Adam Sullivan Pathology Flashcards
Acanthyocytes
Spiculated RBCs
Hyposplenism, liver disease, Abetalipoproteinaemia
Basophilic RBC stippling
Accelerated erythropoiesis or defective Hb synthesis -> small rRNA dots on periphery.
Lead poisoning, megaloblastic anaemia, MDS, liver disease, Hbopathy
Burr cells
aka echinocyte (irregularly shaped)
uraemia, GI bleed, stomach Ca
Heinz bodies
Inclusions in RBCs
G6PD deficiency
Also chronic liver disease
Associated with Bite cells as liver takes a bite out of RBC to remove Heinz body
Howell-Jolly body
Basophilic nuclear remnants
Hyposplenism (or post-splenectomy).
Also megaloblastic anaemia, hereditary spherocytosis.
Leucoerythyoblastic anaemia
nucleated RBCs and primitive WBCs in peripheral blood
Due to marrow infiltration - myelofibrosis, malignancy
Pelget Huet cells
Hyposegmented PMNs
Congenital
- lamin B receptor mutation
Acquired
- MDS
- myelogenous leukaemia
Right shift
Hypersegmented PMNs (>5)
Megaloblastic anaemia, uraemia, liver disease
Rouleaux
Red cells stack together due to hyperviscosity.
Myeloma, paraproteinaemia, chronic inflammation.
Schistocytes
Fragmented RBCs
MAHA - DIC, TTP, HUS
Pre-eclampsia
Stomatocytes
Rod like RBCs with central pallor. ‘Smiling face’ or ‘Fish mouth’ appearance.
Hereditary stomatocytosis
High alcohol intake + liver disease
Target cells
aka codocytes
Bull’s eye appearance in central pallor.
3H's - hepatic pathology - hyposplenism - Hbopathies - thalassemia (IDA)
Pencil cells
IDA
Causes of microcytic anaemia
FAST
Fe-deficiency
ACD
Sideroblastic anaemia
Thalassemia
Causes of macrocytic anaemia
Megaloblastic:
- B12 or folate
- cytotoxic anti-folate drugs: phenytoin
Non-megaloblastic:
- Alcohol excess or liver disease
- Reticulocytosis - eg. 2nd to haemolysis
- Hypothyroidism
- Pregnancy
Other haem disorder:
- MDS
- myeloma
- myeloproliferative disorders
Plummer-Vinson syndrome triad
IDA + dysphagia + oesophageal webs
Treatment for sideroblastic anaemia
Remove underlying cause (MDS, chemo, irradiation, alcohol excess, lead excess, anti-TB drugs, myeloproliferative)
Pyridoxine (vitamin B6) - promotes RBC production, reducing ineffective erythropoiesis.
Iron, TIBC and Ferritin in:
IDA
Iron - Down
TIBC - Up
Ferritin - Down
Iron, TIBC and Ferritin in:
ACD
Iron - Down
TIBC - Down
Ferritin - Up (acute phase protein)
Iron, TIBC and Ferritin in:
Sideroblastic anaemia
Iron - Up
TIBC - N
Ferritin - Up
Pernicious anaemia serology
Parietal cell autoAb - 90%
IF autoAb - 50%
Hereditary spherocytosis inheritance pattern
AutoD
25% recessive or de novo
Hereditary spherocytosis mutations
Vertical cytoskeleton
Band 3 - Protein 4.2 - Ankyrin - B spectrin
Hereditary spherocytosis tests
Osmotic fragility - increased lysis in hypotonic solution
DAT -ve
Spherocytes on blood film
Hereditary elliptocytosis mutations
Horizontal cytoskeleton
a-spectrin - B-spectrin - protein 4.1
AutoD (except hereditary pyropoikilocytosis = autoR)
G6PD inheritance
X linked
Management of acute haemolysis
Folate Avoid precipitant Transfusion Immunisation vs BBVs ?cholecystectomy Splenectomy. - prophylaxis vs encapsulated bacteria.
Precipitants of oxidative stress if G6PDD
Drugs - antimalarials (primaquine), antibiotics (sulphonamides) Favism (aflatoxin) Acute stressors Moth balls Acute infection
Pyruvate kinase inheritance
AutoR
Does splenic sequestration occur more in adults or children with sickle cell disease
Children.
By adulthood it becomes atrophic.
Diagnosis of Sickle cell disease
Blood film - sickle cells, target cells, boat cells, Howell-Jolly bodies
Sickle solubility test
Hb electrophoresis
Guthrie test at birth
Types of B thalassemia
Absent (B0) or Reduced (B-) B chains, excess a chains
B-thalassemia minor - heterozygous B-/B; B0/B
B-thalassemia intermedia - B-/B-; B0/B
B-thalassemia major - homozygous B0/B0 (infant presentation)
Type of mutation in B thalassemia
point mutation
Type of mutation in a thalassemia
deletion
Types of A thalassemia
Reduced a chain (4 genes), excess B chains
a-thalassemia trait - 1/2 deleted: asymptomatic
HbH disease - 3 deleted: moderate anaemia + splenomegaly
Hydrops fetalis - 4 deleted: lethal
Signs of B thalassemia
Anaemia - severity increases with number of mutations
Skull Xray - skull bossing, maxillary hypertrophy, hairs on end skull
Hepatosplenomegaly
Donath-Landsteiner antibodies
Paroxysmal cold haemoglobinuria
Rare AIHA.
Usually affects children in acute setting after an infection. Sudden haemoglobinuria and jaundice after exposure to cold temperatures.
Donath-Landsteiner Abs = IgG autoAb vs RBC surface Ags.
Increasing intravascular haemolysis at low temperatures.
Type of Ig in Warm AIHA
IgG
WarminG
Type of Ig in Cold AIHA
IgM
I’M cold
Causes of warm AIHA
Idiopathic - mainly
Lymphoma
CLL
SLE
methyldopa
Causes of cold agglutinin disease
Primary idiopathic
Lymphoma
Infections - EBV, mycoplasma
Ham’s test
Paroxysmal nocturnal haemoglobinuria
A pig a night with red urine.
Test - in vitro acid-induced lysis
TTP pentad of symptoms
1) MAHA
2) Fever
3) Renal impairment
4) Neuro abnormalities
5) Thrombocytopenia
Vascular defects: causes of
Congenital
- Osler-Weber-Rendu syndrome (HHT)
- CTD: Ehlers-Danlos, pseudoxanthoma elasticum
Acquired
- senile purpura
- scurvy
- infection
- steroids
Haemophilia A inheritance
X linked recessive
fVIII deficiency. (intrinsic pathway - APTT prolonged)
Haemophilia A management
avoid NSAIDs and IM injections
Desmopressin - increases vWF release which is fVIII carrier
fVIII replacement
Treatment of ITP
> 50,000 platelets - none
20-50,000 platelets + bleeding - steroids + IVIg
<20,000 + bleeding - steroids + IVIg + admission
Vitamin K deficiency causes
Warfarin
Malabsorption/malnutrition
Abx therapy - alters gut flora that produces vitamin K
Biliary obstruction
Antidote to heparine
Protamine sulphate
Heparin-induced thrombocytopenia
Ab vs. heparin bound to platelets.
Assoc. w/ older heparins.
Treat w/ fondaparinux.
Treatment of INR 5-8, no bleed.
Withold few doses, reduce maintenance.
Restart when INR <5
Treatment of INR 5-8, minor bleed.
Stop warfarin.
Slow vitamin K po.
Restart when INR<5
Treatment on INR >8
Stop warfarin
Vitamin K po/IV
If major bleed - PCC, FFP
% Blasts in acute leukaemia
Blasts >20%
Gum hypertrophy differential
Acute leukaemia
Drugs - cyclosporin, phenytoin, amlodipine
Auer rods
AML
ALL chemo regimen
Remission induction - High dose agents often given steroids
Consolidation - High dose multi drug chemo
CNS treatment - intrathecal chemo
Maintenance - 2y in girls, 3y in boys (increased risks of testicular recurrence)
PML mutation
t(15;17): PML-RARA (retinoic acid receptor)
PML (M3 AML) treatment
All-trans retinoid acid
(or arsenic)
- neurotoxicity risk
3 Phases of CML
Chronic Phase
- 10% blasts
- nearly 80% progress to this phase
- manifestations such as splenomegaly
Blast Phase
- > 20% blasts
- resembles acute leukaemia
CML treatment
Oral hydroxyurea/interferon - suppresses WCC
Imatinib TKi - >95% 5 year survival
Dasatinib/nilotinib for resistance
(BMT, allogeneic SCT)
Evan’s syndrome
AIHA + ITP
assoc. w/ CLL
Richter’s transformation
Progression of CLL to lymphoma (DLBC)
Occurs in 3%
Smear cells
CLL
Reed-Sternberg cell
Hodgkin’s lymphoma
Owl eyed cells with that is bi/multinucleate.
Ann Arbor staging for lymphomas
Stage 1 - one LN region (can include spleen)
Stage 2 - 2 or more LN regions, same side of diaphragm
Stage 3 - 2 or more LN regions, opposite sides of diaphragm
Stage 4 - extranodal sites (liver, BM)
A: No constitutional symptoms
B: Constitutional symptoms
Hodgkin’s lymphoma Chemo combination
ABVD
Adriamycin
Bleomycin
Vinblastine
Dacarbazine
Pel-Ebstein fever
Hodgkin’s lymphoma
cyclical 1-2 week fever. Rarely seen.
Pain in lymph nodes after drinking alcohol.
Hodgkin’s lymphoma
Alemtuzumab
anti-CD52 (aka CamPath)
Use in CLL and T cell lymphomas
Also approved for use in MS.
3 types of Burkitt’s lymphoma
1) Endemic
- EBV-associated
- Equatorial Africa. P. falciparum wears down immune system vs EBV.
- Jaw involvement
2) Sporadic
- EBV-associated
- Out of Africa
3) Immunodeficiency
- Non-EBV associated
- HIV/post-transplant pts.
Starry sky appearance on histology
Burkitt’s lyphoma
Translocation in Burkitt’s
t(8; 14) - c-myc overexpression
Translocation in Mantle cell lymphoma
t(11; 14) deregulation - cyclin D1 deregulation.
Aggressive lymphoma
Translocation in Follicular lyphoma
t(14;18)
Chronic Ag stimulants leading to MALT
H.pylori -> gastric MALT
Sjogren’s -> parotid lymphoma
Ig in Multiple Myeloma
IgG
5 solid tumours that metastasise to bone
Lytic
1) breast
2) thyroid
3) renal
4) lungs
Sclerotic
5) Prostate
Clinical, Plasma cell and Monoprotein for Multiple myeloma
CRAB
> 10% plasma cells
> 30g/L monoprotein
Clinical, Plasma cell and Monoprotein for MGUS
no CRAB
<30g/L monoclonal paraprotein
Clinical, Plasma cell and Monoprotein for Smouldering myeloma
no CRAB
> 10% plasma cells
> 30g/L monoprotein
Ig in Waldenstrom’s
IgM
Lymphoplasmacytoid cell
Waldenstrom’s Macroglobinaemia
Apple green birefringence on congo red stain
Amyloidosis
Fanconi anaemia
AutoR
Paediatric: 5-10y
Pancytopenia. Skeletal abnormalities (radii + thumbs). Renal malformation. Microopthalmia. Short. Skin pigmentation.
Dyskeratosis congenita
X linked
Telomere shortening
TRIAD: skin pigmentation + nail dystrophy + oral leukoplakia.
Also BM failure
Schwachmann-Diamond syndrome
AutoR
PRoPoSe
- Pancreastic insufficiency
- Recurrent infection
- Pancytopenia
- Skeletal abnormalities
Neutrophilia
Diamond-Blackfan syndrome
Pure RED cell aplasia.
Neonatal/infant presentation.
AutoR
Paediatric: 5-10y
Pancytopenia. Skeletal abnormalities (radii + thumbs). Renal malformation. Microopthalmia. Short. Skin pigmentation.
Fanconi anaemia
X linked
Telomere shortening
TRIAD: skin pigmentation + nail dystrophy + oral leukoplakia.
Also BM failure
Dyskeratosis congenita
AutoR
PRoPoSe
- Pancreastic insufficiency
- Recurrent infection
- Pancytopenia
- Skeletal abnormalities
Neutrophilia
Schwachmann-Diamond syndrome
Mutation in polycythemia rubra vera
JAK2 (V617F) - point mutation.
Activation of STAT pathway leading to cellular proliferation.
Aquagenic pruritus + peptic ulcers + gout + erthromelagia
Polycythemia rubra vera
Aquagenic pruritus - contact with hot water -> histamine release
Histamine -> peptic ulcer
Erythromelagia (red, painful extremities) and gout due to hyperviscosity.
Treatment for PRV
Venesection - keep haematocrit <45%
Hydroxycarbamide - cytoreductive therapy for maintenance.
Aspirin - reduce thrombosis risk
Tear-drop poikilocytes
Myelofibrosis
aka dacrocytes
Dry tap BM trephine
myelofibrosis.
Fibrotic replacement of BM. High reticulin.
Anagrelide treatment
Used in essential thrombocythemia.
Reduces formation of plts from megakarocytes.
Used in conjunction with aspirin (anti-thrombotic) and hydroxycarbamide (cytoreductive).
Ig in haemolytic disease of the newborn
IgG. Only it can cross the placenta.
Blueberry muffin rash
Congenital rubella
Charcot-Leyden crystals
Eosinophilic proliferation associated with allergic conditions - ASTHMA, parasite infections, ascariasis
Curschmann’s spirals
Spiral mucus plugs in sputum associated with asthma
Clinical diagnosis of chronic bronchitis
Chronic productive cough for most days of the 3 months in the last 2 years.
Histological diagnosis of emphysema
Permanent loss of alveolar parenchyma distal to the terminal bronchiole.
Causes of bronchiectasis
1) Congenital
- CF, immunodeficiency syndromes, Kartagener syndrome
2) Infectious (necrotizing pneumonia)
- bacteria: TB, S. aureus, H. influenzae, Pseudomonas
- viruses: adenovirus, Flu, HIV
- fungi: aspergillus
3) Bronchial obstruction: foreign bodies, tumour,
4) Other: RA, SLE, IBD, Post-transplant
4 types of emphysema
1) centriacinar - smoking
2) panacinar - a1AT deficiency
3) distal acinar - adjacent to fibrosis and atelectasis. Cause of spontaneous pneumothorax
4) Irregular - irregular acinar involvement with fibrosis
Complications of chronic bronchitis
Recurrent infections (most common cause of admission and death)
Chronic hypoxia
Pulmonary HTN
(lung Ca)
Pathogen in Farmer’s Lung
Saccharopolyspora rectivirgula
mouldy hay/grain/silage
Antigen in Pigeon Fancier’s Lung
Proteins in excreta/feathers
Pathogen in Humidifier’s lung
Thermactinomyces spp.
Heated water reservoirs
Pathogen in Malt-workers lung
Aspergillus clavatus/fumigatus
germinating barley
Pathogen in Cheese washer’s lung
Aspergillus clavatus/Penicillium casei
Mouldy cheese
Masson bodies
polyploid plugs of loose connective tissue within alveoli and bronchioles.
Associated with Cryptogenic organising pneumonia.
Can develop into non-caseating granulomas.
Pneumoconiosis definition
A non-neoplastic lung reaction to inhalation of inorganic mineral dusts.
Cryptogenic Fibrosing Alveolitis aka?
Idiopathic Pulmonary Fibrosis
Honeycomb lung
Progressive patchy interstitial fibrosis with cyst formation due to type II pneumocyte hyperplasia.
Usual Interstitial Pneumonia histological pattern: Idiopathic pulmonary fibrosis, EAA, CTD, asbestosis.
Granulomatous lung diseases
TB
Sarcoidosis
Fungi - histoplasma, cryptococcus, coccidioides, aspergillus, mucor
Occupational lung disease
Foreign body - aspiration, IVDU
4 stages of lobar pneumonia
1) Consolidation + congestion - intra-pulmonary fluid
2) Red hepatisation - neutrophilia
3) Grey hepatisation - fibrosis
4) Resolution
Atypical pneumonia pathogens
Coxiella, Mycoplasma, Chlamydia
Viruses: CMV, influenza
Percentage of PEs due to DVTs
95%
Sequelae of large emboli
acute cor pulmonale
cardiogenic shock
death
Pulmonary HTN arterial pressure?
mean pulmonary arterial pressure >25mmHg at rest.
