Long Term Control of BP, Oedema and Dehydration

Question 1

Why must ECF volume and osmolality be maintained?

Answer 1

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

Question 2

Describe how the ECF volume is controlled

Answer 2

• 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

Question 3

Describe how ECF osmolality is controlled

Answer 3

• 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

Question 4

What level is extrarenal Na+ output?

Answer 4

• 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

Question 5

What is effective circulating volume?

Answer 5

• functional blood volume
• reflects extent of tissue perfusion in specific regions
• changes in ECV paralelel to changes in total ECF volume

Question 6

In what circumstances will changes in ECF not be parallel to ECF volume?

Answer 6

• 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

Question 7

Describe volume expansion

Answer 7

• 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)

Question 8

Describe volume contraction

Answer 8

• excessive loss of Na+ into urine

- dramatic shrinkage of ECF volume

Question 9

What states cause a shrinkage of ECF volume?

Answer 9

• hypovolaemic shock
• prolonged use ot diuretics
• osmotic diuresis in poorly controlled diabetes mellitus
• adrenal insufficiency
• recovery phase after AKI/urinary obstruction

Question 10

Describe the RAAS mechanism

Answer 10

• 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

Question 11

What is renin and its function?

Answer 11

• proteolytic enzyme released by granular cells in juxtaglomerular apparatus
• cleaves angiotensinogen to angiotensin I
• cleared by plasma

Question 12

Where is the angiotensin converting enzyme found?

Answer 12

vascular endothelium in lungs and renal afferent and efferent arterioles

Question 13

Describe the effect that angiotensin II has

Answer 13

• 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

Question 14

Describe the sympathetic NS mechanism

Answer 14

• 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

Question 15

Describe the arginine vasopressin (AVP) mechanism

Answer 15

• 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

Question 16

Describe the ANP mechanism

Answer 16

• 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)

Question 17

Describe the action of osmotic diuretics and give an example

Answer 17

• 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

Question 18

Describe the action of loop diuretics and give examples

Answer 18

• 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

Question 19

Describe the action of thiazide diuretics and vie examples

Answer 19

• eg. bendroflumethiazide, hydrochlorothiazide
• inhibit NCC
• reduces Na+ and Cl- reabsorption
• also causes vasofilation
• 2nd/3rd line treatment of hypertension

Question 20

Describe the action of K+ sparing diuretics and give examples

Answer 20

• 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