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
*needed to pass
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 of HIV?
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
How does the human body clear a primary influenza virus infection?
Two mechanisms:
1. Cytotoxic T cells *: kill virus-infected cells
2. Macrophages *: intracellular anti-influenza protein (Mx1) is induced in macrophages by cytokines IFN-a and IFN-B
Future infection is prevented via production of haemagglutinin antibody, and ameliorated by production of neuraminidase antibody
*needed to pass
How does the influenza virus cause pneumonia?
- Attachment of virus to upper respiratory tract epithelium*
- Necrosis of cells followed by inflammatory response
- Interstitial inflammation with outpouring of fluid into alveoli
- Secondary infection by Staph/Strep*
*needed to pass
What organisms cause malaria?
Malaria is a protozoal* infection, caused by the intracellular parasite* Plasmodium
Species includes P. falciparum*, P. ovale, P. vivax, and P. malariae
*needed to pass + one other example of Plasmodium
Describe the pathogenesis of malaria
- Infectious stage (sporozoite) is found in saliva of female anopheles mosquito*
- Sporozoites are released into blood following inoculation, and invade hepatocytes* where they multiply rapidly*
- Hepatocyte ruptures, releasing up to 30,000 merozoites (note that P. vivax and ovale can have a dormant hepatic stage and therefore can relapse)
- Released merozoites from liver bind to surface of RBC* and grow in a vacuole
- In RBCs, merozoites mature to trophozoites (single chromatin), then schizont (multiple chromatin masses), then each chromatin becomes merozoite again
- RBC lyses* and new merozoites infect additional RBCs
- Some gametocytes also form in RBCs and invade mosquito
Note only erythrocytic parasites cause illness (schizont form causes RBC rigidity and leads to their removal in the spleen)
*needed to pass + general concept
How does P. falciparum present clinically?
Fever*
Severe anaemia
AKI
Cerebral symptoms
Pulmonary oedema
DIC
Hepatosplenomegaly
Splenic rupture
Mechanism:
- Congestion and enlargement of spleen -> anaemia, DIC
- Infected RBCs clump -> ischaemia due to poor perfusion -> manifestations of cerebral malaria (vessels plugged with parasitised RBCs, local venous stasis, local hypoxia and inflammatory infiltrate)
- AKI due to Hb casts in tubules, pigment etc in glomeruli
- Release of cytokines TNF, IFN, IL-1 -> pulmonary oedema, fever, shock
*needed to pass + one
How does Plasmodium falciparum infection differ from other forms of malaria?
Pathogenesis for all forms of malaria:
- Sporozoite -> liver -> merozoites formed -> release and bind to RBC -> Hb hydrolysed -> trophozoite -> schizont -> merozoite/gametocyte
P. falciparum specifically:
- Infects RBCs of any age *, causing clumping/rosetting * and so producing ischaemia
- High cytokine production
- High level parasitaemia *
- Severe anaemia
- Cerebral symptoms
- Renal failure
- Pulmonary oedema
- Death
Non-falciparum:
- Infect only new or old RBCs
- P. vivax and ovale form latent hypnozoites (relapses), have low parasitaemia, and cause mild anaemia and rarely splenic rupture and/or nephrotic syndrome
*2/3 needed to pass + one clinical feature
What factors can make people less susceptible to malaria?
Inherited alterations in RBCs *:
- HbS trait *
- HbC
- Duffy Ag negative
Repeated exposure stimulates immune response:
- Antibody and T lymphocytes (P. falciparum avoids this)
- HLA-B53
*needed to pass
What type of virus is measles?
Single stranded RNA virus*
Member of Paramyxovirus* (which also includes mumps, RSV and parainfluenza)
Only one strain of the virus exists which means it is preventable by vaccination (epidemics can occur amongst unvaccinated individuals)
Multiplies in upper respiratory tract epithelial cells, and travels to lymphoid tissues where it replicates in mononuclear cells
*1/2 needed to pass + one other
How is measles spread?
