General Pathology

Pathology For Radiology

Technologist I
Ass. Prof . Dr. Abla Sayed Mahmoud
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 General Pathology

The Contents

Page

 Introduction of pathology..........................................................1

 Cell injury ...................................................................................7

 Reversible cell injury…………………………………...10

 Irreversible cell injury………………………………….12

 Inflammation...…………….......................................................26

 Repair.........................................................................................41

 Infectious diseases…….............................................................52

 Bacterial infections…………………....................52

 Fungal infection.....................................................61

 Cardiovascular diseases ..........................................................62

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Introduction of pathology

Pathology

Is the science that deals with the study of the diseases.

It includes two main parts:

A.General pathology

B. Special ( systemic pathology)

Gross Features = Macroscopic features Change in size, colour & consistency of

the diseased organ

Microscopic Features: Cellular and extracellular changes as detection of

malignant cells.

Types of pathology samples

1-Biopsy: examination of a tissue specimen which may be:

 Punch biopsy

 Core Biopsy

 Incisional biopsy

 Excisional biopsy

 Partial organ excision

 Whole organ

2-Autopsy:

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Examination of tissue obtained from dead bodies.

3-Frozen Section Examination

Used for rapid diagnosis during surgery.

4-Cytology:

 Examination of body fluids or smears to detect any abnormal cells as

malignant cells & inflammatory cells as

a) Body fluid as urine , CSF , ascetic fluid

b) Sputum

c) Discharge: nipple discharge

d) Lavage fluid: bronchial lavage

e) Touch imprint cytology

f) Fine needle aspiration cytology

g) Cervicovaginal smear

h) Bone marrow aspirate

A. Histopathological techniques

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.

B. Cytopathologic techniques

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

Advantages of cytological examination

Compared to histopathologic technique it is:

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

Immunohistochemistry

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

Terminology in pathology:

Lesions: the changes in tissues and cells produced by the diseases.

Pathological features; morphology: changes detected by examination,

microscopic).

Gross picture (macroscopic): Naked eye examination (gross on surgical

removal or post-mortem autopsy).

Microscopic picture: changes detected by microscopic (light or electron)

examination.

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Etiology: factors and causes of disease.

Pathogenesis: Mechanism of disease.

Complication: Secondary effect of disease. Prognosis: The course and fate of

disease

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Cell Injury

ILOS:

By the end of this chapter the student will be able to:

1. Define cellular injury and its deferent types.

2. Understand the mechanism of cell injury.
3. Describe the morphological picture of Different types of necrosis.
4. Understand apoptosis.

5. Describe the pathological features of

apoptosis.

6. Differentiate between necrosis and

apoptosis

Cell injury

Definition: 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
i. Ischemia (obstruction of arterial blood flow), E.g. in myocardial infarction
and atherosclerosis.

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ii. Inadequate oxygenation of the blood e.g. lung disease and carbon monoxide
poisoning
iii. Decreased oxygen-carrying capacity of the blood e.g. anemia iv.
Inadequate tissue perfusion due to cardiorespiratory failure, hypotension, shock etc
2. Infectious agents: Viruses, bacteria, fungi, protozoa, and metazoa all cause
diseases. They may do so by causing cell destruction directly as in virus infections
(for example poliomyelitis) or protozoal infections (for example malaria).
However, in others the damage is done by toxins elaborated by the infecting agent
as in diphtheria and tetanus. Like chemicals, they may have a general effect or they
may show a predilection for certain tissues
3. Physical agents:- Extremes of temperature, radiation and electric shock.
4. Chemical agents: Chemicals With the use of an ever-increasing number of
chemical agents such as drugs, in industrial processes, and at home, chemically
induced injury has become very common. Their effects vary:
• Some act in a general manner, for example cyanide is toxic to all cells.
• Others act locally at the site of application, for example strong acids and
caustics.
• Another group exhibit a predilection for certain organs, for example – the effect
of paracetamol and alcohol on liver. Many toxic chemicals are metabolized in liver
and excreted in kidney, as a result, these organs are susceptible to chemical injury.
5. Mechanical agent: trauma
6. Immunologic reactions:
a. Autoimmune reactions against one's own tissues.
b. Allergic reactions against environmental substances in genetically
susceptible individuals.

7. Nutritional imbalances. poor supply, interference with absorption,

inefficient transport within the body, or defective utilization. It may take the form
of deficiency either of major classes of food, usually protein and energy, or

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vitamins or elements essential for specific metabolic processes, e.g. iron for
haemoglobin production. Often, the deficiencies are multiple and complex. On the
other hand, dietary excess plays an important role in diseases. Obesity has become
increasingly common, with its attendant dangers of type 2 diabetes, high blood
pressure and heart disease.
8. Aging : Alterations in replication and repair abilities, Long term accumulation
of toxins, radiation, injuries, etc.
B. Genetic defect: Abnormalities to the genomes e.g. Down Syndrome

MECHANISM OF CELL INJURY

1. Depletion of ATP

2. Cell membrane damage/defects in membrane permeability:

3. Mitochondrial damage: ➢It is seen specially in hypoxic injury and cyanide

poisoning.

4. Ribosomal damage: ➢It is seen in alcohol damage of liver cells and with
antibiotic use.

5. Nuclear and DNA damage.

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
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A-Reversible injury (Degeneration):

1. Intracellular accumulation of water

a) Cellular Swelling: Is the first manifestation of almost all forms of injury to
cells, it occurs due to incapability of cells to maintain ionic & fluid
homeostasis.
 It is more apparent at the level of a whole organ (gross) than at the cellular
level (light microscope).
 Cellular Swelling also called Hydropic change, vacuolar degeneration.

Gross: Increased weight and increased pallor of the organ.

Mic: Small, clear vesicles within the cytoplasm (distended endoplasmic

reticulum)

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:-

1. Excess alcohol consumption

2. Starvation, Malnutrition

3. Chronic illness, Type Diabetes mellitus

4. Severe anaemia, Ischaemia

5. Septicaemia

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Mechanisms:

a. Increased uptake of triglycerides into the parenchymal cells.

b. Decreased use of fat by cells.

c. Overproduction of fat in cells.

d. Decreased secretion of fat from the cells.

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.

B) Irreversible injury (Cell Death)

- Persistent or excessive injury causes cells pass into irreversible cell injury.
- Two important events indicate that the cells reach (point of no return) or reach
cell death or irreversible cell injury, these include:

1. Irreversible mitochondrial damage (lack of ATP production)

2. Profound damage & disturbances in cell membrane function (this is the
central factor in development of irreversible cell injury).

Clinical Correlation to Cell Membrane Damage

Leakage of intracellular proteins through the damaged cell membrane and
ultimately into the circulation provides a means of detecting tissue-specific cellular
injury and necrosis using blood serum samples. Examples:
• Cardiac muscle enzymes creatine kinase and troponin
• Liver hepatocytes contain transaminases

1- Necrosis

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

living tissue. It is accompanied by acute inflammatory reaction.

Types Of Necrosis

1. Coagulative necrosis
2. Liquifactive necrosis
3. Caseous necrosis
4. Fat necrosis (enzymztic & traumatic)
5. Gangrenous necrosis
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6. Fibrinoid necrosis
1- Coagulative Necrosis:
 This is the most common type of necrosis.
 Caused mostly from sudden cessation of blood flow (ischemia), and less often
from bacterial and chemical agents.
 The organs commonly affected are the heart, kidney, and spleen.
 localized area of coagulative necrosis is called an infarct.
 Protein denaturation is predominant in this type of necrosis.
 Microscopically: The basic outline of the necrotic cell is preserved despite loss of
the nuclei. Finally, lysis and necrotic tissue becomes structureless (Ghost cells).

Nuclear changes: Nuclear changes assume one of three patterns,

Pyknosis is small and dark.
karyorrhexis :Nuclear fragmentation.
Karyolysis:dissolved nucleus

• Fate:- Healing by fibrosis ± dystrophic calcification.

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•
Coagulative necrosis. A, heart infarct. B, Microscopic view of the edge of the infarct, with normal kidney (green) and •
necrotic cells in the infarct (yellow) showing preserved cellular outlines with loss of nuclei and an inflammatory infiltrate.

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.

caseous necrosis

 Microscopic: - granular esinophilic 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 vasculitis e.g. autoimmune collagen
diseases (as rheumatic fever, rheumatoid arthritis, lupus erythematosus…etc), that
lead to immune mediated vascular damage
Microscopic: - Glassy, esinophilic 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

 In degeneration diseases of CNS

 Cell death by cytotoxic T cells in immune mechanisms

Pathological Features

1. Shrinkage of cell size.

2. Nuclear chromatin condensation, DNA fragmentation.
3. Formation of membrane blebs, followed by separation and
formation of apoptotic bodies.
4. Apoptotic bodies are engulfed by phagocytic cells.

