Urine Formation

• Major Waste Products

o Blood Urea Nitrogen (BUN)
→ Protein Metabolism
o Creatinine
→ Muscle Metabolism
o Uric Acid
→ Nucleic Acid Metabolism
o Bilirubin
→ Hemoglobin Breakdown
→ Converted to Urobilin (responsible for the yellow color
of urine)
• Excess substances, drugs, toxins, and metabolites of hormones

If you want to test the renal function, you have to request for the
determination of Blood Urea Nitrogen (BUN) and Creatinine

Basic Functions of the Nephron

(Filtration, Reabsorption, Secretion) Glomerular Filtration

• The amount of a substance that appears in the urine reflects • Where do you filter?
the coordinated action of the nephron’s various segments and o In the glomerular basement membrane or the Glomerular
represents the three general processes of glomerular filtration, Filtration Barrier
reabsorption of the substance from the tubular lumen back into
• What do you filter?
the blood, and secretion of the substance from the blood into
o The blood, but only the plasma
the tubular fluid
• What are the substances present in the blood but NOT in the
• First, filter the blood in the glomerulus, then reabsorb what you
filtrate?
want because once you filter, you cannot select
o Cells and proteins
• Some are not freely filtered so you secrete it through the urine
• How much of the plasma that pass the glomerulus will be
filtered?
EXCRETION RATE = Filtration Rate – Reabsorption Rate + o Only around 20% (Filtration Fraction)
Secretion Rate o Filtration Fraction – the percentage of the plasma that is
being filtered per minute
EXAMPLE: o In males, the Filtration Rate is 90-140%
Filtration Rate = 100 mL/min o In females, the Filtration Rate is 80-125%
Reabsorption Rate = 50 mL/min
Secretion Rate = 25 mL/min

𝐸𝑥𝑐𝑟𝑒𝑡𝑖𝑜𝑛 𝑅𝑎𝑡𝑒 = 100 − 50 + 25 = 75 𝑚𝐿/𝑚𝑖𝑛

 • In clinical practices, the kidney function is usually assessed in
by measuring PCr, which is inversely proportional to GFR
o If there is a fall in GFR → there will be an increase in Plasma
Creatinine
o If there is an increase in GFR → there will be a decrease in
Plasma Creatinine
• A fall in GFR from 120 to 100 mL/min is accompanied by an
increase in PCr from 1.0 to 1.2 mg/dL.
• This does not appear to be a significant change in P Cr but the
GFR has actually fallen by almost 20%

NOTE: RBF is actually RPF** 𝐺𝐹𝑅 = 𝐾𝑓 𝑋 𝑁𝑒𝑡 𝐹𝑖𝑙𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒

• If the RPF is 630 mL/min, you can only filter 125 mL/min
Kf = Glomerular Capillaries Filtration Coefficient
𝐺𝐹𝑅
𝐹𝑖𝑙𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝐹𝑟𝑎𝑐𝑡𝑖𝑜𝑛 = 𝑋 100%
𝑅𝑃𝐹 • Major Determinant of Kf = Capillary Permeability and Capillary
Surface Area
o If the Capillary Permeability increases → Filtration
125 𝑚𝐿/𝑚𝑖𝑛 Coefficient increases → GFR increases
𝐹𝑖𝑙𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝐹𝑟𝑎𝑐𝑡𝑖𝑜𝑛 = 𝑋 100% = 20%
630 𝑚𝐿/𝑚𝑖𝑛 o If the Capillary Surface Area increases → Filtration
Coefficient increase → GFR increases
• Filtration Pressure
• The sum of the Filtration Rates of all functioning nephrons o Represents the sum of the Hydrostatic and Colloid Osmotic
• Index of kidney function Forces that either favor or oppose filtration across the
o This is where you will see if the kidney function is okay or not glomerular capillaries
• Essential in evaluating the severity and course of kidney
disease
• To compute for the GFR, you will use the Clearance Principle

[𝑈𝑠 ] 𝑥 𝑉
𝐶𝑠 =
[𝑃𝑠 ]
S = any substance
C = Clearance, mL/min
Us = Urine Concentration, mg/mL
Ps = Plasma Concentration, mg/mL
V = Urine Flow Rate, mL/min

