6 - Concentration and dilution of urine
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- What two receptors does ADH bind? What are the effects of binding each?
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1.V-1: vasoconstriction
2.V-2: antidiuretic effects - Where is ADH synthesized? Where is it stored and released from?
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*synthesized in the supra-optic nucleus of the hypothalamus
*stored and released from nerve endings in the posterior pituitary - What two blood variables influence the release of ADH?
- Osmolarity and blood volume.
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T/F:
When blood osmolarity is at its normal level of 295-300mOsm/L, there is no detectable ADH in circulation. - False: even under normal conditions there is a baseline amount of ADH in circulation.
- How is blood osmolarity detected for release of ADH? How is blood volume detected?
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*osmolarity is detected by special osmosensor cells in the hypothalamus
*blood volume is detected by atrial stretch receptors - What factors result in a greater release of ADH?
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1.High osmolarity
2.Low blood volume - What factors result in inhibition of ADH release?
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1.Decreases in osmolarity
2.Increases in blood volume - What is the half-life of ADH in circulation?
- 20-30 minutes.
- What happens when ADH binds the V-2 receptor?
- Adenylate cyclase is activated and cAMP produced. cAMP activates PKA which phosphorylates serine residues on AQP-2. This causes AQP-2 to be transferred to the apical membrane.
- Where is AQP-1 found?
- In regions not under the control of ADH (e.g. proximal tubule, vasa recta, dLOH).
- Where is AQP-3 found? How is it affected by ADH?
- On thhe basolateral membrane of most tubular epithelia. It is not under the regulation of ADH.
- Where is AQP-4 found?
- On the hypothalamic glial cells, where it possibly plays a role in osmosensation.
- What kinds of symptoms are seen in humans who are deficient in AQP-1?
- They are normal in the basal state but show an inability to concentrate urine during water restriction. The main effect is seen in the descending loop of Henle.
- Does ADH have any short-term or long-term effects in the ascending loop of Henle?
- No short-term effects but possible long-term up-regulation of Na+/K+/2Cl- transporters.
- What is normal water loss each day, and how is it lost?
- Normal loss is 1.5L each day, with 1.0 liters lost through sweat, feces, etc. and 0.5L lost through urine excretion.
- Identify the condition seen in dehydration that results in maximal release of ADH.
- Hypovolemic hypernaturemia.
- What are 4 symptoms of diabetes insipidus?
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1.Polyuria
2.Polydipsia
3.Nocturia
4.Increased hematocrit
5.Increased plasma osmolarity
6.Low blood pressure - What are two possible causes of central diabetes insipidus?
- A genetic mutation resulting in lack of ADH production or damage to ADH-producing cells.
- What abberent lab value is seen in the nephrogenic but not the central form of diabetes insipidus?
- Patients with nephrogenic diabetes will have high plasma [ADH].
- What is the basic defect in nephrogenic diabetes insipidus? What implications does this have for treatment of these patients?
- ADH is synthesized, but cells are not responsive. This means that exogenous ADH will be an ineffective treatment.
- What are two ways nephrogenic diabetes insipidus can be acquired (i.e. after birth)?
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1.Lithium overdose
2.Excessive fluid intake
3.Pregnancy (although this is really pseudonephrogenic DI) - What 2 forms of congenital nephrogenic diabetes insipidus have been found?
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1.X-linked dominant mutation of the V-2 receptor.
2.Autosomal recessive mutation of AQP-2 - Why is low-dose diuretic an accepted treatment for nephrogenic diabetes insipidus?
- It causes a slight contraction of the ECV which activates mechanisms to conserve salt and by extension, water.