Download AB Balance Lecture 1_2015

Dr. Suzana Voiculescu
Discipline of Physiology and Fundamental Neurosciences
Carol Davila Univ. of Medicine and Pharmacy
Definition
 All the processes inside the body which keep
the H+ concentration within normal values.
 Depends on
 water and ion balance
 blood gas homeostasis
 Blood acidity may be expressed by:
 H+ concentration - 35- 45 mmol/l
 Hydrogen activity, as pH- 7,35- 7,45
pH
 pH= - log [H+]
 The more Hydrogen ions, the more acidic the
solution and the LOWER the pH
 The lower Hydrogen concentration, the more
alkaline the solution and the HIGHER the pH
Acid/ base
 Acids are H+ donors.
 Bases are H+ acceptors.
 Acids and bases can be:
 Strong – dissociate completely in solution
HCl, NaOH
 Weak – dissociate only partially in
solution
 Lactic acid, carbonic acid

Acid and alkali load
 ACID- Diet (acid containing foods)+ production from
metabolism
 ALKALI- Alkali containing foods and production from
metabolism in the end they must be buffered 
leads to extra acid load that must be buffered and then
excreted
Acid load- fixed versus volatile
 FIXED= NON VOLATILE
 Daily production of acids= 50-100 mEq of H+- under
physiological conditions- from cell metabolism
 Dietary acids
 VOLATILE- CO2- it can be excreted through
ventilation
Fixed acids- catabolism
 Protein
 Amioacids
 Uric acid
 Sufphuric acid
 Phosphoric acid
 Carbohydrates
 Pyruvic acid
 Succinic acid
 Lactic acid (anaerobiosis)
 Fats
 Fatty acids
 Ketoacids (diabetes/starvation)- acetoacetic acid,
betahydroxybutyric acid
Volatile acid
 THE ONLY VOLATILE ACID= CARBONIC
ACID(H2CO3)
 THE ACID IS IN EQUILLIBRUM WITH ITS
DISSOLVED GASEOUS COMPONENT (PaCO2)
Carbonic acid
 Metabolism of fats and carbohydrates result in the
production of 15-20 mol of CO2 per day
 Before elimination by the lungs, most of the CO2 is
taken up by red blood cells, reacting with H2O to form
carbonic acid as shown below:
CO2 + H2O ↔ H2CO3(CA) ↔ H+ + HCO3CA= CARBONIC ANHIDRASE- INTRACELLULAR
Acid excretion
 Lungs – excrete volatile acid (CO2)
 Major source of rapid acid excretion
 13000 mEq/ day of carbonic acid
 Kidneys- excrete fixed acids
 40-80 mEq/day
 Fixed acids may increase to 300/ 24 h if necessary
Base excretion
 Only kidney regulated
 Primary base in the organism HCO3-
 The kidney can retain or excrete bicarbonate as
needed
Biological importance of pH
1.
2.
3.
4.
5.
6.
7.
Enzyme activity
Action potential of myelinated nerve
Membrane permeability
Control of respiration
Heart activity
Oxygen Hb dissociation curve
Nerve excitability
Enzymes
 Enzymes are affected by
changes in pH. The most
favorable pH value - the point
where the enzyme is most
active - is known as the
optimum pH
pH and synaptic transmission
 Alkalosis increases transmission- alkalosis> 7.8
seizures
 Acidosis decreases transmission- acidosis< 7 coma
(uremic/ diabetic- ketone bodies )
pH and heart activity
 High H+ in blood H+ diffuses in the cells
electroneutrality law K+ diffuses out of the cells
 Hyperpolarisation of heart muscle
 Low excitability
 Hyperkalemia
Bohr effect
pH and
ventilation
 chemoR
 Peripheral (carotid/
aortic body)
 Central(medulla
oblongata)
Maintainance of AB balance
2 mechanisms:
1.
Buffer systems- composed of a weak acid and it’s salt
with a powerful base, which have two origins:
plasmatic and cellular (mosly erythrocyte)- they
fight against sudden shifts in AB balance (act in
seconds)
2. Biological mechanisms- in which lungs (regulates
AB in minutes) and kidneys play a major role
(regulate AB balance in days)
Buffer systems
 Take up H+ or release H+ as conditions change
 Buffer pairs – weak acid and a base
 Exchange a strong acid or base for a weak one
 Results in a much smaller pH change
 Whenever a buffering reaction occurs, the concentration of one
member of the pair increases while the other decreases.
Buffers
 Cannot remove H+ ions from the body
 Temporarily acts as a shock absorbant to reduce the
free H+ ion.
