General pathology

Lecture 3
Cell death
• Cells can die via one of the following two ways:
1. Necrosis
• In necrosis, excess fluid enters the cell, swells it, & ruptures its membrane
which kills it. After the cell has died, intracellular degradative reactions
occur within a living organism.
• Necrosis does not occur in dead organisms. In dead organisms, autolysis &
heterolysis take place.
• Necrosis occurs by the following mechanisms:
• A. Hypoxia
• B. Free radical-induced cell injury
• C. Cell membrane damage
• D. Increased intracellular calcium level
2. Apoptosis
is the death of single cells within clusters of other cells. (Note that
necrosis causes the death of clusters of cells.) In apoptosis, the cell
shows shrinkage & increased acidophilic staining of the cell. This is
followed by fragmentation of the cells.
• .
VI. Pathologic calcification of death
cells
Pathologic calcification is divided
into 2 types:
• 1. Metastatic calcification
• This is caused by hypercalcemia, resulting from hyperparathyroidism,
sarcoidosis etc…
• 2. Dystrophic calcification
• This occurs in previously damaged tissue, such as areas of old trauma,
atherosclerotic lesions.
• Unlike metastatic calcification, it is not caused by hypercalcemia.
Typically, the serum .calcium level is normal.
 INFLAMMATION
• Definition: Inflammation is a local response (reaction) of living
vasculaized tissues to endogenous and exogenous stimuli. The term is
derived from the Latin "inflammare" meaning to burn.
• Inflammation is fundamentally destined to localize and eliminate the
causative agent and to limit tissue injury.
• inflammation is a physiologic (protective) response to injury, local
response of living tissue to injury due to any agent .
• “inflammation is itself not to be considered as a disease but as a
salutary operation consequent either to some violence or to some
diseases”.
 Causes:
Causes of inflammation are apparently causes of diseases such as:
- physical agents - mechanical injuries, alteration in temperatures and
pressure, radiation injuries.
- chemical agents- including the ever increasing lists of drugs and toxins.
- biologic agents (infectious)- bacteria ,viruses,fungi, parasites
- immunologic disorders- hypersensitivity reactions, autoimmunity,
immunodeficiency states etc
- genetic/metabolic disorders- examples gout, diabetes mellitus etc…
ACUTE INFLAMMATION
• Acute inflammation is an immediate and early response to an
injurious agent and it is relatively of short duration, lasting for
minutes, several hours or few days.
• It is characterized by exudation of fluids and plasma proteins and the
emigration of predominantly neutrophilic leucocytes to the site of
injury.
The five signs of acute inflammation
are
1. Redness (rubor) which is due to dilation of small blood vessels within damaged
tissue as it occurs in cellulitis.
2. Heat (calor) which results from increased blood flow (hyperemia) due to
regional vascular dilation
3. Swelling (tumor) which is due to accumulation of fluid in the extravascular
space which, in turn, is due to increased vascular permeability.
4. Pain (dolor), which partly results from the stretching & destruction of tissues
due to inflammatory edema and in part from pus under pressure in as abscess
cavity. Some chemicals of acute inflammation, including bradykinins,
prostaglandins and serotonin are also known to induce pain.
5. Loss of function: The inflammed area is inhibited by pain while severe swelling
may also physically immobilize the tissue.
Type of inflammation
• Depend on defense mechanism and duration of response classify to
1- acute 2- chronic
Acute inflammation :
is categorized into an early vascular and a late cellular
responses.
1) The Vascular response has the following steps:
• a) Immediate (momentary) vasoconstriction in seconds due to
neurogenic or chemical stimuli.
• b) Vasodilatation of arterioles and venules resulting in increased
blood flow.
• c) After the phase of increased blood flow there is a slowing of blood
flow & stasis due to increased vascular permeability that is most
remarkably seen in the post-capillary venules. The increased vascular
permeability oozes protein-rich fluid into extra
• vascular 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. The
presence of the exudates clinically appears as swelling. Chemical
mediators mediate the vascular events of acute inflammation
2) Cellular response
The cellular response has the following stages:
• A. Migration, rolling & adhesion of leukocytes
• B. Transmigration of leukocytes
• C. Chemotaxis
• D. Phagocytosis
Normally blood cells particularly erythrocytes in venules are confined
to the central (axial) zone and plasma assumes the peripheral zone. As
a result of increased vascular permeability , more and more neutrophils
accumulate along the endothelial surfaces
 Effects of acute inflammation
A. Beneficial effects
1. ¾ Dilution of toxins: The concentration of chemical and bacterial
toxins at the site of inflammation is reduced by dilution in the
exudate and its removal from the site by the flow of exudates from
the venules through the tissue to the lymphatics.
