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Kidneys and Renal functions > Renal Blood Flow & Glomerular Filtration > Flashcards

Renal Blood Flow & Glomerular Filtration Flashcards

1
Q

How much of our body weight is taken up by the kidneys?

A

2 kidneys - 0.5% of body weight

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2
Q

How much of the cardiac output do kidneys receive?

A

20% resting CO due to kidneys role in Extracellular fluid (ECF) & blood volume regulation as well as rapid waste disposal

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3
Q

What are the main functions of the kidneys?

A
  • Control volume & composition of body fluids
  • Get rid of waste material from body
  • Acid-Base balance
  • Endocrine organ – EPO, Renin & Vit D
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4
Q

What is the functional unit of the kidney?

A

Nephron ~4cm long

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5
Q

How many nephrons are in a kidney?

A

1 million nephrons per kidney

Kidney cannot regenerate nephrons

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6
Q

What are the 2 components of the nephron?

A
  • glomerulus

- tubule

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7
Q

What are the 2 stages of urine formation?

A
  1. Glomeruli produce liquid

2. Tubules modify the volume + composition

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8
Q

What is the fate of the fluid filtered by the glomerulus?

A

Nearly all fluid filtered through glomerulus is reabsorbed back from tubule → blood.
Remainder excreted as urine at rate of 1 ml/min (equivalent to ~1.5L/day)

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9
Q

What rate of urine production is considered renal failure?

A

urine output is <5ml/day then = renal failure

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10
Q

How much fluid does the glomerulus filter everyday?

A

A huge filtration rate (180 L/day)

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11
Q

Why is there such a high GFR?

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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12
Q

What is the normal GFR?

A

glomerular filtration rate (GFR) of 120 ml/min

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13
Q

How is the glomerular filtrate formed?

A

Glomerular Filtration formed by passive ultrafiltration of plasma across the glomerular membrane, (Starling’s Law of Capillary fluid filtration)

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14
Q

What determines the GFR?

A

Autoregulation

Renal sympathetic vasomotor nerve activity

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15
Q

What is the glomerulus composed of?

A

consists of a clump of fenestrated capillaries & Bowman’s Capsule

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16
Q

Explain how the glomerulus and bowmans capsule are located

A

The glomerulus is completely enclosed by epithelium of the Bowman’s Capsule (BC); they are specialised to form podocytes

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17
Q

What is the GFR composed of?

A

Glomerular fluid is a passive ultrafiltrate of plasma (proteins filtered out)

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18
Q

What s the [ ] of small solutes in GFR?

A

For small solutes, such as NaCl, glucose and urea, concentration in glomerular fluid = concentration in plasma as they easily pass through

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19
Q

Explain the [ ] of larger solutes in GFR compared to plasma

A

For plasma proteins, concentration in glomerular fluid = almost zero

Urine is routinely tested for protein (proteinuria)
Proteinuria = sign of renal/urinary tract disease

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20
Q

What drives the ultrafiltration process?

A

A net pressure drop (imbalance of stralin’g forces) across glomerular membrane drives the ultrafiltration process

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21
Q

How does the Glomerular membrane filter solutes?

A

Glomerular membrane sieves out solutes from plasma by molecular size

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22
Q

How is fluid pushed out of the vessels?

A

In the kidney the capillary pressure is highest compared to other arterioles in the body ~50 mmHg. This results in an outward force i.e. pushing fluid out of the blood vessel.

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23
Q

What 2 other components of pressure are acting oppositely to the capillary pressure?

A

There are 2 components of pressure acting in the opposite direction to this: one is the colloid osmotic pressure exerted by proteins in the blood (25mmHg) & the other is the pressure in the Bowman’s space (10mmHg).

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24
Q

What is the net effect of all the pressures in the capillaries?

A

The net effect is an outward force of approximately 15mmHg that drives fluid out of the capillary into the BC

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25
Q

How can we determine the net filtration force?

A

Pc - (πp + Pu)

Pc - capillary blood pressure (~50 mmHg)
πp - plasma colloid osmotic pressure (~ 25 mmHg)
Pu - pressure in Bowman’s space (~10 mmHg)

26
Q

Outline the movement of fluid from the capillaries

A
  1. As blood flows through capillary there’s slight drop in
    pressure from afferent end to efferent end
  2. Plasma gets more concentrated as blood flows due to
    fluid loss; observed in kidneys only
  3. Net filtration force > net absorptive force resulting in
    GFR of 20% = colossal compared to 1% elsewhere
27
Q

Explain how the blood pressure affects capillary filtration

A

Starling force balance is reversed (absorption) in peritubular capillaries
As you enter the glomerulus; BP in afferent arteriole > colloid osmotic pressure (COP) resulting in a net filtration pressure out of the capillaries → tubule

28
Q

How is fluid reabsorbed into capillaries?

A

As we travel out of the glomerulus → efferent arteriole, the pressure begins to drop and the COP rises because fluid is lost from capillaries ∴ [protein] is increasing , exerting a greater force driving fluid back from the tubule→ capillary

29
Q

What is the product of ultrafiltration and reabsorption?

A

Leftover is a small concentrated volume of urine

30
Q

What is myeloperoxidase?

A

an albumin-size protein, which is held up at the filtration slits

31
Q

What is the use of myeloperoxidase?

A

Myeloperoxidase produces a black precipitate which is held up at filtration slits in a positive reaction - used to demonstrate filtration

32
Q

What does myeloperoxidase show us?

