Mrcp Revision Notes

MRCP Revision Notes

Index Cardiology 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

Angina Pectoris Exercise ECG Myocardial Infarction Post Myocardial Infarction Complications Heart Failure B-type Natriuretic Peptide Hypertrophic Cardiomyopathy Dilated Cardiomyopathy Peripartum Cardiomyopathy Myocarditis Restrictive Cardiomyopathy Cardiogenic Pulmonary Edema Atrial Fibrillation Atrial Flutter Long QT Syndrome Torsades De Pointes Wolff-Parkinson White Syndrome Supraventricular Tachycardia Ventricular Tachycardia Ventricular Fibrillation Atrioventricular Block Arrhythmogenic Right Ventricular Cardiomyopathy Brugada Syndrome Aortic Stenosis Heyde Syndrome Aortic Regurgitation Bicuspid Aortic Valve Mitral Stenosis Mitral Regurgitation Mitral Valve Prolapse Tricuspid Regurgitation

32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63

Prosthetic Heart Valves Infective Endocarditis Rheumatic Fever Acute Pericarditis Constrictive Pericarditis Cardiac Tamponade Congenital Heart Defects Tetralogy of Fallots Atrial Septal Defect Lutembacher Syndrome Patent Foramen Ovale Ventricular Septal Defect Patent Ductus Arteriosus Eisenmenger Syndrome Coarctation of the Aorta Aortic Dissection Hypertension Malignant Hypertension Hypertensive States of Pregnancy Pre-eclampsia Pulmonary Hypertension Deep Venous Thrombosis Cholesterol Embolism Vasovagal Syncope Carotid Sinus Hypersensitivity Atrial Myxoma Septic Shock Cardiac Action Potential Heart Sounds Jugular Venous Pulse Waveform Exercise Physiological Changes ECG

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03 Bronchiolitis Obliterans 04 COPD Page 1

MRCP Revision Notes 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Alpha-1 Antitrypsin Deficiency Allergic Bronchopulmonary Aspergillosis Aspergilloma Invasive Aspergillosis Bronchiectasis Cystic Fibrosis Primary Ciliary Dyskinesia Yellow Nail Syndrome Community Acquired Pneumonia Bacterial Pneumonia Mycoplasma Pneumonia Legionnaires' Disease Aspiration Pneumonia Lung Abscess Hospital-acquired Pneumonia Pneumocystis Jiroveci Pneumonia Histoplasmosis Nocardiosis Viral Pneumonia Eosinophilic Pneumonia Loeffler Syndrome Tuberculosis Idiopathic Pulmonary Fibrosis Sarcoidosis Pneumoconiosis

30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53

Coal Workers' Pneumoconiosis Silicosis Asbestosis Hypersensitivity Pneumonitis Pulmonary Alveolar Proteinosis Pulmonary Alveolar Microlithiasis Acute Respiratory Distress Syndrome Pulmonary Embolism Hepatopulmonary Syndrome Altitude Illness Lung Cancer Small Cell Lung Cancer Non-small Cell Lung Cancer Superior Vena Cava Syndrome Pneumothorax Pleural Effusion Familial Mediterranean Fever Mesothelioma Lymphangioleiomyomatosis Obstructive Sleep Apnea Narcolepsy Respiratory Failure Chest X Ray Oxygen Dissociation Curve

16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

Chronic Pancreatitis Pancreatic Pseudocyst Pancreatic Cancer Crohn Disease Ulcerative Colitis Celiac Disease Tropical Sprue Bacterial Overgrowth Syndrome Whipple Disease Irritable Bowel Syndrome Diverticulitis Peutz-Jeghers Syndrome Melanosis Coli Angiodysplasia of the Colon Mesenteric Ischemia

Gastroenterology & Hepatology 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15

Dyspepsia Gastroesophageal Reflux Disease Achalasia Pharyngeal Pouch Esophagitis Barrett Esophagus Esophageal Cancer Esophageal Varices Helicobacter Pylori Peptic Ulcer Disease Mallory-Weiss Tear Zollinger-Ellison Syndrome Gastric Cancer MALT Lymphoma Acute Pancreatitis

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MRCP Revision Notes 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50

Hirschsprung Disease Colorectal Cancer Gardner Syndrome Foodborne Illness Bacterial Gastroenteritis Salmonellosis Amebiasis Giardiasis Viral Gastroenteritis Pseudomembranous Colitis Cryptosporidium Mycobacterium Avium Intracellulare Autoimmune Hepatitis Primary Biliary Cirrhosis Primary Sclerosing Cholangitis Paracetamol Toxicity Drug-Induced Liver Disease Hemochromatosis Wilson Disease Non-alcoholic Fatty Liver Disease

51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70

Gilbert Syndrome Liver Cirrhosis Ascites Spontaneous Bacterial Peritonitis Budd-Chiari Syndrome Hepatorenal Syndrome Hepatitis A Infection Hepatitis B Infection Hepatitis C Infection Pyogenic Liver Abscess Amoebic Liver Abscess Hydatid Cysts Ascending Cholangitis Hepatocellular Carcinoma Cholangiocarcinoma Cholelithiasis Acute Fatty Liver of Pregnancy Intrahepatic Cholestasis of Pregnancy HELLP Syndrome Hyperemesis Gravidarum

21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

Goodpasture Syndrome Renal Artery Stenosis Acute Pyelonephritis Xanthogranulomatous Pyelonephritis Nephrolithiasis Renal Cell Carcinoma Wilms Tumor Bladder Cancer Benign Prostatic Hyperplasia Prostate Cancer Testicular Cancer Epididymitis Testicular Torsion Cervical Cancer Bartter Syndrome Renal Tubular Acidosis Tumor Lysis Syndrome Refeeding Syndrome Hyperkalemia Hypokalemia

Nephrology & Minerals Metabolism 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20

Acute Renal Failure Acute Tubular Necrosis Rhabdomyolysis Interstitial Nephritis Contrast Induced Nephropathy Renal Papillary Necrosis Chronic Renal Failure Medullary Sponge Kidney Polycystic Kidney Disease Nephrotic Syndrome Minimal Change Disease Membranous Glomerulonephritis Focal Segmental Glomerulosclerosis Amyloidosis Nephritic Syndrome Diabetic Nephropathy IgA Nephropathy Poststreptococcal Glomerulonephritis Mesangiocapillary Glomerulonephritis Rapidly Progressive Glomerulonephritis

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MRCP Revision Notes 41 42 43 44 45 46

Hyponatremia Hypernatremia Calcium Metabolism Hypercalcemia Hypocalcemia Metabolic Acidosis

47 48 49 50 51 52

Metabolic Alkalosis Respiratory Alkalosis Respiratory Acidosis Hypomagnesemia Hypophosphatemia Renal Replacement Therapy

34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67

Milk-Alkali Syndrome Hypoparathyroidism Pseudohypoparathyroidism Cushing Syndrome Pseudo-Cushing Syndrome Primary Aldosteronism Addison Disease Congenital Adrenal Hyperplasia Pheochromocytoma Menstrual Cycle Menopause Amenorrhea Polycystic Ovarian Syndrome Premature Ovarian Failure Androgen Insensitivity Syndrome Gynecomastia Multiple Endocrine Neoplasia Polyglandular Autoimmune Syndrome Carcinoid Syndrome Glucagonoma Insulinoma VIPoma Breast Cancer Ovarian Cancer Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus Maturity Onset Diabetes of the Young Gestational Diabetes Diagnosis of Diabetes Mellitus Diabetic Ketoacidosis Hyperosmolar Hyperglycemic State Familial Hypercholesterolemia Familial Hypertriglyceridemia Hyperlipoproteinemia Type III

Endocrinology & Diabetes 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33

Acromegaly Growth Hormone Deficiency Diabetes Insipidus Syndrome of Inappropriate Antidiuretic Hormone Hyperprolactinemia Prolactinoma Pituitary Apoplexy Sheehan Syndrome Kallmann Syndrome Klinefelter Syndrome Hyperthyroidism Thyroid Storm Hypothyroidism Myxedema Crisis Graves' Disease Hashimoto Thyroiditis Postpartum Thyroiditis Subacute Thyroiditis Toxic Multinodular Goitre Thyrotoxicosis Factitia Riedel Thyroiditis Subclinical Hyperthyroidism Subclinical Hypothyroidism Euthyroid Sick Syndrome Amiodarone-Induced Thyrotoxicosis Thyroid Cancer Hyperparathyroidism Primary Hyperparathyroidism Secondary Hyperparathyroidism Tertiary Hyperparathyroidism Malignancy-associated Hypercalcemia Familial Hypocalciuric Hypercalcemia Idiopathic Hypercalciuria

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MRCP Revision Notes 68 Metabolic Syndrome 69 Obesity Management

70 Anorexia Nervosa 71 Bulimia Nervosa

Hematology & Oncology 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

Iron Deficiency Anemia Anemia of Chronic Disease Thalassemia Sickle Cell Anemia Sideroblastic Anemia Leukoerythroblastic Anemia Pure Red Cell Aplasia Megaloblastic Anemia Polycythemia Vera Hemolytic Anemia Autoimmune Hemolytic Anemia Cold Agglutinin Disease Hereditary Spherocytosis Glucose-6-Phosphate Dehydrogenase Deficiency Paroxysmal Nocturnal Hemoglobinuria Microangiopathic Hemolytic Anemia Disseminated Intravascular Coagulation Hemolytic Uremic Syndrome Thrombotic Thrombocytopenic Purpura Idiopathic Thrombocytopenic Purpura Henoch-Schonlein Purpura Coagulation Cascade Hemophilia Von Willebrand Disease Thrombophilia Heparin-Induced Thrombocytopenia Antithrombin III Deficiency

28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53

Factor V Leiden Thrombophilia Protein C Deficiency Essential Thrombocythemia Thrombocytopenia Acute Myeloid Leukemia Acute Promyelocytic Leukemia Chronic Myeloid Leukemia Leukemoid Reaction Acute Lymphoblastic Leukemia Chronic Lymphocytic Leukemia Aplastic Anemia Myelodysplastic Syndrome Myelofibrosis Hairy Cell Leukemia Hodgkin Lymphoma Non-Hodgkin Lymphoma Burkitt Lymphoma Mantle Cell Lmphoma Multiple Myeloma Monoclonal Gammopathy of Undetermined Significance Hyperviscosity Syndrome Waldenstrom Macroglobulinemia Cryoglobulinemia Asplenia Transfusion Reactions Hypereosinophilic Syndrome

09 10 11 12 13 14 15 16

Raynaud Phenomenon Mixed Connective-Tissue Disease Rickets Paget Disease Osteomalacia Osteoporosis Corticosteroid Induced Osteoporosis Still Disease

Rheumatology & Autoimmune Disorders 01 02 03 04 05 06 07 08

Rheumatoid Arthritis Systemic Lupus Erythematosus Drug-Induced Lupus Erythematosus Systemic Scleroderma Dermatomyositis and Polymyositis Polymyalgia Rheumatica Fibromyalgia Sjogren Syndrome

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MRCP Revision Notes 17 18 19 20 21 22 23 24 25 26 27 28 29

Osteoarthritis Gout Pseudogout Septic Arthritis Osteomyelitis Relapsing Polychondritis Elbow Pain De Quervain Tenosynovitis Adhesive Capsulitis Supraspinatus Tendonitis Avascular Necrosis Baker Cyst Charcot Arthropathy

30 31 32 33 34 35 36 37 38 39 40 41

Reactive Arthritis Ankylosing Spondylitis Psoriatic Arthritis Wegener Granulomatosis Microscopic Polyangiitis Churg-Strauss Syndrome Polyarteritis Nodosa Behcet Disease Giant Cell Arteritis Takayasu Arteritis Kawasaki Disease Antiphospholipid Syndrome

28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54

Motor Neuron Disease Multifocal Motor Neuropathy Myasthenia Gravis Lambert-Eaton Myasthenic Syndrome Myotonic Dystrophy Hereditary Spastic Paraplegia Neuroleptic Malignant Syndrome Botulism Inclusion Body Myositis Acid Maltase Deficiency Critical Illness Myopathy Central Pontine Myelinolysis Hypokalemic Periodic Paralysis McArdle Syndrome Becker Muscular Dystrophy Mitochondrial Myopathies Locked-in Syndrome Cerebrovascular Accident Glasgow Coma Scale Intracranial Hemorrhage Cerebral Infarction Localization of Brain Lesion Aphasia Localization of Cerebral Stroke Lacunar Stroke Transient Ischemic Attack Lateral Medullary Syndrome

Neurology 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

Alzheimer Disease Lewy Bodies Dementia Pick Disease AIDS Dementia Complex Transient Global Amnesia Normal Pressure Hydrocephalus Parkinson Disease Multiple System Atrophy Progressive Supranuclear Palsy Progressive Multifocal Leukoencephalopathy Tremors Essential Tremor Creutzfeldt-Jakob Disease Chorea Huntington Disease Dystonia Oculogyric Crisis Tourette Syndrome Friedreich Ataxia Ataxia Telangiectasia Wernicke Encephalopathy Epilepsy Hemiballismus Restless Legs Syndrome Multiple Sclerosis Guillain-Barre Syndrome Miller Fisher Syndrome

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MRCP Revision Notes 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91

Basilar Artery Occlusion Vertebral Artery Dissection Pontine Hemorrhage Lateral Pontine Syndrome Cavernous Sinus Thrombosis Cerebral Venous Thrombosis Carotid Artery Dissection Carotid Artery Stenosis CADASIL Syndrome Idiopathic Intracranial Hypertension CSF Analysis Meningitis Neisseria Meningitidis Listeria Monocytogenes Herpes Simplex Encephalitis Cerebral Abscess Cryptococcus Meningitis Facial Nerve Paralysis Bell Palsy Ramsay Hunt Syndrome Rinne and Weber Test Vertigo Benign Paroxysmal Positional Vertigo Meniere Disease Acoustic Neuroma Glomus Jugulare Tumor Craniopharyngioma Optic Neuritis Miosis and Mydriasis Argyll Robertson Pupils Adie Syndrome Oculomotor Nerve Palsy Trochlear Nerve Palsy Abducens Nerve Palsy Internuclear Ophthalmoplegia Posterior Communicating Artery Aneurysm Visual Field Defects

92 Ptosis 93 Horner Syndrome 94 Nystagmus 95 Migraine 96 Tension type Headache 97 Cluster Headache 98 Chronic Paroxysmal Hemicrania 99 Medication Overuse Headache 100 Trigeminal Neuralgia 101 Post Lumbar Puncture Headache 102 Anterior Spinal Artery Syndrome 103 Brown-Sequard Syndrome 104 Subacute Combined Degeneration of Spinal Cord 105 Transverse Myelitis 106 Arnold-Chiari Malformation 107 Syringomyelia 108 Phrenic Nerve Palsy 109 Cervical Spondylosis 110 Cervical Disc Prolapse 111 Traumatic Brachial Plexopathy 112 Brachial Neuritis 113 Carpal Tunnel Syndrome 114 Radial Nerve Palsy 115 Ulnar Nerve Palsy 116 Lumbar Disc Prolapse 117 Metastatic Spinal Cord Compression 118 Cauda Equina Syndrome 119 Lumbar Spinal Stenosis 120 Femoral Nerve Palsy 121 Meralgia Paresthetica 122 Sciatic Nerve Palsy 123 Peripheral Neuropathy 124 Alcoholic Neuropathy 125 Diabetic Neuropathy 126 Charcot Marie Tooth Disease

Ophthalmology 01 Retinal Vein Occlusion 02 Retinal Artery Occlusion 03 Hypertensive Retinopathy Pass-MRCP.com

04 Diabetic Retinopathy 05 Age-Related Macular Degeneration 06 Retinitis Pigmentosa Page 7

MRCP Revision Notes 07 08 09 10

Cataract Ectopia Lentis Uveitis Conjunctivitis

11 12 13 14

Herpes Simplex Keratitis Trachoma Glaucoma Retinoblastoma

08 09 10 11 12 13 14

Post-traumatic Stress Disorder Chronic Fatigue Syndrome Generalized Anxiety Disorder Phobic Disorders Somatoform Disorders Obsessive-Compulsive Disorder Personality Disorders

