2.
Regulation of water and electrolyte balances
Learning Objectives:
1. Review the functional anatomy of the urinary system.
2. Discuss urine formation.
3. Discuss micturition reflex.
4. Discuss regulation of water and plasma volume.
5. Discuss regulation of significant ions in the body.
6. Discuss the homeostasis of body fluids and electrolytes.
7. Discuss the role of urinary system in regulation of acid-base
balance.
8. Discuss the endocrine function of the kidneys.
9. Discuss changes in aging urinary tract.
INTRODUCTION
• When we talk about urinary system, we do not call them
excretory system because when we talk about excretory
system, you excrete metabolic waste products.
• Basically, we call them urinary system because they
primarily form urine. Because if we talk about excretory
system, we’ll be talking about 4 systems.
o If you excrete your excessive waste products in
gas form, we will be talking about excretion of gas
by respiratory system.
o Excretion of lipid-soluble substances will be
through your gastrointestinal tract.
o Excretion of water-soluble substances will be
through your integumentary system (sweat) and
through your urinary system (kidneys).
KIDNEYS
• 2 kidneys à left and right
• Renal hilum – entering and exiting of different structures;
space in the concavity (medial portion) of the kidney
o Where the renal artery, renal vein, lymphatics,
nerve supply and ureters enter and exit
• Bean-shaped
FUNCTIONS OF THE KIDNEY
1. Excretion of metabolic waste products and foreign
chemicals
• Many calls it as ‘metabolic waste products,’ Doc
Vila called it as “excessive.”
• For example, when you take a megadose of
Vitamin C since it is water-soluble, the excess will
be urinated. Thus, Doc Vila calls it as excessive
waste products.
• Lipid-soluble substances accumulate in the body.
• Electrolytes are water-soluble substances;
therefore, it can be easily urinated if it is excessive
in our body.
• If there are anomalies/abnormalities on the
reabsorption of electrolytes.
• On the other hand, you regulate the water and
electrolytes therefore, it also regulates the fluid
osmolarity.
↑ Fluid Intake → Blood Absorption (↑ Blood Volume) → ↑ Venous
Return → ↑ End Diastolic Volume → ↑ Stroke Volume → ↑ Cardiac
Output (↑ Heart Rate) → ↑ Blood Pressure → ↑ Filtration Rate →
↑ Urine output
Review: SV = EDV-ESV; CO = SV x HR; and BP = CO x Total PR
3. Regulation of body fluid osmolarity and electrolyte
concentration
• Osmolarity = electrolyte concentration / the
amount of solvent (water)
• If the electrolyte concentration is high, then you
will become hyperosmolar. If the electrolyte
concentration is low, then you will become
hypoosmolar.
• Normal osmolarity of the plasma (Posm): 280-300
mOsm/L
o However, the range will be narrower
(285-295 mOsm/L) when you’re in clinics.
o 1 milliequivalent = 1mOsm
• Computation of plasma osmolarity:
o Normal range for Sodium in plasma: 135-
145 mOsm/L
o Posm = 2 Na+
o Twice of 135 is 270; Twice of 145 is 290.
o So, you would see the range of your
sodium would somehow approximate the
plasma osmolarity.
• Generally, the patient is given isotonic IV fluid. If
the patient is hypertonic and is given an isotonic,
somehow you will be able to dilute the
hypertonicity but it will not correct the
hypertonicity.
• After you know the tonicity, compute for the
sodium electrolyte concentration.
• Considerations in plasma osmolarity:
o Fasting blood sugar (Glucose) – divide by
18 if the FBS is in mg/dL. If it is in
millimoles, you just add it.
o Blood urea nitrogen (BUN) – divide by 2.8
if the BUN is in mg/dL or mg%. If it is in
millimoles, don’t divide, just add them.
4. Regulation of arterial blood pressure
• Intermediate regulation – renal fluid shift (If the
blood pressure is high, the renal blood flow,
filtration rate and the amount of urine is also high)
• Long-term regulation – Renin-Angiotensin-
Aldosterone + ADH
• JG cells is located in the distal tubules in kidneys.
• Renin is released when the pressure is low
therefore, the renal blood flow is low. The filtration
rate is also low, the filtrated Na+ is also low. The
macula densa is stimulated by the low filtrated
Na+, therefore it will send signal to JG cells through
extraglomerular mesangial cells (EGMC) to
produce renin.
Page 1 of 12
 • Renin (formerly known as angiotensinogenase)
will go to the liver to convert angiotensinogen to
angiotensin I.
• Angiotensin I will go to the lungs to be converted
into angiotensin II by angiotensin-converting
enzyme (ACE).
• ACE can also be seen at the blood vessels
(endothelium). Thus, we can convert the
angiotensin I to angiotensin II in the blood vessels.
• However, most of the conversion of the
angiotensin I to angiotensin II is in the lungs
because you have plenty of ACE.
• Angiotensin II will go to the zona glomerulosa of
