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Infectious disease Department of pathology Hui Li [email protected]. Infectious Disease Common Features 1. Etiology: pathogenic microbes parasite 2. 3. epidemiology source of infection route of transmission Susceptible population Pathogenesis entry cell toxin /enzyme, vessel injury immune response Leprosy (麻风) Introduction History Epidemiology Harm Etiology M. leprae Discovered in Norway in1873 by Dr. Armauer Hansen Acid-fast obligate in tracellular bacterium Prefer low tempreture (32 to 34℃) and grow slowly virulence is based on properties of its cell wall Human being seems to be the only victim Transmission Contained in secretion Respiratory pathway Abrasion or wounds Taken up by macrophages disseminates through the blood Clinical course Latant period: 2-4 years Cellular immunity Humoral immunity Lepromin test Pathogenesis A bipolar disease tuberculoid leprosy (T-cell mediated immune response ) lepromatous leprosy (Immunity anergic) Lepromin test Pathogenesis Why leprosy runs varying courses in different persons? Individuals who recognized certain M. leprae antigens and had no disease showed different alleles at the human Bcg locus which was verified to control responses to intracellular bacteria and parasites Types according to pathological changes Tuberculoid leprosy Lepromatous leprosy Borderline leprosy Indeterminate leprosy Tuberculoid leprosy (60-70%) Intact cellular immune response Slow course, spanning decades Limited lesions Few bacilli within the lesion Mainly involve skin and nerves Clinical feature: lepromin test (+) low infectivity good prognosis Tuberculoid leprosy Granuloma similar to hard tubercles 1. epithelioid macrophages 2. giant cells 3. without caseous necrosis 4. Peripheral: CD4+ Th1 IL-2 and IFN-γ 5. few surviving mycobacteria Tuberculoid leprosy Skin lesions: macula or papula gross: flat and red irregular shapes with indurated, elevated, hyperpigmented margins and depressed pale centers Tuberculoid leprosy Skin lesions LM: tuberculoid granuloma enclose blood vessles , cutaneous appendages and nerves extend to the basal cells of epidermis Tuberculoid leprosy Peripheral neuropathy: rigid and swollen nerves From small dermal nerves to nerve trunk N. auricularis magnus (耳大), N. auricularis posterior(耳后) LM Granulomatous inflammatory reactions Fibrosis,absence of nerves Tuberculoid leprosy Clinical pathologic conference Anesthesias, atrophy, contractures, paralysis, liable to trauma, autoamputation of fingers or toes, Lepromatous leprosy (20%) anergic immunity lepromin test (-) Large amouts of bacilli infectious Acute deteriorate, poor prognosis Generally involved the skin, peripheral nerves, anterior eye, upper airways, testes, lymph node, viscera Lepromatous leprosy large aggregates of lipid laden macrophages (lepra cells), often filled with masses of acid-fast bacilli Lack CD4+ TH1 cells at the margins but instead contain many CD8+ suppressor T cells Lepromatous leprosy Skin lesions: Macular, papular, or nodular lesions form on the face, ears, back, extremites leonine faces hypoesthetic or anesthetic Lepromatous leprosy Skin lesions: LM: large amounts of lepra cells and a few lymphcytes infiltration enclose vessels and appendages Clear line (grenz zone ) Lepromatous leprosy Peripheral nerves:ulnar and peroneal nerves Symmetrically invaded with mycobacteria, with minimal inflammation Loss of sensation and trophic changes. Lymph nodes: foamy histiocytes in the paracortical areas, with enlargement of germinal centers splenic red pulp Liver testes Comparison Tuberculoid type Lepromatous type Incidence 70% 20% Immune response Intense Subdued Skin lesion Macula or papula, Protuberant, large tuberculoid, few bacilli amount of bacilli Lepromin test (+) (-) Humoral antibody (+/-) (+++) Involved tissue Limited to skin and nerves Extend to other organs process Develop slowly Relative fast Infectivity Weak Strong Sexually Transmitted Disease STD Venereal Diseases, VD five classic