Lecture 39 to 42 Organ tissue infection Flashcards Preview

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Flashcards in Lecture 39 to 42 Organ tissue infection Deck (27)
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1
Q

Viral infections of the liver

A
  • Hep A to G and TT virus
  • Yellow fever virus
  • Herpes viruses 1, 3, 4, 5
  • Rubella (congenital rubella syndrome)
2
Q

Hep A

A
  • naked, icosahedral picornaviridae family
    • ss RNA
  • resists heating, disinfectants, heating, salt water, stomach pH
  • sensitive to chlorine, formalin, and UV
  • Etiopath:
    • fecal-oral route
    • incubation period: 15 to 45 d (short incubation period, infectious)
    • Entry: shellfish, oral and anal sex
    • virus shedding before sx
    • 2 weeks viremia
    • virus replicates in Kupffer’s cells and hepatocytes
  • Sx: abrupt, sx, fever, nausea, vomiting and jaundice
    • recovery complete in 8 to 12 weeks
  • non-lytic pircornavirus replicating without much pathology
  • damage due to immunpath including CMI, immune complex, and complement
  • does not initiate a chronic infectior or liver cancers
  • daycare and restaurants
  • Dx: ELISA
  • Rx: passive Ig
  • Control: handwashing, vaccination, inactivated vaccine
3
Q

Hep B

A
  • Hepadnaviridae family
  • partially ds DNA virus w sphrical, complex envelope w RT
  • infected serum has dane particles and viral surface Ag (detectable)
  • Etiopath: blood, sex, IV drugs, every bodily fluid is infectious
  • strict liver tropism
  • genome can integrate into host chromosome
  • infected cells release HBsAg particles lacking DNA (just empty shells)
  • Incubation period: 50 to 180 d
4
Q

surface antigen (HBsAg)

A
  • S, M, L glycoproteins w common C-terminal;
  • L-glycoprotein is the attachment protein and alos binds the envelope to the core
  • pleomorphic
5
Q

soluble antigen (HbeAg)

A
  • associated w core protein, cleavage product of viral core protein; does not assemble into virus; secrete into serum instead
  • high HBV titers in serum
  • indicator of serum infectivity
6
Q

core antigen (HBcAg)

A
  • observed in infected hepatocytes
  • has protein kinase activity
  • no free HBcAg in serum bc HBcAg -> highly immunogenic -> tyr-arg content high
7
Q

Events during Hep B Acute infection

A
  • HBeAg present in serum 1 to 3 mo
  • HBsAg prsent in serum 1 to 5 mo
  • anti-HBc-Ab 1st to appear
  • No HBsAg and HBeAg during window period (5 mo); only anti-HBc Ab in window (Exam q)
  • Note: Presence of HbSAg >6 mo = chronic state
8
Q

Development of chronic HBV carrier state

A
  • NO WINDOW PERIOD
  • viremia continues for years
  • HBsAg and HBeAg detectable for years
  • anti-HBc-Ab always present
9
Q

Control of HBV infections

A
  • screening of all blood for HBsAg
  • inactivated vaccines (Hepatavax) and recombinant vaccines (Recombivax) for high risk individuals
10
Q

Hep C

A
  • icosahedral, enveloped flavivirus (+ ss RNA)
  • HCV only flavivirus not transmitted thru insects
  • reservoir: humans & chimps
  • 70% persistent infection
  • Transmission: sex (20%). IV drugs (60%), blood transfusions
  • Incubation 40 to 120 d
  • Predictor of disease is high ALT
  • Epidemiology: Types 1b and 2 a/c commonly involved in HCC

Etiopath:

  • virus coats itself w LDL & VLDL and enters hepatocytes via cell surface receptor
  • bud from ER and remains there
  • inhibits apoptosis and IFN-alpha by binding to TNF and protein kinase receptors to establish persistence (no cell death)
  • proliferation: Beta-catenin/Wnt pathway -> MYC, cyclin D, WISP-2 in nucleus -> cell proliferation
  • also core protein -> p21WAF1 (cyclin-dependent) -> inactivates p53
  • other than hepatocytes, CD81 and other lymphocytes susceptible

Signs of chronic liver disease

  • portal HPT
  • jaundice
  • scratch marks/pruritis due to obstructive jaundice
  • finger clubbing
  • palmar erythema
  • shifting dullness on percussion of ab due to ascites
  • tachycardia to anemia

Control:

  • no vaccine bc multiple genotypes
  • Pegylated IFN-alpha: Types 2 & 3 more responsive to IFN-alpha therapy than type 1b
  • protease inhibitors: Bocepravir & Telaprevir

