Proximal Tubule Transport Systems

Question 1

Where does the proximal tubule begin?

Answer 1

At the urinary pole of bowman’s capsule

Question 2

Which nephrons have longer PST segments?

Answer 2

Cortical nephrons have longer PST segments than juxtamedullary which start and end deeper

Question 3

How much of the ultrafiltrate does the PT absorb?

Answer 3

2/3 (has a “leaky” epithelium)

Question 4

Describe some properties of the PCT?

Answer 4

Tall brush border and lots of vacuolar-lysosomal systems, extensive basolateral membrane invaginations, interdigitation with neighboring cells, extensive elongated mitochondria. Frequent apical vesicles that are involved in protein reabsorption

Question 5

Describe some properties of the PST

Answer 5

Shorter brush border, smaller mitochondria and less complicated BLM struc than PCT

Question 6

Which part of the PT has a higher Na/K ATPase activity?

Answer 6

PCT, because does more of the absorbing

Question 7

Proteins involved in intercellular/paracellular traffic

Answer 7

Zona occludens (tight jxn) forms a continuous band around the luminal portion of the cells (proteins=e cadherin, integrins, caludins etc)

Question 8

How are glucose, citrate, lactate, urate, ketones, H+, bicarb and AAs reabs?

Answer 8

In the PT by specific co transporters with Na on the apical membrane

Question 9

What is the charge of the beginning and end of the PT?

Answer 9

Goes from negative to positive

Question 10

Where is water permeability highest of all nephron segments?

Answer 10

PT

Question 11

How is Cl reabs?

Answer 11

Mostly paracellularly in the proximal PT and transcellularly in the late PT (makes sense with charge change)

Question 12

How is K+ reabs in the PT?

Answer 12

Paracellular pathway in early PT due to solvent drag. Later, - charge drives K+ paracellular reabs.

–>not under any hormonal control in this portion, unlike distal nephron (aldo)

–>BLM Na-K ATPase maintains high intracellular K concentration, favoring passive k secretion across both apical and BLM

Question 13

What % of filtered bicarb is reabs in the PT?

Answer 13

80%

Question 14

How is bicarb reabs in the PT?

Answer 14

Early PT: Bicarb combines with H+ and then diffuses as CO2 + H20 into the cell where it once again becomes bicarb and gets pumped out via Na+ co-transporter

Late PT: Cl, HCO3- exchanger on BLM

Question 15

How are Ca and Mg reabs in the PT?

Answer 15

Passive paracellular diffusion

Ca: 50-60% reabs in PT, mostly late when PD is +
Mg: only 5-15% is reabs

Question 16

What protein fxns as a paracellular ca channel?

Answer 16

Claudin-2

Question 17

What factors decrease phosphate reabs?

Answer 17

FGF-23, PTH, high Pi intake

Question 18

What factors inc phosphate reabs?

Answer 18

Phosphate deficiency

GH

Question 19

How does phosphate get reabs in the PT

Answer 19

Coupled to Na+ via co-transporters

-80% of it is reabs in the PT

Question 20

How is glucose reabs in the PT?

Answer 20

Early: SGLT2 (1 Na-1 glucose co transporter) has high capacity, low affinity for glucose

Late PT: SGLT1 (2-Na: 1 glucose co transporter) has low capacity, but high affinity

-Nearly all filtered glucose is reabs in the PT

Question 21

How is urate handled in the kidney?

Answer 21

More than 90% is reabs in the early PCT and is indirectly linked to Na reabs

Question 22

What increases excretion of uric acid?

Answer 22

volume expansion and high urate flow rate and high dose asprin

Question 23

What decreases excretion of uric acid?

Answer 23

Inhibited by low dose aspirin and volume contraction (including with diuretics)

Question 24

What is the megalin-cubulin complex?

Answer 24

PT apical receptors that mediate reabs of filtered proteins, including albumin, immunoglobulin light chains, and other small mcs from the glomerular ultrafiltrate and allow for their lysosomal breakdown.

Leaves urine protein-free and accounts for much of the conservation of carrier bound vitamins. Also contributes to toxicity of some drugs, which are filtered and taken up into the PT cells to which they are toxic.

Question 25

Where does ammoniagenesis occur and how is it made?

Answer 25

In the cells of the PT, glutamine is taken up by the mitochondria and converted to glutamate then to alpha ketoglutarate which then enters the TCA cycle. Each cycle generates 2 ammonium and 2 bicarbs. Acidosis stimulates this fxn

Question 26

What diuretics work in the PT?

Answer 26

Osmotic diuretics (like mannitol) and carbonic anhydrase inhibitors

Question 27

What is fanconi syndrome?

Answer 27

Generalized dysfxn of the PT
-phosphate, glucose, AA and bicarb wasting in variable degrees

-Impaired fxn of PT induced by accumulation of lysosomal AAs or other compounds, organelle dysfxn, disruption of PT endosomal structures and endocytotic fxn, drug toxicity or immunologic injury affecting the NA-K-ATPASE**

Question 28

What happens to kids who have fanconi syndrome?

Answer 28

Rickets, impaired growth

Question 29

What happens to adults who have fanconi syndrome?

Answer 29

Osteomalacia and osteoporosis

Question 30

What can cause fanconi syndrome?

Answer 30

• Paraproteinemias (multiple myeloma due to light chain tox is most common in adults)
• Exogenous factors like drugs and heavy metals
• Inherited causes