Features Necrosis Apoptosis

Groups of cells, disrupting tissue

Affect Single cells within living tissues
structure

Active process—energy-
Process A passive process—not energy-dependent
dependent

Induce a significant inflammatory

Inflammation No inflammatory response
response

Cell size Enlarged Reduced

Nucleus Pyknosis / karyorrhexis / karyolysis Fragmented

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Plasma
Disrupted Intact
membrane

Types Always pathologic May be pathologic or physiologic

Intracellular accumulation

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.

2- Extracellular accumulation include

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.

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Hyaline Degeneration

The term hyaline usually refers to an alteration within cells or in the

extracellular space that gives a homogeneous glassy pink appearance in
routine histologic sections stained with hematoxylin and eosin. It is widely
used as a descriptive histologic term rather than a specific marker for cell
injury.
Examples of Intracellular Hyaline Change:

1- Russel bodies: This is hyaline change in plasma cells in chronic

inflammation due to distension with immunoglobulins.
2- Mallory alcoholic hyaline change in hepatocytes due to chronic
alcoholism.
3- Neurofibrillary tangle which is aggregation of proteins that are present in
the brain of Alzheimer disease.
Examples of Extracellular Hyaline Change:
 Hyalinosis of collagenous fibrous tissue in old scars and keloid.
 Hyalinosis of mesenchymal soft tissue tumor as leiomyoma.
 Hyalinosis of organized (fibrotic) thrombi.
 Hyalinosis of wall of arterioles in long-standing hypertension and diabetes
mellitus, especially in kidney.
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.
Cholesterol and Cholesteryl Esters.
In hypercholesterolemia , Turn macrophages into foam cells.
Examples:
1. Fibrofatty plaques of atherosclerosis.
2.Xanthomas and xanthelasma: clusters of foam cells in tumor-like masses
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Pathological Pigments

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

A . Lipofuscin pigment is is an insoluble pigment, also known as

lipochrome or wear-and tear pigment (aging pigment).
- Lipofuscin is derived through lipid peroxidation of cellular membranes.
- not injurious to the cell or its functions; it is a sign of free radical injury
and lipid peroxidation throughout the cell life.
- It appears as a yellow brown, finely granular cytoplasmic, often
perinuclear pigment.
- It is seen in the liver and heart cells of aging patients or patients with
severe malnutrition and cancer.

B. Melanin an endogenous, non-hemoglobin-derived, Most common ; brown

black pigment normally present in hair , skin, choroid of eye, meninges and
adrenal medulla.

Synthesized in melanosomes of melanocytes within the basement membrane of the

epidermis

Transferred by melanocytes to adjacent clusters of keratinocytes & macrophages

(melanophores) ,Formed from tyrosine via tyrosinase

Increased melanin may be observed in the following conditions:

1. Prolonged exposure to the sun.
2. Melanocytic nevi and melanomas.
3. Chloasma of pregnancy: Brown patches in the skin of the face, nipple
and genitalia due to hormonal changes.
4. Cafe au lait patches in neurofibromatosis.

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Decreased melanin may be observed in the following conditions:

1. Albinism: this is generalized hypopigmentation due to tyrosinase
deficiency. It is an inherited autosomal recessive defect characterized by
absence of melanin pigment in hair, skin, iris and choroid of the eyes.
2. Leukoderma: Patchy skin hypopigmentation. May be congenital or
acquired as in leprosy.

Albinism Leukoderma

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

1. Hemosiderosis When accumulation of hemosiderin is primarily within tissue

macrophages & is not associated with tissue damage, it is called hemosiderosis.
2. Hemochromatosis When there is more extensive accumulation of hemosiderin,
often within parenchymal cells, which leads to tissue damage, scarring & organ
dysfunction, it is called hemochromatosis.

D. Bilirubin

Bilirubin is a yellowish pigment, mainly produced during the degradation of

hemoglobin. Excess accumulation of bilirubin causes yellowish discoloration of the
sclerae, mucosae, & internal organs. Such a yellowish discoloration is called jaundice.
Jaundice is most often caused by 1. Hemolytic anemia Hemolytic anemia is
characterized by increased destruction of red blood cells. 2. Biliary obstruction This is

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obstruction of intrahepatic or extrahepatic bile ducts. It can be caused by gallstones. 3.

Hepatocellular disease This is associated with failure of conjugation of bilirubin.

■ Exogenous coming from outside the body

It is which introduced into the body by inhalation ,ingestion or inoculation

Inhaled pigments:

Anthracosis inhalation of carbon particles engulfed by macrophages. This pigment

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

coal dust in coal workers Produces occupational lung disease called

PNEUMOCONIOSIS

Ingested pigment

• ingestion of certain metal produce pigmentation. Eg: Argyria- c/c ingestion

of silver compound produce pigmentation in skin ,bowel, kidney.
• Chronic lead poisoning may produce blue lines on teeth and at the gum line
• Melanosis coli result for prolonged ingestion of Cathartics
• Carotenaemia is yellowish-red colouration of the skin

Injected pigment (tattooing )

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

dermal macrophages. and lies permanently in the connective tissue.

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
Occurs locally in dying tissue.

Gross: fine, white granules, often felt as gritty deposits

Microscopic: By H&E the calcium salts have a basophilic, amorphous granular,

sometimes clumped, appearance. It is located either intracellular, extracellular, or in
both locations.
Examples:
 Atheromatous plaques
 Goitre
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 Degenerated tumors as leiomyoma & necrotic tumors as

breast cancer.
 Degenerated valves as in chronic Rheumatic valvulitis & in old
age.
 Caseous tuberculous lesions
 Dead parasites and ova as bilharziasis
 Fat necrosis and Thrombi, particularly venous thrombi
(phlebolith).

Metastatic Calcification

Definition: This is calcification of normal tissues due to hypercalcaemia.

It almost always results from hypercalcemia secondary to some disturbance in
calcium metabolism.

Causes of hypercalcemia include increased calcium absorption from

intestine and/or increased calcium mobilization from bone as in cases of:

There are four principal causes of hypercalcemia:

(1) Hyperparathyroidism due to primary hyperthyroidism or produced by other

tumors.
(2) Destruction of bone tissue, occurring with primary tumors of bone marrow
(e.g., multiple myeloma).
(3) Vitamin d–related disorders, including vitamin d intoxication, sarcoidosis.
(4) Renal failure, which causes retention of phosphate, leading to secondary
hyperparathyroidism.
Sites: Any tissue, but principally tissues with relative alkalinity including:
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-Tissues that secrete acidic products as stomach mucosa, renal tubules

(nephrocalcinosis) and lung alveolar walls.

Remark: Pathological Calcification is the only one in substance accumulations

which is irreversible.

Features Dystrophic calcification Metastatic calcification

Reflect deranged of calcium

Pathogenesis Sign of cell injury
metabolism

site Dead or damage tissue Normal tissue

Serum calcium Normal High

Calcium metabolism Normal Abnormal

Patient with
Example Wall of chronic abscess
hyperparathyroidism

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Inflammation

ILOS

1- Understanding the sequence of vascular

and cellular events in acute inflammation.

2- Learn the role of chemical mediators of

acute inflammation

3-Know the three possible outcomes of acute

inflammation

4- Understand the morphological patterns of

acute inflammation

Understand the causes, patterns and

principal cells of chronic and granulomatous
inflammation

6- Understanding the systemic manifestation

of 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

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 Parasites ---------- Eosinophils

 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
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1- Local vascular changes:-

 Transient Vasoconstriction: by a neural mechanism It lasts for few

seconds or minutes followed by vasodilatation

 Permanent Vasodilatation (result of redness and hotness in inflamed area).

 Increase hydrostatic pressure: lead to transudation of fluid into

extracellular space.

 Slow circulation (Stasis) The increased vascular permeability oozes

protein-rich fluid into extravascular tissues. Due to this, the already dilated
blood vessels are now packed with red blood cells resulting in stasis. The
protein-rich fluid which is now found in the extravascular space is called
exudate. T

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)

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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
It is mediated by platelet-endothelial cell adhesion molecule-1 (PECAM-1)
expressed on both the endothelium and the leucocytes.

Passive escape of red cells (diapedesis)

4. Chemotaxis: It is the directed movement of emigrating leukocytes to the site of

injury.

