deck_1648468 Flashcards
What happens in terms of plasma osmolality when water intake is less than water excretion?
• Plasma osmolarity increases
In what situation does plasma osmolarity decrease?
• When water intake is greater than water excretion
What is the typical osmolarity of urine?
• 50-1200 Osm/l
Do changes in water balance affect volume?
• No, they effect osmolarity • Problems with Na+ balance affect
What is the osmolarity of body fluids?
275 - 295 mOsm/kg
What do problems with Na+ balance cause?
• Changes in ECF volume
Where is plasma osmolality sensed?
• By hypothalamic osmoreceptors in the organum vasculoum of the laminae terminals (OVLT) of the hypothalamus
Where is the OVLT found?
• Anterior and ventral to the third ventricle
What is special about the OVLT?
• Fenestrated leaky endothelium which exposes it directly to systemic circulation
What are the two efferent pathways which regulate osmolarity?
• Thirst • ADH
Which method of regulation is the first line of defence in modulating osmolarity?
ADH
What two changes trigger release of ADH?
• Increase in osmolarity of the blood • Baroceptors detecting decreased stretch (low blood volume)
What are the effectors of thirst, and what is affected?
• Brain - Drinking behaviour
What is the effector of ADH, and what is the consequence?
• Kidney • Renal water excretion
When is ADH released?
• When water is lost and osmolarity increases by 1%, osmoreceptors in the hypothalamus initiates release of ADH from posterior pituitary
How is ADH secretion inhibited?
Decreased osmolarity
What is thirst stimulated by?
• Large increase in fluid osmolarity •
What is drinking induced by?
• Increase in plasma osmolarity • Decrease in ECF volume
When is ADH released stimulated?
• When there is a 1% increase in plasma osmolarity due to loss of water
Describe ADH
• Small peptide hormone • 9 AA long
What initiates the release of ADH?
• Osmoreceptors in the OVLT of the hypothalamus initiate the release of ADH from the posterior pituitaruy
What does ADH act on to regulate volume and osmolarity of urine?
• The kidney
What happens if ADH is low?
• Water diuresis will occur due to decreases reabsorption
What happens if ADH is high?
• Small volume of urine excreted
What are the three main effects of ADH?
• Increases the permeability of the collecting duct to water via the addition of aquaporin • Increases permeability of collecting duct to urea • Increases activity of Na/K/Cl- co-transporter in the TAL of the loop of henle (Assists in generation of hypertonic medullary intersticium)
Where is ADH secreted from?
• The posterior pituitary
Where is ADH synthesised?
• As a preprohormone in the • Supraoptic nuclei of hypothalamus • Paraoptic nuclei of hypothalamus • Is then sent to posterior pituitary and stored
Outline the effects of ADH on the nephron
• Vasoconstriction at glomerulus • Increased Na/K+/2Cl- cotransport absorption at ascending limb of loop of henle • Increased water reabsorption in late DT and Cortical collecting duct via addition of aquaporin 2 to the apical membrane • Increased K+ secretion of and Urea reabsorption in cortical collecting duct • Insert aquaporin 2 in the apical membrane of cells in collecting duct
What exactly does ADH in relation to Urea?
• Increases permeability of medullary region of collecting duct, causing its reabsorption • Rise in urea concentration in the tissues allows it to passively move down its conc gradient into the ascending limb
What is the apical membrane of the collecting duct like the absence of ADH?
Does not contain aquaporin 2, so no water reabsorption
What is Urea recycling?
• ADH increases permeability of medullary part of collecting duct to urea, causing its reabsorption • This causes water to follow (THE POINT OF ADH! :D) • Rise in urea conc in the tissues causes Urea to passively move down its conc gradient into TAL, which is permeable to Urea but not to H20 (NO WATER REABSORPTION!) • Urea then passes into collecting duct, where it is reabsorbed
What does the basolateral membrane of a cell always contain?
• Aquaporin 3 and 4 • Constantly permeable to water • Allows water that enters across the apical membrane to pass into peritubular blood
How is hypo-osmotic urine generated?
