PHYSIOLOGY DEPARTMENT

BODY FLUIDS & ELECTROLYTES BALANCE

ACID-BASE BALANCE (RENAL PHYSIOLOGY)

by
MR ODEYEMI SAMUEL

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 OUTLINE
• BODY FLUID AND ELECTROLYTE
BALANCE

• ACID BASE BALANCE

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Functions of kidney
• (1) Homeostasis (maintaining composition of internal
environment - ECF, blood, and plasma).Blood plasma in
equilibrium with ECF - so controlling blood composition will
control the composition of the ECF.

• (2) Regulates electrolytes (Na/K, Cl, Ca, Mg, PO4) in blood.

Controls release of ions into urine. Proper ECF (ion) helps
maintain plasma volume (osmotic pressure).

• (3) Regulates water balance in the body - through conservation

or excretion into the urine.
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Functions of kidney
(4) Maintain pH by controlling H+ and HCO3 excretion into
urine. Diarrhea, acidosis & dehydration
• Acidosis - losing lots of bicarb. Diarrhea - losing lots of water
leads to dehydration. Kidneys can deal with acidosis and
dehydration, but not diarrhea.

• (5) Excrete metabolic waste products - filters the blood.

Endogenous substances - (nitrogenous -creatinine, urea, uric
acid, ammonia)

• (6) Excretion of foreign compounds from the body (Exogenous

substances
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such as drugs and chemicals - at least the one that are
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Functions of kidney
(7) Secretes hormones: Erythropoitein and renin, i.
Erythropoietin, Thrombopoietin1,25-
dihydroxycholecalciferol (calcitriol), Prostaglandins.

• (8) Metabolic Functions: converts Vit D into active form

(calcidiol —> calcitriol).

(9) Gluconeogenesis: During prolonged fasting, the

kidneys synthesize glucose from amino acids and other
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Urine

Formation
Urine formation is a blood cleansing function. Normally, about 1,300
mL of blood (26% of cardiac output) enters the kidneys.

Kidneys excrete the unwanted substances along with water from the
blood as urine. Normal urinary output is 1 L/day to 1.5 L/day.

When blood passes through glomerular capillaries, the plasma is

filtered into the Bowman capsule. This process is called glomerular
filtration.

Filtrate from Bowman capsule passes through the tubular portion of

the nephron. While passing through the tubule, the filtrate undergoes
various changes both in quality and in quantity.

Many wanted substances like glucose, amino acids, water and

electrolytes are reabsorbed from the tubules. This process is called
tubular reabsorption.
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Processes of Urine Formation
The processes of urine
formation include:

A. Glomerular filtration
B. Tubular reabsorption
C. Tubular secretion.

Among these three

processes filtration is the
function of the glomerulus.
 Reabsorption and secretion
are the functions of tubular
portion of the nephron.

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•

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Processes of Urine formation
•

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Glomerular

filtration
Glomerular filtration is the process by which the blood is filtered
while passing through the glomerular capillaries by filtration
membrane.
The structure of filtration membrane is well suited for filtration.
Filtration Membrane
Filtration membrane is formed by three layers:
1. Glomerular capillary membrane: is formed by single layer of
endothelial cells. It has many pores called fenestrae or filtration
pores with a diameter of 0.1 μ.

2. Basement membrane: this is formed by fusion of basement

membrane of both capillary and visceral layer.

3. Visceral layer of Bowman capsule: This layer is formed by a single

layer of flattened epithelial cells resting on a basement membrane
which is connected to basement memb by pedicle(feet). Epithelial
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Glomerular filtration
• What is filtered out of the glomerulus (into tubule)?
• Water (plasma)
• Electrolytes (Na, K, Cl, Ca).

• Small Proteins (cutoff ~ 70 kDa) anything smaller gets through filtration

slits, anything bigger cannot get through unless there is a kidney
dysfunction. Looking at protein content in the urine has a high diagnostic
value).

• Albumin ~69 kDa , urine:plasma ratio <1% - vast majority of albumin does
not get filtered (stays in the plasma). During intense exercise some albumin
can leak out.

