Path

Question 1

HLA Class II Molecules

Answer 1

HLA-DR
HLA-DP
HLA-DQ

Question 2

HLA Class I Molecules

Answer 2

HLA-A
HLA-B
HLA-C

Question 3

HLA Matching in Organ Donation

Answer 3

Clinically most important
HLA-A
HLA-B
HLA-DR

Score in series e.g. 0:0:0
Would no mismatches across HLA-A, HLA-b and HLA-DR between recipient and donor

As two alleles from each, opportunity to match 6 alleles
Maximum of 6 mismatches (MM)
6 MM= bad
0 MM = good

Sibling to sibling:
25% - 6MM
50% - 3MM
25% - 0MM

HLA matching is an important part of organ allocation procedure
Bone marrow
Kidney

HLA matching not as important (Size is more important)
Heart
Lung

Question 4

T Cell Mediated Transplant Rejection

Answer 4

T cell mediated
Phase 1 - Recognition
Acute Rejection
Direct: donor APC presents to recipient CD8 or CD4 T cell which recognises APC as foreign and leads to destruction

Chronic Rejection
Indirect: Indirect is recipient APC finding a foreign protein (HLA molecule) and presenting to immune system

Phase 2 - T cell activation by foreign antigen
First signal is the inetreaction of APC with the T cell receptor
Second signal is co-stimulatory signals that enhance T cells activation
Third signal is when activated T cell produces cytokines, IL-2 autocrine effect

Phase 3 - Effector cells
Recruited all the immune cells
They recognise the HLA molecule as foreign 
Infiltrate organ
Cause damage to the organ 
Produce lytic enzymes
Direct cytotoxicity 
Antigen-dependent cell mediated cytotoxicity 

Graft infiltration by alloreactive CD4+ cells
Cytotoxic” T cells
Release of toxins to kill target
Granzyme B
Punch holes in target cells
Perforin
Apoptotic cell death
Fas -Ligand

Macrophages
Phagocytosis
Release of proteolytic enzymes
Production of cytokines
Production of oxygen radicals and nitrogen radicals

Question 5

Symptoms of acute T-cell mediated rejection

Answer 5

Deteriorating graft function
Kidney transplant: Rise in creatinine, fluid retention, hypertension
Liver transplant: Rise in LFTs, coagulopathy
Lung transplant: breathlessness, pulmonary infiltrate

Pain and tenderness over graft

Fever

Question 6

Antibody Mediated Rejection

Answer 6

Phase 1 – exposure to foreign antigen

Phase 2 - proliferation and maturation of B cells with antibody production

Phase 3 – effector phase; antibodies bind to graft endothelium (capillaries of glomerulus and around tubules, arterial)

Antibodies
Anti-A or anti-B antibodies are naturally occurring

Anti-HLA antibodies are not naturally occurring
Pre-formed – previous exposure to epitopes (previous transplantation, pregnancy, transfusion)
Post-formed - arise after transplantation

Path
Endothelium with foreign HLA antigens
Antibody against epitope on ENDOTHELIUM
Recruit complement
Complement is activated
(can detect complement for diagnosis on biopsy)
Cause formation of membrane attack complex –> cell lysis
Also liberate C3a and C5a –> potent chemotactic
Recruit inflammatory cells directly to the endothelium through the Fc receptors on macrophages and NK cells and polymorphs

Question 7

Histology of T and B cell rejection

Answer 7

In T cell
Heavy monocytic infiltrates

In B cells
Discrete accumulation of inflammatory cells including polymorphs
Stain for complement

Question 8

Prevention and Treatment of Transplant Rejection

Answer 8

Preventing rejection:
A. AB/HLA matching

B. Screening for anti-HLA antibodies
Before transplantation
At time of transplantation: when a specific deceased donor kidney has been assigned to the patient
After transplantation, repeat measurements to check for new antibody production

3 main types of assay
Cytotoxicity assays
Flow cytometry
Solid phase assays

C. Immunosuppression: dampen the immune system of the recipient
Induction agent ex. OKT3/ATG, anti-CD52, anti-CD25
Base-line immunosuppression: CNI inhibitor + MMF or Aza, with or without steroids = calcineurin inhibitor (cyclosporine) and anti-proliferative drug (micophenolate)

Treatment of episodes of acute rejection:
Cellular: steroids, ATG/OKT3
Antibody-mediated: IVIG, plasma exchange, anti-C5, anti-CD20

Always balance the need for immunosuppression with the risk of infection/malignancy/drug toxicity

Question 9

Graft vs Host Disease

Answer 9

Eliminate hosts immune system (total body irradiation; cyclophophamide; other drugs)

Replace with own (autologous) or HLA-matched donor (allogeneic) bone marrow

Allogeneic HSCT leads to reaction of donor lymphocytes against host tissues

Related to degree of HLA-incompatibility

Also graft-versus-tumour effect

GVHD prophylaxis: Methotrexate/Cyclosporine

Preparative regimen for haematopoietic transplant has a role to play in developing graft vs host disease
Injury in recipients GI tract
Helps to prone donor T cells
Form immune reaction against recipients tissue

Skin: rash
Gut: nausea, vomiting, abdominal pain, diarrheoa, bloody stool
Liver: jaundice

Treat with corticosteroids

Question 10

Post transplantation infections

Answer 10

Bacterial, viral, fungal

Opportunistic
Cytomegalovirus
BK virus
Pneumocytis carinii

Question 11

Post-transplantation Malignancy

Answer 11

Viral associated (x 100)
Kaposi’s sarcoma (HHV8)
Lymphoproliferative disease (EBV)

Skin Cancer (x20)

Risk of other cancers eg lung, colon also increased (x 2-3)

Question 12

Causes of microcytic Anaemia

Answer 12

FAST
Fe Iron deficiency anaemia
Anaemia of chronic disease
Sideroblastic anaemia
Thalassaemia

Question 13

Faecal calprotectin

Answer 13

Marker of GI inflammation

Produced by neutrophils

Question 14

Coeliac Disease HLA associations

Answer 14

HLA-DQ2

HLA-DR8

Question 15

Histopathological Changes in Coeliac Disease

Answer 15

Villous height is reduced and crypts become hyperplastic, resulting in reduced or reversed villous: crypt ratio

Although height of villi are reduced, mucosal thickness remains the same due to crypt hyperplasia

Villous atrophy results in decreased surface area –> malabsorption

Increased to >20 IELs/100 epithelial cells
These lymphocytes are 𝛄ƍ T cells

Question 16

Causes of Increased Intra-epithelial lymphocytes

Answer 16

Coeliac Disease 
Dermatitis herpetiformis
Cows milk protein sensitivity
IgA deficiency
Tropical sprue
Post infective malabsorption
Drugs (NSAIDs)
(Lymphoma)

Question 17

Causes of Villous Atrophy

Answer 17

Coeliac 
Giardiasis
Tropical sprue
Crohn’s disease
Radiation/chemotherapy
Bacterial overgrowth
Nutritional deficiencies
Graft versus host disease
Microvillous inclusion disease
Common variable immunodeficiency

Question 18

Complications of Coeliac Disease

Answer 18

Malabsorption

Osteomalacia and osteoporosis (bone scan every 3 years)

Neurological disease
Epilepsy
Cerebral calcification

Lymphoma

Hyposplenism

Question 19

Positive Anti-TTG on gluten free diet

Answer 19

The TTG antibody should be negative

It can only be positive in two cases:
Not sticking to gluten free diet
Developed lymphoma

Question 20

Coeliac Associated Conditions

Answer 20

Dermatitis herpetiformis (prevalence = 100%)
Type 1 diabetes mellitus (prevalence = 7%)
Autoimmune thyroid disease
Down’s syndrome

Question 21

Recombinant Cytokines

Answer 21

IFN-alpha
Hepatitis C
Hepatitis B
Kaposi’s Sarcoma (HHV-8)

IFN-gamma
Chronic granulomatous disease

Question 22

T Cell Inhibiting APC

Answer 22

T cell expresses CTLA4, binds to CD80/CD86 on APC

Transmits inhibitory signal

Question 23

Iplimumab

Answer 23

Block CTLA4 (inhibitory signal from T cell --> APC)
Leading to great T cell response

Indications
- Advanced melanoma

Question 24

APC inhibiting T cell

Answer 24

PD-1 is expressed on T cells
PD-1 Ligand expressed on APC

APC causes inhibition of T cell

PD-1 also expressed on some malignant cells

Question 25

Pembrolizumab and Nivulomab

Answer 25

Antibody binds to PD-1 Blocks immune checkpoint Allows T cell activation Indications Advanced melanoma

Question 26

Corticosteroids

Answer 26

Reduces prostaglandin synthesis Corticosteroids inhibit phospholipase A2 - Blocks arachidonic acid and prostaglandin formation Inhibits phagocyte migration and function Decreased traffic of phagocytes to inflamed tissue Decreased phagocytosis Decreased release of proteolytic enzymes Inhibits lymphocyte proliferation Sequestration of lymphocytes in lymphoid tissue Affects CD4+ T cells > CD8+ T cells > B cells Blocks cytokine gene expression Decreased antibody production Promotes apoptosis

Question 27

Cytotoxic Anti-Proliferative Drugs

Answer 27

Cyclophosphamide Mycophenolate Azathioprine Methotrexate Inhibit DNA synthesis --> affect rapidly dividing cells ``` Toxicity Bone marrow suppression Infection Malignancy Teratogenic ```

Question 28

Cyclophosphamide

Answer 28

Alkylates guanine base of DNA Damages DNA --> prevents cell replication Affects B cells > T cells Indications: Multi-system connective tissue disease/vasculitis with severe end-organ involvement SLE, Granulomatosis with polyangiitis, Side Effects Toxicity to proliferating cells (bone marrow, sterility) Haemorrhagic cystitis Malignancy (Bladder, haematological, Non-melnoma skin) Infection: PCP

Question 29

Azathioprine

Answer 29

Metabolsied by liver Azathioprine --> 6-mercaptopurine 6-mercaptopurine blocks de novo purine synthesis --> inhibits DNA replication Preferentially inhibits T cell Indications Transplant Autoimmune Autoinflammatory disease (IBD) Side Effects Bone Marrow Supression (1 in 300 have polymorphism of Thiopurine methyltransferase --> inability to metabolise azathiopurine --> accumulation) Check TPMT levels before prescribing Hepatotoxicity Infection

Question 30

Mycophenolate Mofetil

Answer 30

Blocks de novo nuceltodie synthesis --> prevents DNA replication T cell > B cells Indications As alternative to azathioprine in transplants As alternative to cyclophosphamide in autoimmune and vasculitis Side Effects Bone marrow suppression Infection: Herpves virus reactivation Progressive multi-focal leukoencephalopathy (PML) (JC virus)

Question 31

Plasmapheresis

Answer 31

Patient’s blood passed through cell separator Removal of pathogenic antibody Own cellular constituents reinfused Plasma treated to remove immunoglobulins and then reinfused (or replaced with albumin in ‘plasma exchange’) Problems Rebound antibody production limits efficacy, therefore usually given with anti-proliferative agent Indications Severe antibody-mediated disease Goodpastures syndrome Anti-glomerular basement membrane antibodies Severe acute myasthenia gravis Anti-acetyl choline receptor antibodies Severe vascular rejection Antibodies directed at donor HLA molecules

Question 32

Cyclosporin and Tacrolimus

Answer 32

Block Calcineurin (normally activates NFATc which is transcription factor for cytokines) Prevents cytokine transcription factor --> prevents lymphocyte proliferation Indications Transplant --> Improves graft survival ``` Side effects Nephrotoxic Neurotoxic Hypertension Diabetogenic (particularly tacrolimus) Dysmorphism (Cyclosporin only) ```

Question 33

Tofacitinib

Answer 33

JAK signalling inhibitor Indications: Rheumatoid Arthitis

Question 34

Apremilast

Answer 34

PDE4 inhibitor Indications: Psoriasis and Psoriatic arthritis

Question 35

Anti-Thymocyte Globulin

Answer 35

Antibody against human thymocyte Lymphocyte depletion Modulation of T cell activation and migration Indications; Allograft rejection (renal or heart) Give daily infusion ``` Toxicity Infusion reactions Leukopenia Infection Malignancy ```

Question 36

Basiliximab

Answer 36

Anti-CD25 (IL-2 R alpha-chain) Prevents T cell proliferation Indications: pre and post-transplant Prophylaxis against transplant rejection Toxicity Infusion reactions Infection Concern over long-term malignancy

Question 37

Abatacept

Answer 37

Fusion: Antibody-CTLA4 CTLA4 normally on CD4 cell --> binds to APC CTLA4 binds to APC but has antibody on the other end, blocks T cell from binding --> prevents T cell activation Indications Rheumatoid arthritis Weekly subcut Monthly IV Toxicity Infusion reactions Infection (TB, HBV, HCV)

Question 38

Rituximab

Answer 38

Anti-CD20 (Mature B cell) --> depletion of mature B cell Indications Lymphoma Rheumatoid arthritis (2 doses every 6-12 months IV) SLE Toxicity Transfusion reaction Infection (progressive multifocal leukoencephalopathy, JC virus) Exacerbated CV disease

Question 39

Natalizumab

Answer 39

Anti-a4 integrin a4 expressed with b1 or b7 integrin a4b1 bind to VCAM1 and MadCAM1 on endoethelium to mediate cell rolling Inhibits T cell migration Indications Multiple sclerosis (Crohn Disease) IV every 4 weeks Toxicity Infusion reaction Infection (Progressive Multifocal Luekoencephalopathy) Hepatotoxicity Concern over long-term malignancy

Question 40

Tocilizumab

Answer 40

Anti-IL-6R Reduces Activation of: Macrophages T cells B cells Indications Castleman's disease Rheumatoid arthritis IV or SC ``` Toxicity Transfusion reactions Infection Hepatotoxicity Elevated lipids Concern over long-term malignancy ```

Question 41

Agents directed at cytokines

Answer 41

``` Infliximab – anti-TNFa Adalimumab – anti-TNFa Certolizumab – anti-TNFa Golimumab – anti-TNFa Etanercept – TNF receptor p75-IgG fusion protein ``` Ustekinumab – anti-IL-12 and IL-23 Secukinumab – anti-IL-17 Denosumab – anti-RANK ligand

Question 42

Agents directed at cell surface antigens

Answer 42

