Renal blood flow and glomerular filtration Flashcards
1
Q
The two kidneys make up 0.5% of the total body weight, yet receive 20% of cardiac output. Why is this?
A
This large blood flow is not related to the metabolic needs of the kidney but is a function of the major role that the kidney plays in the regulation of ECF and blood volume regulation and rapid waste disposal.
2
Q
What are the main functions of the kidney?
A
- Control volume & composition of body fluids
- To get rid of waste material from body
- Acid-Base balance
- As an endocrine organ – EPO, Renin & Vit D
3
Q
How long is the average nephron?
A
4 cm
4
Q
What 2 elements does the nephron have?
A
- Glomerulus
- Tubule
5
Q
How many nephrons per kidney?
A
1 million
- The kidney cannot generate new nephrons
6
Q
What are special circulatory features of nephron?
A
Glomerular & peritubular capillaries
7
Q
What two stages is urine formed in?
A
- Glomeruli produce the liquid
2. Tubules modify its volume & composition
8
Q
How much of the fluid filtered through the glomerulus is reabsorbed back into the blood and how much is excreted?
A
Nearly all of the fluid filtered through the glomerulus is reabsorbed back from the tubule into the blood, with the remainder being excreted as urine at a rate of 1ml/min (equivalent to ~1440ml/day or ~1.5L/day).
9
Q
What value of urine output equates to renal failure?
A
< 5ml/day
10
Q
Why is there such a huge filtration rate of 180 litre/day?
A
A high rate of formation of glomerular fluid is needed to wash out the waste products fast enough to keep their blood level low
11
Q
How is glomerular fluid formed?
A
By passive ultrafiltration of plasma across the glomerular membrane, as described by Starling’s principle of capillary fluid filtration
12
Q
What is the glomerular filtration rate set by?
A
1) Autoregulation
2) Renal sympathetic vasomotor nerve activity
13
Q
What does the glomerulus consist of?
A
A clump of capillaries & Bowman’s capsule
14
Q
What is the glomerulus completely enclosed by? What are they specialised to form?
A
The epithelium of the basement membrane: they are specialised to form podocytes
* the epithelium is invaginated (pushed in) to coat the outer surface of the capillaries
15
Q
What does the glomerulus consist of?
A
- enters as an artery (afferent arteriole) and also leaves as an artery (efferent arteriole)
- leaves before it forms peritubular capillaries around/adjacent to the tubule
- blood again meets up along the glomerular capillaries
16
Q
Describe the mechanism of glomerular fluid formation
A
- Glomerular fluid is a passive ultrafiltrate of plasma
- The key features are:
- for small solutes, such as NaCl, glucose & urea, concentration in the glomerular fluid is the same as concentration in the plasma
- for plasma proteins, concentration in the glomerular fluid is almost zero. This is why urine is routinely tested on wards for proteins (proteinuria).
- net pressure drop across the glomerular membrane drives the ultrafiltration process
17
Q
What is proteinuria a sign of?
A
A sign of renal/urinary tract disease
18
Q
What does the glomerular membrane sieve out?
A
Solutes from plasma, by molecular size
19
Q
Mass of urea
A
60 daltons
20
Q
Mass of Glucose
A
180 daltons
21
Q
Mass of Albumin
A
69,000 daltons
22
Q
Radius of Urea
A
0.2 mm
23
Q
Radius of Glucose
A
0.4 mm
24
Q
Radius of Albumin
A
3.6 mm
25
ratio of concentration of urea in the glomerular filtrate to the ratio of urea in the plasma
1.0 (therefore the same)
26
ratio of concentration of glucose in the glomerular filtrate to the ratio of glucose in the plasma
1.0 (therefore the same)
27
Ratio of concentration of albumin in the glomerular filtrate to ratio of albumin in the plasma
<0.1
28
What drives glomerular fluid formation (filtration)?
An imbalance of Starling forces
29
What is the filtration fraction?
GFR/Plasma flow
= (120 ml/min)/(600 ml/min)
= 20%
30
What is the capillary pressure in the kidney and how does this compare to the rest of he body?
The capillary pressure is ~50 mmHg
| - This results in an outwards force i.e. pushing fluid out of the blood vessel
31
What are the two components of pressure that act in the opposite direction to capillary pressure?
* colloid osmotic pressure exerted by proteins in the blood (25mmHg)
* pressure in the Bowman’s space (10mmHg).
32
What is the difference in pressure in the afferent and efferent end?
As the blood flows through the capillary there is a slight drop in pressure from the afferent end to the efferent end.
