Pathology - Infectious Disease

Question 1

What type of organism is clostridia and what diseases do they cause

Answer 1

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

Question 2

How does botulism toxin cause disease

Answer 2

-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

Question 3

What is the pathogenesis of gas gangrene

Answer 3

-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

Question 4

How does neisseria meningitidis cause infection and what are the clinical consequences

Answer 4

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

Question 5

What are 2 clinically significant neisseria

Answer 5

1) menigitides: causes meningococcal disease (meningitis or other form of sepsis)
2) gonorrhoea: causes urethritis, prostatitis, PID, septic arthritis, blindness

Question 6

What causes meningitis

Answer 6

neisseria
e coli (neonates)
group B strep (n)
strep pnuemonia (old, infants)
listeria (old)
haemophilus (infants)
enterovirus
measles
TB
auto-immune

Question 7

What are the virulence factors of staph aureus

Answer 7

-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

Question 8

What diseases are caused by staph aureus

Answer 8

skin infections (abscess, cellulitis, impetigo)
osteomyelitis
pneumonia
endocarditis
food poisoning
TSS

Question 9

What are some conditions caused by the different types of staph infections

Answer 9

1) staph aureus: skin infections, osteomyelitis, pneumonia
2) staph epidermidis: most common cause of infective endocarditis in prosthetic valves
3) staph saprophyticus: UTI

Question 10

What are the risk factors for toxic shock syndrome and what are it’s features

Answer 10

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

Question 11

Name some bacteria that cause wound infections

Answer 11

staph aureus
strep pyogenes
clostridium perfringens
pseudomonas aeruginosa
clostridium tetani

Question 12

Describe streptococci and name some different types of streptococci and what infections they cause

Answer 12

-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

Question 13

What are some post-infectious syndromes caused by streptococci infections

Answer 13

rheumatic fever
scarlet fever
immune complex glomerulonephritis
erythema nodosum
arthritis

Question 14

What are virulence factors of streptococcus infections

Answer 14

-capsules - resist phagocytosis
-produce M proteins that inhibit complement activation
-produce exotoxins that cause fever and rash
-produce pneumolysin that destroys cell membranes

Question 15

What is the pathological sequelae of HIV infection and what are the modes of transmission

Answer 15

-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

Question 16

Describe the structure of the influenza virus

Answer 16

-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

Question 17

What is the pathological basis for pandemics and epidemics

Answer 17

-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

Question 18

How does the body clear a primary influenza infection

Answer 18

-initially via CD8+ cytotoxic T cells and cytokines stimulating macrophages
-immunity acquired by antibodies

Question 19

How does influenza cause pneumonia

Answer 19

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

Question 20

What are clinical conditions caused by herpes simplex virus

Answer 20

-HSV-1: cold sores, gingivostomatitis, corneal blindness
-HSV-2: genital sores, encephalitis, increased risk of HIV transmission

Question 21

How does reactivation occur after primary herpes simplex infection

Answer 21

-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

Question 22

Describe the pathogenesis of glandular fever, clinical features and outcomes

Answer 22

-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

Question 23

What type of virus is measles, how is it spread, describe clinical manifestations and immune response

Answer 23

-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

Question 24

Describe the pathogenesis of herpes zoster

Answer 24

-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

Question 25

What are the complications of chickenpox (acute varicella infection)

Answer 25

interstitial pneumonia
encephalitis
transverse myelitis
shingles
bacterial superinfection

Question 26

What is croup and what causes it

Answer 26

-acute laryngotracheobronchitis causing inflammatory narrowing of the airway (barking cough, stridor)
-caused by viruses (parainfluenza, RSV, adenovirus, influenza)

Question 27

What is the clinical spectrum of a candida infection

Answer 27

-superficial mucosal: mouth, vagina, esophagus
-superficial cutaneous: nappy rash, balanitis, folliculitis, onychomycosis
-invasive: endocarditis, meningitis, pneumonia

Question 28

What mechanisms allow candida to cause disease

Answer 28

phenotypic switching
adhesion to host cells
secretion of invasive enzymes and adenosine that blocks neutrophils

Question 29

What organisms cause malaria and describe the pathogenesis

Answer 29

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

Question 30

How does P falciparum differ from other forms of malaria

Answer 30

can infect RBC of any age
causes RBC to clump
has antigenic variation to escape antibody responses

Question 31

How does P falciparum present clinically

Answer 31

fever
severe anaemia
acute renal failure
splenic rupture
cerebral symptoms
pulmonary oedema
DIC

Question 32

What factors make people less susceptible to malaria

Answer 32

inherited alterations in RBC (sickle cell)
repeated exposure stimulating immune response
HLAB53

Question 33

Which markers will be elevated in acute Hep B infection?

Answer 33

• HBsAg
• HBeAg
• HBV-DNA
• Anti-HBc IgM antibody

Question 34

What type of immune response occurs in measles?

Answer 34

• Adaptive (acquired) immune response
• T cells → control the infection and cause the rash
• B cells → antibodies to protect against re-infection

Question 35

What are the three cell surface receptors for the measles virus?

Answer 35

• CD46 (inactivates C3 convertase)
• SLAM (signaling lymphocytic activation molecule – involved in T cell activation)
• Nectin 4 (adherens junction protein)

Question 36

What disease states can EBV cause?

Answer 36

• Infectious mononucleosis
• Burkitt’s lymphoma

Question 37

What are the complications of glandular fever?

Answer 37

• Hepatitis
• Splenic rupture
• Transformation to lymphoma

Question 38

What is meant by viral “drift” and “shift”?

Answer 38

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.

Question 39

What are some common gram positive organisms?

Answer 39

• Staph
• Strep
• Enterococcus
• Nocardia
• Clostridium (anerobic)

Question 40

Describe the pathophysiology of syphilis.

Answer 40

• 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

Question 41

Manifestations of primary syphilis

Answer 41

-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

Question 42

Manifestations of secondary syphilis

Answer 42

-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%

Question 43

Manifestations of tertiary syphilis

Answer 43

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.