LOs: 21-24 Flashcards

1
Q

21 Causes of FUO:
Infections:

Blood cultures

  • Endocarditis (1 cause)
  • AIDS (1 cause)
  • Endemic areas (1 infection, 1 cause)

Imaging studies

  • Chest radiograph / CT (3)
  • Abdomen CT (2)

Biopsies

  • Lymph node (5)
  • Liver (2)

Bone marrow biopsy & culture

  • Neoplastic disorders (3)
  • Intracellular infections (1)

Elderly (3)

A
  • Bartonella
  • Mycobacteria
  • TB, Histoplasma capsulatum
  • Lymphoma, histoplasmosis, sarcoidosis
  • Intra-abdominal abscesses, lymphoproliferative disorders
  • Lymphoma, toxoplasmosis, Kikuchi’s disease, TB, sarcoidosis
  • Granulomatous hepatitis, TB
  • Lymphoma, leukemia, multiple myeloma
  • Disseminated histoplasmosis
  • TB
  • Endocarditis
  • Intraabdominal abscess
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2
Q

21 Treatments for FUO:

Not ___

Except

  • Culture-negative endocarditis
  • Presuemd temporal arteritis
  • Suspected military TB in elder pts & in pts w/ AIDS; pts w/ connective tissue diseases taking corticosteroids, methotrexate, or infliximab; recipients of solid organ transplants
A

Empiric (antiTB drugs, antibiotics, steroids)

  • Antibiotics
  • Corticosteroids
  • AntiTB
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3
Q

21 H&P for FUO:
Infections:

Medical/Surgical History

  • Previously treated chronic infections (2)
  • Transfusions (3)

Medications (___)
- Drug therapy (4 drugs)

Social History

  • Recreational drugs (2)
  • Sexual activity (HIV)
  • Animal/insect exposure (5)
  • Dietary habits (2)
  • Recreational activities (3)
  • Travel history (2)

Physical Exam

  • Eyes (2)
  • Oropharynx (1)
  • Temporal artery (1)
  • Thyroid gland (1)
  • Lymphatic system (1)
  • Genital area (1)
  • Joints (1)
  • Pulses in extremities (1)
  • Skin rash (2)
A
  • TB, endocarditis
  • Hepatitis C, CMV, West Nile Virus

Drug therapy

  • Antimicrobials
  • Steroids
  • NSAIDs
  • Antipyretics
  • Infective endocarditis, osteomyelitis
  • HIV
  • Salmonellosis, brucellosis, toxoplasmosis, cat-scratch disease, Q fever
  • Brucellosis, Salmonella
  • Sporotrichosis, leptospirosis, histoplasmosis
  • TB, malaria
  • Conjunctivae, endocarditis
  • Oral thrush
  • Temporal arteritis
  • Thyroiditis
  • Endocarditis
  • Syphilis
  • Arthritis
  • Arteritis
  • Endocarditis, Rocky Mountain Spotted Fever
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4
Q

21 Common categorical causes of FUO & examples (4)

A

Classic FUO

Nosocomial FUO

  • C. difficile
  • Drug fever

Neutropenic FUO

  • Candida
  • Aspergillus

HIV-Associated FUO

  • HIV
  • Mycobacteria
  • Toxoplasma
  • CMV
  • Pneumocystis
  • Salmonella
  • Cryptococcus
  • Histoplasma
  • Non-Hodgkin’s lymphoma
  • Immune reconstitution inflammatory syndrome
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5
Q

22 Definitions:

Inhalation

Aspiration

Respiration

A

Breathing in exogenous flora

Breathing in endogenous flora

Exposes us to microbes with every breath

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6
Q

22 Respiratory Tract Defense Mechanisms:

Microbial (1)

Mechanical (3)

Innate (2)

Humoral (2)

Cellular (2)