• Hemoglobin ~68 kDa, urine:plasma ration <5% - only filtered if not

bound to haptoglobin (when Hb bound to haptoglobin its way to big to get
through the filtration slits). Some Hb can be seen with intravascular RBC
breakdown.
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Glomerular filtration
• What is NOT filtered?
• Most plasma proteins (albumin, globulins usually too large to
pass through).

• Red/White blood cells and platelets (too large).

• Negatively charged compounds have more difficulty being

filtered.

• Because they are repelled by negatively charged proteoglycans

on the glomerulus basement membrane.

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Filtration Forces
• Filtration Forces Equation:
• Net Filtration Pressure (how much overall pressure there is that
pushes/pulls on the filtrate) = Capillary blood pressure in glomerulus –
Plasma colloid osmotic pressure – Bowmans capsule hydrostatic
pressure.

• (1 )Capillary Blood Pressure (favours filtration):

• Pressure “pushing” plasma into bowmans capsule.

• High pressure – pushes filtrate into capsule

•
• Is controlled by the diameter of afferent and efferent arterioles.

• If diameter of afferent arteriole > efferentcauses a backlog of blood

in the glomerulus that increases capillary blood pressure in glomerulus
that favours filtration.
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Filtration Forces
• (2) Plasma Colloid Oncotic Pressure (opposes filtration of
plasma):
• Plasma proteins (albumin and globulins) are too large for
filtration they kind of keep water/plasma around them.

• Osmotic force of non-filtered protein “pulls” plasma back into

glomerulus from Bowman’s capsule. Opposes capillary blood
pressure.

• (3) Bowmans Capsule Hydrostatic Pressure (opposes filtration):

• the filtrate already in Bowman’s capsule Pushes filtrate out of
bowmans capsule, back into the glomerulus.
• Until it moves out of the capsule new fluid can’t move in.
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Filtration Forces
•

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Glomerular Filtration Rate (GFR)
 Glomerular filtration rate (GFR) is defined as the total quantity of
filtrate formed in all the nephrons of both the kidneys in the given
unit of time.

 Human cardiac output (CO) = 6L/minutes (stroke volume – 100ml/beat

(HR- 60bpm))
 Renal arteries receive = 20% of CO (1.2L/min)
 Packed cell volume = 50% ,(so renal arteries receive- 600ml plasma/m)
 Filteration fraction = in humans- 20% of the plasma entering glomerulus is
filtered into Bowman’s capsule (125ml/min)
 125ml/min X 1440min/day = 180L/day

Hence,
Normal GFR is 125 mL/minute or about 180 L/day.
No animal can actually urinate 180 L/day – so obviously something
is happening to reabsorb the filtrate
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Filtration Forces and GFR
• Four forces act on the
filtration membrane
• 1) Blood hydrostatic pressure
(increase GFR)

• 2) Blood colloid osmotic

pressure (decrease GFR)

• 3) Bowman`s space hydrostatic

pressure ( decrease GFR)

• 4) Bowman`s space oncotic

pressure ( increase GFR)

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Factors affect the GFR
• 1) Filtration coefficient
a. Permeability increased in hypoxia & toxicity.
b. Contraction and relaxation of mesangial cells.

•2) Hydrostatic pressure in Bowman's capsule decrease the GFR in acute

obstruction of urinary tract.

• 3) Blood hydrostatic pressure ( GFR is constant from 80 mmHg to 200

mmHg) decreases in acute renal failure lead to decline in GFR

• 4) Renal blood flow & afferent and efferent arteriole resistance ?!

• 5) Blood oncotic pressure( Hyperproteinemia lead to decrease in GFR)

•
•6) Sympathetic stimulation ( little important ) decrease
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Regulation of GFR (renal blood flow)
1. Autoregulation 2 Tubuloglomerular Feedback

• (Kidney controlling itself) o

Kidneys try to maintain
constant blood flow to the
glomerulus.
•Easiest way: change afferent
arteriole diameter.

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Regulation of GFR (renal blood flow)
•

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Tubular Reabsorption
Tubular reabsorption is the process by which water and other
substances are transported from renal tubules back to the
blood.

When the glomerular filtrate flows through the tubular portion

of nephron, both quantitative and qualitative changes occur.

Large quantity of water (more than 99%), electrolytes and

other substances are reabsorbed by the tubular epithelial cells.

