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CVPR > CVPR Week 7: Renal tubular absorption and secretion > Flashcards

CVPR Week 7: Renal tubular absorption and secretion Flashcards

1
Q

Average GFR

A
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2
Q

Identify

A
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3
Q

Question 1

A
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4
Q

Tubular reabsorption selectivity

A

Tubular reabsorption is highly selective

  • Glucose, amino acids are nearly completely resorbed
  • Majority of sodium, chloride and HCO3- also highly resorbed however their are mechanisms to allow for variability
  • Waste products such as urea and creatinine are poorly resorbed so that large amounts are excreted in the urine
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5
Q

Kidney solute reabsorption summary

A
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6
Q

What is reabsorbed where?

A
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7
Q

What is reabsorbed in the proximal convoluted tubule?

A
  • Glucose 100%
  • Amino acids 100%
  • Urea 50%
  • Sodium 70%
  • Potassium 70%
  • Phosphate 70%
  • Calcium 70%
  • Magnesium 30%
  • H2O 70%
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8
Q

What is reabsorbed in the proximal straight tubule?

A

Phosphate 15%

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9
Q

What is reabsorbed in the thick ascending limb

A
  • Sodium 25%
  • Potassium 20%
  • Calcium 25%
  • Magnesium 60%
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10
Q

What is reabsorbed in the distal convoluted tubule

A

Sodium 5%

Calcium 8%

Magnesium 5%

H2O and urea is variable

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11
Q

What is reabsorbed in the collecting duct?

A

Sodium 3%

H2O and urea are variable

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12
Q

What is reabsorbed in the bladder?

A

Potassium 1-100%

Magnesium 5%

Phosphate 15%

Sodium < 1%

Calcium < 1%

H2O and urea are variable

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13
Q

What is filtered load?

A

Total substance filtered into Bowman’s space per time

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14
Q

Filtered Load equation

A

Filtered Load = GFR x [Plasma concentration S] x % unbound S

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15
Q

What is the excretion rate?

A

The amount of substance excreted per time

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16
Q

Excretion rate equation

A

Excretion rate = V’ x [urine concentration S]

where V’ is the micturation rate

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17
Q

How to determine the rate of absorption or secretion?

A

Reabsorption/Secretion rate = filtered load - Excretion rate

or

Urinary excretion = filtered load - tubular reabsorption + tubular secretion

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18
Q

Examples of net reabsorption and net secretion calculations

A
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19
Q

Types of reabsorption (transport mechanisms)

A

Active transport

Passive transport

carrier-mediated transport

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20
Q

Types of active transport

A

Primary active transport

Secondary active transport

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21
Q

Active transport description

A

requires energy expenditure for transport which is usually in the form of ATP

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22
Q

Primary active transport

A

direct energy expenditure to facilitate transport

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23
Q

Secondary active transport

A

Transport which is due to an ion gradient indirectly created by ATPase pump

Typically 2 or more substances are coupled across a membrane protein one moving down its concentration gradient to move the other substance

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24
Q

Example of primary active transport

A

Na+ via Na-K-ATPase pump present throughout the renal tubule

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25
Q

Example of secondary active transport

A

Glucose via the SGLT1 and SGLT2 pumps

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26
Q

Passive transport description

A

no energy required, substance moves along its concentration gradient

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27
Q

Example of passive transport

A

Water reabsorption by tubules is passive and follows Na+ reabsorption

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28
Q

Na-K-ATPase pathway

A
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29
Q

Sodium reabsorption mechanisms in the renal system

A
  • Na-K-ATPase is extensively located on the basolateral membranes throughout the renal tubule
  • there is an extensive brush border on the luminal membrane in the proximal tubule to increase surface area for diffusion of Na+ into the proximal tubular cells (20-fold increase)
  • Sodium co-transporters on the luminal membrane pull sodium, along with carrier substances, into the proximal tubular cells (amino acids, glucose)
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30
Q

What is reabsorbed or secreted in the early proximal tubule?

