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Flashcards in Renal Physiology Deck (125):
1

Effect of sympathetics on renal function

  • Decrease in RPF
  • Decrease in GFR
  • Decrease in pressure of peritubular capillary
  • Increase in oncotic pressure in peritubular capillary

2

Filtered Load

FL = GFR * Px

3

Excreted Load

EL = Vu*Ux

4

Fractional Excretion

Fraction of filtered load of a solute that is excreted.

FE = EL/FL = (Vu*Ux) / (GFR*Px) = Cx/Ccr

If

If > 1 secreted

5

Fractional Filtration

FF = GFR/RPF

Normally about 20%

6

Renal Blood Flow (RBF)

RBF = RPF/(1-hematocrit)

Normally about 1000 ml/min or about 20% of Cardiac Output

7

ADH

Primary determinant of plasma osmolality through the control of water reabsorption or excretion in the distal nephron

  • Increases permeability of CCD and MCD to water
  • Increases permability of MCD to urea
  • Stimulates the Na-K-2Cl pump in the thick ascending limb of the LOH
  • Stimulates production of renal prostaglandins

 

8

Renin-Angiotensin II System

Primary "Low Blood Volume (low pressure) Response System"

  • Causes vasoconstriction of both efferent and afferent arterioles that limits the fall in GFR relative to RBF in low volume states
  • Stimulates aldosterone release
  • Stimulates synthesis of vasodilatory prostaglandins
  • Inhibits renin release
  • Increases sodium and water reabsorption in the proximal tubule

9

Aldosterone

  • Increases Na+ and Cl- reabsorption in the CCD and MCD
  • Increases isoosmotic reabsorption of water
  • Increases K+ and H+ secretion in the collecting ducts
  • Primary determinant of urinary K+ excretion (balance of reabsorption and secretion)

10

Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP)

Part of low pressure, high blood volume response system

  • Causes renal vasodilation and increases both RBF and GFR
  • Increase Na+ excretion (natriuresis) and water excretion (diuresis)

11

Urodilatin

ANP-like hormone produced within the nephron in response to hypervolemia

  • Increases Na+ excretion (natriuresis) and water excretion (diuresis)

12

Prostaglandins

PGE2 and prostacyclin are vasodilators that modulate RBF by antagonizing the vasoconstrictor effects of sympatheics and angiotensin II

13

Parathyroid Hormone

Released in response to low plasma Ca2+ concentration

  • Activates calcitriol
  • Increases active reabsorption of Ca2+ in the distal tubule
  • Decreases proximal tubule reabsorption of phosphate (i.e., increases phosphate excretion)

14

Calcitriol

Most active form of Vitamin D

  • Increases Ca2+ and Phosphate reabsorption
  • Negative feedback on PTH release

15

Catecholamines

NE and EPI

  • Vasoconstricts afferent and efferent arterioles (alpha-1)
  • Decreases RBF and GFR
  • Stimulates Na+ reabsorption in proximal tubule and LOH
  • Activates renin-angiotensin system via ß1 receptors in JGA of afferent arteriole

16

Kinins

Vasodilators that appear to antagonize neurohumoral vasoconstriction similar to the prostaglandins

  • May have role in Na+ and water handling in the collecting duct by antagonizing ADH-mediated water reabsorption

17

How does afferent arteriole constriciton change renal function?

Decreases GFR and RPF

18

How does efferent arteriole constriction change renal function?

Increases oncotic pressure and and decreases hydrostatic pressure

Increases GFR

Decreases RPF

Increases FF (GFR/RPF)

 

 

19

How does an increase in plasma protein concentration change renal function?

Decreases GFR, which decreases the FF

20

How does a decrease in plasma protein concentration change renal function?

Increases GFR, which increases FF (GFR/RPF)

21

What is responsible for most of renal oxygen consumption?

NaK-ATPase Pump

Which is responsible for the active reabsorption of Na+

22

How are the glomerular and peritubular capillaries arranged? Why is this important?

They are arranged in series.

This allows solutes and fluids filtered at the glomerulus and reabsorbed in the tubules to be reabsorbed by peritubular capillaries and returned to systemic circulation.

