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In this unit, we explore basic ideas about what "diseases" are, how they are produced, and how they are recognized. Details and further explanations are available in Chapter I of Robbins. Chapter I deals with cellular injury and cellular reactions to injury. "Injury" refers to the various agents and modalities that act on cells (such as, chemicals, toxins, organisms, intracellular accumulations, temperature changes, radiation, etc.). Cells can react by modifying themselves slightly and thus adapt to the injury (such as hypertrophy, hyperplasia, atrophy, and metaplasia, hydropic swelling, and fatty change). Such adaptations may be reversible. Cells can also react by becoming permanently altered and then living a new "lifestyle" (such as radiation changes in cells). They may also react to injury by being overwhelmed, and unable to continue life, and so they die. When cells die, they can do so in a pre- and proscribed manner of planned cell death, called apoptosis. Degeneration of cells after the death of the organism is termed autolysis (cells basically rot). Cells which die before the death of the organism undergo necrosis, a process which will be explored with examples, and contrasted with apoptosis and autolysis.


General: Pathology, general pathology, systemic pathology, anatomic pathology, clinical pathology, disease, etiology, pathogenesis, lesion, symptom, sign, presentation, natural history, course, complication, prognosis, diagnosis, Rudolf Virchow. Cellular Injury: Cellular adaptation, cellular injury (reversible and irreversible), point of no return, cell death, hypoxia Morphology of Injured Cells: Cellular swelling (hydropic change), cell necrosis (vs. cell death); types of necrosis (coagulation, liquefaction, fat, and caseous); special types of necrosis: gangrenous, fibrinoid; infarct, abscess, apoptosis. Intracellular Accumulation: Fatty change, or steatosis (vs. fatty replacement); storage diseases (e.g., Gaucher's disease). Pigments: Lipochrome, melanin, hemosiderin, bilirubin, opaque black pigment (anthracotic pigment).

Deposits: Dystrophic calcification vs. metastatic calcification, hyalin, amyloid, cholesterol, urates.

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Hypoxia Physical Agents: (mechanical trauma, burns, frostbite, sudden changes in pressure (barotrauma), radiation, electric shock). Chemical Agents: glucose, salt, water, poisons (toxins), drugs, pollutants, insecticides, herbicides, carbon monoxide, asbestos, alcohol, narcotics, tobacco. Infectious Agents: prions, viruses, rickettsiae, bacteria, fungi, parasites. Immunologic Reactions: anaphylaxis, autoimmune disease. Genetic Derangements: Congenital malformations, normal proteins (hemoglobinopathies), enzymes (storage diseases). Nutritional Imbalances: protein-calorie deficiencies, vitamin deficiencies; excess food intake (obesity, atherosclerosis).


Cellular adaptive changes (hypertrophy, hyperplasia, atrophy, and metaplasia). See Lecture III. Hydropic Degeneration (Cell Swelling): The result of excess fluid in the cell cytoplasm. Fatty Change (Steatosis): Excess fat in the form of small or large droplets (micro- or macrovesicular steatosis).


A category of disease first discovered in 1963 (the diseases have been with us longer). The result of an inborn error of metabolism, an enzyme deficiency or lack of function, such that catabolism of the substrate is incomplete, so that it

accumulates in the lysosomes (in the cytoplasm), causing the cells to become morphologically and functionally deranged. A classic example is Gaucher's disease, in which a deficiency of the enzyme glucocerebrosidase results in the accumulation of (you guessed it) glucocerebroside in the phagocytic cells of the body, but also in the central nervous system. Others include Tay-Sach's Disease, Niemann-Pick Disease, Mucopolysaccharidoses, Glycogen Storage Diseases (Pompe disease, von Gierke's disease, and McArdle syndrome), and Ochronosis.