A
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31
Q

Features of carrier-mediated transport

A
  • There is a limit because a limited number of carriers exist on a cell membrane and therefore the system can become saturated maximizing reabsorption or secretion
  • Carriers are stereospecific such as recognizing d-glucose but not I-glucose
  • Competition similar sized and shaped molecules can compete for transporter space such as lithium for sodium
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32
Q

Carrier-mediated transport speed of transport

A

There is a limit because a limited number of carriers exist on a cell membrane and therefore the system can become saturated maximizing reabsorption or secretion

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33
Q

Carrier-mediated transport specificity

A

Carriers are stereospecific such as recognizing d-glucose but not I-glucose

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34
Q

Carrier-mediated transport competition

A

Competition similar sized and shaped molecules can compete for transporter space such as lithium for sodium

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35
Q

Kinetics of carrier-mediated transport

A
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36
Q

Facilitated glucose transport (transport type)

A

Secondary active transport

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37
Q

Facilitated glucose transport mechanism

A

is a two-step process

Step 1

  • Glucose is initially reabsorbed from the luminal epithelial cells via SGLT cotransporter
  • 2 Na+ molecules transported for each one molecule of glucose
  • Protein rotates in the cell membrane and releases the Na+ and glucose into the ICF
  • Electrochemical gradient of Na+ drives reaction (from Na-K-ATPase)

Step 2

  • Glucose transported from cell to capillary by faciliated diffusion
  • GLUT 1 and GLUT 2 transporter
  • Moving down concentration gradient, no energy required
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38
Q

Glucose filtered loads

A

Glucose is freely filtered at the basement membrane filtered load rises with increasing serum concentration

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39
Q

At what levels can all the glucse be reabsorbed?

A

200 mg/dL

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40
Q

Glucose levels and reabsorption

A

Levels > 200 mg/dL some of the glucose is unable to be reabsorbed and once > 350 mg/dL, all of the glucose co-transporters are saturated thus reaching the transport maximum Tm

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41
Q

Question 2

A
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42
Q

Glucose titration curves

A
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43
Q

How is urea reabsorbed?

A

Passive urea reabsorption

  • Urea is reabsorbed and secreted in different segments of the nephron
  • driven by passive diffusion
  • Concentration gradient between tubular fluid and blood and epithelial cell membrane permeability to urea
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44
Q

Where is urea reabsorbed?

A

About half is reabsorbed in the proximal tubule

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45
Q

Urea rate of diffusion

A

Urea diffuses at slightly a slower rate than water

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46
Q

Passive urea reabsorption mechanism

A
  • The urea is secreted in the descending loop of Henle due to high medullary urea concentrations reaching 110% of filtered urea load and bend of loop
  • Ascending loop of Henle distal convoluted tubule and cortical collecting ducts impermeable to urea
  • Inner medullary collecting ducts there facilitated urea reabsorption via urea transporter 1 which is upregulated in presence of ADH
  • Thus the final excretion of filtered urea is variable
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47
Q

Regulation of urea transporter 1 levels

A

upregulated in the presence of ADH

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48
Q

Urea handling in the nephron

A
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49
Q

Secretion of para-aminohippuric acid

A

example of secretion of an organic anion in promimal tubular cells

transporter responsible for secretion of penicillin

many transporters exist within promal tubular cells for secretion of organic acids and bases

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50
Q

Question 3

A
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51
Q

PAH titration curve

A
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52
Q

Question 4

A
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53
Q

How is HCO3- reabsorbed in the kidney?

A

the majority of filtered HCO3- is reabsorbed via secondary active transport

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54
Q

Na+ - H+ exchanger

A

Na+ - H+ exchanger is responsible for reclamation

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55
Q

Reabsorption of filtered HCO3-

A
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56
Q

Question 5

A
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57
Q

Sodium balance

A
58
Q

What percentage of sodium is usually secreted?

A

1% of sodium is typically excreted

59
Q

Positive Na+ balance results in

A

expanded extracellular fluid volume, hypertension and potentially edema but does not equal a change in serum Na concentration

60
Q

How are changes in serum Na+ concentration reflected?

A

Changes in serum Na+ concentration are reflected by increases or decreases in total body water composition rather than Na+ balance

61
Q

Where is most of the Na+ reabsorbed?

A

approximately 2/3 of Na+ in the proximal tubule where water reabsorption follows sodium reabsorption

62
Q

Where does sodium reabsorption occur?