B. Phagocytosis - it is the process by which the phagocytic cells recognize then

engulf abnormal particles such as bacteria, dead cells, fibrin and articles to be
phagocytized. foreign bodies, followed by their degradation.

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

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

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.

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Chemical mediators responsible for vascular and cellular events. Knowledge of

those mediators is basis of anti-inflammatory drugs.

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

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.
Spread (Septicemia , toxemia, lymphangitis, lymphadenitis Thrombophlebitis)
Fibrosis (Scarring):
a. After extensive tissue destruction.
b. When the inflammatory injury involves tissues that are incapable of
regeneration.
c. When there is abundant fibrin exudation.

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Abscess Formation
Progression to Chronic Inflammation

Types of Acute inflammation

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

• 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

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A. Suppurative/ Purulent acute inflammation.

I. Localized suppurative/ purulent acute inflammation

1- Abscess
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.

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 General Pathology

3- Complications
1-Spread of infection:
a) Direct enlarged in size.
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).

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 General Pathology

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.

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
Pus Thick, less red cells, few Thin, sanguineous, and extensive

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 General Pathology

necrotic tissue necrosis

Spread Less More

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:- -

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 General Pathology

 Catarrhal rhinitis (common cold)

 Catarrhal appendicitis
4. Pseudomembranous /Membranous inflammation

 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’’?

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 General Pathology

1. All show the same microscopic features of chronic

inflammation (chronic inflammatory cells, fibrosis….)
2. We can‘t identify the cause .
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.

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 General Pathology

Types of granulomas:
1. Infectious granulomas: Most of these granulomas are necrotizing.
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 and

event plasma proteins 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

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 General Pathology

Repair
ILOs:
By the end of this chapter the student should be able to:

1. Define repair
2. Describe repair in different organs.
3. Differentiate between different types of repair.
4. Analyze factors controlling repair and their complications.
5. To understand the mechanism of repair in different organs.
6. Compare between types of wound repair.

Repair/Healing

Definition: Repair (healing) is the restoration of tissue architecture and

function after an injury.

Repair of damaged tissues occurs by two processes:

A. Regeneration, which restores normal cells.
Regeneration may occur by proliferation of differentiated cells that survive the
injury and retain the capacity to proliferate.
In epithelia of the skin and intestines, tissue stem cells and their progenitors
contribute to the restoration of damaged tissues.

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 General Pathology

B. Scarring, the deposition of connective tissue.

If the injured tissues are incapable of regeneration, or if the supporting structures
of the tissue are too severely damaged to support regeneration of the tissue cells,
repair occurs by the laying down of connective (fibrous) tissue, a process that may
result in scar formation. Although the fibrous scar is not normal, it usually provides
enough structural stability that the injured tissue is able to function.
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)
Labile cells include:
 Hematopoietic cells in the bone marrow
 Most surface epithelia, such as the stratified squamous epithelia of the
skin, oral cavity, vagina, and cervix; the cuboidal epithelia of the ducts draining
exocrine organs (e.g., salivary glands, pancreas, biliary tract); the columnar
epithelium of the gastrointestinal tract, uterus, and fallopian tubes; and the
transitional epithelium of the urinary tract.

2) Stable cells (quiescent cells)

 Cells have limited ability to proliferate

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

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 General Pathology

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

 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

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 General Pathology

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

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
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 General Pathology

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)

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

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 General Pathology

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 .

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

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 General Pathology

 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

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

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 General Pathology

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

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)

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 General Pathology

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.

BONE HEALING

The repair of a bone fracture consists of three phases, which overlap each other.

I. The inflammatory phase: The bone fracture damages the bone matrix, the cells,
the blood vessels and the surrounding soft tissue. As a result there is a mass of
clotted blood at the fracture site called a hematoma . Bone cells will die due to
lack of nutrition. An inflammatory response is induced and helps to immobilize
the fracture. There is influx of macrophages, neutrophils and platelets which
release several cytokines and growth factors.
II. The reparative phase: It occurs in the first few days, overlapping the
inflammatory phase. In this phase granulation tissue also called soft callus will
form. First capillaries will grow into the hematoma and the phagocytic cells will
remove the debris.

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 General Pathology

Healing of bone fracture

Fibroblasts invade the fracture site and produce collagen fibers. From the nearby
endosteum and periosteum, cartilage and osteogenic cells enter the fracture site
resulting in internal & external fibrocartilaginous calli, respectively. This
fibrocartilaginous callus will be converted into hard callus (woven bone) by
endochondral ossification.

III. The remodeling phase

It begins in middle of repair phase and continues long after clinical union.
Remodeling of fracture repair consists of resorption of poorly located trabeculae by
osteoclasts and new bone formation along lines of mechanical stress. Eventually,
the woven bone is replaced by lamellar bone.

Factors that influence fracture healing

1. Nutritional factors: vitamin D and calcium deficiency delay fracture healing.

2. Chronic illness e.g diabetes mellitus: fracture healing takes 1.6 times longer in
diabetic patients versus non-diabetic patients.
3. Medications affecting healing e.g. systemic corticosteroids, NSAIDs (prolong
healing time) and quinolones (toxic to chondrocytes).
4. Radiation (high dose): affects the remodeling system and diminishes
cellularity
5. Impaired blood supply
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 General Pathology

6. Infection
7. Soft tissue interposition
8. Inadequate immobilization

Complications of bone repair:

1. Delayed union: fracture takes longer than normal to heal.

2. Non-union: there are no signs of healing after >3-6 months. This may lead to
persistent pain and tenderness at fracture site, joint stiffness and pseudoarthrosis
(creation of a false joint).
3. Malunion: fracture does not heal in normal alignment.

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 General Pathology

Infectious Diseases

ILOS
.
1. Know different types of infections.
2. Understand the pathogenesis of some different types of
infections.
3. Discuss morphological changes associated with

different types of infections.

4. Understand the effect of infection

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

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 General Pathology

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.
 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)

Pathological & Clinical Manifestations of Toxemia:

a) Signs & symptoms of toxaemia: Fever, weakness, pallor, headache, rigors.

b) Degenerations: Mostly affect parenchymal cells as liver, kidney & heart in
the form of cloudy swelling, hydropic degeneration or fatty degeneration. Tissue
necrosis may also develop.
c) Acute adrenal insufficiency due to hemorrhagic necrosis of adrenal·cortex.
d) Bone marrow depression causing anemia. Leukopenia (instead
of leukocytosis) may occur in severe cases.
e) Acute respiratory distress syndrome due to diffuse alveolar damage
(DAD).
f) Septic endotoxic shock & disseminated intravascular coagulation {DIC) .
g) Amyloidosis may occur in cases of chronic toxemia (e.g. tuberculosis &
chronic lung abscess)
h) Selective effects of exotoxins e.g.:
-Enterotoxin of cholera, voluminous watery diarrhea and dehydration
-Diphtheria toxins neural paralysis and myocardial damage.
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 General Pathology

-Clostridium tetani toxinssevere muscle contractions (tetanic spasm).

Septicaemia
Definition: A fatal condition, large numbers of virulent bacteria circulate and
multiply in blood accompanied by severe toxaemia.

1- Predisposing factor: Low immunity as diabetics, terminal cancer

& immunosuppressive therapy.

2- Source of infection: Septicaemia may complicate many conditions as:

a) Severe infections as meningococcus meningitis.

b) Ordinary infections as abscesses, cellulitis, puerperal sepsis, acute
osteomyelitis, post-operative infections, infected wounds and even infection
following pin prick in low resistant patients.

