Renal Blood Flow & Glomerular Filtration Flashcards
How much of our body weight is taken up by the kidneys?
2 kidneys - 0.5% of body weight
How much of the cardiac output do kidneys receive?
20% resting CO due to kidneys role in Extracellular fluid (ECF) & blood volume regulation as well as rapid waste disposal
What are the main functions of the kidneys?
- Control volume & composition of body fluids
- Get rid of waste material from body
- Acid-Base balance
- Endocrine organ – EPO, Renin & Vit D
What is the functional unit of the kidney?
Nephron ~4cm long
How many nephrons are in a kidney?
1 million nephrons per kidney
Kidney cannot regenerate nephrons
What are the 2 components of the nephron?
- glomerulus
- tubule
What are the 2 stages of urine formation?
- Glomeruli produce liquid
2. Tubules modify the volume + composition
What is the fate of the fluid filtered by the glomerulus?
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)
What rate of urine production is considered renal failure?
urine output is <5ml/day then = renal failure
How much fluid does the glomerulus filter everyday?
A huge filtration rate (180 L/day)
Why is there such a high GFR?
High rate of formation of glomerular fluid is needed to wash out the waste products fast enough to keep their blood level low
What is the normal GFR?
glomerular filtration rate (GFR) of 120 ml/min
How is the glomerular filtrate formed?
Glomerular Filtration formed by passive ultrafiltration of plasma across the glomerular membrane, (Starling’s Law of Capillary fluid filtration)
What determines the GFR?
Autoregulation
Renal sympathetic vasomotor nerve activity
What is the glomerulus composed of?
consists of a clump of fenestrated capillaries & Bowman’s Capsule
Explain how the glomerulus and bowmans capsule are located
The glomerulus is completely enclosed by epithelium of the Bowman’s Capsule (BC); they are specialised to form podocytes
What is the GFR composed of?
Glomerular fluid is a passive ultrafiltrate of plasma (proteins filtered out)
What s the [ ] of small solutes in GFR?
For small solutes, such as NaCl, glucose and urea, concentration in glomerular fluid = concentration in plasma as they easily pass through
Explain the [ ] of larger solutes in GFR compared to plasma
For plasma proteins, concentration in glomerular fluid = almost zero
Urine is routinely tested for protein (proteinuria)
Proteinuria = sign of renal/urinary tract disease
What drives the ultrafiltration process?
A net pressure drop (imbalance of stralin’g forces) across glomerular membrane drives the ultrafiltration process
How does the Glomerular membrane filter solutes?
Glomerular membrane sieves out solutes from plasma by molecular size
How is fluid pushed out of the vessels?
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.
What 2 other components of pressure are acting oppositely to the capillary pressure?
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).
What is the net effect of all the pressures in the capillaries?
The net effect is an outward force of approximately 15mmHg that drives fluid out of the capillary into the BC
How can we determine the net filtration force?
Pc - (πp + Pu)
Pc - capillary blood pressure (~50 mmHg)
πp - plasma colloid osmotic pressure (~ 25 mmHg)
Pu - pressure in Bowman’s space (~10 mmHg)
Outline the movement of fluid from the capillaries
- As blood flows through capillary there’s slight drop in
pressure from afferent end to efferent end - Plasma gets more concentrated as blood flows due to
fluid loss; observed in kidneys only - Net filtration force > net absorptive force resulting in
GFR of 20% = colossal compared to 1% elsewhere
Explain how the blood pressure affects capillary filtration
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
How is fluid reabsorbed into capillaries?
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
What is the product of ultrafiltration and reabsorption?
Leftover is a small concentrated volume of urine
What is myeloperoxidase?
an albumin-size protein, which is held up at the filtration slits
What is the use of myeloperoxidase?
Myeloperoxidase produces a black precipitate which is held up at filtration slits in a positive reaction - used to demonstrate filtration
What does myeloperoxidase show us?
