Dr. Elizabeth S.

Montemayor
3
OS206 Abdomen and Pelvis

Lec 2: Overview of Renal Physiology

2. Calcitriol (an active metabolite of vitamin D)
Lecture Outline: 
 
o Recall: Previtamin D in skin (through sun
I.   Functional Renal Anatomy 
A. Major Functions of the Kidney  exposure), also from diet (milk), deep sea
B. The Nephron  fish (salmon) is converted to:
C. Renal Vasculature  25(OH)D (calcidiol) in the liver and
D. Basic Renal Processes  processed by the prostate gland,
II.   Renal Blood Flow 
breast, colon, lungs, immune cells to
III.  Glomerular Filtration 
A. Filtration Membrane 
1,25(OH)2D used for regulation of cell
B. Glomerular Filtration Rate  growth or immune function.
C. Autoregulation  1,25(OH)2D (calcitriol) in the
V.   Clearance Principle  mitochondria of the convoluted &
VI.  Appendix  straight proximal tubules of the
kidney. It increases GI Ca absorption,
stimulates osteoclastic Ca resorption
FUNCTIONAL RENAL ANATOMY from bone, facilitates the effect
parathyroid hormone (PTH) has on
A. MAJOR FUNCTIONS OF THE KIDNEYS bone resorption, & increases renal
tubular absorption of Ca. It is
Regulation of body fluid osmolality and volumes
essential for muscle and bone health
Regulation of electrolyte balance
and aids in the regulation of blood
Regulation of acid-base balance
pressure.
Excretion of metabolic end-products (urea, uric acid
3. Erythropoietin
& creatinine) & foreign substances (drugs,
o Produced by the by the peritubular
xenobiotics, etc.)
capillary endothelial cells in the kidney to
Production and secretion of hormones. The kidneys
stimulate RBC production in the erythroid
function as endocrine glands that produce and
marrow
secrete renin, calcitriol and erythropoietin.
o As the pluripotential stem cell differentiates,
1. Renin
it begins to produce receptors for
o manufactured, produced and secreted by
erythropoietin.
granular cells in juxtaglomerular apparatus. o In the presence of erythropoietin, the
o activates the Renin-angiotensin-
differentiated/dedicated stem cells become
aldosterone system
progenitor cells.
i. The kidney produces renin, w/c o In the absence of erythropoietin, a dedicated
converts angiotensinogen (from liver)
stem cell will undergo apoptosis.
into angiotensin I. This is the first step o As they differentiate into precursor cells,
and the rate-limiting step of the renin-
erythropoietin receptors are lost & depend
angiotensin-aldosterone system
on other substrates for further differentiation.
ii. Angiotensin I is converted into o Feedback mechanism:
angiotensin II by ACE (angiotensin
Hypoxia is the most potent stimulator of
converting enzyme)
erythropoietin. In hypoxic conditions,
iii. Angiotensin II produces the following
erythropoietin is secreted stimulating the
effects:
marrow to produce RBCs. Increase in RBC
formation of aldosterone
production leads to increase in O2 circulation
(important in Na and fluid retention,
and removal of hypoxic stimulus.
more importantly enhances Na
o Decreased RBC production is a cause of
retention, w/c leads to an increase
in blood volume and pressure)
anemia seen in chronic renal failure.
Direct systemic vasoconstriction
w/c can lead to hypertension
B. THE NEPHRON
Cardiac and vascular basic structural and functional unit of the kidney
hypertrophy Each human kidney contains approx. 1 Million
Indirect increase of blood volume nephrons, w/c consists of specialized tubular structure
through stimulation of the thirst & closely associated blood vessels.
mechanism. Number of nephrons at birth remains constant through
Stimulation of ADH (antiduiretic adulthood. Implication: premature babies who are born
hormone) secretion by the posterior with less nephrons are at greater risk for end-stage
lobe of the pituitary gland w/c also renal disease
leads water conservation The nephron consists of:
a. Renal corpuscle:
o Generally, it affects the adrenal cortex,
a. Glomerulus
kidney, intestine, CNS, PNS, vascular
a tuft of capillaries supplied by the
smooth muscle and the heart to maintain or
afferent arteriole and drained by the
increase extracellular volume (ECV), total
efferent arteriole
peripheral resistance and cardiac output.
covered by epithelial cells - podocytes

