1/2 micro, immuno and histo Flashcards
MOA of tenofovir
Nucleotide analogue
MOA of ritonavir
Protease inhibitor
MOA of entecavir
Nucleoside analogue
Telaprevir MOA
NS3/4 protease inhibtor
Ledipasvir MOA
NS5 protease inhibitor
Investigations for sporadic CJD
EEG- periodic triphasic complexes
MRI- basal ganglia and cortical increased signal
CSF- 14-3-3 protein, S100
DIAGNOSIS CONFIRMED ON BRAIN BIOPSY showing spongiform vaculoation and PrP amyloid plaques
What are familial prion disease
Fatal familial insomnia
Gerstmann-straussler strackman
All will present with family history of someone dying of MS, dementia etc
Live vaccines
Influenza under 18s
Yellow fiver
MMR
BCG
Heyerotypic vaccine
BCG- bacille calmette guerin
Toxoid vaccines
Diphteria
Tetanus
Conjugated vaccines
HIB
Pneumococcus
Meningococcal
Example of inactivated vaccines
Pertussis
Cholera
Hep A
Polio
Influenza for vulnerable populations
Examples of subunit vaccines
HPV
Hep B
Examples of viral vectored vaccines
Ebola
AZ COVID vaccine
Examples of M-RNA vaccines
Pfizer
Moderna
Complication of viral vectored vaccines
Vaccine induced thrombocytopenia and thrombosis
Capillary leak syndrome
Seen in AZ covid vaccine
Complication of pfizer vaccine
Myocarditis
Viral, bacterial, parasitic and amoebic cause of encephalitis
Viral- HSV, enteroviruses and western nile
Bacterial- listeria
Amoebic- naegleri fowleri
Parasitic- toxoplasmosis
What activates aciclovir by phosphorylating it and is responsible for the susceptibilty to resistance
Thymidine kinase
What is mechanism of resistance to antivirals in CMV
Protein kinase mutation
Second line for HSV
Foscarnet and cidofovir
Management of adenovir
Cidofovir
Treatment for different candida infections
Oral thrush- topical nystatin
Vulvovaginitis- topical clotrimazole or oral fluconazole
Localised cutaneous- topical clotrimazole
Oesophagitis- oral fluconazole
Management of cryptococcus
Flucytisine and amphotericin B
What measure serologically in candida
Beta d glucan
Management of aspergillus
Voriconazole
Why do typical antifungals not work on PJP
Lack ergosterol in cell membrane
How do the antifungals work
Polyenes- bind sterols in cell membranes (affects function)
Azoles- Inhibit lanosterol 14 alpha demethylase which converts lanosterol to ergosterol (affects synthesis)
Pyrimidine analogues (flucytisine)- affects DNA synthesis
Echinocandins- Inhibit beta d glucan
Bacterial UTI caused by indwelling catheter
Klebsiella
What bacteria appears comma like
Cholera
Leishmaniasis species causing cutaneous vs mucocutaneous leishmaniasis
Cutaneous- L. tropica, L. major
Mucocutaenous- L. braziliensis
Management of c diff
1st line- oral vancomycin
If life threatening- vancomycin PO and metronidazole IV
What is pulvinar sign
Increased nuclei in thalamus
What causes chagas disease and what is presentation
Trypanosoma cruzi
- GI and cardiac symptoms
- purple eyelids
Cardiomyopathy most sinister symptom which must be investigated
What are the two types of african trypanosoma
Trypanosoma brucei rhodiense- acute from east and south
Trypanosoma brucei gambiense- gradual onset from west and central africa
How does trypanosoma brucei present
Fever
Painless ulcer at site of infectoin
Encephalitis- poor sleep, mood changes
Rhodiense- acute
Gambiense- common and gradual
How do mucous membranes prevent infections
Contain lactoferrin which starves bacteria of oxygen
IgA
Lysozome which breaks down cell walls
How is acute GVHD prevented
Ciclosporin
Methotrexate
Corticosteroids
What defines refractory anaphylaxis
No improvement in resp and cardio symptoms in response to 2 doses of IM adrenaline
Failed return to normal of tryptase
Systemic mastocytosis
Hereditary alpha tryptassaemia
What can give delayed food induced anaphylaxis
Occur 3-6 hours after eating red meat
IgE antibody to alpha-1,3-galactose
What is mechanism in oral allergy syndrome
