Pathology Course Kindly Sponsored by: Edited by: Michelle Kunc, Jhia Teh, Sally Barker and Yvonne Tsitsiou 1 Introduction The Medical Education Society (MedED) was established in 2004 by three students who were keen to develop schemes whereby senior students tutor younger ones - ‘peer-to- peer’ learning. It was decided that teaching would be outside the formal curriculum and the topics covered would reflect learning needs identified by members of the society and student body. This year we have coordinated PACES and Pathology revision courses, which are being delivered by past ICSM students. We hope you enjoy our Year 5 events and find their content useful for your revision. We would like to thank all the doctors involved in the production of this guide for their support and for taking time out of the schedules to come back and teach us. We would also like to thank the previous MedED guide editors: • 2016-2017: Daniel Campioni-Norman, Rhys Smith, Helen-Cara Younan and Rebekah Judge • 2017-2018: Charlie Caird, Stephanie EzeKwe, Mohammad Fallaha, Samyukta Sundar • 2018-2019: Sophia von Widekind, Lasith Ranasinghe, Daniel Huddart, Alex Huddart If you have any questions please contact us at [email protected]. Please note: MedED does not represent the ICSM Faculty or Student Union. This guide has been produced by students and the Pathology Course lecturers. We have made every effort to ensure that the following information is accurate and reliable. However, this guide should not be used to replace formal ICSM teaching and education materials. With best wishes, The MedED Team Kindly sponsored by: 2 Contents: Haematology Page 5 Dr Jack Stuart and Dr En Lin Goh Peripheral Blood Films 6 Leukaemia 20 Anaemia 7 Lymphoma 23 Macrocytic Anaemia 9 Multiple Myeloma and other Haemolytic Anaemias 10 paraproteinaemias 26 Inherited Haemolytic Anaemias 10 Myelodysplastic Syndromes 27 Acquired Haemolytic Anaemias 13 Aplastic Anaemia 29 Haemostasis 14 Myeloproliferative Disorders 30 Bleeding Disorders 15 Blood Transfusions 31 Venous Thrombosis 17 Microbiology Page 34 Dr Nina Shehata and Dr Aurelien Gueroult Tuberculosis and other Mycobacteria 35 Virology Summary Table 51 Respiratory Tract Infections 36 Serology in hepatitis 57 Infective Endocarditis 38 Neonatal and Childhood Infections 58 GI infections 39 PUO + Fever in the Returning Traveller 60 Urinary Tract Infection 42 + Malaria Wound, Bone and Joint Infections 42 Zoonoses 62 CNS Infection and Meningitis Fungal Infections and Their Diagnoses 65 Sexually Transmitted Infections 44 Antifungals 65 Antimicrobial agents 48 Prion Disease 65 Microbiology in Immunocompromised 49 Reference Table of Common Bugs 67 hosts Infleunza virus 50 Chemical Pathology Page 68 Dr Aziz Younes and Dr Shivam Patel Fluid Balance 69 Therapeutic Drug Monitoring 86 Sodium 69 Calcium 86 Potassium 74 Disorders of Calcium Balance 87 Acid-Base 76 Enzymes and Cardiac Markers 90 Liver Function Tests 78 Lipoprotein Metabolism 91 Porphyrias 80 Nutrition 92 Pituitary 81 Metabolic Disorders 93 Thyroid 82 Hyper- and hypoglycaemia 96 Adrenals 85 Paediatric clinical chemistry 99 Renal physiology 100 Immunology Page 103 Dr Alice Lee and Dr Simon Erridge Primary Immune Deficiencies 104 Transplantation 127 Hypersensitivity Disorders 113 HIV 130 Immune Therapies 121 Vaccination 134 3 Histopathology Page 138 Dr Matthew Machin and Dr Samyukta Sundar Cardiac Pathology 140 Cerebral Pathology 187 Lung Pathology 146 Neurodegenerative diseases 191 GI Disease 151 Metabolic Bone Diseases 193 Pancreatic Disease 159 Non-neoplastic Bone Disease 194 Liver Pathology 162 Neoplastic Bone Disease 196 Urological Pathology 168 Skin Pathology 198 Renal Pathology 171 Connective Tissue Diseases 202 Gynaecological Pathology 178 Vasculitides 203 Breast Pathology 183 Amyloidosis 204 Sarcoidosis 205 4 Haematology 5 Peripheral Blood Films Observation Description Underlying Condition Acanthocytes Abetalipoproteinaemia, liver RBCs show many spicules (Spur/spike cells) disease, hyposplenism Lead poisoning, megaloblastic Accelerated erythropoiesis or Basophilic RBC anaemia, myelodysplasia, liver defective Hb synthesis, small dots stippling disease, haemoglobinopathy e.g. at the periphery are seen (rRNA) thalassaemia Burr cells Uraemia, GI bleeding, stomach Irregularly shaped cells (Echinocyte) carcinoma Glucose-6-phosphate Inclusions within RBCs of Heinz bodies dehydrogenase deficiency, chronic denatured Hb liver disease Post-splenectomy or hyposplenism (e.g. sickle cell disease, coeliac Basophilic (purple spot) nuclear disease, congenital, UC/Crohn's, Howell-Jolly bodies remnants in RBCs myeloproliferative disease, amyloid) Megaloblastic anaemia, hereditary spherocytosis Leucoerythroblastic Marrow infiltration- nucleated Marrow infiltration