Rx: curable w combined oral therapy (unlike Hep B)

  • Declastavir inhibits NS5A, RNA synthesis, viral assembly/secretion
  • Sofosbuvir -> uridine analogue -> binds to NS5B (HCV DNAP)
  • Labs: not cirrhotic
  • PLT low due to unknown mechanism; splenomegaly

11
Q

Outcomes of HCV infection

A
  • IL28B polymorphism alters outcome -> inactive or altered gene -> little/no virus clearance in non-icteric state (see fig.)
  • virus persistence
    • mitochondria damage -> recruitment of Drp1 -> asymmetric fragmentation -> 1 healthy + 1 damaged mitochondria
    • Drp1 -> less interferon production
    • Drp1 -> inhibits apoptosis
12
Q

Hep D

A
  • -ve ssRNA, circular, enveloped
  • 4 genotypes by HLA epitope analysis
  • requires presence of replicating HBV which provides the viral coat (containing HBsAg in addition to delta Ag)
  • LARGE form HDAg: involved in viral packaging & suppressing HBV replication.
  • small form HDAg: transactivating replication of HDV RNA.
  • Transmission: blood and IV drugs
    • vertical transmission rare but possible
    • co-infection w HBV leads to severe and fatal course
    • HDV infection subsequent (super infection) to HBV results in milder hepatitis.
  • Etiopath: still unclear
    • persistent infection assoc. w hepatic inflammation, incr. ALT, and interference of JAK-STAT pathway.
  • Dx: anti-delta IgM and/or IgG
  • Control: vaccinate high risk against Hep B
  • Rx: higher IFN-alpha
13
Q

Hep E

A
  • small, naked icosahedral + ss RNA virus
  • Hepeviridae family
  • Epi: 5 types
    • Types 1 & 2: humans (younger Pt)
    • 3 & 4: humans, pigs (older Pt)
    • 5: birds
  • Transmission: fecal-oral, tranfusion, zoonotic
  • Epi: contaminated water, S. and E. Asia
  • Control: better hygience, no vaccines
14
Q

Hep G

A
  • enveloped + ss RNA virus
  • flaviviridae family
  • transmisible to chimps
  • Etiopath:
    • causes synctial giant cell hepatitis
  • Control:
    • no vaccines, source of infection not known
15
Q

Hep TT

A
  • icosahedral, naked -ss RNA, circular
  • circinoviridae family
  • Torque-Tine
    • index Pt
    • transfusion and dialysis transmitted hepatitis
  • Epi: 12% of Japanese and 60-70% of Norwegians have anti-viral Ab
  • At least 2 genotypes w many subtypes reported
  • Transmission: dialysis, breastfeeding, sex, transplacental
  • Control: no vaccines available
16
Q

Yellow Fever virus

A
  • flavivirus, class IVa
  • Vector: Aedes (Africa) & Hemagogus spp. (S. America)
  • Incubation period: 6-7 d w abrupt fever, myalgia, prostration
  • Sx: usually resolves in 4 to 5 d
    • severe cases include jaundice, hemorrhage, hemoptysis, collapse
  • Dx: serology & PCR
  • Prevention: live attenuated 17D strain; protection for 10 years
  • Control: mosquito control
17
Q

Herpesviridae family summary

A

Alpha

  • replication time: 6 to 8 h
  • CPE: cytolytic
  • Latency: neurons
  • HHV-1, 2, 3

Beta

  • replication time: 12 to 24 h
  • CPE: cytomegaly
  • Latency: glands
  • HHV-5, 6, 7

Gamma

  • replication cycle: variable
  • HHV-4, 8
  • CPE: lymphoproliferative
  • latency: lymphoid
18
Q

HHV-4 (EBV)

A
  • Epi: 15% of cases have hepatitis
    • 90% of population seropositive
  • Etiopath: EBV binds to CD21 and goes latent in B cells
  • Sx: atypical lymphocytosis, fever, liver failure is rare
    • asx in children bc immune system not fully developed
    • mononucleosis: pharyngitis, major fatigue, fever, lymphadenopathy, splenomegaly
      • C&C: no contact sports due to risk of splenic rupture
    • lymphoproliferative disease, hairy cell leukoplakia
    • malignancies: Burkitt’s lymphoma, nasopharyngeal carcinoma, Hodgkin lymphoma
  • Dx: heterophile Ab, elevated transaminases & ALP & Downey cells on BS
  • Prevention and control: no vaccine available
19
Q