``` Rabbit anti-thymocyte globulin Basiliximab – anti-CD25 Abatacept – CTLA4-Ig Rituximab – anti-CD20 Natalizumab – anti-a4 integrin Tocilizumab – anti-IL-6 receptor ```

Question 43

Anti-TNFa Antibodies

Answer 43

Infliximab Adalimumab Certolizumab Golimumab ``` Indications Rheumatoid arthritis Ankylosing spondylitis Psoriasis and psoriatic arthritis IBD SC or IV ``` ``` Toxicity Infusion or injection reaction Infection (TB, HBV, HCV) Lupus-like syndrome Demyelination Malignancy ```

Question 44

Etanercept

Answer 44

TNF Antgaonists - Inhibits TNFa and TNFb ``` Indications and dosing Rheumatoid arthritis Ankylosing spondylitis Psoriasis and psoriatic arthritis Subcutaneous weekly ``` ``` Toxicity Injection site reactions Infection (TB, HBV, HCV) Lupus-like conditions Demyelination Malignancy ```

Question 45

Ustekinumab

Answer 45

Anti-p40 (IL-12 and IL-23) IL-12: p40+p35 IL-23:p40+p19 Inhibits IL-12 and IL-23 IL-12 and IL-23 on NK cell and T cell Indications Psoriasis and psoriatic arthritis Subcut every 12 weeks Complications Injection reaction Infection (TB) Concern regards long-term malignancy

Question 46

Secukinumab

Answer 46

Anti-IL-17A Dimer of IL-17A or IL-17A/F Binds to IL-17RA/RC receptor IL-17AR on keratinocyte Indications Psoriasis and psoriatic arthritis Ankylosing spondylitis SC load and then monthly Action Inhibits IL-17A Toxicity Infection (TB)

Question 47

Denosumab

Answer 47

Anti-RANKL Inhibits RANK mediated osteoclast differentiation and function Indications Osteoporosis Subcutaneous every 6 months Toxicity Infection Avascular necrosis of jaw

Question 48

HIV-1

Answer 48

``` HIV-1 Retrovirus positive sense ssRNA virus 9 genes Reverse transcriptase: RNA --> DNA DNA then integrated into host DNA Infects CD4+ T cell and CD4+ monocyte Receptor = CD4 Co-receptor = CCR5 or CXCR4 ```

Question 49

Immunity against HIV-1

Answer 49

Non-specific activation of NK cells and complement associated with slower disease course Acquired immunity – B cells Anti-gp120 and anti-gp41 (Nt) antibodies are thought to be important in protective immunity. Non-neutralising anti-p24 gag IgG also produced. HIV remains infectious even when coated with antibodies. CD8+ T cells Secrete soluble molecules (cytokines and chemokines such as MIP-1a, MIP-1b, and RANTES) which are able to prevent infection by blocking entry of virus into CD4+ T cells. Recognise processed antigen - (peptides) - in the context of class I HLA molecules

Question 50

HAART

Answer 50

HAART = 2NRTIs + PI (or NNRTI)

Question 51

Management of Anaphylaxis

Answer 51

IM adrenaline 0.5mg (may repeat) Oxygen by mask IV Intravenous anti-histamines (10mg Chlorpheniramine) Nebulised bronchodilators (driven by oxygen) Intravenous corticosteroids (Hydrocortisone 200mgs) Intravenous fluids (if hypotensive)

Question 52

Causes of recurrent meningococcal meningitis

Answer 52

``` Immunological Complement deficiency (susceptible to encapsulated bacteria) Antibody deficiency (susceptibility to upper and lower respiratory tract infections) ``` Neurological: any disruption to BBB Occult skull fracture Hydrocephalus

Question 53

Features of immune deficiency (SPUR)

Answer 53

Serious Persistent Unusual Recurrent

Question 54

Management of Complement Deficiency

Answer 54

Meningovax Pneumovax HIB vaccines Daily prophylactic penicillin

Question 55

Anti-CCP

Answer 55

Anti-citrullinated peptide antibodies 70% Sensitivity for RA 95% Specificty for RA Antibodies against citrullinated proteins

Question 56

Rheumatoid Arthritis HLA Associations

Answer 56

HLA-DR1 HLA-DR4

Question 57

Rheumatoid Factor

Answer 57

IgM Antibody against Fc portion of human IgG 60-70% Sensitivity for RA 60-70% Specificity for RA

Question 58

Genetic Predisposition to Rheumatoid Arthritis

Answer 58

5%DZ and 30%MZ twins Peptidylarginine deaminase polymorphisms PAD Type 2 & 4 Increase citrullination of proetins PTPN 22: Protein tyrosine phosphatase non-receptor 22 Lymphocyte-specific tyrosine phosphatase --> supresses T cell activation activation 1858T allele increases susceptibility to rheumatoid arthritis, SLE, type 1 diabetes HLA HLA-DR1 HLA-DR4

Question 59

Treatments for Rheumatoid Arthritis

Answer 59

``` Standard Mx Methotrexate Sulphasalazine Hydroxychloroquine Leflunomide ``` Further Mx TNFalpha antagonist Inhibits downstream events in inflammation. Rituximab Antibody specific for CD20 Depletes B cells (not plasma cells) Abatacept CTLA-4 – Ig fusion protein Binds to ligands of CD28 (CD80 and CD86) and thereby inhibits T cell activation Tocilizumab Antibody specific for IL-6 receptor – widespread effects Before Starting Biologics: Screen for exposure to TB using CXR and TB ELISPOT Screen for exposure to Hepatitis B Screen for exposure to Hepatitis C Consider possibility of HIV infection Prior history of septic arthritis/infected joint prosthesis Educate patient to stop drug and seek advice if acute infection Consider need for vaccinations Consider risk of malignancy Prior history of malignancy Advise re sun exposure/skin protection

Question 60

Serum Sickness

Answer 60

Penicillin can bind to cell surface proteins Acts as “neo-antigen”: stimulates very strong IgG antibody response Individual is “sensitised” to penicillin Subsequent exposure to penicillin stimulates Formation of immune complexes with circulating penicillin Production of more IgG antibodies Fever Arthralgia of large joints Vasculitic skin rash Renal function deteriorates

Question 61

Sjögren's syndrome

Answer 61

Chronic auto-immune disease of salivary glands Primary: by itself Secondary: as a result of connective tissue disorder ``` F>M Dry mouth Dry eyes Dry skin Chronic cough Muscle and joint pains Thyroid problems ``` Increase risk of lymphoma ANA +ve SA/Ro SB/La (far more specific)

Question 62

Antithrombin

Answer 62

Inhibits factor IIa and factor Xa

Question 63

Tissue factor pathway inhibitor

Answer 63

Inhibits VII --> VIIa

Question 64

Protein C and S

Answer 64

Inhibits factor Va and VIIIa

Question 65

Antithrombotic Mediators on Endothelium

Answer 65

``` Endothelial expression TFPI Endothelial Protein C TFPI Heparans ``` Secretes Anti-platelet mediators Prostacyclin NO ENDOTHELIUM DOES NOT EXPRESS TISSUE FACTOR

Question 66

Pregnancy and Susceptibility to Thrombosis

Answer 66

Decrease Protein S Increase Factor VIII, Increase Fibrinogen Stasis Compression

Question 67

Malignancy and Susceptibility to Thrombosis

Answer 67

Tissue Factor on tumour Increased Inflammation Decreased Flow

Question 68

Anticoagulant Drugs

Answer 68

Heparin LMWH Unfractionated Potentiate Antithrombin, Factor IIa and Xa Immediate acting (potentiate anti-coagulant activity) ``` Warfarin Vitamin K antagonist Inhibits vitamin K dependent factors: II VII IX and X Delayed action Reduce procoagulant activity ``` New oral anticoag (rivoraxaban) are immediate

Question 69

Heparin

Answer 69

Three forms LMWH (subcut) Unfractionated (IV only) Pentasaccharide (subcut) Provide immediate effect (eg for treatment of thrombosis) Disadvanatges Long term disadvantage – have to be given by injections, risk of osteoporosis Difficult to dose: Variable renal dependence Low molecular weight heparin (LMWH) Reliable pharmacokinetics so monitoring not usually required Can use anti-Xa assay in at-risk eg: Renal failure (CrCl<50) Extremes of weight or risk In anti-Xa assay you measure ability to potentiate antithrombin in its inhibition of thrombin and Xa Unfractionated heparin Much more complex, Variable kinetics Variable dose-response Always monitor therapeutic levels with APTT or anti-Xa

Question 70

Direct acting anticoagulants

Answer 70

Anti-Xa Rivaroxaban, apixaban, edoxaban Anti-IIa Dabigatran ``` Properties Oral administration Immediate acting –peak in approx. 3-4 hours (cf LMWH) Short half-life No monitoring ``` New agents Oral admin Reliable dose response, No monitoring

Question 71

Warfarin

Answer 71

Oral Only anti-coagulant that can be used for metallic heart valves Indirect effect by preventing recycling of Vit K Action is delayed II, VII, IX & X Takes some time to fall Levels of anticoagulant protein C and protein S also fall (also vit K factors, transient increase thrombotic risk at onset)

Question 72

Reversal of Heparin

Answer 72

Protamine

Question 73

Low molecular weight heparin (LMWH) dosing

Answer 73

Thromboprophylaxis Tinzaparin 4500U Clexane 40mg

Question 74

Risk Factors for VTE

Answer 74

``` Patient Factors Age > 60yrs Previous VTE Active cancer Acute or chronic lung disease Chronic heart failure Lower limb paralysis (excluding acute CVA) Acute infection BMI>30 ``` ``` Procedure (circumstance) Hip or knee replacement Hip fracture Other major orthopaedic surgery Surgery > 30mins Plaster cast immobilisation of lower limb ```

Question 75

Bleeding risk assessment

Answer 75

``` Patient Factors Bleeding diathesis (eg haemophilia, VWD) Platelets < 100 Acute CVA in previous month (H’gge or thromb) BP > 200 syst or 120 dias Severe liver disease Severe renal disease Active bleeding Anticoag or anti-platelet therapy ``` Procedure Neuro, spinal or eye surgery (v high risk if bleeding occurs) Other with high bleeding risk Lumbar puncture/spinal/epidural in previous 4 hours

Question 76

Treatment of DVT/PE

Answer 76

``` Start LMWH eg Tinzaparin 175u/kg + warfarin Start Warfarin at the same time, measure INR Stop Hep when OK Stop LMWH when INR >2 for 2 days ``` Continue for 3-6 months, takes this for patients to settle Patients with cancer: continue LMWH not warfarin. ``` OR Start Rivaroxaban (NEW WAY) ``` DOES NOT DISSOLVE CLOT, STOPS PROPAGATION OF CLOT

Question 77

Thrombolysis

Answer 77

About to die or critical limb Only for life threatening PE or limb threatening DVT Risk of haemorrhage(Intracranial Haemorrhage) 4% Reduces subsequent post-phlebitic syndrome Indications broadening slowly Same treatment for stroke, potentiate fibrinolysis (TPA) tissue plasminogen activator

Question 78

Risk of VTE recurrent

Answer 78

Higher risk (put on on long-term anticoag) Idiopathic thrombosis (no external stimulus) Male Have higher d-dimer after coming off anticoagulant --> high risk of recurrence

Question 79

Presentation of Anaemia in Cancer

Answer 79

Fe Deficiency (Occult blood loss) GI cancer: Gastric, colonic Urinary tract cancer: Renal cell carcinoma, bladder cancer Anaemia of Inflammation Leucoerythroblastic anaemia --> bone marrow infiltration Cancer Myrelofibrosis Severe Infection Haemolytic anaemias Immune mediated Non Immune; fragmentation (micro-angiopathic haemolytic anaemia)

Question 80

Leucoerythroblastic anaemia

Answer 80

Bone Marrow Infiltration Cancer Haematopoietic: Leukaemia, Lymphoma, Myeloma Non-Haematopoietic: Breast, Bronchus, Prostate Severe Infection: Miliary TB Severe Fungal Infection Myelofibrosis Dry tap apriate of BM MASSIVE Splenomegaly

Question 81

Myelofibrosis

Answer 81

Bone marrow failure due to progressive scarring Leukoerythroblast changes Dry tap on BM aspirate Massive splenomegaly May eventually develop a serious form of acute leukaemia

Question 82

Haemolytic Anaemia

Answer 82

Inherited: Defects of the red cell. OR Acquired: Defects of the environment in which the Red cell finds itself, the red cell itself is fine ``` Anaemia (though may be compensated) Reticulocytosis Raised Bilirubin (unconjugated) Raised LDH Reduced haptoglobins ``` In bone marrow failure, you can't increase red cell output so you don't see reticulocytosis and the anaemia is not compensated

Question 83

Inherited Haemolytic Anaemias

Answer 83

Membrane Spherocytosis Elliptocytosis Haemoglobin Mutation of beta chain, structurally abnormal beta chain --> Structural (sickle cell disease) Quantitative (thallasaemias) imbalance between alpha and beta chains Enzymes G6PD Continual Red Cell breakdown --> pigment stones

Question 84

Acquired Haemolytic Anaemia

Answer 84

Immune OR Non-Immune DAT test +ve --> IMMUNE Diseases that produce autoimmune haemaolytic immune - Cancer of immune system: lymphoma or lymphocytic leukaemias - Disease of the immune system: SLE or Sjorgen’s - Infection (disturbing the immune system) e.g. Mycoplasma Mycoplasma = Cold agglutinin disease is an autoimmune disease characterized by the presence of high concentrations of circulating antibodies, usually IgM, directed against red blood cells In autoimmune haemolytic anemia you also get acquire spherocytes DAT NEG --> NON-immune These diseases damage the red cells but are not immune mediated Infection (malaria) gets into red cell Micro-angiopathic Haemolytic anaemia (MAHA) Red cell fragments low platelets (activation of clotting system) DIC/bleeding Underlying adenocarcinoma (prostate or stomach)

Question 85

Coombs Test

Answer 85

Direct coombs = DAT Test Used to test for autoimmune hemolytic anemia Tests for presence of IgG on Red cells Blood sample is taken and the RBCs are washed (removing the patient's own plasma) and then incubated with anti-human globulin (also known as "Coombs reagent"). If this produces agglutination of RBCs, the direct Coombs test is positive# AND Indirect coombs Used in prenatal testing of pregnant women and in testing blood prior to a blood transfusion Detects antibodies against RBCs that are present unbound in the patient's serum Serum is extracted from the blood sample taken from the patient. Then, the serum is incubated with RBCs of known antigenicity; that is, RBCs with known reference values from other patient blood samples. Finally, anti-human globulin is added. If agglutination occurs, the indirect Coombs test is positive.

Question 86

micro-angiopathy haemolytic anaemia from an adenocarcinoma

Answer 86

Low grade DIC Occult cancer secreting pro-thrombotic factors into blood Activated coagulation pathway Coagulation systemic throughout blood – not confined to local site ``` In microvasculature Blood flow slow Pro-coagulation factors At sites of slow flow, fibrin able to be formed Fibrin goes across blood vessel Causes red cell trauma Fragmented cells Platelets consumed s part of process ```

Question 87

Polycythaemia

Answer 87

Appropriate e.g. high altitude True: polycythaemia vera Secondary: Ectopic Erythropoietin Hepatocellular carcinoma Renal cancer Bronchial cancer

Question 88

Causes of Neutrophilia

Answer 88

TIMUC Corticosteroids (demargination of neutrophils --> apparent increase) Underlying neoplasia Tissue inflammation (e.g.colitis, pancreatitis) Myeloproliferative/ leukaemic disorders Infection -itis Reactive: Neutrophil count up to 15 --> infection or malignant Presence bands, toxic granulation, and signs of infection/inflammation Malignant: Neutrophil count 250 --> leukaemia Find neutrophils along with immature cells: Neutrophilia basophilia plus immature cells myelocytes, and splenomegaly. Suggest a myeloproliferative (CML) Neutropenia plus precursors cells (Myeloblasts) (AML)

Question 89

Eosinophilia

Answer 89

Reactive eosinophilia Parasitic infestation allergic diseases e.g. asthma, rheumatoid, polyarteritis,pulmonary eosinophilia. Underlying Neoplasms, esp. Hodgkin’s, T-cell NHL (reactive eosinophilia)- lymphoma secretes eosinophil secreting factor Drugs (reaction erythema mutiforme) Chronic Eosinophilic leukaemia Eosinophils part of the “clone” FIP1L1-PDGFRa Fusion gene

Question 90

Monocytosis

Answer 90

