Acid-Base balance and imbalance

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Acid- Base Balance and Imbalance
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pH Review

• pH - log H
• H is really a proton
• Range is from 0 - 14
• If H is high, the solution is acidic pH lt 7
• If H is low, the solution is basic or alkaline
  pH gt 7

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• Acids are H donors.
• Bases are H acceptors, or give up OH- in
  solution.
• 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-base equilibrium

• Acid- a compound that acts as a proton donor in
  aqueous solution.
• Base- a compound that acts as a proton acceptor
  in aqueous solution.
• Conjugate pair- an acid together with its
  corresponding base.
• alkali a compound that liberates hydroxyl ions
  when it dissociates.
• Ampholyte - a compound that can act as both an
  acid and a base e.g water that dissociates to
  give a proton and a hydroxyl ion

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Bronsted acid and base concept

• When a Bronsted acid loses a proton, a bronsted
  base is produced. The original acid and
  resulting base are referred to as a conjugate
  acid conjugate base pair.
• The substance that accepts the proton is a
  different Bronsted base by accepting a proton,
  another Bronsted acid is produced. Thus in every
  ionisation of an acid or base, two conjugate
  acid conjugate base pairs are involved

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HA B A- HB Conjugate acid1 conjugate base2
? conjugate base1 conjugate acid2 Strong
acid A substance that ionises completely in
aqueous solution HCl H2O ? H3O Cl-
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• The hydronium ion or conjugate acid of water is
  the actual form of the hydrogen ion in solution.
  Therefore simple dissociation is considered
• HCl ? H Cl-
• The hydronium and proton mean the same
• Strong base
• A substance that ionises extensively in solution
  to yield OH- ions.

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• pH and pOH
• pH is the negative logarithm of the hydrogen ion
  activity
• pOH is the negative logarithm of the hydroxyl
  ion activity
• pH - log H log 1 H

log 1 OH-
pOH - log OH-
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Ionisation of Weak acids

• Consider
• R-NH2 HOH
• Conju.base1 conju.acid2

- R-NH3 OH conju.acid1 conju.base2
The two conju.acid conju.base pairs involved
are R-NH3 /R-NH2 and HOH/OH-. The ionisation can
be described by an ionisation constant Ki
R-NH OH- 3 R-NH2H2O
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Weak acids, their conjugate bases, and buffers

• Weak acids have only a modest tendency to shed
  their protons (definition of an acid).
• When they do, the corresponding negatively
  charged anion becomes a willing proton acceptor,
  and is called the conjugate base.
• The properties of a buffer rely on a balance
  between a weak acid and its conjugate base.
• And a titration curve looks like this

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Titration of acetic acid with sodium hydroxide
_ _ _ _ _ _ _
CH3COO-
pH 7
CH3COOH CH3COO-
Buffering region only small pH
pKa 4.76
changes result
from addition of base or acid
pHpKa 4.76
50 dissociation CH3COOH
0 equiv. of NaOH 1.0 added
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• A buffer is a solution of a weak acid and its
  conjugate base that resists changes in pH when
  small amounts of an acid or base are added.
• A buffer works best in the middle of its range,
  where the amount of undissociated acid is about
  equal to the amount of the conjugate base.
• One can soak up excess protons (acid), the other
  can soak up excess hydroxide (base).

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• An acidic buffer contains a weak acid and a
  salt of the weak acid (conjugate base).
• A basic buffer contains a weak base and a salt
  of the weak base (conjugate acid).
• Together the two species (conjugate acid
  conjugate base) resist large changes in pH by
  partially absorbing additions of H or OH- ions
  to the system.

H

• If is added it reacts partially with

conju.base to form conju.acid. Thus some H is
taken out of circulation.
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• If OH- is added it reacts partially with
  conjugate acid to form water and a conjugate
  base, taking some OH- out of circulation.

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Insights in practice

• pH control is important, as many enzymes have a
  narrow range in which they function optimally.
• Buffering capability is essential for the
  well-being of organisms, to protect them from
  unwelcome changes in pH.
• For example, the stomach is about pH 1, yet the
  adjacent portion of is near pH 7think about (or
  look up) how that might happen Hint what is one
  function of the pancreas?.
• Many compounds and macromolecules in addition to
  bicarbonate can serve a buffering function
  proteins comprise one of the major classes.

