GP Flashcards
Define Asthma
Chronic cough, dyspnoea and wheeze, characterised by reversible airway obstruction, airway hypersensitivity and inflamed bronchioles
This can be allergic/IgE mediated, or non IgE mediated (exercise, cold air and stress)
Pathophysiology of asthma
Allergen picked up by dendritic cells and presented to Th2 cells, which respond by releasing cytokines, releasing IgE which bind to mast cells, causing mast cell degranulation. This releases histamine, leukotrienes, prostaglandin.
This causes chronic airway inflammation causing:
- Bronchoconstriction and smooth muscle spasm
- Mucus hypersecretion
Common triggers of asthma
- Pollen, dust mites, grass
- Cold air
- Exercise
- Pets
- Tobacco smoke
- Occupational allergens (bakers, manufacturers, lab work, welding)
- Household mould
Signs/symptoms of asthma
Episodic shortness of breath, usually after trigger exposure.
- Diurnal PEFR variation (worse at night/early morning)
- Usually dry cough
- Expiratory wheezing/dyspnoea
- Chest tightness
Asthma patient mucus microscopy result
Will contain spiral mucus plugs - casts from small bronchioles
Investigations in Asthma
Spirometry:
-FEV1/FVC <80% (obstructive picture)
- Bronchdilator reversibility
FeNO (Fraction of exhaled Nitric Oxide) - 40ppb in adults, 35 in kids. (parts per billion)
GOLD: PEFR - measure multiple times a day for 2-4 weeks. >20% variability diagnostic
Patient taking regular aspirin/NSAIDs comes in with asthma-esque symptoms. What is this suggestive of?
Samter’s triad
What is Samter’s triad
Inflammation and swelling of the airways in response to aspirin or NSAIDs
Leads to:
- Chronic asthma-esque history
- Recurrent nasal polyps
- Aspirin intolerance
Asthma management algorithm
1) SABA (Salbutamol)
2) SABA + lowdose ICS (beclometasone)
3) SABA + lowdose ICS + LTRA (montelukast)
4) SABA + lowdose ICS + LABA (Salmeterol) + LTRA in adults, - LTRA in kids.
What are the goals of stepwise management in asthma
- Aim to use the lowest effective doses possible, only stepping up if previous treatment ineffective
- Step down treatment every 3 months and reasess
- Annual asthma reviews for stable asthma
Give the PEFR, speech, resp and cardio ranges of moderate, severe and life threatening asthma exacerbations
PEFR
- M - 50-75% of best/predicted
- S - 33-50%
- LT - <33%
Speech
- M - normal
- S - cant complete sentences
- LT - Silent, exhausted, confused, coma
Resp
- M - RR<25/min
- S - RR>25/min
- LT - O2 sats <92%, chest silent, reduced respiratory effort or cyanosis
Cardio
- M - Pulse <110
- S - Pulse >110
- LT - Bradycardia, dysrhythmia, hypotension
Signs of acute asthma exacerbation
- Progressively worsening dyspnoea
- Accessory muscle usage
- Tachypnoea
- Cyanosis
- Silent chest
Define bronchodilator reversibility
> 12% increase in FEV1, and >200ml increase in FVC
Management of acute asthma attack
Hospital if life threatening or near-fatal asthma attack (High pCO2/need for ventilation), or if bronchodilator irreversible.
- Salbutamol up to 10mg/hour (1 puff every 30-60 seconds up to 10 puffs)
- Ipratropium bromide (SAMA)
- 3-5 days oral prednisolone for ALL kids with exacerbation
- MgSO4 if PEFR <50% and no bronchodilator response
Checks to do at annual asthma review
- Inhaler technique
- Symptom scoring
- Check HPC
- Review treatment
- Check growth in children, and potentially do spirometry
Extrinsic pathway of coagulation cascade
3,7,10
endothelial damage = 3 (tissue factor) -> 3a.
3a = 7 -> 7a
7a + calcium -> activate 10 to 10a
Intrinsic pathway of coagulation cascade
12,11,9,8,10
Collagen exposure causes activation of 12 -> 12a
12a = 11 -> 11a
11a activates 8 and 9 to 8a and 9a.
8a and 9a activate 10 to 10a.
