MRCP Revision Notes

Index

Cardiology 01 Angina Pectoris 32 Prosthetic Heart Valves 02 Exercise ECG 33 Infective Endocarditis 03 Myocardial Infarction 34 Rheumatic Fever 04 Post Myocardial Infarction Complications 35 Acute Pericarditis 05 Heart Failure 36 Constrictive Pericarditis 06 B-type Natriuretic Peptide 37 Cardiac Tamponade 07 Hypertrophic Cardiomyopathy 38 Congenital Heart Defects 08 Dilated Cardiomyopathy 39 Tetralogy of Fallots 09 Peripartum Cardiomyopathy 40 Atrial Septal Defect 10 Myocarditis 41 Lutembacher Syndrome 11 Restrictive Cardiomyopathy 42 Patent Foramen Ovale 12 Cardiogenic Pulmonary Edema 43 Ventricular Septal Defect 13 Atrial Fibrillation 44 Patent Ductus Arteriosus 14 Atrial Flutter 45 Eisenmenger Syndrome 15 Long QT Syndrome 46 Coarctation of the Aorta 16 Torsades De Pointes 47 Aortic Dissection 17 Wolff-Parkinson White Syndrome 48 Hypertension 18 Supraventricular Tachycardia 49 Malignant Hypertension 19 Ventricular Tachycardia 50 Hypertensive States of Pregnancy 20 Ventricular Fibrillation 51 Pre-eclampsia 21 Atrioventricular Block 52 Pulmonary Hypertension 22 Arrhythmogenic Right Ventricular 53 Deep Venous Thrombosis Cardiomyopathy 54 Cholesterol Embolism 23 Brugada Syndrome 55 Vasovagal Syncope 24 Aortic Stenosis 56 Carotid Sinus Hypersensitivity 25 Heyde Syndrome 57 Atrial Myxoma 26 Aortic Regurgitation 58 Septic Shock 27 Bicuspid Aortic Valve 59 Cardiac Action Potential 28 Mitral Stenosis 60 Heart Sounds 29 Mitral Regurgitation 61 Jugular Venous Pulse Waveform 30 Mitral Valve Prolapse 62 Exercise Physiological Changes 31 Tricuspid Regurgitation 63 ECG

Pulmonology 01 Bronchial Asthma 03 Bronchiolitis Obliterans 02 Occupational Asthma 04 COPD

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MRCP Revision Notes

05 Alpha-1 Antitrypsin Deficiency 30 Coal Workers' Pneumoconiosis 06 Allergic Bronchopulmonary Aspergillosis 31 Silicosis 07 Aspergilloma 32 Asbestosis 08 Invasive Aspergillosis 33 Hypersensitivity Pneumonitis 09 Bronchiectasis 34 Pulmonary Alveolar Proteinosis 10 Cystic Fibrosis 35 Pulmonary Alveolar Microlithiasis 11 Primary Ciliary Dyskinesia 36 Acute Respiratory Distress Syndrome 12 Yellow Nail Syndrome 37 Pulmonary Embolism 13 Community Acquired Pneumonia 38 Hepatopulmonary Syndrome 14 Bacterial Pneumonia 39 Altitude Illness 15 Mycoplasma Pneumonia 40 Lung Cancer 16 Legionnaires' Disease 41 Small Cell Lung Cancer 17 Aspiration Pneumonia 42 Non-small Cell Lung Cancer 18 Lung Abscess 43 Superior Vena Cava Syndrome 19 Hospital-acquired Pneumonia 44 Pneumothorax 20 Pneumocystis Jiroveci Pneumonia 45 Pleural Effusion 21 Histoplasmosis 46 Familial Mediterranean Fever 22 Nocardiosis 47 Mesothelioma 23 Viral Pneumonia 48 Lymphangioleiomyomatosis 24 Eosinophilic Pneumonia 49 Obstructive Sleep Apnea 25 Loeffler Syndrome 50 Narcolepsy 26 Tuberculosis 51 Respiratory Failure 27 Idiopathic Pulmonary Fibrosis 52 Chest X Ray 28 Sarcoidosis 53 Oxygen Dissociation Curve 29 Pneumoconiosis

Gastroenterology & Hepatology 01 Dyspepsia 16 Chronic Pancreatitis 02 Gastroesophageal Reflux Disease 17 Pancreatic Pseudocyst 03 Achalasia 18 Pancreatic Cancer 04 Pharyngeal Pouch 19 Crohn Disease 05 Esophagitis 20 Ulcerative Colitis 06 Barrett Esophagus 21 Celiac Disease 07 Esophageal Cancer 22 Tropical Sprue 08 Esophageal Varices 23 Bacterial Overgrowth Syndrome 09 Helicobacter Pylori 24 Whipple Disease 10 Peptic Ulcer Disease 25 Irritable Bowel Syndrome 11 Mallory-Weiss Tear 26 Diverticulitis 12 Zollinger-Ellison Syndrome 27 Peutz-Jeghers Syndrome 13 Gastric Cancer 28 Melanosis Coli 14 MALT Lymphoma 29 Angiodysplasia of the Colon 15 Acute Pancreatitis 30 Mesenteric Ischemia