26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49

Chickenpox In Utero VZV Infection Herpes Zoster Infectious Mononucleosis Cytomegalovirus Parvovirus B19 Infection Measles Mumps Dengue Fever Ebola HIV Human Papillomavirus Toxoplasmosis Malaria Schistosomiasis Cutaneous Larva Migrans Strongyloides Stercoralis Visceral Larva Migrans Filariasis Cysticercosis Candidiasis Vaginal Discharge Vaccines Reye Syndrome

Psychiatry 01 02 03 04 05 06 07

Depression Schizophrenia Delirium Bipolar Disorder Postpartum Psychiatric Disorders Electroconvulsive Therapy Panic Disorder

Infectious Diseases 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Streptococcus Staphylococcus Aureus Toxic shock Syndrome Gonorrhea Chlamydial Genitourinary Infections Diphtheria Leprosy Syphilis Jarisch-Herxheimer Reaction Yaws Tetanus Anthrax Psittacosis Leptospirosis Brucellosis Q Fever Rabies Cat Scratch Disease Typhus Lyme Disease Leishmaniasis African Trypanosomiasis Chagas Disease Herpes Simplex Virus Acute Herpetic Gingivostomatitis

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MRCP Revision Notes

Dermatology & Allergic Disorders 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

Anaphylaxis Hereditary Angioedema Contact Dermatitis Urticaria Atopic Dermatitis Eczema Herpeticum Pompholyx Erythroderma Erysipelas Cellulitis Necrotizing Fasciitis Gangrene Impetigo Herpes Labialis Vitiligo Pityriasis Versicolor Pityriasis Rosea Acne Vulgaris Rosacea Seborrheic Dermatitis Hypertrichosis Alopecia Alopecia Areata Tinea Capitis Tinea Corporis Tinea Cruris Lichen Planus Lichen Sclerosus Discoid Lupus Erythematosus Psoriasis Scabies Acanthosis Nigricans Morphea Erythema Ab Igne Erythema Gyratum Repens

36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69

Granuloma Annulare Oral Hairy Leukoplakia Dermatitis Herpetiformis Pemphigus Vulgaris Bullous Pemphigoid Pemphigoid Gestationis Polymorphic Eruption of Pregnancy Erythema Multiforme Stevens-Johnson Syndrome Toxic Epidermal Necrolysis Drug-Induced Hypersensitivity Syndrome Porphyria Cutanea Tarda Erythema Nodosum Pyoderma Gangrenosum Necrobiosis Lipoidica Pretibial Myxedema Livedo Reticularis Malignant Melanoma Cutaneous Squamous Cell Carcinoma Keratoacanthoma Actinic Keratosis Cutaneous Basal Cell Carcinoma Kaposi Sarcoma Keloids Genital Herpes Genital Ulcers Vascular Ulcers Hyperhidrosis Onycholysis Onychomycosis Koebner Phenomenon Phototoxicity Gingival Hyperplasia Diabetic Foot

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04 Digoxin 05 Adenosine 06 Amiodarone Page 9

MRCP Revision Notes 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39

Flecainide ACE Inhibitors Diuretics Calcium Channel Blockers B-Blockers B-Agonists Alpha Blockers Smoking Cessation Theophylline Sildenafil Antiemetics Octreotide Metformin Sulfonylurea Thiazolidinediones Exenatide Dipeptidyl Peptidase-4 Inhibitors Types of Insulin Cholesterol Lowering Drugs Breastfeeding Contraindications Corticosteroids Oral Contraceptive Pills Hormone Replacement Therapy Selective Estrogen-receptor Modulator Salicylate Toxicity Heparin Warfarin Iron Tablets Toxicity Allopurinol Bisphosphonates Methotrexate Cytotoxics and DMARDs Monoclonal Antibodies

40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 01

Dopamine Agonists Benzodiazepines Phenytoin Triptans Botulinum Toxin Selective Serotonin Reuptake Inhibitors Serotonin Syndrome Tricyclic Anti-Depressants St John’s Wort Antipsychotics Lithium Palliative Care Prescribing Antibiotics Penicillin Quinolones Antituberculous Drugs Antiviral Drugs Anti-retroviral Drugs Isotretinoin Alcohol Withdrawal Syndrome Opioid Toxicity Cocaine Toxicity MDMA Toxicity Organophosphate Toxicity Ethylene Glycol Toxicity Carbon Monoxide Poisoning Methemoglobinemia Cyanide Poisoning Lead Poisoning Zinc Deficiency Scurvy 71 Pellagra

08 09 10 11 12 13 14

Ehlers-Danlos Syndrome Fabry Disease Fragile X Syndrome Galactosemia Hereditary Hemorrhagic Telangiectasia Homocystinuria Lesch-Nyhan Syndrome

Genetics & Hereditary Disorders 01 02 03 04 05 06 07

Patterns of Inheritance Neurofibromatosis Tuberous Sclerosis Acute Intermittent Porphyria Alport Syndrome Cystinuria Down Syndrome

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MRCP Revision Notes 15 16 17 18

Marfan Syndrome McCune-Albright Syndrome Phenylketonuria Pseudoxanthoma Elasticum

19 20 21 22

Refsum Disease Turner Syndrome Von Hippel-Lindau Disease Wiskott-Aldrich Syndrome

13 14 15 16 17 18 19 20 21 22

Inflammatory Mediators Layers of the Skin Foramina of the Skull Renal Anatomy Relative Risk Incidence and Prevalence Sensitivity and Specificity Study Design Fitness to Fly Driver and Vehicle Licensing Agency Rules (DVLA)

Basic Sciences & Statistics 01 02 03 04 05 06 07 08 09 10 11 12

Human Leukocyte Antigen Hypersensitivity Reactions Immunoglobulins Antineutrophil cytoplasmic antibodies (ANCA) Primary Immunodeficiency Inflammatory Markers Rheumatoid Factor Alkaline Phosphatase Atrial Natriuretic Peptide Nitric Oxide Endothelin Interferons

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MRCP Revision Notes

Cardiology Angina Pectoris Angina pectoris is the sensation of chest pain due to ischemia of the heart muscle from obstruction or spasm of the coronary arteries. Features of pain:  Chest discomfort rather than actual pain located in the epigastrium, back, neck area, jaw, or shoulders  The pain is precipitated by physical activities (running, walking), cold weather, heavy meals, and emotional stress  No autonomic symptoms as diaphoresis  Lasts less than 15 minutes  Relieved by rest or sublingual nitroglycerin within about 5 minutes Diagnosis of stable angina is unlikely if the chest pain is:  Continuous  Very prolonged  Unrelated to activity

 

Brought on by breathing in Associated with symptoms such as dizziness, palpitations, tingling or difficulty swallowing

Diagnosis  ECG is normal during episodes and will show more than 1 mm ST depression  Troponin will be less than 0.03, Levels > 0.03 are indicative of unstable angina  An exercise ECG may be used to confirm the chest pain is caused by myocardial ischemia  MPS (Myocardial perfusion scintigraphy) with SPECT (Single photon emission computed tomography), CT coronary angiography or stress echocardiography are non-invasive functional testing  Coronary angiogram second-line investigation when the results of non-invasive functional imaging are inconclusive

Management Providing immediate relief  Relief of symptoms by short-acting nitrate as sublingual nitroglycerin  Dose is to be repeated the after 5 minutes if the pain has not been relieved  Call an emergency ambulance if the pain has not been relieved 5 minutes after taking a second dose Pass-MRCP.com

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MRCP Revision Notes Anti-anginal drug treatment  B-blocker or a calcium channel blocker as first-line treatment for stable angina. Decide which drug to use based on comorbidities, contraindications (asthma in B-blockers and headache and heart failure in calcium channel blocker) and the person's preference  If the person's symptoms are not satisfactorily controlled on a B-blocker or a calcium channel blocker, consider either switching to the other option or using a combination of the 2  Alternatives for B-blocker or a calcium channel blocker are long-acting nitrate, ivabradine, nicorandil and ranolazine Revascularization options CABG (Coronary artery bypass graft) and PCI (Percutaneous coronary intervention) are considered for patients with stable angina whose symptoms are not satisfactorily controlled with optimal medical treatment. CABG is indicated over PCI for people with multi-vessel disease whose symptoms are not satisfactorily controlled with optimal medical treatment and who:   

Have diabetes Are over 65 years Have anatomically complex 3-vessel disease with or without involvement of the left main stem

Secondary prevention of cardiovascular disease  Aspirin 75 mg daily  ACE inhibitors for people with stable angina and diabetes  Statin cardiovascular disease prevention

Unstable Angina Unstable Angina differs from stable angina by:  

The pain is prolonged, at rest, frequent, poor response to nitrates. ECG findings are more prominent

 

Troponin level > 0.03 but less than 0.1 Angiography will show fixed lesion (atheromatous plaque)

Unstable angina and NSTEMI are often indistinguishable; they are considered the same management in the 2014 guidelines.

Prinzmetal angina Pure vasospastic angina i.e. in the presence of angiographically normal coronary arteries, it occurs in young age with on risk factors and not related to exertion. Diagnosis is done by provocative test and ECG monitoring. Management is by nitrates and calcium channel blockers.

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MRCP Revision Notes

Exercise ECG Exercise testing is noninvasive procedure for evaluating for inducible ischemia in the patient with angina. Exercise testing can be done on a motorized treadmill or with a bicycle ergometer. Bruce protocol is an exercise protocol in which the treadmill speed increases every 3 minutes until limited by symptoms with ECG should be monitored continuously. The test is positive in:  ST segments depression  Development of angina symptoms  Ventricular arrhythmias

 

Inadequate blood pressure response Inadequate heart rate response

Indications of referral to coronary angiography (severe cases with poor prognosis):  ST-segment depression >2 mm at low workloads (< 6 minutes on the Bruce protocol)  Heart rates response < 70% of age-predicted maximum  Hypotension

Myocardial Infarction Myocardial infarction (MI) (heart attack) is the irreversible necrosis of heart muscle secondary to prolonged ischemia. Pain of MI differs from angina pain in:  Prolonged (>30 min)  Gradual  More sever

  

At rest Not relieved by nitrates Associated with autonomic symptoms



Rise and fall in serum cardiac markers

Diagnosis Diagnosis of MI can be made on the basis of the first two criteria  

History of ischemic discomfort Evolutionary ECG changes

ECG ECG must show new ST elevation (greater than 2 mm) in two or more adjacent ECG leads. The evolution of new Q waves is diagnostic. Coronary territories on ECG  Left anterior descending artery obstruction causes anteroseptal MI in V1-V4 Pass-MRCP.com

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MRCP Revision Notes



Right coronary artery obstruction causes inferior wall MI in II, III, aVF



Left anterior descending or left circumflex artery obstruction cause anterolateral MI in V4-6, I, aVL

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MRCP Revision Notes

 

Left circumflex artery obstruction causes lateral wall MI in I, aVL +/- V5-6 Posterior MI occurs with inferior or lateral wall MI, it is presented by ST depression in V1 to V3 with upright T waves and dominant R waves

Cardiac enzymes Troponin Serum levels increase within 3-12 hours from the onset of chest pain, peak at 24-48 hours, and return to baseline over 514 days. Level above 0.1 ng/ml indicates a myocardial infarction.

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MRCP Revision Notes Creatine Kinase CK-MB levels increase within 3-12 hours of the onset of chest pain, reach peak values within 24 hours, and return to baseline after 48-72 hours, so it is a good indicator of reinfarction. Sensitivity and specificity are not as high as they are for troponin levels. Myoglobin Myoglobin levels are highly sensitive but not specific. Urine myoglobin levels rise within 1-4 hours from the onset of chest pain.

Acute management (NICE guidelines 2013) Initial management includes:   

Aspirin and clopidogrel Intravenous B-blocker Intravenous morphine

 

Subcutaneous low-molecular-weight heparin Repeated doses of sublingual GTN

Anticoagulations used in MI  Clopidogrel is an ADP receptor antagonist  Glycoprotein IIb/IIIa receptor antagonist (abciximab, tirofiban)  Fondaparinux is antithrombin III activator  Dipyridamole is an antiplatelet (phosphodiesterase inhibitor) mainly used in combination with aspirin  Bivalirudin is a reversible direct thrombin inhibitor

Reperfusion therapy Reperfusion therapy is the mainstay management of MI; it includes percutaneous coronary intervention (PCI), thrombolysis and CABG. Percutaneous coronary intervention Primary PCI is the preferred coronary reperfusion strategy for people with acute STEMI. It should be delivered within 12 hours of onset of symptoms and within 120 minutes of the time if fibrinolysis has been given and failed in revascularization. Bivalirudin in combination with aspirin and clopidogrel is recommended for the treatment of adults with STEMI undergoing primary PCI. Complications of stenting  Stent thrombosis occurs in 1-2% of patients, most commonly in the first month. It presents with acute myocardial infarction, management is by abciximab, thrombolytic therapy and re-stenting.  Restenosis is due to excessive tissue proliferation around stent. It occurs in around 5-20% of patients, most commonly in the first 3-6 months. It presents with the recurrence of angina symptoms. Drug eluting stent in association with clopidogrel and aspirin continued for at least 1 year has been shown to reduce the relative risk of re-stenosis.

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MRCP Revision Notes CABG CABG may be needed for patients who fail to respond to PCI with stenting or patient with stenosis of the left main stem artery and in patients who develop major or mechanical complications. Thrombolysis Fibrinolysis is indicated in acute STEMI presented within 12 hours of onset of symptoms if primary PCI cannot be delivered within the next 120 minutes. ECG should be done after 60-90 minutes after administration. For those who have residual ST-segment elevation suggesting failed coronary reperfusion: offer immediate coronary angiography with considered PCI and do not repeat fibrinolytic therapy. Common side-effects include hemorrhage, hypotension and allergic reactions. Contraindications to thrombolysis  Active internal bleeding (hematemesis)  Recent hemorrhage, trauma or surgery  Coagulation and bleeding disorders  Intracranial neoplasm  Stroke within 3 months

   

Aortic dissection Recent head injury Pregnancy Severe hypertension

Secondary prevention (NICE guidelines 2013) Secondary prevention for myocardial infarction within 12 months:  ACE inhibitor  Dual antiplatelet therapy (aspirin plus a second antiplatelet agent) (clopidogrel is alternative to aspirin and superior to it in case of other vascular disease as carotid artery stenosis)  B-blocker (Calcium channel blockers are alternatives except in left ventricular systolic dysfunction)  Statin  Aldosterone antagonists for symptoms and/or signs of heart failure and left ventricular systolic dysfunction Secondary prevention for myocardial infarction after a year:  ACE inhibitor  Single antiplatelet therapy (clopidogrel is alternative to aspirin and superior to it in case of other vascular disease as carotid artery stenosis)  B-blocker should be continued after 12 month in patient who have left ventricular systolic dysfunction  Statin

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MRCP Revision Notes

Post Myocardial Infarction Complications Acute mitral regurgitation Acute mitral regurgitation occurs due to rupture of papillary muscle. The posteromedial papillary muscle is twice as likely to rupture as is the anterolateral papillary muscle as the anterolateral papillary muscle is supplied by two arteries (left anterior descending and left circumflex coronary arteries), whereas the posteromedial papillary muscle is supplied only by the right coronary artery. It is presented by a harsh systolic murmur at the apex which, in association with acute pulmonary edema 2-5 days after MI. Echocardiography is used for diagnosis. Emergency surgical repair is the management of choice. Ventricular septal rupture Ventricular septal rupture and cardiogenic shock are the most common cause of death following acute myocardial infarction, they account for 60% of early death post MI. Ventricular free wall rupture occurs about 10 times more frequently than ventricular septal rupture. Anterior myocardial infarction is typically associated with apical ventricular septal rupture whilst inferior myocardial infarctions are more commonly associated with basal ventricular septal rupture. Ventricular septal rupture is presented 5-10 days after MI by a harsh pan-systolic murmur loudest at the left sternal edge, pulmonary edema and cardiogenic shock. Ventricular septal rupture and papillary rupture are difficult to distinguish clinically, diagnosis by echocardiography or right heart catheter (shows left to right shunt in ventricular septal rupture). Immediate surgery is the management of choice. Cardiogenic shock Cardiogenic shock occurs in about 7% of cases of myocardial infarction. Intra-aortic balloon pump (IABP) is the management of choice in case of low cardiac muscle function. IV dopamine and IV saline are of choice in case of preserved cardiac muscle function. Dressler syndrome Dressler syndrome is acute pericarditis occurs 2-6 weeks following a MI. The underlying pathophysiology is thought to be an autoimmune reaction. It is characterized by a combination of fever, pleuritic pain, pericardial effusion, widespread ST elevation on ECG and a raised ESR. NSAIDs are the management of choice and corticosteroids have been used in patients with severe symptoms.

