2.Kul PA-Adaptasi, Jejas, Dan Kematian Sel

8/10/2019 2.Kul PA-Adaptasi, Jejas, Dan Kematian Sel

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Riza Novierta Pesik


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CAUSES of CELL INJURY :

1.Oxygen Deprivation2. Physical agents

3. Chemical agents & drugs4. Infectious agents

5. Immunologic reactions

6. Genetic Derangements

7. Nutritional Imbalances


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CELL INJURY & NECROSIS

1.Cellular response, d.o : type of injury, its duration & severity2.Consequences of cell injury, d.o : type, state & adaptability of the

injured cell

3.Intracellular system(4) :

. maintenance of the integrity of the cell membranes

. aerobic respiration

. protein synthesis

.preservation of the integrity of the genetic apparatus of the cell

4.Injury at one locus leads to wide-ranging secondary effects

5.Morphologic changesof the cell injury become apparent onlyafter some critical biochemical system within the cell has been

deranged


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GENERAL BIOCHEMICAL MECHANISMS :1. ATP depletion

2. Oxygen&oxygen derived free radicals

3. Intracellular Ca2+& loss of Ca2+homeostasis4. Defects in membrane permeability

5. Irreversible mitochondrial damage


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ISCHEMIC & HYPOXIC INJURY

Hypoxiaglycolytic energy production can

continue

Ischemia

compromises the delivery ofsubstrates for glycolysis

Ischemia tends to injure tissues fasterthanhypoxia


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FREE RADICAL-INDUCED CELL INJURY

Initiated within cell by :

1. Absorbtion of radiant energy

2. Enzymatic metabolism of exogenous chemicals

or drugs

3. Reduction-oxidation reactions that occure

during normal metabolic processes4. Transition metals

5. Nitric oxide (NO)

The Effects to injured cell:

- Lipid peroxidation of membranes

- Oxidative modification of proteins

- Lesions in DNA


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CHEMYCAL INJURY


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MORPHOLOGY of REVERSIBLE CELL INJURY & NECROSIS

Reversible Injury :

- cellular swelling

- fatty change

Necrosis :

- coagulative necrosis

- liquefactive necrosis

- gangrenous necrosis- caseous necrosis

- fat necrosis


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NECROSIS

Definition :

A spectrum of morfology changes that follow cell death in

living tissue, largely resulting from the progressive

degradative action of enzymes on the lethally injured cell.

Is the result of :1. Enzymic digestion of the cell : autolysis, heterolysis

2. Denaturation of proteins

The processes require hours to develop, and so there wouldbe no detectable changes in cell if it caused sudden

death


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COAGULATIVE NECROSIS


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LIQUEFACTIVE NECROSIS


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CASEOUS NECROSIS


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FAT NECROSIS


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APOPTOSIS

Definition:

Its a form of cell death designed to eliminate unwanted

host cells through activation of coordinated, internally

programmed series of events effected by dedicated set

of gene products


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APOPTOSIS OCCURS IN :

1. Programmed destruction of cells during embryogenesis

2. Hormone-dependent involution in the adult

3. Cell deletion in proliferating cell populations

4. Cell death in tumors

5. Death of neutrophils during an acute inflamatory response6. Death of immune cells

7. Cell death induced by cytotoxic T cells

8. Pathologic atrophy in parenchymal organs after duct

obstruction9. Cell injury in certain viral diseases

10.Cell death produced by a variety of injurious stimuli


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SUBCELLULAR RESPONSES TO CELL INJURY

-Lysosomal catabolism

- Induction (hypertrophy) of Smooth Endoplasmic

Reticulum

-Mitochondrial alterations

- Cytoskeletal abnormalities

LYSOSOMAL CATABOLISM


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LYSOSOMAL CATABOLISM

Induction (hypertrophy) of Smooth Endoplasmic


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Induction (hypertrophy) of Smooth Endoplasmic

Reticulum

Electron micrograph of liver from phenobarbital-treated rat showing marked

increase in smooth endoplasmic reticulum.

(from Jones AL, Fawcett DW: Hypertrophy of the agranular endoplasmic reticulum in

hamster liver induced by phenobarbital. J Hystochem Cytochem 14:215, 1996. Courtesyof Dr. Fawcett

Mitochondrial alterations


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Mitochondrial alterations

Enlarged, abnormally shaped mitochondria from the liver of the patient with alcoholic

cirrhosis. Note also crystaline formations in the mitochondria.

