20. infectious pathology Flashcards
1
Q
Sarcoidosis
A
is a systemic disease characterized by formation of noncaseating granulomas in different tissues and organs.
Classically seen in African American females
Aetiopathogenesis unknown
2
Q
pathogenesis of sarcoidosis
A
likely due to disordered immune regulation, genetic predisposition and environmental triggers
↑CD4:CD8 T cells ratio
IL2 and IFNγ, and IL-8, TNF, macrophage inflammatory protein 1α (MIP1α)
Anergy to candida and PPD
Polyclonal hypergammaglobulinaemia
2
Q
clinical presentation of sarcoidosis
A
bilateral lymphadenopathy
eye uvitis
skin erythema nodules
spelenomegaly
3
Q
syndromes associated with sarcoidosis
A
lofgen syndrome
heerfordt syndrome
mikuliciz syndrome
3
Q
lofgen syndrome
A
acute form of sarcoidosis
classic triad
4
Q
heerfordt sydrome
A
LMN facial N. palsy
parotid gland enlargemnet
uveitis
5
Q
mikuliciz syndrome
A
lacrimal and salivary gland enlargemnet
6
Q
langhan giant cells with
A
schauman body
asteroid body
7
Q
Diagnosis
A
Is a diagnosis of exclusion
Clinical and image finding
Biopsy- AFB, PAS
Kviem-Siltzbach test
7
Q
Lab finding
A
Elevated serum ACE
Hypercalcemia (1- α hydroxylase activity of epithelioid histiocytes converts 25-dihydroxyvitamin D to 1,25-dihydroxyvitamin
8
Q
Actinomycosis
A
is a rare, chronic and slowly progressive granulomatous disease
caused by filamentous, Gram-positive, anaerobic bacteria from the Actinomycetaceae family (genus Actinomyces) such as Actinomyces israelii
normal flora oral , gi , urogenitial
8
Q
4 main types of actinomycosis
A
cervico facial - common
thoracic - like pnemonia at first
abdominal - appendix cecum and liver
pelvic - iud compli.
9
Q
histology of actinomycosis
A
granules of gram postive bacteria
splendore heoppli rxn
yellow sulfur granules with sinus
9
Q
Syphilis
A
Venereal disease which involves multiple systems (‘the great imitator’)
Caused by the spirochete Treponema pallidum
10
Q
t. pallidum crcts
A
gram negative
obligate
spirochete
seen by dark field microscopy
11
Q
histologic hallmark of syphyllis
how spirochetes attacks mechanism
A
obliterative endarteritis
bind to host fibronectin
type 4 hypersensitivity
12
Q
stages of syphyllis
A
4
primary
secondary
latent
teritiary
13
Q
primary
A
painless chancre
14
Q
secondary
A
condyloma lata
rash (soles and mucosa)
lymphadenophaty
15
Q
latent
A
asymptomatic
16
Q
teritiary 3 manifestation
A
neurosyphillis
aortitis
gumma formation
17
Q
neurosyphillis type
A
tabes dorsalis
meningovascular syphhilis
argyll roberston pupil
18
Q
tabes dorsalis
A
affects dorsal column and dorsal spinal roots
leads to
loss of proprioception
high step page giat and
sensory ataxia
19
Q
argyll robertson pupil
A
prostate pupil
dont constrict for light but does for objects
lesion of intercalates neurons in midbrain
20
aortitis and anerysm why
affects vasa vasorum
21
gumma formation in
liver hepar lobatum
skin
bone
22
congenital syphillis stages
early and late
23
early congenital syphilis
snuffles - rhinitis
hepatosplenomegaly
wimbers sign - bilateral destruction of tibial metaphysis
24
late syphilis
hutchinsons triad
hutchinson incisors
interstitial keratitis
sensorineural deafness
25
congenital common manifest
saddle nose
saber shin
26
Typhoid Fever
by
Caused by Gram-negative bacillus, Salmonella enterica serotype Typhi (formerly S. typhi).
S. enterica serotypes Paratyphi A, B, or C, can cause a similar illness
Humans are the only reservoir for Salmonella enterica serotype Typhi
IP 7-14 days on average
27
salmonella typhi antigens
H antigen - flagellar
O antigen - somatic
Vi antigen - LPS
28
pathogenesis
The bacteria multiply by attaching to microvilli of the intestinal surface (M cells) perforate through the intestinal wall and are phagocytosed by macrophages
S. typhi alters its structure to resist destruction and allows it to exist within the macrophage
(faculitative intracellular )
Bacterial multiplication in Mononuclear Phagocytic system
spread via lymphatics to get access to reticuloendothelial system and then disseminate throughout the body.
