Pathology Lecture given August 17, 2011 by Noel C. Santos, M.D. AUF School of Medicine, Dept. of Pathology

1. Infectious Disease By Noel C. Santos, M.D.

2. Spectrum of Inflammatory Response to Infection Suppurative (PMN) Inflammation Mononuclear and Granulomatous Inflammation Cytopathic-Cytoproliferative Inflammation Necrotizing Inflammation Chronic Inflammation and Scarring

3. SUPPURATIVE INFLAMMATION Purulent, abscess, liquefaction necrosis

4. GRANULOMATOUS INFLAMMATION

5. CYTOPATHIC-CYTOPROLIFERATIVE INFLAMMATION

6. NECROTIZING INFLAMMATION

7. CHRONIC INFLAMMATION AND SCARRING

8. DIAGNOSING INFECTION History Physical Examination Laboratory Examination Direct Evidence: demonstration of the organism Indirect Evidence: exposure or response (immunologic or Ab)

9. Special Techniques for Diagnosing Infectious Agents Gram stain Most bacteria Acid-fast stain Mycobacteria, nocardiae Silver stains Fungi, legionellae, pneumocystis Periodic acid-Schiff Fungi, amebae MucicarmineCryptococci GiemsaCampylobacteria, leishmaniae, malaria Antibody probes Viruses, rickettsiae Culture All classes DNA probes Viruses, bacteria, protozoa

10. DEMONSTRATION OF THE ORGANISM Microscopy Culture Histology Immunologic (Ab & Ag) DNA (PCR)

12. Gram Stain Gram Positive: violet to black Gram Negative: pink to red COCCI BACILLI

18. Other Staining Techniques Acid Fast Stain Chemical Stains Negative “Stain”

22. Histopathologic Examination Routine H & E stain Histo/Cyto Chemical stains PAS Silver stains Reticulin stains

35. Non-painful lesion in the genitalia

36. Sexual contact 3 weeks ago

37. How will you directly demonstrate the organism?

41. HIV patient, male, homosexual Difficulty of swallowing

44. Few days later developed dyspnea with gelatinous sputum

45. Later died……

47. Media man with high grade fever, chills, body ache Headache later developed seizures Transported to US and later died

48. Plasmodium vivax Plasmodium falciparum

49. 25 year-old male Flu-like syndrome: fever, body malaise, body ache Lymph node enlargement

50. INFECTIOUS DISEASE Causative Agents Mode of Transmission How microbes cause disease? How the host responds? Immunologically Inflammatory response How to approach? History and physical examination What useful laboratory methods to use? CORRECT DIAGNOSIS PROPER TREATMENT

51. BACTERIAL INFECTIONS

52. Mechanisms of Bacteria Induced Injury Fast-growers deprive the host tissues of nutrients, and lower tissue pH. Many bacteria produce one or more factors leukocidins, hemolysins, hyaluronidases, coagulases, fibrinolysins, and enzymesexotoxins Broken-down cell walls release endotoxins (lipopolysaccharide protein complexes) which cause high fever, capillary permeability, shock, DIC.

53. Respiratory Infections Viral Respiratory infections Bacterial Respiratory infections Haemophilus Influenza Tuberculosis Fungal Respiratory infections

54. HaemophilusInfluenzae Infection This coccobacillus causes infections (especially meningitis and pneumonia) in children who are not fully immune-protected Older children are more prone to conjunctivitis ("pink eye") epiglottitis("croup") laryngotracheobronchitis

55. HaemophilusInfluenzae Infection The most virulent strain is type B, which has a capsule. With the introduction of the Hib vaccine for toddlers, the occurrence of serious H. flu B infections has dropped 71%

56. Clinical spectrum HaemophilusInfluenzae Infection acute epiglottitis - may suffocate the child less than 24 hours H. Influenzae pneumonia - pediatric emergency may result in airway obstruction, high mortality rate May cause suppurative meningitis < 5 years old acute conjunctivitis

57. Tuberculosis infects 1/3 of world population kills 3 million patients each year resurgence of MTB because of AIDS increased in MDRTB slow to grow mutation in the RNA polymerase and catalase