Common pathway of coagulation cascade
10a and 5a and calcium -> 2 to 2a (thrombin).
2a activates 1 (fibrinogen) to 1a (fibrin)
2a activates Stabilising factor (13) to 13a, which forms stable clot with 1a and calcium.
What is PT, and how is this used to calculate INR. Reasons INR may be raised
Prothrombin time - Coagulation speed through extrinsic pathway (3,7,10)
INR = (patient’s PT/reference PT)
Vit K deficiency, Anticoags, liver disease, disseminated intravascular coagulation
What is APTT and what conditions affect this BUT NOT PT
Activated Partial Thromboplastin Time
Coagulation speed through intrinsic pathway
Affected by:
haemophilia A, B and Von Willebrand Disease
What is acute bronchitis
Self limiting chest infection. Assoicated with oedematous large airways and sputum productions, may cause wheeze but no other focal chest signs (crackles, dullness to percussion, bronchial breathing etc).
How does bronchitis present
Cough
Sore throat
Rhinorrhoea
Wheeze (not always present)
Investigations and management in bronchitis
Clinical diagnosis
Analgesia, fluid intake.
Only do antibiotics if:
- Systemically very unwell
- Pre-existing comorbidities
- CRP 20-100
What is allergic rhinitis
IgE mediated T1 hypersensitivity reaction. Environmental allergens cause allergic inflammatory response in nasal mucosa.
Can be:
- Seasonal (hay fever)
- Perennial (year round - dust etc)
- Occupational (school/work etc)
Nasal spray technique
Left hand when spraying into right nostril. Slightly outwards, away from nasal septum. Do not sniff, shouldnt taste in back of throat
General anaemia signs
Pale skin
Conjunctival pallor
Bounding pulse/tachycardia
Dizziness
Fatigue
Postural hypotension
General anaemia symptoms
Tiredness, short of breath, headaches, palpitations, dizziness, syncope
Causes of microcytic anaemia
TAILS
T - Thalassaemia!
A - Anaemia of chronic disease
I - Iron deficiency anaemia!
L - Lead poisoning
S- Sideroblastic anaemia!
Causes of normocytic anaemia
Can be haemolytic or non haemolytic.
AAAH
A - Acute blood loss
A - Anaemia of chronic disease
A - Aplastic anaemia
H - Haemolytic anaemias (other card)
Normocytic haemolytic causes of anaemia (5)
Normocytic
Sickle cell
G6PD
AHA
Hereditary spheryocytosis
Malaria
Causes of macrocytic anaemia
Can be Megaloblastic (large RBC) or normoblastic.
Megaloblastic - Due vitamin deficiency leading to impaired DNA synthesis preventing cells from dividing normally.
- B12 deficiency
- Folate deficiency
- Secondary to methotrexate
Normoblastic -
- Alcohol
- Hypothyroidism
- Liver disease
- Drugs such as azathioprine
- Pregnancy
How is iron normally stored and made available?
- Iron exists bound to haem/myoglobin (Fe2+) or unbound (Fe3+)
- Fe2+ absorbed directly into duodenum so Fe3+ must first be turned into Fe2+ by ferri-reductase enzymes
- Fe2+ ions bind to ferritin in duodenal cells for storage
- When iron required, Fe2+ turned into Fe3+ by hephaestin
- Fe3+ binds to transferrin for transport where it is delivered to tissue
What is iron deficiency anaemia and give some causes
Anaemia caused by low blood iron (Most common anaemia). Microcytic anaemia
Bowel Cancer
Pregnancy
Blood loss (menorrhagia)
IBS/IDS
Coeliac
H Pylori infection (also proton pump inhibitor use)
Broader causes of iron deficiency anaemia
Increased loss (e.g. chronic GI blood loss) (Most common)
> Colon cancer
> Gastric ulceration
> NSAID/Aspirin use
Malabsorption (Coeliac, helicobacter pylori, gastrectomy)
Increased need (pregnancy, growing children)
Dietary deficiency (rarer)
Signs of iron deficiency anaemia
Pallor
Conjunctival pallor
Atrophic Glossitis (smooth tongue due to atrophy of papillae on surface of tongue)
Koilonychia (spoon shaped nails)
Angular cheilosis (mouth corner ulcers)
Dry rough skin
Dyspnoea, fatigue, headache, restless leg syndrome
Investigations of iron deficient anaemia
1st - FBC -> low MCV, low Hb (MICROCYTIC)
Serum iron
Serum ferritin
Transferrin saturation (serum iron/total iron binding capacity) ALL LOW
TIBC will be high (negative correllation)
Signs specific to iron deficiency anaemia
Pica - Cravings for non food items as food
Hair loss
Restless leg syndrome
Why is acid required for iron absorption?
