• prolonged exposure of cells to adverse or exaggerated normal stimui which evokes various changes at the level of individual cells, tissues, or whole organs

• once the cause is removed, most cells that have adapted to chronic stimulation revert to normalcy once again, while some do not, leading to detrimental results

1.Atrophy

2. Hypertrophy

3. Hyperplasia

4. Metaplasia

5. Dysplasia

6. Anaplasia

physiologic atrophy

examples

• thymus undergoing involution

• ovaries, uterus and breasts after menopause

• bones and muscles in the elderly become thin and prone to fx

pathologic atrophy

example

physiologic hypertrophy

example

pathologic hypertrophy

examples

• enlargement of the heart that occurs as an adaptation to increased workload

• concentric enlargement of the left ventricular is typically seen in hypertension and is an adaptive response to left ventricular pressure overload

• endometrial hyperplasia due to estrogens

• hyperplastic polyps of the colon or stomach

• squamous metaplasia of the bronchial epithelium due to smoking

• gastric or glandular metaplasia of GE junction in Barrett Esophagus

dysplasia examples

• cervical dysplasia (cervical intraepithelial neoplasia CIN) based on PAP smears

• association with cervical cancers with HPV

• undifferentiated and uncontrolled growth of cells

• The hallmark of malignant transformation

• also known as: malignancy, carcinoma, cancer, neoplasm

squamous cell carcinoma of the cervix

cancer of the lung

malignant melanoma

renal cell carcinoma

1. the cells and the nuclei display marked cellular pleomorphism (variation in size and shape)

2. the nuclei are irregular and hyperchromatic

3. extremely high nuclear/cytoplasmic ratio (N/C ratio), about 1:1 instead of 1:4 or 1:6

4. large nucleoli present within the nucleus

5. large numbers of abnormal mitotic figures

• seen when environmental chenages exceed the capacity of the cell to maintian normal homeostasis

• may be reversible if the stress is removed in time or if the cell is able to withstand the assault

• if the stress is severe, may lead to cell death

typically mild or short-lived

characterized by swelling (hydropic degeneration), and reflects the increased influx of water into the cytoplasm and mitochondria from altered permeability of the plasma membrane

ex: hypoxia, causes dysfxn of the ATP-driven NA+K+ pump altering the permeablilty, once ATP fxn is restored, the NA+ and H2O are pumped out of the cell and the swelling disappears

reversible cell injury:

changes in the mitochondria

swollen mitochondria generate less energy, so instead of oxidative ATP production, the cell reverts to anaerobic glycolysis which results in the excessive production of lactic acid, the cell pH becomes acidic which further slows cell metabolism.

Other organelles, like the RER swell and fragment, resulting in decreased protein synthesis

what determines reversible from irreversible cell injury?

if acute stress to which a cell must react exceeds its ability to adapt, the resulting changes in structure and fxn lead to the death of the cell

Morphologically recognized by changes in the nucleus or by rupture of the cell membrane and loss of cell integrity- seen by light microscopy and E.M.

1.Pyknosis

2.Karyorrhexis

3.Karyolysis

cytoplasm is fragmented and lost

the dead cell, clinically, releases thier cellular enzymes into the ECF and circulation

cytoplasmic enzymes (AST, LDH) are released from damaged cells and can be measured in the blood where they are useful signs of cell injury.

High levels of these enzymes are typically found in pts with MIs or viral hepatitis

formation of plaque in vessels

diabetes accelerates this condition

death of cells or tissues within a living organism

seen only in the living with inflammation

Types:

Coagulative

Liquefactive

Caseous

Fat

the death of cells or tissues

seen in tissues only after death

• most common form of necrosis
• occurs when cell proteins are altered or denatured similar to the coagulation that occurs when cooking eggs
• histologically, the cell outlines are preserved and the cytoplasm appears finely granular
• typically occurs in solid internal organs (heart, kidney, spleen liver) and most often caused by anoxia (heart tissue -MI)

• a process by which dead cells liquify under the influesnce of certain cell enzymes. Tissue becomes soft and gel-like

• Occurs most often in the brain where the cells lose thier contours and liquify

• typical of brain infarcts and bacterial infections in which a cavity may develop (abscesses in the lungs)

forms of cagulative necrosis in which a thick, yellowish chessy substance forms

typically found in TB (lung granulomas -> Ghon Complex) and some fungal infections (Histoplasmosis)

• a specialized form of liquefaction necrosis caused by the action of lipolytic enzymes

• limited to fat tissue, usually around the pancreas where enzymes are released into the adjacent fat tissue usually after a rupture causing degradation of fat into glycerol and free fatty acids which rapidly bind w/ Ca2+, forming soaps and causing white, calcified specks

inflammation and secondary liquefaction of coagulated necrotic tissue from a bacterial infection which frequently occur after an infarction of the intestines or in a limb and are usually caused by atherosclerosis or diabetes

ex: advances decubitus ulcers

calification of calcium salts in necrotic tissues

refers to the macroscopic deposition fo calcium in injured or dead tissues. represents an extracellular deposition of calcium from the circulation into dead or dying necrotic tissue, often visible to the naked eye, and range from gritty, sand-like grains to firm, rock-hard material

dystrophic calcification examples

1. Calcification in atherosclerotic coronary arteries contributes to narrowing of the vessels

2.Calcifications of the mirtal or aortic valves leading to impeded blood flow (stenosis)

3. Calcifications seen around breast cancers that can be visualized by mammography

4. Infant periventricular calcifications seen in congenital Toxoplasmosis

Metastatic Calcification examples:

Seen in various disorders including:

Hyperparathyroidism, vitamin D toxicity, and chronic renal failure.

Formation of calcium carbonate stones in sites such as the gall bladder, kidney and bladder are due to precipitation of the salts from the solution into tissues