``` Rare but seen in certain chronic infections and primary haematological disorders TB, brucella, typhoid Viral; CMV, varicella zoster sarcoidosis chronic myelomonocytic leukaemia (MDS) ```

Question 91

Lymphoid Vs Myeloid Clinical Distinguishing Factor

Answer 91

If you have splenomegaly and hepatomegaly and no lymph nodes --> Myeloid disorder Haemopoiesis can go back to where it occurred in fetal, in liver If you have splenomegaly and hepatomegaly and lymphadenopathy --> lymphoid disorder

Question 92

Lymphoma Associated with Antigenic Stimulation

Answer 92

H.Pylori : Gastric MALT (mucosa associated lymphoid tissue) lymphoma Sjogren’s syndrome : Parotid lymphoma Autoimmune thyroid disease --> thyroid marginal lymphomas Coeliac disease: small bowel T cell lymphoma EATL (enteropathy associated T-Cell lymphoma)

Question 93

Lymphoma Associated with Translocation

Answer 93

Lymphoma associated translocations e.g. t(8,14) ``` Involve the Ig Locus Ig promoter highly active in B cells Bring intact oncogenes close to the Ig promoter Oncogenes may be anti apoptotic, proliferative. bcl2 bcl6 Myc cyclinD1 ```

Question 94

Risk Factors for Lymphoma

Answer 94

Constant antigenic stimulation Infection( direct viral infection of lymphocytes) Loss of T cell function (HIV and Immunosuppression)

Question 95

Lymphoma and Infectious Agents

Answer 95

1) Direct Viral Integration HTLV1 infects T cells by vertical transmission Carribean and Japan May develop Adult T cell leukaemia lymphoma (2.5% at 70 years) 2) Immunosuppression + EBV infection EBV infects B lymphocytes Carrier state and regulated by healthy T cells Iatrogenic supression of T cells (to prevent transplant rejection increase in B cell lymphomas) 3) HIV 60 fold increase in lymphoma in HIV (high grade B-NHL) Loss of T cell regulation of EBV infected B cells

Question 96

Immuno Markers

Answer 96

B Cell CD20 Immature blast B cell = TDT Cyclin D1 not normally expressed by B cells, Expression of cyclin D1 indicative of mantle cell lymphoma CD5 expression in B cells indicative of mantle B cell lymphoma OR small lymphocytic lymphoma (CD5 is normally a T cell marker) T Cell CD3 CD5

Question 97

Mantle Cell Lymphoma

Answer 97

Middle aged male Lymph node, GI tract Present in mantle zone Median survival 3-5 yrs B cell expressing cyclin D1 CD5 Translocation t(11,14) = diagnostic

Question 98

Follicular Lymphoma

Answer 98

Lymphadenopathy in the elderly CD10 bcl-6 +ve t(14,18) involving bcl-2 gene

Question 99

Small Lymphocytic Leukaemia

Answer 99

Middle aged/ Elderly Nodes or blood Small lymphocytes, naive or post-germinal centre B cell CD5 CD23 Indolent Undergo Ritcher transformation into high grad elymphoma

Question 100

Marginal Zone / MALT lymphoma

Answer 100

Arise at extranodal sites e.g. Gut, lung, Spleen In response to chronic stimulation form antigen e.g. H.Pylori Post germinal centre memory B cell Indolent, but can transform into high grade lymphoma Can treat if remove antigen stimulation early

Question 101

Burkitt's Lymphoma

Answer 101

Jaw or abdominal mass in Children EBV associated Immunodeficiency Sporadic Stary-sky appearance C-myc t(8,14) Aggressive

Question 102

Diffuse Large B Cell

Answer 102

Middle aged/Elderly Lymphadenopathy Germinal centre or post-germinal centre B cell Sheets of large lymphoid cells p54 positive

Question 103

Peripheral T Cell Lymphoma

Answer 103

Middle aged/ Elderly Lymphadenopathy and extra nodal sites Large T lymphocytes Associated with reactive cells e.g. eosinophils Aggressive

Question 104

Special Forms of T Cell Lymphoma

Answer 104

Adult T Cell Leukaemia / Lymphoma HTLV-1 Japan and Caribbean endemic Enteropathy associated T cel lymphoma Longstanding Coeliac Cutaneous T cell lymphomas Mycosis fungiodes Anaplastic large cell lymphoma

Question 105

Anaplastic Large Cell Lymphoma

Answer 105

Children/ Young adults Lymphadenopathy Large epitheloid lymphocytes T cell or null phenotype t(2,5) Alk-1 Agressive BUT alk-1 expression = better prognosis

Question 106

Non-Hodgkin's Lymphoma

Answer 106

Multiple nodal sites Spreads discontinuously B Cell T Cell

Question 107

Hodgkin's Lymphoma

Answer 107

Single nodal site Spreads continuously Split into Classical and Lymphocyte predominant ``` Classical Three subtypes Nodular sclerosing Mixed cellularity Lymphocyte rich and Lymphocyte depleted ``` Lymphocyte predominant = some relation to non-hodgkin's lymphoma

Question 108

Classical Hodgkin's Lymphoma

Answer 108

Young/Middle aged Single site of nodes germinal centre or post-germinal centre B cell EBV associated Sclerosis Mixed cellularity Reed-Sternberg and Hodgkin cells with eosinophils Rarely Alcohol-induce pain

Question 109

Nodular Lymphocyte Predominant Hodgkin's Lymphoma

Answer 109

Isolated lymphadenopathy Germinal centre B cell B cell rich nodules with scattered L&H cells NO ASSOCIATION WITH EBV Can transform into high grade B cell lymphoma

Question 110

B Cell Non-Hodgkin Lymphomas

Answer 110

``` Low Grade Follicular lymphoma Small lymphocytic lymphoma/ Chronic lymphocytic leukaemia Marginal zone lymphoma Mantle zone lymphoma ``` High Grade Diffuse large B cell lymphoma Intermediate Burkitt's Lymphoma

Question 111

Staging of Hodgkin Lymphoma

Answer 111

``` Stage I; one group of nodes II; >1 group of nodes same side of the diaphragm III; nodes above and below the diaphragm IV; extra nodal spread ``` Suffix A if none of below, B if any of below Fever Unexplained Weight loss >10% in 6 months Night sweats

Question 112

Treatment of Hodgkin Lymphoma

Answer 112

Chemotherapy for all cases (ABVD) ABVD 2-6 cycles +/- Radiotherapy PET CT Interim: post x2 cycles, response assessment End of Treatment: Guides need for radiotherapy Relapse then Autologous Stem cell transplant as salvage ``` Chemotherapy ABVD Adriamycin Bleomycin Vinblastine DTIC ABVD, is given at 4-weekly intervals. ``` ``` Effective treatment Preserves fertility (unlike MOPP the original chemo) Can cause (long term) Pulmonary fibrosis cardiomyopathy ```

Question 113

Treatment of Diffuse Large B Cell Lymphoma

Answer 113

``` International Prognostic Index (IPI) Age > 60y serum LDH > normal performance status 2-4 stage III or IV more than one extranodal site ``` Treated by x 6-8 cycles of R-CHOP (Rituximab-CHOP) ``` Combination drug regimens e.g. CHOP Cyclophosphamide Adriamycin Vincristine Prednisolone ``` Doxorubicin Relapse: Autologous Stem Cell transplant salvage 25% of patients

Question 114

Chronic Lymphocytic Leukaemia

Answer 114

Proliferation of mature B-lymphocytes ``` Age at presentation median 72 Commonest leukaemia in the western world Lymphocytosis between 5 and 300 x 109/l Smear cells Normocytic normochromic anaemia Thrombocytopenia Bone marrow Lymphocytic replacement of normal marrow elements ``` Mature B cells (CD19) co-expressing CD5 Further immuno studies CLL score 4-5 ``` CLL Score (Need 4/5) CD5 CD23 FMC7 CD79b SmIg ``` Binet and Rai staging CD38 expression = bad prognosis Deletion of 17p (TP53) = bad prognosis unmutated IgH gene = bad prognosis CD5 also expressed in Mantle Cell Lymphoma Normally a T cell marker

Question 115

Treatment of CLL

Answer 115

Prophylaxis and treatment of infections Aciclovir PCP prophylaxis for those receiving fludarabine or alemtuzumab (Campath) IVIG is recommended for those with hypogammaglobulinemia and recurrent bacterial infections Immunisation against pneumococcus, and seasonal flu Auto-immune phenomena 1st Line Steroids 2nd Line Rituximab Irradiated Blood products if risk of TA GVHD

Question 116

Variants of CLL

Answer 116

Transformation to high grade lymphoma = Richter’s syndrome ~1% per year Treat as high grade lymphoma with CHOP-R

Question 117

BCR Kinase inhibitors

Answer 117

New drugs in CLL Ibrutinib Idelalisib

Question 118

Myelodysplastic Syndromes

Answer 118

Typically a disorder of the elderly. (over 60) Common in 70s Symptoms/signs are those of general marrow failure Develops over weeks & months Development of clone marrow stem cells with abnormal cell development - -> functionally defective blood cells - -> numerical reduction Cytopenia Anaemia --> tiredness, lethargy, severely anaemic --> heart failure Neutropenia --> infection Thrombocytopenia --> bleeding AND Increased risk of transformation to leukaemia

Question 119

Myelodysplastic Features in Bone Marrow and Blood

Answer 119

Pelger Huet = bilobed neutrophils Ring sideroblast = iron arranged in ring Dysgranulopoiesis of neutrophils = abnormal granules Myelokathexis of neutrophils = abnormal appearance of neutrophils and pre-cursors in bone marrow Dyserythropoiesis of red cells = Abnormal red cells in the bone marrow (bridge sand blebbing) Dysplastic megakaryocytes = Abnormally small megakaryocytes INCREASED PROPORTION OF BLAST CELLS (normally <5%) --> prognostic significant More than 20% = defined as having an Acute Leukaemia Auer rods stain deep red They are indicative of acute myeloid leukaemia

Question 120

WHO classification of MDS

Answer 120

Refractory anaemia (RA) - without ringed sideroblasts - with ringed sideroblasts (RARS) Refractory cytopenia with multilineage dysplasia (RCMD) Refractory anaemia with excess of blasts (RAEB) - RAEB-I (BM blasts 5-9%) - RAEB-II (BM blasts 10-19%) 5q- syndrome Unclassified MDS: MDS with fibrosis, childhood MDS, others

Question 121

The Revised International Prognostic Scoring System IPSS-R

Answer 121

``` BM blasts % Karyotype Hb Neutrophils Platelets ``` 0 = Good 4=Bad Used to predict risk of development of AML Treatment choices

Question 122

Prognosis of MDS

Answer 122

Deterioration of blood counts Worsening consequences of marrow failure Development of acute myeloid leukaemia – Develops in 50%< 1 year – Some cases of MDS are much slower to evolve – AML from MDS has an extremely poor prognosis and is usually not curable As a rule of thumb • 1/3 die from infection • 1/3 die from bleeding • 1/3 die from acute leukaemia

Question 123

Treatment of MDS

Answer 123

Prolong survival: - allogeneic stem cell transplantation (SCT) - intensive chemotherapy ``` Supportive care Blood product support Antimicrobial therapy Growth factors (Epo, G-CSF) EPO = red cells G-CSF = neutrophils ``` ``` Biological Modifiers Immunosuppressive therapy Hypomethylating agents Azacytidine Lenalidomide (5q- syndrome) ``` Oral chemotherapy Hydroxyurea Low dose chemotherapy Subcutaneous low dose cytarabine Intensive Chemotherapy/SCT AML type regimens Allo/VUD standard/ reduced intensity

