PHYSIO B 1.1 RENAL PHYSIOLOGY PT. 1 [DR.

VILA]
FEU-NRMF INSTITUTE OF MEDICINE
11.03.14 11.04.14 [1MD-D]

Physiologic Anatomy:

Kidneys
o Part of the urinary system
o Formation of urine
o Excretion of waste products, specifically
water-soluble waste products
o A small portion of water-soluble waste
products is excreted via the skin as sweat,
but majority is excreted by the kidneys as
urine
Function:
o Excretion of metabolic waste products
o Regulate water and electrolyte balance
o Regulate body fluid osmolality and blood
pressure
*Body fluid: specifically extracellular fluid (ECF)
ECF as:
1. Intravascular fluid within blood vessels
2. Interstitial fluid space bet. blood vessels
and cells
3. Transcellular fluid space other than
intravascular and interstitium (ex.) CSF,
perilymph,
endolymph,
peritoneal,
pericardial, etc.

Renal hilum where blood vessels, nerves and

lymph enter, where ureter exits

*Vascular Physio Review*

Increase fluid intake increase BV increase VR
increase EDV increase SV increase CO
increase BP

Interlobar artery

2 layers:
o Outer cortex
o Inner medulla (landmark: renal pyramids)
Apex (renal papilla) of renal pyramids drains into
minor calyx major calyx renal pelvis ureter
Blood supply:
Renal artery
Segmental artery

Arcuate artery
Interlobular artery

BP= CO x TPR
CO= HR x SV
SV= EDV ESV
o
o

Afferent arteriole
Glomerular capillay

Regulate arterial BP
Regulate acid-base balance
o 3 systems maintaining acid-base
balance: Blood, respiratory and
renal
o Normal blood pH: 7.35 7.45
(slightly basic)
Regulate gluconeogenesis

Peritubular capillary
Vasa Recta
(Cortical nephron) (Juxtamedullary nephron)
*True capillary peritubular capillary

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Blood Supply:

Renal Blood Flow:

o About 22% of
(1100mL/min)

the

cardiac

output

Structural & Functional unit of the kidney:

Nephron:
o 1 million per kidney
o After 40 years old, there will be a
decrement of 10% per 10 years

Starlings forces:
1. Capillary Hydrostatic Pressure
2. Capillary Osmotic Pressure of Plasma
Protein Pressure
3. Interstitium/tissue HP
4. Interstitium/ tissue OPPP
o
o

Hydrostatic Pressure drive away fluid

Osmotic Pressure of Plasma Proteins
attracts fluid (contributed largely by
proteins)

Forces favoring filtration:

o cHP & iOPP
Forces favoring reabsorption:
o cOPP & iHP
Glomerular capillary:
o High pressure capillary bed
o 60mmHg
o Favors filtration

Types of nephron:
1. Cortical outer-cortex and mid-cortex
o Shorter loop of Henle
o More numerous
o Supplied by peritubular capillary
2. Juxtamedullary
o Longer and straighter loop of Henle
o Supplied by vasa recta
o Concentrates urine
Nephron from renal corpuscle (glomerulus +
Bowmans capsule) to distal tubule
Urineferous tubule connecting tubules and
collecting tubuless
Urge to urinate: 150mL (for a normal 70kg person)
Urinary/micturition reflex: 700mL or 1L

Peritubular capillary / vasa recta

o Lower pressure
o 13mmHg
o Favors reabsorption
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Filtration barrier:

1. Basement membrane
o Lamina densa: central dense layer
o Lamina rara interna and externa
proteoglycans which contribute to
the membranes negative charge
2. Glomerular endothelium
o fenestrated, with fixed negative
charges that inhibit passage of
plasma proteins
3. Layer of epithelial cells
surrounding the glomerulus

(podocytes)

Glomerular capillary:
o Fenestrated capillary without diaphragm
o Size selective does not allow large
molecules to pass through
o Shape selective basal lamina is usually
electronegative, therefore does not allow
negative substances to pass through
o Shape selective

Reabsorption = cOPPP + iHP

= 13mmHg + 37mmHg
= 50mmHg
Filtration

= cHP + iOPPP
=60mmHG + 0mmHg (zero pressure
because no proteins were filtered)

