Mixed Q’s 5 Flashcards
Botulinum toxicity features?
Blocks presynaptic ACh
Impaired nicotinic and muscarinic neurotransmission
Symmetrical descending paralysis with cranial nerve involvement 2o eating home canned foods
Treatment of pts with cryptococcal meningitis?
Amphotericin B and flucytosine
Cryptococcal meningitis features?
Slowly worsening headache
Fever
Lethargy
LP: low glucose high protein, predominant lymphocytes
NMDA receptor excess activation ?
Is a glutamate receptor and Ca ion channel found in neurons
Excessive activation of the NMDA receptor causes neuronal death through uncontrolled Ca influx.
The receptor is blocked by Mg —> decreased influx of Ca and Na
Pathology behind raised intracranial pressure?
Idiopathic
2o cerebral venous sinus thrombosis decreased resorption of cerebrospinal fluid
What is the benefit of giving dexamethasone prior to Abx therapy in bacterial meningitis?
Decreases inflammatory response in the CSF
Virulence factor of Neisseria meningitidis?
Use Pili to attach to and colonise the nasopharyngeal epithelial surface
Negative equilibrium indicates the membrane is permeable to ?
K or CL-
Positive equilibrium indicated membrane is permeable to (Na and Ca)
Cryptococcus Neoformans appearance on histopathology?
Encapsulated yeast with thick polysaccharide capsule ( clean on H&E tissue stain)
Upregulation of which channels lead to pain at site of neuroma after nerve injury?
Na channel upregulation
Febrile seizures features?
6/12 - 5 years
Temp >38
Hyperthermia induced neuronal dysfunction triggering a short generalised seizure.
Age related sleep changes features?
Decreased total sleep time
Increased nighttime waking
Sleepiness earlier in the evening
Earlier morning waking
Increased daytime napping
Frontal lobe dysfunction?
Change in personality, languages, motor function and executive function. Abstraction ability ( asking about similarities between 2 related objects) affected
Buildup of very long chain and branched chain fatty acids is due to a dysfunction in which cellular structure?
Peroxisome
Multiple ring enhancing lesion in a patient with AIDS ?
Toxoplasmosis encephalitis
Cryptococcus Neoformans primary site of infection?
Lungs / inhalation
Soil contaminated by bird droppings
Shingles occurs because of ?
Reactivation of latent pathogen in neural ganglia
Influx of ca is important in voltage gated neurotransmission because ?
It’s essential for fusion and release of neurotransmitter vesicles
Drugs that bind to GABA-A receptors affect on resting membrane potential?
Will increase CL influx causing membrane potential to become more hyper polarised i.e. negative
Guillian Barre syndrome features?
Symmetric Ascending weakness
Immune mediated polyneuropathy
Follow campylobacter jejuni diarrhoeal illness
Hydrocephalus presentation?
Macrocephaly
Poor feeding
Poor growth
Developmental delays
Untreated —> muscle spasticity
Guillemot Barre Syndrome features?
Symmetric ascending weakness immune mediated polyneuropathy
Follows campylobacter jejuni
diarrhoea illness
Alzheimer’s disease pathogenesis ?
Neuro degeneration lead into cerebral atrophy
Beta amyloid plaques
Tau proteins microtuble associated protein polymerised and hyperphosphorylated
Rabies attaches to which receptor?
Nicotinic acetylcholine receptors present in neuromuscular junctions
Tay-Sachs disease features?
AR
Beta heoxsaminidase A deficiency
Accumulation of GM2 ganglioside
Progressive neurodegenreation ( developmental regression)
Exaggerated startle reflex
Cherry red macula
Osmotic demyelination syndrome (central pontine myelinosis features?
2o rapid correction if chronic hyponatremia esp alcoholic
Quadriplegia
Pseudobulbar palsy (dysarthria, dysphagia, dysphonia)
Reduced level of consciousness
Myasthenia gravis pathogenesis?
Decreased number of functional acetylcholine receptors
Reduced amplitude of motor endurance plate potential
Mgx of myasthenia gravis?
Cholinesterase inhibitor e.g pyramidine
Selective muscarinic inhibitors e.g glycopyrollate can reduce the SE
Reye’s syndrome features?
