Mohammed A. Almeziny
BPharm.RPh. Msc. PhD
Clinical Pharmacist
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Homeostasis of pH is tightly controlled
Extracellular fluid = 7.4
Blood = 7.35 – 7.45
< 6.8 or > 8.0 death occurs
Acidosis (acidemia) below 7.35
Alkalosis (alkalemia) above 7.45
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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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Cardiovascular
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Pulmonary
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(e.g., impaired oxygen delivery, respiratory muscle
fatigue, dyspnea),
Renal
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(e.g., impaired contractility, arrhythmias),
(e.g., hypokalemia)
Neurologic
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(e.g., decreased cerebral blood flow, seizures, coma).
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Acids take in with foods
Acids produced by metabolism of lipids and
proteins
Cellular metabolism produces CO2.
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Balance maintained by:
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Buffering systems
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Lungs
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Kidneys
1-Buffer systems
 Prevent major changes in pH
 Act as sponges…
H+
 3 main systems
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Bicarbonate-carbonic acid buffer
Phosphate buffer
Protein buffer
H+
H+
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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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Major intracellular buffer
H+ + HPO42- ↔ H2PO4-
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OH- + H2PO4- ↔ H2O + H2PO42-
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Includes hemoglobin, work in blood and ISF
Carboxyl group gives up H+
Amino Group accepts H+
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Exhalation of carbon dioxide
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respiratory control center in the medulla to increase
the rate and depth of ventilation.
 Peripheral chemoreceptors (located in the carotid arteries
and the aorta)
 activated by arterial acidosis, hypercarbia (elevated PaCO2),
and hypoxemia (decreased PaO2).
 Central chemoreceptors (located in the medulla).
 activated by cerebrospinal fluid (CSF) acidosis and by
elevated carbon dioxide tension in the CSF
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Powerful, but only works with volatile acids
Doesn’t affect fixed acids like lactic acid
CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3Body pH can be adjusted by changing rate and
depth of breathing
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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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Buffers function almost instantaneously
Respiratory mechanisms take several minutes
to hours
Renal mechanisms may take several hours to
days
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pH< 7.35 acidosis
pH > 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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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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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 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
Respiratory Alkalosis
Metabolic Acidosis
Metabolic Alkalosis
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Carbonic acid excess caused by blood levels of
CO2 above 45 mm Hg.
Hypercapnia – high levels of CO2 in blood
Chronic conditions:
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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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Acute conditons:
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Adult Respiratory Distress Syndrome
Pulmonary edema
Pneumothorax
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Kidneys eliminate hydrogen ion and retain
bicarbonate ion
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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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Restore ventilation
Treat underlying dysfunction or disease
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Carbonic acid deficit
pCO2 less than 35 mm Hg (hypocapnea)
Most common acid-base imbalance
Primary cause is hyperventilation
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Conditions that stimulate respiratory center:
Oxygen deficiency at high altitudes
 Pulmonary disease and Congestive heart failure –
caused by hypoxia
 Acute anxiety
 Fever, anemia
 Early salicylate intoxication
 Cirrhosis
 Gram-negative sepsis
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Kidneys conserve hydrogen ion
Excrete bicarbonate ion
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Treat underlying cause
Breathe into a paper bag
IV Chloride containing solution – Cl- ions
replace lost bicarbonate ions
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Bicarbonate deficit - blood concentrations of bicarb
drop below 22mEq/L
Causes:
Loss of bicarbonate through diarrhea or renal dysfunction
 Accumulation of acids (lactic acid or ketones)
 Failure of kidneys to excrete H+
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Normal AG
 Hypokalemic
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Diarrhea
Fistulous disease
Ureteral diversions
Type 1 RTA
Type 2 RTA
Carbonic
anhydrase inhibitors
Hyperkalemic
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Hypoaldosteronism
Hydrochloric acid or
precursor
Type 4 RTA
Potassium-sparing
diuretics
 Amiloride
 Spironolactone
 Triamterene
Elevated AG
 Renal Failure
 Lactic Acidosis (see Table
10-5)
 Ketoacidosis
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Drug Intoxications
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Starvation
Ethanol
Diabetes mellitus
Ethylene glycol
Methanol
Salicylates
AG, anion gap; RTA, renal tubular acidosis.
