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LR Renal > Physiology: Glomerular Filtration & Renal Blood Flow > Flashcards

Physiology: Glomerular Filtration & Renal Blood Flow Flashcards

1
Q

What is glomerular filtration? Briefly describe it

A

GF is the first step in the formation of tubular fluid

A portion of the plasma flowing through the glomerulus (~20%) is filtered across into the lumen of the Bowman’s capsule to become tubular fluid

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2
Q

What are the 3 barriers to filtration?

A
  • Glomerular capillary endothelium
  • Basement membrane (between the endothelium of the glomerular capillaries and the podocytes of the inner layer of Bowman’s capsule)
  • Slit processes of the podocytes (of the inner layer of the Bowman’s capsule)
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3
Q

What particular component of plasma are the 3 filtration barriers barriers to?

A
  • Glomerular capillary endothelium: barrier to rbc’s
  • Basement membrane: barrier to plasma proteins
  • Slit processes of the podocytes: barrier to plasma proteins
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4
Q

So fluid filtered from the glomerulus into the Bowman’s capsule must pass through the 3 layers that make up the glomerular membrane.

Describe how the capillary endothelium cells act as a barrier to rbc’s

A

Pores between the single endothelial cell layer are not large enough to permit the passage of rbc’s through to the Bowman’s capsule

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5
Q

How does the permeability of glomerular capillary endothelium compare to that of a normal capillary?

A

Even though they are not large enough for rbc’s to pass through, the pores between the endothelial cells are larger than normal, making glomerular endothelium ~100x more permeable than normal endothelium

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6
Q

So fluid filtered from the glomerulus into the Bowman’s capsule must pass through the 3 layers that make up the glomerular membrane.

Describe how the basement membrane (aka basal lamina) acts as a barrier to plasma proteins

A

It is an acellular layer made up of collagen and glycoproteins

These give it a net -ve charge which acts as a barrier to large plasma proteins ~ large plasma proteins cannot enter the Bowman’s capsule

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7
Q

So fluid filtered from the glomerulus into the Bowman’s capsule must pass through the 3 layers that make up the glomerular membrane.

Describe how the podocytes act as a barrier to plasma proteins

A

Filtration slits between podocytes allow only small substances to pass into the Bowman’s capsule to form the initial tubular fluid

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8
Q

Glomerular filtration is a passive process. What are the 4 forces that drive filtration?

A

Glomerular capillary blood pressure (hydrostatic)
Capillary oncotic pressure
Bowman’s capsule hydrostatic pressure
Bowman’s capsule oncotic pressure

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9
Q

Does glomerular capillary blood pressure favour or oppose filtration?

Give its approximate value

A

Glomerular capillary blood pressure is the most important hydrostatic pressure

It favours filtration

Approximate value: 55mmHg

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10
Q

What is glomerular capillary oncotic pressure?

A

A plasma protein concentration gradient that exits because plasma proteins are retained in the capillaries and excluded from the Bowman’s capsule

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11
Q

Does glomerular capillary oncotic pressure favour or oppose filtration?

Give its approximate value

A

Opposes filtration
(because the high protein content in the capillaries wants to pull the filtrate back in)

Approximate value: 30mmHg

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12
Q

Does Bowman’s capsule hydrostatic pressure favour or oppose filtration?

Give its approximate value

A

Opposes filtration
(because tubular fluid formed by the filtration process opposes further filtration)

Approximate value: 15mmHg

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13
Q

Does Bowman’s capsule oncotic pressure favour or oppose filtration?

Give its approximate value

A

Favours filtration

Approximate value: 0mmHg
as no plasma proteins enter the Bowman’s capsule

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14
Q

How is net filtration pressure calculated?

A

Forces favouring filtration - forces opposing filtration

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15
Q

Calculate net filtration pressure using the approximate values for the 4 forces that drive glomerular filtration

A

Net filtration pressure
= forces favouring filtration - forces opposing filtration
= (glomerular capillary BP + BC oncotic pressure) - (glomerular capillary oncotic pressure + BC hydrostatic pressure)
= (55 + 0) - (30 + 15)
= 10 mmHg

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16
Q

What is meant by the term ‘Starling Forces’?

A

The balance of hydrostatic and osmotic pressures

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17
Q

What is glomerular filtration rate (GFR)?

