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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
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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
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Definition
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Acid/ baseAcids 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
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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
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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
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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
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Volatile acid THE ONLY VOLATILE ACID= CARBONIC
ACID(H2CO3)
THE ACID IS IN EQUILLIBRUM WITH ITS DISSOLVED GASEOUS COMPONENT (PaCO2)
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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+ + HCO3-
CA= CARBONIC ANHIDRASE- INTRACELLULAR
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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
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Base excretion Only kidney regulated
Primary base in the organism HCO3-
The kidney can retain or excrete bicarbonate as needed
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Physiological variations of pH Circadian rhythm (night CO2 accumulation)
Age (anabolism in children/newborns; catabolism in aged)
Physical effort (lactic acid)
Digestion (gastric- alkalosis; intestinal- acidosis)
Altitude (hyperventilation)
Temperature variations (inversely prop)
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1. Enzyme activity
2. Action potential of myelinated nerve
3. Membrane permeability
4. Control of respiration
5. Heart activity
6. Oxygen Hb dissociation curve
7. Nerve excitability
Biological importance of pH
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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
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pH and synaptic transmission Alkalosis increases transmission- alkalosis> 7.8
seizures
Acidosis decreases transmission- acidosis< 7 coma
(uremic/ diabetic- ketone bodies )
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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
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Bohr effect
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pH and ventilation
chemoR
Peripheral (carotid/ aortic body)
Central(medulla oblongata)
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Maintainance of AB balance2 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 (regulate AB in minutes) and kidneys play a major role (regulate AB balance in days)
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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.
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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
Buffers
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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
Blood Bicarbonate Important for metabolic acids
Haemoglobin Important for carbon dioxide
Plasma protein Minor buffer
Phosphate Concentration too low
ICF Proteins Important buffer
Phosphates Important buffer
Urine Phosphate Responsible for most of 'Titratable Acidity'
Ammonia Important - formation of NH4+
Bone Ca carbonate In prolonged metabolic acidosis
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Buffering power of a buffer 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:
pK of buffer systemhighest when pK=pH
The relative conc of buffer components: the highest when components ratio is 1:1
The amount of buffer comp
Open/ closed system (if the system can equillibrate with the environment)
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Bicarbonate buffer
The most important extracellular buffer (35% of total buffering cap of total blood, 75% of plasmatic one)
Noncarbonic acids!
Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3)
Maintain a 20:1 ratio : HCO3- : H2CO3
HCl + NaHCO3 ↔ H2CO3 + NaCl
NaOH + H2CO3 ↔ NaHCO3 + H2O
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Bicarbonate buffer system Pk=6,1 plasma conc 25 mEq/l Base:acid= 20:1
H2CO3+ NaHCO3
H2CO3- forms from CO2 + H2O (carbonic anhidrase) H2CO3 H+ + HCO3- NaHCO3 Na+ + HCO3-
CO2 + H2OH2CO3H+ + HCO3-
Na+
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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)
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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 consumesmore CO2 is used to bring H2CO3 back to normal low CO2 inhibits respiration
Also: NaHCO3 Na+ + HCO3- high HCO3- urine excreted
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Protein buffer systems Plasmatic- albumins
Intracellular- very imp HB in RBC !
Proteins are highly concentrated inside the cells
Low importance in plasma (low conc-7% of buffering cap of whole blood/10% of plasmatic one)
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Protein buffer systems 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
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Amphoteric substances
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Hemoglobin buffer system Main non-bicarbonate buffer system in the blood
35% of total blood buffering cap
Extracellular acidity buffering (RBC mb highly permeable)
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pH and CO2 influence on Hbaffinity for O2 H+ in blood links to His residues and -NH2 terminal
groups tensed Hb moleculeO2 release
pCO2 in blood links to the 4 -NH2 globin groups/ val residues carbaminoHb O2 release
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Hamburger/ reversed Hamburger phenomenon Hamburger ph- RBC bicarbonate synthesis
Reversed Hamburger ph- RBC carbonic acid synthesis
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HAMBURGER REVERSED HAMBURGER
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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 twice the concentration 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+.
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Interstitial buffer systems Bicarbonate
- interstitial fluid volume= 3x plasma- important for noncarbonic acid buffering
- concentration= plasma one
Phosphate
Low imp (low conc)
Proteins
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Cellular buffers- others than RBC 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
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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)
sodium dihydrogen phosphate (NaH2PO4) is its weak acid, and monohydrogen phosphate (Na2HPO4) is its weak base.
HCl + Na2HPO4 NaH2PO4 + NaCl
NaOH + NaH2PO4 Na2HPO4 + H2O
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Phosphate buffer system Low imp in the plasma (low conc)
Plasma conc= 2mEq/l
pK=6,8 (intracellular pH)
Basis/acid=4:1
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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 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
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Muscle Half the cellular mass
Most intracellular buffering
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Buffer system take home message Carbonate and Hb- most efficient (Hb most efficient
releases bicarbonate)
Bicarbonate- most imp extracellular
Proteins and phosphates- most imp intracellular
Anemia lowers buffering capacity
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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 hydrates (CA) and forms H2CO3 H+ + HCO3-
H+ influences central chemoR
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Acid base balance and lungs
Low pH hyperventilation
High pHhypoventilation
Ex: ventilation increases 4-5 x when pH is 7!
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Kidneys and AB balanceKidneys 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
reabsorption2. H+ combines with urinary buffers TITRABLE ACIDS
and AMMONIUM3. Low amount free in the urine
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Anatomy
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Urine formation
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Filtration
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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
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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
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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(aldosterone)
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Bicarbonate reabsorption
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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- reabsorption in the blood
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H+ secretion and bicarbonate reabsorption
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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
Minimum urinary pH= 4.5 (0,03 mEq/l)
Any H+ that exceeds this limit (up to 500 mEq/day)urinary buffers that DO NOT generate extra H+-phosphate (titrable acidity) and NH4+
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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+
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Formation and excretion of titrable acid (TA)- phosphate BS pK HPO42- /H2PO4-= 6,8 and 90% of the buffering activity
of HPO42- occurs above a pH of 6.8- more efficient (more concentrated)
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
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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
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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+
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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)
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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
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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 !!