Differential Diagnosis and Medical Therapeutics a Treatise on Clinical Medicine

Differential Diagnosis and Medical Therapeutics A Treatise on Clinical Medicine

Third Edition

P Siva Rama Krishna Rao BSc MBBS (Madra) MD (Andhr) FRCP (Glasg) FRSM (London) FICA (NY) FCCP (USA) FIMSA (India) FIAMS (India) FICP (India) Formerly Professor and Head Department of Medicine Andhra Medical College First Physician King George Hospital Visakhapatnam, Andhra Pradesh, India Additional Director in the office ofBrothers Directorate of Medical Education Government of Andhra Pradesh

Forewords iv Rao David R London Jaypee

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Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine First Edition: 2000 Second Edition: 2010 Third Edition: 2015 ISBN 978-93-5152-310-9 Printed at Foreword to the Third Edition

Dr P Siva Rama Krishna Rao is a popular physician, reputed teacher and a physician with a vast experience. I am privileged to be his student when I was pursuing my Postgraduate Course in General Medicine. He has put in an enormous hard work in bringing out the textbook Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine and presently updated it as the 3rd edition with inclusion of topics like dementia and essentials of electrocardiography. He has provided a systematic approach to the common symptoms with the flowcharts to arrive at the final diagnosis. I am sure that this book would be of immense value to the undergraduate and postgraduate students and practitioners of medicine. I am particularly impressed by the flowcharts which depict not only the various causes of the symptom but also the salient features regarding the pathological and clinical aspects of the disease. It makes fluent, interesting and absorbing reading going through the various chapters with slick narration. I immensely suggest that this textbook should be possessed by all the students of medicine both undergraduate and postgraduate as well as practitioners, who find readymade solutions to the various clinical problems they encounter in their daily practice. I feel very happy to write the foreword to this book that is well compiled with a comprehensive and profound knowledge of medicine by my teacher, philosopher and guideBrothers Dr P Siva Rama Krishna Rao. IV Rao MD (General Medicine) Vice Chancellor Dr NTR University of Health Sciences Vijayawada, Andhra Pradesh, India

Jaypee Foreword to the First Edition

It gives me great pleasure to write a foreword to Common Clinical Challenges—A Treatise on Maladies and Remedies. The approach adopted by the author should be of great help to those who are facing difficulty in the management of medical emergencies. The idea of taking symptom complexes and then describing the diagnostic possibilities with guides to the management both of the disease itself and of the symptoms, that it occasions, will be valuable to all who have to deal with problems of this sort. The demand placed on the medical profession is ever-increasing for a variety of reasons: the complexity of medical practice steadily increases as more and more diagnostic and therapeutic possibilities become available, and as populations age, so the incidents of disease increase. Added to these are, on the one hand, ever-increasing consumer demand, while, on the other, governments’ attempt to hold down healthcare costs. All this means that doctors simply have to raise their game. This requires a process of continuing professional development to keep up-to-date and to ensure that professional performance is kept to an acceptable level. Included in this process is continuing medical education that nowadays can be derived from a variety of modalities, including distance learning. However, despite electronic means of communication and the visual display unit (VDU), most people find the printed word still the best way of assimilating new information and Dr P Siva Rama Krishna Rao’s book is an excellent example of this. My hope is that it will be valuable to all who have to deal with the clinical differential diagnosis that he has identified. It should be of particular use to general practitioners, accident and emergency physicians and indeed all those who encounter this aspect of medicine. It is the sort of book that should be presented not only on the shelves at home and in libraries, but also at all the sites whereBrothers emergency medicine is practised.

David R London Registrar Royal College of Physicians of London United Kingdom

Jaypee Preface to the Third Edition

Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine is updated and throughly revised by reviewing every chapter and appendix with exquisite exposition. Therapeutics has been revisited with vigor. Flowcharts continue to highlight the salient features. Efforts persisted to dispense the knowledge effectively, facilitating one to arrive at a diagnosis with ease. Two additional subjects are added: one on “Essentials of Electrocardiography” and another on “Dementia”, making a total of 37 chapters and 5 appendices. The former is made easy for any doctor to opine with confidence and the latter is full of expansive expression. Tremendous effort involving countless hours is behind this endeavour of lucid narration, which will serve as a clinical treasure-house. Understanding Medicine in depth cannot be realised in toto, even after years of study, as it is fathom deep and extensive. That is the reason why no book on medicine is complete, with obvious persisting lacunae existing. These are addressed to wherever possible. Hence, this treatise with abundant assimilable information, arranged in an orderly manner can be entertained, as an alternative textbook and a constant companion for students. Also, it will be a guiding force, for those practicing medicine, who intensely desire to enrich themselves, for gaining exhilarating confidence to deal with any case, towards correct diagnosis and then design the successful strategy, for effective treatment. It is no exaggeration if it is stated that this will be a valuable accompaniment at every stage of professionalism, particularly while crossing the bridge from graduation to internship (Foundation period) enabling the doctors’ clinical acumen to grow freely. Brothers As many as thirty outstanding review comments including four from abroad are incorporated. The book, indeed, will be a boon particularly for the problem-based learners and also for those, who desire to equip with practical knowledge.

