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kidneys > Renal blood flow and glomerular filtration > Flashcards

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.

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2
Q

What are the main functions of the kidney?

A
  1. Control volume & composition of body fluids
  2. To get rid of waste material from body
  3. Acid-Base balance
  4. As an endocrine organ – EPO, Renin & Vit D
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3
Q

How long is the average nephron?

A

4 cm

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4
Q

What 2 elements does the nephron have?

A
  • Glomerulus

- Tubule

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5
Q

How many nephrons per kidney?

A

1 million

  • The kidney cannot generate new nephrons
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6
Q

What are special circulatory features of nephron?

A

Glomerular & peritubular capillaries

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7
Q

What two stages is urine formed in?

A
  1. Glomeruli produce the liquid

2. Tubules modify its volume & composition

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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).

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9
Q

What value of urine output equates to renal failure?

A

< 5ml/day

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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

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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

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12
Q

What is the glomerular filtration rate set by?

A

1) Autoregulation

2) Renal sympathetic vasomotor nerve activity

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13
Q

What does the glomerulus consist of?

A

A clump of capillaries & Bowman’s capsule

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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

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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
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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
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17
Q

What is proteinuria a sign of?

A

A sign of renal/urinary tract disease

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18
Q

What does the glomerular membrane sieve out?

A

Solutes from plasma, by molecular size

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19
Q

Mass of urea

A

60 daltons

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20
Q

Mass of Glucose

A

180 daltons

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21
Q

Mass of Albumin

A

69,000 daltons

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22
Q

Radius of Urea

A

0.2 mm

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23
Q

Radius of Glucose

A

0.4 mm

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24
Q

Radius of Albumin

A

3.6 mm

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25
Q

ratio of concentration of urea in the glomerular filtrate to the ratio of urea in the plasma

A

1.0 (therefore the same)

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26
Q

ratio of concentration of glucose in the glomerular filtrate to the ratio of glucose in the plasma

A

1.0 (therefore the same)

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27
Q

Ratio of concentration of albumin in the glomerular filtrate to ratio of albumin in the plasma

A

<0.1

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28
Q

What drives glomerular fluid formation (filtration)?

A

An imbalance of Starling forces

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29
Q

What is the filtration fraction?

A

GFR/Plasma flow
= (120 ml/min)/(600 ml/min)
= 20%

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30
Q

What is the capillary pressure in the kidney and how does this compare to the rest of he body?

A

The capillary pressure is ~50 mmHg

- This results in an outwards force i.e. pushing fluid out of the blood vessel

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31
Q

What are the two components of pressure that act in the opposite direction to capillary pressure?

A
  • colloid osmotic pressure exerted by proteins in the blood (25mmHg)
  • pressure in the Bowman’s space (10mmHg).
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32
Q

What is the difference in pressure in the afferent and efferent end?

A

As the blood flows through the capillary there is a slight drop in pressure from the afferent end to the efferent end.

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33
Q

What happens to the concentration in the plasma as the blood flows along?

A

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.

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34
Q

What is the relationship between net filtration force and net absorptive force?

A

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
Q

What happens to Starling force in peritubular capillaries?

A

The Starling force balance is reversed (absorption) in peritubular capillaries

36
Q

What structures are observed when a podocyte is viewed under a Scanning Electron Microscope?

A
  • ## the podocytes interlock to form filtration slits: forms a sieve
37
Q

What is the basal lamina?

A

Basement membrane

38
Q

What are filtration slits?

A
  • Foot processes (pedicel) of an epithelial cell (ep) or ‘podocyte’
  • gaps between the processes are called filtration slits
39
Q

What is the basement membrane made up of?

A

A complex mesh: proteins, actin, fibrils, tubulins.

40
Q

What is unique about Albumin?

A

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
Q

How wide is the average filtration slit?

A

30 nm wide

42
Q

What is the function of the central spine with lateral rungs?

A
  • Subdivides filtration slit into pores 4 nm wide.
  • Made of proteins: nephrin & podocin
  • Deficiency of these proteins: causes nephrotic syndrome.
43
Q

Describe the composition of Ferritin

A

Has an iron (Fe) core

44
Q

What is Myeloperoxidase?