29
Morphology of organs
Peyer’s patches enlargement
Superficial longitudinal mucosal ulcers aligned along Peyer’s patches
Lymphadenopathy
Hepatospleenomegaly
30
Sign and symptom
Constipation or mild diarrhea
Stepwise fever
Relative bradycardia (pulse-temperature)
Headache, fatigue, malaise, loss of appetite, cough, Skin rash or rose spots
Hepatosplenomegaly(HSM)
31
Neurologic manifestations
"Typhoid encephalopathy": altered consciousness, delirium, and confusion.
Acute psychosis
Meningeal signs
32
Neurologic manifestations tests
kernig and brudzinski
33
Diagnosis
CBC: Leukopenia with relative lymphocytosis. Rarely thrombocytopenia
Serologic test-
-Widal test ( agglutinating antibodies against O-somatic and H-flagellar antigens) is positive after the first week.
False positive; cross reactivity with other bacteria, vaccination, and endemic areas.
-Rising titer is more important and a value 1:160 is convincing
-‘Typhidot’ is a rapid test used to diagnose typhoid fever, and is negative in the first week and positive thereafter.
34
Complication
Intestinal haemorrhage and perforation (5% and in 3rd week)
Metastatic abscesses in other organs
Osteomyelitis (sickle cell disease), endocarditis, glomerulonephritis, meningitis , encephalitis etc..
35
chronic carriers how
Chronic typhoid fever (3-5%): Gall bladder (stones)or renal diseases predispose to carrier. Vi antigens for S.typhi is used to screen the carrier.
Relapse (10-20%)
36
Schistosomiasis
Acute and chronic parasitic disease caused by blood flukes of the genus Schistosoma
also called bilharziais
37
types of schistosoma species
s. hematobium - urogenital
s. mansoni
s. japonicum
s. mekongi
s. intercallatum - intestinal liver
38
life cycle
39
where do schistosomas mature
potal vasculature
40
male and female pair by
BATT
41
pathogensis
due to host inflammatory reactions
42
acute schistosoma cytokines
TNF a
IFN y
IL 1
IL6
IL12
More Th1
43
Chronic schistosoma cytokines
IL4
IL5
IL10
IL13
More Th 2
44
clinical feature of acute schistosoma (Katayamas syndrome)
fever
abdominal pain
diarhea
cough
RES enlargement
45
clinical features of chronic schistosoma
egg deposit in tissue
inflammation
repair by fibrosis
45
instestinal schistosoma characteristic
Patches or polyps
Fibrosis and obstruction
Granuloma around the egg
Present with chronic bloody diarrhea and abdominal pain
45
liver schistososma plus main feature
Reason for most deaths
Perisinusoidal and periportal fibrosis (Symmers’ pipe stem fibrosis)
Portal hypertension HSM, esophageal varices, ascites etc…
46
lung schistosoma
In patients with portal hypertension
Eggs pass through portocaval
anastomosis
Granulomatous pulmonary arteritis
Pulmonary hypertention
Rt. Sided heart failure (Cor pulmonale)
46
Urinary schistosoma
Ureteric obstruction obstructive uropathy
Squamous metaplasia squamous cell carcinoma
Bladder calcification
Recurrent gross hematuria “men menstruation”
Membranoproliferative glomerulonephritis (MPGN) and/or membranous nephropathy
47
Genital schistosomiasis
Reported in endemic areas
Usualy caused by S. hematobium fallopian tube involvment Ectopic pregnancy and placenta rarely described
Sandy patch/rice grain (most common), Polyps /nodules / Ulcers
48
Neuroschistosomiasis
Most frequently due to embolization of eggs, but some cases of adult schistosomes traveling to the CNS vasculature have been reported.
S. japonicum primarily involves the brain, while S. mansoni and S. haematobium primarily affect the spinal cord. However, occasional cases of cerebral schistosomiasis due to S. mansoni continue to be reported
49
Amoebiasis
Protozoal disease by genus Entamoeba hystolytica (lytic action on tissues by protase and ionophore)
Feco oral transmission (poor sanitation)
No animal reservoir
It is endemic in Ethiopia
The two common species of intestinal Entamoeba with identical morphology are E. histolytica and E. dispar (nonpathogenic)
50
Amoeba proteins involved in tissue invasion
Cysteine proteases, which lyse proteins of extracellular matrix.
Lectins on parasite surface that bind to carbohydrates on colonic epithelium and RBCs.
Channel forming proteins that contains an ameba pore that makes pores in plasma membrane and lyses it
51
The parasite occurs in 2 forms
Trophozoite: active adult form, in the tissues and diarrhoeal stools, and PAS+, fail to survive outside and destroyed by gastric secretions.