A
  • approximately 2/3 of Na+ in the proximal tubule where water reabsorption follows sodium reabsorption
  • 25% is reabsorbed in the thick ascending loop of Henle which is impermeable to water by the Na/K/2Cl- cotransporter
  • 5% is absorbed in the early distal convoluted tubule which is also impermeable to water
  • 3% is absorbed in the late distal convoluted tubule and collecting duct
63
Q

Explain Na+ handling in the nephron

A
64
Q

Explain reabsorption and secretion in the late proximal tubule

A
65
Q

Question 6

A
66
Q

Permeability of the thin descending loop of Henle

A

The thin descending loop of Henle is permeable to small solutes, urea and water

67
Q

Permeability of the thin ascending loop of Henle

A

The thin ascending loop of Henle remains permeable to small solutes but is no longer permeable to water

68
Q

Describe the osmolarity of the ultrafiltrate throughout the loop of Henle

A

In the thin descending loop of Henle the osmolarity of ultrafiltrate increases towards the bottom of the loop of Henle

In tthe ascending thin loop of Henle small solutes leave and the ultrafiltrate becomes more hypo-osmolar

69
Q

Describe secretion and reabsorption in the thick ascending limb of the loop of Henle

A

Secondary active reabsorption of Na+ via the Na/K/2Cl- cotransporter energy driven by Na/K/ATPase

70
Q

Diuretic effect on diuresis

A

diuretic blocking reabsorption in the proximal tubule has a small effect on diuresis

71
Q

Loop diuretics bind to?

A

loop diuretics bind to the chloride portion of the Na/K/2Cl- cotransporter inactivating the channel

72
Q

Sodium balance in the early distal tubule

A

5% of Na+ is reclaimed here via the Na/Cl cotransporter secondary active transport driven by Na/K/ATPase

73
Q

Early distal tubule permeability to water

A

Remains impermeable to water

74
Q

Thiazide-type diuretics bind to?

A

the Cl- portion of the Na/Cl cotransporter in the distal tubule and inactivate this channel

75
Q

Describe reabsorption and secretion in the early distal tubule

A
76
Q

What binds to the Na/Cl cotransporter in the early distal tubule

A

thiazide diuretics

77
Q

What binds to the Na/K/2Cl cotransporter in the thick ascending limb of the loop of Henle?

A

Loop diuretics (i.e. Furosemide)

78
Q

Types of cells in the late distal tubule

2 listed

A
  • Principal cells
  • α-intercalated cells
79
Q

Principal cells of the late distal tubule function

A
  • Na+ and water reabsorption
  • K+ secretion
80
Q

α-intercalated cells in the late distal tubule function

A
  • K+ reabsorption
  • H+ secretion
81
Q

The importance of the late distal tubule and collecting duct in sodium balance

A

Though the cells of the DCT and collecting duct only account for 3% of Na+ reabsorption they are hormonally influenced and are a major determinant of overall Na+ balance

82
Q

How much sodium reabsorption do the distal convoluted tubule and the collecting ducts account for?

A

DCT and collecting duct only account for 3% of Na+ reabsorption but play a major role in determining the overall Na+ balance through hormones

83
Q

ENaC AKA

A

Epithelial Sodium Channel

84
Q

Amilorone site of action

A

ENaC

85
Q

Triamterene site of action

A

ENaC

86
Q

Aldosterone effect on principal cells

A
  • Aldosterone causes an upregulation ENaC channels and the Na/K/ATPase in the principal cells
87
Q

How do principal cells reabsorb Na+

A

reabsorb Na+ via the Epithelial Sodium Channel (ENaC) which is the site of action for amiloride and triamterene

88
Q

Drugs that target ENaC

A
  • Amiloride
  • Triamterene
89
Q

Drugs that target the aldosterone receptor on principal cells

A
  • Spironolactone
  • Eplerenone
90
Q

Spironolactone site of action

A

Aldosterone receptor of principal cells

91
Q

Where are principal cells located?

A

the late distal tubule

92
Q

What do principal cells do?

A
  • Na+ and water reabsorption
  • K+ secretion
93
Q

Antidiuretic hormone release results in?

A

Aquaporin2 channel insertion into the luminal membranes of the DCT and collecting duct increasing their permeability to water

94
Q

What happens when the Aquaporin-2 channel inserts into the luminal membranes of the DCT and collecting duct

A

Increased permeability to water

95
Q

Describe reabsorption and secretion in the DCT and collecting duct

A
96
Q

Early proximal tubule major functions

A

Isosmotic reabsorption of solute and water

97
Q

Early proximal tubule cellular mechanisms

A
  • Na+/glucose
  • Na+ /amino acid
  • Na+ /phosphate cotransport
  • Na+/H+ exchange
98
Q

Early proximal tubule Hormone actions

A
  • PTH inhibits Na+ phosphate cotransport
  • Angiotensin II stimulates Na/H exchange
99
Q

