Proximal Tubule Transport Systems Flashcards
Where does the proximal tubule begin?
At the urinary pole of bowman’s capsule
Which nephrons have longer PST segments?
Cortical nephrons have longer PST segments than juxtamedullary which start and end deeper
How much of the ultrafiltrate does the PT absorb?
2/3 (has a “leaky” epithelium)
Describe some properties of the PCT?
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
Describe some properties of the PST
Shorter brush border, smaller mitochondria and less complicated BLM struc than PCT
Which part of the PT has a higher Na/K ATPase activity?
PCT, because does more of the absorbing
Proteins involved in intercellular/paracellular traffic
Zona occludens (tight jxn) forms a continuous band around the luminal portion of the cells (proteins=e cadherin, integrins, caludins etc)
How are glucose, citrate, lactate, urate, ketones, H+, bicarb and AAs reabs?
In the PT by specific co transporters with Na on the apical membrane
What is the charge of the beginning and end of the PT?
Goes from negative to positive
Where is water permeability highest of all nephron segments?
PT
How is Cl reabs?
Mostly paracellularly in the proximal PT and transcellularly in the late PT (makes sense with charge change)
How is K+ reabs in the PT?
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
What % of filtered bicarb is reabs in the PT?
80%
How is bicarb reabs in the PT?
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
How are Ca and Mg reabs in the PT?
Passive paracellular diffusion
Ca: 50-60% reabs in PT, mostly late when PD is +
Mg: only 5-15% is reabs
What protein fxns as a paracellular ca channel?
Claudin-2
What factors decrease phosphate reabs?
FGF-23, PTH, high Pi intake
What factors inc phosphate reabs?
Phosphate deficiency
GH
How does phosphate get reabs in the PT
Coupled to Na+ via co-transporters
-80% of it is reabs in the PT
How is glucose reabs in the PT?
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
How is urate handled in the kidney?
More than 90% is reabs in the early PCT and is indirectly linked to Na reabs
What increases excretion of uric acid?
volume expansion and high urate flow rate and high dose asprin
What decreases excretion of uric acid?
Inhibited by low dose aspirin and volume contraction (including with diuretics)
What is the megalin-cubulin complex?
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.
Where does ammoniagenesis occur and how is it made?
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
What diuretics work in the PT?
Osmotic diuretics (like mannitol) and carbonic anhydrase inhibitors
What is fanconi syndrome?
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**
What happens to kids who have fanconi syndrome?
Rickets, impaired growth
What happens to adults who have fanconi syndrome?
Osteomalacia and osteoporosis
What can cause fanconi syndrome?
- Paraproteinemias (multiple myeloma due to light chain tox is most common in adults)
- Exogenous factors like drugs and heavy metals
- Inherited causes
