6/7 - Integration of salt and water balance

Question 1

What should I know

Answer 1

1. Hormonal mechanisms that control fluid and sodium balance
2. Know the control and actions of ADH (anti-passing urine) and ang ll

Question 2

Why do we need a kidney?

Answer 2

• There is always a gap between intake and output of body fluids. The kidney allows you to maintain a large range of fluid intakes and keep osmolality and volume relatively constant
• the kidneys are important for BP, acid base, osm, blood filtering and hormone release

Question 3

What hormones do the kidneys release?

Answer 3

• renin (RLS for ang ll production)

- erythropoietin to stimulate RBC production and so is important in determining the O2 carrying capacity of the blood

Question 4

What happens with dehydration summary

Answer 4

1. water deficit OR increase in salt
2. increase in ECF osmolality
3. osmoreceptors sense increase and signal adh secretion from post pit
4. increase in adh permeability in distal tubules and collecting ducts
5. increased water retention reduced excretion
   > feel thirsty when either salt increases or fluid decreases

Question 5

Do barorecptors influence osmoreceptors?

Answer 5

Yes

Question 6

Where do you find osmoreceptors?

Answer 6

Osmoreceptors are found in supraoptic and paraventricular nuclei

Question 7

How do osmoreceptors work?

Answer 7

They sense both changes in osmolality and circulating blood volume and result in adh release.
Inputs to the hypothalamus from the medullary vasomotor center which receive input from the baroreceptors increase adh release in response to a reduced circulating volume.

Question 8

How do changes in omsol cause a response from osmoreceptors

Answer 8

Small changes in osmol cause small deformations of neurons. In hyperosmotic fluid the size of the neuron changes and opens gap junction channels which causes the neuron to depolarise or repolarise and hence send a signal to the hypothal (if structures are cross-linked)

Question 9

What is adh released in response to

Answer 9

An increase of less than 1% osmolarity or decreased volume (greater than 10%) of the ECF

Question 10

What is ADH secretion most sensitive to?

Answer 10

Secretion of ADH in response to increased osmolarity has a LOWER threshold and higher sensitivity/slope than its response to a decreased EC volume

Question 11

Physiological stimuli to adh secretion

Answer 11

1. Increased plasma osmol 1-2%

2. Decreased ECF vol 7-10%

Question 12

Non-physiological stimuli to adh secretion

Answer 12

• pain, stress
• drugs: nicotine, SSRIs
• Carcinomas
• CNS disorders
• alcohol inhibits ADH secretion

Question 13

How does ADH work?

Answer 13

Enters the blood/renal interstitial fluid and causes insertion of AQP2 on the tubular lumen causing increased water reabsorption and reduced ECF osmol until the signal decreases (FB loop)
Occurs by ADH stimulating V2 receptor > cAMP > PKA > protein phosp

Question 14

What is thirst driven by?

Answer 14

High osmol not vol

Question 15

What senses changes in BV?

Answer 15

Cardio-pulmonary volume receptors - also sends info to osmoreceptors

Question 16

Where does adh act?

Answer 16

Distal tubule, cortical collecting tubule and outer and inner medullary collecting ducts

Question 17

What is it called if ADH levels are low

Answer 17

Either central or nephrogenic diabetes insipidus

Question 18

Central Diabetes Insipidus (neurogenic or pituitary DI)

Answer 18

• inadequate ADH secretion/production
• is a problem with hypothal or pp
• may be due to brain injury, tumor or infection
• rarely hereditary
• can be treated with ADH analogues as receptors work fine
• ADH is absent

Question 19

Nephrogenic DI

Answer 19

• collecting tubule is unresponsive to ADH
• conc urine cannot be produced
• can be caused by certain drugs i.e. lithium
• less commonly hereditary i.e. congenitial defect in the V2 receptor or Aquaporin2
• is NOT currently treatable
• sufficient ADH is being released by kidney is unresponsive

Question 20

What receptor does ADH work on?

Answer 20

V2

Question 21

How to tell apart neurogenic/central diabetes insipidus and nephrogenic?

Answer 21

• is there ADH circulating
• Are they responsive to ADH
• water deprivation test

Question 22

What is the water deprivation test?

Answer 22

Used to decipher between the 2 types of DI. An ADH analogue is given. If urine osmol increases i.e. there is a response to ADH and more water is reabs then it is central DI

Question 23

What is SIADH

Answer 23

Syndrome of inappropriate ADH secretion

Question 24

SIADH

Answer 24

• defect in appropriate ADH secretion
• higher than normal ADH levels and so patient reabsorbs and retains water inappropriately and their ECF omsol decreases.
• if their water intake is not tightly controlled then a hypo-osmolar state can result which is not good

Question 25

What is SIADH commonly caused by?

Answer 25

• brain injury or tumour
• anti-cancer drugs
• cancer

Question 26

SIADH treatment

Answer 26

Restrict water intake instead give an isotoinc fluid so their osmol doesn’t drop

Question 27

What results did they see when they injected kidney into a rabbit?

Answer 27

Increase in BP. Due to RAAS (something produced by kidney that led to a increased BP)

Question 28

What 3 factors promote renin secretion by JG cells in the afferent arteriole?

Answer 28

1. Decrease in afferent arteriole pressure
2. Increase in sympathetic activity
3. Reduction in NaCl delivery to macula densa cells (reduced renal perfusion)

Question 29

Where are MD cells

Answer 29

TAL/distal convoluted tubule

Question 30

Primary difference between ADH and ang 2

Answer 30

ADH just affects water reabs while ang 2 primary increases Na reabsorption in the prox tubule which then brings water with it usually

Question 31

How to correct osmol

Answer 31

ADH > drag in water

- why adh is very sensitive to osmol changes

Question 32

Correct vol

Answer 32

Usually to bring salt back and forth which brings water with it via ang 2
- renin is released in response to smaller changes in BP or BV

Question 33

If the right renal artery becomes abnormally constricted, what will happen to renin secretion by each of the kidneys?

Answer 33

R: the right kidney receives reduced renal perfusion and afferent arteriole pressure and so renin secretion will increase. Sensed by the infrarenal baroreceptor and reduced flow to MD cells. The increase in renin secretion will increase ang 2 and increase arterial BP both of which will act on the L kidney to REDUCE renin secretion.