Early proximal tubule diuretic classes w/ actions

A
  • osmotic diuretics
  • carbonic anhydrase inhibitors
100
Q

Late proximal tubule major functions

A

Isosmotic reabsorption of solute and water

101
Q

Late proximal tubule cellular mechanisms

A

NaCl reabsorption driven by Cl- gradient

102
Q

Late proximal tubule hormone actions

A

none

103
Q

Late proximal tubule diuretic classes w/ actions

A

Osmotic diuretics

104
Q

Thick ascending limb of the loop of Henle major actions

A
  • Reabsorption of NaCl without water
  • Dilution of tubular fluid
  • single effect of countercurrent multiplication
  • Resorption of Ca2+ and Mg2+ driven by lumen-positive potential
105
Q

Thick ascending limb of the loop of Henle cellular mechanisms

A

Na/K/2Cl cotransport

106
Q

Thick ascending limb of the loop of Henle hormone actions

A

ADH stimulates Na/K/2Cl cotransport

107
Q

Thick ascending limb of the loop of Henle diuretic w/ actions

A

Loop diuretics

108
Q

Early distal tubule major functions

A
  • Reabsorption of NaCl without water
  • Dilution of tubular fluid
109
Q

Early distal tubule Cellular mechanisms

A

NaCl cotransport

110
Q

Early distal tubule hormone actions

A

PTH stimulates Ca2+ reabsorption

111
Q

Early distal tubule diuretics w/ actions

A

Thiazide diuretics

112
Q

Late distal tubule and collecting ducts (principal cells) major functions

A
  • Reabsorption of NaCl
  • K+ secretion
  • Variable water reabsorption
113
Q

Late distal tubule and collecting ducts (principal cells) cellular mechanisms

A
  • Na+ channels (ENaC)
  • K+ channels
  • AQP2 water channels
114
Q

Late distal tubule and collecting ducts (principal cells) hormone actions

A
  • Aldosterone stimulates Na+ reabsorption
  • Aldosterone stimulates K+ secretion
  • ADH stimulates water reabsorption
115
Q

Late distal tubule and collecting ducts (principal cells) diuretics w/ actions

A

K+ sparring diuretics

116
Q

Late distal tubule and collecting ducts (α-intercalated cells) major functions

A
  • Reabsorption of K+
  • Secretion of H+
117
Q

Late distal tubule and collecting ducts (α-intercalated cells) cellular mechanisms

A
  • H/K/ATPase
  • H/ATPase
118
Q

Late distal tubule and collecting ducts (α-intercalated cells) hormone actions

A

Aldosterone stimulates H+ secretion

119
Q

Late distal tubule and collecting ducts (α-intercalated cells) diuretics w/ actions

A

K+ sparring diuretics

120
Q

Major mechanisms affecting Na+ balance

4 listed

A
  • SNS
  • ANP
  • Starling forces in peritubular capillaries
  • Renin-Angiotensin-Aldosterone System
121
Q

How does the SNS affect the Na+ balance?

2 listed

A
  • Decreased blood volume detected by carotid baroreceptors
  • vasoconstriction of afferent arterioles and increased proximal tubule Na+ reabsorption
122
Q

How does ANP affect Na+ balance?

3 listed

A
  • Stretch of atria
  • Vasodilation of afferent arterioles and vasoconstriction of efferent arterioles (increase GFR)
  • Decreases Na+ reabsorption in DCT and collecting duct
123
Q

How do Starling forces in peritubular capillaries affect Na+ balance?

A
  • Glomerulotubular balance - expansion of ECF decreases oncotic pressure minimizing fluid reabsorption
124
Q

How does the Renin-Angiotensin-Aldosterone System affect Na+ balance?

A
  • Activated in response to decreased renal perfusion pressure
125
Q

Increased Na+ intake results in?

A
126
Q

Reduced Na+ intake results in?

A
127
Q

Question 7

A
128
Q

Mechanism of isosmotic reabsorption in the proximal tubule

A
129
Q

Question 8

A
130
Q

Question 9

A
131
Q

Potassium balance

A
132
Q

Describe K+ handling in the nephron

A
133
Q

Describe K+ handling in the late distal tubule and collecting duct

A
134
Q

Question 10

A
135
Q

Clearance of weak acid/base

A
136
Q

Clearance of weak acid/base and urine pH

A
137
Q

Clinical considerations of diuretics

A
138
Q

Clinical considerations of SGLT inhibitors

A

Treatment of diabetes

139
Q

Clinical considerations of ACE-inhibitors/Angiotensin receptor blockers

A

management of hypertension

140
Q

Clinical considerations of carbonic anhydrase inhibitors

A

Acetazolamide - acidifying agent for severe alkalosis

141
Q

Disease Clinical considerations

A

CVPR (93 decks)

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