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RED - Kidney Pharmacology & Therapeutics > K4; Loop of Henle > Flashcards

K4; Loop of Henle Flashcards

1
Q

What is osmotic pressure?

A

The pressure applied by a solution to prevent the flow of water (osmosis) across a semi-permeable membrane; directly related to the concentration of osmotically-active particles in that solution.

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2
Q

In a high osmotic pressure/hyperosmotic environment, what is the ratio of solute to water?

A
  • High [solute]
  • Low [water]
    »> Concentrated
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3
Q

In a low osmotic pressure/hyposmotic environment, what is the ratio of solute to water?

A
  • Low [solute]
  • High [water]
    »> Dilute
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4
Q

What is an osmoe?

A

1 mole solute particles (6.02 x 10^23; Avogadro’s)

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5
Q

What is the difference between osmolality and osmolarity?

A
  • Osmoles per kg solution

- Osmoles per L solution

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6
Q

What is the normal serum osmolality and how does it differ to the corresponding osmolarity?

A
  • Normal serum = 290 mOsm/kg
  • Very similar osmolarity
  • As the body fluid is a dilute solution; difference between osmolarity and osmolality is negligible as 1L water = 1kg water and weight of solute is minor
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7
Q

What 2 things ensure that the kidney conserves water and concentrates urine?

A
  1. ) High osmolality in the renal medullary interstitium; provides osmotic gradient for water reabsorption, passing out the tubule. LoH responsible. (PCT = isosmotic fluid, DCT = hyposmotic fluid)
  2. ) Action of ADH/AVP; increase water (& urea) permeability
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8
Q

What is the general structure of the Loop of Henle?

A
  • U-shape (hairpin) that dips into the medulla
  • Thin descending limb: from PCT, ends in hairpin turn, plunges from cortex to medulla
  • Thin ascending limb (only present in nephrons with long LoH)
  • Thick ascending limb: carries fluid up and out of the medulla into the DCT in the cortex
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9
Q

What is the cellular make-up/structure like for the thin descending and ascending limb?

What does this tell you about these sections?

A
  • Descending: cells interlock sparsely (leaky)
  • Poorly differentiated surfaces, few mitochondria
  • Thus suggests not much reabsorption/less active transport
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10
Q

How does the thick ascending limb differ from the thin descending/ascending limbs in structure and thus function?

A
  • Abundant mitochondria; lots of active transport

- Apical membrane is invaginated to form many projections (microvilli); increasing SA for reabsorption

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11
Q

Is the thin descending limb permeable to H2O/Na+/Cl-?

A
  • Permeable to H2O (leaky cells)

- Impermeable to Na+/Cl- (little reabsorption)

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12
Q

Is the thin ascending limb permeable to H2O/Na+/Cl-?

A
  • Impermeable to H2O (cells interlock better)

- Permeable to Na+/Cl- (differential expression)

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13
Q

What is the thick ascending limb permeable and impermeable to?

A
  • Permeable to Na+/Cl-/HCO3-/Ca2+/K+

- Impermeable to H2O

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14
Q

What transporters/carriers etc feature on the thick ascending limb?

A
  • Na+/K+ ATPase in basolateral membrane maintains low Na+ in tubular cell
    (Allows for Na+ to flow into the cell down its concentration gradient)
  • Via Na+/K+/2Cl- symporter in the apical; an electroneutral transporter where Na+/2Cl- are moving down its concentration gradient allow K+ to be taken into the cell against its concentration gradient
  • K+ channel in apical membrane enables K+ cycling back into the lumen from Na+/K+/2Cl- function
  • Na+/H+ antiporter enables Na+ reabsorption and H+ secretion so it can be cycled for HCO3- reabsorption (via H2CO3 formation etc)
  • K+/Cl-/HCO3- leave cell through respective pathways
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15
Q

What occurs to the tubular lumen as a result of ion movements into the tubular cell?

What are the consequences of this?

A
  • Becomes slightly positive at +10mV relative to interstitial fluid
  • Allows for paracellular diffusion of K+/Na+/Ca2+/Mg2+/NH4+ moving down their electrochemical gradient
    (in particular the divalent Ca2+/Mg2+)
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16
Q

What happens to the tubular fluid after passing the thick ascending limb of the LoH?

A
  • Impermeable to H2O
  • Losing solutes not losing H2O (no reabsorption)
  • Thus hyposmotic
17
Q

Which nephron has the long LoH?

A
  • Juxtamedullary nephron (not cortical); plays key role in concentrating urine
18
Q

What does countercurrent multiplication achieve?

A

Maintains flow of solutes and H2O in and out of the medulla to produce high medullary osmolality

19
Q

What are the steps in the renal medulla becoming hyperosmotic?