Pathological Features of septicemia:-

1- Effects of Acute Toxemia:

a) Constitutional signs & symptoms of toxaemia: Fever, weakness, pallor,

headache & rigors.

b) Degenerations & necrosis, particularly of parenchymal cells

c) Acute adrenal insufficiency due to hemorrhagic necrosis of adrenal cortex.

d) Bone marrow depression causing anemia .Leukopenia (instead of

/eukocytosis) may occur in severe cases .
e) Acute respiratory distress syndrome due to diffuse alveolar damage
(DAD). f)Septic endotoxic shock

2- Vascular & Hematological Disorders:

a) Blood: Hemolysis of RBCs. This leads to red staining of the intima of blood
vessels

b) Capillary hemorrhages (due to capillary destruction by bacterial toxins &

54
 General Pathology

enzymes). This leads to petechial hemorrhages in different parts of the body as in

skin & mucus membranes.
2- Serous Membranes: Serofibrinous or suppurative inflammation of pleura,
peritoneum, pericardium....
3- Heart: a) toxic myocarditis b) acute infective endocarditis c) pericarditis.
4- Liver & Kidney: Toxic injury (cloudy swelling, fatty change, necrosis).
5- Spleen: Acute splenic swelling

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 :

 Pulmonary pyaemia: Due to septic thrombophlebitis of one of the

systemic veins as a complication of abscess, cellulitis, osteomyelitis or other
infections.
 Systemic pyaemia: It may be due to the same causes of pulmonary
pyaemia if some septic emboli are too small and could by-pass the lungs to reach
the left side of the heart.
Systemic pyaemia may be also due to septic thrombophlebitis of
pulmonary veins in case of pulmonary infections. Septic vegetations of mitral or
aortic valves in cases of acute infective endocarditis can similarly lead to systemic
pyaemia.
 Portal pyaemia: It is due to septic thrombophlebitis of one of the
venous tributaries of the portal vein e.g. in cases of acute cholecystitis or
acute appendicitis. Septic emboli in the portal circulation cause pyaemic liver
abscesses.

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.
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 General Pathology

Predisposing factor:

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

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

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 General Pathology

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

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
 Direct spread to the surroundings.
 Lymphatic spread to the draining lymph nodes.
 Blood spread: Effects largely depend on number of bacteria:

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

LEPROSY
Definition: Leprosy (Hansen disease) is a chronic, slowly progressive,
destructive infective granulomatous disease involving peripheral nerves, skin, and
mucous membranes, caused by Mycobacterium leprae.

Incidence: Although leprosy is now rare in developed countries, 15 million

people are infected worldwide, primarily in tropical areas. Lesions tend to occur in
the hands and face.

Route of transmission: Leprosy is transmitted from person to person, and

probably involves inoculation of bacteria carried from nasal secretions into the
respiratory tract or into open wounds.

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 General Pathology

Types:
 Tuberculoid leprosy: Termed ‗‗tuberculoid‘‘ because the lesions resemble
lesions of tuberculosis but lack caseous necrosis. Occurs in patients with high
resistance. It is the mildest form of leprosy.
Leprosy lesions show circumscribed dermal granulomas, composed of epithelioid
macrophages, Langham‘s giant cells, and lymphocytes. In contrast to lesions of
lepromatous leprosy, Nerve fibers are swollen and infiltrated with lymphocytes.
 Lepromatous leprosy: (little resistance), it is severest form exhibits multiple
tumor like lesions of the skin, eyes, testes, nerves, lymph nodes, and spleen.
Nodular infiltrates of foamy macrophages loaded with bacilli. Dermal infiltrates
cause extensive disfigurement of facial regions.

SYPHILIS

Definition: Syphilis is an infective disease caused by Treponema pallidum

spirochetes.
Etiology & Mode of Infection: The spirochaetes can be transmitted in one of 2
ways:

Acquired Syphilis:

a) Venereal Type (most common). Bacteria are transmitted by sexual contact.

b) Non-venereal type: 1) Touching syphilitic lesions. 2)Blood transfusion from
syphilitic donor.
Congenital Syphilis: Transplacental transmission from syphilitic mother to her
fetus.

Syphilitic Tissue Reaction: Syphilis is characterized by:

• Progressive endarteritis obliterans.

• Chronic proliferative inflammatory reaction, rich in plasma cells, poor in fluid
exudate.
• Granulation tissue and fibrosis.
• Considerable necrosis mainly in gummatous lesions of the tertiary stage.

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 General Pathology

ACTINOMYCOSIS

Definition & Aetiology:

• Actinomycosis is chronic suppurative granulomatous disease caused by gram-

positive anaerobic bacteria "Actinomyces Israeli", normally present in the oral
cavity and intestine as harmless commensals.
• It is not known what local circumstances make these organisms pathogenic and
invade tissues to cause disease.

PATHOLOGY:
 Gross Features: Multiple abscesses with indurated fibrotic walls. The
abscesses open onto skin by multiple sinuses that discharge pus and bacterial
colonies, the later grossly resemble sulphur granules.
 Microscopy:
1- Bacterial colonies: consist of peripherally arranged red-stained clubs and
centrally interlacing gram-positive branching filaments which are stained deep
blue.
2- Inflammatory cells (neutrophils, pus cells, foam macrophages, lymphocytes,
and plasma cells) surround the colonies.
3- Granulation tissue and fibrosis are seen at the periphery.

Types:
1- Cervicofacial Actinomycosis: This is the most common type (60%):
Bacterial invasion of buccal mucosa may sometimes follow dental extraction.
Develop in jaws, neck and face.

Blood spread pulmonary actinomycosis. No lymphatic spread.

2- Intestinal Actinomycosis (20%):

Invasion of intestinal mucosa by intestinal or ingested bacteria.

Ileocecal indurated swelling composed of abscesses extension to retroperitoneum

or anterior abdominal wall.

Blood spread leads to actinomycotic liver abscesses.

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 General Pathology

3- Pulmonary Actinomycosis (15%):

The organisms reach the lungs by:

a) Inhalation

b) by direct spread from liver actinomycosis

c) by blood spread from cervicofacial actinomycosis.

The lungs (particularly the bases) show indurated abscesses that may open into
the chest wall by sinuses discharging pus and sulphur granules. The pleura
contains pus (empyema).

Blood spread systemic lesions in brain, kidneys bones...etc.

4- Actinomycosis of skin (5%).

CAT SCRATCH DISEASE

 Aetiology:

Gram-negative bacteria, transmitted by the scratch of cats, but may be also

transmitted by thorns or splinters.

 Pathology:

 Most patients are children and the disease is self-limiting.

 An inflammatory skin nodule may or not develop at site of infection. However,
lymph node enlargement (& sometimes matting) is the most prominent feature of
the disease.

Microscopically there are characteristic necrotizing granulomas showing central

micro abscesses (neutrophils and necrosis), peripherally surrounded by palisaded
epithelioid cells and multinucleated giant cells.

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 General Pathology

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:

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 ,kidney.
, itching & regional lymph node enlargement.

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 General Pathology

CARDIOVASCULAR SYSTEM (C.V.S.)

Rheumatic Fever
 Autoimmune consequence of infection (pharyngeal infection not the skin
infection) with Group A beta haemolytic streptococcal infection
 Generalized inflammatory response affecting brains, joints, skin,
subcutaneous tissues & the heart

Pathogenesis:

• The disease occurs after a latent period of two to three weeks following an
infection with group A p- hemolytic streptococci.

• An M protein, present on the surface of specific strains of streptococci,

evoked the production of antibodies that are cross-reactive with human
cardiac muscle and valve components, i.e. streptococcal antigen is
immunologically closely related to the heart muscle and valve components.
 Cardiac injury occurs through the activation of complement and Fc
receptor-bearing cells (including macrophages). CD4+ T cells that recognize
streptococcal antigen also can cross-react with host antigens and elicit cytokine-
mediated inflammatory responses

 Predisposing factors:

Family history of rheumatic fever

Low socioeconomic status (poverty, poor hygiene, medical deprivation)
Age: 6-15 years

- Clinical manifestations:

Fever, arthralgia, ECG changes, raised E.S.R. and leucocytosis.

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 General Pathology

о Elevated antistreptolysin О titre and С reactive protein in blood.

 NB: Rheumatic fever licks the joints but bites the heart. Although the joints
are the most frequent site affected, the involvement is reversible but the heart
suffers the most disabling often irreversible damage

- Cardiac lesions of rheumatic fever:

Acute rheumatic fever affects the three cardiac layers of the heart,
pericardium, myocardium and endocardium, i.e. "pancarditis".

(1) Pericarditis: It is either serofibrinous, or serous inflammation with fibrin

threads on both pericardial layers giving a "bread and butter" appearance on
separating the two pericardial layers (Fig. 1.21).

Fate: Generally resolves without sequelae or rarely fibrosis occurs with adhesions
which may be diffuse or localized (Milk spots).

(2) Myocarditis: It takes the form of scattered Aschoff bodies, which are
pathognomonic for rheumatic fever. They can be found in the
pericardium, myocardium, or endocardium (including valves).

Gross: The heart is enlarged, flabby with scattered pin head sized pale greyish foci
which appear after four weeks.

Microscopic: Aschoff bodies are seen within the interstitial connective tissue
between the muscle fibres and in relation to intramyocardial blood vessels.

Aschoff bodies: are formed of central fibrinoid necrosis, surrounded by

lymphocytes, plasma cells, Anitschkow cells or caterpillar cells which are
activated macrophages, the chromatin is disposed in the center of the nucleus in the
form of a slender ribbon that resemble an attenuated body with innumerable finger-
like projections and Aschoff multinucleated giant cells which are fused activated
macrophages.

