a. Hyperplasia (e.g., endometrial hyperplasia caused by estrogen excess)
Hypertrophy and hyperplasia depend on the regener- ative capacity of cells.
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Chapter 1 Cell Injury 9
Figure 1-2 Squamous dysplasia of the cervix, a precursor of squamous cell carcinoma. There is a complete lack of orientation of the squamous cells throughout the full thickness of the epithelium. The arrow points to one of the many atypical nuclei
b. Metaplasia (e.g., squamous metaplasia of the main- stem bronchus in smokers)
c. Infection (e.g., human papilloma virus type 16, causing cervical dysplasia)
d. Ultraviolet light (e.g., solar damage of skin, causing squamous dysplasia)
2. Microscopic features of dysplasia (Figure 1-2) a. Increased mitotic activity, with normal mitotic
spindles
b. Disorderly proliferation of cells with loss of cell maturation as cells progress to the surface
c. Nuclear variation in size, shape, and density of chromatin
3. May be a transitional stage linking neoplasia to meta- plasia or to hyperplasia; if the irritant is removed (e.g., cessation of smoking), dysplasia may not progress to cancer.
4. Examples
a. Squamous dysplasia associated with squamous cell carcinoma (e.g., squamous dysplasia of the main- stem bronchus in a smoker)
b. Glandular dysplasia associated with adenocarci- noma (e.g., Barrett's esophagus, endometrial hyperplasia)
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Hyperplasia and metaplasia may be early precursors of neoplasia.
A B 10 Pathology
Figure 1-3 Dry and wet gangrene of the feet. Dry gangrene (A) involving the second toe of the right foot shows coagulation necrosis The dark black area of gangrene is bordered by the light-colored, parchment-like skin The tip of the third toe has early signs of gangrene. Wet gangrene (B) involving the hallux area of the left foot shows liquefactive necrosis caused by a superimposed infection of anaerobic bacteria, usually Clostridium perfringens The taut skin and areas of ulceration extend from the metatarsal head to the lateral border of the big toe
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VII. Cell Death
• Cell death occurs when cells or tissues are unable to adapt to injury.
A. Necrosis: death of groups of cells, often accompanied by an inflammatory infiltrate
1. Coagulation necrosis: preservation of the structural outline of dead cells
a. Mechanism: denaturation of enzymes and struc- tural proteins by intracellular accumulation of lactate or heavy metals (e.g., lead, mercury); inacti- vation of intracellular enzymes prevents dissolu- tion (autolysis) of the cell.
b. Infarcts: gross manifestations of coagulation necrosis secondary to the sudden occlusion of a vessel
(1) Usually wedge-shaped and occur when dichot- omously branching vessels (e.g., pulmonary artery) are occluded
(2) Pale (ischemic): increased density of tissue (e.g., heart, kidney, spleen) prevents red blood cells from diffusing through necrotic tissue.
Dry gangrene of the toes in individuals with diabetes mellitus is a form of infarc- tion that results from ischemia. Coagula- tion necrosis is the primary type of necro- sis present in the dead tissue (Figure 1-3, A) . (3) Hemorrhagic (red): loose-textured tissue (e.g.,
lungs, small bowel) allows red blood cells to diffuse through necrotic tissue.
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Chapter 1 Cell Injury 11
Figure 1-4 Acute myocardial infarction (MI) showing coagulation necrosis This section of myocardial tissue is from a 3-day-old acute MI The outlines of the myocardial fibers are intact;
however, they lack nuclei and cross-striations A neutrophilic infiltrate is present between some of the dead fibers
c. Microscopic features (Figure 1-4)
(1) Indistinct outlines of cells within dead tissue (2) Absent nuclei or karyolysis (fading of nuclear
chromatin)
2. Liquefactive necrosis: necrotic degradation of tissue that softens and becomes liquified
a. Central nervous system infarction: autocatalytic effect of hydrolytic enzymes generated by neuroglial cells produces a cystic space.
b. Abscess in a bacterial infection: hydrolytic enzymes generated by neutrophils liquefy dead tissue.
Wet gangrene of the toes of individuals with diabetes mellitus is a superimposed anaerobic infection of dead tissue. Liquefactive necrosis is the primary type of necrosis present in the dead tissue (Figure 1-3, B).
3. Caseous necrosis: variant of coagulation necrosis associ- ated with acellular, cheese-like (caseous) material
a. Gaseous material is formed by the release of lipid from the cell walls of Mycobacterium tuberculosis and systemic fungi (e.g., Histoplasma) after destruction by macrophages.
b. Microscopic features
(1) The acellular material in the center of a granu- loma contains activated macrophages, helper T cells, and multinucleated giant cells (see Chapter 2).
(2) Some granulomas do not exhibit caseation (e.g., sarcoidosis).
4. Enzymatic fat necrosis: peculiar to adipose tissue located around an acutely inflamed pancreas
Most common cause of caseous necrosis:
tuberculosis
Enzymatic fat ne- crosis is associated with acute
pancreatitis.
12 Pathology
a. Mechanisms
(1) Activation of pancreatic lipase (e.g., alcohol excess): hydrolysis of triacylglycerol in fat cells (2) Conversion of fatty acids into soap (saponifi- cation): combination of fatty acids and calcium b. Gross appearance: chalky yellow-white deposits
are primarily located in peripancreatic and omental adipose tissue.
c. Microscopic appearance: pale outlines of fat cells filled with basophilic-staining calcified areas d. Distinction from traumatic fat necrosis: occurs in
fatty tissue (e.g., female breast tissue) as a result of trauma; is not enzyme-mediated
5. Fibrinoid necrosis: limited to small muscular arteries, ar- terioles, venules, and glomerular capillaries
a. Mechanism: deposition of pink-staining proteina- ceous material in damaged vessel walls