L6: Chronic Inflammation

Learning Obejectives

• Define chronic inflammation

• Distinguish the two major chronic inflammatory processes

• Identify the histologic hallmarks of chronic inflammation and illustrate its effects

• List the major causes of granulomatous inflammation

• Describe the characteristic morphological features of granulomatous inflammation.

• Compare the differences between acute and chronic inflammatory responses.

Definitions of chronic inflammation

• a prolonged process where destruction and inflammation proceed at the same time

Major chronic inflammatiory processes

Following acute inflammation

• acute inflammation not resolved because of

  • persistence of inciting stimulus

  • interference of normal healing processes

  • repeated bouts of acute inflammation

• mixture of reactions occur

  • acute inflammation

  • demolition

  • repair with fibrous scarring (due to repeating scarring)

  • regeneration

• lesion may occur: chronic suppurative inflammation

• examples

  • empyema thoracis

  • chronic osteomyelitis

  • chronic pyelonephritis

Distinct process from the outset

• viral infection

• persistent infection by microorganism

  • limited resistance by the body

  • usually intracellular organisms with low toxicity

• insoluble particles

  • silica, asbestos, or other foreign bodies

• persistant state of hypersensitivity

  • non-infective condition: allergy

  • autoimmune condition: rheumatoid arthritis

• unknown aetiology: sarcoidosis, Crohn’s disease, diabetes, Alzheimer’s

Histological hallmarks of chronic inflammation

Infiltration by immune cells

Macrophage

• transformed from mococytes when reaching extra-vascular tissue

• macrophage accumulation persist until injurious agent is eliminated

• accumulation due to

  • continued recruitment from circulation

  • local proliferation

  • prolonged survival and immobilisation at the site of inflammation

• effects of the biological active products released

  • tissue damage

  • influx of other cell types

  • fibroblast proliferation

  • vascular proliferation

  • collagen deposition

  • fibrosis

  • functional impairment of tissues and organs

Lymphocyte

• produce lymphokines: major stimulators of monocytes and macrophages

• cause monocyte chemotaxis, macrophage activation and differentiation

• products produced by activated macrophages → influence B cells and T cells function

Polymorphonuclear leukocytes

• neutrophils: collect to form pus

• eosinophils: respond to IgE and resiponsible to parasitic infection

• mast cells: allergic reaction

Plasma cells

• produce antibodies against

  • persistent antigen in inflammatory site

  • altered tissue components

Granulation tissue formation

• consists of fibroblasts, small blood vessels and inflammatory cells

• pyogenic membrane: pus-filled cavity lining by acutely inflamed granulation tissue

• haemorrhage from thin-walled capillaries due to vascularity

Fibrosis and tissue destruction

• chronic rheumatic valvulitis: valvular stenosis and regurgitation

• chronic gastric ulcer: pyloric stenosis

• rheumatoid arthritis: fibrous ankylosis → severe limitation of movement

• chronic peptic ulcer: endartertis (progressive proliferation of tunica intima → gradual obstruction of small arteries)

Regeneration

• epithelial overgrowth

  • example: edge of gastric ulcer and gall bladder epithelium into muscle wall in chronic cholecystitis

Granulomatous inflammation

Characteristics

• granuloma: collections of modified macrophages (epithelioid cells)

• epithelioid cells

  • abundant, pale pink plump cytoplasm

  • resemble as an epithelial cell

  • less phagocytic

Factors determining its formation

• presence of indigestible organisms or particles

• presence of cell-mediated immunity to inciting agents

Causes

• Bacterial: Mycobacterium tuberculosis, Mycobacterium leprosum, Syphilis

• Parasitic: Schistosomiasis

• Fungal: Cryptococcus

• Inorganic metal and dusts: Silicosis, Berylliosis

• Unknown: Sarcoidosis

Differences between chronic and acute inflammation

• etiological onset

  • brief & intense vs persistent and indolent

• duration

  • days vs weeks to months

• nature

  • exudative vs proliferative

• consequence

  • resolution vs destruction