Inflammation: Acute vs. Chronic

• Inflammation is a local physiological response to tissue injury and a manifestation of disease.

Beneficial Effects of Inflammation

• Destruction of invading organisms.
• Walling off of an abscess cavity to prevent the spread of infection.

Disadvantages of Inflammation

• Space-occupying lesions compressing vital surrounding structures, like abscesses in the brain.
• Fibrosis that distorts tissues and alters their function.

Classification of Inflammation

• Acute inflammation is an initial and transient series of tissue reactions to injury.
• Chronic inflammation is a subsequent and prolonged tissue reaction following the initial response.
• The two main types are also characterized by cell type differences.

Acute Inflammation

• The initial tissue reaction to injurious agents, may last from a few hours to a few days.
• The acute inflammatory response is the same regardless of what causes it.
• The process is described by the suffix "-itis," preceded by the organ or tissue involved, like appendicitis.

Causes of Acute Inflammation

• Microbial infections, such as bacteria and viruses.
• Hypersensitivity reactions, like caused by parasites or tubercle bacilli.
• Physical agents, such as trauma, ionizing radiation, heat, or cold.
• Chemicals, like corrosives, acids, alkalis, or reducing agents.
• Bacterial toxins.
• Tissue necrosis, such as ischaemic infarction.

Appearance of Acute Inflammation

• Redness (rubor) due to the dilatation of small blood vessels.
• Heat (calor) due to increased blood flow (hyperaemia) at a specific region or systemic fever.
• Swelling (tumor) from oedema, which is the accumulation of fluid in the extra-vascular space.
• Pain (dolor) that results from stretching and distortion of tissues. Chemical mediators also contribute, like bradykinin and prostaglandins.
• Loss of function.

Early Stages of Acute Inflammation

• Changes in vessel caliber and blood flow.
• Increased vascular permeability and the formation of fluid exudate.
• Formation of the cellular exudate, which involves the emigration of neutrophil polymorphs into the extravascular space.

Vessel Caliber Changes

• Acute inflammation causes vascular dilatation.
• Precapillary sphincters open, causing blood to flow through all capillaries.

Increased Vascular Permeability

• Hydrostatic pressure at the arterial end forces fluid out into the extravascular space.
• More fluid leaves vessels than returns in acute inflammation creating a net escape of protein-rich fluid to the tissues.
• The net escape of protein-rich fluid is called exudation, a fluid exudate is created.

Fluid Exudate Features

• Vascular permeability causes large molecules, like proteins, to escape from vessels.
• Exudate fluid has elevated protein levels.
• Immunoglobulins are present, important in microorganism destruction, as well as coagulation factors that result in fibrin deposition in extravascular tissues.
• Acutely inflamed surfaces are commonly covered by fibrin (fibrinous exudate).
• Exudates have a high protein content from increased vascular permeability, but transudates have a low protein content because of normal vessel permeability.

Cellular Exudate Formation

• Neutrophil polymorphs in the extra-vascular space is a diagnostic feature of acute inflammation.
• Neutrophil lifespan is 1-3 days.
• Cells in normal circulation are confined to the central stream of blood vessels away from the endothelium.

Neutrophil Stages to Reach Tissues

• Margination: Loss of intravascular fluid causes an increase in plasma viscosity and a slowing of flow. This stasis at the site allows neutrophils to flow in the plasmatic zone.
• Neutrophil adhesion: Called "pavementing" of neutrophils, results from adhesion molecule interaction on neutrophil and endothelial surfaces and is intensified by chemical inflammatory mediators.
• Neutrophil emigration: Neutrophils pass through the walls of small veins. The defect appears self-sealing, with no endothelial cell damage.
• Diapedesis: Red blood cells may also escape, but the process depends on hydrostatic pressure. Large amounts of red blood cells in extravascular spaces implies severe vascular injury.

Later Stages of Acute Inflammation

• Chemotaxis: Neutrophils are drawn to certain chemical substances.
• Chemical mediators: Spread of acute inflammatory response is due to chemicals released from injured tissues.
• Histamine and thrombin up-regulate adhesion molecules on endothelial cells early.
• Endogenous chemical mediators results in vasodilation, neutrophil emigration, chemotaxis, increased vascular permeability, itching, and pain.

Chemical Mediators Released from Cells

• Histamine, Prostaglandins, PGE2/I2, VIP, Nitric oxide, PAF.
• The complement system includes Kinin, Kinins, Complement systems, Activated complement, Plasmin, Fibrinolytic system, Coagulation system, Fibrin, and Fibrin split products,
• Neutrophil polymorphs move via chemotaxis, adhere to microorganisms, and can phagocytose.

Neutrophil Polymorph

• Phagocytosis occurs when neutrophils and macrophages ingest particles or microorganisms.
• Intracellular killing of microorganisms happens at this stage.
• Lysosomal products are released, which both damage local tissue and attract other inflammatory cells.

Macroscopic Types of Acute Inflammation

• Serous inflammation: abundant protein-rich fluid exudate, low cellular content, e.g., peritonitis, synovitis.
• Catarrhal inflammation: mucus hypersecretion, e.g., common cold.
• Fibrinous inflammation: inflammatory exudate contains plentiful fibrinogen, e.g., acute pericarditis, "bread and butter" appearance.
• Haemorrhagic inflammation: severe vascular injury or depletion of coagulation factors, e.g., acute pancreatitis due to proteolytic destruction of vascular walls.
• Suppurative (purulent) inflammation: formation of pus consisting of dying and degenerate neutrophils, infecting organisms, and liquefied tissues.
• Membranous inflammation: epithelium is coated by fibrin, desquamated epithelial cells, and inflammatory cells, e.g., pharyngitis or laryngitis due to Corynobacterium diphtheriae.
• Pseudomembranous inflammation: superficial mucosal ulceration with an overlying slough of disrupted mucosa, fibrin, mucus, and inflammatory cells, e.g., pseudomembranous colitis due to Clostridium difficile after broad-spectrum antibiotic treatment. Necrotizing (gangrenous) inflammation: e.g., gangrenous appendicitis.

