Transcript Acid- Base Pathophysiology

Acid- Base Pathophysiology
Randall L Tackett, PhD
University of Georgia
College of Pharmacy
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
Blood pH =
7.35-7.45
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
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
pH
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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
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
Carbonic Acid- Bicarbonate
System
• Primary extracellular fluid buffer system
• Maintains a ration of bicarbonate to
carbonic acid of 20:1
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 5075%)
• Responds rapidly and helps buffer pH until
the renal mechanism kicks in
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
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
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
Acid-Base Imbalances
• pH< 7.35 acidosis
• pH > 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.
Compensation
• If underlying problem is metabolic,
hyperventilation or hypoventilation helps:
respiratory compensation.
• If problem is respiratory, renal
mechanisms can result in metabolic
compensation.
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
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
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
Respiratory Acidosis
• Acute conditions:
– Adult Respiratory Distress Syndrome
– Pulmonary edema
– Pneumothorax
Compensation for Respiratory
Acidosis
• Kidneys eliminate hydrogen ion and retain
bicarbonate ion
Signs and Symptoms of
Respiratory Acidosis
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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
Respiratory Alkalosis
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Carbonic acid deficit
pCO2 less than 35 mm Hg (hypocapnea)
Most common acid-base imbalance
Primary cause is hyperventilation
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
Compensation of Respiratory
Alkalosis
• Kidneys conserve hydrogen ion
• Excrete bicarbonate ion
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+
Symptoms of Metabolic Acidosis
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Headache, lethargy
Nausea, vomiting, diarrhea
Coma
Death
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)
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
Compensation for Metabolic
Alkalosis
• Alkalosis most commonly occurs with
renal dysfunction
• Respiratory compensation difficult –
hypoventilation limited by hypoxia
Symptoms of Metabolic Alkalosis
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Respiration slow and shallow
Hyperactive reflexes ; tetany
Often related to depletion of electrolytes
Atrial tachycardia
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
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
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
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