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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
Charge and glomerular filtration
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
26
Example of anions repelled by glomerular basement membrane
Albumin Phosphate Sulfate Organic anions
27
Protein binding and glomerular filtration
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
28
Which protein found in urine is produced by tubule
Tamm Horsfall
29
Tamm Horsfall function
Affects substances that bind to proteins eg drugs, calcium, thryroxine
30
Glomerular filtration rate
Filtration volume per unit time (mins) Kf (PG - PBS) - (oncotic forces)
31
Net filtration
Normally always positive
32
Kf
Filtration coefficient product of the permeability of the filtration barrier and on the surface area available for filtration
33
Glomerular filtration rate units
ml/min/1.73m^2
34
What determines glomerular filtration rate
Net filtration pressure Permeability of the filtration barrier Surface area available for filtration
35
Surface area available for filtration of 2 kidneys
1.2-1.5 m^2
36
What causes a decreased filtration surface/rate
-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)
37
Active surface area of the kidneys depends in
Number of working nephrons
38
How to measure glomerular filtration rate
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
39
Properties of a good marker
Freely filtered Not secreted or absorbed by tubules Not metabolised — all the marker will end up in the urine, no more and no less
40
Normal glomerular filtration rate
125 ml/min
41
What is commonly used as a GFR marker
Creatinine
42
Why is creatinine usually used as a marker
Muscle metabolite Constant production
43
Disadvantages of using creatinine for GFR
Serum creatinine concentration will vary with muscle mass Freely filtered at the glomerulus Some additional secretion by the tubules
44
Things affecting creatinine
Dietary protein intake Medications Creatinine supplements Age/gender/ethnicity/height/weight Renal tubular handling
45
Other markers used to calculate GFR
Cystatin C Inulin (gold standard)
46
Why is urea not used as a marker for GFR
Partially reabsorbed
47
Cystatin C- endogenous
Non-glycosylated protein produced by all cells Freely filtered but reabsorbed and metabolised
48
What is Cystatin C influenced by
Thyroid disease Corticosteroids Age Sex Adipose tissue
49
Inulin- exogenous
Gold standard Freely filtered Not secreted or absorbed Not metabolised
50
Why is Inulin not used to calculate GFR
requires continuous infusion, multiple blood & urine tests, time consuming
51
Inulin examples
51Cr EDTA 99mTc-DTPA Radioisotopes Iohexol
52
As rate of flow increases in afferent
GFR decreases (curve- convex up)
53
As rate of flow increases in efferent
GFR increases peaks then decreases
54
Range of glomerular filtration rate
80-180 mmHg
55
Function of regulation of glomerular filtration
Aim to maintain renal blood flow and GFR over range 8–180 mmHg Protects against extreme of pressure Independent of renal perfusion
56
How is glomerular filtration regulated
Renal autoregulation Neural regulation Hormonal regulation Intrarenal baroreceptors Extracellular fluid volume Blood colloi osmotic pressure Inflammatory mediators
57
Renal auto regulation
Myogenic mechanism- intrinsic ability of renal arterioles Able to constrict or dilate
58
Myogenic mechanism of renal autoregulation
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
59
Where does renal autoregulation occur
Only in pre-glomerular resistance vessels
60
Function of myogenic mechanism of renal autoregulation
Stabilises RBF and GFR minimises impact of changes of blood pressure on Na+ secretion Without = increase in BP leads to increase GFR and losses
61
Tubuloglomerular feedback
Juxtaglomerular apparatus Stimulus NaCl concentration Influences afferent arteriolar resistance
62
Tubuloglomerular feedback mechanism
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
Neural regulation of GFR
Sympathetic nervous system Vasoconstriction of afferent arterioles Important in response to stress, bleeding or low BP
64
Hormonal regulation of GFR
Renin-Angiotensin-Aldosterone system Atrial Natriuretic peptide (ANP)
65
Renin-Angiotensin-Aldosterone system
Renin released from juxtaglomerular apparatus Initiates cascade Aldosterone influences Na reabsorption at distal tubule which influences blood volume and pressure