HHV-5

A
  • Epi: in developed countries, most people have Ab against CMV
  • Sx: mostly subclinical
  • Transmission: urine, breast milk, serum, semen, genital secretions; children shed virus for a long time
  • Sx: usually asx in immunocompetent individuals
    • CMV retinitis
    • Heterophile -ve mononucleosis
    • blueberry muffin baby: transplacental transmission leading to thrombocytic purpura
  • Dx: owl eye cells, cotton wool retinitis, RIA & ELISA, viral detection from urine and saliva, EM observation of virus in urine
  • Rx:
    • Gancyclovir (CMV resistant to Acyclovir bc it lacks viral thymidine kinase);
    • human leukocyte IFN
20
Q

Leptospirosis

A
  • transmission: zoonotic and from contaminated water; most common from leptospira interogans
  • incubation period: 1 to 3 wk
  • Sx: severe Weil disease (jaundice & renal failure), meningitis, nephritis, rash, hemmorrhage (in severe cases), early myalgia, hepatitis, renal disease, conjunctivitis, thrombocytopenia
21
Q

Granulomatous hepatitis

A
  • non-infectious causes include vasculitis and quinine
  • infectious causes include
    • Coxiella burnetti
    • Mycobacteria
    • Histoplasma capsulatum
    • Brucella
22
Q

Liver abscesses

A
  • liver abscess can be a common cause of pyrexia of unknown origin
  • jaundice rare
  • elevated ALP and ESR
  • Bacterial causes
    • E. Coli
    • Klebsiella
    • Serratia
    • other enterobacteriae
    • enterococcus
    • Staph. milleri
    • Staph. Aureus
  • Amoebic
    • Entomoeba histolytica
  • Schistosome
    • S. mansoni
    • S. japonicum
    • S. haematobium
  • Hydatids
    • Echinococcus granulosus
    • Echinococcus multilocularis
  • Fasciola hepatica and other flukes
23
Q

hepatitis in the neonate or immunocompromised

A
  • HHV-1, 3, 5
  • rubella
24
Q

Viral Infections of eyes

A
  • adenoviruses most common cause of eye infections
  • Epi: in healthy individuals, adenovirus can be found in tonsils, nasopharynx, and intestinal tract.
  • Transmission: oro-fecal and respiratory tract
  • sx: respiratory, renal, gastro
    • respiratory: fever, rhinitis, cough, exudative pharyngitis (< 3 YO)
    • acute & chronic conjunctivitis, laryngitis, croup, pharyngoconjunctivitis, bronchitis, pneumonia
    • hemorrhagic cystitis: hematuria
    • gastroenteritis
  • Etiopath:
    • direct innoculation to nasal or conjuctival mucosa by hands or towel
    • adenovirus enters and replicates in epthelial cells producing cell necrosis and inflammation
    • viremia spreads to lymphoid tissue, kidney, bladder
  • Pathology
    • epithelial cell necrosis w mononuclear cell inflammation.
    • intranuclear inclusions (Cowdry type A) seen in some cases
    • Dx: virus isolation, 4x increase in Ab titers
    • Prevention and control: inactivated vaccine (serotype 3, 4, 7); live vaccine reccomended for military
25
Q

Bacterial Infections of Eyes

A
  • Chlamydia trachomatis
    • Epi: spread thru contact; serotypes A-C -> trachoma (granular conjunctivitis) and blindess; serotypes D-K -> conjunctivits; some serotypes can infect urinary tract and cause conjuctivitis in neonates
  • N. menigitidis: most common; conjunctiva neonaturm
  • N. catarrahalis: cataracts in areas w sand and limited water
  • S. Aureus: purulent infections of the eyes
26
Q

Fungal endophthalmitis

A
  • fusarium incarnatum
  • bipolaris hawaiiensis
27
Q

Infection of parotids and testes

A
  • mumps virus
    • paramyxovirus: enveloped virus w helical nucleocapsid containing - ss RNA
    • 3 major peplomers (HA, NA, F)
    • neutralizing Ab persists for years
    • Transmission: droplets and saliva contract
    • Incubation: 2- 3 wk
    • Epi: affects children 5 to 9 yo during winter and spring every 3 wks; immunity from natural infection is lifelong
    • Sx:
      • parotitis most common
      • meningitis
      • orchitis common in adult males
      • additional complications include Cochlear inflammation, Arthritis, Mastitis, Myocarditis
      • Note: Pt infectious before any sx; virus shed through urine and saliva
    • Dx: RT-PCR, ELISA, HI, neutralizing Ab
    • Prevention and control: MMR vaccination