Infectious disease -Intestinal disease - page 446 Department of pathology, GXMU Typhoid fever Amebiasis bacillary dysentery

Introduction Infectious source: patients & healthy carriers Transmit Pattern: Fecal-oral route Pathogen: bacilli or parasites

Inflammation type Most common location Intestinal ulcer Diarrhea Key points

Typhoid fever 伤寒 Salmonella typhi 伤寒杆菌 Typhoid nodule 伤寒小结 Diarrhea腹泻 Relative bradycardia 相对缓脉 Peyer’s patches 派伊尔氏淋巴集结 / 集合 淋巴小结 Glossary-Typhoid fever

Typhoid fever 公元 3 世纪之初期，张仲 景博览群书，广采众方，凝 聚毕生心血，写就《伤寒杂 病论》。伤寒，又谓， “ 伤于 寒邪 ”, 中医所说的伤寒，广 义上指的是外感热病的总称， 狭义指的是外感风寒之邪， 感而即发的疾病。

Typhoid fever- Typhoid fever- Introduction  Thomas  Thomas Willis can be regarded as the pioneer in typhoid fever. Until his classic description in 1659 and its translation into English in 1684, little had been done to separate this disease from the other disease with fever.  A  A systemic infection disease presenting as continued fever with relative badycardia,and abdominal symptoms and psychosis confusion.  Is  Is characterized by involvement of mononuclear phagocytic system (MPS), with typhoid nodule formation, especially in the Peyer’s patches and solitary lymph follicles of lower ileum.

Epidemiology Distribution   Is still a very important problem in many developing countries   17 Million cases occur per year worldwide, 7 million distribute in Asia, 4 million in Africa, 0.5 million in Latin America   Can be prevented by vanccine High population densities and poor sanitation

Pathogen   Salmonella typhi (typhoid bacilli)   typhoid bacilli are rod-shape, 2-3um long and um in diameter   Three antigenic structures: O antigens; H Vi antigens   Endotoxin Widal reaction flagellum

Transmission  Patients  Healthy carriers (“Typhoid Mary” ) (“Typhoid Mary” )  Fecal-oral pattern  Flies

Tyhpoid Mary in the cartoons Meet the ladies who drive heroes crazy. These are the women you kill for, the women you die for.

Tyhpoid Mary in the movie "Elektra" Movie Photo (Center) Natassia Malthe (Typhoid Mary) and Will Yun Lee (Kirigi) in 20th Century Fox's "Elektra." - A generic term for a carrier of a dangerous disease who is a danger to public because they refuse to take apporpriate precaution

Pathogenesis Invade the mucosa Taken up by macrophages and transported to regional lymph node Ingestion multiplies in lymphoid tissue Bacteremia phase Reinfects lymphoid tissue – endotoxin and delayed hypersensitivity reaction Toxemia phase Incubation period – the first week Intestinal illness – the second week Systemic illness – at the end of the first week

Pathological Changes Typhoid nodule (granuloma) formation ? Typhoid Cells o It is a localized accumulation of large mononuclear cells o such as rheumatism, tuberculosis

Typhoid cells and typhoid nodules (granuloma) is hallmark histologic finding in typhoid fever Typhoid cell Erythrophagocytosis

Typhoid nodule formation in the liver Typhoid cells and typhoid nodules (granuloma) is hallmark histologic finding in typhoid fever

Intestinal lesion  Lower ileum and cecum  4 stages (last 4 weeks) Hyperplasis of Peyer’s pathes Hyperplasis of Peyer’s pathes Necrosis Necrosis Ulceration Ulceration Healing Healing

Peyer’s patches: a collection of lymphoid follicles Locate in mucosa and extend into sumucosa Terminal ileum contains most peyer’s patches

1 st Stage (First week): Hyperplasia of peyer’s pathes The phagocytes in Peyer’s patches of the ileum and the solitary lymph follicles are proliferation and Hyperplasia Macroscopilly Projected on the mucosal surface Microscopilly Typhoid granuloma with a large number of typhoid cells can be seen obviously Clinical Blood culture † † † † Stool culture -

2 nd Stage(The second week) : Necrosis Yellow or greenish-brown From center to peripheral Clinical Blood culture † † † Stool culture †

Clinical Stool culture ††† Widal reaction ††† 3 rd Stage(The third week) : Ulceration Rounded or oval, deep ulcer,which long axis is in the direction of the long axis of the bowel (Longitudinal ulcer-typical finding of typhoid by macroscopically). Compare: Transverse Ulcer?

