Renal Physiology and Fluid Balance

Important for Na, K and Acid balance

1. Fluid and ion homeostasis

2. Waste excretion
3. Drug removal
4. Hormone production
5. Glucose synthesis
 The Nephron

Functional unit of the kidney!

contains oxygenated
blood
1. Renal Corpuscle
-Glomerulus and Bowman’s capsule

2. Tubule
-proximal
-descending/ascending Loop of Henle
-distal Blood enters from renal arteries into
the glomerulus and then the fluid
-collecting duct enters the bowman's capsule. From here
the fluid is carried around into
covoluted tubular network. First to
Glomerulus -> bundle proximal tubule then to loop of Henle
of vasculature and lastly to the distal tubule from
surrounded by Bowman's where it enters the collecting duct and
Capsule that makes feeds into renal pelvis.
renal corpuscle

Fig. 13.3
 Cortical and Juxtamedullary nephrons
nephron classified based on length of
loop of Henle and site of these
structure

The renal corpuscle of ALL nephrons

is in the cortex

• Cortical nephrons (80%)

 outer 2/3 of cortex

• Juxtamedullary nephrons
(20%)
 inner 1/3 cortex
• Long Loop of Henle
• produce concentrated
urine

Fig. 13.5
 3 critical functions of nephrons:
Nephron's major function is glomerular
filtration
Blood comes from afferent arterioles,
enters renal corpuscle where major non
discriminative filtration takes place ->
plasma filtration from blood occurs here
and fluid enters the bowman's capsule from
where it is distributed into the tubular
network. Some of the fluid is taken back
into efferent arterioles Some of the fluid
is reabs by peritubular capillaries.
Further extraction can also take place

Fig. 13-6
 The Pathway of Filtration through Nephrons
Glomerulus
Renal corpuscle
Bowman’s capsule

Proximal convoluted tubule

Proximal
tubule
Proximal straight tubule

Descending thin Loop of Henle

Loop of
Ascending thin Loop of Henle
Henle
Ascending thick Loop of Henle Renal tubule

Distal Tubule Distal convoluted tubule

Cortical collecting duct

Collecting
Duct
Medullary collecting duct

Renal Pelvis
The blood supply

Renal Artery

Afferent Arteriole

Glomerulus

Efferent Arteriole

Peritubular Capillaries
Or Vasa Recta (juxtamedullary)

Venules

Renal Vein
 The process of filtration occurs in the glomerulus:

What determines filtration?

Ions and other

substances cross the
pores while RBC and
plasma proteins are
retained

“into”

“out of”
Medical Dictionary, © 2009 Farlex and Partners
“Filtration barrier”
YES - water, ions, small molecules
NO -RBCs, WBCs, plasma proteins
(albumin, immunoglobulins)
 The Glomerulus
“into” “out of”

Glomerulus is made up
of enodthelial cell
and basement membrane,
whereas the tubule is
made up of epithelia
cells -> thus, it has
no vasoactive capacity

Capillary – composed of endothelial cells

Tubule – composed of epithelial cells

Fig. 13-7
 Podocytes & the Filtration Barrier
Movement of filtrate

1. Pores between endothelial cells

2. Basement membrane
3. Podocyte filtration slits
Fig. 13-7
Glomerular Filtration Rate (GFR)
• Defined as the rate of filtration through the
glomerulus! into Bowman's capsule
 Overall Picture of Plasma Filtration and Fluid
Reabsorption

1. RECALL: 20% of Cardiac Output

enters Kidney 100% 80%

OF THIS:

2. In Glomerulus, 20% of plasma is 20%

filtered into tubule
(80% remains in vasculature)
>19%
3. >19% of Fluid is reabsorbed back
into blood
>99%
4. So, >99% of plasma fluid returns
to systemic circulation;
<1%
<1% is excreted

Fig. 13-6
GFR is determined by:
1. Net filtration pressure (largely controlled by plasma
hydrostatic pressure; PH)