P Siva Rama Krishna Rao

Jaypee Preface to the First Edition

This book on Common Clinical Challenges—A Treatise on Maladies and Remedies is an exposition of common medical encounters in day-to-day practice, by an author with varied experience of about five decades, right from the days of clinical student of medicine, house officer, postgraduate student, tutor, assistant professor, professor/head, Department of Medical Institutions. There has been an active involvement in the training programmes for undergraduates and postgraduates and committed patient care, all through these years continuously are rich contributing factors in this endeavour. This manual is a practical clinical guide to diagnosis and principles of treatment of some of the age-old medical problems. The overall emphasis is on clinical access to these problems and the importance of fundamental clinical skills of history-taking and systemic problem-oriented physical examination in search of a correct diagnosis is highlighted. In addition, a sensible order of investigations to be adopted during the diagnostic work-up is detailed, instead of indulging in the endless array of investigations. The pattern followed for each symptom runs through basic fundamental concepts, appended causes, essentials of diseases therein, clinical approach with illustrations wherever necessary and diagnostic flow charts followed by symptomatic as well as specific treatment. The student burdened with his ever-crowded curriculum or the practitioner anxious to keep abreast of the times may find it useful as it is easily readable and assimilable. The guiding principle throughout this endeavour is to inculcate knowledgeable medical practice enabling the growth of the Doctor’s clinical acumen and competence to establish an early diagnosis confidently, after which an effective treatment can be instituted. This is not a textbook of description of diseases to bestowBrothers theoretical knowledge, but an attempt to bridge the gap between theory and practice of medicine and reinforce the ability to apply the knowledge coherently to various clinical situations. As a matter of fact, any book is likely to become out-of-date within a few years as theory-cum-practice of medicine is ever-changing and advancing. In such a live science and art of medicine, new concepts and technical innovations demand voluminous output of information and explanation. Such information has been freely drawn from many related books and, for that matter, my own colleagues in various specialities. The idea of writing such a symptom-oriented-approach book is a real challenge to one who has spent most of his life in the practice of medicine facing ever so many specific problem areas. I hope all the thirty-six symptoms, specially identified in relation to day-to-day practice of general medicine, some of which even poorly understood, are presented with lucidity, in a practical and clinically useful manner, for medical personnel at any stage ranging from an examination performing student to a practitioner, or even a mature physician for that matter. Solid 2,500 hours or so are bestowed to bring out this treatise, fulfilling the desired aim of this book. Suggestions offered to further improve the style and pattern of presentation in subsequent editions will be gracefully acknowledged.Jaypee P Siva Rama Krishna Rao Acknowledgements

