Infectious diseaseInfectious disease -Intestinal disease - page 446 -Intestinal disease - page 446

Department of pathology, GXMUDepartment of pathology, GXMU

Typhoid feverTyphoid fever

AmebiasisAmebiasis

bacillary dysenterybacillary dysentery

Introduction

Infectious source: patients & Infectious source: patients & healthy carriershealthy carriers

Transmit Pattern: Transmit Pattern: Fecal-oral routeFecal-oral route

Pathogen: bacilli or parasitesPathogen: bacilli or parasites

Inflammation typeInflammation type

Most common locationMost common location

Intestinal ulcerIntestinal ulcer

DiarrheaDiarrhea

Key points

Typhoid feverTyphoid 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 Willis can be regarded as the Thomas Willis can be regarded as the

pioneer in typhoid fever. Until his claspioneer in typhoid fever. Until his classic description in 1659 and its translatsic description in 1659 and its translation into English in 1684, little had beeion into English in 1684, little had been done to separate this disease from tn done to separate this disease from the other disease with fever.he other disease with fever.

A systemic infection disease presentinA systemic infection disease presenting as continued fever with relative badg as continued fever with relative badycardia ,and abdominal symptoms anycardia ,and abdominal symptoms and psychosis confusion.d psychosis confusion.

Is characterized by involvement of moIs characterized by involvement of mononuclear phagocytic system (MPS), nonuclear phagocytic system (MPS), with typhoid nodule formation, especwith typhoid nodule formation, especially in the Peyer’s patches and solitially in the Peyer’s patches and solitary lymph follicles of lower ileum.ary lymph follicles of lower ileum.

EpidemiologyEpidemiology

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

PathogenPathogen Salmonella typhi (typhoid bacilli) typhoid bacilli are rod-shape, 2-3um long and 0.4-

0.6 um in diameter Three antigenic structures: O antigens; H antigen

s; Vi antigens Endotoxin

Widal reaction

flagellum

TransmissionTransmission

PatientsPatients Healthy carriersHealthy carriers (“Typhoid Mary” )(“Typhoid Mary” ) Fecal-oral Fecal-oral

pattern pattern FliesFlies

Tyhpoid Mary in the cartoons 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 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

PathogenesisPathogenesis

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 ChangesPathological Changes

Typhoid nodule (Typhoid nodule (granulomagranuloma) formation) formation

? ?

Typhoid CellsTyphoid 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

Erythrophagocytosis

Typhoid nodule formation in the liver

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

Intestinal lesionIntestinal lesion

Lower ileumLower ileum and cecum and cecum

4 stages (last 4 weeks)4 stages (last 4 weeks)

Hyperplasis of Peyer’s pathesHyperplasis of Peyer’s pathes

NecrosisNecrosis

UlcerationUlceration

HealingHealing

Peyer’s patches:

a collection of lymphoid follicles

Locate in mucosa and extend into sumucosa

Terminal ileum contains most peyer’s patches

11stst Stage (First week): Stage (First week): Hyperplasia of peyer’s pathesHyperplasia 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 -

22ndnd Stage(The second week) : Stage(The second week) : NecrosisNecrosis

•Yellow or greenish-brown

•From center to peripheral

Clinical

Blood culture † † †

Stool culture †

Clinical

Stool culture †††

Widal reaction †††

33rdrd Stage(The third Stage(The third week) : week) : UlcerationUlcerationRounded 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 ††††

44thth Stage (The Stage (The fourth week): fourth week): Healing Healing

Extraintestinal LesionsExtraintestinal Lesions

Spleen (Sinus histiocytes) -Splenomegaly Spleen (Sinus histiocytes) -Splenomegaly Liver (Kupffer) - hepatomegaly Liver (Kupffer) - hepatomegaly Lymph nodesLymph nodesBone marrowBone 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 featuresClinical features

Bacteremia: blood culture / stool and urine cultureBacteremia: blood culture / stool and urine culture ToxemiaToxemia : D : Disorientation, delirium, delirium （（暂时精神乱暂时精神乱）） ,,

RestlenessRestleness ，， Headache , Headache , Rose spots,Rose spots, Continued Continued fever(fever( 稽留热稽留热 ) ,diarrhea) ,diarrhea , ,Relative BradycardiaRelative Bradycardia

Splenomegaly and/or hepatomegaly Splenomegaly and/or hepatomegaly Leukopenia(Leukopenia( 白细胞少症状白细胞少症状 ))

Hemorrhage Hemorrhage

Perforation Perforation

ComplicationsComplications

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 Stage 2nd Stage 3rd Stage 3th 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 dysenteryBacillary 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 pathogenesisEtiology and pathogenesis

