CELLULAR ADAPTATIONS OF

GROWTH &
DIFFERENTIATION

Departemen Patologi Anatomi Fakultas

Kedokteran Universitas Sumatera Utara
Medan

Definitions
Pathology is a dicipline bridging clinical
practice & basic sience
To render diagnosis & guide therapy
Identity changes in :
Gross
Morphology (microscopy) appearance of cell
tissues

The scientific focus of pathology is :

Etiology
On the cause of disease

Pathogenesis
Mechanisme of its development & the
pathways by which morphologic changes
occur

Normal Homeostasis
If cell adjusting structure & function
to accommodate changing demands &
extracellular stresses

Stages in the cellular response to stress & injurious

stimuli

Stresses/pathologic stimuli the cell:

Can undergo

Adaptation
Atrophy
Hypertrophy
Hyperplasia
Metaplasia

Irreversible injury & ultimately dies

Perubahan sel & jaringan :

Agenesis

Hyperplasia

Aplasia

Metaplasia

Hypoplasia

Dysplasia

Atrophy

Anaplasia

Hypertrophy

Granuloma

Agenesis

Aplasia

Complete absent of an
organ
E.g. :

Anlarge is present but

never develops
E.g. :

Renal agenesis
Ovarial agenesis
Tubal agenesis, etc.

Lung aplasia with tissue

containing rudimentary
duct & connective tissue

Hypoplasia

Anlarge develoved incompletly but the tissue

histhologicaly normal
Ex. : microcephaly

Atrophy

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. Interrruption 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)

Atrophy The adjacent image is 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.

The mechanism of atrophy :

synthesis
catabolism
Influenced by a number of hormones
e.g. :
Insulin
Tyroid stimulating hormon
Glucocorticoids

Hypertrophy
in the size of cell accompanied by augmented
functional capacity
Hypertrophy 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

Hypertrophy Here is another section

of myocardium in an area adjacent to
a healed myocardial infarct ("heart
attack"). Since cardiac muscle cannot
regenerate, fibrous connective tissue
fills in the defect. Nearby viable
muscle cells increase in size to
compensate for cells that died. In this
section enlarged nuclei indicate that
the cells have undergone hypertrophy
(increase in volume of cells).

Hypertrophy At higher
magnification, the enlargment
of cardiac muscle cells and
nuclei is apparent. Since cardiac
muscle cells cannot divide, they
adapt by increasing their size
(hypertropy).

Hyperplasia
the number of cells in an organ / tissue

Hyperplasia can be :
1. Physiologic hyperplasia
Hormonal hyperplasia
Compensatory hyperplasia

2. Pathologic hyperplasia
Excessive hormonal / growth factor stimulation
e.g. : Endometrial hyperplasia

1. Hormonal stimulation
Estrogen endometrium (hyperplasia)
Gynecomastia
2. Increased functional demand
- secondary polycytemia
- lymphocyte hyperplasia
3. Persistent Cell Injury
- chronic inflammation in the skin and
the epi
thelium of viscera
- hyperplasia of the bladder epithelium

Metaplasia
Reversible change in which 1 adult cell type is replace by another
adult cell type (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

Metaplasia is usually reversible if the stimulus is

removed

Metaplasia of normal columnar (left) to squamous epithelium

(right) in a bronchus, shown (A) schematically and (B)
histologically

Dysplasia
Cellular alteration in the size, shape & organization of the
cellular component of a tissue

1. Variation in the size & shape of cells

2. Enlargment, irregularity & hyperchromatism of the
nuclei
3. Disorderly arrangement of the cells within the
epithelium
The most common in the cervix & bronchus

Dysplasia is a preneoplastic lession in the sense

that it is a necessary stage in the multistep cellular
evolution to cancer.

Dysplasia included in the morphological classification of the

stage if intraepithelial neoplasia

Anaplasia
Normal cell primitive cell
E.g. : Malignant cell
Carcinoma
Sarcoma
Adenocarcinoma
Lymphoma
Etc.

