Urinary Concentrating Mechanism and Water Homeostasis

Question 1

describe the origin and effects of antidiuretic hormone in the distal nephron

Answer 1

ADH is produced in the hypothalamus and stored in the posterior pituitary gland; acts on V2 receptors in collecting duct cells for osmoregulation and water retention

Question 2

explain the processes regulating the secretion of antidiuretic hormone

Answer 2

primary stimulus for release: blood osmolarity: as detected by specialized cells in the hypothalamus called osmoreceptors

secondary stimulus: blood volume and pressure; as perceived by baroreceptors/stretch receptors in locations with low pressure (left atrium, large veins; respond to blood volume) that respond to volume and high pressure (aortic arch, carotid sinus; respond to blood pressure) that respond to pressure

other stimuli for release include angiotensin II, pain, nausea, and certain drugs

stimuli have a synergistic interaction

Question 3

predict physiologic conditions in which antidiuretic hormone secretion is stimulated or inhibited (3)

Answer 3

1. insufficient water in the body increases blood osmolarity and decreases blood volume
2. increased blood osmolarity is sensed by osmoreceptors in the hypothalamus, and is the primary stimulus to increase ADH release
3. decreased blood volume leads to decreased blood pressure, which increases concentration of angiotensin II, which also increases ADH release

bleeding can cause decrease in blood volume; vomiting can cause decrease in blood volume AND increase in blood osmolarity

additionally, low water intake (dehydration) increases plasma osmolarity, which is sensed by osmoreceptors in the hypothalamus to tell the posterior pituitary to increase ADH

opposingly, high water intake decreases plasma osmolarity, which is sense by osmoreceptors in the hypothalamus that tell the posterior pituitary to decrease ADH

Question 4

beginning with the proximal tubule, contrast the tubular fluid and the interstitial fluid osmolality changes that allow either a dilute or concentrated urine to be produced and excreted

Answer 4

proximal tubule: will reabsorb 65% water regardless of body needs, as well as 2/3 solutes and small molecules (permeable to both water and solutes, largely isoosmotic tubular fluid relative to plasma)

thin descending limb of loop of Henle reabsorbs 15% water regardless of body needs (permeable to water but impermeable to solutes, largely hyperosmotic tubular fluid relative to plasma)

thin and thick ascending tubules (early distal) are permeable to solutes but impermeable to water, so hypoosmotic tubular fluid relative to plasma)

late distal tubule and collecting ducts reabsorb 5-24% of water (5% during water loading and 24% during dehydration); this section is what allows the animal to produce dilated or concentrated urine based on needs (permeable to solutes, but water permeability depends on ADH)

Question 5

name the osmoles that contribute to the hyperosmolarity of the medullary interstitium

Answer 5

sodium, chloride, urea

Question 6

describe the countercurrent multiplier mechanism of the loop of Henle as a contributor to the hyperosmolar medullary interstitium

Answer 6

loop of Henle reabsorbs proportionally more salt than water, gradually trapping salt in the medullary interstitium, relying heavily on the active transport of Na+ and Cl- by the thick ascending limb (distal straight tubule) utilizing the Na-K-2Cl co transporter

Question 7

describe countercurrent exchange in the vasa recta as a contributor to the hyperosmolar medullary interstitium (4)

Answer 7

1. renal medullary flow is slow and low (just enough to supply the needs of the tissues wile minimizing solute loss from the medullary interstitium)
2. vasa recta serve as countercurrent exchangers, minimizing the washout of solutes from the medullary interstitium, preserving the high solute concentration
3. descending into the medullary hypersomolarity, water moves out of the vasa recta, so NaCl and urea passively move into the vasa recta
4. ascending out of the medullary hyperosmolarity, water moves into the vasa recta, so NaCl and urea passively move out, returning solutes to the interstitium with a net effect of removing reabsorbed water while leaving most solutes behind

Question 8

describe urea recirculation as a contributor to the hyperosmolar medullary interstitium (6)

Answer 8

1. urea is freely filtered in the glomerulus
2. then 50% reabsorbed in the proximal tubule via the paracellular route (leaky tight junctions)
3. urea diffuses back into the tubule in the thin loop of Henle because interstitial urea concentration is high due to step 5
4. small amounts are reabsorbed in the thick ascending loop, distal tubule, and outer collecting duct (less permeable to urea)
5. large amounts are reabsorbed in the medullary collecting duct, where ADH is present (as water leaves tubular fluid, luminal urea concentration rises, favoring urea reabsorption
6. recirculation of urea helps keep urea in the renal medulla, contributing to the hyperosmolarity of the interstitum; if ADH levels are high, there will be more water, and therefore more urea reabsorbed in the medullary collecting duct, causing the medullary interstitium to become more hyperosmolar

Question 9

describe the net action of urea (reabsorption or secretion), and what the percent of filtered urea that appears in the urine depends on

Answer 9

net reabsorption of urea occurs (more reabsorption than secretion)

the percent of filtered urea that appears in the urine depends on the urine flow rate (high flow = more urea in urine, low flow = les urea in the urine)

this is one of the reasons why urea is not the best marker of GFR, depends on other things

Question 10

explain the mechanisms by which animals can produce urine of different concentrations and volume

Answer 10

in the distal loop of Henle, distal tubule, and collecting tubule and ducts, tubular fluid osmolarity is lower than plasma osmolarity, allowing for the reabsorption of solutes without reabsorption of water; this allows the animal to achieve dilute or concentrated urine depending on the body’s needs and regulated by the number of aquaporins ADH inserts into the principle cells of the collecting ducts to reabsorb more or less water (as long as there is a hyperosmolar medullary interstitium too!)

if body has too much water, ADH levels are low and the animal will produce a large volume of dilute urine

if the body does not have enough water, ADH levels are high and the animal will produce a small volume of concentrated urine

urine osmolarity can be as high as the osmolarity of the renal medullary fluid in the papilla (hairpin turn of loop of Henle, most concentrated)

Question 11

list conditions in which response to antidiuretic hormone and the urinary concentrating mechanism are impaired (loss of medullary hyperosmolarity) (2)

Answer 11

1. central diabetes insipidus: no ADH released even though signals are sent; this results in hypoosmolar/dilute urine (water loss) where animal will remain dehydrated unless it drinks enough to replace water loss
2. nephrogenic diabetes insipidus (loss of ADH action in kidney): ADH released but kidney does not respond; this also results in hypoosmolar/dilute urine (water loss) where the animal will remain dehydrated unless it drinks enough to replace water loss

Question 12

predict urine specific gravity ranges in healthy animals subjected to water shortage or abundance

Answer 12

water shortage: well-concentrated/hypersthenuria

water abundance: isosthenuria or even more severe hyposthesnuria