Advanced Pathophysiology Lecture 1.3 Cellular Adaptation, Accumulations, and Death

What are the three major responses to cellular injury?

• physical cellular changes/adaptations,

• abnormal intracellular accumulations,

• cellular or tissue death.

How can cells adapt to chronic stress without immediately dying?

Within limits, cells may change:

• shape,

• size,

• growth pattern,

• metabolic activity.

Major adaptation patterns include:

• atrophy,

• hypertrophy,

• hyperplasia,

• metaplasia,

• dysplasia.

What is atrophy?

Atrophy is a decrease in cell size caused by decreased metabolism and protein synthesis. The cells remain alive, although an entire organ may become smaller.

What examples of atrophy are given?

• Alzheimer’s disease: progressive neurodegenerative disease; the image shows narrowed cerebral gyri and widened sulci from brain atrophy.

• Muscle immobilized beneath a cast.

• Muscle below a spinal cord injury.

What is hypertrophy?

Hypertrophy is an increase in the size of existing cells, not an increase in cell number. It usually occurs because of increased workload or increased protein synthesis.

What are physiologic and pathologic examples of hypertrophy?

• Physiologic: skeletal muscle growth with weight lifting; uterine enlargement in pregnancy.

• Pathologic: left ventricular enlargement from chronic high workload such as hypertension.

Why can severe left ventricular hypertrophy eventually impair cardiac function?

A very thick ventricular wall can reduce the size of the ventricular chamber, potentially decreasing filling and cardiac output despite the increased muscle mass

What is hyperplasia, and how is it different from hypertrophy?

Hyperplasia = increased number of cells.
Hypertrophy = increased size of individual cells.

Both may enlarge an organ, but by different mechanisms.

What examples of hyperplasia are listed?

• callus formation,

• prostate enlargement,

• thyroid enlargement,

• breast enlargement during pregnancy,

• healing wounds.

What is metaplasia?

Metaplasia is a reversible replacement of one mature cell type with another in response to repeated harmful exposure.

How does cigarette smoke produce metaplastic changes in the respiratory tract?

Normal mucus-producing respiratory cells are repeatedly exposed to irritating smoke chemicals and may be replaced by cells that are more resistant to the injury

Why is metaplasia clinically important?

Although adaptive and potentially reversible, persistent metaplastic change may become premalignant

What is dysplasia?

Dysplasia is abnormal change in:

• cell structure,

• size,

• number,

• function

What examples of dysplasia are listed?

• Dysplastic nevi: atypical moles with increased risk of malignant transformation.

• Cervical dysplasia: abnormal cervical epithelial cells that can precede cervical cancer.

How does ATP depletion lead to intracellular water accumulation (Pathway)?

↓ ATP → Na/K pump failure → Na⁺ accumulates in cell → water follows Na⁺ → cell swells.

K⁺ moves outward and hyperkalemia may be present.

What organelle changes accompany cellular water accumulation?

• Water collects in ER vacuoles.

• Protein synthesis decreases.

• Calcium accumulates.

• Lysosomal membranes may fail.

• Lysosomal enzymes damage organelles.

• Cell death may follow.

What are the vacuoles seen during cellular injury?

They are water-filled spaces or bubbles within the injured cell and are described in the slide as a change that may precede cell death.

How does intracellular calcium accumulation occur during cellular injury, and why is it harmful?

Ischemia or direct membrane injury permits calcium to accumulate inside cells. Excess intracellular Ca²⁺:

• further damages the cell,

• injures mitochondria.

How can calcium accumulation produce tissue calcification?

Calcium can combine with phosphorus and precipitate in tissues. A calcified heart valve is shown as an example.

Extravasation of IV calcium can also directly kill surrounding tissue.

Are intracellular pigments always directly harmful?

Not necessarily. The slide states that pigment accumulation is often not directly harmful, but it can indicate impaired cellular function.

What are examples of intracellular pigments or accumulations?

• Melanin

• Hemosiderin, which may accumulate with bruising or venous stasis

• Fat accumulation in liver cells from excess alcohol

Fatty liver means excessive lipid accumulation in hepatocytes.

What are the six cellular accumulations?

• Water

• Lipids

• Glycogen

• Protein

• Pigments

• Calcium

How can abnormal lipid accumulation injure or indicate dysfunction in cells?

Lipids may accumulate when cells cannot adequately metabolize or export fat. The slide example is fatty liver from excess ethanol, in which hepatocytes accumulate triglyceride.

How can glycogen accumulate abnormally inside cells?

Excess glycogen may accumulate when glucose or glycogen metabolism is abnormal, such as in poorly controlled diabetes or glycogen-storage diseases. The swollen cells contain excess glycogen within the cytoplasm.

How can proteins accumulate abnormally inside cells?

Proteins may accumulate because:

• too much protein is produced,

• proteins are improperly folded,

• transport or degradation fails.

Misfolded proteins may impair ER function and contribute to cellular stress.

What systemic responses can occur when significant cellular injury affects tissue?

Tissue injury can stimulate:

• inflammation,

• recruitment of white blood cells,

• release of inflammatory mediators,

• fever,

• leukocytosis,

• acute-phase protein production,

• leakage of intracellular enzymes into blood that can serve as markers of tissue injury.

What is coagulative necrosis, and where is it commonly found?

Coagulative necrosis occurs after ischemia or infarction in tissues such as:

• heart,

• kidney,

• adrenal gland.

The overall tissue architecture remains temporarily preserved because ischemic protein denaturation interferes with rapid enzymatic digestion.

What is liquefactive necrosis, and what conditions commonly cause it?

Liquefactive necrosis involves digestion of dead tissue until it becomes soft or liquid.

It is associated with:

• brain infarction/stroke,

• nervous tissue injury,

• infections such as infected wounds.

White blood cells and digestive enzymes contribute to liquefaction.

What is fat necrosis, and what produces its characteristic soap-like appearance?

Fat necrosis occurs particularly in:

• breast,

• pancreas,

• abdomen.

Damaged fat cells release lipase, which breaks down fat. Fatty acids then combine with ions such as Ca²⁺, Mg²⁺, and Na⁺, producing soap-like deposits.

What is caseous necrosis, and what disease is the classic example?

Caseous necrosis combines features of coagulative and liquefactive necrosis. Macrophages wall off an infectious organism, producing tissue with a white, cheese-like appearance.

The classic example is tuberculosis, a bacterial infection commonly affecting the lungs.

What is gangrenous necrosis associated with?

It occurs when a large amount of tissue dies, often because of:

• arteriosclerosis,

• acute arterial embolism,

• severe ischemia.

Compare dry, wet, and gas gangrene.

• Dry gangrene: severe ischemic tissue death without major bacterial infection.

• Wet gangrene: dead tissue becomes infected with bacteria.

• Gas gangrene: bacterial infection produces gas within damaged tissue.

What is apoptosis, and how is it different from destructive necrosis?

Apoptosis is genetically programmed cell death involving orderly disassembly of cellular proteins and DNA with minimal damage to surrounding tissue.

It removes:

• unwanted cells,

• functionally abnormal cells,

• old/senescent cells.

Necrosis is generally a more disruptive death caused by injury.