basolateral side. The NH4+ molecules are transported across the luminal side by an antiporter than brings Na+ into the cell.
NH4 cation sits instead of potassium on cotransporter (swing) in ThAL (1Na, 1K, 2Cl). Sits on K position and enters epithelial cell at ThAL. NH4+ has thus reached the intercellular space of the thick ascending limb. There it dissociates into NH3 + H+. H+ is extruded by the Na/H antiporter. NH3 diffuses across the membranes and interstitium into the cortical collecting duct. Meets up with the H+ again and diffuses out into the lumen and is excreted.
If a patient has hypokalemia he activates the HKATPase, excrudes more H+ into tubular fluid and needs more buffer in tubular fluid. Hypokalemia thus activates ammoniagenesis.
In collecting duct when there is hypokalemia you want to extrude H+ in order to keep K+ and you need a buffer - ammonia.