Acute liver failure and encephalopathy in child who took aspirin
Causing mitochondrial toxicity
Diffuse astrocyte swelling
Commonest cause of bacterial meningitis?
Strep pneumoniae
Ectopic pregnancy should be suspected in ?
Abnormally rising b-hcg
2o amenorrhea
Endometrium will be showing pregnancy changes
Raised Acetylcholinesterase and AFP in amniocentesis suggests?
Neural tube defect
DiGeorge is due to what genetic mutation?
Ch 22q11.2 microdeletion
DiGeorge features?
Hypo calacaemia/hypoparathyroidiam
Thymic aplasia( T cell deficiency)
Dysmorphic face ( cleft palate)
Cardiac anomalies (tetralogy of fallout)
Frontotemporal dementia due to abnormal accumulation of ?
Pathologically ubiquinated TDP-43 and neurofibrillary tangles due to abnormal TAU protein
Rapid corrections of chronic hyponatremia leads to ?
Osmotic demyelination syndrome …a cerebral demyelination abnormality
Migraine features?
Episodic neurologic disorder resulting in severe, unilateral pulsatile headaches assoc with photophobia, photophobia N+V
+/- aura
Cerebral palsy cause?
Periventricular focal necrosis /
(Periventricular leukomalacia ( white matter necrosis)
Narcolepsy features?
Chronic sleep disorder characterised by
daytime sleepiness
cataplexy
REM sleep related phenomenon (hallucinations, sleep paralysis)
Guillain barre histology ?
Endoneurial inflammatory infiltrate seen on light microscopy
Haemorrhage and necrosis of the mnamillary bodies causes?
Wernicke’s encephalopathy
2o thiamine deficiency
By way of deficiency of erythrocytes transketolase activity impairing glucose production and use
Neuro imaging findings in Huntington’s disease?
Atrophy of the caudate nuclei and enlargement of the front horns of the lateral ventricle
Optic neuritis and intranuclear opthalmoplegia in MS is usually due to which mechanism?
Reduced saltatory conduction
2o demyelination
HSV-1 encephalitis features?
Headache
Fever
Altered mental state
Seizure
Pathology:- haemorrhagic necrosis of temporal lobe
Findings in irreversible ischaemic injury in brain ?
12-24hrs
Shrinkage of cell body
Pykinosis of nucleus
Loss of nissl bodies
Cytoplasmic eosinophilia
Route of entry of primary amoebic meningoencephalitis?
Caused by protozoa naegleria fowleri
Penetrated olfactory mucosa and migrates retrograde through the olfactory nerve
Multiple sclerosis findings ?
Demyelinating plaques lesions
Hyperintense lesions on T2 weighted MRI of the brain and spinal cord
ALS pathology?
Degeneration and atrophy of the corticospinal tract and precentral gyrus (UMN)
Degeneration of anterior horn of the spinal cord and cranial nerve motor nuclei (LMN)
Glutamate neurotransmitter features?
Main excitatory neurotransmitter of the CNS
Induces postsynaptic neuron depolarisation
Calcium entry programs the neurons to be more sensitive with repeat stimulation
Function long term learning and memory
Signs of vitamin A toxicity?
Benign intracranial HTN
Headache
Vomiting
Papilloedema
Dry skin
Hepatomegally
Cholinesterase inhibitors (donepezil, galantamine) use in Alzheimer’s?
May temporarily improve cognitive function but do not alter the disease progression
Guillain Barre pathology?
Molecular mimicry
Ab against infectious agents cross react with myelin and Schwann cells leading to immune mediated demyelination ( Tcell response)
Microscopy:- segmental demyelination + endoneurial infiltration with lymphocytes and macrophages
Subarachnoid haemorrhage is usually due to?
Saccular ( berry) aneurysm
Essential tremor features?
Tremor worse on extension of arms and at the end of intended action
Assoc with head tremor
No other neuro findings
AD
+ve Fhx
Mechanism of action of B blockers in essential tremor and SE?
Blocks interaction of norepinephrine with at adrenergic synapse
SE :- b2 block —> bronchoconstriction
Von Hippel Lindau disease features?
Mutation in VHL tumour suppressor gene on chromosome 3
Cerebellar haemangoblastoma
Congenital cysts in kidneys, liver and/or pancreas
AD
Treatment of trigeminal neuralgia?
