Lecture 13: Integration of Salt and Water balance

Question 1

ADH

Answer 1

= AVP = Arginine vasopressin
Function: Increased Water reabsoprtion into ICF/ECF –> concentrated urine + decreased flow
Location: DT + Collecting Tubule (+ collecting duct epithelia) –> Acts at end of circuit as is final bulk water changes
- allows for conservation of water during dehydration

Question 2

Location of ADH release

Answer 2

ADH = Nonapeptide
Hypothalamus –> osmoreceptor, baroreceptor, cardiopulmonary receptor stimulation) stimulate Supraoptic and Paraventricular neuron –> release of synthesised precursor protein to Posterior Pituitary –> posterior pituitary storage granules situate at nerve terminals

Question 3

What sort of peptide is ADH

Answer 3

Nonapeptide

Question 4

Acute vs Chronic ADH release

Answer 4

Acute: Osmolality change
1. Osmoreceptors in hypothalamus
Chronic: Blood Volume Change
1. Baroreceptors (change pressure)
2. Cardiopulmonary Volume receptors --> STRETCH of atrium and ventricles sensed

Question 5

Sensitivity of osmoreceptor, baroreceptor and cardiopulmonary receptor to changes

Answer 5

ECF Osmolality change (acute): <1% change (lower threshold (starts earlier), higher sensitivity(quicker/steeper gradient))
ECF Blood Volume change (chronic): >10% change (longer period passes + slower increased release)

Question 6

Physiological and Non physiological causes of ADH release

Answer 6

Physiological:
1. Increased plasma osmolality
2. Decreased ECF volume
Non-Physiological:
1. Pain, stress
2. Drugs: narcotics, carbazapine, vincristine, chloropropamide, ifosfamise, nicotine, SSRI
3. Carcinomas (esp. small cell)
4. Pulmonary disorders
5. CNS disorders
(6. Alcohol inhibits ADH secretion)

Question 7

Inhibition of ADH secretion

Answer 7

ADH

Question 8

Is the descending limb of LOH permeable to water?

Answer 8

Yes

Question 9

To what extent can ADH reduce water loss

Answer 9

1L/hour 15mL/hour

Question 10

SIADH

Answer 10

Syndrome of Inappropriate ADH release
Increased plasma ADH --> inappropriate water retention ( -ve Free water clearance) --> significantly low osmolality (hypo-osmotic state) --> tasteless urine
Causes:
1. Brain injury/tumour
2. Some anti cancer drugs
3. Lung cancer and some other cancers
Treatment:
Restricted water consumption --> decreased H2O input --> relatively less able to be retained

Question 11

Central and Nephrogenic Diabetes insipidus

Answer 11

Low/absent ADH levels –> First sign: High urine volume

Question 12

Central Diabetes Insipidus

Answer 12

Head Trauma/ brain injury/tumour/infection –> disruption of osmoreceptors –> Central DI –> changing osmolality but unable to produce ADH –> increased urine volume and decreased urine taste

• Rarely hereditary
• Treatment: ADH analogs

Question 13

Nephrogenic Diabetes Insipidus

Answer 13

ADH release from posterior pituitary --> non-functional V2 receptor in kidney's nephron's CD/DT --> ADH unable to make any changes --> increased volume and diluteness of urine
Causes: 
1. Drugs (Lithium)
2. Hereditary (less common): 
- Congenital V2 defect
Inherited AQP-2 defect
No Treatment available

Question 14

Test to differentiate between Central and Nephrogenic Diabetes Neuropathy

Answer 14

Water Deprivation Test

• give DDADH –> Increase in Central DI not nephrogenic
• • grapht

Question 15

ADH cellular mechanism

Answer 15

ADH binds to V2 receptor on distal tubule –> AQP2 receptor inserts into tubular lumen –> Water enters cell and is reabsorbed

Question 16

What are causes of significant volume change causing Renin release?

Answer 16

Severe sweating/diarrohea –> haemorrhage/ salt and water loss –> large change in effective circulating volume –> primary stimulus to the granular cells of the juxtaglomarular apparatus –> renin release

Question 17

What are the primary stimuli for renin release?

Answer 17

1. Afferent arteriolar pressure
2. Sympathetic activity
3. Macula Densa NaCl delivery

Question 18

What is the most powerful sodium retaining hormone in the body?

Answer 18

Angiotensin II

Question 19

What are the primary resulting steps after angiotensin II release?

Answer 19

1. Aldosterone release
2. Vasoconstriction of vascular beds
3. Enhances tubuloglomerular feedback

Question 20

What is the experiment, which tested the relationship b/w Kidney and CVD

Answer 20

significant #case of hypertension is related to kidney function
Experiment: Artificially constricted kidney –> measured blood pressure –> BP is elevated and then remains high
Treatment: Hypertensive medication includes ACE inhibitors (vascular bed) and ARBs Angiotensin II Receptor Blockers

Question 21

What was the first experiment which hinted at the relationship b/w the kidneys having an effect on blood pressure?

Answer 21

Extracts taken from rabbit kidney –> injected into another animal –> increase in blood pressure
- indicated that there was something in the kidney that has a vasoconstrictor role –> can cause an increase in BP
(renal pressor agent angiotensin II)
Graph***

Question 22

What occurs at the cellular level with the RAAS system?

Answer 22

1. Increased renin secretion
2. Increased angiotensin
   a. Increased aldosterone
   b. Constriction of efferent arteriole
   c. binds to AT1 –> reabsorption of AT1