Cell Injury and Diseases

Cell Injury

• Definition: A sequence of events (biochemical and morphologic) upon exposure of the cell to injurious agents.
• Causes:
• Injurious agents
• Excess fat in diet
• Viral hepatitis

Types of Cell Injury

• Reversible cell injury (Degeneration)
• Irreversible cell injury (Cell Death)

Reversible Cell Injury

• Definition: Characterized by accumulation of excess water or fat in cells.
• Microscopic picture:
  • Cellular swelling (cloudy swelling and hydropic swelling)
  • Accumulation of water in the cell (small amount)
  • Cytoplasm: fine granules
• Organs affected:
  • Liver
  • Kidney
  • Heart
• Clinical Picture:
  • Liver: no significant change
  • Kidney: proteinuria
  • Heart: dilatation
• Fate:
  • Can recover with removal of injurious agent
  • Persistence of injurious agent leads to irreversible cell injury

Irreversible Cell Injury (Cell Death)

• Definition: Death of large groups of cells or tissues within the living body.
• Causes:
  • Injurious agents
• Microscopic picture:
  • Nuclear changes
  • Cytoplasmic changes
• Fate:
  • Cell death

Bilharziasis (Schistosomiasis)

• Chronic, specific, granulomatous infection caused by Schistosoma species, endemic in Egypt
• Life cycle and pathogenesis:
  • Acute schistosomiasis: severe febrile illness, peak after 2 months
    • Early stage: TH1 cells dominate, producing IFN-γ, stimulating macrophages to secrete cytokines TNF, IL-1, and IL-6, leading to fever
  • Chronic schistosomiasis: dominant TH2 response, although TH1 cells persist
    • Parasite egg proteins stimulate mast cells to produce IL-4, leading to TH2 differentiation
    • Both TH1 and TH2 cells contribute to granuloma formation around eggs

Bilharzial Lesions

• Lesions produced by Cercaria:
  • Acute allergic dermatitis at skin penetration sites
  • Gross picture: maculopapular skin rash
  • Microscopic picture: dilated capillaries, neutrophils, eosinophils, and macrophages
• Lesions produced by adult worms:
  • Dead worms: severe inflammation, necrosis, and thrombophlebitis
  • Living worms: brown bilharzial pigment in liver, spleen, and other tissues
• Lesions produced by ova:
  • Recurrent bleeding due to injury by ova spines, leading to anemia
  • Trapped ova: sensitization of T lymphocytes, leading to inflammatory response and granuloma formation

Bilharzial Antigens

• From worms or ova, causing hyperplasia of lymphoid and reticuloendothelial cells

Liver Bilharziasis

• Common in patients with intestinal bilharziasis
• Portal tracts show major changes:
  • Ova are carried as emboli through the portal vein and trapped in small and large portal tracts
  • Granulomas form, leading to fibrosis
• Dead worms: trapped in venules, leading to thrombophlebitis
• Angiomatoids: dilated capillaries in fibrotic portal tracts, representing dilated collateral channels between branches of the hepatic artery and portal veins
• Hepatic lobules: minimal lesions, preserved architecture, and minimal steatosis
• Fine bilharzial periportal fibrosis:
  • Gross picture: normal-sized liver with finely granular surface and dark brown cut surface
  • Microscopic picture: portal tracts show ova, granulomatous inflammation, and fibrosis
• Coarse bilharzial periportal fibrosis:
  • Gross picture: reduced liver size, firm with irregular surface, and dark brown cut surface
  • Microscopic picture: portal tracts show ova, granulomatous inflammation, and fibrosis

Effects and Complications

• 1. Portal Hypertension:
  • Pathogenesis: portal fibrosis leads to compression of portal veins, and angiomatoids convey high pressure of the hepatic artery to the portal veins
  • Effects: splenomegaly, ascites, and opening of porto-systemic venous collaterals
• 2. Portal Vein Thrombosis: may occur due to vascular stasis
• 3. Mild disturbances of liver functions: lowering of plasma proteins
• 4. Ascites: due to portal hypertension and lowering of plasma proteins
• 5. Ammonia Encephalopathy: hepatic portal fibrosis allows ammonia to escape through open porto-systemic collaterals, leading to encephalopathy and coma
• Causes of death in hepatic bilharziasis:
  1. Bleeding (hematemesis)
  2. Superimposed chronic viral hepatitis (relatively common) leading to cirrhosis and liver failure