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S2B5 Physiology > Regulation of Fluid Osmolality > Flashcards

Regulation of Fluid Osmolality Flashcards

1
Q

What percent of calcium is available for glomerular filtration?

Why?

A

50%

~50% of plasma Ca2+ is unbound (can be filtered)

~50% of plasma Ca2+ is bound to plasma albumin & other anions

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2
Q

What balaning factors control plasma calcium levels?

Under normal conditions, the kidney absorbs what percent of the filtered Ca2+?

A

Balance between gastrointestinal reabsorption and renal excretion

normally, the kidney reabsorbs 99% filterd Ca2+

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3
Q

What percent of the filtered load of Ca2+ is reabsorbed in the proximal tubule & how does this occur?

A
  • Proximal tubule
    • 70%
    • Passive reabsorption as a the result of a favorable concentration gradient dependent on the reabsorption of Na+ & other solutes
    • Parallels Na+ reabsorption both via both transcellular and paracellular pathways
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4
Q

What percent of the filtered load of Ca2+ is reabsorbed in the Loop of Henle & how does this occur?

A
  • Loop of Henle
    • 20%
    • the lumen (+) potential created by the recycling of K+ in the thick ascending limb (via Na-K-2Cl activity) results in the passive paracellular reabsorption of Ca2+ (Na+ and Mg2+).
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5
Q

What type of diuretic diminishes Ca2+ reabsorption in the Loop of Henle?

Why?

A

loop diuretics

they block the Na-K-2Cl pump in the Loop of Henle, decreasing the (+) lumen potential & diminishing the paracellular reabsorption of Ca2+, Mg2+, and Na+

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6
Q

Describe how Ca2+ is absorbed in the Distal Tubule

A
  • Ca2+ enters the cell through channels in the luminal membrane and the gradient for Ca2+ to enter the cell is maintained by Calcium Binding Protein. This keeps the Ca2+ bound up inside the cell until it can be reabsorbed, maintaining a low free calcium level & a steep electrochemical gradient.
  • Ca2+ is reabsorbed at the basolateral membrane in exchange for 3Na+ via 3Na-Ca exchanger (active reabsorption)
  • Also a Ca-ATPase in the basal membrane
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7
Q

Describe the effect of Parathyroid hormone on Ca2+ reabsorption

A
  • Distal tubule
    • Parathyroid hormone is release in response to low plasma Ca2+
      • enhances 3Na-Ca exchanger
      • increases Cl- entry into the cell, which aids in calcium entry
      • activates calcitriol
    • Calcitriol
      • metabolite vitamin D3
      • induces the synthesis of the calcium binding protein, enhancing the gradient in favor of calcium entry from the lumen
      • increase Ca2+ absorption in the gut
        • balance of reabsorption of Ca2+ in the gut & reabsorption of Ca2+ in the lumen
      • increases resorption of bone (calcium & phosphate)
      • decreases phosphate reabsorption in the proximal tubule b/c we reach the tubular transport maximum– which increases phosphate excretion
    • Net effect of PTH
      • ​Increases plasma Ca2+ and HPO42- levels
      • BUT, decreases the Tm for 2Na+ - HPO42- and increases phosphate excretion so that plasma phosphate levels are unchanged
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8
Q

What percent of the filtered load of phosphate is reabsorbed in the proximal tubule?

How does this happen?

What is the important role that HPO42- plays?

A
  • Proximal tubule
    • 80%
    • 2Na+ - HPO42- co-transporter
    • exhibits a transport meximum and renal threshold
    • filtered load typically exceeds the transport maximum adnd there is phosphate left in the tubule
      • it acts as a H+ acceptor for acid excretion
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9
Q

What percent of the filterd load of HPO42- is reabsorbed in the distal tubule?

A
  • Distal tubule
    • 10%
    • mechanism unknown
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10
Q

What is important about the presence of phosphate in the filtrate?

A
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11
Q

What controls intracellular fluid volume?

