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General Pathology
For Health sciences students
First edition

By

Ass. Prof . Dr. Abla Sayed Mahmoud

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 The Contents
Page

 Introduction of pathology...................................................................1
 Inflammation...…………….................................................................1
 Pathogenesis of inflammation ..................................................3
 Types of Acute inflammation...................................................8
 Chronic inflammation..............................................................13
 Repair ..................................................................................................15
 Types of repair....................................................................................19
 Healing of injury bone.............................................................24
 Cell injury ...........................................................................................26
 Reversible cell injury……….………………………………..28
 Irreversible cell injury………………………………………..35
 Infectious diseases……… ...................................................................41
 Bacterial infections………………………………....................41
 Fungal infection.........................................................................44

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 Introduction of pathology

Pathology
Pathology Is the scientific study of disease. It is concerned with the causes and
effects of disease, and the functional and structural changes that occur.

Changes at the molecular and cellular level correlate with the clinical manifestations
of the disease. Understanding the processes of disease assists in the accurate
recognition, diagnosis and treatment of diseases.

Disease is an alteration from the normal function/ structure of an organ or system,

which manifests as characteristic groups of signs and symptoms.

Diseases are often classified as either congenital or acquired disorders. Congenital

diseases are present from birth, causes can be either genetic or non-genetic, whereas
acquired disorders result of factors originating in the external environment.
There are different diagnostic modalities used in pathology. Most of these diagnostic
techniques are based on morphologic changes.

I- Diagnostic techniques used in pathology

The pathologist uses the following techniques to the diagnose diseases:

a. Histopathology

b. Cytopathology

c. Hematopathology

d. Immunohistochemistry

e. Microbiological examination
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f. Biochemical examination

g. Cytogenetics

h. Molecular techniques

i. Autopsy

A. Histopathological techniques

Histopathological examination studies tissues under the microscope. During this study,
the pathologist looks for abnormal structures in the tissue.

Tissues for histopathological examination are obtained by biopsy.

Biopsy is a tissue sample from a living person to identify the disease.

�Biopsy can be either: incisional or excisional.

Once the tissue is removed from the patient, it has to be immediately fixed by
putting it into adequate amount of 10% Formaldehyde (10% formalin) before
sending it to the pathologist.

The purpose of fixation is:

1. To prevent autolysis and bacterial decomposition and putrefaction

2. To coagulate the tissue to prevent loss of easily diffusible substances

3. To fortify the tissue against the deleterious effects of the various stages in the
preparation of sections and tissue processing.

4. To leave the tissues in a condition this facilitates differential staining with dyes

and other reagents.

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Once the tissue arrives at the pathology department, the pathologist will exam it
macroscopically (i.e. naked-eye examination of tissues).Then the tissue is processed to
make it ready for microscopic examination.

The purpose of the tissue processing

 The whole purpose of the tissue processing is to prepare a very thin tissue (i.e. five
to seven μm or onecell thick tissue) which can be clearly seen under the
microscope.

The tissue is processed by putting it into different chemicals. It is then impregnated

(embedded) in paraffin, sectioned (cut) into thin slices, & is finally stained.

The stains can be Hematoxylin /Eosin stain (H&E) or special stains such as PAS,
Immunohistochemistry, etc...

The H&E stain is routinely used. It gives the nucleus a blue color & the cytoplasm & the
extracellular matrix a pinkish color. Then the pathologist will look for abnormal structures
in the tissue.

Histopathology is usually the gold standard for pathologic diagnosis.

B. Cytopathologic techniques

Cytology is the study of cells from various body sites to determine the cause or nature of
disease.

Applications of Cytology:

The main applications of cytology include the following:

1. Screening for the early detection of asymptomatic cancer

2. Diagnosis of symptomatic diseases and tumors.

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 Cytopathology may be used alone or in conjunction with other modalities to
diagnose tumors revealed by physical or radiological examinations.

It can be used in the diagnosis of cysts, inflammatory conditions and infections of

various organs.

3. Surveillance of patients treated for cancer

For some types of cancers, cytology is the most feasible method of surveillance to detect
recurrence.The best example is periodic urine cytology to monitor the recurrence of
cancer of the urinary tract.

Advantages of cytologic examination

Compared to histopathologic technique it is:

 Cheap,
 Takes less time and
 Needs no anesthesia to take specimens.

Cytopathologic methods

There are different cytopathologic methods including:

1. Fine-needle aspiration cytology (FNAC)

In FNAC, cells are obtained by aspirating the diseased organ using a very thin needle
under negative pressure.

FNAC is cheap, fast, & accurate in diagnosing many diseases.

2. Exfoliative cytology

Refers to the examination of cells that are shed spontaneously into body fluids or
secretions.

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Examples include: sputum, cerebrospinal fluid, urine, effusions in body cavities
(pleura,pericardium, peritoneum), nipple discharge and vaginal discharge.

3. Abrasive cytology

Refers to methods by which cells are dislodged by various tools from body surfaces (skin,
mucous membranes, and serous membranes). E.g. preparation of cervical smears with a
spatula or a small brush to detect cancer of the uterine cervix at early stages.

C. Hematological examination

This is a method by which abnormalities of the cells of the blood and their precursors in
the bone marrow are investigated to diagnose the different kinds of anemia & leukemia.

D. Immunohistochemistry

This is a method is used to detect a specific antigen in the tissue in order to identify the
type of disease.

