definitions -...

1

CELLULAR ADAPTATIONS OF GROWTH &

DIFFERENTIATION

• Departemen Patologi Anatomi FakultasKedokteran 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

2

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

3

Stages in the cellular response to stress & injurious

stimuli

Stresses/pathologic stimuli the cell:

Adaptation

• Atrophy

• Hypertrophy

• Hyperplasia

• Metaplasia

Irreversible injury & ultimately dies

Can undergo

4

Perubahan sel & jaringan :

Agenesis

Aplasia

Hypoplasia

Atrophy

Hypertrophy

Hyperplasia

Metaplasia

Dysplasia

Anaplasia

Granuloma

• Complete absent of an

organ

• E.g. :

– Renal agenesis

– Ovarial agenesis

– Tubal agenesis, etc.

Agenesis Aplasia

• Anlarge is present but

never develops

• E.g. :

– Lung aplasia with tissue

containing rudimentary

duct & connective tissue

5

• Anlarge develoved incompletly but the tissue

histhologicaly normal

• Ex. : microcephaly

Hypoplasia

• Decrease in the:

– Size

– Function of a cell

• But not dead

Atrophy

6

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.

7

The mechanism of atrophy :

• ↓ synthesis

• ↑ catabolism

• Influenced by a number of hormones

e.g. :

• Insulin

• Tyroid stimulating hormon

• Glucocorticoids

• ↑ in the size of cell accompanied by augmented functional capacity

• Hypertrophy is a response to trophic signals

• Commonly a normal procesess

Hypertrophy

8

… 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).

9

Hyperplasia

↑ the number of cells in an organ / tissue

1. Physiologic hyperplasia

– Hormonal hyperplasia

– Compensatory hyperplasia

2. Pathologic hyperplasia

– Excessive hormonal / growth factor stimulation

e.g. : Endometrial hyperplasia

Hyperplasia can be :

10

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)

Metaplasia is 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.

11

Metaplasia of normal columnar (left) to squamous epithelium

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

histologically

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

Dysplasia

The most common in the cervix & bronchus

12

Dysplasia included in the morphological classification of the

stage if intraepithelial neoplasia

Dysplasia is a preneoplastic lession in the sense

that it is a necessary stage in the multistep cellular

evolution to cancer.

• Normal cell � primitive cell

• E.g. : Malignant cell

– Carcinoma

– Sarcoma

– Adenocarcinoma

– Lymphoma

– Etc.

Anaplasia

13

2 principal pattern of cell death :

• Commonly : coagulative necrosis

• Cellular swelling

• Protein denaturation

• Organellar breakdown

• Cell rupture

NECROSIS

• Regulated event

• Programmed deathAPOPTOSIS

14

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

15

• 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

… CAUSES OF CELL INJURY

• Sufficiently concentrated :

– Glucose

– Salt

– O2

• Air pollutants

• Insecticides

• Asbestosis

• Ethanol

• Cellular metabolism (i.e.

waste products)

• Tape worms

• Rickettsia

• Virus

• Bacteria

• Fungi


Chemical agent & drugs Microbiology Agents

16


• Anaphylactic reaction

• Autoimmune diseases

Immunologic Reaction

Genetic Defects

• Congenital malformation

• Sickle cell anemia

• G-6-PD

Nutritional Imbalance

• Protein calori insufficiency

• Vitamins defficiency

• Diabetes

Aging

17

Cellular

response to

injurious

stimuli

depends on :

• Injury type

• Duration

• Severity

Current

Status :

• Nutritional

• Hormonal

• Adaptibilityof the cell

Intercellular

systems :

• Cell membrane integrity

• Aerobic respiration

• Protein synthesis

• Integrity genetic apparatus

O2 & oxygen

derived free

radicals :

• Ischemic

• Hypoxic injury

Mechanism of Cell Injury

The ultrastructural features of these stages of cell injury.

Normal cell & changes in reversible & irreversible cell injury

(necrosis)

18

• 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

the mitochondria

• Damage of :

– Mitochondrial matrix

– Plasma membrane

• Swelling of lysosomes

• Accumulation of

amorphous calcium

• Rich dentities in

mitochondrial matrix

Reversible injury Irreversible injury

20

Figure 1-6.

Cellular features of

necrosis (left) &

apoptosis (right)

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

Forms & Morphology of Cell Injury

21

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

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

Necrosis

22

The morphologic appearance of necrosis isthe result of two essentially processes :

1. Enzymatic digestion of the cell2. Denaturation of protein

Autolysis : is a cell death by hydroliticenzymes.

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).

23

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).

24

Types of Necrosis

Depends on :

1. Cells compotitions

2. Speed of necrosis

3. Type of injuries

25

• 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 brainE.g. : Myocardial Infarction (occlusion of arterial supply )

Coagulative Necrosis

• 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

26

• 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

27

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

28

• 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 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.)

29

CELLULAR ADAPTATIONS OF GROWTH ANDDIFFENTIATION

Environment adaptation of the cell1. 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 syphilis,

etc

non-

infection :sarcoidosis

Crohn’s

disease

30

NECROBIOSIS

• Gradual cell damage

• Progressive

• Singly or small group cells.

• Reversible (+/-)

• Example : hepar cell � deg.

cell death � healing � fibrosis.

Alterations in structure and function that may

lead to cell death, or at least diminished capacity

of the cell to respond an injury

CELLULAR AGING

• Reduced cell in :

– Pleomorphic vacuolated mitochondria

– Repair of chromosomal damage

31

… 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

32

DEGENERATION

Cloudy swelling

Fatty change

Hydropic Atropy

Hyaline Mucoid AmyloidCalcifica-

tion

Ballooning degeneration

33

Hydropic change of gestational mole

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

34

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

O1

O1 Owner, 11/20/2009

definitions -...

Documents