L6 Control Of ECFI

Question 1

Control of ECF

Answer 1

Regulation of ECF volume and ECF osmolarity accomplished by controlling Na and water

Na regulation responds primarily to changes in blood volume: driven by mainly changes in BP, primary effector is renin-angiotensin-aldosterone system (RAAS), RAAS activity increases when BP decreases

Water regulation responds to changes in osmolarity and volume of ECF: primary effector is ADH

Question 2

Hormones in regulation of NaCl and water reabsorption

Answer 2

RAAS

Atrial natriuretic peptide (ANP)

ADH

Question 3

Aldosterone

Answer 3

Stimulates Na reabsorption in late distal tubule and CD(principal cells)
Also stimulates K secretion, Na retention entails loss of K+

Increase in ATII or plasma K+ stimulate aldosterone release

Only 2-3% of the filtered Na under the control of aldosterone, still amounts to 30g of NaCl/day

Aldosterone binds you intracellular mineralocorticoid receptor (MR) in principal cells

Also-MR complex stimulates transcription resulting in up reg of: apical ENaCs, apical K+ channels, Na-K ATPase, mitochondrial metab, H+-ATPase

Aldosterone is antagonized by spironolactone, a weak diuretic

Question 4

Angiotensin II

Answer 4

Many effects:
Powerful vasoconstrictor
Stimulates release aldosterone
Stimulates H/Na exchanger (NHE) in proximal nephron
Stimulates thirst(dipsogen)
Overall, increases salt retention and elevated arterial BP
Also influences RBF and GFR

Question 5

AT II, RBF, and GFR

Answer 5

AT II reduces RBF due to its effects on efferent arteriole

Effects on GFR depend on local concentrations of the hormone

Low levels: primarily causes vasoconstriction of efferent arteriole, GFR maintained or may be increased

High levels: have increased effects on afferent arterioles, reduce glomerular filtration coefficient at mesangial cells and greatly reduces RBF, GFR decreases

also stimulates production of PGE2 and PGI2 which cause vasodilation of both afferent and efferent arterioles (protective for RBF)

Question 6

Control of AT II Formation

Answer 6

AT II levels controlled by renin (JGA)

Renin released by JGA has 3 components:

• intrarenal baroreceptors: granular cells of JGA respond to pressure in afferent arterioles, release of renin inversely related to pressure in afferent arterioles
• macula densa: senses flow to distal tubule, proportional to GFR; renin release inversely related to GFR
• renal sympathetic nerves (RSN): end near granular cells; stimulation of RSN increases renin release via stimulation of beta receptors

Question 7

Atrial natriuretic peptide

Answer 7

ANP, ANF

released from atria when pressures are high

Increases GFR and the filtered load of NaCl: ANP dilates the afferent arteriole and constricts the efferent arteriole

Decrease NaCl reabsorption by the CD at several steps: directly inhibits secretion of renin and aldosterone and directly inhibits Na uptake by medullary CD

Question 8

Regulation of NaCl and water reabsorption ADH

Answer 8

Most important hormone regulating water balance

Released from pituitary when plasma osmolarity increases or plasma conc decreases

Receptors for ADH in basolateral membrane collecting duct, activation results in cAMP production , causes insertion of aquaporins

ADH has little effect on NaCl excretion

Hypothalamic is osmoreceptors sensitive to small changes in plasma conc osm ~1%

Hypovolemia stimulates ADH secretion (5-10% change in volume- via arterial and left atrial Baroreceptors)

Question 9

ADH

Answer 9

Increase permeability of CD to water

Increase Na/K/2Cl (NKCC2) transporters in LOH (increases medullary gradient)

Increases permeability of inner medullary CD to urea

Question 10

Solutes and water may be adjusted separately

Answer 10

Water diuresis after ingesting 1 liter of water

Note the excretion of a large volume of dilute urine

However the total amount of solute excretion remains relatively constant

Question 11

Osmolar clearance

Answer 11

Clearance is the ml/min of blood plasma cleared of a given substance

Osmolar clearance Cosm is the ml/min of blood plasma cleared of osmotically active particles

Cosm= UosmV / Posm

Normally 1-2ml/min

Question 12

Reduced Cosm

Answer 12

<1

Positive osmolar balance- gaining osmolar (and water)- progression toward edema

Decreases GFR, increased aldosterone, or any disease that decreases the ability of the kidney to eliminate solute

Question 13

Increased Cosm

Answer 13

> 2

Dumping osmolytes leads to loss of ECF

if taking diuretics, reduced aldosterone, or any disease that reduces the ability of the kidney to reabsorb normally

Unregulated diabetic keto acidosis = dumping osmolytes and see increased Cosm