Renal Blood Flow and GFR Flashcards
Essentially, what is the kidney important in
Excretion and retention of nutrients
What is GFR a key parameter in
Kidney failure
What is meant by Glomerular filtration
Definition: formation of an ultrafiltrate of plasma in the glomerulus
What is meant by renal failure
An abrupt fall in glomerular filtration is renal failure
Abnormalities in renal circulation lead to reduced glomerular filtration i.e. renal failure.
What type of process is glomerular filtration
Passive process: fluid is ‘driven’ through the semipermeable (fenestrated) walls of the glomerular capillaries into the Bowmans capsule space by the hydrostatic pressure of heart.
Hydrostatic pressure of blood (generated by heart) drives blood through fenestrations
Describe the movement of filtrate from the glomeruli to the Bowman’s Capsule
The filtration barrier (fenestrated endothelium of capillaries and semipermeable Bowman’s capsule) is highly permeable to: fluids small solutes (these are “freely filtered”: same concentration in filtrate and plasma)
But impermeable to:
cells
proteins
drugs etc carried bound to protein
What does this filtering produce
A clear fluid (ultrafiltrate), completely free from blood and proteins, is produced containing electrolytes and small solutes = ‘primary urine’
Ultrafiltrate= soluble components of plasma in the absence of cells or proteins.
Do we excrete the primary urine
No -things will be reabsorbed
If something is reabsorbed, what will its conc in the urine be
Low
What is the space between the foot processes of the podocyte called
fenestration slits
Why do we measure renal function in terms of flow
It is easier to measure than pressure
Where do substances leaving the kidney leave
Renal vein and ureter
What is the amount of something excreted equal to
Amount filtered + amount secreted - amount reabsorbed
Where do the secretions come from
Peritubular capillaries (lead from efferent arteriole) Don't go through filtering process
What are the glomerular filtration pressures
Driving force = hydrostatic pressure in glomerular capillaries (due to blood pressure) (Pgc)
Opposing pressures: hydrostatic pressure of tubule (Pt)
osmotic pressure of plasma proteins in glomerular capillaries (πgc)
Together these determine the net ultrafiltration pressure (Puf)
What is glomerular filtration pressure (net) equal to
Puf = Pgc- Pt- πgc
Normal GFP value = 10-20mmHg.
Define GFR
GFR = The amount of fluid filtered from the glomeruli into the Bowmans capsule per unit of time (ml/min).
Sum of filtration rate of all functioning nephrons
What is the formula for GFR
GFR = Puf x Kf
Where Kf is an ultrafiltration coefficient (membrane permeability and available for filtration).
Any changes in filtration forces or Kf will result in GFR imbalances.
What can result in changes in Kf
o Kidney disease = reduce number of functioning glomeruli = reduce surface area = reduce Kf = reduce GFR.
o Dilation of glomerular arterioles by drugs/hormones = more surface area = increase Kf = increase GFR.
Kidney disease and inflammation will also increase permeability
How do we get to the value for GFR
§ Renal blood flow (RBF) = approx. 1L/min – which is one fifth of cardiac output = 5.04L/min.
§ Renal plasma flow (RPF) = approx. 0.6L/min – just the plasma in the renal blood.
§ Filtration fraction (FF) = 0.2 – ratio between RPF and amount of filtrate filtered by glomerulus, which is normally 20%.
Glomerular filtration rate (GFR) = RPF x FF
Approx 120ml/min
What does renal blood flow deliver
Delivers oxygen, nutrients and substances for excretion
What does GFR depend on
Glomerular capillary pressure (Pgc)
Plasma oncotic pressure (πgc)
Tubular pressure (Pt)
Glomerular capillary surface area or permeability (Kf).
GFR is not a fixed value but is subject to physiological regulation. This is achieved by neural or hormonal input to the afferent/efferent arteriole resulting in changes in Puf.
Why is autoregulation important
Exercise- hydrostatic pressure would increase- so would GFR- urinate more- this doesn’t make sense physiologically
Describe myogenic autoregulation
Vascular smooth muscle constricts when stretched.
Keeps GFR constant when blood pressure rises.
