INTRO basis of disease

pathophys

What is the difference between hypertrophy and hyperplasia?

Hypertrophy = increase in cell size

Hyperplasia = increase in cell number

Hyperplasia can only occur in tissues capable of mitosis

Cardiac muscle undergoes hypertrophy, not hyperplasia

Why can't cardiac muscle respond to hypertension with hyperplasia?

Cardiac myocytes are terminally differentiated and have minimal ability to undergo mitosis, so they adapt by increasing cell size (hypertrophy).

What is metaplasia?

A reversible change in which one mature adult cell type is replaced by another mature adult cell type.

How does metaplasia occur?

Through reprogramming of undifferentiated stem cells, causing them to produce a different mature cell type.

Why is squamous metaplasia protective in smokers?

Squamous cells are more resistant to chronic irritation and inflammation than ciliated columnar cells.

Why does metaplasia increase cancer risk?

Chronic irritation → continued cell turnover → accumulation of mutations → dysplasia → cancer.

What is dysplasia?

Disordered cell growth characterized by abnormal size, shape, and appearance due to sequential mutations in proliferating cells.

Why is dysplasia considered a precursor to cancer?

Because dysplastic cells have accumulated mutations and abnormal growth patterns that can progress to malignancy.

What are the three major mechanisms of cell injury?

ATP depletion

Free radical formation

Disruption of intracellular calcium homeostasis

What happens when ATP is depleted?

• Na/K pump failure

• Cellular swelling

• Increased intracellular calcium

• Switch to anaerobic metabolism

• Increased lactic acid

• Decreased intracellular pH

Why does ATP depletion cause cellular swelling?

Na/K ATPase fails → intracellular sodium accumulates → water follows sodium into the cell.

Why does lactic acid increase during hypoxia?

Cells switch from aerobic metabolism to anaerobic glycolysis.

What pushes a cell beyond the point of no return?

Severe ATP depletion, calcium overload, membrane damage, lysosomal rupture, and loss of membrane integrity.

What are the three major targets of free radical injury?

• Lipid peroxidation

  Oxidative modification of proteins

  DNA damage

How do free radicals damage cell membranes?

By causing lipid peroxidation, resulting in membrane instability and leakage.

What is ischemia-reperfusion injury?

Additional tissue damage caused when blood flow returns to previously ischemic tissue due to generation of reactive oxygen species.

Why can reperfusion paradoxically damage tissue?

Reintroduction of oxygen generates reactive oxygen species that damage lipids, proteins, and DNA.

List the mechanisms of heat injury.

• Accelerated metabolism

• Enzyme inactivation

• Membrane disruption

• Blood vessel coagulation

• Protein coagulation

List the mechanisms of cold injury.

• Vasoconstriction

• Increased blood viscosity

• Ice crystal formation

• Capillary stasis

• Arteriolar/capillary thrombosis

Why does frostbite cause tissue injury?

both direct cellular damage from ice crystals and ischemic injury from reduced blood flow.

What protease family mediates apoptosis?

Caspases.

Why does apoptosis not cause inflammation?

Apoptotic cells are rapidly cleared before intracellular contents leak out.

Why does necrosis cause inflammation?

Membrane rupture releases intracellular contents that trigger inflammatory responses.

List three physiologic roles of apoptosis.

• Embryogenesis

• Intestinal epithelial turnover

• Immune cell regulation

• Endometrial shedding during menstruation

What causes dry gangrene?

Interference with arterial blood supply.

What causes wet gangrene?

Interference with venous blood supply.

What are the two major components of acute inflammation?

• Vascular reaction

• Cellular reaction

What causes vasodilation during acute inflammation?

Histamine and nitric oxide.

What is the purpose of increased vascular permeability?

allows plasma proteins and immune cells to enter injured tissue.

What are three functions of complement activation?

• Increased vascular permeability

• Leukocyte adhesion/chemotaxis

• Opsonization and phagocytosis

What is leukocyte margination?

Movement of leukocytes from the center of blood flow toward the endothelial surface.

What is leukocyte rolling?

Transient weak adhesion causing leukocytes to tumble along the endothelium.

What is leukocyte adhesion?

Firm attachment of leukocytes to endothelial cells.

What is diapedesis (emigration)?

Movement of leukocytes through the endothelium into tissue.

What is chemotaxis?

Directed movement of leukocytes toward chemical signals released at the site of injury.

What is the sequence of leukocyte recruitment?

Margination → Rolling → Adhesion → Emigration → Chemotaxis → Phagocytosis

Which immune cells dominate chronic inflammation?

Macrophages and T lymphocytes.

What cytokine is heavily involved in chronic inflammation?

TNF (Tumor Necrosis Factor).

What molecules released during chronic inflammation contribute to tissue damage?

Reactive oxygen species (ROS) and reactive nitrogen species (RNS).

How does chronic inflammation lead to fibrosis?

Persistent macrophage/T-cell activation stimulates fibroblast proliferation and collagen deposition.