Clinical Widal reaction †††† 4 th Stage (The fourth week): Healing

Extraintestinal Lesions  Spleen  Spleen (Sinus histiocytes) -Splenomegaly  Liver  Liver (Kupffer) - hepatomegaly  Lymph  Lymph nodes  Bone  Bone marrow The reaction tends to be similar everywhere, with proliferation of large mononuclear cells and foci of necrosis Phagocytes proliferate in Reticuloendothelial system( 网状内皮系统, mononuclear phagocytic system )

Clinical features  Bacteremia:  Bacteremia: blood culture / stool and urine culture  Toxemia  Toxemia : D, Disorientation, delirium （暂时精神 乱）,Restleness ， Headache 乱）,Restleness ， Headache, Rose spots, Continued fever( 稽留热 ) fever( 稽留热 ),diarrhea,diarrhea,Relative Bradycardia  Splenomegaly  Splenomegaly and/or hepatomegaly  Leukopenia( 白细胞少症状 ) Hemorrhage Perforation Complications

Continued fever( 稽留热 ) and Relative Bradycardia: the classical type of pyrexia with its step-ladder rise during the first week, its maintenance during the second and third weeks, and its fall in the fourth week Blood culture Stool culture Widal reaction Splenomagly Rose spots 1st Stage2nd Stage3rd Stage3th Stage Psychosis confusion Leukopenia Days Stage

rose spots: 2-4mm in diameter appear on the trunk of patients;

Summary 1 Pathogen: Salmonella typhi 2 Inflammation: Granuloma 3 Pathological stages: Longitudinal ulcer 4 Clinical features: Continued fever, diarrhea, relative badycardia, abdominal symptoms and psychosis confusion

Bacillary dysentery 细菌性痢疾 Shigella bacteria 志贺氏菌属 / 痢疾杆菌 tenesmus里急后重 Glossary-Bacillary dysentery

Bacillary dysentery is an acute infectious inflammatory disease of the colon caused by Shigella bacteria; characterized by bloody mucoid diarrhea, tenesmus( 里急后重 ) and abdominal pains. It commonly occurs in summer and fall. Introduction

Etiology and pathogenesis  Patients  Healthy carriers  Fecal-oral route Four species of Shigella: S.Flexneri 福氏 S.Flexneri 福氏 S.Sonnei ( the most comon cause ) 宋内氏 S.Sonnei ( the most comon cause ) 宋内氏 S.Boydii 鲍氏 S.Boydii 鲍氏 S.Dysenteriae 志贺氏 S.Dysenteriae 志贺氏 -Minimal infective dose is less than 1000 organisms -Minimal infective dose is less than 1000 organismsEndotoxin

Pathological changes and clinical types  Location:  Location: large intestine, sigmoid, rectum(only involve the superficial layer)  Three  Three types Acute bacillary dysentery Chronic bacillary dysentery Toxic bacillary dysentery

Acute bacillary dysentery Acute catarrhal inflammation Acute pseudomembranous inflammation （ Fibrinous inflammation ） fall off Lyse Irregular,map-like,shallow ulcers congestion edema infiltration pseudomembrane

A pseudomembrane covered on the mucosal surface, yellowish or yellow-greenish in color

Plaques of yellow fibrin and inflammatory debris are adherent to a reddened colon mucosa..

Pseudomembrane Mucosa Submucosa The Pseudomembrane consist of a large deal of fibrin, necrotic epithelium, neutruphils, RBC and bacteria. but the submucosa isn’t greatly involved. Bloody mucoid Diarrhea?Tenesmus?

Shallow, irregular, ragged Map-like ulcers Superficial scar formation Stenosis,hemorrhage and perforation are uncommon Compare: Transverse Ulcer and longitudinal ulcer

Clinical features  Bloody mucoid diarrhea are more commonly  Abdominal discomfort and tenesmus  Fever,headache,tireness and anorexia( 食欲 减退 )  May last 1 to 2 weeks Passage of stools per day is usual,stools compose of blood,mucus and neutrophilics

Chronic bacillary dysentery Transformed from acute bacillary dysentery. The clinical course exceed 2 monthes S.flexneri infection are more common Pseudomembrane,Ulcerations(new lesions) and granulation tissue organization(old lesions) progress repeatedly Polypi formation & stenosis of the bowel occur Bacillary culture from stool is persistent positive

Toxic bacillary dysentery 2~7y children S.flexneri & S.sonnei infection Intestinal lesions are mild while general toxic symptoms are severe Toxic shock & breath failure occur rapidly

Complications Bacteremia and septicemia (Malnourished children) Hemolytic uremic syndrome ( 溶血性尿毒症综合 征 ) Central nervous system lesions Myocarditis

Summary 1 Pathogen: Shigella bacteria 2 Inflammation: Fibrinous inflammation 3 Pathological stages: Map-like ulcer 4 Clinical features: Bloody mucoid diarrhea and tenesmus

