Lecture 10: Na+ and Circulating Volume Regulation

Question 1

Sources of body water

Answer 1

1. Organic nutrient oxidation
2. Liquid/food ingestion

Question 2

5 sites of H2O loss

Answer 2

1. Skin
2. Airways
3. GI
4. Urinary
5. Menstrual flow

Question 3

Insensible H2O loss

Answer 3

Occurs through skin and airways via continuous evaporation; involuntary.

Question 4

Na+ transporters by tubule segment

Answer 4

PT: SGLTs, GLUTs, Na/K ATPases
Ascend. Henle: NKCCs, Na/K ATPases
DT: NCCs
CDs: ENaCs

Question 5

Basolateral Na+ transport by tubule segment

Answer 5

All Na+/K+ ATPases

Question 6

Tubular H2O transport

Answer 6

H2O follows ions by osmosis
- Permeability depends on aquaporin regulation (always high in PT, regulated only in CDs)

Question 7

ADH secretion

Answer 7

Post. pituitary secretes vasopressin (ADH) to collecting duct receptors

Question 8

AQP2

Answer 8

Aquaporin that is under control by ADH; ADH triggers membrane fusion

Question 9

AQP3/4

Answer 9

Basolateral aquaporins that are constitutively active

Question 10

Diabetes insipidus

Answer 10

Low collecting duct H2O permeability due to defective ADH control. Can be central or nephrogenic.

Question 11

Central diabetes insipidus

Answer 11

Defect in synthesis/secretion of ADH by hypothalamus/post. pituitary

Question 12

Nephrogenic diabetes insipidus

Answer 12

Defect in kidney ADH response

Question 13

H2O diuresis

Answer 13

Aka non-osmotic diuresis. Increase in urine flow without an increase in solute excretion

Question 14

Osmotic diuresis

Answer 14

Increase in urine flow due to increased solute excretion

Question 15

Obligatory H2O loss

Answer 15

= 0.444 L/day. Represents limit of kidneys’ ability to make hyperosmotic urine

Question 16

Site of urine concentration/dilution

Answer 16

Medullary collecting ducts

Question 17

What drives concentration of urine?

Answer 17

The highly hyperosmotic medullary interstitial fluid

Question 18

What creates the hyperosmotic gradient of the medulla IF?

Answer 18

1. Juxtamedullary nephron loops of Henle countercurrent
2. NaCl reabsorption in ascending limbs
3. H2O impermeability of ascending limbs
4. Medullary urea trapping
5. Vasa recta hairpin loops

Question 19

Countercurrent multiplier system

Answer 19

Loop of Henle turn
- Descend. limb: no NaCl reabsorption, very H2O permeable
- Thick ascend. limb: NKCCs for net Na+, Cl- reabsorption, H2O impermeable
Urine flow at the end of ascend. limb is much less than start of descend. limb

Question 20

Vasa recta hairpins

Answer 20

Vasa recta hairpin turns minimize solute diffusion loss in IF, maintaining Osm gradient. Removed Na+, Cl-, H2O is carried away by bulk flow

Question 21

Medullary urea trapping

Answer 21

Osmotically active urea is recycled between tubule segments and thus trapped in interstitum

Question 22

Hormonal control of urea recycling

Answer 22

ADH increases medullary CD urea reabsorption, thus increasing H2O reabsorption in descend. Henle and concentrating the urine

Question 23

What initiates regulatory responses for renal Na+ control?

Answer 23

Primarily cardiovascular baroreceptors and kidney Na+ sensors initiate responses, thus also controlling ECF volume long-term

Question 24

RAAS response

Answer 24

1. Renin from JG cells (JGA) cleaves angiotensinogen to angiotensin I (from liver)
2. Capillary endothelial ACE cleaves angiotensin I to II
3. Angioten. II stimulates aldosterone secretion by adrenal cortex
4. Aldosterone stim. arteriole constriction, Na+/Cl- reabsorption, K+ secretion, H2O reabsorption

Question 25

3 ways low Na+ stimulates renin secretion

Answer 25

1. Renal sympathetic nerves (directly innervate JGA, activated by CV baroreceptors) 2. Intrarenal baroreceptors (afferent arteriole stretch) 3. Macula densa (senses tubular fluid Na+, secretes paracrine factors to JGA)

Question 26

Lisinopril

Answer 26

ACE inhibitor

Question 27

Losartan

Answer 27

Angiotensin II receptor inhibitor

Question 28

Eplerenone

Answer 28

Kidney aldosterone receptor inhibitor

Question 29

Atrial Natriuretic Peptide

Answer 29

- Secreted in cardiac atria - Inhibs. Na+ reabsorption, increases GFR - Inhibits aldosterone secretion - Lowers renin secretion, stims. vasodilation - Stimulated by excess Na+ (more vol. -> more atrial distension)

Question 30

Natriuresis

Answer 30

Osmotic uresis caused by increased Na+ excretion

Question 31

Pressure natriuresis

Answer 31

Osmotic uresis where increased pressure causes increased Na+ excretion leading to increased H2O excretion; 2 mechanisms

Question 32

2 mechanisms of pressure natriuresis

Answer 32

1. Inhibition of RAAS 2. Local activity on renal tubules

Question 33

Types of diuretics

Answer 33

1. Loop 2. K+ sparing 3. Osmotic

Question 34

Loop diuretics

Answer 34

Inhib. ascending Henle Na+ reabsorption via NKCCs; can lower K+ e.g. furosemide

Question 35

K+-sparing diuretics

Answer 35

Act elsewhere beyond Henle; block aldosterone or block cortical CD Na+ channel e.g. spironolactone, triumterene, amiloride

Question 36

Osmotic diuretics

Answer 36

Substances that are filtered but not reabsorbed, increasing H2O in urine e.g. mannitol

Question 37

Effective Circulating Volume

Answer 37

Degree of filling in arterial system; reflects extent of tissue perfusion

Question 38

Renal sympathetic activity

Answer 38

- Increases renin secretion - Decreases urinary Na+ excretion and renal blood flow - Mediated by α1 receptors constricting afferent arterioles

Question 39

Aldosterone effects

Answer 39

Effects on distal tubule principal cells Short term: increased ENaC, Na/K ATPase activity Long term: increased synthesis of ENaC, Na/K ATPases

Question 40

Angiotensin II effects

Answer 40

- Upreg. NHE in proximal tubule - ADH release, thirst sensation (hypothalamic AII receptors)

Question 41

Peritubular capillary Starling forces and ECF volume

Answer 41

Increased ECF vol.: decreased capillary oncotic P, increased cap. hydrostatic P -> less reabsorption Lower ECF vol.: higher cap. oncotic P, lower cap. hydrostatic P -> more reabsorption