Question 124

Bone Marrow Failure

Answer 124

Failure of stem cell Depending on whereabouts in lineage the stem cell fails --> different outcome Could fail to make lymphocytes and myeloid Or either depending on location of failure Results from damage or suppression of stem or progenitor cells PLURIPOTENT HAEMATOPOIETIC CELL - Impairs production of ALL peripheral blood cells - rare COMMITTED PROGENITOR CELLS - Result in bi- or unicytopenias

Question 125

Causes of Bone Marrow Failure

Answer 125

Primary Congenital Fanconi's Anaemia --> MULTIPOTENT Diamond-Blackfan Anaemia --> Red cell progenitor Kostmann Syndrome --> neutrophil progenitor Acquired Primary: Idiopathic aplastic anaemia --> MULTIPOTENT ``` Secondary Bone Marrow Infiltration (haematological = leukaemia, lymphoma, myelofibrosis, non-haematological = solid tumour) Radiation Drugs Chemicals (Benzene) Autoimmune Infection (Parvovirus, Hepatitis) ```

Question 126

Drugs causing Bone Marrow Failure

Answer 126

Cytotoxic Antibiotics Chloramphenicol Sulphonamide Diuretic Thiazide Anti-Thyroid Carbomazole

Question 127

Aplastic Anaemia

Answer 127

Aplastic Anaemia = Pancytopenia Subtype of Bone Marrow Failure in which all three cell lines are NOT produced CLASSIFICATION: 1. Severe aplastic anaemia (SAA) 2. Non-severe aplastic anaemia (NSAA) Camitta criteria: 2 out of 3 peripheral blood features 1. Reticulocytes < 1% (<20 x 109/l) 2. Neutrophils < 0.5 x 109/l 3. Platelets < 20 x 109/l AND Bone marrow <20% cellularity MULTIPOTENT defect - “Stem cell” problem (CD34, LTC-IC ``` Causes Primary Idiopathic - 70% (Telomeric shortening is a feature of both idiopathic aplastic anaemia and dyskeratosis congenita) Fanconi's Anaemia Dyskeratosis congenita Schwman-Diamond Syndrome ``` ``` Secondary Radiation Drugs: chloramphenicol Infection: hepatitis SLE ``` Immune attack: Humoral or cellular (T cell) attack against multipotent haematopoietic stem cell.

Question 128

Dyskeratosis Congenita

Answer 128

3 patterns of inheritance Abnormal telomeric structure and function is implicated. Telomere length is reduced X-linked recessive trait = mutated DKC1 gene - defective telomerase function Autosomal dominant trait = mutated TERC gene RNA component of telomerase Autosomal recessive trait, gene not yet been identified Progressive bone marrow failure --> aplastic anaemia Cancer predisposition Somatic abnormalities Triad of: Reticulated skin hyperpigmentation, Nail dystrophy Oral leukoplakia Tx: Supportive Blood/platelet transfusions Antibiotics Drugs to promote marrow recovery Oxymetholone Growth factors Haemopoietic stem transplantation Telomeric shortening is a feature of both idiopathic aplastic anaemia and dyskeratosis congenita

Question 129

Schwman-Diamond Syndrome

Answer 129

Congenital disorder characterized by: Exocrine pancreatic insufficiency Bone marrow dysfunction --> Aplastic anaemia Skeletal abnormalities Short stature

Question 130

Differential Diagnoses of Pancytopenia & Hypocellular Marrow

Answer 130

Hypoplastic MDS / Acute Myeloid Leukaemia Hypocellular Acute Lymphoblastic Leukaemia Hairy Cell Leukaemia Mycobacterial (usually atypical) infection Anorexia Nervosa Idiopathic Thrombocytopenic Purpura

Question 131

Management of Bone Marrow Failure

Answer 131

Seek a cause (detailed drug & occupational exposure history) Supportive Blood/platelet transfusions (leucodepleted, CMV neg, irradiated) Antibiotics Iron Chelation Therapy (avoid iron overload) Drugs to promote marrow recovery Oxymetholone (=anabolic steroid) Growth factors Immunosuppressive therapy (due to t cell attack of bone marrow) Stem cell transplantation

Question 132

Treatment for Idiopathic Aplastic Anaemia

Answer 132

Immunosuppressive therapy – older patient Anti-Lymphocyte Globulin (ALG) Ciclosporin Androgens – oxymethalone Stem cell transplantation Younger patient with donor (80% cure) VUD/MUD for > 40 yrs (50% survival)

Question 133

Fanconi's Anaemia

Answer 133

Autosomal recessive/ X-linked - -> abnormalities in DNA repair - -> chromosoma fragility *in vitro addition of diepoxybutane or Mitomycin --> chromosomal breakages Normal blood count at birth Marrow failure and pancytopenia slowly progress onset at 5-10 years 10% result in acute leukaemia Tx: Supportive Androgens

Question 134

full blood count in pregnancy

Answer 134

Mild anaemia (due to net dilution) Red cell mass rises (120 -130%) Plasma volume rises (150%) Macrocytosis Normal Check Folate or B12 deficiency Neutrophilia Thrombocytopenia increased platelet size Incidental thrombocytopenia in third trimester Not due to volume expansion As plasma volume expansion finished by end of second trimester

Question 135

Causes of Thrombocytopenia in Pregnancy

Answer 135

1) Physiological (normal to have lower platelets in pregnancy) 2) Pre-Eclampsia (HELLP) 3) Immune thrombocytopenia 4) MAHA = Schisyocytes HELLP (remits after delivery) TTP and HUS (do not remit after delivery) 5) All others: Bone marrow failure Leukaemia Hypersplenism Lower the platelets --> more likely pathological *NEED >70 for epidural

Question 136

Iron Deficiency in pregnancy

Answer 136

``` May Cause: Anaemia IUGR Prematurity Postpartum haemorrhage ```

Question 137

Coagulation changes in pregnancy

Answer 137

Increase in: von Willebrand Factor VIII PAI-2 (placenta produced) Decrease in: Protein S

Question 138

Antiphospholipid Syndrome

Answer 138

Recurrent miscarriages Lupus anticoagulant positive Anti-cardiolipin antibody Obstetric outcome improved with herparin and aspirin

Question 139

Myeloproliferative Disorders

Answer 139

``` Ph Neg Polycythaemia vera (PV) Essential Thrombocythaemia (ET) Primary Myelofibrosis (PMF) ``` Ph Pos Chronic myeloid leukaemia (CML)

Question 140

Myeloproliferative Disorders Gene Mutation

Answer 140

JAK2 = PV Calreticulin MPL

Question 141

Polycthaemia vera treatment

Answer 141

Venesection Hydroxycarbamide Aspirin

Question 142

Essential thrombocythaemia treatment

Answer 142

Aspirin Anagrelide Hydroxycarbamide

Question 143

Treatment of Primary Myelofibrosis

Answer 143

Anaemia --> transfusion Splenectomy --> symtpomatic relief Thrombocytosis --> hydroxycarbamide Ruxolotinib = JAK2 inhibitor Bone marrow transplant

Question 144

Treatment of CML

Answer 144

Imatinib | 2nd generation: Dasatanib, and Nilotinib

Question 145

Treatment of Multiple Myeloma

Answer 145

Melphalan (mustard-type alkylating agent) Steroids Proteasome inhibitors IMIDs“ - Thalidomide, Lenalidomide, Pomalidomide

Question 146

Treatment of Graft vs Host Disease

Answer 146

``` Corticosteroids Cyclosporin A FK506 Mycophenylate mofetil Monoclonal antibodies (against T cells) Photopheresis Total lymphoid irradiation ```

Question 147

Prevention of GvHD

Answer 147

``` Methotrexate Corticosteroids Cyclosporin A CsA plus MTX FK506 ``` T-cell depletion

Question 148

T(15,17)

Answer 148

T(15,17) Translocation of retinoic acid receptor Acute promyelocytic leukaemia Responsive to trans retinoic acid (ATRA) aka tretinoin

Question 149

AML Disease Hotspots, Mutations and Translocations

Answer 149

Duplication +8 +21 gives predisposition Loss deletions and loss of 5/5q & 7/7q Common mutations NPM1 CEBPA FLT3: internal tandem duplication = bad prognosis Translocations = Core binding Factor Changes --> cause arrest of cell development t(8;21) fuses RUNX1 (encoding CBFα) with RUNX1T1 15% of adult AML inv(16) fuses CBFB with MYH11 12% of adult AML inv(16) , t(16;16) --> eosinophilic subtype

Question 150

Acute Promyelinocytic Leukaemia

Answer 150

t(15,17) = PML:RARA Causes thrombocytopenia Can present with haemorrhage of easy bruising Because of coagulation defects and low platelets Hyperactive fibrinolysis Can cause DIC Treated with ARTA – all trans retinoic acid (not chemotherapy) Nearly all curable Block in differentiation is further down pathway – excess of promyelocytes

Question 151

AML vs CML Cytochemistry

Answer 151

Cytochemical stain AML ALL Myeloperoxidase + (Gr) - Sudan black + (Gr) - Non-specific esterase + (Mo) - All negative = ALL

Question 152

AML vs ALL immunohistochemistry

Answer 152

ALL: Precursor-B-cell: CD19, CD20, TdT, CD10 +/- B-cell: CD19, CD20, surface Ig T-cell: CD2, CD3, CD4, CD8,TdT AML: MPO, CD13, CD33, CD14, CD15 glycophorin (E), platelet antigens Both: CD34, CD45, HLA-DR

Question 153

Clinical features of AML

Answer 153

Bone marrow failure Anaemia Neutropenia Thrombocytopenia ``` Local infiltration into tissues Splenomegaly Hepatomegaly Gum infiltration (if monocytic) Lymphadenopathy (only occasionally) Skin, CNS or other sites (Cranial nerve palsy) ``` Complications septic shock Complicated by renal failure DIC

Question 154

Clinical features of ALL

Answer 154

Bone marrow failure — effects of Anaemia Neutropenia Thrombocytopenia ``` Local infiltration Lymphadenopathy (± thymic enlargement) Splenomegaly Hepatomegaly Testes, CNS, kidneys or other sites Bone (causing pain) ``` Lymphoid cells are more likely to enter lymph nodes T cells --> thymus enlargement Bone pain in long bones of children

Question 155

Hereditary Haemolytic Anaemias

Answer 155

Red cell membrane defects Hereditary spherocytosis Hereditary elliptocytosis Haemoglobin defects Sickle cell anaemia Glycolytic pathway defects Pyruvate kinase deficiency Pentose shunt defects G6PD deficiency

Question 156

Paroxysmal Nocturnal Haemoglobinuria

Answer 156

Destruction of red blood cells by the complement system Only hemolytic anemia caused by an acquired (rather than inherited) intrinsic defect in the cell membrane (deficiency of glycophosphatidylinositol leading to the absence of protective proteins on the membrane) GPI anchor missing GPI binds complement regulatory proteins Red urine in the morning

Question 157

cholelithiasis in chronic haemolytic anaemia

Answer 157

Coinheritance of Gilbert syndrome further increases risk of cholelithiasis in chronic haemolytic anaemia

Question 158

Reduced/absent haptoglobins

Answer 158

Intravascular haemolysis

Question 159

Hereditary spherocytosis

Answer 159

Vertical interaction Band 3 Protein 4.2 Ankyrin Beta Spectrin Autosomal dominant Osmotic fragilty test Reduced binding of dye eosin-5-maleimide Blood film Looks spherical Looks dense Mean cell haemoglobin conc is increased

Question 160

Hereditary elliptocytosis

Answer 160

Horizontal interaction Alpha Spectrin Beta Spectrin Protein 4.1 Hereditary pyropoikilocytosis = homozygous form

Question 161

Glucose-6-phosphate dehydrogenase deficiency

Answer 161

X-linked Enzyme catalyses first step in pentose phosphate(hexose monophosphate) pathway - generates NADPH required to maintain intracellular glutathione(GSH) Clinical effects Neonatal jaundice Acute haemolysis(triggered by oxidants/infection) Chronic haemolytic anaemia(rare) Drugs, infections or fava beans --> Acute haemolysis ``` Blood Film Nucleated red blood cells Bite cells Hemighosts Poikilocytes Contracted cells **Heinz bodies formed of denatured haemoglobin = Characteristic of oxidative haemolysis ```

Question 162

Agents triggering haemolysis in G6PD

Answer 162

Anti-malarials Primaquine Antibiotics Sulphonamides Ciprofloxacin Nitrofurantoin ``` Other drugs Dapsone Vitamin k Fava beans Mothballs ```

Question 163

Pyruvate kinase deficiency

Answer 163

Echinocytes (sea urchin)

Question 164

Pyrimidine 5’-nucleotidase deficiency

Answer 164

Pyrimidine nucleotides are toxic to red cells but red cells need to retain and salvage purine nucleotides eliminating pyrimidine nucleotides = pyrimidine 5’ nucleotidase Prominent basophilic stickling Lead also inhibits this enzyme

Question 165

Ham's Test

Answer 165

=Flow cytometry of GPI-linked proteins Paroxysmal nocturnal haemoglobinuria

Question 166

Heinz Bodies

Answer 166

Marker of oxidative stress =G6PD (and bite cells present)

Question 167

JAK2 V617F

Answer 167

Polycthaemia vera

Question 168

Idoiopathic erythrocytosis

Answer 168

Isolated erythrocytosis

Question 169

von Willebrand's

Answer 169

Type 1 Partial quantitative deficiency Type 2 Qualitative deficiency Type 3 Total quantitative deficiency (similar to haemophilia A as apparent factor VIII def)

Question 170

Inhibitors of Cell wall Synthesis

Answer 170

Beta-Lactams Penicillins Cephalosporins Carbapenems Glycopeptides Vancomycin Teiciplanin

Question 171

Penicillins

Answer 171

Penicillin Gram positive organisms = streptococci, clostridia Broken down by beta-lactamase Amoxicillin Gram positives and extended to cover enterococci and gram negatives Broken down by beta-lactamse (staph aureus and many gram negs produced) Co-amoxiclav (augmentin) = amoxicillin + clavulanic acid Flucloxacillin Resistant to beta-lactamase Used for staph aureus ``` Piperacillin Similar to amoxicillin Extends coverage to pseudomonas and other non-enteric gram negatives Broken down by beta-lactamase Tazocin = piperacillin + tazobactam ```

