Pathology - Infectious Disease Flashcards
What type of organism is clostridia and what diseases do they cause
gram positive
anaerobic
bacillus
spore-producing
1) perfringens: cellulitis, gas gangrene, food poisoning
2) tetani: spastic paralysis
3) boltulinum: flaccid paralysis
4) difficile: pseudomembranous colitis
How does botulism toxin cause disease
-causes release of exotoxin neurotoxin that blocks ACh, leading to flaccid paralysis
-the A fragment cleaves the protein synactobrevin which is needed for fusion of NT vesicles
What is the pathogenesis of gas gangrene
-C. perfringens release both enzymes and toxins
1) enzymes: hyaluronidase, collagenase = degrade extracellular matrix proteins
2) toxins: alpha toxin = phospholipase C. Degrades lecithin, destroys RBC/platelets/muscles, nerve damage
How does neisseria meningitidis cause infection and what are the clinical consequences
gram neg
encapsulated
aerobic
diplococci, coffee bean shaped
high LPS
-common coloniser of the oropharynx, spread by respiratory droplets
-most people develop an immune response and clear it
-invasive when new serotype is encountered, which may invade respiratory epithelium and blood stream
-capsule inhibits opsonisation and thus evades immune system
consequences: sepsis, necrotising vasculitis, seizures, SIADH, CVA, hydrocephalus, meningitis, hearing loss, death
What are 2 clinically significant neisseria
1) menigitides: causes meningococcal disease (meningitis or other form of sepsis)
2) gonorrhoea: causes urethritis, prostatitis, PID, septic arthritis, blindness
What causes meningitis
neisseria
e coli (neonates)
group B strep (n)
strep pnuemonia (old, infants)
listeria (old)
haemophilus (infants)
enterovirus
measles
TB
auto-immune
What are the virulence factors of staph aureus
-surface proteins - host cell adherence
-secrete enzymes - degrade proteins
-secrete toxins that damage host (alpha, beta, delta, gamma, leukocidin)
-contain a capsule that allows attachment
-secrete lipase that degrades lipids on skin surface
What diseases are caused by staph aureus
skin infections (abscess, cellulitis, impetigo)
osteomyelitis
pneumonia
endocarditis
food poisoning
TSS
What are some conditions caused by the different types of staph infections
1) staph aureus: skin infections, osteomyelitis, pneumonia
2) staph epidermidis: most common cause of infective endocarditis in prosthetic valves
3) staph saprophyticus: UTI
What are the risk factors for toxic shock syndrome and what are it’s features
Condition caused by bacterial toxins, usually strep or staph infections
risks: use of tampons, post operation wound infections, post partum, nasal packs, staph or strep skin infections
features: hypotensive shock, acute renal failure, coagulopathy, respiratory failure, soft tissue necrosis, rash
Name some bacteria that cause wound infections
staph aureus
strep pyogenes
clostridium perfringens
pseudomonas aeruginosa
clostridium tetani
Describe streptococci and name some different types of streptococci and what infections they cause
-gram positive cocci that grow in chains or pairs
1) alpha strep
-strep pneumonia: CAP
2) beta strep
-strep pyogenes: pharyngitis, scarlet fever, impetigo, rheumatic fever, TSS, glomerulonephritis
-strep agalactiae: neonatal sepsis
3) viridans group
-strep viridans: endocarditis
-strep mutans: dental caries
What are some post-infectious syndromes caused by streptococci infections
rheumatic fever
scarlet fever
immune complex glomerulonephritis
erythema nodosum
arthritis
What are virulence factors of streptococcus infections
-capsules - resist phagocytosis
-produce M proteins that inhibit complement activation
-produce exotoxins that cause fever and rash
-produce pneumolysin that destroys cell membranes
What is the pathological sequelae of HIV infection and what are the modes of transmission
-infects CD4+ T cells causing immunosuppression and leading to opportunistic infections and neoplasms
-transmission: 75% sexual (globally heterosexual is more common), IVDU, mother to infant in utero, breastmilk
Describe the structure of the influenza virus
-single stranded RNA virus bound by nucleoprotein that determines type (A, B, C)
type A: infects humans, pigs, horses, birds
type B and C: only infects humans, more common in children who then develop antibodies
-lipid bilayer that contains haemaglutinin and neuraminidase that determines subtype
What is the pathological basis for pandemics and epidemics
-pandemics only occur in flu a, epidemics occur in flu a and flu b
1) Epidemic = disease that affects a large number of people within a community
-caused by antigenic drift when virus acquires mutations in H or N to escape antibodies