Cytoskeletal abnormalities


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Cytoskeletal abnormalities

A. The liver of alcohol abuse (chronic alcoholism). Hyaline inclusions in the hepatic

parenchyal cell in the center appear as eosinophilic networks disposed about the nuclei.

B. Electron micrograph of alcoholic hyalin. The material is composed of intermediate

(prekeratin) filaments and amorphous matrix.


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Riza Novierta Pesik


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CELLULAR ADAPTATIONS of GROWTH and DIFFERENTIATION

PHYSIOLOGIC

PATHOLOGIC

- Hyperplasia

- Hypertrophy

- Atrophy

- Metaplasia


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HYPERPLASIA

Definition:

constitutes an increase in the number of cells in an organ or

tissue, which may then have increased volume.

Physiologic Hyperplasia :1. Hormonal hyperplasia

2. Compensatory hyperplasia

Pathologic Hyperplasia:1. Excessive hormonal stimulation

2. Effects of GFs on target cells

3. Neoplasia


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HYPERTROPHY


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HYPERTROPHYDefinition:

Refers to an increase in the size of cells and, which such change, an

increase in the size of the organ

Hypertrophyphysiologicpathologic

ATROPHY


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ATROPHYDefinition:

shrinkage in the size of the cell by loss of cell substance

Physiologic :

1. During early development

2. Uterus after parturition

Pathologic, d.o. the basic cause, can be local&general :

1. Decreased workload (atrophic of disuse)

2. Loss of innervation (denervation atrophy)

3. Diminished blood supply4. Inadequate nutrition

5. Loss of endocrine stimulation

6. Aging (senile atrophy)

7. Pressure


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METAPLASIA

Definition :

A reversible change in which one adult cell type

(epithelial or mesenchymal) is replaced by another adult

cell type.

INTRACELLULAR ACCUMULATION


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1. A normal cellular constituent accumulated in

excess : water, protein, lipid, carbohydrates

2. An abnormal substance :

- Exogenous : mineral, products of infectious agents

- Endogenous : product of abN synthesis ormetabolism

3. A pigment

Accumulated : transiently/permanently,

harmless/severely toxic,

In cytoplasm(frequenly in lysosomes) /the nucleus


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INTRACELLULAR ACCUMULATIONS


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General mechanisms of intracellular


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accumulation :

1. Abnormal metabolism, as in

fatty change in the liver.

2. Mutation cx alterations inprotein folding & transport, as

in alpha 1-antitrypsin def

iciency

3. Deficyency of critical enzymesthat prevent breakdown of

substrates that accumulate in

lysosomes, as in lysosoma

storage diseases

4. Inability to degradephagositosed particles, as in

hemosiderins and carbon

pigment accumulation


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STEATOSIS (FATTY CHANGE)

: abN accumulations of triglycerides withinparenchymal cells.

Occurs in : liver, heart, muscle, kidney.

Causes : toxins

protein malnutritionDM, obesity, anoxia.

alcohol abuse


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FATTY CHANGE

CHOLESTEROLOSIS


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CHOLESTEROLOSIS

Cholesterol-laden macrophages(foam cells)

from a focus of gallblader cholesterolosis. The gallblader mucosa is in

the upper left.


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PROTEINS

Protein reabsorbtion droplets in the renal tubular epithelium.

(Courtesy of Dr.Helmut Remke, Dept. Of Pathology, Brigham and

Womens Hospital.)

LIPOFUSCIN GRANULES


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in cardiac myocytes (deposits indicated by arrows)


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HEMOSIDERIN GRANULES in liver cells

H&E section showing golden-brown, finely granular pigment.

HEMOSIDERIN GRANULES i li ll


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HEMOSIDERIN GRANULES in liver cells

Prusian blue reaction, specific for iron.

PATHOLOGIC CALCIFICATION


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Dystrophic Calcification

- in areas of necrosis

- in the atheromas of advanced atherosclerosis- in aging

- in damaged heart valves


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METASTATIC CALCIFICATIONHypercalcemia

1. Increased secretion of PTH2. Destruction of bone tissue

3. Vit.D-related disorders

4. Renal failure

HYALINE CHANGE: it usually refers to an alteration within cells or in

extracellular space, which gives a

homogeneous, glassy, pink appearance in

routine histologic sections stained with H&E.


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2.Kul PA-Adaptasi, Jejas, Dan Kematian Sel

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