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MRCP Revision Notes

Left ventricular aneurysm Left ventricular aneurysm occurs after 3 months of MI. It is presented by persistent ST elevation and absent Q waves with episodes of ventricular tachyarrhythmia. Diagnosis is by 24 ECG monitor with echo. Management is by implantable cardioverter defibrillator if ventricular tachyarrhythmia develops.

Heart block Heart block is commonly associated with inferior myocardial infarctions as the AV node is supplied by the right coronary artery. If the patient is asymptomatic, he should continue to be monitored. Complete heart block in anterior myocardial infarction signifies an extensive area of infarction. It is an indication for temporary pacing.

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MRCP Revision Notes

Heart Failure NYHA classification    

NYHA Class I: no symptoms, ordinary physical exercise does not cause undue fatigue, dyspnea or palpitations NYHA Class II: mild symptoms, comfortable at rest but ordinary activity results in fatigue, palpitations or dyspnea NYHA Class III: moderate symptoms, comfortable at rest but less than ordinary activity results in symptoms NYHA Class IV: severe symptoms, symptoms of heart failure are present even at rest with increased discomfort with any physical activity

Diagnosis of acute heart failure (NICE guidelines 2014)  Take a history; perform a clinical examination and standard investigations (ECG, CXR and blood tests).  In people presenting with new suspected acute heart failure, use a single measurement of serum natriuretic peptides (BNP) and if less than 100 ng/L rule out the diagnosis of heart failure.  In people presenting with new suspected acute heart failure with raised natriuretic peptide levels perform transthoracic Doppler 2D echocardiography to establish the presence or absence of cardiac abnormalities.

Management Acute decompensating (NICE guidelines 2014)  Immediate treatments should be started with diuretics such as furosemide.  For people already taking a diuretic, consider a higher dose of diuretic than that on which the person was admitted unless there are serious concerns with patient adherence to diuretic therapy before admission.  Closely monitor the person's renal function, weight and urine output during diuretic therapy.  Do not routinely offer nitrates to people with acute heart failure.  Do not offer sodium nitroprusside or inotropes to people with acute heart failure. Treatment after stabilization  In a person presenting with acute heart failure who is already taking B‑blockers, continue the B‑blocker treatment unless they have a heart rate less than 50 beats per minute, second or third degree AV block, or shock.  Start or restart beta‑blocker treatment during hospital admission in people with acute heart failure due to left ventricular systolic dysfunction, once their condition has been stabilized – for example, when intravenous diuretics are no longer needed.  Offer an angiotensin‑converting enzyme inhibitor and an aldosterone antagonist during hospital admission Chronic management Drugs shown to improve mortality in patients with chronic heart failure:  

ACE inhibitors B-blockers (carvedilol and bisoprolol)

 

Hydralazine with nitrates Spironolactone

ACE-inhibitors and a B-blocker are first line drugs, second-line drugs is either an aldosterone antagonist or a hydralazine in combination with a nitrate. Pass-MRCP.com

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MRCP Revision Notes Ivabradine was licensed by NICE in 2012 as adjuvant for first and second line for treating chronic heart failure. It is indicated if regular heartbeat of 75 beats per minute left ventricular ejection fraction is below 35%. It should be started after 4 weeks of starting treatment with standard drugs. No long-term reduction in mortality has been demonstrated for furosemide. It is only used if there is worsening symptoms or fluid retention. Digoxin has no role in reducing cardiovascular mortality but only used for symptomatic relief. It is recommended for worsening or severe heart failure due to left ventricular systolic dysfunction despite first- and second-line treatment for heart failure. Anticoagulation with warfarin is indicated in:  Low ejection fraction  Intracardiac thrombus

 

Previous thromboembolic event Left ventricular aneurysm

Cardiac resynchronization therapy Cardiac resynchronization therapy by biventricular pacing is indicated in patient with LBBB or widened QRS complexes (>120 ms) that are:  

NYHA class III-IV Ejection fraction less than 35%



On optimal medical therapy

Implantable cardioverter defibrillators Implantable cardioverter defibrillator is indicated in heart failure with symptomatic or asymptomatic arrhythmias. Cardiac transplantation Cardiac transplantation is indicated if significant symptoms persist despite maximal medical therapy. It is contraindicated at ages above 55-60 years and in co-morbidities other than the heart (as renal failure). Left ventricular assist device LVAD in patients is indicated if significant symptoms persist despite maximal medical therapy and heart transplantation is contraindicated.

B-type Natriuretic Peptide BNP is produced by the left ventricular myocardium in response to strain. It is used to rule out a diagnosis of heart failure (< 100pg/ml makes a diagnosis of heart failure is unlikely). It is also a marker of prognosis and guiding treatment.

BNP level is increased in:    

Heart failure Myocardial ischemia Left ventricular hypertrophy Pulmonary embolism

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  

Age > 70 Renal failure Liver cirrhosis

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MRCP Revision Notes Drugs reduce B-type Natriuretic Peptide levels include ACE inhibitors, angiotensin-2 receptor blockers and diuretics.

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MRCP Revision Notes

Pulmonology Bronchial Asthma Bronchial asthma is widespread reversible inflammatory narrowing of the air passages manifested by paroxysmal attacks of dyspnea and wheezy chest. Types Extrinsic or atopic asthma Atopic asthma is presented in early childhood. It occurs mostly in atopic individuals and usually with + ve family history of atopy e.g. urticaria or allergic rhinitis. It is usually seasonal and mediated by IgE. Intrinsic or cryptogenic asthma Cryptogenic asthma starts in middle age (late onset) with -ve family history for atopy. It is usually triggered by respiratory tract infections, chemicals or drugs. Signs and symptoms  It is manifested by paroxysmal attacks of cough, dyspnea, chest tightness and expiratory wheezing  It is usually provoked by exposure to allergens, emotional stress, viral infection and nonspecific precipitating events  Patients with episodic asthma are usually free of symptoms between bouts Classifications of asthma exacerbations Moderate asthma  Worsening symptoms



Peak flow 50-80% best or predicted

Acute severe asthma  PEF 33-50% best or predicted  Respiratory rate ≥25/min

 

Heart rate ≥110/min Inability to complete sentences in one breath

   

Cyanosis Poor respiratory effort Arrhythmia Exhaustion, altered conscious level

Life-threatening asthma  PEF <33% best or predicted  SpO2 <92%  PaO2 <8 kPa  Elevated pCO2 (4.6-6.0 kPa)  Silent chest

Diagnosis  CXR is normal in between attacks, but may show hyper inflated chest and diminished peripheral lung vascular shadows during attacks

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MRCP Revision Notes

 

ABG in mild cases shows hypocapnea due to hyperventilation but in severe cases there is hypoxemia, hypercapnea and respiratory acidosis Blood may show elevated IgE, eosinophilia and leukocytosis

Respiratory function tests show (obstructive RF):  Reduced FEV1, FVC  Reduced FEV1/FVC ratio  Increased residual volume RV

 

Reduced TLCO Increased KCO

Spirometry shows (diagnostic procedure):  Diurnal variation of peak expiratory flow rate (PEFR) greater than 20% is diagnostic  Reversibility of airflow obstruction (increase of FEV1 ≥ 15% after inhaling a short-acting bronchodilator) unlike COPD which shows irreversibility  Bronchial provocation testing (Cold air challenge ,Methacholine, histamine tests)

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MRCP Revision Notes Management Acute attacks  Nebulized B 2 agonists in 15-30 minute intervals with supplementation of with high flow oxygen via reservoir bag are the 1st line in acute severe attacks  Ipratropium bromide nebulizers and IV hydrocortisone are 2nd lines  IV magnesium sulphate is indicated in severe life-threatening attacks. It should be stopped if respiratory rate fall below 25/min Indications for admission to the ICU for intubation and ventilation Any patient fails to respond to maximal medical therapy and show the below signs should be referred immediately to the ICU for intubation and ventilation:    

PaO2 <8 kPa Elevated pCO2 (4.6-6.0 kPa) Poor respiratory effort Exhaustion, altered conscious level

Current guidelines do not support the routine use of non-invasive ventilation in management of severe asthma Chronic asthma Stepwise stable management (NICE guidelines 2017)  Short-acting beta2 agonist (SABA) as reliever therapy  Add low dose of ICS (inhaled corticosteroids) as the first-line maintenance therapy for continuous symptoms  If uncontrolled add long-acting beta2 agonist (LABA) and a trial of adding LTRA (Leukotriene antagonists) to low dose ICS  If uncontrolled switch ICS and LABA maintenance therapy to a MART regimen (Maintenance and reliever therapy is a single inhaler containing both ICS and a fast-acting LABA as formoterol)  If uncontrolled increase the ICS to a moderate maintenance dose  If uncontrolled increase the ICS to a high maintenance dose and trial of an additional drug as LAMA (long-acting muscarinic receptor antagonist) or theophylline Management of bronchial asthma in pregnancy The BNF advises that ‘inhaled drugs, theophylline and prednisolone can be taken as normal during pregnancy and breast-feeding. Drugs used in management of bronchial asthma B2 agonists B2 agonist acts by activating the Gs protein activating adenylate cyclase increasing cAMP which leads to muscular relaxation and bronchodilation. Examples include short acting (Salbutamol) and long acting (salmeterol, formoterol).

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MRCP Revision Notes Adverse effects  Tachycardia, palpitation and hypokalemia  Salmeterol and formoterol should be used with caution in severe liver cirrhosis.  Salmeterol may produce an acute exacerbation of asthma through an acute hypersensitivity reaction Leukotriene antagonists Leukotriene antagonists act by reducing the degranulation of mast cells triggered by the interaction of antigen and IgE. They have little inhibitory effect on mediator release from human basophils They are licensed for use in asthma with allergic rhinitis and have been shown to be as effective as doubling the dose of inhaled steroid. They are also useful in exercise induced bronchial asthma and aspirin sensitive asthma. Omalizumab Omalizumab is a recombinant monoclonal antibody; it binds IgE without activating mast cells. It is used in patients with moderate to severe asthma. Omalizumab reduces the need for corticosteroids.

Occupational Asthma Occupational asthma accounts for 5 to 10% of adult onset asthma. It is caused by agents that are encountered at work. The commonest occupations associated with occupational asthma include:    

Paint sprayers (isocyanates) Chemical processors (acids, detergents, bleaches) Cigarette factory workers (tobacco dust) Tea sifters and packers (tea dust)

  

Laboratory technicians (rats, mice, rabbits, locusts) Plastics workers (polyethylene, polyvinyl) Bakers (flour and enzymes as amylase used in the baking)

Signs and symptoms  Dyspnea wheeze and cough which occur during the working week and remit during holidays  The symptoms do not usually develop immediately on early exposure but begin days, months or even years later Diagnosis  Serial measurements of PEFR are recommended at work and in holidays  Bronchial provocation testing Management  Avoidance of further exposure to the occupational offending allergen  Regular use of bronchodilators

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MRCP Revision Notes

Bronchiolitis Obliterans Bronchiolitis obliterans is irreversible obstructive lung disease in which the bronchioles are compressed and narrowed by patchy chronic inflammation, concentric submucosal and peribronchiolar fibrosis and smooth muscle hypertrophy. Signs and symptoms Bronchiolitis obliterans presents with features of bronchial asthma like dry cough, dyspnea and expiratory wheeze but unremitting symptoms as COPD. Diagnosis  CXR varies from normal to a reticular or reticulonodular pattern  HRCT shows thickened airway walls  Lung biopsy shows intraluminal polyps of organizing connective tissue (confirm the diagnosis)

Management  Lung transplantation is the main line of management  Corticosteroids may be used to delay disease progression

COPD Chronic obstructive pulmonary disease is progressive decline in lung function as a result of irreversible airflow obstruction. Types  Chronic bronchitis (Blue Bloater) is excessive secretion of bronchial mucus manifested by daily productive cough for 3 months or more in at least 2 consecutive years  Emphysema (Pink Puffer) is abnormal permanent enlargement of air spaces distal to the terminal bronchioles and loss of elastic recoil

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MRCP Revision Notes Causes  Smoking (even passive smoking) is the commonest cause (15 % of smokers develop progressive disabling symptoms in their 40s and 50s)  Genetic causes as alpha 1-antitrypsin deficiency  Industrial causes of COPD (cadmium, coal, cotton, cement and grain) Signs and symptoms Diagnosis of COPD should be considered in patients over the age of 35 who have a risk factor (generally smoking) and who present with one or more of the following symptoms:   

Exertional breathlessness Chronic cough Regular sputum production

 

Frequent winter 'bronchitis' Wheeze

Signs  Barrel chest  Cor pulmonale for advanced disease Diagnosis (NICE 2010)  Full blood count shows secondary polycythemia  CXR shows hyperinflation, bullae and flat hemidiaphragm



HRCT is more sensitive and specific for the diagnosis of emphysema (shows bullae)

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MRCP Revision Notes

 

Sputum examination may reveal exacerbating organisms (strept pneumoniae, H influenza or Moraxella catarrhalis) ABG shows hypoxia, hypercapnea, respiratory acidosis (HCO3 levels increase in chronic cases [compensation] and decreases in exacerbations [decompensation])

Pulmonary functions tests show (obstructive pattern)  FEV1 < 80%  FEV1/FVC < 70%  RV increase  TLC increase

  

RV/TLC ratio increase indicating air trapping KCO decrease (unlike BA) Spirometry with reversibility will show minimal reversibility (less than 10-15%)

Consider alternative diagnoses if:  Older people without typical symptoms of COPD where the FEV1/FVC ratio is < 0.7  Younger people with symptoms of COPD where the FEV1/FVC ratio is ≥ 0.7 Staging of COPD by using the FEV1 (NICE 2010)  Stage I: Mild COPD: FEV1/FVC<0.70 and FEV1≥ 80%  Stage II: Moderate COPD: FEV1/FVC<0.70 and FEV1 50-79%  Stage III: Severe COPD: FEV1/FVC<0.70 and FEV1 30-49%  Stage IV: Very severe COPD: FEV1/FVC<0.70 and FEV1 <30%

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MRCP Revision Notes Management (NICE guidelines 2010) Management of acute exacerbation COPD Acute exacerbation COPD is associated with respiratory acidosis, bicarbonate levels are decreased and hydrogen levels are raised due to carbon dioxide retention  





Initial management (nebulizers, antibiotics and IV hydrocortisone) COPD patients is at risk of hypercapnea so O2 must be aimed at 88-92% as higher levels will causes loss of hypoxic drive which is mediated by carotid body. Once the pCO2 is back to normal the target oxygen saturations should be 94-98%. Non-invasive ventilation (NIV) should be used as the treatment of choice for persistent hypercapnic ventilatory failure during exacerbations not responding to medical therapy. BiPAP is superior to CPAP in type 2 respiratory failure. BiPAP reduces rates of intubation, lowers hospital mortality rates and lead to shorter hospital stays Mechanical ventilation is indicated when the patient does not improve on non-invasive ventilation or the pH falls below 7.26. Target inspiratory positive airways pressure (IPAP) of 10 cm water and expiratory positive airways pressure (EPAP) of 4 cm water.

Stable management General measures  Smoking cessation advice  Pneumococcal and annual influenza vaccination  Pulmonary rehabilitation Bronchodilator therapy Short-acting B2 agonists (SABA) are first-line treatment, if the patient remains breathless or have exacerbations the next step is determined by the FEV1:   

FEV1 > 50%: long-acting B2-agoinst (LABA) or long-acting muscarinic antagonist (LAMA) FEV1 < 50%: LABA + inhaled corticosteroid (ICS) or LAMA (ICS decreases exacerbations with no effect on mortality) For patients with persistent exacerbations or breathlessness LAMA and LABA + ICS inhaler irrespective of their FEV1

Long-term oxygen therapy (LTOT) LTOT is indicated in patients with COPD who have a PaO2 less than 7.3 kPa when stable or a PaO2 greater than 7.3 and one of the following:    

Secondary polycythemia Nocturnal hypoxemia (oxygen saturation is less than 90% for more than 30% of the time) Cor pulmonale Pulmonary hypertension

Patients should breathe supplemental oxygen for at least 15 hours per day. Greater benefits are seen in patients receiving oxygen for 20 hours per day.

