Last edited: 9/13/2021

1. FILTRATION, REABSORPTION, AND SECRETION

Filtration, Reabsorption, and Secretion Medical Editor: Mariel Antoinette L. Perez

OUTLINE II) GLOMERULUS

I) NEPHRON OVERVIEW
II) GLOMERULUS
III) PROXIMAL CONVOLUTED TUBULE (PCT)
IV) LOOP OF HENLE
V) DISTAL CONVOLUTED TUBULE
VI) COLLECTING DUCT
VII) SUMMARY
VIII) APPENDIX
IX) REVIEW QUESTIONS
X) REFRENCES

I) NEPHRON OVERVIEW

(A) DIFFERENT PARTS Figure 2. Structure of Glomerulus and Macula Densa

Glomerular Capillaries (A) NET FILTRATION PRESSURE (NFP)
Bowman’s Capsule
• There’s a mixture of pressures
o Visceral layer
• The NFP should be approximately 10 mmHg
o Parietal layer (1) Glomerular Hydrostatic Pressure (GHP)
Force that pushes plasma out of the glomerular capsule
into the bowman’s space
Proximal Convoluted Tubule (PCT) Directly dependent on systolic blood pressure
Loop of Henle o BP = GHP
Distal Convoluted Tubule o BP = GHP
Average value: 55 mmHg
(2) Colloid Osmotic Pressure (COP)
Exerted by plasma proteins like albumin
Keeps water in the blood
Average value: 30 mmHg
(3) Capsular Hydrostatic Pressure
Due to the pressure build-up in the Bowman’s capsule

Average value: 15 mmHg

(4) Colloid Osmotic Pressure
As long as the filtration membrane is intact, there should
be no proteins in the Bowman’s capsule
Average value: 0 mmHg

(B) GLOMERULAR FILTRATION RATE

Figure 1. Nephron Overview [Meltzer]
(B) DEFINITION
We have 1.2 million nephrons per kidney
o We usually have two kidneys  total of 2.4 million
nephrons
Amount of plasma fluid or volume being filtered across
this glomerular membrane into the bowman’s capsule per
minute
NFP α GFR
o NFP is directly proportional to the GFR
On average, 125 mL/min
o Per min., 1.2L goes to AA  625mL used in filtration
process  only 20% (125mL) is filtered

(C) ARTERIOLES
The glomerulus is one of the only examples in the body
wherein the capillary bed is both being fed and drained
by an arteriole
(1) Afferent Arterioles

Filtration, Reabsorption, and Secretion RENAL PHYSIOLOGY: Note #6. 1 of 5

(2) Efferent Arterioles (1) Osmolality Classification
Hypertonic
o osmolality
Due to this mechanism, a lot of fluid and filtrate o solutes (e.g., Na+,Cl–), H2O
substances will accumulate in the Nowman’s capsule and o hypertonic
drained into the next structure (PCT) Hypotonic
o osmolality
III) PROXIMAL CONVOLUTED TUBULE (PCT) o solutes (e.g., Na+,Cl–), H2O
One of the most important sites of a nephron Isotonic
o solutes = H2O
(A) TUBULAR REABSORPTION
Movement of substances in filtrates from the kidney (D) RENAL PYRAMID
tubule into the blood (1) Renal Cortex
Depending upon the chemicals being reabsorbed, it could
o Outer layer
be active or passive
o Lighter granulated tissue
A lot of filtrates are reabsorbed here
o Where PCT, DCT, and glomerular capillaries are
o Sodium (Na+), Potassium (K+), Water (H2O), Chloride
located
(Cl–), Magnesium (Mg2+), Calcium (Ca2+), Bicarbonate
(HCO3–), small proteins, lipids (2) Renal Medulla
65% of Na+ are reabsorbed o Striated due to the kidney tubule
o Some substances (i.e., glucose, amino acids) will go
with Na+ via a cotransport mechanism IV) LOOP OF HENLE
 These will be reabsorbed depending on the
Osmolality value before entering Loop of Henle
presence of Na+
o 300 mosm
o 100% glucose will be ideally reabsorbed
 Isotonic with blood plasma
 Glucosuria: traces of glucose in the urine
• Identifiable in diabetic patients Na+/K+/2Cl– Transporter
 Amount of Na+ being reabsorbed can increase (so o Pumps out Na+, K+, and 2 Cl– ions from the filtrate as
that glucose will follow) until blood glucose levels blood goes up the ascending limb of Loop of Henle
reach above 180 mg/dL  Happens along the entire length of ascending limb
• Transporters will saturate when it reaches o 25% Na+ is reabsorbed
transport maximum  solutes get lost in the o 30% of K+ is reabsorbed
urine o 30% of Cl– is reabsorbed