Stomach acids keep iron in soluble Fe2+ form. When acid drops it changes to Fe3+, which is insoluble
Management of iron deficient anaemia with side effects
Treat underlying cause
Oral iron supplements: ferrous sulphate, ferrous fumarate
Side effects: constipation, diarrhoea, nausea, black stools
Specific anaemia signs that point you places
Iron deficiency
- Koilonychia
- Angular Cheilosis
- Atrophic glossitis
- Brittle hair/nails
Haemolytic anaemia
- Jaundice
Thalassaemia
- Bone deformities
CKD
- Oedema, HTN, excoriations
What should be checked in unexplained iron deficiency
- Colonoscopy
- Oesophogastroduodenoscopy (OGD)
What is pernicious anaemia
Autoimmune B12 deficiency destruction of intrinsic factor (megaloblastic)
Intrinsic factor is secreted by parietal cells and is essential for absorption of B12 in ileum. Antibodies form against intrinsic factor or parietal cells, causing atrophy of gastric mucosa, preventing absorption of vitamin B12.
Other causes of B12 deficiency
Atrophic gastritis (e.g. 2ndary to H pylori), gastrectomy, malnutrition (e.g. alcoholism)
What blood group is more at risk of pernicious anaemia
A
Features of pernicious anaemia
Lethargy pallor dyspnoea + neurological symptoms:
- Pins and needles, numbness, typically symmetrical and affects legs>arms.
- memory loss, poor concentration, confusion, depression, irritability
Investigations in pernicious anaemia
FBC + blood film
- Macrocytic anaemia
- Hypersegmented neutrophil polymorphs and oval macrocytes
B12+folate
Antibitodies
- Anti-IF (intrinsic factor) highly specific but only 50% sensitive
- Anti gastric parietal cell antibodies high sensitivity low specificity
Schilling test (not done routinely anymore)
- Give radiolabelled B12, check absorption. Then give IF and check again if B12 absorption increases
Management of pernicious anaemia
B12 supplement - Oral Cyanocobalamin or IM hydrocobalamin
Folic acid - Never give without B12 - prevent degeneration of the spinal cord
Not a management but it also increases risk of gastric cancer whod have thought
What causes macrocytosis without anaemia
Alcohol!
What does SCT screeninng screen for
Sickle cell
Thalassaemia
Haemoglobin disorders
Define thalassaemia, with epidemiology
Autosomal recessive haemoglobinopathy that causes a microcytic anaemia. Prevalent in areas of malaria (Mediterranean, south Asian, African) as thalassaemia protective against it. (selective advantage)
Either reduction in alpha or beta chains, causing a hypochromic, microcytic anaemia
Pathophysiology and subtypes of alpha thalassaemia
Autosomal recessive, leads to deletions of up to 4 alpha genes on chromosome 16 (2 on each)
1 deletion - Silent carrier (1 or 2, hypochromic and microcytic but normal Hb)
2 deletions - Alpha thalassemia minor/trait. Mild symptoms.
3 deletions - Haemoglobin H (HbH) disease. HbH has 4 beta chains (inability to produce alpha chains). Moderate hypochromic, microcytic anaemia.
4 deletions - Hb Bart’s Hydrops Fetalis syndrome (Alpha thalassaemia major). Hb has high affinity for O2 so tissues not oxygenated. Cardiac failure and massive hepatosplenomegaly causes oedema all over (Hydrops fetalis). Fetus usually dies before birth or in first year.
How does severe hypoxia lead to splenomegaly
Hypoxia causes bone marrow, liver and spleen to increase RBC production. Causes enlargement of liver, spleen and bone marrow.
Pathophysiology of beta thalassaemia
Autosomal recessive point mutations on 2 beta genes on chromosome 11, causing impaired or absent beta chain synthesis.