PatientsPatients Healthy carriersHealthy carriers Fecal-oral route Fecal-oral route

Four species of Shigella:Four species of Shigella: S.Flexneri S.Flexneri 福氏福氏 S.Sonnei (S.Sonnei (the most comon causethe most comon cause) ) 宋内氏宋内氏 S.Boydii S.Boydii 鲍氏鲍氏 S.Dysenteriae S.Dysenteriae 志贺氏志贺氏 --Minimal infective dose is less than 1000 organisMinimal infective dose is less than 1000 organis

msmsEndotoxinEndotoxin

Pathological changes and clinical typesPathological changes and clinical types

Location: large intestine, sigmoid, Location: large intestine, sigmoid,

rectum(only involve the superficial layer)rectum(only involve the superficial layer)

Three typesThree types

Acute bacillary dysenteryAcute bacillary dysentery

Chronic bacillary dysenteryChronic bacillary dysentery

Toxic bacillary dysentery Toxic bacillary dysentery

Acute bacillary dysenteryAcute bacillary dysentery

Acute catarrhal inflammation

Acute pseudomembranous inflammation

（ Fibrinous inflammation ）

fall offfall offLyse Lyse

Irregular,map-like,shallow ulcersIrregular,map-like,shallow ulcers

congestioncongestion

edemaedema

infiltrationinfiltration

pseudomembrane

A pseudomembrane covered

on the mucosal surface , yell

owish or yellow-greenish in co

lor

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 un

common

Compare: Transverse Ulcer and longitudinal

ulcer

Clinical featuresClinical features

Bloody mucoid diarrhea are more commonlBloody mucoid diarrhea are more commonlyy

Abdominal discomfort and tenesmusAbdominal discomfort and tenesmus Fever,headache,tireness and anorexia(Fever,headache,tireness and anorexia( 食欲食欲

减退减退 ) ) May last 1 to 2 weeks May last 1 to 2 weeks

                                             

Passage of 10-40 stools per day is usual,stools compose of blood,mucus and neutrophilics

Chronic bacillary dysenteryChronic 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 dysenteryToxic bacillary dysentery

•2~7y children

•S.flexneri & S.sonnei infection

•Intestinal lesions are mild while general toxic sy

mptoms are severe

•Toxic shock & breath failure occur rapidly

ComplicationsComplications

•Bacteremia and septicemia (Malnourished childr

en)

•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

AmebiasisAmebiasis 阿米巴病阿米巴病

Entamoeba histolyticaEntamoeba histolytica 溶组织阿米巴溶组织阿米巴

amebic abscesseamebic abscesse 阿米巴脓肿阿米巴脓肿

Amebic dysenteryAmebic dysentery 阿米巴痢疾阿米巴痢疾

cystscysts 包囊包囊

trophozoitestrophozoites 滋养体滋养体

Flask-shaped ulcersFlask-shaped ulcers 烧瓶状溃疡烧瓶状溃疡

AmoebomaAmoeboma 阿米巴肿阿米巴肿

Glossary-Bacillary dysenteryGlossary-Bacillary dysentery

Amebiasis Amebiasis

Refers to the infection caused by Refers to the infection caused by Entamoeba histEntamoeba histolyticaolytica

Transmit: Fecal-oral route Fecal-oral route May penetrate the mucosa and possibly invade l

ocally(Intestinal amebiasis) or by hematogenous spread to other organs such as liver, lung, brain and cause the organs of amebic abscesse

Human beings are the only known host of the Human beings are the only known host of the ameba

Introduction

EpidemiologyEpidemiology

Worldwide distribution Worldwide distribution 50 million new cases annually; 50 million new cases annually; 50 to 100 thousand deaths among them50 to 100 thousand deaths among them Higher morbidity in rural areaHigher morbidity in rural area Risk groupsRisk groups

Travelers, recent immigrants are most at risk

Intestinal amebiasisIntestinal 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 pathogenEtiology 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 Pathology

Most frequently in Most frequently in cecumcecum,,

less frequency in the less frequency in the ascending colonascending colon,,

sigmoid, rectum, and appendix. sigmoid, rectum, and appendix.