Amebiasis阿米巴病 Entamoeba histolytica 溶组织阿米巴 amebic abscesse 阿米巴脓肿 Amebic dysentery 阿米巴痢疾 cysts包囊 trophozoites滋养体 Flask-shaped ulcers 烧瓶状溃疡 Amoeboma Amoeboma阿米巴肿 Glossary-Bacillary dysentery

Amebiasis  Refers  Refers to the infection caused by Entamoeba histolytica   Transmit: Fecal-oral route   May penetrate the mucosa and possibly invade locally(Intestinal amebiasis) or by hematogenous spread to other organs such as liver, lung, brain and cause the organs of amebic abscesse  Human  Human beings are the only known host of the ameba Introduction

Epidemiology  Worldwide distribution  50 million new cases annually;  50 to 100 thousand deaths among them  Higher morbidity in rural area  Risk groups Travelers, recent immigrants are most at risk

Intestinal amebiasis   An infection disease caused by E. histolytica that inhabits the intestinal tract.   Fecal-Oral transmission   Diarrhea - -- Amebic dysentery   Low grade fever

Encysted organism becomes small trophozoites Small trophozoites develop adult trophozoites Ingestion of cysts become a commensal or a highly invasive pathogen Lyse host tissue Become cysts Etiology and pathogen intestinal alkaline medium Move to cecum

Pathogenesis of Amebiasis Adult Trophozoites... Attach to mucosal epithelial cells (MEC) Lyse MEC (contact-dependent cytolytic mechanism) Ulcerate and invade mucosa Cause dysentery spread to other organs via blood to cause a Amebic abscesses in extraintestinal sites Contact lyse by enzyme or Enzymatic necrosis

Pathology Most frequently in cecum, Most frequently in cecum, less frequency in the ascending colon, sigmoid, rectum, and appendix. less frequency in the ascending colon, sigmoid, rectum, and appendix. Pinpoint-sized ulcers Pinpoint-sized ulcers Fastener-shaped ulcers Fastener-shaped ulcers Flask-shaped ulcers Flask-shaped ulcers Large, undermined edges ulcers Large, undermined edges ulcers Location: Ulcer formation:

Pinpoint-sized ulcers

Flask-shaped ulcer mouth neck bottom mucosa submucosa

Flask-shaped ulcer

Amoebae are found in the base and at the margins of ulcers, chiefly in the submucosa

some RBCs are phagocytized by the trophozoites (erythrophagocytosis)

Trophozoite vascular invasion

- Chronic intestinal amebiasis - Palpable mass,tumour-like of granulation tissue that may obstruct colon. -May be mistaken for carcinoma of colon in clinical Amoeboma ( 阿米巴肿 ):

Extraintestinal amebiasis -Amebic liver abscesses  The most frequent complication  Cause by the entry of amebic trophozoites via portal vein  Focal enzymatic necrosis of hepatoctyes(abscesses)  Abscesses are not true abscesses (neutrophil leucocytes are absence)  Systemic spread of trophozoires,resulting in amebic abscesses in the brain and lung

Liver ‘abscess’- no real pus -May be Single or multiple, most frequently right-sided -Contain amebic ‘“ pus,” which has the typical reddish- brown hue (likened to anchovy paste 果 酱样 ) of liquefied liver -There are many residual bile ducts and blood vessels within the lesion. The lining is rough and shaggy. -There is a connective tissue wall in older ‘abscesses’. - Trophozoites of E. histolytica may be found in the abscess wall

The contents are odorless, pasty, semifluid, and reddish- brown hue (likened to anchovy paste

Amebic lung abscesses Direct extension of hepatic abscesses through the diaphragm （横隔） into the right lobe of the lung; may also arise via Direct extension of hepatic abscesses through the diaphragm （横隔） into the right lobe of the lung; may also arise via bloodstream

Summary 1 Pathogen: Entamoeba histolytica 2 Inflammation: Enzymatic necrosis 3 Flask-like ulcer 4 Clinical features: Low grade fever reddish- brown hue (likened to anchovy paste) diarrhea

Typhoid Fever Bacillary Dysentery Intestinal Amebiasis LocationLower ileum and cecum sigmoid, rectumcecum InflammationTyphoid granuloma Fibrinous - pseudomenbran e Necrosis UlcerLongitudinal ulcer Map-like ulcerFlask-like ulcer ClinicalContinued fever, diarrhea, disorientation, Bradycardiah Bloody mucoid diarrhea, tenesmus reddish- brown hue (likened to anchovy paste) diarrhea

Washing hands after going to the toilet, and before handling or eating food. How to prevent these intestinal infectious diseases?

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