-Glomerular blood pressure (higher than other capillary pressures)

2. Filtration co-efficient (Kf) (anatomical)

-thought to be a constant except in kidney disease

-determined by surface area and permeability

GFR = Kf x net filtration pressure

 Determinants of Net Filtration Pressure

Glomerular Bowman’s
capillary space

πGC
PGC
PBS
No pi BS is present as
there shouldn't be any
Balance of pressures: proteins in BS unless
the person has kidney
disease

Forces mmHg
A. Causing Filtration:
Glomerular capillary blood pressure (PGC) 55
primary pressure
driving fluid out

B. Opposing Filtration:
Bowman’s space Fluid Pressure (PBS) 15
Plasma Protein Osmotic Pressure (πGC) 30

NET filtration pressure (PH) = PGC – PBS – πGC = 10 mmHg

Table. 13-1
 How does blood pressure affect GFR?

This is a DIRECT effect

BP will PGC and therefore PH, causing an GFR

Fig. 13-9
 What is the impact of vasoconstriction / vasodilation of the
AFFERENT arteriole?

Fig. 13-10
What is the impact of vasoconstriction /vasodilation of the
EFFERENT arteriole?

Efferent vasoconstriction Changes occur due to

changes in volume.
Vasoconstriction
increases volume in
glomerulus causing
increase in pressure
which increases
PGC pressure thereby
increasing GFR.
Similarly, if efferent
Efferent vasodilation
arterioles vasodilate,
more volume leaves,
volume decrease,
pressure decreases and
GFR decreasses.

GFR
PGC

GFR
 Local Regulatory Mechanisms that Maintain
GFR when MAP changes

1. Myogenic Mechanism / flow autoregulation

-based on stretch of afferent arteriole (pressure)

Flow autoregulation -
When MAP increases, PH increases, GFR increases
afferent arteriole constricts
PH and GFR returned to normal
controlled by CV
system

2. Juxtaglomerular (tubuloglomerular) feedback

-based on amount of flow through the tubule
 The juxtaglomerular apparatus: Anatomy

MD sense flow through the distal

tubule and secrete paracrine factor
for changing afferent arteriole ->
signals go from MD to granular
cells in afferent arterioles to
control BF into glomerulus
(vasoconstriction or vasodilaiton)
The Juxtaglomerular Apparatus =
Macula Densa = specialized epithelium that sense distal tubule FLOW
 secrete paracrine factors that affect afferent arteriole diameter
Granular cells = specialized endothelium within afferent arteriole
 produce factors in response to macula densa factors & SNS
Fig. 13-11
 The juxtaglomerular apparatus:
Feedback Loop

Macula Afferent arteriole Decreased glomerular

GFR Tubule flow
densa vasoconstriction capillary pressure
secretion
(-)

(reduced filtration)

high tubule flow  more work (ATP consumption) by tubule epithelial cells
vasoconstrictor will
thereby decrease NFP
leading to decrease in

**In kidney, adenosine is a vasoconstrictor!!!

Gfr

decre
ase Macula Afferent arteriole Increased glomerular
GFR Tubule flow
densa vasodilation capillary pressure
secretion
(-)

(increased filtration)
 Process of Reabsorption:
Transepithelial transport

 Substances within the tubule (filtrate) are transferred to the

peritubular capillaries
= trans-epithelial transport

 Process is highly selective(ie. Which substances are re-

absorbed) and variable through-out the length of the
nephron and under physiological control
Aldosterone -> Na+/K+
Vasopressin -> H20 in
principal cells in
distal ends
ANP/BNP -> block Na+
reabsorption and
passive water
reabsorption in distal
ends
 Process of Reabsorption:
Transepithelial transport

Fig. 13-14
 Not all substances handled equally in tubules!
Plasma clearance rate = volume of plasma from which a substance is completely removed/time

No reabsorption Complete reabsorption Partial reabsorption No reabsorption

“Inulin” “Glucose” “Sodium, urea” + secretion
“H+, K+”