I would like to acknowledge my gratitude to the following institutions and individuals for their invaluable assistance: King George Hospital and Andhra Medical College, Visakhapatnam, Andhra Pradesh, India—Department of Cardiology, Department of Endocrinology and Diabetology, Department of Gastroenterology, Department of Nephrology and Department of Neurology. Visakhapatnam Port Trust Golden Jubilee Hospital—Dr B Satyanarayana (Chief Medical Officer) and Dr ML Kasturi (General Physician), who particularly assisted in the collection of some of the illustrations; Dr A Ranga Rao (General Surgeon), Dr PV Rao (Orthopaedic Surgeon) and Dr PK Bhaskara Rao (Dermatologist). Bharat Heavy Plates and Vessels Hospital, Visakhapatnam—Dr PS Krupakar (Chief Medical Officer), Dr S Subba Rao (Deputy Chief Medical Officer), Dr BK Arunabala (Gynaecologist), Dr BK Satyanarayana and Dr K Subrahmanyam (Medical Officers). Visakhapatnam Steel Plant Hospital—Dr C Harendra (Consultant ENT Surgeon). Apollo Hospital, Hyderabad, Andhra Pradesh, India—Dr K Saratchandra (Cardiologist). St Andrews Healthcare, Northampton, United Kingdom—Dr (Mrs) Sunitha Rani Bonthala. University College Hospital, London, United Kingdom—Dr Latha Bonthala. Though most of the illustrative material of clinical photographs, radiology and imaging, ECGs, ECHOs, colour Doppler, isotope scanning, endoscopic pictures, etc. are all personal collections from the patients’ records and other sources, I must particularly thank Dr G Saigopal, Professor of Cardiology, and Cardiologist and Dr E Pedaveera Raju, Professor of Gastroenterology and Gastroenterologist, Andhra Medical College, Visakhapatnam and Dr Vaheesan, VITA Diagnostics Ltd, MR and CT Imaging Centre,Brothers Visakhapatnam, who have readily lent some of the illustrations. I also wish to thank Professor DV Krishna Rao, Department of Physics, Andhra University and Professor A Appa Rao, Department of Computer Sciences, Andhra University for rendering photographic services, for offering computer services in the preparation of flow charts and Dr (Mrs) Ch Suguna for assisting drawing of line diagrams. I am particularly grateful to V Sree Rama Murty for secretarial work throughout the preparation of the primer, without whose help probably this gigantic attempt would not have been possible. I must specially thank Shri Jitendar P Vij (Group Chairman), Mr Ankit Vij (Managing Director), Mr Tarun Duneja (Director-Publishing) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India, for having recognised the merits of the presented material and to have come forward enthusiastically for publishing and for cooperating patiently throughout this period in bringing out this edition. Jaypee Book Reviews from Distinguished Stalwarts and Journals on “Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine”

1. Well complied with comprehensive and profound knowledge of medicine. Dr IV Rao, Vice Chancellor, Enormous hard work has been put in bringing out this book by providing a University of Health Sciences, systemic approach to the common symptoms with flow charts, to arrive at Vijayawada, Andhra Pradesh, India. the final diagnosis. I am sure, that this book would be of immense value to undergraduate and postgraduate students and practitioners of medicine. I am particularly impressed with flow charts. 2. Congratulations on your wonderful book. Professor BM Hegde, Vice Chancellor, Manipal Academy of Higher Education, Mangaluru, Karnataka, India. 3. The book is full of in depth knowledge and clinical acumen. Dr M Paul Anand, Congratulations for excellent work done. Executive Editor of API, Textbook of Medicine, Mumbai, Maharashtra, India. 4. A much-needed book in these days of investigations and invasive Dr V Parameswara, Consulting medicine. First of its kind published in India—an excellent piece of work. Physician and Cardiologist, Bengaluru, Karnataka, India. Former President of the Association of Physicians of India and Indian Medical Association. 5. The book is a clinical treasure for common problems faced in clinical Professor Dr Arul Rhaj, practice penned down by Great Teacher. Symptoms are selected Chairman, Common Wealth Health carefully and explained properly. The guidelines on treatment makes this Professions Alliance, UK. Former description complete. Algorithm for each clinical problem is another feather President of Common Wealth Medical on the cap. This will be of great benefit to undergraduate and postgraduate Association, UK and Indian Medical students in Medicine and for practicing physicians. Congratulations. Association Tuticorin, Tamil Nadu, India. 6. You have done a good job presenting clinical problems in an analytical Dr KV Thiruvengadam manner. Former Head of the Department BrothersMedicine, Madras Medical College, Chennai, Tamil Nadu, India. 7. I am sure the book will be useful for the clinicians practicing in our country. Dr Sukumar Mukherjee, Former Head of the Department of Medicine, Kolkata, West Bengal, India. Former President of the Association of Physicians of India. 8. Problem-oriented approach of 37 symptoms complexes, discussed Dr Mrs Sachdev Former Professor analytically with good coverage. of Medicine, Lady Hardinge Medical College, New Delhi, India. 9. His rich experience as a teacher and clinician has brought out this book Dr BK Sahay Former Professor and which emphasizes importance of bedside clinical medicine in tackling day- Head Department of Medicine, Osmania to-day problems. It will be useful for under and postgraduates as well as Medical college, Hyderabad, Telngana, clinicians. India. Former President, of the Association of Physicians and Dean of Indian College of Physicians. 10. Your effort has seen the light of day. You deserve congratulations on this Dr KV Krishna Das book. Former Head Department of Medicine, Jaypee Medical College, Thiruvananthapuram, Kerala, India. 11. This is an excellent book for all the students and teachers in Medicine. Dr PC Bhattacharya The book, very simply written in a concise and rational manner will greatly Former Head Department of Medicine, help the under and postgraduates in a concise and rational manner will Gauhati Medical College, Guwahati, greatly help the under and postgraduates in particular, clinicians in general Assam, India. to establish foundation of clinical medicine with ease and confidence. I recommend this book as an alternative textbook for undergraduate students. xviii Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