Carbamazepine
Increases Na channels inactivation by reducing high frequency firing
SE of volatile anaesthetics?
Increase cerebral bld flow ( risk of increase ICP)
Management of cerebral palsy?
GABA agonist
CP —> symptoms of spasticity due to loss of descending inhibitory control.
GABA is the inhibitory neurotransmitter
Weakening diaphragmatic contraction during maximal ventilation with intact phrenic nerve stimulation suggests?
Neuromuscular junction pathology
Abnormally rapid 1o muscle fatigue
UMN facial palsy features?
Spares the forehead
Contralateral
Which symptoms of Parkinson’s are helped with Carbidopa and which are not?
Blocks levodopa to dopamine in periphery
Improve tremor and movement
SE N+V
No effect or worsen and agitation
Histopathology specific to MS ?
Demylinating plaques containing foci of periventricular inflammatory infiltrates made up pf T lymphocytes and macrophages
Pathogenesis of migraines?
Genetic predisposition to increased cerebral excitability —> activation of trigeminal afferents and release of calcitonin gene related peptide (CGRP) —> vasodilation and inc transmission of pain signals
Meningioma in the cerebellopontine angle features?
Can compress CN VIII causing hearing loss, tinnitus, imbalance
Loss of which neurotransmitter is found in Huntington’s disease?
GABA
Pathogenesis of irreversible CNS ischaemic injury?
Liquefactive necrosis
Restriction of which food group will help in impaired ornithine transport?
Protein ( decrease amino acid turnover for urea cycle)
Ependymomas features?
Childhood brain tumour
Ependymal cells of ventricles
ICP - headache, papilloedema
2o blocking flow of CSF
What is the genetic defect in ataxia telengectasia ?
Defect in DNA break repair
Classic findings:- cerebellar ataxia, telangiectasia and recurrent sinopulmonary infections
Characteristics of REM sleep?
Dreaming
Voluntary muscle paralysis
Final 1/3 of night
Nightmares / vivid dreams
Commonest cause of death in Friedrich’s ataxia ?
HCM
What are the compensatory mechanisms in prodromal Parkinson’s disease?
Upregulation of tryrosin hydroxlase activity
Presynatic Dopamine reuptake is inhibited
Dopamine levels is still low because of a loss in total dopaminergic neurons
Proliferation of dopamine receptors
Speed of neuronal conduction down an axon depends on which 2 constants ?
The length (space) constant
Time constant
Demyelination in MS decreases the length constant and increases the time constant
Histologic appearance of Schwannoma?
2 types of cellular pattern Antoni A (hypercellular) Antoni B (hypocellular) and positive S-100
What is oppositional defiant disorder?
Behavioural disorder of childhood
Argumentative and defiant towards authority figure
>6/12
What is delusional disorder?
1 or more delusions for 1 or more months in the absence of other psychotic symptom.
Outside of the delusion can function normally.
Transtheoretical stage of change what is preparation?
Pt has committed to behavioural change but has yet to institute a specific course of action
How to diagnose ADHD?
Evidence of inattentive / hyperactive, impulsive symptoms over >6/12 in >2 settings
What is body dysmorphic disorder?
Fixation on a perceived defect in appearance and repetitive behaviours in response to the fixation
What is transference?
Unconscious recreation and experience, thoughts, behaviours associated with past relationships
What is bulimia nervous?
Recurrent episodes of binge eating followed by compensatory behaviour to prevent weight gain ( fasting , exercising, vomiting, using laxatives)
What is tardive dyskinesia
Abnormal involuntary movement of the mouth, tongue, face , extremities and truck assoc with prolonged exposure to antipsychotics
Hypersensitivity of D2 receptors following prolonged block
What is antisocial behaviour?
Pattern of violating rights of others, engaging in unlawful behaviour and lacking remorse.
Must be >18 to diagnose
What is specific phobia?
Anxiety disorder
High levels of anxiety and panic attack triggers by exposure or anticipation of exposure of feared stimulus
How do antipsychotics work and SE ?
Work by blocking D2 receptors in mesolimbic dopamine pathway
Blockage in the tuberoinfundibular pathway can cause hyperprolactinaemia — > galactorrhoea and amenorrhoea
Enzymes that require B1 and co-factor?
