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Renal physiology

by
Dr. Isam Eldin Mohamed Abd Alla
Urinary system
Functional Anatomy of the kidney
The kidney is made of an outer cortex &
inner medulla.
The functional unit of the kidney is called
the nephron.
Each kidney contains 1.3 million nephrons.
Kidney
The nephron is made of:
• Glomerulus: A network (tuft) of blood
capillaries located inside Bowman`s
capsule. Derived from afferent arteriole
& drain into efferent arteriole
• These capillaries have the highest
hydrostatic pressure.
• It is the site of filtration of the plasma.
• Renal tubules: small tubes including:
 proximal convoluted tubules PCT.
 loop of Henle HL, with descending &
ascending limbs
distal convoluted tubules DCT,
 collecting duct CD.
Nephron
• These tubules drain the glomerular
filtrate from Bowmans capsule.
• They modify the filtrate by the process of
reabsorption & secretion.
• Then the modified filtrate flows as urine
to the renal pelvis.
• 85% of the nephrons are called Cortical
nephrons– their glomeruli in outer cortex &
have short loops of Henle that extend only
short distance into medulla- blood flow is
rapid.
• the remaining 15% are called
Juxtamedullary nephrons , their glomeruli
in the inner part of cortex & have long
loops of Henle which extend deeply into
medulla.–blood flow through vasa recta in
medulla is slow.
• Renal blood flow: RBF
• The renal artery → segmental arteries →
interlobar arteries that communicate with
one another via arcuate arteries.
• The arcuate arteries give branches called
interlobular arteries → Afferent arterioles
→ Glomerular capillaries → Efferent
arterioles → Peritubular capillaries & vasa
recta →Interlobular veins → Venous return of
blood is via similarly named veins till the
renal vein.
Renal blood flow
• The kidneys receive about 25% of the
cardiac output
• RBF is the major factor in the process of
urine formation.
• 94% of RBF flows to the cortex because
it contains most of the nephrons.
• RBF ↑by the following renal
vasodilators:
• Acetlylcholine from the parasympathetic
nerves endings.
• Dopamine, hormone secreted from the
adrenal medulla.
• Atrial natriuretic poly peptide ANP,
secreted by the heart atria & Brain- type
natriuretic poly peptide BNP secreted by
the heart ventricles and the brain. These
two hormones are secreted when the
heart is extended by increase in blood
volume.
• Prostaglandin E2, a local hormone that ↑
RBF to the cortex, but Prostaglandin F2α ↓
the flow to the medulla.
• Nitric oxide NO. produced locally from
the endothelium.
• NOTE : RBF ↑ after high proteins diets.
RBF decreases by the following renal
vasoconstrictors:
• Norepinephrine secreted by sympathetic
nerves endings & adrenal medulla in cases
of hypotension and exercise & sresses.
• Angiotensin II , a hormone produced in
response to hypotension & sympathetic
stimulation..
• Myogenicity of vascular smooth muscles
which is a contraction in response to
stretch caused by increase in blood
pressure
• Myogenicity, AngiotensinII & Nitric oxide
are called autoregulation of renal blood
flow ,
• The autoregulation can maintain
constant renal blood flow despites of
blood pressure changes between 90—
220 mmHg,
• Accordingly the GFR and urine output
decrease when the arterial blood pressure
is lower than 90 mmHg & increase when
the arterial blood pressure is higher than
220 mmHg.  
Glomerular filtration
• Is the first step in the process of urine
formation.
• Occurs in the glomeruli of the
nephrons by forceful
movement of plasma across
the filtration membrane.  
• Filtration membrane is made of
Glomerular capillaries endothelium
which contains pores (fenestrated).
Bowmans capsule visceral epithelium
which contains processes (podocytes)
between them formed the filtration slits.
Fused basement membrane of the
capillaries endothelium & Bowmans
capsule visceral epithelium, contains the
negatively charged sialoproteins.
• The glomerular filtrate contains all
the component of the plasma EXCEPT
the plasma proteins.
Glomerular filtration rate GFR:

