1. Acid- Base Pathophysiology
Randall L Tackett, PhD
University of Georgia
College of Pharmacy

2. 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

3. Blood pH =

4. 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

5. 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

7. 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

8. 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

11. Carbonic Acid- Bicarbonate System
Primary extracellular fluid buffer system
Maintains a ration of bicarbonate to carbonic acid of 20:1

12. 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

13. 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

14. 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

15. 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

16. 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.

17. Compensation
If underlying problem is metabolic, hyperventilation or hypoventilation helps: respiratory compensation.
If problem is respiratory, renal mechanisms can result in metabolic compensation.

18. 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

19. 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

21. 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

22. Respiratory Acidosis Acute conditions:
Adult Respiratory Distress Syndrome
Pulmonary edema
Pneumothorax

23. Compensation for Respiratory Acidosis
Kidneys eliminate hydrogen ion and retain bicarbonate ion

24. 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

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

27. 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

28. Compensation of Respiratory Alkalosis
Kidneys conserve hydrogen ion
Excrete bicarbonate ion

30. 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+

31. Symptoms of Metabolic Acidosis
Headache, lethargy
Nausea, vomiting, diarrhea
Coma
Death

32. 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)

34. 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

35. Compensation for Metabolic Alkalosis
Alkalosis most commonly occurs with renal dysfunction
Respiratory compensation difficult – hypoventilation limited by hypoxia

36. Symptoms of Metabolic Alkalosis
Respiration slow and shallow
Hyperactive reflexes ; tetany
Often related to depletion of electrolytes
Atrial tachycardia

38. 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

39. 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

40. 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

41. 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