12. Congratulations Dr P Siva Rama Krishna Rao. This book is an honest Dr MP Srivastava effort by learned author of excellent and elaborate analysis of common Former Head Department of Medicine, symptoms in clinical practice. This book will be an asset for clinicians, University College of Medical Sciences, teachers, under and postgraduate students in medicine. New Delhi, and Vice-dean of India College of Physicians. 13. Long-felt need. Dr AK Das Director—Professor Medicine and Dean, JIPMER, Puducherry. Former President of the Association of Physicians of India and Dean of Indian College of Physicians. 14. The book is excellent. Recommending to undergraduates and post- Professor Dr PC Manoria graduates. Bhopal. Former Dean of Indian College of Physicians. 15. Our postgraduates and undergraduates are very much impressed with the Professor Dr MBR Sarma contents. Head, Department of Medicine, Kakinada, Andhra Pradesh, India 16. It is exciting. Congratulations. Dr Manatosh Panja Dean of Indian College of Physicians; Former Professor of Cardiology, Kolkata. Former President of CSI and the Association of Physicians of India. 17. I am certain that it is a useful book with all your 50 years of experience Dr P Krishnam Raju distilled into it. Professor of Cardiology, Hyderabad, Telangana, India 18. The book by our beloved teacher, Former Professor and Head of Dr Sarat Chandra Department of Medicine, Andhra Medical College and renowned Physician, Cardiologist, Hyderabad, Telangana, serves the purpose of under and postgraduates alike in evaluation of India patients’ condition with its symptom-oriented approach. Congratulations for Editor, India Heart Journal. this magnificent task. Brothers 19. It is very difficult to write a book which is acceptable to others. This book Dr CP Thakur is very useful to all Medical Professionals and also for laymen, if they are Consultant Physician, Patna Former interested. Union Minister for Health and Family Planning” Government of India. 20. This book is responsible for my success in the postgraduate medicine Dr S Udaya examination (MD), along with all my co-students. Nizam’s Institute of Medical Science, Hyderabad, Andhra Pradesh, India. 21. The approach adopted by the Author, one of the eminent teachers of our Professor MV Nagaraj, Reviewer time, has proved to be of great help to those faced with management of British Medical Journal, South Asia common clinical problems including medical emergencies. The book is Edition, June 2002, Manipal, Karnataka, very useful to all the medical students, both undergraduates and post- India. graduates, specialists and practicing Doctors. 22. There is crying need for a book that deals with day-to-day maladies, a Dr VR Joshi Practitioner faces. Dr Rao has single handedly produced an important Emeritus Editor, Journal of Association clinical companion. The contents reflect amply the depth and width of of Physicians of India, June 2002, Author’s knowledge and clinical skills. The book has its worth as a ready Mumbai, Maharashtra, India. reckoner.Jaypee 23. The book is an honest effort of senior Medical Teacher to place on Dr Madhuchand Karr record, his experience and judgement in dealing with various symptom Reviewer, Journal of Indian Medical complexes. A practical clinical book—will be a useful companion to Association, November 2001 Kolkata, Medical Practitioners as well as Medical Students and even health care West Bengal, India. professionals. 24. The Author has discussed each symptom in fairly good deal using easy Dr Harihara Subramanian, language. To decide on diagnosis and management from the symptoms Reviewer, The Antiseptic, January 2003. presented requires in-depth understanding and in this context, the treatise Madurai, Tamil Nadu, India. is most welcome. Book Reviews xix