E. Autopsy

Autopsy is examination of the dead body to identify the cause of death. This can be for
forensic or clinical purposes. However, for most diseases, diagnosis is based on a
combination of pathological investigations.

Inflammation

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 • Definition: - A local protective response of living vascularized tissues to kill
and remove injurious agents& prepare for repair.

Add the suffix “itis” to organ name

Examples:- - Tonslitis, Rhinitis,
Except: - - pleurisy is inflammation of pleura
- Pneumonia is inflammation of lung
Effects of Inflammation
1- Disposal and isolate of the irritants
2-Disposal of the consequences of injury (e.g. necrotic cells).
3-Neutralize & inactivate the toxins
4- Prepare for healing (Repair)

Causes of inflammation

1) Microbial infections→ Bacteria& their toxins, viruses, fungi and parasites

2) Physical irritants → Burns, excess cold, ultraviolet light, irradiation
3) Mechanical irritants.→ Trauma
4) Chemical irritants. →Strong alkali, strong acid,
5) Immunological reaction→→ hypersensitivity, autoimmune disease
Systemic symptoms

1. Fever
2. Constitutional symptoms: nausea, malaise and anorexia
3. High erythrocyte sedimentation rate (ESR)
4. Changes in WBCs counts
A. Leucocytosis ( increased number of WBCs)
 Bacteria ----------- Neutrophils
 Parasites ---------- Eosinophils

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  Viruses ----------- Lymphocyts
B. Or Leucopenia ( decreased number of WBCs)
 Some viral infections, salmonella infections.
5. Immunologic reactions - increased level of some substances (C-reactive
protein)
Local Cardinal Signs Of Inflammation:-

1. Redness
2. Hotness
3. Swelling
4. Pain

Types of Inflammation

1. Acute inflammation: rapid onset and short duration (days or weeks).

2. Chronic inflammation: Gradual onset and longer duration (several months
Pathogenesis of inflammation
1- Local vascular changes:-
1- Changes in vascular caliber and blood flow

 Transient Vasoconstriction: by a neural mechanism It

lasts for few seconds or minutes followed by vasodilatation
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  Permanent Vasodilatation (result of redness and hotness
in inflamed area).

 Increase hydrostatic pressure: lead to transudation of

fluid into extracellular space.

 Slow circulation (Stasis)

2- Cellular events

A. Exudation of leucocytes

1. Changes in the formed elements of blood

In normal flowing blood, erythrocytes and leukocytes are confined to the central
(axial) column surrounded by plasma. When blood slowing occurs, some leukocytes
(mainly neutrophils and monocytes) fall out of the central column and begin to line
the endothelium (margination).
2. Adhesion (pavementing) of the marginating leukocytes to the
endothelial surface occurs, aided by complementary receptors on the surfaces
of leukocytes and endothelial cells in a way like a key and lock. These
receptors include selectins, immunoglobulins and integrins.

3. Emigration of leucocytes (neutrophils and monocytes)

Adherence of leukocytes to the endothelium →leukocyte stability →insertion of

leukocyte pseudopodia into the junction between the endothelial cells → escape
of leukocytes into the extravascular space (emigration).

In most types of acute inflammation, neutrophils emigrate first, followed 24

hours later by monocytes

Passive escape of red cells (diapedesis)

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4. Chemotaxis: It is the directed movement of emigrating leukocytes to the site of
injury. The aim of this movement is to reach the organisms or particles to be
phagocytized.
B. Phagocytosis - it is the process by which the phagocytic cells recognize then
engulf abnormal particles such as bacteria, dead cells, fibrin and foreign bodies,
followed by their degradation.

a) Recognition and attachement of bacteria (opsonization): bacteria are

coated by an opsonin which is an immunoglobulin or complement factor.

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 b) Engulfment: phagocytic leukocytes surround the opsonised bacteria and send
pseudopodia around the bacteria or the object to be engulfed. Fusion of
pseudopodia →phagocytic vacuole (phagosome).

c) Degranulation: performed granule-stored products are discharged or secreted

into phagosomes

d) Degradation: killing bacteria may be done through oxygen dependant

mechanisms (formation of hydrogen peroxide or superoxide which are
bactericidal)or through oxygen-independent mechanism(lysosomes which
have strong bactericidal activity).

The functions of this inflammatory fluid

1. Dilution of toxins
2. Delivery of antibodies and antibiotic
3. Brings chemical mediators derived from the plasma e.g. complement

4. Helps localizing infection by surrounding the inflammed area and blocking

some lymphatics.

5. Forms a network upon which phagocytic cells can remove towards their
target.

6. Fibrin also allows movement of proliferating fibroblasts during the repair.

Chemical mediators of acute inflammation

Definition: - Any substances that secreted and activated to help inflammatory
process acts on blood vessels, inflammatory cells or other cells.
Chemical mediators responsible for vascular and cellular events. Knowledge of
those mediators is basis of anti-inflammatory drugs.
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Sources of chemical mediators
1- Exogenous
• Bacterial as E.coli • Endotoxins
2- Endogenous
 Cell -Derived chemical mediators produced locally by cells at the site of
inflammation e.g. Leukocytes ,Endothelial cell, Fibroblasts& Some mediators
are derived from Necrotic cells...... etc (e.g Histamine)
 Circulating plasma proteins “synthesized by liver”, found in inactive
forms then activated

The fate of acute inflammation

1. Resolution→→ tissue return to the normal status due to Minimal tissue
damage e.g. lobar pneumonia.
 Inflammatory fluid: - passes into lymphatic vessels.
 Dead cells :- Phagocytosis of dead neutrophils and necrotic debris by
macrophages
 Repair by regeneration is the replacement of damaged cells by new
cells of the same type.
2. Spread (Septicemia , toxemia, lymphangitis, lymphadenitis Thrombophlebitis)
3. Fibrosis (Scarring)
4. Abscess Formation
5. Progression to Chronic Inflammation

Types of Acute inflammation

Acute inflammation is classified according to present or absent of pus into:-

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 • Suppurative/ Purulent acute inflammation.

