Regulation of Body Fluid Volume and Osmolarity

Question 1

Balance concept

Answer 1

Multiple sources of input and output

Urine output is the only output that can be precisely controlled

Question 2

Regulation of ADH secretion

Answer 2

Same as arginine vasopressin…systemic vasoconstrcitive effects

ADH - synthesized in supraoptic and paraventricular nucelii of the hypothalamus…transported down axon, stored in nerve temrinals in posterior pituitary

Question 3

What can trigger ADH change

Answer 3

HT osmoreceptors - increase Posm—-increase ADH—-increase H2O reabsorption—-decreased Posm

Volume receptors

Decreased volume —-increased ADH—-increase H2O reabsorption—–increasePvol

Osmoreceptors HIGHER than baroreceptor system

Question 4

Hypothalamic osmoreceptors

Answer 4

Located outside of BBB…ogranum vasculosum of the lamina terminalis

Hypertonicity casues osmoreceptor cell shrinkage (AQP-2med)

Cell shrinkage inceeases AP discharge—-increase ADH

And activates transient receptor potential vanilloid (TRPV) channels

Question 5

Volume status influence on ADH secretion

Answer 5

Set point = plasma osmolality at which ADH secretion=0

Decrease volume…decrease set point and increase sensitivity to changes in osmolality

Increase volume—-increase set point and decrease sensitivity to osmolality

Question 6

Relationship bt plasma ADH and urine concentrating ability

Answer 6

Small changes in ADH elicit large changes in urine osmolarity

Increase osmolarity with decrease urine volume

As ADH increases, urine osmolarity will increase

Question 7

Thirst mechanism

Answer 7

Renal response only minimizes the LOSS

ADH also regulates the thirst drive

The thirst is regulated by the hypothalamic osmoreceptors (same way as the secretion of ADH)

Question 8

SIADH causes and effects

Answer 8

HEad trauma, encephalitis, meningitis
ADH secreting tumors in lung and panres
Drug-induced

Increased ADH—increase H2Oreabsorption—decreased hyponatremia

Decreased serum Na—-decreased plasma osm—-influx of H2O into cells—-coma

Question 9

V1/V2/V3

Answer 9

V1 - vasoconstrictive effects

V3 - anterior pituitary gland

V2 - in the collecting tubule…(distal nephron)

Question 10

Tx of SIADH

Answer 10

ADH receptor antagonists

Selective and non-selective (V2R is selective)

Question 11

D.I

Answer 11

Cause - hypothalamic (decreased ADH)

Or nephrogeneic (renal unresposiveness)...mutations in ADH receptor----decreased AVP binding----decreased cAMP----decreaseH2O insertion
OR decreased syntehssis and translocation of AQPs OR drugs or hypokalameia 

Decreased ADH—decreased H2O reabsorption—-hyperneatremia

INcreased serum Na—increase plasma osm—-efflux of H2O out of brin cells —-coma

Question 12

POtential t of NDI due to mutations in ADH

Answer 12

Most are a result of misfolding and retention…membrane permeable AVP antagonists can correct misfolidng…receptor locates to the membrane

Question 13

Free water clearance

Answer 13

Provides non-invasive assessment of diluting efficiency of the thick ascending limb

Amount of distilled water that must be added to or removed from urine to create an isotonic fluid

Ideally assessed at maximal diuresis

Lower with impaired thick ascending limb function

Would be zero when urine is isotonic

Question 14

Maintenance of ECF

Answer 14

Directly related to total body sodium

H2O shifts extracellular and intracellular

Effects on ADH secretion, thus distal neprhon H2Oreabsorption

Effects on thirst

Question 15

Kidney maintenance of ECF volume

Answer 15

Adjusting NaCl excretion to mtch NaCl intake

Rate primarily regulated by changes in renal tubular Na reabsorption

Na excretion primarily regulated by action of aldosteron on cortical collecting tubule****

Decreased NaCl—increased aldosterone—-increased Na reabsorption—decreased Na excretion

Aldosterone regulates the excretion of approximately 5% of the filtered load of sodium

Retaining just a fraction of a percentage of salt woudl obligate retention of 1L of H2O

Question 16

Will a change in total body Na content change Na concentration in the ECF?

