Long Term Control of BP, Oedema and Dehydration Flashcards
Why must ECF volume and osmolality be maintained?
Volume:
- to maintain BP
- important for tissue perfusion and function
- maintained by adjusting total body content of NaCl
Osmolality:
- to maintain cell volume
- important for cell function
- maintained by adjusting total body H20 content
Describe how the ECF volume is controlled
- changes in ECV is sensed by carotid sinus, aortic arch, renal afferent arteriole, or atria
- activates hormonal transducers (RAAS, SNS, ANP, AVP (arginine vasopressin))
- short term: exerts effects in the heart and blood vessels to adjust BP
- long term: exert effects on the kidney causing Na+ excretion
Describe how ECF osmolality is controlled
- changes in plasma osmolality sensed by hypothalamic osmoreceptors
- activates hormonal transducers (AVP and thirst)
- exerts effects on the kidney to cause renal H20 excretion
- exerts effects on brain to cause drinking behaviour resulting in H20 intake
What level is extrarenal Na+ output?
- usually negligible
- unless large fluid loss such as:
- GI tract (vomiting and dairrhoea)
- skin (excessive sweating, burns)
- causes kidneys to respond by reducing Na+ excretion
What is effective circulating volume?
- functional blood volume
- reflects extent of tissue perfusion in specific regions
- changes in ECV paralelel to changes in total ECF volume
In what circumstances will changes in ECF not be parallel to ECF volume?
- in disease states
- congestive heart failure, nephrotic syndrome, liver cirrhosis
- total ECF grossly expanded (oedema/ascites)
- but ECV is low so increasing Na+ retention
- can exacerbate systemic congestion as there is a mismatch in Na+ intake and excretion
Describe volume expansion
- when Na+ persists in face of impaired Na+ excretion
- body retains isosmotic fluid
- expansion of plasma fluid volume and interstitial fluid compartment
- in severe cases, interstitial volume increase so severe that subepidermal tissues swell (causes pitting oedema)
Describe volume contraction
- excessive loss of Na+ into urine
- dramatic shrinkage of ECF volume
What states cause a shrinkage of ECF volume?
- hypovolaemic shock
- prolonged use ot diuretics
- osmotic diuresis in poorly controlled diabetes mellitus
- adrenal insufficiency
- recovery phase after AKI/urinary obstruction
Describe the RAAS mechanism
- angiotensinogen is converted to angiotensin I by renin
- angiotensin I is converted to angiotensin II by the angiotensin converting enzyme (ACE)
- angiotensin II acts on AT1 receptors
What is renin and its function?
- proteolytic enzyme released by granular cells in juxtaglomerular apparatus
- cleaves angiotensinogen to angiotensin I
- cleared by plasma
Where is the angiotensin converting enzyme found?
vascular endothelium in lungs and renal afferent and efferent arterioles
Describe the effect that angiotensin II has
- increases vasoconstriction and TPR in vascular smooth muscle cells of blood vessels
- increases release of ADH, reabsoprtion of H20 in kidneys, and ECV
- increases stimulation of secretion of aldosterone from adrenal glands, Na+ reabsorption and ECV in renal tubules of kidney
Describe the sympathetic NS mechanism
- enhanced activity of renal sympathetic nerves directly causes:
- increased vascular resistance
- increased Na+ reabsorption by tubule cells
- indirectly causes:
- enhanced renin release from granular cells
- together decrease GFR and enhance Na+ reabsorption
- increases Na+ retention and ECV
Describe the arginine vasopressin (AVP) mechanism
- ADH
- released by posterior pituitary in response to increases in extracellular osmolality
- promotes water reabsorption in distal nephron
- also released in response to large reductions in ECV (eg. haemorrhage)
- also causes vasoconstriction and increases renal Na+ retention
Describe the ANP mechanism
- released by atrial myocytes in response to stretch
- increases GFR and renal blood flow
- inhibits Na+ transport in inner medullary collecting duct
- decreases renin release
- inhibits aldosterone release from adrenals
- decreases AVP release
(promotes natriuresis diuresis)
Describe the action of osmotic diuretics and give an example
- mannitol
- modifies content of filtrate
- freely filtered across glomerulus, but cannot be reabsorbed along tubules
- mainly affects PCT and descending loop of Henle
- the presence of solutes that cannot be reabsorbed reduces passive H20 absorption
- increases H20 excreted
- small secondary increase in Na+ excretion
- for acute renal failure
Describe the action of loop diuretics and give examples
- eg. furosemide, bumetanide
- inhibits NKCC in thick ascending limb of loop of Henle
- causes a reduction in reabsorption of Na+, K+ and Cl-
- used in treatment of hypertension where renal function is impaired
- thiazides preferred when renal function preserved
Describe the action of thiazide diuretics and vie examples
- eg. bendroflumethiazide, hydrochlorothiazide
- inhibit NCC
- reduces Na+ and Cl- reabsorption
- also causes vasofilation
- 2nd/3rd line treatment of hypertension
Describe the action of K+ sparing diuretics and give examples
- powerful antihypertensive in combination with loop/thiazide diuretics
- aldosterone antagonists (eg. spironolactone and epleronone): competitively inhibit mineralcorticoid receptor
- ENaC inhibitors (eg. amiloride, triamterence): block epithelial Na+ channel
- reduces driving force for K+ secretion in CT
- combined with loop diuretics to prevent hyperkalaemia