Inflammation: Types, Causes, and Aims

• Inflammation is the response of living tissues to injury, involving vascular and cellular reactions
• This response aims to eliminate injurious agents, remove necrotic cells, and prepare tissue for repair

Aims of Inflammation

• Isolating and eliminating the injury
• Destroying invading organisms and inactivating toxins
• Achieving healing and repair

Causes of Inflammation

• Biological causes include bacteria, viruses, fungi, and parasites
• Physical agents include excessive heat or cold, radiation, and electricity
• Chemical agents include acids, alkalis, along with organic and inorganic compounds
• Mechanical causes involve wounds, crushing injuries, fractures and foreign bodies

Types of Inflammation

• Acute inflammation is characterized by rapid onset, short duration, a high dose of irritant, and acute inflammatory cells
• Chronic inflammation is characterized by gradual onset, long duration, a low dose of irritant and chronic inflammatory cells
• Subacute inflammation is graded in-between acute and chronic

Nomenclature

• Inflammation nomenclature generally uses the Greek, Latin, or English name of the organ, adding the suffix "itis"
• Gastritis is inflammation of the stomach
• Orchitis is inflammation of the testis
• Glossitis is inflammation of the tongue
• Hepatitis is inflammation of the liver
• Appendicitis is inflammation of the appendix
• Exceptions to this naming convention include Pneumonia where Pneumonia means inflammation of the lung
• Another exception is Pleurisy, where Pleurisy means inflammation of the pleura

Acute Inflammation

• Acute inflammation is defined as the immediate response of living tissue to an injury
• The aim is to deliver leukocytes and mediators to the injury site via the bloodstream

Cardinal Signs of Acute Inflammation

• Redness is due to vascular dilatation
• Hotness is due to increased blood flow
• Pain results from the direct action of chemical mediators on sensory nerve endings
• Pain can also occur due to pressure on nerve endings caused by inflammatory edema
• Swelling results due to accumulation of inflammatory edema
• Loss of function is due to swelling and pain

Pathogenesis of Acute Inflammation - Local Reactions

• Local tissue destruction occurs
• Vascular response includes transient vasoconstriction
• Vascular response includes vasodilatation
• Vascular response includes slowing of the bloodstream
• Vascular response includes dilatation of lymphatics
• Cellular responses involve exudation of leukocytes
• Cellular responses involve phagocytosis

Acute Inflammatory Reactions - Local Reactions

• Local tissue destruction is usually at the irritant's site and depends on its severity
• Transient vasoconstriction results from direct stimulation of the vascular wall of arterioles
• Vasodilatation results from local axon reflex and histamine release
• Slowing of the bloodstream is caused by vasodilatation
• Slowing of the bloodstream is caused by the opening of new capillary buds
• Slowing of the bloodstream is caused by increased vascular permeability
• Slowing of the bloodstream is caused by increased blood viscosity from fluid exudate, swelling, and roughness of the vascular endothelium
• Dilatation of lymphatics occurs, as lymph flow increases during inflammation
• Lymphatic dilation allows drainage of excess extravasated fluid from the interstitial tissue back to the blood

Inflammatory Fluid Exudate

• This is formed by an increase in capillary hydrostatic pressure
• This is formed by increased capillary permeability due to vasodilatation, endothelial injury, and histamine release
• This is formed by increased osmotic pressure within interstitial tissues because of protein breakdown
• Inflammatory Exudate Composition:
  • High protein content (4-8gm%)
  • High specific gravity (above 1018)
  • Turbid and yellowish appearance due to abundant leukocytes
• Fluid Exudate Functions:
  • Dilutes toxins to minimize their cellular effects
  • Transports fibrinogen which is changed to a fibrin network, which: -Helps movement of acute inflammatory cells to the site of the irritant -Entangles to localize the area of infection -Acts as a scaffold for fibroblasts to start repair
  • It transports antibodies of different types to the inflammation site

