Inflammation and Acute inflammation

Inflammation
Definition
Inflammation is defined as the local response of living mammalian tissues to injury due to any
agent. It is a body defense reaction in order to eliminate or limit the spread of injurious agent,
followed by removal of the necrosed cells and tissues.

Types
Depending upon the defense capacity of the host and duration of response, inflammation can
be classified as acute and chronic.
A. Acute inflammation is of short duration (lasting less than 2 weeks) and represents the early
body reaction, resolves quickly and is usually followed by healing. The main features of acute
inflammation are:
1. accumulation of fluid and plasma at the affected site;
2. intravascular activation of platelets; and
3. polymorphonuclear neutrophils as inflammatory cells.
B. Chronic inflammation is of longer duration and occurs either after the causative agent of
acute inflammation persists for a long time, or the stimulus is such that it induces chronic
inflammation from the beginning.
The characteristic feature of chronic inflammation is presence of chronic inflammatory cells such
as lymphocytes, plasma cells and macrophages, granulation tissue formation, and in specific
situations, as granulomatous inflammation.

Causes
1. Infective agents like bacteria, viruses and their toxins, fungi, parasites.
2. Immunological agents like cell-mediated and antigenantibody reactions.
3. Physical agents like heat, cold, radiation, mechanical trauma.
4. Chemical agents like organic and inorganic poisons.
5. Inert materials such as foreign bodies.

Events
1.Acute inflammation
Main events:
Vascular events
● Vasodilation
● Increased vascular permeability
Cellular events
● Neutrophil recruitment -> emigration out of circulation -> chemotaxis to site of injury ->
activation -> phagocytosis and clearance
2. Chronic events
Main events:
● Inflammation and tissue injury
● Attempts at repair
 ● Immune response

SIGNS OF INFLAMMATION.
The 4 cardinal signs of inflammation are:
● Redness (rubor) – secondary to vasodilation and increased blood flow
● Heat (calor) – localised increase in temperature, also due to increased blood flow
● Swelling (tumour) – results from increased vessel permeability, allowing fluid loss into
the interstitial space
● Pain (dolor) – caused by stimulation of the local nerve endings, from mechanical and
chemical mediators

To these, fifth sign functio laesa (loss of function) was later added by Virchow.

Acute inflammation
Definition
Acute inflammation is an immediate, adaptive response with limited specificity caused by
several noxious stimuli, such as infection and tissue damage (tissue necrosis).
It can be divided into following two events: I. Vascular events. II. Cellular events.

Events
It can be divided into following two events:
I. Vascular events.
II. Cellular events.

Cellular events
The cellular phase of inflammation consists of 2 processes:
1. exudation of leucocytes; and
2. Phagocytosis

1. Exudation of leucocytes
In acute inflammation, the exudation of leukocytes is a crucial aspect of the body's defense.
Polymorphonuclear neutrophils (PMNs) are the initial defenders, followed by monocytes and
macrophages. The migration of leukocytes involves several key changes:

​ Changes in formed elements of Blood:

