DR.

ELSIE

PATHOLOGY

DR.
RANIA
 Introduction
Pathology: scientific study of diseases.

Importance:

Pathology is a clinical knowledge service that is

fundamental to modern medical practice.

It is used in the diagnosis, treatment and management of

many clinical conditions.

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 OBJECTIVES
Definition of pathology.
Description and explanation of cell injury and
cellular adaptation.
Description & comparison between acute and chronic
inflammation.
Discussion on tissue repair.

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 OBJECTIVES

Identification of circulatory disturbances:

edema, thrombosis, embolism infarction, hemorrhage & shock.

Definition of neoplasia, comparison between benign and malignant

tumors, identification of the etiology of the tumors, and description of
some common tumors.

Identification of pathologic lesions, specific for each body system.

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 Development of Disease
Disease:
An abnormal variation of
the structure and function
of any organ or tissue of
the body.

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TERMS RELATED TO DISEASE
DEVELOPMENT
Etiology: predisposing factors, causes.

Pathogenesis: mechanisms that lead to production of

the disease

Morphologic changes: gross and microscopic

changes

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 TERMS RELATED TO DISEASE
DEVELOPMENT
Clinical features: symptoms and signs

Fate: end results of the disease

Complications: bad effects of the disease.

Prognosis: forecast of the probable course or

outcome of a disease

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 Classification of Diseases:
Congenital:

The patient is born with the disease (due to genetic

abnormality or an acquired injury in utero).

Acquired:

Have no genetic basis.

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 DIVISION OF PATHOLOGY
General pathology :
Study of basic reactions of cells and tissues to abnormal
stimuli.
Systemic pathology:
Concerned with the study of specific responses of
specialized organs and tissues to well defined stimuli.

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Cell Injury, Necrosis& Apoptosis

The basis of all diseases is injury to the smallest

unit of the body (the cell).

A normal cell is in a steady state, if able to handle

physiologic demand according to its adaptive
capacity.

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 Causes of Cell Injury

Hypoxia: oxygen deprivation

Biological agents: bacteria, viruses, fungi, and parasites.

Chemical agents: strong alkalis and acids, insecticides, alcohol,

narcotics and air pollutants.

Physical agents: excessive heat and cold, radiation, mechanical

trauma and electric injury.
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 Causes of Cell Injury

Endogenous toxins: uremia, jaundice, & diabetic ketosis.

Immunologic reactions and autoimmune diseases.

Nutritional imbalances: protein calorie malnutrition, starvation,

obesity, diabetes mellitus, and vitamin deficiencies.

Genetic abnormalities.

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 Types of Cell Injury
Irreversible:

Necrosis : cell death

Apoptosis : programmed
single cell death

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 Types of Cell injury

Reversible:

Hydropic swelling: excess water in the cell

Fatty change: accumulation of fat in the cells of some

organs.

Reduce oxidative phosphorylation: decrease energy

stores (ATP)
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 CELLULAR DEATH
NECROSIS

Morphologic changes that follow

cell death in living tissue.

Causes of necrosis:

Same causes of cell injury.

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 “Types” of Necrosis
1. Coagulative necrosis:

It is the most common type of necrosis occurs in most

organs including heart, kidney and spleen.

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 “Types” of Necrosis
1. Liquefactive Necrosis:
The necrotic tissue undergoes rapid
softening by hydrolytic enzymes
e.g. infarction of the nervous tissue,
suppurative inflammation.
Gross appearance: the affected
tissue appears as homogeneous
structure.

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 “Types” of Necrosis
1. Caseous Necrosis:
Characteristic of tuberculosis.
Affected tissue undergoes slow
partial liquefaction forming yellow
cheesy material.
Grossly: soft friable tissue
resembling clumpy cheese.

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 “Types” of Necrosis
1. Gangrenous Necrosis:
It is a term used to describe
necrosis & putrifaction.
Common sites: lower limbs, gall
bladder, GIT, and testes.
Dry gangrene:
Wet gangrene:

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 “Types” of Necrosis
1. Fatty Necrosis:

Focal areas of fat destruction,

typically resulting from release of
activated pancreatic lipases into
the substance of the pancreas and
the peritoneal cavity.