1 partially or completely defective gene (Bᵀ B) - Beta Thalassaemia Minor (trait). Asymptomatic or mild/absent anaemia with hypochromic and microcytic cells.
2 partially defective genes or 1 and 1 completely defective(Bᵀ Bᴼ). - Beta Thalassaemia intermedia. Moderate anaemia, splenomegaly
2 completely defective genes (Bᴼ Bᴼ) - Beta Thalassaemia Major. Complete absence of beta globin, severe anaemia and lifelong transfusion is needed. Hepatosplenomegaly.
Free alpha chains accumulate in RBCs and damage membrane -> Haemolysis, causing jaundice and secondary haemochromatosis
Why does thalassaemia sometimes not present at birth
HbF still in circulation at first
Signs/symptoms of thalassaemia
- Chipmunk facies (more in beta) - enlarged forehead/cheeks due to extramedullary haematopoiesis
- Hair on end appearance on X ray
- Growth retardation
- Hepatosplenomegaly
- Jaundice
- (OEDEMA IN Hb Barts (Hydrops fetalis))
Anaemia symptoms: Pallor, palpitations, fatigue, failure to thrive
Investigations in thalassaemia
FBC/Blood film - Microcytic, hypochromic anaemia. High iron/ferritin
Blood film: Microcytic hypochromic RBC. Target cells
Hb electrophoresis: HbH (Beta tetramers) in alpha, HbA2 in beta (+low HbA)
Skull X ray: Hair-on-End appearance
Management of thalassaemia
- Blood transfusions
- Iron chellation (oral deferiprone)
- Splenectomy
- Stem cell transplant is only curative option
Complications of thalassaemia
GASH
Gallstones
Aplastic crisis (parvovirus B19)
Secondary haemochromatosis
Hypersplenism
Normocytic anaemia types
Haemolytic
- Sickle cell
- Hereditary spherocytosis
- G6PD deficiency
- Malaria
- Autoimmune haemolysis
Define sideroblastic anaemia with its causes:
Condition where red cells fail to form haem, whose biosynthesis partly occurs in mitochondrion. This leads to deposits of iron in the mitochondria that form a ring around a nucleus caused a ring sideroblast. May be congenital or acquired
Congenital: delta-aminolevulinate synthase-2 deficiency
Acquired
- Myelodysplasia
- Alcohol
- Lead
- Anti-TB medications
Investigations in sideroblastic anaemia
FBC
- Hypochromic microcytic anaemia (more in congenital)
Iron
- High ferritin, iron and transferrin saturation
Blood film
- Basophilic stippling of RBC
Bone marrow
- Prussian blue staining shows ringed sideroblassts
What does Lead poisoning cause defect in
Defective ferrochelatase and ALA Dehydratase function
Features of lead poisoning
Abdominal pain
Peripheral neuropathy
Blue lines on gum margin
Fatigue, constipation, neuropsychiatric features
Investigations in lead poisoning
Blood lead level >10mcg/dL
FBC - Microcytic anaemia.
Blood film - RBC abnormalities, basophilic stippling, clover-leaf morphology
How is lead chelated
Dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
Dimercaprol
Sickle cell pathophys
Autosomal recessive gene mutation on beta globin chain (where valine replaces glutamic acid on 6th amino acid) causes “HbS” variant. (HBB gene on chromosome 11)
Under stress (infection, hypoxia, dehydration, acidosis, cold temperature), RBCs sickle, and HbS polymerises, leading to haemolysis or capillary obstruction (sickle cell crises).
initially, they can return to normal shape but eventually lose membrane flexibility and remain sickled.
Sickle cell relation to malaria
Sickle cell more common in Africa, India, Middle East.
Sickle cell trait (one copy of gene) reduces severity of malaria, causing selective advantage of sickle cell trait in areas with malaria
Classical signs of any haemolytic anaemia
Jaundice, Scleral icterus, gallstones
(caused by haemolysis, releasing bilirubin into the blood)
What are the 4 sickle cell crises
- Sequestration Crisis. RBCs sickle in spleen. Abdominal pain secondary to splenomegaly. Autosplenectomy.
- Aplastic crisis. Infection with parovirus B19 causes bone marrow suppression. causing sudden onset pallor, fatigue, anaemia. Reduced reticulocyte count.