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 General Pathology

(3) Endocarditis:

a- Inflammation of the endocardium lining the cardiac chambers (mural

endocardium), especially that of left atrium, which is swollen, oedematous and
red. Erosion by the flowing blood will lead to thrombosis. A focus of rough
wrinkled endocardium in the posterior aspect of the left atrium, referred to as (Mac
Galium's patch) denotes previous rheumatic involvement.

b- Inflammation of valvular endocardium.

I- Acute rheumatic valvulitis:

□ The valves are swollen, congested and oedematous, specially the mitral
and aortic valves (70 - 75%) which are more subjected to pressure and
more susceptible to damage than the tricuspid and pulmonary valves.

□ The condition is complicated by endothelial damage followed by platelet

and fibrin thrombi called rheumatic vegetations.

Rheumatic vegetations:

Gross: They are multiple beaded thrombi (platelet and fibrin), which occur along
the line of closure 2 - 3 mm from the free margin of the valve, firmly adherent to
the atrial surface of mitral valve or ventricular surface of aortic valve. The thrombi
are pale, pin head size and never give emboli. Microscopic: They are aseptic and
formed of platelets and fibrin on the valve, with lymphocytes, plasma cells and
Aschoff giant cells in the subendocardium.

II- Chronic rheumatic heart disease:

□ It is characterized by organization of the acute inflammation and

subsequent scarring.

□ Aschoff bodies are replaced by fibrous scar and they are rarely seen.

□ Valve cusps and leaflets become permanently thickened and retracted.

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 General Pathology

□ The mitral valves exhibit leaflet thickening with intercommissural

adhesions leading to marked stenosis with fish mouthor button hole
appearance.

□ The chordae tendeneae become thickened, fused and shortened leading to

constant traction on the valve and funnel shape appearance of the valve.

B- Extracardiac manifestations:

(1) Joints and adjacent musculo-fascial tissues: Fleeting arthritis with effusion,
muscle pain and weakness. It affects large joints e.g. knees, elbow, wrists and
shoulders.

(2) Serous membranes: pericardial and sometimes pleural effusion

(3) Skin rash known as erythema marginatum with central pale area and red margin.

(4) Small subcutaneous palpable nodules may be present over the body
prominences subjected to pressure, for example the tibial surface

(5) Central nervous system involvement may appear in the form of chorea

This is involunatary spasmodic muscular movements

Complications:

1. Arrhythmias (particularly atrial fibrillation in the setting of mitral stenosis).

2. Acute heart failure

3. Embolism (from the mural thrombus)

4. Infective endocarditis

5. Congested lung and pulmonary hypertension.

6.

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 General Pathology

ENDOCARDITIS
Definition:

Inflammation of the heart valves as well as the mural endocardium.

Types: Endocarditis may be classified into:

1-Infective Endocarditis
a) Acute infective endocarditis.

It refers to destructive infections, frequently caused by a highly virulent organism

attacking a previously normal valve, and capable of causing substantial morbidity
and mortality even with appropriate antibiotic therapy

Age: 50-60 years.

Causes:

- The commonest organism is staphylococcus aureus, less common is

streptococci andpneumococci.

- Fungal endocarditis occurs after severe debilitating illness, after cardiac

surgery, immunosuppressive steroid therapy or cancer therapy.

Gross: Bulky friable and destructive vegetations that occur commonly on mitral
and aortic valves, causing ulceration, erosion and perforation of the valve and
myocardium. The infected vegetations are easily detachable leading to embolic
manifestations (septic infarcts).

Microscopic: It is an acute suppurative inflammation in the substance of the cusps.

The vegetation is composed of tangled mass of fibrin, blood platelets, inflammatory
cells and colonies of bacteria on ulcerated valve.

Fate and complications:

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 General Pathology

1. Local: Ulceration, perforation or rupture of the cusps and chordae tendeneae

may occur.

2. General: Septic emboli forming distant septic infarcts, pyaemic abscesses

(systemic pyaemia). Also toxaemia or septicaemia may occur.

(b) Subacute infective endocarditis:

It refers to infections by organisms of low virulence involving a previously

abnormal heart, especially scarred or deformed valves. Most of the patients
survive with appropriate therapy.

Age: Young age and children.

Causes: Bacteremia of low virulent organism (e.g. Streptococcus viridans)

following tooth extraction or tonsillitis. This organism is a normal inhabitant of the
mouth and upper respiratory tract. It settles on a diseased valve (rheumatic valve or
in congenital anomalies).

Gross: The vegetation is less bulky than the acute type, friable and easily detached.
It is formed mainly on mitral and aortic valve and extending to adjacent
endocardium.

Microscopic: The vegetations are composed of platelets, fibrin, polymorphs and

colonies of bacteria. They often have granulation tissue at their bases (suggesting
chronicity). Chronic inflammatory infiltrate, fibrosis, and calcification may
develop over time.

Fate and complications:

(1) The valvular lesions heal with scarring leading to deformity, so the preexisting
rheumatic or congenital lesions become more severe.

(2) Embolic manifestations:

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 General Pathology

i- Detached parts of the vegetations leading to aseptic infarcts due to the low
virulence of organisms and the formation of antibodies. This may appear in spleen,
kidneys and brain.

ii- Mycotic aneurysm in the cerebral, superior mesenteric, renal and limb arteries
due to lodgment of low grade infected emboli in the arterial wall via the vasa
vasorum.

(3) Capillary lesions due to allergic vasculitis leading to:

a- Skin lesions in the form of splinter haemorrhages or Osier's nodule

b- Glomerulonephritis due to glomerular trapping of antigen-antibody complexes

causing hematuria, albuminuria or renal failure

c- Petechial haemorrhages in the skin, retina, conjunctiva, serous sacs and mucous
membranes.

(4) General manifestations of toxaemia.

Causes of death:

• Congestive heart failure.

• Embolic manifestations.

• Renal failure.

• Secondary bacterial infection due to lowered resistance

2- Non-infective Endocarditis:
a)Rheumatic endocarditis
b)Verrucous endocarditis (Libman-Sacks in SLE)
c)Nonbacterial thrombotic endocarditis: In cancer & uremia

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 General Pathology

CORONARY (ISCHEMIC) HEART DISEASE

IHD are disorders of the heart resulting from an imbalance between cardiac
blood supply (perfusion) and myocardial oxygen demand

Chronic Ischaemia (Arteriosclerotic)

Aetiology:
1-Major cause: Coronary atherosclerosis
2-Less common causes:
 Paroxysmal tachycardia
 Aortic incompetence or stenosis
 Severe anemia
Pathology:
Myocardial degeneration→fibrosis, sub-endocardial fibrosis, and Valve fibrosis
Effects and Complications:
1-Arrythmias: affection of conductive system.
2-Angina pectoris.
3- Chronic heart failure.
4- Sudden complete occlusion.

- Angina pectoris:

It is an intermittent chest pain caused by transient, reversible myocardia

ischemia.

Anginal pain is probably a consequence of the ischemia-induced release of

adenosine, bradykinin and other molecules that stimulate the autonomic afferents.

Myocardial Infarction:

It is also commonly referred to as heart attack.

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 General Pathology

Definition: It is necrosis of heart muscles resulting from ischemia.

- It is common in males between 45-54 years.

- It is 4-5 times common in males as in females; risk becomes equal in both

sexes at 70 years.
Aetiology:
1-Coronary atherosclerosis →complete coronary occlusion due to:
a) Advanced atherosclerotic lesions
b)Thrombosis developing over an atheroma.
c) Intimal hemorrhage under the atheroma
2-Rare causes include:
a)Severe coronary spasm
b)Severe hypotension
c)Coronary embolism
d)Polyarteritis nodosa
e)Dissecting aneurysm, thrombosis of coronary ostia.

Pathogenesis:
♦ MI is due to sudden thrombotic occlusion of atherosclerotic stenosed
coronaries by atherosclerosis.

♦ Vasospasm and platelet aggregation can contribute.

♦ MI especially subendocardial type may occur without thrombotic occlusion

as follows:

a- A stenosed artery with excessive exertion leads to increased heart rate and
decreased 02 flow with consequent MI without thrombosis.

b- During night, slow heart rate leads to diminished coronary perfusion followed
by MI in already stenosed coronaries.

