VIVA: Pathology - Infectious diseases Flashcards
What is the clinical spectrum of Candida infection?
- Benign commensal
- Superficial mucosal infection*: mouth, vagina, oesophagus
- Superficial cutaneous infection*: intertrigo, nappy rash, balanitis, folliculitis, paronychia, onychomycosis
- Chronic mucocutaneous (e.g. in T cell defects, endocrinopathy)
- Invasive (disseminated)*: myocarditis, myocardial abscess, infective endocarditis, meningitis, cerebral abscess, renal/hepatic abscess, endophthalmitis, pneumonia
- needed to pass with one example from each
What mechanisms enable Candida to cause disease?
- Phenotypic switching* to adapt rapidly to changes in host environment
- Adhesion to host cells* via adhesins (several types)
- Production of enzymes* (aspartyl proteases, catalases) which degrade ECM proteins and may aid intracellular survival
- Secretion of adenosine which blocks neutrophil degranulation
- 1/3 needed to pass
What type of organisms are Clostridia?
3/4 to pass:
- Gram positive
- Bacilli
- Anaerobic
- Spore-forming
Name the Clostridia organisms and the diseases they cause in humans
3/4 to pass:
- Clostridium perfringens, Clostridium septicum: gas gangrene, necrotising cellulitis
- Clostridium tetani: tetanus
- Clostridium botulinum: botulism (paralytic food poisoning)
- Clostridium difficile: diarrhoea, pseudomembranous colitis
How does botulism toxin cause disease?
- Normally ingested
- In the cytoplasm, the A fragment cleaves the protein synactobrevin which is needed for fusion of neurotransmitter vesicles
- Results in flaccid paralysis*
- needed to pass + concept
What is the pathogenesis of gas gangrene?
2/3 to pass (+ alpha toxin):
- C. perfringens and C. septicum release enzymes including hyaluronidase and collagenase
- Also produce alpha-toxin which is a phospholipase C and has multiple actions including degradation of muscle and RBC membranes -> results in release of phospholipid derivatives including prostaglandins -> ITP, derangements in cell metabolism, cell death
What is croup?
Acute laryngotracheobronchitis* in children:
- Inflammatory/spasmodic narrowing of the airway* produces barking cough and inspiratory stridor
Causes are predominantly viral, especially parainfluenza virus* (RSV, adenovirus and influenza are others)
- needed to pass
Describe the main characteristics of acute inflammation
- Relatively rapid onset
- Alterations in vascular calibre that increase blood flow*
- Leaky microvasculature*: structural changes in microvasculature that permit plasma proteins and leucocytes to leave the circulation, causing oedema
- Emigration of leucocytes (especially neutrophils)*, their accumulation at site of infection, and activation to eliminate offending agent
- Duration of hours to days
- needed to pass
Which bacterial class does Escherichia coli belong to?
- Gram negative bacilli*
- Facultative anaerobe*
- Normal enteric pathogen
- needed to pass
What is the difference between an endotoxin and an exotoxin?
Endotoxins are lipopolysaccharides (LPS) in the outer membrane of the cell wall of Gram negative bacteria which cause injury via the host immune response
Exotoxins are proteins that are secreted by the bacterium and cause direct injury
List some types of infections that can be commonly caused by E. coli?
3 to pass:
- UTI
- Prostatitis
- Epididymo-orchitis
- Infectious enterocolitis
- Cholecystitis
- Bacterial pneumonitis
Describe the pathogenesis of glandular fever
- Caused by Epstein Barr virus (EBV)* which is transmitted by close contact (saliva)
- Envelope glycoprotein binds to B cells
- Viral infection begins in the naso-/oro-pharyngeal lymphoid tissues (especially tonsils)*
- B cell infection causes lysis of infected cells and virion release (minority)*, or latent infection (EBV genes expressed)
- Symptoms appear on initiation of host immune response (by cellular CD8+ cytotoxic T cells and natural killer cells)
- Atypical lymphocytes are characteristic
- Also see reactive T cell proliferation in lymphoid tissues, causing lymphadenopathy and splenomegaly
- IgM Ab (to viral capsid Ag) and later IgG response
- In the healthy host, viral shedding ceases with few resting B cells but acquired defects may result in B lymphomas
What are the clinical features of glandular fever?