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OS206
Lec 2: Overview of Renal Physiology
b. Bowman’s capsule
visceral layer – formed by podocytes
parietal layer
Bowman’s space – capsular space
bet. the visceral and parietal layer;
lumen of the proximal tubule (at the
urinary pole)
Figure 1. Cellular Features of Renal Corpuscle
b. Renal tubule
a. Proximal convoluted tubule (PCT)
several coils that descends toward the
medulla
PCT cells
extensively amplified apical
membrane (urine side) – brush
border
highly invaginated basolateral
membrane (blood side) – many
mitochondria
b. Loop of Henle
Straight part of the proximal tubule
Descending thin limb, DTL (ending in
hairpin turn)
Ascending thin limb, ATL (in
nephrons w/ long loops of Henle)
DTL and ATL – poorly developed
apical and basolateral
membrane; few mitochondria
Thick ascending limb
abundant mitochondria; extensive
infoldings of the basolateral
membrane
Macula densa (portion of the thick
ascending limb passing between
afferent and efferent arterioles)
c. Distal Convoluted Tubule
d. Collecting Duct (cortical CD J outer
medullary CD J inner medullary CD);
2 types of cells
i. Principal cells – moderately
invaginated basolateral
membrane; few mitochondria
ii. Intercalated cells – high
density of mitochondria
inner medullary CD – poorly
developed apical and basolateral
surfaces; few mitochondria
Alphius | Bryan| Jean | Marivic Thurs., Dec. 10, 2009
Mark | Marvin | Mau |Schubert
Dr. Elizabeth S. Montemayor
3
Abdomen and Pelvis
Figure 2. Tubular Segments of a [Juxtaglomerular] Nephron
There are two types of nephrons:
1. Cortical or superficial (~85%) – glomeruli are
near the periphery of cortex and nephron loops
in the outer medulla; characterized by a short
loop of Henle and an almost absent thin
ascending limb
2. Juxtamedullary – glomeruli are near the
corticomedullary junction and have relatively
long nephron loops that extend deep into the
medulla.
The efferent arteriole of juxamedullary
nephron forms not only a network of peritubular
capillaries, but also a series of vascular loops
called the vasa recta.
*** Vasa recta
series of vascular loops that descends into
medulla, form capillary networks
surrounding collecting ducts and
ascending limbs of Henle’s loop
blood returns to the cortex in the
ascending vasa recta
receives < 0.7% of renal blood flow
Functions: 1) conveys oxygen and
important nutrients to nephron segments;
2) delivers substances to the nephron for
secretion; 3) serves as a pathway for the
return of reabsorbed water and solutes to
the circulatory system, & 4) concentrates
and dilutes urine
***The renal medulla (pyramid) consists of two zones:
Outer zone
a. Outer stripe
b. Inner stripe
Inner zone
All segments of Henle’s Loop end at the same area of
the medulla, i.e. for a juxtamedullary nephron, the
straight part of the proximal tubule nephron will always
end at the junction between the inner and outer
medullary stripe.
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OS206
Lec 2: Overview of Renal Physiology
Figure 3. Two Types of Nephrons. Schematic of relations
between blood vessels and tubular structures and differences
between cortical and juxtamedullary nephrons. See Netter (4e),
plate 336 for another depiction.
C. VASCULAR SUPPLY
Extrarenal vasculature: arteriole JcapillaryJvenule
Renal vasculature:
arteriole J capillary J arteriole J capillary
Main renal artery (from abdominal aorta) J segmental
arteries (3-5;in the renal sinus ) J interlobar arteries
(pass through the renal columns) J arcuate artery
(traverses the base of the medullary pyramids) J
interlobular arteries (important because this is where
the arterioles come from) J afferent arterioles J
glomerular capillary J efferent arterioles J
o In cortical nephrons, these send branches to
peritubular capillaries (formed within the
cortical area, forming a complex system in
the tubules) J interlobular vein J arcuate
vein J interlobar vein J renal vein J IVC
o In juxtamedullary nephrons,
peritubular capillaries J vasa recta J
interlobular vein J …. J IVC
***the vessels of the venous system, run parallel to the
arterial vessels.
Figure 4. Vascular Supply of the Kidney. Please take note that
the renal artery normally lies posterior to the renal vein. This
is not shown in the figure above. The figure highlights the course
of blood as it is supplied to and drained from the kidney.
Alphius | Bryan| Jean | Marivic Thurs., Dec. 10, 2009
Mark | Marvin | Mau |Schubert
Dr. Elizabeth S. Montemayor
3
Abdomen and Pelvis
C. BASIC RENAL PROCESSES
The coordinated actions of the nephron’s various
segments determine the amount of substance that
appears in the urine. This represents 3 general
processes:
1. Glomerular Filtration - Filtration of plasma in the
glomerulus, ultrafiltrate then collects in the
urinary space of Bowman's capsule and flows
downstream to the tubular lumen
2. Tubular Reabsorption - Transport of
substances out of tubular lumen which are
returned to the systemic circulation via the
peritubular capillaries
3. Tubular Secretion - Transport of substances
from the peritubular capillaries into the tubular
lumen.
***In Focus: Glomerular filtration
RENAL BLOOD FLOW
Average renal blood flow of 1800 L/day urine flow of
2L/day
In resting subjects, the blood flow to the kidneys ≈ 1.25
L/min ≈ 25% of cardiac output received by an organ less
than 0.5% of total body weight.
Cortex receives bulk of the blood flow (82%) while the rest
goes to the medulla and the papilla. The papilla is the
most hypoperfused part of kidney, making it more prone to
necrosis; however, it still gets more perfusion than the
heart, brain and lungs.
Table 1. Comparison of the distribution of blood flow to the different
organs
Organs Blood Flow, mL/(g*min)
Kidney 4.0
Heart 0.9
Brain 0.6
Liver 0.2
Resting muscle 0.1
Roles served by renal blood flow (from the lecture)
Sustains filtration and excretion of end-products
such as urea and creatinine
Achieves rapid changes in body fluid
volumes and composition through
changes in renal excretion of water and
solutes
Serves a hemodynamic reserve function in
case if extreme emergency (shock) by
redistributing blood to other organs. That
is, RBF can be reduced to very low levels
to help sustain the blood flow in other
organs (brain, heart, etc)
Delivers sufficient oxygen and nutrients to
the kidneys.
Roles served by renal blood flow (more from
Berne)
Deliver sufficient oxygen, nutrients and
hormones to the cells of the nephron and
returning carbon dioxide and reabsorbed fluid
and solutes to the general circulation
Indirectly determines the GFR
Modifies the rate of solute and water reabsorption by the
proximal tubule.
Participates in the concentration and dilution of urine
Delivers substrates for excretion in the urine
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 Dr. Elizabeth S. Montemayor
3
OS206 Abdomen and Pelvis