25. Professor Rao with teaching experience of three decades is successful in Dr PS Shankar, providing a Clinical Guide to diagnosis and principles of treatment of the Editor, Medicine Update December listed medical problems. The book is highly recommended to the Medical 2001, Mumbai. Maharashtra, India. Students and Practitioners. Congratulations. 26. It is an excellent and elaborate analysis of the common symptoms Dr PD Gulati encountered in clinical practice. Editor, Journal of International Medical Sciences Academy, July-September. 2001, New Delhi, India. 27. Idea of taking symptom complexes and then describing diagnostic Professor David R London possibilities with guides to management of both disease itself and Registrar of Royal College of symptoms will be valuable to all, particularly general practitioners and Physicians of London, London, UK. accidents and emergency Physicians. It should be present not only in the shelf at home, but also in libraries. 28. It is a valuable edition in day-to-day clinical practice and a good reference Professor Rameshwar L Bang, Faculty for the clinicians of all ranks in their career endeavour. of Medicine, Kuwait University, Kuwait. 29. This book is a guide to all clinicians, as it has an amazingly comprehensive Professor Antoinette Pereira collection of bedside Clinical Medicine, which is the result of lifetime Faculty of Medical Sciences, University experience of an outstanding Clinician and Teacher. It would add value of Sri Jayewardenepura, Sri Lanka. to anyone’s collection of Medical Books, be he/she a Medical Student or Practising Clinician. 30. Topics are presented in an unique manner to understand the differential Dr CK Rao diagnosis and up-to-date therapeutic approaches. This is of great value President/CEO Citrus Valley Physicians to Clinicians, both under and postgraduate students and residents, and Group, California, USA. extended health care professionals. Brothers

Jaypee Contents

1. Acute Abdominal Pain 1 4. Chronic Diarrhoea 55 Causes of Acute Abdominal Pain 1 Physiology 55 Clinical Approach 6 Pathophysiology 55 Treatment of Acute Abdominal Pain 11 Aetiology 56 Specific Treatment for Specific Diseases 11 Clinical Approach 63 2. Bleeding Disorders 18 Treatment of Chronic Diarrhoea 66 Specific Treatment for Specific Diseases 66 Normal Haemostasis 18 Classification of Haemorrhagic Disorders 20 5. Coma 73 Clinical Approach 28 Pathophysiology 73 Investigations 29 Grading of Coma 74 Treatment of Bleeding Disorders 31 Persistent Vegetative State 74 Symptomatic Treatment 31 Brain Death 74 Specific Treatment for Specific Diseases 31 Causes of Coma 74 3. Chest Pain 38 Clinical Approach 81 Causes of Chest Pain 38 Treatment of Coma 85 Chest 38 6. Cyanosis 93 Pulmonary 42 Central Cyanosis 93 Mediastinal (Chest) 43 Brothers Peripheral Cyanosis 93 Oesophageal (Chest) 43 Other Clinical Types of Cyanosis 94 Musculoskeletal 43 Mechanism of Cyanosis 94 Neurovascular (Chest) 43 Causes of Cyanosis 95 Abdomen (Alimentary Affections) 44 Clinical Approach 99 Endocrinal 45 Treatment of Cyanosis 101 Psychogenic 45 Specific Treatment for Specific Diseases 103 Clinical Approach 45 Treatment of Chest Pain 47 7. Dementia 107 Specific Treatment for Specific Causes 48 Anatomical and Physiological Basis of Cardiac Causes 48 Dementa 107 Pulmonary Causes 52 Classification of Dementia 108 Mediastinal Causes 52 Causes of Dementia 108 Oesophageal Causes 52 Clinical Approach 111 MusculoskJaypeeeletal Causes 52 Treatment of Dementia 112 Neurovascular Causes 54 Huntington’s Disease 115 Abdominal 54 Prion Disease 115 Endocrinal 54 Vascular Dementias 115 Psychogenic 54 Secondary Dementias 115 xxii Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