58. Mycobacterium aerobic, non spore forming , non motile with waxy coat - acid fastness M. tuberculosis (inhalation of infective droplets) M bovis ( drinking infected milk) M. avis and M. intracellulare - no virulence M. leprae - leprosy

59. Types of Tuberculosis Primary Infection Secondary Infection Disseminated Tuberculosis

60. Primary Tuberculosis Begins with inhalation of MTB and ends with T cell mediated response. + PPD test 3 ways by which Mycobacteria activated T cells interacts with macrophages helper T cells secrete interferon suppressor T cells lyse macrophages infected cells CD4 - and CD 8 - cells lyse macrophage Ghon’s complex

61. Secondary Tuberculosis Reinfection or reactivation of dormant disease. Most often occurs in the apex of lung two features are caseous necrosis and cavities

62. Mophology of MTB Chronic ganulomatous inflammation with caseation necrosis. Miliary TB - hematogenous dissemination of Tbculous lesion small yellow white - millet seeds most frequent in lung, lymph nodes meninges

63. Mycobacterial infection in AIDS patients HIV infected T cells and macrophages - failure to kill mycobacterium Granuloma are less well formed are more necrotic contains more abundant acid fast organisms.

64. Gastrointestinal Infections Viral Enteritis Bacterial Enteritis Shigella bacillary dysentery Typoid fever Cholera Parasitic Intestinal Infection

65. Three Mechanisms of bacterial diarrhea 1.They can invade the gut wall directly. Diarrhea results from the inflammatory exudate, and the stools will contain polys. 2.They can release enterotoxins, either into the gut or into food. 3.They can attach to mucosal cells and cause them to secrete too much water ("enteroadhesive bacteria").

66. Shigella Bacillary Dysentery Dysentery refers to diarrhea with abdominal cramps and tenesmus stools with mucus and blood caused by Shigelladysenteriae S. flexneri S. boydii S. sonnei. Gram negative facultative anaerobes

67. Pathogenesis of Shigella Bacillary Dysentery transmission - fecal oral route Shigella bacteria invades mucosal cells dysentery occurs when bacteria escape phagolysosome and destroy host cells. Shiga toxin - causes hemorrhagic colitis and HUS ( binds to glycolipids and block protein synthesis) in HLA B 27 - chronic arthritis (Reiter’s syndrome)

68. Morphology of bacillary dysentery Hyperemic and edematous colonic mucosa enlarged lymphoid follicles fibrinosuppurativeexudate covers mucosa Histology - mononuclear leucocytic infiltrates within l. propia ulcers covered with neutrophilic reaction

69. Typhoid fever Causative agent Salmonellae flagellated, gram-negative bacteria water and food borne gastroenteritis. Salmonella typhi S. enteritidis S. typhimirium

70. Pathogenesis of Typhoid fever Invade intestinal epithelial cells controlled by invasion genes and induce by low oxygen tension Invade tissue macrophages induced by acidic pH

71. Morphology of Typhoid fever S. enteritidis and typhimirium lesion are Iimited to ileum and colon - erosion of epithelium S typhi - proliferation of phagocytes with enlargement of RES - 2nd week mucosa over swollen node are shed Histopathology - erythrophagocytosis enlarged spleen, random liver necrosis gallstone

72. Cholera Vibrio cholera Gram negative bacteria cause of epidemics characterized by watery diarrhea 140 serotypes, O1 & O139 severe diarrhea

73. Pathogenesis of Cholera Do not invade epithelial cells secrete enterotoxin (cholera toxin) flagellar proteins are involved in attachment

74. Morphology of cholera Do not invade GUT mucosa minor histopathologic changes. Congestion of mucosal lamina propia Mononuclear cell infiltrate Peyer patches hyperplasia.

75. Staphylococcus are normal inhabitants of the nose and skin of most healthy people. (Their favorite habitat is the hair follicles.) Virulence factors include coagulase,hemolysin, and protein A (which ties up Fcportions of antibodies).