Causes of pulmonary HTN
Pre-capillary
- chronic hypoxia -> vasoconstriction
- embolic
Capillary
- pulmonary fibrosis
Post-capillary
- vena-occlusive disease
- Left heart disease
Pathological mechanism for ARDS
Diffuse alveolar damage (epithelial +/ endothelial)
- > Exudative phase (neutrophilia)
- > hyaline membranes
- > organizing phase (-> diffuse alveolar damage)
Factors in smoke that contribute to cancer
Tumour initiator
- polycyclic aromatic hydrocarbons
Tumour promoters
- N nitrosamines, nicotine, phenols
Complete carcinogens
- Nickel, arsenic
Keratinisation and intercellular prickles are associated with which type of lung cancer
Squamous cell
Causes of lung Ca in non-smokers
Asbestos
Radiation
Heavy metals
Genetics
(passive smoking)
Pre-invasive states of adenocarcinoma
Atypical adenomatous hyperplasia
- pre-cancerous
Bronchioalveolar carcinoma
- non-invasive
Malignant epithelial lung tumour with glandular differentiation and mucin production.
Adenocarcinoma
Lung cancer associated with women and non-smokers
adenocarcinoma
4 sites of lung mets
1) Brain -> fits
2) Skin -> lumps
3) Liver -> pain and deranged LFTs
4) Bone -> pain and fracture
Paraneoplastic syndrome associated with which type of lung Cancer: Cushings
Small cell carcinoma -> ACTH
Paraneoplastic syndrome associated with which type of lung Cancer: hypercalcemia
Squamous cell carcinoma -> PTH + PTHrP
Paraneoplastic syndrome associated with which type of lung Cancer: SIADH
Small cell -> ADH
Paraneoplastic syndrome associated with which type of lung Cancer: serotonin
Carcinoid
Latency period of mesothelioma
25-45 years
In what way does a K-ras mutation predict responsiveness to erlotinib.
It predicts poor response.
Erlotinib is an anti-EGFR TKi.
K-ras mutations occur in 15-30% of lung Ca
Conversely can get responder mutations, with EGFR amplification.
Lung cancer molecular therapeutics: ERCC1 positive
Predicts poor response to cisplatin chemotherapy
Lung cancer molecular therapeutics:: EML4-ALK1
Gain-of-function kinase. Predicts that TKi of no benefit.
Fitz Hugh Curtis syndrome
Ascending inflammation from PID to liver resulting in peri-hepatitis. Diaphragmatic irritation leads to RUQ pain that is worsened by breathing, coughing, laughing.
Violin string peri-hepatic adhesions.
2 main organisms associated with PID
Chlamydia & Neisseria
Cervical excitation it most commonly associated with….
PID
Endometriosis definition
Presence of endometrial glands or storm in abnormal locations outside the uterus.
Chocolate cysts in the ovaries
Endometriosis
endometriomas
Red-blue to brown ‘powder burn’ nodules
Endometriosis
Adenomyosis definition
Ectopic endometrial tissue within the myometrium
Proportion of those with post-menopausal bleeding who have malignancy
10%
Types of endometrial carcinoma
Endometrioid (80%)
- related to oestrogen excess, obesity
- atypical endometrial hyperplasia precursor
Non-endometrioid (20%)
- papillary, serous and clear cell tumours.
- Particular genetic mutations (P53, PI3KCA, PTEN)
- elderly women with endometrial atrophy
Papillary hidradenoma
Benign vulval carcinoma
Ectopic breast tissue found on labia.
Main type of vulval carcinoma
Squamous cell carcinoma (85%)
Paget’s disease of the vulva
Adenocarcinoma-in-situ
3 main categories of primary ovarian carcinoma
Epithelial (70%)
Germ cell (20%)
Sex cord/stroma (10%)
What proportion of malignant ovarian tumours does epithelial type account for?
95%
4 subtypes of epithelial ovarian carcinoma
Serous
Mucinous
Endometrioid
Clear cell
Psammoma bodies is associated with which ovarian carcinoma
Serous carcinoma
Most common subtype of epithelial carcinoma. Mimics columnar epithelium of the tubule, usually cystic.
What type of ovarian carcinoma is associated with pseudomyxoma peritonei?
Mucinous (epithelial) carcinoma.
Mucinous adenocarcinoma that has metastasised from intestines (probably appendiceal primary)
Which type of epithelial ovarian Ca forms tubular glands?
Endometrioid. It mimics the endometrium.
10-20% associated with endometriosis; often co-exists with endometrial Ca
Which ovarian Ca is associated with a histological hobnail appearance with abundant clear cytoplasm?
Clear cell (epithelial) Ca.
Clear cytoplasm is intracellular glycogen.
Strong association with endometriosis.
3 Subtypes of Germ cell ovarian carcinoma
Dysgerminoma
Teratoma
Choriocarcinoma
Which germ cell ovarian Ca is the female equivalent of the testicular seminoma
Dysgerminoma
Compare mature and immature teratomas
Mature teratoma: Benign dermoid cysts; differentiation of germ cells into mature tissues (skin, hair, teeth, bone, cartilage)
Immature teratoma: Malignant, solid masses containing immature, embryonal tissues. Grows rapidly, invades and metastatises, results in adhesions.
Which germ cell ovarian Ca produces hCG
choriocarcinoma
3 types of sex cord/stromal ovarian Ca
Fibroma
Granulose-Theca cell tumour ( differentiation of sex cord to female structure)
Sertoli-Leydig cell tumour (differentiation of sex cord to male structure)
Meig syndrome
Triad - benign ovarian tumour (fibroma) + ascites + pleural effusion
Occurs in 50% of fibromas
What hormone do fibromas produce?
None
Benign tumour derived from cells of ovarian stroma.
What hormone does a Granulosa-Theca cell tumour produce?
E2
Oestrogen effects - irregular menstruation, breast enlargement, endometrial/breast Ca
What hormones does a Sertoli-Leydig cell tumour produce?
Androgens
Defeminisation - breast atrophy
Virilisation - hirsutism, deep voice, enlarged clitoris.
3 types of familial ovarian Ca
1) Familial Breast-Ovarian Ca syndrome
- BRCA1
2) Site specific ovarian Ca
3) Lynch type II - associated with HNPCC
Krukenberg tumour
Malignant tumour in the ovary that has metastasised from the GI tract. Most commonly gastric adenocarcinoma. 80% both ovaries.
Mucin-producing signet rings.
Compare type I and type II ovarian Ca
Type I
- low grade
- indolent
- large mass from precursor
- Kras, BRAF mutations
Type II
- high grade
- aggressive
- mainly serous tumours
- > 75% p53 mutations
How does HPV result in dysplasia and neoplasia?
Viral proteins affect cell cycle regulation.
E6 binds to p53
E7 binds to RB
CIN gradings
CIN 1 = lower 1/3 of epithelium has dysplasia
CIN 2 = lower 2/3
CIN 3 = full thickness, but basement membrane intact.
60-90% CIN 1 revers to normal over 10-23m
10% CIN 3 progresses to cervical Ca in 10y
What proportion of cervical carcinomas are adenocarcinomas?
~20%
70-80% SCC
Monitoring and diagnosing autoimmune disease and HIV.
- How to monitor the activity of SLE?
Options: C3 & C4 levels, HIV test, White cell count and differential, anti-SCL-70, anti-Sm.
C3 + C4 levels
Monitoring and diagnosing autoimmune disease and HIV.
- How to monitor a patient with HIV?
Options: C3 & C4 levels, HIV test, White cell count and differential, anti-SCL-70, anti-Sm.
WCC and differential
Monitoring and diagnosing autoimmune disease and HIV.
- Antibody useful to diagnose someone with systemic sclerosis?
Options: C3 & C4 levels, HIV test, White cell count and differential, anti-SCL-70, anti-Sm.
SCL-70
How would you treat a patient with rheumatoid arthritis who is not responsive to methotrexate and another DMARD?
Options: cyclophosphamide, tocilizumab, ustekinemab, denosumab, IFN-gamma, IFN-alpha, tacrolimus,
Tocilizumab (anti-IL-6R mAb)
This is the best answer as there is no anti-TNF medications amongst the options
How to treat a patient with Wegener’s Granulomatosis who has severe flare of disease?
Options: cyclophosphamide, tocilizumab, ustekinemab, denosumab, IFN-gamma, IFN-alpha, tacrolimus,
Cyclophosphamide
- DNA alkylating agent
A patient with osteoporosis who cannot tolerate a bisphosphonate or something.
Options: cyclophosphamide, tocilizumab, ustekinemab, denosumab, IFN-gamma, IFN-alpha, tacrolimus,
Denosumab
mAB vs. RANKL. Less osteoclast activation.
How to treat chronic granulomatous disease?
Options: cyclophosphamide, tocilizumab, ustekinemab, denosumab, IFN-gamma, IFN-alpha, tacrolimus,
IFN-gamma
A biologic that can be used to treat psoriasis
Options: cyclophosphamide, tocilizumab, ustekinemab, denosumab, IFN-gamma, IFN-alpha, tacrolimus,
Ustekinemab
mAb vs. IL-12 + IL-23. Reduced inflammatory response.
HIV: Neutralising antibodies are formed against this.
options: gp120, p24, CCR5, CCR7, protease.
gp120
HIV: Non-neutralising antibodies are formed against this.
options: gp120, p24, CCR5, CCR7, protease.
p24
HIV: A co-receptor required for entry.
options: gp120, p24, CCR5, CCR7, protease.
CCR5
Co-receptor with CXCR4
HIV: An enzyme that can be the target of HIV medication.
options: gp120, p24, CCR5, CCR7, protease.
Protease
HHV1 =
Herpes Simplex Virus 1
Associated predominantly with oral herpes
HHV2 =
Herpes Simplex Virus 2
Associated predominantly with genital herpes
HHV3 =
Varicella Zoster Virus
Chickenpox or Shingles
HHV4 =
EBV
Infectious mononucleosis, Burkitt’s lymphoma,
hairy leukoplakia
HHV5 =
CMV
Glandular-fever like illness, retinitis
HHV6 + 7=
Roseolovirus
Sixth disease (roseola infantum)
HHV8 =
KSHV
Kaposi’s sarcoma
Pathogen associated with acute mastitis
Staphylococcus
Most often during lactation or breastfeeding.
Treatment with antibiotics +/- surgical drainage
Aim for continued expression of milk
Painful, red breast with fever
acute mastitis
Inflammatory breast condition associated with keratinising squamous epithelium.
Occurs mostly in smokers, and not associated with lactation.
Periductal mastitis.
Keratinising epithelium extends deep into nipple duct orifices.
Granulomatous inflammation and dilation of large breast ducts associated with thick, proteinaceous white nipple secretions.
Mammary duct ectasia.
Benign condition occurring mainly in multiparous women 40-60y. Poorly defined palpable periareolar mass.
Also associated with breast pain, breast mass and nipple retraction.
Can mimic cancer on mammogram
Which benign breast neoplasm is particularly associated with bloody discharge?
Duct papilloma.
Which breast neoplasm is associated with a sclerosing lesion consisting of central scarring surrounded by proliferating glandular tissue in a stellate pattern?
Radial scar.
Can resemble neoplasm on mammogram
Presence of a BRCA mutation gives what lifetime risk of invasive breast Ca?
85%
Lifetime risk of Breast cancer
1 in 8
Breast screening programme Age range: Frequency: % abnormal for further assessment: Lives saved/year:
Age range: 47-73
Frequency: 3y
% abnormal for further assessment: 5
Lives saved/year: 1250
Looks for abnormal areas of calcification or mass within a breast. Particularly looking for DCIS or early invasive breast Ca
Which breast neoplasm lacks E-cadherin expression?
LCIS
ALWAYS incidental on biopsy.
RF for subsequent invasive breast Ca
What proportion of DCIS appears as micro calcification on mammogram and what proportion has clinical symptoms?
85% microcalcification
10% symptomatic - lump, discharge, Paget’s ezcematous change of the nipple.
Grading of cytology and biopsy
C/B1 = inadequate C/B2 = benign C/B3 = equivocal, probably benign C/B4 = equivocal, probably malignant C/B5 = malignant
(B5a - DCIS, B5b - invasive)
Histological grading
Score out of 3 for
1) nuclear pleomorphism
2) tubule formation
3) mitotic activity
Grade 1 = well differentiated = 3-5
Grade 2 = moderate - 6-7
Grade 3 = poorly - 8-9
Low grade ER/PR positive tumours have a good prognosis because they respond to which treatment?
Tamoxifen
oestrogen antagonist.
Which breast cancer is associated with atypical sheets of cells with lymphocytic infiltrate and central necrosis?
Basal-like carcinoma
Has a propensity for vascular invasions and distant mets.
A breast cancer is triple negative but stains positive for CK 5,6 and 14.
Basal-like carcinoma.
Triple negative : ER/PR/HER2 -ve
CK 5/6/14 = basal cytokeratins.
A group of fibroepithelial breast neoplasms that arise from interlobular stroma (can be from existing fibroadenomas) that are mostly benign but can be very aggressive.
Phyllodes tumour
Treat with WLE/mastectomy to limit local recurrence. Mets are rare.
What is the most important prognostic factor in breast cancer?
Axillary node status
Hence importance of axillary node biopsy
Name the tissue in which each type of macrophage is found:
Kupffer cell Mesangial cell Osteoclast Sinusoidal lining cell Alveolar macrophage Microglia Histiocyte Langerhans cell Macrophage like synoviocytes
Liver Kupffer cell Kidney Mesangial cell Bone Osteoclast Spleen Sinusoidal lining cell Lung Alveolar macrophage Neural tissue Microglia Connective tissue Histiocyte Skin Langerhans cell Joints Macrophage like synoviocytes
Enzyme that converts O2 into ROS such as superoxide and hydrogen peroxide
NADPH oxidase
Depletion of what leads to neutrophil death as a result of the process of phagocytosis?
Glycogen reserves
Do NK cells target intracellular or extracellular pathogens?
Intracellular pathogens.
Intracellular infection leads to ‘altered self’ as a result of abnormal/absent HLA class I expression. Reduced inhibitory interaction with NK cells plus up-regulation of activatory ligands (heparin sulphate proteoglycans) leads to NK activation.
Which chemokine receptor mediates the migration of mature dendritic cells via lymphatics to lymph nodes?
CCR7
Lymphocytes that express inhibitory receptors capable of recognising HLA class I molecules and have cytotoxic capacity
NK cells
Is the spleen primary or secondary lymphoid tissue?
Secondary
Primary lymphoid tissue are organs involved in lymphocyte development. I.e. bone marrow and thymus.
Secondary lymphoid tissues are anatomical sites of interaction between naïve lymphocytes and microorganisms such as the spleen, MALT and LNs.
Which of these do ALL T cells express?
CD4 CD8 CD17 CD3 CD25
CD3
Which Th cell subtype expresses CD25 and FOXP3
Treg cells
Do CD8 cytotoxic lymphocytes target intracellular or extracellular pathogens?
Intracellular.
Recognise intracellular-derived proteins expressed on HLA class 1.
Kill cells directly: Perforin (pore forming) and granzymes
Expression of Fas ligand
Play an important role in promoting germinal centre reactions and differentiation of B cells into IgG and IgA secreting plasma cells
Th1 cells
CTLs
T follicular helper cells
Tregs
T follicular helper cells
Cell dependent on the presence of CD4 T cell help for generation.
Pre-B cells
IgA
IgG secreting plasma cell
IgM secreting plasma cell
IgG secreting plasma cell
Are generated rapidly following antigen recognition and are not dependent on CD4 T cell help
Pre-B cells
IgA
IgG secreting plasma cell
IgM secreting plasma cell
IgM secreting plasma cell
Immune complexes are the trigger in what complement activation pathway?
Classical pathway
ICs are bound by C1 leading to activation and resulting cascade also involving C4 and C2 before converging on C3.
Which complement activation pathway is dependent on acquired immune response?
Classical pathway.
Relies on generation of Abs to produce ICs.
What are the 2 ligands for CCR7 and important in directing dendritic cell trafficking to lymph nodes
CCL19 + CCL21
Definition of PUO
Fever >38.3C persisting for >3/52 without diagnosis despite 1/52 of Ix.
Causes of PUO
30% infection
30% malignancy
30% AI
10% undiagnosed
4 types of PUO
- Classical PUO
- Healthcare-associated PUO (following >24hrs in hospital)
- Neutropenic PUO (neutropenia <500/uL)
- HIV-associated PUO
Empirical Abx regimen for prosthetic valve with suspected infective endocarditis
Vancomycin
Gentamicin
Rifampicin
Empirial Abx regimen for native valve:
acute -
indolent -
acute = flucloxacillin indolent = penicillin + gentamicin
Abx regimen for S.viridans infective endocarditis
Benzylpenicillin + Gentamicin
Abx regimen for MSSA infective endocarditis
Flucloxacillin
For 4/52 due to abscess risk.