venereal diseases Syphilis Gonorrhea chancroid granuloma inguinale lymphogranuloma venereum Sexually Transmitted Disease, STD In the past decade, the spectrum of sexually transmitted disease (STD) has widened considerably Syphilis (Lues) An important STD Multiple clinical presentations (thus designatied the great imposter) chronic and slowly progressive involve many vital organs in late period Etiology Pathogen: Spirochete Treponema pallidum can not be cultured detectable by silver stains, darkfield examination Transmission Mode: sexual intercourse (>95%) Acquired sypilis transplacental transmission Congenital sypilis Pathogenesis Traverse abraded skin and mucosa Enter lymph circulation Latent period: 10-90 days, average at 21 days Travel through blood and reach various organs and tissue Pathogenesis Scarce protein on surface (Weak antigenicity) Down-regulation of TH1 cells Inadequate cellular and humoral immune response Relapse syphilis and tertiary syphilis Latent syphilis Morphology May affect nearly any organ or tissue in the body Two morphologic patterns of tissue injury 1. Obliterative endarteritis 2. Gumma Morphology 1. Obliterative endarteritis Perivascular inflammation concentric endothelial and fibroblastic proliferative thickening of the small vessels a surrounding mononuclear (principally plasma cell) inflammatory infiltrate, known as cuffing Morphology 2. Gumma (syphiloma) late lesion occurred in any site (liver, bone, testes) Vary in size gray, tough and rubbery, like gum Absorbed, fibrosis, scarring Scarcely calcification Morphology Resemble the lesion of tuberculosis. a center of coagulative necrosis surrounded by many mononuclear leukocytes admixed with macrophages (some resembling epithelioid cells) Acquired syphilis Three distict stages Primary Early stage (contagious Secondary Tertiary Late stage Primary syphilis Chancre After latent period (about 3 weeks) At the site of inoculation, penis, vulva or cervix indurated, button-like papule at first Erodes Accompanied by lymphadenopathy A single, painless, copper-colored, Clean-based, shallow ulcer, with elevated and indurated margin Primary syphilis Chancre LM: obliterative endarteritis perivascular plasma cell cuffing Dark field examination of the exudate Spontaneous healing Secondary syphilis Mucocutaneous rash 1-3 monthes after the primary syphilis Widespread patchy or diffuse Bilateral, symmetric, maculopapular, red-blown Condylomata lata LM: typical vasculitis Nonspecific lymphadenopathy Secondary syphilis Fever, malaise, weight loss Serologic test (+) Spontaneous healing after 1-3 monthes Relapse Latent syphilis asymptomatic serologic tests (+) Tertiary syphilis After a latency period of 10-20 years May affect any part of the body Cardiovascular system (80-90%) Central nervous system (5-10%) Liver, bone, testes, etc. Gumma and scar tissue formation Tertiary syphilis Syphilitic aortitis Confined to thoracic aorta Obliterative endarteritis of nutrient arteries wrinkling or “tree bark-resembling ” of the intimal surface Secondary atherosclerotic plaques Syphilitic aneurysm Aortic insufficient Tertiary syphilis Neurosyphilis Meningovasxular syphilis Tabes Dorsalis General paresis Tertiary syphilis Bone: septal perforation (saddle nose) Liver: hepar lobatum Testes Congenital syphilis Onset after the fourth month Early congenital syphilis (perinatal period) Mucocutanous lesion Rashes ( vesicular or bullous ) Extensive desquamation of the skin Diffuse interstitial inflammation, prominent fibrosis Lung, liver, spleen, etc. Osteochondritis and perichondritis Saddle nose, saber shins, hemolytic anemia, jaundice Congenital syphilis Congenital syphilis Late congenital syphilis Older than two Hutchinson’s teeth Cranial nerve deafness Interstitial keratitis May remain latent until adolescence Clinical Stages and Features Typhoid Fever (伤寒) introduction An acute infectious disease caused by Salmonella typhi. Characterized by striking systemic phagocytes hyperplasia and ulceration of the small