• Substances used to measure GFR:

o Inulin
o Creatinine – used in clinical setting

Inulin Creatinine
Freely filtered Freely filtered
Not secreted Not secreted
Not reabsorbed Not reabsorbed How do you filter?
Not metabolized Not metabolized • There are 2 forces that will favor fluid filtration:
Not stored Not stored o CHP
o TCOP
Not synthesized Not synthesized
• There are 2 forces that will favor fluid reabsorption:
Non toxic Non toxic
o PCOP
o THP
If you have Renal Disease, chances are you experience no
manifestations unless your functioning nephrons are only at
25% or below, that’s when you will experience manifestations. 1. Capillary Hydrostatic Pressure (CHP)
→ Tends to push the fluid OUT of the vessel
→ Pushing Pressure
A fall in GFR may be the first → Favor fluid filtration
and only clinical sign of kidney
→ 60 mmHg
disease.
2. Tissue Colloid Osmotic Pressure (TCOP)
A 50% loss of functioning → Tends to pull the fluid OUT
nephrons reduces the GFR only → 0 mmHg – primarily governed by proteins (since you
by about 25%. The decline in cannot filter the protein in the glomerulus, this is
GFR is not 50% because the usually 0 mmHg)
remaining nephrons
compensate
 1. Plasma Colloid Osmotic Pressure (PCOP)
→ Pulling of substance into the vessel by proteins
→ 32 mmHg
→ In other parts of the body, it is usually 25-28 mmHg
✓ It is higher in the kidneys because once plasma
undergoes filtration, the water will be filtered but
the proteins will remain → protein will be
concentrated → 32 mmHg
2. Tissue Hydrostatic Pressure (THP)
→ Pushing of substance into the vessel
→ 18 mmHg

Total Filtration Pressure = 60 mmHg

Total Reabsorption Pressure = 50 mmHg

Net Filtration Pressure = 60 – 50 = 10 mmHg

• Filtration is higher so it will favor filtration • From the Renal Artery to the Glomerular Capillary, the
Hydrostatic Pressure is higher the PCOP
• From the Efferent Arteriole to the Renal Vein, the PCOP is
greater than the hydrostatic pressure

𝐺𝐹𝑅 = 𝐾𝑓 𝑋 𝑁𝑒𝑡 𝐹𝑖𝑙𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒

𝐺𝐹𝑅 = 𝐾𝑓 𝑋 (𝑃𝐶𝑎𝑝 + 𝑇𝐶𝑂𝑃 − 𝑃𝐶𝑂𝑃 + 𝑇𝐻𝑃)
𝐺𝐹𝑅
𝐾𝑓 =
𝑁𝑒𝑡 𝐹𝑖𝑙𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒

125 𝑚𝐿/𝑚𝑖𝑛
𝐾𝑓 = = 12.5 𝑚𝐿/𝑚𝑖𝑛/𝑚𝑚𝐻𝑔
10 𝑚𝑚𝐻𝑔

• Means that there are about 12.5 mL/min/mmHg pressure

difference
• If you calculate per 100g:
= 4.2 mL/min/mmHg (0.01 mL/min/mmHg)

Kf will decrease if permeability and surface area decrease.

NFP will decrease if Pcap and TCOP decrease or if PCOP and THP
increase.

What is the most common cause of decreases in GFR?

o Kf due to decrease in surface area

A reduction in the GFR in disease states is most often due to

decreases in Kf because of the loss of filtration surface area.
The GFR also changes in pathophysiological conditions because
of changes in Starling’s Forces

• Changes in Renal Blood Flow

o Increase in Renal Blood Flow → Increase in GFR
• Changes in gCHP
o Changes in systemic blood pressure
• The pressure of Afferent Arteriole is GREATER THAN Efferent o Afferent arteriolar constriction
Arteriole o Efferent arteriolar constriction
• Changes in THP (Pressure in Bowman’s Capsule)
Afferent End Efferent End o Ureter obstruction
o Edema of kidney inside the tight renal capsule
CHP 60 mmHg 58 mmHg
TCOP 0 mmHg 0 mmHg • Changes in PCOP (Changes in concentrations of plasma
proteins)
THP -15 mmHg -15 mmHg
o Dehydration
PCOP -28 mmHg -35 mmHg
o Hyperproteinemia
Net Filtration 17 mmHg 8 mmHg
• Changes in Kf
Pressure
o Changes in glomerular capillary permeability
o Changes in effective surface area
• PCOP – while you’re filtering the water, the proteins become
concentrated → increase in Plasma Colloid
 • If there is an increase in pressure in the Afferent Arteriole →
Decrease in radius → Pressure inside is maintained (Laplace
• Law)
o If your Mean Arterial Blood Pressure is between 70 – 160 Tension = Pressure x Radius
mmHg → whether it increase or decrease, there will be no
effect in gCHP or GFR • Increase in Pressure → Radius will decrease → Tension inside
o Above 160 mmHg → increase GFR will be maintained
o Below 70 mmHg → decrease GFR • Decrease in Pressure → Radius will increase → Tension inside
will be maintained