8. Dyspepsia 116 15. Gynaecomastia 229 Classification 116 Pathophysiology 229 Acute Dyspepsia 116 Causes of Gynaecomastia 229 Chronic Dyspepsia 116 Pathological Gynaecomastia 230 Clinical Approach 120 Clinical Approach 232 Specific Treatment for Specific Diseases 121 Treatment of Gynaecomastia 234 9. Dysphagia 128 16. Haematemesis and Melaena 239 Anatomical and Physiological Causes of Haematemesis and Melaena 239 considerations 128 Treatment of Haematemesis and Melaena 246 Causes of Dysphagia 129 Specific Treatment for Specific Diseases 246 Clinical Approach 134 17. Haematuria 253 Treatment of Dysphagia 136 Causes of Haematuria 253 10. Dyspnoea 141 General (Systemic) Diseases 262 Mechanism of Dyspnoea 142 Clinical Approach 263 Causes of Dyspnoea 142 Treatment of Haematuria 267 Clinical Approach 152 18. Haemoptysis 273 Treatment of Dyspnoea 154 Pathogenesis of Haemoptysis 273 Specific Treatment for Specific Diseases 155 Causes of Haemoptysis 273 11. Epileptic Seizures 165 Clinical Approach 277 Aetiological Classification of Epileptic Treatment of Haemoptysis 278 Seizures 165 19. Headache 284 Clinical Presentation 170 Mechanism of Headache 284 Clinical Approach 173 Brothers Causes of Headache 284 Treatment of Epileptic Seizures 176 Clinical Approach 289 Specific Treatment for Specific Diseases 178 Treatment of Headache 291 12. Erectile Dysfunction 184 20. Jaundice 299 Anatomical and Physiological Basis of Metabolism of Bilirubin 299 Male Sexual Dysfunction 184 Classification and Causes of Jaundice 300 Causes of Erectile Dysfunction 185 Clinical Approach 312 Clinical Approach 189 Treatment of Jaundice 315 Treatment of Erectile Dysfunction 191 21. Low Backache 323 13. Fatigue 196 Causes of Backache 323 Mechanism of Fatigue 196 Clinical Approach 332 Causes of Fatigue 196 Treatment of Low Backache 334 Clinical Approach 202 22. Obesity 340 TreatmentJaypee Of Fatigue 205 Specific Treatment for Specific Diseases 206 Chemical Composition of Body Compartments 340 14. Goitre 215 Pathophysiology 340 Thyroid Function 215 Causes of obesity 342 Causes of Goitre 215 Complications of Obesity 344 Clinical Approach 221 Clinical Approach 345 Treatment of Goitre 224 Treatment of Obesity 346 Contents xxiii

Pharmacotherapy 347 30. Pruritus 463 Specific Treatment for Specific Underlying Pathophysiology of Pruritus 463 Cause 348 Clinical Perspective 464 23. Oedema 351 Causes of Pruritus 464 Pathophysiology 351 Clinical Approach 471 Causes of Oedema 352 31. Pyrexia of Unknown Origin 482 Clinical Approach 356 Pathogenesis of Fever 482 Treatment of Oedema 358 Causes of Pyrexia of Unknown Origin 482 24. Oliguria 364 Clinical Approach 488 Treatment of Pyrexia of Unknown Origin Renal Functions 364 (PUO) 491 Pathophysiology 364 Acute Renal Failure (ARF) 364 32. Rashes 498 Causes of Oliguria 365 Terminology 498 Clinical Approach 369 Pathogenesis 499 Treatment of Oliguria 371 Causes of Rashes 499 Clinical Approach 506 25. Pain in the Extremities 376 Differential Diagnosis of Eruptions 506 Causes of Pain 376 Treatment of Rashes 509 Clinical Approach 381 Treatment of Pain in the Extremities 383 33 Shock 516 Pathophysiology of Shock 516 26. Palpitations 388 Classification and Causes 517 Causes of Palpitations 388 Clinical Features of Shock 518 Pathological 389 Specific Types of Shock 519 Clinical Approach 395 Brothers Clinical Approach 521 27. Paraplegia 403 Treatment of Shock 523 Causes of Paraplegia 403 Circulatory Devices 525 Spastic Paraplegias 403 Desired Targets 525 Flaccid Paraplegias of Acute Onset 408 Treatment of Complications of Shock 525 Clinical Approach 412 34. Syncope 529 Treatment of Paraplegia 414 Aetiopathogenesis 529 28. Polyarthritis 421 Types of Syncope 529 Mechanism of Arthritic Pain 421 Clinical Approach 533 Pathogenesis of Swollen Joints 421 Treatment of Syncope 535 Causes of Oligo and Polyarthritis 422 35. Vertigo and Dizziness 541 Clinical Approach 433 Causes of vertigo and Dizziness 541 TreatmentJaypee of Polyarthritis 436 Clinical Approach 545 29. Polyuria 444 Treatment of Vertigo and Dizziness 550 Physiology of Urine Formation 444 36. Vomiting 555 Mechanism of Polyuria 445 Pathophysiology 555 Causes of Polyuria 445 Causes of Vomiting 555 Clinical Approach 452 Clinical Approach 558 Treatment of Polyuria 455 Treatment of Vomiting 560 xxiv Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