76. Two types of Staphylococcus Coagulase-positive staphylococcus (Staphylococcus pyogenes var. aureus) is a potent pathogen. It tends to produce localized infection Coagulase-negative staphylococci (Staphylococcus epidermidis) are skin commensals and opportunists which infect prosthetic heart valves

77. Staphylococcus It is the chief cause of bacterial skin abscesses. Furuncles are single pimples, while carbuncles are pimple clusters Metastatic infections (most commonly, to the heart valves, kidney or the cavernous sinus) Impetigo is a pediatric infection limited to the stratum corneum of the skin -- look for honey-colored crusts.

78. Staphylococcal Infections surgical wounds staphylococcal pneumonia Staphylococcal endocarditis -- a destructive infection of the heart valves

79. Staphylococcal Infections food poisoning due to strains which have produced enterotoxin B, a pre-formed toxin in un-refrigerated meat or milk products Other toxin-related staphylococcal diseases are toxic-shock syndrome (GI upsets, shock, conjunctivitis, rash, liver failure, kidney failure, and loss of skin,

80. Streptococcus live in the throats of healthy carriers cause sporadic and epidemic human disease. Lancefield groups:

81. Lancefield groups of Streptococcus Group A: Strep. pyogenes, with many serotypes, is the familiar pathogen of "strep throat", common skin infections Group B: Newborns, less often, severely compromised adults Group D: Enterococcus (lately Strep. fecalis), causes urinary tract infections, as well as endocarditis Strep. bovis sepsis

82. Streptococcal Infections Streptococcal pharyngitis - is a disease of young people. Complications include retro-pharyngeal abscess, CellulitisLudwig's angina. Scarlet fever - is a strep throat caused erythrogenic toxins.

83. Streptococcal Infections Streptococcal skin infections may mimic any staphylococcal infections (even impetigo), but spreading cellulitis with obvious lymphangitis ("red streaks") is more typical. Erysipelas is a severe skin infection caused by group A strep; geographic of red, thickened, indurated areas of the skin are characteristic.

84. Streptococcal Infections Streptococcal toxic-shock syndrome is mistaken for "evidence of child abuse" Phlegmasia alba dolens ("milk leg") - group A strep infection of deep venous thrombi. Streptococcal pneumonia, like its staphylococcal counterpart, often superinfects viral pneumonia.

85. Streptococcal Infections Post-streptococcal hypersensitivity diseases: rheumatic fever post-streptococcal glomerulonephritis erythemanodosum.

86. Pneumococcus (Strep. pneumoniae) It caused lobar pneumonia. This is still a common terminal infection in debilitated people, though it can strike the young and healthy pneumococcal bronchopneumonia, middle ear infections, sinusitis, and meningitis Spontaneous pneumococcal peritonitis complicates ascites in cirrhotics and nephrotic syndrome patients.

87. Pseudomonas "the water bug" famous opportunists that flourish in people exposed to antibiotics that kill other microbes. Pseudomonas infections are especially common on the burn unit, the ears of diabetics, and the blood of those with severe neutropenia.

88. Pseudomonas The pus may be fluorescent, and grape fragrance is common. Pseudomonas sepsis is often preceded and/or followed by a necrotizing pneumonia. Ecthymagangrenosum is a severe pseudomonas soft tissue infection. bacterial infection centered on the blood vessels, with thrombosis and bleeding, think of a pseudomonas etiology.

90. Chlamydia

91. Herpes genitalis - HSV-2

92. Syphilis (Lues) - Treponemapallidum

93. Yaws - Treponemapallidum, subsppertenue

94. Lymphogranulomavenereum (LGV) - Chlamydia trachomatis

95. Granulomainguinale (Donovanosis) - Calymmatobacteriumgranulomatis

96. Chancroid - Hemophilusducreyi

97. Benign Genital Warts (Condylomataacuminata) - Human papillomavirus (HPV)

99. epididymitis

100. proctitis

101. cervicitis

102. endometritis

103. salpingitis

104. perihepatitis

106. prepubertal vaginitis

107. ?prostatitis,

108. amniotic infection syndrome,

109. disseminated gonococcal infection,

110. chorioamnionitis

111. premature rupture of membranes, and

113. Thank you and good morning!!!