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NB- о Angiography performed within 4 hours of the onset of MI demonstrates

coronary thrombosis in 90% of cases. While, 12 to 24 hours after onset of
symptoms, evidence of thrombosis is seen in only 60% of patients, even without
intervention.

о Thus, at least some occlusions clear spontaneously through lysis of the thrombus
or relaxation of spasm.

о This sequence of events in a typical MI also has therapeutic implications:

Early thrombolysis by streptokinase or tissue plasminogen activator and/or

angioplasty can be highly successful in limiting the extent of myocardial
necrosis,

Gross and microscopic appearances of MI

Elapse d Gross changes Light microscopy

time
0.5-2 None Usually none, variable waviness of fibers 1
hours at border

4-12 Occasionally dark Beginning coagulative necrosis, edema

hours mottling hemorrhage
12-24 Dark mottling Ongoing coagulative necrosis; cytoplasmic
hours eosinophilia, nuclear pyknosis, marginal
contraction band necrosis

1-3 Pallor and mottling with - Coagulative necrosis with loss of nuclei 1
Days yellow-tan infarct center & striations & interstitial neutrophilic
infiltrate.
3-7 Hyperemic border, -Beginning of disintegration of dead
Days central yellow-tan myofibers with dying neutrophil; early
softening. phagocytosis of dead cells by
macrophages at infarct border.

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 General Pathology

7-10 Maximally yellow tan Well-developed phagocytosis of dead

days soft, with depressed cells; early formation of fibrovascular
red-tan margins granulation tissue at margins

10-14 Red-gray depressed -Well-established granulation tissue with

days infarct borders new blood vessels and collagen
depjosition
2-8 Gray white scar Increased collagen deposition, with
Weeks progressive from border decreased cellularity
toward core of infarct

>2 Scarring complete Dense collagenous scar

[months

Patterns of myocardial infarction

(I) Subendocardial Infarctions: This is a multifocal area of necrosis, extending

from the subendocardium to involve 1/3 to 1/2 of thickness of the left ventricle. It
is not accompanied by thrombosis in 90%, but by arrhythmias thus, being
dangerous.

(2) Transmural infarctions: involve the full thickness of the ventricle

(3) Microscopic infarcts: occur in the setting of small vessel occlusions

These can occur in cases of vasculitis, embolization of valve vegetations or
mural thrombi, or vessel spasm due to elevated catecholamines either
endogenous (e.g., pheochromocytoma or extreme stress), or exogenous
(e.g., cocaine)

Complications of transmural infarction:

1. Arrhythmia.

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 General Pathology

2. Acute left ventricular failure and sudden death.

3. Rupture of papillary muscle, ventricle and perforation of the

interventricular septum leading to acute left ventricular failure, cardiac
tamponade and left to right shunt.

4. Mural thrombosis resulting in embolisation.

5. Fibrosis leading to aneurysmal dilatation and embolisation.

6. Pericarditis which may be fibrinous or hemorrhagic.

7. Congestive heart failure (CHF).

CONGENITAL HEART DISEASES

Congenital heart diseases are abnormalities of the heart or great vessels that are
present at birth.
Aetiology: One of the following during pregnancy:
1-Viral diseases as German measles.
2-Drugs as thalidomide.
3- Exposure to radiations.
4-Nutritional deficiencies
5- Maternal diabetes

Classification:

I-Acvanotic group (Left to risht shunt).

a- Atrial septal defects (ASDs).

b- Ventricular septal defects (VSDs) and patent ductus arteriosus (PDAs).

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 General Pathology

II.Cyanotic roup (Risht to left shunt).

(1) Fallot's tetralogy.

(2) Transposition of great vessels.

III .Coarctation of the aorta (no shunt).

ATRIAL SEPTAL DEFECT

• A pathological defect within the atrial septum  free communication
between left and right-sided blood.
• There is left to right shunt through the ASD.
- Small ASD insignificant effects.
- Large ASD (3 cm)  hypertrophy & dilatation of the right side & sometimes
cardiac failure.
• In advanced cases pulmonary hypertension occurs  reversal of the shunt
(from right to left)  cyanosis (Eisenmenger's syndrome).
• Subacute infective endocarditis may develop at the edges of the defect

VENTRICULAR SEPTAL DEFECT

1-Large defects (90% of cases): in membranous part of the septum, just below the
aortic valve.

- Effects:

1 - Small VSDs may be asymptomatic

2- Larger VSD, result in:

□ Chronic severe left-to-right shunting, often complicated by pulmonary

hypertension and congestive heart failure.

□ Progressive pulmonary hypertension, with resultant reversal of the shunt and

cyanosis occurs earlier and more frequently than with ASDs.

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 General Pathology

Patent ductus arteriosus:

♦ During intrauterine life, the blood passes from the pulmonary artery through the
ductus arteriosus into the aorta bypassing the oxygenated lungs.

♦ Shortly after birth, this ductus is usually constricted in response to increased

arterial oxygenation, decreased pulmonary vascular resistance and declining local
levels of prostaglandin E2.

♦ PDA becomes obliterated by about the 8th week after birth.

Effects of PDA:

1- A small PDA generally causes no symptoms.

2- Larger PDA can lead to cyanosis and congestive heart failure.

FALLOT'S TETRALOGY
It consists of:
1) VSD.
2) Pulmonary stenosis.
3) Right ventricular hypertrophy.
4) Over-riding aorta receiving blood from both ventricles (leading to cyanosis).
Manifestations: Cyanosis, secondary polycythemia and clubbing of fingers.

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 General Pathology

A.Pulmonary stenosis
B. VSD
C. Overriding of aorta
(aorta opening in both
Rt. & lt. ventricles)
D. RV hypertrophy .

Fallot`s tetralogy

Coarctation of the aorta:

It means narrowing or constriction of the aorta.

(a) Infantile (preductal) type: In which the narrowing of the aorta occurs
proximal to the ductus arteriosus which remains patent, through which the blood
flows from the pulmonary artery to the aorta. It is fatal.

(b) The adult (postductal) type: In which the narrowing of the aorta occurs distal
to the ductus arteriosus, which is usually closed. Clinical: Increased pressure in the
arm, head and neck, with decrease pulse and blood pressure in the legs.

Complications of congenital heart diseases:

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 General Pathology

1- Cyanosis: develops early in life in Fallot's tetralogy.

2- Predisposition to subacute infective endocarditis.

3- Heart failure unless corrected by operation.

4- Pulmonary hypertension.

Pericarditis

Pericarditis means inflammation of the pericardium.

Types:

A- Acute pericarditis:

7- Serous pericarditis:

Causes:

• Viral infections (e.g. Coxsackie virus B3 Echovirus, mumps and

Influenza).

• Non-bacterial inflammation as; rheumatic fever, SLE and systemic

scleroderma.

• Idiopathic.

Fate: It resolves spontaneously in days or weeks.

It usually does not encroach upon the cardiac function.

2. Fibrinous or serofibrinous pericarditis.

It is the commonest form of Pericarditis

Causes:

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 General Pathology

• Rheumatic fever.

• Myocardial infarction.

• Uraemia.

• Trauma.

• Lung diseases as pneumonia.

Fate: о Resolution with digestion of the fibrin.

о Organization leads to mild adhesive pericarditis or only plaque like fibrous

thickening of serosal membranes.

3. Suppurative or purulent pericarditis:

It is infection of the pericardial space by bacteria or fungi.

Causes:

a. Direct extention of infection from; pneumonia, empyema, mediastinal

infection, steomyelitis of ribs, subphrenic abscess or myocarditis.

b. Blood-borne infection as in septicaemia or pyaemia.

c. Lymphatic: subphrenic or hepatic abscess.

d. Penetrating chest wound.

Fate: The outcome is organization with marked adhesions resulting in mediastino-

pericarditis or constrictive pericarditis.

4. Haemorrhagic pericarditis:

It denotes inflammatory exudates mixed with blood. Causes: •

T.B.

• Malignant neoplasms

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 General Pathology

• Pericarditis in patients with underlying blood disease

• Severe bacterial infections.

Fate: The outcome is as suppurative pericarditis.

NB: It must be differentiated from haemopericardium in which the fluid is

purely blood of non-inflammatory origin

B. Chronic pericarditis:

1. Tuberculous Pericarditis:

Causes: a- Blood borne.

b-Direct extension or by lymphatic from pulmonary tuberculosis or tuberculous

mediastinal lymph nodes.

Microscopic: It appears as fibrinous inflammation with granulation tissue,

tubercles and sometimes areas of caseation.

Occasionally the exudate may be haemorrhagic.

Fate: Healing by organization results in constrictive pericarditis or adherent

mediastinopericarditis.