● Early vasodilatation increases blood flow, but later, stasis occurs.
 ● Stasis leads to alterations in the normal axial flow, causing margination where
neutrophils move closer to the vessel wall.
● Due to slowing and stasis, the central stream of cells widens and peripheral
plasma zone becomes narrower because of loss of plasma by exudation. This
phenomenon is known as margination.
​ Rolling and Adhesion:
● Marginated neutrophils roll slowly along the vessel wall.
● Transient bonds form between leukocytes and endothelial cells.
● Selectins, integrins and Immunoglobulin gene superfamily adhesion molecule
bring about rolling and adhesion phases
​ EMIGRATION:
● Neutrophils adhere to endothelium, move between cells, and throw out
cytoplasmic pseudopods.
● They damage the basement membrane with collagenases, escaping into the
extravascular space.
● Basement membrane repair follows immediately.
● Neutrophils dominate the first 24 hours, while monocyte-macrophages appear in
24-48 hours. Neutrophils live briefly (24-48 hours), monocyte-macrophages last
longer.
● Simultaneously, red blood cells passively escape through endothelial gaps
(diapedesis), causing a hemorrhagic appearance in the inflammatory exudate.
​ CHEMOTAXIS:
● Chemotaxis is the guided movement of leukocytes through barriers towards
interstitial tissues, facilitated by chemotactic factors.
 2. Phagocytosis
Phagocytosis is defined as the process of engulfment of solid particulate material by the cells
(cell-eating). The cells performing this function are called phagocytes. There are 2 main types of
phagocytic cells:
i) Polymorphonuclear neutrophils (PMNs)
ii) Macrophages.
Neutrophils and macrophages on reaching the tissue spaces produce several proteolyitc
enzymes. These enzymes degrade collagen and extracellular matrix. The microbe undergoes
the process of phagocytosis by polymorphs and macrophages and involves the following 3
steps:
1. Recognition and attachment
2. Engulfment
3. Killing and degradation

​ RECOGNITION AND ATTACHMENT:

● Macrophages initiate phagocytosis by expressing surface receptors like the
mannose and scavenger receptors, recognizing microorganisms.
● Opsonins, such as IgG, C3b, and lectins, enhance phagocytosis by establishing
bonds between bacteria and phagocytic cells.
​ ENGULFMENT:
● The opsonized particle on the phagocyte's surface is engulfed as cytoplasmic
pseudopods form around it, creating a phagocytic vacuole.
● The phagosome, internalized in the cell cytoplasm, fuses with lysosomes,
forming a phagolysosome.
​ KILLING AND DEGRADATION:
● Phagocytes proceed to kill and degrade microorganisms using antibacterial
substances and hydrolytic enzymes.
● Some bacteria, like tubercle bacilli, may resist this mechanism.
 GANGRENE

Gangrene
Gangrene is a form of necrosis of tissue with superadded putrefaction. The type of necrosis is
usually coagulative due to ischaemia
There are 2 main forms of gangrene—dry and wet

Dry Gangrene
● This form of gangrene begins in the distal part of a limb due to ischaemia.
● The typical example is the dry gangrene in the toes and feet of an old patient due to
arteriosclerosis.
● Causes-thromboangiitis obliterans (Buerger’s disease), Raynaud’s disease, trauma,
ergot poisoning.
● It begins in the toes, the furthest from the blood supply, where limited blood hinders
bacterial growth. It slowly ascends until reaching a point with sufficient blood supply to
maintain tissue viability.
● A line of separation is formed at this point between the gangrenous part and the viable
part.
● MORPHOLOGIC FEATURES. Grossly, the affected part is dry, shrunken and dark black,
resembling the foot of a mummy. It is black due to liberation of haemoglobin from
haemolysed red blood cells which is acted upon by hydrogen disulfide (H2S) produced
by bacteria resulting in formation of black iron sulfide

Wet Gangrene
● Occurs in naturally moist tissues and organs such as the mouth, bowel, lung, cervix,
vulva etc.
● Other examples- Diabetic foot, Bed sores occurring in a bed-ridden patient
● Wet gangrene usually develops rapidly due to blockage of venous, and less commonly,
arterial blood flow from thrombosis or embolism.
● The affected part is stuffed with blood which favours the rapid growth of putrefactive
bacteria. The spreading wet gangrene generally lacks clear-cut line of demarcation and
may spread to peritoneal cavity causing peritonitis.
● MORPHOLOGIC FEATURES. Grossly, the affected part is soft, swollen, putrid, rotten
and dark. The classic example is gangrene of bowel. The part is stained dark due to the
same mechanism as in dry gangrene

Gas Gangrene:
● Special form of wet gangrene caused by gas-forming clostridia (gram-positive anaerobic
bacteria).
● Entry through open contaminated wounds, especially in muscles, or as a complication of
colon surgery.
● Clostridia produce toxins causing local necrosis, edema, and systemic manifestations.
● Morphologic Features: Grossly: Swollen, edematous, painful, and crepitant affected area
with gas bubbles accumulation.Subsequently turns dark black and foul-smelling.
Necrotising stomatitis (Noma or Cancrum oris) occurs more commonly in poorly-nourished
children like in kwashiorkor; infectious diseases such as measles, immunodeficiencies and
emotional stress. The lesions are characterised by necrosis of the marginal gingiva and may
extend on to oral mucosa, causing cellulitis of the tissue of the cheek. The condition may
progress to gangrene of the cheek.