Respiratory droplet spread
Describe some of the clinical manifestations of measles infection
Viral pneumonia (60% of deaths)
Secondary bacterial infection
Conjunctivitis and keratitis (scarring and blindness)
Acute measles encephalitis* (1:1000; adults > kids)
Subacute sclerosing panencephalitis (1:100,000)
Diarrhoea (enteropathy)
Immunosuppression
Croup
*needed to pass + one other
What immune responses occur as a result of measles infection?
T-cell mediated immunity controls the infection and produces the rash via a hypersensitivity reaction to viral antigens in the skin (no rash if there is a deficiency in cell-mediated immunity)
Antibody-mediated immunity to measles virus protects against re-infection
What are the clinical features of measles?
Fever*
Rash* (blotchy, red/brown, begins in face and spreads downwards)
Conjunctivitis*
Cough/coryza*
Koplik spots (oral mucosal ulceration)
Lymphadenopathy
*3 needed to pass
What are the cell-surface receptors for the measle virus?
- CD46 (complement regulatory protein): present on all nucleated cells where it functions to inactivate C3 convertases, binds viral haemagglutinin protein
- SLAM (Signalling Lymphocytic Activation Molecule): only present on immune cells where it is involved in T cell activation, binds viral haemagglutinin protein
How does Neisseria meningitidis cause infection?
4/7 to pass:
- Common coloniser of the oropharynx, present in 10% of population at any one time and can be carried for months
- Most people develop immune response and clear it, and are then protected against later infection from this serotype (however there are >13 serotypes)
- Invasive disease caused by exposure to new serotype (outbreaks can occur in young people living in crowded quarters who encounter new strains)
- Spread by respiratory droplets
- Invades respiratory epithelium then bloodstream
- Capsule allows Neisseria to evade immune response by preventing opsonisation and protecting against destruction by complement
- Mortality still ~10% despite antibiotic treatment
What are the clinical consequences of N. meningitidis infection?
4 to pass:
- Death
- Sepsis
- Necrotising vasculitis
- Seizures
- SIADH
- CVA
- Hydrocephalus
- Meningitis
- Sensorineural hearing loss
- Cognitive impairment
Apart from Neisseria, what else can cause meningitis?
Other bacteria*:
- In infants: E. coli, GBS
- Strep pneumonia
- Listeria
- Haemophilus
Viral:
- Enterovirus
- Measles
Other:
- TB
- Rickettsial
- Carcinoma
- Autoimmune
- Chemical
- Fungal
*2 specific bacteria plus viral as a group
What are the microbiological features of Neisseria?
Aerobic
Gram negative diplococci
Coffee bean shaped
Required chocolate blood agar for culture growth
13 serotypes
What are the two clinically significant Neisseria?
Meningitidis
Gonorrhoeae
Describe the virulence factors of Staph aureus
Surface proteins:
- Involved in adherence
- Express receptors for fibrinogen (and others) to bind to host endothelial cells, and artificial materials
- Evade host immune response
Secreted enzymes:
- Degrade proteins (promoting invasion and destruction)
- Degrade skin lipids (associated with ability to produce abscess)
Secreted toxins*:
- Damage host cells
- Alpha toxin: membrane depolarisation/damage
- Beta toxin: sphingomyelinase
- Exfoliative A and B toxin
- Gamma toxin, leukocidin
- Superantigens: causes TSS and food poisoning
*needed to pass with example + one other group
What are the risk factors for toxic shock syndrome?
2 to pass:
- Use of tampons
- Nasal packs
- Post-operative wound infection
- Post-partum
- Staph or strep skin infection
What are the clinical features of toxic shock syndrome?