• Non- Suppurative/ Non- Purulent acute inflammation.

Pus is purulent thick, turbid yellowish inflammatory exudate

Compositions of pus
1. Large number of neutrophils and pus cells
2. The liquefied necrotic material
3. bacteria
4. Fluid exudates

A. Suppurative/ Purulent acute inflammation.

I. Localized suppurative/ purulent acute inflammation

1- Abscess

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Definition:- Acute localized bacterial infection accompanied by neutrophilic
infiltrate in the inflamed tissue, result in necrosis
Sites: - common in skin, subcutaneous tissue and may occurs internal organs as
brain, lung, liver, kidney, etc.
Cause: - Staphlococcus aureus secreted coagulase enzyme that lead localization

Pathological Features
- Early: Two zones necrotic tissue and inflammatory cells.
- Later: Three zones
a) A central necrotic core.
b) A mid zone of pus.
c) The peripheral zone: pyogenic membrane which is formed by fibrin
and help in localize the infection.

Fate of abscess
1- Small abscess: Pus is absorbed, followed by healing.
2- Large abscess: absorption of pus is slow, a large abscess  pointing & rupture
(spontaneous evacuation if not surgical drainage)  healing.
3- Complications
1-Spread of infection:
a) Direct enlarged in size.
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 b) Lymphatic  lymphangitis and lymphadenitis.
c) Blood spread may lead to Septicaemia, Pyaemia
2- Complications of evacuation and healing:
a) Ulcer →→ A local defect of the surface of an organ or tissue, which
is produced by the sloughing (shedding) of inflammatory necrotic
tissue
b) Sinus. →→is blind ended tract between abscess and epithelial
surface due to chronic discharge to surface
c) Fistula.→→ is a track connecting two epithelial lined surfaces

d) Keloid
e) Hemorrhage e.g. hemoptysis with lung abscess.
f) Rupture: e.g. brain abscess.
3-Chronicity. Examples: - Chronic lung abscess.
4-Other complications: Compression effects: e.g. in case of brain abscess

2- Carbuncle
Definition: - It is multiple communicating deep subcutaneous abscesses, opening
on skin by multiple sinuses. Carbuncle is common in special patient→ diabetics
(low immunity).
Sites: - common in special sites in the back of the neck and scalp, where the skin
and subcutaneous tissues are thick and tough due to dense fibrous septa dividing
the subcutaneous tissue into compartments.

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 3- Furuncle or boil
• Definition: - It produces a small abscess related to hair follicle.

II. Difuse suppurative/ purulent acute inflammation

Cellulitis
Definition: - it is diffuse acute suppurative inflammation with pus formation.
Cellulitis is common in special patient→ diabetics (low immunity).

Features
Abscess Cellulitis
Localized suppurative
Type Diffuse suppurative inflammation
inflammation
Cause Staphlococcus aureus Streptococcus haemolyticus
organisms secreted coagulase organisms secreted hyaluronidase
Pathogenesis enzyme that lead to fibrin & streptokinase enzymes that
deposition localization dissolve the fibrin
Site Any tissue Loose connective tissue
Thick, less red cells, few Thin, sanguineous, and extensive
Pus
necrotic tissue necrosis
Spread Less More

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 B. Non- suppurative/ Non- purulent acute inflammation.

1. Serous inflammation

• Characterized by: - excessive clear fluid poor in both inflammatory cells &
fibrin.
Examples:-
 Skin blisters due to skin burns.
 Inflammation of serous membranes (pleura, pericardium and peritoneum)

2. Fibrinous inflammation

Characterized by: - an inflammatory exudate rich in fibrin, with poor fluid.

Examples:-
 Lobar pneumonia
 Inflammation of serous membranes. e.g. fibrinous pericarditis
3. Catarrhal inflammation

Characterized by: - A mild form of acute inflammation of mucous membranes

with excess mucus secretions

Examples:- -
 Catarrhal rhinitis (common cold)
 Catarrhal appendicitis
4. Pseudomembranous /Membranous inflammation

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  Occur in mucous membrane with dirty grayish false membrane forming on
surface e.g. toxins of diphteria and irritant gases.

5. Allergic inflammation.

Characterized by: - the presence of excessive serous fluid and many eosinophils in
the inflammatory exudate.
Examples:-
 Allergic rhinitis.
 Allergic conjunctivitis.
Chronic Inflammation
Definition:- Inflammation of prolonged duration “weeks to years ”, in which
inflammation, tissue destruction occur in same time.
Causes
 May follow acute inflammation due to failure of immunity
 May start chronic by gradual onset (not preceded by acute inflammation) due
to one or more of the following:
1. Infection with resistant organisms e.g. T.B.
2. Non-living irritants as foreign bodies e.g. talc or silicosis (inhalation
of silica particles into lungs)
3. Development of autoimmunity e.g. rheumatoid arthritis.
Types of chronic inflammation
1. Chronic Non-specific Inflammations:
 Usually follow acute inflammation, e.g. chronic abscess.
 Why termed "nonspecific’’?
1. All show the same microscopic features of chronic inflammation
(chronic inflammatory cells, fibrosis….)
2. We can’t identify the cause .

