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SF 3 - Test 3 > 1 - Tubular Secretion > Flashcards

1 - Tubular Secretion Flashcards

1
Q

Objectives: Understand the principles of renal tubular secretion

A
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2
Q

Objectives: Explain major examples of substances secreted

PAH

Clinical measurement?

What does secretion exhibit?

By what equation can it be used to measure the above?

A
  • Organic Anion
  • Used to measre effective renal plasma flow (ERPF)
  • Secretion exhibits competition, TM limitation
  • Undergoes no significant tubular reabsorption–e.g. Amount entering = amount excreted
  • Equation:
    • Excreted Load = Filtered Load + Secreted Load
    • (UPAH x V) = (PPAH x CIN) + TPAH
    • mg/min = mg/min + mg/min (units)
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3
Q

Objective: When given the Effective Renal Plasma Flow (ERPF), how can the true RPF be obtained?

A
  • By dividing ERPF by Extraction Ration (E) for PAH
    • E = fraction of substance which is removed from the plasma by kidneys
    • E = (A-V) / A
      • A = [Concentration] in Renal Arterial Plasma
      • V= [Concentration] in Renal Venous Plasma
  • RPF = ERPF / EPAH = CPAH / EPAH
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4
Q

Objectives: Explain renal handling of weak organic acids and bases

A
  • In nonionized form (HA, B) can undergo passive reabsorption or passive secretion
  • Tubular transports is thus pH dependent
    • ​Acidic Tubular Fluid: Weak acids are uncharged and move by diffusion
      • Acidosis: Urine = acidic, excretion of organic anions decreases because they are reabsorbed
      • Alkalosis: Urine = alkaline, excretion of organic anions increases because they become “trapped” and are unable to be reabsorbed
    • Alkaline Tubular Fluid: Weak bases are uncharged and move by diffusion
      • Urine is normally acidic, thus weak bases are charged, and excreted
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5
Q

Explain tubular secretion for organic anions and organic cations

A
  • Organic Anions:
    • Low Sensitivity
    • Maximum transport rate
    • Mechanisms:
      • Enter: OAT; a-KG Antiporter mechanism
        • ​NaDC (Na in) maintains gradient
      • Exit: MRP2, OAT4
    • Exampls: cAMP, cGMP, Postaglandins, Vitamin C, antibiotics, diuretics
  • Organic Cations:
    • Low Sensitivity
    • Maximum transport rate
    • Mechanisms:
      • Enter: Passive Diffusion or OCT-uniporter
        • ​OCTs more against gradient, driven by cell-negative potential difference
      • Exit: OC-H Antiporters (OCTN), MDR1
    • Examples: Creatinine, dopamine, epinephrine, norepinephrine,
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6
Q

Explain renal handling of urate (uric acid)

What is it an example of?

How is this related to gout?

A
  • >90% filtered urate is reabsorbed in early proximal tubule
  • Active tubular secretion in late proximal tubule
    • This portion is homeostatically regulated
  • Example of bi-directional transport
  • Hyperuricemia = Gout
    • Decreased Filtration Rate + Maintained Tubular Reabsorption
    • Increased Reabsorption
    • Decreased Secretion
    • Increased Production
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7
Q

Explain renal handling of potassium

What is it an example of?

A
  • Kidneys primary regulator of K+ balance; net reabsorption of filtered K+; bi-directional transport
  • Proximal Tubule - 67% Reabsorbed
  • Thick Ascending Limb of LoH - 20% Reabsorbed
  • Will continue to reabsorb at Distal Tubule and beyond; increasing with high K diet
  • Mainly regulated via Secretion via Aldosterone homeostatic regulation (principal cells)
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8
Q

Explain the mechanisms for K+ transport

Proximal Tubule

Distal Tubule

How is K+ secretion determined?

How do diuretics affect this?

How does low K+ intake affect this?

A
  • Proximal Tubule - Both active and passive
    • Active - Pumps on luminal/basolateral cell membranes
    • Passive - most K+ reabsorption in Prox. Tubule
  • Distal Tubule - K+ reabsorption and secretion are both passive and active and cell specific
    • Determinants:
      • [K+] gradient between principal cell and tubule fluid
        • K+ secretion will increase when ICF [K+] is high and/or TF [K+] is low
      • Flow Rate of Tubular Fluid (Increase = Increase Secretion)
        • Increased TF Flow = Low TF [K+] = Increased [K+] gradient = Increased Secretion into TF
        • Diuretics decrease Na+ reabsorption in Ascending Thick Limb of the LoH, and causes increased TF flow in Late Distal Tubule, which increases K+ secretion
        • Low K Intake ICF [K] is low, and luminal permeability to potassium will be low–increased flow will have no effect on K secretion
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9
Q

How is K+ secretion determined?

How do diuretics affect this?

How does low K+ intake affect this?

A
  • [K+] gradient between principal cell and tubule fluid
    • K+ secretion will increase when ICF [K+] is high and/or TF [K+] is low
  • Flow Rate of Tubular Fluid (Increase = Increase Secretion)
    • Increased TF Flow = Low TF [K+] = Increased [K+] gradient = Increased Secretion into TF
    • Diuretics decrease Na+ reabsorption in Ascending Thick Limb of the LoH, and causes increased TF flow in Late Distal Tubule, which increases K+ secretion
    • Low K Intake = ICF [K] is low, and luminal permeability to potassium will be low–increased flow will have no effect on K secretion
  • Electrical gradient across luminal embrane of K+ secreting cells
    • Na+ reabsorption causes lumen to become more negative, enhancing secretion of K+
    • Poorly rebsorbed anions (Bicarb) in the TF will maintain lumen negative potention and promote K+ secretion
  • Aldosterone
    • ​Stimulates secretion of K+/H+ and reabsorption of Na+
    • Increases Na / K channels, and Na-K-ATPase Activity
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10
Q

What are the primary causes for hypermineralcorticoidism?

A
  • Hypertension (Increased Na+ Reabsorption)
  • Hypokalemia (Increased K+ Secretion)
  • Metabolic Alkalosis (Increased H+ Secretion)
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11
Q

What does alkalosis result in?

A

Increase [K+] in prinicpal cells

Leads to increased [K+] secretion and potassium depletion

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12
Q

What is the result of Acute vs Chronic Acidosis on K+ renal handling?

A
  • Acute Acidosis:
    • Decrease [K+] in principal cells
    • Decrease [K+] secretion
    • = Acute potassium retention
  • Chronic Acidosis:
    • Depression of H2O and NaCl reabsorption in Proximal Tubule
    • Increase Distal TF Flow
    • Increased K+ secretion into TF
    • = Chronic potassium depletion
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13
Q

Explain a clinical solution to Aspirin Poisoning

A

Alkalinizing the urine

Acetylsalicylate ion formed and “trapped” in nephron, thus increasing excretion of aspirin

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14
Q

Explain the concept of forced diuresis

A
  • Forced Diuresis is intentional change of pH of urine
  • Forces excretion of acidic or alkaline drugs, will excrete OPPOSITE of blood/urine pH
  • Forced Alkaline Diuresis: Furosemide (diuretic) + Sodium Bicarbonate
    • Excrete Acidic Drugs: Salicylates, Barbiturates, Lithium
  • Forced Acidic Diuresis: Furosemide (diuretic) + Vitamin C
    • Excrete Basic Drugs: Cocaine, Amphetamine, Quinine, Strychnine
    • *Forced acidic rarely used, only enhances renal clearance a bit
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15
Q
A
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SF 3 - Test 3 (12 decks)

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