MANUAL OF

PRACTICAL MEDICINE

R Alagappan MD FICP

Formerly

Director-Professor and Head

Institute of Internal Medicine

Madras Medical College

and

Senior Physician

Government General Hospital

Chennai, Tamil Nadu, India

New Delhi | London | PanamaThe Health Sciences Publisher

Sixth Edition

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Jaypee Brothers Medical Publishers (P) Ltd

HeadquartersJaypee Brothers Medical Publishers (P) Ltd4838/24, Ansari Road, DaryaganjNew Delhi 110 002, IndiaPhone: +91-11-43574357Fax: +91-11-43574314Email: jaypee@jaypeebrothers.com

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© 2018, Jaypee Brothers Medical Publishers

The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book.

All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book.Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book.This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought.Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the �������������� �����CD/DVD-ROM (if any) provided in the sealed envelope with this book is complimentary and free of cost. Not meant for sale.

� ������������������������������������������ jaypee@jaypeebrothers.com

Manual of Practical Medicine

First Edition: 1998; Second Edition: 2002; Third Edition: 2007; Fourth Edition: 2011; Fifth Edition: 2014

Sixth Edition: 2018

ISBN 978-93-5270-238-1

Printed at

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Dedicated toMy beloved Wife

Dr R Gomathy MBBS DGO DMCH

for her patience and constant encouragementJayp

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I have the pleasure of introducing the sixth edition of Manual of Practical Medicine. The speed of increase of medical literature places an enormous strain on the editor in keeping up the size of the manual. The manual has grown in size and complexity, mirroring the growth in different fields of internal medicine.

The basic principles of history taking and the clinical examination have not been changed. All the chapters have been revised and updated. A large number of diagrams and CT images have been incorporated for easy understanding.

I place my sincere thanks and regards to Shri Jitendar P Vij (Group Chairman), Mr Ankit Vij (Group President) and Miss Ritu Sharma (Director–Content Strategy) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India for their constant encouragement in updating this manual.

I dedicate this edition to my beloved wife, Dr R Gomathy, whose love, affection, patience and constant encouragement helped me in many ways to bring out successfully several editions of this manual.

I profusely thank the postgraduates in internal medicine, Dr Karthikeyan Subbian and Dr Jayaprakash Thangavel, for their devoted time consuming hard work in revising and updating this edition. They helped me a lot in obtaining many new diagrams and also in replacing some of the old images.

I offer my heartfelt thanks to Dr KG Srinivasan, Consultant Radiologist of KGS Advanced MR, CT Scan and Ultrasound and Doppler Scan, for his generous contribution of MR, CT images to various chapters of this manual and a small write-up on CT PET scan. He is a role model to be emulated by everyone for the rare combination of qualities—wisdom, politeness and hard work.

I do hope and wish that the sixth edition of this manual will be a good and complete guide for medical students and practicing physicians.

R Alagappan

Preface to the Sixth Edition

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Medicine is an everchanging science. The vast clinical experience, the technological advancement in the field of investigatory modalities, tremendous explosion in the invention and addition of newer drugs in the field of pharmacology, and a wide variety of interventional therapeutic advancements have contributed to the voluminous growth of medical literature.

Human brain cannot remember all the facts. It is impossible to learn, register, remember and to recall all the medical facts in the course of time-bound undergraduate and postgraduate medical education. It is the realisation of these difficulties that prompted me to write this manual. Hence, an earnest attempt has been made to merge the clinical methods and the principles of internal medicine and to present both in a condensed form. To keep the size of the volume compact and small, only certain important clinical topics are included in this manual. Even references are not included since high-tech reference system is available in all the good libraries.

The manual will be of practical value to the medical students and practicing physicians with an emphasis not only on clinical methods, clinical features, various essential investigations, but also on the management of various important clinical disorders.

I am deeply indebted to three of my postgraduate students Dr K Narayanasamy (MD), Dr Rajesh Bajaj (MD), and Dr S Sujatha (MD) who have helped me in preparation of the manuscript, computer and laser printing and up to the stage of submission to the publishers. But for their untiring efforts and hard work, the timely publication of this manual would not have been possible.

I wish to acknowledge the contribution of my associates and colleagues in securing the clinical photographs, echocardiograms, X-rays, CT films, nuclear imaging photographs and computer line diagrams for this manual: C Lakshmikanthan, R Alagesan, P Thirumalai, K Kannan (Madurai), CU Velmurugendran, SG Krishnamoorthy, S Sethuraman, P Raja Sambandam, MA Muthusethupathy, P Soundarrajan, AS Natrajan, D Sivagnanasundaram, C Panchapakesa Rajendran, KR Suresh Bapu, Thirumoorthy and Hari Ramesh.

I wish to thank my postgraduate students who did the proofreading of the entire manual.

Last, but by no means the least, I wish to acknowledge the help and encouragement provided by the editorial department and the editorial staff of M/s Jaypee Brothers Medical Publishers, New Delhi, India for their kind cooperation in bringing out this manual.

I do wish that this manual will be a good guide and primer to the internal medicine students and practicing physicians.

R Alagappan

Preface to the First Edition

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Contents

1. Introduction to Internal Medicine ........... 1 � History Taking 2 � General Examination 4

� Examination of the Skin 4 � Hair 6 � Face 8 � Eyes 9 � The Tongue 9 � Characteristic Types of Facies 12 � Constitution 12 � Stature 13 � State of Nutrition 16 � Posture 17 � Hands and Fingers 18 � Feet and Toes 20 � The Skin in Clinical Medicine 21 � Nails in Clinical Medicine 23

� Temperature 25 � Normal Temperature Regulation in the Body 25 � Factors Determining Rate of Heat Production 25 � Fever 26

� Pain 31 � Chest Pain 31 � Abdominal Pain 33 � Pain due to Disorders of GIT 33 � Renal Pain 35 � Peripheral Vascular Pain Arterial Occlusion 35 � Venous Pain 35 � Neurogenic Claudication 35

� Oedema 35 � Aetiology and Types of Oedema 36 � Pathophysiology of Oedema 36 � Characteristic Features of Oedema of Various

Aetiologies 36 � Shock 38

� Control of Arterial Blood Pressure 38 � Control Mechanism 38 � Classification 38

� Fundamentals in Genetics 40 � Normal Chromosome Number and Structure 41 � Chromosomal Abnormalities 41 � Single Gene Disorders 42 � Mosaicism 43 � Chimerism 43 � Multifactorial or Polygenic Inheritance 43 � Genomic Imprinting 44 � Trinucleotide Repeat 44 � Mitochondrial Disorders 44 � Common Chromosomal Disorders 44

� Immunology 45 � The Immune System and the Basis of Immunity 45 � Clinical Aspects of Immunology 46 � Immunoglobulins 46 � Disorders of Immunoglobulins 48 � Immunodeficiency States 48 � Hypersensitivity Reactions 49

� Histocompatibility Antigens 50 � Transplant Rejection 50 � Autoimmune Diseases 50 � Immunology and Malignancy 50

2. Nutrition .................................................. 51 � Classification of Nutrients 52

� Water 52 � Macro-nutrients 52

� Classification of Nutritional Disorders 53 � Pathological Causes of Nutritional Disorders 54 � Effects of Malnutrition 54 � Protein–Energy Malnutrition 54

� Vitamins 56 � Vitamin A (Retinol) 56 � Vitamin D 58 � Vitamin E 60 � Vitamin K 61 � Thiamine (Vitamin B1) 61 � Riboflavin (Vitamin B2) 62 � Niacin (Nicotinic Acid and Nicotinamide) 62 � Pyridoxine (Vitamin B6) 63 � Biotin 63 � Vitamin B12 and Folate 63 � Vitamin C (Ascorbic Acid) 63

� Inorganic Nutrients 65 � Sodium 65 � Potassium 65 � Calcium 66 � Phosphorus 66 � Iron 67 � Iodine 67 � Zinc 67 � Fluorine 67 � Magnesium 68 � Manganese 68 � Copper 69 � Cobalt 69 � Nickel 69 � Chromium 69 � Selenium 69

� Obesity 69 � Types of Obesity 70 � Aetiology 70 � Pathology 71 � Prognosis 71

� Anorexia Nervosa and Bulimia 72 � Anorexia Nervosa 72 � Bulimia 72

3. Infectious Diseases ................................. 73 � Bacterial Infections 74

� Staphylococcal Infections 74 � Streptococcal Infections 76 � Meningococcal Meningitis 78 � Gonococcal Infection 78

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� Diphtheria 79 � Tetanus 80 � Botulism 81 � Gas Gangrene (Clostridial Myonecrosis) 82 � C. difficile Infection (Pseudomembranous Colitis) 82 � Listeriosis 82 � Anthrax 83 � Haemophilus influenzae 84 � Legionella (Legionnaires Disease) 84 � Whooping Cough (Pertussis) 85 � Gram-negative Enteric Bacteria 85 � Escherichia coli 85 � Campylobacter 86 � Enteric Fever 86 � Shigellosis: Bacillary Dysentery 88 � Cholera 88 � Brucellosis (Undulant Fever) 90 � Plague 90 � Helicobacter pylori 91 � Anaerobic Infections 92 � Nocardiosis 93 � Atypical Mycobacteria 94 � Extrapulmonary Tuberculosis 95 � Leprosy (Hansen’s Disease) 96 � Chancroid 98 � Granuloma Inguinale 99 � Chlamydial Infections 99 � Mycoplasma Infections 102

� Spirochetal Diseases 103 � Syphilis 103 � Yaws (Framboesia) 107 � Endemic Syphilis (Bejel) 107 � Pinta 107 � Leptospirosis (Weil’s Disease) 107 � Relapsing Fever 108 � Rat-bite Fever 109 � Lyme Borreliosis 109

� Rickettsial Infections 110 � Epidemic Louse-Borne Typhus 110 � Endemic Flea-Borne Typhus (Murine Typhus) 110 � Scrub Typhus (Tsutsugamushi Fever) 111 � Rocky Mountain Spotted Fever 111 � Rickettsialpox 111 � Tick Typhus (Rickettsial Fever) 111 � Ehrlichiosis and Anaplasmosis 111 � Diagnosis of Rickettsial Infections 111 � Q-Fever 111 � Kawasaki Disease 112

� Viral Diseases 112 � Classification of Viral Disorders 112 � Viral Infections and Cancer 113 � Viral Pathogenesis 113 � Immunity-Viral Diseases 113 � Diagnostic Virology 113 � Viral Respiratory Disorders 114 � Parainfluenza 114 � Influenza 114 � Respiratory Syncytial Virus Infections 114 � Herpes Virus Infections 115 � Varicella Zoster Infections 117 � Epstein-Barr Virus (HHV-4) and Infectious

Mononucleosis 119 � Cytomegalovirus 121

� Human Herpesviruses Types—6, 7 and 8 122 � Human Papillomavirus and Parvovirus Infections 122 � Parvovirus Infections 123 � Variola (Small Pox) 124 � Measles (Rubeola) 124 � Rubella (German Measles) 125 � Mumps 126 � Poliomyelitis 126 � Rabies 127 � Dengue Fever (Break-bone Fever) 129 � Yellow Fever 129 � Japanese B Encephalitis 130 � Chikungunya Virus Infection 130 � Gastrointestinal Virus Infections 130 � Hepatitis Viruses (A–E) 130 � Coxsackie Virus Infections 130 � Human Immunodeficiency Virus (HIV) Infection and

Acquired Immunodeficiency Syndrome (AIDS) 132 � Protozoal Infections 141

� Malaria 141 � Amoebiasis 146 � Giardiasis 147 � Cryptosporidiosis 148 � Trichomoniasis 148 � Balantidiasis 149 � Isosporiasis 149 � Leishmaniasis 149 � Trypanosomiasis 151 � Toxoplasmosis 154 � Pneumocystis jiroveci 155

� Helminthic Infestations 156 � Classification of Helminths that Infest Humans 156 � Ankylostomiasis (Hookworm) 156 � Ascariasis 156 � Strongyloidiasis 159 � Enterobius Vermicularis (Threadworm or

Pinworm) 160 � Trichuris Trichiura (Whipworm) 161 � Tissue-dwelling Human Nematodes 161 � Lymphatic Filariasis 163 � Tropical Pulmonary Eosinophilia 164 � Loiasis 165 � Onchocerciasis (River Blindness) 165 � Dracunculiasis (Guinea Worm Infection) 166 � Zoonotic Nematodes 166 � Trichinosis (Trichinellosis) 166 � Cutaneous Larva Migrans (CLM) 167 � Trematodes (Flatworms/Flukes) 168 � Schistosomiasis (Blood Flukes) 168 � Hepatobiliary Flukes 170 � Intestinal Flukes 170 � Lung Flukes 170 � Cestodes (Tapeworms) 170 � Taenia Saginata 170 � Taenia Solium and Cysticercosis 171 � Echinococcosis 174 � Hymenolepiasis Nana 175 � Diphyllobothrium latum 175

� Fungal Infections 176 � Candidiasis 176 � Histoplasmosis 178 � Coccidioidomycosis 179

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� Pneumocystosis (Pneumocystis jiroveci Pneumonia) 180

� Cryptococcosis 181 � Aspergillosis 181 � Mucormycosis (Zygomycosis/Phycomycosis) 183 � Penicillium Marneffei Infections 184 � Mycetoma (Maduromycosis and

Actinomycetoma) 184 � Immunisation Against Infectious Diseases 185

� Milestones in Vaccine Evolution 185 � Adult Immunisation 185

4. Cardiovascular System ......................... 189 � Symptoms and Signs 190

� Dyspnoea 190 � Angina Pectoris 191 � Palpitation 192 � Syncope 192 � Cyanosis 193 � Arterial Pulse 194 � Blood Pressure 198

� Examination of Neck Veins 201 � Jugular Venous Pressure 201 � Jugular Venous Pulse 202

� General Examination 204 � External Features of Cardiac Disease 204 � Eyes in Cardiology 204 � Inspection 205 � Palpation 205 � Percussion 208 � Auscultation 208 � Heart Sounds 209 � Heart Murmurs 213 � Dynamic Auscultation 217

� Electrocardiogram 218 � Electrical Axis 218 � Left Atrial Enlargement 219 � Right Atrial Enlargement 219 � Left Ventricular Hypertrophy 219 � Right Ventricular Hypertrophy 221 � Biventricular Hypertrophy 222 � Right Bundle Branch Block 222 � Left Bundle Branch Block 222 � Hemiblocks (Fascicular Blocks) 223 � Bi-fascicular Block 223 � Tri-fascicular Block 223 � ECG in Coronary Artery Disease 224 � ECG in Electrolyte Imbalance 226 � ECG Changes with Drug Intoxication 228 � ECG in Acute Pulmonary Embolism 229 � ECG Features of COPD 229 � ECG Features of Hypothermia 229 � ECG in Various Arrhythmias 229