Lec 2: Overview of Renal Physiology

The blood flow through any organ may be represented by
GLOMERULAR FILTRATION
Q = ∆P / R
where:
A. FILTRATION MEMBRANE
Q = blood flow ≈ RBF
∆P = mean arterial pressure – mean venous pressure “making urine is just like making coffee”
R = total renal vascular resistance essentials:
filtration membrane
Accordingly, renal blood flow, RBF is equal to the
solid parts and large molecules suspended in
pressure difference between the renal artery and the plasma or blood
renal vein (VP) divided by the total renal vascular ultrafiltrate
resistance
||> GLOMERULAR FILTRATION
KVenous Pressure LRBF and KR L RBF
Ultrafiltration of plasma
Consider the forces that determine overall renal blood flow.
performed because the Glomerular Filtration
The basic equation demonstrates that virtually all factors
that influence total renal blood flow must do so by altering
Membrane is an extremely fine molecular sieve
either the arterial blood pressure or the renal vascular ||> GLOMERULUS
resistance. Pathway of fluid: ECL → BM → SM
Glomerular Filtration Membrane has three
layers for filtration:
1.) Endothelial Cell Layer (ECL)
contains blood vessels and capillaries
has sieve-like fenestrations (500-1000
Å) that allow the passage of small
molecules whilst restraining the
passage of large molecules
most permeable
2.) Basement Membrane (BM)
least permeable
two layers:
Figure 5. Pressure changes across renal vasculature. The a. Lamina Densa - central dense
generally accepted pressure gradient through the renal vascular layer
system. Areas of large pressure drops are main points of
b. Lamina Rara Interna & Externa -
autoregulation.
thinner and more electrolucent
The following notes come from 2013 trans. Those that outermost and innermost layers
were mentioned/emphasized in the lecture are in bold. 3.) Slit Membrane (SM)
There is a wide range of pressure in the kidneys the “diaphragm” of the glomerulus
because it reflects systemic pressure. lies in between the podocytes of
Main point of resistance: afferent arteriole endothelial cells (“interdigitations”)
provides dissipation of pressure moderately permeable because of the
very high venous resistance to blood flow presence of slit pores (250 Å)
Hydrostatic pressure drops dramatically Table 2. Filterability of some substances
between the beginning of the afferent Substance MW Molecular [ Filtrate/
arteriole & glomerular capillary. radius (Å) Plasma ]
Afferent arteriole has great influence on Water (H2O) 18 0.1 1.0
glomerular capillary by increasing or Glucose 180 0.36 1.0
Inulin 5000 1.4 1.0
reducing resistance
Hemoglobin 17000 2.0 0.03
Second drop at the efferent arteriole; 2nd point
Serum Albumin 69000 3.6 0.001
of resistance. Cationic Dextran (+) 3.6 0.42
Most active segments are the afferent and efferent Neutral Dextran 3.6 0.15
arterioles: segments that regulate blood flow Anionic Dextran (-) 3.6 0.01
Pressure at the glomerular and peritubular ↑ molecular size, the harder it is for the molecule to
capillaries are constant. Initial pressure of efferent pass thru the filtration membrane
arteriole is the same as final pressure of afferent ↑ filtrate to plasma ratio of a substance, the better
arteriole. it is filtered
Each of the capillary networks is exquisitely
||> FACTORS AFFECTING FILTERABILITY
designed to serve the functional needs of the
kidney. 1.) Size (most important factor)
Every day 180 liters of fluid pass through the substances of MW up to 5000 and radius
glomerular capillaries as filtrate. less than 15 Å are freely filtered
About 99% is recovered from the tubules ↑ size, ↓ filterability
and carried back into the general circulation
2.) Shape
via the peritubular capillaries.
slender and flexible = ↑ filterability
Remaining 1% continues on to its final
spherical and non-deformable = ↓ filterability
presentation as urine.

