Reg of BF Osmolarity-Rao Flashcards
In what way does the kidney indirectly maintain constant body water content?
By regulating the body fluid osmolarity, the kidney maintains constant body water content
Under what conditions does the kidney respond by increasing water excretion?
Increased TBW and/or reduced osmolarity (both would happen with increased water intake)
Under what conditions does the kidney respond by reducing water excretion?
reduced TBW and/or increased osmolarity (both would happen in dehydration)
How is the body water balance maintained centrally?
Changes in plasma osmolarity by as little as 1mosm/L is sensed by osmoreceptors in the hypothalamus, which are stimulated to or inhibited from causing thirst and signaling release of ADH from post pit depending on if the osmolarity is increased or decreased
What is an indicator of TBW?
Plasma Osmolarity
How is plasma osmolarity calculated?
Posm= 2x[Na] + [Glc]/18 + [BUN]/2.8= 285mosm
How do plasma osmolarity and TBW relate to each other?
Assuming that solute concentration is unaffected, they are inversely related (low osmolarity means elevated TBW and vice versa)
Why is the kidneys ability to conserve water limited compared to its capacity to increase water excretion?
A minimum of 500 ml of water is required to be eliminated each day to excrete metabolic wastes
What two conditions can lead to water excretion of 18L per day (very high)?
Excessive water drinking or lack of AVP
What do the hypothalmic osmoreceptors respond to?
Shrinkage of the cells there due to increased plasma osmolarity
Once stimulated, what two things do the osmoreceptors do?
- They result in an increase in intracellular Ca2+ in nerve endings that end in the posterior pituitary, causing the fusion and secretion of AVP vesicles.
- (If osm due to Na and not urea) they stimulate the thirst center to encourage drinking more water
Where does AVP act? What is the result?
It acts on the principal cells of the late distal tubule and collecting duct, increasing water reabsorption→which returns plasma osmolarity back to normal (reduces it), which feedbacks and inhibits the osmoreceptors
In addition to increasing water reabsorption, what else does vasopressin do?
It acts as a vasoconstrictor
How long does ADH circulate? Why?
Not very long, it is rapidly degraded in PT and liver
How does AVP increase water reabsorption in late DT/CD?
It binds to V2 receptors on principal cells→ complex activates AC-cAMP-PKA pathway→PKA phosphorylates AQP-2’s in vesicles and stimulates their insertion into the lumenal membrane, allowing water to diffuse down their concentration gradient
What is the result of high plasma osmolarity on AVP levels? What does this cause? To what extent does it cause this?
High AVP levels in response to high plasma osmolarity, results in concentration of the urine as high as 1200mOsm in order to conserve water
How are AVP levels affected by low plasma osmolarity? What does this result in?
Low pl osmolarity results in low AVP levels, there is dilution of the urine to as low as 50mOsm as very little water is reabsorbed
At what plasma osmolarity does AVP start to increase? What about the thirst mechanism?
pl osm→270mOsm/kg
thirst kicks in at 280mOsm (or when AVP alone is not working)
What is a cause of water diuresis?
increased ECFV (increase in venous filling in thorax)
What is the result of severe cases of volume depletion (diarrhea/vomiting)?
increased AVP secretion
Is increased AVP release more sensitive to decrease in ECFV or increased plasma osmolarity?
More sensitive to increased plasma osmolarity; a higher threshold of ECFV decrease of 10-15% is required for AVP release
Can AVP levels increase more in response to increased plasma osmolarity or reduced ECFV?
ECFV→AVP as high as 50 pg/ml
Osmolarity→AVP as high as 18
Can reduced ECFV override reduced osmolarity and increase AVP levels? If so when?
Yes, for instance, when there is hyponatremia in response to GI fluid loss→ the reduced PV overides the reduced pl osm
What causes hyponatremia due to GI fluid losses? How does GI loss cause hyponatremia?
Patient has severe diarrhea and vomiting and cannot eat solid food, but consumes a lot of fluid: results in volume depletion→increased AVP→increased ECFV→reduced osmolarity→hyponatremia
What are symptoms of hyponatremia? How do you treat it?
lethargy, hyporeflexia, mental confusion; treat with infusion of isotonic saline, avoiding quick change is essential
What are other conditions that cause hyponatremia but with no change in ECFV (euvolemic)?