intestine Main manifestations: chills, fever, leukopenis, bradycardia, splenomegaly, rose spots of the skin, etc Epidemic 贵州、云南、广西、浙江、江苏和新疆 Etiology Salmonella typhi. Flagellated, gram-negative rod bacteria Virulence: endotoxin flagellar (H) antigen cell wall (O) lipopolysaccharide antigen polysaccharide virulence (Vi) antigen located in the cell capsule A story: Typhoid Marry source of transmission ill persons feces, urine, vomitus, and oral secretions Chronic carriers feces Pathogenesis feces, urine of patients or carrier fly Food and water mouth Stomach, small intestine mononuclear phagocytes mononuclear phagocytes hyperplasia bacteremia Toxemia, septicemia hepatomegaly, splenomegaly, lymphadenopathy chills, fever, rose spots, etc Morphology Characteristics of pathological changes: typhoid cell: large, rich in cytoplasm, often contains ingested bacteria, cell debris, and erythrocyte typhoid granuloma Diagnostic value Morphology typhoid nodule pathology intestine Peyer’s patches in the ileum is the most affected part 1st week Gross: sharply delineated, plateau-like elevations up to 8 cm in diameter, with enlargement of draining mesenteric lymph nodes LM: typhoid granuloma, edema, hyperemia CF: High fever, bradycardia, splenonegaly, rose spots Morphology 2. Necrosis: 2nd week Gross: the lesion of Peyer’s pathch is necrotic and stained by bile. LM: Structureless eosinophilic substance CF: bacteremia, toxemia Morphology 3. Ulceration: 3rd week Necrotic tissue is dissolved by enzyme oval ulcers with their long axis in the direction of bowel flow CF: bleeding, perforation, abdominal pain, diarrhea pathology 4. Healing: 4th –5th week Granulation tissue forms with small scar formation CF: symptoms subside and disappear, widal’s test (+) pathology organs related to reticuloendothelial system mesenteric lymphnode In the terminal ileum Typhoid cell, Typhoid granuloma spleen: enlarged, soft and cherry red in color prominent sinus histocytosis and reticuloendothelial proliferation organs related to reticuloendothelial system liver: enlarged and swelling with tense capsule and round edges, typhoid cell, typhoid granuloma small, randomly scattered foci of parenchymal necrosis Bone marrow: typhoid granuloma with scattered foci of necrosis Failure of normal hematopoiesis Salmonella typhi.(+) Morphology 1. 2. 3. 4. 5. Cholecystitis: chronic carrier CNS Myocardium Skin and muscle: rose spot septicemia Complication and prognosis 4-5 weeks Chloramphenicol remains to be effective since its introduction in 1948 Complications: intestinal hemorrhage perforation and peritonitis lobular pneumonia Bacillary Dysentery (Shigellosis) (细菌性痢疾) introduction An acute inflammation of the colon, caused by shigella. Summer Morphological features: pseudomembranous inflammation and irregular superficial ulcerations Main clinical manifestations: fever, abdominal pain, diaerhea, Tenesmus, pus-mucin-blood mixed stool Etiology and epidemiology Causative agent: Shigella, gram-negative facultative anaerobes Shigella dysenteriae Shigella Flexneri Shigella Boydii Shigella Sonnei Infect only humans Etiology and epidemiology Transmission Source : Carrier, patient Route : Fecal-oral Contaminated food or water Pathogenesis Invade the intestinal mucosal cells but do not usually go beyond the lamina propria Proliferation within the epithelial cells, destroy host cells Endotoxin Shigella dysenteriae: exotoxin cytotoxic enterotoxin neurotoxicant Types Acute bacillary dysentery Chronic bacillary dysentery Toxic bacillary dysentery Acute bacillary dysentery A. Colon: rectum, sigmoid flexure mucous infl. Hyperemic, edematous Pseudo-membranous infl. mucosa necrosis, exudation, hemorrhage Irregular superficial ulcerations necrotic tissue shed off Acute bacillary dysentery Gross: Pseudomembranous inflammation Acute bacillary dysentery LM: Psuedomembrane • Infiltration of Inflammatory cells •Necrotic tissue •Fibrin exudation •Red blood cells Acute bacillary dysentery B. Lymphdenopathy of mesentery mild splenomegaly