Cellular Responses

• Consist of exudation of leukocytes
• Consist of phagocytosis

Leukocyte Exudation Stages

• The escape of leukocytes from the blood into interstitial tissue follows these steps:
  • Margination: leukocytes leave the axial zone due to stasis and adhere to the endothelial wall
  • Rolling: leukocytes stick transiently along the endothelial cells, mediated by P-selectin and E-selectin
  • Adhesion: leukocytes firmly adhere to endothelial cells via adhesion molecules such as integrins, Inter-Cellular Adhesion Molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) & Platelet- Endothelial cell Adhesion Molecule-1(PECAM-1)
  • Emigration: White blood cells pass through capillary pores using pseudopodia, moving outside via ameboid movement Chemotaxis: leukocytes are attracted to the injury site along a concentration gradient of chemotactic substances such as bacterial products, cytokines, and components of compliment system like C5a and Leukotriene B4 (LT-B4)

Phagocytosis

• It is defined as the engulfment and destruction of bacteria and dead tissue by phagocytic cells
• Phagocytosis involves these steps:
  • Recognition and Attachment: leukocytes (neutrophils, macrophages, eosinophils, monocytes, and natural killer cells) use cell surface receptors to recognize and attach to bacteria with the help of specific antibodies (opsonins)
  • The process is called opsonization i.e preparing for eating
  • The two major opsonins are IgG and C3b
  • Engulfment: phagocytic cells emit cytoplasmic pseudopods around bacteria after activation of actin filaments beneath the cell wall, enveloping it in a phagocytic vacuole, i.e phagosome
  • The phagosome membrane fuses with the lysosome membrane, releasing lysosomal granules (phagolysosome)
  • Killing and Degradation involve the release of lysosomal enzymes or oxygen-derived free radicals

Systemic Reactions

• Changes in blood cells occur
• Leukocytosis is an increased number of leukocytes (Normal: 4000-10,000/cm)
• Neutrophils increase in pyogenic infections
• Eosinophils increase in parasitic infestation and allergic lesions
• Lymphocytes increase in chronic infections and viral inflammation
• Monocytes increase in typhoid fever & malaria
• Leukopenia is a decrease in the number of leukocytes during typhoid fever and viral infections
• Anemia can occur, with a decrease in red blood cells due to toxic depression of the bone marrow
  • Haemolysis of RBC's occurs in Malaria & haemolytic streptococcal infections.
• Acute phase reactions take place
  • Fever results from the action of cytokines IL1, IL6, and TNF on the thermoregulatory center of the hypothalamus
  • Constitutional symptoms, i.e loss of appetite, anorexia, malaise, and drowsiness.
  • Increased C-reactive protein levels
• Changes in organs occurs
  • Reactive hyperplasia of the draining lymph nodes
  • Parenchymatous organs undergo degenerative changes due to toxaemia
  • Septicaemia occurs by multiplication of virulent organisms in the blood

Chemical Mediators of Inflammation - Cell Derived

• Histamine is released from basophils and mast cells causing vasodilatation and increased vascular permeability
• Serotonin is released from platelets; causing vasodilatation and increased vascular permeability
• Prostaglandins are released from mast cells and leucocytes causing vasodilatation, pain, and fever
• Leukotrienes are released from mast cells and leucocytes to increase vascular permeability, chemotaxis, and leukocyte activation
• Cytokines (IL1, TNF) are released from macrophages, endothelial cells and mast cells, causing endothelial activation, fever, pain, and hypotension

Chemical Mediators of Inflammation - Plasma Derived

• Kinins are produced in the liver and released to plasma
• Kinins cause vasodilatation, increased vascular permeability, smooth muscle contraction, and pain
• Complement products are produced in the liver and released to plasma
• Compliment products: The C3a increases vascular permeability
• Compliment products: The C5a increases vascular permeability & chemotactic activity

Acute Inflammation Course

• Resolution means the complete restoration of the inflamed area to its normal state and occurs when the irritant is mild and tissue damage is minimal
• Progression and spread the irritant is severe and tissue damage is extensive
• Healing by fibrosis (Organization) means the damaged tissue is replaced by fibrous tissue
• Chronicity occurs where the irritant remains for a while and inflammation is changed

Types of Acute Inflammation

• Acute inflammation is categorized by suppression and non-suppuration

Inflammations: non-suppurative

• Catarrhal inflammation
• Fibrinous inflammation
• Serous inflammation
• Serofibrinous inflammation
• Membranous inflammation
• Allergic inflammation
• Haemorrhagic inflammation
• Necrotizing inflammation

Acute Suppurative Inflammations

• Localized (abscess, carbuncle, furuncle)
• Diffuse (cellutitis)

Catarrhal Inflammation

• Involves cute non-suppurative inflammation affecting mucous membranes
• Characterized by excess mucous secretion, as seen in catarrhal rhinitis, and appendicitis

