Infectious diseases Flashcards
what are 2 phases of the metabolic response to injury/sepsis
ebb + flow phase
separated by resuscitation
both can lead to multiple organ failure
ebb = hypometabolic, low core body temp, more catecholamines, poor tissue perfusion
flow = hypermetabolic, high core body temp, less catecholamine, no tissue perfusion
how do the 2 phases of metabolic response to injury differ
ebb = hypometabolic, low core body temp, more catecholamines, poor tissue perfusion
flow = hypermetabolic, high core body temp, less catecholamine, no tissue perfusion
both can lead to multiple organ failure
how does simple starvation + injure differ metabolically
starvation = metabolic adaptation to slower rate (so lower resting energy expenditure)
so lean tissue conserved - as body fuels/proteins conserved
injury (catabolic weight loss) = no adaptation, causing high metabolic rate spending lots of resting energy
so lean tissue breakdown (body fuels/proteins wasted) - even with nutrient intake
what is main fuel in starvation + stress
starvation = fat (ketosis - physiological response to alternative energy supply)
stress = fat + AA (causing muscle breakdown, occurs due to higher counter regulatory hormones to allow proteolysis)
why does ketosis occur
physiological response of body to need for alternative energy supply
brain needs glucose so adapts to ketones as they can cross BBB
what is serum analysis of starvation
high serum urea + ketones
high urea = protein/muscle breakdown, AKI
high ketone = alternative energy supply using TG-FFA breakdown
how does low glucose affect insulin + glucagon
low glucose = low insulin + high glucagon
causes degradation of glycogen, fat stores, protein
so muscle adapts to ketone to prevent protein breakdown
adipose tissue is sensitive to glucagon that stimulates lipase so more TG->FFA
what is insulin action
increase glucose uptake into skeletal muscle, adipose (by increasing sensitivity to more insulin)
suppress hepatic gluconeogenesis
directly inhibit lipolysis by ketones
how does DKA + alcohol ketoacidosis differ
DKA = high glucose + high ketones + metabolic acidosis
as glucose can’t be used, so ketones used instead as alternative energy supply
alcoholic ketoacidosis = not significant hyperglycaemia + high ketones + metabolic acidosis
when malnourished, ethanol metabolised to acetic acid (ketone) causing high ketones levels without high glucose
what hormones are involved in ketoacidosis
high glucagon + low insulin
ketosis occurs in liver
after prolonged starvation/fasting, when OAA depleted from gluconeogenesis
so acetyl-CoA can’t enter Kreb cycle
causes excess acetyl-CoA which is converted in liver mitochondria to ketones (acetone, acetoacetate, B-hydroxybutyrate)
what is major ketone in fasting ketosis
B-hydroxybutyrate
ketone = water-soluble, fat derived
physiological response to low glucose supply
what is SIRS criteria
2 or more:
temp <36 or >38
HR >90bpm
RR >20, PaCO2 <4.3/<32
WCC <4,000 or >12,000
how does severe sepsis + septic shock differ
severe sepsis = SIRS + associated organ failure, hypoperfusion, hypotension (SBP <90)
septic shock = severe sepsis + arterial hypotension unaffected by fluid resus
what is SEPSIS 6
take: lactate, urine output, blood culture
give: O2, IV fluids, IV antibiotics
why is glucose high in critical illness
stress mediators oppose anabolic actions of insulin = so more tissue lipolysis, skeletal muscle proteolysis + suppressed hepatic gluconeogenesis
high catecholamines (cortisol) has catabolic effect increasing gluconeogenesis (so more glycogen breakdown) = inhibits GLUT4 translocation in muscle/adipose so peripheral insulin resistance
what is immune system role in protein/lipid metabolism in illness
pro-inflammatory cytokines TNF reduces ability to use lipids as energy source
so skeletal muscle is major substrate for glucose (75%)
decrease in muscle -> insulin resistance
high catecholamines -> browning of fat (so hyper metabolic response + cachexia)
how does starvation effect endocrine system
sick euthyroid = low/N TSH, low/N T4, low T3
chronic undernutrition lowers metabolic rate so less T4 -> T3
HPO (ovarian) axis suppressed
hypogonadotrophic hypogonadism (low GnRH, low LH/FSH) = amenorrhoea, infertility
increased HPA axis
more stress so high cortisol (glucocorticoid)
breakdown protein - loss of collagen (osteopenia), loss of muscle (weakness)
what is sepsis
life-threatening organ dysfunction as dysregulated host response to infection
irrespective of organism/focus
how do SIRS + sepsis differ
sepsis = SIRS + infection
