Endocrine Control of Body Fluid Volume Flashcards
Osmolarity of tubular fluid?
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)
Osmolarity of interstitial fluid around the collecting duct?
Collecting duct is bathed by progressively increasing conc. (300-1200 mosmol/l) of surrounding interstitial fluid as it descends through the medulla
Major sites for regulation of ions and water balance?
Distal tubule
Collecting duct
Hormones regulating ion and water balance?
- Anti-diuretic hormone (AKA vasopressin) - most important for water reabsorption
- Aldosterone - increases Na+ reabsorption and also increases H+/K+ secretion
Above two are the most important
- Atrial natriuretic hormone - decreases Na+ reabsorption
- PTH - increases Ca2+ reabsorption and decreases phosphate reabsorption
Describe what happens in the distal tubule
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
2 segments of the distal tubule and the transportation occuring at each?
Early distal tubule:
• Na+/K+/2Cl- transport (allows NaCl reabsorption)
Late distal tubule:
• Ca2+ secretion
• H+ secretion
• Na+ and K+ reabsorption
2 segments of the collecting duct?
Early collecting duct:
• Similar to the late distal tubule
Late collecting duct:
• Low ion permeability
• Permeability to water (and urea) is influenced by ADH
Synthesis, storage and release of ADH?
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
1/2-life of ADH?
A peptide hormone that has a short 1/2-life of 10-15 minutes
Receptors to which ADH binds?
Renal tubular cells have type 2 vasopressin receptor
Smooth muscle cells (of blood vessels) have type 2 vasopressin receptors
Effect of ADH on the water permeability of the collecting duct?
- Binds to type 2 vasopressin receptor and causes increased cAMP
- There is increased expression of aquaporins (apical water channels)
This increases the permeability of the cell for reabsorption of H2O
Effects of maximal ADH conc. in the plasma?
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)
Effects of minimal ADH conc. in the plasma?
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)
How does a water deficit trigger release of ADH?
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
How does atrial pressure affect ADH secretion?
Decreased atrial pressure increases ADH release (this requires large changes in plasma volume)
Other stimulants and inhibitors of ADH?
Stimulatory:
• Nicotine
Inhibitory:
• Stimulation of stretch receptors in upper GI tract exerts
• Alcohol
Types of diabetes insipidus?
Central
Nephrogenic
They are typically hereditary
Presentation of diabetes insipidus?
Polyuria (up to 20L/day)
Polydipsia
Treatment of diabetes insipidus?
Can use ADH replacement for central type
Summary of tubular flows and osmolarities?
REFER TO POWERPOINT FOR IMAGE (SLIDE 17)
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
What is aldosterone?
Steroid hormone secreted by the adrenal cortex in response to:
• Rising [K+] or falling [Na+] in the blood
• Activating of RAAS
Effects of aldosterone?
Stimulates Na+ reabsorption and K+ secretion
Na+ retention contributes to increased blood volume and BP
How does [K+] affect aldosterone secretion?
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
How does [Na+] affect aldosterone secretion?
Decrease in [Na+] promotes the indirect secretion of aldosterone by means of the juxtaglomerular apparatus
Describe RAAS
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
Triggers for renin release from granular cells in the JGA?
- Reduced pressure in the afferent arteriole:
• More renin release, more Na+ reabsorbed and BP restored - Macula densa cells sense the amount of NaCl in the distal tubule:
• If NaCl reduced, increased renin released thus more Na+ reabsorbed - Increased sympathetic activity as a result of reduced BP:
• Granular (renin-secreting) cells directly innervated by sympathetic NS cause renin release
Mechanism of action of aldosterone in increasing Na+ reabsorption in the distal and collecting tubule?
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
Pathophysiology of fluid retention heart failure?
Failing heart means there is a decreased CO and BP; the low BP stimulates RAAS, allowing increased salt and water retention
Treatment of heart failure?
Low salt diet
Diuretics (loop)
ACEIs (stop fluid and salt retention and arteriolar constriction)
Production and release of ANP?
Stored in atrial muscle cells and released when they are mechanically stretched, due to increased PV
Effects of ANP?
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
2 mechanisms controlling micturition?
- Micturition reflex
- Voluntary control (can override the micturition reflex) - deliberately tightening the external urethral sphincter and pelvic diaphragm
Difference between water diuresis and osmotic diuresis?
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.