2. ¾ Protective antibodies: Exudation results in the presence of plasma
proteins including antibodies at the site of inflammation. Thus,
antibodies directed against the causative organisms will react and
promote microbial destruction by phagocytosis or complement-
mediated cell lysis.
3. ¾ Fibrin formation: This prevents bacterial spread and enhances
phagocytosis by leukocytes.
Beneficial effects
4. ¾ Plasma mediator systems provisions: The complement,
coagulation, fibrinolytic, & kinin systems are provided to the area of
injury by the process of inflammation.
5. ¾ Cell nutrition: The flow of inflammatory exudates brings with it
glucose, oxygen and other nutrients to meet the metabolic
requirements of the greatly increased number of cells. It also removes
their solute waste products via lymphatic channels.
6. ¾ Promotion of immunity: Micro-organisms and their toxins are
carried by the exudates, either free or in phagocytes, along the
lymphatics to local lymph nodes where they stimulate an immune
response with the generation of antibodies and cellular immune
mechanisms of defense.
B. Harmful effects
• ¾ Tissue destruction Inflammation may result in tissue
necrosis and the tissue necrosis may, in turn, incite
inflammation.
• ¾ Swelling: The swelling caused by inflammation may have
serious mechanical effects at certain locations. Examples
include acute epiglottitis with interference in breathing; Acute
meningitis and encephalitis with effects of increased
intracranial pressure.
• ¾ Inappropriate response: The inflammatory seen in
hypersensitivity reactions is inappropriate (i.e. exaggerated)
Fate of acute inflammation
• 1- resolution
• 2- healing
• 3- ulcer
• 4- fistula
• 5- suppuration
• 6- scar formation
• 7- chronic inflammation
CHRONIC INFLAMMATION
• Definition: Chronic inflammation can be defined
as a prolonged inflammatory process (weeks or
months) where an active inflammation, tissue
destruction and attempts at repair are
proceeding simultaneously.
Causes of chronic inflammation:
1. Persistent infections
• ¾ Certain microorganisms associated with intracellular infection such
as tuberculosis, leprosy, certain fungi etc characteristically cause
chronic inflammation.
• ¾ These organisms are of low toxicity and evoke delayed
hypersensitivity reactions.
2. Prolonged exposure to nondegradable but partially toxic substances
either endogenous lipid components which result in atherosclerosis or
exogenous substances such as silica, asbestos.
3. Progression from acute inflammation: Acute inflammation almost
always progresses to chronic inflammation following: Persistent
suppuration as a result of uncollapsed abscess cavities, foreign body
materials (dirt, cloth, wool, etc), sequesterum in osteomylitis, or a
sinus/fistula from chronic abscesses.
4. Autoimmunity. Autoimmune diseases such as rheumatoid arthritis
and systemic lupus erythematosis are chronic inflammations
• Morphology chronic inflammation
cells involved in chronic inflammation
1- Monocytes and Macrophages are the prima Dona (primary
cells) in chronic inflammation. Macrophages arise from the
common precursor cells in the bone marrow, which give rise to
blood monocytes. These cells are then diffusely scattered in
various parts of the body, in the liver (Kupffer cells), spleen,
lymph nodes (sinus histiocytes), lungs (alviolar macrophages),
bone marrow, brain (microglia), skin(Langerhan’s cells), etc….
These cells constitute the mononuclear- phagocytic system.
2- Macrophages are scavenger cells of the body.
Other cells in chronic
inflammation:
1. T-Lymphocytes are primarily involved in cellular immunity with
lymphokine production, and they are the key regulator and effector
cells of the immune system.
2. B-lymphocytes and Plasma cells produce antibody directed either
against persistent antigen in the inflammatory site or against altered
tissue components.
3. Mast cells and eosinophils appear predominantly in response to
parasitic infestations & allergic reactions.
Classification of chronic
inflammation:
Chronic inflammation can be classified into the following two types based
on histologic features:
1) Nonspecific chronic inflammation: This involves a diffuse accumulation
of macrophages and lymphocytes at site of injury that is usually
productive with new fibrous tissue formations. E.g. Chronic cholecystitis.
2) Specific inflammation (granulomatous inflammation):Definition:
Granulomatous inflammation is characterized by the presence of
granuloma.
A granuloma is a microscopic aggregate of epithelioid cells. Epithelioid cell
is an activated macrophage, with a modified epithelial cell-like appearance
SYSTEMIC EFFECTS OF chronic
INFLAMMATIONS
The systemic effects of inflammation include:
1. a. Fever
2. b. Endocrine & metabolic responses
3. c. Autonomic responses
4. d. Behavioral responses
5. e. Leukocytosis
6. f. Leukopenia
7. g. Weight loss