� Congenital Heart Diseases 239 � Classification of Congenital Heart Diseases 239 � Cardiac Malposition 240 � Cardiac Abnormalities with Various Genetic

Disorders 243 � Maternal Disease causing CHD 243 � Atrial Septal Defect 244 � Ventricular Septal Defect 245 � Patent Ductus Arteriosus 247 � Eisenmenger Syndrome 248

� Tetralogy of Fallot 249 � Pulmonary Stenosis 252 � Congenital Aortic Stenosis 253 � Coarctation of the Aorta 254 � Anomalous Pulmonary Venous Connection 256 � Ebstein’s Anomaly 257 � Complete Transposition of the Great Vessels

(D-Transposition) 258 � Congenitally Corrected Transposition of the Great

Vessels 259 � Truncus Arteriosus 259 � Tricuspid Atresia 260 � Congenital Complete Heart Block 260 � Idiopathic Dilatation of the Pulmonary Artery 261 � Congenital Abnormalities of the Coronary

Arteries 261 � Rheumatic Fever 262

� Valvular Heart Disease 264 � Mitral Stenosis (MS) 264 � Mitral Regurgitation (MR) 268 � Mitral Valve Prolapse Syndrome (MVPS) 270 � Aortic Stenosis (AS) 271 � Aortic Regurgitation (AR) 273 � Tricuspid Stenosis (TS) 275 � Tricuspid Regurgitation (TR) 277 � Pulmonary Stenosis (PS) 277 � Pulmonary Regurgitation (PR) 277 � Infective Endocarditis (IE) 278

� Cardiac Failure 281 � Aetiology 282 � Pathophysiology 282 � Classification of Cardiac Failure High Output and Low

Output Failure 282 � Treatment of Cardiac Failure 284

� Systemic Hypertension 290 � Recommendations of the Eighth Joint National

Committee (JNC 8) 290 � Strategies in the usage of Antihypertensive Drugs 291 � Causes of Isolated Systolic Hypertension 291 � Factors Influencing Prognosis 292 � Non-drug Therapy 293 � Drug Therapy 293 � Special Considerations in Antihypertensive

Therapy 298 � Acute Coronary Syndrome (ACS) 300

� Unstable Angina 300 � Myocardial Infarction (MI) 304

� Incidence 304 � Risk Factors 304 � Symptoms 305 � Signs 305

� Myocarditis 312 � Giant Cell Myocarditis 313

� Cardiomyopathies 313 � Dilated (Congestive) Cardiomyopathy 313 � Tako Tsubo Cardiomyopathy 314 � Arrhythmogenic Right Ventricular Dysplasia

(ARVD) 314 � Restrictive (Obliterative) Cardiomyopathy 314 � Hypertrophic Obstructive Cardiomyopathy 315 � Primary Cardiomyopathies 317 � Secondary Cardiomyopathies 317 � Peripartum Cardiomyopathy (PPCM) 317

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� Pericarditis 318 � Aetiologic Classification 318

� Cardiac Tamponade 320 � Causes 320

� Cardiac Arrest 320 � Causes 320 � Cardiopulmonary Resuscitation (Basic Life

Support) 321 � Cardioversion (DC Shock) 322

� Cardiac Surgery 323 � Cardiac Transplantation 323

� Contraindications to Cardiac Transplantation 323

5. Respiratory System ............................... 325 � Anatomical Landmarks 326 � Bronchopulmonary Segments 326

� Borders of the Lung 326 � Pleural Border 326

� Pulmonary Circulation 327 � Systemic Circulation (Bronchial Circulation) 327 � Symptoms and Signs 327

� Cough 327 � Sputum 327 � Haemoptysis 328 � Dyspnoea 329 � Chest Pain 330

� General Examination 330 � Clubbing 330

� Examination of the Neck 332 � Scalene Lymph Node 332 � Significant Node 332 � Lymphatic Drainage of

the Lung and Pleura 332 � Presence of Veins over the Chest Wall 333

� External Manifestations of Respiratory Diseases 333 � Examination of the Respiratory System 333

� Inspection of Upper Respiratory Tract 333 � Inspection of Lower Respiratory Tract 333 � Position of Trachea 334 � Position of Apex Beat 334 � Symmetry of Chest 334 � Chest Deformities 334 � Spinal Deformity 335 � Movement of the Chest 335

� Palpation 337 � Tracheal Tug-Oliver’s Sign 337 � Inspiratory Tracheal Descent 337 � Confirmation of Apical Impulse 337 � Measurement of the Chest Expansion 338 � Assessing Symmetry of Chest Expansion 338 � Assessment of Anterior Thoracic Movement 338 � Assessment of Posterior Thoracic Movement 338 � Tenderness over the Chest Wall 339 � Detection of Subcutaneous Emphysema 339 � Tactile Fremitus 339 � Friction Fremitus 339 � Vocal Fremitus 339

� Percussion of the Lung Fields 339 � General Principles 339 � Areas of Percussion 340

� Auscultation 342 � General Principles of Auscultation 342 � Auscultatory Areas 342

� Technique of Auscultation 342 � Importance of Auscultation 342 � Breath Sounds 342 � Added Sounds 343 � Voice Sounds 344 � Miscellaneous Sounds 344 � Other Features of Clinical Significance 345 � Others 345

� Cavity 346 � Thick-walled Cavity 346 � Thin-walled Cavity 346

� Fibrosis 347 � Types of Fibrosis 347

� Investigations 347 � Sputum Examination 347 � Lung Function Tests 347 � Bed Side Lung Function Tests 347 � Spirometry 347 � Lung Volume Estimation 348 � Peak Expiratory Flow Rate 349

� Chest X-ray 349 � Causes of Bilateral Hilar Enlargement 349 � Causes of Unilateral Hilar Enlargement 349 � Unilateral Hypertransradiant Hemithorax 349 � Hemithorax Opacity 349 � Widespread Alveolar Opacities 350 � Honeycomb Lung (Air Containing Cysts 0.5–2.0 cm

in Diameter) 350 � Miliary Mottling (0.5–2 mm Opacities) 350 � Solitary Pulmonary Nodule 350 � Multiple Medium Sized Pulmonary Nodules

(5–10 mm) 351 � Lung Cavities 351 � Unilateral Elevated Hemidiaphragm 351 � Bilateral Elevated Hemidiaphragm 351

� CT Scan 352 � Ultrasound Scan 352 � MRI Scan 352 � Gas Diffusion Capacity 352

� Arterial Blood Gas Analysis 352 � Ventilation-Perfusion Imaging 352 � Pulmonary Angiography 352 � Bronchoscopy 352 � Pleural Aspiration and Percutaneous

Pleural Biopsy 353 � Oxygen Therapy 353

� Respiratory Diseases 353 � Classification of Respiratory Diseases 353 � Bronchial Asthma 353 � Obstructive Sleep Apnoea-Hypopnoea Syndrome

(OSAHS) 358 � Chronic Obstructive Pulmonary Disease (COPD) 360 � Bronchiectasis 363 � Cystic Fibrosis 366 � Tuberculosis 368 � Pneumonia 374 � Lung Abscess 377 � Pleural Effusion 378 � Pneumothorax 383 � Interstitial Lung Disease 384 � Bronchogenic Carcinoma 385 � Mediastinal Mass 387 � Acute Respiratory Distress Syndrome (ARDS) 389

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� Pulmonary Hypertension 392 � Cor Pulmonale 395 � Pulmonary Thromboembolism 396

� Lung Transplantation 399 � Indications 399 � Types 399 � Prognosis 399

6. Abdomen ............................................... 401 � Clinical Examination 402

� Signs and Symptoms 402 � General Examination 404 � Signs of Liver Cell Failure 404 � Regions of Abdomen 405 � Inspection 405 � Palpation 408 � Percussion 411 � Auscultation 413 � Causes of Hepatomegaly 414 � Causes of Painful Hepatomegaly 414 � Causes of Pulsatile Liver 414 � Causes of Splenomegaly 415 � Causes of Hepatosplenomegaly 415 � Causes of Hepatosplenomegaly +

Lymphadenopathy 415 � Gastrointestinal System 415

� Dysphagia 415 � Achalasia Cardia 418 � Gastro-oesophageal Reflux Disease 418 � Peptic Ulcer Disease 418 � Zollinger-Ellison Syndrome 422 � Endoscopy 422 � Gastrointestinal Bleeding 422 � Diarrhoea 424 � Malabsorption 426 � Tuberculosis of Abdomen 427 � Inflammatory Bowel Disease 429 � Irritable Bowel Syndrome 432 � Ischaemic Colitis 433 � Carcinoid Tumours 433 � Gastric Ulcer and Malignancy 434

� Hepatology and Pancreas 435 � Hepatic Segments 435 � Liver Function Tests 435 � Jaundice 437 � Congenital Jaundice 438 � Familial Defects in Hepatic

Excretory Function 440 � HIV and the Liver 441 � Pregnancy and the Liver 441 � Viral Hepatitis 441 � Chronic Hepatitis 444 � Prevention of Hepatitis 447 � Autoimmune Hepatitis 447 � Polycystic Liver Disease 448 � Liver Abscess 448 � Amoebic Abscess 449 � Steatosis 449 � Nonalcoholic Fatty Liver Disease 449 � Cirrhosis of Liver 450 � Variceal Bleeding 455 � Ascites 457 � Fulminant Hepatic Failure 459 � Hepatic Coma (Hepatic Encephalopathy) 460

� Hepatorenal Syndrome 461 � Hepatocellular Carcinoma (Hepatoma) 462

� Metabolic Liver Disease 463 � Wilson’s Disease 463 � Haemochromatosis 465 � Reye Syndrome (Fatty Liver with

Encephalopathy) 466 � Budd-Chiari Syndrome 466 � Acute Pancreatitis 467 � Chronic Pancreatitis 470 � Tropical Pancreatitis 471

� Liver Transplantation 471 � Cadaver Donor Selection 471 � Indications 471 � Contraindications 472 � Immunosuppression 472 � Live Donor Transplantation 472 � Auxiliary Liver Transplantation 472 � Split Liver Transplantation 472 � Bioartificial Liver 473 � Success Rate 473 � Molecular Adsorbent Recirculating System

(MARS) 473

7. Haematology ......................................... 475 � Haematopoiesis and Haematopoietic Growth

Factors 476 � Cell Divisions 476 � Haematopoiesis 476 � Normal Haematopoiesis 476 � Antigen Designation—Cellular Distribution 477 � Haematopoietic Stem Cells 477 � Haematopoietic Stem Cell Differentiation 477 � Nature of the Marrow Stem Cell 478 � Stem Cell Diseases 478 � Therapeutic Application of Stem Cells 478 � Haematopoietic Growth Factors 478 � Major Growth Factors 478

� Normal Reference Values in Haematology 480 � Absolute Reticulocyte Count 480 � Reticulocyte Index 481 � Peripheral Film Morphology 481 � WBC Count 482 � Erythrocyte Sedimentation Rate 482 � Automated Full Blood Analysis 482

� Anaemia 482 � WHO Definition 482 � Practical Classification of Anaemia 482 � Classification of Anaemia (Based on Reticulocyte

Index) 483 � Symptoms and Signs 483 � Iron Deficiency Anaemia 483 � Megaloblastic Anaemia 486 � Anaemia of Chronic Disease (ACD) (Sideropenic

Anaemia, Simple Anaemia) 489 � Haemolytic Anaemia 490 � Hereditary Spherocytosis (HS) 491 � Sickle Cell Disease 492 � Thalassaemia 494 � Pancytopenia 495 � Aplastic Anaemia 495

� Blood Transfusion 497 � Indications 497 � Manipulation of Blood Products 497

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� Disorders of the White Cells 498 � Neutrophils 498 � Lymphocytes 498 � Eosinophils 499 � Monocytes 499 � Basophils 500

� Myeloproliferative Disorders 500 � WHO Classification of Myeloid Leukemia 500 � Polycythaemia Vera 500 � Essential Thrombocythaemia (Primary

Thrombocytosis) 502 � Primary Myelosclerosis (Myelofibrosis) 503 � Myelophthisic Anaemia 503

� Haematological Malignancies 504 � Lymphoid Malignancies 504 � Leukaemias 504 � Myelodysplastic and Preleukaemic Syndromes

(MDS and PLS) 514 � Lymphomas 515

� Plasma Cell Dyscrasias 519 � Plasma Cell Disorders 519

� An Approach to Bleeding Disorders 522 � History 522 � Examination 522 � Bleeding Disorders 524 � Immune Thrombocytopenic Purpura (ITP) 524 � Thrombotic Thrombocytopenic Purpura (TTP) 525 � Haemolytic Uraemic Syndrome (HUS) 526 � HIT—Heparin-induced Thrombocytopenia (White Clot

Syndrome) 526 � Disorder due to Deficiency of Clotting Factors 527

� Bone Marrow Transplantation 529 � Indications 529 � Types of Bone Marrow Transplantation 530 � Selection of the Donor 530 � Preparation of the Patient 530 � Marrow Aspiration and Infusion 530 � Bone Marrow Transplantation (BMT) in

Leukaemia 531 � Autologous BMT 531

� Haematopoietic Stem Cell Transplantation 531 � Allogeneic Stem Cell Transplant 531 � Autologous Stem Cell Transplant 531 � Peripheral Blood Stem Cell

Transplantation (PBSCT) 532

8. Nephrology ........................................... 533 � Urine Analysis 534

� Methods of Collection of Urine Specimens 534 � Dipstick Testing 534 � Microscopic Analysis 534 � Haematuria 534 � Urinary Casts 535 � Leucocytes in Urine 536 � Renal Tubular Cells 536 � Crystals 536 � Proteinuria 536 � Reducing Substances in Urine 538 � 24-hour Urine Studies 538 � Blood Tests for Evaluating Glomerular Disorders 539 � Serum and Urine Protein Electrophoresis 539 � Urine Eosinophils 539 � Renal Ultrasonography 539

� IV Urography 539 � Radionuclide Scanning 539 � MRI Imaging and Angiography 539 � Creatinine Clearance (ClCr) 539

� Urinary Tract Infection 539 � Definitions 539 � Risk Factors Associated with Urinary Tract

Infection 540 � Pathogenesis 540 � Symptoms of UTI 540 � Principles of Treatment of UTI 541 � Recommendations for Use and Care of Urinary