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MRCP Revision Notes

31 Hirschsprung Disease 51 Gilbert Syndrome 32 Colorectal Cancer 52 Liver Cirrhosis 33 Gardner Syndrome 53 Ascites 34 Foodborne Illness 54 Spontaneous Bacterial Peritonitis 35 Bacterial Gastroenteritis 55 Budd-Chiari Syndrome 36 Salmonellosis 56 Hepatorenal Syndrome 37 Amebiasis 57 Hepatitis A Infection 38 Giardiasis 58 Hepatitis B Infection 39 Viral Gastroenteritis 59 Hepatitis C Infection 40 Pseudomembranous Colitis 60 Pyogenic Liver Abscess 41 Cryptosporidium 61 Amoebic Liver Abscess 42 Mycobacterium Avium Intracellulare 62 Hydatid Cysts 43 Autoimmune Hepatitis 63 Ascending Cholangitis 44 Primary Biliary Cirrhosis 64 Hepatocellular Carcinoma 45 Primary Sclerosing Cholangitis 65 Cholangiocarcinoma 46 Paracetamol Toxicity 66 Cholelithiasis 47 Drug-Induced Liver Disease 67 Acute Fatty Liver of Pregnancy 48 Hemochromatosis 68 Intrahepatic Cholestasis of Pregnancy 49 Wilson Disease 69 HELLP Syndrome 50 Non-alcoholic Fatty Liver Disease 70 Hyperemesis Gravidarum

Nephrology & Minerals Metabolism 01 Acute Renal Failure 21 Goodpasture Syndrome 02 Acute Tubular Necrosis 22 Renal Artery Stenosis 03 Rhabdomyolysis 23 Acute Pyelonephritis 04 Interstitial Nephritis 24 Xanthogranulomatous Pyelonephritis 05 Contrast Induced Nephropathy 25 Nephrolithiasis 06 Renal Papillary Necrosis 26 Renal Cell Carcinoma 07 Chronic Renal Failure 27 Wilms Tumor 08 Medullary Sponge Kidney 28 Bladder Cancer 09 Polycystic Kidney Disease 29 Benign Prostatic Hyperplasia 10 Nephrotic Syndrome 30 Prostate Cancer 11 Minimal Change Disease 31 Testicular Cancer 12 Membranous Glomerulonephritis 32 Epididymitis 13 Focal Segmental Glomerulosclerosis 33 Testicular Torsion 14 Amyloidosis 34 Cervical Cancer 15 Nephritic Syndrome 35 Bartter Syndrome 16 Diabetic Nephropathy 36 Renal Tubular Acidosis 17 IgA Nephropathy 37 Tumor Lysis Syndrome 18 Poststreptococcal Glomerulonephritis 38 Refeeding Syndrome 19 Mesangiocapillary Glomerulonephritis 39 Hyperkalemia 20 Rapidly Progressive Glomerulonephritis 40 Hypokalemia

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MRCP Revision Notes

41 Hyponatremia 47 Metabolic Alkalosis 42 Hypernatremia 48 Respiratory Alkalosis 43 Calcium Metabolism 49 Respiratory Acidosis 44 Hypercalcemia 50 Hypomagnesemia 45 Hypocalcemia 51 Hypophosphatemia 46 Metabolic Acidosis 52 Renal Replacement Therapy

Endocrinology & Diabetes 01 Acromegaly 34 Milk-Alkali Syndrome 02 Growth Hormone Deficiency 35 Hypoparathyroidism 03 Diabetes Insipidus 36 Pseudohypoparathyroidism 04 Syndrome of Inappropriate Antidiuretic 37 Cushing Syndrome Hormone 38 Pseudo-Cushing Syndrome 05 Hyperprolactinemia 39 Primary Aldosteronism 06 Prolactinoma 40 Addison Disease 07 Pituitary Apoplexy 41 Congenital Adrenal Hyperplasia 08 Sheehan Syndrome 42 Pheochromocytoma 09 Kallmann Syndrome 43 Menstrual Cycle 10 Klinefelter Syndrome 44 Menopause 11 Hyperthyroidism 45 Amenorrhea 12 Thyroid Storm 46 Polycystic Ovarian Syndrome 13 Hypothyroidism 47 Premature Ovarian Failure 14 Myxedema Crisis 48 Androgen Insensitivity Syndrome 15 Graves' Disease 49 Gynecomastia 16 Hashimoto Thyroiditis 50 Multiple Endocrine Neoplasia 17 Postpartum Thyroiditis 51 Polyglandular Autoimmune Syndrome 18 Subacute Thyroiditis 52 Carcinoid Syndrome 19 Toxic Multinodular Goitre 53 Glucagonoma 20 Thyrotoxicosis Factitia 54 Insulinoma 21 Riedel Thyroiditis 55 VIPoma 22 Subclinical Hyperthyroidism 56 Breast Cancer 23 Subclinical Hypothyroidism 57 Ovarian Cancer 24 Euthyroid Sick Syndrome 58 Type 1 Diabetes Mellitus 25 Amiodarone-Induced Thyrotoxicosis 59 Type 2 Diabetes Mellitus 26 Thyroid Cancer 60 Maturity Onset Diabetes of the Young 27 Hyperparathyroidism 61 Gestational Diabetes 28 Primary Hyperparathyroidism 62 Diagnosis of Diabetes Mellitus 29 Secondary Hyperparathyroidism 63 Diabetic Ketoacidosis 30 Tertiary Hyperparathyroidism 64 Hyperosmolar Hyperglycemic State 31 Malignancy-associated Hypercalcemia 65 Familial Hypercholesterolemia 32 Familial Hypocalciuric Hypercalcemia 66 Familial Hypertriglyceridemia 33 Idiopathic Hypercalciuria 67 Hyperlipoproteinemia Type III