Question 172

Cephalosporins

Answer 172

3 Generations (increasing activity against gram negative bacilli with each gen) Need to add in metronidazaole to cover anaerobes First generation = Cephalexin Second generation = Cefuroxime Third generation = Cefotaxime, Ceftriaxone, Ceftazidime Ceftriaxone = 1st line meningitis Ceftazidime = psudomonas coverage, give in cystic fibrosis

Question 173

Carbapenems

Answer 173

Meropenem, Imipenem, Ertapenem Stable to extended spectrum beta-lactamase (ESBL) Broad spectrum Broken down by carbapenemase enzyme --> breaks down all three types of beta-lactams (penicillins, cephalosporins, and carbapenems) Multi-drug resistant acinetobacter and klebsiella species

Question 174

Glycopeptides

Answer 174

Vancomycin and Teicoplanin Unable to penetrate gram negative outer cell wall Active against gram positives Inhibit cell wall synthesis Bind to D-Ala D-Ala and prevent cross-linking Slowly bactericidal Nephrotoxic: must monitor levels and check for accumulation MRSA oral for serious C.Diff

Question 175

Antibiotics inhibiting Protein Synthesis

Answer 175

Aminoglycosides Gentamicin Amikacin Tobramycin Tetracyclines Doxycycline Macrolides Erythromycin Clarithromycin Azithromycin Linocosamides Clindamycin Streptogramins Synercid Chloramphenicol Oxazolidinones Linezolid

Question 176

Aminoglycosides

Answer 176

Gentamicin Akimacin Tobramycin ``` 30S ribosomal subunit Streptococci are intrinsically resistant (requires specific transporter) no activity against anaerobes Ototoxic and nephrotoxic used synergistically with beta-lactams ``` Bactericidal Gentamicin and tobramycin active against pseudomonas

Question 177

Tetracyclines

Answer 177

Doxycycline Activity against intracellular pathogens Chlamydia Mycoplasma Rickettsiae Bacteriostatic Reversibly bind to 30S subunit Light-sensitive rash Do not give to children or pregnancy women

Question 178

Macrolides

Answer 178

Erythromycin Clarithromycin Azithromycin Bind to 50S subunit Bacteriostatic Minimal activity against gram negatives USed for streptococcal infections and mild staphylococcus in penicillin-allergic patients Also active against atypical pneumonias Campylobacter Legionella

Question 179

Chloramphenicol

Answer 179

Broad spec Used in eye preparations Risk of aplastic anaemia Grey baby syndrome Bacteriostatic 50S subunit

Question 180

Oxazolidinones

Answer 180

Linezolid Highly active against gram positive (including MRSA and VRE) Not active against gram negatives Bind to 23S of 50S subunit May cause thrombocytopenia and neurological problems

Question 181

Inhibitors of DNA synthesis

Answer 181

Flouroquinolones Ciprofloxacin Levofloxacin Moxifloxacin Nitroimidazoles Metronidazole Tinidazole

Question 182

Fluoroquiniolones

Answer 182

Ciprofloxacin Levofloxacin Moxifloxacin Act on alpha subunit of DNA gyrase Bactericidal Gram negatives including pseudomonas Levofloxacin and moxifloxacin also against gram positive and intracellular bacteria e.g. chlamydia ``` Use for UTIs Pneumonia Atypical pneumonia Bacterial gastroenteritis e.g. salmonella ```

Question 183

Nitroimidazoles

Answer 183

Metronidazole Tinidazole Active against anaerobes and protozoa (Giardia) Bactericidal

Question 184

Inhibitors of RNA synthesis

Answer 184

Rifampicin Rifabutin

Question 185

Rifampicin

Answer 185

Mycobacterium e.g. TB Binds to DNA-dependent RNA polymerase Bactericidal Monitor LFTS induces CYP450 Turns secretions orange

Question 186

Daptomycin

Answer 186

Cell membrane toxin MRSA and VRE

Question 187

Antibiotics inhibiting Folate Metabolism

Answer 187

Sulfonamides: Sulphamethoxazole Diaminopyrimidines: Trimethoprim

Question 188

Co-trimoxazole

Answer 188

trimethoprim + sulphamethoxazole Used in PCP

Question 189

Eagle Effect

Answer 189

Penicillins don't work unless dividing If large bacterial burden --> no active replication as nutrient deficiency --> penicillins won't work

Question 190

Cytomegalovirus

Answer 190

Usually minimally symptomatic and self-limiting Can cause mild mononucleosis-like illness and hepatitis Groundglass appearance on CT Owl's eye inclusion Retinal haemorrhages Remains latent in bone marrow and monocytic cells

Question 191

Epstein-Barr Virus

Answer 191

Exudative pharyngitis Atypical lymphocytosis Infectious mononucleosis Associated with lymphoproliferative disease in immunosupressed Burkitt's Post-transplant lymphoproliferative disease (PTLD)

Question 192

Antivirals for CMV

Answer 192

Ganciclovir (given to all transplant recipients) Valganciclovir (pro-drug of ganciclovir) Foscarnet Cidofovir All very toxic

Question 193

Classification of Human herpesvirus

Answer 193

Alpha = rapid growth and latency in sensory ganglia HSV-1 - oral HSV-2 - genital VZV Beta = slow-growth restricted range CMV HHV-6 HHV-7 Gamma = oncogenic EBV HHV-8

Question 194

HHV-8

Answer 194

Kaposi's sarcoma Multicentric Castleman's disease

Question 195

Timing of Vaccine Ractions

Answer 195

Inactivated: within 48 hours Live attenuated, need time to replicate Measles: rash, fever, malaise 6-11 days Rubella: pain, stiffness, swelling of joints 2nd week Mumps: parotid swelling 3rd week

Question 196

Acellular vaccines

Answer 196

Pertussis Diptheria toxoid Hib polysaccharide

Question 197

Diptheria

Answer 197

Bacteria = corynebacterium diptheria or corynebacterium ulcerans Airborne Bull neck Early: mild fever, swollen neck glands, anorexia, malaise, cough 2-3 days: grey membrane of dead cells form in throat, tonsils, larynx or nose "pseudomembrane" Untreated: Infectious for up to 4 weeks 5-10% extensive organ damage: neurological and heart damage

Question 198

Tetanus

Answer 198

Clostridium tetani: forms spores that can survive in environment Non-communicable: infection by contamination of cut with soil or manure Incubation 4-21 days No natural immunity, ever if you have had tetanus, need to be immunised Muscle stiffness, lock-jaw Followed by neck stiffness, difficulty swallowing, stiffness of stomach muscles, muscle spasm, sweating and fever Complications: fractures, laryngospasm, PE, aspiration, Death neonatal tetanus due to infection of umbilical cord stump

Question 199

Pertussis

Answer 199

Whooping cough Bordatella pertussis 3 x 2 week phases: Catarrhal phase: URI Paroxysmal phase: paroxysms of coughing, inspiratory whoop, vomiting, apnoeic episodes Convalescent phase: resolution but dry cough may persist for months Acellular pertussis vaccine

Question 200

Poliomyelitis

Answer 200

Transmission through contact with faeces or pharyngeal secretions Can be asymptomatic Mild-influenza-like illness <1% result in flaccid paralysis (develops 1-10 days after prodromal illness)

Question 201

Meningococcal vaccines

Answer 201

Meningococcal C: conjugate vaccine (polysaccharides chemically joined to tetanus or diptheria carrier proteins) Men B: recombinant vaccine Men ACWY: quadrivalent

Question 202

Pneumococcal vaccines

Answer 202

PPV:purified polysaccharide vaccine = pneumovax II 23 serotypes PCV: conjugated pneumococcal vaccine = Prevanar 13 13 valent

Question 203

Measles

Answer 203

Morbillivirus negative sense SSRNA Airborne Incubation: 7-18 days Prodromal period: High fever and 3Cs Cough Coryza Conjunctivitis Enanthem phase Koplik spots Exanthem phase Rash develops from face and upper neck --> hands and feet over 3 days Lasts 5-6 days Recovery: persistent cough ``` Complications Severe diarrhoea Pneumonia Otitis media (supresses immune system for 6 weeks, infections occur) Convulsions Encephalitis subacute sclerosing panencephalitis (SSPE) Death 1 in 5,000 ```

Question 204

Mumps

Answer 204

Paramyxovirus SSRNA Cause epithelial cells to fuse, multi-nucleated giant cell Airborne Incubation: 14-25 days Headache, fever, parotid swelling (unilateral or bilateral) Meningism: photophobia, neck stiffness ``` Complications: Pancreatitis Orchitis Oophoritis Neurlogical complications: meningitis, bilateral/unilateral deafness ```

Question 205

Rubella

Answer 205

Togavirus Direct droplet contact Incubation:14-21 days Infectivity until 5-7 days after the rash onset Usually mild illness Swollen lymph glands, low grade fever, malaise Conjunctivitis Maculo-papular rash on face, neck, and body Swollen joints

Question 206

Congenital rubella syndrome

Answer 206

Cardiac defects Auditory Ophthalmic Neurological Risk 90% <10 weeks 10-20% 10-16 weeks Rare >20 weeks

Question 207

Causes of Meningitis

Answer 207

Acute Neisseria meningitides = gram negative diplococci Streptococcus pneumoniae = gram positive diplococci Haemophilus influenzae B Listeria monocytogenes = gram positive rod Group B streptococcus = gram positive cocci E.Coli = gram negative rod Chronic TB Spirochetes (leptospirosis) Cryptococcus (Cryptococcus neoformans) Aseptic Cocksackie B viruses Echviruses

Question 208

Septicaemia (4 processes)

Answer 208

1) Capillary leak Lack of albumin and other plasma proteins --> hypovolaemia 2) Coagulopathy Bleeding and thrombosis Exposure to tissue factor Activation of protein C 3) Metabolic derangement Acidosis 4) Myocardial failure - -> Multi-organ failure

Question 209

Chronic Meningitis

Answer 209

4+ days usually TB Can result in tuberculous granulomas, tuberculous abscesses, cerebritis CT changes = leptomeningeal enhancement

Question 210

Encephalitis

Answer 210

HSV most common viral cause Arboviruses (neonates, younger adults) Western equine encephalitis (infants, children) St Louis encephalitis (>40 yrs) California encephalitis (school-aged) Eastern equine encephalitis (infants/children) Rabies All more common in summer/autumn Bacterial = listeria Amoebic Toxoplasmosis

Question 211

India Ink

Answer 211

Cryptococcus

Question 212

Ziehl-Neelsen stain

Answer 212

TB

Question 213

Gram positive rod

Answer 213

Listeria

Question 214

Gram negative diplococci

Answer 214

Neisseria Meningitdes

Question 215

Gram positive diplococci

Answer 215

Streptococcus pneumoniae

Question 216

Management of Meningitis

Answer 216

Ceftriaxone 2g IV BD IF > 50 yrs OR immunocompromised add Amoxicillin 2g IV 4-hourly

Question 217

Management of meningo-encephalitis

Answer 217

Aciclovir 10mg/kg IV TDS Ceftriaxone 2g IV BD IF > 50 yrs OR immunocompromised add Amoxicillin 2g IV 4-hourly

Question 218

Hypoxia, worse on exertion

Answer 218

PCP pneumocytis jiroveci pneumonia Co-trimoxazole

Question 219

Gram stain and Grocott stain | Branching long Gram positive rods

Answer 219

Actinomyces Lung abscess Alcoholics

Question 220

Auramine stain

Answer 220

Mycobacterium

Question 221

Microcytic Anaemia (FAST)

Answer 221

Fe (Iron deficiency anaemia) Anaemia of chronic disease Sideroblastic anaemia Thalassaemia

Question 222

Normocytic Anaemia (AHHA RAP?)

Answer 222

Acute blood loss Hypothyroidism Haemolysis Anaplastic (bone marrow failure) Renal failure Anaemia of chronic disease Pregnancy

Question 223

Macrocytic Anaemia (FAT RBC M)

Answer 223

Fetus (pregnancy) Anti-folates (e.g. phenytoin) Thyroid (hypothyroidism) Reticulocytosis (release of immature cells e.g. haemolysis) B12 or folate deficiency Cirrhosis (alcoholic liver disease) Myelodysplastic syndrome

Question 224

Plummer-Vinson

Answer 224

Oesophageal webs Iron deficiency anaemia

Question 225

Causes of Iron-deficiency Anaemia

Answer 225

Increased loss = blood loss Increased utilisation Pregnancy, lactation Growing children Decreased intake Prematurity Infants and the elderly Decreased absorption Coeliac Post-gastric surgery Intravascular haemolysis MAHA PNH

Question 226

Cytokine driven inhibition of red cell production

Answer 226

Anaemia of chronic disease IFNs, TNF and IL-1 reduce EPO production ``` Rheumatoid Malignancy TB, osteomylitis (chronic infection) Vasculitis (Renal Failure) ```

Question 227

Sideroblastic Anaemia

Answer 227

Ringed sideroblasts in bone marrow

Question 228

Treatment of Sideroblastic Anaemia

Answer 228

Treat cause + Pyridoxine (Vitmain B6) --> promotes red cell production

Question 229

Hypersegmented polymorphs Leucopenia Macrocytosis Thrombocytopenia

Answer 229

Megaloblastic blood film

Question 230

IM hydroxocobalamin

Answer 230

Replenish vitamin B12 | megaloblastic anaemia

Question 231

Intravascular haemolytic anaemia

Answer 231

Increase free plasma Hb Decreased haptoglobins Haemoglobinuria Methaemalbuminaemia

Question 232

Acquired Haemolytic Anaemias

Answer 232

Immune Autoimmune: warm or cold Alloimmune - haemolytic transfusion reactions ``` Non-immune Mechanical e.g. metal valves, trauma Paroxysmal nocturnal haemoglobinuria MAHA Infections (malaria) Drugs ```

Question 233

Inherited Haemolytic Anaemias

Answer 233

Membrane Hereditary spherocytosis Hereditary eliptocytosis Enzyme defect G6PD deficiency Pyruvate kinase deficiency Haemoglobinopathies Sickle cell disease Thalassaemias

