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Flashcards in Renal Q2 Deck (169):
1

What is the principal mechanism for modifying the composition of the filtered fluid?

Tubular reabsorption

2

Movement from the lumen into the Peritubular capillary is...

Movement from the Peritubular capillary into the lumen is...

Tubular reabsorption

Tubular secretion

3

Amount excreted =

Amount filtered (+ secreted) - amount reabsorbed

4

If amount X excreted

A % of X was reabsorbed

5

What are 2 examples of substances that are fully reabsorbed?
(amount excreted = 0)

Glucose

Bicarb

6

T/F
A homeostatic mechanism is altering the amount of reabsorption of the filtered load

**Are there exceptions to this????

True

7

What are the 2 membranes of Renal Epithelial cells?

Luminal

Basolateral

8

What type of transport occurs across both membranes (luminal and basolateral) of renal epithelial cells?

What type of transport occurs between renal epithelial cells across tight junctions by simple diffusion?

What type of transport is most common?

Transcellular

Paracellular

Transcellular

9

What does the Transcellular route require on both membranes?

Transport proteins

10

What does Passive Transport require?

favorable electrochemical gradient

11

Name 4 types of Transport.

Simple diffusion
Ion channels
Facilitated (uniporter, symporter, antiporter)
Energy Dependent (ATPases)

12

What is the rate limiting step in the reabsorption of sodium (and many other solutes)?

Na/K pump
(ATP ase)

13

What is the Glucose transporter of the kidney?

GLUT 2

14

How does the Collecting tubule transports Sodium out through the Luminal membrane?

Na+ selective channels through luminal side

exits cell via Na/K pumps (ATP powered)

15

How does the Proximal tubule transport Sodium out through the Luminal membrane?

Na+ crosses lumen via Na+/Glc symporter

exits cell via Na/K pump (ATP powered)

16

What fraction of glomerular filtrate is reabsorbed by the Proximal Tubule?

2/3

17

How much water is filtered per day?

How much is reabsorbed at the Proximal Tubule?

180L

120L

18

How is Glucose reabsorbed in the Proximal Tubule?

Na+ symporter on Luminal side
(Downhill Na+ carries Glc Uphill)

*SGLT-1/SGLT-2 are Na+/Glc cotransporters

GLUT2 (uniporter) on basolateral membrane

19

What is one of the principal techniques used to assess tubule function?

In vivo micropuncture

20

What are 2 of the anatomical limitations of In Vivo Micropuncture?
(what can't the pipette reach)

Collecting tubule

Juxtamedullary nephron

*these aren't accessible from the surface of the kidney

21

What 3 solutes are absorbed early in the Proximal Tubule?

Glucose

Amino Acids

Bicarb

22

What solute is absorbed late in the Proximal Tubule?

Cl-

23

What is absorbed throughout the entire length of the Proximal Tubule?

Water

24

The filtration of water and solute at the Lumen of the Proximal Tubule is what type of fluid reabsorption?

Isosmotic

25

If there is an isotonic relationship between the tubular fluid and interstitial fluid in the Proximal Tubule, what accounts for the Isosmotic fluid reabsorption?

Small transepithelial osmotic gradient

(tubular fluid osmolality slightly lower than EC fluid)

26

What are the 2 phases of Proximal Tubule reabsorption?

Water/Solutes from Lumen > Interstitium

Interstitium > Peritubular Capillaries

27

What are 2 Starling forces within Peritubular capillaries that promote fluid uptake?

Low hydrostatic pressure

High Oncotic pressure

28

What happens to the fluid if it's not taken up into the capillaries?

Excreted in the Urine

29

T/F
The Proximal tubule reabsorbs a constant percentage of the filtered load (67%)

True

30

The constant percentage of filtered load reabsorbed by the Proximal Tubule is know as...

Glomerulotubular Balance

31

Why is Glomerulotubular Balance important?

Delivers fluid to distal nephron continuously

32

Name 2 ways Efferent Arteriole resistance increases Proximal Tubule reabsorption (export)

Peritubular pressure goes down

Increased filtration fraction causes increases Oncotic pressure within Peritubular capillaries

33

Where are pipette A and B sampled in In Vivo Micropuncture?

