Endocrine Control of Body Fluid Volume

Question 1

Osmolarity of tubular fluid?

Answer 1

When leaving the loop of Henle to enter the distal tubule, the fluid is hypo-osmotic to plasma (100 mosmol/l)

Surrounding interstitial fluid of the renal cortex (300 mosmol/l)

Question 2

Osmolarity of interstitial fluid around the collecting duct?

Answer 2

Collecting duct is bathed by progressively increasing conc. (300-1200 mosmol/l) of surrounding interstitial fluid as it descends through the medulla

Question 3

Major sites for regulation of ions and water balance?

Answer 3

Distal tubule

Collecting duct

Question 4

Hormones regulating ion and water balance?

Answer 4

1. Anti-diuretic hormone (AKA vasopressin) - most important for water reabsorption
2. Aldosterone - increases Na+ reabsorption and also increases H+/K+ secretion

Above two are the most important

3. Atrial natriuretic hormone - decreases Na+ reabsorption
4. PTH - increases Ca2+ reabsorption and decreases phosphate reabsorption

Question 5

Describe what happens in the distal tubule

Answer 5

Tubular fluid is hypo-osmotic (100 mosmol/l) to the plasma

AND

Distal tubule has LOW permeability to water and urea (this depends on circulating levels of ADH)

Thus, urea is conc. in the tubular fluid, helping to establish the osmotic gradient within the medulla

Question 6

2 segments of the distal tubule and the transportation occuring at each?

Answer 6

Early distal tubule:
• Na+/K+/2Cl- transport (allows NaCl reabsorption)

Late distal tubule:
• Ca2+ secretion
• H+ secretion
• Na+ and K+ reabsorption

Question 7

2 segments of the collecting duct?

Answer 7

Early collecting duct:
• Similar to the late distal tubule

Late collecting duct:
• Low ion permeability
• Permeability to water (and urea) is influenced by ADH

Question 8

Synthesis, storage and release of ADH?

Answer 8

An octapeptide that is synthesised in the hypothalamus and transported in nerves for storage in the posterior pituitary

Released into blood when action potentials down the nerves lead to Ca2+ dependent exocytosis; the primary stimulant is an increase plasma osmolarity, e.g: dehydration

Question 9

1/2-life of ADH?

Answer 9

A peptide hormone that has a short 1/2-life of 10-15 minutes

Question 10

Receptors to which ADH binds?

Answer 10

Renal tubular cells have type 2 vasopressin receptor

Smooth muscle cells (of blood vessels) have type 2 vasopressin receptors

Question 11

Effect of ADH on the water permeability of the collecting duct?

Answer 11

1. Binds to type 2 vasopressin receptor and causes increased cAMP
2. There is increased expression of aquaporins (apical water channels)

This increases the permeability of the cell for reabsorption of H2O

Question 12

Effects of maximal ADH conc. in the plasma?

Answer 12

Membrane is not highly permeable, so water moves from the collecting duct lumen along the osmotic gradient into the medullary interstitial fluid, i.e: the tubular fluid equilibriates with the interstitium via aquaporins

This enables hypertonic urine formation (small amount of very conc. urine)

Question 13

Effects of minimal ADH conc. in the plasma?

Answer 13

Membrane has a low permeability, i.e: the collecting duct is impermeant to water so there is not water reabsorption

Urine is hypotonic (large amount of very dilute urine)

Question 14

How does a water deficit trigger release of ADH?

Answer 14

Increases in osmolarity are sensed by hypothalamic osmoreceptors

This stimulates hypothalamic neurones, triggering:
• Thirst (behavioural intake of water)
• Increased ADH release

ADH causes:
• Arteriolar vasoconstriction
• Increased water permeability of the distal and collecting tubules, allowing reabsorption of water

Thus, there is output of a small amount of very conc. urine, allowing plasma volume to increase

Question 15

How does atrial pressure affect ADH secretion?

Answer 15

Decreased atrial pressure increases ADH release (this requires large changes in plasma volume)

Question 16

Other stimulants and inhibitors of ADH?