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Lec 2: Overview of Renal Physiology
3.) Electrical Charge
(+) charge = ↑ filterability
(-) charge = ↓ filterability
***the glomerular filtration membrane bears
negative charges due tah glycosaminoglycans,
e.g. heparan sulfate [recall: like charges repel]
B. GLOMERULAR FILTRATION RATE
total amount of filtrate formed by the Kidneys per
unit time (normally in minutes).
This is not how much blood passes through the
glomerulus each minute, but instead; it is how much
filtrate is removed from the blood each minute.
unit = mL/min.
mL
normal value = 125 /min.
a test for Kidney Function
||> STARLING HYPOTHESIS
the net movement of fluid out of a capillary is given
by (equation from Berne):
Jv = Kf [(Pcap – Pif) – σ(πcap – πif)]
where
1.) Jv = Net fluid movement between compartments
≈ GFR
2.) Kf = Coefficient of [Ultra]Filtration
= a constant of proportionality
= two components:
a.) capillary surface area
b.) capillary hydraulic conductance
= area x hydraulic conductance
= ↑Kf, more water-permeable capillary
= ↓Kf, less water-permeable capillary
3.) σ = Reflection Coefficient
= a correction factor
= can have a value from 0 to 1
***Dr. Montemayor didn’t really expound nor gave much
attention to this. Anyway, glomerular capillaries have a σ
value very close to 1
4.) Pcap = Capillary Hydrostatic Pressure
= pressure brought about by water within
capillaries directing water OUT of the
capillary
5.) Pif = Interstitial Hydrostatic Pressure
= pressure brought about by water within
the interstitium directing water INTO the
capillary
6.) πcap = Capillary Oncotic (or Osmotic) Pressure
= pressure brought about by the presence
of proteins within the capillaries directing
water INTO the capillary (recall the
concept of gradients…water flows from
higher concentration to lower concentration)
7.) πif = Interstitial Oncotic (or Osmotic) Pressure
= pressure brought about by the presence
of proteins within the interstitium directing
water OUT of the capillary (again…recall
thuh concept of gradients…water flows from
higher concentration to lower concentration)
Alphius | Bryan| Jean | Marivic Thurs., Dec. 10, 2009
Mark | Marvin | Mau |Schubert
Dr. Elizabeth S. Montemayor
3
Abdomen and Pelvis
Figure 6. Glomerular Filtration is promoted by Capillary
hydrostatic pressure and opposed by capsular hydrostatic
pressure and blood colloid osmotic pressure.
Key:
PH = Pcap = Capillary hydrostatic pressure
π = πcap = Capillary [colloid] oncotic (or osmotic) pressure
gradient due to proteins in plasma but not in
Bowman’s capsule
Pfluid = Pif = Fluid pressure created by fluid in Bowman’s capsule
πif = Interstitial [colloid] oncotic pressure gradient due to
proteins in in Bowman’s capsule. w/c promotes
filtration. Under normal conditions, the
concentration of protein in the glomerular filtrate is so
low that the πif ~ zero.
NFR = Net Filtration Rate: Effective driving force for
filtration.
= (Pcap – Pif) – σ(πcap – πif)
= Normally, 10 mm Hg (assuming σ ≈ 1)
GFR = Kf × net filtration pressure
Since normal value of GFR is 125
mL
/min, the normal Kf is
ml
calculated to be about 12.5 /min·mmHg of filtration pressure
Nice to know: when Kf is expressed per 100 g of kidney wt., it’s
about 4.2 ml/min/mm Hg, a value about 400 times as high as the Kf
of most other capillary systems of the body; the average Kf of many
other tissues in the body is only about 0.01 ml/min/mm Hg per 100
grams. This high Kf for the glomerular capillaries contributes
tremendously to their rapid rate of fluid filtration. However, changes
in Kf probably do not provide a primary mechanism for the normal
day-to-day regulation of GFR. (Guyton&Hall, 11e)
||> PRESSURE PROFILE
in a SKELETAL MUSCLE capillary:
hydrostatic pressure is high at the arterial end
and low at the venous end; oncotic pressure is
constant.
filtration occurs at arterial end; absorption
occurs at venous end
initial hydrostatic pressure is 35 mmHg
in a GLOMERULAR capillary:
hydrostatic pressure profile is higher (> 55 mm
Hg, initially) and declines only very little with
distance, Hydrostatic pressure remains
essentially constant from afferent arteriole to
efferent arteriole (see Fig 5)
oncotic pressure increases due to filtration of
protein-free fluid (↑ protein content inside