The reabsorbed substances move into the interstitial fluid of

renal medulla. And, from here, the substances move into the
blood in peritubular capillaries.

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Tubular Reabsorption
• Question: If human kidneys
produce 180L of filtrate every day,
why don’t we produce that much
urine every day? Avg person
plasma vol. (10% of the time) is
only 2-4 L.

•Answer: fluid and solutes are

reabsorbed from the tubular
portion of the nephron. Body
conserves valuable material not
lose them in the urine. Have an
important role in water balance.
180 L, 99% reabsorbed
•Hence, 1.5 L of urine is produced
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 Concept of Reabsorption
• Question • Answer
• kidney Does not excrete •Most solutes (~99%) pass
glucose/AA very wasteful. through tubule cells due to tight
• Bicarbonate junctions b/w cells
variable
(transcellular).
between the acid/base balance
of the body.
• Only half the urea is excreted • Water can sometimes pass b/w
cells (paracellular) – through
“leaky” junctions in some
• why doesn’t the body just regions.
excrete it all.
•Substances are able to pass
• Water/solutes absorbed in through various junctions by
different amounts at each region various means such as diffusion,
of the nephron. Reabsorption active transport etc.
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Routes of Reabsorption
 1. Transcellular Route
 (a). Tubular lumen into tubular cell
through apical (luminal) surface of
the cell membrane
 (b). Tubular cell into interstitial
fluid
 (c). Interstitial fluid into capillary.

2. Paracelluar Route
 (i). Tubular lumen into interstitial
fluid present in lateral intercellular
space through the tight junction
between the cells

 (ii). Interstitial fluid into capillary

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Tubular Epithelium
•

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 Mechanism of Reabsorption
Basic transport mechanisms involved in tubular reabsorption are
of two types: (1). Active reabsorption (2). Passive reabsorption.

1. Active reabsorption is the movement of molecules against the

electrochemical (uphill) gradient. It needs liberation of energy,
which is derived from ATP.
Substances reabsorbed actively from the renal tubule are sodium,
calcium, potassium, phosphates, sulfates, bicarbonates, glucose,
amino acids, ascorbic acid, uric acid and ketone bodies.

2. Passive reabsorption is the movement of molecules along the

electrochemical (downhill) gradient. This process does not need
energy.
Substances reabsorbed passively are chloride, urea and water.
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 Mechanism of Reabsorption
Passive simple diffusion
•No energy required, substances pass through membrane (if lipophilic) or through
a transmembrane protein channel (hydrophilic) – rate of diffusion increases
concentration gradient and there is NO saturation.

Facilitated diffusion (passive).

• Substance binds to carrier protein on membrane and changes conformation
which translocates the substance to the other side of the membrane – can become
saturated
• Ions/charged molecules don’t get through the cell membranes easily.

Simple diffusion: linear increase in rate with increase in electrochemical

gradient.
•The higher the concentration gradient the rate of transport gets faster

Facilitated diffusion: requires specific carriers – can be saturated.

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Mechanism of Reabsorption
Primary Active Transport
 Movement of substance against electrochemical gradient
requires energy. ATPase pumps may be located on apical or
basalateral surface of tubular cells.

Secondary Active Transport

 Substance does not directly require ATP for transport. It can
co-transport with another molecule that itself will require an
active process elsewhere.

Pinocytosis (eg. Peptides) – for large substances

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Reabsorption in the proximal Tubules
• Most filtered sodium (2/3) is reabsorbed here – fairly constant! (so not a
major site of regulation – but can be regulated a little bit with angiotensin
II and sympathetic neurons that try to increase blood volume and blood
pressure).
• Na+ cotransport (secondary active transport)
Glucose (SGLT), A.A, phosphate.
• Passive Reabsorption (still Na+ dependent)
Chloride (electrical gradient),
Water – follows chloride
K+ and Urea – follows water/Cl- (osmotic pull AKA
solvent drag – depends on flow rates).

• Calcium and phosphorus – depends on filtrate concentration and

parathyroid hormone (PTH).