23

What is the balance of Starling forces in glomerular capillaries?

Capillary Pressure > Oncotic Pressure

Always results in filtration

24

What is the balance of Starling forces in peritubular capillaries?

Oncotic Pressure > Hydrostatic Pressure

Always results in reabsorption

25

What is the importance of autoregulation of RBF and GFR?

What accompanies this autoregulation as arterial pressure increases?

It uncouples renal function from changes in arterial pressure and ensures maintenance of renal function.

Pressure diuresis occurs when arterial pressure is increased meaning urine output is increased as a compensatory mechanism to maintain normal blood pressure

26

What are the mechanisms of autoregulation of GFR and RBF?

  1. Myogenic Vasoconstriction
    1. Occurs in afferent arterioles in response to sudden increases in renal perfusion pressure
    2. This stretches the arteriole causing vasoconstriction which reduces flow and hydrostatic pressure in glomerular capillaries
      1. Autoregulation of GFR is secondary to autoregulation of RBF
  2. Tubuloglomerular Feedback
    1. Macula densa provides feedback regarding flow and solute delivery (Cl-) to the afferent arteriole
    2. If GFR too high and increased flow, then the afferent arteriole vasoconstricts leading to a decrease in RBF and GFR
    3. If GFR and flow too low → vasodilation of afferent arteriole leads to increased RBF and GFR
      1. This also results in an increase in renin release via prostaglandin PGE2 and NO

27

What can override the autoregulatory mechanisms?

  • Extrinsic Control
    • Neural and Humoral Control

28

How does neural control affect RBF and GFR?

  1. Afferent and Efferent Arterioles are innvervated by sympathetic nerve fibers
  2. Low level stimulation constricts both afferent and efferent arterioles resulting in less of a decrease in GFR and RBF
  3. Greater stimulation causes parallel reductions in GFR and RBF
  4. Appears to be solely related to maintenance of arterial pressure and not the preservation of renal function (intrinsic control)

29

How does humoral control affect RBF and GFR?

Hormones and endogenous substances produce either renal vasoconstriction or vasodilation

  • Renal Vasoconstrictors
    • Angiotensin II
    • Catecholamines
    • ADH
  • Modulate/Antagonize Constrictor Effects
    • Prostaglandins
    • Kinins
  • Renal Vasodilation
    • ANP
    • Urodilatin

30

What is the limiting element of the glomerular filtration barrier?

Basement Membrane

31

What are the principal determinants of glomerular barrier permeability?

  • Size and number of pores in glomerular barrier
  • Presence of fixed negative charges in barrier (mainly basement membrane)
    • Negatively charged glycoproteins retard the movement of negatively charged macromolecules like plasma proteins
    • Nephrotic Syndrome results in a loss of these fixed negative charges

32

What is back-leak and how does it occur?

Back-leak is the bulk flow of water and solutes into the proximal tubule 

  • Occurs with afferent and efferent arteriolar vasodilation in hypervolemic states that leads to a decreased filtration fraction (GFR/RPF)
  • Balance of Starling forces in peritubular capillaries become less favorabe for reabsorption, so water and solutes reabsorbed in the proximal tubule are not readily taken up into the peritubular capillaries → leads to a progressive rise in interstitial hydrostatic pressure

33

Hypovolemia Effects

Decreased GFR and RBF

  • Arterial pressure falls
    • Decreased PG and RBF
  • Leading to decreased baroreceptor activity and a reflex increase in sympathetic discharge causing vasoconstriction
    • Decreased PG and RBF (PG reduction less than RBF)
      • Constriction of Afferent decreases PG and RBF
      • Constriction of Efferent increases PG and decreases RBF
  • Also occurs with increased renin release and increased circulating levels of angiotensin II
  • Increased concentration of plasma proteins → increases oncotic pressure in systemic capillaries → decreases GFR
  • Decreased Kf
    • Mesangial contraction → reducing glomerular perfusion, decreasing surface area for filtration
    • Podocytes may also contract and reduce the size of slit pores 
    • Efferent vasoconstriction → filtration equilibrium being reached sooner along length of glomerular capillaries