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Necrosis and Crystal Deposits


Coagulative: Caused by ischemia. Ischemia results in decreased ATP, increased cytosolic Ca++, and free radical formation, which each eventually cause membrane damage.
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Decreased ATP results in increased anaerobic glycolysis, accumulation of lactic acid, and therefore decreased intracellular pH. Decreased ATP causes decreased action of Na+ / K+ pumps in the cell membranes, leading to increased Na+ and water within the cell (cell swelling). Other changes: Ribosomal detachment from endoplasmic reticulum; blebs on cell membranes, swelling of endoplasmic reticulum and mitochondria. Up to here, the changes are reversible if oxygenation is restored by reversing the ischemia. If the ischemia continues, necrosis results, causing the cytoplasm to become eosinophilic, the nuclei to lyse or fragment or become pyknotic (hyperchromatic and shrunken). In the early stages of necrosis, the cells remain for several days as ghosts of their former selves, allowing one to still identify them and the tissue (in contrast to the other types of necrosis). The cellular reaction is polys, followed by a granulation tissue response. (See Inflammation and Repair).

Example: Infarct: localized area of ischemic necrosis as in myocardial infarct.

Liquefactive: Usually caused by focal bacterial infections, because they can attract polymorphonuclear leukocytes. The enzymes in the polys are released to fight the bacteria, but also dissolve the tissues nearby, causing an

accumulation of pus, effectively liquefying the tissue (hence, the term liquefactive). Example: Abscess

Caseous: A distinct form of coagulative necrosis seen in mycobacterial infections (e.g., tuberculosis), or in tumor necrosis, in which the coagulated tissue no longer resembles the cells, but is in chunks of unrecognizable debris. Usually there is a giant cell and granulomatous reaction, sometimes with polys, making the appearance distinctive.

Example: Tuberculosis.

Fat Necrosis: A term for necrosis in fat, caused either by release of pancreatic enzymes from pancreas or gut (enzymic fat necrosis) or by trauma to fat, either by a physical blow or by surgery (traumatic fat necrosis). The effect of the enzymes (lipases) is to release free fatty acids, which then can combine with calcium to produce detergents (soapy deposits in the tissues). Histologically, one sees shadowy outlines of fat cells (like coagulative necrosis), but with Ca++ deposits, foam cells, and a surrounding inflammatory reaction.

Lysis of tissues by their own enzymes, following the death of the organism. Therefore,the key difference is that there is no vital reaction (i.e., no inflammation). Autolysis is essentially rotting of the tissue. Early autolysis is indistinguishable from early coagulative necrosis due to ischemia, unless the latter is focal.

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Planned or programmed cell death. A recently popularized concept, referring to orderly and often single cell death, used to explain such diverse processes as destruction of cells during embryogenesis, developmental involution of organs (thymus, e.g.), cell breakdown during menstrual cycles, involution of the ovary, death of crypt epithelium in the gut, and pathologic atrophy of hormone dependent tissues. Usually recognized by single cell necrosis without an inflammatory response.


Calcium: Deposits of hematoxylin (blue) stained chunky or granular material in the cells or tissues. Comes in two major types.

Dystrophic Calcification: Calcium deposits in areas of tissue damage, scarring or necrosis. Patient's calcium and phosphate levels are normal. Example: calcification in coronary artery in atherosclerosis, or calcification of the aortic valve in calcific aortic stenosis. Metastatic Calcification: Calcium deposits in tissues due to increased Calcium and or Phosphate concentrations in the tissues. The tissues were formerly normal. Examples are calcification of the lung and other tissues in hyperparathyroidism, or as a result of phosphate infusions given therapeutically.

Cholesterol: Deposits of extracellular lipid, in the form of crystals. The lipid is dissolved out with solvents during tissue processing, leaving only cholesterol clefts behind. Usually the cholesterol is deposited in damaged scarred tissue in the coronary arteries (atherosclerosis), but it can be deposited in a more soluble form in foam cells (such as in xanthomas, or in xanthomatous deposits in hypercholesterolemia, cholesterolosis of the gall bladder, etc.). Often associated with calcium deposits (dystrophic calcification) in the case of atherosclerosis. Urates: Urate crystals are deposited in gout, as the result of hyperuricemia. They are usually deposited in cartilage of the ear, and in soft tissues around joints. The deposits can excite a giant cell response and scarring of the tissues. The resulting lesion is called a tophus, or gouty tophus, and has a chalky white appearance grossly. Urates dissolve in water and hence in formalin. To be preserved, they must be submitted in 100% alcohol. Calcium Pyrophospate: This crystal is deposited in the soft tissues around joints as well, and can mimic gout in its presentation, gross and microscopic appearance. The condition is therefore known as pseudogout. The crystals can be distinguished microscopically using polarized light and a red filter.