Acid- Base Pathophysiology

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Acid- Base Pathophysiology

• Randall L Tackett, PhD
• University of Georgia
• College of Pharmacy

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General Concepts

• Acid High concentration of hydrogen ions
  (donates H)
• Base High concentration of hydroxide ions
  (accepts H)
• pH
• Describes the acidity or alkalinity of a
  substance
• pH scale represents the hydrogen ion concentration

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Blood pH 7.35-7.45
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pH

• Small changes in pH produce major disturbances
• Most biological processes function within a
  narrow pH range
• Affects electrolyte and hormone functions
• Body produces more acids than bases
• Metabolic processes produce CO2

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pH and Cell Membrane

• Selectively permeable
• Permeability of cell membrane influenced by pH
• Affects the degree of ionization and the
  concentration of ionized substances
• Changes in ionization results in loss of
  substances from the cell

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pH

• Kidneys most effective regulator of pH
• Can excrete large amounts of acid
• Conserves and also can excrete bases
• Rates of correction
• Buffers - immediately
• Respiratory system - minutes to hrs
• Renal mechanisms - several hrs to days

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Acid-Base Balance

• Intake of normal diet produces 50 to 100 mEq of
  hydrogen per day
• Hydrogen is normally excreted in urine and
  combined with phosphate and ammonia

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Carbonic Acid- Bicarbonate System

• Primary extracellular fluid buffer system
• Maintains a ration of bicarbonate to carbonic
  acid of 201

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Respiratory System

• Adjusts rate and depth of respiration
• Increased rate and depth - CO2 excreted
• Decreased rate and depth - CO2 conserved
• Limited gain - cannot completely compensate for
  changes in pH (only 50-75)
• Responds rapidly and helps buffer pH until the
  renal mechanism kicks in

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Renal System

• Regulates amount of bicarbonate absorbed or
  excreted
• Also regulates ammonia and electrolytes
• Slower onset but more prolonged action
• Infinite gain - can completely correct
  abnormalities in pH

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Acid-Base Balance

• Metabolic acidosis begins to occur when GFR
  decreases by 30 to 40 due to
• Decreased ammonia synthesis
• Decreased bicarbonate reabsorption
• Phosphate buffers remain effective until late
  stages of renal failure
• Bicarbonate levels stabilize at end-stage renal
  failure because hydrogen is buffered by anions
  from bone

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Assessment of Acid-Base

• Blood and urine pH
• Arterial blood gases (ABG)
• Anion gap
• Representative of the unmeasured anions in the
  plasma
• Aids in the differentiation of cause of metabolic
  acidosis

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Acid-Base Imbalances

• pHlt 7.35 acidosis
• pH gt 7.45 alkalosis
• Response to acid-base imbalance is called
  compensation
• 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 helps
  respiratory compensation.
• If problem is respiratory, renal mechanisms can
  result in 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
• 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 edema
• 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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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, anemia
• 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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Metabolic Acidosis

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

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Phosphate and Calcium Balance

• Changes in acid-base balance affect phosphate and
  calcium
• In early renal failure, phosphate excretion
  decreases and plasma phosphate levels increase
  due to decreased GFR
• Elevated plasma phosphate binds calcium producing
  hypocalcemia

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Phosphate and Calcium Balance

• Decreased calcium stimulates the release of
  parathyroid hormone which releases calcium from
  bone and enhances urinary phosphate secretion
• Phosphate and calcium levels return to normal
• Incremental losses of GFR decreases effectiveness
  of parathyroid hormone

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Phosphate and Calcium Balance

• When GFR declines to 25 of normal, parathyroid
  hormone is no longer effective in maintaining
  serum phosphate
• Persistent reduction of GFR and
  hyperparathyroidism results in
• Hyperphosphatemia
• Hypocalcemia
• Dissolution of bone

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Phosphate and Calcium Balance

• Hypocalcemia and bone disease are accelerated by
• Impaired synthesis of 1,25 vitamin D3
• Lack of vitamin D reduces intestinal absorption
  of calcium and impairs resorption of phosphate
  and calcium from bone