Pyruvate dehydrogenase ( pyruvate to acetyl coA)
Alpha ketoglutarate dehydrogenase ( citric acid cycle)
(Alpha ketoglutarate to succinylco-A0
Symptoms of opioid withdrawal?
Mydriasis
Abdo pain
Diarrhoea
Piloerection
Lacrmiation
Yawning
What is panic disorder?
Recurrent unexpected anxiety attacks assoc with
Somatic symptoms
And worry about additional attacks and avoidance behaviour
Obstructive sleep apnoea features?
Sleep related apnoea and chocking loud snoring
Disrupted non restful sleep
Excessive daytime somnolence
Schizoid personality disorder features?
Persistent pattern of social detachment, prefers solitary activities and Ltd emotional expression when interacting with others
What is projection?
Defence mechanism
Attributing one’s unacceptable feelings of thoughts to another person who may not have them
What is reaction formation?
Defence mechanism
Replacing unacceptable feelings and impulses with their extreme opposite
Features of fetal alcohol syndrome?
Facial dysmorphisim (short palpebral fissure, thing upper lip, smooth filtrum.
Growth retardation
Neurological abnormalities
Behavioural difficulties
Neural tube defects causes?
Folate deficiency
Valproate
Methotrexate
trimethoprim -suflamethoxazole
What molecular change is seen in labour as a result of rising oestrogen ?
Gap junctions which facilitate communication and coordination between cells and help in labour contractions
What is the function of primase?
It’s a DNA dependent RNA polymerase that incorporates RNA primers into replicating DNA
By product is uracil
What is genomic imprinting?
Offspring’s genes are expressed in a parent specific manner. Caused by DNA methylation an epigenetic process where genes are silenced by attaching methyl groups to cytosine residues in DNA molecule
What is an ecological study?
Observational study analysing population level data rather than individual
What is epistasis?
The allele of one gene affect the phenotypic expression of alleles in another gene e.g. albinism masks the expression of skin hair, colour etc
What is pleitropy?
A single gene influences multiple phenotypes e.g PKU many effects - skiing pigmentation, learning difficulties
Naloxone works on which receptor?
Pure opioid receptor
Greatest affinity for Mu receptor
Which medication can be used as a mood stabiliser and antiepileptic?
Valproate
What medication can be uses as 1st line for psychomotor agitation associated with alcohol withdrawal?
Benzodiazepines
What is the dysregulation in neuroleptic malignant syndrome?
Dopamine dysregulation
1st line therapy for alcohol use disorder and mechanism?
Naltrexone :- Mu opioid receptor blocker
Inhibits reward and reinforcing effect of alcohol
2nd line disulfiram (aldehyde dehydrogenase inhibitor ) unpleasant SE if they drink
Mechanism of action of 2nd gen antipsychotics ?
Dopamine D2 antagonist
5HT2A antagonist
Mechanism of action of benzos?
Bind and allosterically modulate the GABA A receptor —> increase in CL ion channel opening and Cl influx
How can risperidone and similar drugs cause hyperprolactinaemia?
Prolactin controlled by inhibitory effect of hypothalamic dopamine.
Blocked by these drugs ( D2 receptor blockers) — > high prolactin
Pathology in hypertensive crisis?
Increase in tackle of tyramine in pts taking MAO I —> failure of monoamine breakdown —> tyramine induced hypertensive crisis
Which drug interactions can cause lithium toxicity?
NSAIDS
ACE I
Thiazide diuretics
Tetracycline
Metronidazole
Management of bulimia?
Nutritional rehabilitation
CBT
SSRI (Fluoxetine)
Neuroleptic malignant syndrome features?
Adverse reaction to antipsychotic medication/ dopamine antagonist
Severe lead pipe rigidity
Hyperthermia, HTN
Inc SNS activity
Mental status changes
Buspirone mechanism of action and uses?
Nonbenzodiazepine anxiolytic (partial agonist 5HT1A receptor )
No muscle relaxant or anticonvulsant properties
No risk dependence
Use in general anxiety disorders
Potential SE of TCA?
Strong anticholinergic properties
Confusion
Constipation urinary retention
Also
Tremor
Arrhythmias
Hypotension
Sedation
Mechanism of action of benzos?
Bind and modulate GABA A receptors
Increased frequency of opening of Cl channel
Possible major SE of clozapine?