C. Healed pericarditis:

 Adhesive pericarditis: In which there is delicate adhesions either diffuse or

focally obliterating the pericardial sac.

It rarely causes impairment of cardiac function.

 Constrictive pericarditis:

It means the formation of dense fibrous or fibrocalcific scar around the heart,
causing severe cardiac dysfunction.

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 General Pathology

It follows suppurative or haemorrhagic pericarditis.

The heart is small and cannot expand adequately during diastole.

Constriction of the venae cavae during the fibrotic process may block the venous
return leading to congestive heart failure.

Pericardial effusions:

It means accumulation of fluid in the pericardial sac

A— (serous):

It is the accumulation of transudate in the pericardial sac.

Causes: It occurs in generalized oedema e.g. cardiac, renal and nutritional. Fate:
Absorption occurs with removal of the causes leaving a normal pericardium.

B- Haemopericardium:

Pure blood or serosanguinous fluid in the pericardial sac. Causes:

1. Rupture of the heart:

a- Traumatic - e.g. stab wound.

b- Spontaneous - e.g. myocardial infarction.

2. Rupture of the intrapericardial portion of

DISEASES OF BLOOD VESSELS

ARTERIOSCLEROSIS

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 General Pathology

Arteriosclerosis literally means "hardening of the arteries"; it is a generic term

reflecting arterial wall thickening and loss of elasticity.

Three patterns are recognized, with different clinical and pathologic

consequences.
a) Atherosclerosis
b) Monckeberg‘s sclerosis (medial calcification) :

- This is a degenerative disease of unknown cause characterized by

dystrophic calcification of the media.

- It is common in muscular arteries in elderly people.

- The disease produces no clinical effects because the lumen is not

narrowed.

c) Arteriolosclerosis:

- It affects small arteries and arterioles.

- Hyaline and hyperplastic arteriolosclerosis, will be described in relation to

hypertension.

ATHEROSCLEROSIS (ATHEROMA)
Definition:
Patchy thickening of the intima of arteries by lesions composed of deposited lipids
surrounded by proliferated connective tissue.

Atheromatous plaque:

• It consists of a raised lesion with a soft, yellow core of lipid (mainly

cholesterol cholesterol esters) and covered by a firm white fibrous cap.

• It is the most frequent and clinically important arterial disease.

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 General Pathology

• Atherosclerosis causes more morbidity and mortality (roughly half of all

deaths) in Western world than any other disorder. It is manifested as:

b- Coronary artery disease.

c- Carotid atherosclerotic disease and stroke.

Risk Factors for atherosclerotic arterial disease:

1) Increasing age: Significant disease is rare under 30 years of age.

2) Lack of physical exercise and stressful life patterns.

3) Sex: Males are affected more than females. Female incidence increases
after the menopause.

4) Family history of ischemic heart disease in a patient or a sibling under the

age of 55 years.

5) Hyperlipideniia: Is the major risk factor in patients under 45 years of age. It

may be due to genetic defects or secondary to other diseases as nephrotic
syndrome, diabetes, hypothyroidism or high fat intake.

NB: Any increase in LDL (low density lipoprotein) content of plasma increases
the risk for atherosclerosis but increase in plasma HDL (high density lipoprotein)
is protective against atherosclerosis (as in premenopausal females).

6) Hypertension: The major risk factor in patients over 45 years of age.

7) Cigarette smoking: Ten cigarettes per day increases the risk three folds.

8) Diabetes mellitus: Both type I and type II diabetes mellitus are associated with
two fold increase in risk.

NB: The risk factors impose more than a simple additive risk.

Pathogenesis of atherosclerosis:

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 General Pathology

The mechanism responsible for lipid deposition in the intima and formation of
atheromatous lesions is unknown. The following theories are to be considered

A) Reaction to endothelial injury:

1. Non-denuding enodthelial injury is believed to lead to adherence of blood

monocytes which are activated, imbibe LDL and actively enter the intima and
become macrophages.

2. Active macrophages release free radicals that oxidise LDL. The oxidised LDL
is toxic to endothelium causing endothelial loss and exposure of subendothelial
connective tissue to blood components. This leads to platelet adhesion forming
microthrombi.

3. Platelets release various factors one of which has been identified as being
mitogenic causing migration of smooth muscle into the intima and proliferation
there.

4. Activated macrophages and smooth muscle cells secrete numerous cytokines

e.g. platelet derived growth factor (PDGF), tumour necrosis factor (TNF),
fibroblast growth factor (FGF) and interleukin 1, some of which may also have
mitogenic capability.

5. The smooth muscle cells, macrophages and matrix accumulate LDL from the
plasma, a process that is enhanced by the presence of increased LDL in the blood.
Smooth muscle cells and endothelial cells have LDL receptors on their surfaces.

NB: The nature of the initial endothelial injury is unknown: Physical tear injuries
are maximal at sites of arterial branching which are the sites most involved.

B) Thrombus encrustation theory:

• It states that small thrombi collected over foci of endothelial injury and the
organization of such thrombi resulted in plaque formation.

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 General Pathology

• The lipid here is derived from the breakdown of platelets and leucocytes
rather than serum lipoproteins.

• Endothelial injury may be due to: aging process, hypertension, viruses,

stress, cigarette smoking or immune complex deposition.

NB: Thrombosis is now thought not to be the initial event but it probably plays a
role in the development and enlargement of the lesion.

Pathologic features of atherosclerosis:

The lesions of atherosclerosis are:

1- Fatty streaks

2- Fibrous athermatous plaque.

3- Acute plaque changes (complicated lesion). The latter two are responsible for
clinically significant disease.

A. Fatty streaks:

They are thin, flat, yellow streaks in the intima, very hard to be seen
macroscopically but can be stained with Sudan III.

Sites: They occur maximally around the aortic valve ring and thoracic aorta.

Microscopic: They consist of macrophages and smooth muscle cells whose

cytoplasm is distended with lipid to form foam cells.

 They are present very early in life, often in the first year irrespective of sex,
race or environment.

 They increase in number until about the age of 20 years and then remain
static or decrease.

 There is controversy about whether some fatty streaks progress into fibrous
atheromatous plaques or whether they are independent of atherosclerosis.

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 General Pathology

B. Fibrous atheromatous plague:

This is the basic lesion of clinical atherosclerosis.

Gross: It appears as yellow-white elevation on the intimal surface of the artery.

The centre of the plaque consists of semisolid yellow material.

Sites:

• In the aorta and most commonly in the abdominal aorta.

• Involvement of muscular arteries such as the coronary, carotid,

vertebrobasilar, mesenteric, renal and iliofemoral arteries and is associated
with luminal stenosis.

• Plaques tend to be most prominent at points of branching of the major

arteries.

• In severe disease plaques become confluent.

Microscopic:

It consists of three zones which vary in thickness in different plaques

1. Fibrous cap; under the endothelium, consisting of dense collagen,

scattered smooth muscle cells and macrophages.

2. The lipid zone; consists of foam cells (lipid laden macrophages and
smooth muscle cells), extracellular lipid, cholesterol crystals and necrotic
debris.

3. The basal zone; composed of smooth muscle cells and connective tissue.

 Vascularization of the plaque occurs by in growth of poorly supported vessels

from the media.

 Different plaques contain varying amounts of these three layers, some are
mainly fibrous and others are predominantly fatty.

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 General Pathology

 Dystrophic calcification is common and occurs in the lipid zone.

C. Acute plaque changes:

 Plaque rupture causes acute catastrophic vessel thrombosis.

 Thrombosis cause complete occlusion of the artery.

 Ulceration of the endothelium overlying the plaque may cause the lipid
contents of the plaque to be discharged into the circulation as cholesterol emboli.

 It may also precipitate thrombosis over the ulceration.

 Haemorrhage into the atheroma that may expand its size sufficiently to
occlude the lumen of the artery.

 Haemorrhage may cause also ulceration and thrombosis.

Effects and complications of atherosclerosis :

1. The Aorta:

 Weakening of the wall with dilatation i.e. atheromatous aneurysm.

 Mural thrombosis may occur with detachment and embolic manifestations.

2. In the medium sized vessels:

■ Narrowing of the lumen leading to ischaemia.

■ Complete occlusion leading to cut of blood supply (infarction) These may be

due to thrombosis, haemorrhage or ulceration of the plaque.

HYPERTENSION
Definition:

It is a permanent elevation of the blood pressure above 140 mm Hg (systolic) and

90 mm-Hg. (diastolic).

