Chronic Inflammation

• Chronic inflammation is characterized by a gradual onset and long duration

Pathological Features of Chronic Inflammation

• Chronic inflammation can arise in one of two ways: it may follow acute inflammation due to failure of the defense mechanisms to eradicate the injurious agent or it may be chronic from the start
• Chronic inflammation may be chronic from the start due to an infection with organisms that are usually less toxic than those causing acute inflammation, but are more resistant, e.g. tuberculosis
• Chronic inflammation may be result of prolonged exposure to non-degradable material, e.g. silicosis, an inflammation of the lungs caused by inhalation of silica particles as in miners
• Chronic inflammation may the the result of development of autoimmunity, i.e. antibodies are produced against the individual's own tissues, e.g. rheumatoid arthritis

Types of Chronic Inflammation

• There is chronic non-specific inflammation which usually follows acute inflammation, e.g. chronic abscess & chronic pyelonephritis, also termed "non-specific"

• Chronic non-specific inflammation exhibits similar microscopic features, irrespective to the cause, including chronic inflammatory cells, fibrosis, and vascular thickening

• There is chronic specific inflammation, which usually starts chronic and exhibits typical microscopic features like chronic inflammatory cells, fibrosis, and vascular thickening

• Chronic specific inflammation features vary depending on the specific type, such as bilharzia ova in cases of bilharziasis and silica particles in cases of silicosis

• Most chronic specific inflammations occur in the form of granulomas

Granulomas

• A granuloma is a particular form of chronic inflammation characterized by nodular collections of modified macrophages, lymphocytes, plasma cells, and sometimes neutrophils
• Modified macrophages often acquire pink cytoplasm and are called epithelioid cells
• Epithelioid cells commonly coalesce, forming multinucleate giant cells
• Some granulomas show central necrosis

Granulomas - Diseases and Causes:

• Granulomas caused by Bacteria: Tuberculosis from Mycobacterium Tuberculosis, Leprosy from Mycobacterium leprae, Syphilis from Treponema pallidum, Cat-Scratch disease from Gram-negative bacillus
• Granulomas caused by Parasitic diseases: Schistosomiasis from Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum
• Granulomas caused by Fungal diseases: Cryptococcosis from Cryptococcus Neoformans, Coccidioidomycosis from Coccidioides Immitis
• Granulomas caused by Inorganic Metals and Dusts: Asbestosis, Silicosis, Sarcoidosis by Immune mediated causes

Sarcoidosis

• Sarcoidosis definition: Granulomatous disease of unknown cause
• Sarcoidosis most frequently presents between the ages of 20-40, with no sex predilection
• Microscopically, sarcoidosis shows small non-caseating granulomas
• Microscopic examination shows Langhan's giant cells, Schaumann bodies (rounded calcified laminated bodies), and Asteroid bodies (star-shaped inclusions)

Diagnosis of Sarcoidosis

• Diagnosed by clinical and radiographic features
• Diagnosed by lymph node or lung biopsy showing non-caseating granulomas
• Diagnosed by laboratory findings of elevated calcium in blood and urine, also elevated ACE levels (Angiotensin converting enzyme)

Syphilis

• Syphilis definition: Chronic specific infective granulomatous disease caused by Treponema pallidum
• Syphilis may be spread methods of infection including:
• Direct (STD) sexually transmitted disease
• Transplacental
• Blood transfusion (accidentally)

Reaction to Tissue Damage

• Thick walled blood vessels
• Fibrosis
• Perivascular chronic inflammation with infiltrate, especially plasma cells

Sarcoidosis Summary

• Sarcoidosis summary: Multisystem disease of unknown cause characterized by naked non-caseating granulomas in many tissues and organs, mostly in the thoracic organs (90% of cases)

Syphilis Summary

• Syphilis summary: It is a chronic specific, infective, venereal, granulomatous disease caused by Treponema pallidum
• Primary Syphilis presents as a chancre
• Secondary Syphilis presents as skin rash, mucous patches, condyloma lata, and generalized lymphadenopathy
• Tertiary Syphilis presents as syphilitic gumma and diffuse lesions