Agranulocytosis
Need to check absolute neutrophil count
Management of OCD?
1st line SSRIs
CBT
Which medications will increase concentration of methadone if taken concurrently?
CyP3A4 inhibitors
Fluconazole, ketoconazole
Ciprofloxacin
Clarithromycin
Cimetidine
Fluvoxamine
Alcohol withdrawal is caused by increase in which CNS receptor?
NMDA glutamate receptor
(Chronic Alcohol down regulates inhibitory GABA receptors and upregulates excitatory NMDA receptors)
Non bacterial thrombotic endocarditis features?
Valvular deposition of sterile plt rich thrombi. Seen in advanced malignancy and SLE
Causes of concentric left ventricular hypertrophy?
Aortic stenosis
Prolonged HTN
Changes seen 0-4 hr after MI ?
Normal myocardium
Changes seen after 4 hrs
Membranous nephropathy features?
Immune complex deposition in sub epithelial glomerular capillary wall causing diffuse thickening of the glomerular basement membrane no increase in cellularity.
Spike and dome appearance on silver stain
Membranous nephropathy associations?
Malignancy
Viral hepatitis
SLE
Uterine sarcoma features?
Abnormal / post menopausal bleeding
Bulk symptoms ( pelvic pressure, bloating)
Uterine mass
Histopathology:- nuclear atypia, abundant mitosis and areas of tumour necrosis
Temporal lobe epilepsy pathology?
Due to hippocampal sclerosis
Atrophy of the hippocampal neurons with reactive gliosis ( astrocyte proliferation) in response
What are highly proliferative cells?
Skin
Stem cells
Haemotogenous progenitors
Intestinal crypt cells
Pathologonomic cell finding in Hodgkin’s lymphoma?
Reed - sternberg cells ( owl eyes)
Causes of wide splitting of S2?
Pulmonic stenosis
Pulmonary HTN
RBBB
Ankylosing spondylitis features?
Inflammatory spondyloarthropathy charticterised but erosion and new bone formation mostly in vertebral body.
Back pain
Stooped posture
Tender at tendon insertions
Raised ESR
Age <40
Tuberous sclerosis presentation?
AD
Benign multiple hamartomas in the brain ( cortical glioneuronal hamartomas and subependymal nodules) and skin
Hypopigmented macules (ash leaf spots )
Present with seizures
NAFLD features?
Asymptomatic
Metabolic syndrome
AST/ALT <1
Can progress to cirrhosis
CEA use in colon cancer?
Carcinoembryonic antigen (CEA) if still high after surgery indicates residual disease
low sensitivity and specificity for screening and diagnosis
Hypersensitivity penumonitis features?
Exaggerated immune response to inhaled antigen (mold, animal protein)
Cough, dyspnoea
CXR diffuse interstitial opacities (interstitial fibrosis
Brocheoalveolar lavage :- high lymphocyte count >20%
What do Granulosa cell tumours secrete and features?
Oestrogen
They are ovarian sex cord stromal tumours
Symptoms:- PMB, endometrial hyperplasia , large unilateral adnexal mass
Histology :- cuboidal cells nuclear grooves
Cause of distal muscle hypertrophy in Duchennes muscular dystrophy?
Pseudohypertrophy - fibrofatty muscle replacement
Back pain features suggestive of malignant cause?
Persistent pain at night
No relief with rest
Onset at age >50
Systemic symptoms
UMN signs?
Spastic paralysis
Hyperreflexia
Upgoing planter reflex
What are chiari malformations?
Congenital disorder result from under development of the posterior fossa causing parts of cerebellum and medulla to herniate through the foramen magnum
Chiari I benign in adults
Chiari II severe in neonates
Administration of which would help in haemophilia?
Haemophilia A decrease factor VIII
Haemophilia B decrease level IX
Addition of thrombin helps bld to clot
What is a case control study looking at ?
Group of pts with disease and group of pts without the disease assess frequency of past exposure to estimate associated and risk factors and outcomes
Management of atypical ‘walking’ pneumonia?
Usually due to mycoplasma pneumoniae ( of chlamydia pneumoniae)
Both organisms don’t have a cell wall
Mgx requires a bacterial protein inhibitor e.g macrolide / tetracycline
Features of vertebral osteomyelitis and investigation?
