General Pathology of Infectious Diseases

General Pathology of Infectious Disease Transmission and Dissemination of Microbes Host barriers to infection Spread and dissemination of microbes Release of microbes from the body Sexually transmitted infections Host Barriers to Infection Skin (Less virulent agents) GI, respiratory & urogenital tract  Innate (Physical, NK, MQ, plasma pr) Acquired (B & T lymphocytes)  N. gonorrhea, V. cholera: high number Shigella, Giardia, M tuberculosis: Low number Skin Dense keratinized layer Low pH (5.5), presence of fatty acids, shedding Normal skin flora (bacteria, fungi) Infection: 1- Superficial: dermatophyte 2- Healthy skin: Schistosoma (Collagenas, elastase) S. aureus, HPV, t. pallidum (heat & humidity) 3- Breaks: Wounds (staph, fungi) & burns (Pseudomonas Aeroginosa) Diabetic & pressure related foot sores (multibacterial) Intravenous catheters (staph or grbacilli) Needle sticks (HBV,HCV,HIV). Insect or animal bites (arboviruses, rickettsiae, bacteria, protozoa, helminths) Gastrointestinal tract Acidic gastric secretions (vibrio cholerae suseptible, Shigella & Giardia cysts resistant) Viscous mucous layer Lytic pancreatic enzymes & bile detergents Mucosal antimicrobial peptides (defensins) Normal flora Secretory IgA antibodies (MALT, M cells) Defecation Infections: 1- Disrupted defence mechanisms:  Loss of gastric acidity  Antibiotics that unbalance the normal bacterial flora (pseudomembranous colitis)  Stalled peristalsis or mechanical obstruction (blind loop syndrome)  Resistance of nonenveloped viruses against bile and digestive enzymes (HAV, rotaviruses, reoviruses, Norwalk agents) 2- Entropathogenicty of organisms:  Releasing powerful enterotoxins (staphylococci)  Exotoxins (Vibrio. cholerae, toxigenic E.coli)  Invasion (Campylobacter, Shigella, Salmonella)  Systemic infection (S.typhi)  Fungal infection in immunosuppressed (Candida)  Intestinal protozoal cyst (G.lamblia: brush border, Cryptosporidia: entrocyte, E.histolytica: cytolysis)  Intestinal helminths (Dis: in large numbers, in ectopic sites): Ascaris lumbricoides, hookworms  (IDA), Diphyllobothrium latum (B 12 deficiency), T.spiralis , Echinococcus spp (Tissue). Respiratory tract Mucocilliary blanket (large microbes) Alveolar macrophages (<5µm) Infections:  Damage to mucocilliary defense (smokers, CF, intubation, aspiration of gastric acid)  Attaching to epithelial cells (influenza virus: Hemaglutinin, neuraminidase)  ciliostatic substances → Impair ciliary activity (H. infl & B.pertussis)  After viral infections (S.pneumonia, staphylococci spp)  Escape phagocytosis (M. Tuberculosis )  Depression of cellular immunity (P. jiroveci, Aspergillus)  Growth requirements (rhinoviruses 33°c) Urogenital Tract Regular flushing Anatomy Low pH of vagina  Attachment (gonococci, E.coli)  Obstruction of urinary flow/reflux  Antibiotics (kill the lactobacilli)  Attaching to cervical or vaginal wall (HPV, T. pallidum) Spread and Dissemination of Microbes Confined to the lumen (cholera) Adhere to or proliferate on or in epithelial cells (dermatophytes, papilloma viruses) Invasive by virtue of their lytic enzymes (hyaluronidase by strep and staph)  Spread by planes of least resistance, regional lymphatics and vascular anatomy→bacteremia→colonization of distant organ  In blood: Free (some viruses, most bacteria & fungi, some protozoa, all helminths) within host cells (HSV, HIV, mycobacteria, leishmania & toxoplasma in leukocytes, some viruses eg. Colorado tick fever virus and some parasites by RBCs Secondary foci, bacteremia, sepsis The major manifestations of infectious disease may arise at sites distant from those of microbe entry (chickenpox, measles, poliovirus, sch mansoni, rabies). In e挀椀LO 椀� kin, lhroat lnH㄀唀enz a Dlp nth,e 爀椀a Shl攀팀Ja d猀�ntery Asce渀椀di 渀椀g p yelon epn ri琀椀 s ung, in1est ne , , rinary rac i tJen ue g M laria Lymp ha-c .. � Ty phus Lungs Ch ckenpox Yaws Sa.I va.爀礀 g land Mumps Aabies easies ubella , · El猀攀vi攀爀 2 005 He a ·to n s m ge ou h ritis elon e py p itis E He Y 氀氀 瀀洀 f e o w 攀Ⰰ 瘀攀  Vertical transmission:  The placental-fetal route (ascending, blood stream)→placentitis  Stillbirth and premature delivery (bacterial & mycoplasma)  Maldevelopment of the fetus (congenital syphilis, rubella)  During passage through the birth canal→ gonococcal or chlamydial conjunctivitis  Through maternal milk→ CMV,HBV,HTLV-1, HIV  Vertical transmission of HIV & HBV Release of microbes from the body Spores, cyst, eggs are resistant forms Skin shedding Coughing, sneezing Voiding of urine or feces Insect vectors Sexual route Kissing, talking (EBV, CMV, Mumps Virus) Fecal-oral route (HAV, HEV, poliovirus, rotavirus) Larval penetration of skin (hookworms, schistosomes) Through blood and blood products (HBV,HCV,HIV) From animals to human→Zoonotic infections direct: Listeriosis eating: Trichinella From animals by vectors (eg Lyme) Sexual route: HPV, HSV, HBV, HIV T.pallidum, N. gonorrhoeae, Candida spp, Chlamydia trachomatis Trichomonas spp, phthrius pubis Sexually transmitted infections     Groups at increased risk: Adolescents Men who have sex with the men People who use illegal drugs Sexual abuse Initial site of infection: urethra, vagina, cervix, rectum, oral pharynx Short-lived outside of the host Infectious in the absence of symptoms Infection with one STI increases the risk for additional STIs  Can be spread from a pregnant woman to the fetus and cause severe damage to the fetus or child (Syphilis, C. trachomatis, HSV, HIV) Can be prevented by treatment (HIV 25% 2%