When have haye fever, get cross reaction to some homologous proteins in apples, pears, carrots and nuts but not cooked
What is in goods syndrome and what is presentation
Thymoma with lack of T and B cell lineages
Susceptibiliy to opportunistic infections- PJP, CMV, candida
What tests are done which can determine HIV treatment
Test for HLAB5701 to avoid prescribing abacavir as severe risk of SJS
Tropism test for CCR5 to determine if CCR5 antagonist therapy would work
What is genetic defect in cyclic neutropenia
Neutrophil elastase
What is genetic defect of Kostmann syndrome
Autosomal recessive- HCLS-1 associated protein X-1 which prevents maturation of neutrophils
Pathophysiology and presentation of leukocyte adhesion deficiency
CD18 which is involved in clearance of neutrophils
delayed separation of umbilical cord
very high neutrophil counts in blood (20-100 x106/L)
Absence of pus formation
Presentation of chronic granulomatous disease
Granulomas
Hepatomegaly and lymphadenopathy
Recurrent infections from PLACESS often affecting skin
Pseudomonas
Listeria
Aspergillosis
Candida
Ecoli
S aureus
Serratia
Treatment of chronic granulomatous disease
Intereron gamma
Presentation of each of the complement pathway defects
Classical- severe skin disease, SLE and susceptibility to encapsulated bacteria
Alternative- encapsulated bacteria susceptibility
Mannose binding- encapsulated bacteria susceptibility but is cocontaminant immunodeficiency
Presentation of SCID
Opportunistic- candida, PJP, CMV
Viral chest and GI infections- adenovirus, parainfluenza
RARELY BACTERIAL
Skin disease
Presents by 3 months
What is defect in CVID
MHC III
Presentation of x-linked agammaglobulinaemia
Encapsulated infections of ENT, GI and RESP
By age 5
Blood findings
- neutropenia
- low B cells
- low Ig
Pathophysiology of IPEX
Mutations in Foxp3 which is needed for the development of CD25+ T reg cells. Menas is failure to negatively regulate T cell responses
Increased prevalence of autoimmune diseases
- DM
- Hypothyrodism
- enteropathy
- eczema
(Diarrhoea, DM, dermatitis)
Management of ank spond
NSAIDS
Anti-TNF alpha
Anti- IL17- secukinumab
What is the genetic HLA association of
- goodpasture syndrome
- RA
- coeliac
- graves
- SLE
- haemochromatosis
GP= DR15
RA= DR1 and DR4
Coeliac- DQ2 and DQ8
Graves= DR3
SLE- DR3
Haemochromatosis- A3
What are 2 examples of genetic polymorphisms seen in polygenic autoimmune disease
Protein tyrosine phosphatase non-receptor 22
Cytotoxic t lymphocyte associated protein 4
What is Protein tyrosine phosphatase non-receptor 22 polymorphism associated with
SLE
RA
T1DM
What is Cytotoxic t lymphocyte associated protein 4 polymorphism associated with
Hashimotos
SLE
T1DM
Genetic predispositions to RA
HLA DR4
Peptidyl arginine deaminase as increases citrullination of proteins
What is predominant cell infiltrated in T1DM
CD8 T-cell
Antibodies in optic neuritis vs neuromyelitis optica spectra disorders
Optic neuritis- ant- oligodendrocyte myelin
Neuromyelitis optica spectra disorders- anti aquaporin 4
Antibody for homogenous staining
DS-DNA
Antibodies for speckled staining
Ro
La
U1RNP
Smith
What do anti ….. represent
- SCL70
- p-anca
- c-anca
- anti Jo
- topoisomerase
- myeloperoxidase
- proteinase 3
- anti t-RNA synthetase
After positive ANA what do
Check staining under microscope
Then ELISA for specific antibodies
Then stain on crithidia lucillae to confirm DS DNA
What stain can be used to confirm DS-DNA
Crithia lucillae
What tests do for HIV
4th gen ELISA then to confirm use western blot
Rapid point of care tests (saliva or blood sample) available which provide answer in 20 minutes however less sensitive than 4th gen test
What are the phases of T cell mediated transplant rejection
Phase 1- presentation of donor HLA by an APC
Phase 2- T cell activation and inflammatory cell recruitment
Phase 3- effector phase with organ damage
What are phases of B cell mediated transplnat rejection