the adrenal cortex to produce aldosterone.
• Aldosterone reabsorbs sodium.
• Site of action:
a. distal tubule
b. thin ascending limb (TAL)
c. Collecting tubules
• Where sodium is, chloride follows because you
need the electronegativity. If sodium and chloride
is back in the blood, therefore the osmolarity will
become high and by the principle of osmosis,
water follows.
• If the water is high, it will affect the blood volume,
venous return, stroke volume, cardiac output, and
blood pressure.
• Extremes of blood pressure: positive feedback,
thus cannot be controlled. It will continue to rise
until the blood vessel ruptures that will result to
hemorrhage (death).
↓ Blood Pressure (↓ renal blood flow → ↓renal filtration rate) →
↓ Na+ will stimulate Macula Densa to release signal to JG Cells to
release Renin (Angiotensinogenase) → Inside the liver, by the
enzyme Angiotensinogen → Angiotensin I → In the lungs, by the
enzyme Angiotensin Converting Enzyme (ACE) → Angiotensin II
(Can be further converted to Angiotensin III) → In the Adrenal
Cortex (Zona Glomerulosa) → Release Mineralocorticoid
(Aldosterone) → ↑ Blood Pressure
5. Regulation of acid-base balance
• 1st buffer: Intracellular and extracellular buffer
o RBCs (hemoglobin), carbonates,
phosphates
• 2nd buffer: Respiratory tract (lungs)
o If you have high amount of acids such as
CO2, you will increase respiration.
o If you are alkalotic (low CO2), slow
respiration.
• 3rd buffer: Kidneys
o Excrete acids and bicarbonates
o You can only alkalinize your urine up to
pH of 8 and acidify up to pH of 5.
However, pH of 8 and 5 are pathologic.
6. Endocrine function and Gluconeogenesis
• Erythropoietin (EPO) is synthesized in the kidneys
and is directly poured into the blood, hence it is
called endocrine.
• EPO:
o 80% from the kidney
o 20% from the liver
o 5% from the bone marrow
• During extreme conditions, it has a capability to
undergo gluconeogenesis.
EXTERNAL STRUCTURE OF THE KIDNEYS
• Gerota’s fascia, pararenal fat & perirenal fat – thick
protection of the kidneys
• Two kidneys à if you remove one, the remaining kidney
will hyperfunction. The BUN must be monitored. If the BUN
is high, nitrogenous waste products are not excreted. The
nitrogenous waste products might penetrate in the brain,
you might have encephalopathy.
• The renal pelvis, the renal vein and the lymphatics exits in
the renal hilus.
• The lymphatics, the renal artery and the nerves (innervating
the kidney) enters the renal hilus.
• Renal pelvis – formed by union of the major calyces.
• Major calyx – formed by the union of minor calyces.
• Renal cortex – outer portion
• Renal medulla – inner portion
o Renal pyramids – triangular structure; base is directed
towards the cortex and apex is directed towards on the
minor and major calyces.
o Renal papilla – directed on the minor calyx.
o Renal pyramids contain the collecting ducts.
• Collecting ducts forms the renal pyramids that drains the
urine, therefore it is non-modifiable (already urine in the
minor calyx). If it is in the tubules that is still being modified,
it is called as filtrates or tubular fluid.
• You can call it urine once the tubular fluid drains into the
minor calyx.
• The urine will drain to the major calyces to renal pelvis
going to the ureter. The ureter drains to the urinary bladder.
It will wait there until it distends. Once distended and filled
with 150-200 mL of urine, there will be an urge to urinate.
• The detrusor muscles expand that is innervated by sacral
nerves that will send signal to the pons to urinate through
the fibers.
• Barrington center in the pons is responsible for voluntary
urination that will communicate with the cerebrum (primary
motor area) to execute voluntary urination.
• Micturition reflex is a reflex that will allow to contract the
external urethral sphincter. Then, the urine will pass
through the urethra.
o Length of urethra: In females, 5 cm or 2 inches. In
males, 20 cm or 10 inches.
o 3 segments of the urethra: the prostatic, the
membranous and the pineal
• Flow of urine: tubules à renal pyramids à renal papilla à
minor calyces à major calyces à renal pelvis à ureter à
urinary bladder à once it is time to void the urine, it will
pass the urethra
BLOOD SUPPLY OF THE KIDNEY
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• Physiologically, urine does not contain bacteria. Urine INTERNAL STRUCTURE OF THE KIDNEYS
comes from the blood, specifically from the plasma.
• A true capillary should be found between an arteriole and a
venule. The pressure in the arteriole is high and the
pressure in the venule is low.
• The pressure in the arteriolar end favors filtration (the fluid
will go out of the capillary). The pressure in the venular end
favors reabsorption (the fluid will go back to the capillary).