Abx regimen for MRSA infective endocarditis
Vancomycin +
Gent/Rifampicin/Fuicidin
Abx regimen for enterococcal infective endocarditis
Ampicillin + Gentamicin
Congenital rubella syndrome symptoms
Eyes - cataracts, micropthalmia, glaucoma, retinopathy
Ears - deafness
Brain - microcephaly, meningoencephalitis, developmental delay
CVS - PDA, PAS, ASD/VSD
Other - growth retardation, bone disease, hepatosplenomegaly, thrombocytopenia, rash
Congenital CMV
IUGR, microcephaly
RCHEP
- retinitis
- colitis
- hepatitis - HSM, jaundice
- encephalitis - SNHL, CP, epilepsy, cognitive impairment, chorioretinitis
- pneumoniitis
15% Cytomegalovirus inclusion disease
6 historical childhood rashes
1 - measles 2- scarlet fever 3 - Rubella 4 - Duke's disease - no longer used. Assoc. w/ Strep pyogenes. 5 - Parvovirus B19 'slapped cheek' 6 - Roseola
Owl eye inclusions
CMV
What particular pathogen are deep ear swabs in a septic neonate looking for?
Group B strep
Bacteria with a fried egg appearance
Mycoplasma
TORCH symptoms
Thrombocytopenia
Other - eyes, ears (cataracts, choroidoretinitis)
Rash
Cerebral - microcephaly, meningoencephalitis
Hepatosplenomegaly
Treatment for Listeria infection
Ampicillin
True or false: Malaria is a zoonosis
False
Zoonosis are diseases and infections that are transmitted naturally between humans and vertebrate animals.
Malaria is transmitted by the Anopheles mosquito, not a vertebrate.
Negri bodies are pathognomonic of what?
Rabies
Eosinophilic CNS inclusions.
What is the tick and pathogen and Lyme disease
Tick = Ixodes spp.
Pathogen = Borrelia burgdoferi
What is acrodermatitis chronic atrophicans a late sign of?
Lyme disease
Treatment for Lyme disease
Doxycycline 2-3/52
Which chromosome is the Prion protein gene found?
Which codon of the gene has the mutation?
Ch20
Codon 129
Which prion disease has periodic triphasic changes on EEG?
Sporadic CJD
14-3-3 and S100 are proteins found the CSF that indicate what?
Signs of neuronal damage.
Found in sporadic CJD due to rapid neurodegeneration.
Pulvinar sign is an MRI finding in what disease?
variant CJD
Posterior thalamus (putamen) highlighted on T2 MRI
Tonsillar biospy is 100% sensitive and specific in which type of prion disease.
vCJD.
What is the most common type of prion disease?
sporadic CJD accounts for 80%
1/million/year
What is Gerstmann-Straussler-Scheinker syndrome?
Inherited prion disease aka GSS
Autosomal Dominant
Slowly progressive dysarthria and cerebellar ataxia.
Which present first in vCJD neurological or psychiatric symptoms?
Psychiatric - anxiety, paranoia, hallucinations
Later, neurological - ataxia, myoclonus.
What is Schmidt’s syndrome?
Addison’s disease and primary hypothyroidism (Hashimoto’s)
aka. AI polyendocrine syndrome type 2
Initial treatment of phaeochromocytoma
Urgent alpha blockade with phenoxybenzamine.
Can add B-blockade but not alone as it drives up BP due to B2-mediated vasodilation inhibited.
What are the contraindications for the combined pituitary function test?
Ischaemic heart disease
Epilepsy
Untreated hypothyroidism
Test is physiologically stressful not good for underlying disease.
Hypothyroidism impairs GH and cortisol response so unreliable result.
How can a non-functioning pituitary adenoma produce a hyperprolactinaemia?
Adenoma presses on the stalk resulting in pituitary failure. Prevents dopamine reaching the pituitary.
Lack of inhibitory dopamine results in hyperprolactinamia.
All other pituitary hormones are low. None respond in combined pituitary function test.
Causes of bones, stones, moans and groans of hypercalcemia
Bones - bone resorption resulting in pain and fractures. Also osteitis fibrosa cystic
Stones - Ca oxalate renal stones
Groans - constipation and acute pancreatitis
Moans - psychosis and depression
(Also don’t forget polyuric polydipsia)
Brown tumours are associated with what condition?
Hyperparathyroidism
Aka osteitis fibrosa cystica.
Excess osteoclasts activation leads to these pseudo-tumours of fibrotic and cystic bone tissue. Radiolucent on Xray
Which metabolic bone disease is associated with hyperphosphatemia?
Renal osteodystrophy.
Osteoporosis circumscripta found on skull Xray is suggestive of what?
Paget’s disease
Side effects of heparin
Bleeding
Heparin-induced thrombocytopenia - Ab vs. heparin bound platelets
Osteoporosis
Side effects of heparin
Bleeding
Heparin-induced thrombocytopenia - Ab vs. heparin bound platelets
Osteoporosis
Latter are more associated with unfractionated heparin that LMWH.
Treatment pathway for VTE/PE
not involving rivaroxaban
(Thrombolysis only for life-threatening PE or limb threatening DVT)
LMWH + Warfarin
When INR in therapeutic range (2.5) then LMWH is stopped.
Continue warfarin for 3-6m (unless risk of recurrence)
In pregnancy and Ca continue LMWH rather than warfarin.
TEDS for 2 years to prevent postphlebitic syndrome.
Treatment regimen for hyperkalemia
10ml 10% Calcium gluconate
50ml 50% dextrose + 10U of insulin
Nebs salbutamol
Treat underlying cause.
Only treat when K>6.5 or ECG changes present.
In which part of the kidney is Bartter syndrome associated?
Thick ascending limb of the loop of Henle.
hypokalemic metabolic alkalosis.
Which urine measurement can distinguish Bartter and Gitelman syndromes?
Urinary Ca.
Bartter syndrome -> hypercalciuria (renal stones)
Giteman syndrome -> hypocalciuria (and hypomagnesia).
Both give a hypokalemic metabolic alkalosis.
Acute management of anaphylaxis
Elevate legs 100% O2 IM adrenaline 500mcg inhaled bronchodilators IV Hydrocortisone 100mg IV Chlorphenamine 10mg IV fluids
How does the pattern of paralysis compare between Clostridia botulinum poisoning and Guillain-Barre syndrome
Botulinum poisoning has a descending paralysis as it blocks ACh release from peripheral nerves.
In contrast GBS presents with an ascending paralysis.
What toxins do B.cereus produce?
A heat stable emetic toxin that acts as a superAg stimulating cAMP production.
A heat labile diarrhoeal toxin which has a longer incubation time of 18hours.
EPEC diarrhoea presents mainly in which age group
Children - Infantile diarrhoea. P for Paeds.
Slow onset fever + constipation + relative bradycardia + rose spots + splenomegaly.
Enteric fever
Salmonella typhi + paratyphi. Multiples in Peyers patches. Only transmitted between humans.
Where in the world is Yersinia enterocolitis associated most?
Scandinavia
It is a cause of enterocolitis, mesenteric adenitis w/ necrotising granulomas associated reactive arthritis and erythema nodosum.
Vibrio parahaemolyticus key features.
Gram negative comma shaped, oxidase positive.
Ingestion of raw undercooked seafood. Common in Japan and cruising in the Caribbean.
3/7 (self-limiting) diarrhoea
Treat with doxycycline.
Vibrio vulnificus key features
Gram negative comma shaped, oxidase positive.
Cellulitis in shellfish handlers
Fatal septicaemia with D&V in HIV pts.
Treat with doxycycline.
Gram positive bacillus. Aesculin positive.
Associated with GI watery diarrhoea, cramps, headache, fever, little vomiting.
Particularly perinatal infection and immunocompromised patients.
Associated with refrigerated food.
Listeria monocytogenes
Treat with ampicillin. Also can use ceftriaxone and cotrimoxazole.
An HIV positive patient presents with severe diarrhoea. Stool sample reveals oocysts that stain positive with a modified Kinyoun acid fast stain.
Cryptospiridium parvum
It infects the jejunum.
Treat with paromomycin. Nitazoxamide in kids.
Mets to bone in adults
Breast, Prostate, Lungs, Thyroid, Kidneys, Testes
Boners Penetrate Ladies That Kiss Testicles
Mets to bone in children
Neuroblastoma, Wilm’s tumours, Osteosarcoma, Ewing’s, Rhabdosarcoma
Naughty willies only Ellie recalls.
A bone tumour of the axial skeleton that on Xray reveals a lytic lesion with fluffy calcification
Chondrosarcoma
A bone tumour presenting in a 15 year old that histology reveals sheets of small blue round cells that form rosettes. Immunohistochemistry reveals positive CD99 staining, negative ALP staining.
Ewing’s sarcoma
Aka peripheral primary neuroectodermal tumour (PPNET)
A locally aggressive tumour presenting the knee of a 30 year old lady. Histology reveals multinucleate osteoclast-like cells on a background of spindle/ovoid cells.
Giant cell tumour (borderline malignancy)
Gardner syndrome
Familial colorectal polyposis with multiple osteomas (often in skull), epidermoid cysts, thyroid Ca
Phenotypic variant of FAP due to APC mutation.
Ollier’s syndrome
Multiple enchondromas
Benign tumours of cartilage
Maffuci’s syndrome
Multiple enchondromas + haemangiomas.
Where do enchondroma tumours mainly develop?
Hands
Benign tumours of cartilage that are well demarcated and push on bone but do not invade. Can lead to finger fractures.
Cotton wool calcification on Xray
McCune Albright syndrome
Polyostotic fibrous dysplasia + cafe au last spots + precocious puberty (due to endocrine excess)
Due to a GNAS1 mutation that affects GPCR signalling.
Xray appearance of soap bubble osteolysis and shepherd’s crook deformity. Histology with chinese letter appearance.
Fibrous dysplasia
Who should be given CMV -ve blood transfusion?
Pregnant or neonatal transfusions
What type of blood should be given to immunosuppressed patients to reduce risk of transfusion-associated graft-versus-host disease?
Irradiated blood.
Signs of TACO
4 of
- acute respiratory distress
- tachycardia
- raised BP
- acute/worsening pulmonary oedema
- positive fluid balance.
Within 6 hours.
Familial mediterranean fever
A. Reflects genetic abnormality affecting the innate immune system, often in a site-specific manner
B. Single gene mutation involving MEFV and affecting the inflammasome complex, resulting in recurrent episodes of serositis
C. May describe damage resulting from the immune response to ongoing infection
D. Reflects genetic abnormality affecting the adaptive immune system and is often associated with presence of auto-antibodies
E. Single gene mutation involving FOXp3 resulting in abnormality of T reg cells
Single gene mutation involving MEFV and affecting the inflammasome complex, resulting in recurrent episodes of serositis
IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X linked)
A. Reflects genetic abnormality affecting the innate immune system, often in a site-specific manner
B. Single gene mutation involving MEFV and affecting the inflammasome complex, resulting in recurrent episodes of serositis
C. May describe damage resulting from the immune response to ongoing infection
D. Reflects genetic abnormality affecting the adaptive immune system and is often associated with presence of auto-antibodies
E. Single gene mutation involving FOXp3 resulting in abnormality of T reg cells
E. Single gene mutation involving FOXp3 resulting in abnormality of T reg cells
Ankylosing spondylitis
A. Polygenic auto-inflammatory disease. ~30% patients have a mutation of CARD15 which may affect response of myeloid cells to bacteria.
B. Mixed pattern auto-inflammatory / auto-immune disease with >90% heritability that results in inflammation typically involving the sacro-iliac joints and responds to TNF alpha antagonists
C. Polygenic auto-inflammatory disease resulting in a large vessel vasculitis and requiring immediate treatment with high dose corticosteroids
B. Mixed pattern auto-inflammatory / auto-immune disease with >90% heritability that results in inflammation typically involving the sacro-iliac joints and responds to TNF alpha antagonists
Crohn’s disease
A. Polygenic auto-inflammatory disease. ~30% patients have a mutation of CARD15 which may affect response of myeloid cells to bacteria.
B. Mixed pattern auto-inflammatory / auto-immune disease with >90% heritability that results in inflammation typically involving the sacro-iliac joints and responds to TNF alpha antagonists
C. Polygenic auto-inflammatory disease resulting in a large vessel vasculitis and requiring immediate treatment with high dose corticosteroids
A. Polygenic auto-inflammatory disease. ~30% patients have a mutation of CARD15 which may affect response of myeloid cells to bacteria.
Giant cell arteritis
A. Polygenic auto-inflammatory disease. ~30% patients have a mutation of CARD15 which may affect response of myeloid cells to bacteria.
B. Mixed pattern auto-inflammatory / auto-immune disease with >90% heritability that results in inflammation typically involving the sacro-iliac joints and responds to TNF alpha antagonists
C. Polygenic auto-inflammatory disease resulting in a large vessel vasculitis and requiring immediate treatment with high dose corticosteroids
C. Polygenic auto-inflammatory disease resulting in a large vessel vasculitis and requiring immediate treatment with high dose corticosteroids
HLA DR4
A. Tyrosine phosphatase expressed in lymphocytes associated with development of auto-immune disease including rheumatoid arthritis
B. MHC class II molecule that is associated with development of auto-immune disease including rheumatoid arthritis
C. Receptor for CD80/CD86, expressed on T cells, that influences T cell activation and is associated with auto-immune disease including diabetes and thyroid disease
D. Antigen presenting molecule that is strongly associated with development of Anti-GBM antibodies
B. MHC class II molecule that is associated with development of auto-immune disease including rheumatoid arthritis
PTPN22
A. Tyrosine phosphatase expressed in lymphocytes associated with development of auto-immune disease including rheumatoid arthritis
B. MHC class II molecule that is associated with development of auto-immune disease including rheumatoid arthritis
C. Receptor for CD80/CD86, expressed on T cells, that influences T cell activation and is associated with auto-immune disease including diabetes and thyroid disease
D. Antigen presenting molecule that is strongly associated with development of Anti-GBM antibodies
A. Tyrosine phosphatase expressed in lymphocytes associated with development of auto-immune disease including rheumatoid arthritis
HLA DR15
A. Tyrosine phosphatase expressed in lymphocytes associated with development of auto-immune disease including rheumatoid arthritis
B. MHC class II molecule that is associated with development of auto-immune disease including rheumatoid arthritis
C. Receptor for CD80/CD86, expressed on T cells, that influences T cell activation and is associated with auto-immune disease including diabetes and thyroid disease
D. Antigen presenting molecule that is strongly associated with development of Anti-GBM antibodies
D. Antigen presenting molecule that is strongly associated with development of Anti-GBM antibodies
CTLA4
A. Tyrosine phosphatase expressed in lymphocytes associated with development of auto-immune disease including rheumatoid arthritis
B. MHC class II molecule that is associated with development of auto-immune disease including rheumatoid arthritis
C. Receptor for CD80/CD86, expressed on T cells, that influences T cell activation and is associated with auto-immune disease including diabetes and thyroid disease
D. Antigen presenting molecule that is strongly associated with development of Anti-GBM antibodies
C. Receptor for CD80/CD86, expressed on T cells, that influences T cell activation and is associated with auto-immune disease including diabetes and thyroid disease
Central tolerance of T cells
A. T cells that express FoxP3 and CD25 and secrete cytokines IL-10, TGF beta to suppress activation of other T cells
B. Within the thymus cells that bind with low affinity to HLA molecules die by neglect and those that bind with high affinity to HLA molecules are deleted
C. T cells that recognise HLA/peptide complexes on cells that do not express co-stimulatory molecules subsequently fail to respond to stimulation with antigen
D. Cells that bind to polyvalent antigens in the bone marrow are deleted
B. Within the thymus cells that bind with low affinity to HLA molecules die by neglect and those that bind with high affinity to HLA molecules are deleted
T reg cells
A. T cells that express FoxP3 and CD25 and secrete cytokines IL-10, TGF beta to suppress activation of other T cells
B. Within the thymus cells that bind with low affinity to HLA molecules die by neglect and those that bind with high affinity to HLA molecules are deleted
C. T cells that recognise HLA/peptide complexes on cells that do not express co-stimulatory molecules subsequently fail to respond to stimulation with antigen
D. Cells that bind to polyvalent antigens in the bone marrow are deleted
A. T cells that express FoxP3 and CD25 and secrete cytokines IL-10, TGF beta to suppress activation of other T cells
Central tolerance of B cells
A. T cells that express FoxP3 and CD25 and secrete cytokines IL-10, TGF beta to suppress activation of other T cells
B. Within the thymus cells that bind with low affinity to HLA molecules die by neglect and those that bind with high affinity to HLA molecules are deleted
C. T cells that recognise HLA/peptide complexes on cells that do not express co-stimulatory molecules subsequently fail to respond to stimulation with antigen
D. Cells that bind to polyvalent antigens in the bone marrow are deleted
D. Cells that bind to polyvalent antigens in the bone marrow are deleted
T cell anergy
A. T cells that express FoxP3 and CD25 and secrete cytokines IL-10, TGF beta to suppress activation of other T cells
B. Within the thymus cells that bind with low affinity to HLA molecules die by neglect and those that bind with high affinity to HLA molecules are deleted
C. T cells that recognise HLA/peptide complexes on cells that do not express co-stimulatory molecules subsequently fail to respond to stimulation with antigen
D. Cells that bind to polyvalent antigens in the bone marrow are deleted
C. T cells that recognise HLA/peptide complexes on cells that do not express co-stimulatory molecules subsequently fail to respond to stimulation with antigen
3 broad treatment options for Multiple myeloma
1 - conventional chemo - includes alkylating agents
2- auto SCT - treatment of choice for most
3- allo SCT - only suitable in younger pts (
CD associated with plasma cells in myeloma
CD138
Classification system for Oesophagitis
Los Angeles classification
Percentage of symptomatic GORD with Barrett’s
10%
autoAbs in pernicious anaemia
Parietal cell autoab 90%
IF autoAb 60%
linitis plastica + signet ring cells
Gastric adenocarcinoma variants
Which is more common gastric or duodenal ulcers
Duodenal are 4x more common
3 key histological features of a duodenal biopsy in Coeliac
Villous atrophy
Crypt hyperplasia
Intraepithelial lymphocytes
What is a CH50 immunological test?
