Lecture 17: Tubular Reabsorption And Secretion Flashcards

1
Q

Describe the passive transport route

A
  • For a substance to be reabsorbed, it must first be transported:
  • Across the tubular epithelial membranes into the renal interstitial fluid.
  • Through the peritubular capillary membrane back into the blood.
  • Water is transported from the lumen through the tubular cells into the interstitium via both transcellular and paracellular routes by osmosis.
  • See Slide 5
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2
Q

Describe ultrafiltration and bulk flow

A
  • Water is transported by way of specific water channels:
  • Aquaporins (AQP):
    • Aquaporin-1 is widespread, incl. renal tubules.
    • Aquaporin-2: Present in apical membranes of collecting tubule cells and Controlled by ADH
  • -Aquaporin-3: Present in basolateral membranes of collecting tubule cells.
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3
Q

Describe ATPases

A
  • ATPases establish ionic gradients across nephron cell membranes:
  • Gradients drive reabsorption or secretion of many other solutes.
  • These are then transported by way of “secondary” active transport.
  • Symport(cotransport):
    • Solute moves with Na+ gradient
  • Antiport (countertransport)
    • Solute moves opposite to Na+ gradient
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4
Q

Describe ATPases and their association with channel movement

A
  • ENaC channel
  • Found in apical membrane of nephron cells
  • Closed by drug amiloride
  • Opened by a number of hormones
  • CFTR (chloride) channels and K+ channels also found in apical membranes of some segments of nephron.
  • Uniporters are also found in cell membranes:
  • Driven by concentration gradient of substance concerned
  • Transport occurring through channels or uniporters
  • Facilitated transport
  • i.e.: glucose transport
  • Transport directly coupled to an energy source
  • = active transport
  • Transport that is coupled indirectly to an energy source (i.e., ion gradient)
  • = secondary active transport
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5
Q

What enzymes are primary active transporters?

A
  • Na+K+ATPase
  • H+ATPase
  • H+K+ATPase
  • Calcium ATPase
  • Study Fig. 28-2
  • See Slide 12
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6
Q

Describe secondary active transport

A
  • Reabsorption of glucose or amino acids by renal tubule are examples of secondary active transport:
  • Sodium-glucose co-transporters on brush border of proximal tubule cells:
    • SGLT2: Reabsorbs 90% of glucose in early proximal tubule
    • SGLT1: Reabsorbs 10% of glucose in late proximal tubule
  • See Slide 14
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7
Q

List substances that are actively secreted into the renal tubules.

A
  • Creatinine

* Para-aminohippuric acid

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8
Q

Describe the transport maximum

A
  • Limit to the rate at which the solute can be transported:
  • Due to saturation of a specific transport system
  • Threshold for glucose reabsorption:
  • Transport max. for glucose = 375 mg/min
  • Filtered load for glucose = 125 mg/min
  • GFR x plasma glucose = 125 ml/min x 1 mg/ml
  • See Slide 18
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9
Q

What are some reasons that some passively reabsorbed substances do not have a transport maximum

A
  • Rate of diffusion is determined by electrochemical gradient of the substance
  • Permeability of the membrane for the substance
  • Time that the fluid containing the substance remains within the tubule
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10
Q

What is the Gradient-Time Transport

A
  • Rate of transport depends on:
  • The electrochemical gradient
  • Time the substance is in the tubule:
    • Depends on tubular flow rate
  • Characteristic of some passively reabsorbed substances
  • Includes some other substances that are actively transported
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11
Q

What is solvent drag

A
  • Passive water reabsorption by osmosis is coupled mainly to sodium reabsorption.
  • Osmotic movement of water can also carry some solutes =
  • Solvent drag
  • See slide 22
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12
Q

Describe the proximal tubule

A
  • Highly metabolic w/large numbers of mitochondria
  • Extensive brush borders on luminal surfaces
  • Extensive intercellular and basal channels on interstitial surfaces
  • Reabsorb:
  • 65% of filtered sodium, chloride, bicarbonate and potassium
  • Reabsorb all filtered glucose and amino acids
  • See Slides 26-29
  • Secretes:
  • Organic acids, bases and hydrogen ions into tubular lumen
  • Sodium reabsorption:
  • In first half of proximal tubule:
    • Reabsorption is via co-transport along with glucose, amino acids, and other solutes.
  • In second half of proximal tubule:
    • Reabsorption is mainly with chloride ions
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13
Q

Describe sodium transport in the proximal tubule

A
  • Most Na+entry is via antiport with H+
  • Na+ is pumped out of cell via Na+K+ATPase pump
  • 3Na+: 2K+
  • K+ can easily diffuse back out of cell.
  • Electrical gradient:
  • Cytoplasm = -70 mV
  • Tubular lumen = -3 mV
  • Concentration gradient:
  • Luminal Na+ concentration = 140 mOsm
  • Cytoplasmic Na+ concentration = 30 mOsm
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14
Q

Describe Hydrogen and bicarbonate ions in the proximal tubule

A
  • [H+] increases in lumen due to antiport transport with Na+
  • H+combines with luminal bicarbonate
  • Forms carbonic acid
  • Carbonic anhydrase in lumen splits carbonic acid into carbon dioxide and water.
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15
Q

Describe what occurs when carbon dioxide and water enter cell in the proximal tubule

A
  • Carbon dioxide and water combine to form carbonic acid.
  • Carbonic acid dissociates to form bicarbonate ion and H+
  • Bicarbonate ion diffuses out of cell into interstitial space.
  • H+removed from cell via:
  • Antiport with Na+
  • H+ATPase
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16
Q

