HLA-DR sub-types and associated autoimmune conditions

HLA DR sub-types
HLA-DR is a major histocompatibility complex, MHC CLass II cell surface receptor, encoded by the human leukocyte antigen complex on chromosome 6.
HLA-DR is important for understanding of graft-versus host disease, organ transplant rejections, and also involved in several autoimmune conditions, disease susceptibility and disease resistance.

HLA-DR molecules are upregulated in response to signalling. In the instance of an infection, the peptide (such as the staphlococcal enterotoxin I peptide show in the two illustrations) is bound into a DR molecule and presented to a few of a great many T-cell receptors found on T-helper cells. These cells then bind to antigens on the surface of B-cells stimulating B-cell proliferation.

References:
HLA types associated with disease: http://en.wikipedia.org/wiki/HLA_DR
British Transplant Society - Publishes guidelines on ethics, criterias, and guidelines on various transplants: http://www.bts.org.uk/

Drugs that cause prolonged QT interval

Drugs commonly asked in MRCP exams:
Quinidine
Erythromycin, clarithromycin
Amiodarone
Sotalol
Tricyclic antidepressants
Chloroquine
Phenothiazine
Non-sedating anti-histamines
Ciprofloxacin

ECG: Causes of Axis Deviations

The normal axis is generally between -30 and +90 degrees.Right axis deviation is defined as axis located between 90 degrees and 180 degrees. Left axis deviation defined as the axis located between -30 degrees and -90 degrees.
The left table summaries the easy way to determine the cardiac axis (http://sitemaker.umich.edu/ecgtutorial/axis)

Left axis deviation
Left bundle branch block
Atrial spetal primum defect
Wolf-parkinsons white disease Type A
Inferior MI
Left anterior hemiblock
(N.B: LVH itself does not cause Left axis deviation)

Right axis deviation
Maybe normal variant in young adults
Right bundle branch block
Acute right heart strain - e.g. PE
Left posterior hemiblock
Right ventricular hypertrophy - e.g. Chronic lung disease +/- pulmonary hypertension
Dextrocardia
Anterolateral Myocardial Infarction
Wolff-Parkinson Wright Syndrome Type B
Atrial septal defect secundum
Severe pulmonary stenosis
Fallot's tretralogy / VSD

Tutorial link: https://courses.stu.qmul.ac.uk/smd/kb/resources/ECG_workshop/session2.htm

Causes of Extrinsic Allergic Alveolitis

Commonly asked extrinsic allergic alveolitis:
Bird fancier's lungs: Parakeet, pigeon, chicken, turkey proteins etc from avian droppings or feathers
Cheese worker's lungs: Penicillum casei
Chemical worker's lung: Isocyanates from polyurethane foam, varnishes, lacquer
Coffee worker's lung: from Coffee bean dust
Compost lung: Aspergillus
Contaminated basement (Sewage): Cephalosporium
Farmer's lung: Thermophilic actinomycetes in mouldy hay, grain, silage
Fish food / meal lung: ? ageng from fish food
Hot tub lung: Cladosporium sp from mold on ceiling
House worker / cleaner: Bacillus subtilis enzymes from detergents
Humidifier or airconditioner lung (Ventilation pneumonitis): due to aureobasidium pullulans, candida albicans, other microorganisms from contaminated water in humidification or forced-air conditioning systems
Lab worker's lung: From rat urine
Lycoperdonosis: due to puffball spores (Lycoperdon)
Farmer's lungs (Micropolyspora faeni)
Malt worker's lung (Aspergillus clavatus or fumigatus)
Maple bark disease: Cryptostroma corticale from maple bark
Miscellaneous Medications lung disease: amiodarone, bleomycin, efaviren, hydralazine, hydroxyurea, isoniazid, methotrexate, paclitaxel, penicillin, procabazine, propranolol, sulfazsalazine
Pituitary snuff taker's lung: due to animal protein from pituitary snuff
Potato riddler's lung: thermophilic actinomycetes, aspergillus from mouldy hay around potatoes)
Sauna taker's lungs: Aureobasidium sp & other organisms from contaminated sauna water
Sausage worker's lung: Penicillium nalgiovense from dry sausages
Tobacco worker's lung: Aspergillus sp from mould on tobacco
Wood worker/ trimmer's lung: due to Rhizopus sp, Mucor Sp, aspergillus sp from contaminated wood dust
Sugarcane or Bagassosis Lung (Thermophilic actinomycetes from 'moldy' sugarcane)
Mushroom worker's lungs (Thermophilic actinomycetes from mushroom compost)
BAL: Shows increased lymphocytes in EAA (Eosinophils not typically elevated in blood).

