Lecture 37: Glomerular Filtration Rate Flashcards
what is glomerular filtration
process by which water and some solutes pass from glomerular capillary into Bowman’s capsule
what are the 3 barriers to filtration
- capillary endothelium
- podocyte foot processes
- basement membrane
what are the 2 parts of the nephron
- renal corpuscle (glomerulus and Bowman’s capsule
- renal ducts (incl. CD)
how much cardiac output do the kidneys receive
25%
what is renal blood flow
volume of blood delivered to the kidneys every minute
why is renal circulation unique
has 2 sets of capillary beds
- one in glomerulus
- other around the tubules and LoH
describe the structure of the glomerulus in terms of bv
- arterioles either side of cap bed rather than venule after cap bed
- arterioles defined by muscular layer and pressure within
- caps very tightly spread
- cap function is NOT to deliver O2 and nutrients
- afferent arteriole is larger in diameter than efferent arteriole which adds to pressurisation of glomerulus
describe the specialisation vasa recta in the nephron
peritubular caps (which supply tubules) have additional branches that lead towards LoH
describe the overall structure of the glomerulus
- vascular component (aff. and eff. arteriole) and capsular structure (Bowman’s capsule)
- in junction between aff. eff. and DCT lies an arr. of cells called juxtaglomerular apparatus
- caps (cap bed) lies within glomerulus itself
- caps surrounded by epi cell called podocyte which has branching arms called end-feet which encapsulate caps in highly specialised arr.
what is the role of juxtaglomerular apparatus cells
- cells on the vascular side sense BP changes and respond to it
- cells on tubule side sense changes in [Na+] and respond to adjust it
what is important about the gaps between end-feet of podocytes in glomerulus
- allow for passage of water and solutes out of blood and into filtrate i.e. glomerular filtration
- lined w/ proteins jutting out into slit which act to control movement of small prots out of blood
outline how the glomerulus is specialised for filtration
- caps are fenestrated with glycocalyx
- podocytes with gaps between end-feet
- basement membrane between caps and podocytes
(these 3 things provide a selectivity filter)
describe role of glycocalyx
pecialised prots within fenestrae gaps that act as a barrier to loss of large molecules and cells from blood
describe role of basement membrane
- relatively thick layer of filamentous proteins e.g. collagen, laminin and proteoglycans
- prevent movement of smaller proteins out of blood
- BM provides structural integrity
describe the filtrate composition
- water
- glucose
- electrolytes e.g. Na+, K+, Ca2+,
- amino acids
- fatty acids
- urea
- protein smaller than 3.5nm
all above can pass easily across filtration barrier
all below are too big to pass through
- RBC
- WBC
- platelets
what is proteinuria
protein present in urine
what is haematuria
blood in urine
under what circumstances might haematuria and proteinuria occur
- diabetes
- damage to glomerulus
- hypertension
- kidney disease
under what circumstances might leucocytes be present in urine
infection e.g. UTI
what is the equation of net filtration pressure in general capillaries
NFP = (HPc - HPif) - (πc – πif)
- HP is the hydrostatic pressure
- c is the capillary (HPc = BP)
- if is the interstitial fluid
- π is the osmotic pressure
(πc is the osmotic pressure exerted by blood contents and πif is osmotic pressure exerted by interstitial fluid contents)
describe the cap NFP at arterial end vs venous end
arterial end
- +ve NFPout
venous end
- -ve NFPin
give the glomerular NFP equation
NFP = (HPgc - HPbc) - (πgc – πbc)
compare HPgc to HPc
HPgc > HPc
what is HPgc determined by
- arterial pressure
- eff > aff. arterial resistance
what is HPbc determined by
- pressure of filtrate in capsule, tubules and CD (HPbc < HPgc)
what is πgc determined by
prots in plasma
what is πbc determined by
prots in filtrate
what is GFR determined by
NFP and filtration co-efficient
give the GFR equation
GFR = NFP x Kf
what is Kf in the GFR equation