• HCO3-
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is “absorbed” in proximal tubule 31
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Reabsorption in the loop of Henle
Water reabsorbed in the descending loop
• ¼ of the total filtered Na+ load reabsorbed in the thick ascending loop.
(1) Different transporter: Na+, K+, 2Cl- symporter for reabsorption

(2) Na transport here creates osmotic gradient in the medulla

(facilitates urine concentration).

Why is the symporter clinically relevant?

Diuretics – inhibits the symporter in the thick ascending limb
of the loop of henle. Sodium becomes stuck in the tubule lumen (if
sodium stays, water stays too).

Na+ reabsorption in the distal nephron (AKA collecting duct)

65% in proximal tubule
25% ascending loop of Henle
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Reabsorption in the Distal Tubules & CT
•

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Hormones regulating tubular reabsorption

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RAAS

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Tubular Secretion
 Tubular secretion is the process by which the substances are
transported from blood into renal tubules.

 It is also called tubular excretion. In addition to reabsorption from

renal tubules, some substances are also secreted into the lumen
from the peritubular capillaries through the tubular epithelial cells.

 Dye phenol red was the first substance found to be secreted in renal
tubules in experimental conditions.

 Later many other substances were found to be secreted which

include
Paraaminohippuric acid (PAH), Diodrast, 5hydroxyindoleacetic
acid (5HIAA), Amino derivatives, Penicillin.
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Tubular Secretion
• Some waste products cannot be filtered at the glomerulus:
Too large to pass through filtration slits
Bound to proteins that are too large
Negative charged, so repelled by negative charge on basement membrane
• Secrete them into the tubule (After the glomerulus) from the peritubular capillaries.
• Examples:
• 1) Hydrogen Ions (H+)
Secreted along most of nephron
Proximal tubule: Na+/H+ antiporter
Distal tubule/Collecting duct: K+/H+ antiporter (reabsorbed K+ and
secretes H+)
• Solves the acidosis
Useful in acidosis – to rid of hydrogen ions

•2) Potassium (K+)

• Reabsorbed in proximal tubule automatically
• Variable reabsorption/secretion in distal nephron:
Decreased BP: RAAS activation
Aldosterone release to conserve Na+
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Tubular Secretion
• Tubular secretion/reabsorption play a big part in potassium and
sodium balance
• Secretion of other drugs/toxins/metabolites:
•Varying degrees of transporter-substrate specificity

• Transporters include P-glycoprotein, Organic anion transporters

are efficient at secreting foreign compounds into the urine.

• Renal secretion after hepatic metabolism

Phase I reactions in liver
Phase II reactions – conjugation reactions
Hydroxylation, glucuronidation, acetylation, etc
to make drugs hydrophilic (allows urinary
excretion).
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Tubular Secretion
SUBSTANCES SECRETED IN DIFFERENT SEGMENTS OF
RENAL TUBULES
1. Potassium is secreted actively by sodium potassium pump in
proximal and distal convoluted tubules and collecting ducts

2. Ammonia is secreted in the proximal convoluted tubule

3. Hydrogen ions are secreted in the proximal and distal

convoluted tubules. Maximum hydrogen ion secretion occurs
in proximal tubule

4. Urea is secreted in loop of Henle.

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Concentration of urine
 Every day 180 L of glomerular filtrate is formed with large
quantity of water.

If this much of water is excreted in urine, body will face serious
threats. So the concentration of urine is very essential.

Osmolarity of glomerular filtrate is same as that of plasma and

it is 300 mOsm/L. But, normally urine is concentrated and its
osmolarity is four times more than that of plasma, i.e. 1,200
mOsm/L.

Osmolarity of urine depends upon two factors:

1. Water content in the body
2. Antidiuretic hormone (ADH).
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Concentration of urine
FORMATION OF DILUTE URINE
When, water content in the body increases, kidney excretes dilute urine.
This is achieved by inhibition of ADH secretion from posterior pituitary.
So water reabsorption from renal tubules does not take place leading to
excretion of large amount of water. This makes the urine dilute.

FORMATION OF CONCENTRATED URINE

When the water content in body decreases, kidney retains water and
excretes concentrated urine. Formation of concentrated urine is not as
simple as that of dilute urine.