Pipette A - Proximal convoluted tubule

Pipette B - Distal convoluted tubule

34

What are the samples from In Vivo Micropuncture compared to?

A (Proximal tubule) compared with Plasma

A and B (Proximal and Distal) compared to ascertain late Proximal tubule and Loop of Henle

35

What is the advantage to In Vitro Microperfusion?

Any segment of nephron can be analyzed

36

What is the Primary site of secretion of organic anions and cations?

Proximal Tubule

37

What are 3 reasons a substance must be secreted?
(can't be filtered by Glomerulus)

Molecular size
Charge
Plasma binding protein

38

Name 2 anionic Organic Ion Transporters on the basolateral membrane.
(used in Secretion)

OAT-(1,3)
NaDC


*(Na-dicarboxylate co-transporter)

39

Name 2 anionic Organic Ion Transporters on the Luminal membrane
(used in secretion)

OAT4
MRP2

40

Name a cationic Organic Ion Transporter on the Basolateral side.

Name 2 cationic Organic Ion Transporter on the Luminal side.

OCT

OCTN
MDR1

41

What is the rate limiting step in Tubular Secretion?

Na/K ATPase

42

T/F
Organic anion and cation transporters are non-selective

True

*relatively non-selective

43

How might the secretory system in the kidney be manipulated to enhance the effect of drugs?

Block transporters with inert substances increases uptake

44

What are 2 drugs that are completely dependent on tubular secretion to be effective?

Furosemide

Bemetanide

*Diuretics

45

T/F
The Proximal Tubule is the only site of secretion in the nephron.

False

46

Equations for the following:

Amount filtered

Amount excreted

Amount reabsorbed

Filtered: GFR x Plasma conc.

Excreted: Volume x Urine conc.

Reabsorbed: Amount filtered - Amount excreted

47

How do we experimentally illustrate the transport maximum concept?

Renal handling of Glucose

48

The plasma concentration at which Tm is exceeded is called?

Threshold

49

The variance in Tm between individual nephrons is called?

Splay

50

The maximal transport capacity when all carriers/channels are maxed is called...

Tm

51

What is the relationship between GFR and Threshold?

Generally GFR is proportional, but Glucose Threshold is exceeded/excreted until 2mg/ml, then curves toward proportionality

*normal plasma glc conc. well below threshold

52

T/F
Diabetes mellitus is a compensatory response of the kidneys to lower Plasma Glucose

False

53

Why is there Glc in urine (glcosuria) in Diabetes Mellitus?

Filtered load of Glc (GFR x Pglc) >>> Tm

54

Why can Inulin and Creatinine be used to measure GFR?
(2 reasons)

Not reabsorbed or secreted

Not metabolized or produced by Kidney

55

T/F
The clearance of Inulin or Creatinine is equal to the GFR

True

56

What is the Clearance Forumula?

Cx = V x Ux / Px

Clearance of X = Volume plasma cleared / time

57

For inulin and creatinine, all of the plasma filtered by the glomeruli is effectively "cleared"

True

*not reabsorbed

58

T/F
Using inulin or creatinine when testing GFR will yield slightly different results. The same inert substance should be used with each test to ensure consistent results.

True

59

Using Inulin or Creatinine in addition to another solute will tell us what?

How much solute is cleared

60

Why does the amount of PAH into the kidney = Renal Plasma Flow?

All PAH excreted

61

T/F
The amount of PAH in the renal artery will equal the amount in the urine

PAH will not be present in the renal vein

True

True

62

T/F
The same fundamental formula is used to measure Renal Plasma Flow and GFR

True

63

How do we calculate renal blood flow from renal plasma flow?

Add the Hematocrit back in

*about .45
(45%)

64

What progressively increases from the cortex/medulla border to the papilla tip?

Interstitial osmolarity

65

What establishes the increasing hypertonicity as you travel deeper into the nephron?

Interstitial NaCl and Urea

66

T/F
The absolute values for the osmolarity changes to the interstitium are universal

False

Rats have 2x concentration

67

Why is the unique environment of the Interstitium so important?

Essential for urine concentration

68

Are there examples of the same kind of Interstitial environment found in the nephron elsewhere in the body?