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68 Metabolic Syndrome 70 Anorexia Nervosa 69 Obesity Management 71 Bulimia Nervosa

Hematology & Oncology 01 Iron Deficiency Anemia 28 Factor V Leiden Thrombophilia 02 Anemia of Chronic Disease 29 Protein C Deficiency 03 Thalassemia 30 Essential Thrombocythemia 04 Sickle Cell Anemia 31 Thrombocytopenia 05 Sideroblastic Anemia 32 Acute Myeloid Leukemia 06 Leukoerythroblastic Anemia 33 Acute Promyelocytic Leukemia 07 Pure Red Cell Aplasia 34 Chronic Myeloid Leukemia 08 Megaloblastic Anemia 35 Leukemoid Reaction 09 Polycythemia Vera 36 Acute Lymphoblastic Leukemia 10 Hemolytic Anemia 37 Chronic Lymphocytic Leukemia 11 Autoimmune Hemolytic Anemia 38 Aplastic Anemia 12 Cold Agglutinin Disease 39 Myelodysplastic Syndrome 13 Hereditary Spherocytosis 40 Myelofibrosis 14 Glucose-6-Phosphate Dehydrogenase 41 Hairy Cell Leukemia Deficiency 42 Hodgkin Lymphoma 15 Paroxysmal Nocturnal Hemoglobinuria 43 Non-Hodgkin Lymphoma 16 Microangiopathic Hemolytic Anemia 44 Burkitt Lymphoma 17 Disseminated Intravascular Coagulation 45 Mantle Cell Lmphoma 18 Hemolytic Uremic Syndrome 46 Multiple Myeloma 19 Thrombotic Thrombocytopenic Purpura 47 Monoclonal Gammopathy of Undetermined 20 Idiopathic Thrombocytopenic Purpura Significance 21 Henoch-Schonlein Purpura 48 Hyperviscosity Syndrome 22 Coagulation Cascade 49 Waldenstrom Macroglobulinemia 23 Hemophilia 50 Cryoglobulinemia 24 Von Willebrand Disease 51 Asplenia 25 Thrombophilia 52 Transfusion Reactions 26 Heparin-Induced Thrombocytopenia 53 Hypereosinophilic Syndrome 27 Antithrombin III Deficiency

Rheumatology & Autoimmune Disorders 01 Rheumatoid Arthritis 09 Raynaud Phenomenon 02 Systemic Lupus Erythematosus 10 Mixed Connective-Tissue Disease 03 Drug-Induced Lupus Erythematosus 11 Rickets 04 Systemic Scleroderma 12 Paget Disease 05 Dermatomyositis and Polymyositis 13 Osteomalacia 06 Polymyalgia Rheumatica 14 Osteoporosis 07 Fibromyalgia 15 Corticosteroid Induced Osteoporosis 08 Sjogren Syndrome 16 Still Disease

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17 Osteoarthritis 30 Reactive Arthritis 18 Gout 31 Ankylosing Spondylitis 19 Pseudogout 32 Psoriatic Arthritis 20 Septic Arthritis 33 Wegener Granulomatosis 21 Osteomyelitis 34 Microscopic Polyangiitis 22 Relapsing Polychondritis 35 Churg-Strauss Syndrome 23 Elbow Pain 36 Polyarteritis Nodosa 24 De Quervain Tenosynovitis 37 Behcet Disease 25 Adhesive Capsulitis 38 Giant Cell Arteritis 26 Supraspinatus Tendonitis 39 Takayasu Arteritis 27 Avascular Necrosis 40 Kawasaki Disease 28 Baker Cyst 41 Antiphospholipid Syndrome 29 Charcot Arthropathy

