Lecture 5 - Renal Transport Processes

Question 1

What is the primary regulatory process of kidney function?

Answer 1

Reabsorption

Question 2

Flow and transport rate through the proximal tubule vs the rest of the nephron?

Answer 2

Proximal tubule: high flow and high transport rate

Rest: low flow and low transport rate

Question 3

List the 11 substances reabsorbed in the proximal tubule and the % reabsorption.

Answer 3

1. H2O (70%)
2. Na+ (70%)
3. K+ (80%)
4. HCO3- (85%)
5. HPO4– (70-80%)
6. AAs (100%)
7. Glucose (100%)
8. Cl- (60%)
9. Ca++ (60%)
10. NH3
11. SO4–

Question 4

List the 4 substances reabsorbed in the distal tubule.

Answer 4

1. Na+
2. K+
3. HCO3-
4. Cl-

Question 5

Where are the tight junctions between the cells in the proximal tubule located?

Answer 5

Near apical membrane (soda can plastic wrapper analogy)

Question 6

4 types of solute active transports? Provide an example for each.

Answer 6

1. Primary active transport: Na+/K+-ATPase
2. Secondary active transport: SGLT-1/2 glucose transporter with Na+
3. Tertiary active transport
4. Endocytosis: macromolecules (e.g. large proteins) are engulfed by the plasma membrane

Question 7

What is secondary active transport?

Answer 7

Transporter protein couples the movement of an ion down its electrochemical gradient, created using energy, to the uphill movement of another molecule or ion against a concentration/electrochemical gradient

Question 8

3 types of passive solute transport? Common thread?

Answer 8

ALL DOWN CONCENTRATION GRADIENTS:

1. Simple diffusion
2. Facilitated diffusion (with carrier)
3. Osmosis

Question 9

List the pumps of the proximal tubule cells.

Answer 9

LUMENAL

1. Na+/H+ lumenal exchanger
2. SGLT-1/2 lumenal glucose transporter
3. Na+/HPO4– lumenal co-transporter
4. AA Na+ lumenal dependent transporter
5. K+ active channel

BASOLATERAL:

5. Basolateral Na+/K+-ATPase
6. GLUT on basolateral membrane for glucose facilitated diffusion
7. Anion exchangers on the basolateral membrane
8. Facilitated diffusion transporters for AAs on the basolateral membrane

Question 10

Concentration of plasma Na+?

Answer 10

140 mEq/L

Question 11

Concentration of plasma K+?

Answer 11

4.5 mEq/L

Question 12

Describe the transport of water in the proximal tubule.

Answer 12

With each solute transported transcellularly, water follows paracellularly

Question 13

Does the transport of solutes in the proximal tubule occur entirely transcellularly?

Answer 13

NOPE, some paracellularly

Question 14

4 important characteristics regarding the proximal tubule with regard to transport?

Answer 14

LEAKY

1. It is highly permeable
2. High transport rate
3. Low concentration and electrical gradients between lumen and blood due to the fast transport
4. Low resistance

Question 15

4 important characteristics regarding the cortical collecting duct with regard to transport?

Answer 15

TIGHT

1. It is not permeable (no paracellular transport, not even of water under normal conditions)
2. Low transport rate, but very efficient
3. High concentration and electrical gradients between lumen and blood due to the selective transport
4. High resistance

Question 16

List the pumps/channels of the cortical collecting duct cells. Common thread?

Answer 16

ALL HIGHLY REGULATED:

1. Na+ channel
2. K+ channel
3. H+ ATP-ase to secrete
4. Na+/K+-ATPase on basolateral membrane
5. Cl-/HCO3- exchanger

Question 17

How do the cells of the proximal tubule change from segments S1 to S3?

Answer 17

1. Less mitochondria, because lower rate of transport

2. Deeper microvilli, because need for higher affinity to glucose since 80% of it has already been absorbed in S1 and S2

Question 18

Na+ concentration in the peritubular capillaries?

Answer 18

10 mEq/L

Question 19

Describe the transport of glucose in the proximal tubule.

Answer 19

At normal plasma glucose, the rate of glucose delivery is easily handled by transport capacity in the proximal tubule so that no glucose is excreted

BUT, past this point, which is the tubular maximum for glucose, Tmg, (375 mg of glucose/min) the reabsorption is maximal and cannot be increased, so that we start excreting glucose

Mechanism:

1. SGLT-2 Na+ glucose symporter (1 Na+ for 1 glucose) takes up glucose in S1/S2 and SGLT-1 (2 Na+ for 1 glucose and HIGHER affinity and LOWER capacity)
2. Glucose exits via a GLUT uniporter on the basolateral membrane

Question 20

What is the Tmg dependent on?

Answer 20

Capacity of nephrons to transport glucose per unit time

Question 21

What is the renal threshold for glucose?

Answer 21

Plasma glucose (in mg%) at which glucose first appears in the urine

Question 22

How do we call the curves of excretion and reabsorption of glucose vs plasma glucose? Why?