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 2. Chronic Specific Inflammations:
 Usually start chronic.
 Show microscopic features of chronic inflammation with additional
features specific for each type as (bilharzia ova in cases of bilharziasis).
 The majority of chronic specific inflammations occur in the form of
granulomas.
Granulomas/ granulomatous inflammation
Definition:- A special form of chronic inflammation characterized by nodular
collections of many macrophages with mixture of lymphocytes, plasma cells, giant
cells.

Characterized by: -
 The macrophages have an important role in formation of granuloma.
 The macrophages commonly change into  epithelioid cells (large pink,
activated macrophages that look like epithelial cells)
 Sometimes these epithelioid cells fuse together, forming giant cells, with
multiple nuclei inside (multinulcleated giant cells)
 Some granulomas may exhibit central necrosis.
 Old granulomas surrounded by fibrosis.
Types of granulomas:
1. Infectious granulomas: Most of these granulomas are necrotizing.
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 Examples:- T.B, Leprosy, Syphilis, Bilharziasis
2. Foreign body granulomas: Mostly non-necrotizing granulomas.
Examples:- Silicosis & Surgical suture
3. Granulomas of unkown aetiology: Mostly non-necrotizing granulomas.
Examples:- Sarcoidosis& Crohn's disease.

Acute Chronic
Features
Inflammation Inflammation
Response Immediate reaction of Persisting reactions of tissue to
tissue to injury injury
Onset Rapid Slow

Duration Short (hours to days) Longer (months to years)

Predominant cells Neutrophil `Lymphocytes and macrophages

Main pathological Exudation of fluid and Proliferation of blood vessels

event plasma proteins and fibrosis

Tissue injury and Usually mild and self- Often severe and progressive
fibrosis limited

Vascular response Prominent Less prominent may be subtle

Example Abscess T.B

Repair

Repair/Healing

Definition: - Replacement of damaged tissue by new healthy one.

Damage → Inflammation→ removing of dead tissue & Replacement by new

healthy one

Types of repair
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 1. Regeneration
Replacement of dead tissue by same type of tissue .Seen with mild and
superficial injury
2. Fibrosis/ Scar (Fibrosis= Gliosis in CNS)
Replacement of dead tissue by connective tissue. Seen with severe injury

Tissues of the body divided into three types according to Proliferative

Capacities :

1) Continuously dividing(labile) tissues

2) Stable tissues
3) Permanent tissues

1) Labile cells / Tissue

 cells are continuously proliferating & continuously dying

 can easily regenerate after injury
 contain a pool of stem cells (self-renewal and differentiation)
Examples:- -

 Skin epidermis
 GIT epithelium
 Bone marrow cells
Stem cells

 Self-renewal capacity
 Asymmetric replication
 Capacity to develop into multiple differentiations
 Extensive proliferative potential

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2) Stable cells (quiescent cells)

 Cells have limited ability to proliferate

 Normally in G1 stage, but can proliferate in response to injury

Examples:-

 Parenchyma of most solid tissue(Liver, kidney, and glands ), peripheral

nerves
 Endothelial cell, fibroblast and Smooth muscles.

3- Permanent cell:

• Non-dividing , non-proliferated in postnatal life

• Normally in G0 stage, never proliferate

• Response to injury always by fibrosis (scar)

Examples:-
 Cardiac muscle
 Skeletal muscle
 Neurons (CNS)

Factors affecting efficiency & type of repair

A. General factors

1. Age
2. Nutritional Deficiency
3. Drugs
4. Endocrine diseases
5. General heath (Infection /tumor)
B. Local factors

1. Severity of tissue damage

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  With mild to moderate injury (e.g. hepatitis A infection) →→ cells damage
with survival of supporting tissue(reticular tissue)  regeneration
→Normal Liver
 With severe injury (e.g. hepatitis C infection) →→ gross tissue damage
including supporting tissue → post necrotic scaring (fibrosis)Liver
cirrhosis.

2. Blood supply

3. Persistent infection or foreign body present.

4. Ability of tissue to proliferate (type of injured cells)

C. Factors affecting mechanism of repair

1. Growth factors.

2. Cell to cell interactions

3. Cell to matrix interactions

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 Types of repair

1-Healing by regeneration
Definition: - Proliferation of cells to replace the damaged components by same type
of cells and return to a normal state
Occurs in
• All the time in labile tissues
• Limited form in stable tissues according to severity of injury
Examples:-
1. Healing of epidermis
2. Healing of mucous membrane
3. Healing of liver cells
4. Healing of bone fractures
5. Healing of Peripheral nerve
2- Healing By Fibrosis
Definition: - Replace the damaged components by scar formation due to deposition
of connective (fibrous) tissue
Occurs in
• With severe injury of all types of tissues
• All the time in permanent cells
Examples:-
1. Healing of myocardial infarction.
2. Healing of CNS infarction or brain abscess
3. Severe destruction of connective tissue frame work (as in liver cirrhosis)
4. With extensive cell injury e.g. necrosis
5. In chronic inflammation
6. Wound healing (primary and second intension)

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 2- Angiogenesis
Definition: - Formation of new blood vessels by action of growth factors include
VEGF, PDGF, FGF &TGF – beta.
Source:-
1. Proliferation from endothelial precursor cells.
2. Budding from pre-existing vessels

3- Fibrogenesis
Definition: - Migration and proliferation of fibroblasts to the site of damage by
action of growth factors include PDGF, FGF, TGF – beta & Cytokins e.g. TNF,
IL-1

Function of fibroblasts: - collagen deposition early fibroblasts deposit collagen

type III then I.

