Lec 26 Flashcards
Primary hormone for water regulation
vasopressin
Osmolality change to cause vasopressin secretion
1% or 3mOsmol/kg
Osmolality amount to equal 0 vasopressin
decreases by about 10mOsmol/kg @ 280mOsmol/kg
Osmolality by which Maximum effective concentration of vasopressin is reached
increases by 10mOsmol/kg @ 300mOsmol/kg
Plasma volume change to cause vasopressin secretion
15% decrease in Blood volume to evoke change (less sensitive than osmolality)
Thirst
As blood volume depletes thirst increases and AVP is released after a 15% decrease
Vasopressin:target
Nephrons of the kidneys
Portions of a nephron affected by Vasopressin
Cortical collecting duct(CCT)[most], Outer medullary collecting duct(OMCD) , Inner medullary collecting Duct (IMCD)[least]
Changes in permeability of specific compartments of the nephron
is due to Vasopressin
Renal Medulla : osmolality
very high 1200 (increase in water permeability in collecting ducts=concentrated urine)
What is the concentration/osmolarity of urine as it enters the distal convoluted tubules?
100 mOsm/liter
In the face of excess water: is vasopressin present?
No, collecting tubules impermeable to H20 to get rid of it
Dilute urine
Due to no vasopressin, low osmolality, large volume of dilute urine, no h20 reabsorbed
Concentrated urine
due to vasopressin present, high osmalality, distal and collecting tubules permeable to h20, Peritubular capillaries reabsorb h20.
Peritubular capillaries
absorb scarce H2O in urine when vasopressin is present making ducts permeable.
Osmolarity of Urine in the face of water deficit
1200 mOsm/L
Osmolarity of Urine in the face of excess water
100 mOsm/L
Aquaporins
A tetramer* – (monomers made up of 269 AA) integral membrane proteins whose role is to allow h20 flow. 13 members are present and 6 of them are found in the kidney
Exploding cell assay
demonstrate the existence of water channels using Xenopus oocytes. Channels = increased permeability
AQP1
high water permeability (proximal tubules and thin descending limb)
AQP2
variable water permeability of the collecting ducts is due to the regulation of AQP2 by Vasopressin
Nephron structures that contain AQP1
Proximal convoluted tubule (PCT)
Proximal straight tubule (PST)
Thin descending limb (tDLH)
Action of Vasopressin: AQP2
activated AC, increases cAMP that acts on AQP3 and AQP4 to release H20. cAMP also leads to a translocation of AQP2 to the membrane abutting the tubule membrane and an increase in AQP2 synthesis. (acts on CREB)
CREB
cAMP response element binding protein - synthesizes more AQP2 to be translocated to the lumen membrane
Diabetes Insipidus
rare condition marked by excessive thirst and the excretion of large quantities of dilute urine. Similar to Osmotic diuresis )diabetes melitus) and chronic renal failure, both have high rates of solute excretion.
Diabetes Mellitus
osmotic diuresis , gets rid of large amounts of dilute urine
Central/Neurogenic DI
Central/Neurogenic = failure of vasopressin secretion causing large decrease in urine production and large increase in urine osmolality in response to treatment with vasopressin or a synthetic analogue called desmopressin.
Desmopressin
a treatment for Central/Neurogenic DI and bed wetting- increase in urine osmolality-
* a longer lasting analogue of vasopressin contains D-Arg @ position 8
Nephrogenic DI
inability of the kidneys to respond normally to vasopressin. Treated with replacement therapy with a diuretic to reduce elevated Na concentrations. Nephrogenic DI can be caused by Mutations in the gene for AQP2.
Mutations in gene for AQP2
leads to Nephrogenic DI
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
(tumor, meningitis, trauma, or drugs)excessive secretion of vasopressin, decreased osmolality, low levels of plasma Na (hyponatremia) and cell swelling. Treatment = fluid restriction and infusion of hypertonic Na.
Suckling
oxytocin release is stimulated by suckling due to mechanoreceptors in the nipple stimulating the Hypothalamus .
releases PRL, OT, and GnRH
Parturition
childbirth; initiated by oxytocin by an increase in the number of oxytocin receptors in the myometrium that occurs in the response to increased levels of estrogen prior to birth.
Milk ejection reflex(milk let down)
Suckling causes Hypothalamus to send nervous pathway to posterior pituitary to increase Oxytocin.
Milk secretion
Suckling causes hypothalamus to inhibit Dopamine release from arcuate nucleus that removes the inhibition . the anterior pituitary increases the release of prolactin. causes milk secretion
4 effects of Suckling
- stimulates sensory nerves from the breast to the spinal cord to the brain
- arcuate nucleus of the hypothalamus, inhibits Dopamine release. Increasing PRL release
- supraoptic and paraventricular nuclei of the hypothalamus triggers production and release of OT in the posterior pituitary
- in preoptic area and arcuate nucleus, GnRH is inhibited. thus inhibiting the release of FSH and LH and inhibits the ovarian cycle.
