HYPOXIA

1
HYPOXIA

• Ischemia ( loss of blood supply ).
• Inadequate oxygenation
• ( cardiorespiratory failure ).
• Loss of oxygen-carrying capacity of the blood (
  anemia or CO poisoning ).

2
HYPOXIC INJURY

• Loss of oxidative phosphorylation and ATP
  generation by mitochondria.
• Decreased ATP (with increase in AMP) stimulating
  fructokinase and phosphorylation, resulting in
  aerobic glycolysis.
• Depleted glycogen.
• Reduced intracellular pH Lactic acid and
  inorganic phosphate.
• Clumping of nuclear chromatin.

3
Four biochemical themes

• Oxygen-derived free radicals.
• Loss of calcium homeostasis and increased
  intracellular calcium.
• ATP depletion.
• Defects in membrane permeability.

4
PHYSICAL AGENTS

• Trauma
• Heat
• Cold
• Radiation
• Electric shock

5
CHEMICAL AGENTS AND DRUGS

• Endogenous products urea
• Exogenous agents
• Therapeutic drugs hormones
• Nontherapeutic agents
• lead or alcohol

6
MECHANISMS OF CHEMICAL INJURY

• Directly Mercury of mercuric chloride binds to
  SH groups of cell membrane proteins, causing
  increased permeability and inhibition of
  ATPase-dependent transport.

7
MECHANISMS OF CHEMICAL INJURY

• By conversion to reactive toxic metabolites which
  in turn cause cell injury either by direct
  covalent binding to membrane protein and lipid,
  or more commonly by the formation of free
  radicals.

8

• CCl4 in SER of liver cell (P-450)