Renal regulation of ECF Osmolarity and volume Flashcards
How will increases and decreases in osmolarity affect cells?
increased osmolarity will shrink cells
decreased will cause swelling
How does ECF osmolarity increase stimulate ADH release?
- ECF increases so osmolarity decreases
- Aquaporin channels of the osmoreceptores in the hypothalamus open allowing water out the cell
- cells shrink which is sensed by stretch sensitive channels
- these channels open allowing sodium and calcium in causing depolarisation
- action potential travels to supraoptic and paraventricular nuclei which signal to posterior pituitary to release ADH
Where does ADH act and what does it do?
Distal Convoluted tubule and collecting duct where inserts aquaporins into wall of ducts to allow more water to flow into blood (diluting concentrates so decreases osmolarity)
How does the body react when ECF osmolarity decreases?
- Aquaporin channels now allow water into the cell by osmosis
- this results in expansion of the cell and inactivation of stretch receptors
- so no depolarisation and therefore action potential sent so no ADH release
- no ADH means no aquaporin channels in DCT and CD so water lost in urine
What cells sense blood pressure changes and where are they located?
Baroreceptors sense stretch in vessel walls
located in carotid sinus and arch of aorta
Other than changes in ECF osmolarity what influence secretion of ADH
Blood pressure
Low BP will increase ADH release so more water retained and blood volume increases to increase BP
How does decrease in BP increase ADH?
Baroreceptors no longer sense stretch on blood vessel so reduce AP sent to supraoptic nerve and paraventricular (usually inhibit SON and PAN) so ADH stimulation possible
What factors effect the release of aldosterone?
increased: - Plasma K+ - ACTH - Ang II decreased: - Plasma PH - Atrial stretch - BP
What does release of aldosterone do in the kidneys?
- increase sodium and water reabsorption
- increase potassium secretion into urine
Through what protein is aldosterone effect in the kidneys achieved?
Increase in expression of sodium/potassium ATPase
At what point in the kidneys and through what channels does potassium move in and out of blood/urine?
- proximal convoluted tubule most moves back into blood (through potassium channels)
but some can move back into urine through Na/K channels - Ascending Loop of Henlé moves back into blood via Na/Cl/K cotransporter and K channels and out again through Na/K
- Also through DCT and collecting duct reabsorbed into blood
In hyperkalaemia how does nephron adapt to decrease potassium absorption into blood?
- Increase expression of Na/K channels in DCT and collecting ducts
- allowing for far more excretion of K
What is primary hyperaldosteronism and what is it also called?
Conns syndrome - not due to excessive renin secretion
What is secondary hyperaldosteronism?
Caused by excessive Renin secretion / Overactivity of RAAS system
Why does hyperaldosteronism cause hypokalaemia?
Aldosterone removing too much potassium from the blood
How is hyperaldosteronism treated?
Surgery or aldosterone antagonists
What causes primary hypoaldosteronism?
- Primary adrenal insufficiency
- Congenital adrenal hyperplasia
- medications e.g. ACE inhibitors/diuretics
What causes secondary hypoaldosteronism?
- diseases of pituitary or hypothalamus (dec ACTH)
- decreased Ang II production
- renal diseases e.g. diabetic neuropathy
- drugs e.g. NSAIDS (which effect kidneys)
What can hypoaldosteronism cause?
Hyperkalaemia - which causes:
- Palpitations
- muscle pain
- muscle weakness
- abnormal heart rhythms
- cardiac arrest
- death
How can you differentiate between primary and secondary hypoaldosteronism?
ACTH stimulation test:
Primary = low aldosterone response
Secondary = High aldosterone response
How is RAAS system involved in regulation of ECF osmolarity?
- ECF osmolarity dec
- if due to less sodium being reabsorbed
- This is detected by kidneys and renin released
- renin release means more angiotensinogen > Ang I > Ang II
- Ang II acts on adrenal cortex to release more aldosterone
- aldosterone increases Na/K pump expression so more sodium reabsorbed
How does increased sympathetic nerve activity increase CO and BP?
- Increases renin release
1) resultant increase in Na reabsorption will increase water reabsorption also - Inc water = inc Blood volume
- inc blood volume increase BP and CO
2) Ang II increase (due to renin) will also act on brain to increase ADH secretion which will further increase water reabsorption and blood volume
How is Blood pressure balanced using RAAS?
Blood pressure decrease stimulates renin increase which through above mechanisms will increase BP again
Where is the negative feedback loop in the regulation of the ECF osmolarity?
If triggered by ECF osmolarity, hypothalamus will act to stop ADH release and decrease water reabsorption
How does sodium reabsorption stimulate renin secretion?
- Sodium reabsorbed through: Na/Cl/K cotransporter, Na/H exchanger in Macula densa cells of DCT
- sensed and Prostaglandin released from DCT to juxtaglomerular cells of afferent arteriole
- which triggers production of renin from juxtaglomerular cells and secretion into arteriole
What else triggers secretion of renin?
Sympathetic nerve fibres which release adrenaline which act on beta one receptors and use cAMP to then signal renin release
What is the negative feedback loop for Renin secretion?
Stretch receptors in afferent arteriole will inhibit cAMP when increased stretch of blood vessel so less renin secreted
less renin also means less sodium reabsorbed
What stimulates release of ANP?
- Decreased Blood volume
- Cardiac distension
- sympathetic stimulation
- Ang II
What does ANP do?
- decreases renin
- increases GFR
- Vasodilation
What are the resulting effects of ANP?
- dec BP
- dec BV
- Natriuresis (potassium sparing)
Why is ANP useful in CHF and hypertension?
as decreases BP without effecting potassium
Why is ADH production in hypothalamus separate from thirst?
1) Thirst then able to anticipate fluid loss e.g. during food intake
2) thirst surpassed rapidly after drinking before osmolarity is actually normalised
3) Osmotic threshold for activation of thirst higher than for ADH release
- means can increase fluid into body rather than just limiting excretion of fluid
What activates thirst?
- high plasma osmolarity
- inputs from brain e.g. when anticipating food
- inputs from body e.g. sensing salt in mouth or hypovolemia