i.e. myelofibrosis, (myelophthisic) RBCs and primitive WBCs into malignancy anaemia peripheral blood Congenital (lamin B Receptor mutation) Pelger Huet Cells Hyposegmented neutrophil Acquired (myelogenous leukaemia and myelodysplastic syndromes) Red Blood cells of multiple Polychromasia colours (particularly grey-blue), Premature/inappropriate release (sign of due to differing amounts of Hb in from BM reticulocytes) RBC Immature RBCs (mesh-like network of ribosomal RNA ↑in haemolytic anaemias Reticulocytes becomes visible with certain ↓aplastic anaemia, chemo stains i.e. new methylene blue) Hypermature white cells - Megaloblastic anaemia, uraemia, Right shift hypersegmented polymorphs (>5 liver disease lobes to nucleus) Chronic inflammation, Rouleaux formation Red cells stacked on each other paraproteinaemia, myeloma Microangiopathic anaemia, e.g. Fragmented parts of RBCs – DIC, haemolytic uraemic syndrome, Schistocytes typically irregularly shaped, thrombotic thrombocytopenic jagged and asymmetrical purpura, pre-eclampsia Hereditary spherocytosis, Spherocytes Sphere shaped RBC Autoimmune Haemolytic Anaemia Central pallor is straight or curved Hereditary stomatocytosis, high Stomatocytes rod-like shape. RBCs appear as alcohol intake, liver disease ‘smiling faces’ or ‘fish mouth’ Target cells Bull’s-eye appearance in central Liver disease, hyposplenism, (codocyte) pallor thalassaemia, IDA 6 Anaemia Hb: Men: <135 g/L (13.5g/dL), Women: < 115g/L (11.5g/dL) Causes: reduced production of RBCs or increased loss of RBCs (haemolytic anaemias) or increased plasma volume (pregnancy). Symptoms: fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia. Signs: pallor, in severe anaemia (Hb < 80g/L) → hyperdynamic circulation e.g. tachycardia, flow murmurs (ejection-systolic loudest over apex) → heart failure. Low MCV (microcytic Normal MCV (normocytic High MCV (macrocytic anaemia) (FAST) anaemia) anaemia) (FATRBC) Fe-deficiency anaemia Acute blood loss Fetus (pregnancy) Anaemia of chronic disease Anaemia of chronic disease Antifolates (e.g. phenytoin) Sideroblastic anaemia Bone marrow failure Thyroid (hypothyroidism) Reticulocytosis (release of Thalassaemia (in the Renal failure larger immature cells e.g. with absence of anaemia) haemolysis) Hypothyroidism B12 or folate deficiency Cirrhosis (Alcohol excess or Haemolysis liver disease) Pregnancy Myelodysplastic syndromes Iron-Deficiency Anaemia (IDA) Signs: Koilonychia, atrophic glossitis, angular cheilosis, post-cricoid webs (Plummer-Vinson syndrome), brittle hair and nails. Blood film: Microcytic, hypochromic, anisocytosis (varying size), poikilocytosis (shape) pencil cells. Causes: Bleeding until proven otherwise. Classification Causes Discussion Blood Loss Gastrointestinal loss – Meckel’s diverticulum (older children) – Peptic ulcers / Gastritis (chronic NSAID use) – Polyps/colorectal Ca (most common cause in adults >50yrs) – Menorrhagia (women <50 yrs) – Hookworm infestation (developing countries) Increased Pregnancy/lactation utilisation Infants/children - growth Decreased Prematurity Loss of Fe each day fetus is not in Intake Infants/children/elderly utero Suboptimal diet Decreased Coeliac Absence in villous surface in duodenum absorption Post-gastric surgery Rapid transit, ↓ acid which helps Fe absorption Intravascular Microangiopathic Chronic loss of Hb in urine → Fe deficiency haemolysis Haemolytic anaemia PNH 7 2013 NICE guidelines for Iron deficiency anaemia: if no obvious cause then patients should have OGD + colonoscopy, urine dip, coeliac investigations. Treatment: Treat the cause. Oral iron (SE: nausea, abdominal discomfort, diarrhea/constipation, black stools). With severe symptomatic anaemia: IV iron such as Ferrinject / Monofer (anaphylaxis risk) Anaemia of Chronic Disease Cytokine driven inhibition of red cell production - Inflammatory markers like IFNs, Causes: TNF and IL1 reduce EPO receptor • Chronic infection (e.g. TB, osteomyelitis) production (and thus EPO • Vasculitis synthesis) by kidneys. • Rheumatoid arthritis • Malignancy etc. - Iron metabolism is dysregulated. IL6 and LPS stimulate the liver to Ferritin (intracellular protein, iron store) is high in ACD: Fe make hepcidin, which decreases sequestered in macrophage to deprive invading bacteria of iron absorption from gut (by Fe (unless the patient has co-existing iron deficiency inhibiting transferrin) and also anaemia) causes iron accumulation in macrophages. In renal failure: not cytokine driven but due to EPO deficiency. Sideroblastic Anaemia Ineffective erythropoiesis → iron loading (bone marrow) causing haemosiderosis (endocrine, liver and cardiac damage due to iron deposition) Diagnosis: Ring sideroblasts seen in the marrow (erythroid precursors with iron deposited in mitochondria