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SUGER > Glomerulus > Flashcards

Glomerulus Flashcards

1
Q

Importance of peritubular capillaries

A

Many process of secretion and reabsorption are active

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2
Q

3 components of glomerular barrier

A

Podocytes (visceral epithelium)
Glomerular basement membrane
Fenestrated capillary endothelium

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3
Q

At the hilum of every glomerulus

A

Juxtaglomerular cells and macula densa

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4
Q

Modified muscular layer of afferent arterioles

A

Increased number of smooth muscle cells
Less actin/myosin but many granules (renin)

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5
Q

Where is renin released from

A

Smooth muscle cells of afferent arteriole- juxtaglomerular apparatus

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6
Q

What causes renin release

A

Low blood pressure —> less distended walls —> renin release

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7
Q

Renal blood flow

A

1 L/min

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8
Q

Urine flow

A

1 ml/min

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9
Q

What percentage of cardiac output does each kidney receive

A

10%

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10
Q

Kidney blood supply

A

Abdominal aorta
Renal artery
Interlobar artery
Arcuate artery
Interlobular artery afferent arteriole

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11
Q

Kidney blood drainage

A

Glomerular capillary
Efferent arterioles
Peritubular capillaries
Vasa recta
Interlobular veins
Arcuate veins
Interlobar veins
Renal vein
Inferior vena cava

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12
Q

2 capillary beds in kidney

A

Glomerular capillaries
Peritubular capillaries

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13
Q

3 stages of nephron function

A

Glomerular filtration
Tubular secretion
Tubular reabsorption

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14
Q

Glomerular filtration

A

Passage of fluid from the blood into bowman space to form the filtrate

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15
Q

Function of distal part of nephron

A

Secretion and reabsorption

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16
Q

Factors determining glomerular filtration

A

Pressure
Size of molecule
Charge
Rate of blood flow
Protein binding

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17
Q

Pressure factors that favours filtration

A

Glomerular capillary blood pressure (PG)

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18
Q

Pressure factors that opposes filtration

A

Fluid pressure in Bowman’s space (PBS)
Osmotic forces due to protein

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19
Q

Hydrostatic pressure in the glomerulus

A

60 mmHg

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20
Q

Oncotic pressure in the glomerulus

A

28 mmHg

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21
Q

Hydrostatic pressure in the bowman’s capsule

A

15 mmHg

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22
Q

Pressure and filtration

A

pressure forces fluid and all solutes smaller than a certain size through a membrane.
This occurs in therenal corpusclesof the kidneys across the endothelial-capsular membrane.

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23
Q

Size of molecules that can pass freely during glomerular filtration

A

Small molecules and ions up to 10 KDa can pass freely
Eg glucose, uric acid, potassium, creatinine

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24
Q

Size of molecules that cannot freely pass during glomerular filtration

A

Larger molecules increasingly restricted
Eg plasma proteins
> 10KDa

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25
Q

Charge and glomerular filtration

A

Fixed negative charge in glomerular basement membrane (glycoproteins and proteoglycans) repels negatively charged anions
Fractional clearance of different charged molecules
Eg albumin, phosphate, sulfate, organic anions

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26
Q

Example of anions repelled by glomerular basement membrane

A

Albumin
Phosphate
Sulfate
Organic anions

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27
Q

Protein binding and glomerular filtration

A

Albumin has a molecular weight of around 66kDa but is negatively charged ∴ cannot easily pass into the tubule

Filtered fluid is essentially protein-free

Tamm Horsfall protein in urine produced by tubule

Affects substances that bind to proteins e.g. drugs, calcium, thyroxine etc

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28
Q

Which protein found in urine is produced by tubule

A

Tamm Horsfall

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29
Q

Tamm Horsfall function

A

Affects substances that bind to proteins eg drugs, calcium, thryroxine

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30
Q

Glomerular filtration rate

A

Filtration volume per unit time (mins)
Kf (PG - PBS) - (oncotic forces)

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31
Q

Net filtration

A

Normally always positive

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32
Q

Kf

A

Filtration coefficient

product of the permeability of the filtration barrier and on the surface area available for filtration

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33
Q

Glomerular filtration rate units

A

ml/min/1.73m^2

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34
Q

What determines glomerular filtration rate

A

Net filtration pressure
Permeability of the filtration barrier
Surface area available for filtration

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35
Q

Surface area available for filtration of 2 kidneys

A

1.2-1.5 m^2

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36
Q

What causes a decreased filtration surface/rate

A

-when mesangial cells among the capillaries of the glomerolus contract (by Angiotensin II and ThromboxanE A₂)
- when podocytes are relaxed /flattened they cover more of filtration surface
- in many renal diseases reduce the filtration surface (nephrons are destroyed)