• Reabsorb solute from nephron • No ADH stimulation means no aquaporin in the DCT and collecting ducts • Limited water reuptake in latter DCT and limited in collecting duct • Tubular fluid rich in water passes through the hyperosmotic ranal pyramid with no change in water
What is required if body needs hyperosmotic urine?
• Kidney must reabsorb as much water as possible • Requires a hypertonic interstitium • ADH secreted and assists
What is the corticopapillary osmotic gradient?
• Osmotic potential of medulla increases as you go down • Isosmotic at cortico-medullary borderMedullary intersticium hyperosmotic at papilla
What is the max osmolarity of the medullary interstitcium?
100 mOsmol/kg
What are the three key mechanisms involved in establishing the cortiocopapillary osmotic gradient?
• Active NaCl transport out of TAL • Recycling of urea • Unusual arrangement of blood vessels in medulla descending components act in close opposition to ascending components
How does the action of the thick ascending limb of the loop of henle generate the medullary gradient?
• Diluting action on filtrate • Removes solute without water , increasing osmolarity of the intersticium
What do loop diuretics do?
• Block NaK2Cl transporters • Medullary intersticium becomes isosmotic and copious dilute urine is produced
How is movement of urea significant?
• Permeable to most membranes • Moves out of collecting duct, water follows • Water is taken into peritubular capillaries
Outline the process of countercurrent multiplication
• Tubule filled with isotonic fluid • Na+ ions pumped out at ascending loop into intersticium, raising osmotic pressure outside tubule and lowering it inside • Fresh fluid enters descending limb which is permeable to water. Water leaves and enters medullary intersticium • More fluid enters from glomerulus, pushing concentrated fluid into TAL • Na+ pump in ascending limb pumps out more into intersticium
What is the final gradient of countercurrent multiplication limited by?
• The diffusional process
What is the max conc difference between inside and outside of the tubule?
• 200 mOsmol
What is counter current multiplication maintained by?
• Counter current exchange at the vasa recta
What is counter current exchange?
• Flow of blood in organised vasa recta opposite to flow of fluid in tubules maintains concentration gradient
What is the dilemma surrounding blood flow to the medulla?
• Must maintain concentration gradient (medullary hyper-tonicity) • Need to deliver nutrients
What are the two ways in which vasa recta preserve the hypertonicity of the medullary intersticium?
• Low blood flow to prevent wash out • Travel in counter current direction
What is the configuration for the vasa recta known as?
• Hair pin configuration
What is the exchange which occurs in vasa recta as it moves along the loop of henle?
• Isosmotic blood in descending limb of vasa recta enter hyperosmotic milieu of medulle • Ions diffuse into vasa recta and water diffuses out • Osmolarity of vasarecta increases until in reaches tip of hairpin loop, where it is isosmotic with medullary intersticium • Blood ascending has higher solute concentration than medulla, so solute moves out and water moves inLittle net dilution
Where is the vasa recta most concentrated?
• At the bottom of the hair pin bend
What happens as the vasa recta moves up the ascending portion of the loop of henle?
• Solutes conc outside becomes less concentrated • Water moves into vasa recta and solutes move out
What is SIADH?
• Syndrome of inappropriate Anti-Diuretic Hormone secretion
Give a mechanism by which SIADH can come about
• Secretion of ADH is not inhibited by the lowering of blood osmolarity
What are the consequences of SIADH?
• Excessive amounts of water retained, causing blood osmolarity to drop and causing hyponatraemia
Give four causes of SIADH
• Malignant tumours secreting ADH analogues • Head trauma causing ADH release • Non-malignant pulmonary disordersDrugs
Give five symptoms of hyponatremia
• Nausea • Vomiting • Headache • Confusion Lethargy
What can NIADH be treated with?
• ADH receptor antagonists • Treating underlying causeHypertonic saline infusion
Other than NIADH, give another condition which comes about as a result of abnormal ADH secretion
Diabetes insipidus
What are two causes of Diabetes insipidus?
• Failure of ADH secretion - Causes Central Diabetes Insipidus • Inadequate response of kidneys to ADH - Causes Nephrogenic Diabetes Insipidus
