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Learning objectives for PMDC in Chronic Inflammation
Chronic inflammations/ Granulomatous diseases. The systemic effects of acute and chronic
inflammation and their possible outcomes. Significance of ESR. Examples of induced hypothermia in medicine.
Pathogenesis, clinical features and lab. Diagnosis of Gout.
Management of acute and chronic Gout.
Definition of Chronic Inflammation
Inflammation of prolonged duration (weeks or months) in which active inflammation, tissue destruction and attempts at repair are proceeding simultaneously
Aetiology: Onset & Causes
A. Chronic inflammation from onset (de novo)1. Persistent infection by certain
microorganism2. Prolonged exposure to toxic/aggressive
agent3. Autoimmunity: RA, SLE, Hashimoto’s
thyroiditis, Chronic gastritis of pernicious anaemia
4. Unknown cause: Sarcoidosis, Crohn disease, ulcerative colitis
B. Chronic inflammation developing from acute inflammation(Acute to Chronic)
A. Chronic inflammation from onset (de novo)
1. Persistent infection by certain microorganism
2. Prolonged exposure to toxic/aggressive agent
3. Autoimmunity: RA, SLE, Hashimoto’s thyroiditis, Chronic gastritis of pernicious anaemia
4. Unknown cause: Sarcoidosis, Crohn disease, ulcerative colitis
1.Persistent infection by certain microorganism
Mycobacterium tuberculosis, Mycobacterium lepri, Treponema pallidum, certain viruses, fungi, parasite- low toxicity, delayed hypersensitivity and granulomatous inflammation
Helicobacter pylori- Chronic gastritis, gastric ulcer, duodenal ulcer
2.Prolonged exposure to toxic/aggressive agent
Aggressive action of acid pepsin in gastric juice causing peptic ulcer
Cigarette smoking causing Chronic bronchitis
Toxic plasma lipid components- atherosclerosis
Talc, suture, other nondegradable material Silica- silicosis of lung
B. Chronic inflammation developing from acute inflammation(Acute to Chronic)
Persistence of injurious agent, eg, organism in abscess
Interference in healing process, eg, sequestrum(dead bone) in chronic suppuratve osteomyelitis
Drainage is delayed or inadequate, eg, lung abscess
Recurrent bouts of acute inflammation, eg, chronic pyelonephritis, chronic cholecystitis, chronic gout.
Histological types of Chronic Inflammation1. Specific Chronic Inflammation:
histologically distinctive. Granulomatous inflammation is specific inflammation
2. Nonspecific Chronic Inflammation: not histologically distinctive
Granuloma:
Granuloma is a microscopic aggregation of macrophages and epitheloid cells which are modified macrophages, surrounded by a collar of mononuclear leucocyte, principally lymphocyte.
Usually giant cells and occasionally plasma cells are present.
Giant cell of Granuloma:Large cell with more than one nucleus.Formed by fusion of macrophages or epitheloid cell. 20 or
more small nuclei are present.Types:1.Langhans’ giant cells- nuclei are arranged in horse-shoe
pattern. Found in tuberculosis and sarcoidosis2.Foreign body giant cells- haphazardly scattered nuclei.
Found in foreign body granuloma.3.Aschoff giant cell- rheumatic lesion4.Giant cell of ‘Giant cell tumor of bone’- osteoclast type5.Tuton giant cell- in Xanthoma6.Giant cell to reaction to sodium urate crystal in gout** Physiological Giant cell- Osteoclast, megakaryocyte
etc
Malignant giant cell:
Found in- Anaplastic tumor Hodgkin’s disease: Reed-Stenberg giant cell Choriocarcinoma Poorly differentiated astrocytoma
Classification of Granulomatous inflammation
Aetiological classification1. Infectious agent- bacteri, helminth, fungi2. Physical & chemical agents- exogenous &
endogenous3. Autoantigen: Wegener’s grnulomatosis, Giant cell
arteritis4. Unknown: Sarcoidosis, Crohn’s diseaseClassification on Pathogenesis1. Immune granuloma2. Foreign body granulomaHistological classification1. Non caseating granuloma2. Caseating granuloma3. Suppurative granulomatous inflammation4. Diffuse granulomatous inflammation
A. Infectious agentBacteria:1. Mycobacterium tuberculosis- tubercle-
noncaseating/hard & caseating/soft2. Mycobactrium lepri- tuberculoid & lepromatous3. Treponema pallidum- GummaHelminth:1. W. bancrfti2. A. lumbricoides3. SchistosomaFungi:Rhinosporidiosis seeberiCryptococcus neoformans, Coccidioido immitis &
Histoplasma capsulatum
Nonspecific chronic Inflammation
Chronic inflammatory ulcer- peptic ulcer Chronic suppuratve inflammation- chronic
abscess, chronic pyelonephritis, chronic osteomyelitis
Chronic fibrinous, serous or serofibrinous inflammation following acute inflammation
Chronic catarrhal inflammation- chronic allergic rhinitis
Chronic necrotizing inflammation- chronic amoebiasis
Systemic effects of Acute Inflammation
Fever: Leucocytosis, specially neutrophilic leucocytosis-
due to stimulation of bone marrow leading to release of immature cells in the circulation(shift to the left)
Synthesis of ‘acute phase protein’- liver synthesizes acute phase protein like C reactive protein(CRP), Fibrinogen and Serum Amyloid A(SAA).
CRP is a marker of activity and very useful prognostic test for active Rheumatic fever and other conditions where there is increased tissue necrosis like MI. As it is not influenced by other factors, so it is more useful than ESR.
Increased Fibrinogen level is responsible for high ESR. SAA is responsible for deposition of amyloid in different tissues
Others- lethargy, anorexia, sweating, tachycardia, hypotension, hypoglycaemia leading to shock due to liberation of different cytokines, particularly IL1, TNF.
Systemic effects of Chronic Inflammation Fever
Anaemia Leucocytosis- lympho or monocytosis ESR- elevated Amyloidosis