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37
Q

Active surface area of the kidneys depends in

A

Number of working nephrons

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38
Q

How to measure glomerular filtration rate

A

Calculated by measuring excretion of marker

CM = (UM*V)/PM

V = urine flow rate (ml/min)
UM = urine concentration of marker
PM = plasma concentration of marker

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39
Q

Properties of a good marker

A

Freely filtered
Not secreted or absorbed by tubules
Not metabolised
— all the marker will end up in the urine, no more and no less

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40
Q

Normal glomerular filtration rate

A

125 ml/min

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41
Q

What is commonly used as a GFR marker

A

Creatinine

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42
Q

Why is creatinine usually used as a marker

A

Muscle metabolite
Constant production

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43
Q

Disadvantages of using creatinine for GFR

A

Serum creatinine concentration will vary with muscle mass
Freely filtered at the glomerulus
Some additional secretion by the tubules

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44
Q

Things affecting creatinine

A

Dietary protein intake
Medications
Creatinine supplements
Age/gender/ethnicity/height/weight
Renal tubular handling

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45
Q

Other markers used to calculate GFR

A

Cystatin C
Inulin (gold standard)

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46
Q

Why is urea not used as a marker for GFR

A

Partially reabsorbed

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47
Q

Cystatin C- endogenous

A

Non-glycosylated protein produced by all cells
Freely filtered but reabsorbed and metabolised

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48
Q

What is Cystatin C influenced by

A

Thyroid disease
Corticosteroids
Age
Sex
Adipose tissue

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49
Q

Inulin- exogenous

A

Gold standard
Freely filtered
Not secreted or absorbed
Not metabolised

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50
Q

Why is Inulin not used to calculate GFR

A

requires continuous infusion, multiple blood & urine tests, time consuming

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51
Q

Inulin examples

A

51Cr EDTA

99mTc-DTPA

Radioisotopes

Iohexol

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52
Q

As rate of flow increases in afferent

A

GFR decreases (curve- convex up)

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53
Q

As rate of flow increases in efferent

A

GFR increases peaks then decreases

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54
Q

Range of glomerular filtration rate

A

80-180 mmHg

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55
Q

Function of regulation of glomerular filtration

A

Aim to maintain renal blood flow and GFR over range 8–180 mmHg
Protects against extreme of pressure
Independent of renal perfusion

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56
Q

How is glomerular filtration regulated

A

Renal autoregulation
Neural regulation
Hormonal regulation
Intrarenal baroreceptors
Extracellular fluid volume
Blood colloi osmotic pressure
Inflammatory mediators

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57
Q

Renal auto regulation

A

Myogenic mechanism- intrinsic ability of renal arterioles
Able to constrict or dilate

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58
Q

Myogenic mechanism of renal autoregulation

A

Negative feedback loop
Increase BP —> stretches blood vessel walls, opening stretch-activated cation channels —> membrane depolarises —> opens voltage-gates Ca2+ channels and increases intracellular calcium —> smooth muscle contraction —> increases vascular resistance —> minimises changes in GFR

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59
Q

Where does renal autoregulation occur

A

Only in pre-glomerular resistance vessels

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60
Q

Function of myogenic mechanism of renal autoregulation

A

Stabilises RBF and GFR
minimises impact of changes of blood pressure on Na+ secretion
Without = increase in BP leads to increase GFR and losses

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61
Q

Tubuloglomerular feedback

A

Juxtaglomerular apparatus
Stimulus NaCl concentration
Influences afferent arteriolar resistance

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62
Q

Tubuloglomerular feedback mechanism

A

Increase in arterial blood pressure
-increase glomerular blood flow and glomerular capillary pressure
Increase single nephron GFR
Increases delivery of NaCl to macula densa
Afferent arteriolar constriction:
-decreases glomerular blood flow and capillary pressure

63
Q

Neural regulation of GFR

A

Sympathetic nervous system
Vasoconstriction of afferent arterioles
Important in response to stress, bleeding or low BP

64
Q

Hormonal regulation of GFR

A

Renin-Angiotensin-Aldosterone system
Atrial Natriuretic peptide (ANP)

65
Q

Renin-Angiotensin-Aldosterone system

A

Renin released from juxtaglomerular apparatus
Initiates cascade
Aldosterone influences Na reabsorption at distal tubule which influences blood volume and pressure

66
Q

Atrial natriuretic peptide

A

Released by atria
Stimulus of blood volume
Vasodilation of afferent arterioles

67
Q

Intrarenal baroreceptors

A

Respond to changes in pressure in glomerulus
Influence diameter of afferent arterioles

68
Q

Extracellular fluid volume

A

Changes in blood volume
Resultant hydrostatic pressure affects GFR

69
Q

Blood colloid osmotic pressure

A

Oncotic pressure exerted by proteins influences GFR

70
Q

Inflammatory mediators

A

Local release of prostaglandins, nitric oxide, bradykinin, leukotrienes, histamine, cytokines and thromboxanes influence GFR