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 Fate of Necrosis
Local:
In small areas, repair by fibrous tissue occurs.
In large areas, cyst will form.
General:
Release of enzymes due to tissue destruction into the
blood: CK, LDH, and transaminases.

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 APOPTOSIS
Falling or dropping off
Programmed cell death

Especially during fetal development

In response to hormonal cycles (e.g. endometrium)

Normal turnover in proliferating tissues (e.g. intestinal epithelium)

An active process regulated by genes and involves RNA and protein synthesis.

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 CHARACTERISRICS OF
APOPTOSIS
1) Cells shrink, not swell

2) Nuclei condense and DNA fragments

3) Cells fragment into membrane-bound bits

4) Bits are phagocytized by macrophages

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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 Intact: may be released in apoptotic bodies
cell

Adjacent Inflammation Frequent No

Physiologic or Invariably pathologic: end of Often Physiologic: means of eliminating unwanted

Pathologic Role irreversible cell injury cells. Pathologic after DNA damage

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 Cellular Adaptation
Cellular adaptations are those in which new physiologic &
morphologic changes occur in response to excessive
physiologic or pathologic stimuli, but preserving the cell
viability and modulating its functions.

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 ADAPTIVE CHANGES

Hyperplasia.

Hypertrophy.

Atrophy.

Metaplasia .

Dysplasia.
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 HYPERPLASIA
Definition:
It is an increase in the number of cells in tissue or organ.
Some cell types are unable to exhibit hyperplasia (e.g. nerve,
cardiac, & skeletal muscle cells).

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CAUSES OF HYPERPLASIA
Physiologic causes:
Compensatory, e.g. after partial hepatectomy.
Hormonal stimulation, e.g. breast development at puberty.
Pathologic causes:
Prostatic hyperplasia of aging.

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MEDIATORS OF HYPERPLASIA

Growth factors, cytokines.

Increased DNA synthesis and

cell division.

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 SUMMARY
Hyperplasia Neoplasia

There is a cause. No apparent cause.

It is reversible when the
cause is removed.
Proliferation of the cells
is limited.
Not reversible.
Proliferation of cells is
not limited.

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 HYPERTROPHY
Increase in cell size and function activity due to
increased synthesis of intracellular components.

In some cases it occurs with hyperplasia, as in

pregnancy, the uterine enlargement is caused by
hypertrophy and hyperplasia of the smooth muscle
fibers.

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 CAUSES of HYPERTROPHY
1.

1. Increased mechanical demand:

Physiologic: striated muscles in
athletes.
2. Increased endocrine stimulation:
Puberty: growth hormone,
androgens and estrogen.
Gravid uterus: estrogen.

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MEDIATORS of HYPERTROPHY

Growth factors.

Cytokines.

Hormones.

Increased expression of genes.

Increased protein synthesis.

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Hypetrophy Normal Muscle

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ATROPHY
Definition: decrease in cell size and functional ability.
Causes of atrophy:
Decreased work load (disuse atrophy).
Ischemia : due to atherosclerosis.
Malnutrition.
Aging.

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MORPHOLOGY of ATROPHY

Gross:

Small size of the organ.

Microscopic:

Small shrunken cells.

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Muscular atrophy, Microscopic Appearance

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ATROPHY
Physiologic:
Post menopausal atrophy of breasts, uterus and
ovaries.
Aging: atrophy of heart, brain, and skin.
Postpartum involution of uterus.
Pathologic:
Disuse atrophy e.g. muscles after prolonged
immobilization.

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 METAPLASIA
Definition: a reversible replacement of
one differentiated cell type to another,
usually in response to chronic irritation.

The aim of this replacement is for better

toleration of the environmental stress.

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 DYSPLASIA
Definition:
It is an abnormal organization of individual cells.

Normal squamous Severe

epithelium dysplasia
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 DYSPLASIA
Mild and moderate degrees of dysplasia are reversible.
Severe degree is premalignant (intraepithelial neoplasia
“IEN” or carcinoma in situ “CIS”).
Examples:
Dysplasia of cervical epithelium in chronic cervicitis.

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 7

INFLAMMATION,
HEALING & REPAIR
 INFLAMMATION

A response of vascularized living tissues to

injury.

Protective response with the ultimate goal of

eliminating the injurious agent

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 Etiologies
Microbial infections: bacterial, viral, fungal, etc.