Hx of new or worsening back pain with recent endocarditis or bacteraemia
Initial investigation :- blood culture and spine MRI
Nontyphoidal salmonella features?
G-ve non lactose fermenting oxidase -ve rod
Gastroenteritis fever, vomiting and diarrhoea
After eating poultry, eggs
Invasive disease causes osteomyelitis esp in sickle cell and impaired immunity, extremes of age
Haemolytic uraemia syndrome features?
Complication of EHES infection Renal insufficiency, thrombocytopenia and microangiopathic haemolytic anaemia
Cause: shiga toxin producing bacterial E.coli O157:H7 (EHES) or shigella
Bloody diarrhoea
EHES from undercooked beef
Cryptosporidium presentation and features?
Severe watery diarrhoea and wt loss in pts with AIDS
Self ltd watery diarrhoea <2/52 in healthy pts
Diagnosis:- acid fast staining oocysts in stool
Basophilic organism on mucosal intestinal brush border
Thayer martin medium
Chocolate sheep blood Agar used to identify neisseria organisms
Infused with vancomycin to inhibit G+ve bacteria
Colistin and trimethoprim to inhibit G-ve bacteria
Nystatin to inhibit yeast
Tenofovir mechanism of action and complication
Nucleotide reverse transcriptase inhibitor
Prevents transcriptase from converting HIV RNA into complementary double stranded DNA inhibiting viral replication
Complication:- proximal tubule dysfunction ( loss of brush border)—> glycosuria, phosphaturia, proteinuria
What antiretroviral therapy do you use during pregnancy to reduce risk of transmission?
Triple therapy made up of 2 nucleoside/nucleotide reverse transcriptase inhibitors
third drug :- protease inhibitor, non nucleoside reverse transcriptase inhibitor or integrase inhibitor
MALT lymphoma features ?
Due to chronic stimulation for gastric MALT lymphoma its H pylori
MALT lymphoma are extranodal marginal zone lymphoma involving mucosa associated with lymphoid tissue —> aberrant B cell production
Form of non Hodgkin’s lymphoma
CMV colitis features?
Common cause of colitis in AIDs pts
Reactivation disease
Abdo pain, fever, diarrhoea, wt loss
Colonoscopy:- erythema, erosions, ulceration
Biopsy:- large cells with prominent basophilic intranuclear inclusions
Protease inhibitors mechanism of action in HIV
Block viral protease from cleaving gag-pol polyproteins ( inhibits production of functional viral encoded enz.)
resulting in immature virions that are non infectious
Mefloquine chemoprophylaxis fro malaria mechanism of action
Must continue for 4/52 after return
Destroys replicating parasites within RBC but ineffective against schizonts in liver
P. falciprum matures in liver for 8-30/7
Ovale and vivax can remain dormant in liver for months
G6PD deficiency
Assoc with fatty acid synthesis
Rate limiting enz of the pentose phosphate pathway
Major source of NADPH
starting substrate :- glucose -6-phosphate
End product:- rib u lose -5-phosphate
Triggered by eating broad beans, haemolysis
Blotchy red muscle fibers on comprise trichome stain
Characteristics of mitochondrial myopathies
Red ragged muscle fibers
Show maternal inheritance
5 alpha reducatase deficiency
Impaired conversion of testosterone to DHT
N testosterone and oestrogen levels
Symptoms:- external female genitalia, internal male genitalia, 1o amenorrhoea , vagina ends in blind pouch, develop body hair but no breast development
Paget’s disease of the breast
Malignant breast condition / intraepithelial adenocarcinoma
Unilateral painful/pruritic eczema toys rash on nipple and alveolar
Biopsy :- infiltration of the nipple/ areolar epidermis by pagets cells
Herpes zoster opthalmicus
Reactivation of VZV in ophthalmic division of CN V1
Painful dermatomal rash and ocular involvement
What kind of medium is Thayer martin antibiotic media
Selective —> inhibits growth of contaminants isolates neisseria
What cellular process contributes to the formation of granuloma
Cytokines secretion by CD4 T lymphocytes
Activate macrophages —> join together to form langhans giant cells
Severe combined immunodeficiency (SCID)
Genetic defect in T cell development which also leads to defect in B cell
Causes:- recurrent infection with viral, fungal, opportunistic and bacterial infection + failure to thrive and diarrhoea
Candida skin test
Used to asssess the activity of cell mediated immunity if shows response incact CD4 cell response.