Starling’s Forces:
1. Capillary Hydrostatic Pressure
2. Capillary Osmotic Pressure of Plasma Protein Pressure
3. Interstitium/tissue Hydrostatic pressure
4. Interstitium/ tissue Osmotic Pressure of Plasma Protein
Pressure • Nephron – functional and structural unit of urinary system
• Hydrostatic Pressure – drive fluid away • Cortical nephrons – where peritubular capillaries located
• Osmotic Pressure of Plasma Proteins – attracts • Juxtamedullary nephrons – near in the medulla; where vasa
fluid (contributed largely by proteins) recta located.

Renal Blood Flow:

1. Renal Artery – one of paired branches of abdominal aorta
2. Segmental artery
3. Interlobar artery
4. Arcuate artery
5. Interlobular artery – also called as radial artery
6. Afferent arteriole – high pressure
7. Glomerular capillaries – 60 mmHg; filters 20% (22%) of the
plasma to become the urine
CO = SV x HR
HR = 60-100 bpm; SV = 70 mL
NEPHRON
CO = 70 mL x 60 bpm = 4,200 mL or 4.2 L
CO = 70 mL x 100 bpm = 7,000 mL or 7 L
Normal range: 4.2-7 L
Average: 1200mL/min or 5 L (22% CO)
o The glomerular capillaries are found in between two
arterioles. Thus, the pressures at the start and end of
the glomerular capillaries are high.
o The entire glomerular capillaries favor FILTRATION
only.
8. Efferent arteriole – high pressure
9. Peritubular capillaries – 13 mmHg; a true capillary
o It can FILTER and REABSORB, but mostly it is
responsible for reabsorption.
o Found in a cortical nephron
10. Venule • The structural and functional unit of the urinary system
11. Interlobular veins • 1 million per kidney; However, every 10 years after 40 y/o
12. Arcuate veins the number of nephrons in the kidneys decreases up to
13. Interlobar vein 10%.
14. Segmental vein • Begins from renal corpuscle and ends in the distal
15. Renal vein convoluted tubule
o Modify filtrate even in the absence of hormone
(Obligatory Filtration: 67%-100%)
CAPILLARY CHARACTERISTICS PRESSURE
PARTS:
Glomerular Specialized capillary High pressure
1. Renal corpuscle – Bowman’s capsule + glomerular
Capillary (found in between 2 Begins: 60 mmHg capillaries
arterioles) Ends: 59 mmHg
• Bowman’s capsule:
Favors fluid filtration
o Parietal layer
Peritubular True capillary (found Lower pressure o Bowman’s space – also called as urinary space
Capillary in between an Begins: 18 mmHg (however, it is not yet a urine, still as
arteriole and a Ends: 8 mmHg filtrates); between the layers connected to
venule) PCT; the space between visceral and parietal
Favors filtration, but layer
mostly reabsorption o Visceral layer – the swellings like bullae that
Found in cortical covers glomerular capillaries; adherent to
nephron glomerular capillary

Page 3 of 12
 a. Afferent arteriole – commonly larger and thicker
blood vessel than the efferent arteriole found before
the glomerular capillaries. The origin of the afferent
arteriole is the interlobular arteriole.
o Lining epithelium: simple squamous cells
b. Glomerular capillaries – enclosed by the Bowman’s
capsule.
o Lining epithelium: simple squamous cells
c. Efferent arteriole
o Lining epithelium: simple squamous cells
d. Peritubular capillaries – near the proximal tubule,
collecting tubule, distal tubule; extension of efferent
arteriole in the cortex.
e. Vasa recta – descend in the medulla as straight
vessels
• Association (countercurrent mechanism):
o thick ascending limb with proximal portion of
peritubular capillaries
o descending limb with distal blood vessel
2. Proximal Tubule
• Convoluted or straight
• Lining epithelium: simple cuboidal with brush borders
3. Loop of Henle
a. Descending limb – shorter thick and longer thin
descending loop; near to the proximal tubule
b. Main Loop
c. Ascending limb – thick ascending limb is longer than
thin ascending limb; near to the distal tubule
• Lining epithelium: thick segment is made up of simple
cuboidal and thin segment is simple squamous.
4. Distal Tubule
• Found in between the afferent and efferent arteriole.
• Lining epithelium: simple cuboidal with few brush
borders; the portion near the afferent arteriole is
simple columnar
5. Collecting Tubule
• Drain the tubular fluid/filtrates into the collecting ducts
6. Collecting Ducts
• Drain the collecting tubules (branches)
• Collecting ducts in the medulla will form renal pyramids
*According to Guyton, there is a connecting tubule which
connects collecting tubule to collecting ducts.
The filter will go to the Bowman’s space then goes to the lumen
of the Proximal tubule, LoH, Distal tubule, Collecting tubule until
it drains to the collecting ducts until the distal end of the
collecting ducts (URINE) towards the minor calyces.
FILTRATION BARRIER
• The blood enters from the afferent arteriole towards the
glomerular capillaries, you filter the plasma it will become
as filtrates at the Bowman’s space.
• The filtrates will pass the filtration barrier composed of:
o capillary endothelium
o interstitial space,
o visceral layer of Bowman’s capsule (podocytes
with pedicels).
• The simple squamous cells of the Bowman’s capsule is
called as podocytes. The podocytes has several pedicels
(foot processes) because it should cover the capillary
(fenestrated without diaphragm = HOLES, therefore the big
particles like protein and bacteria can pass through).
• The fenestra will be narrowed by the pedicels of the
podocyte, thereby making the filtration barrier size