Catheters 541 � Urinary Antiseptics 543 � Prophylaxis for UTI 543

� Glomerulopathies 543 � Classification 543 � Classification of Nephritic Syndrome Based on

Complement Levels 543 � HIV-associated Nephropathy 543 � Nephrotic Syndrome 544 � Glomerulonephritis 547 � Alport Syndrome 549 � Fanconi Syndrome 549 � Chronic GN 550 � Tubulointerstitial Disease of Kidney 550 � Acute Interstitial Nephritis 551 � Renal Biopsy—Indications 551 � Contraindications to Renal Biopsy 551 � Chronic Interstitial Nephritis 551 � Polycystic Kidney Disease 551

� Acute Kidney Injury/Acute Renal Failure (ARF) 552 � Causes of ARF 553 � Acute Tubular Necrosis 553 � Renal Tubular Acidosis (RTA) 555

� Chronic Kidney Disease 556 � Chronic Renal Failure (CRF) 556

� Dialysis 560 � Haemodialysis (HD) 560 � Haemofiltration 560 � Intermittent Peritoneal Dialysis 560 � Continuous Ambulatory Peritoneal Dialysis

(CAPD) 560 � Renal Transplantation 561

� Rejection 561 � Immunosuppressive Therapy in Renal

Transplant ation 561 � Fluid and Electrolyte Imbalance 561

� Sodium 561 � Potassium 563

� Acid-Base Balance and its Disorders 564 � Definitions 565 � Hydrogen Ion Homeostasis 565 � Approach to Acid-Base Disorders 567

9. Nervous System .................................... 569 � Higher Functions 570

� Definitions 570 � Examination of Higher Mental Functions 572

� Consciousness 572 � Causes of Coma 572 � Approach to Coma 573 � Appearance and Behaviour 577

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� Emotional State 577 � Orientation 577 � Handedness 577 � General Intelligence 577 � Memory 578 � Perceptions 578 � Visuospatial Functions 578 � Sleep 579 � Speech and Language 583 � Cognitive Scales 588

� Examination of the Cranial Nerves 589 � First Cranial Nerve (Olfactory Nerve) 589 � Second Cranial Nerve (Optic Nerve) 590 � The Oculomotor (Third), Trochlear (Fourth), and

Abducent (Sixth) Cranial Nerves 597 � Fifth Cranial Nerve (Trigeminal Nerve) 605 � Seventh Cranial Nerve (Facial Nerve) 607 � The Eighth Cranial Nerve (Vestibulocochlear Nerve) 611 � The Ninth and Tenth Cranial Nerves (Glossopharyngeal

and Vagus Nerves) 615 � Eleventh Cranial Nerve (Accessory Nerve) 615 � The Twelfth Cranial Nerve (Hypoglossal Nerve) 617

� Spinomotor System 617 � Corticobulbar and Corticospinal (Pyramidal)

System 618 � Extrapyramidal System 619 � Neuromuscular System (Lower Motor Neurons) 620 � Cerebellum 640

� Sensory System 643 � Positive Phenomena 643 � Negative Phenomena 643 � Cutaneous Afferent Innervation 643 � Sensory Pathways 644 � Modalities of Sensation to be Tested 645 � Arrangement of Sensory Fibres 645 � Sensory Dermatomes 645 � Proprioceptive Sensations 647 � Vibration Sense 648 � Muscle Sensitivity 648 � Cortical Sensations 649

� Epilepsy 652 � Classification of Seizures 652 � Precipitating Factors for Epilepsy 652 � Causes 653 � Age-related Causes of Seizures 653 � Status Epilepticus 657 � Epilepsy in Pregnant Women 659 � Psychogenic Seizures 660

� Neurocutaneous Syndromes 660 � Neurofibromatosis 660 � Tuberous Sclerosis 661 � Von Hippel-Lindau Syndrome 661 � Sturge-Weber Syndrome 661 � Ataxia Telangiectasia 661

� Cerebrovascular Disorders 662 � Stroke 662 � Young Stroke 669 � Subclavian Steal Syndrome 673 � Lacunar Infarction 673 � Cortical Venous Thrombosis (Dural Sinus

Thrombosis) 674 � Intracerebral Haemorrhage (ICH) 675 � Subarachnoid Haemorrhage (SAH) 678

� Brain Death 681 � Essential Neurological Signs 681

� Headache 681 � Pain Sensitive Structures 681 � Pain Insensitive Structures 682 � Mechanisms of Production of Headache 682 � Headache Caused by Systemic Illness 682

� Neoplastic Disease of the Central Nervous System 685 � Spinal Cord Tumours (Excluding Secondaries) 685 � Cerebral Tumours 685 � Ring Enhancing Lesion—Differential Diagnosis 687

� Movement Disorders 688 � Classification 688 � Parkinson’s Disease 688 � Parkinsonism Plus Syndromes 691

� Motor Neuron Disease 691 � Genetic Classification 691 � Amyotrophic Lateral Sclerosis 692 � Progressive Muscular Atrophy (Predominant LMN

Involvement) 692 � Progressive Bulbar Palsy 693 � Primary Lateral Sclerosis (Predominant UMN

Involvement) 693 � Pseudobulbar Palsy (UMN Fibres Corticobulbar Tracts)

of Cranial Nerves 693 � Variants of Motor Neuron Disease 693 � Spinal Muscular Atrophy (SMA) 695

� Ataxic Disorders (Cerebellar and Spinocerebellar) 695 � Hereditary Ataxia 695

� Congenital Ataxias 696 � Ataxic Disorders with Known Metabolic or Other

Causes 697 � Ataxic Disorders of Unknown Aetiology of Early

Onset 698 � Ataxic Disorders of Unknown Aetiology of Late

Onset 699 � Multiple Sclerosis 702 � Clinical Features not Suggestive of MS 704 � Features that Differentiate MS from Other

Demyelinating Disorders 704 � Meningitis 706 � Types of CNS TB 706 � Complications of TB Meningitis 708 � Corticosteroids in CNS Tuberculosis 708 � Encephalitis 708 � Slow Virus Disease 709 � Autonomic Nervous System 712 � Horner’s Syndrome 713

� The Spine 713 � Curvature Disorders 713

� Spinal Cord 715 � Vascular Syndromes of Spinal Cord 716 � Spinal Cord Disorders 717 � Traumatic Lesions of the Spinal Cord 718 � Tuberculosis 718 � Syphilis 719 � Epidural Abscess 719

� Epidural Haemorrhage and Haematomyelia 719 � Cervical Spondylosis 720 � Lumbar Canal Stenosis 721 � Paraplegia 723 � Syringomyelia 730

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� Subacute Combined Degeneration (Posterolateral Sclerosis of the Spinal Cord) 731

� Other Causes of Posterolateral Column Syndrome 732

� Craniovertebral Junction (CVJ) Anomalies 732 � Classification 732

� Peripheral Neuropathy 735 � Pathogenesis 735 � Classification of Peripheral Neuropathy 735 � Symptoms 736 � Guillain-Barré Syndrome 738 � Chronic Inflammatory Demyelinating

Polyneuropathy 739 � Hereditary Sensory Motor Neuropathy (Charcot-Marie

Tooth Disease) 740 � Polymyositis 741

� Classification 741 � Muscular Dystrophies 742

� Classification 742 � Mitochondrial Myopathy 744

� Congenital Myopathies 744 � Central Core Disease 744 � Nemaline Myopathy 744 � Centronuclear Myopathy 744 � Myotonia Congenita (Thomson’s Disease) 745 � Paramyotonia Congenita 745 � Myasthenia Gravis 746 � Myasthenic Syndrome (Eaton-Lambert

Syndrome) 748

10. Endocrine and Metabolic Disorders .... 749 � Hypothalamus and Pituitary Gland 750

� Anatomy 750 � Anterior Lobe 750 � Neurohypophysis 750

� Hypopituitarism 750 � Aetiology 750

� Hypersecretory Disorders of Anterior Pituitary 752 � Acromegaly and Gigantism 752 � Hyperprolactinaemia 755 � Pituitary Tumours 756 � Pituitary Hyperplasia 757 � Empty Sella Syndrome 757 � Craniopharyngioma 757

� Disorder of the Neurohypophysis 757 � Diabetes Insipidus 757 � Syndrome of Inappropriate Antidiuretic Hormone

Secretion 760 � Thyroid Disorders 761

� Anatomy and Physiology of Thyroid Gland 761 � Hyperthyroidism 762 � Hypothyroidism 767 � Thyroiditis 770 � Malignant Tumours of the Thyroid 773 � Medullary Carcinoma 774

� Disorders of Parathyroid Gland and Calcium and Phosphorus Metabolism 774

� Anatomy and Physiology 774 � Actions of Parathormone 774 � Actions of Calcitonin 774 � Parathormone Related Peptide (PTHrp) 775 � Causes of Hypercalcaemia 775 � Primary Hyperparathyroidism 776

� Hypercalcaemia in Malignancy 778 � Endocrine Causes of Hyperparathyroidism 778 � Secondary Hyperparathyroidism (Increased PTH and

Calcium may be Normal or Low) 778 � Tertiary Hyperparathyroidism 778 � Hypocalcaemic Disorder 778

� Adrenal Glands 780 � Anatomy and Physiology 780 � Primary Hyperaldosteronism 780 � Secondary Hyperaldosteronism 781 � Cushing’s Syndrome 781 � Adrenal Insufficiency 784 � Adrenal Crisis 787 � Phaeochromocytoma 788 � Sexual Disorders 790

� Diabetes Mellitus (DM) 792 � Aetiologic Classification of Diabetes Mellitus 793 � Risk Factors for Type 2 Diabetes Mellitus (Statistical Risk

Disease) 794 � Diagnosis 795 � Insulin Therapy 795 � Type 2 Diabetes Mellitus 802 � Acute Complications of Diabetes 810 � Long-term Complications of Diabetes 816 � Diabetic Foot 823 � Diabetic Nephropathy (DN) 824 � Pregnancy and Diabetes 825 � Surgery and Diabetes 827 � Hypoglycaemia in Adults 828 � Fed (Reactive) Hypoglycaemias 832

� Hyperlipoproteinaemias 833 � Structure 833 � Classification of Lipoproteins and their

Composition 833 � Osteomalacia 838

� Aetiology 838 � Osteoporosis 839

� Aetiology 839 � Male Osteoporosis 841 � Paget’s Disease 842

11. Connective Tissue Disorders ................ 843 � Arthritis 844

� Approach to Musculoskeletal Pain 844 � Classification 844 � Rheumatoid Arthritis 844 � Drug Therapy 849 � Osteoarthritis (OA) 853 � Spondyloarthropathy 853 � Systemic Lupus Erythematosus (SLE) 857 � Mixed Connective Tissue Disease 861 � Progressive Systemic Sclerosis 862 � Vasculitis Syndromes 865 � Polyarteritis Nodosa 866 � Churg-Strauss Disease (Allergic Angiitis or

Granulomatosis) 868 � Wegener’s Granulomatosis (WG) 868 � Temporal Arteritis (Giant Cell Arteritis, Cranial

Arteritis) 869 � Takayasu’s Arteritis (Aortic Arch Syndrome) 870 � Kawasaki Disease (Mucocutaneous Lymph Node

Syndrome) 870 � Behçet’s Syndrome 871

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� Sjogren’s Syndrome (SS) (Autoimmune Exocrinopathy/Autoimmune Epithelitis) 871

� Antiphospholipid Antibody Syndrome (APS) 872

12. Oncology ............................................... 875 � Basic Concepts 876

� Genes and Cancer 876 � Tumour Suppressor Genes and Familial Cancers 876 � Cell Biology of Cancer 876

� Aetiology of Cancers 878 � Carcinogens 878

� Clinical Features of Cancer 880 � General Features 880 � Specific Clinical Features 881 � Investigations 883 � Diagnosis 884 � Staging 884 � Performance Status 885 � Cancer Screening 885 � Complications 886 � Vaccination of Cancer Patients 886

� Paraneoplastic Syndromes 887 � Endocrine Syndromes 887 � Haematologic Syndromes 888 � Neurologic Syndromes 889

� Oncologic Emergencies 890 � Superior Vena Caval Obstruction 890 � Increased Intracranial Pressure (Brain Metastasis) 891 � Meningeal Carcinomatosis 891 � Intracerebral Leucocytostasis (Ball’s Disease) 891 � Seizures 891 � Spinal Cord Compression 891 � Malignant Effusions 892 � Airway Obstruction 892 � Haemoptysis 892 � Intestinal Obstruction 893 � Urinary Obstruction 893 � Biliary Obstruction 893 � Other Emergencies 893

� Metastatic Cancer of Unknown Primary Site 894 � Biologic Behaviour 894 � Clinical Evaluation 895 � Pathological Evaluation or Biopsy 895

� Principles of Cancer Therapy 896 � Surgery 896 � Radiation Therapy 896 � Chemotherapy 897 � Therapy of Selected Cancers 905

� Symptom Control in Severe Cancer 907 � Pain 907 � Nausea and Vomiting 907 � Pruritus 908 � Hiccup 908 � Breathlessness 908 � Cachexia/Anorexia 908 � Constipation 908 � Complications of Therapy 908 � Late Effects of Cancer Therapy 910

13. Geriatric Medicine ................................ 913 � Ageing 914

� Postulated Mechanisms for Ageing 914 � Some Physiological Effects of Ageing 914

� Characteristics of Disease in Old Age 914 � Giants of Geriatric Medicine 916 � Principles of Management of Geriatric Problems 918 � Drugs Cleared by the Kidney which should be Closely

Monitored in the Elderly 919

14. Substance Abuse ................................... 921 � Alcohol 922

� Risk Factors for Alcoholic Liver Disease 922 � Effect of Alcohol on Liver 922 � Alcohol and Central Nervous System (CNS) 924 � Tobacco Alcohol Amblyopia 925 � Nutritional Deficiency Syndrome 925 � Pregnancy and Alcohol 926 � Gastrointestinal 926 � Haematology 926 � Cardiovascular System 926 � Respiratory System 926 � Genitourinary System 926 � Bone 927 � Endocrine 927 � Skin 927 � Alcohol and Malignancy 927 � Alcohol and Lymphatic System 927 � Alcohol and Drug Interactions 927 � Psychological 927 � Social 927 � Alcoholic Coma 927 � Alcohol Withdrawal 927 � Alcohol Dependence—Drugs Used for

Management 928 � Smoking 928

� Contents of Cigarette Smoke 928 � Pharmacology of Cigarette Smoke 928 � Characteristics of Smokers 929 � Clinical Correlations 929 � Passive Smoking 930 � Smoking and Drugs 930 � Types of Smoking 930 � Cessation Process 931 � Cessation Methods 931