34

Hypervolemia Effects

Increased GFR and RBF

  • Increased baroreceptor activity, which decreases sympathetic discharge to resistance vessels (limited degree of vasodilation)
  • Increase in blood volume causes stretching of atria → releases ANP from atrial myocytes → ANP and urodilatin vasodilate increase GFR and RBF and increase Na+ excretion
  • Intrarenal baroreceptors respond to stretch by decreasing renin release that lowers angiotensin II levels
  • Increase in prostaglandins
  • Increased mean arterial pressure causes small increases in PG and RBF
  • Afferent and Efferent arteriole dilation → Increases RBF and PG
    • Afferent dilation → Increases RBF and PG
    • Efferent dilation → Decreases PG and Increases RBF
  • Dilution of plasma proteins → decreased oncotic pressure in systemic capillaries
  • Increase Kf
    • Relaxation of mesangial cells
    • Filtration equilibrium reached further along the length of the glomerular → greater capillary surface area is utilized for filtration

35

Clearance Equation

Cx = (Vu * Ux) / Px

36

What solutes can be used to estimate GFR?

Inulin

Creatinine

37

Renal Plasma Flow (RPF)

Clearance of PAH, which is avidly secreted by tubules, is used to estimate RPF

CPAH = RPF = (Vu * UPAH) / PPAH

 

*Averages 625 ml/min*

38

Fraction Reabsorption

FR = 1 - FE

39

Fraction Excretion of H2O

FEH2O = Vu / GFR = PCR / UCR

40

Function of the Glomerulus

  • Creates ultrafiltrate of plasma
  • Controls GFR
  • Activation of Renin-Angiotensin-Aldosterone System (RAAS)

41

Proximal Tubule Function

  • Isosmotic reabsorption of about 65% of filtered load of Na+, Cl-, and H2O
  • Reabsorbs almost all filtered glucose and amino acids
  • Reabsorbs most of filtered K+, HCO3-, Ca2+, Mg2+, and phosphate
  • Secretes H+, NH3, and organic acids and bases (Some K+)
  • Relatively leaky junctions allow diffusion of solutes via paracellular route
  • Fluid leaving is isotonic to plasma

42

Loop of Henle Function

  • Reabsorbs about 20% of the filtered load of Na+ and water
  • Thin descending limb permeable to water
    • Larger amount of solute is reabsorbed in ascending limb → net solute reabsorption in loop is greater than water reabsorption
  • Fluid leaving is hypotonic to plasma
  • Thin Ascending Limb
    • Impermeable to water
    • Permeable to Na and Cl
    • Contains a urea transporter (moves urea into tubule down concentration gradient)
  • Thick Ascending Limb is impermeable to water (diluting segment)
    • Allows for formation of steep osmotic gradient b/t tubule and interstitium - countercurrent multiplier
    • Na+, K+, and Cl- actively reabsorbed in thick ascending limb (Na-K-2Cl co-transporter) → hypertonic interstitium
      • Increases driving force for water reabsorption from thin descending limb and medullary collecting ducts
      • Excess Na+ and Cl- are removed from the medullary interstitium by vasa recta

43

Distal Nephron Function

  • Fine tunes urine volume and solute concentration as 85% of water and solutes are already absorbed
  • Consists of:
    • Distal Tubule
    • Cortical Collecting Tubules
    • Medullary Collecting Ducts

44

Distal Tubule Function

  • Reabsorbs small fraction of filtered Na+ and Cl-
  • Site of active control of Ca2+ reabsorption and excretion

45

Cortical Collecting Tubules Function

  • Principal Cells
    • Reabsorb Na+ and Cl-
    • Secrete K+ (aldosterone sensitive)
  • Intercalated Cells
    • Secrete H+
    • Reabsorbe K+
    • Secrete HCO3- in metabolic alkalosis
  • Reabsorb water in presence of ADH

46

Medullary Collecting Ducts Function

  • Reabsorbs Na+ and Cl- (aldosterone sensitive)
  • Inhibit tubular reabsorption of Na+ (ANP and BNP sensitive)
  • Water and Urea reabsorption (dependent on ADH levels)
  • Secrete H+ and NH3 
  • Can either reabsorb or secrete K+

47

Where does reabsorption of glucose occur?

