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Glomerular Filtration

Glomerular Filtration
• Glomerular filtration:
the movement of fluid
from blood into the
lumen of the nephron.
• In a resting adult, the
kidneys receive 1.2–
1.3 L of blood per
minute, or just under
25% of the cardiac
output.
Renal Blood Flow
• Norepinephrine
(noradrenaline) constricts the
renal vessels, with the
greatest effect exerted on the
interlobular arteries and the
afferent arterioles.
• Angiotensin II exerts a
constrictor effect on both the
afferent and efferent
arterioles.

• Dopamine is made in the kidney and causes renal


vasodilation and natriuresis.
Renal Blood Flow
• Prostaglandins increase
blood flow in the renal
cortex and decrease
blood flow in the renal
medulla.

• Prostaglandins increase blood flow in the renal cortex


and decrease blood flow in the renal medulla.
• Acetylcholine also produces renal vasodilation.
• A high-protein diet raises glomerular capillary pressure
and increases renal blood flow.
Glomerular Membrane
1. Fenestrated endothelium of
glomerular capillaries, allow all blood
components except blood cells to
pass through.
2. Basement membrane, electrically
repels many negatively charged
macromolecular anions such as
plasma proteins
3. Foot processes of podocytes of the
glomerular capsule form the filtration
slits
-> Filtrate composition: same as plasma
free protein
• The endothelium of the
glomerular capillaries is
fenestrated
• The endothelium of the
glomerular capillaries is
completely surrounded by the
glomerular basement
membrane along with
specialized cells called
podocytes.

• Podocytes have numerous pseudopodia that


interdigitate to form filtration slits along the
capillary wall.
• The glomerular basement membrane, the basal
lamina, does not contain visible gaps or pores.
• Stellate cells called mesangial cells
are located between the basal
lamina and the endothelium.
• Mesangial cells are especially
common between two neighboring
capillaries, and in these locations
the basal membrane forms a
sheath shared by both capillaries.

• The mesangial cells are contractile and play a role in


the regulation of glomerular filtration.
• Mesangial cells secrete the extracellular matrix, take up
immune complexes, and are involved in the
progression of glomerular disease.
Glomerular Filtration Rate
• GFR: is the amount of plasma ultrafiltrate formed each
minute~ 125 ml/minute
• GFR is directly proportional to each of the following
factors:

• Kf, is glomerular ultrafiltration coefficient (glomerular capillary wall


hydraulic conductivity, its permeability & effective filtration surface
area).
• PGC is the mean hydrostatic pressure in the glomerular capillaries,
• PT is the mean hydrostatic pressure in the tubule (Bowman’s space),
• πGC the oncotic pressure of the plasma in the glomerular capillaries,
• and πT the oncotic pressure of the filtrate in the tubule (Bowman’s
space).
Control of GFR
• Auto regulation is a local
control process in which
the kidney maintains a
relatively constant GFR in
the face of normal
fluctuations in blood
pressure;

1) a myogenic response; intrinsic ability of vascular


smooth muscle to respond to pressure changes
2) a tubuloglomerular feedback; is a paracrine
signaling mechanism through which changes in
fluid flow through the loop of Henle influence GFR.
1. Myogenic mechanism
• Rising systemic blood
pressure stretches
vascular smooth
muscle, causing
afferent arterioles to
constrict, restrict
blood flow into the
glomerulus
Hormones and Autonomic Neurons Also Influence GFR
• Neural control of GFR is mediated by sympathetic
neurons that innervate both the afferent and
efferent arterioles.
• Sympathetic innervation of α-receptors on vascular
smooth muscle causes vasoconstriction.
• If sympathetic activity is moderate, there is little
effect on GFR.
• If systemic blood pressure drops sharply, however,
as occurs with hemorrhage or severe dehydration,
sympathetically induced vasoconstriction of the
arterioles decreases GFR and renal blood flow.
• This is an adaptive response that helps conserve
fluid volume
• A variety of hormones also influence arteriolar
resistance.
• Among the most important are angiotensin II,
a potent vasoconstrictor, and prostaglandins,
which act as vasodilators.
• These same hormones may affect the
filtration coefficient by acting on podocytes or
mesangial cells.
Measuring GFR
• Substance to be used to measure GFR must be
freely filtered through the glomeruli and must
be neither secreted nor reabsorbed by the
tubules, also should be nontoxic and not
metabolized by the body.
• Inulin, a polymer of fructose with a molecular
weight of 5200, meets these criteria in
humans and most animals and can be used to
measure GFR.
Clearance
• Renal plasma clearance is the volume of plasma
from which a substance is completely removed by
the kidney in a given amount of time (usually
minutes) .
• Therefore, if the substance is designated by the
letter X, the GFR is equal to the concentration of
X in urine (UX ) times the urine flow per unit of
time (V) divided by the arterial plasma level of X
(PX ), or UXV/PX.
• This value is called the clearance of X (CX ).
Clearance of Inulin

Figure 19-16: Inulin clearance


• Creatinine:
– End product of muscle creatine metabolism
– Used in clinical setting to measure GFR but less
accurate than inulin method
– Small amount secrete from the tubule
• Para-aminohippurate (PAH):
– An organic anion not present in body
– Freely filtered, secreted but not reabsorbed by
nephron
– Non-toxic, neither synthesized nor metabolized
in kidney
– Low concentrations are enough (10 mg/100 ml
plasma)
– RPF = ClearancePAH = UPAH.V / PPAH
Effective Renal Plasma Flow (ERPF)
THANK YOU
Reference
• Barret KE, Barman SM, Boitano S & Brooks HL,
Ganong’s Review of Medical Physiology, 24th edition,
McGraw Hill Companies, 2012.
• Silverthorn DE, Human Physiology an integrated
approach, 6th edition, Pearson, 2013.
• Sherwood L, Fundamentals of Physiology a human
perspective, 3rd edition, Thomson Brooks/Cole, 2006.
• Martini FH, Nath JL, Bartholomew EF, Fundamentals of
Anatomy & Physiology, 9th edition, Pearson Education
Inc. 2012.
• Hall, JE. Guyton and Hall Textbook of Medical
Physiology. 13th edition. Elsevier. 2019.

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