Neurology 01 Alzheimer Disease 28 Motor Neuron Disease 02 Lewy Bodies Dementia 29 Multifocal Motor Neuropathy 03 Pick Disease 30 Myasthenia Gravis 04 AIDS Dementia Complex 31 Lambert-Eaton Myasthenic Syndrome 05 Transient Global Amnesia 32 Myotonic Dystrophy 06 Normal Pressure Hydrocephalus 33 Hereditary Spastic Paraplegia 07 Parkinson Disease 34 Neuroleptic Malignant Syndrome 08 Multiple System Atrophy 35 Botulism 09 Progressive Supranuclear Palsy 36 Inclusion Body Myositis 10 Progressive Multifocal Leukoencephalopathy 37 Acid Maltase Deficiency 11 Tremors 38 Critical Illness Myopathy 12 Essential Tremor 39 Central Pontine Myelinolysis 13 Creutzfeldt-Jakob Disease 40 Hypokalemic Periodic Paralysis 14 Chorea 41 McArdle Syndrome 15 Huntington Disease 42 Becker Muscular Dystrophy 16 Dystonia 43 Mitochondrial Myopathies 17 Oculogyric Crisis 44 Locked-in Syndrome 18 Tourette Syndrome 45 Cerebrovascular Accident 19 Friedreich Ataxia 46 Glasgow Coma Scale 20 Ataxia Telangiectasia 47 Intracranial Hemorrhage 21 Wernicke Encephalopathy 48 Cerebral Infarction 22 Epilepsy 49 Localization of Brain Lesion 23 Hemiballismus 50 Aphasia 24 Restless Legs Syndrome 51 Localization of Cerebral Stroke 25 Multiple Sclerosis 52 Lacunar Stroke 26 Guillain-Barre Syndrome 53 Transient Ischemic Attack 27 Miller Fisher Syndrome 54 Lateral Medullary Syndrome

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MRCP Revision Notes

55 Basilar Artery Occlusion 92 Ptosis 56 Vertebral Artery Dissection 93 Horner Syndrome 57 Pontine Hemorrhage 94 Nystagmus 58 Lateral Pontine Syndrome 95 Migraine 59 Cavernous Sinus Thrombosis 96 Tension type Headache 60 Cerebral Venous Thrombosis 97 Cluster Headache 61 Carotid Artery Dissection 98 Chronic Paroxysmal Hemicrania 62 Carotid Artery Stenosis 99 Medication Overuse Headache 63 CADASIL Syndrome 100 Trigeminal Neuralgia 64 Idiopathic Intracranial Hypertension 101 Post Lumbar Puncture Headache 65 CSF Analysis 102 Anterior Spinal Artery Syndrome 66 Meningitis 103 Brown-Sequard Syndrome 67 Neisseria Meningitidis 104 Subacute Combined Degeneration of Spinal 68 Listeria Monocytogenes Cord 69 Herpes Simplex Encephalitis 105 Transverse Myelitis 70 Cerebral Abscess 106 Arnold-Chiari Malformation 71 Cryptococcus Meningitis 107 Syringomyelia 72 Facial Nerve Paralysis 108 Phrenic Nerve Palsy 73 Bell Palsy 109 Cervical Spondylosis 74 Ramsay Hunt Syndrome 110 Cervical Disc Prolapse 75 Rinne and Weber Test 111 Traumatic Brachial Plexopathy 76 Vertigo 112 Brachial Neuritis 77 Benign Paroxysmal Positional Vertigo 113 Carpal Tunnel Syndrome 78 Meniere Disease 114 Radial Nerve Palsy 79 Acoustic Neuroma 115 Ulnar Nerve Palsy 80 Glomus Jugulare Tumor 116 Lumbar Disc Prolapse 81 Craniopharyngioma 117 Metastatic Spinal Cord Compression 82 Optic Neuritis 118 Cauda Equina Syndrome 83 Miosis and Mydriasis 119 Lumbar Spinal Stenosis 84 Argyll Robertson Pupils 120 Femoral Nerve Palsy 85 Adie Syndrome 121 Meralgia Paresthetica 86 Oculomotor Nerve Palsy 122 Sciatic Nerve Palsy 87 Trochlear Nerve Palsy 123 Peripheral Neuropathy 88 Abducens Nerve Palsy 124 Alcoholic Neuropathy 89 Internuclear Ophthalmoplegia 125 Diabetic Neuropathy 90 Posterior Communicating Artery Aneurysm 126 Charcot Marie Tooth Disease 91 Visual Field Defects

Ophthalmology 01 Retinal Vein Occlusion 04 Diabetic Retinopathy 02 Retinal Artery Occlusion 05 Age-Related Macular Degeneration 03 Hypertensive Retinopathy 06 Retinitis Pigmentosa

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MRCP Revision Notes

07 Cataract 11 Herpes Simplex Keratitis 08 Ectopia Lentis 12 Trachoma 09 Uveitis 13 Glaucoma 10 Conjunctivitis 14 Retinoblastoma