15. Imaging Modalities in Internal Medicine .................................. 933

� X-ray 934 � Chest Film 934 � Plain Abdominal Film 934 � Plain X-ray Skull 938 � X-ray Hands 940

� Contrast Studies 941 � Intravenous Urography Pyelography (IVU or IVP) 941 � Angiography 942

� Radioisotope Scanning 942 � Cardiac Scanning 942 � Brain Scanning with 99mTc 942 � Ventilation/Perfusion Scan (V/Q Scan) 943 � 99mTc Bone Scan 943 � Renal Scan 943 � Adrenal Scan 943 � Hepatobiliary Scan 943 � Thyroid Scan 943 � White Cell Scan 943 � Gallium-67 Scan 944

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� Positron Emission Tomography (PET) 944 � Single Photon Emission Computed Tomography

(SPECT) 944 � Ultrasound 944

� Abdominal Scan 944 � Echocardiography 945

� Thyroid Scan 947 � Orbit and Eye 947 � Large Veins and Arteries 947 � Special Techniques 947

� Computed Tomography (CT) Scan 947 � CT Brain 947 � CT Chest 948

� CT Angiography 948 � Benefits 950 � Risks 951 � CT Coronary Angiography 951 � CT—Abdomen 951

� Magnetic Resonance Imaging (MRI) 953 � Advantages of MRI 954 � Diffusion-weighted MRI 954 � Disadvantages of MRI 955

16. Procedures ............................................ 957 � Pleural Aspiration 958

� Indications for Pleural Aspiration 958 � Indications for Therapeutic Aspiration 958 � Site of Aspiration 958 � Pleural Aspiration Needle 958 � Procedure 958

� Pleural Biopsy 958 � Lumbar Puncture 959

� Indications 959 � Contraindications 959 � Lumbar Puncture Needle 959 � Procedure 959

� Queckenstedt’s Test 960 � Procedure 960 � Cisternal Puncture 960

� Pericardiocentesis 960 � Indications 960 � Needle 960 � Procedure 960 � Aftercare 961

� Ascitic Fluid Aspiration (Paracentesis) 961 � Indications 961 � Procedure 961 � Aftercare 962

� Bone Marrow Aspiration 962 � Indications 962 � Contraindication 962 � Needles 962 � Procedure 962

� Trephine Biopsy 963 � Liver Biopsy 963

� Indications 963

� Contraindications 963 � Liver Biopsy Needles 963 � Procedure 963 � Aftercare 964

� Kidney Biopsy 964 � Contraindications 964 � Procedure 965 � Aftercare and Complications 965

� Setting up a Drip 965 � Indications 965 � Precautions 966 � Procedure 966

� Administration of Intravenous Cytotoxics 966 � Procedure 966 � Contraindications for Cytotoxic Therapy 967 � Problems 967

� Percutaneous Central Venous Cannulation 967 � Procedure 967 � Maintenance of Central Venous Cannulation 969

� Passing a Nasogastric Tube 969 � Procedure 969 � Problems 969 � Aftercare and Complications 969

� Urethral Catheterisation 970 � Indications 970 � Contraindications 970 � Choice of Catheters 970 � Procedure 970 � Problems 971

� Arterial Puncture 971 � Contraindications 971 � Site of Puncture 971 � Procedure 971

� Tracheostomy 971 � Indications 971 � Types 971 � Tracheostomy Tubes 972 � Procedure 972 � Postoperative Care 972 � Removal of Tube 972

� Endotracheal Intubation 972 � Types 972 � Procedure 973

Laboratory Reference Values............... 975 � Serum Biochemistry 975 � Serum Enzymes 975 � Haematologic Values 976 � Urine 976 � Stool 976 � Sweat 976 � Hormones 976

� Cerebrospinal Fluid 977

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Nutrition

2CHAPTER

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Balanced nutrition is essential to maintain health and to prevent diseases. We eat intermittently but the energy needs are continuous. Neurophysiologic mechanisms control appe tite and eating behaviour. Energy needs of the body during feeding are met by the nutrients absorbed from gastrointestinal tract and at other times, body’s needs are met by the release of energy from stores. The excess amino acids, fatty acids and glucose are stored as proteins, triglycerides and glycogen. The above process is under the control of insulin.

Nutrition plays a major role in causing certain systemic disorders: Coronary heart disease, diabetes mellitus, hypertension (excess lipids, obesity, sodium intake), renal stones, gall-stones, dental caries, and carcinomas of stomach, liver and large bowel. Either excess or poor nutrition can cause disease and diseases can cause malnutrition.

CLASSIFICATION OF NUTRIENTS

1. Water2. Macro-nutrients

�— Carbohydrates�� Energy yielding

�� Monosaccharides (glucose, fructose, ribose)�� Disaccharides (lactose, maltose, sucrose)�� Polysaccharides (starch)

�� Non-energy yielding �� Dietary fibres

�— Fats�— Proteins

3. Micro-nutrients�— Organic micro-nutrients

� Vitamins (not synthesised in the body)�— Inorganic micro-nutrients

�� Electrolytes (sodium, potassium, chlorine)�� Minerals (calcium, phosphorus, iron,

mag ne sium)�� Trace elements (zinc, copper, iodine, sele-

nium, chromium and manganese).

Water

Water accounts for 60 to 65% of the body weight (75% at birth and 50% in old age). Water is distributed between intra cellular (40%) and extracellular (Plasma and interstitial fluid 20%) compartments. Daily water intake for an average adult will vary between 1 and 3 litres depending on the climate.

Macro-nutrients

Carbohydrates—Energy Yielding CarbohydratesAn average adult consumes 55 to 65% of calories as carbo hydrates and they form the major source of energy. 200 gm of carbohydrate is required/day. 1 gm of carbohydrate yields 4 kilocalories (1 kcal = 4.184 kilo joules). Ketosis is likely to occur when the intake is less than 100 gm/day.

Source of Carbohydrates

�� Available as sugars—mono and disaccharides Intrinsic sugars—fruits and milk (good for health) Extrinsic sugars—cane sugar and beet-root sugar

(dental caries)�� Available as polysaccharides—starch, glycogen

Starch is available in cereals (wheat, rice, maize, etc.), roots (Potatoes and Cassava), plantains and legumes.

Glycaemic Index

Two hours plasma curve after 50 gm of carbohydrate in a given food divided by a curve of 50 gm glucose in water. Glycaemic index is high for glucose, bread, and potatoes and low for legumes and whole grain cereals. Carbo-hydrates with low glycaemic index are preferable for diabetic patients.

Non-energy Yielding CarbohydratesDietary Fibre

It is the natural packing of plant foods and not digested by human enzymes. They are of two types:

1. Water Soluble Fibres

Oat bran, beans, pectin and guar gum. They act in upper GIT and induce early satiety, flatten glucose tolerance curve and decrease serum cholesterol.

2. Water Insoluble Fibres

Wheat bran—hemicellulose of wheat because of increased water holding capacity increases the bulk of stool and prevents constipation, diverticulosis and cancer colon. Flatus formation is common with fibre diet.

Daily requirement is 15 to 20 gm/day.

FatsAn average adult consumes 30 to 40% of calories as fats. 1 gm of fat yields 9 kcal of energy. It is the cause for obesity in sedentary people.

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There are three types of fats.�� Saturated fats: Ghee, palmitic acid, myristic acids—

they increase plasma LDL and total cholesterol. They predispose to CAD.

�� Monounsaturated fatty acids: Oleic acid�� Polyunsaturated fatty acids: Linoleic acid in plant

seed oils and its derivatives—gamma linolenic acid, arachidonic acids are the essential fatty acids. They are precursors of prostaglandins, eicosanoids and they form part of the lipid membrane in all cells.

The omega 3 series of polyunsaturated fatty acids occur in fish oil. By antagonising thromboxane A-2, they inhibit thrombosis. Their use is advocated to prevent hyper-lipidaemia and CAD and to reduce triglycerides.

Stage I Diet

It is advocated to prevent hyperlipidaemia and CAD. It consists of 10% of each type of fats with daily cholesterol less than 300 mg/day.

Stage II Diet

It is advocated in hyperlipidaemia when stage I diet fails to achieve the goal. It consists of 7% of each type of fat with daily intake of cholesterol less than 200 mg.

Proteins

Proteins form the basic building units of tissue. They play the major role in the formation of enzymes and hormones and also in the transport mechanisms. Unlike carbohydrates and fats, no proteins are stored in the body. The amino acids in excess proteins are trans aminated and the non-nitrogenous portion is stored as glycogen or fat. Protein requirements are highest during growth spurts—infancy and adolescence. (Protein requirement during these stages—1.5 to 2 gm/kg/day). There are 20 different amino acids of which 9 amino acids are essential—tryptophan, threonine, histidine, leucine, isoleucine, lysine, methionine + cysteine, phenylalanine + tyrosine and valine. They are essential for the synthesis of different proteins in the body. Proteins of animal origin—eggs, milk, meat—have higher biological value than the proteins of vegetable origin. An average adult requires 10 to 15% of total calories as proteins.

It is equivalent to 1 gm/kg body weight.

Recommended Daily Protein Intake

Clinical condition Protein requirement (g/Kg)

Normal 0.8

Illness/Injury (Metabolic stress) 1.0–1.5

Acute renal failure 0.8–1.0

Haemodialysis 1.2–1.4

Peritoneal dialysis 1.3–1.5

Daily Energy Requirements

Energy requirements depend on—age, sex, body weight, lactation, climate, (lower calories for tropical climate and higher calories for colder climate).

Types of work Males/kcals/d Females/kcals/d

Rest 2000 1500

Light 2500 2000

Moderate 3000 2250

Heavy 3500 2500

Growing children, pregnant and lactating mother need more calories. Brain uses glucose at the rate 5 gm/hour (Preference for ketones when ketone levels are high).

Balanced Diet

Balanced diet contains carbohydrates, protein, fat, mineral, vitamins and trace elements in adequate quantum and proportion in order to maintain good health.

CLASSIFICATION OF NUTRITIONAL

DISORDERS

�� Under-nutrition: �— Quantitative deficiency

�� In children—marasmus�� In adults—various forms of starvation, anorexia

nervosa, bulimia, etc.�� Malnutrition:

�— Qualitative deficiency�� Protein deficiency—PCM or PEM �� Vitamin D—rickets �� Vitamin C—scurvy, etc.

�� Excess nutrition: �— Quantitative—obesity

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�� Excess nutrition:�— Qualitative–

�� Excess cholesterol—hyperlipidaemia�� Excess vitamins—hypervitaminosis A, D, etc.

�� Effect of toxins in food: Migraine, urticaria, coeliac disease, and lathyrism.

Pathological Causes of

Nutritional Disorders

�� Defective intake: It can be due to:

�— Poor economic status�— Loss of appetite—excess coffee, tea, alcohol,

smoking Systemic disorders—renal failure, liver cell failure Psychiatric disorders—depression, anorexia nervosa�— Persistent vomiting—organic obstruction, bulimia�— Food faddism�— Prolonged parenteral therapy.

�� Defective digestion and absorption:�— Hypo or achlorhydria�— Various types of malabsorption syndromes

(steatorrhoea, GJ)�— Prolonged use of antimicrobials.

�� Defective utilisation:�— End organ failure—cardiac failure, hepatic failure,

renal failure�— Severe systemic infections�— Malignancy of various organs.

�� Excessive loss of nutrients: Protein losing enteropathy, nephrotic syndrome, enteric fistulas.

�� Altered metabolism:�— Hyperthyroidism, diabetes mellitus, etc.�— Trauma, prolonged fever, malignancy, burns, and

surgery. �� Increased requirements:

�— Pregnancy and lactation�— Growth—infancy, childhood, adolescence.

Effects of Malnutrition

�� Reduced inflammatory response (cellular and humoral) to infection

�� Inability to cough due to muscle wasting, leading to pneumonia and bronchopneumonia

�� Impaired wound healing�� Reduced haemopoiesis

�� Prolonged drug metabolism�� Altered mental function�� Inadequate water intake—dehydration�� Bedsores and ulcers on pressure points.

Protein Energy Malnutrition

It may be primary due to inadequate intake of protein (famine), or secondary due to defective intake, or digestion, or absorption, or altered metabolism and/or increased demand. The commonly associated illnesses with secondary protein energy malnutrition (PEM) are AIDS, CRF, inflammatory bowel disease, intestinal mal absorp tion, and malignancy.

PEM in Young ChildrenThere are two types of malnutrition: (i) Marasmus, (ii) Kwashiorkor and a combined form—marasmic-kwashiorkor.

Marasmus

Body weight is reduced below 60% of the WHO standard. Early weaning from breastfeeding and poor diet low in energy, protein and essential nutrients are the causes. Poor hygiene leading to gastroenteritis and further malnutrition.

Clinical Features

�� Child is wasted, with bone and skin with no sub-cutaneous fat and poor muscle mass (Fig. 2.1).

�� Gaseous distension of abdomen with diarrhoea can occur.

�� In contrast to kwashiorkor, there is no oedema, skin or hair changes. There is no anorexia.

Kwashiorkor

It is almost a pure form of protein malnutrition, occurring in the second year of life in a child weaned from breastfeeding on to a starchy diet with low protein. Secondary infection like-malaria, AGE, measles, etc. (increased protein requirement) further precipitate protein malnutrition.

Clinical Features (Fig. 2.2)

�� The child is apathetic, irritable and drowsy. �� Fairly intact subcutaneous fat and pitting oedema.�� The child is stunted and puberty is delayed.

Skin changes (Fig. 2.3): Maximal around napkin area—sym metrical–pigmented and thickened-Flaky paint mosaic like appearance with fissuring (Crazy pavement appearance). It is also seen over the areas of pressure and trauma.

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Nutrition 55

and increased energy losses. Depletion of vitamins and minerals can also occur.

Starvation induced undernutrition can be:�� Mild undernutrition: 80% of the standard weight or

BMI 20 to 18.�� Moderate undernutrition: 70% of the standard weight

or BMI 18 to 16.�� Severe undernutrition: Less than 70% of the standard

weight or BMI less than 16.

Clinical Features

�� Loss of weight and weakness�� Craving for food and intolerance to cold�� Nocturia and amenorrhoea�� Loss of libido and impotence�� Lax, dry skin with loss of turgor�� Loss of hair with thinning�� Muscle wasting and loss of subcutaneous fat�� Oedema with normal albumin level�� Subnormal temperature—bradycardia—hypotension�� Distended abdomen with diarrhoea�� Depression, introversion and loss of initiative�� Depressed tendon jerks and secondary infections.