Proximal Tubule Only

48

Where are organic solutes (glucose, amino acids, etc.) reabsorbed?

Proximal Tubule

49

How is most glucose reabsorbed?

Na+-Glucose Symporter driven by NaK-ATPase Pump

50

What is the energy source driving the Na-Glucose symporter?

The electrochemical gradient for Na+ generated by NaK-ATPase Pump

51

On the basolateral membrane, how does glucose exit the tubular cells?

GLUT uniporter

52

Fanconi Syndrome

Impaired proximal tubular reabsorption

53

Cystinuria

Defective cystine reabsorption; stone formation

54

Substances that exhibit tubular maxima and renal thresholds

  1. Glucose
  2. Amino Acids
  3. Phosphate
  4. Uric Acid
  5. Ketone Bodies
  6. Vitamins

55

What form of a weak acid or base is lipid soluble?

Nonionized Form

 

Can passively diffuse across the epithelium down the prevailing concentration gradient

56

What form of a weak acid or base is not lipid soluble and becomes diffusion trapped?

Ionized form

57

Alkalinizing the urine will enhance secretion and excretion of what?

Weak Acids

58

Acidizing the urine enhances the secretion and excretion?

Weak Bases

59

What volume state will enhance tubular solute and water reabsorption?

Hypovolemic

60

What volume state will reduce reabsorption of weak acids and bases?

Hypervolemic

61

What are the sites of Na+ reabsorption?

  1. Proximal Tubule (65%)
  2. Loop of Henle (20%)
  3. Distal Tubule (5-10%)
  4. Collecting Tubules and Ducts (About 5%)

62

What is glomerulotubular balance?

It is a load-dependent phenomenon due to changes in filtered load of glucose, phosphate, amino acids, bicarbonate etc that influence Na reabsorption and to relative changes in Pc and oncotic pressure in the peritubular capillaries that reflect changes in GFR and influence the reabsorptive potential

63

What percentage of the filtered load of Na is normally excreted?

0.6%

64

At steady state, what equals the daily intake of Na?

Daily Urinary Excretion of Na

65

What percentage of total renal energy is expended by NaK-ATPase Pump?

90%

66

What is the most abundant anion in glomerular filtrate?

Cl-

67

Unidirectional Na Transport

Na passively enter the proximal tubular cells through Na channels down its electrochemical gradient accompanied by Cl

 

Na is then actively extruded across basolateral surfaces by NaK-ATPase pump

68

Na-H Exchange

Secondary active transport, Na reabsorption into proximal tubular cells is coupled w/ secretion of H into tubular lumen 

 

Accounts for large fraction of total Na reabsorption in the proximal tubule and is coupled with the reabsorption of HCO3- and Cl-

 

Is stimulated by angiotensin II and sympathetic stimulation (may account for ability of angiotensin II to increase Na reabsorption in hypovolemic states)

69

What is the osmolality of tubular contents in the proximal tubule?

Isotonic

70

Cl-driven Na Reabsorption

As solutes and water are reabsorbed early in proximal tubule, Cl in the latter proximal tubule increases resulting in the development of a favorable concentration gradient for passive reabsorption of Cl through leaky tight junction and is accompanied by Na and water.

 

Accounts for about 30% of proximal tubular Na and Water reabsorption

71

What portion of the loop of Henle is impermeable to solutes and permeable to water?

Thin Descending Portion

72

What portion of the loop of Henle is permeable to Na and Cl?

Thin Ascending Limb

 

Na and Cl leave the tubule by passive diffusion down a favorable concentration gradient

73

What portion of the nephron is impermeable to water?

  1. Thin Ascending Limb
  2. Thick Ascending Limb
  3. Distal Tubule

74

What portion is referred to as the diluting segment?