Does infusion of isotonic saline or hemorrhage affect Na ECF concentration?

Answer 16

No

No

Question 17

Total body Na changes sense

Answer 17

Changes in ECV (effective criculating volume)

This is monitored by baroreceptors in ECV

Decreased volume means less salt in the urine…more volume means more salt excreted

Question 18

Rate limiting step in aldosterone release from adrenal cortex

Answer 18

Renin release by kidney

Can be controlled by renin inhibitors, ACE inhibitors
Angiotensin 2 receptor antagonists, aldosterone antagonists

Question 19

RAAS steps

Answer 19

Kidney produce renin…cleaves angiotensinogen from liver into angiotensin 1…this is cleaved into angiotensin 2 by ACE…this goes to the adrnela cortex which produces aldosterone

Question 20

Renin secretion control (think hemorrhage)

Answer 20

Intrarenal barorecpeotr-decrease BP - decrease pressure in AA – increase rnein

Sympathetic nerves - decrease BP —-increase RSN — increase renin

Macula densa —-decrease BP —-decrease Pgc —–decrease GFR—–decreased flow —–increase renin

Question 21

Response to AII

Answer 21

Rapid - Help restore normal BP despite low ECV—-increase TPR and CO

Long-onset - restore normal ECV…decrease NaCl and H2O excretion…increase NaCl and H2O intake

Question 22

Aldosterone escape

Answer 22

Sustained increases in aldosterone secretion results in relatively transient Na retention

Increased aldosterone—increased ECV—increased BP

A 15-25 mm Hg increase in BP - pressure netriuresis and pressure diuresis…aldosterone escape

Question 23

Effects of rapid changes in Na intake

Answer 23

Renal adjustments for changes in H2O intake are rapid but renal compensation for Nal can take days

ADH vs. aldosterone

During transition, NaCl excretion does NOT match intake

Question 24

INcreased ECV due to rapid salt intake

Answer 24

INcreased ECV…increase ANP from atrial myocytes

INcrease ANP —-incrase NaCL and H2O excretion due to vasodilation fo affarent arteriole—increased GFR
Inhibition of aldosterone secretion via (driect action on zona glomeruloa cells and inhibiton of renin release)
Inhibitoon of NaCl reabsroption in proximal and collecting tubule
Antagonized ADH action via inhibition of ADH release and inhibition of ADH action on collecting tubule

Question 25

Diruetics

Answer 25

Inhibit enzymesm other things that are involved in transepithelial Na reabsorption

Clasified according to site of action

Proximal tubuele carbonic anhydrase inhibitors (decrease Na/HCO3 reabsorption)

Thick ascending (loop) - Decrease Na/K/Cl activity

Distal tubule (decrease NCC acitivity)

Collecting tubule K sparing diruetics (inhibit luminal Na channels)

Also collecting tubule aldosterone receptor antagonists

Question 26

Bartters syndrome

Answer 26

Mutations in one or more ascending limb transport proteins leading to

Renal salt wasting (decreased NaCl reabsorption and increase excretion)

Volume depletion - (increased NaCl excretion and increased H2O excretion)

Hyperreninemic hyperaldosteronism

Hypercalciuria (decrease lumen + charge)

Hypokalemic metabolic alkaloss

Question 27

Inappropriate renal homeostatic response

Answer 27

Edema - accumulation of fluid in excess IS space due to decreased plasma protein—-increase IS volume and decreased ECV…and decreased ECV leads to increased aldosterone and rentention of NaCl/H2O…this further decreases plasma protein and further increases the IS volume**

The decreased ECV (effective circulating volume) does not reflect a decrease in total ECF volume, just redistributed