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kidney pharmacology > proximal tubule > Flashcards

proximal tubule Flashcards

1
Q

proximal tubule function

A

absorptive role with a high permeability to water

bulk reabsorber

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2
Q

epithelium type in proximal tubule

A

leaky

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3
Q

Ussing model explained

A

sodium potassium ATPase is confined to the basolateral membrane, which keeps intracellular sodium low and potassium high

the sodium gradient then powers movement across the apical membrane, resulting in the unidirectional flux of sodium

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4
Q

proximal tubule structure

A

one cell type present

apical brush border microvilli

3 nephron subdivisions, S1,S2,S3

S1+S2 form the proximal convoluted tubule

S3 straight tubule

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5
Q

what proportion of sodium and water are filtered at the proximal tubule?

A

2/3

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6
Q

how do the reabsorptive processes differ in the different halves of the tubule?

A

first half, sodium uptake coupled with organic solutes, glucose and amino acids, phosphate and bicarbonate

second half, sodium uptake coupled with chloride

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7
Q

stages of glucose reabsorption

A
  1. sodium moves from apical membrane into the epithelial cell via a sodium, glucose symporter SGLT
  2. glucose then diffuses across the cell and move into the blood via GLUT
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8
Q

differen carriers in different regions

A

SGLT2 in S1 and S2, one sodium and one glucose

SGLT1 in S3, two sodiums and one glucose

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9
Q

why is doubling the sodiums important?

A

enables more glucose to be scavenged by the blood

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10
Q

what glucose stereoisomer is transported through GLUT?

A

D glucose not L

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11
Q

transport maximum definition

A

finite transport capacity due to the use of carrier proteins, around 250mg per minute

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12
Q

what happens if transport maximum is exceeded?

A

overspill of glucose present in the urine

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13
Q

stages of amino acid reabsorption?

A
  1. sodium moves from lumen across the apical membrane down its concentration gradient
  2. amino acid moves alongside the sodium through symporters
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14
Q

what do different symporters carry?

A

cationic basic amino acids, anionic acidic amino acids, neural amino acids and glycine+ imino acids

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15
Q

what stereoisomer is carried?

A

L-amino acids

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16
Q

cystinuria explained

A

defect in the cationic pathway which predisposes an individual to form kidney stones

17
Q

explain stages of bicarbonate ion absorption

A
  1. hydrogen ions are transported into the lumen from the cell, via the apical sodium hydrogen exchanger
  2. hydrogens in the lumen then react with bicarbonate ions to form carbonic acid
  3. carbonic acid dissociates into water and carbon dioxide, catalysed by carbonic anhydrase present on the apical membrane
  4. water and carbon dioxide then diffuse across the apical membrane
  5. within the cell, the carbon dioxide is hydrated to form carbonic acid in the presence of carbonic anhydrase
  6. carbonic anhydrase dissociates into hydrogen and bicarbonate ions
  7. the hydrogen ions are then pumped out at the apical pump whereas bicarbonate ions leave the basolateral membrane via a cotransporter, where 3 HCO3- are moved with one sodium
18
Q

where is the energy derived from for the basolateral movement of sodium?

A

the bicarbonate electrochemical gradient allows sodium to move against its electrochemical gradient

19
Q

where does chloride absorption take place?

A

halfway along the proximal tubule

20
Q

paracellular pathway of chloride absorption

A
  1. glucose movement with sodium create a negative lumen and positive interstitium
  2. results in chloride moving via tight junctions down the electric gradient into the interstitium
21
Q

transcellular pathway of chloride absorption

A
  1. apical sodium hydrogen antiporter, builds up hydrogens in the lumen
  2. hydrogen reacts with formate to produce formic acid
  3. formic acid is uncharged so diffuses into the cell
  4. dissociates into hydrogen and formate
  5. formate diffuses down its gradient out of the cell at the apical membrane and allows the movement of choline in the opposite direction
  6. chloride then diffuses into the interstitium via the potassium chloride symporter
22
Q

calcium transcellular reabsorption

A
  1. moves through apical ECaC channels down their concentration gradient
  2. chaperoned across the cell by binding to calcium binding proteins
  3. basolateral calcium atpase, 2 hydrogens in, 1 calcium one or calcium sodium transporter, 3 sodium in and one calcium out
23
Q

what stimulates calcium transport?

A

parathyroid hormone and vitamin D

24
Q

example of organic anion secreted by the proximal tubule

A

PAH- para-amino hippurate

25
Q

stages of secretion

A
  1. basolateral transporter, sodium out alpha ketoglutarate in
  2. alpha ketoglutarate then diffuses out of the basolateral membrane down its electrochemical gradient on an anion exchanger linked to PAH
  3. PAH then accumulates within the cell and diffuses down its electrochemical gradient at the apical membrane down an anion exchanger, in exchange for hydroxyl ions
26
Q

why does chloride concentration in the filtrate initially rise?

A

mass absorption of glucose of sodium leads to water loss, which increases the chloride concentrations

27
Q

how else is sodium absorbed?

A

paracellularly

initial transcellular movement leads to paracellular absorption of chloride, which increases the positivity of the lumen

sodium then moves down its electrochemical gradient from the lumen to the interstitium paracellularly

28
Q

water reabsorption explained

A
  1. moves paracellularly through solvent drag due to sodium and glucose absorption
  2. moves transcellulary through constitutively expressed aquaporin 1 channels
29
Q

a word that describes the movement of solutes in the proximal tubule

A

isosmotic

30
Q

explain the isosmotic nature of reabsorption

A

the water follows the ions, so the concentrations are always the same

no osmotic difference between the lumen and interstitial fluid so water absorption appears isotonic

31
Q

synonym for glucose overspill

A

glycosuria

32
Q

glycosuria definititon

A

excretion of glucose into the urine due to elevated blood glucose levels

33
Q

when does glycosuria occur?

A

exceeds transport maximum , renal threshold

prevents reabsorption

34
Q

what is Tm?

A

transport maximum

point at which increases in concentration of a substance does no result in an increase of movement

35
Q

endogenous compound that is secreted

A

uric acid

36
Q

what is uric acid?

A

product of the metabolic breakdown of purine nucleotides

37
Q

exogenous compound that is secreted?

A

penicillin

38
Q

explain excretion of penicilin

A

not filtered out in glomerulus

instead moves from peritubular capillaries into the lumen of the nephron via acidic carriers

removed via urine

kidney pharmacology (7 decks)

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