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MRCP Revision Notes Oral therapy Oral corticosteroids Maintenance use of oral corticosteroid therapy in COPD is not normally recommended. Some patients with advanced COPD may require maintenance oral corticosteroids when these cannot be withdrawn following an exacerbation. Oral theophylline NICE only recommends theophylline to people who cannot use inhaled therapy or in patients who remain symptomatic on monotherapy by combining theophylline with LAMA or with LABA Mucolytic therapy Mucolytic drug therapy should be considered in patients with a chronic cough productive of sputum. Do not routinely use mucolytic drugs to prevent exacerbations in people with stable COPD. Anti-tussive therapy Anti-tussive therapy should not be used in the management of stable COPD. Management of cor pulmonale Patients presenting with cor pulmonale should be assessed for the need for long-term oxygen therapy. Edema associated with cor pulmonale can usually be controlled symptomatically with diuretic therapy. Not recommended drugs for the treatment of cor pulmonale:  

Angiotensin-converting enzyme inhibitors Calcium channel blockers

 

Alpha-blockers Digoxin

Lung reduction surgery Patients with severe COPD who remain breathless with marked restrictions of their activities of daily living, despite maximal medical therapy (including rehabilitation), should be referred for consideration of lung volume reduction surgery if they meet all of the following criteria:  

FEV1 more than 20% predicted PaCO2 less than 7.3 kPa

 

Upper lobe predominant emphysema TLCO more than 20% predicted

Indications of lung transplantation  Limited activities of daily living  Limited life expectancy without transplantation  Exhaustion of medical therapy Before Lung transplantation you must be take concern about patient age, cost effectiveness, other management options and adequate function of other organ systems (renal and hepatic failure).

Alpha-1 Antitrypsin Deficiency Alpha-1 antitrypsin deficiency is an inherited condition caused by lack of protease inhibitor normally produced by the liver protects the lungs connective tissue from neutrophil elastase. Pass-MRCP.com

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MRCP Revision Notes Alpha-1 antitrypsin gene is located on chromosome 14, it is inherited in an autosomal recessive / co-dominant fashion alleles classified by their electrophoretic mobility - M for normal, S for slow, and Z for very slow. Genotypes of Alpha-1 antitrypsin deficiency  In PiMM genotype alpha-1 antitrypsin is 100%  In PiMS genotype alpha-1 antitrypsin is 80%  In PiSS genotype alpha-1 antitrypsin is 60%  In PiMZ genotype alpha-1 antitrypsin is 60%

 

In PiSZ genotype alpha-1 antitrypsin is 40% In PiZZ genotype alpha-1 antitrypsin is 10-15% which is the severest form of alpha 1-antitrypsin deficiency

It is remembered by 1M=50%, 1S=30% and 1Z=10% Signs and symptoms  Recurrent respiratory infections or asthma that does not respond to treatment  Lungs show panacinar emphysema in 2% of cases  Liver cirrhosis in 15% of patients Diagnosis  A1AT concentrations  HRCT chest shows panacinar emphysema especially in lower lobes Management  Stop smoking as smoking acts synergistically to promote the development of emphysema  Intravenous infusions of alpha-1 antitrypsin, derived from donated human plasma. Other treatments currently being studied include recombinant and inhaled forms of A1AT  In severe cases, liver transplantation may be necessary

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MRCP Revision Notes

Gastroenterology & Hepatology Dyspepsia Dyspepsia is a condition of impaired digestion. It is characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness. Causes  Functional dyspepsia  GERD  Peptic ulcer disease  Esophageal and gastric cancer  Cholelithiasis and chronic pancreatitis

 

Drug Causes (NSAIDs, bisphosphonates and steroids) Drugs reducing lower esophageal sphincter pressure (calcium channel blockers, nitrates and theophylline)

Management (NICE Guidelines 2004)  Testing and eradication therapy for H pylori  Low-dose PPI or H2RA for 4 weeks  If symptoms recur; PPI to be taken at the lowest dose possible to control symptoms Urgent referral for endoscopy (alarm signs) Patients aged 55 with recent, unexplained and persistent (4-6 weeks) symptoms or patient under 55 years with:    

Chronic gastrointestinal bleeding Progressive weight loss Progressive dysphagia Persistent vomiting

  

Iron deficiency anemia Epigastric mass Suspicious barium meal

Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) is reflux of gastric contents into the esophagus. Causes  Drugs as calcium antagonists, nitrates, theophylline, bisphosphonates, corticosteroids and non-steroidal antiinflammatory drugs  Poor esophageal peristalsis  Delayed gastric emptying  Hiatus hernia Signs and symptoms Esophageal symptoms Pass-MRCP.com

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MRCP Revision Notes  

Heartburn Regurgitation

Extraesophageal symptoms  Cough and wheezes  Hoarseness, sore throat Complications  Esophagitis  Anemia  Benign strictures



Dysphagia

 

Noncardiac chest pain Enamel erosion or other dental manifestations

 

Barrett esophagus Esophageal cancer

Diagnosis  24-hr esophageal pH monitoring is the gold standard test for diagnosis  Peptest (salivary pepsin) is simple and non-invasive but sensitivity is 30% only  Testing for Helicobacter pylori after 2‑weeks washout period of proton pump inhibitor (PPI) Management (NICE guidelines 2014)  Simple lifestyle advice, including advice on healthy eating, weight reduction and smoking cessation  Empirical full-dose PPI therapy for 4-8 weeks. If symptoms recur after initial treatment, offer a PPI at the lowest dose  Surgical fundoplication is indicated for patients cannot tolerate acid suppression therapy

Achalasia Achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES) in response to swallowing. It presents in middle-age and is more common in women. Symptoms  Long history of dysphagia of both liquids and solids from the start  Regurgitation (cough, aspiration pneumonia and bronchial asthma)  Chest pain

  

Heartburn Halitosis Dysplastic changes (15-fold increase in esophageal cancer)

Diagnosis  CXR shows wide mediastinum and fluid level

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

Barium swallow shows dilated esophagus and lower end narrowing (bird's beak deformity)



Esophageal manometry is the main diagnostic procedure; it shows increased lower esophageal sphincter tone

Differential diagnosis (causes of dysphagia)  Esophageal cancer (dysphagia more to solids and progress to both)  Neurogenic causes (Mythenia gravis, Motor neuron disease, Scleroderma) dysphagia more to liquids  Achalasia equally for both from start  Pharyngeal pouch (regurgitation of rotten food) Pass-MRCP.com

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MRCP Revision Notes 

Obstruction if felt high in the neck (compression web, pharyngeal pouch, thyroid swelling) associated with nasal regurgitation, coughing and chocking

Management  Pneumatic dilation may give temporary relief  Laparoscopic cardiomyotomy is the management of choice  Drug therapy (calcium channel blockers, nitrate) and intra-sphincteric injection of botulinum toxin are alternatives in patients who are unfit for surgery

Pharyngeal Pouch Pharyngeal pouch (Zenker diverticulum) is a diverticulum of the mucosa of the pharynx, just above the cricopharyngeal muscle. Signs and symptoms  Dysphagia and sense of a lump in the neck  Regurgitation of rotten food in the mouth  Halitosis

 

Chronic cough Gurgling neck mass appears only on swallowing

Diagnosis  Simple barium swallow will reveal the diverticulum (procedure of choice)



Upper GI endoscopy

Management  If small and asymptomatic, no treatment is necessary  Larger symptomatic cases is managed by surgical resection of the diverticulum

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Autoimmune Hepatitis Autoimmune hepatitis is a chronic continuing hepatocellular inflammation and necrosis. It has a tendency to progress to cirrhosis. It occurs with other autoimmune disorders, hypergammaglobulinemia and HLA B8, DR3. Types  Type I affects both adults and children and is associated with anti-nuclear antibodies (ANA) and/or anti-smooth muscle antibodies (SMA)  Type II occurs predominantly in children and is associated with anti-liver/kidney microsomal type 1 antibody (LKM1)  Type III is associated with soluble liver-kidney antigen Signs and symptoms Autoimmune hepatitis present as acute or chronic hepatitis or fulminant hepatic failure. Symptoms of acute hepatitis include marked by fever, hepatic tenderness, and jaundice. Extrahepatic symptoms associated with autoimmune hepatitis include:   

Mild pruritus and skin rashes Secondary amenorrhea Cushingoid features and hirsutism

 

Arthralgia Chest pain from pleuritis

Diagnosis  CBC shows eosinophilia, thrombocytopenia and mild leukopenia  Coombs-positive hemolytic anemia  Elevated serum aminotransferase levels (1.5-50 times reference values)  Elevated serum immunoglobulin levels, primarily immunoglobulin G (IgG)  Mild to moderately elevated serum bilirubin and a sharp increase in the alkaline phosphatase  Positive specific antibodies  Liver biopsy Management  Corticosteroids, either alone or in combination with azathioprine is the mainstay therapy  Liver transplantation is effective for patients in whom medical therapy has failed or for those with decompensated cirrhosis

Primary Biliary Cirrhosis Primary biliary cirrhosis (PBC) is a chronic autoimmune disease of the liver that leads to progressive cholestasis and often end-stage liver disease. PBC is presents frequently in women especially between the fourth and sixth decades. PBC is associated with HLA DR3. Causes (autoimmune diseases) Pass-MRCP.com

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MRCP Revision Notes  

Sjogren syndrome (most common cause) Rheumatoid arthritis

Signs and symptoms  Pruritus and jaundice  Right upper quadrant discomfort  Hepatosplenomegaly

 

Systemic sclerosis Thyroid disease

 

Hyperpigmentation Sicca syndrome as xerophthalmia and xerostomia

Diagnosis  Significant elevations of the alkaline phosphatase with mild elevation of aminotransferases (cholestatic picture)  Positive antimitochondrial antibody (AMA) (diagnostic) in 98% of cases and smooth muscle antibodies in 30% of cases  Raised serum IgM  ERCP shows intrahepatic biliary obstruction  Definitive diagnosis is made with percutaneous liver biopsy which shows intra-hepatic biliary obstruction Management  Ursodeoxycholic acid is of choice, it is used to slow the progression of the disease  Corticosteroids and methotrexate may produce improvement in biochemical and histologic findings  Pruritus is managed by antihistamines followed by cholestyramine followed by rifampicin followed by plasmapheresis  Liver transplantation for advanced cirrhosis and intractable pruritus

Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is a progressive course of cholestasis with inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. PSC is strongly associated mainly with ulcerative colitis (80% of cases) and is often complicated by cholangiocarcinoma development. Initial presentation consists of fatigue, jaundice, pruritus, and right upper quadrant pain. Progressive disease causes cirrhosis with symptoms of variceal bleeding, ascites and hepatic encephalopathy. Diagnosis  Significant elevations of the alkaline phosphatase with mild elevation of aminotransferases (cholestatic picture)  Raised serum IgM and hypergammaglobulinemia  ANCA may be positive  Endoscopic retrograde cholangiopancreatography (ERCP) is diagnostic; it shows multiple strictures and dilations of the intrahepatic and extrahepatic biliary ducts

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MRCP Revision Notes

Management  Drug therapy is aimed at treating symptoms and managing complications (ursodeoxycholic acid immunosuppressants and steroids)  Liver transplantation is the management of choice

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MRCP Revision Notes

Nephrology & Mineral Metabolism Acute Renal Failure Acute renal failure is as a sudden, rapidly progressive decrease in kidney function, resulting in an inability to maintain adequate renal function. Signs and symptoms  Non-specific symptoms (nausea, vomiting and malaise)  Sudden increase in BUN or serum creatinine  Oliguria (decline in urinary output to 0.5 mL/kg/h)  Pericardial effusions and pericarditis  Arrhythmias due to hyperkalemia  The lung may show crepitations  Bleeding and clotting  Encephalopathy with confusion and seizures Diagnosis  Elevated BUN and creatinine (serum creatinine concentration will increase by 1-1.5 mg/dL daily)  Hyperkalemia, hypocalcemia, metabolic acidosis and hyperphosphatemia  Anemia can occur as a result of decreased erythropoietin production

Causes of acute renal failure Prerenal azotemia Prerenal azotemia is due to renal hypoperfusion, it represents 40-80% of cases. Causes  Decrease in intravascular volume (hemorrhage, GI losses, dehydration, excessive diuresis, etc.)  Changes in vascular resistance (sepsis, anaphylaxis, anesthesia, etc.)  Decrease cardiac output (cardiogenic shock, congestive heart failure, pulmonary embolism and cardiac tamponade) Diagnosis  The BUN-creatinine ratio > 20:1  FeNa (fractional excretion of sodium) < 1%

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Urinary Na < 20 mEq/L Urine osmolality > 500 mosm/kg

Intrinsic renal failure Intrinsic renal disorders represents up to 50% of all cases of acute kidney injury. Causes  Acute Tubular Necrosis  Acute Glomerulonephritis Pass-MRCP.com

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Acute Interstitial Nephritis

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MRCP Revision Notes Diagnosis  The BUN-creatinine ratio < 20:1 (acute glomerulonephritis > 20:1)  FeNa > 1% (<1 in acute glomerulonephritis)  Urinary Na > 20 mEq/L in acute tubular necrosis (acute glomerulonephritis < 20 mEq/L, variable in acute interstitial nephritis)  Urine osmolality is variable (250-300 mosm/kg in acute tubular necrosis)  Specific gravity < 1010 Postrenal Azotemia Postrenal azotemia represents 5-10% of cases Causes  Urethral obstruction, bladder obstruction and obstruction of both ureters  Benign prostatic hyperplasia Diagnosis  The BUN-creatinine ratio > 20:1  FeNa (fractional excretion of sodium) is variable

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Urinary Na is variable Urine osmolality <400mosm/kg

2013 NICE guidelines of management of acute kidney injury Indications of urgent referring for renal replacement therapy (hemodialysis):   

Hyperkalemia Metabolic acidosis Symptoms or complications of uremia (pericarditis or encephalopathy)

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Fluid overload Pulmonary edema

Acute Tubular Necrosis Acute tubular necrosis is an acute renal failure due to tubular damage; it accounts for 85% of intrinsic acute kidney failure causes.