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Headache, lethargy
Nausea, vomiting, diarrhea
Coma
Death
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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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Treat underlying cause
IV Bicarbonate solution
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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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Respiratory compensation difficult –
hypoventilation limited by hypoxia
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Respiration slow and shallow
Hyperactive reflexes ; tetany
Often related to depletion of electrolytes
Atrial tachycardia
Dysrhythmias
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Treat underlying disorder
Electrolytes to replace those lost
IV chloride containing solution
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0.1 N HCL
Infusion rate 0.2 mmol/kg/hr
Central line
Acetazolamide
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Disorder
Metabolic
acidosis
Respiratory
acidosis
Metabolic
alkalosis
Respiratory
alkalosis
Arterial
pH
Primary
Change
Compensatory
Change
↓
↓HCO3-
↓PaCO2
↓
↑PaCO2-
↑HCO3-
↑
↑HCO3-
↑PaCO2
↑
↓PaCO2-
↓HCO3-
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Arterial Blood Gas (ABG)
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Arterial carbon dioxide tension (PaCO2).
Serum bicarbonate (HCO3-).
Arterial oxygen tension (PaO2)
pH
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<7.35, the patient is considered academic
>7.45, the patient is considered alkalemic
ABGs
Normal Range
pH
7.36–7.44
PaO2
90–100 mmHg
PaCO2
35–45 mmHg
HCO3-
22–26 mEq/L
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The concentration of all the unmeasured anions
in the plasma eg lactate, acetoacetate, sulphate.
Anion gap = [Na+] - [Cl-] - [HCO3-]
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Reference range is 8 to 16 mmol/l.
Adjusted AG = AG + 2.5 × (normal albumin –
measured albumin in g/dL
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Clinical Use of the Anion Gap
To signal the presence of a metabolic acidosis
and confirm other findings
 Help differentiate between causes of a
metabolic acidosis
 To assist in assessing the biochemical
severity of the acidosis and follow the
response to treatment
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Osmolality mOsm/kg H2O= (1.86[Na])+([glucose
(mmol/L)])+([BUN mmol/L])
Osmolal gap= measured Osmolality- Calculated
Osmolality
exists when the measured and calculated values
differ by >10 mOsm/kg
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Obtain a detailed patient history and clinical
assessment.
Check the arterial blood gas, sodium, chloride,
and HCO3-. Identify all abnormalities in pH,
PaCO2, and HCO3-.
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Determine which abnormalities are primary
and which are compensatory based on pH.
If the pH is <7.40, then a respiratory or metabolic
acidosis is primary.
 If the pH is >7.40, then a respiratory or metabolic
alkalosis is primary.
 If the pH is normal (7.40) and there are abnormalities
in PaCO2 and HCO3-, a mixed disorder is probably
present because metabolic and respiratory
compensations rarely return the pH to normal.
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Consider other laboratory tests to further
differentiate the cause of the disorder.
If the AG is normal, consider calculating the urine
AG.
 If the AGis high and a toxic ingestion is expected,
calculate an osmolal gap.
 If the AG is high, measure serum ketones and
lactate.
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Always calculate the AG. If ≥20, a clinically
important metabolic acidosis is usually present
even if the pH is within a normal range.
If the AG is increased, calculate the excess
AG(AG-10). Add this value to the HCO3- to
obtain corrected value.
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If corrected value >26, a metabolic alkalosis is also
present.
If corrected value is <22, a nonanion gap metabolic
acidosis is also present.
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Consider other laboratory tests to further
differentiate the cause of the disorder.
If the AG is normal, consider calculating the urine
AG.
 If the AGis high and a toxic ingestion is expected,
calculate an osmolal gap.
 If the AG is high, measure serum ketones and
lactate.
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Compare the identified disorders to the patient
history and begin patient-specific therapy.
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