selective and shape selective.
• Charge selective – every epithelium lies on a basal lamina
that has lamina rara/lucida and lamina densa.
o Lamina lucida – made up of collagen type 1
o Lamina densa – made up of collagen type 4
• Lumen of glomerular capillaries (paracellular/transcellular)
à lamina rara interna à lamina densa à lamina rara
externa à Bowman’s space
• The portion near the afferent arteriole is simple columnar
(macula densa) located in the distal tubule.
• JG cells – located at the tunica media of the afferent
arteriole, instead of becoming muscles, it becomes cellular,
that secretes renin.
• Extraglomerular mesangial cells (EGMC) – in between
the JG cells and macula densa; also known as Lacis cells,
Polkissen, erythropoietin-producing organ cell (EPO).
• Low RBF = Low GFR = Low amount of filtration
o Macula detects the sodium concentration. If low,
it will send signals to EGMC to stimulate JG cells to
secrete renin. Renin (formerly known as
angiotensinogenase) will go to the liver to convert
angiotensinogen to angiotensin I.
!! UPDATED VERSION !!
• JG cells are not only present in afferent arteriole (1st best
answer), it can also be seen at the efferent arteriole (2nd
answer) because the distal tubule passes through the
middle.
• Macula densa is found in between distal tubule and TAL
(thick ascending limb of LoH). (1st best answer)
o 2nd answer: distal tubule
o 3rd answer: TAL
• Juxtaglomerular apparatus is composed of the following:
o macula densa
o extraglomerular mesangial cell
o juxtaglomerular cells
Page 4 of 12
 • Mesangial cell – is an intraglomerular cell; found INSIDE the Principles of Filtration Barrier
glomerulus 1. Size selective – anything greater than 9nm or 500
• Extraglomerular cell – a part of JG apparatus angstrom cannot pass through
• The distal (late) portion of distal tubule until the collecting o e.g. protein bound are not filtered, thus should not
ducts, there are two types of cells: be seen in the urine if the filtration barrier is intact
1. Principal cells – responsible for regulating/ o Diabetes mellitus, antibodies – there is a presence
handling of electrolytes (reabsorption, secretion) of protein because the barrier is not intact
2. Intercalated cells – regulation of acid-base (maluwag)
balance (H for acid, HCO3- for base) o Amino acids can be filtered and reabsorbed.
a. Alpha – for acid; secretes H o Osmotic and oncotic pressure are higher.
b. Beta – for base; secretes HCO3- 2. Charge selective – basement membrane is negative
charge; allows positive charge electrolytes to pass through
TWO TYPES OF NEPHRON 3. Shape selective
1. Cortical nephron – located in the cortex
2. Juxtamedullary nephron – located near the medulla Components of Glomerular Membrane
o ‘Juxta’ = beside the medulla • Capillary Endothelium
• Basement Membrane
DIFFERENCES BASED ON ITS: • Podocytes
A. Location
o Both are located in the cortex.
o Juxtamedullary à near the medulla, yet still in
cortex (ONLY the LoH and distal portion of the
collecting duct are found in the medulla)
B. Number MESANGIAL CELL
o Cortical nephrons are more numerous. • Inside the renal corpuscle
C. Length of LoH extending into the medulla • Modified smooth muscle
o The LoH of cortical nephron is shorter o has capability to
o The LoH of juxtamedullary nephron is deeper into contract; when the
the medulla. mesangial cell contracts,
D. Function the holes open/widens,
o Cortical nephron is for the dilation of the filtrates. thus no size selectivity
o Juxtamedullary nephron is for the concentration of o has receptor for
the tubular filtrate. angiotensin II (for
E. Association with peritubular capillaries/vasa recta contraction of smooth
o Both are associated with peritubular capillaries, muscle)
but only juxtamedullary nephron has relation with • Modified macrophage
vasa recta. o The unfiltered substances will clog the filtration
o Cortical nephron – more associated with barrier, then it will not be able to filter. The water-
peritubular capillaries soluble substances that is supposed to be secreted
o Juxtamedullary nephron – associated with vasa are retained in the blood that will cause toxic
recta manifestations.
• Renal cortex – isotonic o Mesangial cell will remove the debris in the blood.
• Renal medulla – hypertonic
FILTRATION COEFFICIENT
Cortical Nephrons
[FILTRATE]/
– almost all parts are located SUBSTANCE MOL. WT. MOL. RAD.
[WATER]
in the cortex Water 18 0.10 1.0
– have short loop of Henle Glucose 180 0.36 1.0
– more abundant Inulin 5,000 1.4 1.0
– have peritubular capillaries Hemoglobin 17,000 2.0 0.03
Juxtamedullary Nephron Catanionic dextran 3.6 0.42
– some parts are located in Anionic dextran 3.6 0.15
the cortex and some in the Anionic dextran 3.6 0.01
medulla Serum albumin 69,000 3.6 0.001
– have long loops of Henle • Water is the reference point for the filtration which is 1.0.
– less abundant o < 1.0 = not filtered
– have vasa recta (peritubular o ≥ 1.0 = filtered
capillaries) • Glucose and Inulin have a coefficient so it is easily filtered.
• Glucose has 1.0 so it can be filtered (urine), but it will be
completely reabsorbed.
• Inulin is very filterable but it is not reabsorbed, thus can be
seen in the urine.
• Kapag lumalayo ‘yung value sa 1.0, the molecular weight is
increasing, so it cannot be filtered.
• The molecular radius is increasing as the filtration
coefficient decreases.

