Glomerular filtration and renal blood flow Flashcards
What is glomerular filtration?
Process whereby a proportion of the plasma enters the bowman’s capsule and forms the initial tubular fluid
Which structures compose the glomerular epithelium? What does each form a barrier to?
Capillary endothelium - RBC
Basal lamina/basement membrane - proteins
Slit processes of podocytes - proteins
Across which structure does the process of filtration occur?
Glomerular epithelium
What feature of the basement membrane allows it to act as a barrier to plasma proteins?
Negatively charged glycoproteins repel negatively charge plasma proteins
Which (starling) forces comprise net filtration pressure?
Capillary hydrostatic pressure
Bowman’s oncotic pressure
Capillary oncotic pressure
Bowman’s hydrostatic pressure
Which of the forces involved in net filtration favour it?
Capillary hydrostatic pressure
Bowman’s oncotic pressure
Which of the forces involved in net filtration oppose it?
Bowman’s hydrostatic pressure
Capillary oncotic pressure
Is glomerular filtration an active or passive process?
Passive
What is oncotic pressure?
The pressure of plasma proteins (drags fluid towards it)
Why is capillary blood pressure constant throughout the nephron?
Because of the back pressure created by the afferent arteriole being of larger diameter than the efferent arteriole
Why is bowman’s oncotic pressure 0 in a healthy adult?
Plasma proteins should be unable to cross the glomerular membrane
What is GFR?
Glomerular filtration rate - the rate at which protein free plasma is filtered from the glomeruli into the bowman’s capsule per unit time
Write the equation to calculate GFR
GFR = filtration coefficient x net filtration pressure
What is the filtration coefficient?
A measure of how holey (i.e permeable to substances) the glomerular membrane is
What is the average GFR in a healthy adult?
125ml/min
Which starling force is the major determinant of GFR?
Capillary hydrostatic (blood) pressure
How is GRF regulated?
Extrinsic mechanisms (sympathetic activity) Intrinsic mechanisms/autoregulation (myogenic, tubuloglomerular feedback)
How does arterial blood pressure affect GFR?
Increase in BP –> increase in capillary hydrostatic pressure –> increase in net filtration pressure –> increase in GFR
(and vice versa)
How does vasoconstriction and vasodilation affect GFR respectively?
Vasoconstriction - decreased blood flow –> decreased GFR
Vasodilation - increased blood flow –> increased GFR
Do changes in systemic arteriolar pressure always cause changes in GFR?
No - autoregulation helps prevent short term changes in mean arterial BP from affecting renal blood flow and GFR
How is mean arterial blood pressure calculated?
1/3 pulse pressure plus diastolic pressure
How is autoregulation of GFR protective?
Helps prevent serious electrolyte imbalance
Explain myogenic autoregulation
Vascular smooth muscle within the kidneys contracts when stretched (i.e by increased blood pressure) thereby limiting blood flow
Explain tubuloglomerular autoregulation
Increased GFR causes increased salt flowing through the tubules which is detected by the macula densa and results in the constriction of afferent arterioles
How does the macula densa cause constriction of afferent arteriole?
Release of vasoactive mediators which cause vasoconstriction
When does extrinsic control of GFR override intrinsic control?
When extrinsic changes are severe enough
How does increased hydrostatic pressure within the Bowman’s capsule change GFR? In which pathology might this be seen?
It decreases it
Kidney stones
How does increased capillary oncotic pressure change GFR? In which pathology might this be seen
It decreases it
Diarrhoea (dehydration causes proportional increase in plasma proteins)
How does decreased capillary oncotic pressure change GFR? In which pathology might this be seen?
It increases it Severe burns (due to leakage of plasma proteins from the damaged skin)
How does a decrease in the filtration coefficient change GFR?
It decreases it (due to decreased surface area for filtration)
What is plasma clearance?
The efficiency of the kidneys at clearing the plasma of a substance (the volume of plasma completely cleared of a substance per minute)
What is the value of kidney plasma clearance?
Plasma clearance is a value unique to each substance being cleared
What are the units of plasma clearance?
ml/min
Write the equation used to calculate plasma clearance
Plasma clearance = rate of excretion / plasma concentration
i.e plasma clearance = [urine concentration x urine output]/plasma concentration
For which substances does plasma clearance equal GFR?
Inulin
Creatinine (almost)
Why are substances which have a plasma clearance equal to GFR useful?
They provide a clinical measure of GFR
Why is creatinine used as a measure of GFR over inulin?
Creatinine is endogenous and therefore does not need to be infused
NB - creatinine is secreted a little bit so doesn’t give 100% accuracy
Which important substance is filtered and completely reabsorbed (i.e clearance = 0) but not secreted?
Glucose (in a healthy adult)
Which importance substance is filtered and partially reabsorbed (i.e clearance
Urea
Which important substance is filtered and completed secreted (i.e clearance > GFR)?
Hydrogen ions
How can we tell if a substance is reabsorbed, secreted or neither using clearance and GFR values?
Clearance GFR - secreted
NB - GFR is taken to be 125ml/min
Which substance is used clinically to measure renal plasma flow?
Para-amino hippuric acid (PAH)
How is PAH treated by the kidneys?
Filtered
Completely secreted
Not reabsorbed (i.e completely cleared from plasma)
What is creatinine?
A muscle metabolite produced at a nearly constant rate
Which three properties should substances used as clearance markers have?
Non-toxic Inert Easy to measure GFR - not absorbed or secreted RPF - not absorbed but completely secreted
What is the filtration fraction?
Fraction of plasma flowing through the tubules that gets filtered
Write the equation used to calculate filtration fraction
Filtration fraction = GFR / RPF
Write the equation used to calculate renal blood flow
Renal blood flow = renal plasma flow x 1/(1-haematocrit)
