L18*-Physiology of the renal system IV-Osmoregulation Flashcards
(19 cards)
How is urine osmolality regulated in CD?
primarily determined by ADH(vasopressin)
Hypothalamic Osmosensors
Explain a summary of ADH
-synthesised in the hypothalamus
- known as arginine vasopressin (AVP) or vasopressin.
- Released from the terminals of the hypothalamic neurones found within the posterior pituitary gland.
- acts in the distal tubule and collecting duct to 👆se water permeability by 👆sing AQP2.
Diuresis = production of urine so antidiuretic hormone(ADH) to oppose the production of urine.
Describe the cellular pathway of regulating AQP2(mainly) on the apical membrane and AQP3 using ADH.
hint :- name the 2 pathways from cAMP to insert more AQP2.
- Most of the water movement in collecting duct is through AQP which is the transcellular pathway. There is also paracellular pathways of water movement in CD.
-AQP3 is constitutively expressed in the basolateral membrane > constantly produced at a steady level, rather than being turned on by external signals. it doesn’t require activation as it is always on. - Insertion of AQP2 highly regulated so cells can insert them or pull them off the membrane. This insertion is regulated by ADH.
1) - PKA -FAST
1. V2 receptors (from a family of GPCRs) for ADH sit on the basolateral membrane.
2. This receptor is available for hormones coming from the circulation bc medullary interstitial space is the interstitial space where which the capillaries exchange substances.
3. V2 receptor is Gs coupled > activates the protein kinase A > 👆se in cAMP production
4. These phosphorylated proteins drive the insertion of vesicles.
5. With the stimulation, the vesicles will be inserted onto the apical membrane to allow more water reabsorption > reduce urine output.
2) - transcription - SLOW
1. cAMP causes positive nucleus transcription.
2. which synthesises AQP2
3. Vesicle containing AQP2 and AQP2 is inserted on the membrane when the vesicles are fused with the apical membrane.
Briefly explain the water permeability/ osmolality form the PCT down to the collecting duct if there is NO ADH.
Osmolality of the PCT is around 285 mOsm.kg-1
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As the filtrate descends down the loop of Henle, its surrounded by high osmolality outside. So the water leaves through D.L of loop of Henle. Salts are pumped out through NKCC2 transporter, the osmolality drops lower than the normal plasma levels.
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if there is no ADH, no or little water reabsorption so the filtrate stays dilute
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dilute urine > very low osmolality
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very high urine output
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so high flow rate in the nephron ( ml.min-1)
Briefly explain the water permeability/ osmolality form the PCT down to the collecting duct if there is MAXIMUM ADH.
lots of insertion of AQP2
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lots of reabsorption in both distal tubule and collecting ducts.
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osmolality of urine is very high
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concentrated urine/urea ?
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low volume of urine
Explain urea
-Urea has a role in maintaining osmolality in the renal medulla.
- In the presence of selective protein starvation, urea production is low and so the kidney has a lower capacity to concentrate urine.
-The urea transporter UT-A1 is also regulated by ADH, in a similar way as for AQP2. > keeps the osmolality in the interstitial space high >aids water reabsorption
Explain Diabetes Insipidus
- Due to a loss of ADH secretion (central diabetes insipidus), or a loss in the sensitivity of the kidney to ADH, often because of a problem with the V2 receptors (nephrogenic diabetes insipidus).
- This means that they are unable to produce
concentrated urine, leading to polyuria (with low osmolality), dehydration, and hypovolaemia. This then causes polydipsia (drinking too much). - If fluid intake is inadequate, they become
hypernatraemic >high [Na+]
Explain the cause and management of Central Diabetes Insipidus
- Causes: head injury, tumors, infection.
- Management:
- give desmopressin (ADH analogue).
- Paradoxical use of thiazide diuretics. Suggested mechanisms of action include: protection against hypernatraemia, encouragement of proximal tubule water reabsorption, and/or an increase in aquaporin expression (not linked to its action on the NCC cotransporter.
Name causes and treatments for nephrogenic diabetes insipidus >lack of sensitivity bc kidney doesn’t response.
- Causes:
o Toxicity (eg. Lithium)- lithium is used for treatment in bipolar disease and other psychiatric conditions.
o Hypercalcaemia
o Genetic, due to mutations in either V2 or AQP2. - Treatment:
o NOT with desmopressin (as insensitive to it bc kidney doesn’t response)
o Thiazide diuretic
o Low salt die
Explain SIADH
-Syndromes in Inappropriate ADH (SIADH) - TOO MUCH ADH so kidneys retain too much water, fluid overload.
* Symptoms are related to inappropriately high ADH, commonly caused by head injury (and many other interesting rarer causes).
* Produce concentrated urine
* Become hyponatraemic - dilute sodium by retaining too much water.
* Treatments include:
V2 receptor antagonists - vactanes- reduce the sensitivity of kidney to ADH.
o Fluid restriction
o Give urea!
Explain Thirst in terms of ADH and other factors.
-Inadequate(insufficient, not enough) water intake causes an increase in osmolality of the plasma.
* As for the regulation of ADH release, osmolality is detected in the anteroventral third ventricle (AV3V) region.
* AV3V neurones project to the median preoptic area of the hypothalamus, which increases thirst.
How does drinking sea water causes dehydration ?
-Osmolality of the sea water is way higher than the maximum osmolality that our kidney can produce.
??????????
-use more water to get rid of the salt.
anything with osmolality >1400mOsm.kg-1 is bad for us.
salt loading ????????😕intake of salt through food.
you you have salty snacks in the bar do you get more thirsty and buy more drinks.
What is the effect of osmolality on the circulating [ADH] (and ADH secretion)
[ADH] is proportional to the rate of secretion at equilibrium with first order clearance.
Explain osmolytes
- The dominant osmolytes in the circulation are Na+ and Cl-, but they aren’t the dominant osmolytes ingested. Much larger quantities of carbohydrates, fat, and proteins are consumed than the mass of:
o Potassium: 3.5g
o Sodium: 2.4g - Excluding fat, all of these intakes reach the
circulation from the gut in a water-soluble form, and therefore contributes osmolytes which can affect osmolality.
Explain Fates post-absorption
- The carbohydrates, converted to simple sugars, are transporter into cells, so don’t contribute significant to osmolality except in the context of diabetes mellitus.C6H12O6 is oxidized to CO2 (rapidly excreted), and water, so only transiently increase osmolality.
- Similarly, proteins are broken down into amino acids which are rapidly taken up by cells, so plasma change in osmolality is small. The nitrogen can be removed through urea (circulating concentration 2.5-6.7mM), which has a high renal clearance; so while the flux is high, the contribution to osmolality is low.
Explain Hyperosmolar hyperglycemic state (HHS)
In diabetes mellitus, the glucose concentration can get so high that it becomes a large contributor to the osmolality.
* Often occurs when glucose is higher than 33mM, giving an osmolality of around 320 mOsm.kg-1
* This hyperosmolality gives strong thirst drive, which if insufficient leads to cellular dehydration, and if sufficient to lower glucose leads to hyponatraemia.
* Causes altered mental status, seizures, and other neurological signs. Also, increases blood viscosity and clotting risk.
How can glucose act as a osmotic diuretic ?
People with diabetes meilitus , have really increasing glucose concentration that hits the tubular maximum in PT, which means glucose cant be reabsorbed. So glucose stays in the filtrate and that high [glucose] so have a high urine output.