• Before constriction → pressure is increased

• After constriction → pressure is decreased • Tubuloglomerular Feedback Mechanism
• The lower the gCHP, the lower the GFR • Juxtaglomerular Apparatus
• Afferent Arteriolar Dilatation: gCHP increases, GFR increases • Mechanism that responds to changes in the NaCl composition
of tubular fluid (NaCl-dependent Mechanism)

• gCHP Increases → GFR increases

• Efferent Arteriolar Dilatation: gCHP decreases, GFR decreases

• Increase in pressure in Bowman’s Capsule → GFR decreases

• What will increase THP?
o Urinary Tract Obstruction
→ Ureter Obstruction – the area before obstruction has an
increase in pressure → increase pressure in Bowman’s
Capsule → GFR decreases
o Edema of Kidney inside the tight renal capsule
→ Acute Condition – kidney will not be distended since it
is non-distensible → it will not expand → pressure
inside will increase → increase THP → decrease GFR

Decrease in ABP → Decrease in gCHP → Decrease GFR

• Changes in concentration of plasma proteins • We need to correct the decrease in GFR
• Hyperproteinemia or Dehydration → increase PCOP → increase
osmolarity → attract more fluid → GFR decreases Since GFR is decreased, then the NaCl being filtered will also be
• Overhydration or Hypoproteinemia → decrease PCOP → GFR decreased. Macula Densa will detect this decrease in NaCl
increases filtration → send information to the JG Cells → JG Cells will
increase RENIN → increase Angiotensin II → Increase in
Efferent Arteriolar Resistance → Increase in GFR

Macula Densa will also dilate the Afferent Arteriole → Decrease

• Intrinsic Regulation in Afferent Arteriolar Resistance
o Autoregulation
• Extrinsic Regulation Increase in ABP → Increase in gCHP → Increase GFR
o Renal Innervation (exclusively innervated by sympathetic)
o Humoral (hormones) Macula Densa will detect this increase → decrease Renin → no
o Urine Composition Angiotensin II → no constriction of Efferent Arteriole →
Decrease GFR

Afferent Arteriole won’t be dilated → Decrease GFR

• Inherent mechanism of the
kidney in maintaining renal
blood flow and GFR at
relatively constant level over
an Arterial Pressure range
between 70-160 mmHg
(Other references: 90-180
mmHg)
o Myogenic Theory
o Metabolic Theory
• Influenced by nervous
mechanism, hormones, autocoids, and other factors

• Mechanism that responds to changes in Arterial Blood Pressure

(Pressure-Sensitive Mechanism)
• Ability of individual blood vessels to resist stretching during
increased ABP
• ABP is decreased → decreased GFR – need to increase GFR
• When GFR was decreased, the filtered NaCl was also decreased
→ Macula Densa will detect this
• Macula Densa will decrease the reabsorption of NaCl → ATP
formation and ADP formation in the Macula Densa decreases
also → Decrease in Calcium in Afferent Arteriole
o ATP wouldn’t bind with P2X
o Adenosine wouldn’t bind with A1
• Decrease in Ca++ in Afferent will lead to vasodilation →
Decreased Afferent Arteriolar Resistance
• Renin Secretion will also increase → increase Angiotensin II →
vasoconstriction → Increased Efferent Arteriolar Resistance

• ABP is increased → increased GFR – need to decrease GFR

• Increase in the reabsorption in Macula Densa → Increased
formation of ATP and ADP → Increased Calcium in Afferent →
Vasoconstriction
• Renin Secretion will not increase → no Angiotensin II →
decreased Efferent Arteriolar Resistance

Afferent RBF GFR

Constriction ↓ ↓
Dilation ↑ ↑
• Endothelial Cells release Nitric Oxide
Efferent RBF GFR • Nitric Oxide can cause vasodilatation
Constriction ↓ ↑ • Endothelin will also be increased → vasoconstriction
Dilation ↑ ↓ • Endothelial Cells can also release Prostacyclin and
Prostaglandin → vasodilatation
Afferent will always be the basis since it is the one dictating the
regulation.

• Note: Sympathetic causes vasoconstriction in increasing

strength
• Mild and moderate sympathetic activation → little effect on
both RBF and GFR
• Strong activation → decreases RBF and GFR