Question 234

Hereditary Spherocytosis

Answer 234

=spherocytes Autosomal dominant Spectrin or ankyrin Extravascular=splenomegaly Increased osmotic fragility DAT negative Tx: splenectomy, folic acid

Question 235

Hereditary eliptocytosis

Answer 235

=eliptocytes Autosomal dominant Spectrin mutations Ranges from hydrops fetalis to asymptomatic

Question 236

South East Asian Ovalocytosis

Answer 236

Autosomal Recessive heterzygoues = Protection against malaria

Question 237

Glucose -6 - Phosphate Dehydrogenase deficiency

Answer 237

X-linked Deficiency in G6PD Rapid anaemia and jaundice Heinz bodies and bite cells Take enzyme level 2-3 months after attack as enzymes level present in new cells Intravascular haemolysis = dark urine

Question 238

Pyruvate Kinase Deficiency

Answer 238

Autosomal Dominant Severe neonatal jaundice Splenomegaly Haemolytic anaemia

Question 239

Sickle cell mutation

Answer 239

Codon 6 which is part of coding for beta chain GAG ==> GTG single base mutation Glu to Val

Question 240

Vaso-occlusoive crisis of Sickle Cell Disease (SICKLED)

Answer 240

Stroke Infections (hyposplenism, CKD) Crises (splenic, sequestration, chest, and pain) Kidney (papillary necrosis, nephrotic syndrome) Liver (gallstones) Eyes (retinopathy) Dactilitis Mesenteric ischaemia Priaprism

Question 241

Diagnosis of Sickle Cell

Answer 241

Sickle cells and target cells in blood film Sickle solubility test Hb electrophoresis Gurthrie test

Question 242

Treatment for Sickle cell

Answer 242

Folic acid Penicillin V Pneumovax Hib vaccine Hydroxycarbamide

Question 243

Warn autoimmune haemolytic anaemia

Answer 243

37 C IgG +ve coombs Blood film - spherocytes ``` Primary idiopathic Lymphoma CLL SLE Methyldopa ``` Mx Steroids Splenectomy Immunosuppression

Question 244

Cold autoimmune haemolytic anaemia

Answer 244

<37 C IgM +ve coombs Raynaud's Primary idiopathic Lymphoma Infections: EBV, MYCOPLASMA Mx Avoid the cold Chlorambucil

Question 245

Donath Landsteiner antibodies

Answer 245

Paroxysmal cold haemoglobinuria

Question 246

Paroxysmal cold haemoglobinuria

Answer 246

Caused by viral infection Measles Syphilis VZV Donath Landsteiner antibodies IgG adhere in cold ---> complement mediated lysis in warm

Question 247

Treatment of paroxysmal nocturnal haemoglobinuria

Answer 247

Acquired, loss of GPI Ham's Test Non-immune Morning haemoglobinuria Thrombosis --> Budd-Chiari syndrome ``` Mx Eculizimab Folate, iron supplements Antibiotics Vaccines ```

Question 248

MAHA

Answer 248

Mechanical destruction Schistocytes TTP DIC HUS

Question 249

Thrombotic Thrombocytopenic Purpura

Answer 249

Pentad MAHA Fever Renal impairment Neurological abnormalities Thrombocytopenia

Question 250

Intrinsic Pathway

Answer 250

APTT Monitor: unfractionated heparin

Question 251

Extrinsic Pathway

Answer 251

PT Monitor: Warfarin

Question 252

Factor Xa activity

Answer 252

Monitor LMWH in renal impairment and those who are underweight or overweight

Question 253

Osler Weber Rendu

Answer 253

= Hereditary Haemorrhagic Telangiectasia Autosomal dominant Abnormal vessel formation Nosebleeds GI bleeds

Question 254

Platelet Disorders

Answer 254

Reduced function Congenital: storage pool disease and Thrombasthenia (glycoprotein deficiency) Acquired: Aspirin, Uraemia Low number Decreased production: bone marrow failure Increased destruction: ITP, drugs, HUS, DIC, TTP

Question 255

Heparin

Answer 255

Potentiates anti-thrombin III which inactivates thrombin and factors 9, 10, 11

Question 256

Treatment of DVT/PE

Answer 256

LMWH 175units/kg AND Warfarin Continue LMWH until INR is 2.5 Monitor:

Question 257

INR 3.5

Answer 257

Prosthetic metal valve

Question 258

INR 2.5

Answer 258

1st episode DVT or PE AF

Question 259

Gum infiltration + Hypokalaemia

Answer 259

AML

Question 260

Leukaemia + DIC

Answer 260

Acute Promyelocytic Leukaemia

Question 261

Sudan Black B stain

Answer 261

AML

Question 262

Smear cells

Answer 262

SMEAR CLLS = CLL

Question 263

Small mature lymphocytosis

Answer 263

CLL

Question 264

Bad prognostic markers of CLL

Answer 264

LDH raised CD38+ 112q23 deletion

Question 265

Good prognostic markers of CLL

Answer 265

Hypermutated Ig gene Low ZAP-70 expression 13q14 deletion

Question 266

Treatment of CLL

Answer 266

Chlorambucil Fludarabine Alemtuzumab (anti-CD52) Steroids SCT

Question 267

Reed-Sternberg cells

Answer 267

Hodgkin's lymphoma

Question 268

Subtypes of Hodgkin's lymphoma

Answer 268

Nodular sclerosing Mixed cellularity Lymphocyte rich Lymphocyte depleted Nodular lymphocyte predominant (non-classical Hodgkin's) - NON classical = NOT EBV ASSOCIATED

Question 269

Hodgkin's lymphoma

Answer 269

Reed-sternberg cells EBV-associated Spreads continuously from single lymph node group B symptoms Pain in lymph nodes after alcohol

Question 270

Staging of Lymphoma

Answer 270

Stage 1 one LN region (LN can include spleen) Stage 2 two or more LN regions on same side of diaphragm Stage 3 two or more LN regions on opposite sides of diaphragm Stage 4 Extranodal sites e.g. liver, brain A= no B symptoms B = B symptoms

Question 271

Treatment of Hodgkin's Lymphoma

Answer 271

ABVD Adriamycin Bleomycin Vinblastine Decarbazine

Question 272

Autologous Stem Cell Transplant

Answer 272

Self--> Self Multiple myeloma Lymphoma

Question 273

Allogenic Stem Cell Transplant

Answer 273

Leukaemia

Question 274

High Grade NH Lymphoma

Answer 274

V aggressive - Burkitt's Aggressive Diffuse large B cell Mantle Cell

Question 275

Low Grade NH Lymphoma

Answer 275

Follicular Marginal Zone Small Lymphocytic

Question 276

T(8,14)

Answer 276

Burkitt's Lymphoma

Question 277

Mycosis fungoides

Answer 277

Cutaneous T cell lymphoma

Question 278

HTLV-1

Answer 278

Adult T cell lymphoma/leukaemia

Question 279

c-myc over expression

Answer 279

Burkitt's lymhoma

Question 280

Alk-1 protein expression

Answer 280

Anaplastic Large cell lymphoma

Question 281

T(2,5)

Answer 281

Anaplastic Large Cell lymphoma

Question 282

Coeliac Disease

Answer 282

Enteropathy-associated T cell lymphoma

Question 283

Starry-Sky appearance

Answer 283

Burkitt's lymphoma

Question 284

Sheets of large lymphoid cells

Answer 284

Diffuse large B cell lymphoma

Question 285

Angular nuclei

Answer 285

Mantle cell lymphoma

Question 286

T(14,18)

Answer 286

Follicular lymphoma

Question 287

H.pylori lymphoma

Answer 287

Mucosal associated lymphoid tissue lymphoma

Question 288

T(11,14)

Answer 288

Mantle Cell lymphoma

Question 289

Ritcher's Transformation

Answer 289

From chronic lymphocytic leukemia (CLL) and hairy cell leukemia ---> DLBL

Question 290

BLIMP1 | XBP1

Answer 290

Markers of Plasma Cell

Question 291

``` Chromosome 13 deletion OR Translocation at 14q32 OR Hyperdiploid affect chromosomes with uneven numbers (3, 7, 9 etc.) ```

Answer 291

MGUS | additional k-ras or classical oncogenic mutation --> multiple myeloma

Question 292

Monoclonal Gammaglobinopathy of Unknown Significance

Answer 292

Pre-clinical abnormality <10%plasma cells in bone marrow <30g/l monoclonal paraprotein No CRAB

Question 293

Smouldeirng Myeloma

Answer 293

>10% plasma cells in bone marrow >30g/l monoclonal paraprotein BUT no CRAB

Question 294

Waldenstrom's Macroglobinaemia (Lymphoplasmacytoid Lymphoma - LPL)

Answer 294

Elderly men Low grade NHL Lymphoplasmacytoid cell sproduce monclonal IgM (unlike IgG in Multiple myeloma) Infiltrates BM and LN Weight loss, fatigue, hyperviscosity syndrome, Tx: chlorambucil, cyclophosphamide,

Question 295

Apple-green birefringence

Answer 295

Amyloidosis

Question 296

Blood Film Features of Myelodysplastic Syndrome

Answer 296

Hypercellular bone marrow Ring sideroblasts Pelger-Huet anomaly (bilobed neutrophils) Dysganulopoieses of neutrophils Myelokathexis of neutrophils & precursors Dyserythropoiesis of red cells Dysplastic megakaryocytes – e.g. micro megakaryocytes PROGNOSTIC SIGNIFICANCE: Increased proportion of blast cells in marrow (normal < 5%)

Question 297

Myelokathexis of neutrophils

Answer 297

Shattered nuclei in bone marrow =myelodysplastic syndrome

Question 298

International Prognostic Scoring System for Myelodysplastic Syndrome

Answer 298

Predict development of acute myeloid leukaemia Blast cell proportion Karyotype: Chromosomal Abnormalities Haemoglobin level Platelet level Neutrophil level Very good: -Y, del(11q) Good: normal, -Y, del(5q), del(12q), del(20q) Intermediate: del(7q), +8,+19 Poor: complex (3 abnormalities), -7, double abnormalities inc. -7 or del(7q) Very Poor: > 3 abnormalities

Question 299

Treatment of MDS

Answer 299

Supportive care Blood product support Antimicrobial therapy Growth factors (Epo, G-CSF) Biological Modifiers Immunosuppressive therapy Azacytidine Lenalidomide (5q- syndrome)

Question 300

Inherited Aplastic Anaemia

Answer 300

Fanconi's Anaemia Dyskeratosis Congenita Schwachman-Diamond Syndrome Diamond-Blackfan Syndrome

Question 301

Fanoni's Anaemia

Answer 301

AR 5-10 years Skeletal abnormalities (Radii, thumbs) Renal malformations Microopthalmia Short stature Skin pigmentations Increased AML

Question 302

Dyskeratosis Congenita

Answer 302

C-linked Telomere shortening (Chromosomal instability) Triad Skin pigmentation Nail dystrophy Oral leukoplakia Bone marrow failure

Question 303

Schwachman-Diamond Syndrome

Answer 303

AR Skeletal abnormalities Pancreatic dysfunction Endocrine dysfunction Hepatic impairment Increased AML

Question 304

Diamond-Blackfan

Answer 304

Pure red cell aplasia Normal WCC and platelets Dysmorophic

Question 305

Myeloproliferative disorders

Answer 305

Ph positive CML Ph negative Polycthaemia vera Myelofibrosis Essential thrombocytosis

Question 306

Polycythaemia

Answer 306

Primary Polycythaemia vera Familial polycythaemia Secondary (due to Increased EPO) Altitude Renal cancer Chronic Hypoxia

Question 307

Anagrelide

Answer 307

treatment of essential thrombocytosis

Question 308

Lowenstein-Jensen Medium

Answer 308

TB

Question 309

Gram +ve rods Acid fast Aerobic Intracellular

Answer 309

TB

Question 310

Treatment TB meningitis

Answer 310

1 year TB therapy | + corticosteroids

Question 311

Post infleunza infection + cavitation on CXR

Answer 311

Staph aureus pneumonia

Question 312

Rusty sputum | Lobar pneumonia on CXR

Answer 312

Steptococcus pneumonia positive diplococci

Question 313

Smoker/COPD with pneumonia

Answer 313

Haemophilus influenzae negative cocco-bacilli

Question 314

Pneumonia in alcoholic

Answer 314

Klebsiella negative rod enterobacter

Question 315

negative coccus pneumonia in a smoker

Answer 315

M.catarrhalis

Question 316

Typical Pneumonia

Answer 316

=signs of pneumonia on examination Streptococcus pneumonia Haemophilus influenza M.catarrhalis Staph Aureus Klebsiella pneumonia

Question 317

Atypical Pneumonia

Answer 317

Not classic signs of pneumonia on examination Legionella Mycoplasma Chlamydia pneumonia Chlamydia psittaci Bordatella pertusis TB

Question 318

Air conditioning Hepatitis Hyponatraemia

Answer 318

Legionella pneumophilia

Question 319

Joint pain Cold agglutins Erythema multiforme

Answer 319

Mycoplasma

Question 320

Respiratory tract infections in HIV

Answer 320

PCP TB Cryptococcus neoformans

Question 321

Neutropenia and Respiratory tract infections

Answer 321

Fungi - Aspergillus

Question 322

Bone marrow transplant and Respiratory tract infections

Answer 322

Aspergillus CMV

Question 323

TWAR agent

Answer 323

Chlamydia pneumonia

Question 324

Mild-moderate CAP antibiotics

Answer 324

Amoxicillin OR Macrolide

Question 325

Moderate-severe CAP antibiotics

Answer 325

Clarithromycin AND Co-amoxiclav OR Cefuroxime

Question 326

Atypical CAP Antibiotics

Answer 326

e.g. chlamydia , mycoplasma Macrolide Tetracycline

Question 327

Hospital Acquired Pneumonia Antibiotics

Answer 327

1st Line: Ciprofloxacin +/- vancymycin

Question 328

Aspiration Pneumonia Antibiotics

Answer 328

Cefuroxime AND Metronidazole

Question 329

Legionella Antibiotics

Answer 329

Macrolide AND Rifampicin

Question 330

Staph Aureus pneumonia Antibiotics

Answer 330

Flucloxacillin

Question 331

Psuedomonas spp. Antibiotics

Answer 331

Piperacillin + tazobactam (Tazocin) OR Ciprofloxacin +/- Gentamicin

Question 332

MRSA antibiotic

Answer 332

Vancomycin

Question 333

Gonorrhoea Mx

Answer 333

Ceftriaxone IM 250 mg single dose OR Cefixime PO 400mg single dose if resistant --> Spectinomycin 2g single dose (binds to the 30S subunit of the bacterial ribosome)

Question 334

Spectinomysin

Answer 334

Treatment of resistant gonorrhoea Binds to the 30S subunit of the bacterial ribosome

Question 335

Treatment of Chlamydia

Answer 335

Azithromycin 1g (4 capsules) Single dose OR Doxycycline 100mg BD 7 days

Question 336

Treatment of LGV

Answer 336

Doxycycline 100mg BD for 21 days

Question 337

Syphilis

Answer 337

Gram neg spirochaete Treponema pallidum IM ben pen

Question 338

Argyll-Robertson Pupil

Answer 338

Accommodates but does not react Tertiary syphilis

Question 339

Jarisch-Heimer reaction

Answer 339

Fever, headache, myalgia, exacerbation of syphilitic symptoms AFTER Treatment with IM ben Pen

Question 340

Chancroid

Answer 340

Haemophilus ducreyi Gram neg cocoobacillus Painful ulcers

Question 341

Granuloma inguinale

Answer 341

Klebsiella granulomatis Gram neg bacilus Large expanding ulcer Beefy red appearance Tx: azithromycin

Question 342

Molluscum contagiosum

Answer 342

poxvirus dsDNA In adults = HIV

Question 343

Cryptococcal Meningitis Tx

Answer 343

Amphotericin B

Question 344

Herpes Encephalitis

Answer 344

HSV-1

Question 345

Mollaret's meningitis

Answer 345

Recurrent aseptic meningitis HSV-2

Question 346

Pleiocytosis

Answer 346

HSV meningitis

Question 347

Tzank cells

Answer 347

Multinucleated giant cells VZV

Question 348

VZV Tx

Answer 348

If adult Neonate Immunocompromised Eye involvement Aciclovir 800mg TDS

Question 349

Owl's eye inclusion

Answer 349

= CMV

Question 350

Treatment of CMV

Answer 350

Ganciclovir

Question 351

Infectious Mononucleosis

Answer 351

Triad: Fever Pharyngitis Lymphadenopathy

Question 352

CMV in BMT

Answer 352

=Pneumonitis

Question 353

CMV retinitis

Answer 353

=AIDS

Question 354

Paul Bunnel monospot

Answer 354

=CMV

Question 355

HHV-8

Answer 355

Kaposi's sarcoma Castlemann's syndrome Tx: ganciclovir

Question 356

PUO

Answer 356

Fever > 38.3º C On several occasions persisting without diagnosis for at least 3 weeks in spite of at least 1 weeks investigation

Question 357

Classical PUO

Answer 357