MRCP Part II - some useful notes

Prolonged APTT
- Heparin
- Anti-phospholipid syndrome
- Haemophilia
* When Factor VIII level normal, this suggests diagnosis of Haemophilia B (IX deficiency). Bleeding time, thrombin time, and PT will be nomral

4 'Ts' for Anterior Mediastinal Mass
- Thymoma
- Teratoma / Germ Cell Tumour
- Thyroid
- Terrible Lymphoma

Causes of TTP - causes
- Infection (e.g. Gastrointestinal, genitourinary sepsis; rocky mountain spotted fever, anthrax)
- Pregnancy, oral contraceptives
- Drugs related (Clopidogrel, ticlopidine, ciclosporin, tacrolimus, quinine, high-dose chemotherapy) possibly due to antibody formation
- Autoimmune / vasculitis (SLE)
- HIV infection
- Metastatic Cancer
- Recent cardiovascular procedures (Catheterisation, angioplasty, vascular bypass, prosthetic heart valve)
- Severe hypertension (>200 / 120 mmHg)

* Aetiology - due to deficiency of ADAMTS 13, a metalloproteinase found in plasma responsible for cleaving the ultra-high molecular weight forms of von Willebrand factor secreted by endothelial cells, contributing to pathogenic platelet aggregation & adhesion.
* Classical manifestations: thrombocytopenia, purpura microantiopathic haemolytic anaemia, neurological findings (confusion, delirium, seizures, hemiparesis, aphasia, malaise, fatigue), renal failure, fever (variably present). Additionals inclue nausea, vomiting, abdominal pain, hypertension, arthalgias, splenomegaly. Mortality high. Severity estimated by degree of anaemia, thrombocytopenia, and LDH.
In contrast to HUS, HUS tends to have higher platelets, more severe renal failure, and neurological manifestations absent.
* Laboratory features:
- Anaemia-mild to very severe
- Thrombocytopenia - invariably present may be very severe
- Blood film - polychromasia (increased young red cells), nucleated red blood cellls
- Raised serum LDH
- Increased indirect (unconjugated) bilirubin
- Reduced haptoglobin
- COOMBs test negative
- ADAMTS 13 activity decreased
- Proteinuria, microscopic haematuria
- Elevated urea, creatinine.
- PT, APTT, fibrinogen - may be normal or mildly abnormal (If major consumption of clotting factors, diagnosis of TTP doubtful; prolonted APTT suggests circulating anticoagulant - lupus anticoagulant or antiphospholipid syndrome)
- ANA - present in ~20 %
- COmplement, platelet associated IgG usually normal

Normal Reference Values of Blood Count Differentials
'Nobody Likes My Education Background'
Neutrophils 60%
Lymphocyes 30%
Myelocytes 6%
Eosinophils 3%
Basophils 1%
(60, 30, 6, 3, 1 %)

Approach to bilateral parotidomegaly

'SLAM' the face

(S)
- Sjogren's disease (Look for dry eyes / month)
- Sarcoidosis (hilar lymphadenopathy, lupus pernio, hepatomegaly)

(L)
- Lymphoma / Leukaemia (anaemia, oral ulcers, bruising, hepatomegaly, splenomegaly, lymphadenopathy)

(A)
- Amyloidosis
- Alcoholic excess (evidence of chronic liver disease, neuropsychiatric manifestations, CAGE questionnaire)

(M)
- Mumps (also examine male genitalia)& many infections (e.g. HIV, EBV, CMV, coxsackie A, influenza, TB)
- Metabolic (starvation / bulimia, hyperlipidaemia) & endocrine (e.g. DM, chronic pancreatitis, acromegaly, hypothyroidism)