PHYS - Ion Transport

Question 1

MOVEMENT IN A TUBULE

Answer 1

• Filtration – diffusion of water/molecules from glomerulus into bowman’s space
• Reabsorption – transport/diffusion from PCT into peritubular capillaries
• Secretion – transport/diffusion from peritubular capillaries into PCT
• Excretion – removal from body with urine
• Pathways for transport
  
  • Transcellular – through BM and apical membrane
  • Paracellular – between cells, through TJs
• Transport proteins:
  
  • Active – require energy
    
    • Primary (ex: H+ ATPase)
    • Secondary
      
      • Symport (Na+/Cl-)
      • Antiport (Na+/H+)
  • Passive – utilizes gradients
    
    • Simple diffusion (Ca2+)
    • Facilitated diffusion (urea)

Question 2

RENAL HANDLING OF SODIUM

Answer 2

• Na+ gradient from lumen into capillaries is used to transport other molecules
  
  • Except in the collecting duct! No Na+ permeability
  • PCT → glucose/AA’s OUT; H+ IN
  • LoH → K+/Cl- IN
  • DCT → Cl- IN
• Movement of Na+ through tubule
  
  • 100% filtration of Na+ into urinary space/bowman’s space
  • 67% reabsorbed in PCT → 33%
  • Some secretion in descending loop → 8%
  • 25% reabsorbed in ascending loop → 3%
  • Reabsorption influenced by aldosterone in collecting duct → 0.5%
  • Fractional excretion = 0.5%
• Even though Na+ is reabsorbed, concentration of Na+ in tubule remains relatively constant because H2O is reabsorbed with it

Question 3

RENAL HANDLING OF CHLORIDE

Answer 3

• As Na+ is reabsorbed, H2O decreases and luminal [Cl-] increases, creating a concentration gradient for passive transport of Cl- reabsorption
• Na+ reabsorption also makes the membrane potential more negative, creating an electrochemical gradient for Cl- reabsorption

Question 4

POTASSIUM HOMEOSTASIS

Answer 4

• Potassium homeostasis: equal amount of K+ is excreted (through urine and feces) as dietary intake
• H+/K+ movements are maintained by extracellular concentrations
  
  • Metabolic acidosis = decreased pH₀ (increased [H+]₀) → H+ IN/K+ OUT
  • Hypokalemia = decreased [K+]₀ → K+ OUT/H+ IN
  • Metabolic alkalosis = increased pH₀ (decreased [H+]₀) → H+ OUT/K+ IN
  • Hyperkalemia = increased [K]₀ → K+ IN/H+ OUT
• Extrarenal potassium homeostasis
  
  • K+ IN
    
    • Insulin (stimulates Na-H antiporter; increased pH)
    • β-agonists (stimulate Na+/K+ ATP pump)
    • Aldosterone (stimulate Na+/K+ ATP pump)
    • Alkalosis
  • K+ OUT
    
    • Hypoosmolarity (hypokalemia)
    • Exercise
    • Cell lysis

Question 5

RENAL HANDLING OF POTASSIUM

Answer 5

• Renal handling
  
  • 100% filtration into bowman’s space
  • Reabsorption in PCT → 50% left in tubule
    
    • Na+/K+ pump
    • Paracellular diffusion
  • Some secretion in descending loop
  • Reabsorption in ascending loop → 8% left in tubule
  • Reabsorption/Secretion in DCT → 8-100% in tubule
  • Reabsorption in collecting duct (reversed by aldosterone)
  • Fractional excretion = 10-20%
• Physiological factors affecting K+ secretion
  
  • Intracellular [K+]
  • Aldosterone
    
    • Aldosterone heavily influenced by [K+]
    • Hyperkalemia induces aldosterone secretion
      
      • Aldosterone release also stimulated by angiotensin II
    • Increases K+ excretion
• K+ levels cell relatively normal despite large fluctuations in dietary intake of K+ because of aldosterone
  
  • Therefore, K+ is important in BP regulation

Question 6

EFFECTS OF DIURETICS

Answer 6

• Potassium losing diuretics
  
  • Furosemide and Thiazide
  • Increase H2O/urine by preventing Na+ reabsorption
  • Increases flow through collecting duct → [Na+] inside duct depolarizes the membrane causing K+ secretion
  • Result: increased H2O, Na+, and K+ secretion
• Potassium sparing diuretics
  
  • Amiloride
  • Blocks Na+ reabsorption and conductance, membrane stays hyperpolarized, closer to E_K → reduced K+ influx
  • Result: increased H2O/Na+ excretion, K+ spared

Question 7

DISORDERS OF DISTAL NEPHRON TRANSPORTERS

Answer 7

• Bartter’s Syndrome (Type I)
  
  • Mutation in Na/K/Cl transporter in ascending limb
    
    • Loss of Na+ reabsorption
  • Acts like a K+ losing diuretic (increased K+ IN tubule)
  • Results in:
    
    • Low potassium
    • Alkalosis
    • Polydipsia (loss of Na+)
    • Polyurea (loss of H2O with Na+)
    • Normal to low BP
• Gitelman’s Syndrome
  
  • Mutation in Na/Cl transporter in DCT
    
    • Loss of Na+ reabsorption
  • Acts like a K+ losing diuretic
  • Results in:
    
    • Low potassium (increased Na+ conductance, K+ IN tubule)
    • Alkalosis
    • Polydipsia
    • Polyuria
    • Normal to low BP
• Liddle’s Syndrome
  
  • Pseudohyperaldosteronemia
  • Increase in number and time open of Na+ channels in principle cells
  • Increased Na+ reabsorption= depolarized membranes
  • Results in:
    
    • Low potassium
    • Alkalosis
    • Na+ reabsorption = no polyuria/polydipsia
    • Increased H2O retained → HT