bbs ii slide cell injury death and adaption

Departemen Patologi Anatomi Fakultas

Kedokteran Universitas Sumatera Utara Medan - 2011

Blok BBS 2

[image:2.612.128.487.95.368.2]

Table 1-1. Cellular Responses to Injury

Nature &Severity of Injurious Stimulus Cellular Response Altered physiologic stimuli: Cellular adaptations:

• demand, trophic stimulation (e.g. growth

factors, hormones) • Hyperplasia, hypertrophy

• nutrients, stimulation • Atrophy

• Chronic irritation (chemical /physical) • Metaplasia

O2 supply; chemical injury; microbial

infection Cell injury:

• Acute & self-limited • Acute reversible injury • Progessive & severe (including DNA damage) • Irreversible injury ➙cell death

Necrosis Apoptosis

• Mild chronic injury • Subcellular alterations in various organelles

Metabolic alterations (genetic / acquired) Intracellular accumulations; calcifications Prolonged life span with cumulative

sublethal injury Cellular aging

Stresses/pathologic stimuli the cell

Adaptation

• Atrophy

• Hypertrophy

• Hyperplasia

• Metaplasia

Irreversible injury & dies

Perubahan sel & jaringan

Agenesis

Aplasia

Hypoplasia

Atrophy

Hypertrophy

Hyperplasia

Metaplasia

Dysplasia

Anaplasia

Granuloma

•

Complete absent of

organ

•

e.g. :

– Renal agenesis

– Ovarial agenesis

– Tubal agenesis, etc.

Agenesis

Aplasia

•

Is present

•

But never develops

•

e.g. :

– Lung aplasia with tissue

•

Developved incompletly

•

But the tissue histhologicaly normal

•

e.g. : microcephaly

Hypoplasia

•

Decrease in the:

–

Size

–

Function of a cell

•

But not dead

Causes of atrophy :

1. _{functional demand (immobilitation in fracture, prolonged}

bed rest)

2. Inadequate supply O₂ (ischemia)

3. Insufficient nutrients (starvation, inadequate nutrition, chronic disease)

4. Interruption of trophic signals transmitted by chemical

mediators (endocrine system/neuromusculator transmission)

e.g. : thyroid, adrenal cortex, ovarium, testis.

5. Persistent cell injury by chronic inflamation

e.g. : chronic gastritis, prolonged pressure 6. Aging : brain, heart (Senile Atrophy)

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The mechanism of atrophy :

e.g. :

• Insulin

• Tyroid stimulating hormon

• Glucocorticoids

Synthesis

Catabolism

↑ Hormones

•

size of cell accompanied by ↑ functional

capacity

•

Is a response to trophic signals

•

Commonly a normal procesess

… hypertrophy

Physiological (hormonal) hypertrophy

• in puberty

• _{production of sex hormon}

• Hypertrophy breast tissue

• Abnormal hormon production in cancer

Functional demands

• Exercise

• Pathological conditions (myocardial cell) • Kidney hypertrophy on surgical removed

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Hyperplasia

the number of cells in an organ / tissue

Physiologic hyperplasia

• Hormonal hyperplasia

• Compensatory

hyperplasia

Pathologic hyperplasia

• ↑ hormonal / growth

factor stimulation

• e.g. :

• Endometrial

hyperplasia

Metaplasia

1 adult cell type another adult cell type

(convertion of 1 differentiated cell type of another)

Usually reversible if the stimulus is removed

• Squamous metaplasia of the bronchial epithelium to tobacco

• Lower oesophagus by reflux acidic gastric

• Endocervical metaplasia

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1. Size & shape of cells

variation

2. Nuclei : >>, irregular & hyperchromatism

3. Disorderly arrangement of the cells within the

epithelium

Dysplasia

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Dysplasia is a preneoplastic lession

•

Normal cell

primitive cell

•

E.g. : Malignant cell

–

Carcinoma

–

Sarcoma

–

Adenocarcinoma

–

Lymphoma

–

Etc.

Anaplasia

2 principal pattern of cell death :

• Commonly : coagulative necrosis • Cellular swelling

• Protein denaturation • Organellar breakdown • Cell rupture

NECROSIS

• Regulated event • Programmed death

APOPTOSIS

Term

Definition

Necrosis

Antemortem pathologic cell death

Apoptosis

Antemortem programmed cell death

CAUSES OF CELL INJURY

Hypoxia

Physical Agent

Chemical and drugs

Microbiology Agents

Immunologic Reaction

Genetic Defects

Nutritional Inbalance

Aging

• Anemia

• Ischemia

• Intoxication CO₂

• Aerobic oxidative

respiration

• Mechanical trauma

• Extreme temprature :

heat, cold

• Radiation: X-ray, sun light

• Electric shock

• Athmosphere pressure

Hypoxia Physical Agent

• Sufficiently concentrated :

Glucose, Salt, O₂

• Air pollutants

• Insecticides

• Asbestosis

• Ethanol

• Cellular metabolism (i.e.

waste products)

• Tape worms

• Rickettsia

• Virus

• Bacteria

• Fungi

… CAUSES OF CELL INJURY

Chemical agent & drugs Microbiology Agents

… CAUSES OF CELL INJURY

•

Anaphylactic reaction

•

Autoimmune diseases

Genetic Defects

• Congenital malformation • Sickle cell anemia

• G-6-PD

Nutritional Imbalance

• Protein calori insufficiency • Vitamins defficiency • Diabetes

Aging

Cellular response to injurious stimuli depends on :