Phase 1- B cells recognise foreign HLA
Phase 2- proliferation and maturation of B cells with anti HLA antibodies
Phase 3- effector phase where antibodies bind to graft endothelium
Graft biopsy findings T cell vs B cell
B-cell= complement and antibody deposition in the endothelium
T-cell= tubulitis, arteritis
Prior to transplant how screen for rejection
HLA tissue typing
Screening for anti-HLA or A/B antibodies
What induction agents are given for baseline suppression in prevention of graft rejection
Anti CD52- alemtuzumab
OKT3- muronomab-CD3
Anti-CD25 (IL2-R)- daclizumab
As well as induction agents which baseline immunosuppression agents are given to prevent SOT rejection
Calcineurin inhibitor
Mycophenolate or azathioprine
+/- steroids
How is B vs T cell mediated rejection treated
T-cell= steroids and OKT3- muronomab-CD3
B-cell= rituximab, IVIG, plasma exchange
MOA of the antiproliferative agents
- cyclophosphamide
- ciclosporin
- azathioprine
- mycophenolate motefil
- methotrexate
Cyclophosphamide- alkylates guanine
Ciclosporin- calcineurin inhibitor which reduces IL-2 production
Azathioprine- broken down to 6-mercatopurine which prevents purine synthesis
Mycophenolate- inhibits inoside monophosphate dehydrogenase which prevents guanine synthesis
Methotrexate- Inhibits dihydrofolate reductase which so is anti folate
What is difference between a mature and immature dendritic cell
Immature- phagocyte
Mature- antigen presenting cell
Which antigen confers immunity to Influenza vaccine
Haemoagglutinin
When is IL-2 given to stimulate T cell response
Renal cell cancer
MOA of
- alemtuzumab
- toclilizumab
- basilixumab/daclizumab
- rituximab
Alemtuzumab- CD52
Toclizumab- IL6
Basilixumab- IL2R= CD25
Rituximab- CD20 which depletes B cells but not plasma cells
Which organisms are bloods for IVIG screened for
HIV
Hep B and C
Define atopy and anaphylaxis
Atopy- tendancy to produce IgE
Anaphylaxis- allergic reaction with an A,B o
Which cell is most affected by steroids
CD4+
What is MOA of rapamycin/sirolimus
mTOR which prevents T cell proliferation
MOA of tofacitinab
Inhibits JAK-STAT signalling which prevents cytokine production
What are JAKinibs used in
RA principally
Ank spond
Psoriasis arthritisp
MOA of apremilast
PDE4 inhibitor which modulates cytokine release
Use of apremilast
Psoriasis
Psoratic arthritis
MOA and uses of vedolizumab and natalizumab
Vedolizumab- alpha4beta 7 integrin inhibitor, IBD
Natalizumab- alpha4 integrin inhibitor, crohns and MS
Use of abatecept and MOA
Alpha CTLA4 fusion gene which inhibits CD28 which reduces costimulation of T cells
RA
What is anti-IL23
Guselkumab
What is anti-IL12 and 23
Ustekinumab
Use of ustekinumab and guselkumab
Psoriasis
What is MOA and use of mepolizumab
Anti-IL5
Eosinophilic asthma
What are the mixed pattern disease
Ank spond
Psoriasis
Behcets
What are polygenic autoinflammatory diseases
Takayasus
IBD
Osteoarthritis
GCA
Comparing X-linked SCID to adenosine deaminase deficiency
MOA
- X-linked SCID= gamma chain of IL2R
- ADA= adenosine deaminase deficiency which involved in development of leukocytes
Blood findings
- X-linked= low T cells but B Cells normal however these are immature so noIgG
- ADA= all low
Inheritance and pathophysiology hyper IgM
CD40 mutation
X-linked
What gel and coombs in RA
4
3 if RF positive
What is example of integrase inhibitor
Dolutegravir
What is the maximum number of viral capsids that a molecule of IgM, IgA and IgG may bind to?
IgM- 10
IgA- 4
IgG- 2
Respiratory burst cell
Neutrophil
Antibodies in diffuse systemic sclerosis
Topoisomerase (Scl70)
Fibrillarin
Reticular dysgenesis presentation
Neutropenia
Hearing loss
Lymphopenia
Interleukin responsible for T cell proliferation
IL-2
What type of drug is abacavir
NRTI
Immunodeficiency with only T cells lacking
Digeorge
Immunoglobulins may bind to multiple pathogens at once in order to enhance phagocytosis. What is this process known as?
