1 - Sodium and Water Transport Flashcards

1
Q

Objectives: Describe the mechanisms for sodium, chloride, and water reabsorption in the different nephron segments

A
  • Sodium, Chloride, and Water > 99% Tubular Reabsorption w/no tubular secretion
  • Sodium: Active and Transcellular
    • Movement always downhill
    • Na-K-ATPase moves uphill
    • PT, Ascending Limb of LoH, DCT, CD all reabsorb sodium
  • Water: Osmolarity differences generated by sodium driven
    • Water follows sodium
    • Proximal Tubule (PT) is major site for reabsorption of salt and water
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2
Q

Objectives: Explain obligatory water loss

A

Minimal volume of water in which the average mass of solute excreted per day can be dissolved

~ 0.43 L / day

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3
Q

Objectives: Describe countercurrent multiplier system for urine concentration

A
  • Takes place in Loops of Henle that extend into the medulla
    • Descending Limb only absorbs water
    • Ascending Limb only absorbs Na/Cl
    • Transports of Na/Cl from Ascending Limb to IF forms horizontal gradient
  • Urinary Concentration trakes place as TF flows through medullary collecting ducts towards renal pelvis
    • Medullary IF is hyperosmotic
    • ADH causes water to diffuse out of medullary collecting ducts; thus concentrating the urine
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4
Q

Objectives: Explain the transport and permeability characteristics of ascending and descending limbs, the distal tubule, and the collecting-duct system

A
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5
Q

Objectives: Describe the medullary circulation and its function as a countercurrent exchanger

A

Function of loop countercurrent multiplier system is to increase osmotic concentration of medullary interstitium

In presence of ADH, water is drawn out of medullary collecting ducts, concentrating the urine

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6
Q

Objectives: Explain free water clearance

Equation

ADH Role

A
  • Used to compare rate of solute excretion with rate of water excretion
  • Equation: CH2O = [V - COSM]
    • COSM = Osmolal Clearance = (V*UOSM)/POSM
    • Thus: CH2O=V*( 1- (UOSM / POSM) )
  • ADH enables water regulation independent of chloride/sodium ions, urea
  • Water free of sulutes (“free water”) is generated in Ascending Loops of Henle (salt leaves here, not water)
    • Low ADH: Hyposmotic Urine
    • High ADH: Hyperosmotic Urine
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7
Q

Objectives: What is the role of urea in water regulation

A
  • Urea contributes to the hyperosmolarity of the renal medullary interstitium and to a concentrated urine
  • Glomerulus: Filtered
  • Proximal Tubule: Urea remains, creating gradient
    • Permeable, moves along concentrating gradient
    • 50% reabsorbed
  • Loop of Henle: Secreted into tubule due to high medulla [Urea]
  • Distal Tubule: Decreased urea permeability,
  • Collecting Duct:
    • w/ADH: High urea permeability
    • High ADH (antidiuresis): High urea reabsorption contributes to hyperosmolarity of medulla
    • Low ADH (diuresis): Permeability decrease, less of impact on interstitial osmolality
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8
Q

As GFR changes, how does sodium reabsorption in the proximal tubule change?

A
  • Changes in GFR result in proportional change to filtered load of Na
  • Proximal Tubule still reabsorbs a constant fraction of filtered load of salt and water
  • Absolute amount of filtered salt and water that leaves proimal tubule increases as filtered amount increases
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9
Q

How does the pace of water reabsorption in the proximal tubule keep up with sodium reabsortion?

A
  • Water = Passive
  • Sodium = Active
  • Water permeabiluty of proximal tubule is high
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10
Q

Explain osmotic diuresis

A
  • Increased urine flow due to extra amount of non-reabsorbed solute within tubular lumen
  • Mannitol causes osmotic diuresis
  • Observed in severe diabetes
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11
Q

***Where does water and sodium reabsorption occur in the Loop of Henle?***

What does this enable?

A
  • Descending: Water
  • Ascending: Sodium / Chloride

“Drink Water, And Sip Corona”

Thick Ascending Limb of LoH = Point of Separation of Salt and Water

Thus, Salt and Water excretion can be controlled independently!

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12
Q

What is the major transporter in the thick ascending limb?

What targets this?

What other routes for sodium/potassium are available?

A

Drink Water, And Sip Corona

  • The major transporter in the thick ascending limb is the Na-K-2Cl Symporter (NKCC)
  • Target for nhibition by Loop Diuretics
  • Potassium Channels (transcellular), Sodium Paracellular due to lumen positive potential
  • This is where salt is separated from water, allowing independent control of each!
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13
Q

What is Bartter’s Syndrome?