Cyst: infective stage, Four nuclei, formed stools but not in the tissues.
Transform to trophozoite in the intestine
52
Clinical features
Most infections are asymptomatic
Abdominal pain
Bloody and mucoid diarrhea
Malaise
Other presentations: amoebic liver abscess, and ameboma (tender abdominal mass)
53
Amoebic colitis
Most common type of amoebic infection
Caecum > ascending colon > sigmoid > rectum > appendix
Begins as a small area of necrosis of mucosa which may ulcerate
Flask-shaped ulcers = Undermining ulcer
Margin of the ulcer shows trophozoites + acute on chronic inflammation
54
Amoeboma
Napkin-like constrictive lesion
Inflammatory thickening of the wall of colon
Intestinal obstruction
Ddx: carcinoma of the colon.
Mic: granulation tissue, fibrosis and clusters of trophozoites
55
Extraintestinal Amebiasis
Peritonitis by perforation of amoebic ulcer of colon,
Lungs and pleura by rupture of amoebic liver abscess or hematogenous
Haematogenous spread to cause amoebic carditis and cerebral lesions
Skin ulcer: Perianal, Vulvar and Penile
55
Amoebic liver abscess
40% patients
From peritoneum or portal venous drainage
Amoebic liver abscess may be single or multiple
Multiple zones of liver necrosis confluence ‘liver abscess’ (not true abscess: no neutrophils in or around the cavity)
Fever and RUQ abdominal pain
55
Hydatid Disease
It is caused by ingestion of eggs of echinoccal species shed by dogs or foxes.
Humans are accidental intermediate hosts
56
pathogenesis of haydatid disease
Eggs hatch in the duodenum and the larvae penetrate the intestine and disseminate haematogenously the larvae lodge within the capillaries Many such larvae undergo encystation
~2/3 of human E. granulosus cysts are found in the liver, 5–15% in the lung, and the rest in bones and brain or other organs.
56
Species of echnococal
Three out of four known species are of medical importance in humans.
Echinococcus granulosus: the most common, causes cystic echinococcosis
Echinococcus multilocularis: rare but is the most virulent, causes alveolar echinococcosis)
Echinococcus vogeli: the rarest
57
Morphology of E.granulosus
Unilocular cyst (>10 cmØ/ >5yr)
Enclosing an opalescent fluid
Inner , nucleated, germinative layer and an outer, opaque, non-nucleated layer with delicate laminations.
Outside this opaque layer, there is a host inflammatory reaction that produces a zone of fibroblasts, giant cells, and mononuclear and eosinophilic cells.
In time a dense fibrous capsule forms.
In time, daughter cysts develops.
57
Degenerating scolices of the worm produce a fine, sandlike sediment within the hydatid fluid
(hydatid sand).
57
Complications
Rupture
Anaphylaxis
Dissemination
Infection
Recurrence
58
Onchocerciasis
= River blindness
Caused by a filarial nematode Onchocerca volvulus
leading cause of preventable blindness in sub-Saharan Africa
Affects 17 million people in Africa, South America, and Yemen
Onchocerciasis is endemic in SNNPR, Amhara, Beneshangul-Gumuz and Oromia regions
59
life cycle or pathogeneiss
Bite of a blackfly introduce third-stage larvae into the human skin, which mature into adult parasites (macrofilariae) over 6-12 months In the skin inseminated females produce microfilariae disseminate to the eye chambers
60
skin manifestations
Leopard, lizard, or elephant skin: chronic, itchy dermatitis with focal hyper or hypopigmentation and scaling
Onchocercoma is subcutaneous nodule over bony prominences of adult O. volvulus parasites and body response.
61
eye manifestations
Eosinophilic infiltrate against degenerating microfilariae
Punctate keratitis sclerosing keratitis
Anterior chamber inflammation, iridocyclitis and glaucoma
Choroid and retina: atrophy and loss of vision
62
mazzotti rxn
Mazzotti reaction accentuated keratitis by antifilarial drugs
63
Toxoplasmosis
Infection caused by protozoa, T.gondii
63
T gondii exists in 3 forms
oocyst
bradyzoits
tachyzoits
64
life cycle
from cat feces oocyst or tissue cysts
ingested then tachyzoit
localize as bradyzoit
65
transmission
ingestion
vertical
horizontal .. blood transfusion
66
hosts type
The cat is the only definitive host, Intermediate hosts (birds, rodents) and humans are a dead-end host.