• Injury type • Duration • Severity Current Status : • Nutritional • Hormonal • Adaptibility

of the cell

Intercellular systems :

• Cell membrane integrity • Aerobic

respiration • Protein synthesis • Integrity genetic

apparatus

O₂& oxygen derived free radicals :

• Ischemic • Hypoxic

injury

The ultrastructural features of these stages of cell injury. Normal cell & changes in reversible & irreversible cell injury

•

Reduced of :

– Oxidative

phosphorylation in mitochondria

– Activity Na Pump

•

Cellular swelling

•

Loss of microvilli

Glycogen depleted ↓ protein synthesis

Formation of cell surface blebs

•

Severe vacuolization of

mitochondria

•

Damage of :

– Mitochondrial matrix

– Plasma membrane

•

Swelling of lysosomes

•

Accumulation of

amorphous calcium

•

Rich dentities in

mitochondrial matrix

[image:18.612.127.488.95.365.2]

Figure 1-6.

Cellular features of

Feature Necrosis Apoptosis

Cell size Enlarged (swelling) Reduced (shrinkage) Nucleus Pyknosis → karyorrhexis

→ karyolysis

Fragmentation into nucleosome-size fragments

Plasma membrane Disrupted Intact; altered structure, especially orientation of lipids

Cellular contents Enzymatic digestion; may leak out of cell

Intact; may be released in apoptotic bodies

Adjacent inflammation Frequent No

Physiologic or pathologic role

Invariably pathologic (culmination of irreversible cell injury)

Often physiologic, means of eliminating unwanted cells; may be pathologic after some forms of cell injury, especially DNA damage

1. Reversible acute cell injury

2. Necrosis (cell death after irreversible injury)

3. Apoptosis (cell death by suicide)

4. Subcellular alteration as a respond to chronic or persistent injury stimuli

5. Intracellular accumulations of a number of substance

Morphologic changes that follow cell death in living tissue

1. Intense eosinophilia of the dead cell is due to

loss of RNA & coagulation of protein

2. Nuclei undergo:

1. Pyknosis 2. Karyorhexis 3. Karyolysis

Leaving a shrunken cell devoid of nucleus

3. Protein may be liberated from the dead cell

Necrosis

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Autolysis

: is a cell death by hydrolitic

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Nuclear Changes: This nucleus is faded -- karyolysis.

Karyolytic nuclei suggest that cells have died (undergone necrosis).

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Morphologic changes in reversible and irreversible cell injury (necrosis).

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Types of Necrosis

Depends on :

•

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Coagulative Necrosis

•

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Coagulative & liquefactive necrosis

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• Gumatous Necrosis

• Dead tissue, it is firm & rubbery like caseous necrosis in the

spirochetal infection syphilis.

• Hemorrhagic Necrosis

• Dead tissue suffused with extravasated red cell, when cell

death is due to blockage

• Fat Necrosis

• Not really necrosis.

• Focal areas of fat destruction tipically occuring following

pancreatic injury /after trauma to fat for (ex. in the breast)

• Describes foci of hard yellow material seen in dead adipose

•

Fibrinoid Necrosis

•

Fibrin deposited in damage necrotic vessel

walls in hypertension and vasculitis

•

Gangrene

•

Extensive tissue necrosis ; is complicated to

a variable degree by secondary bacterial

infection

APOPTOSIS

• Responsible for the programmed cell death in several

important physiology processes

• Including :

– During embryogenesis (in implantation, organogenesis, &

developmental involution)

– Hormon dependent physiologic involution (endometrium,

lactating, prostate after castration)

– Cell deletion in proliferating population (intestinal crypt

epithelium / cell dead in tumor)

– Deletion of autoreactive T cell in the thymus,

cell death of cytokine starved lymphocytes

Apoptosis of epidermal cells in an

immune-mediated reaction

A. Apoptotic cells are visible in the epidermis with eosinophilic cytoplasm and small, dense nuclei.

B. High power of apoptotic cell in liver in immune-mediated hepatic cell injury.

Granuloma

•

Special type of chronic inflamation in tissue

reaction.

•

Cause :

infection :

TBC fungal syphilis,

etc

non-infection :

sarcoidosis

Crohn’s disease

NECROBIOSIS

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… Necrobiosis

•

Gradual cell damage

•

Progressive

•

Singly / small group cells

•

Reversible (+/-)

•

Example :

–

Hepar cell

deg.

–

Cell death

healing

fibrosis.

Alterations in structure & function that may lead

to cell death, or at least diminished capacity of the

cell to respond an injury

•

Reduced cell in :

–

Pleomorphic vacuolated mitochondria

–

Repair of chromosomal damage

… Cellular Aging

Morphologic alteration in :

• Pleomorphic vacuolated mitochondria

•

endoplasmic reticulum

• Disorted Golgi Apparatus

• Accumutaion of lipofuscin pigment

Cellular senescence is multifactorial :

The cumulative effects of :

1. Extrinsic influences : free radical damage

DEGENERATION

Cloudy swelling

Fatty

change Hydropic Atropy

Hyaline

Mucoid

Amyloid

Calcification

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