66
Atrial natriuretic peptide
Released by atria Stimulus of blood volume Vasodilation of afferent arterioles
67
Intrarenal baroreceptors
Respond to changes in pressure in glomerulus Influence diameter of afferent arterioles
68
Extracellular fluid volume
Changes in blood volume Resultant hydrostatic pressure affects GFR
69
Blood colloid osmotic pressure
Oncotic pressure exerted by proteins influences GFR
70
Inflammatory mediators
Local release of prostaglandins, nitric oxide, bradykinin, leukotrienes, histamine, cytokines and thromboxanes influence GFR
71
Effect of noradrenaline on GFR
Decrease
72
Effect of adrenaline on GFR
Decrease
73
Effect of endothelin on GFR
Decrease
74
Effect of angiotensin II on GFR
maintains Prevents decrease
75
Effect of endothelial-derived nitric oxide on GFR
Increase
76
Effect of prostaglandins on GFR
Increase
77
What causes vasodilation of afferent arteriole (decreased resistance)
Prostaglandins Nitric oxide High blood pressure
78
What causes vasoconstriction of afferent arteriole (decreased resistance)
Sympathetic nervous system Angiotensin II NSAIDs
79
Vasodilation of efferent arterioles (decreased resistance)
Prostaglandins Increased renal blood flow High blood pressure
80
RBF =
renal blood flow
81
Vasoconstriction of efferent arterioles (increased resistance)
Sympathetic nervous system Angiotensin II
82
How does vasodilation of afferent arteriole effect RBF, PG + GFR
Increase
83
How does vasoconstriction of afferent arteriole effect RBF, PG + GFR
Decreases
84
How does vasodilation of efferent arteriole effect RBF, PG + GFR
Increase
85
How does vasoconstriction of efferent arteriole effect RBF, PG + GFR
Decrease
86
Glomerulonephritis
Umbrella term Causes: infection (bacterial/viral), autoimmune disorders, systemic diseases Presentation: haematuria, proteinuria, hypertension, impaired kidney function
87
Nephrotic syndrome
Umbrella term Increased permeability of glomerular filtration barrier Presentation: triad of oedema + proteinuria + low albumin
88
IgA nephropathy
Deposition of IgA antibody in the glomerulus Resultant inflammation and damage Cause: immune-mediated Presentation: haematuria, potentially following resp/GI infection
89
Membranous nephropathy
Thickening of GBM Most common cause of nephrotic syndrome in adults Cause: primary or secondary Presentation: proteinuria (often leading to nephrotic syndrome)
90
Diabetic nephropathy
Prolonged exposure to high blood glucose Presentation: initially asymptomatic then progresses to proteinuria, hypertension and reduced kidney function
91
Minimal change disease
Type of nephrotic syndrome, only in children Only visible under electron microscope
92
Alport syndrome
Genetic disorder affecting GBM (X linked or autosomal recessive) Progressive kidney damage Potentially includes hearing loss and eye abnormalities
93
Primary function of glomerulus in kidneys
Filtration of blood
94
Which cell type in the glomerulus is responsible for the filtration of blood
Endothelial cells
95
What is the name of the network of capillaries within the Bowman’s capsule where blood filtration occurs
Glomerular capillaries
96
Which hormone regulates the diameter of the afferent and efferent arterioles to control glomerular filtration rate (GFR)
Renin
97
What is the purpose of the glomerular filtration barrier in the nephron
To selectively filter substances based on size and charge
98
Factors affecting GFR
Hydrostatic and oncotic pressure Surface area Permeability
99
Filtration fraction
GFR/ renal plasma flow
100
Clearance
The volume of plasma from which a substance is completely removed by the kidney per unit time
101
What is used clinically to measure GFR
Creatinine
102
What makes up the renal corpuscle
Glomerular tuft and bowman’s capsule
103
Glomerular tuft
Convoluted, interconnected glomerular capillaries protruding into bowman’s capsule
104
Mesangial cells
Specialised pericytes
105
Functions of renal corpuscle
Structural support for capillary Production of extracellular matrix protein Contraction regulates flow and filtration- tubuloglomerular feedback Phagocytosis of breakdown products
106
Bowman’s capsule
Most proximal point in urinary tract, continuous with PCT
107
Total glomerular surface area
1 m^2
108
2 layers of bowman’s capsule