Net filtration pressure = Filtration Reabsorption

= 60mmHg 50mmHg
= +10mmHg
(if positive value= filtration;
negative value= reabsorption)

Intraglomerular mesangial cells:

o Contractile in response to angiotensin
o Phagocytic

Net Glomerular Filtration

Colloid osmotic pressure in Bowmans space is
absent or zero, supposedly, because protein is not
filtered by the glomerulus. Remember, protein
largely contributes to osmotic pressure. Since
walang protein na-filter, walang osmotic pressure.
Colloid osmotic pressure is high in efferent arteriole
and peritubular capillaries.
Why? Since hindi na-filter si protein, pupunta siya
ngayon sa efferent arteriole at peritubular
capillaries, which then contributes to a higher
osmotic pressure, favoring reabsorption.
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JG Apparatus:

1. Macula densa:
o Determine Na content in the filtrate
o Found near distal tubule
o Columnar cells
2. JG cells:
o Secrete renin
o Modified tunica media of the
afferent arteriole
3. Lacis cells:
o Produce erythropoietin
o Mainly serve as communication
between macula densa and JG cells
According to Doc Vila:
**True location of macula densa: Thick ascending
limb of Loop of Henle AND the beginning of the
distal tubule.
** Most of the JG cells are located near afferent
arteriole. However, some are also located near
efferent arteriole.

Urine Formation:

Plasma filtered by glomerulus filtered

substances move into Bowmans capsule pass
through the tubules for reabsorption secretion of
of other substances from peritubular capillaries to
tubules excretion
Therefore:
Excretion = Filtration Reabsorption + Secretion
Waste Materials:
Urea: from amino acids
Creatinine: from muscle degradation
Uric Acid: from nucleic acids
Bilirubin: from hemoglobin
Renal Clearance:
The renal clearance (C) of a substance (s) is the
volume of plasma required to supply the amount of
substance excreted in the urine during a given
period of time.
=

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Principle of clearance: What is taken in

should be equal to what is given out.

Source of input for the kidney: Renal artery

Output: May go into the urine or it may

remain the plasma. Why?
Not all substances are filtered so it goes to
the efferent arterioles and peritubular
capillaries or into the urine.

A. Substance is freely filtered by glomerular

capillaries,
neither
reabsorbed
nor
secreted. Excretion rate = Filtration rate
(Ex: Waste products like creatinine)
B. Subtance is freely filtered, and partially
reabsorbed.
Excretion= Filtration Reabsorption
(Ex: electrolytes like Na and Cl)
C. Substance is freely filtered and completely
reabsorbed. Therefore, no substance is
excreted. (Ex: Glucose and amino acids)
D. Substance is freely filtered, not reabsorbed
and partially secretion. (Ex: Organic acids
and bases)
Glomerular Filtration Rate (GFR)
=
GFR = 125mL/min
7500mL/min
180L/day
= =

The gold standard for measuring the GFR is inulin,

because it is freely filtered, and neither reabsorbed
nor secreted. However, inulin is not produced by
the body and has to be introduced to the subject via
IV infusion.
The routine substance used to determine GFR is
creatinine, because it is naturally produced by the
body. Creatinine is freely filtered, but it is partially
secreted (20%).
For a substance to be used as a measure for GFR:
o Must be freely filtered
o Not reasbsorbed nor secreted
o Not metabolized or synthesized by the body
(especially the kidneys)
o Does not alter filtration rate
Filtration Fraction =

, where RPF = Renal Plasma Flow

Although, nearly all the plasma that enters the

kidneys
passes
through
the
glomerulus,
approximately 10% does not. The portion of filtered
plasma is termed filtration fraction.
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Factors affecting GFR:

BOTH afferent and efferent arterioles VASODILATE:

o More flow
o SAME GFR
Renal Blood Flow:
o 22% of the CO (1,100mL/min)
Based on Ficks Principle:

Q= blood flow
P= arterial pressure
R= resistance to flow
o
o
o

Flow = volume / time

Velocity = distance / time

Vasodilation = Increase flow; decrese velocity

o Increase diameter to accommodate more
substance increase flow
Vasoconstriction = Decrese flow, increase velocity
o Decrease diameter to accommodate less
substance decrease flow
If afferent arterioles VASODILATE:
o More flow
o Less hydrostatic pressure
o Less GFR
If afferent arterioles VASOCONSTRICT:
o Less flow
o More hydrostatic pressure
o More hydrostatic pressure
If efferent arterioles VASODILATE:
o More flow
o Less hydrostatic pressure
o Less GFR

Vasodilate: increase flow, decrease

resistance
Vasoconstrict: increase resistance, decrease
flow

=


Clearance can be used to estimate RBF. Substance
used to measure RBF is para-aminohipuric acid
(PAH). It is freely filtered, neither secreted nor
reabsorbed and not metabolized by the body.