Describe the Thin Descending Segment of the Loop Of Henle

A
  • Highly permeable to water and moderately permeable to most solutes, including urea and sodium
  • Reabsorbs about 20% of filtered water
  • Impermeable to water
17
Q

Describe the thick ascending segment of the Loop Of Henle

A
  • Na+K+ATPase pump in basolateral membranes:
  • Drives reabsorption of K+ into cell against concentration gradient.
  • Sodium, Potassium, Chloride co-transporter:
  • Moves 1-sodium, 2-chloride, 1 potassium into cell.
  • Slight back leak of K+ into lumen:
  • Creates positive charge of +8 mv.
  • Forces Mg++ and Ca++ to diffuse through tubular lumen through paracellular space into interstitial fluid.
  • Impermeable to water
  • Site of action of powerful “loop” diuretics:
  • Furosemide
  • Ethacrynic acid
  • Bumetanide
  • See Slide 34-35
18
Q

Describe the distal tubule

A
  • First portion forms macula densa.
  • Next part is highly convoluted and has characteristics similar to thick ascending segment of loop of Henle.
  • Reabsorbs most of the ions but is impermeable to water and urea:
  • Therefore, referred to as diluting segment.
  • Na+-Cl─ co-transporter (luminal membrane)
  • Na+K+ATPase pump (basolateral membrane)
  • See Slide 39-40
19
Q

Describe the principle cells of the Late Distal Tubule/Cortical Collecting Tubule

A
  • Reabsorb Na+ and water from tubular lumen.
  • Secrete K+ into tubular lumen.
  • Uses Na+K+ATPase pump.
  • Primary site of K+sparing diuretics:
  • Spironolactone, eplerenone, amiloride, triameterene
  • See Slide 42-43
20
Q

Describe the intercalated cells of the Late Distal Tubule/Cortical Collecting Tubule

A
  • Reabsorb K+ from tubular lumen.
  • Secrete H+ into tubular lumen:
  • Mediated by a H+ATPase transporter.
  • H+is generated through the action of carbonic anhydrase.
  • For each H+ secreted, a bicarbonate ion is reabsorbed across the basolateral membrane.

See Slide 45

21
Q

Describe the Medullary Collecting Duct

A
  • Epithelial cells are cuboidal:
  • Smooth surfaces
  • Few mitochondria
  • Permeability to water controlled by ADH.
  • Permeable to urea:
  • Urea transporters
  • Capable of secreting H+ against a large concentration gradient.

See Slides 47-52

22
Q

For aldosterone, describe the source, function, site of actin, and stimulus for secretion

A
  • Source:
  • Adrenal cortex
  • Function:
  • Increases sodium reabsorption and stimulates potassium secretion.
    • Stimulates Na+K+ATPase pump on basolateral side of cortical collecting tubule membrane.
  • Site of action:
  • Major site of action is on the principal cells of cortical collecting ducts.
  • Stimulus for secretion:
  • Increased extracellular potassium
  • Increased levels of angiotensin II
  • Absence of:
  • Addison’s disease
  • Results in marked loss of sodium and accumulation of potassium
  • Hypersecretion:
  • Conn’s syndrome
23
Q

Describe the function and effects of angiotensin II

A
  • Function:
  • Increased sodium and water reabsorption
  • Returns blood pressure and extracellular volume toward normal
  • Effects:
  • Stimulates aldosterone secretion
  • Constricts efferent arterioles
  • Directly stimulates sodium reabsorption in proximal tubules, loops of Henle, distal tubules, and collecting tubules
  • See Slide 57
24
Q

Describe the source, function, and effects of ADH

A
  • Source:
  • Posterior pituitary
  • Function:
  • Increases water reabsorption
  • Effects:
  • Binds to V2receptors in late distal tubules, collecting tubules, and collecting ducts
  • Increases formation of cAMP
    • Stimulates movement of aquaporin-2 proteins to luminal side of cell membranes (form clusters)
25
Q

Describe the source and function on ANP

A
  • Source:
  • Cardiac atrial cells in response to distension
  • Function:
  • Inhibits reabsorption of sodium and water
26
Q

Describe the source and function of parathyroid hormone

A
  • Source:
  • Parathyroid glands
  • Function:
  • Increases calcium reabsorption
27
Q

Define and give the equation for renal clearance

A
  • Renal clearance of a substance:
  • = volume of plasma that is completely cleared of the substance by the kidneys per unit time.
  • Example: If 1 ml of plasma contains 1 mg of a substance, and if 1 mg of this substance is excreted in the urine per minute:
    • Then 1 ml/min of the plasma is cleared of the substance.
  • Cs x Ps = Us x V
  • Cs = clearance rate of substance s
  • Ps = plasma concentration of substance s
  • Us = urine concentration of substance s
  • V = urine flow 63
  • Cs = (Us x V)Ps
28
Q

Describe the renal clearance of inulin

A
  • Inulin:
  • Polysaccharide (mol. Wt. = 5200)
  • Not produced in body
  • For a substance that is completely filtered but not reabsorbed or secreted:
  • The rate at which it is excreted in urine (Us x V) = filtration rate (GFR x Ps)

GFR x Ps = Us x V
GFR = (Us x V)/Ps = Cs

GFR = (Us x V)/Ps = Cs 
* Assume: 
 Ps = 1 mg/ml 
 Us = 125 mg/ml 
 V = 1 ml/min

GFR = (125 mg/ml x 1 ml/min)/1 mg/ml = 125 ml/min
- Thus, 125 ml of plasma flowing through the kidneys must be filtered to deliver the inulin that appears in the urine