A

The rate at which protein-free plasma is filtered from the glomeruli into the Bowman’s capsule per unit time

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18
Q

How is GFR calculated from net filtration pressure?

A

GFR = Kf x net filtration pressure

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19
Q

What is Kf?

A

Filtration coefficient

This means how permeable the glomerular membrane is

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20
Q

Name 2 factors that can alter the filtration coefficient (Kf). What happens to GFR if it is altered?

A

Kf can be altered by disease or drugs

Reduced Kf will reduce GFR, increased Kf will increase GFR

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21
Q

What is the normal value for GFR?

A

~125 ml/min

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22
Q

What force is the major determinant of GFR?

A

Glomerular capillary blood pressure (hydrostatic)

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23
Q

Name a pathology which increases the Bowman’s capsule hydrostatic pressure

How does this affect GFR?

A

Kidney stone causes obstruction and so fluid build up in the nephron -> decreased GFR
(as this force opposes GFR)

24
Q

Name a pathology which increases the capillary oncotic pressure

How does this affect GFR?

A

Diarrhoea causes dehydration which concentrates the plasma proteins in the capillaries -> decreased GFR
(as this force opposes filtration)

25
Q

Name a pathology which decreases the glomerular capillary oncotic pressure

How does this affect GFR?

A

Severe burns cause plasma proteins to be lost from the site of injury -> increased GFR
(as this force opposes filtration)

26
Q

What extrinsic mechanism functions to regulate GFR and renal blood flow?

A

Sympathetic control (e.g., via the Baroreceptor reflex)

27
Q

Describe the effect of increased arterial blood pressure on GFR and renal blood flow

A
  • Increased arterial blood pressure
  • Causes vasodilation of the afferent arteriole
  • This increases blood flow into the glomerulus
  • This increases glomerular capillary blood pressure
  • So net filtration pressure increases
  • Increasing GFR
28
Q

Describe the effect of decreased arterial blood pressure on GFR and renal blood flow

A
  • Decreased arterial blood pressure
  • Causes vasoconstriction of the afferent arteriole
  • This decreases blood flow into the glomerulus
  • This decreased glomerular capillary blood pressure
  • So net filtration pressure decreases
  • Decreasing GFR
29
Q

Describe how the Baroreceptor reflex regulates GFR when arterial blood pressure decreases

A
  • Decrease in arterial blood pressure e.g., haemorrhage
  • Detected by aortic body and carotid sinus baroreceptors
  • Resultant increase in sympathetic activity
  • Generalised arteriolar vasoconstriction
  • Constriction of afferent arterioles
  • Reduced renal blood flow and glomerular capillary blood pressure
  • Reduced GFR
  • Decreased urine output
30
Q

How does decreased urine output help with drop in blood volume e.g., due to haemorrhage?

A

It helps compensate for blood volume loss by preventing further loss of ECF volume

31
Q

Name 2 intrinsic mechanisms that autoregulate GFR and renal blood flow

A

The myogenic mechanism

The tubuloglomerular feedback mechanism

32
Q

What is the role of intrinsic autoregulation of GFR?

A

To prevent short-term changes in systemic arterial pressure from affecting GFR and renal blood flow

e.g., preventing increased BP during exercise from increasing GFR to increase urine output and lower BP

33
Q

Describe the intrinsic myogenic mechanism involved in GFR autoregulation

A

When vascular smooth muscle is stretched by increased arterial blood pressure, it contracts to constrict the arteriole and reduce blood flow to the glomerulus

34
Q

Describe the intrinsic tubuloglomerular feedback mechanism involved in GFR autoregulation

A
  • Macula densa cells in the juxtaglomerular apparatus sense the NaCl content of the tubular fluid
  • Increased GFR increases tubular fluid flow which increases NaCl
  • In response, macula densa cells release vasoactive chemicals which cause the smooth muscle in the afferent arteriole wall to vasoconstrict
  • Vasoconstriction reduces blood flow to the glomerulus, decreasing GFR in a negative feedback loop
35
Q

What is plasma clearance?

A

The volume of plasma completely cleared of a particular substance per minute

36
Q

How is plasma clearance of a substance calculated?