2) Pandemic = epidemic that is spread over multiple countries or continents
-caused by antigenic shift when H and N are replaced by recombination of RNA segments with an animal virus
How does the body clear a primary influenza infection
-initially via CD8+ cytotoxic T cells and cytokines stimulating macrophages
-immunity acquired by antibodies
How does influenza cause pneumonia
1) attachment of virus to upper respiratory tract epithelium
2) necrosis of cells followed by inflammatory response
3) interstitial inflammation with build up of fluid in alveoli
4) secondary infection by staph or strep due to loss of mucociliary clearance
What are clinical conditions caused by herpes simplex virus
-HSV-1: cold sores, gingivostomatitis, corneal blindness
-HSV-2: genital sores, encephalitis, increased risk of HIV transmission
How does reactivation occur after primary herpes simplex infection
-viral nucleocapsids travel to the nucleus in a sensory neurone
-during latency period, only viral mRNA is produced and no viral proteins are made
-reactivation from latency occurs by avoiding immune recognition, inhibiting MHC class I recognition pathway
-spread antidromically along the sensory nerve
Describe the pathogenesis of glandular fever, clinical features and outcomes
-caused by EBV infection transmitted by close contact: saliva, blood, venereal transmission
-begins in nasopharyngeal and oropharyngeal epithelial cells by infection of B cells in underlying lymphoid tissue
-CD8+ cytotoxic T cells recognise and lyse EBV-infected B cells and establishes a latent infection in B cells
clinical features: fever, fatigue, sore throat, lymphadenopathy, splenomegaly, hepatitis
outcomes: most resolve in 4-6 weeks, may cause splenic rupture, may transform into lymphoma
What type of virus is measles, how is it spread, describe clinical manifestations and immune response
-ssRNA paramyxovirus
-transmitted by respiratory droplets
presentation: 4 day fever, cough, coryza, conjunctivitis, koplik spots, blotchy red-brown rash
manifestations: viral pneumonia, conjunctivitis, encephalitis, sclerosing panencephalitis, diarrhoea
immune response:
most develop T-cell mediated immunity to control the infection and produces the rash
antibody mediated immunity protects against re-infection
Describe the pathogenesis of herpes zoster
-transmitted by aerosols and disseminates haematogenously
-initially infects mucus membranes and skin, causing vesicular lesions that rupture then crust over and heal
rash occurs 2 weeks post exposure, begins centrally and spreads centrifugal
-acute VZV infection = chickenpox
-VZV evades immune defenses and establishes as latent infection in sensory neurons in dorsal root ganglion
-reactivation of latent VZV infection (often in the elderly or immunocompromised) = shingles
characterised by vesicular eruption along dermatome of one or more sensory nerves
What are the complications of chickenpox (acute varicella infection)
interstitial pneumonia
encephalitis
transverse myelitis
shingles
bacterial superinfection
What is croup and what causes it
-acute laryngotracheobronchitis causing inflammatory narrowing of the airway (barking cough, stridor)
-caused by viruses (parainfluenza, RSV, adenovirus, influenza)
What is the clinical spectrum of a candida infection
-superficial mucosal: mouth, vagina, esophagus
-superficial cutaneous: nappy rash, balanitis, folliculitis, onychomycosis
-invasive: endocarditis, meningitis, pneumonia
What mechanisms allow candida to cause disease
phenotypic switching
adhesion to host cells
secretion of invasive enzymes and adenosine that blocks neutrophils
What organisms cause malaria and describe the pathogenesis
Plasmodium, spread by anopheles mosquitos
-5 types of plasmodium = falciparum, vivax, ovale, knowles, malariae
1) mosquito salivary glands to human blood (sporozoite)
2) taken up into liver cells, where they multiply (sporozoite)
3) liver cells rupture and release asexual haploid form (merozoite)
4) merozoite invades RBC, where they grow
5) tropozoite matures in RBC to become a schizont and finally a merozoite
6) lysis of RBC causes release of merozoites and infection of more RBCs
How does P falciparum differ from other forms of malaria
can infect RBC of any age
causes RBC to clump
has antigenic variation to escape antibody responses
How does P falciparum present clinically
fever
severe anaemia
acute renal failure
splenic rupture
cerebral symptoms
pulmonary oedema
DIC
What factors make people less susceptible to malaria
inherited alterations in RBC (sickle cell)
repeated exposure stimulating immune response
HLAB53
Which markers will be elevated in acute Hep B infection?