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
What is the conclusion from using myeloperoxidase?
suggests that the primary filtration barrier to molecules of the size of albumin is the slit pore
Explain the glomerular membranes structure
Glomerular membrane is 3 sieves in series of increasing fineness
What are the 3 sieves of glomerular membrane?
- Fenestrated capillaries
- Basement membrane
- Filtration slits of podocytes
What is the effect of nephrotic syndrome on the glomerular membrane?
filtration slits breakdown allowing albumin through
- proteinaemia
What enables a constant GFR?
Autoregulation is the internal mechanism to keep a constant GFR
What causes a change in urine rpoduction?
Changes in urine production (diuresis, antidiuresis) are usually due to changes in tubular reabsorption.
What is autoregulation?
In the normal range of renal arterial pressure even if BP changes up or down, GFR remains constant
What is the effect of increased arterial BP on the GFR?
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
What are the 2 mechanisms responsible for autoregulation?
Bayliss myogenic response Tubuloglomerular feedback (TGF)
What is the bayliss myogenic response?
direct vasoconstriction of afferent arteriole with increase in perfusion pressure
Responds to BP fluctuations in intervals > 3-4 secs
What is the tubuloglomerular feedback mechanims (TGF)?
flow-dependent signal detected in macula densa, that alters tone of afferent arteriole
Responds to slower BP fluctuations (> 20s)
How can we determine blood flow using pressure and resistance?
F = ΔP / R
F - blood flow
ΔP - change in pressure
R - resistance
What does an increase in perfusion pressure cause?
Increase in perfusion pressure → immediate increase in vessel radius (few seconds only) → blood flow goes up briefly
How does the bayliss myogenic response return flow to normal?
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
How does the contraction of afferent arterioles cause a pressure drop?
arteriolar contraction; increased precapillary resistance causes a bigger pressure drop - back to normal
How is BP regulated in arterioles?
Changes in afferent arteriole diameter alters resistance levels
What initiates a TGF response?
To elicit a TGF response, a pressure increase must be transmitted causing an increase in the flow rate through the thick ascending limb
What does an increased ascending limb flow rate cause?
Alters composition of fluid presented to macula densa (alters luminal [NaCl] + osmolality), stimulating secretion of vasoconstrictor near afferent arteriole => increasing pre-glomerular resistance
What does altering NaCl in the TGF response cause?
NaCl elicits an ATP signal by macula densa, leading to contraction of afferent arteriole
What is the Juxtaglomerular apparatus (JGA)?
where blood vessel comes in contact with renal tubule
What effect does an increased [NaCl] have on the JGA?
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
Summarise the TGF response
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
What are the extrinsic controls of GFR?
neurohormonal
Explain how renal sympathetic nerves can reduce GFR
Renal sympathetic nerves (vasoconstrictor, noradrenergic) can reduce the GFR, by resetting autoregulation to a lower level
When do sympathetic nerves reduce GFR?
This happens in 3 conditions-
standing upright (orthostasis)
heavy exercise
haemorrhage & other forms of clinical shock
What is the purpose of reducing GFR?
Conserves body fluid volume during physical stress.
In shock, these sympathetic actions are aided by circulating vasoconstrictor hormones e.g. adrenaline, angiotensin + vasopressin
What are the 2 major clinical disorders of the GFR?
- Glomeruli too leaky to plasma protein
2. GFR too low
Explain the consequences of leaky glomeruli to plasma proteins
Glomeruli too leaky to plasma protein: Nephrotic syndrome (eg. Filtration slit disordered by nephrin deficiency) - Proteinuria - Hypoproteinemia - Oedema => these respond well to steroids
What are the consequences of too low a GFR?
(more common)
Chronic glomerulonephritis → nonfunctioning glomeruli
When GFR < 30 ml/min, this is chronic renal failure.
What would you expect to see in chronic glumerulonephritis?
Whole of the glomerulus is replaced by collagen, hence there is no blood flow or RBC, so no glomerular filtrate