Answer 22

Splay = space between the 2 curvolinear curves => refers to the difference between renal threshold and saturation, Tm

Splay occurs because different kidney nephrons (juxtamedullary vs outer cortical nephrons) do not all have the same tubular maximum for glucose (TmG), aka the same density of glucose transporters, therefore some nephrons may excrete before others

Question 23

What do we call the point where the curves of excretion and reabsorption of glucose vs plasma glucose cross?

Answer 23

Maximal reabsorption capacity for glucose of the kidney

Question 24

Normal fasting BGL? Far or close to Tmg?

Answer 24

70-90 mg%

FAR

Question 25

Consequence of glucose being excreted in urine?

Answer 25

It acts as an osmotic agent and pulls water => diuresis

Question 26

Normal Tmg?

Answer 26

375 mg/min

Question 27

What substance has a fasting blood level close to its Tm? What does this mean?

Answer 27

Phosphate You will excrete it as soon as you ingest it

Question 28

Describe the relationship between plasma glucose and filtered glucose?

Answer 28

Directly proportional and linear since it passes readily through the glomerular pores

Question 29

Normal renal threshold for glucose?

Answer 29

180-200 mg%

Question 30

Where does most of the secretion of organic acids and bases occur?

Answer 30

S2 of the proximal tubule

Question 31

What is the rate limiting step of secretion of organic molecules?

Answer 31

Active transport from the plasma to the cell of the nephron

Question 32

What happens to the organic molecule to be secreted once it has been pumped into the nephron cell?

Answer 32

It passively diffuses down its concentration gradient into the nephron lumen

Question 33

What is another substance similar to PAH? Implications?

Answer 33

Penicilin - cleared so quickly by the kidneys that you need to ingest a lot of it for enough to remain in plasma (used to strain it from urine), so physiologists developed an inhibitor for the penicilin transporter in the nephron

Question 34

Does PAH also have a Tm? What does it mean?

Answer 34

Maximal rate of secretion of PAH after which some of it will remain in the renal vein

Question 35

How does the fact that we lose nephrons as we age impact drug dosage for the elderly?

Answer 35

Should be lower, as the clearance will be lower and there will be risks of toxicity

Question 36

LIST substances that are actively transported in the tubules.

Answer 36

TBD

Question 37

DESCRIBE the renal handling of proteins and small peptides.

Answer 37

1. Peptides and small proteins (e.g. angiotensinogen, growth hormone, insulin) are filtered in considerable quantities 2. Small amount of large proteins is filtered (0.02% of plasma albumin) => 100% reabsorbed by being enzymatically cleaved into AAs: LARGE PROTEINS: 1. Binding to proximal tubule apical membrane receptors (requires energy) 2. Endocytosis by apical membrane 3. Pinched off intracellular vesicle merges with lysosome => degradation into AAs 4. Exit via basolateral membrane via facilitated diffusion to enter peritubular capillaries SMALL PEPTIDES: 1. Catabolized into AAs, di and tripeptides in proximal tubule lumen by brush border peptidases 2. Na+ co-transport into proximal tubule cell 3. Exit via basolateral membrane via facilitated diffusion to enter peritubular capillaries

Question 38

What does the rate of endocytosis of filtered proteins in the proximal tubule depend on? What to note?

Answer 38

Depends on concentration of proteins in glomerular filtrate, until a maximal rate of vesicle formation and Tm for protein uptake is reached => this process is easily saturated so a large increase in filtered proteins causes the excretion of large quantities of proteins

Question 39

Normal excretion of proteins per day?

Answer 39

100 mg/day

Question 40

Where are most organic solutes transported? What to note?

Answer 40

Proximal tubule If they escape reabsorption or are secreted, then they are usually excreted AND urea is the exception

Question 41

Describe the transport of small organic solutes in the proximal tubule.

Answer 41

1. Na+/K+-ATPase on basolateral membrane exports Na+ 2a. Neutral or negative organic solutes enter via Na+ symporters 2b. Positive organic solutes enter via uniporters driven by the negative membrane potential 3. Resulting intracellular accumulation of organic solute establishes favorable gradient for its efflux 4. Exit basolateral membrane via many different pathways

Question 42

Purpose of Na+/H+ lumenal exchanger? Net effect?

Answer 42

HCO3- reabsorption because HCO3- is impermeable intra and paracellularly in proximal tubule! H+ is secreted and reacts with HCO3- to form H2O and CO2 by lumenal carbonic anhydrase, which diffuse into the proximal tubule cells. HCO3- in then reformed by carbonic anhydrase inside the cell and exits via the basolateral membrane via facilitated diffusion NET EFFECT: 1 Na+ reabsorbed = 1 H+ pumped out = 1 HCO3- reabsorbed

Question 43

Where is Ca++ reabsorbed in the nephron? Explain how.

Answer 43

In distal convoluted tubule, particularly under the effects of PTH

Question 44

Does the collecting duct either secrete or reabsorb K+ and HCO3-?

Answer 44

Can do both

Question 45

At which nephron site would penicilin be secreted?

Answer 45

PCT