L8/9 Regulation of Body Fluid Osmolality and Volume Flashcards
Normal plasma osmolality is ____________________, variation in either direction of _____________________ => operation of the body’s osmolality regulating mechanism
Normal plasma osmolality is 280-290mOsm/kg H2O, variation in either direction of ~3mOsm/kg H2O => operation of the body’s osmolality regulating mechanism
What regulates the Osmolality of Body Fluids?
Osmolality of plasma detected by osmoreceptors in supraoptic and paraventricular areas of the anterior hypothalamus=> regulate the release of ADH by posterior pituitary into the bloodstream
ADH is synthesized in the _____________________
Precursor is transported from the hypothalamus to the ________________within nerve fibers and is cleaved to a nonapeptide (9 aa) as it moves down the axons
In nerve terminals, ADH stored as insoluble complexes in _________________
ADH is synthesized in the hypothalamus (supraoptic nucleus)
Precursor is transported from the hypothalamus to the posterior pituitary within nerve fibers and is cleaved to a nonapeptide (9 aa) as it moves down the axons
In nerve terminals, ADH stored as insoluble complexes in secretory granules
When plasma is hyperosmolar ADH released from posterior pituitary binds to ______ receptors on _____________ cells of the collecting duct resulting in increased water reabsorption and excretion of concentrated urine:
○ Binding of _______ by ADH => shuttling of water channels (________) into and out of the apical membrane (____________ are persistently present on basolateral)
○ Further aided by the hyperosmolar gradient in the medullary interstitium (established by thick ascending limb and ADH)
When plasma is hyperosmolar ADH released from posterior pituitary binds to V2 receptors on principal cells of the collecting duct resulting in increased water reabsorption and excretion of concentrated urine:
○ Binding of V2 by ADH => shuttling of water channels (AQP2) into and out of the apical membrane (AQP3/4 are persistently present on basolateral)
○ Further aided by hyperosmolar gradient in the medullary interstitium (established by thick ascending limb and ADH)
How is the volume & pressure of the vascular system assessed?
Baroreceptors: Neuronal endings sensitive to stretch or distortion produced by arterial blood pressure changes, receptors located in both the low-pressure (left atrium and large pulmonary vessels) and the high-pressure (aortic arch and carotid sinus) sides of the circulatory system
Intrarenal baroreceptors: Pressure sensitive juxtaglomerular cells of afferent arterioles, which respond to decreased renal arterial pressure by secreting more renin
Under conditions due predominantly to water gain or loss, the sensory receptors that initiate the reflexes controlling ADH secretion are _________________
Under conditions due predominantly to water gain or loss, the sensory receptors that initiate the reflexes controlling ADH secretion are osmoreceptors
Osmoreceptors only require ~ 1% change while a 5% to 10% decrease in blood volume or pressure is required before ADH secretion is stimulated by baroreceptors
Baroreceptor control of ADH secretion?
Baroreceptors decrease their rate of firing in response to decrease in blood volume (5%-10%) leading to increased release of ADH (inverse relationship)
=> Elevated ADH increases the permeability of the collecting ducts
=> Water retained to help stabilize the extracellular volume
Priority of Kidneys facing circulatory collapse?
Haemorrhage increases ADH release via volume receptor (baroreceptors) response, so that water is retained (osmoregulation subordinated to volume regulation)
When faced with circulatory collapse, kidneys will continue to conserve water, even though by doing so they reduce body fluid osmolality (Reduces Set Point for ADH Secretion)
Differenced between Osmoreceptor and Baroreceptor ADH regulation?
Pituitary gland unable to secrete ADH
Central Diabetes Insipidus
Collecting ducts unable to respond to ADH due to V2 receptor mutation
Nephrogenic Diabetes Insipidus
Plasma ADH levels elevated above expected for body fluid osmolality, blood volume & pressure i.e.usually due to small tumors (i.e.lung oat cell carcinoma) producing ADH
Syndrome of Inappropriate ADH Secretion (SIADH)
Malfunctions of the ADH System?
Central Diabetes Insipidus: Pituitary gland unable to secrete ADH
Nephrogenic Diabetes Insipidus: Collecting ducts unable to respond to ADH due to V2 receptor mutation
Syndrome of Inappropriate ADH Secretion (SIADH): plasma ADH levels elevated above expected usually due to small tumors (i.e.lung oat cell carcinoma) producing ADH
ADH versus Thirst Thresholds?
ADH set point is 285 mOsm, thirst threshold is 295 mOsm so thirst is stimulated at fluid osmolality at which secretion of ADH is already maximal
__________________ denotes the volume of pure (solute-free) water that must be removed from, or added to, the flow of urine (in ml/min) to make it iso-osmotic with plasma.
How is it calculated?
Positive= __________ urine
Negative = ________ urine
Zero = ____________ urine
Free water clearance (CH2O) denotes the volume of pure (solute-free) water that must be removed from, or added to, the flow of urine (in ml/min) to make it iso-osmotic with plasma.
Free Water Clearance (CH2O) = Urine Flow Rate - (Urine Flow Rate (Urine Osmolality/ Plasma Osmolality)
Positive CH2O= hypotonic urine
Negative CH2O = hypertonic urine
Zero CH2O = Urine iso-osmotic w/ plasma