2 principal pattern of cell death :

NECROSIS

APOPTOSIS

Commonly : coagulative necrosis

Cellular swelling
Protein denaturation
Organellar breakdown
Cell rupture

Regulated event
Programmed death

Term

Definition

Necrosis

Antemortem pathologic cell death

Apoptosis

Antemortem programmed cell death

Autolysis

Postmortem cell death

CAUSES OF CELL INJURY

Hypoxia
Physical Agent

Chemical and drugs

Microbiology Agents
Immunologic Reaction
Genetic Defects
Nutritional Inbalance
Aging

 CAUSES OF CELL INJURY

Hypoxia

Anemia
Ischemia
Intoxication CO2
Aerobic oxidative
respiration

Physical Agent
Mechanical trauma
Extreme temprature :
heat, cold
Radiation: X-ray, sun light
Electric shock
Athmosphere pressure

 CAUSES OF CELL INJURY

Chemical agent & drugs
Sufficiently concentrated :
Glucose
Salt
O2

Air pollutants
Insecticides
Asbestosis
Ethanol
Cellular metabolism (i.e.
waste products)

Microbiology Agents

Tape worms
Rickettsia
Virus
Bacteria
Fungi

 CAUSES OF CELL INJURY

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

Mechanism of Cell Injury

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

Normal cell & changes in reversible & irreversible cell injury

(necrosis)

The ultrastructural features of these stages of cell injury.

Reversible injury
Reduced of :
Oxidative
phosphorylation in
mitochondria
Activity Na Pump

Cellular swelling
Loss of microvilli

Irreversible injury
Severe vacuolization of
the mitochondria
Damage of :
Mitochondrial matrix
Plasma membrane

Swelling of lysosomes
Glycogen depleted
Accumulation of
protein synthesis
amorphous calcium
Formation of cell surface
Rich dentities in
blebs
mitochondrial matrix

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

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

Sublethal Damage
1. Recoverable (but necrosis is not)
2. Ultrastructural damage mitochondria
3. Swelling of cellular organelles ( hydrophic deg.)
4. Fatty change is impairment of metabolism

Necrosis
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

1. Protein may be liberated from the dead cell

The morphologic appearance of necrosis is

the result of two essentially processes :
1. Enzymatic digestion of the cell
2. Denaturation of protein

Autolysis : is a cell death by hydrolitic

enzymes.

Heterolysis : cell death by the lysosomes of

invading inflammatory cells.

Nuclear Changes: This nucleus is faded -- karyolysis.

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

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).

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).

Types of Necrosis
Depends on :
1. Cells compotitions
2. Speed of necrosis
3. Type of injuries

Coagulative Necrosis
Implies preservation of basic structural outline of the
coagulated cell / tissue for a span of days.
The structural protein and the enzymatic protein thus
blocking cellular proteolysis
Coagulation necrosis is cahareteristic of hypoxic death of
cells in all tissue except the brain
E.g. : Myocardial Infarction (occlusion of arterial supply )

 Liquefactive/Colliquativa Necrosis
Dead tissue that appears semi liquid as a 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 an amorphous proteinaceaus mass,
no original architecture can be seen histologically
(soft & white resembling cream cheese)
Most often in fact of tuberculous infection with
central necrosis

 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

 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

CLINICAL EFFECTS OF NECROSIS

Abnormal function

Kidney

: renal failure
Cortex in brain : muscle paralysis
Heart
: heart failure
Lung
: hemoptysis
Bacterial infection : gangrene

 Realease of contens of necrotic cells

Liver

: elevation SGOT
Heart : creatine kinase
Systemic effects
Fever

Inflamatoar Reaction

Local effects
Hemorrhage
Ulceration

Apoptosis of epidermal cells in an immunemediated 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.)

CELLULAR ADAPTATIONS OF GROWTH AND

DIFFENTIATION
Environment adaptation of the cell
1. Physiologic Adaptation
- Hormones
- Endogenous chemical mediators
2. Pathologic Adaptation
- Induction of new protein synthesis by target
cell
Cell Injury :
Death of cells ( permanent organ injury )
Sublethal injury ( adaptation )

Granuloma
Special type of chronic inflamation in tissue
reaction.
Cause :
infection :

TBC

fungal

noninfection :

sarcoidosis

Crohns
disease

syphilis,
etc

NECROBIOSIS

Gradual cell damage

Progressive
Singly or small group cells.
Reversible (+/-)
Example : hepar cell deg.
cell death healing fibrosis.

CELLULAR AGING
Alterations in structure and 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 :

1. The cumulative effects of extrinsic influences:
free radical damage
2. Intrinsic molecular program of cellular aging
cell have a finite life span

DEGENERATION

Cloudy
swelling

Hyaline

Fatty
change

Mucoid

Hydropic

Amyloid

Atropy

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 appear homogeneous, glassy, bead-like
structures -- an apearance known as "hyaline.

THANK YOU
SELAMAT BELAJAR