65% of H2O is also reabsorbed because it follows Na+ Some K+ gets pushed back in the lumen  creates a
o Due to obligatory water reabsorption depolarization on the ascending limb’s inner membrane
o Causes Mg2+ and Ca2+ to undergo passive
85-95% of HCO3– are reabsorbed paracellular transport into the medullary space
Questionable amount of Mg2+ will be reabsorbed
o Various literature say different values The ions being pumped out of the ascending limb
contribute to the medullary gradient  becomes saltier
60% of K+ will be reabsorbed down the gradient
50-60% of Cl– will be reabsorbed o Becomes hypotonic
60% of Ca2+ will be reabsorbed  Solutes < H2O
50% of urea will be reabsorbed
Small proteins (insulin, albumin, a bit of hemoglobin) can Water going down the descending limb is inclined to go
get reabsorbed via endocytosis out into the medullary space where it is saltier
Lipids o Water leaks out via the aquaporin-I
o undergo passive diffusion through the phospholipid o Becomes hypertonic
bilayer  Solutes > H2O
 enables them to get reabsorbed in the PCT Counter-Current Multiplier Mechanism
o Water leaks out of the descending limb due to ions
(B) TUBULAR SECRETION
getting pumped out of the ascending limb
Movement of substances from blood into the filtrates in  15% of H2O is reabsorbed
the kidney tubule  Hence, only 20% of H2O is left
active process: requires ATP
o Adenosine Triphosphate V) DISTAL CONVOLUTED TUBULE
o “Energy currency of the cell”
By the time blood reaches DCT, it’s 100-200 mosm
The body may need or want to secrete (excrete) certain o 20% H2O left
substances o 10% Na+ left
o Drugs, H+ or HCO3–, NH4+, traces of creatinine
(A) EARLY DISTAL TUBULE
(C) OSMOLALITY
(1) Sodium-Chloride Symporter
Blood Plasma Osmolality
o 300 mosm (milliosmoles) Specialized transporters on the lumina membrane closest
 Isotonic (similar value) with PCT and start of to the urine
descending limb Na+ and Cl– both go into the cell via protein channels
Only possible due to Na+/K+ pump
General flow of Osmolality (Renal Medullary Gradient)
o 300 mosm  500  700  900  1200 (deep in (2) Sodium-Potassium Pump
renal medulla)
Specialized channels in basolateral membrane
Pumps 3 Na+ ions out and 2 K+ ions in the cell