33
What happens to the concentration in the plasma as the blood flows along?
The plasma also gets more concentrated as the blood flows along due to fluid loss, an unusual effect observed just in the kidneys compared to other capillaries.
34
What is the relationship between net filtration force and net absorptive force?
The plasma also gets more concentrated as the blood flows along due to fluid loss, an unusual effect observed just in the kidneys compared to other capillaries.
35
What happens to Starling force in peritubular capillaries?
The Starling force balance is reversed (absorption) in peritubular capillaries
36
What structures are observed when a podocyte is viewed under a Scanning Electron Microscope?
- the podocytes interlock to form filtration slits: forms a sieve
-
37
What is the basal lamina?
Basement membrane
38
What are filtration slits?
- Foot processes (pedicel) of an epithelial cell (ep) or 'podocyte'
- gaps between the processes are called filtration slits
39
What is the basement membrane made up of?
A complex mesh: proteins, actin, fibrils, tubulins.
40
What is unique about Albumin?
Albumin can fit through the fenestrae, but it is not seen in the urine – so, it is somehow prevented to leave.
* The 30nm slits are divided even more into 4 nm pores, therefore albumin cannot pass (albumin molecule is approx 4 nm across)
41
How wide is the average filtration slit?
30 nm wide
42
What is the function of the central spine with lateral rungs?
- Subdivides filtration slit into pores 4 nm wide.
- Made of proteins: nephrin & podocin
- Deficiency of these proteins: causes nephrotic syndrome.
43
Describe the composition of Ferritin
Has an iron (Fe) core
44
What is Myeloperoxidase?
An albumin-sized protein which is held up at the filtration slits
- it produces a black precipitate in a positive reaction
- it readily traverses the endothelial fenestrations and crosses the basement membrane.
- it then piles up beneath the surface of overlying pedicels and at the slit junctions of adjacent pedicels.
* This suggests that the primary filtration barrier to molecules of the size of albumin is the slit pore.
45
What are the 3 sieves in series that the glomerular membrane is made up of?
1. Fenestrated capillary
2. Basement membrane
3. Filtration slits of podocytes
46
What happens if the filtration slits break down?
Albumin gets through and nephrotic syndrome occurs
47
What is proteinuria?
Proteins in the urine
48
What is Haematouria?
RBCs in the urine
49
How is GFR controlled?
INTRINSIC:
- GFR is mainly held at 120 ml/min
- it is important for the maximum capacity of the tubules that the reabsorption of filtrate must not be overwhelmed by excessive GFR
50
What is autoregulation?
An internal mechanism holding GFR constant
| * GFR and renal blood flow are held constant over a range of arterial pressure
51
What causes changes in urine production?
- changes in tubular reabsorption
| - not usually due to changes in GFR
52
What would happen if there was no auto-regulation?
A relatively small increase in blood pressure would cause a similar 25% increase in GFR
* if tubular reabsorption remained constant then urine flow would increase by 30 fold, thereby depleting blood volume very quickly
53
What is the auto regulation zone where GFR is held constant?
80 - 200 mmHg
54
Autoregulation defintion
When kidneys subject to acute increases in blood pressure, the renal plasma flow (RPF) and GFR remain relatively constant
55
What are the two mechanisms that act together that are responsible for Autoregulation?
BAYLISS MYOGENIC RESPONSE:
- direct vasoconstriction of afferent arteriole with increase in perfusion pressure
TUBULOGLOMERULAR FEEDBACK (TGF):
- flow-dependent signal detected in macula densa, that alters the tone of afferent arteriole
56
What is the equation involved in the Bayliss myogenic response?
F= ΔP/R
```
F= blood flow
ΔP= change in pressure
R= resistance
```
57
According to Bayliss, what happens when there is an increase in perfusion pressure?
There is an immediate increase in vessel radius for a few seconds only and then the blood flow goes up briefly
58
According to Bayliss, what happens when the smooth muscle in the afferent arteriole is stretched?
Contraction occurs, which then results in the reduction in the diameter & increase in resistance, therefore blood flow will return to the original value within 30 seconds
59
how is the relationship between blood flow, pressure and resistance in the kidney different to other places in the body?
F= ΔP/R
* therefore, if the resistance was to remain constant, a 50% increase in pressure would cause a 50% increase in flow
* in the kidney, within a range of 60-80 mmHg, a 50% increase only causes a 6-8% increase in flow
* therefore resistance increases with increasing pressure
* this increase in resistance is localised entirely in the afferent arterioles
60
Can nephrons be regenerated?