Agglutination
Do you stop transfusion in an allergic reaction
If just itching then give antihistamines
If headache or widespread rash then stop
What is JAK
Tyrosine kinase
What is secreted by t reg cells to dampen inhibit other T cells
IL-10
What is difference between abatecept and ipilimumab
T reg cells express CTLA4 which directly inhibits other T cells
Ipilimumab inhibits CTLA4 to prevent inhibtion of T cells
Abatecept enhances CTLA4 to promote inhibtion
What cells express CD25
T reg cells
Wiskoff aldrich syndrome blood findings
Low IgM and high IgA and IgE
Get recurrent ear and lung infections with nose bleeds
In nephrotic syndrome what infections are susceptible to
Encapsulated bacteria
What has defect in MHC 1 and MHC 2
Bare lymphocyte syndrome
How do mycophenolate and cyclophosphamide affect guanine
Mycophenolate affects synthesis of guanine
Cyclophosphamide affects use in replication
Management of SLE
Steroids
Then cyclophosophamide
What is it when get crescents in kidney
Rapidly progressive glomerulonephritis
Difference of C3/Ig staining between causes of rapidly progressive glomerulonephritis
Basement membrane disease- linear
Immune complex- granular
Pauci immune- scanty
Parakeratosis, acanthosis and hyperkeratosis meaning
Parakeratosis- increased nuclei in stratum corneum
Acanthosis- increase stratum spinosum
Hyperkeratosis- increases keratin and size of stratum corneum
What skin pathology is described as sandpaper like texture
Actinic keratosis
What is protein in acute phase protein and dialysis associated amyloidosis
AA amyloidosis- serum amyloid A
Dialysis associated amyloidosis- beta-microglobulin 2
Chronic dermatitis histology
Acanthosis
Crusting
Hyperparakeratosis
T cells and eosinophil infiltrate
What HS is psoriasis
4
Location and appearance of pustular psoriasis
Hands and feet
Red skin with white elevations of pus
What is difference in bullae between pemphigus vulgaris and bullous pemphigoid
Bullae in bullous pemphigoid are tense on erythematous base- DO NOT rupture
Bullae in pemphigus vulagris are easily ruptured which leads to a raw red surface
Nikolsky positive in pemphigus vulgaris
Histopathology difference between bullous pemphigoid and pemphigus vulgaris
Bullous pemphigoid- Subepidermal bulla with eosinophils, linear deposition of IgG along basement membrane
Pemphigus vulgaris- acantholysis, intradermal bulla
netlike pattern of IgG, complement deposition
Histology of dermatitis herpetiformis
Microabscesses which coalesce to form subepidermal bullae
Neutrophil and IgA deposits at tips of dermal papillae
Erythema multiforme lesions
annular target lesions on extensor surfaces of hands and feet
How does herald patch appear
Erythematous patch with white centre seen in pityriasis rosea
What causes persistent ST elevation post MI
Ventricular aneurysm which can develop for over a month after
Histology post MI
- under 6 hours
- 6-24 hours
- 1-4 days
- 5-10 days
- 1-2wks
- weeks-months
- Normal by histology, CK also normal
- Loss of nuclei, necrotic cell death, homogenous cytoplasm
- Infiltration of polymorphs then macrophages
- removal of debris
- granulation tissue, new blood vessels, collagen synthesis, myofibroblasts
- decullarising scar tissue
Histology of the 3 RCC
Clear- nests of epithelium with clear cytoplasm
Papillary- papillary tubulo growth under 5mm
Chromophobe- large cells with distinct borders
Types of renal transitional cell carcinomas
Non-invasive papillary
Infiltrating urothelial carcinoma
Flat urothelial carcinoma in situ
Macroscopic appearance of the renal transitional cell carcinomas
Non-invasive papillary- frond like projections multifocal
Infiltrating urothelial carcinoma- stuck on tumour
Flat urothelial carcinoma- red area or not visible
Histology of 3 benign renal tumours
Papillary- less than 5mm papillary structure tumour
Oncoctoma- oncocytes which have eosinophiliv cytoplasm
Angiomyolipoma- made up of blood, muscles and fat
Management of IE
Subacute
- benzylpenicillin and gentamicin
Acute
- fluclox if MSSA
- rifampicin, gentamicin and vancomycin is MRSA
Presentation of glucagonoma
Necrolytic migrating erythema
What colour are the different parts of oesophagus
Top 2/3rds- squamous white
Bottom 1/3rd- columnar pink
How is chronic hepatits staged and graded
Stage= fibrosis
Grade= inflammation
Histopathology of chronic hepatitis
Portal inflammation
Lobular inflammation