67
T. gondii forms a .............. protected from lysosomal fusion.
parasitophorous vacuole (PV)
68
Acute acquired Toxoplasmosis
10 - 20%
Focal inflammation
Myocarditis, encephalitis, splenomegaly, lymphadenitis
Recovery with in few weeks to months
latent infection
69
chronic toxsoplasmosis:
schizophrenia and other neurologic conditions, hypothesized but studies are inconclusive
70
Congenital toxoplasmosis plus types
Seen in primary infection of mother
early and late
71
tourch group
TORCH group (toxoplasmosis and others [syphilis, tuberculosis, listeriosis], rubella, cytomegalovirus, herpes simplex)
72
Early infection:
low transmission, but severe disease (abortion/stillbirth and/or sever malformation)
73
Late infection:
high transmission, more benign symptoms
73
presentation time
Delayed presentation peaks is in second or third decade, most commonly bilateral chorioretinitis
74
congenital toxo triad
chi
chorioretinitis
intracranial calcification
hydrocephalus
74
Leishmaniasis
Caused by an obligate intracellular kinetoplastid protozoan parasites
75
Life cycle involves two forms:
Promastigotes in the sand fly vector and
Amastigote in the host macrophages.
76
in anergic hosts
Anergic host: dominant Th2 cytokines such as IL-4, IL-13, and IL-10 inhibiting the microbicidal activity of macrophages diffuse lesion
76
leshmania evasion
Promastigotes produce Lipophosphoglycan and gp63
Amastigotes express a proton-transporting ATPase, which maintains the phagolysosome pH at 6.5 (n=pH of 4.5).
76
Host immune reaction
-CMI - Th1- INF Y
leshamania impair Th1
↑ production of hepcidin (iron exporter)
↑ ferritin (binds free iron)
↓ macrophages transferrin receptor and
↑ removal of iron from the phagosome
77
Lipophosphoglycan
activates complement (leading to C3b deposition on the parasite surface) and inhibits complement action (preventing MAC insertion into the parasite membrane).
78
gp63
Gp63 is proteinase againest complement and some lysosomal enzymes. Gp63 also promotes promastigote adhesion to macrophages.
79
Four different types in humans
80
Visceral Leishmaniasis
Species: L. donovani, L. chagasi, L. infantum
81
Cutaneous leishmaniasis
L. major, L. aethiopica
Papule surrounded by induration shallow and slowly expanding ulcer usually heals by involution within 6 to 18 months without treatment
82
Mucocutaneous leishmaniasis
L. braziliensis
83
Diffuse cutaneous leishmaniasis
L. aethiopica
Single skin nodule generalized skin nodule
84
Diagnosis of Leishmaniasis
and test
Cytology/histology
Splenic aspirate: it is the preferred specimen, highest yield and Sn of 93-99%
Bone aspirate: Sn 53-86%
Lymph node aspirate: Sn 53-65%
Skin/mucosa FNAC/biopsy
Leishmanin skin test (Montenegro skin test)
85
Malaria
Malaria is a protozoal disease caused by species of plasmodia
86
transmission
Transmision: through bite of female Anopheles mosquitoes, blood transfusion and transplacental
87
2 types of malaria
88
Benign malaria
P. vivax, P. ovale, P. knowlesi, and P. malariae
low levels of parasitemia
Mild anemia
Rarely splenic rupture and nephrotic syndrome.
89
Malignant malaria
P. falciparum
High levels of parasitemia
Severe anemia
Cerebral symptoms
Renal failure
Pulmonary edema
Death
90
2 stages of malaria
exoerythrocyte stage
erythrocyte stage
91
exoerythrocyte stage
asymtomatic
sporozoite by thrombospondin to hepatocytes
92
in hepatocyte different species
P. vivax and P. ovale form latent hypnozoites in
hepatocytes, which cause relapses of malaria weeks to months after initial infection
other to merozoitas
93
erythrocyte stage 3 phases detail
1 merozoit look like a ring
2 late throphozoit
3 digest hg called schizont
94
Features of P. falciparum account for its severity
P. falciparum infect RBC of any age
RBC rosette
RBC sequestration;
P. falciparum erythrocyte membrane protein 1 (PfEMP1) on RBCs binds to ligands on endothelial cells(CD36, thrombospondin, VCAM-1, ICAM-1, and E-selectin)
Red cell sequestration blocks blood flow ↓tissue perfusion ischemia
95
kidneys malaria
Nephrotoxic (pigment) ATN “blackwater fever”
P. falcipurum= Proliferative glumerulonephritis
P. malarie = Membranous glumerulonephritis
96
Tropical Splenomegaly Syndrome
(Hyperreactive malarial syndrome (HMS))
Exaggerated immune response to recurrent or persistent malarial infection
IgM aggregates are phagocytosed by the cells of the RES, stimulating macrophage and T-cell hyperplasia
Chronic abdominal swelling (64%) and pain (52%)
97
Cerebral malaria
nodule called
The major cause of death in children with malaria.