Causes Ischemic causes  Diarrhea and vomiting  Pancreatitis  Myocardial infarction

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Hepatorenal syndrome Pre-eclampsia and eclampsia

Nephrotoxic causes Endogenous nephrotoxins Pass-MRCP.com

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MRCP Revision Notes  

Burns Rhabdomyolysis

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Massive intravascular hemolysis Hyperuricemia

Exogenous Nephrotoxins  Bence Jones protein  Snake bites  Drugs: aminoglycosides, diuretics, heroin addicts, cyclosporine  Radiographic contrast media Complication  Hyperkalemia, hyponatremia and metabolic acidosis  Infections and Gram-negative septicemia  Pericarditis Diagnosis  Urine osmolality < 350 mosmol/l  Urine sodium excretion > 40 mmol/l  FeNa >1%  Urine sediment with pigmented granular casts and renal tubular epithelial cells Management  Dietary protein restriction  Furosemide is of choice, plasma ultrafiltration in non-responsive to diuretics  Dialysis in life threatening electrolyte disturbances, worsening acidosis and uremic complications (e.g. encephalopathy, pericarditis and seizures)

Rhabdomyolysis Rhabdomyolysis occurs due to muscle injury leading to release of intracellular contents of myocytes into the plasma causing acute tubular necrosis and electrolyte disturbance. Causes  Extensive blunt trauma and crush injury  Prolonged epileptic seizure  Infectious or inflammatory myopathies  Prolonged collapse or coma

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Hypothermia Ecstasy poisoning McArdle syndrome Statins

Diagnosis  Highly elevated creatine kinase  Myoglobinuria  Hypocalcemia, hyperkalemia, hyperphosphatemia and hyperuricemia Pass-MRCP.com

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MRCP Revision Notes Management  IV fluids to maintain good urine output and urine alkalization  Rapid correction of the life-threatening hyperkalemia (IV calcium gluconate)  Hemodialysis if acute renal failure occurs

Interstitial Nephritis Interstitial nephritis accounts for 10-15% of cases of intrinsic renal failure. It is rarely progress to end stage renal disease. Causes  Drugs (70% of cases) e.g. NSAIDs, B- lactams, ethambutol ,cephalosporins, sulphasalazine , phenytoin and allopurinol  Infectious causes e.g. streptococcal infections, CMV, histoplasmosis and Rocky Mountain spotted fever  Immunologic causes e.g. systemic lupus erythematosis, Sjogren syndrome, sarcoidosis and cryoglobulinemia Signs and symptoms  Fever  Maculopapular rash

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Arthralgia Acute renal failure

Diagnosis  Eosinophilia and eosinophilurea  Urine analysis shows proteinuria, RBCs, WBCs and WBCs casts  Renal biopsy shows interstitial edema with a heavy infiltrate of inflammatory cells and tubular necrosis Management  Treatment consists of supportive measures and withdrawal of the offending agent  Short-term corticosteroids accelerate recovery and prevent long-term renal damage  Dialysis may be needed in renal failure

Contrast Induced Nephropathy Contrast-induced nephropathy is the impairment of renal function within 2-3 days of IV contrast administration. Risk factors  Patient is over 75  Chronic kidney disease

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Diabetes Heart failure

Calculation of risk factors rates  Chronic kidney disease or diabetes or heart failure (1 risk factor) = 7%  Patient is over 75 + 1 risk factor = 14% Pass-MRCP.com

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MRCP Revision Notes  

Patient is over 75 + 2 risk factor (chronic kidney disease + diabetes or heart failure) = 25% Patient is over 75 + 3 risk factor (chronic kidney disease + diabetes + heart failure) = 60%

Management  Stopping nephrotoxic medications, analgesics and furosemide prior to the procedure is the primary preventative measure  Acetylcysteine as an antioxidant reduces the risk of nephropathy  IV fluids to maintain renal blood flow if toxicity occurs

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MRCP Revision Notes

Endocrinology & Diabetes Acromegaly Acromegaly results when the anterior pituitary gland produces excess growth hormone. Causes  Most of cases are due to pituitary adenoma Other rare causes  Familial  MEN-1  McCune-Albright syndrome

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Carney syndrome Ectopic GHRH or GH secretion

Signs and symptoms of the tumor  Symptoms of pituitary tumor: hypopituitarism, headaches, bitemporal hemianopia  Raised prolactin in 30% of cases leads to galactorrhea Characteristic changes in appearance (Gigantism):  Tall stature  Mild to moderate obesity  Macrocephaly  Soft tissue hypertrophy  Exaggerated growth of the hands and feet, with thick fingers and toes  Coarse facial features  Frontal bossing  Wide spacing of the teeth and prognathism (the upper or lower jaws protrudes beyond a predetermined imaginary line in the coronal plane of the skull)

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MRCP Revision Notes

Complications  Hypertension  Diabetes  Peripheral neuropathies (e.g., carpel tunnel syndrome)  Cardiomyopathy

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Hyperhidrosis Osteoarthritis and spinal cord compression Colorectal polyps Hyperhidrosis due to sweat gland hypertrophy

Diagnosis  Growth hormone (GH) is not diagnostic as its levels vary during the day  Oral glucose tolerance test shows failure in suppression of GH (Diagnostic)  Elevated IGF-I values indicates GH excess (not specific)  MRI shows a pituitary tumor in 90% of patients

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MRCP Revision Notes

Management  Trans-sphenoidal surgery is first-line treatment for acromegaly in the majority of patient  Somatostatin analogue (octreotide) is effective in reducing GH and shrinking tumor size  Dopamine agonists (bromocriptine, cabergoline) are less effective than somatostatin analogue, they can be used in tumors that secrete both PRL and GH  Pegvisomant is a GH receptor antagonist that blocks hepatic IGF-I production, it decreases IGF-1 levels in 90% of patients to normal, but it doesn't reduce tumor volume  External irradiation is used for older patients or following failed surgical/medical treatment

Growth Hormone Deficiency Causes: Most cases are idiopathic other causes include:   

Genetic causes Brain tumors (Craniopharyngioma) CNS surgery

Signs and symptoms:  Short stature  Small penis  Reduced muscle mass

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CNS radiation Anatomical abnormalities (empty sella syndrome)

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Obesity Poor bone density Hypoglycemia and hypercholesterolemia

DD of short stature:  Achondroplasia  Constitutional Growth Delay Pass-MRCP.com

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MRCP Revision Notes      

Familial short stature Growth hormone resistance Noonan Syndrome Short stature related to a metabolic abnormality (renal tubular acidosis, poorly controlled diabetes mellitus) Short stature related to endocrinopathy (hypothyroidism, Cushing syndrome) Turner Syndrome

Diagnosis  Levels of growth hormone is not diagnostic as levels are nearly undetectable for most of the day  Low levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) {diagnostic but not specific}  Insulin tolerance test with growth hormone measurement is diagnostic, growth hormone releasing hormone (GHRH) testing is alternative Management  Growth hormone replacement by recombinant human growth hormone (rHGH)

Diabetes Insipidus Diabetes insipidus is an uncommon disease characterized by polydipsia and polyuria of large quantities of urine of low specific gravity. Causes Cranial diabetes insipidus (deficiency of vasopressin)  Idiopathic  Post head injury  Sarcoidosis  Pituitary surgery

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Nephrogenic diabetes insipidus (resistance to vasopressin)  Genetic   Electrolytes: hypercalcemia, hypokalemia   Drugs: demeclocycline, lithium   Tubulo-interstitial disease

Wegener granulomatosis Craniopharyngioma Histiocytosis X Wolfram syndrome

UT obstruction Sickle-cell anemia Pyelonephritis

Differential diagnosis (causes of polyuria and polydipsia)  Diabetes mellitus  Hypercalcemia  Cushing syndrome or corticosteroid use  Psychogenic polydipsia (Hysterical polydipsia) is a psychiatric disturbance due to a very large ingestion of water that causes a fall in plasma sodium and osmolality and a concomitant low urine osmolality Pass-MRCP.com

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MRCP Revision Notes Diagnosis  High plasma osmolality, low urine osmolality even after water deprivation  Hypernatremia Vasopressin challenge test Prevent patient drinking water; ask patient to empty bladder and hourly urine and plasma osmolarities. In cranial diabetes insipidus there is a dramatic improvement in urine osmolality (> 50%) following the administration of DDAVP. In nephrogenic diabetes insipidus there is no or little response (< 45%) in urine osmolality. Management  Mild and refractory cases of diabetes insipidus require only adequate fluid intake  Desmopressin acetate in the form of nasal spray or subcutaneous injections is the treatment of choice for central diabetes insipidus  Nephrogenic diabetes insipidus is managed by combined indomethacin with hydrochlorothiazide or amiloride

Syndrome of Inappropriate Antidiuretic Hormone SIADH (syndrome of inappropriate antidiuretic hormone) is excessive release of antidiuretic hormone from the posterior pituitary gland or another source which results in dilutional hyponatremia. Causes  Malignancy e.g. small cell lung cancer, pancreatic and prostatic cancer  Neurological (stroke, subarachnoid hemorrhage, subdural hemorrhage, meningitis, encephalitis)  Infections (tuberculosis, pneumonia)  Drugs (sulfonylureas, SSRIs, TCA, carbamazepine, vincristine, cyclophosphamide)  Porphyria Signs and symptoms (progressive hyponatremia)  Generalized muscle weakness and aches  Myoclonus and hyporeflexia  Cheyne-Stokes respiration  Confusion, delirium and seizures Diagnosis  Hyponatremia  Low plasma osmolarity, high urine osmolarity  Urine volume is low makes urine concentrations of sodium will appear inappropriately high Management  Fluid restriction  Demeclocycline can be useful if fluid restriction fails Pass-MRCP.com

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MRCP Revision Notes 

Slow replacement with IV 0.9% for emergency case (rapidly correction of hyponatremia leads to central pontine myelinolysis)

Type 1 Diabetes Mellitus Type 1 diabetes is an autoimmune destruction of the beta cells in the pancreas causing inability to produce insulin. It is associated with HLA DR-3 or DR-4. It is associated with other autoimmune diseases, such as Graves’ disease, Hashimoto thyroiditis, and Addison disease. Genetic factors  Children whose mother has type 1 DM have a 2-3% risk of developing the disease, whereas those whose father has the disease have a 5-6% risk  Dizygotic twins have a 5-6% concordance rate for type 1 DM  Monozygotic twins will share the diagnosis more than 50% of the time by the age of 40 years Signs and symptoms Onset most often occurs in childhood and symptomatic disease may be sudden.    

Polyuria Polydipsia Polyphagia Unexplained weight loss

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BMI < 25 Diabetic ketoacidosis (DKA) is a common complication

Diagnosis  Positive islet-cell antibodies (85% of cases), insulin antibodies or glutamic acid dehydrogenase antibodies  Low serum insulin levels Management  Lifelong insulin therapy by continuous subcutaneous insulin infusion (2008 NICE guidelines)  Allogeneic pancreatic islet cell transplantation should be considered

Type 2 Diabetes Mellitus Type 2 diabetes mellitus is resulting from the combination of resistance to insulin action, inadequate insulin secretion. Signs and symptoms  Many patients with type 2 diabetes are asymptomatic many years before diagnosis is made  Classic symptoms: Polyuria, polydipsia, polyphagia, and weight loss  Blurred vision (microvascular complications)  Lower-extremity paresthesia Pass-MRCP.com

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MRCP Revision Notes  

BMI >25 Diabetic ketoacidosis (DKA) is a rare complication

Diagnosis  High (Insulin resistance) or low (Beta-cell dysfunction) serum insulin levels

2015 NICE guidelines Type 2 diabetes management in adults 1 - Dietary advice 2 - Blood pressure management  The target of blood pressure is below 140/80 mmHg (below 130/80 mmHg if there is kidney, eye or cerebrovascular damage)  Angiotensin-converting enzyme (ACE) inhibitor is the first-line antihypertensive drug; it is contraindicated in African or Caribbean family origin, pregnant or there is a possibility of pregnancy  Diuretics or calcium‑channel blockers are alternatives  Antiplatelet therapy (aspirin or clopidogrel) are not indicated for adults with type 2 diabetes without cardiovascular disease 3 - Blood glucose management:  Start with a single drug  If HbA1c levels are not adequately controlled by a single drug and rise to 58 mmol/mol (7.5%) or higher: intensify drug treatment (First intensification with dual non-insulin drugs and Second intensification with triple non-insulin drugs or any treatment combination containing insulin)  Aim for HbA1c in management not associated with hypoglycemia to 48 mmol/mol (6.5%) and to 53 mmol/mol (7.0%) and in management associated with hypoglycemia 4 - Drug treatment:  Standard-release metformin as the initial drug treatment for adults with type 2 diabetes  If metformin is contraindicated or not tolerated, consider alternatives as dipeptidyl peptidase‑4 (DPP‑4) inhibitor, pioglitazone or sulfonylurea  Sodium-glucose transport (SGLT-2) inhibitors (canagliflozin, dapagliflozin or empagliflozin) are not licensed by NICE to be used as monotherapy For Insulin therapy:  Start NPH insulin twice daily with or without pre-mixed (biphasic) human insulin  Switch from NPH insulin to detemir or insulin glargine if the patient needs to reduce the frequency of injections from twice to once daily or recurrent symptomatic hypoglycemic episodes or the patient did not reach the target HbA1c  Switch from short‑acting human insulin preparations to short‑acting insulin analogues if the patient prefers injecting insulin immediately before a meal or recurrent hypoglycemic episodes or blood glucose levels rise markedly after meals 5 – Monitoring by HbA1c measurement Indications of self‑monitoring of blood glucose levels for adults with type 2 diabetes:

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MRCP Revision Notes    

The patient is on insulin There is evidence of hypoglycemic episodes The patient is on oral medication that may increase their risk of hypoglycemia while driving or operating machinery The patient is pregnant, or is planning to become pregnant

Short-term self-monitoring is indicated when starting treatment with oral or intravenous corticosteroids or to confirm suspected hypoglycemia. 6 - Management of complications  Amitriptyline, duloxetine, gabapentin or pregabalin as first line for neuropathic pain, capsaicin cream for localized neuropathic pain  Trigeminal neuralgia is managed by carbamazepine  Gastroparesis is managed by domperidone as first line and erythromycin or metoclopramide as alternatives

Metabolic Syndrome Metabolic syndrome is a multiplex risk factor that arises from insulin resistance accompanying abnormal fat deposition. It is a risk factor for coronary heart disease, as well as for diabetes, fatty liver, and several cancers. Signs and symptoms  Hypertension  Hyperglycemia  Hypertriglyceridemia  Reduced high-density lipoprotein cholesterol (HDL-C)

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Abdominal obesity Acanthosis nigricans, hirsutism, peripheral neuropathy, and retinopathy Xanthomas

Diagnosis For a diagnosis of metabolic syndrome at least 3 of the following should be identified:     

Waist circumference > 102 cm in men and > 88 cm women Triglycerides > 1.7 mmol/L HDL-C < 1.03 mmol/L in males and < 1.29 mmol/L in females Blood pressure > 130/85 mmHg or active treatment of hypertension Fasting plasma glucose > 5.6 mmol/L or previously diagnosed type 2 diabetes

Management  Lifestyle change and weight loss are considered the first line management  Statins for elevated LDL-C  Nicotinic acid for decreased HDL-C  Metformin for hyperglycemia Pass-MRCP.com

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MRCP Revision Notes

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MRCP Revision Notes

Hematology & Oncology Iron Deficiency Anemia Iron deficiency anemia develops when body stores of iron drop too low to support normal red blood cell (RBC) production. Causes  Dietary iron deficiency (most common cause)  Dietary substances that diminish the absorption iron include phytates, oxalates, phosphates, and carbonates  Internal and external hemorrhage  Hemosiderinuria, hemoglobinuria, and pulmonary hemosiderosis  Malabsorption of iron due to extensive surgical removal of the proximal small bowel or chronic diseases as celiac syndrome Signs and symptoms  Pallor of the mucous membranes

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Myocardial ischemia Cold intolerance

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Esophageal webbing and gastric atrophy Koilonychia (spoon-shaped nails)

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Angular stomatitis

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Glossitis

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MRCP Revision Notes

Diagnosis  Complete Blood Count shows decreased mean corpuscular volume (MCV) and the mean corpuscular hemoglobin concentration (MCHC) (microcytic hypochromic)

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Low serum iron and ferritin (storage protein) levels with elevated transferrin (transporting protein) and total ironbinding capacity (serum iron and serum iron-binding protein levels)( TIBC) and decreased transferrin saturation (serum iron divided by total iron-binding capacity)

Management  Underlying etiology should be corrected and improve dietary measures  Oral iron therapy (ferrous sulfate 325 mg TDS)  Parenteral iron therapy is reserved for patients who are either unable to absorb oral iron or who have increasing anemia despite adequate doses of oral iron

Anemia of Chronic Disease Anemia of chronic disease is an absolute reduction of the total number of circulating red blood cells due to decreased RBC production. Signs and symptoms  Generalized weakness or malaise  Lightheadedness, dizziness  Syncope or near-syncope  Decreased exercise tolerance Pass-MRCP.com

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Palpitations Cold intolerance Inability to concentrate Skin pallor Page 56

MRCP Revision Notes Diagnosis  Complete blood count shows decreased RBC count with normocytic normochromic picture  Iron studies show low serum iron, TIBC and transferrin levels with elevated ferritin and normal transferrin saturation (due to low iron and TIBC)

Thalassemia Thalassemia is an inherited autosomal recessive blood disorders characterized by formation of abnormal hemoglobin. Types of human hemoglobin  Adults (hemoglobin A) is composed of 2 alpha and 2 beta chains  Fetal hemoglobin F is composed of 2 alpha chains and 2 gamma chains  Hemoglobin A2 is composed of 2 alpha chains and 2 delta chains

Alpha Thalassemia Alpha thalassemia is caused by deficient expression of 1 or more of the 4 alpha-globin genes on chromosome 16 causing reduced synthesis of alpha-globin chains which results in an excess of gamma-globin chains in fetuses and newborns and of beta-globin chains in children and adults. Types  Alpha thalassemia major (hydrops fetalis): Individuals with this disorder cannot produce any functional alpha globin and thus are unable to make any functional hemoglobin A, F, or A2  Hemoglobin H disease: Inheritance of 1 normal alpha-globin gene, excess beta chains aggregate into tetramers named HbH (HbH has a high affinity for oxygen). It is manifested by microcytic, hypochromic RBCs with increased reticulocytes and target cells (densely stained RBC center surrounded by a pale, unstained ring)  Alpha thalassemia trait: Inheritance of 2 normal alpha-globin genes, affected individuals are clinically normal but frequently have minimal anemia (reticulocyte count is normal with reduced MCV and MCH and normal serum iron and ferritin)  Silent carrier: Persons who inherit 3 normal alpha-globin genes

