Renal: Renal Tubules 2

Question 1

what does it mean when its said that the process of reabsorption in proximal tubule is “osmotically neutral”

Answer 1

• In PT, process is osmotically neutral – Sodium, Chloride and Bicarbonate are absorbed at the same time as water, so the osmolarity of the filtrate stays the same

Question 2

what happens to the composition when it gets to the loop of genle

Answer 2

• Once the filtrate arrives at the Loop of Henle, selective changes in composition start to occur, which changes the relative concentration of water and ions and establishes the
  conditions necessary for selective uptake of water in proportion to how much is required by the animal

Question 3

parts of the loop of henle and water permeability

Answer 3

• The Loop of Henle is divided into two parts – the Descending and Ascending limbs.
• Descending limb is highly permeable to water and is less permeable to NaCl. Water is preferentially removed from the filtrate. Urea and some NaCl actually diffuses back into the tubular fluid near the bottom of the loop (where the outside NaCl concentration and osmolarity is high).
• Ascending limb is divided into thin and thick parts
• In the thin ascending limb, a small amount of NaCl is reabsorbed by paracellular diffusion.
• The thick ascending limb is essentially impermeable to water but has very active reabsorption of ions (Na+, K +, Cl - ) through a co transporter (NKCC2) that pulls all three into the cell

Question 4

solute reabsorption in descending LH and thick ascending LH (luminal and basolateral),what diuretic acts here

Answer 4

Descending LH:
* Limited: Some passive NaCl movement both into and out of the tubule.

“Thick” Ascending LH:
* Luminal entry
– Na +-H + antiporter
– Na +-K+-2Cl - cotransporter (site of action of furosemide)

• Basolateral exit
  – Na +-K+ ATPase
  – K+ and Cl - channels

Question 5

dilution at the end of LH, vasa recta and salt, urea transporters, counter current exchange

Answer 5

• By the end of the Loop of Henle (beginning of DT), the tubular fluid is very dilute (~100 mM) due to aggressive removal of NaCl, where water cannot follow.
• The salt that is removed from the fluid is carried deep into the medulla
  by vasa recta so that the interstitium of the renal medulla becomes
  hyperosmotic (>1000 mM) near the hairpin bend in the LH.
• Urea transporters also contribute to hyperosmolarity by transporting urea into the medulla.
• A countercurrent exchange mechanism between the vasa recta and tubule ensures that transfer of solutes is maximized.

Question 6

NaCl movement in the loop of henle

Answer 6

descending - NaCl concentration rising in tubule (water leaving
tubule) and falling in blood (water entering bloodstream)

intersistium - Interstitium is maintained in a hyperosmotic state. By NaCl from fluid and countercurrent exchange with surroundings

ascending - NaCl concentration falling in tubule (salt leaving tubule) and increasing in blood

Question 7

steps in reabsorption in LH

Answer 7

1. Descending loop of Henle passes into an ever increasing concentrated
   environment. Simple squamous epithelium.
2. Descending limb is highly permeable to water and moderately
   permeable to urea, sodium, most other ions
3. In descending limb, water moves
   out of nephron, solutes in. Volume of
   filtrate reduced by another 15%.
4. The wall of the ascending limb of the loop of Henle is not permeable to water.
5. Ascending limb moves Na + across the wall of the basal membrane by active transport.
6. At the end of the loop of Henle, inside of nephron is 100 mOsm/kg.
7. Interstitial fluid in the cortex is 300mOsm/kg.
8. Filtrate within DT is much more dilute than the interstitial fluid which surrounds it.

Question 8

modification of glomerular filtrate in the loop of henle

Answer 8

Descending limb:
* Permeable to Na+,Cl - , urea, and water; progressive increase in concentration (osmolality) with diffusion of Na+ back into tubule; continued water removal via vasa recta

Ascending limb:
* Reabsorption of 30% of Na +; less permeable to water → progressive
decrease in concentration (osmolality)

Distal Tubule (DT):
* Reabsorption of Na+ but impermeable to water. Further slight decrease in osmolarity of tubular fluid

Question 9

sodium reasorption in distal tubule

Answer 9

• Luminal entry
  – Na +-Cl - cotransporter (site of action of thiazide diuretics)
• Basolateral exit
  – Na + via Na +/K + ATPase
  – Cl - via Cl - channel

Question 10

modification of glomerular filtrate; collecting ducts

Answer 10

Collecting Duct (CD):
* Reabsorption of Na+ and production of concentrated or dilute
urine through the action of ADH and aquaporins.
* Sodium reabsorption influenced by hormones.

Question 11

sodium reabsorptionin collecting duct; luminal, basolateral, site of diuretic

Answer 11

• Luminal entry
  – Passively via Na+ channel (site of action of amiloride)
• Basolateral exit
  – Na +-K+ ATPase
• Paracellular - Cl - absorption

Question 12

water reabsorption in the CD; regulated by what, water balance low vs high, aquaporins

Answer 12

This is the site where water reabsorption is selectively regulated by ADH

– If water balance is low, then ADH is high and the animal conserves water by reabsorbing more through ADH stimulated aquaporins. Urine is concentrated

– If water balance is adequate/high then ADH is low and fewer aquaporins are present and the urine is dilute. Because the medulla is hypertonic, if aquaporins are expressed, water will move from the fluid, into the intersitium and ultimately return to the bloodstream

Question 13

concentrating tubular fluid into urine; physiologic processes required

Answer 13

The production of concentrated urine from dilute tubular fluid is an integrated function of the Loop of Henle, the Distal Tubule and the Collecting Duct.