4- Granulation tissue fromation

Definition: - Highly vascularized edematous connective tissue.

Gross: - pink granular soft and fleshy

Microscopic: - Granulation tissue composed of

1. Newly formed capillaries.

2. Proliferating fibroblasts.

3. Inflammatory cells.

4. Edematous stroma .

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 5- Maturation of granulation tissue  permanent scar
 Synthesis of Extracellular matrix (ECM) proteins by action of Growth
factors include PDGF , FGF , TGF & IL-1.

 More collagen type I deposition.

 Capillary resorption by macrophages.

 Formation of a pale, avascular scar.

6- Tissue remodeling
 Degradation of excess collagen and other ECM proteins

 Lead to the formation of an avascular firm white scar tissue.

7- Wound contraction & strength

 Fibroblasts transformed to Myofibroblasts lead to contract the scar &
minimize the scar (decreased in size).
 Increase collagen deposition lead to strength the wound.

Types of Skin Wound Healing

1- First intention healing (primary union)

• Small wounds that easily close edges

• Epithelial regeneration predominates over fibrosis
• Healing is fast, with minimal scarring/infection
Examples:-
 Paper cuts
 Surgical incisions

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2- Second intention healing (Second union)

• Larger wounds that have large gap due to (extensive loss of tissue, necrosis &
infection)
• Large amount of granulation tissue & fibrosis
• Healing is slower, and more scarring/ infection

Examples:
1. Infarction& abscess
2. Infected surgical wound
3. Large burns and ulcers

Features Primary wound healing Secondary wound healing

Wound Small size, small gap & Large size, large gap &
Clean Unclean
Tissue loss No Yes
Chance of Infection Low High
Healing Fast Slow
Margins Surgically clean Irregular
Healing Scanty granulation tissue Granulation tissue fill the
gap
Scar tissue Scanty Abundant
Outcome wounds Nearly linear scar Contracted irregular wound
Complication Less common More common

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Complications of Wound Healing

1. Delayed wound healing

2. Cosmetic Deformities

3. Function loss e.g. contracture is exaggeration in the process of

contraction of the wound (severe burn around a joint)

4. Keloid: excess scar tissue due to overdone repair covered by stretched

epidermis.

5. Chronic Ulcer, Sinus, Fistula.

6. Rarely carcinoma (Marjolin’s ulcer)

Factors delayed wound healing

1. Infection is the most important cause of delay in healing; it prolongs the

inflammation phase of the process increases the local tissue injury.
2. Poor nutrition effects on wound healing(Vitamin C is essential for collagen)
3. Glucocorticoids inhibit inflammation with decreased wound strength and
less fibrosis.
4. Poor blood supply due to diabetes or atherosclerosis.
5. Diabetes mellitus: Increases tendency to infection, so delays repair
6. Foreign bodies left in the wound.
7. Chronic inflammation leads to excess fibrosis as in cirrhosis.

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 Cell Injury
Definition: - Cell injury is a sequence of events that occur if the limits of adaptive
capability of cells to stimulus are exceeded or no adaptive response is possible.

Causes of cell injury

A. Acquired (environmental) causes
1. Oxygen deprivation (Hypoxia or ischemia) →→ is the most common
causes
2. Infectious agents: viruses, bacteria, fungi, parasites.
3. Physical agents:- extremes of temperature, radiation and electric shock.
4. Chemical agents: poisons, air pollutants, insecticides, CO, asbestos, ethanol,
therapeutics drugs.
5. Mechanical agent: trauma
6. Immunologic reactions: hypersensitivity.
7. Nutritional imbalances. Malnutrition, Diabetic Mellitus, Kwashiorkor,
Marasmus, osteoporosis, deficiency Vitamin C
B. Genetic defect. Abnormalities to the genomes e.g. Down Syndrome
Types of Cell Injury:

1- Reversible injury (Degeneration): caused by mild (non-lethal) injury→→

Intracellular accumulation of water, fat, Protein, cholesterol, glycogen, iron, calcium
or pigments.

2- Irreversible injury (Cell Death)

 Necrosis

 Apoptosis

Morphological types of cell Injury

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 1. Cloudy swelling
2. Hydropic swelling
3. Hyaline
4. Mucoid degeneration
5. Amyloidosis
6. Pathological pigments
7. Pathological calcification
8. Necrosis
9. Apoptosis
A-Reversible injury (Degeneration):

1- Intracellular accumulation
- Metabolic derangements in cells can lead to the intracellular accumulation of
abnormal amounts of various substances that remains either transiently or
permanently.
- Cellular accumulations are a sign of injury; also their accumulation can cause
cellular injury
- These accumulated substances included:-
B- Normal cellular substances
 Water
 Lipid
 Protein
 Glycogen
C- Abnormal or exogenous substances
Carbon, silica, Asbestos, bacteria.

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1. Intracellular accumulation of water

a) Cloudy Swelling: Intracellular accumulation of small amount of water  cell

swelling with esinophilic granular cytoplasm.

b) Hydropic Swelling (hydropic degeneration, ballooning degeneration).

