B5.036 Renal Physiology I: Glomerular Filtration Flashcards
homeostatic functions of the kidneys
regulation of extracellular fluid volume
regulation of extracellular fluid electrolyte composition
regulation of extracellular fluid acid base balance
excretory functions of the kidneys
metabolic waste products
foreign substances and toxins
endocrine functions of the kidneys
regulation of BP
erythropoiesis
calcium metabolism
vertebral level of kidneys
T-12 to L3
discuss the structure of the kidney
renal artery and vein, nerves, and renal pelvis enter and exit the organ at the hilum
outer zone = cortex
inner portion = medulla
medulla contains 8-18 pyramids (base directed at cortex)
between pyramids are projections called renal columns
apex of pyramid = papilla
each papilla > minor calix > major calix > renal pelvis > ureter
how many nephrons in a kidney
1 million
2 types of nephrons
cortical- whole structure in renal cortex
juxtamedullary - part of tubular region extends into medulla
what is the renal corpuscle and what is its function?
formed by glomerulus surrounding by Bowman’s capsule
filtering component of the nephron located in the cortex
describe the structure of the glomerulus
afferent and efferent arterioles
mesangial cells between capillary loops
functions of mesangial cells
supporting structures
contractile properties
phagocytic activities
secrete substances can locally regulate glomerular function
describe the structure of Bowman’s space
vascular layer and parietal layer
bowman’s space between layers- receives renal filtrate
what is the ultrafiltrate made up of
plasma without proteins
structure of the renal tubule
3 sections proximal tubule loop of henle distal convoluted tubule convert blood filtrate to urine reabsorb water and some solutes back into blood secrete some solutes into tubular lumen
what is the juxtaglomerular apparatus
interaction between distal tubule and vascular pole of renal corpuscle
tubular epithelial cells + extraglomerular mesangial cells + wall of afferent arteriole
basic functions of the nephron
- filtration
- reabsorption
- secretion
- excretion
substance handled by the kidneys only in filtration
inulin
substances that are primarily reabsorbed
AAs
glucose
Na+
Cl-
substances that are primarily secreted
metabolic products and drugs ex: penicillin furosemide hippurates morphine
substances that can be reabsorbed or secreted depending on the segment
K+
urate
why is the kidney said to be a polarized organ
blood and urine kept very separate
3 factors involved in renal filtration
- properties of the glomerular filtration membrane
- properties of the filtered molecules
- forces involved in filtration
capillary endothelium
single cell layer that has numerous pores or fenestrae
basement membrane
non cellular mesh of negatively charged glycoproteins and proteoglycans
filtration pathway in the renal corpuscle
capillary endothelium
basement membrane
podocytes
more selective in each layer
podocytes
large cells that face the lumen of Bowman’s space
firmly attached to the basement membrane
filtration slits between them
describe the portion of Bowmans capsule not in contact with the glomerular capillaries
flat cells resting on the basement membrane
eventually continues with the epithelium of the renal proximal tubule
what is a slit diaphragm?
located between podocyte foot processes
zipper like structure constituted by numerous cross bridges
major components: nephrin & p-cadherin
discuss the size of pores within the slit diaphragms between podocytes
40 x 140 A
size of albumin
nothing albumin or larger can fit through, thus proteins do not enter into the filtrate
properties of filtered molecules that enter into the ultrafiltrate
ions and small molecules up to 2 nm (7000 Da)
above 3 nm have increasing difficulty filtering
nothing larger than 4 nm can pass
cationic molecules favored over anionic
influence of size and charge on renal filterability
cationic molecules with a radius between 2-4 nm filter in a greater extent than anionic molecules of the same size
due to electrostatic interactions with negatively charged glycoproteins on BM
what molecule was used to demonstrate the influence of charge on filterability
dextrans
exogenous polysaccharides of D-glucose that can be produced in various molecular weights and charges (neutral, cationic, and anionic)
what happens when the negative charge of the filtrating membrane is reduced?