  1. Thin Ascending Limb
  2. Thick Ascending Limb
  3. Distal Tubule

75

Na-K-2Cl Pump

Carrier in the luminal membrane of the thick ascending limb

Stimulated by ADH and Aldosterone to increase medullary interstitial osmolallity facilitating water reabsorption

76

Na-Cl Co-Transporter

  • Found in luminal membrane of distal tubule
  • Important in control of calcium reabsorption

 

Blocked by thiazide diuretics

77

The reabsorption of Na and Cl in the connecting segment and cortical collecting tuble is mediated by?

Principal Cells

78

Aldosterone

  • Stimulates Na reabsorption in principal cells of collecting tubules/ducts
    • Increases NaK-ATPase Activity
    • Increases synthesis and insertion of Na channels
    • Increases the provision of energy for active transport
  • Increases K secretion from principal cells
  • Increases H secretion from intercalated
  • Only increases Na reabsorption by 3%
  • Important in fine control of Na excretion

79

What controls the permeability of the collecting tubules/ducts to water?

ADH

80

What does Na reabsorption decrease in hypervolemic states?

  1. Aldosterone decreases
  2. ANP stimulates guanylate cyclase in medullary principal cells
    1. Cyclic GMP decreases the number of open Na channels in the luminal membrane thereby reducing Na reabsorption
  3. Urodilatin blocks Na and water reabsortption in the medullary collecting ducts

81

What controls extracellular fluid volume?

Kidneys

82

The regulation of effective circulating blood volume is dependent on what?

Control of Na reabsorption and secretion

83

Primary Stimuli for Aldosterone Release

  1. Angiotensin II
  2. Hyperkalemia
  3. Hyponatremia
  4. ACTH

84

Increase in Na intake will?

  • Increase urine Na
  • Decrease Plasma Renin
  • Decrease Aldosterone
  • Increase ECBV

85

ANP and BNP Actions

  • Vasodilate afferent arterial which increases GFR and the filtered load of Na leading to increased excretion
  • Inhibit renin release from afferent arterioles
  • Inhibit Na reabsorption in the collecting tubules causing natriuresis and diuresis
  • Inhibit aldosterone secretion
  • Inhibit ADH release

86

Urodilatin Actions

Inhibits reabsorption of Na and water reabsorption causing natriuresis and diuresis

 

Better correlated w/ hypervolemia

87

In hypervolemic states blood flow is shunted to what nephrons?

  • Cortical Nephrons
    • Have a lower capacity for Na reabsorption than juxtamedullary

 

88

In hypovolemic states blood flow is shunted toward what nephrons?

  • Juxtamedullary Nephrons
    • Thought to be associated w/ action of angiotensin II causing greater vasoconstriction in cortical arterioles

89

Angiotensin II Effects

  1. Stimulate release of aldosterone to increase Na and Water reabsorption
  2. Systemic vasoconstriction to increase blood pressure
  3. Stimulates thirst to increase water intake
  4. Stimulates ADH release to increase distal nephon water reabsorption in severe cases where ther is >10% reduction in ECBV
  5. Causes greater vasoconstriction of efferent arterioles which
    1. Decreases RBF
    2. Maintains adequate GFR
    3. Increase FF which increases peritubular capillary reabsorption
  6. Enhances NE biosynthesis
  7. Greater vasoconstriction of outer cortical afferent arterioles
  8. Stimulates synthesis of dilatory prostaglandins
  9. Stimulates Na reabsorption in proximal tubule via NaK-ATPase
  10. Inhibits renin secretion (negative feedback)

90

K Excretion is controlled by adjusting what?

Tubular K Secretion

91

What is the daily filtered load of K, assuming GFR is 180 and plasma K is 4.5

810 mEq

92

what type of cell mediates K reabsorption? How does this work?

intercalated cells, in distal nephron

active process through K-H ATPase and maybe K ATPase

93

What does H ATPase do?

Actively secretes H into the lumen

94

What cells handle K secretion? Where are they located? K secretion is controlled in part by what? What inhibits K secretion?

principal cells; distal nephron; aldosterone; angiotensin II

95

Entry of K into the cell is active and mediated by what?