capillary)
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Lec 2: Overview of Renal Physiology
||> DETERMINANTS OF GLOMERULAR FILTRATION RATE
1.) Kf or permeability characteristic of glomerulus
depends on:
a. Surface area available for filtration
– ↑ surface area, ↑ Kf, ↑GFR
b. Mesangial cell activity*
c. change in porosity of filtration membrane
– ↑ holes or pores, ↑ fluid mov’t, ↑GFR
– inflammation (e.g. insect bites)
increases porosity
*MESANGIAL CELLS
o another type of cell in the glomerulus but not
located within the capillaries
o provide support for the glomerular capsule
o secrete extracellular matrix
o regulate blood flow
o alter capillary surface area (w/c affects Kf & GFR)
o secrete prostaglandins and cytokines;
o with phagocytic activity
2.) (Pcap – Pif) or the hydrostatic pressure difference
two kinds:
a. Capillary Hydrostatic Pressure
determined by aortic pressure or
changes in the resistance at the
afferent and/or efferent arteriole
b. Hydrostatic Pressure at the Bowman’s
Capsule [space]
a.k.a. Interstitial Hydrostatic
Pressure (Pif). ↑ Pif. ↓ GFR
↑ Pif is observed in patients w/ kidney
stones (nephrolithiasis).
Changes in tubular hydrostatic
pressure: obstruction will increase
tubular pressure to as high as
capillary pressure and therefore no
filtration can occur (GFR is zero).
♣ EFFECTS OF AFFERENT/EFFERENT
DILATION/CONSTRICTION ON DIFFERENT
VARIABLES
– This is the subject of the take-home
simulated laboratory experiment.
Table 3. Effects of afferent and efferent dilation on RBF,
HP, GFR, and FF
RBF ∆HP GFR FF
Afferent Dilation ↑ ↑ ↑ ↔
Efferent Dilation ↑ ↓ ↓ ↓
Afferent ↓ ↓ ↓ ↔
Constriction
Efferent ↓ ↑ ↑ ↑
Constriction*
* to compensate for the loss of nephrons, efferent
arterioles constrict.
Variables: RBF = Renal Blood Flow
∆HP = Difference in Hydrostatic Pressure
GFR = Glomerular Filtration Rate
FF = Filtration Fraction
Legend: ↑= increase, ↓ decrease, ↔ = same
Alphius | Bryan| Jean | Marivic Thurs., Dec. 10, 2009
Mark | Marvin | Mau |Schubert
Dr. Elizabeth S. Montemayor
3
Abdomen and Pelvis
3.) (πcap – πif) as determined primarily by plasma oncotic
pressure. Low plasma oncotic pressure increases
the amount of filtrate.
↑ πcap ↓GFR. ↑ πcap is brought about by
dehydration (↑ osmolarity), multiple myeloma and
hyperviscosity syndrome.
||> SUBSTANCESWHICH AFFECT GLOMERULAR
FILTRATION RATE
1.) Angiotensin
vasoconstrictor
preferentially constricts the efferent arteriole;
making it the preferred inhibitor for renal disease
at higher plasma levels:
contracts all mesangial cells
generalized vasoconstriction (afferent and
efferent)
maintains central arterial pressure in
expense of RBF and filtration
2.) Endothelin – vasoconstrictor
3.) Arginine Vasopressin (AVP) – vasoconstrictor
4.) Prostaglandins – vasodilator*
5.) Nitric Oxide (NO) – vasodilator
6.) Natriuretic Peptides – vasodilator
*2 & 3 lower RBF while 4, 5, 6 counteract the effects of
vasoconstrictors
||> FILTRATION FRACTION and RENAL PLASMA FLOW
♣  FILTRATION FRACTION (FF)
ratio of Glomerular Filtration Rate (GFR) to
Renal Plasma Flow (RPF)*
portion of the Renal Plasma Flow filtered in the
kidneys
represents the portion of the fluid reaching the
kidneys which passes into the renal tubules
normal value: 0.15 to 0.20 (e.g. only ~20% of the
plasma that enters the glomerulus is actually
filtered.
FF = GFR / RPF
♣  RENAL PLASMA FLOW (RPF)
volume of blood plasma delivered to the kidneys
per unit time
the kidneys are hyperfiltrating units
RPF = RBF x (1 – Hct);
Blood consists of about 55% plasma and about
45% cellular components (mostly RBCs ≈
hematocrit, Hct)
mL
normal value: 650 /min
For “higher learning” : The following outlines the computation
of FF from the following “normal” values… Note the
relationship of the different variables.
a. Cardiac output (CO) = 6 L/min
L
b. Renal blood flow (RBF) 20-25% of CO = 1.25 /min
c. Renal plasma flow (RPF) =RBF x (1 – Hct);
If the Hct level of the person is 45%.
RPF = (1250 mL/min)(1 – 0.45) = 687.5 mL/min
d. Glomerular filtration rate (GFR) = 125 mL/min
e. FF = GFR / RPF = 125/687.5 = 0.182
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 Dr. Elizabeth S. Montemayor
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Lec 2: Overview of Renal Physiology