It involves two processes:

1. Development and maintenance of medullary gradient by
countercurrent system
2. Secretion of ADH.
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Nephron
•

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Classification of Nephron
•

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 (1) MEDULLARY GRADIENT
MEDULLARY HYPEROSMOLARITY
Cortical interstitial fluid is isotonic to plasma with the osmolarity
of 300 mOsm/L. Osmolarity of medullary interstitial fluid near
the cortex is also 300 mOsm/L.

 However, while proceeding from outer part towards the inner part
of medulla, the osmolarity increases gradually and reaches the
maximum at the inner most part of medulla near renal sinus.
Here, the interstitial fluid is hypertonic with osmolarity of 1,200
mOsm/L

This type of gradual increase in the osmolarity of the medullary

interstitial fluid is called the medullary gradient. It plays an
important role in the concentration of urine.
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Development of Medullary Gradient
 Kidney has some unique mechanism called
countercurrent mechanism.

 This is responsible for the development and

maintenance of medullary gradient and
hyperosmolarity of interstitial fluid in the
inner medulla.

COUNTERCURRENT MECHANISM
„ Countercurrent Flow
 A countercurrent system is a system of
‘U’shaped tubules (tubes) in which, the flow of
fluid is in opposite direction in two limbs of
the ‘U’shaped tubules

Countercurrent system has two divisions:

1. Countercurrent multiplier formed by loop of
Henle
2.04/06/2024
Countercurrent exchanger formed by vasa 54
Countercurrent Multiplier
• Loop of Henle
• Loop of Henle functions as countercurrent multiplier. It is
responsible for development of hyperosmolarity of medullary
interstitial fluid and medullary gradient.

Loop of Henle of juxtamedullary nephrons plays a major role as

countercurrent multiplier because loop of these nephrons is long
and extends up to the deeper parts of medulla.

Main reason for the hyperosmolarity of medullary interstitial

fluid is the active reabsorption of sodium chloride and other
solutes from ascending limb of Henle loop into the medullary
interstitium.

These solutes accumulate in the medullary interstitium and

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Countercurrent Multiplier
 Due to the concentration gradient, the sodium and chlorine ions
diffuse from medullary interstitium into the descending limb of
Henle loop and reach the ascending limb again via hairpin bend.

 Thus, the sodium and chlorine ions are repeatedly recirculated

between the descending limb and ascending limb of Henle loop
through medullary interstitial fluid leaving a small portion to be
excreted in the urine.

 Apart from this there is regular addition of more and more new
sodium and chlorine ions into descending limb by constant filtration.

 Thus, the reabsorption of sodium chloride from ascending limb and

addition of new sodium chlorine ions into the filtrate increase or
multiply the osmolarity of medullary interstitial fluid and medullary
gradient. Hence, it is called countercurrent multiplier.
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Countercurrent Multiplier
Other Factors Responsible for Hyperosmolarity of Medullary
Interstitial Fluid
In addition to countercurrent multiplier action provided by the loop
of Henle, two more factors are involved in hyperosmolarity of
medullary interstitial fluid.

i. Reabsorption of sodium from collecting duct

Reabsorption of sodium from medullary part of collecting duct into
the medullary interstitium, adds to the osmolarity of inner medulla.

ii. Recirculation of urea

Fifty percent of urea filtered in glomeruli is reabsorbed in proximal
convoluted tubule. Almost an equal amount of urea is secreted in
the loop of Henle. So the fluid in distal convoluted tubule has as
much urea as amount filtered.
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 Countercurrent Multiplier
• ii. Recirculation of urea cont’d
 Collecting duct is impermeable to urea. However, due to the water
reabsorption from distal convoluted tubule and collecting duct in the
presence of ADH, urea concentration increases in collecting duct.

 Now due to concentration gradient, urea diffuses from inner

medullary part of collecting duct into medullary interstitium.

 Due to continuous diffusion, the concentration of urea increases in

the inner medulla resulting in hyperosmolarity of interstitium in
inner medulla.

 By concentration gradient, urea enters theascending limb. From here,

it passes through distal convoluted tubule and reaches the collecting
duct. Urea enters the medullary interstitium from collecting duct.
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Countercurrent Multiplier
 By this way urea recirculates
repeatedly and helps to
maintain the hyperosmolarity
of inner medullary interstitium.
Only a small amount of urea is
excreted in urine.