- Haemolytic crisis - jaundice
- Vaso-occlusive crisis - separate card
(+Acute chest syndrome - acute cough, chest pain, dyspnoea)
Signs and symptoms of sickle cell anaemia and of its crises
Anaemia symptoms and jaundice (haemolytic!), worse after stressors
- Various crises, causing autosplenectomy/splenomegaly, bone and chest pain. (NB femoral head susceptible to avascular necrosis)
- Dactylitis
- Priapism
Signs of the vaso-occlusive crises in different areas in sickle cell anaemia.
Bone, ACS, Spleen, CNS, Genitalia
Bone - Dactylitis, Avascular necrosis, osteomyelitis
Lungs - Acute chest syndrome. Dyspnoea, chest pain, hypoxia. New chest infiltrates
Spleen - auto splenectomy, splenomegaly
CNS - Stroke
Genitalia - Priapism - prolonged, painful erection
Investigations for sickle cell anaemia
1st - Newborn screening - guthrie heel prick
- FBC - normocytic anaemia with reticulocytosis (young RBC)
- Blood film - Sickled RBCs, Howell-Jolly bodies
- GOLD: Hb Electrophoresis - HbS chains with absent HbA
- Sickle cell solubility test - HbS insoluble plasma goes cloudy
General management of sickle cell disease
- Hydroxycarbamide (stimulates HbF (foetal haemoglobin), which does not sickle)
- Prophylactic phenoxymethylpenicillin in children
- Pneumococcal vaccine
- Haematopoietic stem cell transplant Last resort
- Blood transfusions (risk of iron overload so iron chellation must be done too)
Define G6PD deficiency
X linked deficiency of Glucose-6-Phosphate Dehydrogenase enzyme, making RBC more susceptible to damage by oxidation
Role of G6PD normally
- Free radicals produced by body which can damage RBCs through DNA, protein and cell membrane damage.
- Glutathione acts as an antioxidant, donating an electron to free radicals, turning them into water and oxygen, but becoming oxidised itself.
- Glutathione reductase uses NADPH to donate an electron back to glutathione and NADP+ is formed.
- G6PD reduces NADP+ back to NADPH using a G6P (which is a metabolite of glucose, so we have lots of it).
Pathophysiology of G6PD
Defective G6PD enzymes produced with shorter half lives, leading to reduced NADPH and glutathione so RBCs are unprotected from free radical damage. Damaged Hb precipitate in cell to form Heinz Bodies and when spleen tries to remove this, it takes a bite out of the RBC, forming bite cells.
Bilirubin from haemolysis is converted to urobilin, giving urine a dark tea-like colour
Common triggers of G6PD
Fava beans
Soy products
Red wine
Metabolic acidosis
Infections (pneumonia, sepsis)
Malaria drugs (chloroquines)
Signs and symptoms of G6PD
Asymptomatic until exposed to oxidative trigger
Jaundice
Dark Tea-coloured urine (urobilin)
Back pain (indicates kidney damage + urine)
Splenomegaly
Anaemia symptoms (Pallor, fatigue, tachycardia, dizziness, palpitation )
Investigations in G6PD
FBC: Low RBC, High reticulocyte
Blood film: Heinz bodies, bite and blister cells
Unconjugated bilirubin: high
GOLD: G6PD enzyme assay
Define hereditary spherocytosis
Autosomal dominant (can be recessive) haemolytic anaemia caused by a defect in spectrin and ankyrin (membrane proteins) causing RBCs to become spherical.