No response in pts with SCID
Terminal complement deficiency
Deficiency of complements C5-C9 that form MAC
Results recurrent infection with encapsulated bacteria
S pneumoniae, N meningitidis
Chronic granulomatous disease
X linked affecting NADPH oxidase
Child with recurrent infection by catalase positive organism
N Ig
No leukopenia
Due to defective intracellular killing due to impaired respiratory burst
PECAM-1 is assoc with which part of neutrophil function
Transmigration
How does tetanus vaccine protect against developing neuro symptoms from future infection ?
Tetanus vaccine —> inactivated toxoid triggers production of antitoxin antibodies that neutralize the bacterial product i.e toxin
Toxic shock syndrome
Assoc with S. Aureus replicating and release > pyrogenic toxic superantigen (TSST-1) into the blood.
Super Ag binds to MHC-II without processing lead to ++ release inflammatory cytokines
Causes:- hypoBP, high fever, organ failure, diffuse erythematous rash
Congenital TORCH
Presentation:- growth restriction, microcephaly, hepatospleenomegally, diffuse blue rash
Mother will show evidence of previous infection with encapsulated > IgG
IgG crosses placental so new born will have IgG
And evidence of active infection > IgM
Phenotypic mixing of viruses
Coinfection of a host cell by 2 viral strains resulting in a daughter virus that contains nucleocapsid(or envelope) of one parent and unchanged parental genome from the other strain.
Because no genetic exchange — > the next gen vision reverts to original unmixed phenotype
Acute onset bloody diarrhoea in day care setting
Shigella
Other causes:- E.Coli O157:H7, shigella, campylobacter
Aminoglycoside resistance
Methylation of the aminoglycoside binding portion of the ribosome —-> inhibits ability of aminglycoside to interfere with protein translation
Tuberculin skin test cellular reaction
Type IV hypersensitivity reaction
In pts with previous infection already have CD4 T lymphocytes that recognise the protein —> activated with interaction between CD28 on the T cell and CD80/86 on APC
Type I hypersensitivity reaction
Initial exposure allergen promotes class switching to IgE
Following exposure cross linking of IgE resulting in mast cell degranulation and release of histamine
Graft versus host disease
Donor T cells reject the host cells —> MHC
Variable onset
Usually following bone marrow and liver transplant
Presentation:0 maculopapular rash, diarrhoea, jaundice, hepatomegaly
Acute transplant rejection
Occurs within weeks < 6/12
Predominantly cell mediated
Sensitization of host T cell against donor MHC antigens
Dense lymphocytic infiltrate
Defect in interferon gamma signaling
Disseminated mycobacterial infection in early childhood
How do inactivated/ killed vaccine prevent future infection
Produces humoral response —> forming neutralizing antibodies that prevent virus from entering the cell
How do live attenuated vaccine prevent future infections
Generate a strong cell mediated response that can result in destruction of infected cells
Serum sickness
Immune complex mediated
Type III hypersensitivity reaction 7-10/7 after exposure
Immune complexes deposit on skin and joints activating classical complement pathway
Raised levels of C3a and C5a
Pathogenesis of asthma
Excess of Th2 resulting in excess IgE production
Th2 cells released IL 4 stimulates B cells to produce IgE
Endotoxin and major virulence factor of G-ve bacteria
Endotoxin:- lipopolysaccaride
Major virulence factor:- Lipid A
Can lead to septic shock
Causes of hepatic abscess
In underdeveloped countries - foodborne exposure —: entamoeba histolytica
Developed countries :- S. Aureus via haematogenous seeding from the liver
Klebsiella, E.col via ascending cholangitis
Direct invasion G-ve bacteria
How to diagnose C diff infection
PCR for bacterial toxin gene —NAAT (nuclear acid amplification test)
Highly sensitive and specific
Legionnaire disease
Caused by legionellae (G-ve bacillus)
Exposure:- contaminated water source
Symptoms:- high fever, GI symptoms, cough, confusion, hyponatraemia
Sputum gram stain shows ++ neutrophils but no other organisms
Walking pneumonia
Caused by mycoplasma pneumoniae
CXR appears worse than the pt
Symptoms:- low grande fever, chronic nagging cough
Organism requires cholesterol to grow in medium
Preformed inflammatory mediators released during anaphylaxis
Histamine
Tryptase
Leukotrienes
Which mechanism triggers release of vasoactive substances in anaphylaxis
High affinity IgE receptor aggregation (clumping)
Activates tyrosine kinase which triggers mast cell and basophils degranulation
IL 10
Anti inflammatory
Reduces Th1 cytokines ( IL2 and IFN gamma) and reduces MHC II
Chronic granulomatous disease
Disorder of phagocytosis metabolism
Defective NADPH oxidase / respiratory burst
Recurrent infections with catalase +Ve organisms
Dihydrorhodamine (DHR) test ( evaluates for phagocytosis oxidative response) is abnormal/ no increased fluorescence
Polyclonal antibodies vs monoclonal antibodies
Plasma contains polyclonal antibodies that bid to different epitopes on antigens and are therefore better at neutralising complex antigens
Monoclonal antibodies bind to single epitope on antigen therefor less potent immune response
Calcineurin in immunosupression after transplant
Calcineurin is essential in activating Il-2 and promoting growth and differentiation of T cells.