Page 5 of 12
Which is the principal size selective barrier?
– The glomerular basement membrane
Which is the major electrostatic barrier?
– The layers closest to the capillary lumen
o lamina fenestra
o innermost part of the basement membrane

FACTORS AFFECTING THE FILTERABILITY OF

MOLECULES
1. Size
– Substances up with molecular weight up to app. 5000
whose molecular radii are less than 15 Å will have a
plasma: filtrate ratio of 1.
2. Shape
– For a given molecular weight, a slender and flexible
molecule will pass through the glomerular filtration
membrane more easily than a spherical, non-
deformable molecule.
3. Electrical charge
– The glomerular filtration membrane bears fixed (-)
charges. These anionic sites consist of
glycosaminoglycans rich in heparan sulfate.

THE MAIN CELLS OF THE JUXTAGLOMERULAR

APPARATUS
1. Juxtaglomerular granular cells
• Afferent arteriole
• Renin
2. Extraglomerular mesangium
• May serve as the functional link between the macula
densa and the glomerular arterioles
3. Macula densa
• Thick ascending limb / DCT
• NaCl concentration

Page 6 of 12

EXCRETION
• Principle of urine formation
CLEARANCE
• The renal clearance (C) of a substance (s) is the volume of
plasma required to supply the amount of (s) excreted in the
urine during a given period of time:
• INPUT: The plasma goes from the renal artery towards the
afferent arteriole.
• It will go in two ways (OUTPUT):
o Renal vein – plasma substance
o Excrete in urine – urine substance
• The flow of urine in tubule = urine flow rate
• Clearance = urine substance multiplied by urine flow rate
over plasma substance. (Ilan ang natira? Ilang ang nasa
urine?) à 2 output
• Afferent arteriole à glomerular capillaries à (1) filtration
à (2) reabsorb à (3) secretion à (4) excretion
• When reabsorb, mawawala sa tubular fluid = negative
• When secreted, dinagdag/nagkaroon sa tubular fluid =
positive
EXCRETION = Filtration – Reabsorption + Secretion
• Excretion = Filtration
o When filtered, it is not considered as excretion.
o E.g. Glucose – filtered and completely reabsorb,
you will not see glucose in the urine.
o Theoretical value: excreted substance = 10,
filtered substance = 10.
o [Eq.: 10 = 10 – 5 + 5] Therefore, there is an equal
reabsorption and secretion.
o [Eq.: 10 = 10 – 0 + 0] The substance is filtered
and not reabsorbed nor secreted.
• Excretion > Filtration
o Theoretical value: excreted substance = 10,
filtered substance = 8.
o The substance is primarily secreted.
• Excretion < Filtration
o The substance is primarily reabsorbed.
GLOMERULAR FILTRATION RATE
• GFR = Urine creatine x Velocity / Plasma substance creatine
• The commonly used substance is inulin.
• The problem with inulin is that it is NOT SECRETED. It is
freely filtered.
• If there’s a renal obstruction, or renal stones in the minor /
major calyx, people who are genetically stone formers, the
inulin will be kept inside the body then it becomes toxic
(poison).
• That is why creatinine is now used, because normally we
have creatinine in the body. If the BUN and creatinine
exceed, (1) there is a problem in the kidney, (2) should
undergo fasting, no strenuous activity because the skeletal
muscle releases creatinine (it will rise up), high protein diet
causes high creatinine.
• However, the problem with creatinine is that, supposedly
they are not secreted, but they are secreted. They are over
by 10%. When creatinine are measured, the tool used for
creatinine measurement is deficient by 10%. Therefore, it
is equalized.
• Supposedly, inulin is the best substance in measuring the
filtration rate because:
1. The substance should be freely filtered across the
glomerulus into Bowman’s space
2. Should not be reabsorbed or secreted by the nephron
o To show that it is really a reflection of filtration
rate, in which the one being measured is the
filtrability of the kidney / filtration barrier
3. Should not be metabolized or produced by the kidney
4. Should not alter the GFR
• Renal plasma flow and renal blood flow are different.
o RBF consists of 2 compartments (formed elements
and plasma).
• The pressure in the afferent
and efferent arteriole is high
with the difference of 1 mm
Hg.
• Filtration = nagpalabas ng
tubig
• Reabsorption = nagpapasok
ng tubig; tinapon mo na,
kinuha mo pa ulit J
STARLING’S FORCES:
• Capillary Hydrostatic Pressure – nagpapaalis ng water
• Capillary Oncotic Pressure – nagpapastay yung plasma sa
loob ng capillary
• Interstitial Space /Tissue Oncotic Pressure – pinapastay sa
loob ng interstitial space; If higher than oncotic capillary
pressure, the water is in the interstitium = EDEMA.
• Tissue Hydrostatic Pressure – papasukin ang water
Page 7 of 12
• Capillary Hydrostatic Pressure FICK’S PRINCIPLE
o 60 mm Hg at the afferent end • Pressure
o 58 mm Hg at the efferent end difference/gradient – the
• Capillary Oncotic Pressure difference of pressure
o -28 mm Hg at the afferent end from the arteriolar end
o -35 mm Hg at the efferent end towards the venular end.
• Bowman’s Space Hydrostatic Pressure • Flow and velocity are not
o -15 mm Hg at the both ends – the Net Filtration the same. Flow is
Pressure is equal to Filtration minus Reabsorption volume/time. Velocity is
o Factors that cause filtration (magpapalabas ng distance/time.
water): (interstitial oncotic pressure + capillary
hydrostatic pressure) – (interstitial hydrostatic DETERMINANTS OF RENAL BLOOD FLOW
pressure + capillary oncotic pressure)
§ (ICP + CHP) – (IHP + COP)
• Bowman’s Space Oncotic Pressure
o Plasma proteins – greatly responsible for oncotic Comparison of Distribution of Blood Flow to Different Organs
pressure; no filtered proteins but amino acids are Kidney 4.0 ml/g/min
filtered (but they are not proteins, since there are Heart 0.9 ml/g/min
no peptide bonds) and will never be protein in Brain 0.6 ml/g/min
Bowman’s space. Liver 0.2 ml/g/min
o 0 mm Hg at the level of afferent and efferent Resting muscle 0.1 ml/g/min
arteriole • Kidney – take the largest bulk of cardiac output
• The result of the NFR = POSITIVE; the substance are • Resting muscle – if it active muscle, increase blood flow
filtered. It favors filtration at the afferent and efferent end. (skeletal muscle)
• The glomerular capillaries only favors filtration.
Intrarenal Distribution of Blood Flow
• High blood pressure = high RBF = high GFR = high urine % of Kidney % of Blood Blood volume Perfusion rate
output Wt. Flow ml/g tissue ml.g-1 . min -1
• When the afferent arteriole is constricted, the RBF is low, Cortex 75 90 0.2 5.3
low GFR and low urine output. Outer 30 7 0.2 1.4
• When the afferent arteriole is dilated, the RBF is high, high Medulla
GFR and high urine output. Papilla 10 1 0.2 0.4
• Flow and velocity are not the same. Flow is volume/time. • Cortex took up 90% of 20-25% of CO.
Velocity is distance/time. • Outer medulla takes 8%; isotonic
• When the efferent arteriole is constricted, the RBF is low, o Isotonic because most of the blood supply will go
high hydrostatic pressure, high GFR and high urine output. to the renal cortex wherein there will be frequent
• When the efferent arteriole is dilated, the RBF is high, low exchange of fluid. When we say fluid, it includes
hydrostatic pressure, low GFR and low urine output. the water and electrolytes
• Papilla is the inner medulla
o There is less blood flow so there is a less frequent
wash off. So the electrolytes are retained, making
it hypertonic.

