Lecture 37: Glomerular Filtration Rate Flashcards by Matthew Wandabwa

what is glomerular filtration

process by which water and some solutes pass from glomerular capillary into Bowman’s capsule

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what are the 3 barriers to filtration

capillary endothelium
podocyte foot processes
basement membrane

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what are the 2 parts of the nephron

renal corpuscle (glomerulus and Bowman’s capsule

- renal ducts (incl. CD)

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how much cardiac output do the kidneys receive

25%

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what is renal blood flow

volume of blood delivered to the kidneys every minute

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why is renal circulation unique

has 2 sets of capillary beds

one in glomerulus
other around the tubules and LoH

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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

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describe the specialisation vasa recta in the nephron

peritubular caps (which supply tubules) have additional branches that lead towards LoH

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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.

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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

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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

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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)

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describe role of glycocalyx

pecialised prots within fenestrae gaps that act as a barrier to loss of large molecules and cells from blood

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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

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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

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what is proteinuria

protein present in urine

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what is haematuria

blood in urine

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under what circumstances might haematuria and proteinuria occur

diabetes
damage to glomerulus
hypertension
kidney disease

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under what circumstances might leucocytes be present in urine

infection e.g. UTI

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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)

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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)