4 to pass:
- Hypotension (shock)
- Acute renal failure
- Coagulopathy
- Respiratory failure
- Liver disease
- Soft tissue necrosis at site of infection
- Generalised erythematous rash
Name some common bacteria that cause wound infections
Staphylococcus aureus*
Streptococcus pyogenes*
Clostridium perfringens
Clostridium tetani
Aerobic Gram negative bacilli
Pseudomonas aeruginosa
*needed to pass + one other
What diseases are caused by Staphylococcus aureus?
Skin/soft tissue infection:*
- Cellulitis
- Impetigo
- Abscess (furuncle, carbuncle)
- Folliculitis
- Paronychia
- Felon
- Lymphadenitis
- Necrotising soft tissue infection
- Scalded skin syndrome
Non-skin infections*:
- Pneumonia
- Endocarditis
- Osteomyelitis / septic arthritis
- Food poisoning
- Toxic shock syndrome
*needed to pass + 3 example of each
What infections do the different species of Staphylococci cause?
2/3 to pass:
- S. aureus: skin, pneumonia, osteomyelitis, etc
- S. epidermidis: opportunistic (e.g. infective endocarditis on prosthetic valves)
- S. saprophyticus: UTI in women
What is the microscopic appearance of streptococci?
Gram positive cocci in pairs* or chains
*needed to pass
What are some post-infectious syndromes caused by streptococcal infections?
- Rheumatic fever* (+/- complications, chorea)
- Immune complex glomerulonephritis*
- Erythema nodosum
- Rash
- Myoclonus
- Myalgia
- Arthritis
- Neuropsychiatric sequelae, tics
*1 needed to pass + one other
List some infections caused by streptococcus
Cause acute suppurative infections in the skin, throat, lungs, and heart valves*
Alpha haemolytic:
- S. pneumoniae: pneumonia, meningitis
- S. viridans: subacute bacterial endocarditis
B-haemolytic:
- S. pyogenes (group A strep): erysipelas, impetigo, scarlet fever, pharyngitis, toxic shock syndrome
Group B:
- S. agalactiae (group B strep): neonatal sepsis and meningitis, chorioamnionitis
Other:
- S. mutans: dental caries
*needed to pass + 4 specific examples
What factors in streptococci contribute to their virulence?
3 to pass:
- Capsules (pyogenes, pneumoniae): protects from opsonisation and destruction by complement
- M protein: prevents phagocytosis (anti M protein causes rheumatic fever)
- Complement 5a peptidase
- Pneumolysin (S. pneumoniae): lyses target cells, activates complement
- Pyrogenic exotoxin: causes rash and fever
- High MW glucans (S. mutans): induce plaque formation and platelet aggregation
What are the two clinical conditions caused by varicella zoster virus?
Chicken pox
Shingles
Describe the pathogenesis and clinical course of infection with varicella zoster virus
- Starts with aerosol or direct contact spread
- Haematogenous dissemination
- Vesicular skin lesions occur ~2 weeks after aerosol exposure; begins centrally and spreads centrifugally in multiple waves, initially macular with rapid progression to vesicular
- After a few days, vesicles rupture and crust over then heal (unless bacterial superinfection; most heal with no scarring)
- Some virus lies dormant in dorsal root ganglia and is reactivated later in the setting of immunosuppression
Causes milder disease in children compared with adults
What are the complications of chicken pox?
3 to pass:
- Lung: interstitial pneumonia
- Nervous system: encephalitis, transverse myelitis
- Skin and mucous membranes: shingles, bacterial superinfection
- Gut: necrotising visceral lesions
What tissues may be involved in a primary varicella zoster infection?
Mucous membranes
Skin
Neurones
What is shingles? Describe the clinical picture
- VZV evades immune defences and infects neurons in and around dorsal root ganglia, where it is able to remain latent for many years
- Usually a single episode of recurrence occurs in the form of zoster (shingles)
- Reactivation often occurs in the elderly or immunocompromised
- Vesicular eruption occurs along the 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)
- Complications include interstitial pneumonia, visceral lesions, encephalitis etc
