Wilson's disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene, resulting in impaired biliary copper excretion and toxic copper accumulation in tissues.

Pathophysiology

• Basic defect: Decreased biliary copper excretion due to defective ATP7B protein
• Mechanism: Impaired incorporation of copper into ceruloplasmin and reduced copper transport into bile
• Result: Copper accumulation in liver, brain, cornea, and other organs

Clinical Manifestations

Hepatic (Most common initial presentation)

• Acute hepatitis
• Chronic hepatitis
• Cirrhosis
• Fulminant hepatic failure

Neurological

• Movement disorders (tremor, dystonia, chorea)
• Psychiatric symptoms (depression, psychosis, behavioral changes)
• Dysarthria and dysphagia
• Cognitive impairment

Ophthalmologic

• Kayser-Fleischer rings (pathognomonic copper deposits in Descemet's membrane)
• Sunflower cataracts

Other Features

• Renal tubular acidosis
• Hemolytic anemia
• Arthritis
• Cardiomyopathy (rare)

Diagnostic Workup

• Serum ceruloplasmin: Usually decreased (<20 mg/dL)
• 24-hour urine copper: Elevated (>100 μg/24h)
• Hepatic copper content: Gold standard (>250 μg/g dry weight)
• Ophthalmologic examination: Slit-lamp for Kayser-Fleischer rings
• Genetic testing: ATP7B gene mutations
• Brain MRI: "Face of giant panda" sign in severe cases

Treatment

Chelation Therapy

• D-penicillamine: First-line, may worsen neurological symptoms initially
• Trientine: Alternative chelator, better tolerated neurologically
• Tetrathiomolybdate: For neurological presentations

Zinc Therapy

• Zinc acetate/sulfate: Blocks copper absorption, maintenance therapy
• Preferred for asymptomatic patients and maintenance

• Plaque Biofilm:
  • Quorum sensing: bacterial communication
  • Co-aggregation: Gram-negative adherence
• Microbial Shift (Health → Disease):
  • Facultative → Obligate anaerobes
  • Fermenting → Proteolytic
  • Cocci → Rods
  • Non-motile → Motile
• Immunoglobulins:
  • Saliva: IgA
  • GCF: IgG
• Interleukins & MMPs:
  • IL-1β: Most potent bone-destructive cytokine
  • MMP-8 & MMP-1: Collagenases
  • MMP-2 & MMP-9: Gelatinases
  • Activated by neutrophil proteases (e.g., cathepsin G)

⚛️ Hodgkin’s Disease

• Most common subtype: Nodular sclerosis
• Common in India: Mixed cellularity

🧬 Non-Hodgkin’s Lymphoma

• Classification: REAL
• Burkitt lymphoma: Most malignant; t(8;14) & t(2;8) translocations
• EBV association noted
• Angiocentric lymphoma: Non – B-cell

Plaque Formation

• Initial colonizers: Gram – positive bacteria
• Mature plaque: Shift to obligate anaerobes, proteolytic, rods, motile
• Plaque weight: 2×10¹¹ bacteria per gram

Bacterial Complexes

• Red Complex (Most pathogenic): P. gingivalis, T. denticola, B. forsythia
• Green Complex: A. actinomycetemcomitans, E. corrodens, Capnocytophaga
• BANA Test: Detects trypsin – like enzyme in T. denticola, P. gingivalis, B. forsythia

Specific Bacteria

• A. actinomycetemcomitans: Invades host cells, secretes leukotoxin (116 – kDa protein)
• P. intermedia: Increases with steroid hormones (pregnancy/puberty)
• S. oralis: Found in treated gingival sulcus
• S. sanguis: First organism on oral mucosa

Blood Components

• Leukocyte-depleted RBCs: Reduces febrile reactions and CMV transmission
• Platelets: For thrombocytopenia or platelet dysfunction
• Fresh Frozen Plasma (FFP): Contains all coagulation factors
• Cryoprecipitate: High concentration of fibrinogen, Factor VIII, vWF
• Albumin: Volume expansion, hypoalbuminemia

Transfusion Reactions

Most Common: Febrile Non-Hemolytic Transfusion Reaction (FNHTR)

• Incidence: Most frequent transfusion reaction
• Mechanism: Recipient antibodies against donor leukocytes/cytokines
• Presentation: Fever, chills, rigors during or after transfusion
• Management: Stop transfusion, antipyretics, rule out hemolysis
• Prevention: Leukocyte-depleted blood products

Other Important Reactions

• Acute hemolytic: ABO incompatibility (most dangerous)
• Allergic: Urticaria, anaphylaxis (plasma protein sensitivity)
• TRALI: Transfusion-related acute lung injury
• TACO: Transfusion-associated circulatory overload

Pre-transfusion Testing

• ABO/Rh typing
• Antibody screening
• Crossmatching
• Direct antiglobulin test (DAT)

Microbes in Periodontics

Bacteria Associated with Periodontal Health

• Primary Species:

  • Gram-Positive Facultative Bacteria:
    • Streptococcus:
      • S. sanguis
      • S. mitis
      • A. viscosus
      • A. naeslundii
    • Actinomyces:
      • Beneficial for maintaining periodontal health.

• Protective or Beneficial Bacteria:

  • Key Species:
    • S. sanguis
    • Veillonella parvula
    • Corynebacterium ochracea
  • Characteristics:
    • Found in higher numbers at inactive periodontal sites (no attachment loss).
    • Low numbers at sites with active periodontal destruction.
    • Prevent colonization of pathogenic microorganisms (e.g., S. sanguis produces peroxide).

• Clinical Relevance:

  • High levels of C. ochracea and S. sanguis are associated with greater attachment gain post-therapy.

Microbiology of Chronic Plaque-Induced Gingivitis

• Composition:

  • Roughly equal proportions of:
    • Gram-Positive: 56%
    • Gram-Negative: 44%
    • Facultative: 59%
    • Anaerobic: 41%

• Predominant Gram-Positive Species:

  • S. sanguis
  • S. mitis
  • S. intermedius
  • S. oralis
  • A. viscosus
  • A. naeslundii
  • Peptostreptococcus micros

• Predominant Gram-Negative Species:

  • Fusobacterium nucleatum
  • Porphyromonas intermedia
  • Veillonella parvula
  • Haemophilus spp.
  • Capnocytophaga spp.
  • Campylobacter spp.

• Pregnancy-Associated Gingivitis:

  • Increased levels of steroid hormones and P. intermedia.

Chronic Periodontitis

• Key Microbial Species:

  • High levels of:
    • Porphyromonas gingivalis
    • Bacteroides forsythus
    • Porphyromonas intermedia
    • Campylobacter rectus
    • Eikenella corrodens
    • Fusobacterium nucleatum
    • Actinobacillus actinomycetemcomitans
    • Peptostreptococcus micros
    • Treponema spp.
    • Eubacterium spp.

• Pathogenic Mechanisms:

  • P. gingivalis and A. actinomycetemcomitans can invade host tissue cells.
  • Viruses such as Epstein-Barr Virus-1 (EBV-1) and human cytomegalovirus (HCMV) may contribute to bone loss.

Localized Aggressive Periodontitis

• Microbiota Characteristics:
  • Predominantly gram-negative, capnophilic, and anaerobic rods.
  • Almost all localized juvenile periodontitis (LJP) sites harbor A. actinomycetemcomitans, which can comprise up to 90% of the total cultivable microbiota.