- Heart failure
- LIver failure
These both stimulate hypovolemic hormone secretion
What is a symptom of decreased ability to concentrate urine? What are causes of decreased ability to concentrate urine?
Symptom: Nocturia (frequent urination druing nights)
Causes: age, renal failure, others (infection, hypertrophy of prostate)
How is the ability to concentrate urine quantified? How is it calculated? What is the normal value?
Osmolar Clearance (Cosm) Cosm= (UF x Uosm)/Posm Normal Cosm= 2+/-0.5ml/min
What does osmolar clearance represent?
the rate at which solute is removed from plasma and excreted in the urine
What is free water clearance?
the amount of water excreted by the kidneys that is free of solutes
What does the ability to concentrate urine depend on?
the difference between osmolar clearance and clearance of water
How is free water clearance calculated?
two ways:
A) C(H2O)= UF x [1- (Uosm/Posm)]
B) C(H2O)= UF- Cosm
How the free water clearance affect if Uosm is less than Posm (hypo-osmolar plasma)? How does this effect urine and plasma osmolarity?
If Uosm<Posm→ C(H2O) is positive→ dilute urine→ increased plasma osmolarity
How the free water clearance affect if Uosm is greater than Posm (hyperosmolar plasma)? How does this effect urine and plasma osmolarity?
If Uosm>Posm→ negative C(H2O)→concentrate urine→reduce plasma osmolarity
Is the human kidney more efficient in clearing or conserving water?
It is more efficient in clearing water than conservation
Is the osmolarity of the renal medullary high or low? How does this affect water movement?
It is high; this causes water osmosis into interstitium and water is then carried to blood by the vasa recta
What the main mechanism that contributes to the development and maintenance of of renal medullary hyperosmolarity?
The countercurrent mutliplier mechanism→the tubule segments have different permeability characteristics that contribute to the renal medullary hyperosmolarity
What are the five features of the kidney responsible for the development of medullary hyperosmolarity?
- Special anatomical arrangement of L of H and vasa recta and peritubular capillaries
- Active transport of Na+ and co-transport of K+ and Cl- out of TALH into medullary ISF (capable of creating a 200mOsm gradient)
- Active transport of Na out of CD into ISF
- Passive diffusion of urea from the IMCD into medullary ISF
- Diffusion of only small amounts of water from medullary tubules into medullary interstitium
What are the 6 steps involved in causing the hyperosmotic medullary interstitium?
- 300mOsm even distribution
- Active Na transport from thick ascending loop: 200 mOsm gradient
- Water transport in descending limb
- Additional flow of fluid from proximal tubule to LOH pushing the higher osmolar fluid to lumen of ascending limb
- Active transport of NA→new gradient
- Water transport in descending limb
How much does urea contribute to the osmolarity of the ISF?
40%
What allows urea to play its role in hyperosmolarity of medullary ISF?
DIfferential permeability to urea in different tubule segments (it gets recycled back and forth→reabsorbed in CD and can re-enter tubule in LofH???)
What is the source of blood of the medulla?
Vasa Recta
What two special features of the vasa recta (medullary capillaries) preserve medullary interstitial hyperosmolarity?
- Medullary blood flow is low (only 1-2% of the renal flow; 50ml/min)
- Vasa recta serves as countercurrent exchange
What are three causes of impairment of the kidney’s ability to concentrate or dilute urine?
- Defect in production or regulation of AVP secretion
- Inability of CDs to respond to AVP
- Failure to form medullary osmolarity gradient
What does diabetes insipidus (DI) cause?
High rates of production of dilute urine
What is Central/primary DI?
Pituitary gland fails to release AVP (rare congenital); patients get dehydrated very quickly bc they cant retain water
What is Nephrogenic DI? Causes?
Collecting duct does not respond to AVP
Causes: 1. V2 receptor mutation 2. AQP-2 mutation 3. Drugs→lithium, tetracycline
What are 4 causes of loss of medullary hyperosmolarity?
- Diuretics→furosemide, ethacrylic acid inhibits Na+ transport
- Excessive delivery of fluid into L of H
- Decreased urea production→decreased filtered load of urea
- Age and renal failure→reduced number of functional nephrons