Blood flow and glomerular filtration Flashcards
How much of the resting cardiac output do the kidneys receive?
→ nearly a quarter
What is the large blood flow to the kidneys related to?
→ metabolic needs of the kidney
What are the 4 main functions of the kidney?
→Control volume & composition of body fluids
→To get rid of waste material from the body
→Acid-Base balance
→As an endocrine organ – EPO, Renin and Vit D
How long is the average nephron?
→ 4cm
What is the functional unit of the kidney?
→ nephron
What can the kidney not regenerate?
→ new nephrons
Why is the glomerulus unusual?
→ It enters and leaves as an artery
What do the blood vessels form around the tubule?
→ peritubular capillaries
What are the 2 sets of capillaries that a nephron has?
→ Glomerulus
→ Peritubular capillaries
What are the 2 stages of urine formation?
→Glomeruli produce the liquid
→The tubules modifies its volume and composition
How much fluid is filtered through the glomerulus and how much is being excreted as urine?
→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
What urine output equates to renal failure?
→ <5ml/day
Why is there such a high filtration rate?
→A 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 first stage of urine production?
→ Glomerular filtration
How is glomerular fluid formed?
→By passive ultrafiltration of the plasma across the glomerular membrane
→as described by Starling’s principle of capillary fluid filtration
What is the GFR set by?
→Autoregulation
→Renal sympathetic vasomotor nerve activity
What is the glomerulus enclosed by?
→ Completely enclosed by the epithelium of the BC, though they are specialised to form podocytes
What is a passive ultrafiltrate of plasma?
→ Plasma from which the proteins have been filtered out
What is the concentration of small solutes and plasma proteins in glomerular fluid?
→For small solutes, such as NaCl, glucose and urea
The concentration in glomerular fluid = the concentration in plasma
→For plasma proteins
The concentration in glomerular fluid = almost zero
What is proteinuria a sign of?
→Proteinuria is a sign of renal/urinary tract disease
What drives the ultrafiltration process?
→A net pressure drop across the glomerular membrane drives the ultrafiltration process
→imbalance of Starling forces
What does the glomerular membrane sieve out?
→ Solutes from Plasma by Molecular Size
What is the pressure like in the kidney capillaries?
→ The highest compared to arterioles in the body
What does high pressure in the kidney capillaries create?
→ An outward force
What are the 2 components opposing the outward force created by high pressure in the glomerular capillary?
→colloid osmotic pressure exerted by proteins in the blood (25mmHg)
→pressure in the Bowman’s Space (10mmHg)
What is the net effect on glomerular capillaries as a result of the forces acting on it?
→net effect is an outward force of approximately 15mmHg
→drives fluid out of the capillary into the BC
What happens as blood flows through the capillary with respect to pressure?
→As the blood flows through the capillary, there is a slight drop in pressure from the afferent end to the efferent end.
What happens to the plasma as the blood flows along?
→ plasma also gets more concentrated as the blood flows along due to fluid loss
What is the relationship between net filtration force and net absorptive force and what does this result in?
→net filtration force is always more than the net absorptive force
→resulting in a glomerular filtration rate of 20% which is colossal compared to 1% elsewhere in the body
What happens to starling force balances in peritubular capillaries?
→Starling force balance is reversed (absorption) in peritubular capillaries
What is the blood pressure like as you enter the glomerulus and what does this result in?
→The blood pressure in the afferent arteriole is higher than the colloid osmotic pressure (COP)
as you enter the glomerulus
→ resulting in a net filtration pressure out of the capillaries into the tubule.
What is the blood pressure like as you exit the glomerulus and what does this result in?
→As we travel out of the glomerulus into the efferent arteriole,
→the pressure begins to drop and the
→COP rises because fluid is lost from the capillaries, →protein is getting more concentrated
→ exerting a greater force driving fluid back from the tubule into the capillary
What are the gaps called in the capillary membranes?
→The capillary membrane is not continuous but have gaps called fenestrae
Why can blood not pass through fenestrae?
→Normally blood cannot pass through the fenestrae because the blood cells cannot fit and are trapped
What can travel through the fenestrae?
→ Anything that dissolves in water
→ Through the basal lamina (glycocalyx)
What is the size range of fenestrae?
→ 50-100nm
Why does albumin not appear in the urine even though it can fit through the fenestrae and podocytes?
→ The filtration slits are subdivided into much smaller pores that are 4nm wide
→ Made of nephrin and podocin
→ Albumin gets trapped here
What is nephrotic syndrome?
→ Nephrin and podocin are not made
What is myeloperoxidase?