Psychiatry 01 Depression 08 Post-traumatic Stress Disorder 02 Schizophrenia 09 Chronic Fatigue Syndrome 03 Delirium 10 Generalized Anxiety Disorder 04 Bipolar Disorder 11 Phobic Disorders 05 Postpartum Psychiatric Disorders 12 Somatoform Disorders 06 Electroconvulsive Therapy 13 Obsessive-Compulsive Disorder 07 Panic Disorder 14 Personality Disorders

Infectious Diseases 01 Streptococcus 26 Chickenpox 02 Staphylococcus Aureus 27 In Utero VZV Infection 03 Toxic shock Syndrome 28 Herpes Zoster 04 Gonorrhea 29 Infectious Mononucleosis 05 Chlamydial Genitourinary Infections 30 Cytomegalovirus 06 Diphtheria 31 Parvovirus B19 Infection 07 Leprosy 32 Measles 08 Syphilis 33 Mumps 09 Jarisch-Herxheimer Reaction 34 Dengue Fever 10 Yaws 35 Ebola 11 Tetanus 36 HIV 12 Anthrax 37 Human Papillomavirus 13 Psittacosis 38 Toxoplasmosis 14 Leptospirosis 39 Malaria 15 Brucellosis 40 Schistosomiasis 16 Q Fever 41 Cutaneous Larva Migrans 17 Rabies 42 Strongyloides Stercoralis 18 Cat Scratch Disease 43 Visceral Larva Migrans 19 Typhus 44 Filariasis 20 Lyme Disease 45 Cysticercosis 21 Leishmaniasis 46 Candidiasis 22 African Trypanosomiasis 47 Vaginal Discharge 23 Chagas Disease 48 Vaccines 24 Herpes Simplex Virus 49 Reye Syndrome 25 Acute Herpetic Gingivostomatitis

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Dermatology & Allergic Disorders 01 Anaphylaxis 36 Granuloma Annulare 02 Hereditary Angioedema 37 Oral Hairy Leukoplakia 03 Contact Dermatitis 38 Dermatitis Herpetiformis 04 Urticaria 39 Pemphigus Vulgaris 05 Atopic Dermatitis 40 Bullous Pemphigoid 06 Eczema Herpeticum 41 Pemphigoid Gestationis 07 Pompholyx 42 Polymorphic Eruption of Pregnancy 08 Erythroderma 43 Erythema Multiforme 09 Erysipelas 44 Stevens-Johnson Syndrome 10 Cellulitis 45 Toxic Epidermal Necrolysis 11 Necrotizing Fasciitis 46 Drug-Induced Hypersensitivity Syndrome 12 Gangrene 47 Porphyria Cutanea Tarda 13 Impetigo 48 Erythema Nodosum 14 Herpes Labialis 49 Pyoderma Gangrenosum 15 Vitiligo 50 Necrobiosis Lipoidica 16 Pityriasis Versicolor 51 Pretibial Myxedema 17 Pityriasis Rosea 52 Livedo Reticularis 18 Acne Vulgaris 53 Malignant Melanoma 19 Rosacea 54 Cutaneous Squamous Cell Carcinoma 20 Seborrheic Dermatitis 55 Keratoacanthoma 21 Hypertrichosis 56 Actinic Keratosis 22 Alopecia 57 Cutaneous Basal Cell Carcinoma 23 Alopecia Areata 58 Kaposi Sarcoma 24 Tinea Capitis 59 Keloids 25 Tinea Corporis 60 Genital Herpes 26 Tinea Cruris 61 Genital Ulcers 27 Lichen Planus 62 Vascular Ulcers 28 Lichen Sclerosus 63 Hyperhidrosis 29 Discoid Lupus Erythematosus 64 Onycholysis 30 Psoriasis 65 Onychomycosis 31 Scabies 66 Koebner Phenomenon 32 Acanthosis Nigricans 67 Phototoxicity 33 Morphea 68 Gingival Hyperplasia 34 Erythema Ab Igne 69 Diabetic Foot 35 Erythema Gyratum Repens

Pharmacology & Toxicology 01 Pharmacokinetics 04 Digoxin 02 Drug Metabolism 05 Adenosine 03 Cytochrome p450 06 Amiodarone