Interface hepatitis (piecemeal necrosis)
Bridging from portal vein to central vein
What is peacemeal necrosis/ interface hepatitis
Where can’t see border between portal tract and parenchyma due to inflammation
What is critical stage in hepatitis to cirrhosis interface
Bridging from portal vein to central vein
Intrahepatic vs extrahepatic shunting
Extra- When blood backlogs into sites of portosystemic anastamoses
Intra- When blood goes through the liver but does not contact hepatocytes/not filtered
Mutations of haemochromatosis and wilsons
Haemochromatosis- HFE chromosome 6
Wilsons- ATP7b chromosome 13
What is stain for collagen
Trichome- positive= blue
USS difference between PBC and PSC
Dilation of ducts in PSC
What is the main stain for NE tumours
Chromogranin
Can also do synaptophysin, CD56
Then can do individual hormones
How are NE tumours graded
Ki-67 index
Supra vs infra tentorial brain tumour presentation
Supra
- focal neurology
- seziures
- personality
Infra
- cranial nerve
- cerebellar
MRI and histology findings of pilocytic astrocytoma
MRI
- well circumscribed
- in cerebellum
- cystic
Histology
- piloid hair cells
- rosenthal fibres
What tumours are IDH1 mutation seen
Astrocytoma
Oligodendroma
Most common site of brain intra-parenchymal haemorrhage
Basal ganglia
What are the traumatic brain injuries pathophysiology
Contusion- where brain hits skull and get bruising
Diffuse axonal injury- get shearing in trauma leading to coma
Chronic traumatic encephalopathy- effects of repeated trauma to head
Laceration- contusion where pia mater is torn
Long term imaging finding of AD
Cortical atorphy
Widening of ventricles
Narrowed gyri
Widened sulci
Histology of LBD
Lewy bodies
- alpha synuclein
- ubiquitin
How does mutiple system atrophy differ to parksinsons
Alpha synuclein in the glial cells not neurones histologically
Histology of picks disease
Fronto-temporal atrophy
Marked gliosis and neuronal loss
Balloon neurones
Hyperphosphorylated tau positive pick bodies
What parkinsons plus syndromes stain positively for tau
Corticobasal syndrome
Progressive supranuclear palsy
Main history features of the parkinson plus syndromes
Corticobasal- alien limb and unilateral parkinsonism
Multiple system atrophy- alpha synuclein in the glial cells and early autonomic dysfunction
Progressive supranuclear palsy- impaired upwards gaze
What gene is linked to picks disease
Progranulin
Chronic gastritis causes
Autoimmune- pernicious anemia
Bacteria- h pylori in antrum
Chemical- NSAIDS, bile reflux in antrum
Difference between gastritis and ulcer
Ulcers breach through muscularis mucosa into submucosa
Histology of gastric epithelial dysplasia
Cytological and histological features of malignancy but doesnt invade through BM
How are gastric adenocarcinomas classifed
Intestinal- well differentiated
Diffuse- poorly differentiated
What are signet ring cells seen in
Diffuse gastric adenocarcinomas
Biopsies of coeliac
Villous atrophy
Crypt hyperplasia
See flattened villi
Increased intraepithelial lymphocytes- normal range less than 20 lymphocytes/100 enterocytes
Pathophysiology of alpha-1-antitrypsin
Failure to secrete it
Intra cytoplasmic inclusions due to misfolded protein
Causes hepatitis and pneumonitis
Causes of hepatic granulomas
PBC
Drugs
TB
Sarcoid
Pathogens other than H pylori causing duodenal ulcer
CMV
Giardia lamblia- most important
Tropheryma whippeli
What is signifcance of anti-histone autoantibodies in SLE
That it is drug induced lupus from hydralazine etc
Most specific antibodie for SLE
Anti-smith (ribonucleoproteins)
What is mixed connective tissue disease
Where have features of more than 1 connective tissue disorder
Antibody in mixed connective tissue disease and staining pattern
Ant-U1RNP
Speckled
Histology of GCA
Granulomatous transmural inflammation + giant cells +
skip lesions
What is the classfifcation of vasculitidies
Large vessel
- takayasu
- GCA
Medium vessel
- polyarteritis nodosa
- kawasakis
- thromboangiitis obliterans
Small vessel
- microscopic polyangiitis
- granluomatosis with polyangiitis
- IgA nephropathy
- eosinophillic granluomatosis with polyangiitis
Histology of polyarteritis nodosa
fibrinoid necrosis & neutrophil infiltration
Presentation of eosinophilic polyangiitis with granulomatosis
Asthma
Eosinophilia
Allergic rhinits
Vasculitis evidence
What is difference in name of tumour of large vs small nerve tumour