37. Weight Loss 566 iii. Toxicology (Specific Poisons/Overdoses) 593 Basic Principles 566 iv. Laboratory Reference Values 597 Causes of Weight Loss—567 v. Function Tests of Diverse Organs 604 Clinical Approach 571 Suggested Reading 617 Treatment of Weight Loss 573 Index 619 Appendices 579 Note: Algorithms for decision-making detailed at the end i. Essentials of Electrocardiography 579 of all the 37 chapters. ii. HIV/AIDS 586

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Jaypee List of Illustrations

1. Radiogram of small bowel obstruction 41. Skiagram chest of bilateral pulmonary tuberculosis 2. Ultrasound scan of cholelithiasis 42. Skiagram chest of lung abscess (RT) 3. Ultrasound scan of renal calculus 43. Skiagram chest of carcinoma bronchus (RT) 4. Ultrasound scan of acute pancreatitis 44. Thoracic CT scan of bronchogenic carcinoma (LT) 5. Diagram of coagulation pathway 45. Magnetic resonance angiography showing 6. Clinical photograph of vascular purpura microaneurysm of the left internal carotid artery 7. Electrophoretogram in health and disease 46. Cranial CT scan of meningioma (LT) 8. Diagram of coronary circulation 47. Cranial CT scan of glioma of corpus callosum 9. Electrocardiogram of subendocardial infarction 48. Clinical photograph of hypogonadotrophic 10. Electrocardiographic patterns of acute myocardial hypogonadism before and after treatment infarction 49. Normal bile pigment metabolism 11. Echocardiogram of mitral valve prolapse 50. Ultrasound scan of the amoebic abscess of the liver 12. Radiogram of Peptic ulcer perforation 51. Abdominal CT scan of cholangiocarcinoma 13. Electrocardiogram of exercise induced ischaemia 52. Diagram of biliary tract 14. Myocardial perfusion scintigraphy with thallium 53. Endoscopic retrograde cholangiopancreatography 15. Diagram of developmental stages of Entamoeba (ERCP) of choledochal cyst as compared to normal histolytica ERCP 16. Barium enema roentgenogram of ulcerative colitis 54. Abdominal CT scan of carcinoma of the pancreas 17. Diagram of normal metabolism of bile salts 55. Diagram of root compression due to disc prolapse 18. Diagram of carotid-vertebral-arteries and circle of Willis 56. Diagram of lumbosacral plexus 19. Cranial CT Scan of intracerebral haemorrhage and 57. MRI of the lumbosacral spine showing disc prolapse cerebral infarction 58.Brothers Radiogram of osteoarthritis of lumbar spine 20. Diagram of normal and abnormal pupils 59. Radiogram of skull in multiple myeloma 21. Skiagram chest of Fallot’s tetralogy 60. Diagram of pathophysiology of oedema 22. Colour flow Doppler of ventricular septal defect 61. Clinical photograph of periorbital oedema due to 23. MRI scan of brain in Alzheimer’s disease as compared dermatomyositis. to normal MRI scan of brain 62. Diagram of right brachial plexus 24. Radiogram of pancreatic calculi 63. Radiograph of cervical spondylosis 25. Diagram of normal swallowing mechanism 64. Diagram of thoracic outlet and sites of compression 26. Radiogram of carcinoma of the oesophagus 65. Radiograms of bilateral cervical ribs and surgical 27. Skiagram chest of emphysematous bulla removal of the offending left rib 28. Spiral CT showing interstitial lung disease 66. Diagram of conduction of cardiac impulse 29. Skiagram chest of pleural effusion (RT) 67. ECG patterns of extrasystoles 30. Diagram of spirogram in health and disease 68. Electrocardiogram of atrial fibrillation 31. Photograph of Wright’s peak expiratory flowmeter 69. Electrocardiogram of atrial flutter 32. Cranial CT scans of tuberculoma and neurocysticercosis 70. Electrocardiograms of supraventricular tachycardias 33. Diagram of microscopic appearance of abnormal blood 71. Diagram of cross-section of spinal cord cells Jaypee 72. MRI of intramedullary ependymoma 34. Thyroid scintiscan of nodular goitre 73. Diagram of sagittal view of knee joint 35. Clinical photograph of adolescent gynaecomastia 74. Skiagram of hand in rheumatoid arthritis 36. Endoscopic view of oesophageal variceal bleeding 75. Diagram of LE cell phenomenon 37. Gastroscopic view of duodenal ulcer 76. Arthroscopic view of villonodular synovitis of knee 38. Barium radiograph of gastric carcinoma 77. Diagram of structure of nephron 39. Abdominal CT scan of polycystic kidney 78. Diagram of blood glucose curves in oral GTT 40. Microscopic appearance of urinary deposits 79. Ophthalmoscopic appearances of diabetic retinopathy xxvi Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

