5_HST110 Tubular Transport I and II 2017

Question 1

What percent of the 180 L/day of filtered blood is excreted in the urine?

Answer 1

<1%

Question 2

The processes of reabsorption and secretion are mediated by (X) proteins

Answer 2

X = membrane transport

Question 3

What are 3 mechanisms that solutes can be transported across cell membranes?

Answer 3

Passive transport mechanisms
Active transport mechanisms
Endocytosis

Question 4

All water movement in the nephron is (X)

Answer 4

X = passive

Question 5

Diffusion does not require energy (ATP) expenditure, and it can be driven by (X) and (Y)

Answer 5

X = gradients
[chemical (concentration),
electrical (electrical potential difference), and osmotic pressure]

Y = solvent drag

Question 6

Facilitated diffusion: With coupled transporters, at least one solute is transported against its (X) gradient, driven by the passive downhill movement of one of the other solutes, also called (Y)

Answer 6

X = electrochemical
Y = secondary active transport

Question 7

Active transport usually involves movement of solutes (X) a concentration gradient

Answer 7

X = against

Question 8

Endocytosis is important for the reabsorption of (X) and macromolecules by the (Y)

Answer 8

X = small proteins
Y = proximal tubule

Question 9

Tight junctions, dividing the apical and basolateral surfaces/memebranes, have some properties of ion channels, which enable select ions to diffuse across the tight junction based on size and charge. This is important in what type of transport?

Answer 9

Transepithelial transport, paracellular transport

Question 10

What is the transport mechanism of passing from the lumen to the interstitium through cells rather than around them?

Answer 10

Transcellular transport

Question 11

What are the units of osmolality?

Answer 11

mOsm/kg. Reflects the concentration of substances in a fluid

Question 12

Osmolality is only effective in driving osmosis when the barrier is (X) permeable to solutes than to water

Answer 12

X = less

Question 13

Solutes are as permeable as water in the endothelial barrier, so water movement is driven by (X) forces. In the epithelial barrier (tubules), solutes are less permeable than water, so water movement is driven by (Y)

Answer 13

X = Starling
Y = osmotic gradients

Question 14

How many mEq of Na+ and how many L of water a day are reabsorbed by the tubular system?

Answer 14

25000 mEq/day

179 L/day

Question 15

Proximal vs. Distal: Major function

Answer 15

Proximal: High-capacity reaborption of water and solutes
Distal: “Fine tuning” urine composition and volume

Question 16

Proximal vs. Distal: Energy requirement for transport

Answer 16

Proximal: Low-energy or passive
Distal: High-energy, active

Question 17

Proximal vs. Distal: Transport mechanisms

Answer 17

Proximal: Diffusion, facilitated diffusion, coupled transport, solvent drag, active transport
Distal: Active transport

Question 18

Proximal vs. Distal: Permeability to water

Answer 18

Proximal: Permeable throughout
Distal: Mostly impermeable

Question 19

Proximal vs. Distal: osmotic gradient

Answer 19

Proximal: Small
Distal: Large

Question 20

Proximal vs. Distal: Tight junctions

Answer 20

Proximal: Leaky
Distal: Tight

Question 21

Proximal vs. Distal: Regulation of transport

Answer 21

Proximal: Largely unregulated
Distal: Tightly regulated

Question 22

What active transporter is critical for the proximal tubule’s ability to reabsorb solutes and water?

Answer 22

Na+-K+-ATPase at the basolateral membrane

3Na+ out, 2K+ in (interior of cell becomes electrically negative with respect to tubular lumen). Na+ drawn into cell from tubular lumen, prompting more ATPase activity to return to normal concentration (low intracellular Na+)

Question 23

What apical transporters of the 1st half of the PT are important in coupling Na+ reabsorption with H+ export or reabsorption of other organic solutes?

Answer 23

** Important **
Na+-H+ antiporter (NHE3)

Na+ entry coupled with H+ exit into lumen
Responsible for most Na+ reabsorption in PCT

Symporters (coupled transport)
Na+-glucose (SGLT2)
Na+-amino acid
Na+-phosphate
Na+-lactate

Question 24

Glucose and other organic solutes reabsorbed with Na+ leave the cell and enter the blood by (X) mechanisms
(unlike Na+, through its Na+-K+-ATPase). This generates negative transepithelial voltage across PT providing driving force for reabsorption of (Y) in the 2nd half of PCT

Answer 24

X = passive
Y = Cl-

Question 25

What are the transporters for renal handling of glucose? (all filtered is reabsorbed by PT)

Note: Tight junctions have minimal permeability to glucose (no back-leak)

Answer 25

SGLT2 and SGLT1 symporters reabsorb glucose with Na+ from tubular lumen into the cell

GLUT2 uniporter transports

Question 26

Rate-limiting step of glucose transport is the (X) symporter. Therefore, abnormally high filtered loads of glucose will overwhelm the reabsorptive capacity (plasma glucose above (Y) mg/dL though glucose can be detected in urine when plasma levels exceed 180-200 mg/dL). Spilling of glucose into urine is called (Z)

Answer 26

X = SGLT2
Y = 300
Z = glucosuria

Question 27

In the 2nd half of PT, Na+ is mainly reabsorbed with (X)
The rise in tubular [(X)] in the first half of the PCT sets up a (X) concentration gradient between tubular lumen and interstitial space. (X) is reabsorbed both in a (Y) and (Z) fashion

Answer 27

X = Cl-
Y = transcellular
Z = paracellular

Question 28

In the PT, water diffuses passively from lumen into PT cell via two mechanisms due to transtubular osmotic gradient from solute reabsorption