125 mL/min 0 mL/min 0-125 mL/min 125-625 mL/min

Fig. 13-23
Basic concepts of the tubular
reabsorption process
Primary Na+
reabsorption allow for
secondary reabso of
water, Cl- and other
organic substances

1. Na+ absorbed by active transport

2. This creates an electrochemical
gradient that allow anion reabsorption
3. Accumulating ions in interstitial fluid
create an osmotic gradient
4. Water moves by osmosis, following
solute reabsorption

As water is reabsorbed, remaining

solutes become concentrated and
SOME are reabsorbed by diffusion
https://www.youtube.com/watch?v=oXcEAH_yesY
 Sodium Reabsorption

145 mM 15 mM
-3 mV -70 mV

1. Na+ enters cell through Na+ channels, down electrochemical gradient

2. Na+ is pumped to basolateral side of cell by Na+/K+ ATPase

3. Na+ diffuses into peri-tubular capillary Fig. 13-15

 Na+ Reabsorption

• Normally, 99.5% Tubule area % Na+ Role of Na+

of filtered Na+ is reabsorption
reabsorbed Re-
At glomerulus,
reabsorbed into
absorbed
peritubular
capillaries Proximal tubule 67% Plays role in
• 80% of the reabsorbing glucose,
kidney’s total amino acids, H2O, Cl-,
energy use is
devoted to and urea
transporting Na+ Ascending limb 25% Plays critical role in
important for of the loop of Na reabsp here is kidneys’ ability to
facilitating water critical in
movement into PTC. Henle determining urine produce urine of
Proximal tubule is conc
responsible mainly for
reabsortion of Na+
varying concentrations
Distal and 8% Variable and subject to
collecting hormonal control; plays
tubules role in regulating ECF
volume plasma + interstitial
fluid volume
 Water Reabsorption

Water passively moves

through aquaporin in
luminal side. There is
limited movement
through proximal
tubular epithelila
cells due to tight
junctions.

Aquaporins

(limited)

Water Follows Sodium!!!

Because of epithelial tight junctions, not much H2O moves between cells.
Most H2O moves through water channels in the luminal membrane
Fig. 13-19
 normally 100% is
reabsorbed back into
PTC. Glucose is moved
passively and also
Glucose Reabsorption
using secondary active
transport.

Tubular Tubular Interstitial Peritubular 1. Na+ enters cell down

lumen Epithelial cell fluid capillary electrochemical gradient
[glucose] low
using the Na+- glucose
transporter
[Na+] high Glucose comes with it
Na+
against conc. gradient
ATP

Na+ K+ 2. Glucose diffuses out of cell

[glucose] low using transporter down
glucose
glucose
concentration gradient

3. Na+ is pumped to
basolateral side of cell by
Na+/K+ ATPase

Secondary active transporter (Na-glucose) Both reabsorbed

ATP NaK-ATPase by peritubular
Facilitated diffusion carrier (glucose) capillaries
Glucose Reabsorption

• The amount of glucose entering filtrate is proportional to

plasma concentration. Blood filtered in
glomerulus -> conc of
glucose is
proportional to the
plasma conc.

• Na+-glucose transporters have the potential to limit the

maximum rate of reabsorption….
”Transport maximum”

• Are there enough glucose transporters to allow

reabsorption of the filtered glucose?
 Glucose Transport can be saturated
These values cannot be
reabsorbed because the
transporters are
saturated. Filtering
continues, there is no
reabsp, so glucose is
excreted. Tm would be
lower if there were
fewer Na glucose
transporters

Tubular transport
maximum

Determined by # of
transporters & their rate
of action

Transporters are VERY efficient

They will reabsorb EVERY glucose molecule  until maximum (Tm)!