A
  • Cause: Mutations of genes encoding proteins that transport ions in Ascending Limb (including Na-K-2Cl Cotransporter, K Channel, Cl Channel)
  • Symptoms: Large urinary loss of NaCl, Hypokalemia
    • ​Ca2+ and Mg2+ wasting may occur
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14
Q

What is the target of Thiazide Diuretics?

A

Na-Cl (NCC) Symporter on Apical Membrane

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15
Q

What is Gitelman’s Syndrome?

A

Mutations in gene that codes for Na-Cl Cotransporter in the Distal Tubule

Characterized by increased excretion of Na+, Mg2+, Cl-, and K+

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16
Q

What hormones control Apical Sodium Channels?

What hormones control water reabsorption–and through what channel does this occur?

A
  • Aldosterone controls sodium reabsorption
  • Antidiuretic Hormone (ADH) controls water reabsorption via aquaporins
17
Q

What is Liddle’s Syndrome?

A
  • Mutations in gene that codes for epithelial sodium channel (ENaC) in the principal cells of collection duct
  • Induces excess Na+ reabsorption
  • Symtoms: Severe hypertension w/low plasma renin activity, metabolic alkalosis due to hypokalemia and hypoaldosteronism
18
Q

How is water absorbed at the Distal Tubule and Collecting Duct?

A
  • Distal Tubule: Low water permeability
  • Collecting Duct: Aquaporins - ADH
    • High ADH: High Reabsorption = Reduced Urine
    • Low ADH: Low Reabsorption = Increased Urine
19
Q

With countercurrent multiplication, where is the osmolality gradient the highest?

A

At the bend of the loop of henle

20
Q

How is urea recirculated, what what does this result in?

A

Urea reabsorbed from medullary collecting duct diffuses back into thin loop of Henle

Passes through distal tubule, and back to collecting duct, forming a loop

This loop contributes to the hyperosmolarity of the renal medulla, especially when ADH is HIGH

21
Q
A
22
Q

What is the role of the Vasa Recta in countercurrent exchange?

A

Prevents wash out of osmotic gradient set up by Loop of Henle

Passive–do not create medullary gradient, only protect it. Carry salt and water entering medullary interstitium from loops and collecting ducts back to cortex and venous system

23
Q

CH2O > 0

When?

[Urine] vs [Plasma]?

Net Free Water?

Plasma state?

A

UOSM < POSM

Urine is dilute vs plasma

Free Water is lost from body

Plasma is being concentrated

24
Q

CH2O < 0

When?

[Urine] vs [Plasma]?

Net Free Water?

Plasma state?

A

UOSM > POSM

When relatively more solute than water is being excreted

Water is being conserved, and returned to plasma

25
Q

What is Hydropenia (fluid restriction)?

A
  • Urine can be concentrated 4-5x vs blood plasma
    • ​Urine flow can drop, while still diluting enough to excrete solutes
  • CH2O = V - COSM
    • ​< 0 ; free water reabsorbed
26
Q

Explain Fluid Overload (water diureis)

A
  • Increase of urine flow
  • Excretion Load of osmotically active particles is same, because osmolar clearance is indepenent of urine flow
  • CH2O = V - COSM
    • ​> 0 ; Free water is excreted
27
Q

Explain water balance

A

Urine is isotonic to plasma, or CH2O = 0

28
Q

Key Point: By what four mechanisms does reabsorption of sodium drive reabsorption of other substances?

A
  1. Lumen-negative transtubular potential difference, favors paracellular reabsorption of anions (Cl-) by diffusion
  2. Creates transtubular osmolarity difference, favors reabsorption of water by osmosis, causes concentration of luminal solutes, favoring their reabsorption by diffusion
  3. Contransport results in reabsorption of organic nutrients, phosphate, chloride
  4. Achieves secretion of hydrogen ion in PT by countertransport
29
Q

Key Point: What is the major mechanism for chloride reabsorption along the tubule?

Proximal

Thick Ascending Loop

Distal Convoluted Tubule

Cortical Collecting Duct

A
  • Proximal: Paracellular diffusion
  • Thick Ascending Loop: Secondary Active via Na-K-2Cl Transporter
  • Distal Convoluted Tubule:
    • Paracellular Diffusion (lumen-negative)
    • Secondary Active via NaCl Contransporter
  • Cortical Collecting Duct
    • Paracellular Diffusion (lumen-negative)
    • Secondary Active via HCO3-Cl Countertransporter (sodium independent)
30
Q

Osmotic Diuresis

Water Diuresis

Antidiuresis

A
  • Osmotic Diuresis
    • Increased urine flow due to extra amount of non-reabsorbed solute
    • Mannitol can cause
  • Water Diuresis
    • Increased urine flow due to decreased reabsorption of free water
    • High water intake
    • Diabetes Insipidus
  • Antidiuresis
    • Urine flow less that normal
    • Indicates urine is hyperosmotic to plasma (countercurrent multiplication is not occuring)