What is osmolarity?
Measure of the solute concentration in a solution - depends on the number of dissolved solutes present. The greater the number of dissolved particles, the greater the osmolarity
How much more water and salt than we need do we consume to replace that which was lost?
Why do we need to get rid of excess volume, water and salt?
Volume: oedematous and BP rises Water: Dilute salt in body > decreased osmolarity so cells will SWELL Salt: Too high salt levels > cells will SHRINK
What is the most abundant component of the plasma and ECF?
What is the most prevalent solute in the plasma ad ECF?
What does the level of salt determine and what is water balance used for?
Salt determines ECF volume and water balance regulates plasma osmolarity
Of the total body water, how much is intracellular fluid and how much is ECF?
How is water removed from the body?
Skin and sweat: variable and uncontrollable (fever, climate, activity) - 450ml/day Faeces: uncontrollable (diarrhoea) - 100ml/day Urine output: variable and controllable - 1500ml/day
How much of the filtered load reaches the descending loop of Henle, the distal convoluted tubule and the collecting duct?
How is the urine concentrated above normal plasma osmolarity?
A region of hyperosmolar interstitial fluid is produced
How is the region of hyperosmolar interstitial fluid established?
Descending loop impermeable to salts but permeable to water
Ascending loop impermeable to water but 'permeable' (pumps out) salts
Urea permeability of the bottom of the loop and the collecting duct
What is the function of the vasa recta?
It is permeable to water and solutes - water diffuses out of the descending limb and solutes diffuse into the desc. limb In the ascending limb the opposite happens, so O2 and nutrients are delivered without the loss of gradient
What is Vasopressin?
Peptide hormone - 9 a.a. Synthesised in hypothalamus, packaged into granules Secreted from posterior pituitary Binds to specific receptors on basolateral membrane of principal cells in the collecting ducts
What does VP cause in the collecting duct?
Causes the insertion of aquaporins in the cell membranes, increaing water permeability - AQ2 mainly
What does VP stimulate in the CD?
Stimulates urea transport from CD into thin asc. limb of LoH and interstitial tissue by increasing the membrane localisation of UTA1 and UTA3 in the CCD
What is the trigger for ADH release?
Plasma osmolarity above 300mOs - regulated by osmoreceptors in the hypothalamus Marked fall in blood volume and BP - monitored by baroreceptors/stretch receptors
What substance inhibits ADH release?
Ethanol, leading to dehydration as urine volume increases
What is the water permeability like in the nephron?
What happens when there is a decrease in plasma osmolarity? - Water Load
Decreased plasma osmolarity (detected by hypothalamic osmoreceptors) -> decreased ADH release -> Decrease CD permeability -> increase urine flow rate
What happens when there is low ADH/water diuresis?
Solute reabsorption without water reabsorption lowers urine osmolarity to 50mosmol/l SO: large volume of dilute urine
What happens when there is increased plasma osmolarity? - Dehydration
^ Plasma osmolarity -> ^ thirst and ^ ADH release (both detected by hypothalamic receptors) -> ^ ADH release -> ^ CD permeability -> Decrease urine flow rate
What tends to lower plasma osmolarity?
Increased water intake AND decreased fluid loss
What happens when there is high ADH/maximal antidiuresis?
Osmotic equilibration in the cortex and medulla leads to high urine osmolarity - so SMALL volume of concentrated urine
What is the negative feedback loop of increased plasma osmolarity?
What are the 3 classes disorders of water balance?
No/insufficient production of ADH No detection of ADH (mutant ADH receptor) No response to ADH signal (AQ mutant)
Give an example of a water balance disorder and of its symptoms
Diabetes insipidus - unremitting thirst and excretion of large amount of watery urine
Why is the hyperosmolar environment required for retention of water?
Water is reabsorbed by osmosis so need to generate a hyperosmolar env compared to the fluid in the collecting duct
Fluid starts with osmolarity approaching that of plasma and contains solutes that need to be excreted - removal of water would increase the osmolarity, needing to maintain osmotic gradient that allows this to happen as the fluid passes along the latter part of the nephron
What is the importance of the urea permeability in the CD in response to ADH?
Increased urea permeability causes urea to move down its conc gradient into the interstitium and increase the interstitial osmolarity so more water can be reabsorbed
Identify 2 triggers of ADH secretion
Hyperosmolarity identified by osmoreceptors
Low BP identified by baroreceptors