Pathophysiology of Hypoxia and Ischemia

Cell Injury

• Hypoxia deprives cells of oxygen, interrupting oxidative metabolism and ATP generation, affecting all cells in the body.
• Ischemia is characterized by impaired oxygen delivery and removal of metabolic end products, such as lactic acid, commonly affecting blood flow through limited numbers of blood vessels and producing local tissue injury.
• Hypermetabolic states may require more oxygen than can be supplied by normal respiratory function and oxygen transport, leading to hypoxia.

Causes of Cell Injury

Injury from Physical Agents

• Mechanical forces can cause injury or trauma, splitting and tearing tissue, fracturing bones, injuring blood vessels, and disrupting blood flow.
• Extremes of temperature can cause damage to cells, organelles, and enzyme systems.
• Cold exposure increases blood viscosity, induces vasoconstriction, and may lead to hypoxic tissue injury.
• Electrical injuries can affect the body through extensive tissue injury and disruption of neural and cardiac impulses.
• The body acts as a conductor of electrical current, which can cause violent muscle contractions, fractures, and dislocations.

Radiation Injury

• Ionizing radiation impacts cells by causing ionization of molecules and atoms, releasing free radicals that destroy cells and directly hitting target molecules.
• Radiation can immediately kill cells, interrupt cell replication, or cause genetic mutations.
• Most radiation injury is caused by localized irradiation used in cancer treatment.

Chemical Injury

• Chemicals capable of damaging cells are present in air and water pollution, tobacco smoke, and certain foods.
• Chemical agents can injure cell membranes, block enzymatic pathways, coagulate cell proteins, and disrupt osmotic and ionic balance.
• Corrosive substances can destroy cells, while other chemicals may injure cells during metabolism or elimination.

Apoptosis (Programmed Cell Death)

• Apoptosis is a highly selective process that eliminates injured and aged cells, controlling tissue regeneration.
• Two basic pathways for apoptosis exist: the extrinsic pathway, which is death receptor dependent, and the intrinsic pathway, which is death receptor-independent.

Types of Necrosis

• Liquefaction necrosis:

Period of Vulnerability

• The embryo's development is most easily disturbed during organogenesis, which extends from day 15 to day 60 after conception.
• Environmental influences during the first 2 weeks after fertilization may interfere with implantation, resulting in abortion or early resorption of the products of conception.

Genetic and Congenital Disorders

• Infectious agents, such as those in the TORCH group, can cross the placenta and enter the fetal circulation, producing multiple malformations.
• Teratogenic agents, including radiation, chemicals, drugs, and infectious organisms, can produce abnormalities in the developing embryo.

Causes of Cell Injury

• Hypoxia deprives cells of oxygen, interrupting oxidative metabolism and ATP generation
• Ischemia impairs oxygen delivery and removes metabolic end products, leading to local tissue injury
• Hypermetabolic states can cause cells to require more oxygen than normal respiratory function can supply
• Hypoxia causes a power failure in cells, affecting structural and functional components
• Infarction occurs when an artery becomes occluded, causing tissue death, typically with a conical shape corresponding to the affected artery's distribution

Physical Agents of Cell Injury

• Mechanical forces can cause injury or trauma, split or tear tissue, fracture bones, and disrupt blood flow
• Extremes of temperature can release free radicals that destroy cells and directly hit target molecules, causing cell death, interrupted replication, or genetic mutations
• Radiation injury varies with dose, dose rate, and tissue sensitivity
• Ionizing radiation can immediately kill cells, interrupt cell replication, or cause genetic mutations

Chemical Agents of Cell Injury

• Chemicals capable of damaging cells are present in air and water pollution, tobacco smoke, and processed or preserved foods
• Chemicals can injure cell membranes, block enzymatic pathways, coagulate proteins, and disrupt osmotic and ionic balance
• Corrosive substances like strong acids and bases can destroy cells on contact
• Carbon tetrachloride is extremely toxic to liver cells

Pathologic Calcifications

• Dystrophic calcification occurs in dead or dying tissues, involving the macroscopic deposition of calcium salts
• Metastatic calcification occurs in normal tissues due to increased serum calcium levels, often in the lung, renal tubules, and blood vessels

Lead Poisoning

• A blue lead line along the gum margins is a diagnostic feature of lead poisoning

Genetic Control of Cell Function

• RNA assembles amino acids into functional proteins in the ribosome through translation
• Messenger RNA is formed from DNA through transcription
• Complementary RNA bases pair with DNA bases, with uracil replacing thymine to pair with adenine

Pediatric Considerations

• 1 in 150 live births have chromosomal anomalies causing cognitive impairment and birth defects
• Inborn errors of metabolism can be lethal if not treated, prompting mandatory newborn screening in many states
• Creating a family pedigree can help identify genetic disorders and is useful for genetic counseling