Effector Mechanism: Adenosine
C. AUTOREGULATION + +
with increased uptake of Na , K , Cl
-

ability of the kidneys to maintain constancy of a.) increased generation of Adenosine

Renal Blood Flow (RBF) and Glomerular Filtration b.) Adenosine activates Adenosine1
Rate (GFR) over a wide range of Renal Perfusion receptors triggering an increase in
Pressure or Blood Pressure cytosolic Ca2+ in the extraglomerular
Mechanisms: mesangial cells
c.) intensive coupling between
1.) Myogenic Reflex (universal, i.e. peripheral and
juxtaglomerular granular cells
renal)
containing renin and extraglomerular
T=PxR mesangial cells occurs, resulting in
where, afferent arteriole constriction and
T = vascular wall tension renin inhibition
P = transmural pressure gradient
R = inner radius of vessel **the reverse occurs w/ decreased uptake
of Na+, K+, Cl-
In order for T to remain constant: R is forced
to increase when P decreases and vice versa. ♣ JUXTAGLOMERULAR APPARATUS
Mechanism: – layers:
– vascular smooth muscles reflexively a.) Juxtaglomerular Granular Cells
contract (decreasing afferent arteriole • located at the walls of afferent
diameter) when stretched, reducing arterioles
blood flow. • contains specific granules
– vascular smooth muscles reflexively which produce renin
relax and dilate when not stretched, b.) Extraglomerular Mesangium
thereby increasing blood flow. • functional link between Macula
2.) Tubuloglomerular Feedback Mechanism Densa and Glomerular
due to the sensitivity of the macula densa Arterioles
cells of the juxtaglomerular apparatus to the • contains the Extraglomerular
filtrate osmolarity and/or rate of filtrate flow Mesangial Cells
in the terminal portion of the ascending loop c.) Macula Densa
of Henle • specific region of the thick
increase in GFR = increase in filtration = ascending limb which acts as a
increase in delivery of solutes to the tubules sensor arm
to the macula densa • where the cuboidal cells of the
thick ascending limb become
columnar

3.) Sympathetic Control

Sympathetic nerve fibers innervate all blood
vessels of the kidney as an intrinsic regulation
activity.
Minimal influence during normal daily activity
In extreme stress or blood loss, sympathetic
stimulation overrides the autoregulatory
mechanisms of the kidney.
Increased sympathetic discharge causes
intense constriction of all renal blood vessels
w/c has the following results:
The activity of the kidney is temporarily
lessened or suspended as blood is
shunted to other vital organs.
GFR reduction causes minimal fluid
loss from the blood maintaining higher
blood volume and blood pressure for
other vital functions.
Reduction in filtration cannot go indefinitely,
as waste products build up and metabolic
Figure 7. Tubulo-glomerular feedback mechanism. 1)GFR ↑ imbalances increase in the blood.
2) Flow through tubule ↑ 3) Flow past macula densa ↑ 4) IV fluid must soon be administered to
Paracrine from macula densa to afferent arteriole 5) Afferent increase blood volume and pressure
arteriole constricts; Resistance in afferent arteriole ↑; Hydrostatic and to decrease sympathetic discharge
pressure in glomerulus ↓; GFR ↓ and restore normal arteriole diameters
and normalize GFR and filtrate flow.