• Paraaminohipuric Acid (PAH)

o Freely filtered
o Secreted – it will go to the entire blood vessels of
the kidney
o Not reabsorbed
o Not metabolized
o Not stored
o Not synthesized

RENAL BLOOD FLOW Effective Renal Plasma Flow

• 22 – 25% of the cardiac output (1,200 -1300 ml/min)
CO = SV x HR
HR = 60-100 bpm; SV = 70 mL (average) Example:
CO = 70 mL x 60 bpm = 4,200 mL or 4.2 L Concentration of PAH in urine (UPAH) - 14 mg/ml
CO = 70 mL x 100 bpm = 7,000 mL or 7 L Urine flow (V) - 0.9 ml /min
Normal range: 4.2-7 L Concentration of PAH in plasma (PPAH) - 0.02 mg/ml
Average: 1200mL/min or 5 L (22% CO)

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Average PAH extraction ratio – 0.9 • Example: 70% (absorbed sodium in proximal tubule); 50mg
(filtered sodium). How much will be reabsorbed? 35mg
(70% of 50mg). If 100mg filtered sodium, 70mg are
Hematocrit (Hct) = 45% reabsorbed. If 200mg filtered sodium, 140mg are
Blood = 1 reabsorbed.
• The filtration rate is proportional to the amount it will
reabsorb. If the filtration rate is low, the reabsorption is low.

TUBULOGLOMERULAR FEEDBACK
• According to B&L, it is due to the increase in sodium
concentration in the filtrate (stimulus) detected by macula
densa.
• When the blood pressure is high, the RBF is high, high
filtration rate, the sodium concentration in the tubular fluid
is high which is detected by macula densa. Macula densa
will cleave ATP to produce adenosine. When adenosine acts
on the afferent arteriole, particularly the A1 receptor, it will
activate Gq that will release Ca2+ and hence, afferent
arteriolar constriction. When you constrict the afferent
arteriole, the RBF will be down, the filtration rate is low, NA
concentration and filtrate will also be low. (Negative
feedback)
o Adenosine is a vasodilator except when it acts on
adenosine 1 receptor (Gq-related; associated with
IP3 and Ca2+). Calcium + calmodulin will activate
myosin light chain kinase. Myosin light chain
AUTOREGULATION kinase will phosphorylate myosin light chain. In
short, it will cause smooth muscle contraction. If it
• Inherent mechanism of the kidney in maintaining renal
contracts, there will be vasoconstriction.
blood flow and GFR at relatively constant level over an
• According to Guyton, it is due to the low sodium
arterial pressure range between 80 – 170 mmHg [90- 180
concentration in the filtrate (stimulus).
(B&L)/ 75 -160 (Guyton)]
• When the blood pressure is low, the RBF is low, the filtration
o MAP = DBP + (PP/3)
rate is low, the the sodium concentration in the tubular fluid
o MAP = (2DBP + SBP) /3
is also which is detected by macula densa. Macula densa
o MAP = (2DBP/3) + (SBP/3)
will send signal to extraglomerular mesangial cell to tell JG
• Influenced by nervous mechanism (ANS), hormones,
cells to secrete renin. Renin (angiotensinogenase) will go to
autocoids (vasodilators and vasoconstrictors) and other
factors the liver to convert angiotensinogen to angiotensin 1.
Angiotensin 1 will go to the lungs to be converted into
angiotensin 2 (more potent) and 3 by angiotensin-
2 AUTOREGULATORY MECHANISM
converting enzyme (ACE). Angiotensin 2 will constrict
1. Glomerulotuberular balance
afferent and efferent arteriole.
• The amount absorbed is proportional to the filtration rate.
• Angiotensin 2 receptors:
• When the filtration rate is high, high reabsorption.
o Receptor 1 – Gq-mediated; AII acts on the afferent
• When the filtration rate is low, low reabsorption.
arteriole (yield calcium), it will cause constriction
• In proximal tubule, there is an obligatory reabsorption of all
of afferent arteriole.
substances. Why obligatory?
o Receptor 2 – Gi-mediated; cause the release of
o Plenty of microvilli (brush borders)
nitric oxide that will cause vasodilation.
o Plenty of transporters present in the microvilli
• When angiotensin 2 acts on AIIR1 and AIIR2, it will cancel its
(brush borders)
effect giving off normal diameter of afferent arteriole.
• In the absence/presence of the hormone in the proximal
• In efferent arteriole, no AIIR2, we only have AIIR1 that is why
tubule, you still have the most of reabsorption.
it will constrict afferent arteriole.
• In the proximal tubule, there is a 67%-100% of
• Angiotensin II predominantly constrict efferent arteriole.
reabsorption of substances.
When the efferent arteriole is constricted, the RBF is low,
o Ex.: Sodium in the proximal tubule is reabsorbed
the filtration rate is high, the hydrostatic pressure in
by 66.66~67%. Amino acids and glucose in the
glomerulus is high; the sodium concentration is high.
proximal tubule are 100% reabsorbed.
(Negative feedback)
o Aldosterone:
§ Site of action: distal tubule, TAL,
2. Myogenic Mechanism
collecting ducts and collecting tubules
• The problem with myogenic mechanism is that
§ Reabsorbs sodium na hindi na-absorb ng
• An increase blood pressure, the walls of the blood vessels
proximal tubule (sasama si chloride),
will be stretched. The tunica media opens the mechanically-
tataas ang tonicity à susunod water
gated Ca2+ channels causing entry of Ca2+ inside the smooth
o In the presence of aldosterone, the sodium is
muscles and release of Ca2+ from the cisterns of the
mostly absorbed in the proximal tubule.
sarcoplasmic reticulum. Ca2+ binds to calmodulin causing
vasoconstriction.