71
Q

Effect of noradrenaline on GFR

A

Decrease

72
Q

Effect of adrenaline on GFR

A

Decrease

73
Q

Effect of endothelin on GFR

A

Decrease

74
Q

Effect of angiotensin II on GFR

A

maintains
Prevents decrease

75
Q

Effect of endothelial-derived nitric oxide on GFR

A

Increase

76
Q

Effect of prostaglandins on GFR

A

Increase

77
Q

What causes vasodilation of afferent arteriole (decreased resistance)

A

Prostaglandins
Nitric oxide
High blood pressure

78
Q

What causes vasoconstriction of afferent arteriole (decreased resistance)

A

Sympathetic nervous system
Angiotensin II
NSAIDs

79
Q

Vasodilation of efferent arterioles (decreased resistance)

A

Prostaglandins
Increased renal blood flow
High blood pressure

80
Q

RBF =

A

renal blood flow

81
Q

Vasoconstriction of efferent arterioles (increased resistance)

A

Sympathetic nervous system
Angiotensin II

82
Q

How does vasodilation of afferent arteriole effect RBF, PG + GFR

A

Increase

83
Q

How does vasoconstriction of afferent arteriole effect RBF, PG + GFR

A

Decreases

84
Q

How does vasodilation of efferent arteriole effect RBF, PG + GFR

A

Increase

85
Q

How does vasoconstriction of efferent arteriole effect RBF, PG + GFR

A

Decrease

86
Q

Glomerulonephritis

A

Umbrella term
Causes: infection (bacterial/viral), autoimmune disorders, systemic diseases
Presentation: haematuria, proteinuria, hypertension, impaired kidney function

87
Q

Nephrotic syndrome

A

Umbrella term
Increased permeability of glomerular filtration barrier
Presentation: triad of oedema + proteinuria + low albumin

88
Q

IgA nephropathy

A

Deposition of IgA antibody in the glomerulus
Resultant inflammation and damage
Cause: immune-mediated
Presentation: haematuria, potentially following resp/GI infection

89
Q

Membranous nephropathy

A

Thickening of GBM
Most common cause of nephrotic syndrome in adults
Cause: primary or secondary
Presentation: proteinuria (often leading to nephrotic syndrome)

90
Q

Diabetic nephropathy

A

Prolonged exposure to high blood glucose
Presentation: initially asymptomatic then progresses to proteinuria, hypertension and reduced kidney function

91
Q

Minimal change disease

A

Type of nephrotic syndrome, only in children
Only visible under electron microscope

92
Q

Alport syndrome

A

Genetic disorder affecting GBM (X linked or autosomal recessive)
Progressive kidney damage
Potentially includes hearing loss and eye abnormalities

93
Q

Primary function of glomerulus in kidneys

A

Filtration of blood

94
Q

Which cell type in the glomerulus is responsible for the filtration of blood

A

Endothelial cells

95
Q

What is the name of the network of capillaries within the Bowman’s capsule where blood filtration occurs

A

Glomerular capillaries

96
Q

Which hormone regulates the diameter of the afferent and efferent arterioles to control glomerular filtration rate (GFR)

A

Renin

97
Q

What is the purpose of the glomerular filtration barrier in the nephron

A

To selectively filter substances based on size and charge

98
Q

Factors affecting GFR

A

Hydrostatic and oncotic pressure
Surface area
Permeability

99
Q

Filtration fraction

A

GFR/ renal plasma flow

100
Q

Clearance

A

The volume of plasma from which a substance is completely removed by the kidney per unit time

101
Q

What is used clinically to measure GFR

A

Creatinine

102
Q

What makes up the renal corpuscle

A

Glomerular tuft and bowman’s capsule

103
Q

Glomerular tuft

A

Convoluted, interconnected glomerular capillaries protruding into bowman’s capsule

104
Q

Mesangial cells

A

Specialised pericytes

105
Q

Functions of renal corpuscle

A

Structural support for capillary
Production of extracellular matrix protein
Contraction regulates flow and filtration- tubuloglomerular feedback
Phagocytosis of breakdown products

106
Q

Bowman’s capsule

A

Most proximal point in urinary tract, continuous with PCT

107
Q

Total glomerular surface area

A

1 m^2

108
Q

2 layers of bowman’s capsule

A

Basement membrane
Parietal epithelium cells

109
Q

Bowman’s capsule membrane

A

Fenestrated
Negatively charged membrane which repels negative proteins

110
Q

3 layers of glomerulus

A

Endothelial cells- fenestrated
Basement membrane
Podocytes

111
Q

Basement membrane of glomerulus

A

Fusion of 2 basement membranes - capillary and podocyte (basal lamina)
Negatively charged

112
Q

Podocytes

A

Single cell thick
Large number of interdigitating foot processes which act as a filtrate barrier