C. Other organs: heart, liver, kidney cellular degeneration or necrosis Acute bacillary dysentery Clinical manifestation: 1. Toxemia: fever, headache, fatigue, leukocytosis 2. Intestinal lesion abdominal pain, diarrhea with tenesmus, pus-mucus-blood mixed stool, dehydration, etc. Acute bacillary dysentery Prognosis Mostly cured Colonic perforation (rare) Scarcely colonic hemorrhage A few develop into chronic period Chronic bacillary dysentery Chronic bacillary dysentery Characteristics: 1. Associated with species of shigellae: Flexneri 2. Persist several years 3. pathology: ① Chronic ulcer formation; varied in size and depth; ② Fibrosis, the wall of colon is thickened ③ Infiltrated by lymphocytes, monocytes and plasma cells ④ Sometimes the epithelial cells may also proliferate and form polyps Toxic bacillary dysentery Toxic bacillary dysentery Characteristics: 1. toxemia is very severe but the morphological changes are not 2. enlargement of the lymphoid follicles 3. The nature of the inflammation is “serous”, often associated with toxic shock 4. 2-5 years old 5. Shigella Flexneri, Shigella Sonnei “follicular enteritis” The mechanism of toxic shock and DIC Platelet, neutrophils endotoxin Injury of endothelial cell of blood vessel DIC vasoactive substances Spasm of blood vessel Hypoxia Dilatation of capi Blood vol Increase of permeability edema shock parasitosis 寄生虫病 classification protozoal disease 原虫病 trematodiasis 吸虫病 teniasis绦虫病 nematodiasis线虫病 Amoebiasis 阿米巴病 pathogen endamoeba histolytica protozoone epidemiology Worldwide in distribution more prevalent in tropic, subtropics and underdeveloped areas Poor sanitation and poor nutrition entamoeba histolytica life cycle Humans (large bowel) Ingestion of cysts (person to person) Trophozoites,cysts in feces Cysts surveve in food, water entamoeba histolytica source of infection chronic patient and parasite carrier Are killed by dessication ,temperatures above 55℃ be spead by the fecal-oral route routes of infection pathogenesis exopathic factor contact-mediated cytolysis excrete many factors • channel-forming protein • cysteine proteinase pseudopodial movement and phagocytosis internel factor susceptibility of host intestinal dysfunction intestinal concurrent infection A acute amebic dysentery Sites Cecum Ascending colon Sigmoid Rectum Appendix Morphologic Change Gross flask-shaped ulcer (烧瓶状溃疡) morphologic change Microscopically mainly involving the mucosa and sub-mucosa a necrotic process with minimal inflammatory exudate Lymphocytes and plasma cells Trophozoites scattered at the periphery clinical features bloody diarrhea, intestinal pain fever trophozoite(+) prognosis 99% achieved a complete cure a small proportion of cases perforation, haemorrhage progression to chronic inflammation B chronic amebic dysentery Morphologic Change complex • • • • • tissue regeneration Lesion progress Mucosa atrophy inflammatory polyps amoeboma(阿米巴瘤) clinical features Intermittent bellyache, diarrhea intestinal obstruction malnutrition Bacillary dysentery amoebic dysentery Pathogen Epidemiology Shigella, summer and autumn endamoeba histolytica protozoone, sporadic Systemic symptoms Toxemic manifestations including fever No Toxemic manifestations Gastrointestin al symptoms Severe abdominal pain, diarrhea with tenesmus, pus-mucus-blood mixed stool Mild abdominal pain, diarrhea with no tenesmus, jam-like stool signs Tenderness at left lower abdomen Tenderness at right lower abdomen Stool exam pus cell ,red cell, mucus, stool culture, Shigella+ Few leucocyte, many erythrocytes, Charcot-Leyden crystals, Trophozoites + Colonoscopy Irregular Superficial ulcers flask-shaped ulcer amoebic liver abscess Etiology Morphologic Change Gross single the right lobe the abscess contents is chocolate-colored,odorless, like anchovy sauce “巧克力脓肿” Microscopically entensive liquefactive necrosis a scant inflammatory reaction at their margins a shaggy fibrin lining prognosis Usually,Prognosis is good Metronidazole secondary bacterial