Cell Injury (FKG, Juni 2016)

Kuliah FKG
DEPARTEMEN PATOLOGI ANATOMI

FAKULTAS KEDOKTERAN
UNIVERSITAS SUMATERA UTARA
MEDAN - 2016
RESPON SELULAR TERHADAP STRESS &
JEJAS
10/26/2017 DEPARTEMEN PA FK-USU 2016 2

Tabel 1-1. Respon selular terhadap jejas
Nature & beratnya stimulus jejas Respon selular
Gangguan stimulus fisiologi: Adaptasi selular:
demand, trophic stimulation (e.g. growth
Hyperplasia, hypertrophy
factors, hormones)
nutrients, stimulation Atrophy
Chronic irritation (chemical /physical) Metaplasia
Suplai O2 ; jejas kimiawi; infeksi mikroba Jejas sel:
Acute & self-limited Acute reversible injury

Progessive & severe (DNA damage) Irreversible injury cell death
Necrosis
Apoptosis
Mild chronic injury Subcellular alterations in various organelles
Gangguan metabolik (genetik / didapat) Akumulasi intraselular; kalsifikasi
Prolonged life span with cumulative
Cellular aging
sublethal injury

Stresses/stimuli patologi
Sel akan
mengalami
Adaptasi
Atrophy
Hypertrophy
Hyperplasia
Metaplasia
Jejas yang ireversibel & kematian sel

Perubahan sel & jaringan
Agenesis Hyperplasia
Aplasia Metaplasia
Hypoplasia Dysplasia
Atrophy Anaplasia
Hypertrophy Granuloma

Agenesis Aplasia
Tidak terbentuknya Organ terbentuk

organ Namun tidak pernah
Contoh : berkembang
Renal agenesis Contoh:
Ovarial agenesis Lung aplasia dengan
Tubal agenesis, dll. sisa jaringan yang
mengandung duktus &
jaringan ikat

Hypoplasia
Perkembangan yang tidak lengkap

Namun secara histologi jaringannya normal
Contoh: microcephaly

Atrophy
Decrease in the:
Size
Function of a cell
But not dead

Causes of atrophy :
functional Immobilitation in fracture

demand Prolonged bed rest
Inadequate Ischemia
supply O2
Insufficient Starvation
Inadequate nutrition
nutrients Chronic disease

Causes of atrophy :
Interruption of trophic signals
transmitted by chemical
mediators (endocrine
e.g. : thyroid, adrenal
system/neuromusculator
transmission)
cortex, ovarium, testis.
Persistent cell injury e.g. : chronic gastritis,

by chronic
inflamation prolonged pressure
Brain
Aging :
Heart (Senile Atrophy)
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.
Mekanisme terjadinya atrofi
Synthesis
Catabolism
Hormones
e.g. :
Insulin
Tyroid stimulating hormon
Glucocorticoids

Hypertrophy
size of cell accompanied by functional

capacity
Is a response to trophic signals
Commonly a normal procesess

hypertrophy
Physiological (hormonal) hypertrophy
Pubertas
produksi hormon sex
Hipertrofi jaringan payudara
Produksi hormon abnormal pada kanker
Functional demands
Latihan
Keadaan patologi (sel miokard)
Hipertrofi ginjal setelah nefrektomi

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 (400x)
cardiac muscle cells & nuclei.
Cardiac muscle cells cannot divide adapt by
size (hypertropy).

Hyperplasia
the number of cells in an organ / tissue

Hyperplasia:
Hiperplasia Fisiologi Hiperplasia Patologi
Hormonal hyperplasia hormonal / growth

Compensatory factor stimulation
hyperplasia e.g. :
Endometrial
hyperplasia

Metaplasia
1 jenis sel dewasa jenis sel dewasa lainnya

(convertion of 1 differentiated cell type of another)
Most common is the replacment of a glandular epithelium

by a squamous cell.
Squamous metaplasia of the bronchial epithelium to tobacco
Lower oesophagus by reflux acidic gastric
Endocervical metaplasia
Usually reversible if the stimulus is removed

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

Dysplasia
Kelainan seluler dalam ukuran, bentuk dan organisasi

komponen selular dari suatu jaringan
Size & shape of cells variation
Nuclei : >>, irregular & hyperchromatism
Kelainan susunan sel pelapis epitel
The most common in the cervix & bronchus

Dysplasia is a preneoplastic lession
Necessary stage in the multistep cellular evolution
to cancer.