Three physiologic processes are required:
1. Generation of a hypertonic medullary interstitium
2. Dilution of tubular fluid in the ascending Loop of Henle by reabsorption of NaCl but not water
3. Regulated water permeability of Collecting Duct mediated by ADH/Vasopressin

Question 14

steps of water reabsorption in the collecting duct

Answer 14

1. Filtrate which reaches DCT is dilute with respect to interstitial fluid
2. Collecting duct is the primary site where hormonal control of urine volume occurs-finishing touches
3. Duct epithelial cells express ADH receptors and aquaporins
4. In presence of ADH epithelium becomes very permeable to water
5. In absence of ADH, relatively impermeable
6. DCT can also reaborb more sodium ion to further dilute fluid, but this is under hormonal control of aldosterone

Question 15

formation of water pores; mechanism of ADH action (steps)

Answer 15

1. vasopressin binds to membrane receptor
2. receptor activates cAMP second messenger system
3. cell inserts AQP2 water pores into apical membrane
4. water is absorbed by osmosis into the blood

Question 16

urine osmolarity as an indicator of renal function; isotonic, hypertonic, hypotonic

Answer 16

-Isotonic with plasma – Specific Gravity of 1.008 – 1.012. Called Isosthenuria. If the animal has abundant water, this is normal. If it should be concentrating urine (eg. dehydration, first morning urine, water deprived) then it suggest that the kidney tubules aren’t working (or, rarely, the animal isn’t making ADH).

-Hypertonic relative to plasma – SG> 1.012. Hypersthenuric. If the animal is relatively water-deprived, this is normal. Values should be higher than 1.030 in dog and 1.040 in cat if kidneys are working properly. ADH is high.

-Hypotonic relative to plasma – SG<1.008. Hyposthenuria. Seen in animals that have abundant water and can actually dilute their urine actively (suggests that Loop of Henle can make very dilute urine). ADH is very low

Question 17

urine specific gravity and relationship to tubular/kidney function in different species (numbers for adequate and inadequate)

Answer 17

canine = 1.030
feline = 1.040
large animals = 1.025

Question 18

limited water concentration vs abundant water

Answer 18

limited water = small quantity of concentrated urine

abundant water = large quatity of dilute urine

Question 19

potassium homeostasis

Answer 19

excretion equals intake. 90% excreted in urine, 10% in feces

Question 20

how does the body handle a large potassium load (dietary intake) without suffering life threatening hyperkalemia

Answer 20

For example, a 20-kg dog (ECF = 4L) consumes 10 mmol
K+ in a meal.

This would increase ECF [K+] by ~10/4 = ~2.5 mmol/L if there were no “buffering” mechanisms in the body
(Note: Normal levels are between 3.6-5.5 mmol/L)

Question 21

acute regulation; extrarenal homeostasis

Answer 21

• Shifts between extracellular and intracellular compartment
• Potassium loading
  – Rapid uptake by cells that prevents large increase in plasma [K+]
  – Later…..slow release from intracellular pool and excretion by the kidneys

Question 22

major factors and hormones affecting K+ distribution; physiologic and pathophysiologic

Answer 22

Physiologic (keep plasma K+ constant) (all shift K into cells)
– Epinephrine
– Insulin
– Aldosterone

• Pathophysiologic increases (displace plasma K+ from normal sites/mechanisms)
  – Acid-base imbalance (↑plasma [K+] with acidosis)
  – Cell lysis (rhabdomyolysis: “tying up”)
  – Exercise (not really pathophysiologic!!!)

Question 23

longer term regulation of potassium excretion

Answer 23

-80-90%+ of the filtered K + is reabsorbed by the beginning of the distal tubule

-(K + reabsorption 70% PT, 20% Ascending LH)

-K + secretion occurs primarily DT and CD through K + channels

-When K + and Aldosterone are high in the blood, more K+ is excreted from distal nephron

Question 24

regulation of K+ excretion steps

Answer 24

1. High [K+] stimulates Aldosterone secretion which increases K+ excretion
2. High [K+] stimulates K+ secretion by tubular cells directly (also in gut, salivary glands, sweat glands)
3. Increased flow of tubular fluid increases K+ secretion by keeping tubular K+ concentration low

Question 25

renal regulation of other solutes; Ca/P and Mg

Answer 25

-Mostly excreted by paracellular
mechanisms. Osmotic activity moveswater in or out, and dissolved ions follow.
* Ca & P
– Kidneys play roles in Ca & P homeostasis through tubular absorption and excretion
– Vitamin D 3 (Calcitrol) undergoes final activation step in PT epithelium and influences Ca absorption/secretion
* Mg
– Most of filtered load is excreted

Question 26

tubular secretion of other things; metabolic by-products, penicillin, ammonia, hydrogen ions

Answer 26

1. Moves metabolic by-products and dietary molecules not normally produced by the body into tubule of nephron through active or passive processes: pinocytosis, paracellular
   transport.
2. Penicillin and other drugs: actively secreted into nephron
3. Ammonia: produced by epithelial cells of nephron from deamination of amino acids. Diffuses into lumen.
4. Hydrogen ions are moved into by Na+/H+ exchange - major mechanism for body to regulate pH.