infection purulent Lesion progresses rupture into adjacent structures amebic pulmonary abscess single Inferior lobe of right lung An extension of a hepatic abscess cerebral amebic abscess through bloodstream multiple cerebral cortex schistosomiasis 血吸虫病 Endemic parasitoses(地方性寄生虫病) Zoonotic infections(人畜共患) human , ox ,horse, goat Major pathologic manifestation granulomas and fibrosis Epidemiology Asia ,Africa, Latin America China:长江中下游13个省市水稻作物地区 Long history the Western Han Dynasty concerted control the incidence measures somewhat reduced. now its prevalence is increasing! Pathogens Schistosoma japonicum日本血吸虫 China and Asia Schistosoma mansoni曼氏血吸虫 Latin America, central Africa, the Middle East schistosoma haematobium埃及血吸虫 northern Africa Schistosoma japonicum Dioecism(雌雄异体) Male oral sucker ventral sucker Female heme-derived pigments Life cycle of schistosomes HUMANS adult worms in blood (veins) Cercariae penetrate skin of humans (water) Eggs in feces (passed into water) Hatched larvae Cercariae emerge from snail (water) penetrate freshwater snail(intermediae host) Development of other larval stages in snail mucosa ulcers eggs bloodstream Reverse bloodstream intestina cavity liver intestinal wall feces granulomas feces pathogenesis Mechanical damage Immunological damage All kinds of antigens cellular immunity Morphologic changes A caused by worms B caused by eggs Pathology caused by worms cercarial dermatitis itching, local edema larvae angiitis Perangiitis spot hemorrhage allergic reaction Adult worms Local endophlebitis periphlebitis total body anemia allergic reaction B Pathology caused by eggs Immature eggs atypical chronic granulomas Mature eggs acute and chronic granulomas Eosinophilic Abscess Microscopically eggs surrounded by radiating.eosinophilic material Eosinophils, epithelioid cells ,multinucleated giant cells lymphocytes, granulation tissue(scarce ) Pseudotubercle,纤维钙化虫卵结节 eggs Destroyed and calcified granulomatous inflammation replaced by fibrosis, hyalinization,and scar formation Sites intestine, liver et al Heterotopia lung,brain et al Intestinal Pathology sigmoid descending colon rectum Submucosa , lamina propria mucosae acute stage Grossly :white, pinhead-sized granulomas are scattered throughout the gut Microscopically: eosinophilic abscess Clinical manifestations dysentery、 eggs(+) chronic stage grossly:atrophy,caesious,thick fibrous wall Microscopically chronic granulomas Fibrosis Calcification Clinical manifestations detection of eggs in excreta(–) in tissue biopsies(+) advanced stage Lesions are complex the wall is greatly thickened by fibrous tissue polyp、carcinoma Pathology of liver Site left lobe portal area early stage Acute granulomas White or yellow ,pinhead-sized nodules advanced stage surfaces: bumpy Cut surfaces: granulomas and a widespread fibrous portal enlargement without distortion of the intervening parenchyma pipe-stem fibrosis(干线型肝纤维化) clinical menifetation portal hypertension esophageal varices ascites • Pathology of spleen early stage allergic reaction advanced stage congestive splenomegaly hypersplenia Pathology of brain Site parietal lobe of cerebral hemisphere Morphologic changes Acute and chronic granulomas cerebral infarction clinical menifetation epilepsy,lunacy,intracranial hypertension,ocupping symptom Lung Early stage of severe inflammation Acute and chronic granulomas kidney Mesangial proliferative or membranous nephropathy 血吸虫病侏儒 Adenohypophysis, thyroid gland ,sexual gland ,adrenal gland skeleton metabolism and growth development Acute Schistosomiasis Summer fall one month after first infection clinical manifestations intense heat, chill, bellyache, diarrhoea, hepatosplenomegaly, albuminuria et al To involve several organs pathological changes acute granulomas serous inflammation hemorrhagic inflammation questions 1. Please briefly describe the pathological features in the four stages of intestinal typhoid, respectively. 2.Compare the pathologic changes of bacillary dysentery and amoebic dysentery.