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07 Flecainide 40 Dopamine Agonists 08 ACE Inhibitors 41 Benzodiazepines 09 Diuretics 42 Phenytoin 10 Calcium Channel Blockers 43 Triptans 11 B-Blockers 44 Botulinum Toxin 12 B-Agonists 45 Selective Serotonin Reuptake Inhibitors 13 Alpha Blockers 46 Serotonin Syndrome 14 Smoking Cessation 47 Tricyclic Anti-Depressants 15 Theophylline 48 St John’s Wort 16 Sildenafil 49 Antipsychotics 17 Antiemetics 50 Lithium 18 Octreotide 51 Palliative Care Prescribing 19 Metformin 52 Antibiotics 20 Sulfonylurea 53 Penicillin 21 Thiazolidinediones 54 Quinolones 22 Exenatide 55 Antituberculous Drugs 23 Dipeptidyl Peptidase-4 Inhibitors 56 Antiviral Drugs 24 Types of Insulin 57 Anti-retroviral Drugs 25 Cholesterol Lowering Drugs 58 Isotretinoin 26 Breastfeeding Contraindications 59 Alcohol Withdrawal Syndrome 27 Corticosteroids 60 Opioid Toxicity 28 Oral Contraceptive Pills 61 Cocaine Toxicity 29 Hormone Replacement Therapy 62 MDMA Toxicity 30 Selective Estrogen-receptor Modulator 63 Organophosphate Toxicity 31 Salicylate Toxicity 64 Ethylene Glycol Toxicity 32 Heparin 65 Carbon Monoxide Poisoning 33 Warfarin 66 Methemoglobinemia 34 Iron Tablets Toxicity 67 Cyanide Poisoning 35 Allopurinol 68 Lead Poisoning 36 Bisphosphonates 69 Zinc Deficiency 37 Methotrexate 70 Scurvy 38 Cytotoxics and DMARDs 01 71 Pellagra 39 Monoclonal Antibodies

Genetics & Hereditary Disorders 01 Patterns of Inheritance 08 Ehlers-Danlos Syndrome 02 Neurofibromatosis 09 Fabry Disease 03 Tuberous Sclerosis 10 Fragile X Syndrome 04 Acute Intermittent Porphyria 11 Galactosemia 05 Alport Syndrome 12 Hereditary Hemorrhagic Telangiectasia 06 Cystinuria 13 Homocystinuria 07 Down Syndrome 14 Lesch-Nyhan Syndrome

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15 Marfan Syndrome 19 Refsum Disease 16 McCune-Albright Syndrome 20 Turner Syndrome 17 Phenylketonuria 21 Von Hippel-Lindau Disease 18 Pseudoxanthoma Elasticum 22 Wiskott-Aldrich Syndrome

Basic Sciences & Statistics 01 Human Leukocyte Antigen 13 Inflammatory Mediators 02 Hypersensitivity Reactions 14 Layers of the Skin 03 Immunoglobulins 15 Foramina of the Skull 04 Antineutrophil cytoplasmic antibodies (ANCA) 16 Renal Anatomy 05 Primary Immunodeficiency 17 Relative Risk 06 Inflammatory Markers 18 Incidence and Prevalence 07 Rheumatoid Factor 19 Sensitivity and Specificity 08 Alkaline Phosphatase 20 Study Design 09 Atrial Natriuretic Peptide 21 Fitness to Fly 10 Nitric Oxide 22 Driver and Vehicle Licensing Agency Rules 11 Endothelin (DVLA) 12 Interferons

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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  Brought on by breathing in  Very prolonged  Associated with symptoms such as dizziness,  Unrelated to activity 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

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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  Troponin level > 0.03 but less than 0.1 response to nitrates.  Angiography will show fixed lesion (atheromatous  ECG findings are more prominent 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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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  Inadequate blood pressure response  Development of angina symptoms  Inadequate heart rate response  Ventricular arrhythmias

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)  At rest  Gradual  Not relieved by nitrates  More sever  Associated with autonomic symptoms

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

 History of ischemic discomfort  Rise and fall in serum cardiac markers  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

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 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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 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 5- 14 days. Level above 0.1 ng/ml indicates a myocardial infarction.

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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  Subcutaneous low-molecular-weight heparin  Intravenous B-blocker  Repeated doses of sublingual GTN  Intravenous morphine

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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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)  Aortic dissection  Recent hemorrhage, trauma or surgery  Recent head injury  Coagulation and bleeding disorders  Pregnancy  Intracranial neoplasm  Severe hypertension  Stroke within 3 months

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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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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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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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  Hydralazine with nitrates  B-blockers (carvedilol and bisoprolol)  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.

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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  Previous thromboembolic event  Intracardiac thrombus  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  On optimal medical therapy  Ejection fraction less than 35%

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  Age > 70  Myocardial ischemia  Renal failure  Left ventricular hypertrophy  Liver cirrhosis  Pulmonary embolism

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

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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  Heart rate ≥110/min  Respiratory rate ≥25/min  Inability to complete sentences in one breath

Life-threatening asthma  PEF <33% best or predicted  Cyanosis  SpO2 <92%  Poor respiratory effort  PaO2 <8 kPa  Arrhythmia  Elevated pCO2 (4.6-6.0 kPa)  Exhaustion, altered conscious level  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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 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 TLCO  Reduced FEV1/FVC ratio  Increased KCO  Increased residual volume RV