Fig. 13-18
 Glucose Transport can be saturated

Diabetes -> have

glucose in urine
levels

Renal threshold
determines the tubular
maximum

depends on # of
transporters and rate
of action
Renal threshold
= the plasma
concentration of glucose
that results in saturation
Normal Diabetes of the transporters,
< 200 (random) > 200 (random) detected as spillover of
glucose into the urine
Fig. 13-10
What else gets reabsorbed like glucose?

- Other sugars, ie. galactose, fructose

- Many amino acids, ie. glutamate, glycine
- Water soluble vitamins (B-complex, C)
 The Pathway of Filtration through Nephrons
Glomerulus
Renal corpuscle
Bowman’s capsule

Proximal convoluted tubule

Proximal
tubule
Proximal straight tubule

Descending thin Loop of Henle

Loop of
Ascending thin Loop of Henle
Henle
Ascending thick Loop of Henle Renal tubule

Distal Tubule Distal convoluted tubule

Cortical collecting duct

Collecting
Duct
Medullary collecting duct

Renal Pelvis
Features of Nephron Segments

Proximal Tubule: 65% of reabsorption here

Very permeable to H2O
Na+, Cl- and H2O reabsorbed at similar rates
Reabsorption of glucose and amino acids

Descending Loop of Henle

Permeable to H2O; no Na+ reabsorption

Ascending Loop of Henle

Impermeable to H2O; Na+ reabsorption (is controlled by
aldosterone)

Collecting Duct anti-diurectic -> dec

urination frequency.

H2O Permeability controlled by vasopressin site for majority of

water absorp
 Osmotic gradient in the kidney
loop of henle go into
medullary sections
where there is a
Osmolarity is the concentration change in conct
(osmolarity)
of a solution

Interstitial fluid in cortex region is

iso-osmotic
~300 mOsm

Interstitial fluid in medullary

region is hyper-osmotic;
A gradient extending from 300
mOsm to 1200 mOsm (closest
to renal pelvis) Renal pelvis

Fig. 13-24
 Loop of Henle and counter current multiplication

Fluid entering is iso-osmotic

Desc -> water

permeable
Asc -> water
impermeable (K+, Cl-
pumps)

Unique characteristics of the Loop of Henle allow for generation of hyper-osmotic interstitium:
The descending loop of Henle is H20 permeable
The ascending loop of Henle is H20 impermeable, and has Na+Cl-K+ pumps
The loop of Henle is a hairpin loop, so the actions on one
side of the loop will affect the other side.
Fig. 13-25
 Generation of the osmotic gradient

Add more filtrate:

300

3. 1.
2
.

1. In the ascending loop, Na+Cl-K+ pumps move salts into the interstitium,
increasing interstitial fluid osmolarity and reducing the osmolarity of the tubular
fluid. Recall no water can move out of the ascending loop.

2. This increases the osmolarity of the interstitial fluid

3. In the descending loop, H2O diffuses out of the tubule into the interstitium,
following osmotic gradient. It will equilibrate with osmolarity of the interstitium.

This cycle continues…..

Fig. 13-25
 Loop of Henle and counter current multiplication
Note: the pumps can achieve ~ 200 mOsm Ascending limb fluid
is hyposmotic where
difference between interstitium and tubular fluid descending is
in the ascending loop hyperosmotic

As fluid moves through the hairpin

loop, a vertical gradient is established
The highest osmolarity is at the base
of the loop, and osmolarity decreases
as the fluid continues up the
ascending loop, as more and more
salt is actively pumped out

Fig. 13-25
 Which has highest osmolarity in medulla (and urine)?

Longer the loop of

Henle -> more sodium
channels, more
concentrated urine

less area for water

absorption so less
concentrated urine
~500 mOsm

~5500 mOsm

long loop of Henle ->

greater concentrated
urine, more
concentrated urine
 Vasa Recta
parts of PTC. Different names as
they are important for water and ion
movement from the interstitial fluid
back to CV system

Vasa Recta are the specialized capillaries that surround the Loops of
Henle in the medullary region (ie. post – efferent arteriole)

Vasa recta also have a hair-pin configuration

remove water from
intersitium required
for maintaining
Flow is Counter Current with respect to tubular flow concentrated urine. It
helps in maintaing the
gradient.