product of hydraulic conductivity (measure of ease w/ which a fluid can move through a pore) and glom cap SA
give the appx GFR in males and females
males
~125mL/min
females
~105mL/min
GFR also expressed as mL/min/1.73m2
what can make urine appear fizzy
excess proteins
give the equation for clearance rate of a substance from the blood into the urine when any substance (X) is freely filtered and is neither reabsorbed nor secreted by the kidneys
GFR = Urine [X] × Urine flow
Plasma [X]
give examples of substances that can be used to measure clearance rate
- insulin (invasive and inaccurate in practice due to incomplete bladder voiding)
- creatinine (naturally occurring) –> clearance based on serum creatinine level are used to estimate GFR
outline how creatinine clearance is used to estimate GFR and indicate liver function
- creatinine is breakdown product of creatinine phosphate found in muscle
- freely filtered in glomerulus but also actively secreted by peritub. caps. in very small amounts
- so creatinine clearance over estimates actual GFR by 10-20%
- dec. clearance = ^ plasma [creatinine] = dec. renal function
list what factors affect GFR and how
- kidney disease (reduction)
- hypertension (reduction due to glomeruli damage)
- sleep (hormonal and oncotic variations)
- exercise (blood flow diverted to muscles)
- renal blood flow (reduced blood flow = reduced GFR e.g. in renal artery stenosis)
what is one of the main factors controlling renal blood flow
contractile state of renal arterioles
describe glomerulus HP and GFR if aff. arteriole constricts
- vol. of blood flowing to glomerulus (and renal blood flow) dec.
- HP drops because aff. arteriole constricts but eff. arteriole doesn’t
- so NFP and thus GFR both dec.
what is the importance of myogenic constriction in kidney
blood flow auto regulation in kidney which keeps GFR fairly constant over normal range of BP b/c renal blood flow stays fairly constant
when might aff. arteriole constrict butt not eff.
when ADH is released
describe glomerulus HP and GFR if eff. arteriole constricts
- renal blood flow still decreased
- HP actually rises
- blood backs up in glomerulus
- so GFR ^
when might constriction of eff. but not aff. arteriole occur
when ang2 is released
describe glomerulus HP and GFR if both aff. and eff. arteriole constrict
- renal blood flow dec.
- HP largely maintained around normal levels
- thus GFR maintained
- blood can be diverted to other parts of the body
when might both aff and eff arterioles constrict
- flight or fight response
- moderate SNS activity
what effect does increased arterial BP have on glomerulus
- ^ pressure in aff. arteriole
- ^ flow through glom.
- ^ HP in glom
- ^ GFR
what response occurs due to ^ aff. arteriole pressure and what is its effect
- reflex myogenic vasoconstriction
- reduces blood flow through aff. arteriole
- dec. glom HP and GFR
- once aff. BP dec. then myogenic vasoconstriction is relieved and vessel relaxes
- blood flow ^
what occurs at the glomerulus if BP drops significantly
- sensed by juxtaglomerular apparatus in aff. arteriole
- renin released
- activates ang2
- acts on eff. arteriole to ^ vasoconstriction
- ^ HP in glom
- maintaining filtration at reasonably normal levels
how is renal blood flow measured
clearance:
- vol. of plasma which is cleared of a particular substance in 1 min calibrated for amount of blood that is plasma vs RBC
what is an important factor when measuring renal blood flow
choice of substance:
- needs to be cleared in 1 circuit through kidney
- needs to be filtered and secreted as this will take into account tubular blood flow
give example of substance commonly used to measure renal blood flow and why it is good
PAH - para-aminohippuric acid
- > 90% extracted by kidneys in one circuit
- not manufactured/metabolised by body (IV infused)
- doesn’t affect kidney function
what is the issue of using PAH to measure renal blood flow and how is that issue overcome
- PAH confined to plasma
- doesn’t directly measure renal blood flow
Clearance of PAH = plasma vol. delivered to kidneys every min = renal plasma flow
renal blood flow = renal plasma flow/(1-haematocrit)
