Physiology Objectives 27

Physiology Objectives 27

Physiology Objectives 27

1.Proximal tubule movement:

Early tubule:

  1. Luminal membrane:
  2. Na+: enters via Na+/solute cotransport and Na+/H+ countertransport
  3. Cl-:
  4. K+: passively diffuses out of cell
  5. H+: leaves cell via Na+/H+ countertransport
  6. Peritubular membrane:
  7. Na+: actively pumped out of the cell via Na+/K+ ATPase
  8. Cl-: N/A
  9. K+: actively pumped into the cell via Na+/K+ ATPase, passively diffuses out of cell
  10. H+: N/A

Late tubule:

  1. Luminal membrane:
  2. Na+: enters via Na+/H+ countertransport
  3. Cl-: enters via Cl-/formate countertransport
  4. K+: passively leaves cell
  5. H+: leaves via Na+/H+ countertransport and H+ ATPase, enters by forming formic acid and diffusing back into the cell
  6. Peritubular membrane:
  7. Na+: actively pumped out of the cell via Na+/K+ ATPase
  8. Cl-: passively diffuses out of cell, leaves via K+/Cl- cotransport
  9. K+: passively diffuses out of cell, leaves via K+/Cl- cotransport
  10. H+: N/A

Thick ascending limb cells:

  1. Luminal membrane:
  2. Na+: enters via Na+/K+ countertransporter and Na+/2Cl-/K+ cotransporter
  3. Cl-: enters via Na+/2Cl-/K+ cotransporter
  4. K+: enters via Na+/2Cl-/K+ cotransporter and leaves passively
  5. H+: leaves cell via Na+/H+ countertransporter
  6. Peritubular membrane:
  7. Na+: enters actively via Na+/K+ ATPase
  8. Cl-: leaves passively and via K+/Cl- cotransporter
  9. K+: actively pumped in via Na+/K+ ATPase; leaves passively and via K+/Cl- cotransporter
  10. H+: N/A

2.Water/solute movement coupling in proximal tubule:

  1. Early tubule: osmotic gradient caused by solute flow directs water reabsorption
  2. Late tubule: no osmotic gradient; however, high peritubular HCO3- has difficulty reentering the cell, whereas Cl- can cross from lumen into peritubular space. Thus, Cl- flow directs water reabsorption

3.Distal nephron movement:

Early distal tubule cells:

  1. Luminal membrane:
  2. Na+: enters via Na+/Cl- cotransport
  3. Cl-: enters via Na+/Cl- cotransport
  4. K+: N/A
  5. H+: N/A
  6. Peritubular membrane:
  7. Na+: actively pumped out via Na+/K+ ATPase
  8. Cl-: leaves passively
  9. K+: actively pumped in via Na+/K+ ATPase; leaves passively
  10. H+: N/A

Late distal tubule principal cells:

  1. Luminal membrane:
  2. Na+: passively diffuses into cell
  3. Cl-: leaves through K+/Cl- cotransport and is somehow reabsorbed by peritubular fluid (unknown mechanism)
  4. K+: passively diffuses out of cell and leaves through K+/Cl- cotransport
  5. H+: N/A
  6. Peritubular membrane:
  7. Na+: actively pumped out via Na+/K+ ATPase
  8. Cl-: secreted into peritubular fluid (unknown mechanism)
  9. K+: passively diffuses out of cell; actively pumped in via Na+/K+ ATPase
  10. H+: N/A

Late distal tubule α-intercalated cells:

  1. Luminal membrane:
  2. Na+: N/A
  3. Cl-: N/A
  4. K+: actively enters cell via K+/H+ ATPase
  5. H+: actively leaves cell via H+ ATPase and K+/H+ ATPase
  6. Peritubular membrane:
  7. Na+: N/A
  8. Cl-: enters cell via HCO3-/Cl- countertransporter and leaves via passive diffusion
  9. K+: passively diffuses out of cell
  10. H+: N/A

4.Ion/water transport differences:

  1. Proximal nephron: major volumetric reabsorption area for water as well as ions
  2. Distal nephron: minor volumetric reabsorption area for water; ion reabsorption directed by hormones and medullary gradient

5.K+ excretion:

  1. Tubule regulation: increased flow flushes K+ from the tubule and increases K+ secretion into the tubule and therefore increases K+ excretion
  2. Electrical potential regulation: negatively charged lumen increases K+ secretion
  3. Basolateral regulation: Na+/K+ ATPase activity increases cellular [K+] and therefore increases K+ excretion
  4. Luminal regulation: increased K+ channels increase K+ excretion
  5. Dietary K+ intake: high intake leads to increased Na+/K+ ATPase activity and increased basolateral reuptake of K+ (increased K+ excretion)
  6. Dietary Na+ intake: increased Na+ uptake through the luminal membrane leading to increased Na+/K+ ATPase activity; increases volume flow; increased flow into cells decreases electrical potential in lumen (increased K+ excretion)
  7. Alkalosis: increases Na+/K+ ATPase activity; increases volume flow through the tubule; increases luminal K+ channels and the time they remain open (increased K+ excretion)
  8. Acidosis:
  9. Respiratory acidosis: inhibits Na+/K+ ATPase activity (decreased K+ excretion)
  10. Acute metabolic acidosis: inhibits Na+/K+ ATPase activity (decreased K+ excretion)
  11. Chronic metabolic acidosis: increases volume flow through the tubule; stimulates aldosterone (increased K+ excretion)
  12. Aldosterone: increases Na+ reabsorption and increased Na+/K+ ATPase activity; increases luminal K+ channels and K+/Cl- cotransporters (increased K+ excretion)
  13. Diuretics: increased Na+ uptake through the luminal membrane leading to increased Na+/K+ ATPase activity; inhibits Na+/K+/2Cl- cotransporter to increase volume flow and block K+ reabsorption; increased Na+ uptake decreases electrical potential in lumen (increased K+ excretion)
  14. Note: K+-sparing diuretics block luminal Na+ channels (decreased K+ excretion)
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