Intracellular accumulation of larger amounts of water  swollen cells pale, clear
cytoplasmic vacuoles

Examples:

Parenchymatous organs e.g. liver, kidney tubules, heart & other glandular epith. of
organs
Intracellular accumulation of lipids
Steatosis (fatty change)

Definition: intracellular accumulation of triglycerides within parenchymal cells

Site: - Heart, kidney & other organs, but the most common in the liver (hepatic
steatosis).

Causes:-

 Excess alchol consumption

 Starvation.

 Malnutrition

 Chronic illness.

 Diabetes mellitus

 Severe anaemia

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  Ischaemia

 Septicaemia

 Poisons

 Late pregnancy

Clinical Significance:-

Fatty change may progress to cell necrosis

 Diffuse fatty change of heart  heart failure

 Fatty change of liver  progress to liver cirrhosis.

Gross:-

1. Organ enlarged, Smooth & capsule stretched, soft greasy& rounded borders.
Color is yellow; diffuse or patchy.

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 Microscopic:- fat appears as small clear intracellular vacuoles or a single large
vacuole push nucleus eccentric  signet ring appearance., Fat stained orange
with Sudan III stain.

2- Extracellular accumulation include

1- Proteins
 Amyloidosis is extracellular accumulation of abnormal folded protein
→→cell death. Amyloid protein appears as bright pink amorphous,
homogenous, eosinophilic, material, staining red with Congo red stain.

3- Extracellular & intracellular accumulation.

1- Hyaline Degeneration
- Not a distinct chemical entity. Various histological or cytological alterations
characterized by homogeneous, glasslike appearance in hematoxylin and
eosin-stained sections
- Accumulation of protein droplets in proximal renal tubule in renal disease
(Nephrotic syndrome).
- Mallory bodies- alcoholic liver disease ,
- Russel bodies- chronic inflammation.
- Hyaline proteins may deposit extracellular e.g hyalinosis of blood vessels in
hypertension od D.M.

2- Mucoid Degeneration
Accumulation of excessive amount of mucin in unusual location, it is called
mucoid/mucinous degeneration e.g. Cancer with high degree of mucous deg are
called mucinous carcinoma. Extracellular accumulation of mucin is called
myxomatous degeneration.
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3- Pathological Pigments

A- Endogenous: - synthesized within the body itself as:-

a. Lipofuscin pigment is wear and tear pigment with aging is sign of free
radical injury and lipid peroxidation. Lipofuscin pigment deposit mainly in
heart, liver….etc. In tissue sections it appears as a yellow-brown, finely
granular cytoplasmic, often perinuclear, pigment.

b. Melanin an endogenous, non-hemoglobin-derived, brown black pigment

formed by melanocytes in skin mucous membranes &iris.

c. Hemosiderin (iron) is a hemoglobin-derived, golden yellow-to brown,

granular. Systemic overload of iron hemosiderin may be deposited in many
organs and tissues, a condition called hemosiderosis

 patients with congestive heart failure→→ Lung

 In patients with hemochromatosis→→Liver, heart, pancreas
 Hemolytic anemias, in which abnormal quantities of iron are
released from erythrocytes.
 Repeated blood.
Remark: iron stained by the Prussian blue (seen as blue granules) to
differentiated from melanin pigment

d. Bilirubin usually due to

i. Too much produced (e.g., hemolysis)

ii. Not processed (e.g., cirrhosis)

iii. Outflow blocked (e.g. gall bladder stones).

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 B- Exogenous coming from outside the body

a. Anthracosis inhalation of carbon particles engulfed by macrophages. This

pigment blacken the tissues of the lungs e.g. cigarette smoking, coal workers,
air pollutant of urban life.

b. Tattooing is a form of localized, exogenous skin pigment is phagocytosed by

dermal macrophages.

4- Pathological Calcification

Definition: - Abnormal intracellular or extracellular depositions of calcium salts.

Gross: - Calcification appears as fine, white granules or clumps.

Microscopic: - Calcium salts have a basophilic, amorphous granular, sometimes

clumped appearance;

Types of pathological calcification

 Dystrophic calcification
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 • Patients have a normal serum calcium level & absences of any defect
of calcium metabolism
• Dystrophic calcification affects previously damaged & dead tissue as
 Areas of necrosis coagulative,caseous, fat, or liquefactive type.
 The atheromas of advanced atherosclerosis
 Aging or damaged heart valves.
 Sometimes a tuberculous lymph node is virtually converted to
stone.
 Others, old thrombus, hematoma.
 Metastatic calcification

• Patients have an hypercalcemia with disturbance of calcium metabolism

 Causes: Hyperparathyroidism, bony metastases
• Calcification affects normal tissue and previously damaged tissue.
Metastatic calcification may occurs widely throughout the body but
mainly affected kidney, systemic arteries, pulmonary veins &lung.

Remark: Pathological Calcification is the only one in substance accumulations

which is irreversible.

Dystrophic Metastatic
Features
calcification calcification
Reflect deranged of calcium
Pathogenesis Sign of cell injury
metabolism
site Dead or damage tissue Normal tissue

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 Serum calcium Normal High
Calcium metabolism Normal Abnormal
Patient with
Example Wall of chronic abscess
hyperparathyroidism

B) Irreversible injury (Cell Death)

1- Necrosis

1. Definition: Irreversible injury, resulting in death of groups of cells. In living

tissue. It is accompanied by acute inflammatory reaction.

