Regulation of Body Fluid Osmolarity (Rao)

Question 1

How is thirst centrally regulated?

Answer 1

hypothalamus lateral preoptic nucleus contains osmoreceptors that induce THIRST when high osmolarity is sensed (via cell shrinkage)

Question 2

The kidney has a (high/low) capacity to excrete water and a (high/low) capacity to conserve water.

Answer 2

high

low

Question 3

What is the formula for plasma osmolarity?

Answer 3

=2[Na] + [glu]/18 + [urea}/2.8

Question 4

How much water can the body conserve in a day?

Answer 4

1L

Question 5

How is ADH release regulated?

Answer 5

1. in hypothalamus supraoptic and paraventricular nuclei, osmoreceptors sense increased osmolarity (cell shrinkage)
2. signal travels to nerve endings located in posterior pituitary
3. depolarization increases intracellular Ca concentration and ADH vesicles fuse/release hormone

Question 6

What does AVP/ADH do?

Answer 6

vasoconstriction

increases water permeability in CT

Question 7

How is the ADH signal turned “off”?

Answer 7

rapidly degraded in PT and liver

Question 8

How does binding of ADH affect the nephron cells? (What part of the nephron?)

Answer 8

1. ADH binds to basolateral V1/V2 receptor
2. initiates a cascade, which generates cAMP
3. cAMP causes aquaporin2-containing vesicles to fuse with lumenal membrane of the collecting duct epithelial cell
   * this process allows the cell to be permeable or impermeable

Question 9

When plasma osmolarity is high, levels of ADH are (high/low) and the nephrons (concentrate/dilute) urine.

Answer 9

high

concentrate

Question 10

When plasma osmolarity is low, levels of ADH are (high/low) and the nephrons (concentrate/dilute) urine.

Answer 10

low

dilute

Question 11

How do the release of ADH and the thirst response relate to increasing plasma osmolality?

Answer 11

ADH is released in small amounts under nml conditions

At 270mOsm, [ADH] increases as osmolality increases

Above 280 mOsm, up to 18pM of ADH is released

Thirst occurs at a higher plasma osmolality than ADH release

Question 12

How does blood volume affect ADH?

Answer 12

an increase in ECF volume will increase venous filling and DECREASE [ADH]

A 10-15% decrease in ECF vol results in ADH secretion (i.e diarrhea)

Question 13

How does GI fluid loss affect ADH?

Answer 13

even though blood becomes hypo- or iso-osmolar, which should decrease ADH, the DECREASE IN PV induces ADH secretion
*overrides the osmolality system

Question 14

Which requires a less significant decrease in order to induce ADH secretion: ECF volume or blood osm?

Answer 14

blood osm (requires a 10-15% decrease in ECFV, but only a slight decrease in blood osm)

Question 15

What is the appropriate treatment for hyponatremia due to GI fluid loss?

Answer 15

isotonic saline (avoid a quick change in Na levels)

Question 16

Explain how a patient with severe vomiting becomes hyponatremic but has normal ECFV?

Answer 16

ADH released in response to the change in ECFV, resulting in concentrated urine.
Water conservation increases ECFV, but Na/etc will still be low

*this can be due to vomiting, heart failure, liver failure

Question 17

What is nocturia? What causes it?

Answer 17

decreased ability to concentrate urine, resulting in frequent urination at night

causes: age, renal failure, infection, prostate hypertrophy

Question 18

How do you quantify a patient’s ability to concentrate urine?

Answer 18

“osmolar clearance”

C-osm = (UF X U-osm) / P-osm

(nml = 1.5-2.5 mL/min)

Question 19

How do you quantify free water clearance, and what is its significance?

Answer 19

difference between osmolar clearance and clearance of water:

C.H2O   =   [UF - C.osm]
C.H2O  = UF x (1 - U.osm/P.som)

• if urine osm is higher than plasma FWC>1
• if urine osm is lower than plasma FWC<1

Question 20

How does the osmolality of the medula interstitium affect the movement of water?

Answer 20

medulla interstitium has high osmolarity, thus water moves out of the tubules and returns to blood

Question 21

ADH acts on (what segments):

Answer 21

DT
CD -cortical
CD - inner medullary

Question 22

What tubule segment is HIGHLY permeable to water, regardless of ADH?

Answer 22

thin desc limb

Question 23

What tubule segment is highly permeable to urea?

Answer 23

CD - inner medullary

Question 24

What tubule segment has ACTIVE NaCl transport?

Answer 24

thick asc limb (also K*)

Question 25

The CD actively transports ___ into the ISF.

Answer 25

Na

Question 26

What steps are involved in creating hyperosmotic medullary interstitium?

Answer 26

**look in notes–I couldn’t sum this up nicely…

Question 27

What is the function of urea in the tubules?

Answer 27

contributes 40% of osm in medullary ISF-

tubule segments have different permeabilities which affects the hyperosmolarity of medullary ISF

Question 28

Medullary blood flow is __% of renal blood flow.

Answer 28

1-2%

Question 29

What 2 factors preserve hyperosmolarity of the medulla ISF?

Answer 29

1. low medullary blood flow

2. counter current exchange via vasa recta

Question 30

What are 3 causes of defective urine concentration or dilution?

Answer 30

1. abnormal production or regulation of ADH secretion
2. inability of CD to respond to ADH
3. failure to form medullary osm gradient

Question 31

What causes central diabetes insipidus?

Answer 31

inability of the pituitary gland to release ADH

Question 32

What are possible causes of nephrogenic diabetes insipidus?

Answer 32

CD do not respond to ADH
V2 receptor mutation
Aquaporin-2 mutation
Lithium and tetracyclin

Question 33

What causes loss of medullary hyperosmolarity?

Answer 33

1. Diuretics (furosemide/ethacrylic acid, which inhibit Na transport)
2. Excessive delivery of fluid to LOH
3. Decreased urea production or filtered load
4. Age and renal failure (fewer nephrons)