Beta Thalassemia Beta thalassemia is caused by a genetic deficiency in the synthesis of beta-globin chains. Types  Beta thalassemia major occurs in the homozygous state causing severe, transfusion-dependent anemia  Beta thalassemia trait (thalassemia minor) occurs in the heterozygous state, the causes mild to moderate microcytic anemia Complications  Extra-medullary hematopoiesis causing bone deformities  Hypersplenism causing pancytopenia  Gallstones Pass-MRCP.com

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Complications of long-term transfusion therapy (iron overload and transfusion-associated infections) Increased risk for infections resulting from splenectomy Cholelithiasis

Diagnosis  High indirect hyperbilirubinemia, low haptoglobin, and elevated lactate dehydrogenase due to hemolysis  Peripheral blood smear shows mild, isolated microcytic anemia with target cells on beta thalassemia minor and severe microcytic and hypochromic anemia with target cells, Heinz bodies and anisopoikilocytosis in beta thalassemia major

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Normal iron studies Hemoglobin electrophoresis is diagnostic in beta thalassemia trait (minimal elevation of Hb A2 (4-6%)

Management of thalassemia  Supplementation of iron or folic acid in mild anemia  Patients with more severe anemia may require lifelong transfusion therapy with iron chelation  Splenectomy is reserved for patients with symptoms of hypersplenism

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MRCP Revision Notes

Sickle Cell Anemia Sickle cell disease (SCD) is an autosomal recessive disorder resulting from the presence of a mutated form of hemoglobin called hemoglobin S. HbS It is less soluble than HbA and has lower affinity for oxygen. Signs and symptoms  Growth retardation  Acute painful crises due to blockage of the small blood vessels by sickling RBCs (triggered by hypoxemia, dehydration and fever)  Aplastic crisis due to infection with parvovirus B19 (severe anemia with low reticulocyte count)  Splenic sequestration crisis (life-threatening anemia with rapid enlargement of the spleen and high reticulocyte count)  Acute chest syndrome (chest pain, fever, cough, tachypnea and pulmonary infiltrates) due to infection (mycoplasma and chlamydia) or infarction or both  Hemolytic crises causing acute accelerated drops in hemoglobin level  Repeated infections with encapsulated organisms  Hand-foot syndrome (Dactylitis and arthritis)  Priapism  CNS strokes  Cholelithiasis  Leg ulcers Diagnosis  Complete blood count shows hemoglobin levels in the range of 6-8 g/dl with a high reticulocyte count  Blood film shows atypical sickle cells (Drepanocytes)and features of hyposplenism (target cells and Howell-Jolly bodies)

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Hemoglobin electrophoresis is diagnostic

Management  Hydroxyurea increases fetal hemoglobin which protects against sickling  Long-term transfusion therapy (target hemoglobin levels to 10 g/dL)  Opioids for the treatment of severe pain associated with a vaso-occlusive crisis  Splenectomy with antibiotic prophylaxis and vaccinations Pass-MRCP.com

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MRCP Revision Notes 

Stem cell transplantation is limited to patients younger than 16 years with HbSS or HbS-Beta thalassemia or who have evidence of severe disease

Sideroblastic Anemia Sideroblastic anemia is a form of anemia in which the bone marrow produces ringed sideroblasts (abnormal iron granules in the mitochondria positioned around the nucleus). It is presented by general symptoms of anemia including malaise, fatigue, and dyspnea on exertion Causes  Congenital  Idiopathic  Myelodysplasia  Nutritional deficiencies (copper, vitamin B-6)

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Lead poisoning Alcohol Drugs (anti-tuberculous agents, progesterone) Hypothermia

Diagnosis  Dimorphic anemia (normocytic + microcytic) and hypochromia  Iron studies may show increased iron level with decreased TIBC  Bone marrow aspiration and biopsy with staining with Prussian blue stain shows sideroblasts and increased iron stores (diagnostic)

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Rheumatology & Autoimmune Disorders Rheumatoid Arthritis Rheumatoid arthritis (RA) is a chronic autoimmune systemic inflammatory disease of unknown cause leading to articular and extra-articular manifestations. It is associated with HLA DR4. Signs and symptoms  Constitutional symptoms  Joints show morning stiffness, tenderness, swelling and limitation of motion  Joints deformities  Swan neck deformity: DIP flexion with PIP hyperextension

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Boutonniere deformity: PIP flexion with DIP hyperextension

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Z deformity of the thumb: hyperextension of the interphalangeal joint, fixed flexion and subluxation of the metacarpophalangeal joint

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MRCP Revision Notes

Persistent symmetric polyarthritis of hands and feet (hallmark feature)  Upper extremities (metacarpophalangeal, and interphalangeal joints [sparing distal phalangeal joints] , wrists, elbows, shoulders)  Lower extremities (ankles, feet, knees, hips)  Cervical spine Extra-articular manifestations  Pulmonary fibrosis, pleural effusion, pulmonary nodules and bronchiolitis obliterans  Pericarditis  Subcutaneous nodules  Mononeuritis multiplex  Pyoderma gangrenosum  Felty syndrome (RA + splenomegaly + pancytopenia predominantly neutropenia) is associated with HLA-DRW4  Ocular manifestations as keratoconjunctivitis sicca (most common), episcleritis, scleritis and corneal ulceration  Amyloidosis Causes of anemia in rheumatoid arthritis  Anemia of chronic disease (most common cause) (normocytic normochromic)  NSAID induced GIT hemorrhage (hypocytic, hypochromic)  B12-deficiency anemia  Autoimmune hemolytic anemia  Bone marrow hypoplasia due to DMARD therapy Diagnosis (NICE guidelines 2015) Lab findings  CRP level are associated with disease activity and is used for monitoring  Anti-cyclic citrullinated peptide antibodies (anti-CCP) is diagnostic  Rheumatoid factor in 60-80% of patients (not specific)  Antinuclear antibodies (ANA) in 40% of patients Pass-MRCP.com

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MRCP Revision Notes Imaging  Early joint x-ray shows loss of joint space, periarticular osteoporosis and soft-tissue swelling, late x-ray shows periarticular erosions and joint subluxation.

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Arthroscopy shows marked vascular proliferation and thickening of the synovial membrane.

Joint aspiration shows white blood cell count >2000/µL with neutrophil predominance (60-80%) and low glucose levels Poor prognostic features  Female sex  Insidious onset  HLA DR4

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Positive RF Poor functional status at presentation Extra articular manifestations

Management (NICE guidelines 2015) DMARDs with or without steroids are first-line treatment for newly diagnosed active cases; tumor necrosis factor-α (TNF-α) inhibitors (etanercept, infliximab) are used as alternatives or in combination to DMARDs. DMARDs include methotrexate (the most widely used first line) sulfasalazine, leflunomide and hydroxychloroquine. During pregnancy sulfasalazine and azathioprine are safe for management.

Systemic Lupus Erythematosus Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can affect almost any organ system and follows a relapsing and remitting course. More than 90% of cases of SLE occur in women, frequently starting at childbearing age. It is associated with HLA B8, DR2 and DR3. Pass-MRCP.com

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MRCP Revision Notes Signs and symptoms The classic presentation of SLE is a triad of fever, joint pain, and rash         

Dermatologic (malar rash, photosensitivity, discoid lupus) Musculoskeletal (arthralgia, arthropathy, myalgia, frank arthritis, avascular necrosis) Neuropsychiatric (seizure, psychosis) Pulmonary (pleurisy {the most common manifestation}, pleural effusion, pneumonitis, pulmonary hypertension and pulmonary fibrosis) Cardiac (pericarditis, myocarditis and pericardial effusion) Hematologic (leukopenia, lymphopenia, anemia, thrombocytopenia) Mouth ulcers lymphadenopathy Raynaud phenomenon

SLE renal complications  Class I: normal kidney  Class II: mesangial glomerulonephritis  Class III: focal and segmental proliferative glomerulonephritis  Class IV: diffuse proliferative glomerulonephritis (the most common and severe form)  Class V: diffuse membranous glomerulonephritis  Class VI: sclerosing glomerulonephritis Diagnosis  ANA positive in 99% of cases (not specific for diagnosis but good as screening test)  Rheumatoid factor positive in 20% of cases  Anti-double stranded DNA (dsDNA) antibodies: highly specific (> 99%), but less sensitive (70%), it can be used for disease monitoring  Anti-Smith (SM) antibodies: most specific (> 99%), sensitivity (30%)  Hypocomplementemia (C3, C4) due to formation of immune complexes (cryoglobulinemia causes decreased C4 with normal C3) Management  Corticosteroids and hydroxychloroquine are used in SLE without major organ manifestations  Immunosuppressive agents (azathioprine, methotrexate) are indicated in refractory cases or when steroid doses cannot be reduced Pregnancy SLE Unlike many autoimmune diseases systemic lupus erythematous (SLE) often becomes worse during pregnancy and the postpartum period and is associated with a risk of maternal autoantibodies crossing placenta. Fetal lupus is highly associated with anti-Ro antibodies (SSA). It causes complications as congenital heart block. It is managed by prophylactic corticosteroids.

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Drug-Induced Lupus Erythematosus Drug-induced lupus erythematosus (DILE) is a variant of lupus erythematosus that resolves within days to months after withdrawal of the culprit drug in a patient with no underlying immune system dysfunction. Causes  Procainamide  Isoniazid  Minocycline  Hydralazine

   

Chlorpromazine Quinidine Penicillamine Phenytoin

Features are as SLE but it differs in:  Average age of onset of 50-70 years  Female-to-male ratio of 1:1  Renal, central nervous system, cutaneous involvement and Raynaud phenomenon are rare  Pulmonary involvement is common Diagnosis  Anti-histone antibodies is present in in >95% of cases  ANA positive in 100% of cases  Anti-dsDNA is rare  C3/C4 levels are normal

Systemic Scleroderma Systemic scleroderma (sclerosis) is systemic autoimmune disease of unknown origin characterized by excessive deposition of collagen and other connective tissue macromolecules in skin and multiple internal organs. Types  Limited cutaneous scleroderma is limited to the skin on the face, hands and feet  Diffuse cutaneous scleroderma covers more of the skin with a risk of progressing to the visceral organs  CREST syndrome (Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasia) is a subtype of limited systemic scleroderma Other complications  Pulmonary artery hypertension and restrictive lung disease  Arthralgia and myalgia  Myocardial fibrosis causing congestive heart failure and arrhythmias  Chronic renal insufficiency and scleroderma renal crisis  Primary biliary cirrhosis  Sicca syndrome  Cranial nerve palsy Pass-MRCP.com

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MRCP Revision Notes Diagnosis  Elevated CXCL4 (platelet factor 4) serum levels, it is found in systemic scleroderma patients and higher levels correlated with the severity of pulmonary manifestation  ANA are present in about 90%-95% of patients  Topoisomerase I antibodies (Scl-70) are present in 30% of patients with diffuse scleroderma  Anti-centromere antibodies are associated with limited scleroderma and CREST syndrome Management  Scleroderma renal crisis is managed by ACE inhibitors  Disease-modifying treatment (D-penicillamine, methotrexate, mycophenolate mofetil) for inhibiting tissue fibrosis and vascular and immune system alterations Poor prognostic factors (5-year survival is estimated to be about 80%)  Younger age  African descent  Rapid progression of skin symptoms  Greater extent of skin involvement  Anemia  Elevated erythrocyte sedimentation rate (ESR)  Pulmonary, renal, and cardiac involvement

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Neurology Alzheimer Disease Alzheimer disease (AD) is an acquired disorder of cognitive and behavioral impairment that develops in the hippocampus. AD accounts for 50-75% of all cases of dementia. Dementia with Lewy bodies accounts for 20% of cases and Pick disease accounts for 5% of cases. Signs and symptoms Mild Alzheimer disease  Memory loss  Increased anxiety Moderate Alzheimer disease  Increasing memory loss and confusion  Problems recognizing friends and family members  Difficulty with language (reading, writing, working with numbers and aphasia)  Difficulty organizing thoughts and thinking logically  Restlessness, agitation, anxiety, tearfulness, wandering  Muscle twitches (parkinsonian) Severe Alzheimer disease  Patients with severe AD cannot recognize family  Lack of bladder and bowel control Diagnosis  CSF markers as tau and phosphorylated tau are elevated, whereas amyloid levels are decreased  MRI shows widespread cerebral atrophy, particularly the cortex and hippocampus with intraneuronal neurofibrillary tangles and neuronal plaques Management  Cholinesterase inhibitors (Donepezil) slower declines on cognitive and functional measures in mild to moderate cases, common adverse effects include anorexia, hallucinations, syncope, diarrhea and urinary incontinence  N -methyl-D-aspartate (NMDA) antagonist (memantine) slows the intracellular calcium accumulation and thereby help prevent further nerve damage for moderate and severe cases

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Lewy Bodies Dementia Dementia with Lewy bodies (DLB) is a progressive, degenerative dementia of unknown etiology. It accounts for 20% of cases of dementia. Signs and symptoms  Dementia  Fluctuating confusion  Parkinsonian motor features (rigidity and bradykinesia)  Visual and non-visual hallucinations  Recurrent syncope  Sleep-pattern reversal  Neuroleptic sensitivity (should be avoided) such as haloperidol Diagnosis  Cortical brain biopsy shows abnormal proteinaceous (alpha-synuclein) cytoplasmic inclusions (Lewy bodies)  MRI brain shows hippocampal atrophy Management  Acetylcholinesterase inhibitors (Rivastigmine) is first line  Atypical neuroleptics such as clozapine  Dopamine agonists for parkinsonian (may precipitate hallucinations)

Pick Disease Pick disease is a type of fronto-temporal Dementia. It accounts for 5% of dementia cases. Signs and symptoms  Progressive dementia  Progressive aphasia  Behavioral and personality changes (lack of concern, apathy, passivity, low motivation, absence of selfmonitoring, abnormal self-awareness) Diagnosis  CT and MRI shows selective atrophy of the frontal and temporal lobes

AIDS Dementia Complex AIDS Dementia Complex (ADC) is one of the most common and clinically important CNS complications of late HIV-1 infection. Signs and symptoms  Dementia Pass-MRCP.com

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MRCP Revision Notes    

Behavioral changes (loss of attention and concentration) Motor deficits Hyperreflexia Gait instability

Diagnosis  MRI shows widespread cerebral atrophy with widened cortical sulci and enlarged ventricles

Management  Aggressive antiretroviral therapy

Transient Global Amnesia Transient global amnesia (TGA) is a neurological disorder characterized by a temporary but almost total disruption of short-term memory with a range of problems accessing older memories. Features  Anterograde amnesia (inability to form new memory traces) with disorientation in time and in place, but never in persons  Retrograde amnesia for events of the preceding days or weeks and lasting from hours to years  No focal neurological signs or epilepsy  Self-identification, visual-spatial skills and social skills are preserved Pass-MRCP.com

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MRCP Revision Notes Management  Reassurance with neurologist follow-up visits as prognosis is excellent

Normal Pressure Hydrocephalus Normal pressure hydrocephalus (NPH) is a type of brain malfunction caused by decreased absorption of CSF causing ventriculomegaly. Signs and symptoms Patients with NPH present with a gradually progressive disorder with the classic triad of:   

Gait disturbance (bradykinesia, broad-based and shuffling gait) Urinary incontinence Dementia

Diagnosis  CT and MRI shows enlarged ventricles



Diagnostic CSF removal (large volume lumbar puncture) shows improvement in symptoms

Management  Surgical CSF shunting (ventriculo-peritoneal or ventriculo-atrial) is the mainstay management

Parkinson Disease Parkinson disease is a degenerative disorder of the dopaminergic neurons in the substantia nigra of the central nervous system. Pass-MRCP.com