Small- neurofibroma
Larger (spinal cranial nerve)- schwannoma
How does wilsons present
Liver cirrhosis- often in kids
Neuro- dementia, seizures and parkinsons
Also seen in eyes, kidneys and heart
How can haemochromatosis present
Liver- cirrhosis
Heart- cardiomyopathy
Pancreas- DM
Gonads- atrophy and impotence
Joint pain
Causes of acute pancreatitis
Obstrucrive
- gallstones
- tumours
- trauma
Metabolic
- alcohol
- hypercalcaemia
- hyperlipidaemia
- drugs (thiazides)
Poor blood supply
- shock
- hypothermia
Infection
- mumps
How does alcohol cause pancreatitis
Spasm of sphincter of oddi and protein rich pancreatic fluid which less viscous
Causes and histology of chronic pancreatitis+ which cells lose first
Metabolic
- Alcohol
- Haemochromatosis
Duct obstruction
- cystic fibrosis as thick mucin
- tumours
Parenchymal fibrosis with loss of parenchyma
Duct stricture with calcified stones
Lose acinar cells first
Characterisitcs of autoimmune pancreatitis
IgG4 positive plasma cells
Pathological precursors to pancreatic ductal carcinomas
Pancreatic Intraductal Neoplasm
Intraducal Mucinous Papillary Neoplasm
K-ras mutations majority of time
Histology and macroscopic appearance of pancreatic carcinomas
Adenocarcinomas with mucin producing glands set in desmoplastic stroma
Gritty and grey macroscopically
Most common cause of colitis- viral, bacterial, protozoal, fungal
Viral- CMV
Bacterial- salmonella
Protozoa- entamoeba histolytica
Fungal- candida
Who is CMV colitis seen in
Immunosuppressed
Often IBD as treatment is immunosuppresant
What are types of polyps in the bowel
Hyperplastic and sessile serrated lesions
Inflammatory
Hamartomatous (Peutz-jeughers)
Differnece between sessile serrated lesions and hyperplastic polyps
Dysplasia in sessile serrated
Differences between FAP and HNPCC
Both autosomal dominant
FAP
- hundreds of polyps
- rectosigmoid tumours
- tumour suppressor gene mutation
HNPCC
- handful of polyps
- proximal to splenic flexure
- DNA repair genes errors
What are 3 types of renal stones and their risk factors
Caclium oxalate
- hypercalcaemia
- impaired renal absorption of Ca
Magnesium ammonium phosphate
- proteus infection
Uric acid
- gout
- cancer
Causes of acquired cysts on kidney
Renal failure patients on dialysis
What conditions can be cause of acute tubular injury
Acute tubular necrosis
- ischaemia
- toxins
- drugs
Acute tubular interstitial nephritis
- abx
- PPIs
- NSAIDs
- diuretics
What is seen on histology when acute glomerulonephritis is bad enough to cause acute renal failure
Crescents from proliferation of cells in bowmans space
Histology of pauci-immune glomerulonephritis
Scanty glomerular immunoglobulin deposits
Necrosis everywhere as neutrophils activated
Aetiology of thrombotic microangiopathy
HUS
MAHA
- TTP
-DIC
Anti-phosopholipid syndrome
Histology of thrombotic microangiopathy
Damage to endothelium, glomeruli, arterioles and thrombosis
Causes of nephrotic syndrome
Primary disease non immune complex related
- minimal change disease
- FSGS
Primary disease immune complex related
- Membranous glomerulonephritis
Systemic disease
- amyloid
- DM
- SLE
Histology of membranous glomerulonephritis
Subepithelial deposition of immune deposits
What mutation causes pilocytic astrocytoma
BRAF
What mutation in serous ovarian cystadenoma
p53
Mutation in mucinous ovarian cystadenoma
KRAS
What is associated with waxy, fatty casts
Waxy- CKD
Fatty- nephrotic syndrome
Histopathology of HTN nephropathy
Arterial hyalination
Ischaemic glomerular changes
Segmental and global glomerulosclerosis
Pericarditis causes
Fibrinous
- MI
Granulomatous
- TB
Prurulent
- staphylococcus
Causes of microscopic haematuria
IgA nephropathy
Thin basement mebrane disease
Aetiolgy of thin basement membrane
Genetic defect in Type IV collagen synthesis causing BM thickness under 250nm
Inheritance of alport
X-linked dominant
What is hereditary angioedema
Where ger recurrent bouts of facial swelling from C1 esterase inhibitor
What comes under HLA 3
Complements components
Features of APECED
Dysfunctional parathyroid/adrenal gland
Immune deficiency
Gonadal failure
Alpecia and vitiligo
Where is error in APECED
AIRE gene- responsible for expression of self antigens in thymus which prevents production of autoreactive T cells
What componenets are involved in classical vs alternative pathway
Classical- C1,C2, C4
Alternative- B, D, P