Infections Associated with PEM�� Streptococcal and staphylococcal skin infections�� Gastroenteritis and gram-negative septicaemia�� Pulmonary tuberculosis, pneumonia and broncho-

pneumonia�� Helminthic infestations�� Viral infections like measles, herpes simplex.

Systemic Disorders in PEMPEM impairs the function of all organs.

Gastrointestinal Tract

Atrophy of intestinal villi—reduced quantity and quality of gastric, pancreatic and bile secretions, leading to malabsorp tion.

Cardiovascular System

Atrophy and patchy necrosis, reduced myocardial mass and involvement of conduction system. Small heart with reduction in stroke volume and cardiac output.

Respiratory System

Atrophy of intercostal muscles and other muscles of respiration including diaphragm.

Fig. 2.3 Skin changes kwashiorkor

Fig. 2.2 Kwashiorkor—generalised oedema

Fig. 2.1 Marasmus

Hair changes: The hair becomes thin, sparse, brownish and lusterless. They may fall-off and can easily be pulled. Partial correction leading to alternate bands of pigmentation and de-pigmentation of the hair.

Pathology

Acute protein depletion affecting liver, pancreas, and gut. Liver cannot synthesise albumin due to depletion of amino acids leading to hypoproteinaemia and oedema. There may be associated deficiency of vitamins and minerals. PEM can be mild or moderate or severe.

PEM in AdultsThe primary form is more of undernutrition. It may be due to anorexia, insufficient food, increased demand

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Decreased ventilatory derive—impaired lung function and vital capacity.

Endocrine System

Insulin, triiodothyronine and thyroxine levels are decreased and levels of growth hormone and cortisol are increased. These changes lead to increased catabolism of muscle protein and enhancement of lipolysis and gluconeo-genesis. Primary gonadal dysfunction is common in adults.

Immunologic Functions

Impaired cell-mediated and humoral immunity. �� T and B lymphocyte functions impaired.�� Total lymphocyte count is decreased and there is

delayed skin hypersensitivity (tuberculin test, etc.).�� Wound healing is delayed.

Investigations

�� Measure body weight, mid-arm circumference, and skin-fold thickness and calculate BMI.

�� Blood: Hb, TC, DC, ESR—leucopenia, anaemia, throm-bocytopenia, decreased Hb level and normal ESR.

�� Serum proteins: Low albumin.�� Serum T3 and T4: Levels are decreased.�� Cortisol and growth hormone: Levels are increased. �� X-ray chest.�� ECG.

Assessment of PEM Status

Tests Moderate PEM Severe PEMPercentage of pre-morbid wt 80–90 Less than 80

Percentage of ideal body wt 60–80 Less than 60

Hand grip strength 60–70 Less than 60

Serum albumin gm/l 20–30 Less than 20

Serum transferrin gm/l 1–1.5 Less than 1

Total lymphocyte/ml 800–1200 Less than 800

Delayed skin hypersensitivity

Test (Tuberculin, etc.)

5 mm Less than 5 mm

Differentiation between Marasmus and Kwashiorkor

Marasmus KwashiorkorNutrient Deficiency of proteins

and calories and other

nutrients

Protein deficiency

Age Below 1 year 1–4 years

Weight Less than 60% 60–80%

Appearance Emaciated Less degree of emaciation

Weaning Early and abrupt Late gradual

Oedema Absent Pitting oedema

Skin and hair

changes

Mild Marked

Anorexia

and apathy

Absent Present

Liver Not enlarged Fatty enlarged liver

Management

Good nursing, frequent feeding and prevention of intercurrent infections. Protein intake has to be increased—instead of normal 1 gm/kg—increase it to 2 to 3 gm/kg/day. Supplement vitamins and minerals. Correct hypothermia, hypogly-caemia, hypokalae mia, dehydration, acidosis and electro lyte imbalance. The National Institute of Nutrition, Hyderabad recom mends an energy–protein rich mixture to treat PEM at home.

Whole wheat — 40 gm Bengal gram — 16 gm Groundnut — 10 gm Jaggery — 20 gm

It supplies 330 calories and 11 gm of protein. This can be mixed with milk or water and can be taken 5 to 6 times/day.

Prevention of PEM (UNICEF): Mnemonic—GOBI FFF

G for growth monitoring

O for oral re-hydration NaCl (3.5 gm) + NaHCO3 (2.5 gm) + KCl (1.5 gm) +

glucose (20 gm) or sucrose (40 gm/L) of water.

B for breastfeeding

I for immunisation Against measles, diphtheria, mumps, tetanus,

tuberculosis, and polio.

F—Supplementary feeding

F—Female child care

F—Family welfare.

VITAMINS

Vitamins are organic compounds in food, which are required in small amounts and are not synthesised in human body. They are classified into fat-soluble vitamins (A, D, E, and K) and water soluble vitamins (B and C). Fat-soluble vitamins are stored in liver and deficiency manifests only when stores are depleted. Excess intake of fat-soluble vitamins causes hyper vitaminosis. Water-soluble vitamins are not stored and excreted in urine.

Vitamin A (Retinol)

Vitamin A is found in foods of animal origin and the pro-vitamin beta-carotene is present in plant tissues. It is

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necessary for clear vision in dim-light and maintains the integrity of epithelial tissues.

Sources:Liver, egg, chicken, butter, cereals, green leafy vegetables, carrots, yellow pumpkin, papaya, tomatoes, fish liver oils.

Average daily requirement: 1000 μg.A dose of 1 μg is equivalent to 3 international units of

vitamin A and 6 μg of carotenoids.Normal serum level is 20 μg/dl. Less than 10 μg/dl

indicates deficiency.

Functions of Vitamin AVision

It provides the molecular basis for visual excitation in rods and cones. It induces differentiation of epithelial cells. In deficiency states mucous-secreting cells are replaced by keratin producing cells. It is required for growth and reproduction. Anti-infective vitamin—increased incidence of respiratory and gastrointestinal infections in deficient state. It has antioxidant activity. Vitamin A is required for reproduction, growth and maintenance of life.

Skin-mucous membrane: Hyperkeratinisation of the epi-thelium lining the follicles results in follicular hyperkeratosis or phrenoderma. An associated EFA deficiency aggravates this condition.

Causes of Deficiency

�� Intestinal malabsorption and malnutrition�� Defect in storage—liver disease�� Enhanced renal excretion—proteinuria�� Prolonged periods of total parenteral nutrition�� Increased demand—pregnancy.

Clinical Features

�� Night blindness: It is the earliest sign.�� Xerophthalmia: Dry thickened, pigmented bulbar

conjunctiva with oval or triangular glistening white spots—Bitot’s spots (Fig. 2.4).

Cornea become cloudy, soft (keratomalacia) and undergoes ulceration and necrosis. It leads to perforation, prolapse of the iris and endophthalmitis and ultimately blindness.

WHO Classification of Vitamin A Deficiency

�� Primary X-1A — Conjunctival xerosis X-1B — Conjunctival xerosis + Bitot’s spots X-2 — Corneal xerosis

X-3A — Corneal ulcer—< 1/3 of cornea involved X-3B — Corneal ulcer—>1/3 of cornea

involved—keratomalacia.�� Secondary

X-N — Night blindness X-F — Xerophthalmic fundus X-S — Corneal scars

Treatment

�� Night blindness and xerosis—30,000 IU of vitamin A daily for one week.

�� Corneal damage—medical emergency—20,000 IU/kg/day of vitamin A for 5 days.

�� Risk of vitamin A deficiency—2,00,000 IU orally for 2 days (Especially WHO develop measles).

PreventionIn malnourished children—two oral doses of 2,00,000 IU or 1,00,000 IU/IM twice in a year.

Excess CarotenesCarotenaemia�� It is due to excessive intake of vitamin A precursors in

foods, mainly carrots. �� It causes yellow colouration of skin including palms

and soles.�� In contrast to jaundice, the sclerae are not involved

and remains white.�� The serum is also yellow in colour.�� These changes disappear on omission of carrots.

Vitamin A ToxicityHypervitaminosis A is due to excessive intake of fish liver, polar bear liver or therapeutic over dose.

Fig. 2.4 Bitot’s spot

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Acute ToxicityHeadache, nausea, vomiting, abdominal pains, dizziness, papilloedema, bulging fontanelle in infants and followed by generalised desquamation of skin in a few days.

Chronic Toxicity�� Ingestion of 25,000 IU or more/day for a long time. �� Bone and joint pains, hyperostoses, hair loss, dry and

fissured lips.�� Benign intracranial hypertension, pruritus, weight loss

and hepatosplenomegaly.�� Recovery is usual, both in acute and chronic toxicity on

discontinuing vitamin A.

Vitamin D

Vitamin D is essential for the metabolism of calcium and phosphorus and for the formation of bone. It enhances the absorption of above minerals from the gut, their mobilisation from bone and re-absorption of phosphorus and calcium from the kidneys. Vitamin D is not a vitamin but a hormone. Dietary supplements are not required when adequately exposed to sunlight.

There are two forms of vitamin D:1. Vitamin D2 (calciferol or ergocalciferol) is obtained by

ultraviolet irradiation of plant origin ergosterol.2. Vitamin D3—cholecalciferol is formed from 7-dehydro-

cholesterol present in the epidermal cells of skin by exposure to sunlight.

Dietary Sources

Fish liver oil, eggs, liver, milk, cheese, butter.

Daily Requirements

Pre-school children — 10 microgram (400 IU/day)Children and adults — 5 microgram (200 IU/day)Pregnancy and lactation — 10 microgram (400 IU/day)

Metabolism (Fig. 2.5)Vitamin D2 and D3 are identical in potency and generally referred as vitamins D.

First hydroxylation takes place in liver and 25-hydroxy vitamin D is formed. It is further hydroxylated in kidney into the most active 1,25 dihydroxycholecalciferol {1,25(DH2)D3} or (calcitriol).

Vitamin D3 Status – 25 (OH) D Level (ng/ml)Normal — >30Insufficiency — 21 to 29

Deficiency — 10 to 20Severe deficiency — < 10

Predisposing Factors for Vitamin D Deficiency

�� People with darker skin�� Maximum hours spent in indoors�� People who cover their entire body�� Thinner skin in old age�� Breastfed infants without vitamin D supplementation�� Pregnant women�� People who are obese.

Causes of Vitamin D Deficiency

�� Intestinal malabsorption—pancreatic insufficiency, coeliac disease, biliary tract obstruction.

�� Kidney disease—impaired production of D3.�� Lack of exposure to sunlight.�� Defective metabolism—either due to renal disorders

or drugs like phenytoin, rifampin.

In children it causes rickets and in adults osteo malacia.

Fig. 2.5 Vitamin D metabolism

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Vitamin D—Role in Systemic DisordersEmerging evidence in the past decade has implicated the potential role of vitamin D in various chronic systemic disorders and bodily functions. Vitamin D deficiency is now considered as a risk factor for cardiovascular disease and metabolic syndrome. Vitamin D deficiency plays a role in the following systemic disorders:�� Autoimmune disorders

�— Rheumatoid arthritis�— Inflammatory bowel disorders�— Type 1 diabetes mellitus�— Systemic lupus erythematosis�— Psoriasis

�� Cardiovascular disorders�— Hypertension�— Coronary artery disease�— Cardiomyopathy�— Congestive heart failure�— Sudden cardiac death�— Coronary calcifications�— Peripheral vascular disease

�� Endocrine and metabolism�— Primary hyperparathyroidism�— Type 1 and 2 diabetes mellitus�— Metabolic syndrome

�� Haematopoietic system�— Anaemia�— Leukaemia

�� Infections�— Childhood asthma�— Recurrent upper respiratory infections�— Tuberculosis

�� Musculoskeletal system�— Rickets and osteomalacia�— Osteoporosis and fractures�— Myopathy�— Fibromyalgia

�� Malignancies�— Breast cancer�— Colon cancer�— Ovarian cancer�— Pancreatic cancer�— Prostate cancer

�� Nervous system�— Multiple sclerosis�— Stroke�— Headache

�� Psychiatric disorders�— Depression�— Mood swings

�� Reproductive system�— Dysmenorrhoea

�— PCOD�— Gestational diabetes

Rickets�� Age incidence 1 to 2 years.�� Delayed milestones except speech, irritability, and

prominent abdomen.

Skeletal Manifestations

�� In less than 1 year—craniotabes-abnormal softening of the skull in the occipital region.

�� In children 1 year or more—‘hot cross bun’ appearance due to frontal and parietal bossing.

�� Larger head and delayed closure of anterior fontanelle.�� Delayed dentition with defective enamel.�� Permanent teeth also show defective hypoplastic enamel

with grooving, and pitting with high risk of caries.

Rachitic rosary: Costochondral junctions are enlarged and beaded.

Pigeon chest: Forward projection of sternum.

Harrison’s sulcus: A horizontal groove along the attachment of diaphragm due to contraction pulling the softened bony cage.

Spine: Kyphosis, scoliosis and lordosis.

Limbs: Widened epiphyses of wrists and ankles (Fig. 2.6) bending of long bones femur, tibia, fibula—resulting in knock knees and coxa vara (Fig. 2.7).

General manifestations: Hepatosplenomegaly, tetany, con-vul sions, and frequent respiratory infections.

Hypophosphataemic rickets: Either familial inherited or acquired renal tubular defects leading to defective renal tubular re-absorption of phosphates.

Fig. 2.6 Rickets—widening of wrist joints

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�� Defective matrix synthesis:� Fibrogenesis imperfecta�� Miscellaneous:

Aluminium bone disease Parenteral alimentation

Management

�� Vitamin D deficiency can be corrected by daily intake of 2,000 IU or 60,000 IU once a month. Rapid correction can be done by giving 60,000 IU weekly once for 4 to 6 weeks followed by once a month schedule.

�� Twenty-five to fifty microgram (1000–2000 IU) of vitamin D, along with 500 to 1000 mg of calcium daily are sufficient for both rickets and osteomalacia.

�� Duration of therapy: 6 to 12 weeks may be required or 40,000 IU/IM injections once in two weeks. Three to four injections are required.

�� Recurrence can be prevented by daily intake of 400 IU of vitamin D.

�� If osteomalacia is due to renal disease give alfacalcidol 1 μg/day PO and adjust the dose according to plasma calcium. Monitor plasma calcium. Otherwise treatment of osteomalacia is similar to rickets.

Hypervitaminosis DIt causes hypercalcaemia. It is due to excess vitamin D intake.

Clinical Features

�� Constipation, nausea, vomiting, drowsiness and renal damage.

�� Metastatic calcification—kidneys, lungs, gastric mucosa, soft tissues and arteries.