Anaplasia
Normal cell primitive cell

E.g. : Malignant cell
Carcinoma
Sarcoma
Adenocarcinoma
Lymphoma
Etc.

JEJAS SEL

2 jenis kematian sel:
Commonly : coagulative
necrosis
Cellular swelling
NECROSIS Protein denaturation
Organellar breakdown
Cell rupture
Regulated event
APOPTOSIS Programmed death

Term Definition
Necrosis Antemortem pathologic cell death
Apoptosis Antemortem programmed cell death
Autolysis Postmortem cell death

PENYEBAB JEJAS SEL
Hypoxia
Physical Agent
Chemical and drugs
Microbiology Agents
Immunologic Reaction
Genetic Defects
Nutritional Inbalance
Aging
CAUSES OF CELL INJURY
Hypoxia Physical Agent
Anemia Mechanical trauma

Ischemia Extreme temprature :
Intoxication CO2 heat, cold
Aerobic oxidative Radiation: X-ray, sun light
respiration Electric shock
Athmosphere pressure

Chemical agent & drugs Microbiology Agents
Sufficiently concentrated : Tape worms

Glucose, Salt, O2 Rickettsia
Air pollutants Virus
Insecticides Bacteria
Asbestosis Fungi
Ethanol
Cellular metabolism (i.e.
waste products)

Immunologic Reaction
Anaphylactic reaction
Autoimmune diseases

Genetic Defects
Congenital malformation
Sickle cell anemia
G-6-PD
Nutritional Imbalance
Protein calori insufficiency
Vitamins defficiency
Diabetes
Aging

Mekanisme jejas sel
Respon seluler Status : Sistem O2 & radikal

terhadap Intercellular: bebas:
rangsangan jejas Nutrisi
Integritas sel
tergantung pada: Hormon membran
Ischemic
Jenis jejas Kemampuan Aerobic Hypoxic
Lama serta adaptasi sel respiration injury
beratnya jejas Protein synthesis
Integritas genetik

Reversible injury Irreversible injury
Penurunan: Severe vacuolization of
Oxidative mitochondria
phosphorylation dalam
mitokhondria
Damage of :
Activitas pompa Na Mitochondrial matrix
Cellular swelling Plasma membrane
Loss of microvilli Swelling of lysosomes
Glycogen depleted Accumulation of
protein synthesis
Formation of cell surface
amorphous calcium
blebs Rich dentities in
mitochondrial matrix

Figure 1-6.
Cellular features of
necrosis (left) &
apoptosis (right)

FEATURE NECROSIS APOPTOSIS
Cell size Enlarged (swelling) Reduced (shrinkage)
Nucleus Pyknosis karyorrhexis Fragmentation into
karyolysis nucleosome-size
fragments
Plasma membrane Disrupted Intact; altered structure,
especially orientation of
lipids
Cellular contents Enzymatic digestion; may Intact; may be released in
leak out of cell apoptotic bodies
Adjacent inflammation Frequent No
Physiologic / Invariably pathologic Often physiologic, means
pathologic role (culmination of of eliminating unwanted
irreversible cell injury) cells; may be pathologic
after some forms of cell
injury, especially DNA
10/26/2017 DEPARTEMEN PA FK-USU 2016 damage 38
APOPTOSIS of a liver cell in viral hepatitis
The cell is reduced in size and contains brightly eosinophilic cytoplasm and a
condensed nucleus

APOPTOSIS OF EPIDERMAL CELLS IN AN
IMMUNE-MEDIATED REACTION
High power
(hepatic cell injury)

FORMS & MORPHOLOGY OF CELL INJURY
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
NECROSIS
PERUBAHAN MORFOLOGI KEMATIAN SEL PADA JARINGAN

HIDUP
1. Eosinophilia pada sel yang mati o.k. kehilangan

RNA & koagulasi protein
2. Inti mengalami:
1. Karyopyknosis
2. Karyorhexis
3. Karyolysis
Pengerutan inti
3. Protein akan dilepaskan dari sel yang sudah mati

Gambaran morfologi nekrosis akibat 2 proses yang
mendasarinya:
1. Pencernaan sel oleh enzim

2. Denaturasi protein
Autolysis : is a cell death by hydrolitic

enzymes
Heterolysis : cell death by the lysosomes of

invading inflammatory cells.