Function: To remove H2O from the medullary interstitium, maintaining

high osmolarity intersititium required for producing concentrated urine

** vasa recta freely permeable to water and salts

depending on
concentration gradient

** blood flow is slow and hydrostatic pressure is low

 Counter current Exchange

Maintains,
does not Generate,
the osmotic gradient
Ascending limb -> VR
absorbs the ions to
get more concentrated
and during descending
limb it absorbs water
to prevent disruption
of conc in IF.

H20
impermeable

H20
Na+Cl-K+ pumps
permeable
Tubule creates the
gradient, vasa recta
helps maintain it.
water moves from IF
to vasa recta.

active transporters
So far, the tubule has:

1. Generated a hyper-osmotic medullary interstitium

2. Generated a hypo-osmotic filtrate entering the distal

collecting duct

The final stage  selective reabsorption of water in the

collecting duct
Vasopressin

• Produced by hypothalamus, stored in posterior pituitary

gland
 release is stimulated by osmoreceptors
• Acts on collecting duct epithelium
• Stimulates H2O absorption
• Aquaporins (water channels) are in the membrane to absorb
water and transport it across the luminal membrane
• Increased reabsorption/decreased excretion
• Plasma volume conserved
 Vasopressin and water channels
binds Vasopressin R on
basolateral memb, and
increase permeability
of H20 by inserting
new channels in
luminal membrane for
increasing water
reabsorption which
will then move into
peritubular capillary,

Fast acting –> because channels are pre-formed

Fig. 13-26
 Collecting Duct
+ Vasopressin No Vasopressin in absence of
vasopressin, urin
concentration is
dictated by only the
initially some water concurrent exchange of
moves out because 100 fluid.
< 300 mOsm of
isosmotic cortical
region

**The collecting duct passes through the hyper-osmotic

interstitium, so there is high osmotic gradient favouring
H2O reabsorption
Fig. 13-27
 Utilizing Kidney to Maintain Fluid Balance
• Extracellular fluid (ECF) = fluid surrounding cells within the tissue =
INTERSTITIAL FLUID
• This compartment is incompletely separated from the plasma as
there is movement of water and ions between plasma and the ECF IF

through capillary filtration

• ECF volume affects blood pressure ECF includes plasma
and blood volume

• Salt balance is the key to long-term regulation of ECF volume

• ECF osmolarity must be maintained equivalent to that inside
cells, to prevent swelling or shrinking of cells
• Maintaining selective water balance is the key to this

 Hormones: vasopressin, angiotensin II, aldosterone, atrial natriuretic

peptide
 Autoregulatory loops
 regulate re-absorption and excretion to maintain salt and water
balance…..thus, volume regulation
 Signals associated
with vasopressin
release and action

Vasopressin is
the ONLY
hormone that can
regulate
osmolarity!

Fig. 14-4
 How else is Urinary Excretion controlled?

• Modify glomerular filtration

• Modify Na+ reabsorption

• Atrial Natriuretic Peptide ***increases excretion

Na+ excretion

• Aldosterone
decrease excretion
• Angiotensin II
 Long Term Regulation of Blood Volume & MAP
 Requires co-operation with the kidneys
Hormones Involved:
Vasopressin
water levels in blood

Angiotensin II Na+ levels

Aldosterone MAP

H2O and sodium

SV retention
MAP Venous return (kidney)

vasoconstriction
Blood volume

Ang II Vaso
Aldo
 Long Term Regulation of Blood Volume & MAP
 Requires co-operation with the kidneys
Natriuresis ->
excretion of sodium.
Wherever sodium goes, ANP released by
water goes. stretch of atrial
receptors owing to
high MAP

Atrial natriuretic MAP

peptide
 Sodium loss MAP
SV
H2O and Na
Venous return
loss (kidney)