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CLEARANCE PRINCIPLE
Clearance is a term used to describe the rate of
removal or clearing of a substance from the blood;
The principle of renal clearance emphasizes the
excretory function of the kidney. Thus, it is used to
evaluate renal function.
The clearance principle is based on the Fick principle
(mass balance or conservation of mass).
Figure 8. The Principle of Renal Clearnace. The renal artery
is the single input source to the kidney, whereas the renal vein
and ureter constitute the two output routes.
The following equation define the mass-balance
relationship (input = output):
•
Pxa × RPF a = ( Pxv × RPF v ) + (U x × V )
where
The equation above is valid for any substance that is
1. freely filterable at the renal corpuscle (small and
not bound to a protein), across the glomerulus
into the Bowman’s space
2. Neither secreted nor reabsorbed by the tubule
3. Not synthesized nor broken down by the
tubules
Useful derivations: Assume there is a susbtance (W)
that meets the above criteria.
mass of W filtered mass of W excreted
= eqn (1)
time time
mass of W filtered
= Pw × Cw eqn (2)
time
mass of W excreted • Reabosorption Rate
=U w ×V eqn (3)
time
Note:
Pw = concentration of substance w in plasma
Cw = “removal rate” or “clearance”; volume of
plasma cleared of substance w per unit time
(usually in mL/min)
≈ GFR (for substances that meet the above criteria)
Uw = concentration of substance w in the urine
. Cx > Ci
V = volume of urine per unit time (urine flow rate)
Alphius | Bryan| Jean | Marivic Thurs., Dec. 10, 2009 Page 8 of 9
Mark | Marvin | Mau |Schubert
Dr. Elizabeth S. Montemayor
3
Abdomen and Pelvis
Substituting equations (2) and (3) on equation (1) and
rearranging for Cw
•
• U ×V
Cw × Pw = U w × V ⇒ Cw = w
Pw
The definition of clearance as a volume of plasma
from which all the substance has been removed and
excreted into the urine per unit time is somewhat
misleading since for most substances cleared by the
kidneys, only a portion is actually removed and excreted
in a single pass through the kidneys. The volume of
plasma in the above equation is an idealized volume.
Nevertheless, the concept of clearance is important
because it can be used to measure the GFR and renal
plasma flow and to determine whether a substance is
reabsorbed or secreted along the nephron.
Exercise: Compute for the subject's GFR using inulin*
clearance in mL/min
*inulin (from 2013 trans)
o Prototype drug (Considered to be the first pure compound to have been discovered
in any series of chemically or developmentally related therapeutic agents.)
o Polymer of fructose (MW=5000) non-toxic to humans
o Administered intravenously, not produced by the body
o used to help measure kidney function by determining the GFR
o Freely filtered across the glomerulus into Bowman’s space
o Neither reabsorbed, secreted, nor metabolized by nephrons
o Amount of inulin excreted in the urine per minute equals the amount
of inulin filtered at the glomerulus each minute
Given: Plasma inulin conc = 4 mg/L
Urine collected in 10 hrs = 1 L
mg
Urine inulin concentration = 300 /L
mass of inulin filtered mass of inulin excreted
=
time time
•
U inulin × V
GFR =
Pinulin ×
300 mg L × 1 L
= 10 h
4 mg L
300 mg L × 1000 mL
= 600 min
4 mg L
= 125 mL min
Comparing the clearances of other substances
For a certain substance, like inulin filtered
through glomeruli and not reabsorbed or
secreted by tubules, Clearance of inulin equals
Glomerular Filtration Rate:
Cx = Ci = GFR
For a certain substance, x, that is filtered
through glomeruli and reabsorbed by tubules,
Clearance of x equals GFR minus Tubular
Cx = GFR – Tax
Cx < Ci
For a certain substance, x, that is filtered
through glomeruli and secreted by tubules,
Clearance of x equals GFR plus Tubular
Reabosorption Rate
Cx = GFR + TSx
 Dr. Elizabeth S. Montemayor
3
OS206 Abdomen and Pelvis

Lec 2: Overview of Renal Physiology

For a certain substance, x, that is filtered ZÜxxà|Çzá

through glomeruli and reaborbed and secreted Bry‐o‐chem: Woohoo! tis time fo greetin' 'gain!! this'd be a long one since 
along the tubules, Clearance of x equals GFR thuh last one i did wuz real short..well..here it goes! Hello tah thuh whole 
minus net reabsorption plus secretion rate of 2014! our effin openin' number wuz amazin! go europe! special thanks 
tah  nico  'course..galing!  tah  those  who  helped  me  wit'  thuh  voiceovers, 
Cx = GFR – Tax + TSx
thanks  a  bunch!  still  owe  ye  guys  a  lil  sumthin  sumthin..:P  congrats  din 
Cx > Ci sa'tin  fo  doin'  a  good  job  sa  chorale  competition!  anne,  dane,  ate  jana, 
 