A

Commensal flora prevent other pathogens from coming in
- Commensal flora

Breathing out gets rid of dangerous pathogens

  • Airflow
  • Mucociliary elevator
  • Epiglottis

Attack pathogens once they get in

  • TLRs
  • Airway fluid

Attack bacteria, respond to viral infections

  • sIGA
  • IgG neutralizing capsule/virions

Attack bacteria, respond to viral infections

  • Phagocytic (neutrophils, macrophages)
  • T cells (CD4, CD8, Th17)
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7
Q

22 Compromise of a specific defense predisposes to specific infections:

CNS injury

  • Examples (2)
  • Defense
  • Pathology
  • Conditions (2)

T cell injury

  • Examples (2)
  • Defense
  • Pathology
  • Conditions (2)

Humoral deficiency

  • Examples (2)
  • Pathology
  • Conditions (1)
A
  • Traumatic brain injury, cerebral palsy
  • Mechanical protection
  • Muscle/nerve dysfunction prevents airway protection
  • Aspiration pneumonia, abscesses
  • HIV, anticancer chemotherapy
  • Cellular defense
  • Invasion by opportunistic pathogens
  • Fungal and viral pneumonia
  • Immune deficiency, elderly
  • Lack antibody which opsonize encapsulated bacteria
  • Bacterial pneumonia
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8
Q

23 Hepatitis A, B, C, D, & E:

Virus Family

Genome

Transmission

Severity

Chronic Infection & Liver Cancer (y/n)

Prophylaxis

Therapy

HDV

A
A: Picornavirus
B: Hepadnavirus
C: Flavivirus
D: Defective / Unclassified
E: Calcivirus

A, C, E: +RNA
B: incomplete dsDNA
D: -RNA

A, E: fecal-oral
B, C, D: parenteral

A, E: self-resolving
B: sometimes severe
C: moderate
D: severe

A, E: no
B, C, D: yes

A: HAIG, vaccine
B: HBIG, vaccine
D: HBV vaccine
C, E: none

B: Interferon, Lamivudine, Emtricitabine Tenofovir, Telbivudine Entecavir, Adefovir
C: Interferon Ribavirin Boceprevir Teleprevir Sofosbuvir
A, D, E: none

HDV is only seen as a co-infection or super-infection of HBV

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9
Q

23 Hepatitis B Virus (HBV):

Biological Characteristics

  • Genome
  • Genes
  • Surface antigen

Pathogenesis (6)

Diagnosis (2)

Virulence Factors (2)

Prevention (2)

Treatment

  • Acute infection
  • Chronic infection
  • Cirrhosis / end–stage liver disease
A

BC

  • Circular incompletely dsDNA that uses viral reverse transcriptase (unique)
  • 4 genes: surface, core, pol, X
  • Surface antigen is shed w/o necessarily being attached to the virus

P

  • Bloodstream infection
  • Gene product form S ORF (“pre-S1”) binds hepatocyte surface
  • Viral replication w/o cytopathic effect
  • Excess HBsAg functions as immune decoy
  • Cytotoxic T-cell responses do injure liver
  • Oncogenesis: viral DNA integration into host chromosome & X ORF (transcriptional activator)

D

  • Detection of circulating HBV DNA in blood by PCR
  • HBV serology
    • Antigens: surface, core, e
    • Antibodies: anti-HBs, anti-HBc, anti-HBe

VF

  • Chronic infection
  • HBsAg: immune decoy

P

  • Hepatitis B Vaccine: recombinant, made of HBsAg
  • Lamivudine (prevents reactivation)

T

  • AI: HBIG
  • CI: Alpha-interferon, lamivudine, tenofovir, adefovir, entecavir, emtricitabine, telbivudine
  • C/ESLD: liver transplantation
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10
Q

HBV Serology:

Clinical manifestations

  • Acute hepatitis
  • Chronic hepatitis
  • Hepatocellular carcnimoa

Acute Infection (4)

Chronic Infection (3)

A

CM
- Acute hepatitis: asymptomatic, mild, fulminant
o RUQ pain, malaise, jaundice
o Transaminase release from hepatocytes (AST, ALT)
- Chronic hepatitis: ongoing liver damage
- Hepatocellular carcinoma: transformation of hepatocytes