Prevention

Serum calcium level should be monitored regularly for patients on high dose vitamin D therapy. When serum calcium raises above 10.5 mg/dl, vitamin D should be stopped.

Vitamin E

Alpha tocopherol is the most potent of the 8 naturally occurring substances with vitamin E activity. It is one of the main fat-soluble antioxidants in addition to carotenoids. It prevents oxidation of PUFA—polyunsaturated fatty acids in cell membranes by free radicals. It reduces atherogenesis.

Daily requirement: For men — 10 mg For women — 5 mg

Fig. 2.7 Rickets—bow legs

Investigations

�� Hypophosphataemia �� Hypocalcaemia�� Raised serum alkaline phosphatase�� Radiological features: Widened (flaring) and irregular

(fraying) of distal ends of long bones with cupping. Decreased density and increased trabecula tions of shafts with subperiosteal osteoid formation giving a double contour appearance to the shaft.

OsteomalaciaAdults manifest with defective mineralisation of newly formed matrix. It manifests with bone pain, severe malaise, proximal muscle weakness, difficulty in climbing stairs, getting up from sitting position and waddling gait. Bone and muscular tenderness on pressure and associated pseudo-fractures and fractures of ribs and pelvis are common.

Radiological Features

Pseudo-fractures: Linear zones of decalcification along the course of major arteries (Milkman’s line and Looser’s zones).

Common Sites

Pubic rami, ischium, neck of the femur, ribs and vertebrae “Cod-fish”—vertebrae: Compression causing widening of intervertebral space produces biconcave vertebrae. Vitamin D resistant rickets is due to defective tubular clearance of phosphates.

Osteomalacia with normal calcium, phosphate, and vitamin D:�� Primary non-mineralisation defect:

� Hereditary—fluoride therapy

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Sources:

Vegetable oils, whole-grain cereals, nuts.

Deficiency:It occurs in intestinal malabsorption. Deficiency result in decreased proprioceptive and vibra tory sensation due to posterior column degene ration, areflexia, gaze paraesis, and gait disturbance. It produces haemolytic anaemia and retrolental fibroplasia in premature infants.

Vitamin E excess:Headache, malaise, and hypertension. In premature infants parenteral vitamin E therapy may result in ascites, hepatosplenomegaly, cholestatic jaundice, azotaemia and thrombocytopenia. In patients on oral anticoagulants vitamin E excess can antagonize vitamin K and prolong prothrombin time and potentiate the action of anticoagulants.

Vitamin K

Vitamin K1 is present in green leafy vegetables and vitamin K2, which is synthesised by intestinal bacteria. It is a coagulant vitamin required for synthesis of unusual amino acid—gamma carboxyglutamic acid (Gla) which is essential for the production of four coagulation factors—II, VII, IX, and X.

Daily requirement: �� 80 microgram/day.

Sources:�� Leafy vegetables and liver.

Deficiency:�� Newborn—haemorrhagic disease of the newborn is

due to:�— Defective transfer of vitamin K from mother to

foetus �— Lack of bacteria in the intestine�— Breast milk contain little of the vitamin

�� Obstructive jaundice—defective absorption of vitamin K due to lack of bile. It may result in bleeding during biliary surgery.

�� Anticoagulant therapy—warfarin, etc. act by antagonising vitamin K.

�� Prolonged antibiotic therapy—by eliminating bacteria from the gut—reduced synthesis of vitamin K.

Management

When prothrombin time is prolonged, give vitamin K 10 mg IM for 3 to 5 days till prothrombin time is normal.

Vitamin K Excess

It blocks the effects of oral anticoagulants. In pregnant women, it can cause jaundice in the newborn.

Thiamine (Vitamin B1)

Thiamine functions as the co-enzyme, thiamine pyrophosphate. It plays a major role in Kreb’s cycle. In the absence of vitamin B1, cells cannot metabolise glucose aerobically. Brain is totally dependent on glucose for energy and so nervous system is affected early in thiamine deficiency. The total body content is 30 mg. It is essential for the metabolism of carbohydrates and in its absence pyruvic and lactic acids accumulate, which produces vaso-dilatation and increase in cardiac output.

Daily requirement: 1 to 2 mg/day.

Dietary sources:Outer layer of cereals like rice, wheat, millets, pulses, nuts, yeast.

Causes of deficiency: �� Defective absorption—alcoholism, folate deficiency,

chronic malnutrition�� Excess loss—diarrhoea, diuretic therapy, peritoneal

dialysis, haemodialysis�� Increased requirement—pregnancy, lactation,

thyrotoxi cosis, prolonged fever.

Benfothiamine (S-benzoil thiamine-o-monophosphate): It is a fat-soluble derivative of thiamine. It prevents the formation of advanced glycation end products in diabetes mellitus. It is particularly useful in diabetic neuropathy and retinopathy.

Clinical Features

It causes either cardiac involvement (Wet beriberi) or nervous system involvement (Dry beriberi).

Cardiac ManifestationsThey are due to:�� High output state due to peripheral vasodilatation �� Oedema due to retention of sodium and water�� Biventricular failure

Prominent signs are—raised jugular venous pulse, tachycardia, cyanosis, cardiomegaly, hepatomegaly, oedema, etc.

Neurological Manifestations�� Peripheral neuropathy—distal, symmetrical impair-

ment of sensory, motor, and reflex function.

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�� Wernicke’s encephalopathy—(cerebral beriberi)—global confusion, vomiting, nystagmus, ophthalmo-plegia, fever, ataxia, coma.

�� Korsakoff’s syndrome—impaired ability to learn, retro grade amnesia, confabulation (amnestic—confabulatory syndrome).

Investigations

Low blood thiamine level, raised pyruvate and lactate levels. Low blood or erythrocyte transketolase activity, which increases by more than 15% after administration of thiamine, is diagnostic.

Management

of beriberi and the recovery is slow in neurological beriberi.

certain degree of memory impairment may persist.

oral therapy.

Riboflavin (Vitamin B2)

It is in the form of co-enzymes and takes part in various oxidation-reduction reactions.

Daily requirement: 1 to 2 mg/day.

Dietary sources: Milk, cheese, butter, liver, kidney, meat, whole cereals, legumes and green leafy vegetables.

Causes of deficiency: Malnutrition, malabsorption and dialysis.

Clinical Manifestations

Sore throat, glossitis, aphthous ulcers (Fig. 2.8), angular stomatitis, cheilosis, seborrhoeic dermatitis, normochromic anaemia.

Management

Tablet riboflavin 5 mg tid.

Niacin (Nicotinic Acid and Nicotinamide)

Limited amount is synthesised in the body from the essential amino acid—tryptophan (60 mg of tryptophan yields 1 mg of nicotinamide).

Daily requirement: 15 to 20 mg/day.

Dietary sources: Whole cereals, pulses, nuts, meat, fish, liver, kidney yeast and coffee.

Causes of deficiency:�� Chronic small intestinal disorders�� Alcoholics�� Food habit—high intake of maize or millet (sorghum,

jowar).

PellagraChronic wasting disease with signs of dementia, diarrhoea and dermatitis.

Skin changes: Erythema, vesiculation, cracking, exudation, crusting with ulceration.

Dermatitis is bilateral, symmetrical, in the form of hyper-keratosis, hyperpigmentation, and desquamation mostly on exposed parts of the body to sunlight and is due to photosensitivity (Dermatitis in the neck—Casal’s collar).

Diarrhoea: Widespread involvement of mucosa—glossitis, stomatitis, achlorhydria.

Dementia: Fatigue, insomnia, apathy, confusion, disorien-tation, hallucination, loss of memory and organic psychosis.

Other signs: Tachycardia, cyanosis, cardiomegaly, hepato-megaly, oedema, etc.

Management

Nicotinamide 100 mg tid PO or 100 mg IM/IV for 2 weeks followed by niacin 10 mg od.

Niacin excessLarge doses once used for treatment of hypercholes-terolaemia, etc. induce release of histamine resulting in severe flushing, pruritus, gastrointestinal disturbances, and hepatic toxicity with cholestatic jaundice, acanthosis nigricans. Asthma can be precipitated.

Fig. 2.8 Aphthous ulcer

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Pyridoxine (Vitamin B6)

It is available in three forms—Pyridoxine, pyridoxal phos-phates, and pyridoxamine. It acts as a co-factor for many enzymes. Required for protein and fat metabo lism. It is required for synthesis of haem precursors and for synthesis of GABA in brain—gamma amino butyric acid—a neuronal inhibitor and prevents convulsions.

Daily requirement: 1 to 2 mg/day.

Dietary sources: Whole grain cereals, vegetables, yeast, meat, liver.

Deficiency: Deficiency is rare. Many drugs act as pyridoxine antagonists and cause deficiency, e.g. INH, cycloserine, penicillamine, hydralazine, oral contraceptive pills.

Clinical Features

�� Glossitis, angular stomatitis, cheilosis, and neuropathy.�� In certain genetic disorders, pyridoxine metabolism is

abnormal, and in those infants pyridoxine deficiency causes convulsions and later sideroblastic anaemia.

Management

Many drug-induced antagonism of pyridoxine can be prevented by 30 mg of pyridoxine supplementation/day. However, high doses 100 mg/day is required in penicil-lamine therapy.

Pyridoxine excessPerioral numbness, peripheral neuropathy, ataxia, clumsiness of hands and feet.

Pyridoxine can antagonise levodopa, phenytoin, and barbiturates.

Biotin

It functions as a co-factor in carboxylases.

Daily requirement: 50 to 100 microgram/day.

Causes of deficiency: �� Prolonged consumption raw egg whites—which binds

biotin and prevents absorption from the gut.�� Prolonged parenteral nutrition.�� Biotinidase deficiency.

Clinical Features

Perioral dermatitis, conjunctivitis, alopecia, ataxia, para-es thesias, seborrhoeic dermatitis, developmental delay.

Management

Biotin 100 microgram/day.

Vitamin B12 and Folate

The metabolism of these vitamins is dealt with in detail in the chapter on haematology.

Vitamin B12

Salient Features:�� Daily requirement is 1 microgram�� It is present only in animal products �� Milk is the only source for vegetarians �� Vegans are at risk of deficiency �� The store of B12 in liver can last for five years�� Vitamin B12 deficiency causes megaloblastic anaemia

and neurological degeneration �� It is required for the integrity of myelin �� Deficiency causes uneven demyelination �� It causes peripheral neuropathy, sub-acute combined

degeneration of the spinal cord, optic atrophy and cerebral manifestations in the form of dementia.

Folic AcidFolic acid is very essential to prevent neural tube defects, which develops during the first four weeks after conception. Imperfect closure of neural tube results in three major congenital defects:�� Spina bifida�� Anencephaly�� Encephalocele.

Folate is directly involved in DNA and RNA synthesis. Women planning pregnancy and throughout pregnancy should consume diet rich in folate. Folic acid 5 mg/day should be given during pregnancy.

Vitamin C (Ascorbic Acid)

Most animals can synthesise ascorbic acid from glucose but humans cannot. Only L-ascorbic acid and dehydro-ascorbic acid have anti-scorbutic activity. The D-ascorbic acid and other analogues have no anti-scorbutic activity.

Functions of Vitamin C By hydroxylation of proline to hydroxyproline:�� It promotes collagen formation. It aids in the

production of supporting tissues of mesenchyma such as osteoid, dentine, collagen, and intercellular cement substance of capillaries.

�� It enhances the iron absorption from the intestine.

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�� Vitamin C helps in the synthesis of bile acids from cholesterol.

�� It enhances the functions of reticuloendothelial system.

Phagocytic action of leucocytes and the formation of antibodies have been improved by vitamin C.

�� It helps in hydroxylation of tryptophan to serotonin.�� By stimulating the growth of intestinal flora, it augments

the synthesis of vitamin B complex.�� Formation of nitroso-amines (powerful carcinogens)

is prevented. As an antioxidant it reduces the risk for cancer

formation. Antioxidant vitamins are vitamins A, C and E.�� Vitamin C is concentrated in adrenal cortex

(160 mg/100 gm tissue) and in the lens of the eyes. It has some role in adrenal steroidogenesis and in preventing cataract formation.

�� It reduces folic acid to tetrahydrofolic acid (THFA). In combination with folic acid, it helps in the maturation of RBC.

Sources

Indian gooseberry (700 mg/100 g), guava (300 mg/100 g) green leafy vegetables, potatoes, meat (kidney, liver) fish, fruits. Partial loss of vitamin C in fruits and vegetables when stored unprocessed. It is partially preserved by processing (boiling, freezing, steaming, pressure-cooking and canning).

Requirement

50 to 100 mg/day.

Causes of Deficiency

�� Poverty, famine, malnutrition, elderly living alone �� Increased demand—pregnancy, lactation, thyro-

toxicosis�� Decreased absorption—malabsorption syndromes.

Clinical Features

Vitamin C deficiency results in scurvy.

ScurvyThis disease is caused by vitamin C deficiency. It occurs in areas of urban poverty.

Infancy and Childhood

�� Painful swelling over the long bones due to sub-periosteal haemorrhage

�� Gingivitis, swollen, spongy gums if teeth have erupted

�� Easy bleeding from scurvy buds, i.e. papillae in between the teeth

�� Finally, the teeth are lost�� Lassitude, anorexia and pain in limbs�� Epiphyseal separation is common�� Inward sinking of sternum with sharp elevation of

costochondral junctions (scorbutic rosary)�� Purpura and ecchymoses may appear in the skin�� Painful joint swelling due to haemorrhage into the

joint cavities.

Common sites of haemorrhages: Retrobulbar, subarachnoid and intracerebral. Normocytic normochromic anaemia is common.

Adults

�� Total body content of vitamin C is 1.5 gm�� Gum involvement occurs only in people with teeth�� Swollen, spongy gums with increased friability,

bleeding, secondary infection and loosening of the teeth

�� Perifollicular hyperkeratosis with haemorrhage�� Haemorrhage into the muscles of the arms and legs�� Haemorrhage into the joints and in the nail-beds�� Petechial haemorrhages in the viscera and ecchymoses�� Delayed wound healing�� Other clinical manifestations are icterus, oedema,

fever, convulsions and hypotension�� Vitamin C deficiency causes normochromic

normocytic anaemia�� Associated nutritional folate deficiency can result in

macrocytic/megaloblastic anaemia.

Investigations

�� Low ascorbic acid level in platelets and plasma.�� Elevated serum bilirubin value.�� Abnormal capillary fragility.�� Classical X-ray changes of bones.

Management

�� Scurvy is potentially fatal.�� 100 mg of vitamin C tid until a total dose of 4 gm has

been administered and then followed by 100 mg od.

