Transcript Chapter XV Infections Diseases & Parasitic Diseases

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.