Infectious Diseases PDF

INFECTIOUS DISEASES Routes of Microbial Infection Flora Normal - = Flora...

INFECTIOUS DISEASES Routes of Microbial Infection Flora Normal - = Flora Normal & Routes of entry and dissemination of microbes I. e 2.  Mechanisms used by viral and bacterial pathogens to evade innate and adaptive immunity alter surface proteins -interfere ↳ produce escape - alter host gene For mimic/inhibitimmuneanse -Foreign in host persist dormant prevent immune detection interfereul MHC preventimmunesystema Cells cytokines-endothelial cellsright junctions to contract/open - increase vascular permeability  Spectrum of Inflammatory Responses to Infection attract neutrophils immune cells > - singleno edit nucleus pidtreulosis Ireponem - ↓ forms granulomas TB cancerous G - varicela-zoster virus - overwhelming damage Pathogens not effectively recognized Fungi -  Suppurative inflammation Granulomatous inflammation accumulation of neutrophils , cellular debris (pus) & Tissue necrosis ↑ Mechanisms by which viruses cause injury to cells ↳ attachment - 2 - 2 Y - 5 exit Selected Human Viruses and Viral Diseases VIRAL DISEASES  RNA VIRUS MORPHOLOGY Measles Rash: Dilated skin vessels, edema, mononuclear perivascular infiltrate Koplik spots (Pathognomonic): Necrosis, neutrophils, and neovascularization (opening of Stensen duct – near 2nd upper molar) Lymphoid organs: Marked follicular hyperplasia, large germinal centers, (+) Warthin-Finkeldey cells Warthin-Finkeldey cells (Pathognomonic): Multinucleated giant cells with eosinophilic nuclear and cytoplasmic inclusions (also in lung and sputum) Mumps Parotitis (bilateral in 70%): Interstitial edema and mononuclear cell infiltration Orchitis: Edema, mononuclear cell infiltration, hemorrhage; compression of swollen testis against tunica albuginea → infarction → scarring, atrophy, sterility (if severe) Pancreatitis: Parenchymal and fat necrosis and neutrophil-rich inflammation (due to infection and damage of acinar cells in pancreas) Encephalitis: perivenous demyelination and perivascular mononuclear cuffing Dengue Widespread hemorrhage, necrosis with little attendant inflammatory response SARS-Cov-2 Lung: Diffuse alveolar damage, mononuclear cell infiltration Measles Koplik spots Rash Warthin Finkeldey Cells  DNA VIRUS MORPHOLOGY Herpes Simplex (HSV) Mode of transmission: contact Pink to purple intranuclear inclusion bodies (Cowdry Type A) Multinucleated syncytia with inclusions Varicella Zoster (VZV) Mode of transmission: respiratory aerosols and contact Intraepithelial vesicles (“dewdrops on a rose petal”) Intranuclear inclusions in cells at vesicle base Shingles: Mononuclear infiltrates and cells with herpetic intranuclear inclusion bodies in neurons and supporting cells of sensory ganglia Cytomegalovirus (CMV) Enlarged cells with cellular and nuclear pleomorphism Prominent intranuclear inclusions set off from the nuclear membrane by a clear halo (Owl Eye inclusions) Smaller basophilic cytoplasmic inclusions Focal necrosis with minimal inflammation Epstein-Barr Virus (EBV) Peripheral blood: Absolute lymphocytosis with atypical lymphocytes (CD8+): abundant cytoplasm with multiple clear vacuolations; and oval, indented, or folded nucleus; and scattered cytoplasmic azurophilic granules Lymphoid tissues: Discrete and enlarged (posterior cervical, axillary, inguinal nodes) Liver: Atypical lymphocytes in portal areas or sinusoids with isolated cells or foci of parenchymal necrosis (like other forms of viral hepatitis) Spleen: Enlarged with soft, fleshy, hyperemic cut surface; expanded white pulp follicles and red pulp sinusoids; prone to rupture  VZV “dewdrops on a rose petal” rash HSV Cowdry Type A inclusions CMV “owl eye” inclusions BACTERIAL DISEASES GRAM POSITIVE MORPHOLOGY Staphylococci Pyogenic inflammation with local destruction of host tissue Skin: boils, carbuncles, impetigo, and scalded-skin syndrome Pneumonia: Neutrophilic infiltration with more tissue destruction than that of S. pneumoniae Streptococci Diffuse interstitial neutrophilic infiltrates with minimal destruction of host tissue Cutaneous infections resemble those of staphylococci Scarlet fever: Pharyngitis (S. pyogenes) + Skin manifestations (punctate erythematous rash most prominent in the trunk and inner aspects of arms and legs, and face except circumoral