A

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
Q

What are the 3 sieves in series that the glomerular membrane is made up of?

A
  1. Fenestrated capillary
  2. Basement membrane
  3. Filtration slits of podocytes
46
Q

What happens if the filtration slits break down?

A

Albumin gets through and nephrotic syndrome occurs

47
Q

What is proteinuria?

A

Proteins in the urine

48
Q

What is Haematouria?

A

RBCs in the urine

49
Q

How is GFR controlled?

A

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
Q

What is autoregulation?

A

An internal mechanism holding GFR constant

* GFR and renal blood flow are held constant over a range of arterial pressure

51
Q

What causes changes in urine production?

A
  • changes in tubular reabsorption

- not usually due to changes in GFR

52
Q

What would happen if there was no auto-regulation?

A

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
Q

What is the auto regulation zone where GFR is held constant?

A

80 - 200 mmHg

54
Q

Autoregulation defintion

A

When kidneys subject to acute increases in blood pressure, the renal plasma flow (RPF) and GFR remain relatively constant

55
Q

What are the two mechanisms that act together that are responsible for Autoregulation?

A

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
Q

What is the equation involved in the Bayliss myogenic response?

A

F= ΔP/R

F= blood flow
ΔP= change in pressure 
R= resistance
57
Q

According to Bayliss, what happens when there is an increase in perfusion pressure?

A

There is an immediate increase in vessel radius for a few seconds only and then the blood flow goes up briefly

58
Q

According to Bayliss, what happens when the smooth muscle in the afferent arteriole is stretched?

A

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
Q

how is the relationship between blood flow, pressure and resistance in the kidney different to other places in the body?

A

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
Q

Can nephrons be regenerated?

A

Kidneys cannot regenerate new nephrons

61
Q

How is the GFR and RPF maintained?

A

In parallel

62
Q

myogenic and bayliss mechanisms

A

see notes to understand in detail

63
Q

What is Oliguria?

A

Decreased urine production

64
Q

How is Oliguria monitored?

A

Monitored on ward & ICY in patients in shock/hypotension

65
Q

Why does Myogenic refer to?

A

contraction that originates from the cell itself and not from external source

66
Q

Describe the graph that shows how contraction of afferent arteriole regulates glomerular capillary pressure?

A

See graph and attached notes

67
Q

What alters resistance and what further effect does this have?

A

Changes in diameter of afferent arteriole alter resistance, maintaining auto regulation

68
Q

Why is the TGF mechanism needed?

A
  • 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
Q

What are JG cells and what do they store?

A

Modified smooth muscle cells in walls of afferent arteriole proximal to glomerulus: store inactive pro-renin

70
Q

Where is the macula densa formed and why?

A
  • 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
Q

Describe the Tubule-glomerular feedback (TGF) mechanism

A 
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
Q

What must occur in order to elicit a TGF response?

A

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
Q

What effect does NaCl have on the afferent arteriole?

A

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
Q

Describe the mechanism by which TGF controls GFR and RBF

A 
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 &amp; resistance 
                    I
Restoration of RBF/GFR
75
Q

What causes the RAAS response?

A

Sympathetic innervation

76
Q

Via which extrinsic mechanisms is GFR controlled?

A

NEUROHORMONAL:
- renal sympathetic nerves: (vasoconstrictor, noradrenergic) can reduce the GFR) by re-settting auto regulation to a lower level

77
Q

In what three conditions do the renal sympathetic nerves re-set autoregulation to a lower level?

A
  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
Q

What happens when there is a haemorrhage?

A

There will be a decrease in blood volume and sympathetic vasoconstriction
* sets the autoregulation zone to a lower level

79
Q

What are two major clinical disorders of the GFR?

A
  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
Q

What is chronic glomerulonephritis?

A

Infection in the nephrons

81
Q

Describe what can be observed from normal glomerular histology?

A
  • tubules
  • glomerulus
  • red cells inside perfused glomerular capillaries
  • urinary space inside bowman’s capsule
82
Q

Describe what can be observed from a patient with chronic glomerulonephrits?

A

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
Q

Treatment for patient with chronic renal failure

A

The need dietary restrictions and renal dialysis: or a renal transplant of match available

kidneys (6 decks)

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