Functional test for classical complement cascade
What is a AP50 immunological test?
Functional test for alternative complement cascade.
What do absent AP50 and CH50 test results suggest?
Deficiency in final common Complement pathway
C5-9
Which disorders are associated with recurrent meningococcal meningitis?
Complement deficiency - recurrent infection with encapsulated bacteria (Neisseria, HiB, pneumococcus)
Ab deficiency
Neurological - disruption of BBB (occult skull fracture, hydrocephalus)
Which immunological tests indicate active disease in SLE?
Raised anti-dsDNA
Raised ESR
Depleted C3 + C4 (used up as ICs bind to C1q and activate classical complement pathway)
Rituximab
anti-CD20 mAb
Decreases B cells. Used vs. lymphoma and autoimmune disease.
Adalimumab
anti-TNFa mAb
Indications - psoriasis, Crohn’s, RA,
SFx - TB, lymphoms, AI phenomena
What investigations can be used to confirm serum sickness?
Low serum C3 + C4
Specific IgG to neoAg (e.g. penicillin)
Biopsy (skin, kidney) with characteristic features.
Treatment for acute gout
Colchicine and analgesia
How does crystal bifringence compare between gout and pseudogout
gout - negatively birefringent
pseudogout - positively birefringent
A 35 year old woman presents with persistent itchy wheels for the last 2 months. She noticed that when this is at its worst, she also has a fever and feels generally unwell. After an acute attack, she has bruising and post-inflammatory residual pigmentation at the site of the itching.
A. Urticarial vasculitis B. Chronic urticaria C. Allergic asthma D. Idiopathic angioedema E. Panic attack F. Mast cell degranulation G. Coeliac disease H. Extrinsic allergic alveolitis I. Acute urticaria J. C1 inhibitor deficiency K. IgE mediated anaphylaxis
Urticarial vasculitis
A 22 year old woman presents with an intermittently itchy and desquamating skin rash on her abdomen which is unresponsive to antihistamines
A. Allergic bronchopulmonary aspergillosis B. Acute angioedema C. Acute urticaria D. Chronic urticaria E. Anaphylaxis F. Allergic conjunctivitis G. Contact hypersensitivity H. Hereditary angioedema I. Allergic rhinitis J. Allergic asthma
Contact dermatitis
This rash is typical of contact hypersensitivity. The distribution of the rash suggests that the specific agent is nickel, which used to be a component of the studs of jeans and is commonly found in the metal used in belts
Wegener’s granulomatosis
A. Anti-nuclear antibody B. Anti-centromere antibody C. Anti-DNA antibody D. Anti-mitochondrial antibody E. Anti-GAD antibody F. c-ANCA G. Rheumatoid factor H. Coomb's test I. p-ANCA J. Anti-cardiolipin antibody K. Anti-CCP antibody
cANCA
The antiviral which is given to untreated pregnant women with HIV to prevent vertical transmission of the virus during childbirth.
A. Aciclovir triphosphate B.Interferon-b (beta) C.Ribavirin D.Neuraminidase inhibitor E.Zidovudine F.Entecevir G.Oseltamivir H.Aciclovir monophosphate I.Interferon-g (gamma) J.Interferon-α (alpha) K.Foscarnet L.Ganciclovir M.Nevirapine N.Aciclovir O.Cidofovir
Nevirapine
The final metabolite of the antiviral used to treat Herpes Simplex
A. Aciclovir triphosphate B.Interferon-b (beta) C.Ribavirin D.Neuraminidase inhibitor E.Zidovudine F.Entecevir G.Oseltamivir H.Aciclovir monophosphate I.Interferon-g (gamma) J.Interferon-α (alpha) K.Foscarnet L.Ganciclovir M.Nevirapine N.Aciclovir O.Cidofovir
Aciclovir triphosphate
Which option inhibits the action of viral DNA polymerase?
A. Aciclovir monophosphate B.Thymidine C.Guanosine D.Varicella-zoster virus E.Aciclovir diphosphate F.Aciclovir triphosphate GFamciclovir H.Ribavarin I.Influenza J.Cytomegalovirus K.AIDS
Aciclovir triphosphate
Which option is the product of the action of viral tyrosine kinase on aciclovir?
A. Aciclovir monophosphate B.Thymidine C.Guanosine D.Varicella-zoster virus E.Aciclovir diphosphate F.Aciclovir triphosphate GFamciclovir H.Ribavarin I.Influenza J.Cytomegalovirus K.AIDS
Aciclovir monophosphate
Aciclovir diphosphate and triphosphate are the product of cellular tyrosine kinase, whereas aciclovir monophosphate is the product of viral tyrosine kinase
Used for the treatment of severe, resistant herpes infections
A.Ribavarin B.Interferon C.Adefovir D.Ibuprofen E.Aciclovir F.Amantadine G.Citalapram H.Gancyclovir I.Abacavir J.Zidovudine K.Foscarnet L.Doxacyclin M. Loviride
Foscarnet
A nucleoside analogue which inhibits reverse transcriptase
A.Aciclovir B.Efavirenz C.Interferon D.Indinavir E.Human specific immunoglobulin F.Enfuvirtide G.Zidovudine H.Nevirapine I.Ribavarin J. Ganciclovir K.Human normal immunoglobulin L.Zanamivir M.Amantadine
Zidovudine
The drug mechanisms which acts by stopping post-translational cleaving of polyproteins by inhibiting proteases
A.Aciclovir B.Efavirenz C.Interferon D.Indinavir E.Human specific immunoglobulin F.Enfuvirtide G.Zidovudine H.Nevirapine I.Ribavarin J. Ganciclovir K.Human normal immunoglobulin L.Zanamivir M.Amantadine
Indinavir
The drug which can be delivered by inhalation to treat both influenza A and B.
A.Aciclovir B.Efavirenz C.Interferon D.Indinavir E.Human specific immunoglobulin F.Enfuvirtide G.Zidovudine H.Nevirapine I.Ribavarin J. Ganciclovir K.Human normal immunoglobulin L.Zanamivir M.Amantadine
Zanamivir
The drug which works by attenuating or preventing rabies or hepatitis, following a known exposure but before the onset of signs and symptoms.
A.Aciclovir B.Efavirenz C.Interferon D.Indinavir E.Human specific immunoglobulin F.Enfuvirtide G.Zidovudine H.Nevirapine I.Ribavarin J. Ganciclovir K.Human normal immunoglobulin L.Zanamivir M.Amantadine
Human specific Ig
Dry cough, new infiltrates on CXR, dyspnoea and target shaped lesions on the palms. No recent history of herpes.
A. K. pneumoniae B.S. aureus C. C. psittaci D.P. aeuruginosa E.B. pertussis F.L. pneumophila G.C. neoformans H. [None] I M. tuberculosis J.M. pneumoniae K.S. pneumoniae
M. pneumoniae
An 80 year old clown appears at the GP having been discharged from hospital for a complicated bowel resection with a stint in the ITU. He has a cough and fever and is prescribed a macrolide antibiotic because he is penicillin allergic.
A. M tuberculosis B.Chlamydia pneumoniae C.PCP/ P jiroveci D.Chlamydia psittaci E.Anaerobic infection F.MRSA G.S. pneumoniae H.Burkholderia cepacia I.MSSA J.H. influenzae K.M. Catarrhalis L.Legionella pneumophila M.MSSA or MRSA
MSSA
An 18 year old trainee clown is being seen in the cystic fibrosis clinic and is found to be colonised with a particularly persistent organism.
A. M tuberculosis B.Chlamydia pneumoniae C.PCP/ P jiroveci D.Chlamydia psittaci E.Anaerobic infection F.MRSA G.S. pneumoniae H.Burkholderia cepacia I.MSSA J.H. influenzae K.M. Catarrhalis L.Legionella pneumophila M.MSSA or MRSA
Burkholderia cepacia
Alpha-fetoprotein is associated with which liver tumour.
Hepatocellular carcinoma
Cholangiocarcinoma is associated primarily with which cause of cirrhosis?
Primary sclerosing cholangitis
Mets to Liver
Cancer Sometimes Penetrate Benign Liver
Colon, Stomach, Pancreas, Breast, Lung
What is the threshold size for micro to macronodular?
3mm
Spotty necrosis on hepatic histology
Occurs in acute hepatitis due to diffuse lobular hepatocyte injury
Interface hepatitis with piecemeal necrosis
Occurs in chronic hepatitis along with portal and hepatocyte inflammation
Mallory bodies
Hyaline inclusions found in hepatocytes as a result of alcohol hepatitis and Wilson’s disease.
AutoAbs associated with AI hepatitis
Type 1: ANA, Anti-SMA, anti-actin, anti-soluble liver Ag
Type 2: anti-LKM Ig
PBC or PSC?
More common in women
PBC
PBC or PSC?
Associated with UC
PSC
PBC or PSC?
Histology shows bile duct loss with granulomas
PBC
PBC or PSC?
USS shows bile duct dilatation
PSC
PBC or PSC?
> 90% associated with anti-mitochondrial Ab
PBC
PBC or PSC?
Can be treated in the early phase with ursodeoxycholic acid
PBC
PBC or PSC?
ERPC shows beading dilatation of the bile ducts
PSC
due to multifocal strictures.
Prussian blue stain for which genetic cause of cirrhosis?
Haemochromatosis
Shows Fe deposits
Periodic acid Schiff stain for which genetic cause of cirrhosis?
alpha-1 antitrypsin deficiency
Rhodamine stain for which genetic cause of cirrhosis?
Wilson’s disease
Shows Cu
Treatment for Wilson’s
Penicillamine
Recurrent infection with high neutrophil count on FBC but no abscess formation
A IFN gamma receptor deficiency
B Leukocyte adhesion deficiency
C Chronic granulomatous disease
D Kostmann syndrome
Leukocyte adhesion deficiency.
Failure of neutrophils to transmigrate into tissue via binding to endothelial ligands to deal with infections.
Recurrent infection with hepatosplenomegaly and abnormal dihydrorhodamine test
A IFN gamma receptor deficiency
B Leukocyte adhesion deficiency
C Chronic granulomatous disease
D Kostmann syndrome
Chronic granulomatous disease
Failure of oxidative killing due to NADPH oxidase deficiency.
Recurrent infections with no neutrophils on FBC
A IFN gamma receptor deficiency
B Leukocyte adhesion deficiency
C Chronic granulomatous disease
D Kostmann syndrome
Kostmann syndrome
Severe congenital neutropenia
Infection with atypical mycobacterium. Normal FBC.
A IFN gamma receptor deficiency
B Leukocyte adhesion deficiency
C Chronic granulomatous disease
D Kostmann syndrome
IFN gamma receptor deficiency.
Severe recurrent infections from 3 months, CD4 + CD8 T cells absent, B cells present. IgM present, IgA and IgG absent.
A Bare lymphocyte syndrome type II
B X-linked SCID
C DiGeorge’s syndrome
D IFN gamma receptor deficiency
X linked SCID
Recurrent infection in childhood, abnormal facial features, congenital heart disease, normal B cells, low T cells, low IgA and IgG.
A Bare lymphocyte syndrome type II
B X-linked SCID
C DiGeorge’s syndrome
D IFN gamma receptor deficiency
DiGeorge syndrome
Catch-22
14 month old baby with 2 recent serious bacterial infections. T cells present but only CD8+ population. B cells present. IgM present but IgG absent.
A Bare lymphocyte syndrome type II
B X-linked SCID
C DiGeorge’s syndrome
D IFN gamma receptor deficiency
Bare lymphocyte syndrome type II
Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE.
A IgA deficiency
B CVID
C Bruton’s X linked agammaglobulinaemia
D X linked Hyper IgM syndrome
Common variable immune deficiency
Recurrent bacterial infection in a child, episode of pneumocystis pneumonia, high IgM, absent IgA and IgG
A IgA deficiency
B CVID
C Bruton’s X linked agammaglobulinaemia
D X linked Hyper IgM syndrome
X linked hyper IgM syndrome
CD40L mutation
1 year old boy. Recurrent bacterial infections. CD4 and CD8 cells present. B cells absent, IgA, IgG and IgM absent.
A IgA deficiency
B CVID
C Bruton’s X linked agammaglobulinaemia
D X linked Hyper IgM syndrome
Bruton’s X linked agammaglobulinaemia.
Tyrosine kinase defect resulting in the failure to produce mature B cells and a complete absence of Abs.
Recurrent respiratory tract infections, absent IgA, normal IgG and IgM.
A IgA deficiency
B CVID
C Bruton’s X linked agammaglobulinaemia
D X linked Hyper IgM syndrome
IgA deficiency.
Membranoproliferative nephritis and bacterial infections.
A C9 deficiency
B C3 deficiency with presence of a nephritic factor
C MBL deficiency
D C1q deficiency
C3 with presence of a nephritic factor.
Meningococcus meningitis with family history of sibling dying of the same condition aged 6.
A C9 deficiency
B C3 deficiency with presence of a nephritic factor
C MBL deficiency
D C1q deficiency
C9 deficiency
Severe childhood onset SLE with normal levels of C3 and C4
A C9 deficiency
B C3 deficiency with presence of a nephritic factor
C MBL deficiency
D C1q deficiency
C1q deficiency
Recurrent infections when receiving chemotherapy but previously well.
A C9 deficiency
B C3 deficiency with presence of a nephritic factor
C MBL deficiency
D C1q deficiency
MBL deficiency
HMB synthase deficiency results in which porphyria?
Acute intermittent porphyria
Coproporphyrinogen oxidase deficiency results in which porphyria?
Hereditary coproporphyria
Protoporphyrinogen oxidase deficiency results in which porphyria?
Variegate porphyria
Uroporphyrinogen III synthase deficiency results in which porphyria?
Congenital erythropoietic porphyria
Uroporphyrinogen decarboxylase deficiency results in which porphyria?
Porphyria cutanea tarda
Ferrochetolase deficiency results in which porphyria?
Erythropoietic protoporphyria
Accumulation of which toxic haem precursor results in acute neurovisceral attacks in porphyria?
5-ALA
Accumulation of which toxic haem precursor results in skin lesions in porphyria?
Activated porphyrins; oxidised from porphyrinogens.
PBG synthase deficiency results in which porphyria?
ALA dehydratase / plumboporphyria
Which type of porphyria will result in a rise in ALA but NOT PBG
ALA dehydratase / plumboporphyria.
Due to PBG sythase deficiency which produces PBG. Hence accumulation of upstream ALA.
What are the skin changes associated with acute intermittent porphyria?