Classification of systemic hypertension:

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 General Pathology

1- According to the cause hypertension is classified into:

[A] Primary, essential or idiopathic (without a known cause).

[B] Secondary or renal.

2- According to the severity and course; hypertension (primary, secondary) is

classified into "benign" and "malignant".

[A] Primary or essential or idiopathic hypertension.

□ It is the commonest type (95%), occurring after the age of 40 years.

□ It is either benign (95%) or malignant (5%).

• Primary Hypertension
- Contributing factors:
•  SNS activity
• Diabetes mellitus
•  Sodium intake
• Excessive alcohol intake
Secondary Hypertension
- Contributing factors:
• Coarctation of aorta
• Renal disease
• Endocrine disorders
• Neurologic disorders

Clinical Manifestations

Frequently asymptomatic until severe and target organ disease has occurred

– Fatigue, reduced activity tolerance

– Dizziness

– Palpitations, angina

– Dyspnea

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Benign hypertension:

о It is a very common disease which occurs above 50 years.

о It is characterized by a slowly progressive rise (in years) in blood pressure

(below 200/100).

The essential organs affected are:

(1) Heart (hypertensive heart): The left ventricle undergoes concentric

hypertrophy (walls and septum) in response to the resistance of elevated
blood pressure; walls of left atrium become also hypertrophic.

(2) Kidneys (arteriolosclerotic kidney): or benign nephrosclerosis or primary

contracted kidney.

(3) The affected small arteries and arterioles, particularly those of the
kidney show hyalinosis. It is marked by homogeneous, pink hyaline
thickening of the arteriolar walls, with loss of underlying structural details,
and luminal narrowing.

NB: Although the vessels of elderly normotensive patients show the same changes,
hyaline arteriolosclerosis is more generalized and severe in patients with
hypertension. The same lesions are also common in diabetics.

Causes of death:

1. Congestive heart failure (45%) due to increased work load thrown on the
left ventricle.

2. Coronary insufficiency or infarction (45%).

3. Cerebrovascular accident mainly cerebral haemorrhage (5%).

4. Renal failure (5%).

Malignant hypertension:

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 It is a rare disease affecting mainly young adults

 rapidly progressive form of hypertension reaching high levels e.g. 280/180

mmHg.

It is accompanied by:

• Severe headache.

• Eye changes; retinal haemorrhages, exudates and papilledema.

• Severe impairment of the renal function with albuminuria.

Microscopic vascular chanses in malisnant hypertension:

The affected small arteries and arterioles in the body particularly those of the
kidney show the following changes:

1- Hyperplastic arteriolosclerosis; Vessels exhibit "onion-skin," concentric,

laminated thickening of arteriolar walls and luminal narrowing. The laminations
consist of smooth muscle cells and thickened reduplicated basement membrane.

2- Fibrinoid necrosis of the walls of arterioles and smallest arteries. The vessel
walls show a homogenous granular eosinophilic appearance, due to permeation of
the necrotic tissue by plasma constituents.

N.B.: Malignant nephrosclerosis; when the glomerular afferent arteriole is

affected; the fibrinoid necrosis may extend into the glomerulus and rupture of
capillaries may cause haematuria and produce visible flea bite haemorrhages on
the surface of the kidney: (see chapter of kidney diseases). The heart is usually
within normal size.

Causes of death: The disease is serious and of poor prognosis.

(1) Renal failure 95%.

(2) Cerebro-vascular accidents mainly cerebral haemorrhage.

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(3) Coronary insufficiency.

(4) Heart failure.

 Diagnosis:

Requires several elevated readings over several weeks (unless > 180/110)

ANEURYSMS
True Aneurysms
Definition: Localized dilatation of the arterial wall.

Aetiology:
Weakening Of Media:
a)Congenital: At the bifurcation of the arterial wall
b)Atherosclerosis: Abdominal aorta and cerebral arteries
c)Inflammatory

 Cerebrovascular Disease
• Stroke

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• True aneurysm:
• Its wall is formed by one or more layers of the affected vessel
Aneurysms can be classified by shape into:
• о Fusiform aneurysm: or diffuse dilatation affecting a segment of the
artery taking the whole circumference.
• о Saccular aneurysm: or localized dilatation affecting a part of the
circumference to produce a globular sac.

Etiological types of true aneurysm:

(1)Congenital aneurysm: It occurs mainly in the arteries of the circle of Willis at

the base of the brain.

Effects: If rupture, they can cause fatal intracerebral hemorrhage.

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(2) Atheromatous aneurysm: It is the commonest type and occurs mainly in old
people. It is of the fusiform type and affects mainly the abdominal aorta and
common iliac arteries.

Effects: a- Pressure on the surrounding organs.

b- Rupture leading to fatal haemorrhage.

c- Thrombosis and embolism.

(3) Syphilitic aneurysm: It is usually saccular in shape. It occurs mainly in the

ascending and transverse parts of the arch of the thoracic aorta.

Effects: a- Pressure on the trachea and oesophagus.

b- Erosion of the sternum by pressure necrosis with the production of pulsatile

subcutaneous swelling.

c- Rupture with fatal haemorrhage.

d- Thrombosis and embolism.

(4) Mycotic aneurysm: It is due to weakness of the wall due to bacterial

infection. Nearly all are associated with infective endocarditis. It is also seen in the
walls of tuberculous cavities and abscesses. Commonest sites are coronary,
cerebral, and mesenteric arteries.

Effects: Thrombosis - rupture (late).

(5) Aneurysm of polyarteritis nodosa.

(6) Microaneurysms: commonly seen in hypertension and diabetes.

B- False aneurysm:

Its wall is formed by connective tissue which is not part of a vessel wall.
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Types:

(1) Pulsating haematoma: It results from a small perforation in the wall of an

artery due to trauma. The walls of haematoma are formed by the compressed
adjacent tissue e.g. muscle and fascia.

(2) Arteriovenous fistula: Is an abnormal direct connection between arteries and

veins that bypass the intervening capillaries, it may be:

Aortic dissection:

It occurs when the blood passes into the diseased media where it separates the wall
into an inner layer (intima and part of media) and an outer layer (part of the media
and adventitia).

Causes:

1- Myxomatous degeneration of the media due to genetic factors with rupture of

unsupported vasa vasora (intramural haemorrhage).

2- Hypoxic medial damage consequent to narrowing of vasa vasorum by

hypertensive changes.

Effects:

The false lumen may rupture internally to recommunicate with the true lumen or
externally and depending on the site of rupture results in:

1- Haemopericardium with cardiac tamponade.

2- Mediastinal haemorrhage.

3- Haemothorax.

4- Abdominal haemorrhage.

Diseases of Veins

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Varicose veins:

They are dilated, elongated and tortuous veins.

Incidence: More common in females.

Sites: a- In systemic veins: usually in the leg veins.

b- In portal veins: sites of porto-systemic anastomosis. Causes:

1. Deficient support of the venous wall (age).

2. High pressure within the lumen (e.g. prolonged standing, portal hypertension).

Complications:

(1) Oedema.

(2) Thrombosis.

(3) Embolism.

(4) Haemorrhage.

(5) Infection i.e. thrombophlebitis.

(6) Trophic skin changes (e.g. varicose ulcers).

Tumours of blood vessels

Benign tumours:

Capillary and cavernous haemangiomas.

• Glomus tumor (Glomangioma): It is a benign, painful tumor arising from

glomus bodies (involved in thermoregulation). They usually occur under the
fingernails.

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 General Pathology

Malignant tumours:

• Angiosarcoma.

- It most often occurs in the skin, soft tissue, breast, and liver.

- Hepatic angiosarcomas are associated arsenical pesticides, Thorotrast and

polyvinyl chloride.

• Kaposi sarcoma (KS):

It is caused by Kaposi sarcoma herpesvirus (human herpesvirus-8). Four forms of KS

are recognized:

a- Classic KS; affects European and Mediterranean older men.

It manifests as skin lesions usually on the distal lower extremities. b- Endemic

African KS: occurs in younger persons and frequently

involves lymph nodes

c- AIDS-associated KS is now the most common tumor in central Africa.

A severe form, with prominent lymph node and visceral involvement.

It occurs in prepubertal children. d- Transplantation-associated KS; occurs in

patients on immunosuppression for organ transplant. It involves lymph nodes,
mucosa, and viscera. Lesions often regress with reduction of immunosuppression.

Gross: Cutaneous lesions appear as multiple red-purple patches, plaques or

nodules that may disseminate.

Microscopic: There is spindle shaped endothelial cells with slit-like vascular

spaces and extravasated RBCs.

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