 EC- BICARBONATE- SECONDS
 IC- HEMOGLOBIN, PHOSPHATE, PROTEINS
 BONE
The Major Body Buffer Systems
Site
Buffer System
Comment
ISF
Bicarbonate
For metabolic acids
Phosphate
Not important because concentration too low
Protein
Not important because concentration too low
Bicarbonate
Important for metabolic acids
Haemoglobin
Important for carbon dioxide
Plasma protein
Minor buffer
Phosphate
Concentration too low
Proteins
Important buffer
Phosphates
Important buffer
Phosphate
Responsible for most of 'Titratable Acidity'
Ammonia
Important - formation of NH4+
Ca carbonate
In prolonged metabolic acidosis
Blood
ICF
Urine
Bone
Bicarbonate buffer
 The most important extracellular buffer
 Sodium Bicarbonate (NaHCO3) and carbonic acid
(H2CO3)
 Maintain a 20:1 ratio : HCO3- : H2CO3
HCl + NaHCO3 ↔ H2CO3 + NaCl
NaOH + H2CO3 ↔ NaHCO3 + H2O
Buffering power of the bicarbonate
system
 Efficiency of a buffer system depends on the change in pH
when a base or an acid are added- inversely prop (the
smaller the change, the better the buffering effect)
 Buffering power depends on:
 The relatinve conc of buffer components: the highest
when components ratio is 1:1 <-> pH= pK
 The amount of buffer comp
 Open/ closed system (if the system can equillibrate with
the environment)
Bicarbonate buffer system
 Pk=6,1
 H2CO3+ NaHCO3
 H2CO3- forms from CO2 + H2O (carbonic
anhidrase)
 H2CO3  H+ + HCO3 NaHCO3  Na+ + HCO3 CO2 + H2O H2CO3 H+ + HCO3-
Na+
When a strong acid is added to the
solution
 Carbonic acid is mostly unchanged, but bicarbonate
ions of the salt bind excess H+, forming more carbonic
acid.
 H+ + HCO3- H2CO3 H2O+ CO2 (excess CO2-- >
eliminated through respiration)
When a strong base is added to
solution
 Sodium bicarbonate remains relatively unaffected, but
carbonic acid dissociates further, donating more H+ to
bind the excess hydroxide.
 NaOH + H2CO3 NaHCO3 + H2O H2CO3
consumes more CO2 is used to bring H2CO3 back to
normal low CO2 inhibits respiration
 Also: NaHCO3 Na+ + HCO3- high HCO3- urine
excreted
Protein buffer systems
 Proteins are highly concentrated inside the cells
 They buffer extracellular H+ because IC pH is lower
than EC pH ions are slowly diffusing inside the cell
 This process is slow- it takes several hours
 RBC – equilibrium happens fast; Hb is an important
buffer:
 H+ + Hb= HHb
Hemoglobin buffer system
 Hb is an “amphoteric substance”
 • It can act as a proton donor (an acid)
 • It can act as a proton acceptor (a base)
 • Plays a considerable role in acid-base balance
(second most important buffer after bicarbonate)
Blood buffer systems comparison
 Protein buffers in blood include haemoglobin (150g/l)
and plasma proteins (70g/l). Buffering is by the
imidazole group of the histidine residues which has a
pKa of about 6.8. This is suitable for effective buffering
at physiological pH.
 Haemoglobin is quantitatively about 6 times more
important then the plasma proteins as it is present in
about twice the concentration and contains about
three times the number of histidine residues per
molecule. For example if blood pH changed from 7.5
to 6.5, haemoglobin would buffer 27.5 mmol/l of H+
and total plasma protein buffering would account for
only 4.2 mmol/l of H+.
Cellular buffers
 Muscle and bone 60-70% of the total chemical
buffering of the body fluids
 Phosphate buffer system
 Protein buffer system
 Slight diffusion of elements of bicarbonate buffer
through the cell mb (except for RBC- fast)
 Takes hours (2-4) to become maximally effective
Phosphate buffer system
 The phosphate buffer system operates in the urine and
intracellular fluid similar to the bicarbonate buffer
system (in the EC fluid, it’s concentration is 8% of the
bicarbonate one)
 Pk=6.8- but low conc in the plasma
 sodium dihydrogen phosphate (NaH2PO4) is its weak acid,
and monohydrogen phosphate (Na2HPO4) is its weak base.
 HCl + Na2HPO4 NaH2PO4 + NaCl
 NaOH + NaH2PO4 Na2HPO4 + H2O
Bone
 Bone represents an important site of buffering acid
load.