Physical agents: burns, trauma--like cuts, radiation

Chemicals: drugs, toxins, or caustic substances like battery

acid.

Immunologic reactions: rheumatoid arthritis.

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 Cardinal Signs of Inflammation

Redness : Hyperaemia.

Heat or Warmth:

Pain : Nerve, Chemical

mediators.

Swelling : Exudation

Loss of Function:
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FEATURES ACUTE CHRONIC
Cause Pathogens, Injured Tissues Persistent acute inflammation/ FB or autoimmune
reactions

Major Cells Neutrophils Mononuclear cells(monocytes, macrophages,

Involved lymphocytes, plasma cells & fibroblasts

Primary Mediators Vasoactive amines Eicosanoids INF-γ & other cytokines, Growth Factors,
reactive O2 species, hydrolytic enzymes
Onset Immediate (Rapid) (< 48°) Delayed

Duration Short (Few minutes to hours) Up to many months or years

Outcome Healing, Abscess formation, Chronic Tissue destruction & fibrosis

inflammation

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INFLAMMATORY PROCESS

1. Vascular changes
2. Cellular changes

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 A. Vascular Changes:

1. Changes in vascular flow and caliber.

2. Increased vascular permeability

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Changes in Vascular Flow & Caliber - 1

Vasoconstriction: The initial response of arterioles to an

injurious stimulus lasting for a few seconds.
Vasodilatation.

increase in blood flow causing redness (hyperemia),

mild swelling and increase in temperature.

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 Increased Vascular Permeability - 2
Mechanisms:
1. Contraction of endothelial cells resulting in increased
interendothelial spaces
2. Endothelial injury resulting in endothelial cell necrosis and
detachment
3. Transcytosis: increased transport of fluids and proteins
through the endothelial cells.

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 B. Cellular Changes
Margination: WBCs move towards the periphery closer
to the endothelium due to slow blood flow in the dilated
capillaries & venules causing RBCs to stack on each
other leading to rouleaux formation.
Pavementing: WBCs attaches to the endothelium by
adhesion molecules.

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 B. Cellular Changes
Attachment: due to the adhesion molecules normally
present in leukocytes and endothelial cells

Transmigration or diapedesis: attached leukocytes insert

between the pseudopods within the endothelial cells
reaching the extravascular space.

Chemotaxis: leukocyte migration in the extracellular

space towards the chemotactic stimulus.
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 Lymphatics in Inflammation

Lymphatics are responsible for draining edema.

Edema: An excess of fluid in the interstitial tissue or

serous cavities; either a transudate or an exudate

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 EDEMA
TRANSUDATE EXUDATE

An ultrafiltrate of blood A filtrate of blood plasma

plasma mixed with inflammatory
cells and cellular debris.
Permeability of
endothelium is usually Permeability of endothelium
normal. is usually altered
Low protein content High protein content.
(mostly albumin)

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Pus: A purulent exudate exudate rich in leukocytes (mostly
neutrophils) and parenchymal cell debris.

Chemotaxis: It is the attraction of the cells toward a

chemical mediator, released at the site of inflammation.

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 Phagocytosis:
Engulfment of invading microorganisms, damaged

cells and tissue debris.

Phagocytic cells: polymorph nuclear leucocytes (microphages), monocytes

of the blood and tissue macrophages.

Steps of phagocytosis: (1) Recognition and attachment

(2) Engulfment.

(3) Killing or degradation.

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Inflammation Outcome
Fibrosis/Scar

Resolution

Injury Chronic
Acute Inflammation Inflammation
Fungus
Virus
Abscess Cancer
s
T.B.
Ulcer etc.

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Fistula Sinus
 Acute inflammation has 1 of 4 outcomes:

1. Abscess formation

2. Progression to chronic inflammation

3. Resolution: tissue goes back to normal

4. Repair: healing by scarring or fibrosis

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 Abscess Formation:
ABCESS: "A localized collection of pus (suppurative
inflammation) appearing in an acute or chronic
infection, and associated with tissue destruction, and
swelling.
SITE: skin, subcutaneous tissue, internal organs like
brain, lung, liver, kidney etc….
PATHOGENESIS: necrotic tissue is surrounded by
pyogenic membrane, formed by fibrin to help in
localizing infection.

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