47 Obligatory reabsorption and secretion in the proximal convoluted tubule Flashcards

1
Q

Where does most of the recovery of ions, sugars, amino acids, peptides and a considerable amount of the total water occur?

A

First part of proximal tubule

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2
Q

What is the function of proximal tubule?

A
  • Recovery of ions, sugars, amino acids, peptides and a considerable amount of the total water
  • Actively secretes compounds for urinary excretion
  • Metabolises amino acids
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3
Q

What are the two pathways molecules and ions might take across the tubule epithelium?

A
  1. Transcellular route (through the cell body)

2. Paracellular route (through the leaky ‘tight’ junctions between cell bodies)

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4
Q

What are the 5 forces involved in obligatory reabsorption from the proximal tubule?

A
  1. ION GRADIENTS across the basolateral membrane - active transport 3Na out 2K in
  2. This sets up an ELECTROCHEMICAL GRADIENT ~ -3mV (tubule lumen -ve; causes paracellular efflux of cations)
  3. OSMOTIC GRADIENT set up by pumping Na out of the cell into the interstitial space
  4. SOLVENT DRAG - water moving along the paracellular path due to osmotic pressure drags solutes along with it
  5. Chemical concentration of solutes left behind when water leaves the tubule facilitates a CHEMICAL GRADIENT
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5
Q

What occurs at ion gradients across the basolateral membrane?

A

Active transport 3Na out 2K in

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6
Q

What is the electrochemical gradient and what does is cause?

A
  • 3mV

Tubule lumen -ve; auses paracellular efflux of cations

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7
Q

How is the osmotic gradient set up?

A

Pumping Na out of cell into the interstitial space

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8
Q

What is solvent drag?

A

Water moving along the paracellular path due to osmotic pressure drags solutes along with it

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9
Q

How is chemical gradient facilitated?

A

Chemical concentration of solutes left behind when water leaves the tubule

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10
Q

Different transport mechanisms at the proximal convoluted tubule cell?

A
  • Sodium pump
  • Co-transport
  • Counter transport (exchange)
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11
Q

What does the sodium pump do?

A
  • Active transport
  • Sets up Na+ concentration gradient
  • Gradient used by cell to transport other substances (secondary active transport)
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12
Q

What does co-transport with sodium do?

A

Moves substances into cell

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13
Q

What does counter transport (exchange) do with sodium do?

A

Moves substances out of cell

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14
Q

Movements of components occurring at the proximal convoluted tubule?

A
  1. The sodium pump decreases [Na+]i
  2. Sodium conc. gradient is used by the Na+/H+ exchanger to transport H+ OUT of the cell (against its conc. gradient)
  3. H+ combines with filtered bicarbonate to produce carbonic acid which breaks down to H2O and CO2
  4. H2O and CO2 diffuse into the cell
  5. H2O and CO2 produce H+ and bicarbonate
  6. H+ leaves cell (see note 2) into tubule lumen
  7. On basolateral membrane chloride, bicarbonate and potassium leave down their concentration gradients
  8. On basolateral membrane Ca2+ is exchanged for Na+. Ca2+ leaves the cell against its conc. gradient
  9. On apical membrane, Ca2+ enters through a Ca2+ channel. Also via paracellular route
  10. Entry of other solutes: coupled to Na+ entry on apical membrane; facilitated diffusion on the basolateral membrane.
  11. Solvent drag: Due to osmotic gradient from lumen to ISF. Movement of water (solvent) drags other ions through the paracellular route
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15
Q

What is “transport maximum”?

A

The limit of how much solute can be moved across the proximal convoluted tubule
(Tm or Tmax)

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16
Q

What is Tm/ Tmax measured in?

A

mg/min or mol/min (rate)

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17
Q

When can Tmax be exceeded?

A

• If blood conc. is high
-e.g. Glucose/ diabetes mellitus
• Increased plasma conc. or GFR

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18
Q

How does exceeding Tmax affect reabsorption and excretion?

A

Ion/component remains in fluid in tubule and is excreted in urine

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19
Q

Amount filtered (mg/min) =

A

Plasma conc. (mg/ml) x GFR (ml/min)

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20
Q

What is the threshold?

A

Point at which the amount filtered is equivalent to Tmax

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21
Q

What happens above the threshold?

