Urinary 5 Flashcards
How can water intake and excretion affect plasma osmolarity?
If Intake > Excretion then plasma osmolarity decreases
If Intake < excretion then plasma osmolarity increases
How much water and how many osmoles are ingested per day?
Describe how excretion is matched to preserve water balance and plasma osmolarity
Most people ingest 1 - 1.5L of water and 600-1000mOsm/day
Urine osmolarity is therefore 500 - 700mOsm/L as 1 - 1.5L/day must be excreted
There is an inverse relationship between urine output per day and urine osmolarity
Outline the regulation of Plasma osmolarity
Osmolarity sensor:
Hypothalamic osmoreceptors
Two efferent pathways:
ADH:
- Acts on kidney*
- Affects urine output*
Thirst:
- Acts on brain to affect urge to drink
Describe hypothalamic osmoreceptors
Located in the Organum Vasculosum of the Laminae Terminalis (OVLT) of the hypothalamus
They have a fenestrate epithelium that exposes cytosol directly to systemic circulation
Sneses change in plasma osmolarity
Signals secondary responses leading to the two posible outcomes (ADH release and Thirst)
Describe the hypothalamic response to increased or decreased osmolarity
Increased:
Conditions of predominant loss of water and hence increase in osmolarity (As little as 1%) stimulates release of ADH from posterior pituitary
Increased fluid osmolarity also stimulates the hypoathlamus to create thirst, encouraging the intake of water, this is the only way to fully compensate for a deficit of water
Decrease:
Decrease in osmolarity inhibits ADH secretion
What is the ADH negative feedback loop?
ADH is released in response to increased osmolarity
Decreased renal water excretion
Osmolarity decreases
Result is a feedback loop that stabilises osmolarity
Apart from increased plasma osmolarity what can stimulate thirst?
ECF volume decrease
What are the two factors involved in salt appetite?
Hedonistic appetite (Because it tastes good)
Regulatory appetite (to ensure adequate intake)
When does the thirst response stop?
When suffieicent water intake achieved
Before GI absorption, metering mechanism unknown
What is the affect of ADH on the kidney?
Increased levels of ADH result in a smaller volume of urine produced (increased reabsorption)
Glomerulus:
Vasoconstriction (decreased GFR)
Thick ascending limb of loop of henle:
Increased Na+, K+ and Cl- reabsorption
DCT:
Increased water reabsorption in late DCT
Collecting duct:
Increased water and urea reabsorption
Increased K+ secretion
Compare the sensitivity of the mechanisms which trigger ADH release and thirst
ADH release can be triggered by a 1% change in plasma osmolarity
Stimulus for thrist response requires significant increase in osmolarity or decrease in ECF volume (<10% changes)
What is the effect of decreased plasma osmolarity on the kidney?
Lack of ADH stimulation means no aquaporin in later DCT and CD
Limited water intake
Tubular fluid is hypo-osmotic, passes through the hyperosmotic renal pyramid with no change in water content
Loss of large amount of dilute urine
Diuresis
Why is a hyperosmotic interstitium required for reabsorption of water in the Collecting duct?
ADH stimulates the appearance of aquaporins on the apical cell membrane of CD cells
There is no ‘active transport’ of water
Therefore a gradient is required to shift water, moves from the relatively hypoosmotic tubule to the relatively hyperosmotic interstitium
Describe the effects of ADH on aquaporins in the CD
Apical membranes do not contain Aquaporin 2 in absence of ADH
When ADH is released it binds to an extracellular GPCR and stimulates the insertion of aquaporin 2 channels into apical membrane
With the removal of ADH stimulation AQU2 is removed from the apical membrane by endocytosis
What affect does ADH have on the basolateral membrane of CD cells?
No effect
Describe the permeability of the basolateral membrane of CD cells
Contain AQU3 + 4 even in absence of ADH so is always permeable to water
Any water which enters the cell moves through these channels into the interstitium to be reabsorbed into peritubular capillaries
Describe how ADH release is a product of both osmotic and haemodynamic forces
ADH release changes in response to plasma osmolarity
However the magnitude of response and the set point at which that response occurs is governed by haemodynamic forces
Changes in blood pressure and volume effect the ADH response to change in osmolarity
Decreased ECV/Blood pressure:
Set point for ADH release is set to lower osmolarity and the gradient with which the ADH response scales is increased (Smaller increases in osmolarity produce larger ADH responses)
This is because volume conservation is more important than osmolarity should volume crash
Increased ECV/Blood pressure:
Opposite occurs
Set point for ADH release is raised
Gradient for scaling of ADH response is decreased (larger increases in osmolarity produce smaller increases in ADH response)
Describe two clinical concequences of inappropriate ADH secretion
Diabetes Insipidus:
Pituitary gland doesn’t produce adequate ADH or kidney is ADH insensitive
Resulting in losses of large amount of dilute urine
Can be managed with ADH injections or ADH nasal spray
Syndrome of inappropriate ADH hormone secretion(SIADH):
Excessive release of ADH from posterior pituitary or other source
Dilutional hyponatraemia results (increased ECV and decreased osmolarity/Na+ conc.)
Describe the Corticopapillary osmotic gradient
What mechanisms contribute to its formation?
Iso-osmotic at cotico-medullary border
Medullary interstitium is hyperosmotic up to 1000mOsm/L at papilla
Essential mechanisms for it’s production and maintenance:
Active NaCl transport in thick ascending limb
Recycling of Urea
Counter current exchange (vasa recta)
Describe the recycling of urea
Urea is reabsorped from medullary CD
Moves into interstitium and can diffuse back into the Loop of Henle (asc. limb)
High levels of urea in the interstitium causes it to move into the asc. limb passively
ADH decreases fractional excretion and increases recycling
Ok guys, lemme get real with you for a second
This next bit is hard to do in a flashcard, and doesn’t make too much sense to me to break up into multiple flashcards, it’s just something you’ve gotta be able to visualise all happening together.
So, with that said…
Describe the process of counter-current multiplication starting from iso-osmotic tubule and interstitial fluid
Phase 1:
Na+ is pumped out of ascending limb into interstitium to a maximum gradient of 200mOsm/L
- 200mOsm/L in asc. limb*
- 400mOsm/L in interstitium*
Water flows out of the fluid in the decending tubule by osmosis and raises intertubular osmolarity in the descending limb
- Desc. limb becomes 400mOsm/L
Fresh fluid enters from the PCT and the concentrated fluid in the descending limb is moved to the ascending limb
- 400mOsm/L fluid moves into asc. limb*
- Equal with interstitium*
Phase 2:
Na+ pump continues action and produces another 200mOsm/L gradient between ascending limb and interstitium
- 500mOsm/L in interstitium*
- 300mOsm/L in asc. limb*
Osmosis from descending limb is now working over a higher gradient, so fluid in descending limb becomes even more concentrated then before
- 500mOsm/L in desc. limb
More water enters from PCT, same effect as last time
Phase 3:
Na+ pumping continues in asc. limb and raises the interstitial osmolarity further
- 700mOsm/L in asc. limb
All processes occur in tandem
- Quoted osmolarities are typical of the bottom of the loop, once the system is stable a gradient is observed moving down the interstitium, desc. limb and asc. limb of the Loop of Henle. If you can explain why, you’re set.