Beneficial Effects of Acute Inflammation

• Dilution of toxins that are then carried away in lymphatics.
• Entry of antibodies that lead to lysis or phagocytosis of microorganisms.
• Transport of drugs, e.g., antibiotics.
• Fibrin formation impedes microorganism movement.
• Supply of nutrients and oxygen.
• Stimulation of the immune response by drainage of fluid exudate into the lymphatics, allowing antigens to reach local lymph nodes.

Harmful Effects of Acute Inflammation

• Digestion of normal tissues by enzymes results in vascular damage.
• Swelling, such as from acute epiglottitis in children, obstructs the airway, or swelling in enclosed spaces, like the cranial cavity, increases intracranial pressure decreases blood flow to brain.
• Inappropriate inflammatory response, such as type I hypersensitivity reactions.

Outcomes of Acute Inflammation

• Resolution is the complete restoration of tissue after acute inflammation.
• Suppuration is the formation of pus. Pus accumulation forms an abscess. Deep seated abscesses may discharge pus along a sinus tract or fistula.
• Organization is replacement of damaged by granulation tissue, resulting in fibrosis and scar formation. Progression: Agent from acute inflammation is not removed is not resolved, so it progresses to chronic inflammation.

Systemic Effects of Acute Inflammation

• Pyrexia (fever) is due to endogenous pyrogens, e.g., Interleukin-2, acting on the hypothalamus.
• Constitutional symptoms include malaise, anorexia, and nausea.
• Weight loss that occurs due to negative nitrogen balance.
• Reactive hyperplasia of the reticulo-endothelial system include local or systemic lymph node enlargement with splenomegaly.
• Increased erythrocyte sedimentation rate, and leukocytosis.
• Neutrophilia occurs in pyogenic infections.
• Eosinophilia occurs in allergic and paracytic infections.
• Lymphocytosis occurs in chronic and viral infections.
• Anaemia can result from blood loss or haemolysis, and/or is caused by bone marrow suppression. Amyloidosis: prolonged inflammation elevates serum amyloid A protein that becomes deposited in tissues.

Chronic Inflammation

• May happen over a long period, or have a more specific meaning, where cellular reaction differs from acute inflammation.
• Lymphocytes, plasma cells, and macrophages predominate, with granulation and scar tissue present, as well.
• Chronic inflammation is usually primary (ab initio) but may follow acute inflammation.

Causes of Chronic Inflammation

• Primary chronic inflammation.
• Progression from acute inflammation.
• Recurrent acute inflammation.

Specific Cases of Primary Chronic Inflammation

• Resistance of an infective agent to phagocytosis.
• Tuberculosis and viral infections
• Endogenous/Exogenous Materials
• Silica and suture materials.
• Autoimmune components

Progression from Acute Inflammation

• The most frequent type for the progression to chronic inflammation is the suppurative type.
• Good examples of such chronic abscesses include: an abscess in the bone marrow cavity (osteomyelitis), which is notoriously difficult to eradicate.

Recurrent Acute Inflammation

• Multiple recurrent episodes of acute inflammation lead to replacement of the gallbladder wall muscle by fibrous tissue the predominant cell type becomes the lymphocyte rather than the neutrophil polymorph.

Microscopic Appearance of Chronic Inflammation

• Chronic ulcer: Chronic peptic ulcer has a breach of the mucosa, lined with granulation tissue, and extending through the muscle layers.
• Chronic abscess cavity: Osteomyelitis.
• Thickening of hollow viscus wall: Crohn's disease, chronic cholecystitis.
• Granulomatous inflammation: Caseous necrosis, like in fibrocaseous tuberculosis of the lungs.
• Fibrosis, the most prominent feature once the chronic inflammatory cell infiltrate has subsided.

Microscopic Features

• The cellular infiltrate consists of lymphocytes, macrophages.
• New fibrous tissue may be produce from granulation tissue
• Evidence of destroyed tissue that have regenerate
• It isn’t usually possible to predict cause of chronic inflammation
• Healing include regeneration and cell migration that are regulated by growth factors
• Fibrin is deposited in blood vessels while fibrosis describes the texture of the collagen

Cellular Features

• Lymphocytes
• Plasma cells
• Macrophages

Lymphocytes

• The lymphatic tissue infiltrates contains B and T lymphocytes
• B lymphocytes become transformed into plasma cells which produce cells
• The T lymphocyte is responsible for the cell - mediated and recruit/activate other cell types

Macrophages

• Relatively large cells and move with amoeboid motion through tissues
• Considerable phagocytic capabilities
• After neutrophil polymorphs ingest microorganisms, they are destroyed .
• Examples of organisms that can survive inside macrophages include mycobacteria such as Mycobacterium tuberculosis and M. leprae.

Specialized Forms

• Granulomas are aggregate of epithelioid macrophages
• Epithelioid histiocytes resemble epithelial cells and tend to be arranged in clusters
• Cells possess slight phagocytic activity but they are more secretory and can cause necrosis by forming multinucleate giant cells.

Types of granulomatous causes

• Specific infection : mycobacterium, fungal and viral
• Foregin bodies: keratin, necrotic bone and crystals
• Chemicals: Beryllium
• Drug: allopurinol and sulphonamides
• Unknown: Crohn’s disease, sarcoidosis.

Giant Cells (examples)

• Langhans’ giant cell which have nuclei that are arranged around the peripheral area e,g in TB
• Foreign body giant cell which are randomly scattered the cytoplasm