Hypervitaminosis C Large doses interfere with the absorption of B12 resulting in anaemia. Large amount of iron may be absorbed leading to haemochromatosis. Excess amount of oxalate crystals is passed in the urine, which may precipitate oxalate stone formation.

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INORGANIC NUTRIENTS

Fourteen minerals are essential for life. They are sodium, potassium, calcium, magnesium, iron, iodine, copper, zinc, cobalt, phosphorus, sulphur, chromium, selenium, and fluorine.

Sodium

It is the main electrolyte in extracellular fluid (Plasma and interstitial fluid). Along with chlorides, it determines osmo lality of extracellular fluid.

SourceCommon salt—sodium chloride, small amounts in milk and vegetables.

Requirement1 to 2 gm/day but average intake by Indians—10 to 12 gm/day.

HyponatraemiaSerum sodium level less than 130 mEq/L.

Causes

�� Extrarenal losses: Vomiting, diarrhoea, sweating, pancreatitis, burns, peritonitis

�� Renal losses: Diuretics, salt losing nephropathy, ARF, CRF, renal injury, renal tubular acidosis

�� Dilutional hyponatraemia: Increase in total body water content nephrosis, cirrhosis and CCF

�� SIADH–Syndrome of inappropriate ADH secretion�� Addison’s disease�� Hypothyroidism.

Clinical Features

Confusion, anorexia, lethargy, cramps dehydration. When the sodium level falls below 120 mEq/L—seizures, hemiparesis, and coma.

Management

�� Hypovolemic patients—normal saline�� Dilutional hyponatraemia—water restriction�� SIADH—Water restriction + demeclocycline.�� Serum level below 120 mEq/L—hypertonic saline

infusion.

HypernatraemiaWhen the serum sodium is elevated above 150 mEq/L.

Causes

�� Primary aldosteronism�� Cushing’s syndrome�� Congenital adrenal hyperplasia�� Hypertonic saline infusion�� Hypertonic haemodialysis/peritoneal dialysis �� Haemoconcentration due to excessive fluid loss—

vomiting, diarrhoea, diuretics, etc.�� Diabetes insipidus (central type and nephrogenic).

Clinical Features

Altered mental status, twitching, seizures and coma. When serum level exceeds 160 mEq/L—it dehydrates cerebral vessels and causes ruptures of cerebral vessels—leading to permanent neurological deficit.

Management

�� Hypovolemic hypernatremia (haemoconcentration)�— Normal saline followed by 0.45% saline

�� Hypervolemic hypernatraemia �— Loop diuretics, hypotonic fluids or dialysis

�� Central diabetes insipidus �— Desmopressin

PotassiumPotassium is mainly present in the intracellular compartment. Oral intake and renal excretion maintain the extracellular potassium balance. Acidosis shifts potassium out of cells and alkalosis shifts potassium into the cell. It maintains the intracellular osmotic pressure. Extra-cel lular potassium level plays a major role in skeletal and cardiac muscle activities. Normal serum value: 3.5 to 4.5 mEq/L.

SourcesBanana, orange, lime, apple, pineapple, almond, beans, dates, yam, potato, and tender coconut water. It maintains the intracellular osmotic pressure. Extracellular potassium level plays a major role in skeletal and cardiac muscle activities.

Daily Requirement 3 to 4 gm/day.

HypokalaemiaWhen the serum level falls below 3.5 mEq/L.

Causes

�� GIT—loss due to vomiting diarrhoea, fistulae

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�� Renal—diuretics, metabolic alkalosis, renal tubular acidosis

�� Primary aldosteronism�� Cushing’s syndrome�� Drugs—insulin and glucocorticoids.

Clinical Features

�� Muscle weakness, ileus, and polyuria.�� ECG—‘U’ wave, prolonged Q-T interval, flat or inverted.�� T-wave and premature beats. Hypokalaemia

predisposes to digitalis toxicity. �� In severe hypokalaemia—flaccid paralysis and

cardiac arrest.

Management

�� Potassium rich dietary supplements or potassium chloride in liquid form.

�� In severe hypokalaemia—KCl 20 to 40 mEq/hour IV with cardiac monitoring.

HyperkalaemiaWhen the serum level exceeds 5.5 mEq/L.

Causes

�� Acute and chronic renal failure�� Addison’s disease�� Hypoaldosteronism�� Shift of potassium from tissues acidosis, crush injuries,

internal bleeding, blood transfusion.�� Drugs—potassium sparing diuretics, ACE inhibitors �� Pseudohyperkalaemia—due to increased cell

destruction—haemolysis, thrombocytosis, and leukocytosis.

Clinical Features

�� Conduction disturbances and various arrhythmias.�� ECG—Peaked T-waves in pre-cordial leads-absent

P-wave and wide QRS.

Management

�� Furosemide 40 mg IV�� Calcium gluconate 10 ml 10% IV�� Insulin + glucose to shift the potassium into the cells.�� NaHCO3 to correct acidosis.�� Haemodialysis.

Calcium

The total calcium in human body is 1 to 1.5 kg, of which 99% is in bone and 1% is in extracellular fluid. The major quantum of calcium is used in the formation of bone

and teeth. Calcium is essential for transmission of nerve impulses and muscle contraction. It serves as intra cellular messenger of different hormones. It takes part in blood coagulation.

Normal serum value: 9 to 11 mg/dl.

Daily Requirements �� Adults—500 mg�� Pregnant and lactating women—1200 mg�� Post-menopausal women—1200 to 1500 mg.

Dietary SourcesMilk, cheese, yogurt, eggs, fish eaten with bone, almonds and peanuts, leafy vegetables and dried fruits. 100 cc of milk contains 100 mg of calcium. Calcium is absorbed actively from jejunum and passively from ileum. Acidic pH, vitamin D, and presence of protein enhances absorption of calcium. Eighty per cent of calcium taken is lost in stool and some amount is also lost in the urine, and that is the cause for negative balance when the calcium is consumed in small quantum. The metabolism of calcium is intimately related to vitamin D, parathyroid hormone and calcitonin.

Phosphorus

Total body phosphorus is about 1 gm. Similar to calcium 80% is present in bone and teeth and 10% in muscles. It plays a major role in the formation of bone, teeth, production of energy phosphate compounds such as ATP, CTP, GTP, DNA and RNA synthesis and acts as buffer system in blood.

Normal serum level: 3 to 4 mg/dl.

Dietary SourcesMilk, cheese, eggs, cereals, meat. Eighty per cent of ingested phosphorus is absorbed in jejunum and the serum level is controlled by the excretory function of the kidney. Fifteen per cent is excreted in the urine and the remaining 85% are reabsorbed in the proximal tubule and so its level goes up in renal failure. Antacid aluminium hydroxide prevents its absorption.

HypophosphataemiaIt occurs in hyperparathyroidism and rickets. It causes muscle weakness, anorexia, malaise and bone pains. Dietary deficiency is rare and hyper phosphataemia does not produce any adverse symptoms. However, in the presence of hypercalcaemia, hyperphos phataemia can lead to metastatic calcification.

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Iron

The total body iron content is 4 gm. Sixty per cent of that is present in haemoglobin. It is used in erythropoiesis.

Normal serum level: 80 to 120 μgm/dl.

Daily Requirement �� For males—1 mg�� For females—2 mg�� Pregnant/lactating women—3 mg.�� Only 10% of consumed iron are absorbed in

duodenum and upper jejunum and so, the daily intake has to be 10, 20 and 30 mg respectively for the above categories.

Dietary Sources Green leafy vegetables, fruits, onions, cereals, pulses, jaggery, grapes, dates, animal foods like meat, liver, fish, kidney, egg yolk. Food rich in vitamin C enhances absorption of iron.

Iron DeficiencyIron deficiency causes microcytic hypochromic anaemia.

Iron ExcessSiderosis denotes excessive deposition of iron in various sites like liver, pancreas leading to cirrhosis, DM.

Iodine

It is required for the synthesis of thyroid hormones. Total body iodine content is 30 mg and 80% of it is in thyroid.

Normal serum level: 5 to 10 μgm/dl.

Daily Requirement150 to 200 μgm/day.

Dietary Source Seawater, salt, sea-fish, vegetables and milk. Iodine deficiency is common in mountainous terrains such as Alps and Himalayas—endemic thyroid goitres are common.

PreventionFortification of common salt with potassium iodide. Iodized poppy seed oil 1 to 2 ml IM injection will protect the individual against iodine deficiency for 5 years.

Zinc

It acts as a co-factor for a number of enzymes. It improves appetite, wound healing, and sense of well-being. Zinc deficiency causes thymic atrophy. Insulin in the stored form in beta cells of pancreas contains zinc but not when released.

Normal serum value: 100 μgm/dl.

Daily Requirement5 to 10 mg/day.

Dietary SourcesGrains, beans, nuts, cheese, meat and shellfish. Plasma zinc is lowered in acute myocardial infarction, infections, and malignancies. Patients on prolonged IV alimentation (zinc free) may develop acute zinc deficiency leading to diarrhoea, mental apathy, and eczema around mouth and loss of hair (Fig. 2.9). Chronic zinc deficiency leads to dwarfism and hypo-gonadism and ophthalmoplegia. Secondary zinc deficiency is seen in alcoholism and poorly controlled diabetes mellitus.

Fluorine

It plays a major role in the prevention of dental caries. The safe limit of fluorine is 1 part per million in water (1 PPM).

SourceSoft water contains no fluoride. Hard water contains fluoride and sometimes to the tune of toxic level—10 PPM. Sea-fish and tea when taken frequently can contribute as

Fig. 2.9 Acrodermatitis enteropathica (zinc deficiency)

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much as 3 mg/day. Fluoride level more than 2 PPM can cause loss of appetite, AGE, and loss of weight. Fluoride level more than 5 PPM causes mottling of enamel and discolouration of teeth. Fluoride level more than 10 PPM causes osteo sclerosis, increase in bone density and calcification of ligaments (Fluorosis in certain endemic areas).

Prevention of CariesWhen fluorine level is low, addition of traces of fluoride—1 PPM to the public waters supplies.

Magnesium

Total body magnesium is 20 gm and 75% of it is complexed with calcium in bone.

Normal serum level: 2 to 3 mg/dl.

Daily Requirement300 mg/day.

Sources Cereals, beans, leafy vegetables and fish. It is an activator of many enzymes and deficiency causes neuromuscular irritability, tremors and carpo-pedal spasm. Chronic diarrhoea, chronic alcoholism and cirrhosis cause deficiency. Increased magnesium level causes renal damage.

Manganese

Total body content is 15 mg and maximum quantum is in liver. It is an activator of many enzymes, stimulates bone growth and cholesterol synthesis and also takes part in glucose metabolism.

Vitamins and Trace Minerals – Requirement/day – Deficiency-induced Disorders

Nutrient Intake/day Deficiency-induced disorders EvaluationVitamin A (Retinol) 5000 IU Xerophthalmia, Bitot’s spots, night blindness, keratomalacia, follicular

hyperkeratosis, immune dysfunction, impaired embryonic development

Serum retinol

Vitamin B1

(Thiamine) 1–2 mg Peripheral neuropathy, beriberi, cardiomegaly with or without failure,

fatigue, ophthalmoplegia,wernicke’s encephalopathy

RBC transketolase activity

Vitamin B2

(Riboflavin) 1–2 mg Angular stomatitis, sore tongue and mouth (Magenta tongue),

cheilosis, seborrhoeic dermatitis, eye irritation

RBC glutathione reductase activity

Vitamin B3

(Niacin) 15–20 mg Pellagra (Dermatitis, diarrhoea, dementia), sore mouth and tongue Urinary N-methyl-nicotinamide

Vitamin B5

(Pantothenic acid)

5–10 mg Weakness, fatigue, paraesthesias, tenderness of heels and feet Urinary pantothenic acid

Vitamin B6

(Pyridoxine) 12 mg Cheilosis, glossitis, seborrhoeic dermatitis, peripheral neuropathy,

convulsions, hypochromic anaemia

Plasma pyridoxal phosphate

Vitamin B7

(Biotin) 100–200 μg Alopecia, seborrhoeic dermatitis, myalgia, seizures, hyperaesthesia Plasma biotin

Vitamin B9

(Folic acid) 400 μg Megaloblastic anaemia, glossitis, diarrhoea, increased homocysteine Serum folic acid RBC folic acid

Vitamin B12

(Cobalamin) 5 μg Megaloblastic anaemia, decreased vibratory and position sense, ataxia,

paraesthesias, dementia, diarrhoea

Serum cobalamin, serum

methylmalonic acid

Vitamin C (Ascorbic

acid)

100 mg Gingival inflammation and bleeding, purpura, petechiae, ecchymosis,

scurvy, weakness, depression, joint effusion, poor wound healing

Plasma ascorbic acid,

Leukocyte ascorbic acid

Vitamin D

(Ergocalciferol)

400 IU Rickets-skeletal deformity-rachitic rosary, bowed legs, osteomalacia,

osteoporosis, bone pain, muscle weakness, tetany

Serum 25 hydroxy-vitamin D

Vitamin E

(Alpha tocopherol)

10–15 IU Neuropathy, abnormal clotting, retinopathy, haemolysis, spino-

cerebellar ataxia

Serum tocopherol, Total

lipid-TGL:TC

Vitamin K (Phyloquinone) 80 μg Easy bruising/bleeding Prothrombin time

Chromium 30–200 μg Glucose intolerance, peripheral neuropathy, encephalopathy Serum chromium

Zinc 15 mg Impaired taste and smell, alopecia, dermatitis (acro-orificial lesion)

hypogonadism, delayed sexual maturation, growth retardation, dementia

Plasma zinc

Copper 2 mg Anaemia, neutropenia, osteoporosis, defective keratinisation and

pigmentation of hair

Serum copper

Plasma ceruloplasmin

Manganese 1.5 mg Dementia, dermatitis, hypercholesterolaemia, impaired growth and

skeletal development

Serum manganese

Selenium 100–200 μg Cardiomyopathy, muscle weakness Serum selenium, blood

glutathione—Peroxidase activity

Iodine 150 μg Hypothyroidism, goitre TSH, urine iodine

Iron 10–15 mg Hypochromic microcytic anaemia, impaired congenital development,

pre-mature labor, increased peri-natal and maternal mortality

Serum iron,total iron binding

capacity, serum ferritin

Molybdenum Severe neurological abnormalities

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Nutrition 69

SourceNuts and tea-leaves.

Daily Requirement 5 mg/day.

Copper Total body copper is 100 mg and it is present in muscles, bone, liver, kidney, brain, heart and hair. It is present in many enzymes including cytochrome oxidase and ceruloplasmin.