A
  • Substance appears in urine (when normally 100% reabsorbed)

* Conc. of glucose in urine is proportional to plasma concentration

22
Q

How much can the Na-gluocse transporter reclaim?

A

~ 375 mg/min glucose

23
Q

What happens if the plasma conc. or GFR increases?

A
  • There is more than normal limits in the tubule

* Tmax may be exceeded as reabsorption process cannot cope

24
Q

Amount filtered is proportional to the amount present in the ____

A

Plasma

25
Q

The amount of solute appearing in the urine is the amount filtered from glomerulus plus ???

A

The amount secreted

26
Q

What happens to the secretion line once maximum secretion level is reached?

A

Levels off

27
Q

What happens to urea in the proximal convoluted tubule after being filtered in the glomerulus?

A

Simple diffusion reabsorbs 50-60% (rest lost)

28
Q

What happens to lipid-soluble substances in the proximal convoluted tubule after being filtered in the glomerulus?

A

Simple diffusion

29
Q

What happens to phosphate in the proximal convoluted tubule after being filtered in the glomerulus?

A

Sodium-linked transport

Activity of carriers changed by parathyroid hormone

30
Q

What happens to proteins in the proximal convoluted tubule after being filtered in the glomerulus?

A

Small amount digested to amino acids within the tubule cells

31
Q

What % of glucose, amino acids and lactate, are obligatorily reabsorbed in the proximal convoluted tubule?

A

100%

32
Q

What % of bicarbonate are obligatorily reabsorbed in the proximal convoluted tubule?

A

90%

33
Q

What % of water and sodium, are obligatorily reabsorbed in the proximal convoluted tubule?

A

65%

34
Q

What % of potassium are obligatorily reabsorbed in the proximal convoluted tubule?

A

55%

35
Q

What % of chloride are obligatorily reabsorbed in the proximal convoluted tubule?

A

50%

36
Q

What is clearance?

A

Volume of plasma cleared of the substance per unit time (ml/min)

37
Q

What is the clearance range?

A

Zero (fully reabsorbed e.g. glucose, or never filtered e.g. protein)
—->
Equivalent of RPF (all substances filtered ends in urine)

38
Q

What 3 renal processes determine and modify composition of urine?

A
  1. Glomerular filtration
  2. Tubular reabsorption
  3. Tubular secretion
39
Q

How do you calculate the amount excreted by urine?

A

Amount filtered - amount reabsorbed + amount secreted

40
Q

Renal blood flow is large (_____ ml/min) in relation to size of the kidney

A

1100 ml/min

41
Q

What is renal plasma flow?

A

Amount of fluid entering the kidney that is potentially filterable (600 ml/min)

42
Q

How much of renal blood flow is made up of cells?

A

500ml/min out of 1100ml/min

43
Q

Filtration fraction?

A

F.F = GFR/ RPF

= 125/600 = 20%

44
Q

Clearance fraction?

A

C(x) = ( U(x) x V ) / Pa(x)

  • U= urine concentration of x mg/ml
  • V= urine flow rate ml/min
  • Pa= renal arterial plasma conc
45
Q

Input = output of kidney equation?

A
  • Renal artery = Renal vein + Ureter
  • P(a) x RPF(a) = P(v) x RPF(v) + U(x) x V
  • Pa = plasma conc x in renal artery
  • Pv = plasma conc x in renal vein
  • RPF = renal plasma flow
  • V = urine flow rate
  • U = urine conc of x
46
Q

To measure GFR the substance must be…

A
  1. Freely filtered at glomerulus
  2. Neither secreted or reabsorbed
  3. Not metabolised
  4. Not toxic
47
Q

What ideal substance is used to measure GFR?

A

Inulin

- plant sugar and needs to be infused to establish constant plasma concentrations

48
Q

How to measure GFR in inulin?

A

GFR = ( U(in) x V ) / P (in)

49
Q

Clearance ratio greater than 1

A

Substance secreted

50
Q

Clearance ratio less than 1

A

Substance reabsorbed

51
Q

Use of clearance ratios?

A

To determine the renal transport mechanism - net reabsorption, net secretion

52
Q

What can RPF be estimated from?

A

Clearance of Para-aminohippuric acid (PAH)