→ albumin sized protein which is held up at the filtration slits
What does myeloperoxidase produce?
→black precipitate in a positive reaction
How did they prove that albumin cannot pass into urine?
→ Myeloperoxidase injected into plasma
→ Penetrates through basal lamina but piles up at filtration slits
→ None penetrates into urinary space
What can the glomerular membranes be described as?
→3 sieves in series of increasing fineness
What are changes in urine due to?
→ due to changes in tubular reabsorption
What is the mechanism keeping GFR constant?
→The mechanism holding GFR constant is an internal
one called “autoregulation”
What is held constant over a range of arterial blood pressures?
→GFR and Renal blood flow are held constant over a range of arterial pressure
In the normal range of blood pressures what happens to GFR and what is this called?
→In the normal range of arterial pressure, even if BP changes up or down,
→GFR remains constant = AUTOREGULATION
What would happen to GFR if there were no autoregulation and an increase of BP occurred?
→If there was no autoregulation, then a relatively small increase in BP would cause a similar 25% increase in GFR
What would happen if tubular reabsorption were to stay constant?
→then urine flow would increase by 30-fold
(the difference between GFR and tubular reabsorption), →depleting blood volume very quickly
What is the Bayliss’ Myogenic response (BMR) and what does it prevent?
→Direct vasoconstriction of afferent arteriole with an increase in perfusion pressure
→Can prevent changes in response to BP fluctuations that occur in intervals greater than 3-4 seconds
What is Tuboglomerular feedback (TGF) and what does it involve?
→Flow-dependent signal detected in macula densa, that alters the tone of the afferent arteriole
→The method likely involved adenosine/or ATP
What does tuboglomerular feedback respond to?
→Responds to slower BP fluctuations, over intervals of 20 seconds or longer
What do TGF and BMR do together?
→act in concert and stabilise renal function by preventing pressure-induced fluctuations in :
→RBF (Renal Blood Flow),
→GFR
→delivery of filtrate to the distal tubule (“Distal Delivery”)
What does an increase in perfusion pressure lead to?
→immediate increase in vessel radius (few seconds only) →blood flow goes up briefly
What happens if the blood pressure increases to keep the pressure in the bowmans capsule the same?
→vessels just upstream of the glomerular capillaries contract and increase the resistance
→resulting in a drop of pressure
→ keeping the pressure in the Bowman’s capsule (Pgc) still in the same range
What is the equation for flow?
→ Flow = change in pressure / resistance
What must autoregulation be mediated by?
→mediated in part by changes in afferent arteriolar resistance
What happens as the systemic pressure rises?
→increase in afferent arteriolar tone prevents the elevation in pressure from being transmitted to the glomerulus
→allowing Pgc and GFR to remain unchanged
Describe how GFR is decreased through TGF
GFR increases ↓ Flow through tubule increases ↓ Flow past macula densa increases (altering luminal NaCl and luminal osmolality) ↓ Paracrine diffuses from macula to afferent arteriole ↓ Afferent arteriole contracts ↓ Resistance in afferent increases ↓ Hydrostatic pressure in glomerular decreases ↓ GFR decreases
What does an increase in osmolality and NaCl in the juxtaglomerular apparatus result in?
→results in a release of ATP
→ leads to a contraction of the afferent arteriole
→ contributes to the maintenance of pressure in the Bowman’s capsule
What nerves can reduce GFR?
→Renal sympathetic nerves (vasoconstrictor, noradrenergic) can reduce the GFR
→by re-setting autoregulation to a lower level
What 3 situations is extrinsic control of GFR used?
→Standing upright (orthostasis)
→Heavy exercise
→Haemorrhage & other forms of clinical shock
In shock what are sympathetic actions helped by?
these sympathetic actions are aided by →circulating vasoconstrictor hormones → adrenaline →angiotensin → and vasopressin
What is the role of extrinsic GFR?
→The role is to conserve body fluid during physical stress
What are the 2 main clinical disorders of the GFR?
→Glomeruli too leaky to plasma protein:
→GFR too low (more common)
What are the signs of nephrotic syndrome and what do they respond well to?
→Proteinuria
→Hypoproteinaemia
→Oedema
→respond well to steroids
What are the signs of low GFR?
→Chronic glomerulonephritis
→Non-functioning glomeruli
What value of GFR is chronic renal failure?
→When GFR < 30 ml/min, this is CHRONIC RENAL FAILURE
What is chronic glomerulonephritis?
→The whole of the glomerulus is replaced by collagen
→ hence there is no blood flow or RBC
→so no glomerular filtrate
What are gaps between podocytes called?
→ filtration slits