Basement membrane Parietal epithelium cells
109
Bowman’s capsule membrane
Fenestrated Negatively charged membrane which repels negative proteins
110
3 layers of glomerulus
Endothelial cells- fenestrated Basement membrane Podocytes
111
Basement membrane of glomerulus
Fusion of 2 basement membranes - capillary and podocyte (basal lamina) Negatively charged
112
Podocytes
Single cell thick Large number of interdigitating foot processes which act as a filtrate barrier
113
Myogenic auto regulation
Smooth muscle contraction in response to external stretching force Occurs in capillary walls Passive mechanism
114
Tubuloglomerular feedback
Constriction of afferent arterioles to increased NaCl concentration Dilation in response to decreased concentration Fast response via GFR Slow response via RAAS
115
What causes a fast tubuloglomerular feedback response
GFR
116
What causes a slow tubuloglomerular feedback response
RAAS
117
Tubuloglomerular feedback- what detects Na+ concentration
Macula densa cells via NKCC2 transporter
118
Tubuloglomerular feedback- which transporter detects [Na+]
NKCC2 transporter
119
Tubuloglomerular feedback- what regulates it
Na+ concentration
120
Tubuloglomerular feedback- which arterioles are more affected
Afferent> efferent
121
Tubuloglomerular feedback- what compounds are signals to arterioles
Adenosine and nitric oxide
122
Tubuloglomerular feedback- flow rate if high
Constriction of afferent arterioles causes GFR to fall
123
Tubuloglomerular feedback- low flow rate
Dilation of afferent arterioles causes GFR to rise
124
Tubuloglomerular feedback- sympathetic drive
A reduced GFR and renal blood flow increases sympathetic activity causing vasoconstriction Increases HR, BP, CO Tries to shunt blood to muscles
125
To increase GFR
Constrict the efferent arterioles (build up pressure before) Dilate the afferent arterioles (builds up pressure after)
126
To decrease GFR
Constrict the afferent arterioles (reduce blood flow) Dilate the efferent arterioles (allows blood to escape easier)
127
Range for renal perfusion
80-200 mmHg
128
In the average 70kg person, what percentage of plasma passes through the glomerulus
20%
129
What can affect glomerular filtration rate
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
Muscle mass and creatinine
Constantly produced as a muscle metabolite so amount depends on muscle mass
131
Amount of marker in fluid
Concentration x volume
132
GFR equation
[Urine(marker) x urine flow rate] / plasma(marker)
133
GFR in 24 hours
180 L
134
Percentage of glomerular filtrate reabsorbed
99%
135
Total plasma volume
3L Interstitial = 2L transcellular = 1L
136
Net hydrostatic pressure value
35 mmHg
137
Glomerular capillary pressure value
40-50 mmHg
138
Bowman’s space pressure value
10 mmHg
139
Net osmotic pressure value
25 mmHg
140
Oncotic glomerular capillary pressure
25 mmHg and rising due to increased pressure due to colloids
141
Oncotic bowman’s space pressure
0mmHg as no proteins filtered
142
Hydrostatic pressure across length of glomerular capillary
Constant
143
Oncotic pressure across length of glomerular capillary
Increases as proteins become more concentrated Roughly 20% higher Concentration
144
Kf
The filtration coefficient The product of the permeability of the filtration barrier and surface area for filtration (size and number of nephrons)
145
Pressure gradients at end of glomerular capillaries
Reached equilibrium
146
Pressure gradients in peritubular capillaries
High resistance so pressure decreases High oncotic pressure which aids fluid reabsorption
147
Ultrafiltrate
Contains virtually all substances found in plasma in similar concentrations
148
Why are some low molecular weight substances not filtered
Attached to large plasma proteins Eg half the Ca2_ and almost all plasma fatty acids
149
Examples of small molecules and ions up to 10kDa that can freely pass into filtrate
Glucose Uric acid K+ Creatinine
150
If molecular weight less than 70kDa
Can pass through membrane irrelevant of charge or shape
151
Only protein found in filtrate
Tamm-Horsfall protein (uromodulin)
152
Where is Tamm-Horsfall protein produced
Thick ascending limb
153
Neutral dextran
More filtered due to lack of charge (10% more at 70kDa)
154
What can cause damage to the filtration barrier
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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