- HBsAg
- HBeAg
- HBV-DNA
- Anti-HBc IgM antibody
What type of immune response occurs in measles?
- Adaptive (acquired) immune response
- T cells → control the infection and cause the rash
- B cells → antibodies to protect against re-infection
What are the three cell surface receptors for the measles virus?
- CD46 (inactivates C3 convertase)
- SLAM (signaling lymphocytic activation molecule – involved in T cell activation)
- Nectin 4 (adherens junction protein)
What disease states can EBV cause?
- Infectious mononucleosis
- Burkitt’s lymphoma
What are the complications of glandular fever?
- Hepatitis
- Splenic rupture
- Transformation to lymphoma
What is meant by viral “drift” and “shift”?
Antigen drift
There are small changes in the genes of the influenza virus that happen continually over time (i.e. need different influenza strains in the vaccination each year) and can lead to an endemic.
Antigen shift
An abrupt, major change in the virus resulting in the formation of a new virus, usually because of recombination of RNA from animal viruses resulting in a new influenza sub-type (e.g. H1N1, swine flu) and can lead to a pandemic.
What are some common gram positive organisms?
- Staph
- Strep
- Enterococcus
- Nocardia
- Clostridium (anerobic)
Describe the pathophysiology of syphilis.
- Syphilis is a chronic sexually transmitted disease caused by spirochaete Treponema pallidum
- Much of the pathology of syphilis can be attributed to the ischaemia caused by vascular lesions
- Immune response to syphilis can lead to resolution of local lesions, but does not reliably eliminate systemic infections
Manifestations of primary syphilis
-Occurs ~ 3 weeks after infection
-Formation of a single, non-tender, raised chancre located at the site of treponemal invasion e.g. penis, cervix, vaginal wall or anus
-Occurs on the penis or scrotum in 70% men and the vulva or cervix on 50% of women
-Chancre heals with or without therapy
Manifestations of secondary syphilis
-Painless, widespread, superficial lesions in the oral cavity, palms of the hands and soles of the feet
-2-10 weeks after the primary chancre in ~ 75% of people
-Skin lesions frequently occur on the palms or soles of the feet and may be maculopapular/scaly/pustular
-Moist areas of the skin (e.g. anogenital region, axilla or inner thighs) may have condylomata lata (broad, elevated plaques)
-Lymphadenopathy, fever, malaise and weight loss
-Will progress to asymptomatic neurosyphilis in 8-40% and to symptomatic neurosyphilis/meningitis/visual changes/hearing changes in 1-2%
Manifestations of tertiary syphilis
Cardiovascular syphilis:
form of syphilitic aortitis
accounts for > 80% of tertiary syphilis
Dilation of aortic root and arch –> aortic valve insufficiency and aneurysms of the proximal aorta
Neurosyphilis
symptomatic neurosyphilis is divided into three patterns – 1. meningovascular neurosyphilis (chronic meningitis)
2. paretic neurosyphilis (invasion of the brain by Treponema pallidum and produces cognitive impairment and mood alterations)
3. Tabes dorsalis (damage to the sensory axons in dorsal roots causing ataxia, loss of pain sensation, Charcot joints and other sensory disturbances)
Benign tertiary syphilis
Formation of gummas in bone, skin and mucous membranes of the upper airway and mouth.