No

69

T/F
Nephron only interstitium in body that can stand a Hypertonic environment

True

70

How do the transport characteristics of the thin descending and ascending limbs of the Loop of Henle differ?

Thin descending: reabsorbs Water (no NaCl)

This ascending: reabsorbs NaCl (no Water)

71

How much water does the thin descending limb reabsorb per day?

30-40 Liters

72

How much (%) NaCl does the thin/thick ascending loop of Henle reabsorb per day?

20-25% of Filtered load

73

The thin descending limb concentrates fluid from 300 to _____ mOsm/L
(long looped nephrons)

1200

74

The thick ascending limb dilutes fluid from 1200 mOsm/L to _______

100

75

At the tip (of the Loop of Henle), what is the osmolarity of short nephrons?
long looped nephrons?

800 (short looped)

1200 (long looped)

76

What immediately transports water away from the interstituim, thereby preventing the neutralization of the osmotic gradient?

Vasa Recta

(specialized capillaries)

77

What is the common term for the ascending limb of the loop of Henle?

**Why?

Diluting Segment

**resorption results in dilution

78

What is the unique transporter found on the Luminal membrane of the Thick Ascending Limb?

What is on the Basolateral side?

Na/K/2Cl co-transporter

Na/K ATPase

79

What are 2 reasons the tubular lumen must have a high concentration of K+

Na/K/2Cl cotransporter

Generates Lumen positive potential to drive Paracellular transport of other cations

80

How are Na, K, Ca, Mg reabsorbed Paracellularly?

K gradient in Lumen

81

Which class of drugs affect transport in the Thick Ascending Limb?

Name 2

Loop Diuretics

Furosemide
Bumetanide

82

What do Loop Diuretic inhibit?

Na/K/2Cl Cotransporter

83

The Distal Nephron is made up of what two structures/segments?

Distal Convoluted Tubule

Collecting Tubule

84

What fraction of the filtered load of Water and NaCl remain by the time the Distal Nephron is reached?

10% Water

10% NaCl

85

What 2 hormones regulate Water and Na reabsorption in the Distal Nephron?

ADH - water

Aldosterone - Na

86

What happens to the distal collecting tubule in the presence of ADH?

Antidiuresis

Distal Collecting Tubule more permeable to water

87

T/F
In Diuresis, the distal collecting tubule is impermeable to water due to lack of ADH

True

88

Why does tubular fluid become even more dilute from beginning to end of Distal nephron?

NaCl further reabsorbed

89

How does ADH make the collecting tubule cell permeable to water?

What side is affected?

Aquaporin II inserted on Luminal side

90

What second messenger does ADH use to stimulate AQP-2 on the Luminal membrane?

What is the pathway?

cAMP

Basolateral ADH > cAMP > PKA > AQP-2

91

AQP-2 is in what membrane?

AQP-3 is in what membrane?

Luminal

Basolateral

92

Where are Aquaporins in the low ADH state?

Intracellular vescicles

*storage

93

T/F
Both AQP-2 and AQP-3 are under the influence of ADH

False

*AQP-3 on basolateral side constitutively expressed

94

What are the 2 effects of Aldosterone and where does it act?

Reabsorbs Na+

Secretes Potassium

Cortical collecting tubule

95

What is the intracellular mechanism of Aldosterone?

Steroid hormone, so stimulates Transcription factors for Na/K pumps

96

ADH is _____, while Aldosterone ______

Fast acting

Takes hours

97

Circulating Glucocorticoid (cortisol) is prevented from affecting Na reabsorption by what enzyme?

11 B-hydroxysteroid dehydrogenase type 2

*mutations of which cause hypertension (also licorice)

98

What is countercurrent multiplication?

Deposition of NaCl

99

T/F
Without countercurrent multiplication, isotonic fluid of 100 mM NaCl would flow through the ascending limb into the distal tubule

True

100

3 Step model of Countercurrent Multiplication

Step 1: NaCl from ascending tubule flows into interstitium via Active Transport

Step 2: Water from descending tubule follows Na via Passive Diffusion

Step 3: Multiple cycles sets up Vertical Gradient

101

The Vertical Gradient goes from 590 to 315, but the Horizontal Gradient is always within...