A

Clearance
= rate of excretion / plasma conc.
= (urine conc. x rate of urine production) / plasma conc.
(ml/min)

37
Q

Name a substance for which clearance = GFR

A

Inulin (a polysaccharide found in plants (onions and garlic)

38
Q

Why does inulin clearance = GFR?

A

Inulin is freely filtered at the glomerulus i.e., it can bypass all of the barriers to filtration

It is then neither reabsorbed nor secreted within the tubules

39
Q

Suggest how to calculate GFR using inulin clearance

A

Inulin clearance
= rate of excretion / plasma conc.
= (urine conc. x rate of urine excretion) / plasma conc.
= GFR

40
Q

Why is creatinine clearance used to determine GFR instead of inulin?

A

Because inulin is an exogenous substance so must be administered into the patient via IV infusion

This is impractical

41
Q

Why does creatinine clearance not give an exact measurement of GFR?

A

A small amount (~5-10%) is undergoes renal secretion

42
Q

List the properties a substance should have to make it a suitable indicator for GFR measurement

A
  • Endogenous
  • Easy to measure
  • Appears at a constant rate
  • Freely filtered at the glomerulus
  • Not reabsorbed from the renal tubule
  • Not secreted into the renal tubule
  • Doesn’t undergo extra-renal elimination
43
Q

What is the clearance for substances which are…
- Filtered, completely reabsorbed + not secreted
- Not filtered, not reabsorbed + not secreted
…?

A

Clearance = 0 ml/min

as all of the substance is reabsorbed back into the bloodstream and not excreted

44
Q

What is the clearance for substances which are filtered, partly reabsorbed + not secreted?

A

Clearance < GFR (i.e., <125 ml/min)

as only a portion of the filtrate is excreted

45
Q

What is the clearance for substances which are filtered, not reabsorbed + are secreted?

A

Clearance > GFR (i.e., >125 ml/min)

as all of the filtrate is cleared as it is not reabsorbed, then the additional secreted substance is also cleared

46
Q

Suggest clearance values for…

  • Inulin
  • H+
  • Urea
  • Glucose
  • Creatinine
A

Inulin: 125 ml/min (filtered, not reabsorbed, not secreted)

H+: >125 ml/min (filtered, not reabsorbed, secreted)

Urea: <125 ml/min (filtered, partly reabsorbed, not secreted)

Glucose: 0 ml/min (filtered, totally reabsorbed, not secreted)

Creatinine: ~125 ml/ml (filtered, not reabsorbed, slightly secreted)

47
Q

Define…

  • Renal plasma flow (RPF)
  • Renal blood flow (RBF)
A
  • Renal plasma flow (RPF): the volume of plasma (55% of the blood composition) delivered to the kidneys per unit time
  • Renal blood flow (RBF): the volume of blood delivered to the kidneys per unit time
48
Q

List the properties a substance should have to make it a suitable indicator for renal plasma flow measurement

A
  • Non-toxic
  • Inert (not metabolised)
  • Easy to measure
  • Filtered by the glomerulus
  • Completely secreted by the tubules
49
Q

What is the best substance for measuring renal plasma flow and why?

A

Para-amino hippuric acid (PAH - an exogenous organic anion)

It is freely filtered at the glomerulus, not reabsorbed, and the plasma that escapes filtration is completely secreted from the tubule

This means that all of the PAH is excreted/cleared

50
Q

What is the approximate value of renal plasma flow (RPF) in a health adult?

A

PAH clearance = RPF = ~650 ml/min

51
Q

What is filtration fraction?

A

The fraction of plasma that flows through the glomeruli which undergoes glomerular filtration

52
Q

What is the filtration fraction in a normal healthy adult?

A

~20%

The remaining 80% moves onto the peritubular capillaries/vasa recta

53
Q

How is filtration fraction calculated?

A 
FF
= GFR / RPF
= 125/650
= 0.19
= ~20%
54
Q

How is renal blood flow (RBF) calculated from renal plasma flow (RPF)?

A

RBF

= RPF x (1 / (1-Hct)

55
Q

What is Hct?

A

A measurement of blood haematocrit

or packed cell volume - PCV

56
Q

What is the average renal blood flow in a healthy adult?

A

RBF
= RPF x (1/ 1-Hct)
= 650 x 1.85
= ~1200 ml/min

57
Q

For a subject at rest, the kidneys receive ~X% of cardiac output

A

24

LR Renal (16 decks)

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