Karyolysis

Pyknosis

Karyorrhexis

MORPHOLOGIC CHANGES IN REVERSIBLE &
IRREVERSIBLE CELL INJURY (NECROSIS)
A. Normal kidney tubules B. Early (reversible) C. Necrotic (irreversible) injury

with viable epithelial ischemic injury of epithelial cells
cells

TYPES OF NECROSIS
Depends on :
Cells compotitions
Speed of necrosis
Type of injuries

COAGULATIVE NECROSIS
Struktur protein & enzimatik protein menghambat

proteolisis selular
Karakteristik hipoksia kematian sel pada semua

jaringan, kecuali jaringan otak
Contoh:
Myocardial Infarction (occlusion of arterial
supply)

COAGULATIVE NECROSIS
Wedge-shaped kidney infarct
Microscopic view of the edge
(yellow) with preservation of
of the infarct
the outlines
NECROTIC CELLS
IN THE INFARCT
NORMAL
KIDNEY

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.

Liquefactive necrosis
An infarct in the brain, showing dissolution of the tissue

Coagulative &
liquefactive necrosis
A. Kidney infarct B. Liquefactive necrosis

(coagulative necrosis) (kidney caused by fungal
infection).

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
necrosis
CASEOUS NECROSIS
A tuberculous lung with a large area of caseous necrosis containing yellow-
white and cheesy debris

Dead tissue
Gumatous Firm & rubbery like caseous
Necrosis necrosis
In spirochetal infection syphilis.
Dead tissue suffused with

Hemorrhagic extravasated red cel
Necrosis When cell death is due to
blockage

Not really necrosis
Focal areas of fat destruction
tipically occuring following
Fat pancreatic injury /after trauma
to fat for (ex. in the breast)
Necrosis Describes foci of hard yellow
material seen in dead adipose
tissue

FAT NECROSIS IN ACUTE PANCREATITIS
The areas of white chalky deposits represent foci of fat necrosis with calcium soap
formation (saponification) at sites of lipid breakdown in the mesentery
White chalky deposits

Fibrin deposited in
damage necrotic
Fibrinoid vessel walls
Necrosis In hypertension and
vasculitis

Fibrinoid necrosis in an artery
(polyarteritis nodosa)

Extensive tissue necrosis
Complicated to a
Gangrene 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 B. High power of apoptotic cell in liver in
and small, dense nuclei. immune-mediated hepatic cell injury.
10/26/2017 DEPARTEMEN
(Courtesy of Dr. Scott Granter, Brigham and Women's Hospital, PA(Courtesy
Boston, AM.) FK-USUof 2016
Dr. Dhanpat Jain, Yale University, New Haven, CT.) 64
Granuloma
Special type of chronic inflamation in tissue

reaction.
Cause :
TBC
infection : fungal
syphilis, etc
non- sarcoidosis
infection : Crohns disease

TUBERCULOUS GRANULOMAS

NECROBIOSIS
= Kematian sel fisiologis, o.k keadaan tertentu
Seperti:
Basophilia, Erythema
Tumor
Teridentifikasi dengan/tanpa nekrosis

Necrobiosis
Kerusakan sel bertingkat

Progresif
Satu sel / berkelompok
Reversible (+/-)
Contoh:
Sel hati degenerasi
Cell death healing fibrosis.