Arterial pressure rises → afferent arteriole stretches →
arteriole contracts → (vessel resistance increases)→ blood flow reduces and GFR remains constant:
What does freely filtered mean
“Freely filtered”: solute found at same concentration in filtrate and plasma
What is the effect of a severe haemorrhage on GFR
decreases Pgc so will decrease GFR
What is the effect of an obstruction of a nephron tubule on GFR
increases Pt/decreases Kf so decreases GFR
What is the effect of reduced plasma protein conc on GFR
decreases πgc so decreases GFR
What is the effect of a small increase in blood pressure on GFR
no effect due to myogenic autoregulation
How do we measure GFR
Renal clearance
Describe renal clearance
As substances in the blood pass through the kidney they are filtered to different degrees. The extent to which they are removed from the blood is called clearance.
Define renal clearance
Clearance is the number of litres of plasma that are completely cleared of the substance per unit time.
What is the equation for renal clearance
(urine concentration x rate of urine production)/concentration in plasma
UV/P
U = concentration of substance in urine P = concentration of substance in plasma V = rate of urine production
ml/min
How can Renal clearance be used to measure GFR
If a molecule is freely filtered and neither reabsorbed nor secreted in the nephron then the amount filtered equals amount excreted. Thus GFR can be measured by measuring clearance of this molecule
Has to be filtered, but cannot be absorbed or excreted
Describe inulin
Inulin:
- a plant polysaccharide
- freely filtered and neither reabsorbed nor secreted
- not toxic
- measureable in urine and plasma.
But not found in mammals so needs to be transfused therefore use an endogenous molecule with a similar clearance.
clearance = 120ml/min.
What is a practical measurement of GFR
GFR in humans is normally estimated from creatinine clearance.
Creatinine:
a waste product from creatine in muscle metabolism
amount of creatinine released is fairly constant
if renal function stable, amount creatinine in urine is stable
low values of creatinine clearance may indicate renal failure
high plasma creatinine may indicate renal failure
If GFR decreases, what should happen to plasma creatinine
It’s conc should increase
List some values for renal clearance
Na 1.0ml/min K 11.0ml/min Ca 1.8ml/min Mg 3.6ml/min Phosphate 6.4ml/min Glucose 0.05ml/min Urea 17.0ml/min Inulin 120.0ml/min PAH 625.0ml/min
When may plasma creatinine be high without any pathophysiology
In more muscular people
How do we measure renal plasma flow
Measured by PAH (Para aminohippurate) clearance = 625ml/min
Filtered and actively secreted in one pass of the kidney, thus can be used to measure RPF.
In other words the all of the PAH is removed from the plasma passing through the kidney so its clearance equals the renal plasma flow
What isn’t filtered is actively secreted
What does the amount of substance appearing in the urine reflect
The amount of substance appearing in the urine reflects the combined effects of filtration, reabsorption from nephron tubule to blood and secretion from blood into the tubular fluid, such that:
Amount excreted = amount filtered - amount reabsorbed + amount secreted
If a substance is reabsorbed what will its clearance be
Less than GFR
If a substance is neither absorbed nor secreted what will its clearance be
= GFR
If a substance is secreted and not reabsorbed what will its clearance be
> GFR
Describe renal diagnostics
A fall in GFR is the cardinal feature of renal disease
If GFR falls, excretory products will build up in the plasma.
A raised plasma concentration of creatinine is diagnostic of renal disease.
Why do we need to be careful about pharmacokinetics in renal failure
In acute kidney failure- GFR can decrease 4- fold
Drugs will accumulate in the plasma 4-fold- potential overdose
Drugs that treat AF partially bloc AV node- too much will kill you
Excretion of many other substances will also be impaired in renal failure - including some drugs. This needs to be taken into account when calculating drug doses - PHARMACOKINETICS.
Describe the excretion role of the kidney
Excretion of metabolic products e.g. urea, uric acid, creatinine
Excretion of foreign substances (drugs)
Describe the role of the kidney in homeostasis
Homeostasis of: body fluids (cell volume)
electrolytes (cell volume)
acid-base balance
Describe the role of the kidney in regulating BP
Regulate blood pressure - Secrete hormones (renin, erythropoietin) -
What factors can affect net ultrafiltration
Arterial blood pressure: if increases, will increase Pgc and hence Puf and GFR
Plasma protein concentration: if increases, will increase πgc and hence decrease Puf and GFR
Ureteral obstruction: will increase Pt, hence decreasing Puf and GFR