Blood volume
ANP
Atrial Natriuretic Peptide (ANP)

• Secreted from Atria in response to stretch

(ie. excess volume)

 High blood pressure; high fluid volume; high NaCl

• Causes: GFR, Na+ excretion

owing to afferent
arteriole vasodilation
from high MAP

 Reduces plasma volume and Na+ levels

 Atrial Natriuretic Peptide (ANP)

+ vasoconstriction of
efferent arterioles

Fig. 13-17
 Angiotensin II / Aldosterone production
also due to SNS output
Negative feedback loop
system for increasing
BV

Fig. 13-16
Regulation of Renin

• This critical enzyme is the rate limiting step in the

production of Angiotensin II

• Secreted by juxtaglomerular cells in response to

low plasma volume
 SNS stimulation
 Intrarenal
baroreceptors
these are present in
renal vasculature and
respond to reducting
in BP -> send signals
to central command to
increase BP
Regulation of Renin

Net Effect:

Reduced glomerular filtration

Production of aldosterone
Stimulation of Vasopressin release

Plasma volume retention

 Angiotensin II /
Aldosterone function

Corrects Na+, ECF

volume, MAPindirect water
conservation due to
increased ion
retention to fix low
plasma volume

causes release of
Aldosterone from
adrenal cortex

Angiotensin II Aldosterone

increased TPR and

increased MAP

Fig. 13-16
 Potassium Regulation - Aldosterone
In the collecting duct:

1.

2.

3.

1. K+ is filtered
potassium is secreted
2. K+ is secreted** from PTC Why is it important to regulate K+ levels?
3. K+ is NOT reabsorbed K+ is important for
activity of Sodium
**secretion regulated!! potassium exchanger ->
wo K sodium cannot be
moved -> water cannot
be moved
Fig. 13-23d Fig. 13-21
Aldosterone production
Interstitial 1 Plasma aldosterone
Tubular Tubular fluid Peritubular diffuses across cell
lumen Epithelial cell capillary membrane into tubular
epithelial cell

2 Aldosterone bind to
cytoplasmic receptor, then
the complex moves to
1
nucleus and initiates
Aldosterone
2 transcription of target genes
Transcription

mRNA 3 Additional Na+ and K+

channels and Na+ K+
3 ATPase pumps are
Translation new protein Aldosterone R synthesized and inserted
Na+ into the cell membrane
Channels
4 Aldosterone stimulated
(Na+, K+)
4 Na+ K+ ATPase modifiying proteins act on
Modify existing Na+ Na+ existing channels and
K+ channels/pumps ATP pumps to increase their
K+
Na+ transport capacity
Na+
5 ATP K+ 5 The end result is enhanced
K+ K+
reabsorption of Na+ and
increased secretion of K+
**Water follows Na+, so more
K+ excretion water is reabsorbed too
 Aldosterone: summary

Adrenal Cortex

and H2O reabsorption!

Fig. 13-22
 Response to low sodium

Fig. 14-3 – see Figures 13-12 and 13-16 for mechanism details
Regulation of blood
pressure
contribution of
kidneys

1. Direct effect of MAP, will GFR

2. SNS further GFR

3. Effects of hormones
(vasopressin, AngII/Aldo, ANP)

Venous
return
Fig. 13-12
Summary: Response to decreased plasma volume
Blood volume

Blood pressure

De-activate volume receptors in atria

and (-) ANP
Carotid/Aortic Baroreceptors

Activation of homeostatic reflexes

Kidneys CV system Behaviour Kidneys

renin Cardiac output, Thirst and Water channels Vasopressin

Vasoconstriction water intake Na+ channels
Aldosterone
AngII
ECF and ICF Increased H2O
vasoconstriction volume reabsorption

GFR
Blood pressure
Summary: Response to increased plasma volume

Blood volume

Blood pressure

Activation of volume receptors in atria ANP

and
Carotid/Aortic Baroreceptors

Activation of homeostatic reflexes

(-) Vasopressin
CV system Kidneys
(-) AngII
PNS (-) Aldosterone
GFR
Cardiac output,
(-) SNS Vasoconstriction
Water channels
Glomerular Na+ channels
Pc
Increased excretion of
GFR salts and H2O

Blood pressure
 Acidosis and Alkalosis

If GAIN of H+ = LOSS….