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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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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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)  Laboratory technicians (rats, mice, rabbits, locusts)  Chemical processors (acids, detergents, bleaches)  Plastics workers (polyethylene, polyvinyl)  Cigarette factory workers (tobacco dust)  Bakers (flour and enzymes as amylase used in the  Tea sifters and packers (tea dust) 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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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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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  Frequent winter 'bronchitis'  Chronic cough  Wheeze  Regular sputum production

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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 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%  RV/TLC ratio increase indicating air trapping  FEV1/FVC < 70%  KCO decrease (unlike BA)  RV increase  Spirometry with reversibility will show minimal  TLC increase 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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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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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  Alpha-blockers  Calcium channel 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  Upper lobe predominant emphysema  PaCO2 less than 7.3 kPa  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 Page 32

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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 PiSZ genotype alpha-1 antitrypsin is 40%  In PiMS genotype alpha-1 antitrypsin is 80%  In PiZZ genotype alpha-1 antitrypsin is 10-15%  In PiSS genotype alpha-1 antitrypsin is 60% which is the severest form of alpha 1-antitrypsin  In PiMZ genotype alpha-1 antitrypsin is 60% 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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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  Drug Causes (NSAIDs, bisphosphonates and  GERD steroids)  Peptic ulcer disease  Drugs reducing lower esophageal sphincter  Esophageal and gastric cancer pressure (calcium channel blockers, nitrates and  Cholelithiasis and chronic pancreatitis 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  Iron deficiency anemia  Progressive weight loss  Epigastric mass  Progressive dysphagia  Suspicious barium meal  Persistent vomiting

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 anti- inflammatory drugs  Poor esophageal peristalsis  Delayed gastric emptying  Hiatus hernia

Signs and symptoms

Esophageal symptoms

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 Heartburn  Dysphagia  Regurgitation

Extraesophageal symptoms  Cough and wheezes  Noncardiac chest pain  Hoarseness, sore throat  Enamel erosion or other dental manifestations

Complications  Esophagitis  Barrett esophagus  Anemia  Esophageal cancer  Benign strictures

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  Heartburn from the start  Halitosis  Regurgitation (cough, aspiration pneumonia and  Dysplastic changes (15-fold increase in esophageal bronchial asthma) cancer)  Chest pain

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)

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 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  Chronic cough  Regurgitation of rotten food in the mouth  Gurgling neck mass appears only on swallowing  Halitosis

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  Arthralgia  Secondary amenorrhea  Chest pain from pleuritis  Cushingoid features and hirsutism

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)

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 Sjogren syndrome (most common cause)  Systemic sclerosis  Rheumatoid arthritis  Thyroid disease

Signs and symptoms  Pruritus and jaundice  Hyperpigmentation  Right upper quadrant discomfort  Sicca syndrome as xerophthalmia and xerostomia  Hepatosplenomegaly

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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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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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  Urinary Na < 20 mEq/L  FeNa (fractional excretion of sodium) < 1%  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 Interstitial Nephritis  Acute Glomerulonephritis

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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  Urinary Na is variable  FeNa (fractional excretion of sodium) 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  Fluid overload  Metabolic acidosis  Pulmonary edema  Symptoms or complications of uremia (pericarditis or encephalopathy)

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  Hepatorenal syndrome  Pancreatitis  Pre-eclampsia and eclampsia  Myocardial infarction

Nephrotoxic causes

Endogenous nephrotoxins

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 Burns  Massive intravascular hemolysis  Rhabdomyolysis  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  Hypothermia  Prolonged epileptic seizure  Ecstasy poisoning  Infectious or inflammatory myopathies  McArdle syndrome  Prolonged collapse or coma  Statins

Diagnosis  Highly elevated creatine kinase  Myoglobinuria  Hypocalcemia, hyperkalemia, hyperphosphatemia and hyperuricemia

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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  Arthralgia  Maculopapular rash  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  Diabetes  Chronic kidney disease  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%

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 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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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  Carney syndrome  MEN-1  Ectopic GHRH or GH secretion  McCune-Albright syndrome

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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Complications  Hypertension  Hyperhidrosis  Diabetes  Osteoarthritis and spinal cord compression  Peripheral neuropathies (e.g., carpel tunnel  Colorectal polyps syndrome)  Hyperhidrosis due to sweat gland hypertrophy  Cardiomyopathy

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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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  CNS radiation  Brain tumors (Craniopharyngioma)  Anatomical abnormalities (empty sella  CNS surgery syndrome)

Signs and symptoms:  Short stature  Obesity  Small penis  Poor bone density  Reduced muscle mass  Hypoglycemia and hypercholesterolemia

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 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  Wegener granulomatosis  Post head injury  Craniopharyngioma  Sarcoidosis  Histiocytosis X  Pituitary surgery  Wolfram syndrome

Nephrogenic diabetes insipidus (resistance to vasopressin)  Genetic  UT obstruction  Electrolytes: hypercalcemia, hypokalemia  Sickle-cell anemia  Drugs: demeclocycline, lithium  Pyelonephritis  Tubulo-interstitial disease