What hypersensitivity is hyperacute transplant rejection
2
What chemical messenger is key in pathogenesis of systemic sclerosis
TNF-beta
Difference between pathophysiology in pemphigus vulgaris vs pemphigus follaceous
Anti-desmoglein 1= foliaceous
Anti-desmoglein 3= vulgaris
Sterile vegetations on heart valves which cause systemic emboli
Non-bacterial thrombotic endocarditis
Most common cause of bacterial meningitis in children
Strep pneumoniae
Cytology of fibroadenoma
Branching sheets of epithelium in antler horn or honeycomb sheets
Bare nuclei and stroma
Basically a ball of fibrous and glandular tissue
Histology and cytology of intraductal papillomas
Histo- Papillary mass with dilated duct lined by epithelium
Cytology of discharge- branching papillary epithelium
Histology of radial scar
Central fibrous stellate area
If over 1cm is called complex sclerosing lesion
What can appear as stellate area on mammogram
Stellate area
How do phyllodes tumours present
Masses in over 50s
Histology of fibrocystic breast disease
Fibrous tissue containing cysts with flattened and cuboidal epithelium which can be calcified
What is the histology of 3 proliferative breast diseases
Usual type- growth of epithelial and glandular tissue protruding into lumen in fronds
Flat atypia- multiple layers forming a smaller but regular circular lumen
Intralobular neoplasia- solid proliferation of aplastic cells where can just see the lumen
Buzzwords for phyllodes tumour
Anything plant like
- srtichoke
- leaf-like pronds
- branching
Arise from stroma
Fibro-epithelial Tumour with abundant stromal elements
Presentation of duct ectasia
Firm thick, yellow discharge- can easily become infected with proceeding abscesses
Subareolar mass with nipple inversion
Cytology of duct ectasia
Proteinaceous material with macrophages
Histology of duct ectasia
Ductal dilation with proteinaceous material inside
Problem of trastuzumab
Firstly poor progonsis
But also cardiotoxic so must monitor LVF
What do basal cell carcinomas stain for
Triple negative- ER/PR/HER negative
CK5/6/14
Histology of basal cell breast carcinomas
Sheets of atypical cells with lymphocytic infiltrates
Histology of the 4 invasive breast tumours
Ductal- not classified otherwise but big pleiomrophic cells
Lobular- cells aligned in single file/cains
Tubular- well formed tubules
Mucinous- abundant mucin which dissects tissues
How are ductal vs lobular carcinoma in situ picked up
Invasive- incidental as no microcalcifications
Ductal- microcalcifications
TO NOTE- they do not invade the BM
Features of lobular carcinoma in situ
Lack cadherin E
Dont invade BM
Picked up incidentally
Histology of melanoma
Pagetoid cells
Buckshot apperance
Most common type of melanoma
Superficial spreading
Which breast cancer does pagets develop from
Ductal
Histology of ductal carcinoma in situ
Ducts filled with atypical epithelial cells
2 Most common breast lesions that presents with discharge
Papilloma
2nd- duct ectasia
How are aspirates of breast lumps coded
C1- inadequate
C2- benign
C3- atypia, probably benign
C4- suspicion of malignancy
C5- malignant
Histology of fat necrosis
Central focus of necrotic fat cells surrounded by lipid filled macrophages and neutrophilic infiltrates
How to diagnose bone tumours
Jamshidi needle
Xray and histology of fibrous dysplasia
X ray- shepherds crook deformity and soap bubble osteolysis of ribs and gemur
Histology- chinese letters
How do endchondromas appear histologically
Normal cartilage
What appears with cotton wool or popcorn calcifcation
Endochondromas
Histology of giant cell tumours
Sheets of multi-nucleate giant cells (osteoclasts) on background of spindle and ovioid cells
Soap bubble appearance
What is most common malignant bone tumour
Metases however not at below elbow and knee
What are malignant mesenchymal cells seen in
Osteosarcomas
X-ray and histology of chondrosarcoma
Xray- fluffy calcification
Histology- Malignant chondrocytes
X-ray and histology differences between ewings sarcoma and osteosarcoma
X ray
- Ewings sarcoma = onion skinning of periosteum
- osteosarcoma = elevated perisoteum(codmans triangle) and suburst appearance
Histology
- osteosarcoma= ALP, malignant mesenchymal cells, trabecular bone replaced
- ewings sarcoma= CD99 stain, small round cells and T(11;22)
Bony pain at night relieved by aspirin
Osteoid osteoma
X-ray and histology of osteoid osteoma