None.
AIP is due to a HMB synthase deficiency. ALA accumulation results in acute neurovisceral attacks. However, no downstream porphyrinogen means no skin lesions.
Which types of porphyria result in acute neurovisceral attacks and skin lesions?
Hereditary coproporphyria and variegate porphyria.
Accumulation of toxic metabolites that allosterically inhibit HMB synthase resulting in acute neurovisceral attack as well as being porphyrinogens that produce skin lesions.
Which porphyria is associated with photosensitivity not blistering and skin fragility?
What is the diagnostic test?
Erythropoietic protoporphyria.
Measure RBC protoporphyrin.
What is the first line test for an acute attack of porphyria?
Urine PBG (porphobiliogen)
Which factors limit the use of serum creatinine as a marker of GFR?
A It's influenced by intake of fat B It's lower in the black population C It is related to muscle mass D It is reabsorbed in the renal tubules E All of the above
It is related to muscle mass.
It is influenced by protein not fat intake. It is higher in the black population relating to greater muscle mass. It is actively secreted by the renal tubules into urine.
A 50 year old, known alcoholic, presents generally unwell, seemingly intoxicated, with acute kidney injury. Urine microscopy reveals calcium oxalate crystals. What diagnosis do you suspect?
Ethylene glycol poisonong.
Metabolites cause a severe acidosis that causes oxalate to precipitate.
Kimmelstiel-Wilson nodules in the mesangial matrix of the renal glomerulus is due to which underlying condition?
Diabetes.
Results in a nephrotic syndrome.
A liver enzyme raised after a myocardial infarction
A. Gamma glutamyl transpeptidase B. Activated partial thromboplastin time C. Direct bilirubin D. Aspartate transaminase E. Total bilirubin F. Alanine transaminase G. Prothrombin time H. Alkaline phosphatase I. Albumin J. Gamma globulin
AST
A 30-year-old market trader presents with tiredness and jaundice, and further history reveals he suffered from a chest infection one week previously. On examination mild splenomegaly is noted, and blood tests show reticulocytosis, hyperbilirubinaemia, and spherocytosis.
A. Osmotic fragility test B. Anti-gastric parietal cell antibodies C. Anti-GAD D. ANA E. Anti-smooth muscle antibody F. p-ANCA G. Anti-scl70 H. Anti-mitochondrial antibody I. Anti-DsDNA J. Anti-acetylcholine receptor antibody K. Anti-endomysial antibodies L. c-ANCA M. Ham's test
Osmotic fragility test
Spherocytosis: Osmotic fragility test.
A 56-year-old obese woman presents with polyuria and polydipsia. She complains of tiredness and depression. Her fasting glucose is 4.9mmol/L and her OGTT is 4.5mmol/L. She has a corrected calcium of 2.4mmol/L and a PTH of 7.1mmol/L.
A. Diabetes mellitus type 1 B. Crohn’s disease C. Lung cancer D. Primary hyperparathyroidism E. Vitamin D deficiency F. Impaired glucose tolerance G. Psychogenic polydipsia H. Diabetes mellitus type 2 I. Gestational diabetes J. Secondary hyperthyroidism K. Impaired fasting glucose L. Sarcoidosis M. Hypocalcaemia N. Malignancy O. Tuberculosis
Psychogenic polydipsia
A 58-year-old Afro-Caribbean gentleman presents with polyuria, polydipsia and weight loss. He has an oral glucose tolerance test of 10.1mmol/L. His corrected calcium is 2.5mmol/L and his PTH is 7.0pmol/L.
A. Diabetes mellitus type 1 B. Crohn’s disease C. Lung cancer D. Primary hyperparathyroidism E. Vitamin D deficiency F. Impaired glucose tolerance G. Psychogenic polydipsia H. Diabetes mellitus type 2 I. Gestational diabetes J. Secondary hyperthyroidism K. Impaired fasting glucose L. Sarcoidosis M. Hypocalcaemia N. Malignancy O. Tuberculosis
Impaired glucose tolerance
During pregnancy A Less iron is required B There is an increase in haemoglobin concentration C The platelet count falls D The neutrophil count falls
C
Mild anaemia
- Red cell mass rises (120 -130%)
- Plasma volume rises (150%)
Neutrophilia
Thrombocytopenia
- increased platelet size
Peak and trough levels of this drug should be taken
A. Ethosuximide B. Heparin - unfractionated C. Phenobarbitone D. Heparin - Low molecular weight E. Gentamicin F. Aspirin G. Carbamazepine H. Lithium I. Warfarin J. Clonazepam K. Ciclosporin L. Digoxin M. Phenytoin N. Theophylline
Gentamicin
Symptoms of under-treatment and toxicity may be similar
A. Ethosuximide B. Heparin - unfractionated C. Phenobarbitone D. Heparin - Low molecular weight E. Gentamicin F. Aspirin G. Carbamazepine H. Lithium I. Warfarin J. Clonazepam K. Ciclosporin L. Digoxin M. Phenytoin N. Theophylline
Digoxin
Decreased excretion, increased plasma concentration and increased risk of toxicity may occur when this taken in conjunction with thiazide diuretics
A. Ethosuximide B. Heparin - unfractionated C. Phenobarbitone D. Heparin - Low molecular weight E. Gentamicin F. Aspirin G. Carbamazepine H. Lithium I. Warfarin J. Clonazepam K. Ciclosporin L. Digoxin M. Phenytoin N. Theophylline
Lithium
A man was found collapsed on the floor of his room and his breathing was found to be severely depressed. A urine test was found to be positive for 6-MAM.
A. Ethanol B. Organophosphate C. Paracetamol D. Cannabis E. Benzodiazepines F. Heroin G. Ecstasy H. Methanol I. Police brutality J. Methadone K. Aspirin L. Amphetamines M. Carbon monoxide N. Cocaine O. Cyanide P. Strychnine
Heroin
A 30-year-old farmer presents to casualty complaining of diarrhoea and painful mouth ulcers. On questioning he admitted accidentally ingesting liquid paraquat
A. Symptomatic and Supportive treatment B. Glucagon C. Atropine D. Hyperbaric oxygen E. Activated charcoal F. Gastric lavage G. N-acetylcysteine H. Desferrioxamine I. Haemodialysis J. Dicobalt edentate K. Naloxone
Activated charcoal
A 15-year-old girl presents with sweats and hyperventilation indicative of a severe metabolic acidosis; after taking a large number of salicylate tablets
A. Symptomatic and Supportive treatment B. Glucagon C. Atropine D. Hyperbaric oxygen E. Activated charcoal F. Gastric lavage G. N-acetylcysteine H. Desferrioxamine I. Haemodialysis J. Dicobalt edentate K. Naloxone
Haemodialysis
A 26-year-old woman collapses after a massive overdose of atenolol. She remains in cardogenic shock despite initial treatment with IV atropine
A. Symptomatic and Supportive treatment B. Glucagon C. Atropine D. Hyperbaric oxygen E. Activated charcoal F. Gastric lavage G. N-acetylcysteine H. Desferrioxamine I. Haemodialysis J. Dicobalt edentate K. Naloxone
Glucagon
A 25 year old male is admitted with hyperventilation. He is sweating and appears nauseous. He says that he has ringing in his ears. Blood gases show that he has mixed acid-base disturbance
A. Tricyclic antidepressants B. Ecstasy C. Naloxone D. Carbon Monoxide E. Organophosphates F. Desferrioxamine G. Acetylcysteine H. Paracetamol I. Salicylates J. Methanol K. Lithium
Salicylates
Which of the above techniques can be used to test for all classes of drugs of abuse (DOA)?
A. Liver sample B. Barbituates C. Paracetamol D. Blood sample E. Immunoassay F. Benzodiazepines G. Stool sample H. Thin layer chromotography I. Liquid chromotography J. Urine sample K. Drugs of abuse (DOA)
Immunoassay
What sample is required for use with gas chromatography mass spectroscopy? A. Liver sample B. Barbituates C. Paracetamol D. Blood sample E. Immunoassay F. Benzodiazepines G. Stool sample H. Thin layer chromotography I. Liquid chromotography J. Urine sample K. Drugs of abuse (DOA)
Blood sample
Which of the above techniques can be used to test for benzodiazepines and various antipsychotic drugs? A. Liver sample B. Barbituates C. Paracetamol D. Blood sample E. Immunoassay F. Benzodiazepines G. Stool sample H. Thin layer chromotography I. Liquid chromotography J. Urine sample K. Drugs of abuse (DOA)
Liquid chromatography
Most common organism for septic arthritis
Staph aureus - 46%
In which joint does 50% of septic arthritis occur?
Knee
Abx for septic arthiritis?
IV cephalosporin or flucloxacillin
If MRSA then vancomycin
How long for is Abx treatment post osteomyelitis?
3 months of which the first 6 weeks IV
During pregnancy A Less iron is required B There is an increase in haemoglobin concentration C The platelet count falls D The neutrophil count falls
C
Trousseau’s syndrome
Recurrent superficial thrombophlebitis.
Paraneoplastic syndrome due to hypercoagulability. Associated with gliomas as well as pancreatic and lung adenocarcinomas
Ca19.9 tumour marker
Pancreatic cancer
A 76 year woman with known congestive cardiac failure presenting with digoxin toxicity
A. Renal tubular acidosis B. Rhabdomyolysis C. Diabetic ketoacidosis D. Haemorrhage E. Addison's disease F. SIADH G. Diuretic use H. Alcohol abuse I. Cushing’s syndrome J. Artifactual K. Diarrhoea L. Vomiting M. Acute Renal Failure
Diuretic use
A 68 year old woman, K+ = 3.0 mmol/L with a history of congestive cardiac failure complains of general discomfort.
A. Insulin administration B. Cushing's disease C. Artefactual D. Addison's disease E. Burns F. Rhabdomyalysis G. Renal tubular disease H. Hyperkalaemia I. Hypokalaemia J. Diuretic use K. Laxative abuse
Diuretic use
An ECG of a 27 year old man in casualty shows peaked T waves in leads V2 and V3.
A. Insulin administration B. Cushing's disease C. Artefactual D. Addison's disease E. Burns F. Rhabdomyalysis G. Renal tubular disease H. Hyperkalaemia I. Hypokalaemia J. Diuretic use K. Laxative abuse
Hyperkalemia
A 2 month old infant vomits profusely, pH = 7.57, H+= 26 nmol/L, HCO3= 50 mmol/L
A. Insulin administration B. Cushing's disease C. Artefactual D. Addison's disease E. Burns F. Rhabdomyalysis G. Renal tubular disease H. Hyperkalaemia I. Hypokalaemia J. Diuretic use K. Laxative abuse
Hypokalemia
A 47 year old woman complains of tiredness, muscle weakness, mood swings and loss of appetite over several months. K+= 5.9 mmol/L
A. Insulin administration B. Cushing's disease C. Artefactual D. Addison's disease E. Burns F. Rhabdomyalysis G. Renal tubular disease H. Hyperkalaemia I. Hypokalaemia J. Diuretic use K. Laxative abuse
Addison’s disease
A 47 year old female presents to her GP with severe loin pain. On further questioning the patient complains of a 6 month history of recurrent fevers and vomiting with more recent generalised weakness and pain in some of her joints. A subsequent blood test shows hypokalaemia.
A. Delayed separation B. Diuretics C. Renal tubular acidosis D. Vomiting E. Fistula F. Addison's disease G. Drip arm sample H. Diarrhoea I. Corticosteroid use J. Haemolysis K. Renal failure
Renal tubular acidosis
A 45 year old female with long-term poorly controlled asthma presents to her GP complaining of weight gain and excessive sweating. A recent routine abdominal CT scan revealed atrophy of the adrenal glands.
A. Pseudo-Cushing’s Syndrome B. Adrenal Carcinoma C. Aldosterone Secreting Adrenal Adenoma D. Multiple Endocrine Neoplasia Syndrome E. Nelson’s Syndrome F. Iatrogenic Cushing’s Syndrome G. Phaeochromocytoma H. Addison’s Disease I. Schmidt’s Syndrome J. Ectopic ACTH Secretion K. Addisonian Crisis L. Congenital Adrenal Hyperplasia M. Cushing’s Syndrome N. Cushing’s Disease
Iatrogenic Cushing’s syndrome.
Due to the steroids for the poorly controlled asthma.
A 65 year old female presents to her new GP 5 years after an operation on her abdomen. She cannot remember the details of the operation but does remember that she was suffering from severe Cushing’s Disease at the time. She now notes a progressive “tanning” of the skin
A. Pseudo-Cushing’s Syndrome B. Adrenal Carcinoma C. Aldosterone Secreting Adrenal Adenoma D. Multiple Endocrine Neoplasia Syndrome E. Nelson’s Syndrome F. Iatrogenic Cushing’s Syndrome G. Phaeochromocytoma H. Addison’s Disease I. Schmidt’s Syndrome J. Ectopic ACTH Secretion K. Addisonian Crisis L. Congenital Adrenal Hyperplasia M. Cushing’s Syndrome N. Cushing’s Disease
Nelson syndrome
This the rapid enlargement of the pituitary gland that occurs post bilateral adrenalectomy. Associated with muscle weakness and hyper pigmentation.
Schmidt’s syndrome
AI polyendocrine syndrome type II
Addison’s + T1DM + Hashimotos
A 57 year old Type 1 diabetic woman presents with weight loss, weakness and depression. Examination reveals postural hypotension, hyperpigmentation in the palmar creases and widespread patchy vitiligo.
.
A 27 year old woman presents with a three month history of weight gain, deepening voice and secondary amenorrhoea. Examination reveals clitoromegaly, acne, greasy skin and hirsutism. Serum cortisol is grossly elevated and ACTH levels are undetectable.
A. Conn's syndrome B. Iatrogenic Cushing's syndrome C. Carney's syndrome D. Adrenal adenoma E. Cushing's disease F. Addison's disease G. Adrenal carcinoma H. Ectopic ACTH secretion I. Pseudo-Cushing's syndrome J. Iatrogenic Addison's disease K. Phaeochromocytoma L. Congenital adrenal hyperplasia
Adrenal carcinoma
Carney syndrome
AutoD condition describing combination of myxomas of the heart or skin, hyper pigmentation and endocrine overactivity (mainly Cushings)
The commonest enzyme deficiency seen in CAH
A. Reduced Cortisol B. Hyponatreamia with Hyperkalaemia C. 17α-Hydroxylase deficiency D. 11β-Hydroxylase deficiency E. Aldosterone F. Hyponatreamia with Hypokalaemia G. Hypernatreamia with Hypokalaemia H. Normal ACTH levels I. Chromosome 6 J. Raised ACTH K. 21-Hydroxylase Deficiency L. 17-Hydroxyprogesterone M. Hypernatreamia with Hyperkalaemia N. Deoxycortisol O. Pregnanetriol
21-Hydroxylase Deficiency
CYP12 deficiency leads to a mineralocorticoid deficiency (aldosterone) and sometimes a partial cortisol deficiency. Low cortisol negatively feedback to produce high ACTH that stimulates steroid-producing cell hyperplasia.
Levels of this steroid are raised in the serum of CAH patients
A. Reduced Cortisol B. Hyponatreamia with Hyperkalaemia C. 17α-Hydroxylase deficiency D. 11β-Hydroxylase deficiency E. Aldosterone F. Hyponatreamia with Hypokalaemia G. Hypernatreamia with Hypokalaemia H. Normal ACTH levels I. Chromosome 6 J. Raised ACTH K. 21-Hydroxylase Deficiency L. 17-Hydroxyprogesterone M. Hypernatreamia with Hyperkalaemia N. Deoxycortisol O. Pregnanetriol
17-Hydroxyprogesterone
Increased levels are seen in the urine of CAH patients
A. Reduced Cortisol B. Hyponatreamia with Hyperkalaemia C. 17α-Hydroxylase deficiency D. 11β-Hydroxylase deficiency E. Aldosterone F. Hyponatreamia with Hypokalaemia G. Hypernatreamia with Hypokalaemia H. Normal ACTH levels I. Chromosome 6 J. Raised ACTH K. 21-Hydroxylase Deficiency L. 17-Hydroxyprogesterone M. Hypernatreamia with Hyperkalaemia N. Deoxycortisol O. Pregnanetriol
Pregnanetriol
The sodium and potassium pattern seen in CYP21 deficiency.