4 to pass:
- Fever
- Sore throat
- Lymphadenitis
- Splenomegaly
- Fatigue (atypical)
- Hepatitis (atypical)
- Rubella-like rash (atypical)
- Lymphadenopathy (atypical)
What are the outcomes of glandular fever?
3 to pass:
- Most resolve within 4-6 weeks with some persisting fatigue
- Hepatic dysfunction with jaundice and abnormal LFTs
- Splenic rupture
- Other system involvement (nervous, renal, lungs, heart)
- Transformation to B cell lymphomas
Please give some examples of clinical herpes simplex infection
3 to pass:
- Cold sores
- Gingivostomatitis
- Encephalitis
- Genital herpes
- Keratitis (epithelial and stromal)
- Disseminated visceral herpes (with oesophagitis, bronchopneumonia, hepatitis, Kaposi varicelliform eruption, eczema herpeticum)
After primary herpes simplex infection, how does reactivation occur?
- Viral nucleocapsids travel from skin/oropharynx/genitalia to the nucleus in the sensory neuron
- During latent period, only viral mRNA (no viral proteins are made, to escape immune recognition)
- Reactivation from latency occurs by avoiding immune recognition, inhibiting the MHC class I recognition pathway, and eluding humoral immune defences by producing receptors for the Fc domain of immunoglobulin and inhibitors of complement. Occurs antidromically along sensory nerve.
Describe the pathogenesis of herpes zoster
- The patient has had previous exposure* to herpes (chickenpox or subclinical)
- VZV evades immune defences and infects sensory neurons* in and around dorsal root ganglia
- Able to remain latent* here for many years
- Usually a single episode of recurrence in the form of zoster/shingles
- Reactivation* often in the elderly or immunocompromised
- Vesicular eruption along dermatome of one or more sensory nerves*, with associated intense burning, itching and pain due to radiculoneuritis (may also cause nerve dysfunction, e.g. Ramsay Hunt syndrome)
- needed to pass
What are the major pathological sequelae of HIV infection?
Attacks CD4+ T cells resulting in profound immunosuppression, which leads to opportunistic infections, neoplasms and neurological manifestations
What are the modes of transmission?
Sexual contact:
- 75% sexual, heterosexual* globally more common (typically female partners of IVDU)
- Female to male 1/20th as efficient in US, more in Thailand
- Abetted by STIs
Parenteral*:
- IVDUs majorly
- Blood products nearly eliminated
- Needle-stick 0.3%
Vertical:
- Mother-to-infant* in utero, at delivery, in breastmilk
- 7-49%
Not by insect bites
- needed to pass
Describe the structure of the influenza virus
Single stranded RNA* (8 helices) bounded by nucleoprotein that determines type (A, B, C)
Enveloped virus, spherical capsule
Glycoprotein spikes in lipid membrane (determine subtype e.g. H1N1): haemagluttinin, neuraminidase
- needed to pass
What are the types and subtypes of influenza virus?
A, B, C*: determined by nucleoprotein (protein which encapsidates the viral RNA)
A is found in humans, pigs, horses and birds, and is the major cause of pandemics/epidemics (demonstrates antigenic drift and shift)
B and C infect mostly children, who develop antibodies which are effective at preventing re-infection
Haemagglutinin and neuraminidase*: determined by proteins on the bilipid envelope, determines subtype (e.g. H1N1)
What is the pathological basis of influenza pandemics and epidemics?
Antigenic drift*: mutation of NA and HA allowing escape from most host antibodies, responsible for epidemics
Antigenic shift*: HA and NA replaced through recombination of RNA segments with those of animal viruses, responsible for pandemics
Only influenza type A undergoes antigenic drift or shift (type B and C mostly infect children, who develop antibodies effective at preventing re-infection)
- needed to pass