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The Body and pH

• Homeostasis of pH is tightly controlled
• Extracellular fluid 7.4
• Blood in range of 7.35 7.45
• If it is lt 6.8 or gt 8.0 death occurs
• Acidosis (acidemia) below 7.35
• Alkalosis (alkalemia) above 7.45

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Small changes in pH can produce major
disturbances

• Most enzymes function only with narrow pH ranges
• Acid-base balance can also affect electrolytes
  (Na, K, Cl-)
• Can also affect hormones

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The body produces more acids than bases

• Acids are taken in with foods
• Acids are produced by metabolism of lipids and
  proteins
• Cellular metabolism produces CO2.
• CO2 combines with water to form carbonic acid.
  H2CO3 dissociates into hydrogen bicarbonate ions

H
CO2 H20 ? H2CO3 ? HCO3-
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• Acids in the blood of normal individuals
• Strong acid sulphuric acid in dietary sulphates
  , S- containing amino acids
• Weak acids
• Carbonic acid from CO2 in TCA cycle
• Lactic acid from anaerobic glycoysis
• Pyruvic acid from glycolysis
• Citric acid from TCA diet e.g. citrus fruits
• Acetoacetic acid from fatty acid oxidation to
  ketone bodies
• Acetic acid from ethanol metabolism
• Dihydrogen phosphate dietary organic phosphates
• Ammonium ion dietary N-containing cpds

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Control of Acids

• Buffer
• A mixture of undissociated acid and its conjugate
  base (form of the acid that has lost its proton)
• Buffer systems
• Take up H or release H as conditions change
• Buffer pairs are in form of weak acid and a base
• Results in a much smaller pH change

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Bicarbonate buffer system

• Sodium Bicarbonate (NaHCO3) and carbonic acid
  (H2CO3)
• Major source of metabolic acid in body is CO2 in
  TCA cycle
• Maintain a 201 ratio HCO3 H2CO3
• -
• CO2 dissolves in water to produce carbonic acid
  catalysed by carbonic anhydrase. Carbonic acid
  partially dissociates into H and bicarbonate
  anion.

H

• As a base is added is removed, H2CO3

dissociates into H HCO-3 ions, and CO2 reacts
with water to replenish the H2CO3
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Bicarbonate buffer system

• Dissolved CO2 is in equilibrium with alveolar air

CO2 in

• Thus availability of CO2 can be decreased or
  increased through rate of breathing amount of
  CO2 expired

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Bicarbonate Haemoglobin in RBCs

• The bicarbonate buffer system corporates with Hb
  in buffering blood transporting CO2
• Most CO2 from TCA diffuses into interstitial
  fluid plasma then into RBCs.
• RBCs contain carbonic anhydrase that converts CO2
  to H2CO3 with in these cells

H

• As H2CO3 dissociates released is buffered by

combination with Hb (His in Hb acepts the H)
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• The HCO-3 is transported out of RBC in exchange
  for Cl-, thus HCO-3 is relatively high in
  plasma.
• As the RBC approaches the lungs, the direction of
  equilibrium reverses
• CO2 is released from RBC, causing more carbonic
  acid to dissociate into CO2 and water, and more
  H to combine with bicarbonate

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2. Respiratory mechanisms

• Exhalation of carbon dioxide
• Powerful, but only works with volatile acids
• Doesnt affect fixed acids like lactic acid

H

• CO2 H20 ? H2CO3 ?

- HCO3

• Body pH can be adjusted by changing rate and
  depth of breathing

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3. Kidney excretion

• Can eliminate large amounts of acid
• Can also excrete base
• Can conserve and produce bicarb ions
• Most effective regulator of pH
• If kidneys fail, pH balance fails

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Kidney excretion urinary hydrogen, ammonium,
and phosphate ions

• Nonvolatile acid cant be eliminated as CO2
• Is excreted in urine in undissociated form that
  buffers urinary pH btn 5.5 to 7.0

• Acid secretion includes inorganic
  phosphates ammonium ions,

acids uric
e.g. acid,
dicarboxylic acids, and TCA acids citric acid
etc.
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Kidney excretion urinary hydrogen, ammonium,
and phosphate ions

• Sulphuric acid is also a nonvolatile acid that
  dissociates in blood urine
• NB
• Urinary excretion of H2PO4- helps to remove acid
• Whether the phosphate is present in urine as or
  depends on urinary pH pH of blood.
• NH4- is major contributor to buffering urine, but
  not blood

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Kidney excretion urinary hydrogen, ammonium,
and phosphate ions

• Ammonia (NH3) is a base combines with H to
  form ammonium ion.
• Cells in kidney generate NH4 excrete it in
  urine
• As renal tubular cells transport H into urine,
  they return bicarbonate into blood.

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Rates of correction

• Buffers function almost instantaneously
• Respiratory mechanisms take several minutes to
  hours
• Renal mechanisms may take several hours to days

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Acid-Base Imbalances

• pHlt 7.35 acidosis
• pH gt 7.45 alkalosis
• The body response to acid-base imbalance is
  called compensation
• May be complete if brought back within normal
  limits
• Partial compensation if range is still outside
  norms.

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Compensation

• If underlying problem is metabolic,
  hyperventilation or hypoventilation can help
  respiratory compensation.
• If problem is respiratory, renal mechanisms can
  bring about metabolic compensation.

