Regulation of Fluid Osmolarity Flashcards
T or F: dehydration leads to depletion of fluid in all body compartements.
True, with this decrease in volume there is an increase in osmolarity within all compartments
How does the kidney respond to changes in body fluid osmolarity?
Central Regulation senses increased osmolarity and DECREAES H2O secretion via:
• AVP/ADH
• THIRST CENTER is also stimulated
What are the major sources of daily water intake and output?
Input:
• Metabolism (400 mL)
• Food (500 mL)
• Drinking (1500 mL)
Output: • Feces (100 mL) • Skin (400 mL) • Breathing (400 mL) • Urine (1500 mL)
Where is ADH release from and what sensor detects that it needs to be released?
• where does it act in the kidney?
HYPOTHALMUS senses changes in osmolarity and sends signals down to its nerve endings in the Supraoptic and Paraventricular Nuclei in the POSTERIOR PITUITARY.
Works on Collecting Duct
How does ADH (vasopressin) stimulate INCREASED reabsorption in the Collecting Duct?
ADH lands on V2 (or V1, V3) receptor
V2 receptor stimulates cAMP production and PKA activation
PKA phosphorylates Vesicles containing AQUAPORIN-2 which fuses with the membrane
Increase H2O uptake and Increased Urine Results
At what plasma osmolarity does AVP start to kick in?
• when are maximum levels of AVP (ADH/vassopressin) being released?
270 mOsM
at 290 Vasopression (AVP/ADH) reaches a maximum
What system helps to reduce plasma osmolarity when ADH is maxed out?
Thirst Mechanism ONLY KICKS in at high plasma osmolarities to supplement ADH
***Looks like it kicks in at around 280 mOsM
T or F: in addition to being increased by plasma osmolarity, ADH is secreted in response to changes in plasma volume
True
Does ADH secretion increase with an increase or decrease in plasma volume?
Decreases in Plasma volume INCREASES plasma ADH
T or F: the maximal Vasopressin response due to increased fluid osmolarity is greater than the response to decreased fluid volume.
False, the response to decreased fluid volume is nearly 3X as great as the response to osmolarity
What happens to ECFV and Osmolarity in cases of severe diarrhea?
• how does vasopressin respond?
ECFV - Reduced
Osmolarity - Reduced
This means you have competing effects on ADH (vasopressin) release
ECFV response OVERRIDES osmolarity response and AVP (ADH) is released
What happens as a result of ADH response in cases of severe diarrhea and vomiting?
• what if patient drinks a lot of fluid?
• treatment?
ADH acts to upreguated AQP-2
More H2O is taken up and Urinary concentration is increased
Patient drinks lots of Fluid and Plasma gets DILUTED
ECFV increases and HYPONATREMIA results
*Treat these people with Isotonic Saline
What are some symptoms of hyponatremia?
• Treatment?
- Lethargy
- Hyporeflexia
- Mental Confusion
If diarrhea and vomitting have caused hyponatremia then isotonic saline should be administered to slowly
What is a frequent symptom of not being able to concentrate urine?
• causes of this?
Nocturia - frequent urination at night
Causes:
• Age
• Renal Failure
• Infection, Prostate Hypertrophy
How is osmolar clearance measured?
Cosm = (UF x Uosm) / Posm
How do we assess the kidney’s ability to concentrate urine?
OSMOLAR CLEARANCE
Cosm = (UF x Uosm) / Posm
What is the osmolar clearance in a normal kidney?
2 ml/min
What is Free water clearance?
• what do values obtained from free water clearance tell you?
Free Water Clearance:
• the amount of water without any solute that is excreted by the kidney
NEGATIVE FWC:
• Urine is being concentrated to try to reduce plasma osmolarity
POSITIVE FWC:
• Urine is being diluted to increase plasma osmolarity
What parts of the nephron and collecting system ACTIVEY transport Na+?
• channels involved?
Thin Descending Limb - 0
Thin Ascending Limb - 0
Thick Ascending Limb - ++++++++++
• NK2C channel (blocked by loop diuretics)
Distal Convoluted Tubule - +
• NaCl - co-transporter (blocked by thiazide diurectics)
Collecting Duct - Cortical - +
• ENaC?
Collecting Duct - Medullary - +
• ENaC?