area; skin becomes hyperkeratotic and scaly during defervescence) S. aureus skin manifestatation S. aureus scalded skin syndrome S. pyogenes Scarlet fever GRAM POSITIVE MORPHOLOGY Corynebacterium Pseudomembrane: coagulated fibrinosuppurative exudate diphtheriae Intense neutrophilic infiltrate, marked vascular congestion, interstitial edema, and fibrin exudation in the underlying tissue Listeria Exudative inflammation with numerous neutrophils monocytogenes Meningitis: G(+) bacilli in CSF: in Listeria meningitis Neonatal sepsis: Listerial abscesses in placenta and G(+) bacilli in meconium Bacillus anthracis Necrosis and exudative inflammation rich in neutrophils and macrophages Hemorrhagic lesions due to vasculitis Inhalational anthrax: perihilar interstitial pneumonia with macrophages, neutrophils, and pulmonary vasculitis  GRAM MORPHOLOGY NEGATIVE Bordetella Laryngotracheobronchitis: bronchial mucosal erosion, hyperemia, and copious mucopurulent exudate (severe) Peripheral lymphocytosis with hypercellularity and enlargement of mucosal and peribronchial lymph nodes Pseudomonas Fleur-de-lis pattern of necrotizing pneumonia (pale necrotic centers with red, hemorrhagic periphery) Coagulative necrosis due to vasculitis (perivascular infiltration of pseudomonads: “perivascular blue haze”) Ecthyma gangrenosum: Well-demarcated necrotic and hemorrhagic oval skin lesions Yersinia pestis Bubonic plague: Lymph node enlargement → infarction or rupture through skin Pneumonic plague: Severe, confluent, hemorrhagic, necrotizing bronchopneumonia with fibrinous pleuritis Septicemic plague: Necrosis in nodes and organs rich in mononuclear phagocyte, fulminant bacteremia, DIC  OTHER GRAM-NEGATIVE SEXUALLY TRANSMITTED INFECTIONS (STIS) Haemophilus ducreyi Klebsiella granulomatis STI Chancroid Granuloma inguinale, Donovanosis Genital involvement Tender, with shaggy, non-indurated Non-tender, beefy red ulcer with borders with yellow-gray exudate at indurated borders, stricture-forming base Lymph node involvement Prominent: buboes → erosion → Not prominent sinuses Histologic features Layers (superficial → deep) Marked epithelial hyperplasia at Neutrophilic debris and the ulcer borders fibrin (pseudoepitheliomatous Granulation tissue with hyperplasia) necrosis and thrombosed G(-) coccobacilli in macrophages vessels (Donovan bodies) (Giemsa and Mononuclear infiltrate w/ Warthin-Starry stain) G(-) coccobacilli (Gram or Silver stains) Chancroid Granuloma inguinale Mycobacterium tuberculosis If cell-mediated immunity of patient is intact: chronic, granulomatous inflammation – IL-12 - produced by APCs, induces Th1 differentiation (occurs 2-4 weeks post-infection) – IFN-γ - produced by Th1 cells to activate macrophages → epithelioid cells and giant cells If depressed cell-mediated immunity: paucity of granulomas; macrophages filled with AFB – Depressed cell-mediated immunity (i.e. HIV, all stages) increases risk of TB Mycobacterium tuberculosis Mycobacterium tuberculosis  Mycobacterium tuberculosis CLINICOPATHOLOGIC FORMS FORM LESIONS SEQUELAE Primary Ghon focus (consolidation): subpleural, (lower Healing by fibrosis (generally part of upper lobe or upper part of lower lobe) happens in immune-competent Ghon complex: GF + pulmonary hilar node individuals, and with anti-TB involvement therapy) Ranke complex: Healed, calcified, later Latency → reactivation (with manifestation of Ghon complex immune compromise) → Secondary TB Progressive primary TB Progressive Primary Resembles acute bacterial pneumonia Miliary pulmonary TB Lobar consolidation, Hilar adenopathy, Pleural effusion Ghon complex Tuberculosis morphology  Mycobacterium tuberculosis CLINICOPATHOLOGIC FORMS FORM LESIONS SEQUELAE Secondary Simon focus (consolidation): apical pleura Healing by fibrosis Localized caseating destructive lesions Progressive secondary TB Progressive Secondary Spread into adjacent lung → erosion into Healing by fibrosis (Pulmonary)* bronchi or vessels (hemoptysis) → cavitation Miliary pulmonary TB (more contagious/infective) Pleural involvement: effusions, empyema, obliterative fibrous pleuritis Miliary pulmonary Scattered small foci of consolidation throughout Systemic Miliary TB the lungs Mycobacterium tuberculosis EXTRAPULMONARY TUBERCULOSIS Kidneys, Adrenals Bones: Osteomyelitis (Pott disease: vertebrae) CNS: Meningitis Lymph nodes: Scrofula – Most common form of extrapulmonary TB Gastrointestinal tract – Most common segment affected: ileum – Rare; due to ↓ consumption of unpasteurized milk (M. bovis) Mycobacterium avium intracellulare (MAC) COMPLEX Disseminated disease in patients with profound immunodeficiency (AIDS and transplant patients) Histologically, macrophages filled with acid-fast bacilli; rare granulomas, lymphocytes, and tissue destruction Mycobacterium leprae Causes Leprosy (Hansen disease) Three forms; manifestations dictated by host cell-mediated immunity (CMI): – Tuberculoid (paucibacillary) – Lepromatous (multibacillary) – Borderline (indeterminate) Principally affects skin and peripheral nerves – Tuberculoid leprosy: Usually skin and nerves – Lepromatous leprosy: More widespread (skin, peripheral nerves, anterior eye chamber, upper airways until larynx, testes, hands and feet, lymph nodes, and spleen)  Clinical Forms of Leprosy TUBERCULOID LEPROMATOUS Cell-mediated immunity Intact Depressed Immune response Positive Negative Antibodies Th1 > Th2 Th2 > Th1 Peripheral nerve involvement (-) (+) not protective; causes erythema nodosum and glomerulonephritis Morphology Granuloma formation Lipid-laden macrophages (Lepra surrounding nerves cells) with globi (masses of acid-fast bacilli) Acid-fast bacilli Rare (paucibacillary) Many (multibacillary) Treponema pallidum Syphilis – 4 stages; congenital form Characteristic plasma-cell predominant inflammatory infiltrate  Stages of Syphilis STAGE LESIONS MORPHOLOGY Primary Chancre: Painless lesion in penis (males), vulva, Plasma cell-rich infiltrate, macrophages, and cervix (females) → erosion → ulcer with lymphocytes indurated borders (hard chancre) Proliferative endarteritis → intimal fibrosis Lymph nodes: nonspecific acute or chronic lymphadenitis, plasma cell-rich infiltrates, or granulomas Secondary Mucocutaneous lesions (oral cavity, palms, and Same as chancre, but with less inflammation soles) Condylomata lata – warty lesions in perianal and vulvar area and oral cavity Tertiary Aortitis Aortitis: obliterative endarteritis of vasa vasorum of Neurosyphilis proximal of proximal aorta → medial scarring → Gumma loss of elasticity Gumma: central coagulation necrosis with palisading macrophages and fibroblasts, plasma cell-rich infiltrate, scant treponemes  gumma maculopapular rash chancre  Congenital Syphilis ORGAN MORPHOLOGY Bones Osteochondritis and periostitis Tibia: saber shins (excessive new bone growth) Nose: saddle nose (destruction of vomer) Liver Fibrosis (hepar lobatum), mononuclear infiltrates Lung Diffuse interstitial fibrosis Pale, airless lung (oneumonia alba) in stillborn infants Others Triad of late manifestations: Interstitial keratitis Hutchinson teet Eight nerve deafness Hutchinson teeth  Serologic Diagnosis of Syphilis Non-Treponemal Treponemal Clinical Use Screening confirmation Monitoring response to therapy Tests Rapid plasma reagin (RPR) Fluorescent Treponemal Verneral Disease Research Antibody Absorption (FTA – Laboratory (VDRL) ABS) Microhemagglutination assay for antibodies of T. pallidum (MHA – TP) Detects Anticardiolipin antibodies Anti T. pallidum antibodies  Anaerobic Infections Abscess formation: morphologically similar with that of pyogenic organisms Clostridial infections: causes disease through exotoxins ORGANISM AND TOXIN CLINICAL DISEASE MORPHOLOGY C. perfringens Clostridial cellulitis Tissue necrosis → inflammation α-toxin (lecithinase, Gas bubbles; severe sphingomyelinase) Gas gangrene myonecrosis C. difficile Pseudomembranous colitis Volcano-like mucopurulent Toxin A: chemokine exudate Toxin B: cytotoxin FUNGAL DISEASES  YEAST Candida albicans Cryptococcus neoformans Pneumocystis jirovecii Significance Most prevalent fungal pathogen of Important cause of CNS infections Important cause of pneumonia in humans in immunocompromised patients AIDS patients Forms Yeast, pseudohyphae at 20oC, Yeast with thick, gelatinous Cysts: Cup-shaped or oval with germ tubes at 37oC capsule containing PAS and central dot, Gomori Methenamine mucicarmine (+) polysaccharide Silver (+) Involvement Superficial infection on mucosal Lung (primary site of infection) Rapidly progressive bilateral surfaces (Oral thrush, esophagitis) CNS: Meninges, cortical gray pneumonia Invasive: Heart, CNS, Eye, Liver