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MRCP Revision Notes Classifications  Primary or idiopathic  Secondary or acquired  Inherited (Juvenile onset Parkinson an autosomal recessive)  Parkinson plus syndromes as multiple system atrophy and progressive supranuclear palsy Signs and symptoms (classic triad)  Bradykinesia (mask-like face and difficulty in initiating movement)  Resting tremor (pill-rolling) with frequency of 3-5 Hz  Rigidity (lead pipe and cogwheel) Other features  Sleep disturbances  Depression or anhedonia  REM sleep behavior disorder Features of primary Parkinson disease vs. secondary causes  Asymmetrical tremor (most specific)  Rigidity is more common Diagnosis (NICE 2017)  Parkinson disease is a clinical diagnosis Management (NICE 2017)  Levodopa is of choice in the early stages of Parkinson disease and motor symptoms cause impact on the quality of life  Dopamine agonists as Apomorphine and Ropinirole (ergot-derived dopamine agonists as bromocriptine, cabergoline, and pergolide are contraindicated), levodopa or MAO‑B inhibitors (Selegiline) are used in the early stages of Parkinson disease and motor symptoms do not cause impact on the quality of life  Dopamine agonists, MAO‑B inhibitors or COMT (Catechol-O-Methyl Transferase) inhibitors (Entacapone) are added to levodopa in case of developed dyskinesia or motor fluctuations; amantadine is alternative and anticholinergics (trihexyphenidyl, benztropine) are contraindicated  Decarboxylase inhibitor (carbidopa) is added to levodopa to prevent peripheral metabolism of levodopa to decrease systemic adverse effects  Anticholinergic agents are used as first line in drug-induced Parkinson

Multiple System Atrophy Multiple system atrophy (MSA) (Shy-Drager syndrome) is defined as an adult-onset, sporadic, rapidly progressive, multisystem, neurodegenerative fatal disease of undetermined etiology. MSA usually progresses more quickly than Parkinson disease. The average lifespan is 7.9 years and only 20% survive past 12 years. Pass-MRCP.com

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MRCP Revision Notes Signs and symptoms  Parkinsonism (akinetic-rigidity) with poor response to levodopa  Autonomic dysfunction (urinary incontinence or urinary retention, postural hypotension and erectile dysfunction)  Cerebellar signs (ataxia) Diagnosis  MRI shows atrophy of cerebellum and brainstem

Progressive Supranuclear Palsy Progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) is a neurodegenerative disease. It usually develops after the sixth decade of life, and the diagnosis is purely clinical. Signs and symptoms  Prolonged phase marked by fatigue, headaches and depression  Supranuclear ophthalmoplegia (vertical gaze with downgaze typically involved before upgaze)  Pseudobulbar palsy (inability to control facial movements such as chewing and speaking)  Parkinsonism (poor response to L-dopa)  Behavioral, cognitive, and gait disturbances  Frequent falls and impaired postural reflexes  Neck dystonia Management  No medication is effective in halting the progression of PSP  Medications may provide minimal symptomatic improvement as dopamine agonists and TCA

Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy is widespread CNS demyelination due to infection by JC virus. PML occurs almost exclusively in patients with severe immune deficiency as AIDS and chronic immunosuppressive medications. Signs and symptoms  Behavioral changes  Motor weakness



Speech and visual impairment

Diagnosis  MRI shows patchy demyelination  Brain biopsy is diagnostic

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Management  There is no effective treatment so treatment aims at reversing the immune deficiency (antiretroviral or stopping immunosuppressive drugs ) to slow or stop the disease progression

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Ophthalmology Retinal Vein Occlusion Retinal vein occlusion (RVO) is the second most common cause of blindness from retinal vascular disease after diabetic retinopathy. Risk factors include increasing age, hypertension, diabetes, smoking, obesity and hypercoagulable disorders. Classification RVO is classified according to where the occlusion is located in to:   

Central retinal vein occlusion (CRVO) Hemi-retinal vein occlusion (HRVO) Branch retinal vein occlusion (BRVO)

Signs and symptoms  BRVO may be asymptomatic and noted incidentally on funduscopic examination  CRVO is presented with sudden painless monocular vision loss or dense central scotoma  Funduscopic examination shows retinal hemorrhage, edema and dilated veins

Management The treatment is aimed at maintaining visual acuity by monitoring the patient for and treating complications such as macular edema and neovascularization. Pass-MRCP.com

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MRCP Revision Notes  

Macular edema is treated with intravitreal anti-VEGF as first line and/or intravitreal steroids Neovascularization is treated with laser photocoagulation

Retinal Artery Occlusion Retinal artery occlusion represents an ophthalmologic emergency, and delay in treatment may result in permanent loss of vision. Causes  Embolism from heart or temporal arteritis  Coagulopathies as sickle cell anemia, antiphospholipid syndrome and thrombophilia  Carotid atherosclerosis and dissection  Inflammatory endarteritis  Migraine Signs and symptoms  Acute persistent painless loss of central vision  Funduscopic examination shows cherry red spot, ground-glass retina and pale optic disc

Management Early treatment < 2 h from onset of symptoms may be associated with increased visual recovery 

Immediate lowering of IOP using medical management (acetazolamide and mannitol), ocular massage and anterior chamber paracentesis

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Thrombolytics, hyperbaric oxygen and retrobulbar block may be tried

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Psychiatry Depression Depression is a state of low mood and aversion to activity that can affect a person thoughts, behavior, tendencies, feelings, and sense of well-being. Symptoms of classic depression including insomnia, anxiety, irritability, decreased appetite, weight gain or loss, social withdrawal, and decreased sex drive Depressive psychosis is a major depressive episode that is accompanied by psychotic symptoms including delusions and/or hallucinations. Seasonal affective disorder (SAD) is a mood disorder in which people who has normal mental health throughout most of the year experience depressive symptoms in the winter or summer.

Management of depression (NICE guidelines 2018) Mild depression Group-based cognitive behavioral therapy with physical activity program is the management of choice for mild depression Medical treatment is indicated for mild depression with persistent symptoms or with a history of moderate to severe depression. Medical treatment include selective serotonin reuptake inhibitors (1st line) or tricyclic antidepressants Moderate to severe depression Combination of antidepressant medication and a high-intensity psychological intervention

Schizophrenia Schizophrenia is a brain disorder that affects how people think, feel, and perceive the world. The hallmark symptom of schizophrenia is psychosis, such as experiencing auditory hallucinations and delusions. Signs and symptoms The symptoms of schizophrenia may be divided into the following 4 domains:    

Positive symptoms - Psychotic symptoms, such as auditory hallucinations Negative symptoms - Decrease in emotional range, poverty of speech, and loss of interests Cognitive symptoms - Neurocognitive deficits as in working memory and attention and in executive functions Mood symptoms - Patients often seem cheerful or sad and often depressed

Paranoid schizophrenia is associated with fixed false beliefs (delusions) as someone is trying to hurt him or the government is spying on him. Pass-MRCP.com

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MRCP Revision Notes Auditory hallucinations are featured by:  Two or more voices discussing the patient in the third person  Thought echo  Voices commenting on the patient’s behavior Factors associated with poor prognosis  Strong family history and monozygotic twin  Gradual onset  Low IQ

 

History of social withdrawal Lack of obvious precipitant

Management  Atypical antipsychotics diminish the positive symptoms of schizophrenia and prevent relapses  Psychosocial treatment as social skills training and cognitive-behavioral therapy

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Infectious Diseases Staphylococcus Aureus Staphylococcus aureus is facultative anaerobic gram-positive cocci. Virulence factors Enzymes  Staphylococcus aureus produces various enzymes such as coagulase, hyaluronidase, DNAse, staphylokinase and beta-lactamase for drug resistance. Toxins  Depending on the strain, S. aureus is capable of secreting several exotoxins. Superantigens  Superantigens induce toxic shock syndrome. Exfoliative toxins  EF toxins are implicated in the disease staphylococcal scalded-skin syndrome.

Toxic shock Syndrome Toxic shock syndrome (TSS) is a toxin-mediated acute life-threatening illness, usually precipitated by infection with either Staphylococcus aureus or Streptococcus pyogenes (GAS). Staphylococcus toxic shock syndrome (STSS) most commonly occurs in women, usually those who are using tampons, and develops within 5 days after the onset of menstruation. TSS caused by the Streptococcus pyogenes typically presents in people with pre-existing skin infections with the bacteria Signs and symptoms  High fever, shock, malaise and confusion, which can rapidly progress to stupor and coma  Rash (sunburn like) seen early in the course of illness and affects any region of the body, including the lips, mouth, eyes, palms and soles. It desquamates, or peels off, after 10–14 days

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

Multiple organ failure

Diagnosis For staphylococcal toxic shock syndrome, the diagnosis is based upon CDC criteria as follows (all must be present for diagnosis):     

Body temperature > 38.9 °C (102.02 °F) Systolic blood pressure < 90 mmHg Diffuse macular erythroderma Desquamation (especially of the palms and soles) 1-2 weeks after onset Involvement of three or more organ systems

Management  Admission to the intensive care unit particularly in the case of multiple organ failure  The source of infection should be removed (tampon) or drained (abscesses)  Antibiotic treatment should cover both S. pyogenes and S. aureus, this may include a combination of cephalosporins, penicillin or vancomycin, the addition of clindamycin reduces toxin production

Gonorrhea Gonorrhea is a purulent infection of the mucous membrane surfaces caused by Neisseria gonorrhoeae. N gonorrhoeae is spread by sexual contact or through transmission during childbirth. Signs and symptoms In women  Vaginal discharge described as thin, purulent, and mildly odorous  Dysuria  Intermenstrual bleeding  Dyspareunia (painful intercourse) Pass-MRCP.com

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MRCP Revision Notes 

Mild lower abdominal pain

Pelvic inflammatory disease signs symptoms  The above symptoms became more severe  Cervical motion tenderness  Adnexal tenderness and adnexal mass In males  Urethritis with profuse, purulent, and blood tinged discharge  Acute epididymitis In males and females, disseminated gonococcal infection causes arthritis-dermatitis syndrome. Neonatal infection In neonates, bilateral conjunctivitis (ophthalmia neonatorum) often follows vaginal delivery from an untreated mother with a gonococcal infection. Diagnosis  Culture is the most diagnostic test, it shows gram-negative coffee bean-shaped diplococci bacteria  PCR Management  Cephalosporins as ceftriaxone and cefixime are the drugs of choice, doxycycline and ciprofloxacin are alternatives

Chlamydial Genitourinary Infections Chlamydiae are small gram-negative obligate intracellular microorganisms that preferentially infect squamocolumnar epithelial cells. They include the genera of Chlamydia trachomatis, Chlamydophila pneumoniae and Chlamydophila psittaci. Chlamydia trachomatis infection is the most commonly reported bacterial sexually transmitted disease (STD). It account for 60% of cases of non-gonococcal urethritis. Signs and symptoms  Unlike gonorrhea, most men and women who are infected are asymptomatic  Dysuria and yellow muco-purulent discharge from the urethra  Vaginal discharge and vaginal bleeding (postcoital or unrelated to menses)  Dyspareunia  Proctitis  Progression to pelvic inflammatory disease Newborns with chlamydial infection produce:  Pneumonia beginning at 1-3 months Pass-MRCP.com

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MRCP Revision Notes 

Conjunctivitis developing at 1-2 weeks

Diagnosis  Culture on ordinary media is negative  Nucleic Acid Amplification Tests (NAAT) have become the preferred diagnostic and screening test  Molecular techniques for detecting antigen, DNA, or RNA/Rapid tests Management  Azithromycin and doxycycline as first-line drugs for non-gonococcal urethritis including Chlamydia  Azithromycin or amoxicillin are the preferred drug regimens in pregnancy

Leprosy Leprosy is a chronic infection caused by the acid-fast, rod-shaped bacillus Mycobacterium leprae. Leprosy should be considered in anyone who has lived in the tropics or who has traveled for prolonged periods to endemic areas (India, Brazil and Africa). Types  Lepromatous leprosy with minimal cellular immune response  Tuberculoid leprosy with vigorous cellular immune response Signs and symptoms of lepromatous leprosy  Ulcers on hands or feet with ill-defined borders  Iridocyclitis and corneal ulceration  Loss of eyebrows and eyelashes, and nasal collapse (leonine facies)  Erythema nodosum leprosum  Axillary and inguinal adenopathy Signs and symptoms of tuberculoid leprosy  The initial lesion is often a sharply demarcated ovoid or serpiginous, hypopigmented macule accompanied by loss of sensation (loss of sensation is a feature of tuberculoid leprosy unlike lepromatous leprosy)

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MRCP Revision Notes  

Destruction of the normal skin organs such as sweat glands and hair follicles as the disease progresses Wasting and muscle weakness causing foot drop or clawed hands

Diagnosis  Skin biopsy, nasal smears or both for acid-fast bacilli using Fite stain Management  Single-dose treatment with rifampicin, minocycline or ofloxacin in patients with single skin lesion  Multidrug regimen includes rifampicin, dapsone and clofazimine for extensive disease

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Dermatology & Allergic Disorders Anaphylaxis Anaphylaxis is an acute, potentially fatal systemic reaction caused by the release of chemical mediators from mast cells and basophils. It is mediated by IgE bound to mast cells which causes immediate releasing of mediators (Type 1 hypersensitivity reaction). Signs and symptoms  Dermatologic: Flushing, urticaria, angioedema, cutaneous and conjunctival injection  Respiratory: Nasal congestion, wheezing, hoarseness and dyspnea  Cardiovascular: Dizziness, syncope and palpitations  Neurologic: Headache, dizziness and seizure Diagnosis  Plasma and urinary histamine and serum tryptase assessment are signs of mast cells degranulation Management  Supportive care by airway management, cardiac monitoring, IV access and fluid resuscitation  Adrenaline is the drug of choice; doses are IM 0.5 ml of 1/1000 or IV 5 ml of 1/10000 repeated every 15 minutes

Systemic Mastocytosis Systemic Mastocytosis is a neoplastic proliferation of mast cells. Signs and symptoms  Urticaria pigmentosa - produces a wheal on rubbing (Darier sign)  Flushing  Abdominal pain  Hepatosplenomegaly and lymphadenopathy Diagnosis  Monocytosis on the blood film  Raised serum tryptase levels  Increased urinary histamine  Bone marrow aspiration and biopsy is diagnostic Management is symptomatic for anaphylactic manifestations

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Hereditary Angioedema Hereditary angioedema is an autosomal dominant condition associated with low plasma levels of the complement 1 inhibitor (C1-INH) protein. It is associated with episodic attacks of edema formation that can have catastrophic consequences. Acquired angioedema is usually caused by allergy and occurs together with other allergic symptoms and urticaria. It can also occur as a side effect to certain medications as ACE inhibitors. Signs and symptoms HAE causes non-inflammatory swelling of the skin and mucous membranes. The prominent sites include:   

Larynx and tongue causing laryngeal edema and upper airway obstruction Abdominal organs causing vomiting, diarrhea or paroxysmal colicky pain that can mimic appendicitis Subcutaneous tissues causing edema of the face, hands, arms, legs, genitals and buttocks

Diagnosis  Low C1 esterase inhibitor (C1-INH) protein level is diagnostic  Low C4 level  Normal C1q level Management  C1-INH concentrate, selective bradykinin B2 receptor antagonist and kallikrein inhibitor are of choice during attacks  Prophylaxis with danazol

Lichen Planus Lichen planus is a cell-mediated immune response of unknown origin. It may be associated with hepatitis C virus or other autoimmune diseases as ulcerative colitis, alopecia areata, Vitiligo, dermatomyositis, morphea, lichen sclerosis, primary biliary cirrhosis and myasthenia gravis. Signs and symptoms  Itchy, papular, flat-topped and shiny rash overlying network of fine white lines (Wickham striae) which may produce vesicles on sun exposed areas

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

Oral and mucus membranes lesions are white or gray streaks forming a linear or reticular pattern on a violaceous background

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Nail longitudinal grooving and ridging, subungual hyperkeratosis and onycholysis

 

Scarring alopecia Koebner phenomenon (lesions in old scars)

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MRCP Revision Notes Management  Topical steroids for mild and cutaneous disease  Oral steroids or immunosuppression for scalp, nail, and mucous membrane involvement

Actinic Keratosis Actinic keratosis (AK) is a UV light-induced lesion of the skin that may progress to invasive squamous cell carcinoma. The lesions begin as small, rough spots that are easier felt as sandpaper like texture; later the lesions enlarge, usually becoming red and scaly.