AI

  • DNA & antigens (Ag) (surface, core, & e) come first
  • “Window period” is before detectable immune response
  • Anti-HBc IgM comes before IgG (aka anti-HBc total)
  • Symptoms begin w/ effective immune response

CI

  • HBsAg doesn’t clear
  • HBeAg, if not cleared, portends higher infectivity (more viral replication)
  • Anti-HBc doesn’t confer protective immunity
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11
Q

HBV Serology Patterns:

(1) HBV DNA
(2) HBsAG
(3) HBeAG
(4) Anti-HBcAg
(5) Anti-HBsAg

Acute (window)

Acute (active)

Acute (resolved)

Chronic/Persistent

Vaccinated

A

Acute (window)

(1) HBV DNA +
(2) HBsAG +
(3) HBeAG +
(4) Anti-HBcAg -
(5) Anti-HBsAg -

Acute (active)

(1) HBV DNA +
(2) HBsAG +
(3) HBeAG +
(4) Anti-HBcAg +/-
(5) Anti-HBsAg +/-

Acute (resolved)

(1) HBV DNA -
(2) HBsAG -
(3) HBeAG -
(4) Anti-HBcAg +/-
(5) Anti-HBsAg +

Chronic/Persistent

(1) HBV DNA +
(2) HBsAG +/-
(3) HBeAG +
(4) Anti-HBcAg +/-
(5) Anti-HBsAg -

Vaccinated

(1) HBV DNA -
(2) HBsAG -
(3) HBeAG -
(4) Anti-HBcAg -
(5) Anti-HBsAg +

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12
Q

23 Hepatitis Delta Virus:

Biological Characteristics

  • Genome
  • Contains…

Clinical Disease

  • Infection (2)
  • Severity

Diagnosis (1)

Prevention (1)

Treatment (2)

A

BC

  • Defective RNA virus that requires HBV for infection
  • Contains RNA & delta Ag enveloped w/ HBV envelope (HBsAg)

CD

  • Simultaneous infection w/ HBV or superinfection of persistent HBV-infected patients
  • Clinical syndrome of HDV mroe severe than HBV alone

D
- Serology for delta Ag antibody

P
- Hepatitis B vaccine

T

  • Interferon-alpha
  • Liver transplantation
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13
Q

23 Hepatitis C Virus (HCV):

Biological Characteristics

  • Genome
  • Family
  • Presence in blood

Clinical Disease (4)

Virulence Factors (2)

Diagnosis (2)

Treatment (4)

A

BC

  • Enveloped +RNA virus
  • Flavivirus
  • Quasispecies: multiple sequence isolates present at one time for immune evasion

CD

  • Chronic viral infection
  • Chronic hepatitis
  • Cryoglobulinemia
  • Cirrhosis then hepatocellular carcinoma

VF

  • High mutation rate of viral RNA polymerase
  • Protease blocks immune activation

D

  • Serology for anti-HCV antibodies
  • RT-PCR

T

  • Standard: alpha-interferon + ribavirin
  • New protease inhibitors: boceprevir, teleprevir, sofosbuvir, simeprivir
  • Liver transplantation
  • No prophylaxis or vaccine
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14
Q

23 Transplant-Associated Herpesvirus Infections:

Latency

Risk of transmission

Severity

Diseases associated w/ transplantation:

  • HSV-1
  • HSV-2
  • VZV
  • CMV
  • EBV
  • HHV-6
  • HHV-8
A

Life-long latency can be reactivated in immunosuppressed

Risk of transmission by donor organ transplantation to non-immune recipients

More severe disease associated with first-time infection (primary infection) compared with
reactivation (secondary infection).