2 of 5 RENAL PHYSIOLOGY: Note #6 Filtration, Reabsorption, and Secretion

 o Both ions are flowing against their respective
concentration gradients
Requires ATP
(3) Na+ and Cl– Reabsorption
Once inside the cell, both Na+ and Cl– are reabsorbed
back into the blood
o Both ions are flowing along their respective
concentration gradients
5-6% of Na+ is being reabsorbed here
o 4-5% is left
(4) Ca2+ Reabsorption
Hypocalcemia
o Low blood calcium levels [Ca2+]
o Stimulate parathyroid gland to secrete parathyroid
hormone (PTH)
 PTH binds and stimulates the G-protein coupled
receptor on the cell of DCT
 Overall result: cAMP activates Protein Kinase A
Calcium Modulated Channels
o Stimulated by Protein Kinase A via phosphorylation
o Pulls in ~10% Ca2+ into the cell
 Calcium may be bound to protein called calbindin
o Very sensitive to levels of PTH
[Ca2+blood] > [Ca2+cell]
o Even if [Ca2+blood], there’s fewer calcium inside the
cell. [Ca2+] will need to move against its concentration
gradient from the cell to get into the blood
Two mechanisms to reabsorb calcium back into the blood
o Ca2+/Na+ Exchanger
 Proteins on the basolateral membrane
 Pumps Ca2+ out and brings Na+ in
 Secondary active transport
o Ca2+/H+ Exchanger
 Uses ATP
 H+ is pumped in, while Ca2+ is pumped out.
PTH
o Other than Ca2+, it can also affect phosphates
 Phosphates is reabsorbed in PCT
 HPO42– (monohydrogen phosphate)
 Can naturally get reabsorbed (~85%) in the blood
o Presence of PTH causes phosphate excretion
(B) VASA RECTA
Peritubular capillary network present within the deep part
of the medulla
Known as the “Counter-Current Exchanger”
o Maintains the medullary interstitial gradient
 Saltiness of the medulla
 Does not generate the gradient
As the ascending limb goes up, it pumps the solutes out
 pulling water out of the descending limb
o Solutes: Mg2+, Ca2+, K+, Cl–, Na+
Counter-Current Multiplier Mechanism
o Vasa Recta gets saltier as it goes down
 Water wants to flow out towards where it’s salty
• Obligatory Water Reabsorption
 NaCl is pulled into the Vasa Recta
o Processes reverses when vasa recta turns & goes up
 Water now wants to go back inside
 NaCl is being pushed back inside as we go up
Two functions
o Prevents rapid removal of sodium chloride
 When blood enters, it’s 300 mosm
 When blood leaves, it’s 325 mosm
• This implies that the vasa recta kept a bit of
NaCl with it to prevent rapid removal
o Carries Oxygen
Filtration, Reabsorption, and Secretion
 Vasa recta also delivers oxygen and nutrients
(C) LATE DISTAL TUBULE
(1) Aldosterone
Steroid hormone produced by zona glomerulosa in the
adrenal cortex
o Adrenal gland is located on top of the kidneys
o Passes through cell’s lipid bilayer (steroid)
Stimulus
o Angiotensin-II
 Works to increase pressure
o Hyponatremia
 When [Na+] levels in the blood is decreasing
o Hyperkalemia
 When [K+] levels in the blood is increasing
Once inside the cell, it will stimulate special genes 
production of three different proteins
(i) Na+ channel
 Protein embedded in the luminal membrane
 To get Na+ inside the cell
• Possible due to the effects of the Na+/K+ Pump
(ii) Na+/K+ Pump
 Protein found in the basolateral membrane
 Active transport: uses ATP
• Ions move against their concentration
gradients
 Transports 3 [Na+] out and 2 [K+] into the cell
• Na+ leaves the cell  [Na+] in the cell
o Na+ goes inside the cell via Na+ channel
• [K+] enters the cell  [K+] in the cell
(iii) K+ channel
 embedded in the luminal membrane
 To increase K+ out
 Since there’s [K+] inside the cell, the channel will
move it out of the cell where it will eventually be
excreted into the urine
(2) Antidiuretic Hormone (ADH) / Vasopressin
released whenever the plasma osmolality is changing
from the Hypothalamus
o Collection of neurons from the supraoptic nucleus
o Axons move through from the hypothalamus to the
posterior pituitary
Specialized osmoreceptors found in the late distal tubule
and collecting duct
(i) Stimulus
 High plasma osmolality
• There’s a lot of salt and little water
o ADH will reabsorb more water in the blood
 Angiotensin-II
• To increase blood pressure
(ii) Process
 ADH will stimulate the cells to express aquaporins
 Aquaporin-II will open up
 H2O will have to follow the salt and go into the cell
 H2O volume getting pulled into the bloodstream
 blood pressure
RENAL PHYSIOLOGY: Note #6. 3 of 5
 VI) COLLECTING DUCT
(A) PRINCIPAL CELL
Cells that maintain mineral and water balance
(1) Antidiuretic Hormone (ADH) / Vasopressin
(i) Process
ADH binds to V2 (vasopressin) receptor (on the
principal cell) in the collecting duct of the kidneys
Will activate the secondary messenger system
Activates G-stimulatory protein  GTP  adenylate
cyclase
o converts ATP  cAMP
cAMP activates Protein Kinase A
o Phosphorylates the proteins on the vesicles
 Pre-synthesized vesicles with proteins and
channels (aquaporins)
o Stimulates aquaporin-II
 Migrates and fuses with the cell membrane
 Note that aquaporin-III and aquaporin-IV are found
in the basolateral membrane
(ii) Water Reabsorption
 Water goes inside the cell via aquaporin-II
 Passes through aquaporins III & IV on the
basolateral membrane
 Goes into the bloodstream
 Increases blood volume
 Increases blood pressure
 Brings plasma osmolality down
• Reaches normal osmolality value (300 mosm)
• Isotonic
(B) INTERCALATED A-CELL
Responds to acidosis
o Respiratory acidosis
o Metabolic acidosis
Scenario: there’s CO2 in the blood
o In an acidosis, there is low pH = many protons (H+)
o Very little bases to counteract the protons
CO2 + H2O  H2CO3  H+ + HCO3–
o Catalyzed by enzyme carbonic anhydrase
o Carbon Dioxide (CO2) in our blood moves into the
cell, and combines with water to form H2CO3
o Sodium Bicarbonate (H2CO3) is unstable;
dissociates into proton and HCO3–
Pumps Protons (H+) out
o Via the H+/K+-ATPase
 In between the interstitium and the cell
 ATP-dependent pathway
• Both ions are moving against their
concentration gradients
 K+ goes into the cell
 H+ goes out of the cell
Brings Bicarbonate (HCO3–) inside the blood
o via the HCO3–/Cl– transporter
 in between the cell and the blood
 Cl– goes into the cell
 HCO3– goes out of the cell
4 of 5 RENAL PHYSIOLOGY: Note #6
(C) INTERCALATED B-CELL
Responds to alkalosis
o Respiratory alkalosis
o Metabolic alkalosis
The same reaction below as in the intercalated A-cell
o CO2 + H2O  H2CO3  H+ + HCO3–
The difference is that the B cell
o Excretes HCO3–, instead of the proton
o Reabsorbs H+ into the blood instead of bicarbonate
Works to bring the pH back down
(D) MORE EXCRETION
There are also other cells that could be excrete drugs,
toxins, creatinine, ammonia, uric acid, other nitrogenous
waste products, protons, bicarbonate
Ammonia (NH3)
o Can be excreted out into the urine where it combines
with proton (H+) to produce ammonium (NH4+)
(E) UREA RECYCLING
Urea gets reabsorbed in the last part of the collecting duct
o At the end of collecting duct, a lot of H2O was lost
Urea excreted into the urine contributes in urine
concentration
Urea is a lipid-soluble solute
Some urea gets recycled
o Moves out of the collecting duct and accumulates into
the medullary interstitium via facilitated diffusion
 More H2O flows out into the medullary interstitium
VII) SUMMARY
(1) Water reabsorption
65% reabsorbed in the PCT
15% reabsorbed in descending limb of Loop of Henle
20% reabsorption in DCT is variable
o dependent on presence of ADH (stimulates
aquaporin-II expression)
o ADH = more water reabsorption
o ADH = less water reabsorption
(2) Sodium reabsorption
65% reabsorbed in the PCT
25% reabsorbed in the descending limb of Loop of Henle
5-6% reabsorbed in early DCT
o Via Na+/Cl– symporter
4-5% reabsorption dependent on presence of aldosterone
(3) Calcium reabsorption
Dependent on the presence of PTH
Filtration, Reabsorption, and Secretion
 VIII) APPENDIX