``` Abscesses Endocarditis Tuberculosis Complicated urinary tract infections Fever in returning traveller HIV Connective Tissue/Vasculitis Neoplasms ```

Question 358

Fever in the Returning Traveller

Answer 358

``` Malaria 21% Dengue 6% Typhoid 2% Rickettsia 2% Bacterial diarrhoea 3% Urinary tract infections 2% Brucella (indolent) Viral heam’ fever ```

Question 359

Neutropenic fever

Answer 359

Aspergillus

Question 360

Roth Spots

Answer 360

Retinal haemorrhages If fever think endocarditis leukemia, diabetes, subacute bacterial endocarditis, pernicious anemia, ischemic events, hypertensive retinopathy and rarely in HIV retinopathy.

Question 361

Choroid tubercle

Answer 361

=Intraocular TB

Question 362

Histoplasmosis

Answer 362

Immunocompromised Temperate climate Dimorphic fungus Non-specific respiratory symptoms, often cough or flu-like Chest X-ray findings are normal in 40–70% of cases. Chronic histoplasmosis cases can resemble tuberculosis Disseminated histoplasmosis affects multiple organ systems and is fatal unless treated

Question 363

Infective Endocarditis

Answer 363

Prosthetic valve --> think endocarditis Damaged heart valve form rheumatic heart disease --> more likely to get endocarditis Valves involved are mitral valve, aortic valve most commonly Fever 90% Heart murmur 85% Changing murmur 5-10% Fever 80% Chills 40% Weakness 40% Dyspnoea 40%

Question 364

Causes of endocarditis

Answer 364

Viridans streptococci (oral) 60-80% Enterococci 30-40% Staph. aureus 10-27% Gram negative bacilli 1.2-13% Fungi 2-4% Rare..Rothia, Cardiobacterium, etc Coagulase negative staphylococci (CNS) cause most cases of prosthetic valve endocarditis

Question 365

Duke Criteria

Answer 365

Pathologic criteria 1.Microoraginsms demonstrated by culture or histologic examination of a vegetation, a vegetation that has embolised, or an intracardiac abscess specimen 2. Pathologic lesions: vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis..\BIT LATE!! B Clinical criteria Two major criteria One major and 3 minor criteria Five minor criteria

Question 366

Treatment of Endocarditis

Answer 366

For strep. viridans endocarditis Combination of benzylpenicillin and gentamicin For enterococcal endocarditis Combination of ampicillin and gentamicin MSSA endocarditis - flucloxacillin for 4-6 weeks MRSA endocarditis – Vancomycin and gentamicin or rifampicin or fucidin

Question 367

Typhoid

Answer 367

Salmonella typhi and paratyphi Anaerobic gram neg bacillus Enteric fever Infection of Peyer's patches Fever, abdo pain, headache, constipation, relative bradycardia Hepatosplenomegaly Rose spots

Question 368

Malaria Species

Answer 368

P. Falciparum P. Vivax P. Ovale P. Malariae

Question 369

Fever Patterns of Malaria

Answer 369

P. Falciparum = tertian 48 hr OR 24 h P. Vivax = 48 hr P. Ovale = 48 hr P. Malariae = 72 hr (Quartan)

Question 370

P. Falciparum complicated infections

Answer 370

Resists removal from spleen Clumping of red cells in capillary beds Blocks blood flow to organs Haemolytic organs + reduced perfusion = bad - cerebral malaria = confusion, seizures, coma - bilious malaria = vomiting, diarrhoea, jaundice and liver failure lungs kidney spleen =sepsis-like clinical picture

Question 371

Diagnosis of Malaria

Answer 371

Thick film = identifies parasites in red cells Thin film = identifies specific plasmodium species

Question 372

Treatment of P. Falciparum Malaria

Answer 372

Mild Quinine + Doxycycline / Clindamycin OR Malarone OR Riamet Severe Artemisinin combination therapy OR Quinine + Doxycycline/Clindamycin

Question 373

Treatment of P. Vivax / P. Ovale Malaria

Answer 373

Chloroquine and then Primaquine

Question 374

Schnuffer's dots

Answer 374

P. Vivax P. Ovale

Question 375

Young trophozoites (Rings) Absence of mature trophozoites Crescent-shaped gametocytes

Answer 375

P. Falciparum malaria

Question 376

Antibiotics prone to causing C. Diff

Answer 376

The 3 Cs Cephalosporins Clindamycin Ciprofloxacin

Question 377

129 codon MM

Answer 377

CJD

Question 378

Serial EEG: periodic triphasic changes

Answer 378

Sporadic CJD

Question 379

Brucellosis

Answer 379

Gram negative aerobic bacilli Facultative intracellular Untreated diary Undulant fever Malaise, rigors, arthralgia, tiredness Spinal tenderness, lymphadenopathy, splenomegaly, heaptomegaly Epididymo-orchitis Anti-O-polysaccharide antibody WCC normal Tx: tetracycline OR Doxycyline Combined with streptomycin

Question 380

Anti-O-polysaccharide antibody

Answer 380

=Brucellosis

Question 381

Negri bodies

Answer 381

=Rabies

Question 382

Erythema chronicum migrans

Answer 382

Bulls-eye rash | = Lyme disease

Question 383

Treatment for Lyme Disease

Answer 383

Doxycycline 2-3 weks If CNS disease --> Ceftriaxone

Question 384

Q fever

Answer 384

Coxiella burnetii Looks like atypical pneumonia

Question 385

Painless round black lesion + rim of oedema

Answer 385

=Anthrax

Question 386

Massive lymphadenopathy + mediastinal haemorrhage + pleural effusion (resp failure)

Answer 386

Pulmonary Anthrax

Question 387

Leptospirosis

Answer 387

Gram negative aerobic motile spirochaetes Excreted in dog, rate urine Swimming in contaminated water Spiking temp, headache, conjunctival haemorrhage, jaundice, malaise, myalgia, meningism, carditis, renal failure, haemolytic anaemia Amoxicillin, Erythromycin, Doxycyline, Ampicillin

Question 388

Cutaneous Leishmaniasis

Answer 388

Sandfly (South and Central America + Middle East) Skin ulcer at site of bite Multiply in dermal macropahges Heals after 1 year --> leaves depigmented scar Type IV reaction L. major L. tropica

Question 389

L. braziliensis

Answer 389

Muco-cutaneous Leichmaniasis

Question 390

L. donovani L. infantum L. chagasi

Answer 390

Visceral Leichmaniasis Kala-Azar

Question 391

Increase PR interval on ECG with bacterial endocarditis

Answer 391

Periventricular abscess --> need surgical intervention

Question 392

Inx for bacterial endocarditis

Answer 392

at least 3 different blood cultures

Question 393

Amantadine

Answer 393

Targets M2 ion channel mutation S31N in M2 = resistance

Question 394

Neuraminidae inhibitors

Answer 394

Oseltamivir Zanamivir Sialic acid

Question 395

Influenza A

Answer 395

8 RNA segments NA HA

Question 396

CMV complications (RCHEP)

Answer 396

``` Retinitis Colitis Hepatitis Encephalitis Pneumonitis ```

Question 397

Guanosine analogue

Answer 397

Aciclovir Activated by viral thymidine kinase

Question 398

Pyrophosphate analogue

Answer 398

Foscarnet Inhibits nucleic acid synthesis without requiring activation

Question 399

Ganciclovir

Answer 399

Used to treat CMV also EBV and HHV-6 Nucleoside analogue Side effects: bone marrow suppression

Question 400

Nucleoside phosphonate

Answer 400

Cidofovir Used in CMV retinitis And post-transplant

Question 401

Treatment of HSV

Answer 401

IV aciclovir If resistant Valaciclovir and Famciclovir Act Very Fast A V F

Question 402

Treatment for Hepatitis B

Answer 402

Entecavir Peg IFN alpha2 (subcut) Tenfovir

Question 403

Tenofovir

Answer 403

Inhibitor of reverse transcriptase

Question 404

Treatment for Hepatitis C

Answer 404

Peg INF 2b/2a Ribavirin Works bets in genotypes 2 and 3

Question 405

Ribavirin

Answer 405

RNA nucleoside analogue (causes hamolytic anaemia) Used in Hep B AND adenovirus Tx in paediatric post-transplant

Question 406

CMV pos and neg in transplant

Answer 406

Solid organ: Recipient neg --> donor must be neg BM transplant Recipient pos --> donor must be pos

Question 407

HHV-6 treatment

Answer 407

Ganciclovir Foscarnet/Cidofovir

Question 408

Treatment of Pyelonephritis

Answer 408

Co-Amoxiclav +/- Gentimicin OR Cefuroxime +/- Getamicin

Question 409

Four mechanisms of resistance = BEAT

Answer 409

Bypass antibiotic-sensitive step e.g. MRSA Enyme-mediated destruction e.g. beta-lactamase Accumulation reduction e.g. Tetracycline Target change (modify protein targeted by antibiotics) e.g. Quinolone resistance

Question 410

Treatment of Meningitis

Answer 410

Ceftriaxone Corticosteroids Ampicillin

Question 411

Hep B antibodies

Answer 411

HBsAntibody = chronic carrier HBeAntibody --> low infectivity in carrier HBcAntibody IgM --> recent infection IgG --> previous expsoure to HBV (cleared and chronic carriers)

Question 412

Diagnosis of Diabetes

Answer 412

Fasting Glucose >7.0mM If still suspicious but fasting negative --> OGTT 2 hour >11.1 HbA1c >6.5% OR >48mmol/mol

Question 413

Management of Hypokalaemia

Answer 413

3.0-3.5 Oral KCl Sandok Tablets for 48 hours Recheck K+ <3.0 IV KCl Max rate 10nmol/h >20nmol/h highly irritant to veins

Question 414

Gitelman Syndrome

Answer 414

Autosomal recessive kidney disorder Hypokalaemia Low magnesium Decreased excretion of calcium in the urine Elevated blood pH Caused by loss of function mutations of the thiazide-sensitive sodium-chloride symporter Located in the distal convoluted tubule of the kidney

Question 415

Bartter Syndrome

Answer 415

Rare inherited defect in the thick Ascending limb of the loop of Henle Hypokalemia Alkalosis Normal to low blood pressure Polyuria, and polydipsia Calciuria Two types of Bartter syndrome: neonatal and classic

Question 416

Management of Hyperkalaemia

Answer 416

U&Es, ECG, drug review 10ml 10% Calcium gluconate 50ml 50% dextrose + 10 units of insulin Nebulised salbutamol

Question 417

sgk-1

Answer 417

Under control of aldosterone Inhibits Nedd4, normally tags ENac for degredation sgk-1 --> sodium reabsorption

Question 418

Elevated Anion Gap (KULT)

Answer 418

Ketoacidosis (DKA, alcoholism, starvation) Uraemia (renal failure) Lactic acidosis Toxins (ethylene glycol, methanol, paraldehyde, salicyclate)

Question 419

AST : ALT 2:1

Answer 419

Alcoholic liver disease

Question 420

AST : ALT <1:1

Answer 420

Viral liver disease

Question 421

GGT

Answer 421

Raised in alcohol and bile duct disease Found in hepatocytes and epithelium of small bile ducts

