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    By John Santangelo

    Henderson-Hasselbach Equation

    June 2010

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    Blood pH is determined by a balance between

    bicarbonate and CO2

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    Blood pH = 7.36 7.44(slightly Alkaline)

    Enzyme

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    pH (potential of Hydrogen)

    The logarithm of the reciprocal of

    hydrogen-ion concentration in gramatoms per liter; provides a measure on ascale from 0 to 14 of the acidity or

    alkalinity of a solution (where 7 isneutral and greater than 7 is more basicand less than 7 is more acidic);

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    REGULATIONOFACIDBASEBALANCE

    The bodyhas the remarkable ability tomaintain plasma pH within the narrow

    normal range of7.36 to 7.44. It does so

    by means of chemical buffering

    mechanisms, by the kidneys, and by the

    lungs. The pH is defined as hydrogen ion

    concentration; the more hydrogen ions,

    the more acidic the solution. The pH rangethat is considered to be compatible with

    life is (6.87.8)

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    Formulae to describe the carbonic acid -

    bicarbonate buffer system.

    The two headed arrows indicate that the processis reversible

    H + HCO3 H2CO3 H2O + CO2

    Hydronium Ion (H+) + Bicarbonate (HCO3-) Carbonic Acid (H2CO3) Water (H2O) +

    Carbon Dioxide (CO2)

    The Carbon Dioxide (CO2) and Water (H2O) are

    blown off by the Lungs.Hyperventilation will speed up the reaction and a

    blockage in the airways will slow down the

    reaction (Hypoventilation)

    Carbonic Andydrase

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    Using the Hendersen-Hasselbach

    equation,

    pH = 6.10 + Log HCO3-

    PCO2 X 0.030

    In order to keep the pH of blood at 7.4,

    and given pKa = 6.1 for bicarbonate, the

    ratio of bicarbonate to 0.03 pCO2 should

    remain constant. i.e. 20 to 1

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    The Chief Mammalian Blood Buffer is a Mixture of

    Bicarbonate and Carbon Dioxide.

    All body fluids, inside or outside cells have bufferswhich defend the body against pH changes.

    The most important buffer in extracellular fluids,

    including blood, is a mixture of carbon dioxide (CO2)

    and bicarbonate anion (HCO3)

    CO2 acts as an acid (it forms carbonic acid when it

    dissolves in water), donating hydrogen ions when they

    are needed.

    HCO3 is a base, soaking up hydrogen ions when there

    are too many of them.There are also other buffers in blood, such as proteins

    and phosphate, but they are less important.

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    Abnormal acid-base balance

    Acid-base imbalances can be defined as acidosis or

    alkalosis.

    Acidosis is a state of excess H+.

    Acidemia results when the blood pH is less than 7.35.

    Alkalosis is a state of excess HCO3-.

    Alkalemia results when the blood pH is greater than 7.45.

    When the acid-base disturbance results from a primary

    change in HCO3-, it is a metabolic disorder; when the

    primary disturbance alters blood pCO2, it is a respiratory

    disorder.Compensation for these disturbances can be respiratory or

    metabolic (i.e. renal) in nature and is intended to minimize

    further pH changes. The following table mayhelp clarify

    th

    is for you.

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    Acid-baseimbalance

    Plasma pH Primarydisturbance

    Compensation

    R

    espiratoryacidosis - low - increased pCO

    2 - increased renalnet acid excretion

    with resulting

    increase in serum

    bicarbonate

    Respiratory

    alkalosis

    - high - decreased pCO2

    - decreased renal

    net acid excretion

    with resulting

    decrease in serum

    bicarbonate

    Metabolic acidosis - low - decreased HCO3- - hyperventilation

    with resulting low

    pCO2

    Metabolic alkalosis - high - increased HCO3- - hypoventilation

    with resulting

    increase in pCO2

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    Understanding the cause of an acid-base

    imbalance is the key to treating it.

    The simplified approach to understanding therelationship of acid and base starts with

    carbonic acid (H2CO3).

    Carbon dioxide is an acid when dissolved in

    water.Carbon dioxide is produced by metabolism.

    As long as cells are functioning, there will be

    CO2 produced.

    The respiratory mechanism affects the pHwithin minutes.

    Metabolic changes can take days to affect

    pH.

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    Acid-base balance

    H+ importance and concentration in the body

    Chemistry of acid, base and buffers Sources of acids in the body

    Buffer mechanisms in the body

    The chemical buffers

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    H+ importance and concentration in

    the body Hydrogen ions are very small and reactive.

    Normal concentration = 40nmole/L(compare with concentration of 4 and

    140mmole for K and Na). H+ concentration is therefore given within

    the pH scale: pH = -log [H +]

    Normal range for pH ofarterial blood is:

    7.35-7.45 Extreme ranges that may be tolerable with

    life are: 6.9-7.8

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    Chemistry ofacid, base and buffers -I

    Acid - a substance that can donate [H+] Base - a substance that can receive [H+]

    Strong acid - completely dissolved in liquid.