= =

Effective Renal Plasma Flow =

=

Extraction ratio is the difference between

subsances in artery and vein over substamces in
artery

If efferent arterioles VASOCONSTRICT:

o Less flow
o More hydrostatic pressure
o More GFR

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o
Autoregulation:
o Inherent mechanism of kidney in
maintaining RBF and GFR at a relatively
constant level over an arterial pressure
range between 80 170mmHg
o Also influenced by nervous mechanism,
hormones, autocoids and others.
*CVS Review:
Mean Arterial Pressure=
Diastolic Pressure 1/3 Pulse Pressure
= 80- 170mmHg
Mechanisms:
1. Myogenic mechanism
o Pressure-sensitive
o Tendency of vascular smooth muscle to
contract when pressure increases
o When arterial pressure increases, and
afferent arterioles is stretched, smooth
mucscle contract

The increase in resistance of the arteriole

offsets the increase in pressure, therfore
making the RBF and GFR constant, provided
that P and R remain constant.
Based on Ficks Principle:

2. Glomerulotubular Feedback
o The greater amount of substance being
filtered will have a concomittant amount of
substance being reabsorbed to maintain
homeostasis
o Constant proportion of substances
3. Tubuloglomerular Feedback
o JG apparatus
o When GFR increases and Na concentration
also increases, which is detected by the
macula densa

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o
o

o
o

o
o
o
o

This will lead the macula densa to degrade

ATP to adenosine
Adenosine will cause vasoconstriction of
the AFFERENT arteriole due to the presence
Adenosine 1 receptors
Vasoconstriction will then decrease the GFR
back to normal
When GFR decreases, there is low Na
concentration, which is detected by the
macula densa
Macula densa will then cause the JG cells to
secrete renin
Renin will then activate angiotensinogen to
angiotensin I
Angiotensin I will then be converted to
angiotensin II by ACE in the lungs
Angiotensin
II
will
then
cause
vasoconstriction of the EFFERENT arteriole,
causing an increase of GFR back to normal

Nerve Innervation
o Sympathetic NS
o Act via beta receptors present in JG cells
o JG cells secrete renin
o Renin will cause Na reabsorption
particularly in the proximal tubules
o Increase Na Increase fluid intake
increase BV increase VR increase EDV
increase SV increase CO increase
BP
Obligatory reabsorption is seen in the proximal
tubules due to the presence of brush borders.
Tubular Reabsorption

4. Nervous mechanism
o Exclusively Sympathetic NS
o Strong activation of renal sympa:
o Vasoconstrict renal arterioles
o Decrease RBF and GFR
o Moderate or mild activation:
o Little influence on RBF and GFR
5. Hormones and autocoids
o Norepinephrine
o Epinephrine (80% produced by adrenal
medulla)
o Endothelin o Most potent vasoconstrictor
o Released from damaged endothelial
cells of the kidneys
o NE and Epi can constrict the afferent and
efferent arterioles but only if they are in
high amounts
o Angiotensin II o Vasoconstrict EFFERENT arteriole
o Endothelin-derived Nitric Oxide
o Vasodilate
o Increase GFR but eventually
becomes stable
o Prostaglandin and Bradykinin o Vasodilate
o Increase GFR, but eventually
becomes stable

2 reabsorption pathways:
o Transcellular: Luminal and basolateral
membrane
o Paracellular: via tight junctions
Transport Limitation
o

TM Limited (Transport Maxima)

o Glucose, SO4, PO4, amino acids,
lactate, malate and Vitamin C
o Active transport
o Exhibits saturation
o When saturated, rate of transport
remains constant

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Gradient-time Limited
o Na, Cl and HCO3
o Mostly passive, but can also be
active transport
o The greater the concentration
gradient, more substances are
transported
o The longer the time, more
substances are transported

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