L6 Control Of ECF I

Question 1

Regulation of ECF volume and ECF osmolality is accomplished by …

Answer 1

Controlling Na+ and water

Question 2

Na+ regulation responds primarily to changes in _________.

Answer 2

Blood volume

Driven mainly by changes in BP
Primary effector is the renin-angiotensin-aldosterone system (RAAS)
RAAS activity increases when BP decreases

Question 3

Water regulation is responsive to changes in ____________ and volume of ECF.

Answer 3

Osmolarity

Primary effector is the antidiuretic hormone (ADH, or vasopressin)

Question 4

Hormones active in the regulation of NaCl and water reabsorption

Answer 4

Renin-AngiotensinII-Aldosterone

Atrial Natriuretic Peptide (ANP)

Anti-Diuretic Hormone (ADH)

Question 5

Aldosterone stimulates Na+ reabsorption in the _______________.

Answer 5

Principal cells of the late distal tubule and collecting duct.

Also stimulates K+ secretion - Na+ retention entails loss of K+

Question 6

Increases in _________ or ___________ will stimulate aldosterone release

Answer 6

Angiotensin II or plasma [K+]

Question 7

Only ____ of the filtered Na+ is under the control of aldosterone

Answer 7

2% - amounts to 30 g of NaCl/day

Question 8

Where does aldosterone bind?

Answer 8

Intracellular mineralocorticoid receptors (MR) in principal cells

Question 9

After hormone binding, the Aldosterone-MR complex stimulates transcription resulting in up-regulation of:

Answer 9

Apical ENaC (Epitheliam Na+ channels)
Apical K+ channels
Na/K ATPase
Mitochondrial metabolism
H+-ATPase

Question 10

Aldosterone is antagonized by …

Answer 10

Spironolactone, as weak diuretic

Question 11

Factors leading to an increase in Aldosterone secretion

Answer 11

Increased plasma [K+]
Increased plasma [ACTH]
Increased plasma [Angiotensin II]

All three are sensed by the adrenal cortex —> increased aldosterone secretion

Question 12

The many effects of Angiotensin II

Answer 12

Powerful vasoconstrictor
Stimulates release of aldosterone
Stimulates Na+/H+ (NHE) exchange in the proximal tubule
Stimulates thirst (dipsogen)
Functions favor SALT RETENTION and ELEVATION of arterial BP

Question 13

Angiotensin II levels are controlled by _______ released from ______.

Answer 13

Renin, released from JGA in three main ways:

1) Intrarenal baroreceptors - granular cells of JGA respond to pressure in afferent arterioles —> release of renin inversely related to pressure in afferent arterioles
2) Macula densa - senses flow to distal tubule —> renin release inversely related to GFR
3) Renal sympathetic nerves - end near granular cells —> stimulation increases renin release via stimulation of ß receptors

Question 14

How are the different hormones involved in response to hemorrhage?

Answer 14

1) Intrarenal baroreceptors and macula densa (JGA) sense the decreased BP and GFR
2) Granular cells of the JGA stimulate increased renin secretion —> increased plasma concentration of renin
3) Increased plasma renin —> increased plasma angiotensin II
4) Angiotensin II acts on adrenal context, simulating increased aldosterone secretion
5) Increased plasma aldosterone —> increased tubular Na+ reabsorption

Question 15

Atrial natriuretic peptide (ANP, ANF) is released from the ______ when ______.

Answer 15

Released from atria when pressures are high

Question 16

Result of increased ANP release?

Answer 16

Increased GFR and filtered load of NaCl

ANP dilates the afferent arteriole and constricts the efferent arteriole

Question 17

Decreased NaCl reabsorption by the collecting duct in response to ANP stimulation occurs at several steps:

Answer 17

ANP directly inhibits secretion of renin and aldosterone

ANP directly inhibits Na+ uptake by medullary collecting duct

Question 18

The most important hormone regulating water balance

Answer 18

ADH!!!

Question 19

ADH is released from _______ when _____________.

Answer 19

Released from pituitary when plasma osmolality increases OR plasma volume decreases

Question 20

Receptors for ADH in the ______________; activation results in ___________.

Answer 20

Receptors in the basolateral membrane of the collecting duct —> cAMP production —> increased aquaporins on apical surface

Question 21

ADH has little effect on ________

Answer 21

NaCl excretion

Question 22

________ stimulates ADH secretion from the pituitary.

Answer 22

Hypovolemia

Hypothalamic osmoreceptors are sensitive to small changes in plasma osmolality (1%)

Arterial and left atrial baroreceptors sense 5-10% changes in volume)

Question 23

Once again, ADH does what?

Answer 23

Increases permeability of the collecting duct to water
Increases NKCC2 transporters in the loop of Henle (increasing the medullary gradient)
Increases permeability of inner medullary CD to urea

Question 24

Our bodies’ osmolarity averages about ________

Answer 24

290 mOsm/L

Seldom changes by more than ± 2-3%

Question 25

How do baroreceptors control ADH during hemorrhagic events?

Answer 25

1) Decreased plasma volume —> decreased venous, arterial, and atrial pressures
2) CV baroreceptors reflexively increase ADH secretion —> increased plasma ADH
3) ADH acts on collecting duct increase permeability to H2O —> increased H2O reabsorption and decreased H2O excretion

Question 26

How do osmoreceptors control ADH in cases of pure water overload

Answer 26

1) Excess H2O is ingested —> decreased ECF osmolarity
2) Osmoreceptors reflexively mediate decreased ADH secretion —> decreased plasma ADH
3) ADH acts on collecting duct to decrease permeability to H2O —> decreased H2O reabsorption and increased H2O excretion

Question 27

What might you expect to happen after ingesting 1 L of water?

Answer 27

Urine osmolarity would decrease substantially for a time in order to maintain plasma osmolarity. Urine osmolarity would increase again once the excess water was excreted.

Urine flow rate would increase (in order to excrete the excess water), but urinary solute excretion would remain constant

Question 28

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

Answer 28

Clearance

Question 29

_______ is the ml/min of blood plasma cleared of osmotically active particles

Answer 29

Osmolarity clearance - C(osm)

C(osm) = U(osm) x V / P(osm)

Question 30

If P(osm) = 285 mOsm/L
U(osm) = 650 mOsm/L
V = 0.8 ml/min

What is the C(osm)?

Answer 30

C(osm) = (650 mOsm/L)(0.8 ml/min) / (285 mOsm/L)
= 1.82 ml/min

1.82 ml of plasma is cleared of solute each minute

Question 31

Normal value for C(osm)?

Answer 31

1 to 2 ml/min

Question 32

A reduced C(osm) is reflective of…

Answer 32

Positive osmolarity balance - gaining osmoles (and water), possibly progressing toward edema

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

Question 33

An increased C(osm) could indicate…

Answer 33

“Dumping” of osmolytes, leading to a loss of ECF

Diuretics, reduced aldosterone, or any disease that normally reduces the ability of the kidney to reabsorb normally can lead to increased C(osm)