A

Extracellular fluid osmolality

ICF osmolality parallels ECF osmolality

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12
Q

How is ECF osmolality regulated?

How does the kidney respond to a hyperosmolar condition?

How does the kidney respond ot a hypoosmolar condition?

How quickly does correction occur?

A

ECF osmolality is regulated by controlling wter excretion adn intake

  • Hyperosmolar: water deficit
    • correction requires positive water balance
      • thirst & decreased renal water excretion
  • Hyoposmolar: water excess
    • correction requires negative water balance
      • decreased thirst & increased renal water excretion

Renal correction of osmolality disturbances are rapid adn occur within minutes

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13
Q

How should water intake & output be balanced?

A

intake should equal output

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14
Q

Describe the steps involved with a pure water load.

Describe the steps involved in a dehydrated state.

A
  • Pure water load
    • decreased osmolality detected by hypothalmic osmoreceptors
    • decrease secretion of ADH
    • decreased aquaporins in collecting ducts
    • decreased water reabsorption
    • increased water excretion
  • Dehydration
    • incrased osmolality detected by hypothalmic osmoreceptors
    • increased secretion ADH
    • increased aquaporins in collecting ducts
    • increased water reabsorption
    • decreased water excretion
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15
Q

What are the four components that regulate fluid osmolality?

A
  1. Loop of Henle and vasa recta (generate & maintain medullary osmolar gradient that allows us to conserve free water)
    • LOH: down into medullary interstitial space & back up
      • counter-current multiplier (becasue solute is actively pumped out in thick ascending limb)
    • Vasa recta: extensions of peritubular capillaries that extend into the medulary space & come back up
      • counter-current exchanger (pasive process)
  2. Variable permeability of the collecting ducts to water
  3. Osmoreceptors
    • rapidly sense changes in plasma osmolality
    • elicits ADH release
  4. ADH
    • affects permeability of collecting ducts to water
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16
Q

What hormone controls the collecting duct’s permeability to water?

How does this process occur?

A
  • ADH controls permeability of collecting ducts to water (luminal side)
    • stimulates adenylate cyclase and causes water channels (aquaporins; AQP-2) to fuse into the luminal membrane
      • these aquaporins are ususall inside the cell in clathrin coated vesicles
      • this allows water to go into the cell, through the cell & get out the basolateral membrane
    • Basolateral membrane is permeable to water (AQP-3 an AQP-4 = constitutive)
17
Q

Where is blood osmolarity sensed?

How is this possible?

What is the repsonse?

A
  • Osmoreceptors and thirst centers located in the hypothalamus (supraoptic and paraventricular nuclei)
    • sense osmolality of the plasma
    • there is no BBB here
      • ependymal layer that seals off this center to the rest of the brain
  • Response to change in osmolatiry can result in increase or decrease in ADH released from posterior pituitary
18
Q

What is the body’s response to the release of ADH?

A
  • increases permeability of cortical collecting duct and medullary collecting duct to water
  • increases activity of Na-K-2Cl pump in the thick ascending limb in the loop of henle
    • continue to put more solute into the intermedullary space, maintaing the gradient for water reabsorption
  • increases urea reabsorption in medullary collecting duct
    • maintains the medullary gradient & allows us to continue to reabsorb NaCl passively in the thin ascending limg
19
Q

Describe the permeability to solutes & water in the thin descending limb.

How does the tubular fluid change as it moves through this segment?

A
  • Thin descending limb
    • impermeable to solutes
    • permeable to water
    • water leaves the tubule
    • tubular fluid becomes increasingly more hypertonic moving deeper into interstitial gradient
20
Q

Describe the permeability to solutes & water in the thin ascending limb.

A
  • Thin ascending limb
    • impermeable to water
    • permeable to NaCl which diffuses “out”
    • urea diffuses “in”
21
Q

Describe the permeability to solutes & water in the thick ascending limb.

How does the tubular fluid change as it moves through this segment?