100-200 mOsm

102

What section of tubule cannot reabsorb urea?

What sections can?

In what section is Urea passively diffused into the interstiitum?

Cortical/outer medullary collecting tubule

Outer Medullary and Inner Medullary

Inner Medulla

103

Why is ADH important for Urea reabsorption?

Increases permeability of Inner Medullary section of the collecting tubule

104

What is the term for Urea diffusing from Inner Medullary Collecting tubule to the Interstitium, then re-concentrated and reabsorbed?

Urea recycling

105

T/F
Decrease in ADH will decrease Urea excretion

True

106

A decrease in ADH will decrease Urea reabsorption, which decreases general osmolarity. What else, then, is affected by a decrease in ADH?

Decrease in interstitial NaCl

107

What ensures the hypertonic gradient in the medullary interstitium remains Hypertonic

Countercurrent Exchange in the Vasa Recta

108

The osmolality of the Vasa Recta will be higher flowing out than in. Why?

Reabsorbs all water by descending limb

Reabsorbs Most NaCl by ascending limb

109

How is the hypertonicity of the Medulla maintained by the Vasa Recta?

As it flows out, NaCl and Urea flow from Plasma to Interstituim

110

Why is the flow rate of the Vasa Recta higher flowing out than in?

Picks up all water from descending limb

111

What happens to Medullary cells in a hypertonic environment?

In this environment, what diffuses into cells to disrupt proteins?

Shrinkage

Urea

112

What protects Medullary cells from their hypertonic environment full of urea?

What is the Transcription factor?

Organic Osmolytes

TonEB

113

What increases intracellular osmolarity and disrupts Urea effects in the cell?

Osmolytes

*by TonEB

114

What is the Balance Concept?

Water Input = Water Output

115

What are the major sources of Water Input and Output?

Input: Food, Fluid, Metabolism

Output: Insensible losses (feces, sweat, urine)

116

Maximum Diuresis Urine Volume:

Maximum Antidiuresis Urine Volume:

20-25L/day

.5L/day

117

Why can't we shut down water excretion completely in extreme circumstances?

500mL is lowest volume to dissolve solutes that MUST be excreted in solution

118

What class of hormone is ADH?

Peptide hormone

119

Where is ADH synthesized?

Stored and Secreted?

Supraoptic and Paraventricular nucleii of hypothalamus

Posterior Pituitary

120

ADH secretion is regulated by what 2 receptors?

Hypothalamic osmoreceptors

Volume receptors (baroreceptors)

121

What regulatory mechanism of ADH secretion is more sensitive, the osmoreceptors of the hypothalamus or the volume receptors?

Osmoreceptors

122

Do the Barorecptors and Osmoreceptors regulating ADH interact?

Yes. Volume status influences osmolality and ADH secretion

123

What is the plasma osmolality at which ADH secretion = 0

Set point

124

T/F
Small changes in ADH can elicit large changes in urine osmolality

True

125

In a state of water deficit, an increase in ADH will do what?

Minimize further loss of water

*not replace

126

What controls thirst?

Extracellular Osmolarity

127

What can be caused by Trauma, Tumors, or Drugs that affects ADH?

SIADH

Syndrome of Inappropriate ADH secretion

128

In SIADH, there is an overproduction of ADH, leading to Hyponatremia, and can lead to coma

True

129

What are the 2 causes of Diabetes Insipidus?

Hypothalamic

Nephrogenic

130

T/F
In diabetes insipidus, you have no ability to reabsorb water, so urine output is very high. Leads to Hypernatremia.

True

131

2 treatments for Diabetes Insipidus:

synthetic ADH nasal spray

make sure Water output = Water input

132

What is the assessment of the diluting efficiency of the thick ascending limb?

Free Water Clearance

133

The amount of distilled water that must be added to or removed from urine to create an Isotonic fluid is Free Water Clearance, and tells us...

Diluting efficiency of Thick Ascending Limb

134

Is the standard Clearance formula used for Free Water Clearance?

No

Ch2o = V - Cosm

135

When would Free Water Clearance = 0

When excreting Isotonic Urine

136

When Hypertonic urine is excreted, what is the term used?

Free Water Absorption

137

What are 3 reasons ECF volume is directly related to total body NaCl?