severe sepsis = sepsis + organ failure/hypoperfusion/hypotension (SBP <90)
septic shock = severe sepsis + arterial hypotension unaffected by fluid resuscitation + lactic acidosis
SIRS: 2 of
temp <36 or >38
WCC <4,000 or >12,000
HR >90
RR >20, PaCO2 <32
what is toxic shock syndrome
gram +ve bacteria release super antigens (antigens that cause immune response in 20% resting T cells + not restricted by antigen specificity)
staph aureus (burn) - TSS1
strep pyogenes (necrotising fasciitis)
how do gram +ve and -ve stain
-ve = pink stain as thin peptidoglycan + high lipopolysaccharide
e.coli, haemophilus influenza
lipopolysaccharides release ENDOtoxin (PAMP) recognised by TLR4 (PRR) that activate APC
+ve = purple stain as thick peptidoglycan layer + lipotechtic acid
less potent infection
staph aureus, strep pyogenes
forms super antigens (staph aureus, strep pyogenes) - protein EXOtoxin that stimulate immune response in 20% resting T cells, not restricted by antigen specificty
what are 3 shocks in sepsis
distributive = warm peripheries
hypovolaemic = cold peripheries + responds to fluid
cardiogenic = cold peripheries + not fluid responsive
how is sepsis severity determined
SOFA score:
RR >22
GCS <15
SBP <100
what causes malaria
protozoan parasite = plasmodium
p.falcifarum spread by bites of female anopheles mosquitoes (sub-Sahara)
p.falcifarum most common globally
p.vivax most common outside Africa
how do complicated + uncomplicated malaria differ
complicated = parasitaemia >2%
OR parasitaemia <2% + clinical signs
uncomplicated = parasitaemia <2% + no schizont + no clinical signs
what EIR (entomological inoculation rate) is stable + unstable
stable = EIR >10/yr
unstable = EIR <5/yr
how often do fever spikes occur in active malaria
every 48hr = fever spike corresponds with schizont rupture causing haemolytic anaemia
how does malaria obstruct circulation + what is the impact
obstructs circulation by sequestering + rosetting
sequester = binding of 2 infected RBC
rosett = binding of uninfected + infected RBC
PfEMP proteins bind iRBC to vascular endothelium
causes hypoxia + cytokines release which damages tissue
so malaria can evade immune response
what is protective against malaria
HbS sickle cell trait - common in africa
Duffy group + ve protective to p.vivax infection (common outside Africa)
how does malaria present
recent travel to endemic country
pallor + jaundice = haemolytic anaemia
hepatomegaly
how is malaria diagnosed
giema stain on blood film = RBC lyse appearing blue/purple
peripheral blood film = identify parasitaemia (how many schizonts to determine parasite stage)
what are the main infective causes of headache
meningitis
encephalitis - inflamed brain parenchyma
what is aseptic meningitis + meningococcal septicaemia
aseptic meningitis - meningitis not caused by pyogenic bacteria (doesn’t make pus)
meningococcal septicaemia - meningococcal bacteria infecting bloodstream
what is main cause of community-acquired bacterial meningitis in
neonate
child
adult
60yr+ or immunocompromised
neonate - strep agalcteia group B (vertical transmission), e.coli
present with bulging fontanelle
child/adult (adolescent) - neisseria meningitidis group B
vaccine against haemophilus influenza type B
adult - strep pneumonia
immunocompromised - listeria monocytogenes (or TB)
what is most common viral cause of meningitis
NPEV- non-polio human enterovirus
enterovirus species B, cocsackbe virus A9, echovirus A71
how are viral meningitis pathogens spread
feacal-oral route
year-round in tropical/subtropic areas
seasonal in temperate climate
how does bacterial + viral meningitis present
bacterial - sudden onset, systemic upset (sepsis)
viral - gradual onset, less severe
what red-flag features indicate meningitis
headache, fever, neck stiff, photophobia
vomiting
altered conscious, seizures
if viral meningitis:
nuchal rigidity = resisting passive neck flexion
kerning sign = can’t extend knee when hip is flexed
brudinzski sign = when flexing neck, hip/knee spontaneously flex
how do neisseria + strep pneumonia differ
neisseria.m = meningococcus (causes petechial rash)
gram -ve diplococci
commensal organism in URT
strep pneumonia = pneumococcus
gram +ve diplococci
meningitis occurs after pneumonia or ear infection
what are the different rashes in menigitis
petechial/purpuric rash - from meningococcal infection (neisseria)
non-blanching rash - meningococcal septicaemia (when pathogens enter bloodstream)
why does a non-blanching rash occur in meningococcal septicaemia
DIC + subcutaneous haemorrhage
how to investigate meningitis