Na-K ATPase

96

What are factors that influence plasma K concentration?

dietary intake 

Na-K ATPase - increases the cewllular load of K and keeps plasma levels low; inhibition of Na-K ATPase can cause rapid and profound hyperK

Insulin - promotes K uptake, rapid rise in insulin s/p meal prevents increases in plasma K

circulating catecholamines - enhance K uptake via beta 2 receptors; beta blockers can result in large increases in plasma K, especially during exercise

Aldosterone - elevated plasma K stimulates aldosterone release, increasing Na reabsorption leading to K secretion; independent of volume change

97

Hyperkalemia stimulates the secretion of what?

Aldosterone which stimulates NaK-ATPase, which increases cellular uptake of K on the basolateral membrane

 

Also appears to increase the permeability of the luminal membrane to K increasing secretion secondary to increased Na uptake

98

What percentage of total plasma Ca is filtered and why?

50% because 50% is bound to plasma albumin and other ions

99

What percantage of the filtered load of Ca is reabsorbed?

99%

100

Active reabsorption of Ca occurs where?

Distal Tubule

101

What percantage of the filtered load of Ca is reabsorbed in the Proximal Tubule? Loop of Henle?

70%

20%

102

Ca reabsorption in the proximal tubule tends to change in parallel with what other ion reabsorption?

Na Reabsorption

103

In the Loop of Henle what helps drive cation reabsorption?

Na-K-2Cl Pump and subsequent K recycling into the lumen creates a Positive Lumen Potential thus driving cation reabsorption

104

What induces the synthesis of calcium binding protein?

Calcitriol

105

What controls Ca reabsorption in the distal tubule?

Parathyroid Hormone

106

Parathyroid Hormone Effects

  1. Increases resorption of bone
  2. Increases Ca reabsorption in distal tubule
  3. Increases phosphate excretion (decrease reabsorption)

107

Phosphate is reabsorbed in the proximal tubule by what?

Secondary Active Na-phosphate cotransporter

108

How is ECF osmolality controlled?

By altering water intake and renal excretion of water

109

Four System Elements that Control Body Fluid Osmolality

  1. Loop of Henle (Counter-Current Multiplier) and Vasa Recta (Counter-Current Exchanger) - Creation and Maintenance of Medullary Osmotic Gradient
  2. Variable Permeability of Collecting Ducts
  3. Osmoreceptors and Thirst Centers
  4. ADH

110

Countercurrent Exchange Passive or Active?

Passive

111

Countercurrent Multiplier Passive or Active?

Active

112

What about vasa recta blood flow preserves medullary hypertonicity?

It is sluggish, which prevents washout of the medullary gradient

113

What stimulates hypothalamic osmoreceptors?

Increased ECF Osmolality causing shrinkage of the osmoreceptors and increases ADH release

114

What is ADH more sensitive to, plasma osmolality or plasma volume?

Plasma Osmolality

115

Prerenal Azotemia

116

What is the source of secreted H+?

Hydration of CO2

117

What is the minimal urine pH?

4.5

118

What cells are responsible for bicarbonate secretion?

Type "B" Cells (Subpopulation of Intercalated Cells)

119

Total H+ Secreted Equation

=TA + NH4+ HCO3-

120

New HCO3- Production

= TA + NH4+

121

Factors that influence H+ secretion

  1. Availability of Urinary Bases
  2. Increases and Decreases in PaCO2
  3. Aldosterone - parallel increase in H and K secretion
    1. Excess can cause hypokalemia and met. alkalosis
    2. Deficit can cause hyperkalemia and met. acidosis
  4. Primary Hyperkalemia
    1. Via K-H Exchangers
  5. Increase deliver of Na to distal nephron
  6. Renal Tubular Acidosis

122

Type 4 RTA

  • Inadequate production and excretion of NH4+
    • Most often associated w/ aldosterone deficiency or resistance resulting in distal nephron H secretion and hyperkalemia

123

Clearance

Cx = (Vu*Ux)/Px

124

RPF

=(Vu*UPAH) / PPAH

125