Immunosuppressants Tacrolimus, cyclosporine inhibit Calcineurin
Atopic dermatitis
Mutation in epidermal barrier protein (filaggrin)
Pruritic erythematous patches and papules
Assoc:- allergic rhinitis, food allergy, asthma
Labs:- raised IgE, eosinophilia
Cytokines:- IL 4 , IL13 (stimulate IgE production)
Late phase hypersensitivity type 1
Indurated skin lesion hours after exposure
2o IgE stimulating Th2 to release IL5 which activates eosinophils. Releasing major basic proteins causing damage to tissue and indurated lesion
Acute haemolytic transfusion reaction
Antibody type II hypersensitivity reaction
Preexisting anti-ABO antibodies
With Complement activation
Causes:- erythrocytes lysis, vasodilation, hypotension, fever, haemoglobinuria
Sarcoidosis - cytokines seen
Non caesating granulomatous diseas
Cytokines:- APC produce IL12 — stimulates Th1to produce IL 2 and IFN gamma which stimulate Th1 proliferation and macrophages activation —> granuloma formation
Autologous haemopoietic stem cell transplant possible complications
Reinfuse host cells from pts peripheral blood
No risk of transplant rejection
Risk of reactivation of herpesviruses e.g EBV, VZV CMV, HSV because of temporary profound immunosuppression prior to transplant with chemotherapy
Complement pathway in SLE
Activates the classical complement pathway
Autoantibodies binned to host antigen
Low C4 , Low C3, N factor/protein B
Seen in other rheumatologist disease as well
Serum sickness
Immune complex type III hypersensitivity reaction
1-2 weeks after exposure to non human antigen ( e.g .antivenom, MAB, or vaccine)
Deposition of immune complex leads to complement activation
Symptoms:- fever, arthralgia, uritcarial rash
Hyperacute rejection
Antibody mediated type II hypersensitivity reaction Preexisting IgG antibodies in host recognise donor antigens
Within minutes to hours
Features:- mottling, cyanosis, necrosis and thrombosis
TB skin test, candida extract skin reaction,contact dermatitis are types of
type III hypersensitivity reaction
T cell mediated
Occurs within 24-48 hrs
Tissue damage and swelling
SLE
Autoimmune disorder
Symptoms:- migratory arthralgia, pancytopenia, GN
Haematologic abnormalities:- type II hypersensitivity reaction—> abs against bld cells
Lupus neprhitis —> type III —-> immune complex deposition in glomeruli
Hameolytic disease of the newborn
2o maternal sensitisation to RH antigens in RHD+ve fetus.
In subsequent pregnancies maternal anti THD IgG ab cross the placenta causing fatal autimmune haemolysis in fetus
IL 12 deficiency
IL12 stimulates Th1
Low IFN gamma
Susceptible severe mycobacterial infections
Cannot mount strong cell mediated granulomatous reaction
Mgx:- IFN gamma
False negative tuberculin skin test
Pts with active TB and weak/ impaired cell (lymphocytic) immune response (T cell anergy)
Immunocompromised (HIV)
Improper injection technique
Recent infection ( within 8/52)