  • HSV-1: oral & genital lesions
  • HSV-2: anogenital & oral lesions
  • VZV: chicken pox & herpes zoster / shingles
  • CMV: hepatitis
  • EBV: mononucleosis, post-transplant lymphoproliferative disease (PTLD)
  • HHV-6: rash, seizures, post-transplant encephlaitis
  • HHV-8: Kaposi’s sarcoma
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15
Q

23 Epstein-Barr Virus (EBV):

Biologic Characteristics

  • Genome
  • Family
  • Infects…
  • Establishes…

Clinical Disease: Acute Infection (3)

Clinical Disease: Chronic Infection (2)

Pathogenesis

Diagnosis

  • Acute infection
  • Recent or past infection
  • PTLD

Prevention & Treatment for PTLD (3)

A

BC

  • DNA virus
  • Herpesvirus
  • Infects B cells or nasopharyngeal cells by CD-21(-like) receptor
  • Latency & immortalized human B cells

CD: AI

  • Asymptomatic or mononucleosis
  • Fever, pharyngitis, lympahdenopathy, atypical lymphocytosis
  • Complication: hepatitis rash (from amoxicillin or penicillin) or beta-lactam splenic rupture

CD: CI

  • Burkitt’s lymphoma, nasopharyngeal carcinoma, non-Hodgkin’s or Hodgkin’s lymphomas
  • Post-transplant lymphoproliferative disease (PTLD)

P

  • Transmission by saliva (oral secretions)
  • Replication in pharyngeal epithelium
  • Spread via bloodstream to B cells (tonsils, lymph nodes)
  • Latency in B cells –> mononucleosis
  • During latency, EBNA-1 is produced to evade the immune recognition
  • PTLD: lack of CTL recognition of EBV latent antigens allows growth of latently infected B cells
  • Virus gets shed in oral secretions to reinfect new B cells to replenish reservoirs

D

  • AI: monospot test for antibodies
  • RoPI: detect anti-EBV antibodies (IgM)
  • PTLD: qPCR, biposy

P

  • No vaccine or treatment
  • Decrease immunosuppressive therapy
  • Acyclovir & ganciclovir
  • CTL therapy, anti-CD20 therapy
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16
Q

24 Enterobacteriaceae:

Biologic Characteristics

  • Gram+/-…
  • Aerobe/anaerobe…
  • Oxidase+/-
  • Growth on media

Factoids

  • Found in (3)
  • Causes…
A

BC

  • Gram-negative rods
  • Facultative anaerobes
  • Oxidase-negative
  • Growth on simple media w/ glucose & on MacConkey agar

F

  • Sewage, normal GI flora, feces
  • Opportunistic disease
17
Q

24 Escherichia coli:

Biologic Characteristics

  • Differentiation
  • Serotypes: O157:H7, K1

Reservoir/Colonizes…

Transmission

Virulence Factors (3)

A

BC

  • O antigen: carbohydrate chain extending from LPS
  • H antigen: flagellar
  • K antigen: capsular
  • O157:H7: EHEC
  • K1: neonatal meningitis

R

  • People
  • Normal GI flora

T

  • Person to person
  • Contaminated food/water

VF

(1) Fimbrial & afimbrial adhesins
- All produce a common (type 1) pili that attach to mannose receptors
- Pathogenic E. coli have a unique pili (CFA for ETEC) to bind unoccupied receptors
(2) Iron acquisition
- Produce siderophores w/ high affinity for iron
(3) Toxins
- Endotoxin (LPS): outer membrane
- Hemolysin: pyelonephritis
- Heat-stable enterotoxin: increases cGMP
- Heat-labile enterotoxin: increases cAMP
- Shiga toxin: inactivates ribosomes

18
Q

24 Escherichia coli Biotypes (5):

ETEC: Enterotoxigenic

  • Cause…
  • Transmitted by…
  • Colonize…
  • Multiply & produce…

EPEC: Enteropathogenic

  • Cause…
  • Hallmark
  • Adheres to enterocytes using…
  • Delivery of…
  • Formation of…
  • Intimin binding…
  • Causes…