matter, basal nuclei Morphology Thrush: matted organisms and Immunocompromised: Soap Alveolar interstitial thickening inflammatory debris bubble lesions (in meninges or Eosinophilic honeycomb exudate Invasive: Little inflammation, perivascular Virchow-Robin in the lumen of the lung suppurative, or granulomatous spaces) (depending on immune status) Immunocompetent: Granulomas, Suppuration C. albicans C. neoformans  MOLDS Aspergillus Mucor Significance Aflatoxin: ↑ Risk of Liver Cancer (Aspergillus Does NOT cause disease in immunocompetent flavus) patients Involvement Allergic bronchopulmonary aspergillosis Nasal sinuses, lungs: if spores are inhaled Colonizing aspergillosis: Respiratory tract (in Gastrointestinal tract: if spores are ingested patients with cavitation) Rhinocerebral mucormycosis: from nasal sinuses Invasive aspergillosis: Lung, other tissues (heart → orbit and brain (most common in DM patients) valves, brain) Morphology Mold: Fruiting bodies, SEPTATE filaments, Mold: NON-SEPTATE (COENOCYTIC) branching at ACUTE angles (45°) filaments, branching at RIGHT angles (90o) Colonizing: Aspergilloma (fungus ball) with Rhinocerebral: Angioinvasion, necrosis of sparse inflammation or chronic inflammation and periorbital tissues and cranial vault → fibrosis; MINIMAL or NO INVASION Meningoencephalitis with cerebral infarction Invasive: Hemorrhagic infarction: Angioinvasion Lung: Necrotizing pneumonia with sharply delineated, foci and hemorrhagic borders (Target lesions) PARASITIC DISEASES  Protozoans: Malaria Features P. falciparum Most virulent malarial parasite (and most common malarial parasite in the Philippines) Can cause high-level parasitemia, Blackwater fever (acute renal failure) and cerebral malaria (Dürck granulomas) Represents= vascular stasis and small focal inflammatory reactions in cerebral vessels Infects ALL STAGES OF RBCs P. vivax and P. ovale Infects YOUNG RBCs Less virulent infection, no cerebral malaria (+) hypnozoites: form seen in the liver (responsible for RELAPSE when reactivated) P. malariae Infects OLD RBCs Less virulent infection, no cerebral malaria  Nematodes Strongyloides stercoralis – Larvae penetrate skin → lungs → GIT – Autoinfection: filariform (parasitic) larvae hatched in GIT invade colonic mucosa → lungs – Hyperinfection (increased worm burden): may result in the immunocompromised host  Nematodes Trichinella spiralis – Invasive phase: larvae has a widespread penetration across different tissues – Heart: Patchy interstitial myocarditis w/ eosinophils, giant cells – Lung: Focal edema, hemorrhage, eosinophils – CNS: Diffuse lymphocytic and eosinophilic infiltrates – Skeletal muscles: Formation of cysts in striated muscles with richest blood supply: diaphragm, EOMs, laryngeal, deltoid, gastrocnemius, intercostal muscles Nurse cell – skeletal muscle losing striations, and forming a capsule to nurture the growing larva  Nematodes Lymphatic filariasis – Brugia malayi, Wuchereria bancrofti – Lymphatic: Persistent lymphedema (extremities, scrotum, penis, vulva) Hydroceles (testis) → thickening and calcification of tunica vaginalis Elephantiasis: dilated dermal lymphatics, subcutaneous fibrosis, epithelial hyperkeratosis – Lung Eosinophilia (tropical pulmonary eosinophilia) Meyers-Kouwenaar bodies: dead microfilariae surrounded by eosinophilic precipitates  Trematodes Schistosomiasis – Species: S. japonicum, mekongi, mansoni, and haematobium Asia: S. japonicum, mekongi (S. japonicum is endemic in the Philippines) Middle East: S. mansoni o Africa: S. haematobium – Organ involvement Liver: S. japonicum, mekongi, mansoni – Most common cause of death: hepatic cirrhosis Bladder: S. haematobium – Increased risk of bladder squamous cell carcinoma – Main pathology: Granulomatous reaction against schistosome eggs with healing by fibrosis (leading to complications)  Cestodes Taenia solium (pork tapeworm) – Taeniasis: from ingestion of cysticercus → intestinal infection – Cysticercosis: from ingestion of egg Taenia saginata (beef tapeworm) – Causes intestinal disease only Diphyllobothrium latum (fish/broad tapeworm) – Causes intestinal disease only – Leads to vitamin B12 deficiency → megaloblastic anemia Echinococcus granulosus – Causes hydatid disease in liver – Contains hydatid sand (degenerating scolices) – Can cause anaphylaxis, when ruptured The End.