A. Reduced Cortisol B. Hyponatreamia with Hyperkalaemia C. 17α-Hydroxylase deficiency D. 11β-Hydroxylase deficiency E. Aldosterone F. Hyponatreamia with Hypokalaemia G. Hypernatreamia with Hypokalaemia H. Normal ACTH levels I. Chromosome 6 J. Raised ACTH K. 21-Hydroxylase Deficiency L. 17-Hydroxyprogesterone M. Hypernatreamia with Hyperkalaemia N. Deoxycortisol O. Pregnanetriol
Hyponatreamia with Hyperkalaemia
Due to the hypoaldosteronism.
A doctor suspecting his patient is suffering from CAH has just received some results that proves otherwise
A. Reduced Cortisol B. Hyponatreamia with Hyperkalaemia C. 17α-Hydroxylase deficiency D. 11β-Hydroxylase deficiency E. Aldosterone F. Hyponatreamia with Hypokalaemia G. Hypernatreamia with Hypokalaemia H. Normal ACTH levels I. Chromosome 6 J. Raised ACTH K. 21-Hydroxylase Deficiency L. 17-Hydroxyprogesterone M. Hypernatreamia with Hyperkalaemia N. Deoxycortisol O. Pregnanetriol
Normal ACTH levels
Reduced cortisol will feedback to give high ACTH levels in CAH.
A 54 year old businessman comes to you with a wound in his foot that has failed to heal over a few weeks. You notice various other minor lesions on both feet and he tells you that he has recently ‘lost feeling’ in his legs. His BMI is 31 and his blood pressure is 145/95.
A. Lipid profile B. Cortisol measurement C. Ovarian ultrasound D. Chest X-ray E. BMI quantification F. Thyroid autoantibodies G. Genetic testing H. Urine dipstick I. Exercise tolerance test
Urine dipstick
An 11 year old boy is taken to the GP by his parents after complaining that “his wee-wee is a funny colour”. The parents reveal that their son hasn’t been too well lately, “He’s been very tired, feeling sick and has had temperature the last few days. We thought he’s just picked up a virus because he had a sore throat about 10days ago, but now that his urine has gone this smoky colour and his eyes are puffy, we thought we’d bring him in…”
A. Alport's disease B. Henoch-Schonlein purpura C. Wilms tumour D. Bacterial endocarditis E. SLE F. Goodpasture's G. Acute diffuse proliferative glomerulonephritis H. Hypertensive renal damage I. Diabetic nephropathy J. Wegener's granulomatosis K. Polycystic kidney disease L. Cannonball metastases M. Clear cell renal carcinoma
Acute diffuse proliferative glomerulonephritis
A 62-year old man presents with lethargy and tiredness. He tells you that he is ‘on painkillers for back pain after a fall at work 6 weeks ago’. On examination he is pale. Blood tests reveal urea 39.2 mmol/L (normal 1.7-8.3) and creatinine 1158 μmol/L (normal 62-106). His records show that he had a creatinine of 90 μmol/L 3 months ago.
A. Thin membrane nephropathy B. Acute interstitial nephritis C. Nephrotic syndrome D. Hyperkalemia E. Ureteric stones F. Hypokalemia G. IgA nephropathy H. Urethral stones I. Chronic kidney disease J. Renal acidosis
Acute interstitial nephritis
SLE: SOAP BRAIN MD symptoms
Need 4/11 of:
Serositis
Oral ulcers
Arthritis
Photosensitivity
Blood disorders - AIHA, ITP, leucopenia Renal involvement ANA +ve Immune phenomena - dsDNA, anti-Sm Neuro symptoms - psych
Malar rash
Discoid rash
Compare the lung manifestations of limited and diffuse scleroderma.
Limited scleroderma is associated with lung HTN.
Diffuse scleroderma is associated with lung fibrosis (although this can develop lung HTN).
Uveoparotid fever is associated with which underlying condition.
Sarcoidosis
= bilateral uveitis + parotid enlargement +/- facial nerve palsy
Name the cANCA associated vasculitis
Wegener’s granulomatosis
aka Granulomatosis with polyangitis
anti-PR3 +ve
Triad of findings in the anti-PR3 +ve vasculitis
anti-PR3 +ve = Wegener’s
1) Upper resp tract - saddle nose, epistaxis, siusitis
2) Lung - cavitation + haemorrhage.
3) Kidney - crescentic GN
Asthma is associated with which vasculitis?
Churg-Strauss
aka eosinophilic granulomatosis with polyangitis
pANCA anti-MPO
HBV infection is associated with which vasculitis?
Polyarteritis nodosa
Medium vessel vasculitis.
Felty syndrome
RA + splenomegaly + neutropenia
60 year old white women.
TTP classical pentad of clinical features
1 MAHA 2 Thrombocytopenia 3 Fever 4 Neurological abnormalities 5. Renal impairment
All 5 not always present
Due to ADAMTS13 Deficiency which cleaves vWF. Deficiency leads to platelet thrombi formation.
Hurthle cell
Eosinophilic thyroid cell associated with Hashimoto’s and also follicular thyroid cancer
Histology showing orphan annie eye cells and psammoma bodies.
Papillary thyroid Carcinoma
Stony hard thyroid.
Riedel’s thyroiditis
Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
A) Basiliximab B) Abatacept C) Rituximab D) Natalizumab E) Tocilizumab
Basiliximab - anti-IL-2R
Inhibits T cell activation and is effective in RA
A) Basiliximab B) Abatacept C) Rituximab D) Natalizumab E) Tocilizumab
Abatacept - CTLA4-Ig fusion protein
Depletes B cells and is effective in treatment of B cell lymphomas and RA
A) Basiliximab B) Abatacept C) Rituximab D) Natalizumab E) Tocilizumab
Rituximab - anti-CD20
Inhibits T cell migration by may only be used in highly active remitting/relapsing MS
A) Basiliximab B) Abatacept C) Rituximab D) Natalizumab E) Tocilizumab
Natalizumab - anti - alpha4 integrin
Inhibits function of lymphoid and myeloid cels and is used in the management of RA
A) Basiliximab B) Abatacept C) Rituximab D) Natalizumab E) Tocilizumab
Tocilizumab - anti - IL 6R
A 68 year old woman on the Geriatric ward is found to have the following blood results:
Na 138 (134-145) K 3.0 (3.5-5.0) Urea 4.2 (3.0-7.0) Creatinine 74 (60-120) pH 7.31 HCO3 28 (22-28)
A) Spurious sample B) Anorexia C) Diarrhoea D) Renal tubular acidosis E) Insulin overdose F) Bartter syndrome G) Frusemide H) Renal failure I) ACEi
Renal tubular acidosis
This occurs when there is a defect in H+ ion secretion into the renal tubules. Potassium secretion into the renal tubules therefore increases to balance Na reabsorption. This results in hypokalemia with acidosis.
Renal tubular acidosis is classified by according to the location of the defect:
type 1 - distal tubule
type 2 - proximal tubule
type 3 - both distal and proximal tubules
Type 4 results from a defect in the the adrenal glands and in included in the classification as it results in a metabolic acidosis with hyperkalemia.
Blood results: AST 1259 (3-35) ALT 1563 (3-35) GGT 73 (11-51) ALP 46 (35-51) Total bilirubin 15.2 (3-17) Conjugated bilirubin 4.2 (1.0-5.1)
A Alcohol abuse B Gilbert's syndrome C Gallstones D Dublin-Johnson syndrome E NAFLD F Crigler-Najjar syndrome G Alcohol liver disease H Paracetamol poisoning I HCC
NAFLD
NAFLD is due to steatosis, but where the underling cause is not due to alcohol. In such circumstances, etiological factors may include obesity, DM, parenteral feeding and inherited metabolic disorders (glycogen storage disease type 1).
NAFLD may present with RUQ pain or be asympomatic. LFTs will reveal raised AST and ALT (AST: ALT
Blood results: AST 2321 (3-35) ALT 2562 (3-35) GGT 62 (11-51) ALP 182 (35-51) Total bilirubin 14 (3-17) Conjugated bilirubin 3.4 (1.0-5.1)
Paracetamol poisoning
This is a common cause of acute liver failure. The clinical features of acute liver failure reflect the diminished synthetic and metabolic functioning of the liver. Characteristics include reduced blood sugar level, metabolic acidosis, increased tendency to bleed and hepatic encephalopathy.
Biochemical tests will reveal AST and ALT levels >1000 IU/L. AST and ALT levels will be greater than GGT and ALP levels, reflecting the hepatic rather than obstructive picture of the pathology.
Blood results: Ca 1.8 (2.2-2.6) PTH 9.6 (0.8-8.5) ALP 89 (30-150) PO4 1.5 (0.8-1.2) Vit D 76 (60-105)
A Primary hyperPTH B Secondary hyperPTH C Tertiary hyperPTH D PseudohypoPTH E Primary hypoPTH F Osteoporosis G Osteomalacia H Paget's disease I Familial benign hypercalcemia
Familial benign hypercalcemia
This is a genetic condition leading to raised blood calcium levels. The disease results from a mutation in the Ca sensing receptor located on the PTH glands and the kidneys. This receptor defect therefore leads to underestimationof calcium, causing increased PTH production, despite raised Ca. It is important to distinguish these patients from hyperPTH patients as the management differs.
Receptor failure in the kidneys results in a hypocalcuric state by reducing Ca excretion.
A 5 year old girl who is a known CF sufferer is noted by her mother to have developed poor coordination of her hands and on examination her reflexes are absent. Blood tests reveal an anaemia.
Which is deficient?
A Vitamin A B Vit B1 C Vit B2 D Vit B6 E Vit B12 F Vit C G Vit D H Vit E I Vit K
Vitamin E
Vitamin E (tocopherol) is an important anti-oxidant which acts to scavenge free radicalism the blood stream. Deficiency leads to haemolytic anaemia as RBCs encounter oxidative damage and are consequently broken down by the spleen. Hence the anaemia. Spin-cerebellar neuropathy is also a manifestation, which is characterised by ataxia and areflexia.
It has also been suggested to increase the risk of ischaemic heart disease in later life, as LDLs become oxidised perpetuating the atherosclerotic process.
As a fat-soluble vitamin it is act danger of deficiency in pancreatic insufficiency associated with CF.
An 18 month old girl is seen by her GP. Her mother is concerned by the child’s brittle hair and inability to walk. The mother reports her daughter had had 2 previous convulsions.
A PKU B Peroxisomal disorders C Maple syrup urine disease D MCADD E Von Gierke's disease F Fabry's disease G Urea cycle disorder H Homocystinuria I Galactosemia
Homocystinuria
An amino acid disorder in which there is a deficency in the enzyme cystathionine sythnetase. This metabolic disorder presents in childhood with characteristic features such as very fair skin and brittle hair. The condition will usually lead to developmental delay or progressive LDs. Convulsions, skeletal abnormalities and thrombotic episodes have also been reported. Management options include supplementing the diet with vitamin B6 or maintaining the child on a low-methionine diet.
A fair headed 8 month old baby, born in Syria, is seen together with his mother in the paediatric OPD. He is found to have developmental delay and a musty smell is being given off by the baby.
A PKU B Peroxisomal disorders C Maple syrup urine disease D MCADD E Von Gierke's disease F Fabry's disease G Urea cycle disorder H Homocystinuria I Galactosemia
PKU
Another amino acid disorder. Children classical lack the enzyme phenylalanine hydroxyls, but other co-factors may be aberrant. Since the 1960s, PKU has been diagnosed at birth using the Guthrie test but in some countries the test may not be available. The child will be fair haired and present with developmental delay between 6-12 months of age. Later in life the child’s IQ will be severely impaired. Eczema and seizures have also been implicated in the disease process.
A 5 month old boy is seen by the community paediatrician due to concerns of developmental delay. O/E dysmorphic features are noted, as well as a ‘cherry-red spot’ on the baby’s trunk.
A PKU B Peroxisomal disorders C Maple syrup urine disease D MCADD E Von Gierke's disease F Fabry's disease G Urea cycle disorder H Homocystinuria I Galactosemia
Fabry’s disease
A lysosomal storage disorder in which there is a deficiency in a-galactosidase. Presentation is almost always a child with developmental delay together with dysmorphia. Other findings may include movement abnormalities, seizures, deafness and/or blindness. O/E hepatosplenomegaly, pulmonary and cardiac problems may be noted.
The pathognomonic features of lysosomal storage disorders is the presence of a ‘cherry red spot’.
A 14 day old girl of Jewish descent present with lethargy poor feeding and hypotonia. The paediatrician examining also notices excessively sweaty feet.
A PKU B Peroxisomal disorders C Maple syrup urine disease D MCADD E Von Gierke's disease F Fabry's disease G Urea cycle disorder H Homocystinuria I Galactosemia
Maple Syrup urine disease
An organic aciduria, a group of disorders that represent impaired metabolism of leucine, isoleucine and valine. As a result toxic compounds accumulate causing toxic encephalopathy which manifests as lethargy, poor feeding, hypnotic and/or seizures. Characteristic of maple syrup urine disease are a sweet odour and sweaty feet.
The gold standard diagnostic test is gas chromatography with mass spectrometry. Management involves the avoidance of the causative ami
A 9 month old baby is seen in A&E as her mother has reported that she has become floppy. The baby is found to be hypoglycaemic and O/E enlarged liver and kidneys are noted.
Inborn error of metabolism:
A PKU B Peroxisomal disorders C Maple syrup urine disease D MCADD E Von Gierke's disease F Fabry's disease G Urea cycle disorder H Homocystinuria I Galactosemia
Von Gierke’s disease
This is one of nine glycogen storage disorders, in which a defect in the enzyme glucose-6-phosphate results in a failure of mobilisation of glucose from glycogen. The metabolic disease presents in infancy with hypoglycaemia. The liver is usually significantly enlarged and kidney enlargement can also occur.
A 19 year old female student present to the GP with low mood, lethargy and muscle weakness. She is anxious that she is putting on weight and admits purging after meals to keep her weight under control for several months. She has a past Hx of depression and is taking citalopram. O/E, her BMI is 18, she is clinically dehydrated with signs of anaemia including conjunctival pallor. She has bilateral parotidomegaly and the GP notices erosions of her incisors. He orders some blood tests which reveal
Hb 9.5 WCC 7.8 Plts 345 Na 143 K 3.1 Urea 8.5 Cr 64 Arterial pH 7.49
Urinalysis is normal except for acidic urine. What is the cause of the acidic urine?
A AKI B Renal tubular acidosis C Citalopram D Anaemic E Physiological
E Physiological
This patient suffers from bulimia nervosa. The main abnormalities reveal a hypokalemia with arterial alkalosis and paradoxical aciduria. The alkalosis is likely to be due to excessive purging leading to a loss of hydrogen ions. The hypokalemia is secondary to the metabolic alkalosis as K and H are transported across cell membranes by the same transporter. The reduction in plasma H ions leads to increase K uptake leading to hypokalemia. As part of the normal homeostatic mechanism, K is exchanged for H in the DCT of the nephron, resulting in apparent paradoxial aciduria.
AKI would more likely give hyperkalemia and acidosis.
Citalopram, an SSRI, can cause hyponatremia but less likely to cause hypokalemia.
Renal tubular acidosis generally causes a lack of ability to acidify urine and hyperkalemia. The exception is type II RTA with a bicarbonate leak in the PCT where hypokalemia is common but the urine is only acidified during systemic metabolic acidosis.
A 59 year old man present with a fall and haematemesis after a heavy night drinking at the local pub. This is his 3rd admission in a month with alcohol-related problems. He has stopped vomiting, and O/E he is haemodynamically stabl. He has digital clubbing, spider naevi and gynecomastia. He is admitted for neurological obs overnight as he hit his head. The doctors notice the patient suffers from complex opthalmoplegia, confusion and ataxia. Given his neurological symptoms which test would confirm the associated vitamin deficiency?
A Red cell folate B RBC transketolase C RBC glutatione reductase D RBC aspartate aminotransferase activity E Carbohydrate deficient transferrin
B RBC transketolase.
This patients suffers from chronic alcohol abuse with signs of chronic liver disease. He also exhibits the classical triad of Wernicke’s encephalopathy caused by thiamine deficiency. The test for his is measuring RBC transketolase activity. This is a thiamine pyrophosphate requiring enzyme which catalyses reaction in the pentose phosphate pathway essential for regenerating NADPH in RBCs.
Which of the following is NOT a common associated with chronic renal failure?
A Acidosis B Anaemia C Hyperkalemia D Hypocalcemia E Hypophosphatemia
Hypophosphatemia
Patients with CKD normally suffer from hyperphosphatemia. This is due to renal impairment of calcium metabolism which is under the control of PTH and vitamin D. In the evolving stages of CKD, a secondary hyperPTH exists to compensate for the inability of the kidney to retain calcium and excrete phosphate. There hypocalcemia is associated with CKD. This stimulates a physiological secretion of PTH in an attempt to retain Ca. PTH is also responsible for excreting phosphate in the kidney, which is impaired in failure.