Unconsciousness, focal neurological symptoms and coma
Malaria of non immunes
Petechial hemorrhage in subcortical white mater
Degeneration of neurons
Demyelination and pericapillary ring hemorrhage.
Microglial nodule called “Durck’s granuloma” (“malarial granuloma”)
98
kind of lymphoma
↑endemic Burkitt's lymphoma (eBL) in malaria endemic area
99
Tenia versicolor/ Pityriasis Versicolor (PV)
by
risk factors
pathogenesis
under microsope koh
Malassezia furfur (normal skin flora)
Risk factors include sweating and oily skin
Pathogenesis. Malassezia changes from a yeast to hyphaI form under the influence of predisposing factors. Produces dicarboxylic acid, which inhibits tyrosinase in epidermal melanocytes
spaheti meatball
100
Dermatophytoses
by
Superficial fungal infections usually affect all parts of the skin
The commoan dermatophytes include Microsporum, Trichophyton, and Epidermophyton.
101
Candidiasis
by
3 clinical form
under micro koh
C. albicans is present as normal flora of the skin, mouth, vagina and gastrointestinal tract.
thrush
hyperplasia
erythematous
braching budding
102
Mycetoma
common name
Classified as a Eumycetoma (fungal disease) or Actinomycetoma
Usually acquired while performing agricultural work
madura foot
103
Aspergillosis
by
predisposing factors
Aspergillus fumigatus is the most common pathogenic species of the fungus
neurtopenia
corticosteriod
104
2 type of aspergilloma
colonizing
invasive
105
Monod’s sign
106
Mucormycosis (Zygomycosis)
Major predisposing factors are neutropenia, corticosteroid use, DM with ketosis, iron overload, and breakdown of the cutaneous barrier
Most patients are Primarily affect nasal turbinates leading to sinusitis, orbital inflammation with proptosis and menigioencephalitis (rhinocerebral mucormycosis)
Has propensity to invade blood vessel causing cavernous sinus thrombosis and pituitary infarction
black fungus
107
Histoplasmosis
Infects humans by inhaling spores present in soil contaminated from chicken faeces.
Causes enlarged lymphoreticular tissue and destroying adrenal (Addison’s disease)
intracelular
108
Coccidioidomycosis
Infection is acquired by inhalation of the spores of coccidioides immitis
Patients develop delayed type of hypersensitivity reaction to the fungus
Have high rate of infectivity (spores ingested by alveolar macrophages block fusion of the phagosome and lysosome )
109
Cryptococcosis
C. neoformans in pigeon dropping
In immunocompetent
Focal or diffuse lung lesion: chronic granuloma and mucoid type of pneumonia
In immunosuppressed
meningoencephalitis (typically gelatinous meningitis) and disseminated cryptococcosis
110
Measles (ኩፍኝ)
Caused by an ssRNA virus of the paramyxovirus family (Rubeola virus)
111
spread by
Spreads by respiratory droplets multiplies within upper respiratory epithelial cells (via receptors, mainly, CD46 and SLAM) spreads by blood throughout the body replicate in T lymphocytes, macrophages and dendritic cells.
112
manifestations 5
conjuctivitis
lymphadenopathy
kopliks spot
exanthem
warthin finkeldey cell giant cells
113
Herpes Simplex Infection
HSV-1 oral cavity and HSV-2 genitals
Reactivation associated with trauma, URTI, pregnancy menstruation, UV light, immunosuppression
114
hallmark for HSV\
and 3 M for HSV
hallmark of HSV infection is large pink-to-purple intranuclear (Cowdry type A) inclusions, which push nuclear chromatin to periphery
MARGINATION OF CHROMATIN
MOLDING
MULTINUCLEATED GIANT CELL
115
Varicella Zoster virus (VZV)
Causes varicella (chickenpox (ጉድፍ)) and zoster (shingles).
Varicella is usually a disease of children.
Centrifugal: trunk to face and extremities
Dormancy occur in trigeminal and dorsal (sensory) root ganglia.
Reactivation can cause zoster (shingles) with 15% to 20% complaining postherpetic neuralgias
116
Morphology of infectious mononucleosis
EBV
kissing disease
Peripheral blood lymphocytosis (>60% of WBC are atypical T-cells )
Lymphnodes: paracortical zone expansion and B cell proliferation (atypical)
Splenomegaly
Hepatomegaly and Hepatitis
Meningitis and Encephalitis
Pneumonia