• Is the amount of glomerular filtrate


by all nephrons in both kidneys per
unit of time = 125 ml/minute (180
Liters/ day).
• The filtration occurs by Starling`s
forces according to Starling,s
equation:
GFR= kf (PGC- PT-∏GC)
• Kf: Is the filtration coefficient, it is a
product of the surface area &
permeability of the filtration
membrane.
• The filtration membrane surface area
↑ by relaxation and ↓ by contraction
of the mesangial cells found between
the capillaries endothelium & the
• Factors that relax the mesangial cells

• Factors that contract the mesangial cells


• The permeability of the membrane is
very high because the glomerular
capillaries endothelium is fenestrated &
Bowmans visceral epithelium contains
filtration slits.
The neutral molecules in the plasma with
diameter less than 4 nm are freely filtered
across this membrane while those with
diameter more than 8 nm are not filtered.
• The filtration rate of charged molecules
(ions) is slower than that of the neutral
molecules, therefore the smallest plasma
protein (Albumin ) is normally not filtered
because it is relatively large & negatively
charged repelled by the negatively charged
sialoproteins in the basement membrane
of filtration membrane.
• NOTE
• In case of inflammation in the nephron
including the glomerulus
(Glomrulonephritis) the albumin is filtered
& appears in the urine (Albuminuria),
because the inflammation dilates the
membrane dissipating the negative
charges & increase both the surface area &
permeability of the membrane.
• PGC: Is the hydrostatic pressure in the
glomerular capillaries caused by the water
in the blood (blood volume).= 60 mmHg
which is the highest hydrostatic pressure
among the capillaries of the body,
because:
The renal artery is short & straight
branch of abdominal aorta.
The afferent arterioles are short &
straight branches of the interlobular
arteries.
The glomerular capillaries drain into
arteriole (efferent) while other capillaries
drain into venules..
• PGC is the main force of filtration. It ↑by
increase in blood volume & other
causes that ↑the cardiac output. It ↑ also
by dilation of the afferent arterioles &
constriction of the efferent arterioles.
• PT: Is the hydrostatic pressure inside
Bowman,s capsule & renal tubules.= 18
mmHg. is kept at this low value because
the glomerular filtrate is continuously
drained from Bowman,s capsule by the
renal tubules to the renal pelvis & then by
the ureters to the urinary bladder,
 PT increases by oedema or ureteric stones
that obstruct the urine flow, this decreases
the GFR.
• ∏GC: Is the colloids osmotic pressure
(oncotic pressure) in the glomerular
capillaries due to the presence of plasma
proteins (colloids) = 25 mmHg , it acts to
oppose the filtration .
• The net filtration pressure = 60- 18- 25
mmHg = 17 mmHg.
• Measurement of the GFR:
• The GFR is measured by measuring the
renal clearance rate (plasma clearance) of
a substance which is freely filtered by the
glomeruli, neither reabsorbed from, nor
secreted into the renal tubules, eg. Inulin.
Plasma clearamce of a substance X : Is the
volume of plasma completely cleared of X per
unit of time.
• The required criteria of a substance used
for measurement of GFR:
• Freely filterable at the glomerulus
• Does not bind to plasma proteins
• Biologically inert
• Non-toxic, neither synthesized nor
metabolized in kidney
• Neither reabsorbed nor secreted
• Does not alter renal function
• Can be accurately quantified (measured)
• Low concentrations are enough (10-20
mg/100 ml plasma)
• Inulin: Is a Polysaccharide, injected &
infused intravenously, then after a time a
volume urine sample V is collected & the
levels of Inulin in the plasma PIN & in the
urine UIN are measured.
• If a substance is filtered but neither
reabsorbed nor secreted, then the amount
present in urine V. UX = amount of X in plasma
cleared/min (plasma clearance of X)
by glomerulus GFR. PX
• GFR. PX = V. UX = CX.
• GFR.= V. UX /Px = CX
• GFR= Inulin clearance CIN = V. UIN/PIN
• Creatinine clearance CCr is also useful for
measurement of the GFR. but it is not
accurate as Inulin clearance.
• GFR= Creatinine clearance
CCr = V. UCr/PCr/ 

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