Urea recirculation accounts for

50% of hyperosmolarity in inner
medulla. Diffusion of urea from
collecting duct into medullary
interstitium is carried out by
urea transporters, UTA1 and
UTA3, which are activated by
ADH.
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Countercurrent Exchanger
 Vasa Recta
Vasa recta functions as countercurrent exchanger. It is
responsible for the maintenance of medullary gradient, which is
developed by countercurrent multiplier.

Role of Vasa Recta in the Maintenance of Medullary Gradient

Vasa recta acts like countercurrent exchanger because of its
position. It is also ‘U’shaped tubule with a descending limb,
hairpin bend and an ascending limb. Vasa recta runs parallel to
loop of Henle.

Its descending limb runs along the ascending limb of Henle

loop and its ascending limb runs along with descending limb of
Henle loop.
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Countercurrent Exchanger
The blood flows very slowly through
vasa recta. So, a large quantity of
sodium chloride accumulates in
descending limb of vasa recta and flows
slowly towards ascending limb.

By the time the blood reaches the

ascending limb of vasa recta, the
concentration of sodium chloride
increases very much.

This causes diffusion of sodium

chloride into the medullary
interstitium. Simultaneously, water
from medullary interstitium enters the
ascending
04/06/2024 limb of vasa recta. And the 61
Countercurrent Exchanger
Therefore, when blood passes through the
ascending limb of vasa recta, sodium
chloride diffuses out of blood and enters
the interstitial fluid of medulla and, water
diffuses into the blood.

Thus, vasa recta retains sodium chloride in

the medullary interstitium and removes
water from it. So, the hyperosmolarity of
medullary interstitium is maintained.

Recycling of urea also occurs through vasa

recta. From medullary interstitium, along
with sodium chloride, urea also enters the
descending limb of vasa recta. When
blood passes through ascending limb of
vasa
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(2) ROLE OF ADH
Final concentration of urine is achieved by the action of ADH.
Normally, the distal convoluted tubule and collecting duct are
not permeable to water.

But the presence of ADH makes them permeable, resulting in

water reabsorption. Water reabsorption induced by ADH is
called facultative reabsorption of water.

A large quantity of water is removed from the fluid while

passing through distal convoluted tubule and collecting duct.
So, the urine becomes hypertonic with an osmolarity of 1,200
mOsm/L.

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Role of ADH
•

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Role of Kidney in Acid Base Balance
Kidney plays an important role in maintenance of acid-base
balance by excreting hydrogen ions and retaining bicarbonate
ions.

Normally, urine is acidic in nature with a pH of 4.5 to 6.

Metabolic activities in the body produce large quantity of acids
(with lot of hydrogen ions), which threaten to push the body
towards acidosis.

However, kidneys prevent this by two ways:

1. Reabsorption of bicarbonate ions (HCO3 –)
2. Secretion of hydrogen ions (H+).

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Role of Kidney in Acid Base Balance
(1) Reabsorption of bicarbonate ions (HCO3 –):
About 4,320 mEq of HCO3 – is filtered by the glomeruli
everyday. It is called filtered load of HCO3 –. Excretion of this
much HCO3 – in urine will affect the acid-base balance of body
fluids. So, HCO3– must be taken back from the renal tubule by
reabsorption.

2. Secretion of hydrogen ions (H+) :

Reabsorption of filtered HCO3 – occurs by the secretion of H+
in the renal tubules. About 4,380 mEq of H+ appear every day in
the renal tubule by means of filtration and secretion.
 Not all the H+ are excreted in urine. Out of 4,380 mEq, about
4,280 to 4,330 mEq of H+ is utilized for the reabsorption of
filtered HCO3 –. Only the remaining 50 to 100 mEq is excreted.
It results in the acidification of urine.
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Secretion of hydrogen ions (H+)
Secretion of H+ into the renal
tubules occurs by the formation of
carbonic acid.

Carbon dioxide formed in the

tubular cells or derived from
tubular fluid combines with water
to form carbonic acid in the
presence of carbonic anhydrase.

This enzyme is available in large

quantities in the epithelial cells of
the renal tubules. The carbonic acid
immediately dissociates into H+
and HCO3 –
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Secretion of hydrogen ions (H+)
H+ is secreted into the lumen of
proximal convoluted tubule, distal
convoluted tubule and collecting duct.