Key signs of hereditary spherocytosis
Neonatal jaundice
Splenomegaly
Anaemia symptoms
Investigations and diagnostic criteria in hereditary spherocytosis
FBC - Normocytic anaemia AND raised MCHC (mean corpuscular haemoglobin concentration)
Blood film - Spherocytes
High bilirubin and urobilinogen
Diagnostic criteria
- Family history
- Typical features
- Positive lab findings (Spherocytes, Raised MCHC)
Treatment of hereditary spherocytosis
Splenectomy
(Lifelong penicillin to prevent post-splenectomy sepsis)
Blood transfusion + Folic acid
3 consequences of intravascular RBC destruction
1) Jaundice - Unconjugated bilirubin in blood
2) Tea-like urine - Unconjugated bilirubin in blood converted to urobilin by liver
3) Kidney disease - Hb broken down to Haemosiderin which is deposited in renal tubular cells
Investigation and treatment in Autoimmune Haemolytic Anaemia
Coombs test positive (agglutination test)
IgG and CD3 = Warm
CD3 alone = cold
Steroids/splenectomy
What is leukaemia
The uncontrolled proliferation of non functional blood blast cells. Leukaemia cells divide rapidly and take up space in the bone marrow, less energy and space available for normal cells. The lack of functioning blood cells leads to leukaemia symptoms, and increased infection and bleeding risk
General leukaemia symptoms
Bone pain, bleeding, bruising, infections, anaemia
- Lymphadenopathy and lymph node pain
- Petechiae (red dots under skin) or petechial rash
- Hepatosplenomegaly
- Easy bruising
- Fatigue
- Weight loss
- Fever
Define acute lymphoblastic leukaemia with epidemiology
Proliferation of lymphoblasts (mostly B cell). Associated with Down syndrome, radiation and t(12;21). Bimodal age distribution, first peak (75% of cases) at 5 years old, second at 50. In T cell ALL, thymus enlargement may be seen
Investigations in ALL
FBC - anaemia, thromocytopenia, leukocytosis (High WBC, low everything else)
Blood film - Lymphoblasts
Nuclear TdT staining - positive
Bone marrow aspiration GOLD - At least 20% bone marrow infiltration
Treatment of ALL
1 - Supportive with blood and platelet transfusions. IV fluids and a hickman line.
2 - Chemotherapy + Allopurinol (prevent tumour lysis syndrome)
First with prednisolone (4-8 weeks then high dose chemo)
Complications of chemotherapy
Stunted growth in children
Tumour lysis syndrome
Infertility
Neurotoxicity
Infections/immunodeficiency
Neutropenia
Investigations in CLL
FBC - anaemia, thrombocytopenia, lymphocytosis
Blood film - Smudge cells (aged or fragile WBCs rupture to leave smudge) + spherocytes if active haemolysis
Flow cytometry - Positive markers for CLL e.g. CD5, CD19, CD20, CD23
Immunoglobulins - Low (B cells dont fully differentiate into plasma cells)
Complications of CLL
Richter transformation - Transformation into a high grade non-Hodgkin lymphoma. (Rapid progressing lymphadenopathy, fever night sweat weight loss (B), raised LDH
Autoimmune haemolytic anaemia
Small lymphocytic lymphoma (Cells move to lymphatic system and settle at nodes)
Hypogammaglobulinaemia
Acute myeloid leukaemia definition, subtypes and epidemiology
Neoplastic proliferation of myeloblasts, with important subtypes;
APML - t(15;17) promyelocyte accumulation with Auer rods. Can cause DIC.
Acute monocytic leukaemia - Monoblast accumulation without Auer rods. Gums infiltrated.
Affects older people, most common over 75s.
Associated with Pataus (trisomy 13), Downs (trisomy 21) syndrome, benzene + radiation exposure
Symptoms specific to AML
Mouth ulcers
DIC (APML)
Gum infiltration/ hypertrophy
Investigations in AML
FBC - Low RBC, platelets. High WBC
Blood film - Blasts and Auer Rods
Bone marrow aspiration - >20% infiltration into bone marrow
Immunophenotyping - checks cell lineage, confirms AML
Management in AML
IV Fluid via hickman line
Chemotherapy + Allopurinol (prevent tumour lysis syndrome)
All-trans retinoic acid in APML, allows blasts to mature into neutrophils
BM transplant
What are Auer rods
Aggregates of myeloperoxidase found in AML that increase risk of clotting (DIC)
Patient with AML suddenly has lots of blood clots, what complication has occured
Disseminated Intravascular Clotting
CML definition and pathophysiology
Uncontrolled proliferation of myeloid cells - usually granulocytes. Associated with t(9;22) - PHILADELPHIA CHROMOSOME.