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

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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

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 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  BMI < 25  Polydipsia  Diabetic ketoacidosis (DKA) is a common  Polyphagia complication  Unexplained weight loss

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

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 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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 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  Abdominal obesity  Hyperglycemia  Acanthosis nigricans, hirsutism, peripheral  Hypertriglyceridemia neuropathy, and retinopathy  Reduced high-density lipoprotein cholesterol  Xanthomas (HDL-C)

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

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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

 Myocardial ischemia  Esophageal webbing and gastric atrophy  Cold intolerance  Koilonychia (spoon-shaped nails)

 Angular stomatitis  Glossitis

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

 Low serum iron and ferritin (storage protein) levels with elevated transferrin (transporting protein) and total iron- binding 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  Palpitations  Lightheadedness, dizziness  Cold intolerance  Syncope or near-syncope  Inability to concentrate  Decreased exercise tolerance  Skin pallor

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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 Page 57

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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

 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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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)

 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

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 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  Lead poisoning  Idiopathic  Alcohol  Myelodysplasia  Drugs (anti-tuberculous agents, progesterone)  Nutritional deficiencies (copper, vitamin B-6)  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

 Boutonniere deformity: PIP flexion with DIP hyperextension

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

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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

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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.

 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  Positive RF  Insidious onset  Poor functional status at presentation  HLA DR4  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 Page 63

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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  Chlorpromazine  Isoniazid  Quinidine  Minocycline  Penicillamine  Hydralazine  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

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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 self- monitoring, 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

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 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

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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.

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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.

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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  Speech and visual impairment  Motor weakness

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

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 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.

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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  History of social withdrawal  Gradual onset  Lack of obvious precipitant  Low IQ

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)

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 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 squamo- columnar 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

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 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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 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

 Nail longitudinal grooving and ridging, subungual hyperkeratosis and onycholysis

 Scarring alopecia  Koebner phenomenon (lesions in old scars)

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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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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  Lignocaine  Isosorbide dinitrate  Propranolol  Glyceryl trinitrate  Verapamil  Testosterone  Hydrocortisone

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Acetylator status Many drugs are metabolized in the liver by acetylation; some patients may show deficient in hepatic N-acetyl- transferase known as slow acetylators which leads to increased drugs adverse effects.

Drugs affected include:  Procainamide  Isoniazid  Sulfasalazine  Dapsone  Hydralazine  Sulphonamides

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

Drug Time of sample taken Lithium 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.

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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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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 re- entrant 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  Blue-grey skin discoloration  Hypothyroidism and hyperthyroidism  Peripheral neuropathies  Corneal micro-deposits  Epididymitis  Hepatitis  Gynecomastia  Photosensitivity

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

 Cyclosporine  Flecainide  Digoxin  Sildenafil

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 Simvastatin  Warfarin  Theophylline

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 Mechanism of action Ia Disopyramide and Quinidine Block sodium channels Ib Lidocaine Block sodium channels Ic Flecainide Block sodium channels II Propranolol Beta antagonists III Amiodarone Block potassium channels IV Verapamil Calcium channel blockers

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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  Marfan syndrome  Adult polycystic disease  Myotonic dystrophy  Antithrombin III deficiency  Neurofibromatosis  Ehlers-Danlos syndrome  Noonan syndrome  Familial adenomatous polyposis  Peutz-Jeghers syndrome  Hereditary non-polyposis colorectal carcinoma  Retinoblastoma  Hereditary hemorrhagic telangiectasia  Romano-Ward syndrome  Hereditary spherocytosis  Tuberose sclerosis  Huntington disease  Von-Hippel-Lindau syndrome  Hypokalemic periodic paralysis  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  Gilbert syndrome  Congenital adrenal hyperplasia  Hemochromatosis  Cystic fibrosis  Homocystinuria  Cystinuria  Phenylketonuria  Familial Mediterranean Fever  Sickle cell anemia  Fanconi anemia  Thalassemia  Friedreich ataxia  Wilson disease

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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  Hemophilia A and B  Becker muscular dystrophy  Lesch-Nyhan syndrome  Duchenne and Becker muscular dystrophy  Nephrogenic diabetes insipidus  Fabry disease  Retinitis pigmentosa  G6PD deficiency  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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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

 Two or more Axillary or inguinal freckles

 Two or more typical neurofibromas

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 Two or more Lisch nodules (iris hamartoma)

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

Other signs and symptoms  Learning disabilities  Short stature  Larger than average head size  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  Fanconi anemia  Tuberous sclerosis  Coffin-Siris syndrome  McCune-Albright syndrome

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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 Diseases with increased risk Ankylosing spondylitis HLA-B27 Gonococcal arthritis Acute anterior uveitis Reactive arthritis Psoriatic arthritis

Systemic lupus erythematosus HLA-DR2 Narcolepsy Goodpasture syndrome

Autoimmune hepatitis HLA-DR3 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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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

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 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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