EAEC: Enteroaggregative

  • Adheres to enterocytes as…
  • Increases…
  • Makes…
  • Causes…

EIEC: Enteroinvasive

  • Resembles…
  • Causes disease by…
  • Lacks…but has…
  • Causes…

EHEC: Enterohemorrhagic

  • Causes…
  • Transmitted via…
  • Pathogenesis
A

ETEC

  • Watery diarrhea in infants and travelers & food poisoning
  • Ingestion of contaminated food/water
  • Small intestine using unique pili (CFAI, II and III) that are plasmid-encoded
  • STa and/or LT, increasing intestinal fluid secretion

EPEC

  • infant diarrhea in developing countries
  • formation of attaching and effacing (A/E) lesions
  • plasmid-encoded bundle-forming pilus (bfp)
  • effectors (via a type III secretion system) to stimulate signal transduction pathways
  • “Pedestal” to deliver a TIR receptor
  • to TIR associates pedestal w/ enterocytes
  • watery diarrhea

EAEC

  • Aggregates
  • Mucus production, trapping bacteria in a biofilm
  • EAST (an enterotoxin)
  • Diarrhea in HIV+ individuals in developing countries, watery discharge, inflammation, & low-grade fever

EIEC

  • Shigella
  • invading enterocytes, lysing endocytic vesicles and escaping into the cytoplasm, multiply and cause cell destruction
  • Lack known specific pili, but do have common pili, afimbrial adhesions, & a type III secretion system
  • watery diarrhea, sometimes with blood and fecal leucocytes

EHEC

  • Hemorrhagic colitis, bloody stool, uremic syndrome (acute kidney failure) mostly in children
  • ingestion of foods (esp undercooked meat) & petting zoos or infected animals
  • Adhere via intimin, produce Stx, absorbed into the circulation, affects kidneys
19
Q

24 Escherichia coli:

Community-acquired vs. nosocomial UTIs

Virulence factors of uropathogenic E. coli (5)

Neonatal meningitis

Diagnosis (2)

Prevention/Treatment (4)

A

E. coli cause ~80% of community acquired bacterial UTIs but only ~20% of nosocomial UTIs

  • Include both cystitis & pyelonephritis
  • Highest risk: sexually-active women
  • Type 1 (common) pili
  • P-pili (pap pili): associated w/ pyelonephritis, binds to P blood group (Forssman) antigen on kidney
  • Hemolysin
  • Endotoxin
  • Can be invasive

Caused by K1 antigen

  • Homopolymer of sialic acid
  • Inhibits phagocytosis & complement activation (molecular mimicry)
  • MacConkey agar (pink colonies due to lactose utilization)
  • Differentiation b/n biotypes based on serotyping, clinical grounds, & molecular testing
  • Sanitary/hygienic behavior
  • Symptomatic (most)
  • Antibiotics (neonatal meningitis & UTIs)
  • Kidney dialysis & blood transfusion (no antibiotics) for HUS
20
Q

24 Helicobacter pylori:

Biological Characteristics

  • Type
  • Motile/Non-motile
  • Aerobe/Anaerobe
  • Urease

Reservoir/Transmission

Virulence Factors

  • Colonization (2)
  • Disease (4)

Pathogenesis & Disease

  • Most
  • Some
  • Few

Diagnosis (2)

Treatment

A

BC

  • Curved, gram- rod
  • Motile
  • Microaerophile
  • Urease+

R/T

  • Human reservoir
  • Fecal-oral or oral-oral transmission

VF

  • Urease & flagella (for higher pH)
  • VacA, cag pathogenicity island (type IV secretion system & CagA), LPD, & inflammation/urease

P&D

  • Mild GI inflammation (chronic gastritis)
  • Duodenal or gastric ulcers due to inflammation (ammonia/urease, VacA, CagA)
  • Gastric cancer or lymphoma

D

  • Biopsy via endoscopy (expensive, invasive, can exclude malignancy)
  • Breath tests (radioactive label, noninvasive, cheap)

T
>1 antimicrobial (e.g., clarithromycin and bismuth salts) and an acid blocker (e.g., omeprazole)