A 44 year old African man is seen by a volunteer doctor in his village with skin chamges around teh neck. There are erythematous and pigmented areas around the neck in a necklace-like distribution. His family is also complaining of him becoming more forgetful and unable to perform normal daily tasks. This is made particularly distressing given his increase in bowel movements, although he cannot remember how many times he goes. He and his family, like many of the villagers, eat almost exclusively maize, and the doctor has treated several cases of kwashiorkor in the local ar. What is the nutritional deficiency most likely to explain his symptoms?
A Tocopherol B Riboflavin C Retinol D Vitamin B3 E Ascorbate
Vitamin B3
This man with a poor diet, dermatitis, dementia and diarrhoea more likely has a niacin deficiency leading to pellagra. The other name for niacin is vitamin B3.
The rash is known as Casal’s necklace- a distinctive erythematous, pigmented rash in the necklace distribution. The disease is remembered by the 4 Ds: dementia, diarrhoea, dermatitis and death. Neurological symptoms do not exclusively manifest as dementia - other symptoms also include depression, anxiety, tremor, delusions, psychosis and even coma. The diarrhoea occurs in half, furthering the malnutrition. Dermatitis affects the mouth, kips, hands, arms, legs and feet.
Tocopherol = vitamin E. Deficiency causes haemolytic anaemia, spinocerebellar degeneration and peripheral neuropathy
Riboflavin = B2
Retinol = vitamin A. Deficiency causes dry skin and fair and xeropthalmia. Night blindness.
Ascorbate = vitamin C. Scurvy.
Chemo regimen for Hodgkin’s lymphoma
ABVD
= Adriamycin, Bleomycin, Vincristine, Dacarbazine
4 weekly intervals. 2-4 cycles for Ann Arbor stage 1/2; 6-8 cycles for stages 3/4
Effective treatment
Preserves fertility.
Long term consequences - pulmonary fibrosis, cardiomyopathy.
Lesch Nyhan syndrome
Complete HPRT enzyme deficiency resulting in hyperuricemia.
Developmental delay at 6/12
Choreiform movements - basal ganglia deposition
Spasticity and mental retardation
Self-mutilation in 85%
Hyperuricaemia nephropathy -> CRF
A 66 year old man has a gastroscopy and colonoscopy following a blood test which demonstrated a microcytic anaemia. The patient had complained of tiredness and significant weight loss over a 1 month period
A Anisocytosis B Howell-Jolly bodies C Heinz bodies D Rouleaux formation E Spherocytes F Target cells G Cabot rings H Pappenheimer bodies I Tear drop cells
Anisocytosis
Anisocytosis is defined as the variation in the size of circulating RBCs. The most common cause is IDA, but thalassemia, megaloblastic anaemia and sideroblastic anaemia are all causative.
A 36 year old woman presents to her GP after a 1 month history of tiredness and recurrent infections. Blood tests reveal a pancytopenia and a subsequent BM aspirate reveals a dry tap.
A Anisocytosis B Howell-Jolly bodies C Heinz bodies D Rouleaux formation E Spherocytes F Target cells G Cabot rings H Pappenheimer bodies I Tear drop cells
Tear drop cells
Also known as dacrocytes, are caused by myelofibrosis. The pathogenesis of myelofibrosis is defined by the BM underoing fibrosis, usually following a myeloproliferative disorder such as PRV or essential thrombocytosis. BM production of blood cells decreases resulting in a pancytopenia. The body compensates with extra-medullary haematopoiesis causing hepatosplenomegaly. Blood film will demonstrate leuko-erythroblasts, tear-drop cells and circulating megakaryocytes. BM aspirate is described as a ‘dry and bloody’ tap.
A 45 year old woman with known Graves’ disease presents to her GP with increased tiredness. She is found to have a megaloblastic anaemia.
A Anisocytosis B Howell-Jolly bodies C Heinz bodies D Rouleaux formation E Spherocytes F Target cells G Cabot rings H Pappenheimer bodies I Tear drop cells
Cabot rings
Cabot rings are looped strucutres within RBCs which may be caused by megaloblastic anaemia.
Pappenheimer bodies
Granules of iron found within RBCs. Causes include lead poisoning, sideroblastic anaemia and haemolytic anaemia.
Bernard-Soulier syndrome
mutation in GLP-1b glycoprotein, the receptor for vWF in clot formation.
A patient with gum bleeding, epistaxis or prolonged bleeding post-op. Investigations reveal a high/normal APTT, low factor 8 levels, low risocetin cofactor activity, poor risocetin aggregation and a normal PT.
von Willebrands disease
autoD mutation on Ch12.
vWF deficiency results in defect in platelet plug formation as well as low levels of factor VIII activation.
A 34 year old HIV +ve man requires a blood transfusion as part of his regular B-thalassemia major treatment regimen. He soon develops diarrhoea and a maculopapular rash on his limbs.
A Immediate haemolytic transfusion reaction B Febrile non-haemolutic reaction C Iron overload D IgA deficiency E TRALI F Bacterial infection G Delayed haemolytic transfusion reaction H Fluid overload I GvHD
GvHD
Graft vs host disease occurs due to the transfer of donor lymphocytes to the recipient in a blood transfusion in patients who are immunosuppressed. Normally the immune system is strong enough to detect and destroy donor lymphocytes. However, immunosuppressed patients the donor lymphocytes cannot be destroyed, they persist and target host tissue, especially the GI tract and skin.
Symptoms include diarrhoea, maculopapular rash, and skin necrosis.
To minimise GVHD, donor blood is irradiated to remove lymphocytes.
A 56 year old man is given a blood transfusion following severe blood loss after a hip replacement. 3 hours after the transfusion. the patient develops SOB, a dry cough and a fever of 39C
A Immediate haemolytic transfusion reaction B Febrile non-haemolutic reaction C Iron overload D IgA deficiency E TRALI F Bacterial infection G Delayed haemolytic transfusion reaction H Fluid overload I GvHD
TRALI
This is characterised by acute non-cardiogenic pulmonary oedema within 6 hours of transfusion.
The pathogenesis of TRALI involves the presence of anti-WBC Abs in the donor blood that attack host leukocytes.
Clinical features include dry cough, SOB and fever.
A 29 year old woman requires an immediate blood tranfusion after suffering a PPH. However, 30 minutes after her transfusion she develops abdo pain, facial flushing and vomiting. Analysis of the woman’s urine reveals the presence of haemoglobin
A Immediate haemolytic transfusion reaction B Febrile non-haemolutic reaction C Iron overload D IgA deficiency E TRALI F Bacterial infection G Delayed haemolytic transfusion reaction H Fluid overload I GvHD
Immediate haemolytic transfusion reaction
This is characterised by ABO incompatibility and occurs 1-2 hours post-transfusion.
Clinical features include abdo pain, loin pain, facial flushing, vomiting, and haemoglobinuria.
Host IgG and IgM target donor RBCs which are subsequently removed by the reticuloendothelial system.
A 41 year old man is referred to a haematologist by his GP after several recent chest infections and tiredness. O/E bruises are seen on his lower limbs as well as splenomegaly. Initial blood tests reveal a pancytopenia. Further testing demonstrates the presence of tumour cells that express tartrate-resistant acid phosphatase.
A ALL B PML C CML D CLL E Hairy cell leukaemia F T-cell prolymphocytic leukaemia G Large granular lymphocytic leukaemia H Adult T cell leukaemia I AML
Hairy cell leukaemia
This is a haematological malignancy of B lymphocytes and a subtype of CLL. It most commonly occurs in middle-aged men. The cancer derives its name from the fine hair-like projections that are seen on tumour cells on microscopy.
Cell surface adhesions markers include CD25 (IL-2R) and CD11c (adhesion molecule). Diagnosis can be confirmed by the presence of tartrate-resistant acid phosphatase (TRAP) on cytochemical analysis. Clinical features relate to splenomegaly, hepatomegaly and pancytopenia.
A 72 year old man presents with a 1 month history of fever, night sweats and weight loss. Blood tests reveal a monocyte count of 1400/mm3 in the peripheral blood and a bone marrow biopsy demonstrates that myeloblasts constitute 16% of his BM.
A Essential thrombocythemia B Myelofibrosis C Chronic myelo-monocytic leukaemia D Refractory anaemia with excess blasts E PRV F Refractory anaemia with ringed sideroblasts G Refractory anaemia H 5q-syndrome I Multiple myeloma
Chronic myelo-monocytic leukaemia.
This is a myelodysplastic/myeloproliferative disease most commonly affecting the elderly population, defined by a monocytosis of >1000/mm3 and increased number of monocytes in the bone marrow.
Myeloblasts makes up
tdt and CD34 are cell markers for what?
tdt is cell marker for immature lymphoblasts
CD34 is cell marker for immature myeloblasts
Cooley’s anaemia aka
B thalassemia major
A 50 year old diabetic man sees his GP complaining of generalized tirednress and a painful right knee. He is found on examination to have five finger breadthss of hepatomegaly. An Xray of his right knee is reported as showing chondrocalcinosis. His blood tests are likely to reveal:
A Raised MCV B Raised TIBC C Reduced serum ferritin D Reduced Fe levels E Raised transferrin saturation Raised transferrin saturation
This man has hereditary haemochromatosis, an inherited disorder of iron metabolism. It is probably the cause of his diabetes.
Blood tests show deranged LFTs as in this case as well as a raised serum ferritin, raised serum Fe, reduced or normal TIBC and a raised transferrin saturation (>80%).
The transferrin saturation is the ratio of (serum iron to TIBC) x100. It is typically 20-40% but raised in haemachromatosis.
Raised transferrin saturation
This man has hereditary haemochromatosis, an inherited disorder of iron metabolism. It is probably the cause of his diabetes.
Blood tests show deranged LFTs as in this case as well as a raised serum ferritin, raised serum Fe, reduced or normal TIBC and a raised transferrin saturation (>80%).
The transferrin saturation is the ratio of (serum iron to TIBC) x100. It is typically 20-40% but raised in haemachromatosis.
A 46 year old woman is brought to A&E by her daughter, who reports that she had been unwell for a few days with a fever and is now hallucinating. O/E she has a temperature of 38.9C, and is noted to be pale and has widespread purpura over both arms. Blood tests reveal an Hb of 9.1 g/dL, platelet count of 60x10(9)/L, creatinine of 226 and urea 16.7. A blood film is reported as showing the presence of schistocytes. The most likely diagnosis is
A Weil's disease B Glandular fever C ITP D TTP E HUS arms.
TTP
This woman has thrombotic thrombocytopenic purpura.
6 key features: MARCH with low platelets
- MAHA
- A fever
- Renal failure
- CNS - seizures, hallucinations, hemiparesis, decreased consciousness
- Haematuria
TTP typically affects adults and is thought to occur due to a deficiency of ADAMTS13 protease that is responsible for cleaving dimers of vWF. Urgent plasma exchange can be lifesaving in patients with TTP. Mortality rate is >95% if untreated.
This could be HUS but it is less likely given the patient’s age (HUS is associated with young children), the presence of neurological symptoms and the absence of preceding symptoms of gastroenteritis (due to E.coli 0157)
A 62 year old man presents with bruising and tiredness. Examination reveals moderate splenomegaly and his tests reveal a normocytic anaemia and a platelet count of 900 x10 (9)/L, neutrophilia., basophilia, numerous myelocytes and 4% myeloblasts. The neutrophils have low leukocyte alkaline phosphatase levels. Which of the following is likely to be present in this patient?
A t(9;22) B t(8;14) C BCR-ABL fusion gene only D V617F point mutaiton in JAK2 E 5q-syndrome
t(9;22)
This patient exhibits features of CML as evidence by raised myeloid lineage cells including neutrophils, myleocytes and basophils.
Low leukocyte alkaline phosphatase in neutrophils is characteristic of CML, c.f. to a reactive neutrophilia.
A 16 year old with mild vW disease is scheduled for a dental extraction. She has had one previously where she required 2 units of blood transfused. What is the most appropriate treatment for this patient prior to surgery?
A cryoprecipitate B Desmopressin C FFP D Vitamin K E Recombinant fVIII concentrate
Desmopressin
Desmopressin acts to increse vWF and fVIII concetration by encouraging its release from endothelial cell storage sites. Desmopressin is efficacious in mild disease (type I and II) but not severe (type III).
Recombinant fVIII is used in life-threatening surgery or emergency surgery in patients with haemophilis type A, not in mild vWD.
An 80 year old man presents with tiredness and lethargy. Aftern inital work-up, a diagnosis of MDS is suspected. Which of the following is true about this condition?
A A blood film will typically show neutrophil toxic granulation
B If there are 1% blasts of the total WCC, this represents a leukaemic transformaiton
C Cytotoxic chemo is 1st line
D Mortality is more likely to be from infection than leukaemic transformation
E Absence of the short arm of chromosome 5 is a subtype
Mortality is more likely to be from infection than leukaemic transformation.
A - neutrophil abnormalities in MDS are Pelger-Huet abnormalities
B - >20% blasts is a leukaemic transformation
C Most treatment is supportive
E 5q syndrome = long arm
Gaisbock disease
Relative polycythemia associated with hypertension reduced the plasma volume. Often in obese men.
A 4 year old boy is referred to a paediatrician after suffering recurrent chest infections over the preceding few months. The boy has a hisotry of eczema as well as recurrent nose bleeds. Blood tests reveal a reduced IgM but raised IgA and IgE levels.
A Selective IgA deficiency B CVID C Nephrotic syndrome D Bare lymphocyte syndrome E Sickle cell F CGD G Reitcular dysgenesis H Wiskott-Aldrich syndrome I IFN-gamma receptor deficiency
Wiskott-Aldrich syndrome
Wiskott-Aldrich syndrome is an X lnked condition which is caused by a mutation in the WASP gene.
Clinical features include easy bruising, nose bleeds and GI bleeds secondary to thrombocytopoenia. Recurrent bacterial infections also result.
Blood results reveal a reduced IgM level and raised IgA and IgE levels. IgG levels can be variable.
A 20 year old man presents to his GP with signs of mild pneumonia. The patient states he has had several similar episodes in the past. Further investigations by an immunologist reveal the patient has a genetic condition caused by a mutation of MHC III.
A Selective IgA deficiency B CVID C Nephrotic syndrome D Bare lymphocyte syndrome E Sickle cell F CGD G Reitcular dysgenesis H Wiskott-Aldrich syndrome I IFN-gamma receptor deficiency
CVID
CVID presents in adulthood. A mutation in MHC III causes aberrant class switching, increasing the risk of lymphomas and granulomas. Also there is a predisposition to developing AI diseases. Recurrent infections caused by H.influenzae and S.pneumoniae are common. Clinical sequelae include bronchiectasis and sinusitis. Blood tests reveal a reduced B cell count, a normal/reduced IgM and decreased levels of IgA, IgG and IgE
A 34 year old man who has been taking amoxicillin for pneumonia has developed tiredness and palpitations since taking the medication. Blood tests reveal a normocytic anaemia and DAT is positive.
A Stony fruit B HBsAg C Myelin basic protein D Rhesus Ags E Glycoprotein IIb-IIIa F Peanuts G Antiserum H Synovial membrane Ags I Poison Ivy
Rhesus Ags
These are found on RBCs. Abs directed against the Rh Ag results in AIHA. Most commonly the cause id idiopathic, however, CLL, SLE and drugs (methyldopa and penicillin) can trigger AIHA.
A 46 year old with long standing SLE is seen by his rheumatologist. He had previously been treated with steroids but has now developed end-organ involvement of his kidneys, lungs and heart.
A Cyclophosphamide B Mycophenolate C Basiliximab D Abatacept E Ritxuimab F Efalizumab G Infliximab H Ustekinumab I Denosumab
Cyclophosphamide
An alkylating agent. This causes DNA damage and therefore prevents cell replication; affects B cells > T cells.
Indications include multisystem CTD and vasculitis. It also has a role in treating cancers such as leukaemia and lymphoma.
Complications include BM suppression, hair loss and it has carcinogenic properties which may cause transitional cell carcinoma of the bladder.
A 56 year old man who is undergoing kidney transplant surgery is given medication to prevent allograft rejection. The drug prevents guanine synthesis to induce immunosuppresion.