Figure 3. Overview of Filtration, Reabsorption, and Secretion

IX) REVIEW QUESTIONS X) REFRENCES

● Sabatine MS. Pocket Medicine: the Massachusetts General
1) Presence of ADH increases the expression of which
Hospital Handbook of Internal Medicine. Philadelphia: Wolters
of the following? Kluwer; 2020.
a) aquaporin-I ● Le T. First Aid for the USMLE Step 1 2020. 30th anniversary
b) aquaporin-II edition: McGraw Hill; 2020.
● Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL,
c) aquaporin-III Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth
d) aquaporin-IV Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical; 2018
● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
Pearson; 2020.
2) What triggers aldosterone production? ● Boron WF, Boulpaep EL. Medical Physiology.; 2017.
a) hyponatremia Guyton and Hall Textbook of Medical Physiology. Philadelphia, PA:
Elsevier; 2021.
b) angiotensin-II ● Meltzer, J. S. (2019). Renal Physiology. Pharmacology and
c) hyperkalemia Physiology for Anesthesia (Second Edition), 782–794.
d) All of the above https://doi.org/10.1016/b978-0-323-48110-6.00040-5

3) How much H2O is reabsorbed in the DCT?

a) 65%
b) 15%
c) 20%
d) Variable

CHECK YOUR ANSWERS

Filtration, Reabsorption, and Secretion RENAL PHYSIOLOGY: Note #6. 5 of 5