What parts of the nephron and collecting duct system allows for the passive movement of Water?
• channels involved?
Thin Descending Limb - ++++++++++
• Aquaporins 1, 3 and 4.
Thin Ascending Limb - 0
Thick Ascending Limb - 0
Distal Convoluted Tubule - + ADH
• Aquaporin-2 w/ ADH
Collecting Duct - Cortical - + ADH
• Aquaporin-2 w/ ADH
Collecting Duct - Medullary - + ADH
• Aquaporin-2 w/ ADH
What parts of the nephron and collecting duct system allows for the passive movement of NaCl?
Thin Descending Limb - 0 Thin Ascending Limb - ++ Thick Ascending Limb - 0 Distal Convoluted Tubule - 0 Collecting Duct - Cortical - 0 Collecting Duct - Medullary - 0
What parts of the nephron and collecting duct system allows for the passive movement of Urea?
Thin Descending Limb - + Thin Ascending Limb - + Thick Ascending Limb - 0 Distal Convoluted Tubule - 0 Collecting Duct - Cortical - 0 Collecting Duct - Medullary - +++++++
What is the importance of the Medullary collecting duct being permeable to urea?
• Urea can flow out back into the medulla near the LOH to concentrate filtrate in this portion of the nephron
What are 5 key features needed to maintain hyperosmolarity of the medulla?
- Special anatomical arrangement of LOH and Vasa Recta and Peritubular Capillaries
- Active transport of Na+ and co-transport of K+ and Cl- OUT of THICK ascending limb into medullary ISF
- Active transport of Na+ out of collecting duct into ISF
- Passive diffusion of urea from inner medullary collecting duct into medullary ISF
- Diffusion of only small amts. of H2O from medullary tubules to medullary interstitium
How large of a gradient is created by the elecroneutral co-transport via NK2C in the thick ascending LOH?
200 mOsm gradient
Describe the 6 steps in creating the hyperosmolarity seen in the medulla?
- 300 mOsm; evenly distributed
- Active Na+ transport from TALH to make a 200 mOsm gradient
- Descending limb transports H2O out into Hyperosmolar interstitium
- Flow of Fluid pushes the now Higher Osmolar Fluid in the Descending LOH to Ascending LOH
- Na+ is again actively transported out
- Water from descending limb again flows towards the higher gradient
What percentage of the osmolarity in the medullary ISF is due to urea?
40% of osmolarity is due to Urea
How is urea able to contribute to the osmotic gradient in the LOH?
LOH is very slightly permeable to urea
DCT and cortical collecting duct are Impermeable to Urea
*** by the time the fluid arrives at the Medullary Collecting Duct urea is very concentrated and rapidly diffuses Back into the Medulla
What prevents the vasa recta from washing out the hyperosmolar fluid in the medulla?
- Medullary Blood Flow is only 1-2% of renal flow and it only travels at 50 ml/min
• too little flow for H2O to diffuse out and neutralize the gradient - Vasa Recta changes osmolarity to match the gradient in the medulla and cortex as it moves up
What are 3 possible reasons that the kidney would loose its ability to concentrate urine?
- Defect in the production or regulation of AVP secretion
- Inability of Collecting Ducts to respond to AVP
- Failure to form Medullary Osmolarity Gradient
What are the 2 type of diabetes incipidus?
• result of these disorders?
a. Central Diabetes Insipidus
b. Nephrogenic Diabetes Insipidus
***Both result in the kidney being unable to concentrate urine
What causes central Diabetes Insipidus?
Pituitary Gland Fails to Release AVP (ADH/vasopresson)
• with no ADH there is less aquaporin-2 in the Collecting Duct and less reabsorption of H2O (/concentration of urine)
What causes Nephrogenic Diabetes Insipidus?
Mutations/Damage that prevents collecting ducts from responding to AVP leads to Diabetes Insipidus
- V2 receptor Mutation
- Aquaporin-2 mutation
- Drugs: LITHIUM, Tetracycline
What drug could you give to differentiate Nephrogenic Diabets Insipidus from Central Diabetes insipidus?
DDAVP - a person with a central AVP deficiency should respond well to this drug because their receptors are still in tact.
Those with Nephrogenic Changes still won’t be able to concentrate urine