X-ray= central nodus with sclerotic ring(bulls- eye)
Histology- normal bone from osteoblasts
Bone disease with lots of lytic lesions around the joint
Giant cell tumour
Which infection of genital tract is associated with spontaneous abortion and chorioamnionitis
Mycoplasma
Pathogenesis of staph, strep, coliform bacteria and clostridium causing PID
Secondary to abortion
Start in lymphatics then spread by blood and lymph upwards
How does HPV transform cells
Produces 2 proteins- E6 and E7 which inactivate tumour suppressor genes
E6- p53
E7- Rb
Serous cystadenocarcinoma histology
Columnar epithelium
Psammoma bodies
Ciliated epithelium
Histology endometrioid and then clear cell ovarian tumours
Endometrioid= Tubular glands mimicking the endometrium
Clear= hobnail appearance, clear cells with clear cytoplasm
BOTH ASSOCIATED WITH ENDOMETRIOSIS
Difference between immature and mature teratomas in ovaries
Mature
- cystic
- differentiation into mature tissues like skin teeth etc
Immature
- solid
- embryonal tissue
- secrete AFP
What are the ovarian tumours and what in each class
Epithelial
- serous
- mucinous
- clear
- endometrioid
Sex-chord stromal
- fibroma
- sertoli leydig
- granulosa theca
Germ
- teratoma
- choriocarcinoma
- dysgerminoma
What are hormone secreting ovarian tumours
Granulosa theca- E2
Sertoli leydig- Progesterone
Dysgerminoma- HCG
CHoriocarcinoma- HCG
What are cal exner bodies seen in
Sertoli leydig
Mutations in the gynae cancers
p53- serous cystadenocarcinoma, and seroud T2 endometrioid
KRAS- mucinous cystadenocarcinoma
What do dysgerminomas secrete
LDH
HCG
What complement molecules in mannose binding pathway
C2,C4
What triggers MBL vs alternative complement pathway
MBL- cell surface carbohydrates
Alternative- bacterial cell wall
Which cells mastermind the transition from innate to adaptive immunity?
Dendritic
What is receptor in CD4 activating B cells
CD40
Inheritance of kosmann vs cyclic neutropenia
Kostmann- autosomal recessive
Cyclic neutropenia- autosomal dominant
What is DHR test
Add hydrogen peroxide and positive test is FHR becoming fluorescent rhodamine
Other than mycobacterium, what infectoin can IL12/ IFN-gamma make susceptible to
Salmonella
What is most common complement deficiency and what is result
C2
Have SLE and severe skin disease
What are non primary complement deficiencies
Nephritis factor- Antibodies against complement components
SLE- uses up C3 and C4
What is associated with nephritic factor
Glomerulonephritis and partial lipodystrophy (abnormal fat distribution)
What causes a decrease in CH50 and AP50
Deficiencies in terminal pathwayeg- C9
Blood findings of C9 deficiency
Low AP50 and CH50
What happens inf have reduction in factor B
Low AP50
If have deficiency in C1 or C2 what happens blood wise
Low CH50
A 10 year old female patient presents with photosensitive skin rash and mouth ulcers. Investigations show:
C4 levels normal
AP50 normal
CH50 abnormal
What is the most likely diagnosis
C2 deficiency
Treatment of Digeorge immunodeficiency
Thymic transplant- often to quadriceps
How can T cell counts affect IgG
If defective CD4 lack IgG production ability
Differences between selective IgA and CVID
CVID- lack of Ig E, A and G with recurrent GI and resp infections
Selective IgA deficiency- recurrent resp infections
What is name of IL1 R blocker
Anakinra
What cell are PTPN22 and CTLA4 mutations of
T cell regulator
What does APECED stand for
Autoimmune
Polyendocrinopathy
Candidiasis
Ectodermal
Dystrophy
What conditions seen in APECED
Hypoparathyroidism, Addisons, Hypothyroidism, Diabetes, Vitiligo, Enteropathy
How does serum sickness present
Given penicillin and develop skin rash, joint aches and fever
A 12 year old boy presents with haematuria and proteinuria. He has recently been discharged following severe meningococcal septicaemia. There is abnormal fat distribution.
C3 levels are low, and C4 levels are normal.
Nephritic factor
How does LSD use present
Phsically similar to concaine however hallucinations common
How to manage wanting a termination but is pain
Must redo HCG in 48 hours
If increase of over 63% then intrauterine pregnancy likely but need USS in 7 days to confirm
If decrease miscarraig likely
If plateau or slight increase then potential ectopic
What do if evidence of recent FGM on a woman over 18
Report to police
What do about police in women with FGM over 18
Offer to call police but do not have to
