Renal blood flow and glomerular filtration Flashcards

1
Q

What percentage of cardiac output from the heart do the kidneys receive?

A

2 kidneys (0.5% body weight) receive ~20% of resting cardiac output.

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2
Q

What are the 4 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

What are the main 2 stages of urine production?

A

Urine is formed in 2 stages : glomeruli produce the liquid; tubules modifies its volume & composition

Refer to slides

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4
Q

Why such a huge filtration rate, namely 180 litre/day?

A

Answer; a high rate of formation of glomerular fluid is needed to wash out the waste products fast enough to keep their blood level low.

Example; a human produces 36 g urea per day:- yet normal plasma urea is only 0.2 g/litre.- To wash 36 g urea into the urine, 180litre of plasma have to be filtered per day (because 180L x 0.2 g/L = 36g).- This is a glomerular filtration rate (GFR) of 120 ml/min!

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5
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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6
Q

What is the rate of glomerular filtration set by?

A

The glomerular filtration rate (GFR) is set by-

(i) autoregulation:
(ii) renal sympathetic vasomotor nerve activity

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7
Q

Describe the structure and contents of the Bowsman capsule

A

On slide

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8
Q

Describe the mechanisms for the glomerular fluid formation

What drives the ultrafiltration process?

A

The key features of glomerular filtration are therefore –

For small solutes, such as NaCl, glucose and urea, concentration in glomerular fluid = concentration in plasma.

For plasma proteins, concentration in glomerular fluid = almost zero. Hence, urine is routinely tested on wards for protein (proteinuria). Proteinuria is a sign of renal/urinary tract disease.

A net pressure drop across the glomerular membrane drives
the ultrafiltration process.

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9
Q

Describe the mass, radius and filtrate or urea, glucose and albumin in GF

A

On slides

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10
Q

What drives GF?

What pressures are in with GF?

A

An imbalance of starlings forces

Pc, capillary blood pressure, around 50 mmHg
PIp, plasma colloid osmotic pressure (25 mmHg)
Pu, pressure in Bowman’s space (10 mmHg)

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11
Q

How do we calculate the filtration fraction?

Describe the graph of pressure against distance along the capillary

A

GFR/ Plasma flow

on slides

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12
Q

Describe the Blood pressure profile in the kidney: Starling force balance is reversed (absorption) in peritubular capillaries.

A

On slides

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13
Q

Describe the 3D structure of the glomerular membrane

A

On slides

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14
Q

Describe the Electron micrograph of the glomerular barrier

A

On slides

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15
Q

Describe the surface view of filtration slits between foot processes, seen from urinary space

A

On slides

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16
Q

Look at the higher magnification of membrane slits

A

On slides

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.

17
Q

Which layer is the molecular sieve?

A

On image

18
Q

What happens to Myeloperoxidase, an albumin-size protein, is held up at the filtration slits

A
  1. Myeloperoxidase injected into plasma. The black material is enzyme, the reaction product
  2. Penetrates through basal lamina but piles up at filtration slits.
  3. None penetrates into urinary space
19
Q

—so, the glomerular membrane is 3 sieves in series, of increasing fineness

A
  1. Fenestrated capillary
  2. Basement membrane
  3. Filtration slits of podocytes
20
Q

Describe the intrinsic control of GFR

What is the filtration rate?

How does the filtration rate aid reabsorption?

What mechanism maintains a constant GFR?

What are changes in urine production not cause and caused by?

A

[i] Intrinsic control (intra-renal)

  1. GFR is in the main held constant (120ml/min)
  2. Important for capacity of tubules to reabsorb filtrate not be overwhelmed by excessive GFR
  3. The mechanism holding GFR constant is an internal one called ‘autoregulation’.
  4. Changes in urine production (diuresis, antidiuresis) are not usually due to changes in GFR, but due to changes in tubular reabsorption.
21
Q

When there is an acute rise in blood pressure, the renal plasma flow and GFR main constant, what 2 mechanisms are responsible?

A

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

2 mechanisms acting together are responsible for this:

  1. Bayliss myogenic response:
    direct vasoconstriction of afferent arteriole with increase in perfusion pressure
  2. Tubuloglomerular feedback (TGF):
    flow-dependent signal detected in macula densa, that alters tone of afferent arteriole
22
Q

Describe the Bayliss Myogenic response

What is the equation for flow?

What does an increase in perfusion pressure cause?

What happens to contraction when smooth muscle is stretched?

A

F=∆P/R
where F= blood flow, ∆P=change in pressure, R=resistance

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

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

23
Q

Does the contraction of arterioles protect the capillary?

A

Yes, increased precapillary resistance causes a bigger pressure drop

24
Q

How does Tubulo-glomerular feedback (TGF)is a second mechanism contributing to autoregulation?

A

Specifically the delivery of filtrate to the distal segment, which has a more limited capacity for reabsorption, needs to be precisely regulated.
Thus in the vast majority of mammalian nephrons, the early distal tubule makes direct contact with the vascular pole of it’s originating glomerulus. This TGF depends on the unique anatomical relationship between the early distal tubule (cells become specialised to form macula densa) and the vascular region of the glomerulus.

25
Q

How does NaCl contribute towards the maintenance of the GFR?

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.

26
Q

Describe the intrinsic control of GFR

A

[I] Intrinsic control

Autoregulation of GFR by Bayliss myogenic response & TGF.

27
Q

How do Sympathetic nerves re-set GFR autoregulation to a lower level?

A

II] Extrinsic control (neurohumoral)
Renal sympathetic nerves (vasoconstrictor, noradrenergic) can reduce the GFR, by re-setting autoregulation to a lower level.
This happens in 3 conditions-
standing upright (orthostasis)
heavy exercise
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.

28
Q

What are the two major clinical disorders of the GFR?

A

Glomeruli too leaky to plasma protein: nephrotic syndrome (eg. Filtration slit disordered by nephrin deficiency)

  1. Proteinuria
  2. Hypoproteinaemia
  3. Oedema

GFR too low (more common)

  • Chronic glomerulonephritis  nonfunctioning glomeruli
  • When GFR < 30 ml/min, this is chronic renal failure.
29
Q

Describe the histology of glomerular and Chronic glomerulonephritis

A

On image