Kuliah 6

• CASE STUDIES OF PATHOPHYSIOLOGY OF ACUTE AND CHRONIC INFLAMMATION
• Inflammation


  A response of vascularized tissues to infections and tissue damage that brings cells and molecules of host defense from the circulation to the sites where they are needed, to eliminate the offending agents
• Causes of inflammation


  • Infections (bacterial, viral, fungal, parasitic) and microbial toxins
  • Tissue necrosis
  • Foreign bodies (dirt, sutures, splinters)
  • Immune reactions (hypersensitivity)
• Inflammation can be triggered by ischemia, trauma, physical and chemical injury (e.g. thermal injury: burns, frost bite)
• Process of inflammation


  1. The offending agent is recognized by host cells and molecules

  2. Leukocytes and plasma proteins are recruited from the circulation to the site

  3. The leukocytes and proteins are activated and work together to destroy and eliminate the offending substance

  4. The reaction is controlled and terminated

  5. The damaged tissue is repaired
• Acute inflammation


  Initial, rapid response to infections and tissue damage
• Chronic inflammation


  Response of prolonged duration (weeks or months)
• Differences between acute and chronic inflammation

  • Onset: Fast (minutes or hours) vs Slow (days)
  • Cellular infiltrate: Mainly neutrophils vs Monocytes/macrophages and lymphocytes
  • Tissue injury, fibrosis: Usually mild and self-limited vs May be severe and progressive
  • Local and systemic signs: Prominent vs Less
• Bee sting


  • Injury caused by bee sting
  • Bee uses barbed stings, which often remain attached to the skin after a single sting
• Bee stings can happen in any age group and are not selective to a particular gender
• Occupations that may increase the risk of exposure to bee stings: construction workers, landscapers, entomologists, beekeepers and exterminators
• Each year in the US, there are about 62 deaths associated with hymenoptera bites
• Signs and symptoms of local inflammation from bee sting

  • Edema
  • Induration
  • Increased warmth
  • Stinger still attached to the skin
• Symptoms of bee sting

  • Pain
  • Swelling
  • Pruritis
  • Bleeding
• Pathophysiology of bee sting

  1. Hymenoptera injects venom via their ovipositors

  2. Low-molecular-weight proteolytic enzymes (Hyaluronidase, Proteases, Phospholipase) degrade the surrounding tissue

  3. Mast cells and basophil activation

  4. Release of histamine causes vasodilation, edema, pain, erythema, increased warmth

  5. High-molecular-weight components act as allergens

  6. Hypersensitivity type I: IgE-mediated immune response causes systemic vasodilation, angioedema, urticaria, hypotension/shock, and death (anaphylaxis)
• Acute appendicitis is inflammation of the vermiform appendix
• Appendicitis occurs most often between the ages of 5 and 45, with a mean age of 28
• The incidence of appendicitis is approximately 233/per 100,000 people
• Males have a slightly higher predisposition to developing acute appendicitis than females
• Approximately 300,000 hospital visits yearly in the United States for appendicitis-related issues
• The diagnosis of appendicitis can be difficult to confirm preoperatively, and the condition may be confused with mesenteric lymphadenitis, acute salpingitis, ectopic pregnancy, and Meckel diverticulitis
• Cause of appendicitis


  Usually an obstruction of the appendiceal lumen, which can be from an appendicolith (stone of the appendix) or other mechanical etiologies
• Other causes of appendiceal obstruction and appendicitis

  • Appendiceal tumors such as carcinoid tumors, appendiceal adenocarcinoma
  • Intestinal parasites
  • Hypertrophied lymphatic tissue
• When the appendiceal lumen gets obstructed, bacteria build up in the appendix and cause acute inflammation with perforation and abscess formation
• Alvarado's MANTRELS scoring system

  • M = Migratory Pain
  • A = Anorexia
  • N = Nausea and Vomiting
  • T = Tenderness at RUQ
  • R = Rebound tenderness
  • E = Elevated temperature
  • L = Leukocytosis
  • S = Shift to the left WBC
• Score <5: Unlikely, Score 5 – 6: Possible, Score 7 – 8: Likely, Score 9 – 10: Highly likely
• Pathogenesis of acute appendicitis

  1. Acute appendicitis is thought to be initiated by progressive increase in intraluminal pressure that compromises venous outflow

  2. Obstruction leads to appendix distension and muscle spasm, increasing intraluminal pressure and compromising venous outflow

  3. Ischemic injury and stasis of luminal contents, which favor bacterial proliferation, trigger inflammatory responses including tissue edema and neutrophilic infiltration

  4. If left untreated, can lead to colon perforation and peritonitis
• In early acute appendicitis, subserosal vessels are congested, and a modest perivascular neutrophilic infiltrate is present within all layers of the wall
• Appendix luminal obstruction can be caused by fecalith, infections (parasitic), lymphoid hyperplasia, or neoplasm
• Appendicitis pathophysiology


  1. Appendix distention and muscle spasm

  2. Intraluminal pressure compromises venous outflow

  3. Irritated parietal peritoneum stimulates somatic nerve

  4. Bacterial invasion at appendix wall, transmural inflammation

  5. Distension of visceral peritoneum triggers autonomic nerve T9-10
• Appendicitis progression


  • Visceral pain around umbilical
  • Somatic pain at right lower quadrant region
  • Migratory pain
  • Colon perforation leads to peritonitis
  • Fever, anorexia, nausea and vomit if left untreated
• Early acute appendicitis


  • Subserosal vessels are congested, modest perivascular neutrophilic infiltrate in all wall layers
  • Inflammatory reaction transforms normal glistening serosa into dull, granular-appearing, erythematous surface
  • Mucosal neutrophils and focal superficial ulceration often present, but not specific
  • Diagnosis requires neutrophilic infiltration of muscularis propria
• Severe acute appendicitis


  • Focal abscesses may form within the wall (acute suppurative appendicitis)
  • Can progress to large areas of haemorrhagic ulceration and gangrenous necrosis that extend to the serosa (acute gangrenous appendicitis)
  • Often followed by rupture and suppurative peritonitis
• Tuberculosis is a communicable chronic granulomatous disease caused by Mycobacterium tuberculosis
• Tuberculosis usually involves the lungs but may affect any organ or tissue in the body
• The World Health Organization considers tuberculosis to be the most common cause of death resulting from a single infectious agent
• It is estimated that 1.7 billion individuals are infected worldwide, with 8 to 10 million new cases and 1.5 million deaths per year
• Tuberculosis flourishes under conditions of poverty, crowding, and chronic debilitating illness
• In the United States, tuberculosis is a disease of older adults, the urban poor, patients with AIDS, and members of minority communities
• Mycobacterium tuberculosis hominis


  Responsible for most cases of tuberculosis, reservoir of infection typically in individuals with active pulmonary disease