Disorders of pigmentation
Various disorders of melanin pigmentation cause generalised and localised hyperpigmentation
and hypopigmentation:
i) Generalised hyperpigmentation:
a) In Addison’s disease, there is generalised hyperpigmentation of the skin, especially in areas
exposed to light, and of buccal mucosa.
b) Chloasma observed during pregnancy is the hyperpigmentation on the skin of face, nipples,
and genitalia and occurs under the influence of oestrogen.
c) In chronic arsenical poisoning,
ii) Focal hyperpigmentation:
a) Cäfe-au-lait spots are pigmented patches seen in neurofibromatosis and Albright’s syndrome.
b) Peutz-Jeghers syndrome is characterised by focal peri-oral pigmentation.
iii) Generalised hypopigmentation:
a) Albinism, activity of the melanocytes is genetically defective and no melanin is formed.
Albinos have blond hair, poor vision and severe photophobia.
iv) Localised hypopigmentation:
a) Leucoderma is a form of partial albinism and is an inherited disorder.
b) Vitiligo is local hypopigmentation of the skin and is more common. It may have familial
tendency.

DYSTROPHIC CALCIFICATION.
As apparent from definition, dystrophic calcification may occur due to 2 types of causes:
● Calcification in dead tissue
 ● Calcification of degenerated tissue.

Calcification in dead tissue

1. Caseous necrosis in tuberculosis is the most common site for dystrophic calcification.
2. Liquefaction necrosis in chronic abscesses may get calcified.
3. Fat necrosis following acute pancreatitis or traumatic fat necrosis in the breast results in
deposition of calcium soaps.
4. Infarcts may sometimes undergo dystrophic calcification.
5. Thrombi, especially in the veins, may produce phleboliths.
6. Dead parasites like in hydatid cyst, Schistosoma eggs, and cysticercosis are some of the
examples showing dystrophic calcification.
7. Calcification in breast cancer detected by mammography.

Calcification in degenerated tissues

1. Dense old scars may undergo hyaline degeneration and subsequent calcification.
2. Atheromas in the aorta and coronaries frequently undergo calcification.
3. Stroma of tumours such as uterine fibroids, breast cancer, thyroid adenoma, goitre etc show
calcification.
4. Cysts which have been present for a long time may show calcification of their walls e.g.
epidermal and pilar cysts.
5. Calcinosis cutis is a condition of unknown cause in which there are irregular nodular deposits
of calcium salts in the skin and subcutaneous tissue.
6. Senile degenerative changes may be accompanied by dystrophic calcification such as in
costal cartilages, tracheal or bronchial cartilages, and pineal gland in the brain etc.

Fatty change and hyaline change of cell injury

Fatty change and hyaline change are morphologic forms of reversible cell injury

Fatty change:

● It is the accumulation of neutral fat within parenchynal cells. Seen in the liver, heart,
skeletal muscle, kidney and others.
● It common in the liver- •Because the liver plays central role in fat metabolism. The fatty
change may be mild reversible or producing severe irreversible cell injury and death.
This depends on the cause and amount of fat accumulation
● Causes -Starvation,Obesity,Malnutrition,Alcoholism etc
Hyaline change
● It is glassy homogenous, eosinophilic material
● It could be seen intra or extra cellular and it is not specific substance.
● This type of degeneration occur after necrosis of tissue.
● In connective tissue: blood vessels fused together& it seems homogeneous mass.