• Norepinephrine, Epinephrine, Endothelin

o Constrict Afferent and Efferent Arteriole
o Decreases RBF and GFR
o NE and E are metabolized by Renalase
→ If NE and E are already in excess due to massive
activation of Sympathetic NS, the kidney can release
Renalase to metabolize NE and E
• Angiotensin II • Fluid Reabsorbed = 178.5 – 179 L/day
o Constrict Afferent and Efferent* Arteriole • NaCl = 1kg
o Decreases RBF and increases GFR (low or normal • Sugar = 1/4 kg
concentration) – only Efferent is constricted • Vit C = 4 g
o Decreases RBF and GFR (high concentration) • NaHCO3 = 1/2 kg
• Adenosine • Amino Acid = 1/10 kg
o Constrict Afferent Arteriole
o Decreases RBF and GFR GFR = 125 mL/min x 60min = 7500 mL/hour
• Endothelin-Derived Relaxing Factor (NO) 7500 mL/hr x 24 hrs = 180,000 mL/day or 180 L/day
o Causes vasodilatation – decreasing vascular resistance
o Increases GFR and RBF • Urine excreted is only 1 to 1.5 L/day
• Prostaglandin o Remaining 178.5 – 179 L/day → Reabsorbed
o Causes vasodilatation – decreasing vascular resistance
o Increases RBF but not affecting the GFR (dampens effect of
Sympathetic NS)
• Reabsorbs approximately 67% of the filtered water, Na, Cl, K,
• Dopamine
and other solutes
o Causes vasodilatation – decreasing vascular resistance
o Aside from Mg – Loop of Henle
o Increases GFR and RBF
o Inhibits Renin Secretion • 100% of the filtered glucose, amino acids
• Acetylcholine, Bradykinin, Histamine • Secretes organic cations and anions
o Causes vasodilatation – decreasing vascular resistance
o Increases GFR and RBF What are the substances present in the blood, present in the
filtrate, but not in the urine? Glucose, Amino Acids, and some
Stimulus Effect on Effect on proteins. This is because when you filter it, 100% is reabsorbed.
GFR RBF
Vasoconstrictors
Sympathetic ↓ ECFV ↓ ↓
Nerves • Glucose, SO4, PO4, Amino Acid, Lactate, Malate, Vit. C
Angiotensin II ↓ ECFV ↓ ↓
Endothelin ↑ Stretch, A-II, ↓ ↓ ↑ (very high Tm, glucose) → ↑↑↑ reabsorption → ↓ excretion
Bradykinin, → ↓↓↓ Clearance
Epinephrine;
↓ ECFV ↓ (very low Tm, creatinine) → ↓↓↓ reabsorption → ↑ excretion
Vasodilators → ↑↑↑ Clearance
Prostaglandins ↓ECFV; ↑ Shear No ↑
(PGE1, PGE2, stress, A-II Change / • Needs carriers
PGI2) Histamine ↑ • If you’re diabetic, before you have presence of glucose in the
Bradykinin, ATP urine, you need to have a blood sugar of 180 and above in
Nitric Oxide average
↑ Shear stress, Ach, ↑ ↑
Histamine
Bradykinin, ATP
• Na, Cl, and HCO3
Bradykinin ↑ Prostaglandins, ↑ ↑
• They don’t use carrier but are dependent on the gradient.
↓ ACE
Natriuretic ↑ ECFV ↑ No
Peptides (ANP, Change Tubular Secretion
BNP)

A-II – Angiotensin II; ACE – Angiotensin-Converting Enzyme; ECFV –

Extracellular Fluid Volume; Ach - Acetylcholine

Tubular Reabsorption

Amount Secreted = Amount Excreted – Amount Filtered

• Opposite of reabsorption
o Reabsorption – from the tubule to the blood
o Secretion – from the blood to the tubule

Amount Reabsorbed = Amount Filtered – Amount Excreted Quantification:

What happens to the substance if: QF > QE
• The transport of substances from the tubule back to the blood Reabsorbed
What happens to the substance if: QF < QE
• Example:
Secreted
o Amount Filtered: 150
o Amount Excreted: 50
o Amount Reabsorbed: 100
• Quantitatively large
What are the substances that are not freely filtered therefore
are only present in the blood but not in the filtrate and are
therefore not in the urine? Excretion Rate = Zero
Proteins and Cells
What are the substances that are freely filtered, therefore
present in the filtrate, but are 100% reabsorbed, therefore not
present in the urine? Excretion Rate = Zero
Glucose and Amino Acids
What are that substances that are freely filtered, not
reabsorbed, and not secreted? Filtration Rate = Excretion Rate
Creatinine and Inulin
What happens to a substance if Excretion Rate = Filtration
Rate?
Substance is freely filtered, not reabsorbed nor secreted
A substance that has excretion rate greater than filtration rate:
Freely filtered, not reabsorbed but secreted
Paraaminohipuric Acid (PAH) and Hydrogen
What are the substances with excretion rate less than its
filtration rate?
Freely filtered, partially reabsorbed
Most of the substances (Na, Cl, HCO3, Mg, etc)
Freely filtered, reabsorbed, and secreted:
Potassium (normally excretion rate < filtration rate)

TR

GFR TS

Urine
Volume