    Weakacid - partially dissolved in liquid.

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    Chemistry ofacid, base and buffers -II

    Buffer - oppose big changes in the pHof a liquid

    A buffer is usually composed of weakacid (HA) and conjugated base (A-).

    The Hendeson-Hasselebach equation:

    pH=pK+log([A-]/[HA])

    Buffering is most effective for pHvalues within +/- 1.5 pH units of thepK.

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    Sources of acids in the body

    Volatile acids - CO2,

    Non-volatile (Fixed) acids,

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    Sources ofacids in the body

    - volatile acids

    End products of oxidation of glucose

    and fats in aerobic metabolism Glucose, Fat +O2 -> ATP + CO2

    CO2+H2O H2CO3 H++HCO3-

    H2CO3 - carbonic acid is converted toCO2 and expired by the lung - Volatile

    acid.

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    Sources ofacids in the body

    - Non-volatile (fixed) acids

    End products of metabolism of sulfur

    containing amino-acid, ph

    osph

    olipidsor phospoproteins.

    Called Fixed acids because they cant

    be expired by the lungs and are

    secreted by the kidney.

    Amount depends on diet.

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    The main fixed acids

    Sulfuric acid - oxidation of sulfurcontaining acids (e.g., cysteine)

    Phosphoric acid - oxidation of phospho-

    lipids or phospo-proteins. HCl- Conversion of ingested ammonium

    chloride to urea.

    Lactic acid - Anaerobic metabolism of

    glucose Acetoacetic and Butyric acid - Diabetic

    ketoacidosis

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    The buffer systems of the body

    Chemical buffers

    Lung

    Kidney

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    The chemical buffers

    The Bicarbonate buffer

    The Non-bicarbonate buffers: Hemoglobin

    Plasma proteins

    The p

    hosp

    hate buffer

    H2PO4 H+ + HPO4

    2-

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    The importance of the bi-carbonate

    buffer

    pK=6.1

    The total concentration of the buffer pair(CO2, HCO3

    -) is quite high: 24+1.2=~

    26mmol/L The Bi-carbonate buffer is part of an open

    system:

    The lung holds the [CO2] constant by

    adjusting alveolar ventilation The kidneys replace HCO3

    - that is lostduring the buffering process

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    Normal ValuesNormal Values

    pH = 7.35 7.45

    PCO2 = 38 42 mmHg (5.07 5.60 kPa)

    Actual [HCO3-] = 23 27 mmol/l

    Standard [HCO3-] = 23 27 mmol/l

    Buffer bases = 46 52 mEq/l

    Excess Base = - 2; +2 mEq/l

    Total CO2 = 24 28 mmol/l

    HCO3-/H2CO3 = 18 - 22

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    Causes ofAcid Base disturbances

    1. RespiratoryAcidosis.

    2. RespiratoryAlkalosis.

    3. Metabolic Acidosis.

    4. Metabolic Alkalosis.

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    Causes ofAcid Base disturbances

    Respiratory Acidosis:

    This is synonymous with CO2 retention and is

    usually a sign of hypoventilation.

    Causes:1. Central Nervous System (CNS).

    2. Lung & Airway disorders.

    3. Chest wall abnormality.

    4. Muscle disorders.

    5. Neuro Muscular transmission.

    6. Peripheral neuropathy.

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    Inhalation ofCO2 is another cause of respiratory

    acidosis but is only likely to occur under

    situations of rebreathing,

    e.g. under anaesthesia.

    RespiratoryAcidosis is associated with raised

    alveolarCO2

    , raised re-breath

    ingCO2

    andh

    igh

    PCO2 in the arterial blood.

    Compensation for chronic respiratory acidosis is

    loss of(H+)Cl- and retention of(Na+)HCO3- by

    the kidneys.

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    Normal Blood pH is 7.36 to 7.42

    i.e. slightly alkaline

    Either mechanism (respiratory or metabolic)

    can cause an acidosis or an alkalosis.

    Hyperventilation will lead to respiratoryAlkalosis causing Tetany.

    Tetany is a condition of prolonged and painful spasms of the voluntary

    muscles, especially the fingers and toes (carpopedal spasm) as well as

    the facial musculature.

    An airway blockage will lead to respiratory

    Acidosis (Hypoventilation).

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    Respiratory Alkalosis

    is associated with Hyperventilation

    Causes:

    1. Hysterical hyperventilation.

    2. Some cases ofCNS damage.

    3.

    Deliberate

    hyperventilation duringanaesthesia.

    4. Some cases ofhypoxia.

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    RespiratoryAlkalosis is usually

    acute so there is no time for Renal

    Compensation, but if it prolonged,there will Renal excretion of an

    increased quantity ofBase

    (NaHCO3)

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    Metabolic AcidosisDue to increased Acids

    Causes

    a. Increased intake (alimentary or

    parenteral).

    b. Increased production ofAcid.

    c. And, Failure of excretion.