ECF to ICF shifts

ADH secretion/distal nephron reabsorption

Thirst

138

How do kidneys maintain constant ECF?

Adjust NaCl excretion to match NaCl intake

139

Na+ excretion is primarily regulated by _____ on the ________.

(latter is only place Aldosterone affects Na reabsorption )

Aldosterone

Cortical Collecting Tubule

140

In what 3 ways does Aldosterone control reabsorption of Na+?

Na+ channels on Luminal side

Na/K ATPase synth

Increases Krebs enzyme synth
(more ATP for ATPase)

141

The action of Aldosterone takes _______.

The action of ADH takes _______.

Hours

Minutes

142

Why is the measurement of extracellular fluid sodium concentration not a reliable index of total body sodium content?

What is a better measurement for sodium content?

Volume from ICF compensates and returns osmolarity to normal.

ECF Volume

143

What is ECV?

How is it monitored?

Effective Circulating Volume

Baroreceptors

*this is an effective measurement of Sodium

144

What is the rate limiting step in the Renin-Angiotensin-Aldosterone System?

Renin release from Kidney

145

T/F
Renin is a hormone

False

*it's an enzyme

146

Where is Antiotensinogen synthesized?

Liver

*in circulation

147

Where is Angiotensin I converted to Angiotensin II?

Lungs

148

Where is Aldosterone synthesized?

Zona glomerulosa of Adrenal Cortex

149

What is the apparatus that regulates renal blood flow and glomerular filtration rate found by the glomerulus?

Juxtaglomerular apparatus

150

Where is Renin synthesized?

Granular Cells of the Juxtaglomerular Apparatus

151

What are the 3 mechanisms regulating Renin release?

Baroreceptors

Sympathetic nerves

Macula Densa

152

Why doesn't the autoregulatory control of the Macula Densa increase pressure? Why the Renin?

Blood Pressure (macro) has to increase

153

What increases Cardiac Output to help restore "normal" blood pressure despite low ECV>

Angiotensin II's Rapid Onset effects

154

What are the 2 longer onset effects of Angiotensin II?

Decrease NaCl and water excretion

Increase NaCl and water intake

155

T/F
Sustained increases in aldosterone secretion results in relatively transient Na+ retention

True

156

What is the cessation of Sodium retention of Aldosterone due to pressure natriuresis and pressure diuresis?

Aldosterone Escape

157

ECF volume after escape...

Continues to rise?

158

Positive sodium balance:

Negative sodium balance:

Intake > excretion

Excretion > intake

159

What is the most direct indication of a Positive and Negative sodium balance?

Water Retention or Water Excretion

160

Why do the Kidneys have a difficult time with sudden and sustained changes in sodium intake?

Because it operates on Aldosterone and is transcription/channel dependent, Kidney takes days to adjust.

161

Where is Atrial Naturetic Peptide synthesized?

What stimulates its release?

Atrial Monocytes

ECV increase

162

In what 4 ways does ANP excrete salt?

Vasodilation afferent arteriole

Aldosterone inhibition

NaCl reabsorption inhibition

Inhibits ADH release/action on collecting tubule

163

T/F
Under normal circumstances, ANP doesn't do much

True

*things must be whack
**AngII is primary means of regulation

164

What condition is a result of mutations in one or more ascending limb transport proteins?

Bartters Syndrome

165

5 physiological abnormalities of Bartter's Syndrome:

Salt wasting
Volume depletion
Hyperreninemic hyperaldosteronism
Hypercalciuria
Hypokalemic metabolic alkalosis

166

What disease is marked by fluid filled sacs that develop from renal tubular epithelial cells
(and is autosomal dominant 85%)

Polycystic Kidney Disease

167

Name 4 classes of Diuretics

Proximal tubule carbonic anhydrase inhibitors

Thick ascending limb "loop diuretics"

Distal tubule luminal NaCl cotransport inhibitors

Collecting tubule K+ sparing diuretics (inhibit Na channels)

168

What is the accumulation of excess fluid in the interstitial space?

*caused by?

Edema

*Starling forces out of whack

169

How does normal kidney function exacerbate edema?

Reabsorbs Na and Water, which decreases Oncotic Pressure

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