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Clinical course: It describes the evolution of a disease. A disease can have an

acute , subacute , or chronic course.

-An acute disorder is one that is relatively severe, but self-limiting.

-Chronic disease implies a continuous, long term process. A chronic disease can
present with aggravation of symptoms.

-Subacute disease is intermediate or between acute and chronic.

There are different types of studies used to determine risk factors, including

Cross sectional studies can be used to compare the prevalence of a disease in

those who are exposed to with the prevalence of a disease in those who are
unexposed to the factor, such as the prevalence of coronary heart disease in
smokers andnon smokers

Case-control studies are designed to compare persons known to have the

outcome of interest ( cases with those known not to have the outcome of interest
(controls.)

A cohort is a group of persons who were born at approximately the same time
or share some characteristics of interest, persons are followed over a period of
time to observe a specific health outcome.

Q/ metaplasia & dysplasia cause cancer ? Answer/ True

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Causes of cell injury:
1. Injury from physical agents.( Mechanical forces, Extreme of temperature,
Electrical forces)
2. Radiation injury.( Ionizing radiation, Non- ionizing radiation, UV radiation)
3. Chemical injury.
4. Injury from biologic agents.
5. Injury from nutritional imbalance.

Mechanism of cell injury:

1.Free radical formation
2.Hypoxia and ATP depletion.
3.Disruption of intracellular calcium homeostasis

-Reactive oxidative species (ROS) are : O2˙ , OH ˙ , H2O2.

-inhibit reaction of ROS with biologic structures include: Superoxide dismutase
(SOD), catalase, glutathione peroxidase, thioreductase. And non-enzymatic
antioxidants such as vitamin A, E, C, flavinoids, Selenium and zinc.

-Q/ vit. D is Antioxidants? Answer / False

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apoptosis & necrosis
Apoptotic cell removal; (A) shrinking of the cell structures, (B,C) condensation
and fragmentation of the nuclear chromatin, (D,E) Separation of the nuclear
fragments and cytoplasmic organells into apoptotic bodies, (F)engulfment of
apoptotic fragments by phagocytic cells.

Necrosis
1-Unregulated enzymatic digestion of cell components.
2-Loss of cell membrane integrity with uncontrolled release of cell products
3-Initiation of inflammation
4-Interferes with cell replacement and tissue regeneration

Apoptosis is thought to be responsible for several normal physiologic

processes, including:
1-Cell destruction during embryonic development
2-Hormone – dependent involution of tissues
3-Death of immune cells
4-Cell death by cytotoxic T- cells
5-Cell death in proliferating cell population
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Acute inflammation
is rapid in onset (typically minutes), and
is of relatively short duration, lasting
from few minutes to several days
characterized by the exudation of fluid
and plasma
proteins and emigration of leukocytes
Only neutrophils
triggered by a variety of stimuli such as
(infection or tissue injure
Chronic inflammation
is of a longer duration, lasting for days
to years
proliferation of blood vessels
(angiogenesis), tissue necrosis and
fibrosis(scarring)
infiltration with mononuclear cells (
macrophages, lymphocytes and plasma
cells).
Causes of chronic inflammation:
1. Low grade persistent infection or
irritation.
2. Foreign agents such as Talc, silica,
asbestos and surgical materials.
3. Many viruses, bacteria (T.B) , fungi
and larger parasites.
4. Obesity.
5. Diseases that cause extensive and
inappropriate activation of immune
system.
The cardinal signs of inflammation:
1-Redness. 2-Swelling. 3-Heat. 4-Pain. 5-Loss of function.

Stages of acute inflammation:

The vascular stage is characterized by increased blood flow (vasodilatation)

and structural changes (increased vascular permeability) that allow plasma
proteins to leave the circulation.
The cellular stage involves the emigration of leukocytes (mainly neutrophils)
from the microcirculation at the site of injury or infection.

♦Vasodilatation is induced by the action of several mediators mostly histamine

and nitric oxide.

The sequence of events of cellular response includes leukocytes :

1. Margination and adhesion.
2. Transmigration.
3. Chemotaxis.
4. Activation and phagocytosis.

Phagocytosis involves three steps:

• Recognition and adherence.
• Engulfment
• intracellular killing.

-The enhanced binding of antigen to a coated microbe is called opsonization.

A- Plasma –derived mediators ; are products of three systems:

1- Kallikren- kininogen system which generate kinins. e.g., bradykinin

2- Coagulation system which include the fibrin endproducts

3- Complement system .

B- Cell- derived mediators

1- Histamine and serotonin: are vasoactive amines. Histamine cause dilatation of

arterioles and increase permeability of venules. While serotonin cause platelets
aggregation.

2- Arachidonic acid metabolites: include prostaglandins and leukotriens.

3- Omega-3 polyunsaturated fattyacids.

4- Platelets activating factors

5- Cytokines and chemokines

6- Nitric oxide: cause relaxation of smooth muscle, antagonism of platelets

adhesion and aggregation and antimicrobial action.

7- Reactive oxygen species: released from leukocytes, they increase expression of

cytokines and endothelial adhesion molecule causing endothelial cell damage and
increase vascular permeability.

The acute inflammation response involves the production of exudates.They can

be:
Serous, hemorrhagic, fibrinous , membranous and purulent.

A granulomatous lesion is a distinctive form of chronic inflammation. It is a

small (1-2 ) mm lesion in which there is a mass of macrophages surrounded by
lymphocytes. These macrophages resemble epithelial cells and are called
epitheloid cells.
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Cell proliferation refers to the process of increasing cell numbers by mitotic
division.
Cell differentiation is the process whereby a cell becomes more specialized in
terms of structure and function.

Stem cells are undifferentiated cells that have the capacity to generate
multiple cell types In normal tissue: the size of the cell population is determined
by a balance of cell proliferation and death by apoptosis.

Body tissues are divided into three types depending on the ability of their cells
to undergo regeneration:
1-continuously dividing.
2-stable.
3-permanent tissue.

Angiogenesis: is a tightly regulated process that includes migration of

endothelial cells to the site of tissue injury, formation of capillary buds and
proliferation of endothelial cells. Several growth factors induce angiogenesis.

Phases of healing:
1. Inflammatory phase
2. Proliferative phase
3. Remodeling phase
♦ It begins 3 weeks after injury and lasts for 6 months or longer. There is a
continued remodeling of scar tissue by simultaneous synthesis of collagen by
fibroblasts and lysis by collagenases enzymes.
♦ As a result the scar architecture becomes reoriented to increase the tensile
strength of the wound. An abnormality in healing by scar tissue repair is keloid
formation. keloids are benign tumor like masses caused by excess production of
scar tissue.
Factors that affect wound healing
1- Nutritional status
2- Blood flow and oxygen delivery
3- Impaired inflammatory and immune response

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Hypernatremia - hypodipsia: decrease in ability to sense thirst

Hypokalemia - Increased aldosterone ( primary aldosteronism or Conn’ s disease).

Hyperkalemia - Adrenal insufficiency ( addison's disease).

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