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• Myogenic mechanism will not be able to detect the amount • action of NE on β1 adrenergic receptors on JG cells and
of electrolytes in the tubular fluid. That is why, it is a poor renal tubular cells
explanation to the regulation of renal blood flow, and hence • Stimulation of renal nerves (increasing strength) à
urine output. increase sensitivity of JG cells à increase renin secretion à
increase Na+ reabsorption à renal vasoconstriction à
NERVOUS MECHANISM decrease GFR and RBF
• Sympathetic Nervous System – releases NE
o mild and moderate sympathetic activation Excretion of Waste Products and Foreign Chemicals
§ mild = no or very mild effect through the Formation of Urine
o little effect on both the RBF and GFR • Waste Materials – If your kidney shuts down, it will
o strong activation accumulate in the blood and patient will show manifestation
§ moderate to strong = causes of toxicities of these substances.
vasoconstriction of the afferent and o urea – amino acids
efferent arteriole causing decrease in o creatinine – muscle creatine
renal blood flow, hence decrease o uric acid – nucleic acids
filtration rate o bilirubin – hemoglobin
o decreases RBF and GFR • metabolites of various hormones
• There’s NO PARASYMPATHETICS innervation to the kidney • drugs and toxins
• excess substances
HORMONES AND AUTOCOIDS
• Norepinephrine, Epinephrine and Endothelin URINE FORMATION
o vasoconstrictors • Glomerular Filtration
o constrict afferent and efferent arteriole • Tubular Reabsorption
o decreases RBF and GFR • Tubular Secretion
• Angiotensin II
o constrict afferent and efferent arteriole Urinary Excretion Rate = Filtration Rate – Reabsorption Rate +
(predominant) Secretion Rate
o decreases RBF but increases GFR
• Endothelin derived nitric oxide
o causes vasodilatation –– decreasing vascular
resistance
o increases RBF and GFR
• Prostaglandin and Bradykinin
o causes vasodilatation –– decreasing vascular
resistance
o increases RBF and GFR

Major Hormones That Influence the GFR and RBF

Effect On Effect On A. Substance was mainly filtered, it is neither reabsorbed nor
Stimulus
RBF GFR secreted
Vasoconstrictors • Excretion = Filtration
Sympathetic ↓ ECFV
↓ ↓ B. Substance was filtered and partly reabsorbed
Nerves
• Excretion < Filtration
Angiotensin II ↓ ECFV ↓ ↑
Endothelin ↓ ECFV
C. Substance was completely reabsorbed
↑ Stretch, ↑ AII, ↓ ↓ • Excretion = zero
↑ Bradykinin, E D. Substance was filtered and secreted
Vasodilators • Excretion > Filtration
PG1, PGE2, PGI2 ↓ ECFV No change
↑
↑ Shear stress, AII /↑ Determinants of GFR
Nitric Oxide ↑ Shear stress,
Ach, Histamine, ↑ ↑ GFR = Kf x Net Filtration Pressure
Bradykinin, ATP
Bradykinin ↓ ACE
↑ ↑ Kf = glomerular capillaries filtration coefficient
↑ PG
Natriuretic peptide ↑ ECFV No change ↑
Kf = capillary permeability and capillary surface area

Renal Innervation Net Filtration Pressure

• Exclusively innervated by sympathetic nervous system
o Vasoconstriction of afferent and efferent arteriole
o Low RBF; Low GFR; Low urine output
o NE will act on β1 present on the JG cells so that it
will secrete renin. It will trigger RAAS.
• Increases renin secretion and sodium reabsorption
o Direct action of NE, it would reabsorb sodium from
proximal tubule to the collecting tubule
– represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration
across the glomerular capillaries.
– It is the difference between filtration and reabsorption
(filtration - reabsorption).
– Filtration factors: [CHP + IOP] – [COP + IHP]
– Filtration (+); Reabsorption (–)

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Filtration Coefficient (Kf) LIMITATIONS TO TRANSPORT
– Affected by permeability of the capillary as well as the TM LIMITED (TRANSPORT MAXIMA)
surface area of the capillary • Glucose, SO4, PO4, amino acid, lactate, malate and vit. C
– If the capillary is very permeable, the Kf is high, the • Transporter present in the proximal tubule
filtration rate is faster. • If you reach the maximum transport, it will be constant.
• The other substances that is not reabsorbed will be seen in
Total Filtration Pressure the urine.
– Glomerular Capillary Hydrostatic Pressure • The maximal transport is a function of the PCT, not of the
o Pcap or gCHP (60 mmHg) function of the blood, its capacity to hold glucose, especially
– Interstitial Oncotic Pressure that of the kidney — renal threshold
o Лif or TCOP (0 mmHg) • Transport maxima for glucose is
375 mg/min.
Total Reabsorption Pressure § Renal threshold for
– Plasma Oncotic Pressure glucose is 200 mg/dL.
o Лcap or PCOP (32 mmHg) • If GFR is 125 ml/min, glucose
– Interstitial Hydrostatic Pressure should not appear in the urine
o Pif or THP (18 mmHg) until plasma glucose
concentration is > 300mg/dl
FACTORS THAT AFFECT GFR (renal threshold for glucose)
• Glomerular Capillary Hydrostatic Pressure § (125 ml/min X 3 mg/ml
o arterial blood pressure (300 mg/dl) = 375
o afferent arteriolar resistance mg/min
§ Increase resistance in afferent arteriole, • Renal threshold is more
the , the RBF is low, the CHP is low, the important than transport
GFR is low. maxima.
o efferent arteriolar resistance • Beyond 200mg, you begin glycosuria, even if you don’t
§ Increase resistance in efferent arteriole, reach the transport maxima.
it is constricted, the RBF is low, the CHP
is high, the GFR is high. GRADIENT TIME LIMITED
o GFR = 125 ml/min (MEMORIZE!) • Na+, Cl- and HCO3-
o GFR = 7500 ml/hour • The greater the time, the more transport, more
o GFR = 180,000 ml/day or 180 L/day reabsorption.
• Proximal Tubule • Passive transport – when reabsorbing, it is going peritubular
o Reabsorption happens because of the presence of capillaries; the concentration is from high to low.
brush borders and transporters • Example: You filter 100 Na, what left in peritubular
o The proximal tubule reabsorbs approximately; capillaries will be 10. As compared with 50 K, what is left in
§ 67% of the filtered water, Na, Cl, K and peritubular capillaries is 40 K. What will reabsorb faster and
other solutes. more? SODIUM is faster and reabsorb more. The gradient
§ 100% of the filtered glucose, amino acids in Na+ is 90, in K is 10.
§ Also secretes organic cations and anions. • In active transport, less to great. The lesser the gradient,
greater the transport.