Pinpoint-sized ulcersPinpoint-sized ulcers

Fastener-shaped ulcersFastener-shaped ulcers

Flask-shaped ulcersFlask-shaped ulcers

Large, undermined edges ulcersLarge, undermined edges ulcers

Location:Location:

Ulcer formation: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 Extraintestinal amebiasis -Amebic liver abscesses -Amebic liver abscesses

The most frequent complicationThe most frequent complication Cause by the entry of amebic trophozoites via portCause by the entry of amebic trophozoites via port

al veinal vein Focal enzymatic necrosis of hepatoctyes(abscessFocal enzymatic necrosis of hepatoctyes(abscess

es)es) Abscesses are not true abscesses (neutrophil leucAbscesses are not true abscesses (neutrophil leuc

ocytes are absence)ocytes are absence) Systemic spread of trophozoires,resulting in amebiSystemic spread of trophozoires,resulting in amebi

c abscesses in the brain and lungc abscesses in the brain and lung

Liver ‘abscess’- no real pus

-May be Single or multiple, most f

requently right-sided

-Contain amebic ‘“ pus,” which ha

s the typical reddish- brown hue (l

ikened to anchovy paste 果酱样 ) of liquefied liver

-There are many residual bile duc

ts and blood vessels within the le

sion. The lining is rough and shag

gy.

-There is a connective tissue wall

in older ‘abscesses’.

- Trophozoites of E. histolytica m

ay be found in the abscess wall

The contents are od

orless, pasty, semifl

uid, and reddish- bro

wn hue (likened to a

nchovy paste

Amebic lung abscessesAmebic lung abscesses

Direct extension of hepatic abscesses through the Direct extension of hepatic abscesses through the diaphragmdiaphragm （横隔） （横隔） into the right lobe of the lung; into the right lobe of the lung; may also arise via 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 Typhoid FeverFever

Bacillary Bacillary DysenteryDysentery

Intestinal AmIntestinal Amebiasisebiasis

Location Lower ileum and cecum

sigmoid, rectum

cecum

Inflammation Typhoid granuloma

Fibrinous -pseudomenbrane

Necrosis

Ulcer Longitudinal ulcer

Map-like ulcer Flask-like ulcer

Clinical Continued fever, diarrhea, disorientation, Bradyc

ardiah

Bloody mucoid diarrhea , tenes

mus

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?

psychosis confusion, solitary lymph follicles , Paua New psychosis confusion, solitary lymph follicles , Paua New GuineaGuinea, bacilli, outbreak, , bacilli, outbreak, Salmonella typhi -typhoid bacilli, epidemic, Biliary bile Salmonella typhi -typhoid bacilli, epidemic, Biliary bile gallbladdegallbladder,excrete,conver,excrete,convey,contaminate,deny, refuse to cease,y,contaminate,deny, refuse to cease,quarantinequarantine, , authorityauthority,born with this diease, ,born with this diease, PregnancyPregnancy,Ireland,died,seven of eight household members, ,Ireland,died,seven of eight household members, requestrequest,reject,investi,reject,investigate, concept of healthy carrier was not well known, healthy inspector and police gate, concept of healthy carrier was not well known, healthy inspector and police officer, Isolate,release on the condition she would not work with food ,officer, Isolate,release on the condition she would not work with food ,pseudonypseudonymm,seize, ,seize, inactivated inactivated by gastric by gastric acidacid, thoracic,, thoracic,MesentericMesenteric, swollen, , swollen, hypersensitivityhypersensitivity reaction, oval , reaction, oval , LongitudinalLongitudinal Secondary intes Secondary intestinal tinal TuberculosisTuberculosis,peripheral – ,peripheral – preservepreserve,,elevateelevate, granulation tissue, , granulation tissue, hepatomegalhepatomegaly, Splenomegalyy, Splenomegaly,Pulse, ,Pulse, tenesmustenesmus. . ShigellaShigella, stool mass, stool frequency, or stool , stool mass, stool frequency, or stool flfluidityuidity,,species species Sigmoid,rectum,Sigmoid,rectum,diphtheriadiphtheria,,superficialsuperficial,mucus,mucoid, persistent p,mucus,mucoid, persistent positive,sensible,severe, abdominal ,ositive,sensible,severe, abdominal ,Malnourished, Malnourished, Amebiasis, Amebiasis, EntamoebaEntamoeba histolyti histolytica, trophozoites, Amoeboma Ameba, ca, trophozoites, Amoeboma Ameba, Parasitosis Parasitosis parasite,motile, Lyse, Palpable, parasite,motile, Lyse, Palpable, neutrophil leucocyte anchovy paste, neutrophil leucocyte anchovy paste, sphinctersphincter ani –anal, nerve fiber, ani –anal, nerve fiber, irritateirritateFeces, anus, sensitivity, suppress, compatible, serosa, peritonaeum, pyrexia, hemFeces, anus, sensitivity, suppress, compatible, serosa, peritonaeum, pyrexia, hemolysis, renal failure, Rural, resistant/persistant/ olysis, renal failure, Rural, resistant/persistant/