bacterial = CSF sample from LP
viral = PCR
what causes aseptic meningitis
usually viral pathogen
drug - amoxicillin, NSAID, trimethoprim+sulfamethoxazole
malignancy, SLE, Kawasaki disease
what is seen on bacterial + viral meningitis CSF sample
viral - all normal other than high WCC
bacterial - cloudy CSF
high opening pressure, high protein
high neutrophil (polymorphic leukocytes)
LOW glucose
how do HSV1 + HSV2 differ
HSV1 = most common cause of sporadic encephalitis globally
HSV2 = causes benign recurrent aseptic/lymphocitic meningitis
how is meningitis managed
if bacterial = inform PHE
<3months = IV amoxicilline + IV ceftriaxone
3+ months = IV ceftriaxone
if penicillin allergy, chloramphenicol instead
steroids used as adjunct to prevent hearing loss, cerebral palsy
what signs are seen with viral meningitis
nuchal rigidity = resisting passive neck flexion
kerning sign = can’t extend knee when hip is flexed
brudinzski sign = when flexing neck, hip/knee spontaneously flex
what is measles virus
non-segmented, negative sense RNA
only encodes 1 type of antigen (unlike other RNA viruses)
transmitted via resp route (droplets/aeresols suspended in air last for 2hr)
incubation period 12.5 days
morobillus genus, paramyxoviridae family
what gene of measles encodes the 2 non-structural proteins
protein V + C (non-structural proteins of measles)
within phosphoprotein gene
how does measles differ from other RNA viruses
antigenically monotypic
despite its genotypic diversity and that RNA viruses have high mutation rates
how long is the infectious period for measles
begins several days before and lasts several days after rash onset
coincides with peak viraemia, cough/corozya
what rash occurs in measles
macropapular rash - initially face + behind ears, then spreads down trunk
occurs 3-4 days before fever onset
what vitamin deficiency makes children susceptible to measles
Vitamin A
how is measles diagnosed
PCR assay for measles virus RNA
measles-specific IgM in blood
what is HIV incidence
highest in East/South Africa
most new HIV infections in sub-Saharan Africa
how is HIV characterised + how does it present
characterised - high viral load, high risk of transmission
high inflammatory response causes systemic responses
present - fever, sore throat, macropapular rash (similar to EBV)
but symptoms improve few wks later (asymptomatic phase)
what is AIDS
when CD4 count <200cells (marked rebound in HIV viral load)
causes onset of opportunistic infections, malignancy
what is HIV virology
genus - lentivirus
family - retrovirus
made of 2 identical ssRNA molecules
so needs reverse transcriptase RT to form DNA + intergrase IN to combine this viral DNA with the host’s
enclosed in viral capsid
how do HIV 1 + 2 differ
both are zoonotic in origin
HIV1M most common globally (other HIV1 types confined to west/central Africa)
HIV2 rare outside west-Africa
HIV1 (chimp, gorilla) - 4 groups M,N,O,P
HIV2 (sooty mangabey) - 9 groups A-H, J, K
where is the highest HIV1 genetic diversity
central africa
what is structure of HIV1
viral capsid containing 2 identical ssRNA molecules + RT/IN enzymes
glycoprotein GP-120 + GP-41
viral envelope proteins
these attach to CD4-Tcells
with coreceptors: CCR5 (if R5 virus) + CXCR4 (if X4 virus)
how is HIV transmitted
blood Bourne virus
parenteral exposure (sharing needle), sexual exposure, vertical transmission
why can ART antiretroviral treatment not eliminate HIV infection
ART can suppress viral replication but not residual replication
ART can’t eliminate HIV integrated viral DNA from infected host cells
so residual replication can still occur to maintain HIV reservoir
why can host immune response not contain HIV infection
CTL (CD8 cytotoxic T lymphocyte) escape mutants
HIV viral capsid is glycosylated to evade immune system + cellular restriction factors like APOBEC3
what occurs in AIDS stage
CD4 <200cells, causes immunosuppression, opportunistic infections, AIDS-malignancy
more pro-inflammatory cytokines (type 1 IFN, IL6, IL1)
low CD4/CD8 ratio
exhaustion/sensescence of T cells + macrophages
pro-inflammatory state causes premature ageing, multi-organ disease
what is PJP
AIDS related infection, when CD4 <200cells
presents: oral candidiasis
2wk hx of fever, SOB, non-productive cough
9 month of weight loss
if HIV +ve, confirmed PJP (fungal infection)
Cotrimoxazole, prednisolone, fluconazole
how does HIV alter lymphoid structure
changes intestinal lymphoid structure so disturbed gut barrier, causes more microbial translocation
more plasma lipopolysaccharide circulation, so enhanced persistent immune activation