A Cyclophosphamide B Mycophenolate C Basiliximab D Abatacept E Ritxuimab F Efalizumab G Infliximab H Ustekinumab I Denosumab
Mycophenolate mofetil
It is a prodrug of mycophenolic acid which inhibits IMPDH, an enzyme required in guanine synthesis.
Test for Thiamine deficiency
RBC transketolase
Thiamine = B1
Test for Riboflavin deficiency
TBC glutathione reductase
Riboflavin = B2
Test for Pyridoxine deficiency
RBC AST activation
Pyridoxine = B6
A 62 year old woman sees her GP for a regular check up. O/E has notable deformities of her hands, including swan neck and Boutonniere deformities of her fingers. Blood tests reveal a raised CRP. Which of the following investigation results will most likely feature?
A Reduced AH50 and normal CH50 B Reduced C1 inhibitor C Reduced C3 + C4 D Reduced C3 and normal C4 E High CH50
High CH50
As complement are acute phase proteins, a high CH50 indicates acute or chronic inflammation. Together with a raised CRP and clinical features, this patient is likely to have RA.
Reduced C3 and C4 are typically of active SLE.
A reduced C3 but normal C4 can occur in membranoproliferative glomerulonephritis. Anti-nephritic Abs cause consumption of C3.
A reduced AH50 and normal CH50 suggests a deficiency of the alternative pathway of complement; predisposing them to infection by encapsulated bacteria.
Reduced C1 inhibitor levels indicate hereditary angioedema.
A 56 year old diabetic man is undergoing a kidney transplant as a result of CKD. After the operation, the man immediately develops fever and has no urine production. Checks reveal there was an error in ABO matching of the donor and the recipient. Which of the following immune components is the first to initiate a response in this case?
A NK cells B C1 C Neutrophil D MBL E Macrophages
C1
This patient has suffered hyper acute rejection of his graft as a result of ABO incompatibility. This is an example of type II hypersensitivity. These reactions are IgG and IgM mediated; the Ag is fixed to the tissue. Binding of the Ab to the target Ag causes activation of the classical complement pathway, beginning with C1.
Activation of C1 has a number of effects. Fragments of C3a and C5a attract macrophages. C3b binds to target cell surface membranes, which causes recruitment of effector cells such as macrophages, NK cells and neutrophils.
A 10 year old boy is referred to a paediatrician after experiencing a seizure 1 week previously. Blood tests reveal that the seizure may have occurred due to low calcium levels; blood glucose levels are found to be high. The child was already being investigated for ptosis and difficulty with eye movements. What is the most likely diagnosis ?
A Hirata's disease B IPEX C Kearn-Sayre syndrome D POEMS syndrome E APECED type 1
Kearns-Sayre syndrome
Kearns-Sayre syndrome is a myopathic disease caused by deletions of mitochondrial DNA. Initially, the disease process affects the eyelid and extra-ocular muscles leading to ptosis and difficulty with eye movement. Pigmentary retinopathy is another feature. Other clinical manifestations include proximal muscle weakness, cardiac conduction defects, hearing loss and cerebellar ataxia. Endocrine system effects include: hypoPTH (causing hypoCa), primary gonadal failure, DM and hypopituitarism.
Hirata’s disease is defined by fasting hypoglycaemia as well as autoAb vs insulin. Most prevalent in Japan.
IPEX = Immune dysregulation, Polyendocrinopathy, Enteropathy X linked disease. Abnormal FoxP3 resulting in dysfunctional Tregs.
POEMS syndrome =
P - poylneuropathy, papilloedema,pulmonary disease
O - organomegaly, oedema
Endocrinopathy
M-protein
Skin abnormality - hyper pigmentation + hypertrichosis.
Mediated predominantly by antibodies which usually form after the transplantation
Hyperacute rejection
Acute vascular rejection
Acute cellular rejection
Chronic allograft rejection
Acute vascular rejection
Both immunological and non-immunological mechanisms contribute
Hyperacute rejection
Acute vascular rejection
Acute cellular rejection
Chronic allograft rejection
Chronic allograft rejection
Due to presence of pre-formed antibodies
Hyperacute rejection
Acute vascular rejection
Acute cellular rejection
Chronic allograft rejection
Hyperacute
Mediated by activation of CD4 T cells which provide help for a CD8 T cell and B cell response and occurs within 1-4 weeks
Hyperacute rejection
Acute vascular rejection
Acute cellular rejection
Chronic allograft rejection
Acute cellular rejection
Which of the following is raised in osteomalacia?
Acid phosphatase AST ALT ALP Ca Cholesterol Creatinine Fructosamine Glucose HbA1c Potassium Sodium Triglyceride
ALP
Lack of vitamin D leads to secondary hyperPTH.
Leads to hypocalcemia. Stimualtes bone formation so increase in ALP.
Which one of the following with go up after an acute MI
Acid phosphatase AST ALT ALP Ca Cholesterol Creatinine Fructosamine Glucose HbA1c Potassium Sodium Triglyceride
AST
Enzymes released post MI: CK MB (not creatinine) Troponin AST LDH
Gomorra’s methenamine silver stain revealing ‘flying saucer’ shaped cysts on microscopy
Pneumocytis jirovecii
A 34 year old HIV +Ve women is seen in the GP clinic due to 3 days of diarrhoea, headaches and fever. History reveals the patient had recently drunk unpasteurised milk. The causative organism is found to be B-haemolytic with tumbling motility.
A V cholerae B S aureus C Enterobacteriaecae D L monocytogenes E S enteriridis F Shigellae G C jejuni H G lamblia I Entamoeba histolytica
Listeria monocytogenes
B-haemolytic Gram +ve rod that causes non-invasive gastroenteritis. Sources include refrigerated food and unpasteurised dairy products.
Listeria demonstrates ‘tumbling motility’ as a result of flagellar-driven movements.
Neonates and immunocompromised patients are particularly susceptible. More serious complications include septicaemia, meningitis, and encephalitis.
Thin aerobic spirochaete with a positive microscopic agglutination test.
Leptospira interrogans
Mollaret’s meningitis
Recurrent aseptic meningitis due to HSV 1 + @
Lymphogranuloma venereum pathogen
Chlamydia trachomatis
Altered skin pigmentation. Microscopic investigation with potassium hydroxide reveals a ‘spaghetti and meatball’ appearance. Wood’s light may also reveal an orange fluorescence in some cases.
Pityriasis versicolor due to Malassezia furfur fungus
A 32 year old gardener presents to his GP with small raised lesion on his left arm. He remembers working in a garden a few days previously which had been swamped with rose-thorns.
A Cryptococcus neoformans B Pityriasis versicolor C Aspergillus flavus D Histoplasma capsulatum E Phialophora verrucosa F Tinea capitis G Sporothrix schenkii H Tinea corporis I Candida albicans
Sporothrix schenkii
Rose gardener’s disease. This is a fungus found in soil and plants. A prick by thorns causes nodular lesions on the skin surface. Initially the lesions will be small and painless; left untreated they become ulcerated. Infection may spread to joints, bone and muscle by this route. Inhalation of spores may lead to pulmonary disease and systemic infection may lead to CNS involvement. Treatment options include itraconazole, fluconazole and oral KI
Phialophora verrucosa is a copper coloured soil saprophyte found on rotting wood that causes chromoblastomyosis. Infection is characterised by cauliflower lesions.
A 48 year old man presents to his GP with flu-like symptoms.O/E the patient has a maculopapular rash on his trunk. The patient also shows an area where a vague bite mark is visible.
A Psittacosis B Rabies C Brucellosis D Q fever E Leptospirosis F Myco marinium G Lyme disease H Cat scratch disease I Rocky mountain spotted fever.
Rocky mountain spotted fever
This is caused by Rickettsia spp. a Gram -ve bacteria found in North and South America. It is harboured in small wild rodents and domestic animals (transmitted to humans by ticks).
Rickettsia bacteria invade the endothelial lining of the capillaries causing a vasculitis. Clinical features include headache, fever, myalgia, vomiting and confusion. Late signs include a rash that is maculopapular +/ petechial on distal limbs that spreads to trunk and face.
It can cause thrombocytopenia, hyponatremia +/ elevated liver enzymes.
A 34 year old bird handler presents to his GP with a few days history of fever and mild cough and myalgia. The patient states that his shop had recently taken a new shipment of parrots from Central America. Gyms staining of the patient’s sputum reveals cytoplasmic inclusions.
A Psittacosis B Rabies C Brucellosis D Q fever E Leptospirosis F Myco marinium G Lyme disease H Cat scratch disease I Rocky mountain spotted fever.
Psittacosis
Caused by chlamydia psittacosis contracted from a wide variety of birds. Human symptoms include a severe pneumonia +- hepatitis.
Diagnosis is made by visualising cytoplasmic inclusions on Giemsa or fluorescent antibody stained sputum or biopsy sample.
Q fever is caused by Coxiella brunette. Transmission occurs by inhalation of aerosols of urine, faeces or amniotic fluid for infected livestock.
‘Red currant jelly’ blood-stained sputum in an alcoholic with a cavitating lesion on CXR
Klebsiella pneumonia
Oxidase positive organisms: PuNCH Me Very Lightly
Pseudomonas u Neisseria Campylobacter Helicobacteria
Moraxella
e
Vibrio
Legionella
A 22 year old students presents to A&E with a raised erythematous scaly ulcer on his forearm which has not been healing. O/E he is also found to have lymphadenopathy. He recently travelled to South America. A Novy Macneal Nicolle medium is used.
Leishmania major
This is cutaneous leishmaniasis. An itchy, scaly papule develops at the bite site and develops into a crusty ulcer with a raised edge. Local lymphadenopathy can also occur, but the lesion healsh iwthin 8 months leaving a depigmented scar called an oriental sore. The organisms implicated are L. major and L tropica. Diagnosis is made by Giemsa staining of slit skin smears, or from tissue aspirated from the ulcer, cultured on Novy-MacNeal-Nicolle medium.
L.donovani and L. infantum cause visceral leishmaniasis (Kala-azar) in Africa, Asia and Europe. L chagasi causes it in South America. Most common clinical features are fever and splenomegaly.
L braziliensis causes mucocutaneous Leishmaniasis. It may begin in the same way as cutaneous form but years later ulceration can appear in mucous membranes leading to destructive mutilation.
A 65 year old retired mechanic is brought to GP by his family due to their concern over his recent confusion.This has occurred rapidly over the past 4 months and he now struggles to recognise members of his family. His daughter also reports occasionally seeing intermittent, jerky movements of both his arms. The GP organises a CT scan and a dementia screen, which are both found to be normal. Which is the next most useful diagnostic test for the GP to order?
A MRI brain B EEG C ECG D USS of carotids E Tonsillar biopsy
EEG
A 62 year old man has recently been diagnosed with sporadic CJD. His GP is keen to do an LP. Which of the following statements is true regarding this investigation in this situation?
A The LP is used to look for the levels of protein, glucose and polymoprhs.
B The LP is used to look for the level of 14-3-3 protein
C A LP is the most specific test for vCJD
D The LP is not useful in sporadic CJD but is an important test in vCJD
E A tonsillar biopsy would be more useful that an LP for sporadic CJD
The LP is used to look for the levels of 14-3-3
A 33 year old backpacker visits his GP complaining of feeling weak, lethargic and feverish since he returned from his trip to South Africa 3 months previously. He is accompanied by his wife who reports to a change in his behaviour and disturbed sleep patterns since his return. O/E his GP discovers that he has enlarged cervical LNs, and there is a small chancre on his foreaem that is approx 2cm in diameter.
A Plasmodium falciparum B Trypanosoma brucie gambiense C Trypanosoma brucei rhodesiense D Trypanosome cruzi E Leishmania infantum
Trypanosoma brucei gambiense
A young girl returns from visiting her relatives in India , feeling feverish and with flu-like symptoms. A diagnosis of malaria is suspected. Her fevers started on Monday, regressed for a few days and then returned on Thursday. She was well again over the weekend and was then brought to the GP following Monday when her fever returned again.
A P falciparum B P vivax C P ovale D P malariae E P knowlesi
P malariae
Different patterns of fever in malaria.
P malariae - Quartan fever: every 4 days
P falciparum, vivax and ovale: Tertian fever - 3 days
P knowlesi - quotidian fever: daily
Thick and think films showing Maurer’s clefts.
A P falciparum B P vivax C P ovale D P malariae E P knowlesi
P falciparum
C.f. Schuffner’s dots seen in P vivax and ovale.
Appropriate treatment for uncomplicated falciparum malaria
A Discharge with oral quinine and doxy
B Discharge with oral mefloquine and chloroquine
C Admit and give IV paracetamol and observe
D Admit and give IV quinine
E Admit and give oral quinine and doxy
Admit and give oral quinine and doxy
All patients with falciparum malaria should be admitted.
Oral treatment suffices in uncomplicated cases.
A 35 year old man with pain and difficulty bending his L knee. X ray reveals many lytic leasions in the epiphysis of the patient’s knee.
Giant cell tumour
Borderline malignant tumour of giant osteoclast cells. The cells are similar to those found in Paget’s disease as they have multiple nuclei (>20). The osteoclastic cells cause lytic lesions in the epiphyses (especially around the knee) that are visible on Xray and may give a characteristic ‘soap bubble appearance. Histological features include multinucleated giant cells with surrounding ovoid and spindle cells.
A 38 year old woman presents to her GP with generalised bone pain. Xray reveals areas of pseudofracture, especially in the ribs.
Osteomalacia
Insufficient bone mineralisation due to vitamind D deficency. Clinical features include craniotabes, bone pain, proximal weakness and pseudo-fractures (looser zones).
Craniotabes is the descriptive term for teh soft and elastic occipito-parietal bones causing an elastic recoil sensation when pushed.
An 8 year old boy has been diagnosed with precocious puberty. A routine examination by the paediatrician reveals cafe-au-lait spots on the child’s back. The boy has had numerous fractures of his femur and tibia bilaterally after falls.
Fibrous dysplasia
This occurs due to developmental arrest of normal bone structures secondary to osteoblast maturation defect. On xray this may cause a ground glass or soap bubble appearance. Histological investigation reveals trabeculae that lack osteoblastic rimming.
2 possible syndromes
1) mono-ostotic = 70%; mainly femurs
Causes of an elevated anion gap in metabolic acidosis
KULT
Ketoacidosis - DKA, alcoholic, starvation,
Uraemic - renal failure
Lactic acidosis -
Toxins - ethylene glycol, methanol, paraldehyde, salicylate
Which of the following patients is most likely to have a hyper plastic arteriosclerosis with fibrinoid necrosis, petechial haemorrhages and micro infarcts in the kidney, in conjunction with a marked elevated plasma renin?
A A 56 year old man with an acute MI
B A 6 year old boy with albuminuria
C A 62 year old woman with end stage renal failure
D A15 year old with recent streptococcal infection
E A 45 year old woman with scleroderma
A 45 year old woman with scleroderma.
Diffuse scleroderma can be associated with hyper plastic arteriosclerosis and malignant hypertension (resulting in the end organ damage).
an acute MI leads to decreased CO so decreased renal perfusion and ischaemia resulting in ATN.
Albuminuria in a 6 year old is likely due to minimal change disease. Associated with effacement of the podocytes on EM.
End stage renal failure kidneys have thickened arteries, globally sclerotic glomeruli and interstitial scarring with chronic inflammation.
Post-strep glomerulonephritis produces glomerular hypercellularity.
A 21 year old was seen in the surgical OPD complaining of lethargy and generalised weakness over a period of several weeks. Ix showed: Hb 9g/dL; Hct 26.3%; MCV 72fl, platelet count 189x10(9).L, WCC 7.5 x10(9)/l. O/E there was no tenderness and no masses; bowel sounds were present. His stool was positive for occult blood. A small bowel series with Ba enema revealed no masses or perforations, only a solitary 2cm outpouching in the ileum. The presence of which of the following is most likely to have led to these findings?
A antiphospholipid syndrome
B Elaboration of enterotoxin by E.coli
C Inheritance of faulty APC gene
D Proliferation of abnormal submucosal veins
E Ulceration of mucosa by ectopic gastric tissue
Ulceration of mucosa by ectopic gastric tissue.
Aschoff bodies and Anitschkov mycocytes
Acute rheumatic fever
Aschoff bodies = small giant cell granulomas
Anitschkov myocytes = regenerarating myocytes
Most common gene mutation in HOCM
BMHC = Beta myosin heavy chain
Trousseau syndrome
= recurrent superficial thrombophlebitis
Assoc. w/ pancreatic adenocarcinoma, glioma and lung Ca.
Due to hypercoagulability.