Tubular Secretion = Amount Excreted – Amount Filtered

• Transcellular transport – the substance will pass and

reabsorb in the apex. It is buried in the cytoplasm towards
the basolateral membrane, so it can go to the blood.
• Paracellular transport – ‘para’ means beside

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• Normal osmolarity: 280-300 mOsm • The proximal portion of peritubular capillaries, bababa
o 300 mOsm – isotonic (vasa recta) sa gilid katabi ng TAL. Yung distal portion,
• Nagfilter ka, isotonic (fluid in the proximal tubule). katabi ng descending limb.
• As the fluid moves to the descending loop of Henle, the • Vasa recta – countercurrent exchanger
medulla is hypertonic. As the tubular fluid moves
downwards, the osmolarity increases until it reaches 1200
mOsm/L. SUMMARY:
• When it reaches the medulla, it became hypertonic. The 1. Inulin is freely filtered, not reabsorbed nor secreted
water leaves the tubules. The water will go to the medulla. • Excretion = Filtration
Therefore, the tubular fluid lost its water, turns to be 2. Glucose is filtered and reabsorbed
hypertonic until it reaches main LoH, it is very hypertonic. • Excretion = zero (hindi naman daw sinabing
It is believed to be more hypertonic than the medulla. That partial reabsorbed)
is why, sodium and chloride will passively diffuse towards 3. PAH is filtered and secreted
the medulla. Dahil pagbaba ng fluid sa tubules, the filtrate • Excretion > Filtration
will be hypertonic (hypertonic ang medulla). Lumalabas ang 4. Potassium is filtered, reabsorbed and secreted
tubig kaya ang maiiwan lang sa loob ay electrolytes. Marami • Depends on how much is reabsorbed and secreted
kang electrolytes sa medulla, pwede siyang pumasok ng • Excretion < Filtration
tubules making the tubules very hypertonic. Pag dating sa • Excretion > Filtration (more excrete)
main LoH mas hypertonic na siya kaysa sa medulla kaya 5. Sodium is freely filtered and partly reabsorbed
yung NaCl pwwedeng lumabas passively (from greater to • Excretion < Filtration
lesser), bukod sa water na lumalabas.
• As the filtrate goes up to the thick ascending limb, *** Filtration > Excretion = substance was reabsorbed
water. From your TAL to collecting tubules, they are not Filtration < Excretion = substance was secreted
permeable to water. Magiging permeable lang siya sa water
kung may hormones na ADH. The TAL is permeable to
electrolytes. Lalabas ang electrolytes dahil sa transporters
for electrolytes.
SUMMARY:
• You filter isotonic, you reabsorb isotonic so what is left in
the proximal tubule is still isotonic.
• As the fluid moves to the descending LoH, the medulla is
hypertonic. The water leaves the tubules of the descending
LoH, making the filtrate hypertonic because water is being
removed from it. As it moves to the main LoH, it is
considered to be more hypertonic than the medulla, that is
why there is a passive transport of Na and Cl from the
tubular fluid to the medulla.
• As the tubular fluid ascends to the TAL, the TAL is not
permeable to water but electrolytes are transported back to
the medulla. As the electrolytes are transported back to the
medulla, natatanggalan ng electrolytes yung filtrate sa TAL,
the osmolarity is hypotonic until the collecting ducts.
• Isotonic à hypertonic à hypotonic
• The collecting ducts near the medulla is permeable to water
and water. Pwede na siyang dagdagan ng urea, so from
hypotonic magiging isotonic na. Pag dagdag ng dagdag ng
urea, magiging hypertonic.
• Depends on your hydration. If you’re well-hydrated or over-
hydrated, you excrete an isotonic to hypotonic urine. If
you’re dehydrated, there will be secretion of ADH to
reabsorb more water, making your urine hypertonic.
• At the distal portion of the collecting ducts near the papilla,
the tubular fluid is no longer called tubular fluid (cannot be
modified), but called as URINE.
• Althrough out as long as you filtered them, when it reaches
the proximal tubule it is still to be modified.
• If it’s non-modifiable, when reaches the minor calyces down
to urinary bladder, then it is already the urine.

COUNTERCURRENT MECHANISM
• TAL as the countercurrent multiplier; it multiplies the
tonicity, osmolarity of the medulla.
• The medulla is already hypertonic, nilalagyan pa niya ng
mas maraming electrolytes, nagiging more hypertonic.
• Why countercurrent?

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