- BCR-ABL genes fused, permanently activating Tyrosine Kinases, causing proliferation of myeloid cells. Rapid proliferation can lead to Acute Leukaemia (or Blast Crisis)
Phases of CML
Chronic (asymptomatic) <10% blast cells
Accelerated (Further progression) 10-19% blast cells >20% basophils
Blast crisis (terminal phase, mimicks acute leukaemias) >20% blast cells, pancytopenia
Signs of CML
Severe hepatosplenomegaly
Abdominal tenderness/fullness due to hepatosplenomegaly
May show features of gout due to purine breakdown
Investigations in CML
FBC - Very high WCC across spectrum of myeloid cells, low Hb, high Urate
Blood film - Granulocytes
Cytogenetics - Philadelphia chromosome t(9;22)
LDH raised in leukaemia but unspecific
Management of CML
Chemotherapy +- Allopurinol
Tyrosine kinase inhibitor (Imatinib)
Stem cell transplant if severe or if goes to blast phase
Define myelodysplasia/ myelodysplastic syndrome
Dysplasia of myeloblasts in bone marrow but less than 20% infiltration. Causes cytopenia meaning death usually due to infection/bleeding. Increase in blast % causes progression to acute leukaemia
Define lymphoma and give the two types with their differences
Neoplastic proliferation of lymphoid cells (B cells).
- Hodgkins (has Reed-Sternberg cells, spread is contiguous (one node to next) and effects rarely extra nodal)
- Non-Hodgkins (No RS cells, non contiguous spread and goes extra nodal (GI, skin, brain etc)
What type of Hodgkins is most common, what presents with popcorn cells and what is the worst prognosis
Nodular sclerosing MC
Nodular lymphocyte predominant Popcorn cells (RS cell variant)
Lymphocyte depleted has worst prognosis
Risk factors and epidemiology for Hodgkin’s lymphoma
EBV infection history
Family history of lymphoma
Post transplant
HIV
Bimodal (15-35 and >60)
Signs/ symptoms of Hodgkin’s lymphoma
Lymphadenopathy (usually cervical, axillary, inguinal)
- Fixed, hard, rubbery, painless(!). Spread is contiguous
Splenomegaly
Alcohol induces lymph node pain
B symptoms
- Fever, night sweats, weight loss
Pruritus (itching)
Staging/classification used for lymphoma
Ann-Arbor (1,2,3,4/A,B)
1 - 1 region of lymph nodes affected
2 - 2 or more, same side of diaphragm
3 - Involvement on both sides of diaphragm
4 - Widespread involvement including organs
A - No B symptoms
B - B symptoms
Pathology associated with Classical and nodular sclerosing Hodgkin’s lymphoma
Classical - usually painless cervical lymphadenopathy
NS - Mediastinal lymphadenopathy, which may cause cough, chest pain and may compress superior vena cava, dilating neck veins and increaing JVP
Investigations in Hodgkin’s lymphoma
FBC - Low Hb/platelets
CXR - Mediastinal lymphadenopathy and widened mediastinum can be used for Ann Arbor.
PET-CT Scan of thorax/abdomen/pelvis - Staging
Lymph node biopsy GOLD - Reed sternberg cells
Management of Hodgkin’s lymphoma
1A-2A - ABVD chemotherapy
- Adriamycin
- Bleomycin
- Vinblastine
- Dacarbazine
2A-4B - Longer courses of chemotherapy and radiotherapy
Complications of radiotherapy and chemotherapy treatment
Radio - Hypothyroid, lung fibrosis, secondary malignancy
Chemo - Myelosuppression, Nausea, Alopecia, Infertility
Define Non Hodgkin’s lymphoma
All lymphomas without Reed-Sternberg cells. Can spread extra nodally (skin, stomach, GI tract, bone marrow, spinal cord). Usually due to a genetic mutation in lymphocyte.
Signs/symptoms of Non-Hodgkin’s lymphoma
Fixed, hard, rubbery, painless lymphadenopathy. Spread is non-contiguous
May have extra nodal manifestations
Hepatosplenomegaly (more common in NHL)
B symptoms
Fever, night sweats, weight loss
Investigations in NHL
FBC - pancytopenia if BM affected
LDH - Increases as prognosis worsens (increased cell turnover/proliferation)
Lymph node biopsy GOLD - No reed-sternberg/popcorn cells
CXR, PET of chest, abdomen, pelvis - for staging
Lumbar puncture to check for CNS involvement