Kidneys cannot regenerate new nephrons
61
How is the GFR and RPF maintained?
In parallel
62
myogenic and bayliss mechanisms
see notes to understand in detail
63
What is Oliguria?
Decreased urine production
64
How is Oliguria monitored?
Monitored on ward & ICY in patients in shock/hypotension
65
Why does Myogenic refer to?
contraction that originates from the cell itself and not from external source
66
Describe the graph that shows how contraction of afferent arteriole regulates glomerular capillary pressure?
See graph and attached notes
67
What alters resistance and what further effect does this have?
Changes in diameter of afferent arteriole alter resistance, maintaining auto regulation
68
Why is the TGF mechanism needed?
- The delivery of filtrate to the distal segment (this has a more limited capacity for reabsorption) needs to be precisely regulated
- In the majority of mammalian nephrons, the early distal tubule makes direct contact with ten vascular pole of its originating glomerulus
- This TGF depends on the unique anatomical relationship between the early distal tubule and the vascular region of the glomerulus
69
What are JG cells and what do they store?
Modified smooth muscle cells in walls of afferent arteriole proximal to glomerulus: store inactive pro-renin
70
Where is the macula densa formed and why?
* in every nephron, the tubule comes into contact with the bowman's capsule
* further down, it is feeding back to the bowman's capsule
* the area that comes into contact with the afferent and efferent arterioles becomes specialised: this is known as the macula densa
* the macula densa cells and the juxtaglomerular produce inactive pro-renin
71
Describe the Tubule-glomerular feedback (TGF) mechanism
```
GFR increases
I
Flow through the tubule increases
I
Flow past macula densa increases
I
Paracrine diffuses from macula densa to afferent arteriole
I
Afferent arteriole constricts
I
Resistance in afferent arteriole increases
I
Hydrostatic pressure in glomerulus decreased
I
GFR decreases
```
72
What must occur in order to elicit a TGF response?
A pressure must be transmitted and elicit an increase in the flow rate though the thick ascending limb:
* This alters the composition of the fluid presented to the macula densa (altering luminal [NaCl] and luminal osmolality)
* This stimulates the secretion of a vasoconstrictor near the afferent arteriole, ultimately increasing pre-glomerular resistance
73
What effect does NaCl have on the afferent arteriole?
NaCl elicits an ATP signal by the macula densa
- This leads to contraction of afferent arteriole
- This occurs in the JGA, where blood vessel comes in contact with the renal tubule
74
Describe the mechanism by which TGF controls GFR and RBF
```
Change in RBF/GFR
I
Change in NaCl delivery to DCT
I
Macula densa sense the change
(paracrine) I (vasoactive agents)
Afferent arterioles
I
Change in diameter & resistance
I
Restoration of RBF/GFR
```
75
What causes the RAAS response?
Sympathetic innervation
76
Via which extrinsic mechanisms is GFR controlled?
NEUROHORMONAL:
- renal sympathetic nerves: (vasoconstrictor, noradrenergic) can reduce the GFR) by re-settting auto regulation to a lower level
77
In what three conditions do the renal sympathetic nerves re-set autoregulation to a lower level?
1. Standing up right (orthostasis)
2. Heavy exercise
3. Haemorrhage & other forms of clinical shock
* the role is to conserve body fluid volume during physical stress
* in shock these sympathetic actions are aided by circulating vasoconstrictor hormones such as: adrenaline, angiotensin and vasopressin
78
What happens when there is a haemorrhage?
There will be a decrease in blood volume and sympathetic vasoconstriction
* sets the autoregulation zone to a lower level
79
What are two major clinical disorders of the GFR?
1. Glomeruli too leaky to plasma protein: nephrotic syndrome (e.g. filtration slit disordered by nephrin deficiency)
a. proteinuria
b. hypoproteinaemia
c. oedema
2. GFR too low (more common)
a. chronic glomerulonephritis due to non-functioning glomeruli
b. when GFR < 30 ml/min, this is chronic renal failure
80
What is chronic glomerulonephritis?
Infection in the nephrons
81
Describe what can be observed from normal glomerular histology?
- tubules
- glomerulus
- red cells inside perfused glomerular capillaries
- urinary space inside bowman's capsule
82
Describe what can be observed from a patient with chronic glomerulonephrits?
Fibrosed glomeruli: virtually no blood flow or red cells, because the whole of the glomerulus is replaced by collagen: so no glomerular filtrate is produced by these glomeruli
*
83
Treatment for patient with chronic renal failure
The need dietary restrictions and renal dialysis: or a renal transplant of match available
