LOs: 21-24 Flashcards Preview

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Flashcards in LOs: 21-24 Deck (20):
1

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)

- 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

2

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

Empiric (antiTB drugs, antibiotics, steroids)

- Antibiotics
- Corticosteroids
- AntiTB

3

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)

- 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

4

21 Common categorical causes of FUO & examples (4)

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

5

22 Definitions:

Inhalation

Aspiration

Respiration

Breathing in exogenous flora

Breathing in endogenous flora

Exposes us to microbes with every breath

6

22 Respiratory Tract Defense Mechanisms:

Microbial (1)

Mechanical (3)

Innate (2)

Humoral (2)

Cellular (2)

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)

7

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)

- 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

8

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

Virus Family

Genome

Transmission

Severity

Chronic Infection & Liver Cancer (y/n)

Prophylaxis

Therapy

HDV

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

9

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

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

10

HBV Serology:

Clinical manifestations
- Acute hepatitis
- Chronic hepatitis
- Hepatocellular carcnimoa

Acute Infection (4)

Chronic Infection (3)

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

11

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

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 +

12

23 Hepatitis Delta Virus:

Biological Characteristics
- Genome
- Contains...

Clinical Disease
- Infection (2)
- Severity

Diagnosis (1)

Prevention (1)

Treatment (2)

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

13

23 Hepatitis C Virus (HCV):

Biological Characteristics
- Genome
- Family
- Presence in blood

Clinical Disease (4)

Virulence Factors (2)

Diagnosis (2)

Treatment (4)

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

14

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

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

15

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)

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

16

24 Enterobacteriaceae:

Biologic Characteristics
- Gram+/-...
- Aerobe/anaerobe...
- Oxidase+/-
- Growth on media

Factoids
- Found in (3)
- Causes...

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

24 Escherichia coli:

Biologic Characteristics
- Differentiation
- Serotypes: O157:H7, K1

Reservoir/Colonizes...

Transmission

Virulence Factors (3)

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

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

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

24 Escherichia coli:

Community-acquired vs. nosocomial UTIs


Virulence factors of uropathogenic E. coli (5)

Neonatal meningitis

Diagnosis (2)

Prevention/Treatment (4)

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

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

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)