A

Glomerular filtration after iv administration of myeloperoxidase (MPO) with a MW of 160,000-180,000 showed that:

it readily traverses the endothelial fenestrations
crosses the basement membrane
Piles up beneath overlying pedicels surface
Piles up at slit junctions of adjacent pedicels

33
Q

What is the conclusion from using myeloperoxidase?

A

suggests that the primary filtration barrier to molecules of the size of albumin is the slit pore

34
Q

Explain the glomerular membranes structure

A

Glomerular membrane is 3 sieves in series of increasing fineness

35
Q

What are the 3 sieves of glomerular membrane?

A
  1. Fenestrated capillaries
  2. Basement membrane
  3. Filtration slits of podocytes
36
Q

What is the effect of nephrotic syndrome on the glomerular membrane?

A

filtration slits breakdown allowing albumin through

- proteinaemia

37
Q

What enables a constant GFR?

A

Autoregulation is the internal mechanism to keep a constant GFR

38
Q

What causes a change in urine rpoduction?

A

Changes in urine production (diuresis, antidiuresis) are usually due to changes in tubular reabsorption.

39
Q

What is autoregulation?

A

In the normal range of renal arterial pressure even if BP changes up or down, GFR remains constant

40
Q

What is the effect of increased arterial BP on the GFR?

A

When kidney is subject to acute increases in BP, the renal plasma flow (RPF) and GFR remain relatively constant

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

41
Q

What are the 2 mechanisms responsible for autoregulation?

A 
Bayliss myogenic response
Tubuloglomerular feedback (TGF)
42
Q

What is the bayliss myogenic response?

A

direct vasoconstriction of afferent arteriole with increase in perfusion pressure
Responds to BP fluctuations in intervals > 3-4 secs

43
Q

What is the tubuloglomerular feedback mechanims (TGF)?

A

flow-dependent signal detected in macula densa, that alters tone of afferent arteriole
Responds to slower BP fluctuations (> 20s)

44
Q

How can we determine blood flow using pressure and resistance?

A

F = ΔP / R

F - blood flow
ΔP - change in pressure
R - resistance

45
Q

What does an increase in perfusion pressure cause?

A

Increase in perfusion pressure → immediate increase in vessel radius (few seconds only) → blood flow goes up briefly

46
Q

How does the bayliss myogenic response return flow to normal?

A

Bayliss observed that resulting stretch of smooth muscle in afferent arteriole quickly results in contraction → reduction in diameter & increase in resistance
» flow returns to control value in 30s

47
Q

How does the contraction of afferent arterioles cause a pressure drop?

A

arteriolar contraction; increased precapillary resistance causes a bigger pressure drop - back to normal

48
Q

How is BP regulated in arterioles?

A

Changes in afferent arteriole diameter alters resistance levels

49
Q

What initiates a TGF response?

A

To elicit a TGF response, a pressure increase must be transmitted causing an increase in the flow rate through the thick ascending limb

50
Q

What does an increased ascending limb flow rate cause?

A

Alters composition of fluid presented to macula densa (alters luminal [NaCl] + osmolality), stimulating secretion of vasoconstrictor near afferent arteriole => increasing pre-glomerular resistance

51
Q

What does altering NaCl in the TGF response cause?

A

NaCl elicits an ATP signal by macula densa, leading to contraction of afferent arteriole

52
Q

What is the Juxtaglomerular apparatus (JGA)?

A

where blood vessel comes in contact with renal tubule

53
Q

What effect does an increased [NaCl] have on the JGA?

A

increase in [NaCl] and osmolality results in a release of ATP which leads to contraction of the afferent arteriole which contributes to the maintenance of pressure in the BC seen during autoregulation

54
Q

Summarise the TGF response

A

The primary mechanism regarding TGF + auto-regulation is via increase in afferent arteriole resistance due to local release of vasoconstrictors. Superimposed on this is the RAAS

55
Q

What are the extrinsic controls of GFR?

A

neurohormonal

56
Q

Explain how renal sympathetic nerves can reduce GFR

A

Renal sympathetic nerves (vasoconstrictor, noradrenergic) can reduce the GFR, by resetting autoregulation to a lower level

57
Q

When do sympathetic nerves reduce GFR?

A

This happens in 3 conditions-
standing upright (orthostasis)
heavy exercise
haemorrhage & other forms of clinical shock

58
Q

What is the purpose of reducing GFR?

A

Conserves body fluid volume during physical stress.
In shock, these sympathetic actions are aided by circulating vasoconstrictor hormones e.g. adrenaline, angiotensin + vasopressin

59
Q

What are the 2 major clinical disorders of the GFR?

A
  1. Glomeruli too leaky to plasma protein

2. GFR too low

60
Q

Explain the consequences of leaky glomeruli to plasma proteins

A 
Glomeruli too leaky to plasma protein: 
Nephrotic syndrome 
(eg. Filtration slit disordered by nephrin deficiency)
- Proteinuria
- Hypoproteinemia	
- Oedema
=> these respond well to steroids
61
Q

What are the consequences of too low a GFR?

A

(more common)
Chronic glomerulonephritis → nonfunctioning glomeruli
When GFR < 30 ml/min, this is chronic renal failure.

62
Q

What would you expect to see in chronic glumerulonephritis?

A

Whole of the glomerulus is replaced by collagen, hence there is no blood flow or RBC, so no glomerular filtrate

Kidneys and Renal functions (14 decks)

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