113
Q

Myogenic auto regulation

A

Smooth muscle contraction in response to external stretching force
Occurs in capillary walls
Passive mechanism

114
Q

Tubuloglomerular feedback

A

Constriction of afferent arterioles to increased NaCl concentration
Dilation in response to decreased concentration
Fast response via GFR
Slow response via RAAS

115
Q

What causes a fast tubuloglomerular feedback response

A

GFR

116
Q

What causes a slow tubuloglomerular feedback response

A

RAAS

117
Q

Tubuloglomerular feedback- what detects Na+ concentration

A

Macula densa cells via NKCC2 transporter

118
Q

Tubuloglomerular feedback- which transporter detects [Na+]

A

NKCC2 transporter

119
Q

Tubuloglomerular feedback- what regulates it

A

Na+ concentration

120
Q

Tubuloglomerular feedback- which arterioles are more affected

A

Afferent> efferent

121
Q

Tubuloglomerular feedback- what compounds are signals to arterioles

A

Adenosine and nitric oxide

122
Q

Tubuloglomerular feedback- flow rate if high

A

Constriction of afferent arterioles causes GFR to fall

123
Q

Tubuloglomerular feedback- low flow rate

A

Dilation of afferent arterioles causes GFR to rise

124
Q

Tubuloglomerular feedback- sympathetic drive

A

A reduced GFR and renal blood flow increases sympathetic activity causing vasoconstriction

Increases HR, BP, CO
Tries to shunt blood to muscles

125
Q

To increase GFR

A

Constrict the efferent arterioles (build up pressure before)
Dilate the afferent arterioles (builds up pressure after)

126
Q

To decrease GFR

A

Constrict the afferent arterioles (reduce blood flow)
Dilate the efferent arterioles (allows blood to escape easier)

127
Q

Range for renal perfusion

A

80-200 mmHg

128
Q

In the average 70kg person, what percentage of plasma passes through the glomerulus

A

20%

129
Q

What can affect glomerular filtration rate

A

Pressure gradients
Size of the molecule
Charge of the molecule
Rate of blood flow
Surface area- directly proportional to membrane permeability and surface area
Binding to plasma protein eg Ca2+, hormones, fatty acids

130
Q

Muscle mass and creatinine

A

Constantly produced as a muscle metabolite so amount depends on muscle mass

131
Q

Amount of marker in fluid

A

Concentration x volume

132
Q

GFR equation

A

[Urine(marker) x urine flow rate] / plasma(marker)

133
Q

GFR in 24 hours

A

180 L

134
Q

Percentage of glomerular filtrate reabsorbed

A

99%

135
Q

Total plasma volume

A

3L
Interstitial = 2L transcellular = 1L

136
Q

Net hydrostatic pressure value

A

35 mmHg

137
Q

Glomerular capillary pressure value

A

40-50 mmHg

138
Q

Bowman’s space pressure value

A

10 mmHg

139
Q

Net osmotic pressure value

A

25 mmHg

140
Q

Oncotic glomerular capillary pressure

A

25 mmHg and rising due to increased pressure due to colloids

141
Q

Oncotic bowman’s space pressure

A

0mmHg as no proteins filtered

142
Q

Hydrostatic pressure across length of glomerular capillary

A

Constant

143
Q

Oncotic pressure across length of glomerular capillary

A

Increases as proteins become more concentrated
Roughly 20% higher Concentration

144
Q

Kf

A

The filtration coefficient
The product of the permeability of the filtration barrier and surface area for filtration (size and number of nephrons)

145
Q

Pressure gradients at end of glomerular capillaries

A

Reached equilibrium

146
Q

Pressure gradients in peritubular capillaries

A

High resistance so pressure decreases
High oncotic pressure which aids fluid reabsorption

147
Q

Ultrafiltrate

A

Contains virtually all substances found in plasma in similar concentrations

148
Q

Why are some low molecular weight substances not filtered

A

Attached to large plasma proteins
Eg half the Ca2_ and almost all plasma fatty acids

149
Q

Examples of small molecules and ions up to 10kDa that can freely pass into filtrate

A

Glucose
Uric acid
K+
Creatinine

150
Q

If molecular weight less than 70kDa

A

Can pass through membrane irrelevant of charge or shape

151
Q

Only protein found in filtrate

A

Tamm-Horsfall protein (uromodulin)

152
Q

Where is Tamm-Horsfall protein produced

A

Thick ascending limb

153
Q

Neutral dextran

A

More filtered due to lack of charge (10% more at 70kDa)

154
Q

What can cause damage to the filtration barrier

A

Immune conditions
Genetic abnormalities of proteins involved in Podocytes/slit diaphragm
Diabetes - diabetic neuropathy = microalbuminuria (low albumin levels in urine)

SUGER (17 decks)

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