Microscopic:

1- Cellular Changes:
a) Cytoplasmic Changes: Cytoplasm is eosinophilic due to
loss of cytoplasmic RNA (basophilic) and glycogen (granular) with indistinct cell
membranes.
2- Architectural Changes: 2 possibilities:

a) Necrotic tissue rapidly structureless due to cell lysis by lysosomal enzymes

from (dead cells ± inflammatory cells).

b) Necrotic cells preserve the architectural outlines of original tissue despite

loss of the nuclei. Ghosts of cells due to protein denaturation (mainly in ischemia
necrosis). Then lysis later  structureless.

Fate of necrotic tissue:

1-Inflammation due to release of chemical mediators .

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 2-Healing: mainly by fibrosis

3- Dystrophic calcification may occur.

Types Of Necrosis

1. Coagulative necrosis
2. Liquifactive necrosis
3. Caseous necrosis
4. Fat necrosis (enzymztic & traumatic)
5. Gangrenous necrosis
6. Fibrinoid necrosis
1- Coagulative Necrosis:
• Seen in: - infarction of all organs except CNS.
• Gross:- Opaque yellow swollen soft friable tissue
• Microscopic: - Swelling of cells: homogenous dark pink cytoplasm of
necrotic cells (Protein denaturation).

• tombstone (retained outlines but cytoplasmic and nuclear details lost

• Nuclear membrane damage
• Necrotic Area is Pink & Granular Containing Nuclear Debris .
• Inflammatory cells
Nuclear Changes: Due to enzymatic digestion.
• Pyknosis: The nucleus →small and dark.
• Karyorrhexis: Nuclear fragmentation.

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 • Karyolysis: dissolved nucleus

• Fate:- Healing by fibrosis ± dystrophic calcification.

2- Liquefactive Necrosis:
 Seen in: - infarcts of CNS, pyogenic abscess (pus).
 Pathogenesis: - Usually due to predominant of enzymatic dissolution of
necrotic cells (usually due to release of proteolytic enzymes from neutrophils)
over protein denaturation.

• Micro
Cystic space with necrotic cell debris and macrophages
Cyst wall formed by proliferating, capillaries and gliosis or fibrosis

3- Gangrenous Necrosis: usually coagulative or liquefactive followed by

putrefaction by saprophytes bacteria.
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4- Caseous Necrosis:
 Seen in: - mycobacterial infection (tuberculosis)
 Gross: - yellowish white & "cheesy" like necrotic material.
 Pathogenesis:-
Tubercle bacilli are rich in fats that liberated from dead bacteria adds to the
cheesy appearance.

 Microscopic: - granular eosinophilic structure less (fragmented necrotic

cells).

5- Fat Necrosis
a) Enzymatic Fat Necrosis:
 Seen in :- Acute Hemorrhagic Pancreatitis
 Pathogenesis: inflammation →escape of lipase and protease enzymes 
necrosis surrounding peritoneal fat cells.
 Grossly: chalky white hard patches, because necrotic fat cells →fatty acids +
calcium = calcium soaps.

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  Microscopic: - necrotic fat cells, surrounded by chronic inflammatory cells
and fibrosis, with calcification.

b) Traumatic Fat Necrosis:

 Seen in: It is common in the female breast and subcutaneous fat & usually
caused by trauma

 Pathogenesis: Rupture of fat cells->auto-digestion and release of fatty acids,

which combine with calcium.

 Gross: Hard chalky white mass. This mass clinically mistaken for breast
tumor.

Microscopic: - same as enzymatic fat necrosis.

6- Fibrinoid Necrosis:
Seen in: - the walls of blood vessels in vasculitides e.g. autoimmune collagen
diseases (as rheumatic fever, rheumatoid arthritis, lupus erythematosus…etc), that
lead to immune mediated vascular damage
Microscopic: - Glassy, eosinophilic fibrin-like material is deposited within the
vascular walls.
2- Apoptosis (programmed cell death)

 Definition: death of individual cells surrounded by viable cells

 When a cell dies by activation of an internally suicide program. It is an active

process—energy dependent

 Does not elicit inflammatory response

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 Types Of Apoptosis

Physiologic

 During embryogenesis e.g. Removal of interdigital webs of toes and fingers.

 Hormone-dependent e.g. involution of organs as thymus gland in the adult,

endometrial cells loss during menstruation

Pathologic

 Irradiated tissues

Viral infections e.g. Viral hepatitis

 Cell death in tumors

Morphology of Apoptosis

 Cell shrinkage with increased

cytoplasmic density
 Chromosome condensation
 Formation of cytoplasmic blebs and
apoptotic bodies
 Phagocytosis of apoptotic cells or

cell bodies by adjacent healthy cells

Features Necrosis Apoptosis

Groups of cells, disrupting tissue Single cells within living
Affect
structure tissues
A passive process—not energy- Active process—energy-
Process
dependent dependent
Inflammation Induce a significant inflammatory No inflammatory response
- 41 -
 response
Cell size Enlarged Reduced
Pyknosis / karyorrhexis /
Nucleus Fragmented
karyolysis
Plasma
Disrupted Intact
membrane
May be pathologic or
Types Always pathologic
physiologic

