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General Medicine

Disorder Feature
Diabetes + HTN Avoid thiazides
ACE inhibitors Risk of hyperkalemia
SIADH Hyponatremia; often in small cell lung cancer
Hypothyroidism ↓ Alk Phosphatase
Acromegaly ↑ GH; check IGF-1 levels
Addison’s Hypotension, hyperpigmentation

Bacterial Properties Involved in Evasion of Host Defense Mechanisms

Bacteria have evolved various strategies to evade the host's immune defenses, allowing them to persist and cause disease. Understanding these mechanisms is crucial for developing effective treatments and preventive measures against bacterial infections, particularly in the context of periodontal disease. This lecture will explore the bacterial species involved, their properties, and the biological effects of these properties on host defense mechanisms.

Host Defense Mechanisms and Bacterial Evasion Strategies

  1. Specific Antibody Evasion

    • Bacterial Species:
      • Porphyromonas gingivalis
      • Prevotella intermedia
      • Prevotella melaninogenica
      • Capnocytophaga spp.
    • Bacterial Property:
      • IgA- and IgG-degrading proteases
    • Biologic Effect:
      • Degradation of specific antibodies, which impairs the host's ability to mount an effective immune response against these bacteria.
  2. Evasion of Polymorphonuclear Leukocytes (PMNs)

    • Bacterial Species:
      • Aggregatibacter actinomycetemcomitans
      • Fusobacterium nucleatum
      • Porphyromonas gingivalis
      • Treponema denticola
    • Bacterial Properties:
      • Leukotoxin: A toxin that can induce apoptosis in PMNs.
      • Heat-sensitive surface protein: May interfere with immune recognition.
      • Capsule: A protective layer that inhibits phagocytosis.
      • Inhibition of superoxide production: Reduces the oxidative burst necessary for bacterial killing.
    • Biologic Effects:
      • Inhibition of PMN function, leading to decreased bacterial killing.
      • Induction of apoptosis (programmed cell death) in PMNs, reducing the number of immune cells available to fight infection.
      • Inhibition of phagocytosis, allowing bacteria to evade clearance.
  3. Evasion of Lymphocytes

    • Bacterial Species:
      • Aggregatibacter actinomycetemcomitans
      • Fusobacterium nucleatum
      • Tannerella forsythia
      • Prevotella intermedia
    • Bacterial Properties:
      • Leukotoxin: Induces apoptosis in lymphocytes.
      • Cytolethal distending toxin: Affects cell cycle progression and induces cell death.
      • Heat-sensitive surface protein: May interfere with immune recognition.
      • Cytotoxin: Directly damages immune cells.
    • Biologic Effects:
      • Killing of mature B and T cells, leading to a weakened adaptive immune response.
      • Nonlethal suppression of lymphocyte activity, impairing the immune response.
      • Impairment of lymphocyte function by arresting the cell cycle, leading to decreased responses to antigens and mitogens.
      • Induction of apoptosis in mononuclear cells and lymphocytes, further reducing immune capacity.
  4. Inhibition of Interleukin-8 (IL-8) Production

    • Bacterial Species:
      • Porphyromonas gingivalis
    • Bacterial Property:
      • Inhibition of IL-8 production by epithelial cells.
    • Biologic Effect:
      • Impairment of PMN response to bacteria, leading to reduced recruitment and activation of neutrophils at the site of infection.

Drug Mechanism
Clopidogrel Phosphodiesterase inhibition
LMWH Factor Xa + Thrombin inhibition
Pentasaccharides Factor Xa inhibition only

Type Features
Unconjugated Absent in urine (bound to albumin); hemolysis
Conjugated Seen in Dubin-Johnson
Diagnosis BSP test (Dubin-Johnson)
Genetics Crigler-Najjar Type II – Autosomal recessive
Cholestasis ↑ 5’-nucleotidase
Hypothyroid ↓ Alk Phos

Condition Key Highlights
Restrictive CM Most common cause: Amyloidosis
Hypertrophic CM (HOCM) Sudden death in athletes
HOCM Signs Double apex beat
HOCM Drug Warning Digoxin contraindicated

Epithelium Types

  • Parakeratinized: Retains pyknotic nuclei in stratum corneum
  • Orthokeratinized: No nuclei in stratum corneum
  • Keratinization order: Palate > Gingiva > Tongue > Cheek (most to least)

Keratin Distribution

  • K 1, 2, 10, 12: Orthokeratinized areas
  • K 6, 16: Highly proliferative areas
  • K 5, 14: Stratification specific
  • K 19: Parakeratinized areas

Structural Components

  • Stratum spinosum: Contains keratinosomes/Odland bodies (modified lysosomes)
  • Basal lamina: 300 – 400 Å thick, joins epithelium to connective tissue
    • Lamina lucida (rich in laminin)
    • Lamina densa (rich in collagen type IV)
  • Junctional epithelium: 0.25 – 1.35 mm long, formed by oral + reduced enamel epithelium

Clinical Probing

  • Normal probing depth: 2 – 3 mm (requires apical penetration)
  • Stippling: Orange peel appearance, restricted to attached gingiva
  • Loss of stippling: Early sign of gingivitis

⚡️ Acute & Chronic Features

  • Acute RHF: Pulmonary embolism
  • High-output failure causes: Anaemia
  • EF Normal range: 60 – 75%
  • Pulmonary edema Rx: Sublingual nitroglycerin

💊 Drugs & Interventions

  • Nesiritide: BNP analogue
  • Levosimendan: Inotropic for CHF
  • Coenzyme Q: Used in CHF treatment

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