A
  • Thick ascending limb
    • impermeable to water
    • Na-K-2Cl transporter
    • tubular fluid becomes progrssively more dilute
    • fluid leaving LOH is hypotonic
22
Q

Describe the concept of the “counter-current” multiplier in the Loop of Henle. What is the purpose of this?

A
  • Counter-current systems
    • “hairpin” configuration
    • close proximity
    • requires and energy dependent step
      • Na-K-ATPase drives the Na-K-2Cl pump
  • Active transport of NaCl creates an osmotic gradient of ~200 mOsm at each horizontal level (importance of tight junctions)
  • Counter-current flow creastes a steep longitudinal gradient (e.g. ~300 mOsm in the cortex progressing to ~1200 mOsm in deep medulla)
  • This allows us to have a tubular fluid leaving the loop of henle of 100 mOsm, compared to 300 mOsm in the interstitial space, that sets up a standing osmotic gradient so that when ADH opens the water channels, water will move from the tubule into the interstitial space
  • The magnitude of the hyperosmolality of the medullary region is indicative of the extent to which the kidneys can conserve water
23
Q

What are vasa recta & what is their function?

A
  • Extensions of the peritubular capillaries
    • supply oxygen and nutrients to the medullary region
    • sluggish blood flow
    • no energy expenditure
    • “hairpin” configuration allows them to maintain gradient
  • Counter Current exchanger
    • Inflow
      • NaCl enters / water leaves
    • Outflow
      • NaCl leaves / water enters
    • Net effect - removal of reabsorbed NaCl and water
  • plasma leaving vasa recta is slightly hyperosmotic because we have to account for the solute that allows us to have hyposmotic fluid in the tubule
24
Q

What is the impact of increased flow in the vasa recta?

A

There will be less opportunity to equilibrate at each level and more washout of the medullary gradient since there will be a larger concentration of solute in the plasma

that would disipate the longitudinal gradient

Urine concentration??? I DONT KNOW

25
Q

How does volume status impact ADH sensitivity?

A
  • Hypovolemia enhances the sensitivity
  • Hypervolemia depresses the sensitivity
26
Q

Is ADH release more sensitive to changes in volume or osmolality?

A
  • 2-3% increase in osmolality causes rapid ADH release
  • >10% decrease in ECBV (up to ~15%) to get same change in ADH
27
Q

Fill out the provided table

A
28
Q

What is the renal response to increased plasma osmolality?

A
  • ADH release increases
  • Leads to antidiuresis
    • increases permeability of CCD and MCD to water
    • CCD - isotonic
    • MCD - hypertonic
    • (+) urea reabsorption in MCD
  • Urine
    • small volume (~0.5L/day)
    • high osmolality (~1200 mOsm)
29
Q

What is the renal response to a decreae in plasma osmolaltiy?

A
  • ADH release is inhibited
  • Leads to diuresis
    • CCD and MCD become less permeable to water (small arrows)
    • CCD - hypotonic
    • MCD - more hypotonic
  • Urine
    • large volume (12 to 20L/day)
    • low osmolality (~50 mOsm)
30
Q

How do loop diuretics affect the medullayr osmotic gradient?

A

If relying on Na-K-2Cl pump to maintian this active movement of solute from the lumen to the interstitial space (200 mOsm at each level), & we block it with loop diuretics, we will start to see a washout of the medullary osmotic gradient

31
Q

Which line represents max ADH & which line represents no ADH?

A
32
Q

Why is it helpful to know about free water clearance?

What are the 3 situations with relation to the urine?

A

provides information about the ability of the kidney to excrete or retain water

compare plasma concentration to the concentration of the urine to determine if the individual is retaining or losing free water

  • Isotonic urine - no loss/retention of free water
  • Hypotonic urine - losing free water
  • Hypertonic urine - retaining free water
33
Q

What occurs faster?

Osmoregulation or volume regulation?

A

Osmoregulation: fast

Volume regulation: slow

S2B5 Physiology (10 decks)

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