introduction and objectives necrosis

8/3/2019 Introduction and Objectives Necrosis

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INTRODUCTION AND OBJECTIVES:

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.

KEY WORDS AND CONCEPTS:

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).


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Deposits: Dystrophic calcification vs. metastatic calcification, hyalin,

amyloid, cholesterol, urates.

Click here for Glossary

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I. CELL INJURY

Causes

o Hypoxia

o Physical Agents: (mechanical trauma, burns, frostbite, sudden

changes in pressure (barotrauma), radiation, electric shock).

o Chemical Agents: glucose, salt, water, poisons (toxins), drugs,

pollutants, insecticides, herbicides, carbon monoxide, asbestos,

alcohol, narcotics, tobacco.

o Infectious Agents: prions, viruses, rickettsiae, bacteria, fungi,

parasites.

o Immunologic Reactions: anaphylaxis, autoimmune disease.

o Genetic Derangements: Congenital malformations, normal proteins

(hemoglobinopathies), enzymes (storage diseases).

o Nutritional Imbalances: protein-calorie deficiencies, vitamin

deficiencies; excess food intake (obesity, atherosclerosis).

II. REVERSIBLE RESPONSES TO INJURY

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).

III. LYSOSOMAL STORAGE DISEASES

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
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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, vonGierke's disease, and McArdle syndrome), and Ochronosis.

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Necrosis and Crystal Deposits

I. NECROSIS: FOUR MAJOR TYPES

Coagulative: Caused by ischemia. Ischemia results in decreased ATP,

increased cytosolic Ca++, and free radical formation, which each eventually

cause membrane damage.

o Decreased ATP results in increased anaerobic glycolysis,

accumulation of lactic acid, and therefore decreased intracellular pH.

o Decreased ATP causes decreased action of Na+ / K+ pumps in the cell

membranes, leading to increased Na+ and water within the cell (cell

swelling).

o Other changes: Ribosomal detachment from endoplasmic reticulum;

blebs on cell membranes, swelling of endoplasmic reticulum and

mitochondria.o 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
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accumulation of pus, effectively liquefying the tissue (hence, the term

liquefactive).

Example: Abscess

Caseous: A distinct form of coagulative necrosis seen in mycobacterialinfections (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.

II. AUTOLYSIS

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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III. APOPTOSIS

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.

IV. CRYSTALS
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Calcium: Deposits of hematoxylin (blue) stained chunky or granular material

in the cells or tissues. Comes in two major types.

o 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.

o 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 bedeposited 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.

introduction and objectives necrosis

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