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Acidosis

• Principal effect of acidosis is depression of the
  CNS through ? in synaptic transmission.
• Generalized weakness
• Deranged CNS function - the greatest threat
• Severe acidosis causes
• Disorientation
• coma
• death

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Alkalosis

• Alkalosis causes over excitability of the central
  and peripheral nervous systems.
• Numbness
• Lightheadedness
• It can cause
• Nervousness
• muscle spasms or tetany
• Convulsions
• Loss of consciousness
• Death

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Respiratory Acidosis

• Carbonic acid excess caused by blood levels of
  CO2 above 45 mm Hg.
• Hypercapnia high levels of CO2 in blood
• Chronic conditions
• Depression of respiratory center in brain that
  controls breathing rate drugs or head trauma
• Paralysis of respiratory or chest muscles
• Emphysema

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Respiratory Acidosis

• Acute conditions
• Adult Respiratory Distress Syndrome
• Pulmonary oedema
• Pneumothorax

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Compensation for Respiratory Acidosis

• Kidneys eliminate hydrogen ion and retain
  bicarbonate ion

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Signs and Symptoms of Respiratory Acidosis

• Breathlessness
• Restlessness
• Lethargy and disorientation
• Tremors, convulsions, coma
• Respiratory rate rapid, then gradually depressed
• Skin warm and flushed due to vasodilation caused
  by excess CO2

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Treatment of Respiratory Acidosis

• Restore ventilation
• IV lactate solution
• Treat underlying dysfunction or disease

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Respiratory Alkalosis

• Carbonic acid deficit
• pCO2 less than 35 mm Hg (hypocapnea)
• Most common acid-base imbalance
• Primary cause is hyperventilation

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Respiratory Alkalosis

• Conditions that stimulate respiratory center
• Oxygen deficiency at high altitudes
• Pulmonary disease and Congestive heart failure
  caused by hypoxia
• Acute anxiety
• Fever, anaemia
• Early salicylate intoxication
• Cirrhosis
• Gram-negative sepsis

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Compensation of Respiratory Alkalosis

• Kidneys conserve hydrogen ion
• Excrete bicarbonate ion

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Treatment of Respiratory Alkalosis

• Treat underlying cause
• Breath into a paper bag (or using a mask that
  causes you to re-breathe carbon dioxide --
  sometimes helps reduce symptoms.)
• IV Chloride containing solution Cl- ions
  replace lost bicarbonate ions

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Metabolic Acidosis

• Bicarbonate deficit - blood concentrations of
  bicarb drop below 22mEq/L

• Causes
• Loss of bicarbonate dysfunction

through
diarrhea
or renal

• Accumulation of acids (lactic acid or ketones)
• Failure of kidneys to excrete H

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Symptoms of Metabolic Acidosis

• Headache, lethargy
• Nausea, vomiting, diarrhea
• Coma
• Death

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Compensation for Metabolic Acidosis

• Increased ventilation
• Renal excretion of hydrogen ions if possible
• K exchanges with excess H in ECF ( H into
  cells, K out of cells)

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Treatment of Metabolic Acidosis

• IV lactate solution

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Metabolic Alkalosis

• Bicarbonate excess - concentration in blood is
  greater than 26 mEq/L
• Causes
• Excess vomiting loss of stomach acid
• Excessive use of alkaline drugs
• Certain diuretics
• Endocrine disorders
• Heavy ingestion of antacids
• Severe dehydration

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Compensation for Metabolic Alkalosis

• Alkalosis most commonly occurs with renal
  dysfunction, so cant count on kidneys
• Respiratory compensation difficult
  hypoventilation limited by hypoxia

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Symptoms of Metabolic Alkalosis

• Respiration slow and shallow
• Hyperactive reflexes tetany
• Often related to depletion of electrolytes
• Atrial tachycardia
• Dysrhythmias

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Treatment of Metabolic Alkalosis

• Electrolytes to replace those lost
• IV chloride containing solution
• Treat underlying disorder

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Diagnosis of Acid-Base Imbalances

• Note whether the pH is low (acidosis) or high
  (alkalosis)
• Decide which value, pCO2 or HCO - , is outside
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• the normal range and could be the cause of
• the problem. If the cause is a change in pCO2,
  the problem is respiratory. If the cause is HCO
  - the problem is metabolic. (WHY?)
• 3

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3. Look at the value that doesnt correspond to
the observed pH change. If it is inside the
normal range, there is no compensation
occurring. If it is outside the normal range,
the body is partially compensating for the
problem.
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Example

• A patient is in intensive care because he
  suffered a severe myocardial infarction 3 days
  ago. The lab reports the following values from
  an arterial blood sample
• pH 7.3
• HCO3 20 mEq / L ( 22 - 26)
• -
• pCO2 32 mm Hg (35 - 45)

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Diagnosis

• Metabolic acidosis
• With compensation

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