Normal serum value: Ceruloplasmin 25 to 50 mg/dl and its equivalent amount of copper is 3 to 5 μgm.

Daily Requirement 2 to 3 mg/day.

SourceDairy products, cereals, meat, and nuts. Copper containing ceruloplasmin helps in iron transport and in the formation of haemoglobin. Copper deficiency causes iron deficiency anaemia and low ceruloplasmin causes Wilson’s hepatolenticular degeneration due to copper deposition.

CobaltVitamin B12 contains cobalt. Cobalt stimulates production of erythropoietin.

NickelIt is present in certain enzymes like arginase and carbox-ylases. Nickel content of the hair—male 1 PPM and female 4 PPM. Some chocolate preparations contain nickel.

ChromiumTotal body content of chromium is 6 mg and this level decreases with age. Cooking in stainless steel containers improves the chromium of food. Chromium deficiency causes glucose intolerance. Chro mium improves receptor binding of insulin. Tobacco contains large amount of chromium and the carcinogenic effect of tobacco is linked to chromium. (bronchogenic carcinoma).

SeleniumBy its intracellular antioxidant effect, it protects tissues and cell membrane against peroxidation and because of this property, it is considered to have anticancer activity (? human cancer). Selenium deficiency causes cardiomyopathy, and myopathy.

Selenium excess causes alopecia, abnormal nails, emotional lability, and lassitude and garlic odour to breathe.

Dietary Modifications—Diet Therapy

Types of diet DisordersLow protein Chronic renal failure, nephrotic syn drome,

hepatic encephalopathy

High carbohydrate 70% of kcal—Athletes

Low simple sugar Post-gastrectomy state, lactose into lerance

Low energy Obesity, hypertension

High energy Undernourished

Small feedings Gastroesophageal reflux

Low fat Steatorrhoea, gastroesophageal reflux, acute

hepatic, gallbladder or pancreatic disorders,

colon, prostate and breast cancers

Low fat and low

cholesterol

Hyperlipidaemia and coronary heart disease

High fibre Hyperlipidaemia, diabetes mellitus

Low fibre Crohn’s disease, regional enteritis, ulcera tive

colitis

Low sodium Hypertension, congestive cardiac failure ascites,

chronic renal failure

Low potassium Chronic renal failure, hyper kalaemia

High potassium Diuretic therapy, hypokalaemia

High calcium Osteoporosis

Low phosphorus Renal failure

Low oxalate Renal stones

Gluten free Coeliac disease

OBESITY

As per the state of nutrition, the individuals can be classified as normal, overweight and underweight.

The state of nutrition can be assessed in the following ways:�� Ideal body weight (IBW): IBW = 22.5 × (height in metres)2

Overweight — More than 10% of IBW Underweight — Less than 20% of IBW Obesity — More than 20% of IBW�� Body mass index: BMI = Weight in kg/(height in metres)2

BMI — In males—20 to 25 In females—18 to 23 Overweight — BMI is between 25 and 30 Underweight — For males—BMI below 18 For females—BMI below 16 Obesity — BMI is more than 30 Grading of obesity: Grade I: BMI—25 to 30 (overweight) Grade II: BMI—30 to 40 (obese) Grade III: BMI—more than 40 (gross obesity)�� Skin-fold thickness:

It can be estimated by using special pair of calipers over the triceps, biceps, subscapular and suprailiac region.

Normal triceps skin-fold thickness:

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�� Consumption of energy dense foods—sweets, ice-cream, soft-drinks

�� Alcohol—it provides energy and stimulates appetite.

�� Smoking—energy expenditure is more in smokers and their appetite is lost. Most of the smokers are lean. Giving up smoking induces fall in expenditure and increases food intake.

�� Age Physical activity is decreased with aging.�� Familial and genetic factors

�— They play a major role. �— More than 20 genes and 12 chromosomes have

been implicated in obesity.�� Lipoprotein lipase: This enzyme is synthesised

in adipocytes. It induces obesity by causing deposition of fat calories in adipose tissue.

�� Leptin: This hormone is produced by adipose tissue. It acts at the level of hypothalamus to suppress appetite. Elevated levels of leptin are seen in obesity similar to elevated insulin levels in type 2 diabetes mellitus obese. Exact role of leptin in obesity is not known.

Leptin/leptin receptor: Mutation prevents leptin from delivering satiety signal.

�� Pre-opiomelanocortin: Mutation prevents synthesis of MSH and satiety signal.

�� Ag RP: Overexpression inhibits signal via MC4R.�� Secondary obesity due to endocrine causes

�— Hypothalamic disorders: Froehlich’s syndrome Laurence-Moon-Biedl syndrome—obesity, hypo-

go na dism, over eating, visual impairment due to retinitis pigmentosa, etc.

�— Hypothyroidism: Decreased metabolic rate with obesity.

�— Cushing’s disease: Moon facies with central obesity.�— Insulinoma: Some of them are obese. It is due to

increa sed calorie intake secondary to recurrent hypoglycaemia.

Factors increasing appetite Factors decreasing appetite

arcuate nucleus of hypothalamus—

appetite stimulant and reduces

sympathetic output and energy

expenditure

Leptin gene is in chromosome

7q 31.3. Synthesised in adipose

tissue—decreases appetite and

increases energy expenditure

(MCH)

Melanocyte stimulating

hormone (α-MSH)

Coccaine amphetamine related

transcript (CART)

GLP-1 (Glucagon like peptide 1)

Serotonin

Adult males—12.5 mm Adult females—16.5 mm�� Rough calculation of body weight in an adult (Broca’s

index): Height in inches = weight in kg Height in cm - 100 = desired body weight in kg.�� Waist-hip ratio:

�— Waist-hip ratio is useful to assess the prognosis in a case of obesity.

�— Waist-measurement of narrowest segment between ribcage and iliac crest.

Hip-maximal measurement of the hip over the buttocks:

Waist-hip ratio Type of obesity Prognosis0.8 or less Pear-shaped obesity Good

0.9 or more Apple-shaped obesity Increased morbidity

Apple-shaped obesity is nothing but abdominal obesity, which is associated with hyperlipidaemia, insulin resistance, diabetes mellitus and coronary artery disease.

�� Waist circumference: Waist circumference alone is enough to assess the

prognosis in obesity.

Waist Circumference—Morbidity Risk

Sex Moderate HighMale More than 94 cm (37”) More than 102 cm (40”)

Female More than 80 cm (32”) More than 88 cm (35”)

Types of Obesity

�� Generalised obesity: Uniform deposition of excess fat throughout the body.

�� Android obesity: Excess deposition of fat over the waist.�� Gynoid obesity: Excess deposition of fat over the hips

and thighs.�� Superior or central type of obesity: Excess deposi tion of

fat over the face, neck, and upper part of the trunk and the limbs are thin—Cushing’s syndrome.

Aetiology

�� Excess energy intake: With excess feeding, excess calories are stored in

adipose tissue.�� Decreased energy expenditure:

Physical activity is less in the obese than in the lean.�� Behavioural changes:

�— High fat intake results in obesity. �— High fat diets do not switch-off appetite. �— Little is used for energy expenditure and is mostly

stored.�� Frequent snacks in between standard meals.

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Pathology

In obesity, the adipocytes number and size are increased in middle age resulting in obesity. With excess calorie intake the number and size can increase at any age. However, weight reduction causes reduction in size of adipocytes and the number does not decrease. Fat is deposited throughout the body, around internal organs, omentum, and in the intramuscular spaces. There is expan sion of lean body mass with increased size of kidneys, heart, liver and skeletal muscles. There is fatty infiltration of liver.

DrugsDrugs can cause increase in body weight, e.g. corticoste-roids, tricyclic antidepressants, valproate, sulphonylureas, contra ceptives.

Complications

�� Hyperlipidaemias�� Hypertension�� Diabetes mellitus type 2�� Insulin resistance�� Atherosclerosis�� Coronary artery disease�� Cerebrovascular strokes due to hypertension�� Osteoarthrosis of knees, hip, foot, and spine�� Varicose veins, deep vein thrombosis, pulmonary

embolism�� Gallstones

�� Ventral and hiatal hernias�� Hypoventilation syndrome (Pickwickian synd rome)—

hypercapnia, hypoxia, cyanosis, poly cy thae mia, pul-monary hypertension, chronic cor pulmonale.

�� Infertility, hirsutism�� Pregnancy—neural tube defects, pre-eclampsia,

gesta tional diabetes, pre-term labour, increased perinatal mor tality.

�� Cancers—gallbladder, colon, prostate� In post-menopausal women—breast, ovary, endo -

metrium�� Adrenal function—plasma cortisol levels are increased. �� Psychological—depression�� Skin—abnormal skin folds—fungal and bacterial

infec tions—Striae formation—chafing of skin of the thighs and axillae.

Prognosis

Mortality rate is 25% higher if a person is 25% over weight and 50% higher if the person is 40% overweight.

Sustained 10 kg reduction of weight in obese—Benefits:�� It causes a fall of 10 mm Hg systolic and 20 mm Hg

diastolic blood pressure. �� 30% increase in exercise tolerance.�� 30% reduction in DM related mortality. �� Risk of developing DM is 50% less.�� 50% fall in obesity related cancer deaths.�� 10% increase in HDL cholesterol and 10% fall in total

cholesterol.�� There is also 15 to 20% fall in LDL and triglycerides.

Syndromes of Obesity with Hypogonadism and Mental Retardation

Feature Prader-Willi Laurence-Moon-Biedl Ahlstrom Cohen Carpenter

Inheritance Sporadic Autosomal-recessive Autosomal-recessive Autosomal-recessive Autosomal-recessive

Stature Short Normal/rarely short Normal/rarely short Short/tall Normal

Obesity Generalised Generalised Truncal Truncal Truncal and gluteal

Onset Early 1–2 years Early 1–2 years Early 1–2 years 5 years

Craniofacies Narrow bi-frontal diameter,

almond shaped eyes,

V-shaped mouth, high-

arched palate

No typical features No typical features High nasal bridge, high-

arched palate Open

mouth, short-philtrum

Acrocephaly, flat nasal

bridge, high-arched

palate

Limbs Small hands and feet,

hypotonia

Polydactyly Normal Narrow hands and feet,

hypotonia

Polydactyly,

syndactyly, genu

valgum

Gonads Hypogonadism Hypogonadism Hypogonadism

Not in females

Normal/hypogonadism Hypogonadism

Other features Enamel hypoplasia, nasal

speech, hyperphagia

Dysplastic ears

Delayed puberty

Mentation Retardation Normal Normal Retardation Retardation

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Management

DietModerate reduction in energy intake—500 to 600 calories less than the energy expenditures of the individual. Fat intake must be reduced. Avoid frequent snacks and diets with concentrated sugars. Complex carbohydrates with enough protein with adequate amount of fibre, vitamins and minerals are advised, e.g. for 1000 kcal diet-complex carbohydrate 100 gm, protein 40 to 50 gm, fat 30 gm. The aim of diet restriction is to reduce weight by 1 kg/week.

Exercise Brisk walking 40 metres a day or cycling or swimming or games depending upon the individuals choice.

Energy Expenditure during Exercise

Mild exercise: Sitting 80 kcal/hour Standing 120 kcal/hour.Moderate exercise: Fast walking 3.75 mph—250 kcal/hour Swimming—250 kcal/hour Tennis—350 kcal/hour.Vigorous exercise: Cycling 10 mph—600 kcal/hour Running 10 mph—800 kcal/hour.

Drug therapy Indications: BMI > 30 kg/m2 Or BMI > 27 kg/m2 + obesity related diseases.�� Centrally acting anorexiants:

� Sibutramine was the only FDA approved drug, but withdrawn in 2010 due to increased risk of non-fatal MI and stroke. It reduces calorie intake by acting on ventromedial and lateral hypothalamic regions.

�� Peripherally acting drugs:� Orlistat: It inhibits pancreatic and gastric lipase. Dose: 120 mg tid. Adverse effects: It causes fatty/oily stools, flatus,

faecal urgency and deficiency of fat soluble vitamins. Psyllium mucilloid controls GI side effects. Supplement fat soluble vitamins.

�� Endocannabinoid system:� Rimonobant: It is a cannabinoid receptor 1

antagonist. It is withdrawn in 2009 due to neurologic and psychiatric side effects.

�� Drugs under trial:�— Bupropion (dopamine and norepinephrine reup-

take inhibitor) + Naltrexone (opioid antagonist).�— Bupropion + Zonisamide (Anticonvulsant that

has serotonergic and dopaminergic activity.�— Lorcaserin: It is a 5HT2c receptor antagonist.

Very Low Calorie Diets Total intake of calories less than 800 kcal/day and total starvation diet are advised only under medical supervision.

SurgeryIt is advised only when BMI is more than 40 and failure with strict diet restriction and drug therapy. �� Vertical banded gastroplasty—to reduce the volume

of stomach �� Gastric bypass�� Gastric balloon—reduces the volume of stomach �� Wiring the jaws—allows only fluid diet�� Intestinal bypass—jejunoileal bypass induces

malabsorption.

ANOREXIA NERVOSA AND BULIMIA

Two important eating disorders seen in young females because of fear of becoming fat. The exact aetiology is not known, and most investigators favour psychiatric aetiology. The syndromes can overlap.

Anorexia NervosaWeight loss of 25% or more of original body weight in the absence of organic disease.

Bulimia Recurrent episodes of binge eating with vomiting and to lose weight they use laxatives, diuretics and do vigorous exercise.

Diagnostic Criteria and Clinical Manifestations

Anorexia nervosa BulimiaSex Female Female

Age incidence Below 25 years

Cause of weight loss Restriction of diet Vomiting

Binge eating Uncommon Common

Appearance Weight loss more

than 25% wasted

Fairly normal

Ritualised exercise Usual Rare

Amenorrhoea 100% 50%

CVS: (bradycardia hypotension) Common Uncommon

Skin: (hirsutism carotenaemia, dryness) Common Uncommon

Hypothermia Common Uncommon

Oedema +/– +/–

Complications Hypokalaemia

Cardiac

arrhythmias

Hypokalaemia

Cardiac

arrhythmias

Oesophageal/gastric rupture — Common

Above two eating disorders are diagnosed only on clinical grounds. No specific diagnostic laboratory tests exist.

Management

�� There is no specific treatment.�� The benefits of psychiatric intervention are marginal.

Hospi ta lise the anorexia nervosa patients and treat sympto matically. Ryle’s tube feeding and at times total parenteral nutrition. For bulimia, hospitalisation is not required, except for the management of complications. Advised to consume small quantum of feeds to prevent gastric and oesophageal rupture.

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