Answer 16

Stimulatory:
• Nicotine

Inhibitory:
• Stimulation of stretch receptors in upper GI tract exerts
• Alcohol

Question 17

Types of diabetes insipidus?

Answer 17

Central

Nephrogenic

They are typically hereditary

Question 18

Presentation of diabetes insipidus?

Answer 18

Polyuria (up to 20L/day)

Polydipsia

Question 19

Treatment of diabetes insipidus?

Answer 19

Can use ADH replacement for central type

Question 20

Summary of tubular flows and osmolarities?

REFER TO POWERPOINT FOR IMAGE (SLIDE 17)

Answer 20

Flow rate decreases in the loop of Henle due to the large amount of fluid reabsorbed in the PCT

Water leaves the tubular fluid so osmolarity increases

Question 21

What is aldosterone?

Answer 21

Steroid hormone secreted by the adrenal cortex in response to:
• Rising [K+] or falling [Na+] in the blood
• Activating of RAAS

Question 22

Effects of aldosterone?

Answer 22

Stimulates Na+ reabsorption and K+ secretion

Na+ retention contributes to increased blood volume and BP

Question 23

How does [K+] affect aldosterone secretion?

Answer 23

Usually, 90% of K+ is reabsorbed in the early regions of the nephron (mainly in the PCT)

When aldosterone is absent, the rest is reabsorbed in the distal tubule; thus, no K+ is excreted in the urine

An increase in [K+] in the plasma stimulates the adrenal cortex to release aldosterone, which causes K+ secretion

Question 24

How does [Na+] affect aldosterone secretion?

Answer 24

Decrease in [Na+] promotes the indirect secretion of aldosterone by means of the juxtaglomerular apparatus

Question 25

Describe RAAS

Answer 25

Renin secretion is stimulated by:
• Decreased NaCl
• Decreased ECF volume
• Decreased BP

This cleaves angiotensinogen into angiotensin I, which is converted into Ang. 2 by ACE

Question 26

Triggers for renin release from granular cells in the JGA?

Answer 26

1. Reduced pressure in the afferent arteriole:
   • More renin release, more Na+ reabsorbed and BP restored
2. Macula densa cells sense the amount of NaCl in the distal tubule:
   • If NaCl reduced, increased renin released thus more Na+ reabsorbed
3. Increased sympathetic activity as a result of reduced BP:
   • Granular (renin-secreting) cells directly innervated by sympathetic NS cause renin release

Question 27

Mechanism of action of aldosterone in increasing Na+ reabsorption in the distal and collecting tubule?

Answer 27

Increases apical expression of Na+ channels, so more Na+ reabsorbed into the cell

Increases basolateral Na+/K+ pump expression, so Na+ leaves the cell to enter the interstitial fluid

Question 28

Pathophysiology of fluid retention heart failure?

Answer 28

Failing heart means there is a decreased CO and BP; the low BP stimulates RAAS, allowing increased salt and water retention

Question 29

Treatment of heart failure?

Answer 29

Low salt diet

Diuretics (loop)

ACEIs (stop fluid and salt retention and arteriolar constriction)

Question 30

Production and release of ANP?

Answer 30

Stored in atrial muscle cells and released when they are mechanically stretched, due to increased PV

Question 31

Effects of ANP?

Answer 31

Promotes excretion of Na+ and diuresis, thus decreasing PV

Causes vasodilatation and increased GFR so more Na+ and H2O are filtered into the urine

Also, inhibits sympathetic NS so CO and total peripheral resistance (TPR) decrease, reducing BP

Question 32

2 mechanisms controlling micturition?

Answer 32

1. Micturition reflex
2. Voluntary control (can override the micturition reflex) - deliberately tightening the external urethral sphincter and pelvic diaphragm

Question 33

Difference between water diuresis and osmotic diuresis?

Answer 33

Water diuresis - increased urine flow but not an increased solute excretion

Osmotic diuresis - increased urine flow is due to a primary increase in salt excretion

Any loss of solute in the urine must be accompanied by water loss (osmotic diuresis) but the reverse is not true, i.e: water diuresis is not necessarily accompanied by equivalent solute loss.