Regulation of ECF Volume and Osmolality Flashcards
What is the distribution of body water?
- 2/3 in ECF
- 1/3 in ICF (20% plasma, 80% interstitial)
What is osmolarity?
a measure of the concentration of substances
What does increased osmolarity (hypertonicity) lead to?
water leaving the cells → shrinkage
What does decreased osmolarity (hypotonicity) lead to?
water entering cells → swelling
What can disturbances in osmolality lead to?
- pure water loss without losing electrolytes
- increase in osmotically active external substances
What can disturbances in fluid volume lead to?
vomiting and diarrhoea i.e. both fluid and electrolytes are lost
What are the compensatory mechanisms for disturbances in osmolality and fluid volume respectively?
- osmolality = increase total body water
- volume = increase body water and electrolytes
What does thirst do?
increase the water intake and dilute the ECF
What are the 2 responses to increased ECF osmolality?
- thirst
- increased ADH secretion
Where is ADH synthesised and stored?
- synthesised in hypothalamus
- stored in posterior pituitary
When is ADH secretion increased?
- increased plasma osmolality
- decreased ECF volume
- low BP
- pain, emotion, stress, nausea and vomiting
- angiotensin II
When is ADH secretion decreased?
- reduced plasma osmolality
- increased ECF volume
- increased BP
- alcohol
What are the actions of ADH?
- vasoconstriction mediated by V1 receptors in vascular smooth muscle
- water reabsorption and concentration of urine mediated by V2 receptor
- increased reabsorption of urea at the medullary collecting duct
What does increased reabsorption of urea at the medullary collecting duct lead to?
increased solute concentration in the medulla, increasing the efficiency of the countercurrent mechanism
What does the countercurrent mechanism lead to?
an increase in the concentration of urine because ADH is able to reabsorb water more efficiently in the presence of the gradient
Where does ADH act?
only on the distal part of the nephron, mainly on the collecting ducts
What are the 7 steps of the ADH mechanism of action?
- water deficit
- ↑ extracellular osmolarity
- ↑ ADH secretion
- ↑ plasma ADH
- ↑ water permeability in distal tubules and collecting ducts
- ↑ water reabsorption
- ↓ water excretion
What can excess ADH production lead to?
SIADH (syndrome of inappropriate ADH secretion)
What causes nephrogenic diabetes insipidus?
inability of the kidneys to respond to ADH (desensitivity)
What is the mechanism of action in individuals with diabetes insipidus?
- ADH deficiency (central DI)/inability to respond to ADH (nephrogenic DI)
- inability to concentrate urine
- production of large amount of dilute urine causing polyuria
- increased thirst (polydipsia)
When is thirst increased?
- ↑ plasma osmolarity
- ↓ blood volume
- ↓ BP
- ↑ angiotensin II
- dry mouth
When is thirst decreased?
- ↓ plasma osmolarity
- ↑ blood volume
- ↑ BP
- ↓ angiotensin II
- gastric distention
How can nephrogenic DI be distinguished from central DI?
by administration of desmopressin, the synthetic analogue of ADH; urine output will reduce upon desmopressin administration in central DI
What is renin?
an acid protease secreted by granular cells in the juxtaglomerular apparatus into the bloodstream
What is renin secretion caused by?
- hypotension
- increased renal SNS activity
- decreased NaCl concentration
- increased circulating catecholamines
When is renin secretion inhibited?
- increased NaCl absorption from macula densa
- increased afferent arteriolar pressure
- angiotensin II
- ADH
What is angiotensin II?
one of the most potent known vasoconstrictors
What are the 4 steps of angiotensin II production?
- in response to low plasma volume, the juxtaglomerular cells secrete renin
- renin cleaves angiotensinogen to angiotensin I
- angiotensin I make its way through the circulation to come into contact with ACE
- ACE converts angiotensin I to angiotensin II
What does angiotensin II in the kidney do?
- stimulate aldosterone secretion which increases sodium reabsorption
- constrict efferent arterioles more than afferent arterioles
What happens when efferent arterioles are more constricted than afferent arterioles?
- ↓ peritubular capillary hydrostatic pressure
- ↑ tubular reabsorption
- ↑ filtration pressure and GFR
What does more sodium reabsorption lead to?
more water reabsorption
What does increased arteriolar constriction by angiotensin II lead to?
a rise in both systolic and diastolic BP
How is aldosterone secreted?
by angiotensin II from the adrenal cortex
Where does aldosterone act?
distal convoluted tubules
What does aldosterone do?
- increase the insertion of the sodium potassium pump in the basal lateral membrane of the distal convoluted tube
- increase the expression of the sodium channels on the apical membrane of the same cells
What are the effects of aldosterone?
increased sodium reabsorption from the filtrate which stimulates osmosis, increases plasma volume and therefore blood pressure
How can the renin-angiotensin-aldosterone axis be manipulated?
- ACE inhibitors
- angiotensin receptor blockers
- aldosterone antagonists
When are ANPs released?
in response to increased ECF volume which stretches the atria
What do ANPs do?
- dilate afferent arterioles and relax mesangial cells
- this reduces the renin secretion and angiotensin II formation
- increase salt and water excretion