Answer 28

Aquaporin-1 (AQP1) channels (apical AND basolateral membranes)
Paracellular route (with solvent drag)

Question 29

In the PT, increased water in the interstitial space increases (X) and drives the movement of water and solutes into the peritubular capillaries

Answer 29

X = hydrostatic pressure

Question 30

In the PT, proteins are reabsorbed via receptor-mediated (X). Endocytosed proteins are (Y) into amino acids inside the proximal tubular cell and recycled to the body

Answer 30

X = endocytosis (megalin/cubulin mediated)
Y = enzymatically degraded

Question 31

Proximal tubular cells can secrete organic anions and cations into the tubular lumen. Many organic anions and cations compete for the same secretory pathways (transporters are (X) and (Y))

Answer 31

X = nonspecific
Y = saturable

Question 32

Hereditary or acquired proximal tubule dysfunction results in impaired ability to reabsorb solutes. Results in inappropriate urinary excretion of glucose, amino acids, phosphate, and/or low molecular weight proteins

Answer 32

Fanconi Syndrome

Question 33

The (X) of salt and water is characteristic of the LOH

Answer 33

X = separation

Question 34

What percentage of filtrered NaCl and water is reabsorbed by the LOH?

Answer 34

25% NaCl, 15% water

Question 35

The thin descending limb of the LOH exhibits no (X) reabsorption and (Y) water reabsorption (AQP1). Thus, tubular [NaCl] (Z)

Answer 35

X = NaCl
Y = Passive
Z = increases

Question 36

The thick ascending limb of the LOH exhibits (X) NaCl reabsorption and (Y) water reabsorption. Thus, tubular [NaCl] (Z)

Answer 36

X = Passive
Y = no
Z = decreases

Question 37

LOH TAL: Na+ transport steps

Answer 37

1) Na+-K+-ATPase generates electrochemical gradient
2) Na+-K+-2Cl- symporter (NKCC2) reabsorbs Na+ with K+ and 2Cl-
3) K+ channel (ROMK) enables K+ reabsorbed via NKCC2 to recycle back into tubular lumen (“back-leak”)
Required for continued function of NKCC2
4)Na+ leaves cell via Na+-K+-ATPase

Question 38

“Back-leak” of K+ via ROMK generates a lumen-(X) voltage

Answer 38

X = positive

Question 39

TAL ROMK lumen positive voltage drives paracellular uptake of various cations, including (X)

Answer 39

X = Na+, K+, Mg2+, and Ca2+

Question 40

TAL is the main site of (X) reabsorption in the nephron

Answer 40

X = Mg2+

Question 41

TAL is called the (X) segment of the nephron due to the NaCl reabsorption without water

Answer 41

X = diluting

Question 42

Set of autosomal recessive inherited diseases characterized by: hypokalemia and metabolic alkalosis

Patients typically also have hypomagnesemia and hypocalcemia

Functionally resembles a patient on loop diuretics

Answer 42

Bartter’s Syndrome

Question 43

Distal Convoluted Tubule: Na+ reabsorption is mediated by a (X) symporter

Blocked by thiazide diuretics

Answer 43

X = Na+-Cl- (NCC)

Question 44

DCT is also the major site for regulated reabsorption of (X) (under the control of parathyroid hormone) via apical (X) channels

Answer 44

X = calcium, Ca2+

Question 45

Autosomal recessive inactivating mutation in Na+-Cl- symporter gene (SLC12A3)

Characterized by metabolic alkalosis, hypokalemia, and hypocalciuria

Patients typically have hypomagnesemia

Functionally resembles a patient on thiazide diuretics

Answer 45

Gitelman’s Syndrome

Question 46

Steps in CCD Na+ transport

Answer 46

1) Na+-K+-ATPase generates electrochemical gradient
2) Na+ reabsorbed via epithelial Na+ channel (ENaC) at apical membrane (Generates lumen-negative voltage. Blocked by K+ sparing diuretics (e.g. amiloride))
3) Lumen-negative voltage drives secretion of K+ into the lumen via ROMK. Important site of K+ secretion.
4) Na+ leaves cell via Na+-K+-ATPase

Question 47

CCD Acid-Base Balance

α-intercalated cells:
Secrete (X)
   H+-K+-ATPase
   H+-ATPase
Reabsorb (Y) and (Z)

β-intercalated cells:
Secrete (Y) and reabsorb Cl-
Cl-/HCO3- antiporter (Pendrin)
Reabsorb (X)

Answer 47

X = H+
Y = HCO3-
Z = K+

Question 48

CCD Principal cells Principal cells reabsorb water to a varying degree under the hormonal control of (X). Mediated by aquaporin-2 (AQP2) channels in the (Y) membrane and AQP3 and AQP4 channels in the (Z) membrane

Answer 48

X = antidiuretic hormone (ADH)
Y = apical
Z = basolateral

Question 49

Autosomal dominant disorder characterized by early onset:
Hypertension
Hypokalemia
Metabolic alkalosis

Caused by mutations in either the β or γ subunit of ENaC, which increase the number of Na+ channels in the apical cell membrane. Increased Na+ reabsorption leads to increased extracellular volume and hypertension

Answer 49

Liddle Syndrome

Question 50

Na+ and water reabsorption increase in proportion to the increase in GFR and filtered load of Na+. A constant fraction of filtered Na+ (about 65%) is reabsorbed by the proximal tubule despite changes in GFR. What is this called?

Answer 50

Glomerulotubular Balance. Tubule (not glomerulus) is responding. Intrarenal mechanism, not dependent on external neural or hormonal input