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    Increased IntakeTh

    eA

    cid content of th

    e blood can be raised by:Ingestion or injection ofNH4CL or diluteHCL.

    The HCL directly increases the H+.

    The NH4CL produces HCL by the NH3 beingsplit off and converted to Urea.

    Adding NH4CL directly to blood would not

    change the pH without the Liver intervening.

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    Loss of intestinal contents by diarrhoea or smallbowel obstruction causes a loss of fluid of high pH,

    i.e. containing an excess of Base (NaHco3.

    The removal of Base allows the H+ to rise.

    Ingestion of organic acids

    Organic Acids would not usually produces changesin the pH because the liver would metabolize them

    but liver disease could allow organic acids, if

    ingested, to gain access to the systemic circulation.

    Infusion of stored blood will add acid to the bodybecause it contains citric acid.

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    Excess Acid might accumulate in the blood from processes ofmetabolism and cause a fall in blood pH.

    There are two main mechanisms for this:

    HypoxiaHypoxia from any cause, causes anaerobic glycolysis to increase.

    This gives rise to Lactic Acid and not CO2.

    The Lactic Acid lowers the pH

    The causes of Hypoxia are:1. Low oxygen in inspired air

    2. Lung disorders

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    3. Hypoventilation.

    4. Low cardiac output (including shock states)

    5. Blood defect: hypovolaemia, anaemia or CO

    poisioning.

    6. Tissue toxins, e.g. cyanide.

    Circulatory occlusion to any large area will

    cause accumulation of organic acids in the area

    supplied. On restoration of the circulation these

    acids will be distributed systemically.Th

    is is apossible cause of acidosis if the general

    circulation and temperature are not

    maintained.

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    Diabetes and Starvation

    In both these states keto acids are produced and therewill be some attempt at renal excretion (Ketourea).

    Failure of excretion of acid could lead to acidosis.

    Normally, during metabolism some inorganic acids areproduced, i.e. H2SO4 and H3PO4. These cations haveto be excreted by the kidneys covered either by, Na+,K+, (small amount) NH4+ (produced in the kidney)

    Normally the amount involved is not great, but over along period if there is failure of excretion,accumulation will occur with a fall in pH.

    Th

    is is Renal Acidosis

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    Any of these absolute or the relative

    increases in acids can cause a fall in pHand this would be a metabolic acidosis.

    Th

    e final compensatory mech

    anism formetabolic acidosis is induced respiratory

    alkalosis produced byhyperventilation.

    The low pH stimulates the respiratory

    centre.

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    MetabolicAlkalosisThis is due to ingestion or injection of excess

    base. i.e NaHCO3 or NAOH or loss of gastric juice

    containing HCL.

    Acommon cause of alkalosis is excess loss of

    CL-(i.e. HCL or NH4CL) from excessive and

    improperly observed diuretic treatment.

    Metabolic alkalosis is compensated by

    respiratory depression which causes CO2retention but might also cause hypoxia. The pH

    is usually raised but might be high normal if

    there is muchCO2 retention.

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    DiagnosisAcid Base disturbances

    Clinical picture

    Anybody with, Pneumonia, Sweating, Bounding Pulse,probablyhas CO2 retention.

    Intestinal obstruction or severe diarrhoea probablyhas

    acidosis due to loss of base. (NaHCO3)

    A diabetic who is drowsy and hyperventilating with

    urinary glucose and ketones probablyhas keto-acidosis.

    Shock, with poor tissue perfusion mayhave lactic

    acidosis.

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    TreatmentRespiratoryAcidosis is corrected by increased

    ventilation.

    RespiratoryAlkalosis is corrected by reducing

    ventilation or increasing the dead space.

    Metabolic Acidosis

    Treat the cause

    Stop alimentary loss; correct hypoxia; reduce

    renal load by diet; Give insulin; treat shock.

    NaHCO3 is the most commonly used.

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    Metabolic Alkalosis

    Remove the cause.

    1. relieve pyloric obstruction or modify diuretic

    regime.

    2. Ingestion or injection of sufficient NaCL forthe kidney to correct the alkalosis by excretion

    ofNaHCO3.

    3.

    Direct correction of alkalosis wit

    h

    NH4

    CL(orHCL) infusion or ingestion. This is only

    indicated if the alkalosis is very severe or renal

    or cardiac function are poor.

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    Blood gases are measured usingArterial Blood,NOTVenous Blood.

    A glass Syringe is usually used with a smallamount of Heparin as an anticoagulant.

    Care should be taken not to include Air Bubbles

    in the syringe as this would alter the values.

    The blood and syringe should be transported onto the laboratory, on ice, as soon as possible.

    The Radial, Brachial or Femoral Arteries areusually the preferred sites. The Radial artery

    being the most common as it is easier to accessand less painful.

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    Usually there is associated reduction of extracellular

    volume so some Sodium has to be given in the form of

    NaCL solution.

    4. Control of respiratory failure if this is severe.