Bilharziasis Summary

• The disease is endemic in Egypt and caused by schistosoma haematobium and mansoni

Pathogenesis of Bilharziasis

• Cercariae cause maculopapular rash at site of penetration
• Worms cause nothing when living, but allergic necrotizing reaction in the vessel walls when dead

Ova - Bilharziasis

• Cause a local granulomatous reaction resulting in fibrosis.
• Components of the shell cause the reaction
• Antigenic substances from miracidia. cause the reaction
• T- lymphocytes cause the reaction

Bilharziasis of the urinary bladder

• Caused by schistosoma hematobium
• Ova deposition is deposited in the submucosa leading to granulomatous reaction.
• Ova deposition pierces the mucosa at end of micturation leading to terminal hematuria.
  • Site is at the dome, the ureteric orifices, and the bladder neck

Pathological Features of Bilharziasis

• Gross pathological features are granular mucosa, sandy patches which appear as pale irregular sanded areas due to heavy deposition of ova, and bilharzial polyps

Bilharzial Ulcers

• Result from piercing by the ova or stretching of the mucosa over sandy patches
• Cystitis cystica results in mucosal vesicles a few mm in diameter
• Fibrosis occurs in bladder neck or ureter

Brunn's Nests and Cystitis

• Hyperplastic transitional epithelium dipping to form Brunn's nests
• Cystic degeneration of central cells form Cystitis cystica
• Others are lined by columnar epithelium to form Cystitis glandularis

Bilharziasis - Microscopic observations:

• Hyperplasia
• Epithelial dipping can form subepithelial solid nests
• Hydropic degeneration of brunn's nests
• Metaplasia in cystitis cystica precancerous to Adenocarcinoma:
• Squamous metaplasia is precancerous to Squamous cell carcinoma
• Carcinoma in situ progresses to invasive transitional cell carcinoma

Bilharziasis - Submucosa

• Bilharzial reaction in the submucosa is a collection of Eosinophils, Lymphocytes, Plasma cells, Macrophages, Fibroblasts +/-Giant cells

II-Bilharziasis of the Large Intestine

• Caused by schistosoma mansoni
• Site: mostly in rectum; early findings include hyperemia, edema & hemorrhage
• Later findings include bilateral polyps, sandy patches, and Bilharzial ulcers leading to fibrosis
• Microscopically the submucosa exhibits a granuloma forms from a collection of Eosinophils, Lymphocytes, Plasma cells, Macrophages, and Fibroblasts +/-Giant cells

Bilharziasis of the Liver

• Bilharzial hepatic fibrosis effects include the liver enlarging early on
• Effects include, later, the liver shrinking, with a firm irregular outer surface
• On a cut section, thickened portal tracts are visible, with fine delicate grayish bands and coarse thick grayish bands around branches of portal vein (pipe stem fibrosis)

Microscopic Observations for Bilharziasis of the Liver

• Bilharzial granuloma in the portal tracts
• Proliferating capillary
• Bile duct proliferation
• Fibrosis and thickening

Portal Hypertension

• Characterized by high portal venous resistance
• Results in increased portal venous pressure
• Leads to portal hypertension
• Causes splanchnic congestion
• all portal draining areas affected
• Collateral pathways established

Effects of Portal Hypertension

• Congestive splenomegaly
• Creation of Porto-systemic anastomosis include Esophageal varices (fatal hematemesis), Caput medusa (dilated veins around the umbilicus), Piles (bleeding per rectum), Congestion in all portal draining areas
• Ascites is due to Increased pressure in the mesenteric veins causing congestion, and also due to Hypoproteinaemia from defective liver function

Neutrophils, Eosinophils, Lymphocytes and Macrophages in Infections

• Neutrophils increase with bacterial infections
• Eosinophils increase with parasitic infections and allergy
• Lymphocytes increase with viral infections and TB
• Macrophages increase in chronic infections