without  y'all..wala..haha!  go  tenor  2's!  A  hello  tah  mah  feedin'  program 
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐End ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ 
din..na on‐hiatus sa ngayon (parang glee na sa april pa ang balik..)..haha! 
REFERENCES:  we  should  have  sumthin'  befo'  thuh  break  guys,  yea?  hello  'course  tah 
MPS: k‐ab, k‐flo, jb, tin, sam, alex, roland, therese, jason, marcus, karla! go 
1.   Dra. Montemayor’s lecture notes transcribed by Marivic and Bryan  easy on me sa summer initiations! haha! hello tah mah fellow mss apps! 
2.  Physiology 5e by Berne, et al    'course,  would  i  forget  tah  say  hi  tah  iMed!!  ano,  kelan  party?  nga  pala, 
3.   2013 Transcription 
hello  tah  mah  roommates:  poch,  kuya  renzo  and  phantom!  now  fo  thuh 
3.   Textbook of Medical Physiology 5e by Guyton and Hall  
  single greetings: Hello tah: patrick ang sumasayaw na conductor at LO na 
nanonoxic, aa, christelle and mairre (di makasayaw si christelle nung mss 
APPENDIX victory  party..wala  daw  kasi  si  mairre..haha!),  ma‐e..spleen!,  nic!,  jonas 
and his sausage marvyn!, mommy carla that i always greet :D, fellow mpl 
Table 4. baby ko na si bossing!, sa bon‐casti duo,  coy‐tincee‐ricky‐leeann quartet, 
dalvie!, franco and camille, migz and ate abby (ate abby..'yung tanong ko, 
di mo pa sinasagot..:P), lance G!, ching‐lennie couple (wahaha!), southbro 
carlos!, carlo‐glaiza pair, dana na kaya nang mag‐stay awake sa class fo' up 
tah 20 minutes!!, david!, lolo aidz!, robert!, hun shayne!, chesca na nililink 
ko  kay  cons..haha!,  faye!,  rr‐joreb‐luigi  wutta  great  drinkin'  night  we 
had..til next time!, anna clau, april, mervyn na nagpapabati..may bonding 
pa  tayo  bago  mag‐break!,  lau,  jesha..sisiw!,  yhan  na  namimiss  ko 
na..awww,  marivic,  alphius,  dragons  and  virgins,  zane,  jam!,  janna, 
kimongkimongki! peace!, scott!, roni‐jaypang dance pair!, tonch a.k.a. sid 
ng  ice  age/donatello  ng  tmnt,  romeo  and  julieeeeee!,  edge!,  ado!,  kay!, 
karl babe na mahilig kumain sa class, godfrey & bea na magkamukha, jere 
& roger na miss na ang isa't isa, zie!, grace v.!, marvie na miss na miss ko 
na  at  sure  na  miss  na  rin  niya'ko..2  months‐advanced  happy  birthday! 
haha!  overnight  ulit  tayo!  :P,  pito..still  owe  ye  sumthin'  effin  long 
overdue..lol..oyea, belated hb! chill sometime, yea?, peace&bounce! and 
lastly hi tah jhing..thanx a lot! ;) 
 

Woah! Haba pala nun! :| ohwell..haha! Merry Christmas and Happy New 
Year 2014!! Enjoy thuh break!! Chillax lang..sa January na mag‐aral! haha 
b.i.!  
 

o  eto..game:  sa  trans  na  'to  (not  includin'  thuh  greetin'  part)..there're  two 
words (only two!) that are part of mah text/e‐mail/ym language..find 'em and 
show 'em tah me..may libreng dilly bar fro' dq ang pinakaunang makakahanap! 
(trans  group  ko..di  kayo  kasama..haha!)  guess  that's  it!  Happy  Holidays  y'all! 
Out!!

Marivic: Happy Holidays! ☺☺☺ 
 
Waaahh  may  space  pa  kaya  naman    babatiin  ko 
ang  Class  2014  para  sa  matagumpay  na  TRP 
opening number, stage design at chorale number 
ngayong  taon.  Syempre  special  greetings  sa  mga 
kapwa ko aprikano, na binigay ang lahat sa maiksi 
ngunit di‐malilimutang  parte sa opening number! 
Inaantok  na  ako  para  isa‐isahing  batiin  ang  mga 
tao na patuloy na nagbibigay ng kakaibang saya at 
inspirasyon  sa  akin.  Mahaba  pa  ang  ating 
pagsasamahan  at  sana  sa  mga  darating  pang 
panahon ay mas makilala natin ang isa’t isa. Ayun! 
Sa mga nakakasama, nakakausap, nakakatrabaho, 
nakaka‐chat  at  nakakabiruan  ko  sa  araw‐araw 
(kilala nyo na kung sino kayo) inaalay ko ang trans 
na ito sa inyo… At sa iyo ____ hangad namin* ang 
iyong kasiyahan at kapayapaan ng loob. 
 

Ayun.  Sa  mga  naki‐kidney  o  nababato  ngayong 

bakasyon,  sana  ay  matuwa  kayo  sa  trans  namin. 
Sana  palampasin  na  ang  mga  pagkukulang  tutal 
maayos  naman  naming  nagawa  ito.  Sana  ay  
makatulong nang lubos sa inyong pag‐aaral. 
 
Maraming  salamat  kay  Bryan  at  Marivic  na  gaya 
ko ay binuno ang trans na ito.  
 
Maligayang Pasko at Masaganang Bagong Taon sa 
inyong lahat =) Labing‐apat! Walang katapat! 
 
Nagpapasalamat para sa makabuluhang taon, 
Figure 9. Renal blood flow and GFR Alphius

Alphius | Bryan| Jean | Marivic Thurs., Dec. 10, 2009 Page 9 of 9

Mark | Marvin | Mau |Schubert