K12- Cell Injury (New)

Departemen Patologi Anatomi Fakultas Kedokteran Universitas Sumatera Utara Medan - 2011

Blok BBS 2

Stages in the cellular response to stress & injurious stimuli

04/19/23 2DEPARTEMEN PATOLOGI ANATOMI

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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


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Stresses/pathologic stimuli the cell


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Can undergo Can undergo

Perubahan sel & jaringan


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• Complete absent of organ

• e.g. : – Renal agenesis– Ovarial agenesis– Tubal agenesis, etc.

• Is present • But never develops• e.g. :

– Lung aplasia with tissue containing rudimentary duct & connective tissue


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• Developved incompletly• But the tissue histhologicaly normal• e.g. : microcephaly


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• Decrease in the:– Size – Function of a cell

• But not dead


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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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Atrophy A section of heart muscle (myocardium). The spaces between muscle fibers are not present in normal myocardium. The muscle fibers are thinner than normal creating spaces between them, a finding suggesting atrophy.04/19/23 10

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The mechanism of atrophy :

e.g. : • Insulin• Tyroid stimulating hormon• Glucocorticoids


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• ↑ size of cell accompanied by ↑ functional capacity

• Is a response to trophic signals• Commonly a normal procesess


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… hypertrophy


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Hypertrophy Myocardium in an area adjacent to a healed MCI ("heart attack"). Cardiac muscle cannot regenerate, fibrous connective tissue fills in the defect. Viable muscle cells, ↑ size to compensate for cells that died. Nuclei ↑ indicate the cells have undergone hypertrophy (↑ in volume of cells).

Hypertrophy At higher magnification↑ cardiac muscle cells & nuclei. Cardiac muscle cells cannot divide adapt by ↑size (hypertropy).


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↑ the number of cells in an organ / tissue


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Hyperplasia can be :


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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

Most common is the replacment of a glandular epithelium by a squamous cell.


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Metaplasia of normal columnar (left) to squamous epithelium (right) in a bronchus, (A) schematically and (B) histologically


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Cellular alteration in the size, shape & organization of the cellular

component of a tissue

1. Size & shape of cells variation2. Nuclei : >>, irregular & hyperchromatism 3. Disorderly arrangement of the cells within the

epithelium

The most common in the cervix & bronchus


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Dysplasia is a preneoplastic lessionNecessary stage in the multistep cellular evolution

to cancer.


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• Normal cell primitive cell• E.g. : Malignant cell

– Carcinoma– Sarcoma– Adenocarcinoma– Lymphoma– Etc.


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CELL INJURY

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2 principal pattern of cell death :


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Term Definition

Necrosis Antemortem pathologic cell death

Apoptosis Antemortem programmed cell death

Autolysis Postmortem cell death


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CAUSES OF CELL INJURY


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• Anemia• Ischemia• Intoxication CO2

• Aerobic oxidative respiration

• Mechanical trauma• Extreme temprature :

heat, cold• Radiation: X-ray, sun light• Electric shock• Athmosphere pressure

… CAUSES OF CELL INJURY


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• Sufficiently concentrated :Glucose, Salt, O2

• Air pollutants• Insecticides• Asbestosis• Ethanol• Cellular metabolism (i.e.

waste products)

• Tape worms• Rickettsia• Virus• Bacteria• Fungi



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• Anaphylactic reaction• Autoimmune diseases


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The ultrastructural features of these stages of cell injury.

Normal cell & changes in reversible & irreversible cell injury (necrosis)


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• 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


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Figure 1-6. Cellular features of

necrosis (left) & apoptosis (right)


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Feature Necrosis ApoptosisCell size Enlarged (swelling) Reduced (shrinkage)Nucleus Pyknosis → karyorrhexis

→ karyolysisFragmentation 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 NoPhysiologic 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 damage04/19/23 37


Forms & Morphology of Cell Injury


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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. Pyknosis2. Karyorhexis3. Karyolysis Leaving a shrunken cell devoid of nucleus

3. Protein may be liberated from the dead cell


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The morphologic appearance of necrosis is the result of 2 essentially processes :

1. Enzymatic digestion of the cell2. Denaturation of protein


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Nuclear Changes: This nucleus is faded -- karyolysis. Karyolytic nuclei suggest that cells have died (undergone necrosis).04/19/23 41


Nuclear Changes: Pyknosis While cytoplasmic changes associated with cell death are not specific, nuclear changes are. The large arrow indicates a normal-appearing nucleus while the smaller arrow indicates a nucleus that is small and dark -- features of "pyknosis." Pyknotic nuclei suggest that cells have died (are undergoing necrosis).


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Fragmented nuclei suggest that cells have died. Karyorrhexis is the term used for this circumstance. The nucleus indicated by the large arrow may be undergoing karyorrhexis. The smaller arrow indicates a fragmented nucleus: it could be karyorrhexis or a mitotic figure (a cell undergoing mitosis).


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

A, Normal kidney tubules with viable epithelial cells

B, Early (reversible) ischemic injury

C, Necrotic (irreversible) injury of epithelial cells


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Types of Necrosis

Depends on :1.Cells compotitions2.Speed of necrosis3.Type of injuries


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•The structural protein & enzymatic protein thus blocking cellular proteolysis

•Cahareteristic of hypoxic death of cells in all tissue except the brain

e.g. : Myocardial Infarction (occlusion of arterial supply)

Coagulative Necrosis


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• Liquefactive/Colliquativa Necrosis• Dead tissue• Appears semi liquid • Result of dissolution of tissue by the action of

hydrolytic enzymes e.g.: cerebral infarction, necrosis caused by

bacterial inf.

• Caseous Necrosis• Dead cell • Form amorphous proteinaceaus mass• No original architecture can be seen

(histologic) • Soft & white resembling cream cheese• Most often in TBC infection with central

necrosis04/19/23 48


Coagulative & liquefactive necrosis

A. Kidney infarct (coagulative necrosis)

B. Liquefactive necrosis (kidney caused by fungal infection).


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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

tissue


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• 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


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Fibrinoid necrosis in an artery (polyarteritis nodosa)


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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


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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.

(Courtesy of Dr. Scott Granter, Brigham and Women's Hospital, Boston, AM.) (Courtesy of Dr. Dhanpat Jain, Yale University, New Haven, CT.) 04/19/23 54DEPARTEMEN PATOLOGI ANATOMI

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• Special type of chronic inflamation in tissue reaction.

• Cause :


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Necrobiosis is physiological death of a cell, and can be caused by certain conditions


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It can be identified both with/without necrosis

Such as :•Basophilia•Erythema or •Presence of a tumor

… Necrobiosis

• Gradual cell damage• Progressive• Singly / small group cells• Reversible (+/-) • Example :

– Hepar cell deg.– Cell death healing fibrosis.


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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


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… Cellular Aging

Morphologic alteration in :• Pleomorphic vacuolated mitochondria• ↓ endoplasmic reticulum• Disorted Golgi Apparatus• Accumutaion of lipofuscin pigment


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Cellular senescence is multifactorial :

The cumulative effects of :1. Extrinsic influences : free radical damage

2. Intrinsic molecular program of cellular aging cell have a finite life span


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DEGENERATION


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Ballooning degeneration


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Hydropic change of gestational mole


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Fatty Change At higher magnification the intracytoplasmic fat droplets are clearly evident.


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Hyaline Droplet Degeneration Sometimes protein droplets appear within the cy_toplasm of sick cells. These droplets appear homogeneous, glassy, bead-like structures -- an apearance known as "hyaline.”


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THANK YOU

SELAMAT BELAJAR


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K12- Cell Injury (New)

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