Question 422

Raised ALP and Dilated Ducts

Answer 422

=mechanical obstruction Gallstones Cancer

Question 423

Raised ALP and ducts NOT dilated

Answer 423

=injury of the bile duct Primary biliary cirrhosis Primary sclerosing cholangitis Toxic injury of bile ducts (drugs: augmentin) Pregnancy

Question 424

Low urobilinogen

Answer 424

Obstructive jaundice | raised in haemolysis

Question 425

Decreased Albumin

Answer 425

Sepsis Warfarin use Nephrotic syndrome OR protein losing enteropathy e.g. IBD Chronic liver disease

Question 426

Triad of Abdominal Pain Psychiatric Symptoms Neurological symptoms

Answer 426

Porphyria

Question 427

PBG Synthase deficiency

Answer 427

ALA Dehydratase / Plumboporphyria

Question 428

HMB Synthase deficiency

Answer 428

Acute Intermittent Porphyria

Question 429

Coproporphyrinogen oxidase deficiency

Answer 429

Hereditary Coproporphyria

Question 430

Protoporphyrinogen oxidase deficiency

Answer 430

Variegate Porphyria

Question 431

Uroporphyrinogen III synthase deficiency

Answer 431

Congenital eryrthopoietic porphyria

Question 432

Uroporphyrinogen decarboxylase deficiency

Answer 432

Porphyria cutanea tarda

Question 433

Ferrochetolase deficiency

Answer 433

Erythropoietic protoporphyria

Question 434

Glucose level cut-off for triple test

Answer 434

<2.2

Question 435

Homovanillic acid in urine

Answer 435

= Neuroblastoma

Question 436

Waterhouse–Friderichsen syndrome

Answer 436

hemorrhagic adrenalitis or fulminant meningococcemia is defined as adrenal gland failure due to bleeding into the adrenal glands Commonly caused by severe bacterial infection Typically the pathogen is the meningococcus Neisseria meningitidis

Question 437

Treatment for Grave's

Answer 437

Carbimazole Propylthiouracol Inhibit thyroperoxidase enzyme

Question 438

Schmidt's

Answer 438

Polyglandular autoimmune type II Addison's Autoimmune hypothyroidism

Question 439

MEN II

Answer 439

Thyroid (medullar carcinoma) Parathyroid Phaeochromocytoma

Question 440

MEN I

Answer 440

Pituitary Parathyroid Pancreas

Question 441

Cacitonin

Answer 441

Tumour marker for Medullary carcinoma of thyroid Produced by C cells Reduce blood calcium, opposing the effects of PTH

Question 442

Medullary carcinoma

Answer 442

MEN II Calcitonin tumour marker cancer of C cells

Question 443

Thyroglobulin

Answer 443

Tumour marker for Follicular thyroid cancers Produced by follicular cells Precursor of the thyroid hormones; these are produced when thyroglobulin's tyrosine residues are combined with iodine and the protein is subsequently cleaved

Question 444

Treatment of papillary and follicular thyroid cancers

Answer 444

T4 --> suppresses TSH (TSH dependent) removal of thyroid gland Radioiodine to irradicate any remaining cells

Question 445

Ataxia and nystagmus

Answer 445

Phenytoin toxicity Omit dose

Question 446

Arrhythmias, heart block, confusion, xanthopsia

Answer 446

Digoxin toxicity Digibind

Question 447

Tremor, lethargy, fits, arrhythmia, renal failure

Answer 447

Lithium toxicity Haemodialysis

Question 448

Tinnitus, deafness, nystagmus, renal failure

Answer 448

Gentamicin toxicity Omit dose

Question 449

Arrhythmias, anxiety, tremor, convulsion

Answer 449

Theophyline toxicity Omit dose

Question 450

Normal plasma calcium

Answer 450

2.2-2.6

Question 451

Adjusted calcium

Answer 451

= 40 - 0.02[albumin] When you measure calcium you measure the albumin-bound form If you have low albumin, you can get a falsely low Ca2+ measurement --> use adjusted calcium

Question 452

3 Important causes of Hypercalcaemia

Answer 452

Primary hyperparathyroidism Malignancy of bone OR ectopic PTH Sarcoidosis

Question 453

Treatment of Hypercalcaemia

Answer 453

(if unwell or >3.0) FLUIDS FLUIDS FLUIDS IV saline 0.9% (4L/24h) Furosemide IV Pamidronate (30-60mg) Bisphosphonates if bony metastasis (slow invasion and decrease pain)

Question 454

Causes of Hypocalcaemia

Answer 454

Vitamin D deficiency Chronic kidney disease Hypoparathyroidism Pseudohypoparathyrodism Magnesium deficiency DiGeorge

Question 455

Looser's zone

Answer 455

=vitamin D deficiency

Question 456

Radial aspect cystic changes

Answer 456

Primary hyperparathyroidism

Question 457

Management of Sarcoidosis

Answer 457

40mg steroids / day

Question 458

Band keratopathy

Answer 458

=Hypercalcaemia (Not cancer, takes too long to develop and cancer would have killed them by then) Ca deposits in band in front of cornea

Question 459

Causes of Osteomalacia

Answer 459

Vitamin D Deficiency Chronic kidney disease Anticonvulsants Chappatis (phytic acid chelates Vit D in gut)

Question 460

Causes of Hypercalcaemia

Answer 460

PTH raised = don't have cancer Primary PTH adenoma Familial hypocalciuric hypercalcaemia PTH NOT raised = cancer Squamous cell carcinoma Ectopic PTHrP (neonatal marker = poor prognosis) Bony metastasis e.g Breast cancer Myeloma

Question 461

Familial hypocalciuric hypercalcaemia

Answer 461

Calcium sensing receptor (CaSR) mutation Right shift: Higher PTH for a given Ca More PTH --> More Ca in blood, less in urine

Question 462

Diagnostic Criteria for an Acute MI

Answer 462

EITHER 1) Typical rise and gradual fall of troponin OR rapid rise and fall CK-MB with at least one of the following: - ischaemic symptoms - pathological q wave on the ECG - ECG changes indicative of ischaemia - Coronary artery intervention OR 2) Pathological findings of an acute MI

Question 463

PKU

Answer 463

Phenylaline hydroxylase deficiency

Question 464

T cell deficiencies

Answer 464

Bare Lymphocyte Syndrome DiGeorge's Syndrome

Question 465

Regulatory Factor X defect

Answer 465

Bare lymphocyte syndrome

Question 466

Absent MHC Class I

Answer 466

Bare lymphocyte syndrome Type 1

Question 467

Absent MHC Class II

Answer 467

Bare lymphocyte syndrome Type 2

Question 468

Membranoproliferative nephritis and bacterial infections

Answer 468

C3 deficiency with presence of a nephritic factor

Question 469

HLA B27

Answer 469

Ankylosing spondylitis

Question 470

HLA DR15 / HLA DR2

Answer 470

Goodpasture's

Question 471

HLA-DR3

Answer 471

Graves SLE Type I diabetes

Question 472

HLA DR3 / HLA DR4

Answer 472

Type I Diabetes

Question 473

HLA DR4

Answer 473

Rheumatoud arthritis Type I Diabetes

Question 474

PTPN22

Answer 474

Tyrosine phosphatase expressed in lymphocytes Associated with Rheumatoid Arthritis, SLE and Type 1 Diabetes

Question 475

CTLA4

Answer 475

Receptor for CD80/86 expressed by T cells Expressed in Tregs Inhibitory control of cell activation SLE Type 1 diabetes Autoimmune thyroid disease

Question 476

Human Normal Immunoglobulin

Answer 476

Antibody replacement Pooled from 1000s of donors Every 3-4 weeks IV or subcut Used for: CVID Bruton's Post-BMT

Question 477

INF-alpha

Answer 477

Hepatitis B Hepatitis C Kaposi's Sarcoma Hairy cell leukaemia Chronic Myelogenous Leukaemia Malignant Myeloma

Question 478

INF-beta

Answer 478

MS

Question 479

INF-y

Answer 479

Chronic granulomatous disease

Question 480

Dihydrofolate reductase (DHFR) inhitor

Answer 480

Methotrexate

Question 481

GVHD Prophylaxis

Answer 481

Methotrexate/Cyclosporine

Question 482

HIV routine treatment

Answer 482

Atripla = - Emtricitabine - Tenofovir - Efavirenz

Question 483

HIV in pregnancy

Answer 483

Zidovudine

Question 484

CD45 RO

Answer 484

Memory T cells

Question 485

CD45 RA

Answer 485

Naive T cells

Question 486

Effector memory T cells

Answer 486

CCR7- CD26 low Not found in lymph nodes Perforin and IFN-y

Question 487

Central Memory T cells

Answer 487

CCR7+ CD26 high Lymph nodes IL-2

Question 488

Alum

Answer 488

Adjuvant used in human vaccine Activates Gr1 cells to produce IL-4 Primes naive B cells

Question 489

Gas gangrene

Answer 489

Clostridium perfringens

Question 490

Urinary 5-HIAA

Answer 490

Carcinoid syndrome (Bronchoconstriction, Flushing, Diarrhoea) Metabolite of serotonin

Question 491

APC gene

Answer 491

First hit in adenocarcinoma colon cancer | FAP

Question 492

Multiple polyps Mucocutaneous hyperpigmentation Freckles around mouth, palms and soles

Answer 492

Peutz-Jeghers syndrome AD - LKB1 Increased risk of intussusception and malignancy Characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa (melanosis).

Question 493

Juvenile polyposis

Answer 493

AD < 5 yrs May require colectomy

Question 494

Duke's Staging

Answer 494

A: confined to mucosa (95% 5ysr) B1: extending into muscularis propria (67% 5ysr) B2: transmural invasion, no lymph node involved (54% 5ysr) C1: extending to muscularis propria, with LN metastases (43% 5ysr) C2: transmural invasion, no lymph node involved (43% 5ysr) D: distant metastases (<10%5ysr)

Question 495

CCK

Answer 495

causes release of digestive enzyme Produced by I-cells in duodenum

Question 496

Secretin

Answer 496

Controls gastric acid secretion with HCO30 buffering Produced by S-cells of duodenum

Question 497

Coagulative necrosis

Answer 497

Acute pancreatitis

Question 498

Raised serum Lipase

Answer 498

Acute Pancreatitis

Question 499

Causes of Acute Pancreatitis

Answer 499

Idiopathic Gallstones Ethanol Trauma ``` Steroids Mumps Autoimmune Scorpion Hyperlipidaemia ERCP Drugs (thiazides) ```

Question 500

Causes of chronic pancreatitis

Answer 500

Alcoholism Cystic fibrosis Hereditary Pancreatic duct obstruction (stones, tumour, autoimmune IgG4 scerlosing)

Question 501

Fibrosis and loss of exocrine tissue, duct dilation with thick secretions and calcification

Answer 501

Chronic pancreatitis

Question 502

CA19.9

Answer 502

Pancreatic carcinoma (acinar)

Question 503

Functional neuroendocrine tumours

Answer 503

Insulinoma Gastrinoma (Zollinger-Ellison syndrome) VIPoma Glucagonoma

Question 504

Alpha fetoprotein

Answer 504

Hepatocellular carcinoma

Question 505

Benign tumours of liver

Answer 505

Hepatic adenoma = OCP Haemangioma Bile duct adenoma

Question 506

Malignant tumours of the liver

Answer 506

HCC Angiosarcoma Hepatoblastoma (in young children, primitive hepatocytes) Cholangiosarcoma (adenocarcinoma) - PSC, Chronic liver disease, Lynch syndrome II (HNPCC), parasitic liver disease Metastatic: most common Usually form GI tract /breast/ bronchus

Question 507

Cirrhosis Histology

Answer 507

Hepatocyte necrosis Fibrosis Nodules of regenerating hepatocytes Disruption of liver architecture (resistance to blood flow --> portal hypertension)

Question 508

Genetic causes of liver cirrhosis

Answer 508

Haemochromatosis = HFE gene chromosome 6 Wilson's disease = ATP7B chromosome 13 A1AT deficiency Galactosaemia Glycogen storage disease

Question 509

Micronodular cirrhosis

Answer 509

< 3mm Uniform Alcoholic hepatitis Biliary tract disease

Question 510

Macronodular cirrhosis

Answer 510

>3mm Viral hepatocytes Wilson's disease A1AT deficiency

Question 511

Modified Pugh Score

Answer 511

Liver cirrhosis prognosis >10 = v bad <20% 5yrs

Question 512

Causes of Portal Hypertension

Answer 512

Pre-hepatic Portal vein thrombosis (e.g. Factor V Leiden) Hepatic Pre-sinusoidal: Schistosomiasis, PBC Sinusoidal: Cirrhosis Post-sinusoidal: veno-occlusive disease Post-hepatic Budd-Chiari syndrome: occlusion of hepatic vein

Question 513

Bile duct loss + granuloma

Answer 513

Primary biliary cholangitis

Question 514

Low ceruloplasmin

Answer 514

Wilson's

Question 515

Direct Van den Bergh

Answer 515

Conjugated Complete ---> unconjugated

Question 516

Onion-skinning fibrosis + multi-focal strictures

Answer 516

Primary sclerosing cholangitis

Question 517

Rhodanine stain

Answer 517

Copper Wilson's

Question 518

Periodic acid Schiff

Answer 518

Stain A1AT

Question 519

Treatment of Haemochromatosis

Answer 519

Desforrioxamine Venesection

Question 520

Treatment of Wilson's

Answer 520

Penicillamine

Question 521

Macroglossia Heart failure Hepatomegaly

Answer 521

Amyloidosis

Question 522

HLA-DRB1

Answer 522

Goodpasture's

Question 523

Thrombotic microangipathies

Answer 523

Thrombosis +MAHA +Thrombocytopenia +renal failure (mostly in HUS) Causes TTP - diffuse, esp in CNS HUS - confined to kidneys ``` TTP = headache, altered consciousness HUS= renal failure ```

Question 524

Liver cysts and berry aneurysm with reduced GFR

Answer 524

PKD1 Chromosome 16 autosomal dominant

Question 525

Sharply circumscribed, discrete, round, firm, grey-white tumours

Answer 525

Fibroid

Question 526

Tamoxifen

Answer 526

oestrogen receptor antagonist/agonist

Question 527

Herceptin / Trastuzumac

Answer 527

Monoclonal Ig to HER2 (breast cancer)