Urinary Concentration & Dilution Lecture 2024 PDF

1502 Urinary Concentration & Dilution Fall 2024 Lecture 27 Wednesday, Oct 23: 9am Dr. Layla Al-Nakkash...

1502 Urinary Concentration & Dilution Fall 2024 Lecture 27 Wednesday, Oct 23: 9am Dr. Layla Al-Nakkash [email protected] 1 © L. Al-Nakkash 2020  Learning Objectives 1. Describe pathways to maintain body fluid osmolarity. 2. Examine the corticopapillary osmotic gradient. 3. Examine countercurrent multiplication in the Loop of Henle. 4. Examine sodium handling in the nephron and thick ascending limb. 5. Describe the role of the vasa recta in countercurrent exchange. 6. Describe the role of urea in concentrating urine. 2  Osmoregulation Body fluid osmolarity is maintained at 300 mOsm/L In reality it is 290 (simplified to 300) Small changes in osmolarity result in hormonal responses that modify water reabsorption by the kidneys. To return it back to normal Renal mechanisms for water reabsorption are key to maintain constant body fluid osmolarity Variations in water reabsorption result in variations in urine osmolarity. When urine osmolarity = blood osmolarity This is ? An isosmotic urine When urine osmolarity > blood osmolarity This is ? A hyperosmotic urine ( ADH) When urine osmolarity < blood osmolarity This is ? A hyposmotic urine ( ADH) © L. Al-Nakkash 2024 1. Describe pathways to maintain body fluid osmolarity 3  4 1. Describe pathways to maintain body fluid osmolarity  Response to water Deprivation sweat and water 1 Water is lost from the body in the from of ____ vapor this will  ______ plasma osmolarity. (Insensible water loss) 2  Osmolarity will stimulate osmoreceptors in the _________ hypothalamus 3 This stimulates thirst response and secretion of ADH 4 The posterior pituitary secretes ADH: stimulates the kidneys to increase water permeability of the late distal tubule & collecting duct.  water permeability increases water reabsorption in the late distal tubule 5 and collecting ducts. As more water is reabsorbed urine osmolarity increases & urine volume decreases.  water reabsorption results in more water going to the body fluids. 6 Along with increased thirst and more drinking, plasma osmolarity will ___  back to normal value. What type of feedback system is this? negative © L. Al-Nakkash 2024 1. Describe pathways to maintain body fluid osmolarity 5  6 © L. Al-Nakkash 2024 1. Describe pathways to maintain body fluid osmolarity  Corticopapillary Osmotic Gradient This is an osmolarity gradient of interstitial fluid in the kidney from the cortex to the papilla – Cortex osmolarity = 300 mOsm/L similar to other body fluids – Moving from the cortex to outer medulla, inner medulla, and papilla, the interstitial fluid osmolarity increases. – Papilla osmolarity = 1200 mOsm/L © L. Al-Nakkash 2024 2. Examine the corticopapillary osmotic gradient. 7  Corticopapillary Osmotic Gradient Key points to consider: – What solutes contribute to the osmotic gradient? – What mechanisms deposit these solutes in the interstitial fluid? © L. Al-Nakkash 2024 2. Examine the corticopapillary osmotic gradient. 8  Countercurrent Multiplication The FLOW OF TUBULAR FLUID PCT – Glomerular filtration is an ongoing process, i.e. Fluid is constantly entering the nephron. – As new fluid enters the descending limb from the proximal tubule, then an equal volume must leave the ascending limb and enter the distal tubule. – Fluid that enters the descending limb will 300 mOsm/L have an osmolarity = ____________ because it has just come from the PCT. 9 © L. Al-Nakkash 2024 2. Examine the corticopapillary osmotic gradient.  Corticopapillary Osmotic Gradient The corticopapillary gradient is an osmotic gradient present in the interstitial fluid (ISF) of the medulla 300 ISF osmolarity ranges from 300 600 mOsm/L at the corticomedullary border to 1200 mOsm/L in the ISF at the papilla. 900 The corticopapillary gradient is created by the loop of Henle Papilla 1200 utilizing a counter current multiplier process. 10 © L. Al-Nakkash 2024 2. Examine the corticopapillary osmotic gradient.  Countercurrent Multiplication A function of the loop of Henle. The role is to deposit NaCl in the interstitial fluid of the deeper regions of the kidney. https://www.researchgate.net/publication/276533888_Natural_Ventilation_with_Heat _Recovery_A_Biomimetic_Concept © L. Al-Nakkash 2024 3. Examine countercurrent multiplication in the Loop of Henle 11  Countercurrent Multiplication There is an osmotic gradient from the cortex to the medulla in the interstitial space – this helps remove water from urine in the collecting duct. Descending limb: – No active transport of NaCl – Water __________ permeable Ascending limb: https://www.researchgate.net/publication/276533888_Natural_Ventilation_ – Active reabsorption of NaCl with_Heat_Recovery_A_Biomimetic_Concept – Water __________ impermeable © L. Al-Nakkash 2024 3. Examine countercurrent multiplication in the Loop of Henle 12  Sodium handling in the nephron The majority of Na+ reabsorption is in the * proximal convoluted tubule. In the PCT, water 2/3 of Na+ reabsorption is linked to Na+ reabsorption With water * reabsorption. Permeable to water The thick ascending limb 1/4 of Na+ reabsorbs ¼ of the filtered reabsorption load of Na+. Impermeable to water Without water The last step of Na+ reabsorption (~8%) in the DCT and CD (*) is regulated by aldosterone © L. Al-Nakkash 2024 4. Examine sodium handling in the nephron and thick ascending limb 13  Sodium balance: thick ascending limb Reabsorption of ~25% of Na+ occurs here. It is load-dependent, what would this mean? more Na+ delivered → more reabsorbed ↓ NaCl The apical membrane has the Osm Na/K/2Cl cotransporter. The energy driving this cotransporter ↑ NaCl + gradient Osm comes from the Na maintained by the _____________. Na+ /K+-ATPase This is the site of action of loop diuretics: furosemide, bumetanide. ↓ They will _____ NaCl absorption ADH will stimulate this transporter: increasing Na/K/2Cl activity 14 © L. Al-Nakkash 2024 4. Examine sodium balance in the nephron and thick ascending limb 14  Countercurrent Multiplication Fluid becomes more concentrated flowing down the descending limb. Fluid becomes more dilute as it flows up the ascending limb The largest osmotic gradient across the wall of the ascending limb and the interstitial fluid is 200mOsm/L 300-100, 600-400, 900-700 Countercurrent: flow moves in https://www.researchgate.net/publication/276533888_Natural_Ventilation_ opposite directions through the with_Heat_Recovery_A_Biomimetic_Concept two limbs. © L. Al-Nakkash 2024 3. Examine countercurrent multiplication in the Loop of Henle 15  Countercurrent in the Vasa Recta Vasa recta are capillaries that follow the loop of Henle. Hairpin loops Vasa recta undergo countercurrent exchange – a passive process that helps to maintain the osmotic gradient. Vasa recta are freely permeable to small solutes and water, creating good countercurrent exchange. Blue arrows = solute movement Green dashed arrows = water movement 16 © L. Al-Nakkash 2024 5. Describe the role of the vasa recta in countercurrent exchange  Countercurrent in the Vasa Recta Blood entering the descending limb has an osmolarity= 300 mOsm/L. As blood flows down the vasa recta following the direction of the descending limb, small solutes _____ NaCl / urea diffuse into the vasa recta. As blood flows up the capillary the reverse occurs. Solutes diffuse out This process is _______ passive 17 © L. Al-Nakkash 2024 5. Describe the role of the vasa recta in countercurrent exchange  Countercurrent in the Vasa Recta At the bend, blood has an osmolarity = to fluid at the tip of the papilla. 1200 mOsm/L As blood flows up the ascending limb What happens to small solutes? Diffuse out of the ascending limb (blue arrows) What happens to water? Diffuse into the ascending limb (green arrows) Blood in the ascending limb of the vasa recta equilibrates with the interstitial fluid. 18 © L. Al-Nakkash 2024 5. Describe the role of the vasa recta in countercurrent exchange  Urea recycling Urea is generated by the liver. Around 50% of urea in the filtered load is excreted and the remainder is recycled within the kidney. Urea contributes towards a hyperosmotic renal interstitial fluid (__  osmolarity) and to the generation of a concentrated urine. Urea contributes towards the medullary interstitial fluid osmolarity. Low protein diets, decrease urea production and decrease the kidneys ability to concentrate urine. 19 © L. Al-Nakkash 2024 6. Describe the role of urea in concentrating urine  Urea recycling Contributes to the establishment of the corticopapillary osmotic gradient. 1. At the medullary collecting ducts 1. In the cortical and outer medullary 2. collecting ducts: ADH increases water permeability. But not urea permeability 3. 2. Water is reabsorbed from the collecting ducts and urea remains in 4. the tubular lumen. Therefore, ADH causes an increase in tubular fluid [urea]. 20 © L. Al-Nakkash 2024 6. Describe the role of urea in concentrating urine  Urea recycling 3. In the inner medullary collecting ducts: ADH increases water 1. permeability and increases the action of the facilitated transporter for urea. UT1 2. Thus, more ADH→  UT1 3.  urea transport 4. 4. With an increase [urea] of tubular fluid, urea diffuses from the tubular fluid into the interstitial fluid (of the inner medulla). 21 © L. Al-Nakkash 2024 6. Describe the role of urea in concentrating urine  Urea recycling Urea recycling depends on ADH. 1. When ADH levels ↑ (with water deprivation), urea is recycled into the 2. inner medulla adding to the corticopapillary osmotic gradient. 3. When ADH levels ↓ (with water 4. drinking), urea is not recycled. This effect of ADH on urea recycling is how ADH helps maintain the corticopapillary osmotic gradient. 22 © L. Al-Nakkash 2024 6. Describe the role of urea in concentrating urine  ADH increases permeability of the late distal tubule and collecting ducts True / False The corticopapillary osmotic gradient ranges from 100-300 mOsm/L True / False The papilla osmolarity > cortex osmolarity True / False Most Na reabsorption occurs in the collecting duct True / False In the thick ascending limb, Na reabsorption is stimulated by ADH True / False Both descending and ascending limbs are equally water permeable True / False In the inner medullary CD‛s, ADH decreases UT1 and urea transport True / False © L. Al-Nakkash 2024 23  ADH increases permeability of the late distal tubule and collecting ducts True / False   water reabsorption   urine osmolarity The corticopapillary osmotic gradient ranges from 100-300 mOsm/L True / False 300-1200 The papilla osmolarity > cortex osmolarity True / False 1200 > 300 Most Na reabsorption occurs in the collecting duct True / False most is in the PCT ~67% In the thick ascending limb, Na reabsorption is stimulated by ADH True / False ADH increases Na/K/2Cl activity Both descending and ascending limbs are equally water permeable True / False Descending is water permeable Ascending is not water permeable In the inner medullary CD’s, ADH decreases UT1 and urea transport True / False ADH will  UT1 &  urea transport & more urea is recycled into the inner medulla, increasing the osmotic gradient © L. Al-Nakkash 2024 24