Cellular Aging
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
Accumulation of lipofuscin pigment

DEGENERATION
Cloudy Fatty
Hydropic Atropy
swelling change
Hyaline Mucoid Amyloid Calcification

Ballooning
degeneration
Hydropic change
of gestational
mole

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

Hyaline Droplet Degeneration Sometimes protein droplets appear within the
cy_toplasm of sick cells. These droplets
10/26/2017
appear homogeneous, glassy, bead-like
DEPARTEMEN PA FK-USU 2016 76
structures -- an apearance known as "hyaline.
Protein reabsorption droplets
in the renal tubular epithelium

Lipofuscin granules
in a cardiac myocyte
Light microscopy Electron microscopy.
(deposits indicated by arrows) Note the perinuclear, intralysosomal
location

PATHOLOGIC CALCIFICATION
The abnormal deposition of calcium salts,

with iron, magnesium, and other minerals
Dystrophic calcification
Deposition occurs in dead or dying tissues

Calcium metabolic derangements (-)
(i.e., serum levels of calcium normal)

Dystrophic Calcification
Hemosiderin granules in liver cells
Golden-brown, finely Specific for iron
granular pigment (H&E) (Prussian blue reaction)

Calcification of the aortic valve

PATHOLOGIC CALCIFICATION
Metastatic calcification
The deposition of calcium salts in
normal tissues
Reflects some derangement in
calcium metabolism
(hypercalcemia)
SELAMAT BELAJAR
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Cell Injury (FKG, Juni 2016)

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Kuliah FKG

DEPARTEMEN PATOLOGI ANATOMI

10/26/2017 DEPARTEMEN PA FK-USU 2016 2

Suplai O2 ; jejas kimiawi; infeksi mikroba Jejas sel:

Acute & self-limited Acute reversible injury

10/26/2017 DEPARTEMEN PA FK-USU 2016 3

10/26/2017 DEPARTEMEN PA FK-USU 2016 4

10/26/2017 DEPARTEMEN PA FK-USU 2016 5

Tidak terbentuknya Organ terbentuk

10/26/2017 DEPARTEMEN PA FK-USU 2016 6

Perkembangan yang tidak lengkap

10/26/2017 DEPARTEMEN PA FK-USU 2016 7

10/26/2017 DEPARTEMEN PA FK-USU 2016 8

functional Immobilitation in fracture

10/26/2017 DEPARTEMEN PA FK-USU 2016 9

Persistent cell injury e.g. : chronic gastritis,

10/26/2017 DEPARTEMEN PA FK-USU 2016 12

size of cell accompanied by functional

10/26/2017 DEPARTEMEN PA FK-USU 2016 13

10/26/2017 DEPARTEMEN PA FK-USU 2016 14

10/26/2017 DEPARTEMEN PA FK-USU 2016 15

the number of cells in an organ / tissue

10/26/2017 DEPARTEMEN PA FK-USU 2016 16

Hiperplasia Fisiologi Hiperplasia Patologi

Hormonal hyperplasia hormonal / growth

10/26/2017 DEPARTEMEN PA FK-USU 2016 17

1 jenis sel dewasa jenis sel dewasa lainnya

Most common is the replacment of a glandular epithelium

Usually reversible if the stimulus is removed

10/26/2017 DEPARTEMEN PA FK-USU 2016 18

10/26/2017 DEPARTEMEN PA FK-USU 2016 19

Kelainan seluler dalam ukuran, bentuk dan organisasi

Size & shape of cells variation

Nuclei : >>, irregular & hyperchromatism

Kelainan susunan sel pelapis epitel

The most common in the cervix & bronchus

10/26/2017 DEPARTEMEN PA FK-USU 2016 21

Normal cell primitive cell

10/26/2017 DEPARTEMEN PA FK-USU 2016 22

10/26/2017 DEPARTEMEN PA FK-USU 2016 23

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Necrosis Antemortem pathologic cell death

Apoptosis Antemortem programmed cell death

Autolysis Postmortem cell death

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Chemical and drugs

Hypoxia Physical Agent

Anemia Mechanical trauma

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Chemical agent & drugs Microbiology Agents

Sufficiently concentrated : Tape worms

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Respon seluler Status : Sistem O2 & radikal

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2. Necrosis (cell death after irreversible injury)

3. Apoptosis (cell death by suicide)

4. Subcellular alteration as a respond to chronic or