can happen due to immunological or inflammatory damage
proteins can be filtered solely on size, can lead to proteinuria (lack of charge discrimination)
arterial blood flow path through the kidney
aorta > renal artery > interlobar arteries > arcuate arteries > interlobular arteries > afferent arteriole > efferent arteriole
where do arcuate arteries run
between cortex and medulla
venous blood flow path through the kidne
efferent arteriole > peritubular capillaries/ vasa recta > interlobular vein > arcuate vein > interlobar vein > renal vein
function of peritubular capillaries
provide nutrient to tubules and retrieve the fluid the tubules reabsorb
discuss the pressures of the renal circulation
afferent and efferent arterioles are the major resistance sites and thus the major sites for control of flow
hydrostatic pressure > oncotic pressure = filtration in glomerular capillaries
oncotic pressure > hydrostatic pressure = absorption in peritubular capillaries
normal renal blood flow
1.2 L/min
20-25 % of cardiac output
normal renal plasma flow
660 mL/min
glomerular filtration rate (GFR)
125 mL/min
urine excreted = 1, 1.5 L/day
normal filtration fraction
GFR/RPF = 0.2
primary forces involved in ultrafiltration
major force causing filtration = hydrostatic pressure in glomerular capillary bed, 60 mmHg
opposed by smaller hydrostatic pressure within the tubule = 20 mmHg
opposed by colloid osmotic pressure of the blood = 30 mmHg
NET = 60-20-30 = 10 mmHg
what other factors contribute to ultrafiltration other than pressures?
surface area and permeability of the glomerular membrane
make up the ultrafiltration coefficient Kuf = 12
GFR=
Kuf * Puf
effect of afferent arteriole constriction on RBF and GFR
increases resistance to blood flow
causes a fall in RBF
fall in glomerular capillary pressure
decreased GFR
effect of efferent arteriole constriction
increases resistance to blood flow
rise in glomerular capillary pressure tends to increase GFR
decreased RBF
autoregulation of RBF and GFR
tubuloglomerular feedback mechanism
myogenic response
extrinsic regulation of RBF and GFR
sympathetic nerves
renin-angiotensin-aldosterone system
humoral factors: angiotensin II, prostaglandins, NO, bradykinin, endothelin, adenosine
what is the autoregulatory range of renal blood flow
90-180 mmHg
RBF and Pgc do not change significantly when arterial pressure changes within a wide range of values
RBF is fairly independent of renal perfusion pressure
what is the myogenic response
automatic adjustment of afferent arteriole
for example: when the arterial pressure increases, walls of afferent arteriole are stretched, triggering the contraction of the vascular smooth muscle
subsequent increase in resistance counteracts the increment in RBF and both RBF and GFR remain unaltered
what is the tubuloglomerular feedback mechanism
RBF and GFR regulated by changes in tubular flow rate and fluid composition
TGF mechanism mediated by cells of macula densa
when an increase in GFR increases fluid flow and NaCl concentration, there is a contraction of the afferent arteriole which returns RBF and GFR to normal levels
how do macula densa cells work in the TGF mechanism
able to sense changes in NaCl concentration through NA+K+2Cl- transporters present on their membrane
release messengers that target smooth muscle cells to contract afferent arteriole
adenosine
vasoconstrictor
NO
vasodilator
what are granular cells
part of the juxtaglomerular apparatus
modified smooth muscle cells on the wall of the afferent arteriole
responsible for secretion of renin
stimuli of renin-angiotensin system
- increased sympathetic nerve activity
- reduction of renal blood pressure
- decreased Na+ delivery to macula densa
give an overview of the renin-angiotensin system
renin converts angiotensinogen to angiotensin I
ACE converts angiotensin I to angiotensin II
angiotensin II stimulates arteriolar vasoconstriction, sodium reabsorption in the proximal tubules, and activation of aldosterone secretion
effect of aldosterone secretion
increases Na+ reabsorption by the ascending loop of Henle, the distal tubules, and the collecting ducts
increases K+ secretion
increases blood volume and pressure
mechanism of action of angiotensin II on vessels
stimulates entry of Ca2+ into cell
Ca2+ increases actin-myosin coupling and stimulates vasoconstriction
mechanism of action of angiotensin II on adrenals
increases entry of Ca2+ into cell
activates transcription factors and aldosterone synthesis
increases aldosterone secretion from cell
why is important to determine the GFR
diagnosis of renal disease
staging and progression of renal impairment
adjusting the dosage of medications
measurement of glomerular filtration rate
GFR = Ux * V / Px excretion rate / plasma concentration Ux = urine concentration of substance x V = volume of urine per minute Px = plasma concentration of substance x
clearance
term used to describe the rate of removal or ‘clearing’ of a substance from the blood
measures efficiency of kidney
normal GFR
125 ml/min
based on inulin rate of clearance
advantages of using creatinine to measure GFR
end product of protein metabolism
always present in blood at relatively constant concentration
freely filtered and secreted by the proximal tubule
no need for IV infusion
clearance time over long period
no emptying of bladder needed
disadvantages of using creatinine to measure GFR
filtered and secreted
can be overestimated
overestimation and secretion can cancel each other out
GFR variance in the population
normal in young adults 100-125
decreases with age
lower in females than males