Fibrinous Inflammation

• Involves non suppurative acute inflammation with increased vascular permeability
• Has formation of fibrin-rich inflammatory exudate
• Sites include serous membranes like the pericardium, pleura, and peritoneum
• Also occurs in lung alveoli in lobar pneumonia
• Resolution includes fibrinous exudate degraded by fibrinolysis and removal by macrophages to restore tissue structure
• Organization: Unremoved fibrin stimulates fibroblast and blood vessel growth, leading to scarring

Serous Inflammation

• Acute non- and suppurative inflammation is characterized by serous exudate
• Fluid secreted by mesothelial cells collecting in pleural, peritoneal, and pericardial cavities or joint spaces (effusion), or as bullae on mild burns or viral blisters

Serofibrinous Inflammation

• Acute nonsuppurative inflammation characterized by excess inflammatory fluid rich in fibrin, causing the affected membrane to become opaque
• Occurs as pleurisy with effusion

Membranous Inflammation

• Acute non-suppurative inflammation of mucus surfaces, marked by pseudo membrane formation
• Sites include intestine in bacillary dysentery and throat in diphtheria infections
• Bacteria remain on the mucosal surface, producing potent exotoxins that cause patchy tissue necrosis; exotoxins diffuse through necrotic membrane and submucosa, absorbed by the blood to cause toxaemia
• The membrane is greyish white with a loosely attached structure to the mucous membrane. It detaches easily leaving a superficial bleeding ulcer -The pseudomembrane forms a fibrin network that entangles necrotic mucosal cells, bacteria, and PNLs

Allergic Inflammation

• It is an antigen-antibody reaction
• Presents outpouring of excess inflammatory exudate and increased eosinophils in tissues and blood

Haemorrhagic Inflammation

• Destruction of capillaries with escape of considerable numbers of RBCs into the inflammation area
• Smallpox, haemolytic streptococcal infections, etc

Necrotizing Inflammation

• Acute inflammation associated with wide necrosis
• Results from superimposed thrombosis and vascular obstruction
• Vincent angina, cancrum, etc

Acute Suppurative Inflammation

• Acute inflammation characterized by the presence of pus

Suppurative inflammation Types

• Localized: Abscess, carbuncle, furuncle
• Diffuse: Cellulitis

Abscesses

• These constitute a localized area with suppurative inflammation that drains pus through an single opening.
• Typically caused by pathogenic bacteria, especially staphylococci
• It develops in three stages, which include these stages:
  • Early stage: Central necrosis with a peripheral zone of inflammation containing PNLs (pyogenic membrane); Dead neutrophils release proteolytic enzymes, liquefying central zone margins to form pus
  • Intermediate stage: Central necrotic zone reduces by liquefaction on the margins, which produces a mid-zone of pus, and an outer inflammation zone; Staph releases coagulase enzymes, assisting the fibrin production that localizes the abscess
  • Late stage: pus evacuates, cavity collapses, and healing happens by granulation tissue
  • Complications:
    • Chronicity
    • Spread to regional lymph nodes
    • Ulcer: Deficient epithelization
    • Sinus: A blind tract lined by epithelium, connecting abscess cavity to external surfaces
    • Fistula: A tract lined by epithelium, connecting two hollow organs e.g. vesico-vaginal fistula
    • Keloid: excessive fibrosis
    • Cicatrization: joint deformity, stricture of tubular structures
    • Malignant

Carbuncles

• Carbuncles are defined as localized suppurative inflammation that involves multiple communicating suppurative components. They drain pus through several openings
• Common among diabetic patients due to low immunity and susceptibility to infection with Staph. aureus
• Most lie on the back of the neck and buttocks, where the skin and subcutaneous tissues are thick

Furuncles

• Small boils (abscesses) arise in the root of hair follicles, and pyogenic bacteria (often Staph aureus) causes it.
• Sites: Hairy areas of face, scalp, or chest.

Cellulitis

• A diffuse form of acute suppurative inflammation occurs in loose connective tissue
• Hemolytic streptococcus causes it through the production of hyaluronidase, and streptolysin production, to help spread infection
• Sites: Loose connective tissues like subcutaneous tissues, orbit, pelvis, scrotrum.
• Complications: Lymphangitis, lymphadenitis, septicaemia & pyaemia