A
  1. ) Tubular fluid enters LoH from PCT at isotonic osmolality to medullary interstitial fluid concentration (300)
  2. ) Na+/K+ ATPase & Na+/K+/2Cl- symporter (Cl- channel) in (thick) ascending limb actively transport Na+ and Cl- out of lumen into interstitial fluid (tubular fluid osmolality drops); gradient of 200 mOsm/kg develops between tubular and interstitial fluid (200/400)
    - Net diffusion of H2O occurs from descending limb into interstitial fluid by osmosis (aquaporins)
    - Tubular fluid in descending limb increases in osmolality and water leaves until equilibration with interstitial fluid (400)
  3. ) Flow of tubular fluid pushes 200 mOsm/kg out into the DCT
    - Isotonic 300 mOsm/kg fluid enters from the PCT
    - Prior equilibrated 400 mOsm/kg fluid is pushed into the ascending limb
  4. ) Process continues and concentration gradient of 200 mOsm/kg is created across the tubular fluid and interstitial (300/500) via Na+/K+/2Cl- symporter pumping NaCl out of tubular fluid
    - Thus net diffusion of water from descending limb occurs leaving descending limb and passing into interstitial fluid
    - 200 mOsm/kg gradient is present between ascending limb and both the interstitial fluid and descending limb (after equilibration)
    - Gradual increase [solute] in descending limb
    - Gradual decrease in [solute] in ascending limb
  5. ) 200 mOsm/kg gradient is further disrupted as movement of fluid continues (into the DCT)
  6. ) Gradient is re-established following simultaneous active movement of NaCl from ascending limb and passive movement of H2O from the descending limb (as it equilibrates with the renal medulla)
  7. ) Creates a progressive hyperosmotic solution in descending limb (1200 mOsm/kg)
    - And a progressive decrease in solute concentration in the ascending limb from NaCl extrusion; progressively hyposmotic
20
Q

How is the 200 mOsm/kg gradient maintained at the ascending limb in countercurrent multiplication?

A
  • When too much NaCl is in the renal interstitial medulla it passively diffuses back into the tubular fluid
  • This maintains the 200 mOsm/kg gradient
21
Q

What are the key features to countercurrent multiplication/the renal medulla becoming hyperosmotic?

A
  • Tubular fluid progressively concentrated as it flows down the descending limb
  • Medullary interstitial fluid is progressively concentrated to the same degree
  • 200 mOsm/kg gradient maintained across ascending limb tubular membrane
  • Large osmotic gradient from top to bottom of LoH (300 vs. 1200)
  • Active reabsorption of NaCl (via Na+/K+/2Cl- symporters) from tubular fluid to interstitial fluid with passive movement of H2O is essential
22
Q

What are the contributing factors to the hyperosmotic renal medullary interstitium in the outer and inner renal medulla?

A

Outer: 100% NaCl
Inner: 50/50 NaCl/Urea

23
Q

How is urea reabsorbed?

A
  • 50% of urea is reabsorbed at the PCT
  • LoH (thick asc.) & DCT are impermeable
  • [Urea] increases as it passes along the tubule; water and other solutes are reabsorbed
  • Collecting duct is permeable; and high [urea] thus urea diffuses down concentration gradient, moving into the interstitial fluid and increasing hyperosmolality
24
Q

How is urea recycled?

A

Some urea passes from the interstitium into the thin LoH, cycling around and contributing to hyperosmolality.

25
Q

How does ADH affect urea reabsorption?

A
  • ADH increases permeability of CD to urea, further increasing osmolality and thus water reabsorption
  • Following aquaporin 2 expression for water reabsorption, urea transporters are also expressed creating greater osmotic gradient for water to be reabsorbed into the vasa recta of the peritubular capillaries
26
Q

What is countercurrent exchange?

A
  • Medullary capillaries (particularly the hairpin arranged vasa recta) are highly permeable to solutes and water
  • The parallel configuration of the long vascular loops of the vasa recta minimizes washout of built up solute gradient from the medullary interstitium (if there were a one way blood supply; solutes would diffuse from interstitium into blood), preserving hyperosmolality of renal medulla
27
Q

What is the path of solutes/water in the descending vasa recta?

A
  • Solutes enter
  • Water leaves
  • Hyperosmotic
28
Q

What is the path of solutes/water in the ascending vasa recta?

A
  • Solutes leave
  • Water enters
  • Isosmotic once again
29
Q

What is the function of the peritubular capillaries?

A
  • Delivers O2, takes away CO2

- Without disturbing hyperosmolality

RED - Kidney Pharmacology & Therapeutics (5 decks)

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