Distal convoluted tubule and

collecting duct have a special type of
cells called intercalated cells (I cells)
that are involved in handling hydrogen
and bicarbonate ions.

Secretion of H+ occurs by two pumps:

i. Sodium-hydrogen antiport pump
ii. ATP-driven proton pump.

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Secretion of hydrogen ions (H+)
(i). Sodium-hydrogen antiport pump:
When sodium ion (Na+) is reabsorbed from the tubular fluid
into the tubular cell, H+ is secreted from the cell into the
tubular fluid in exchange for Na+.
The sodium hydrogen antiport pump present in the tubular
cells is responsible for the exchange of Na+ and H+. This type of
sodium-hydrogen counter transport occurs predominantly in
distal convoluted tubule.

(ii). ATP-driven proton pump:

This is an additional pump for H+ secretion in distal convoluted
tubule and collecting duct. This pump operates by energy from
ATP.

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Removal of Hydrogen ions And Acidification of Urine
Role of Kidney in
Preventing Metabolic Acidosis
Kidney plays an important role
in preventing metabolic acidosis

Excretion of H+ occurs by three

mechanisms:
1. Bicarbonate mechanism
2. Phosphate mechanism
3. Ammonia mechanism.

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
Bicarbonate mechanism
All the filtered HCO3 – in the renal tubules is reabsorbed. About 80% of it
is reabsorbed in proximal convoluted tubule, 15% in Henle loop and 5% in
distal convoluted tubule and collecting duct. The reabsorption of HCO3 –
utilizes the H+ secreted into the renal tubules.

 H+ secreted into the renal tubule, combines with filtered HCO3– forming
carbonic acid (H2CO3). Carbonic acid dissociates into carbon dioxide and
water in the presence of carbonic anhydrase. Carbon dioxide and water
enter the tubular cell.

 In the tubular cells, carbon dioxide combines with water to form carbonic
acid. It immediately dissociates into H+ and HCO3 –. HCO3– from the
tubular cell enters the interstitium.

 Simultaneously Na+ is reabsorbed from the renal tubule under the

influence of aldosterone. HCO3 – combines with Na+ to form sodium
bicarbonate
04/06/2024
(NaHCO3). Now, the H+ is secreted into the tubular lumen
71
Bicarbonate mechanism
•

04/06/2024 72

Phosphate mechanism
In the tubular cells, carbon dioxide combines with water to form
carbonic acid. It immediately dissociates into H+ and HCO3 –. HCO3 –
from the tubular cell enters the interstitium.

Simultaneously, Na+ is reabsorbed from renal tubule under the

influence of aldosterone. Na+ enters the interstitium and combines
with HCO3 –. H+ is secreted into the tubular lumen from the cell in
exchange for Na+

H+, which is secreted into renal tubules, reacts with phosphate buffer
system. It combines with sodium hydrogen phosphate to form sodium
dihydrogen phosphate. Sodium dihydrogen phosphate is excreted in
urine.

The H+, which is added to urine in the form of sodium dihydrogen,

makes the urine acidic. It happens mainly in distal tubule and
collecting
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duct because of the presence of large quantity of sodium
73
Phosphate mechanism
•

04/06/2024 74

Ammonia mechanism
This is the most important mechanism by which kidneys excrete H+
and make the urine acidic. In the tubular epithelial cells, ammonia is
formed when the amino acid glutamine is converted into glutamic acid
in the presence of the enzyme glutaminase. Ammonia is also formed by
the deamination of some of the amino acids such as glycine and
alanine.

 Ammonia (NH3) formed in tubular cells is secreted into tubular lumen

in exchange for sodium ion. Here, it combines with H+ to form
ammonium (NH4). The tubular cell membrane is not permeable to
ammonium. Therefore, it remains in the lumen and then excreted into
urine.

 Thus, H+ is added to urine in the form of ammonium compounds

resulting in acidification of urine. For each NH4 excreted one HCO3 – is
added to interstitial fluid. This process takes place mostly in the
proximal
04/06/2024 convoluted tubule because glutamine is converted 75into
Ammonia mechanism

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