Infectious diseases

1- Bacterial Infections

 Routes of infection:
1. Exogenous by inhalation, ingestion or local contact with skin or mucous
membranes, blood or blood product transfusion
2. Endogenous from bacteria normally present in the body as intestinal E. coli,
oral streptococcus viridans and respiratory pneumococci. Infection occurs if
immunity is lowered.
 Effects of bacterial infection:
1. Cell injury: Necrosis and degeneration.
2. Inflammation: acute, subacute or chronic.
3. Development of immunity and/ or hypersensitivity.
4. Blood invasion with bacteria and/or bacterial products leading to
a) Bacteremia.
b) Toxemia
c) Septicemia
d) Pyaemia
Bacteremia
Definition: This is transient invasion of blood with bacteria without significant
toxaemia.
examples:
 After tooth extraction (Streptococcus viridans bacteria).
 A septic focus as tonsillitis & sinusitis.
Effects:
 In most cases, no harmful effects.
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  Uncommonly, causing lesions. Specially with a predisposing factor, e.g.
Streptococcus viridans that reach the blood after tooth extraction can
cause subacute infective endocarditis on top of rheumatic valvulitis.
Toxaemia
Definition: the circulation of bacterial toxins in the blood harmful effects may
association with septicemia and pyaemia.
These toxins may be endotoxins (released only from dead bacteria) or exotoxins
(released from alive bacteria)

Septicaemia
Definition: A fatal condition, large numbers of virulent bacteria circulate and
multiply in blood accompanied by severe toxaemia.
Etiology:
Pyaemia
Definition: It is fatal condition, development of multiple small abscesses (pyaemic
abscesses) in one or more organs due to the circulation of septic emboli derived
from septic thrombi.

Types of pyaemia :

1. Pulmonary pyaemia
2. Portal pyaemia
3. Systemic pyaemia.

Tuberculosis

Definition:- Chronic infectious granulomatus inflammation caused by Mycobacterium

tuberculosis( rod shaped Acid fast bacilli )

There are two species:

1. Human tubercle bacilli.
2. Bovine tubercle bacilli.
Predisposing factor:

 Patient :- low socioeconomic status, low immune patients (diabetes mellitus,

cirrhosis, malnutrition and cancer)
 Age :- Extremes of ages due to imperfect immune responses
 Dagnosis Clinically by radiography, culture, or Zeihl Neelsen stain for acid fast
bacilli,) &pathological by FNAC, or excisional biopsy
- 43 -
 Mode of Transmition

In Primary tuberculosis: it is the first time to TB bacilli enter the body reach to
primary site as lung, intestine, tonsils, or skin by

1. Inhalation leads to pulmonary tuberculosis

 infective coughed Or sneezed droplets in the air by a patient with open T.B,
 or contaminated dust
2. Ingestion or Swallowing leads to TB of tonsils or intestine
• infected milk (from diseased cows)
• or contaminated dust
3. Inoculation through skin is extremely rare.
In Secondary tuberculosis: organism reach organ through :-

1. Exogenous→ Re-infection for the second time occurs as in primary TB either by

Inhalation or Ingestion or Inoculation
2. Endogenous from reactivation of lesion containing the living TB bacilli

Sites of secondary tuberculosis :- Many organs of body as kidney, liver, vertebrae

(pott’s disease) female & male genital tracts ………etc.

Primary Tuberculosis (Childhood Type)

Primary tuberculosis complex: - Tubercle bacilli will exist in three sites:

1. Somewhere in the infected primary sites (primary tuberculous focus)
2. In the draining lymphatics (tuberculous lymphangitis).
3. In the draining lymph nodes (tuberculous lymphadenitis).

Primary Pulmonary Tuberculosis

1. Ghon's Focus: Small yellow subpleural granuloma in mid lung field .

2. Tuberculous lymphadenitis in the hilum is a small yellow granuloma in a
hilar lymph node next to a bronchus
3. Tuberculous Lymphadenitis

Microscopic picture:- Granulomas in T B are called tubercles caseating

granuloma , composed of central caseous necrosis surrounded by epitheloid cells ,
Langhan’s giant cells& lymphocytes . Old granuloma surrounded by fibrosis

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Others sites of common tuberculosis infection

1- Primary Intestinal infection, the primary focus lesion is common in the

illocaecal region.

2- Lymph nodes T.B mainly affected cervical L.Ns groups.

Complications of tuberculosis:

1. Spread
2. Hemorrhage
3. Organ destruction and severe fibrosis
4. Recurrence (re-activation)

2- Fungal Infections

Predisposing factors:-
• Low immunity e.g. Corticosteroid administration, prolonged broad spectrum
antibiotic therapy, immunosuppressive therapy or others states of
immunocompromization as diabetes and AIDS
• defects in neutrophillic and macrophage functions

Fungal infections are divided into

1. Superficial fungal infections e.g. Tinea & Some cases of Candidiasis
2. Deep Fungal Infections cause systemic disease e.g. candidiasis

Candidiasis (Moniliasis)

Definition: Infection with the fungus called "Candida albicans". This fungus is a
normal commensal of oral cavity, GIT, vagina and skin.t becomes pathogenic in
the low immunity conditions.

Pathology: There are several patterns:

- 45 -
1- Superficial Candidiasis: Most common .Usually due to prolonged antibiotic use.
Manifestations:
 oral Thrush& Vaginal lesions: White oral mucosal patches
 Cutaneous eczematous lesion: macerations of interdigital skin.
2- Invasive candidiasis: It is often fatal. Seen in Immunosuppression. Many organs
may be involved with micro abscesses as brain, liver ,kid

- 46 -
Inflammation

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