 An acid load, is associated with the uptake of excess
H+ ions by bone which occurs in exchange for surface
Na+ and K+ and by the dissolution of bone mineral,
resulting in the release of buffer compounds, such as
NaHCO3, CaHCO3, and CaHPO4.
 40% of an acute acid load BONES
 Chronic acidosis bone demineralisation
Muscle
 Half the cellular mass
 Most intracellular buffering
Acid base balance and lungs
 CO2 formed by tissue metabolism is eliminated through
respiration
 CO2 regulates ventilation rate and depth indirectly by H+
increase
 CO2 passes the blood brain barrier
 It hidrates (CA) and forms H2CO3 H+ + HCO3 H+ influences central chemoR
Acid base balance and lungs
 High pCO2= hyperventilation
 Low pCO2= hypoventilation
 Ex: ventilation increases 4-5 x when pH is 7!
Kidneys and AB balance
Kidneys excrete nonvolatile acid load
H+ are buffered in the blood, they are not filtered
Kidneys SECRETE H+
IN the tubes:
1. H+ combines with filtered HCO3 bicarbonate
reabsorption
2. H+ combines with urinary buffers TITRABLE ACIDS
and AMMONIUM
3. Low amount free in the urine
Bicarbonate reabsorption
 Bicarbonate freely filtrates
 But ... almost none excreted in urine:
 Proximal tubule reabsorption 85%- Na+/H+ exchanger
 Distal and collecting tubules- 15%- H+ pump and
Na+/H+ exchanger (aldosterone)
Secretion of H+ in proximal tubule
 For each H+ secreted, there is a HCO3-
reabsorption
 Mostly in the proximal tube (85%)
 Secondary active secretion
 Na+ gradient established by Na+-K+ pump in
basolateral membrane of tubular cells
Secretion of H+ in the late distal
and collecting tubules
 In intercalated cells
 Primary active transport- H+ pump (aldosterone)
 For each H+ secreted, a HCO3- is reabsorbed by
Cl-/ HCO3- antiporter
H+ secretion and bicarbonate
reabsorpion
Reabsorption of filtered HCO3-=
new bicarbonate formation!
 HCO3- cannot pass the apical membrane of tubular cell
 They combine with H+ in the lumen H2CO3 H2O +
CO2
 CO2 diffuses in the cell
 CO2+ H2O--- H+ + HCO3 HCO3- reabsorbed in the blood
H+ free excretion in limited
 Excretion of 70 mEq /day of non-volatile acids as free
H+ would require more than 2000 l of urine output/24
h
 Limited by transporter activity
 Minimum urinary pH= 4.5 (0,03 mEq/l)
 Any H+ that exceeds this limit urinary buffers-
phosphate (titrable acidity) and NH4+
Combination of excess H+ with
phosphate and ammonia buffers
 If high amounts of H+ are secreted (> HCO3- filtered),
H+ is buffered by phosphate and ammonia systems in
the tubule
 H+ is eliminated by:
 H+ + NaHPO4- NaH2PO4
 NH3 + H+ NH4+
Formation and excretion of titrable
acid (TA)
 pK HPO42- /H2PO4-= 6,8 and 90% of the buffering
activity of HPO42- occurs above a pH of 6.8
 Daily filtered dibasic phosphate accounts for the
excretion of approx 50% of the daily fixed H+ excretion
 Titrable acid because it is measured by back
titration of the urine with NaOH to a pH of 7.4
 Limited by the quantity of dibasic phosphate filtered
Titrable acidity
 Proximal tubule
 Collecting tubule
 For each H+ buffered by a weak acid and excretion in
the urine as titrable acid, a HCO3- is released in the
plasma
Formation and excretion of
ammonium (NH4+)
 30-40 mEq of fixed acid per day
 Less limited up to 300 mEq/day
 Ammonium- synthesized in proximal tube by
glutamine deamination
 GLUTAMINE GLUTAMATE + NH4+
 NH4+ is transported in the interstitium in the thick
ascending limb substituting a K+ in the Na+/K+/2Cl
carrier
 Then, ammonium dissociates to ammonia in the
medullary interstitium (higher pH)
Cortical collecting duct ammonium
trapping
 Ammonia subsequently diffuses into the medullary
collecting duct
 It is trapped in the increasingly acidic urine as NH4+
 A HCO3- is released in the systemic circ for each
ammonium that is excreted in the urine
Bicarbonate as an open system
 Lungs eliminate CO2 (volatile acid) and determine the
conc of H2CO3 by regulating pCO2 at 40 mmHg
 pCO2  dissolved CO2 by hydration is in
equillibrum with H2CO3
 The kidneys maintain [HCO3-] at 24mEq/l
 Thus pH= 7.4 !!