Acidosis
H+ exceeds HCO3-
May be buffered by other
anions
May be excreted
Alkalosis
HCO3- in body exceeds H+
 Excess HCO3- is excreted in
urine

Fig. 14-6
 Hydrogen ion regulation
Normal H+ concentration is 40 nM:
BUT - You can produce up to 80 mmol of H+ per day!
Gain
• Generation from CO2
• Metabolism of proteins (phosphoric acid, lactic acid)
• Loss of bicarbonate: diarrhea, urine

Loss of bicarbonate ion is equivalent to gaining a H+ ion

Loss
• Metabolism of organic anions
• Loss of H+: vomiting, urine due to loss of HCl

• Hyperventilation loss of CO2

Three Lines of Defense to Regulate [H+]

• Chemical buffer systems (Immediate)

Chemical buffers in
plasma can immediately
regulate pH

• Respiratory system - pH control by breathing (FAST -

minutes) Hypo/Hyperventilation can alter CO2 retention ->
manipluate pH via bicarbonate ions

(what happens when you breathe faster?)

• Kidneys – pH control by excretion (SLOW –hours/days)

• Secretion of H+ ( excretion of acid)

• Reabsorption of HCO3- ( plasma base)
 Buffers
• Act to minimize changes in pH by binding with or releasing free
H+

Unbuffered solution:

H+ dissociates from Cl- and

remains as free H+

Buffered solution:

H+ dissociates from Cl- AND

some H+ bind with HCO3-,
leaving less free H+
Fig. 14-8
 Hydrogen ion regulation:
1) When H+ balances HCO3-

H+ secretion occurs in proximal, distal and collecting tubules

H+ ATPase
a) HCO3- ions are
filtered

b) HCO3- reabsorbed
by generation of new
HCO3- in tubule
epithelium
3 different ways of
getting CO2 into
Epithelial cells

No LUMINAL transporter for HCO3-

Fig. 14-11
 Hydrogen ion regulation:
2) When H+ exceeds HCO3-
Xs H+ should be
removed. The breakdown
will increase HCO3-
and decrease retention
for H+
NET New bicarbonate
production

Allow increased H+
excretion
during acidosis
NET Loss of H+

pH increases

NH3 (ammonia) is produced by metabolism of glutamine –>

also is secreted and buffers H+, becoming NH4+ (ammonium)
Fig. 14-12
Putting it Together
Scenario 1: Respiratory Acidosis

= Excess CO2 retention due to

hypoventilation ventilation
Lungs

Possible causes:
–Lung disease blood CO2
–Inhibition of respiratory control
centre by drugs or disease (-)
blood H+
–Nerve / muscle disorder that
impairs respiratory muscles
–Holding breath
Kidney H+ excretion
(H2PO4- / NH4+)
Compensations:
1.Buffers bind H+
RESULT: blood CO2 high
2.Kidneys secrete excess H+ but pH normal
 Acidosis and Alkalosis: Respiratory and Renal systems cooperate

Scenario 2: Metabolic Acidosis = excess H+ from any source other

than CO2

Muscle Excess production of metabolic acids –

Causes: Etc. lactate, phosphate
Severe diarrhea
Diabetes mellitus Kidney Excess Loss of HCO3-
Strenuous exercise
Kidney Damage (-)
lead to blood H+
hyperventilation

Compensation:
1. Buffers bind H+ Lungs ventilation detected by
2. Lungs release more ventiallatory centers
in medulla

CO2
blood CO2
(Kidneys secrete more
H+) and bicarbonate ions
RESULT: HCO3- low but
blood CO2 low and pH normal