Management  Medical therapy include topical 5-fluorouracil (5-FU), imiquimod cream and topical diclofenac gel  Photodynamic therapy  Surgery as cryosurgery, curettage and shave excision for extensive disease

Keratoacanthoma Keratoacanthoma (KA) is a relatively common low-grade tumor that originates in the pilosebaceous glands and closely resembles squamous cell carcinoma (SCC). Keratoacanthoma typically grows rapidly, attaining 1-2 cm within weeks, followed by a slow involution period lasting up to 1 year and leaving a residual scar. Lesion typically is solitary, roundish, skin-colored or reddish papule that rapidly progress to dome-shaped nodule with a smooth shiny surface and a central crateriform ulceration or keratin plug that may project like a horn.

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MRCP Revision Notes Management is primarily by surgical resection.

Kaposi Sarcoma Kaposi sarcoma is a spindle-cell tumor thought to be derived from endothelial cell lineage. This condition carries a variable clinical course ranging from minimal mucocutaneous disease to extensive organ involvement. It is usually immunocompromised or AIDS-related (CD4 count < 200). It is caused by HHV-8 (human herpes virus 8). Features of cutaneous lesions  Non-pruritic macular, papular, nodular, or plaque-like lesion  Lesions may assume a brown, pink, red, or violaceous color  Lesions may range in size from several millimeters to several centimeters in diameter



Mucous membrane involvement is common (palate, gingiva, and conjunctiva)

Features of organ lesions  Gastrointestinal lesions can occur anywhere in the gastrointestinal tract causing hematemesis, hematochezia, melena and bowel obstruction  Pulmonary lesions cause hemoptysis and chest pain  Rare central nervous system lesions Management  Highly active antiretroviral therapy (HAART) for HIV infection  Local therapy (radiation, laser or surgical excision) for locally advanced symptomatic disease

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Pharmacology & Toxicology Pharmacokinetics The following are the most commonly measured pharmacokinetic metrics:       

Cmax: The peak plasma concentration of a drug after administration Tmax: Time to reach Cmax Volume of distribution: The apparent volume in which a drug is distributed (the parameter relating drug concentration to drug amount in the body) Elimination half-life: The time required for the concentration of the drug to reach half of its original value, it is related to lipid solubility (longer for lipid soluble drugs) and the rate of drug clearance Bioavailability: The proportion of the drug that reaches its site of action, IV administration of a drug provides bioavailability 100% and it decrease if oral drug with first pass metabolism Affinity is the attraction between a drug and its receptor. Affinity and intrinsic activity are determinants of potency of a drug Clearance: The volume of plasma cleared of the drug per unit time; it is estimated by glomerular filtration rate (renal failure delay clearance)

Drug Metabolism Drug metabolism is the metabolic breakdown of drugs through specialized enzymatic systems. It usually involves two types of biochemical reactions; phase I and phase II reactions Phase I modification Phase I reactions occur by oxidation, reduction, hydrolysis, cyclization, decyclization, and addition of oxygen or removal of hydrogen, carried out by mixed function oxidases enzymes as cytochrome P-450. Phase II conjugation Phase II reactions occur by methylation, sulphation, acetylation, glucuronidation and glutathione and glycine conjugation. First pass metabolism This is a phenomenon where the concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism. As a consequence much larger doses are need orally than if given by other routes. Examples of drugs exhibiting extensive first pass metabolism  Aspirin  Isosorbide dinitrate  Glyceryl trinitrate  Testosterone Pass-MRCP.com

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Lignocaine Propranolol Verapamil Hydrocortisone Page 90

MRCP Revision Notes Acetylator status Many drugs are metabolized in the liver by acetylation; some patients may show deficient in hepatic N-acetyltransferase known as slow acetylators which leads to increased drugs adverse effects. Drugs affected include:  Procainamide  Sulfasalazine  Hydralazine

  

Isoniazid Dapsone Sulphonamides

Therapeutic drug monitoring Therapeutic drug monitoring (TDM) main focus is on drugs with a narrow therapeutic range. Examples include Drug Lithium

Time of sample taken 12 hours post-dose

Digoxin

6 hours post-dose

Cyclosporine immediately before next dose Phenytoin

immediately before next dose

Elimination kinetics Zero-order kinetics Zero-order kinetics means elimination of a drug from the body in a constant quantity per time despite the decrease in the concentration of the drug over time. In practice; zero-order kinetics drugs concentration need to be monitored as their metabolism enzymes are saturated. Examples include Ethanol, Phenytoin, Salicylates, Cisplatin, Fluoxetine and Omeprazole First order kinetics First order elimination kinetics means elimination of the drug from the body is proportional to the drug concentration (decline in the concentration decreases elimination). 95% of the drugs follow the first order elimination kinetics roles.

Digoxin Digoxin is a purified cardiac glycoside. The primary mechanism of action is inhibition of the Na+/K+ ATPase in the myocardium causing increase in the force of cardiac muscle contraction and decrease conduction through the atrioventricular node. Pass-MRCP.com

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MRCP Revision Notes Digoxin is usually given orally, but can also be given by IV injection in urgent situations. The half-life is about 36 hours for patients with normal renal function due to large volume of distribution. Digitalizing patient with 1-1.5 mg orally over 24 hours in divided doses then digoxin is given once daily, usually in 125-μg or 250-μg doses. Medical uses  Atrial fibrillation and atrial flutter (beta blockers and/or calcium channel blockers are a better first choices)  Symptomatic treatment for congestive heart failure (no mortality benefit) Precipitating factors for toxicity  Renal failure  Myocardial ischemia  Hypoalbuminemia  Hypothermia  Hypothyroidism  Hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia, acidosis  Drugs: amiodarone, quinidine, verapamil, spironolactone Signs of toxicity  Nausea, vomiting, and diarrhea  Blurred vision and visual disturbances (yellow-green halos)  Confusion, drowsiness, convulsions, insomnia, nightmares and depression  Shortened QRS complex with flattened or inverted T waves in ECG  Atrial or ventricular extra-systoles, paroxysmal atrial tachycardia with AV block  Thrombocytopenia  Gynecomastia Management of toxicity  Correction of hyperkalemia and other mineral deficits  Atropine or temporary pacing for bradyarrhythmia  Phenytoin for ventricular tachycardia, lidocaine is alternative (anti-arrhythmic drugs should be avoided as they can precipitate asystole or VF), DC cardioversion is reserved for resistant cases Digoxin-specific Fab fragment (Digibind) is indicated in:  Hemodynamic instability  Life-threatening arrhythmias  Plasma digoxin level >13nmol/l  Ingestion of more than 10 mg digoxin in adults and 4 mg in children

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MRCP Revision Notes

Adenosine Adenosine is an agonist of the A1 receptor which inhibits adenylyl cyclase thus reducing cAMP and causing hyperpolarization by increasing outward potassium flux. It has a very short half-life of about 8-10 seconds. It is used in diagnosis and management of supraventricular tachycardia (SVT) as it terminates atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular re-entrant tachycardia (AVRT). It causes transient AV block causing worsening of sinus tachycardia, atrial fibrillation and atrial flutter. It has no effect on ventricular tachycardia. The effects of adenosine are enhanced by dipyridamole and blocked by theophylline. Adverse effects  Chest pain  Bronchospasm  Enhances conduction down accessory pathways (exacerbate WPW syndrome)

Amiodarone Amiodarone is a class III antiarrhythmic agent used for various types of cardiac dysrhythmias, both ventricular and atrial. Amiodarone shows B-blocker-like and potassium channel blocker-like actions on the SA and AV nodes; it increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential via sodium-channel effects. Medical uses  Ventricular fibrillation and pulseless ventricular tachycardia  Ventricular tachycardia in hemodynamic stable patient  Atrial fibrillation with acute onset only not long term management Complications and side effects  Pulmonary fibrosis and pleural effusions  Hypothyroidism and hyperthyroidism  Corneal micro-deposits  Hepatitis  Photosensitivity

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Blue-grey skin discoloration Peripheral neuropathies Epididymitis Gynecomastia

Drug interactions Amiodarone is a cytochrome P450 inhibitor which causes reduction of the clearance of many drugs as:  

Cyclosporine Digoxin

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Flecainide Sildenafil Page 93

MRCP Revision Notes  

Simvastatin Theophylline

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Warfarin

Flecainide Flecainide is a class Ic antiarrhythmic agent. It slows conduction of the action potential by acting as a potent sodium channel blocker. Medical uses  Atrial fibrillation (rhythm control)  SVT associated with accessory pathway Adverse effects  Increase mortality post myocardial infarction and is therefore contraindicated  Torsades de pointes (prolongation of the PR interval and widening of the QRS)  Oral paraesthesia  Visual disturbances Vaughan Williams Classification of antiarrhythmic drugs Class Example Ia Disopyramide and Quinidine Ib Lidocaine Ic Flecainide II Propranolol III Amiodarone IV Verapamil

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Mechanism of action Block sodium channels Block sodium channels Block sodium channels Beta antagonists Block potassium channels Calcium channel blockers

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MRCP Revision Notes

Genetics & Hereditary Disorders Patterns of Inheritance Autosomal dominant inheritance Features  Males and females are equally affected.  All individuals inheriting the abnormal gene are affected.  Offspring of affected parents (irrespective of the parental sex) have a 50% chance of inheriting the disease. Examples  Acute intermittent porphyria  Adult polycystic disease  Antithrombin III deficiency  Ehlers-Danlos syndrome  Familial adenomatous polyposis  Hereditary non-polyposis colorectal carcinoma  Hereditary hemorrhagic telangiectasia  Hereditary spherocytosis  Huntington disease  Hypokalemic periodic paralysis

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Marfan syndrome Myotonic dystrophy Neurofibromatosis Noonan syndrome Peutz-Jeghers syndrome Retinoblastoma Romano-Ward syndrome Tuberose sclerosis Von-Hippel-Lindau syndrome Von Willebrand disease

Autosomal recessive inheritance Features  Males and females are equally affected, but are fewer in number than in autosomal dominant conditions.  Not all generations will be affected.  If both parents are carriers for the recessive gene 25% of the offspring will be affected, 50% will become carriers, but will not have the disease and 25% will not have the abnormal gene.  If an affected individual marries a carrier, then 50% off -spring will be affected and 50% offspring will be carriers.  If an affected individual marries another affected, then all offspring will be affected Examples  Ataxia telangiectasia  Congenital adrenal hyperplasia  Cystic fibrosis  Cystinuria  Familial Mediterranean Fever  Fanconi anemia  Friedreich ataxia Pass-MRCP.com

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Gilbert syndrome Hemochromatosis Homocystinuria Phenylketonuria Sickle cell anemia Thalassemia Wilson disease Page 95

MRCP Revision Notes X-linked dominant inheritance Features  Males and females are both affected.  No male-to-male transmission.  Affected males transmit the disease to 100% of their daughters.  An affected female will transmit the disease to 50% of all offspring. Examples  Alport syndrome  Vitamin D resistant rickets X-linked recessive inheritance Features  Only males are affected but not carriers  No male-to-male transmission  Females are carriers  Daughters of affected males will be carriers  Female carrier will have 50% affected sons and 50% daughters who are carriers Examples  Androgen insensitivity syndrome  Becker muscular dystrophy  Duchenne and Becker muscular dystrophy  Fabry disease  G6PD deficiency

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Hemophilia A and B Lesch-Nyhan syndrome Nephrogenic diabetes insipidus Retinitis pigmentosa Wiskott-Aldrich syndrome

Maternal mitochondrial genetic abnormalities Features  During conception, only mitochondria from the ovum are passed on to the zygote.  Affected females will pass the disease to 100% off spring  Affected males will not transmit disease to offspring. Examples  Leber optic atrophy  Kearnes-Sayer syndrome  MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like syndrome)  MERF (mitochondrial encephalopathy and red ragged fibres)

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MRCP Revision Notes

Neurofibromatosis Neurofibromatosis is an autosomal dominant disorder that disturbs cell growth in your nervous system, causing tumors to form on nerve tissue. Neurofibromatosis type I (Recklinghausen syndrome) It is caused by a gene mutation on chromosome 17 which encodes neurofibromin. Clinical diagnosis requires the presence of at least 2 of 7 criteria: 

Six or more café-au-lait spots

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Two or more Axillary or inguinal freckles

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Two or more typical neurofibromas

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MRCP Revision Notes

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Two or more Lisch nodules (iris hamartoma)

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Optic nerve glioma Sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis First-degree relative with NF1

Other signs and symptoms  Learning disabilities  Larger than average head size

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Short stature Hypertension

Neurofibromatosis type II It is caused by gene mutation on chromosome 22; it causes bilateral acoustic neuroma and café-au-lait spots. Causes of café-au-lait spots  Neurofibromatosis type I and II  Tuberous sclerosis  McCune-Albright syndrome

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Fanconi anemia Coffin-Siris syndrome

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MRCP Revision Notes

Basic Sciences & Statistics Human Leukocyte Antigen The human leukocyte antigen (HLA) system or complex is a gene complex encoding the major histocompatibility complex (MHC) proteins in humans. HLA allele HLA-B27

HLA-DR2

HLA-DR3

Diseases with increased risk Ankylosing spondylitis Gonococcal arthritis Acute anterior uveitis Reactive arthritis Psoriatic arthritis Systemic lupus erythematosus Narcolepsy Goodpasture syndrome Autoimmune hepatitis Primary biliary cirrhosis Diabetes mellitus type 1 Dermatitis herpetiformis Coeliac disease Primary Sjogren syndrome Systemic lupus erythematosus

HLA-DR4

Rheumatoid arthritis Diabetes mellitus type 1

HLA-DR3 + DR4

Diabetes mellitus type 1

HLA-DQ2 + DQ8

Celiac disease

HLA-A3

Hemochromatosis

HLA-B5

Behcet disease

Hypersensitivity Reactions Types of hypersensitivity reactions include: Type I Immediate hypersensitivity (anaphylactic reaction) It is mediated by IgE bound to mast cells. Examples include allergic dermatitis

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MRCP Revision Notes Type II Cytotoxic IgG and IgM antibodies react directly with the antigen bound to the cell membrane. Examples include Rh incompatibility, blood transfusion reactions, autoimmune hemolytic anemia and Goodpasture syndrome Type III Immune complex IgG and IgM bind antigen, forming antigen-antibody (immune) complexes. Examples include systemic lupus erythematosus, leprosy, post-streptococcal glomerulonephritis and extrinsic allergic alveolitis Type IV Cell-mediated It is mediated by T-lymphocytes and macrophages. Examples include Lichen planus, Tuberculosis, graft versus host disease, allergic contact dermatitis and chronic extrinsic allergic alveolitis.

ANCA Anti-neutrophil cytoplasmic antibodies (ANCAs) are a group of IgG autoantibodies which are directed against antigens in the cytoplasm of neutrophil granulocytes and monocytes. They are detected as a blood test in a number of autoimmune disorders. Types C-ANCA C-ANCA is directed to proteinase 3 (PR3) antigen. Associations:  

80-90% Wegner granulomatosis 20-40% of microscopic polyangiitis

P-ANCA P-ANCA directed to myeloperoxidase (MPO) antigens. Associations:   

50-80% of microscopic polyangiitis 60% of Churg-Strauss syndrome 25% of Wegner granulomatosis

Rare associations  Inflammatory bowel disease  Connective tissue disorders: RA, SLE, Sjogren syndrome  Autoimmune hepatitis

Sensitivity and Specificity Definitions  True positive cases: Sick people correctly diagnosed as sick Pass-MRCP.com

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MRCP Revision Notes   

False positive cases: Healthy people wrongly identified as sick True negative cases: Healthy people correctly identified as healthy False negative cases: Sick people wrongly identified as healthy

Sensitivity Sensitivity = True positive cases / (True positive cases + False negative cases) A sensitivity of 100% means that the test recognizes all sick people and the negative result is used to rule out the disease. Specificity Specificity = True negative cases / (True negative cases + False positive cases) A specificity of 100% means that the test recognizes all healthy people as healthy and a positive result in a high specificity test is used to confirm the disease.  

Likelihood ratio for a positive test result = sensitivity / (1 - specificity) Likelihood ratio for a negative test result = (1 - sensitivity) /specificity

Positive predictive value Positive predictive value is the proportion of actual positives. PPV = True positive cases / (True positive cases + False positive cases) Negative predictive value Negative predictive value is the proportion of actual negatives. NPV = True negative cases / (True negative cases + False negative cases)

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MRCP Revision Notes

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