80. Intravenous pyelogram showing dilatation of pelvis and 88. Electrocardiograms of ventricular tachycardia and calyces of left kidney with megaureter fibrillation 81. Diagram of action times of different insulins 89. Electrocardiograms of sick sinus syndrome before and 82. Clinical photograph of lipodystrophy of right deltoid after pacing muscle with insulin therapy 90. Diagram of labyrinth and vestibular pathways 83. Diagram of structure of normal skin 91. Diagram of caloric responses in health and disease. 84. Clinical photograph of papular urticaria 92. Nomenclature of different waves, segments intervals, 85. Electrocardiogram pattern of pulmonary embolism of the ECG. 86. Electrocardiogram of partial heart block 93. Structure of HIV. 87. Electrocardiogram of complete heart block

Brothers

Jaypee 17 Haematuria Chapter

Haematuria is the appearance of blood in the urine. PATHOPHYSIOLOGY Normally, urine contains about 1–2 RBCs per high power field (with normal activity) which corresponds to one The capillary endothelium and basement membrane million RBCs in 24 hours urine. The colour of the urine separate the blood circulating through the kidney from varies with the amount of blood present. Urine is bright the urinary space. Normally, a limited number of red red with appearance of frank blood in the presence of large cells may leak into the urinary space. However, when the amounts, whereas it is smoky or cloudy with reddish tinge capillary permeability is altered due to any slight injury, in the presence of small amounts (due to conversion of more number of red cells are likely to leak through. The part of haemoglobin into methaemoglobin in acid urine). injurious factors may be (i) Hypoxia due to severe exercise It may be reddish brown and the brownish discolouration or fever, (ii) Increased renal blood flow, (iii) Increased is attributed to the formation of acid haematin from filtration pressure, (iv) Toxins (infections and chemicals), haemoglobin. Sometimes, traces of blood may be present (v) Immunologic injury, (vi) Neoplastic process, (vii) in urine (with appearance of normal urine colour), which Calculi formation, (viii) Haemostatic abnormalities and (ix) is detectable by the presence of abnormal number of External or iatrogenic trauma. intact red cells in the centrifuged deposit of fresh urine. This is described as microscopic haematuria as against Brothers macroscopic (RBCs may be destroyed or deformed if the CAUSES OF HAEMATURIA specimen is not fresh). Though, the most common cause of red urine is They can best be grouped as due to (i) Local urinary tract haematuria, it can also occur due to diseases and (ii) General (systemic) diseases. The former 1. Presence of blood pigment (haemoglobin) as in can be detailed in relation to the timing of micturition intravascular haemolysis (Table 17.1). 2. Drugs and chemicals like pyridium and phenolphthalein or aniline dyes in sweets 3. Food excessive consumption of vegetables and fruits Beginning of Micturition like beetroot or black berries. Microscopic demonstration of red cells distinguishes Local Urinary Tract Diseases haematuria from the other rare causes of red urine like haemoglobinuria. Urethral Causes Haematuria may be due to bleeding anywhere from Infections (Urethritis) glomerulus of the kidney down to the urethral meatus or Haematuria may occur in acute urethritis due to the prerenal. It may be painful or painless. It may be isolated Jaypee congestion of urethral mucous membrane caused by or associated with proteinuria and microscopic deposits gonococcal infections or exposure to chemicals. Urethral (cells, crystals and casts). Passing of blood in the urine may discharge, burning sensation and history of exposure offer be encountered (i) At the beginning of micturition followed the clue for diagnosis. by clear urine (urethral or prostatic origin); (ii) At the end of micturition preceded by clear urine (vesical origin); Caruncle: Urethral caruncle is granulomatous overgrowth or (iii) Intimately mixed with urine (renal or ureteric or of the posterior lip of the external meatus. It is associated occasionally vesical, i.e. from any part of urinary tract other with painful urination. It is commonly seen after menopause. than urethra or prerenal origin). It is recognised easily on inspection. 254 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

TABLE 17.1: Causes of haematuria II. General (systemic) diseases I. Local urinary tract diseases a. Haematological 1. Beginning of Micturition: Blood in the urine at this stage is i. Bleeding disorders invariably either from urethra or prostate. ii. Sickle cell disease The urethral causes are b. Infections A. Infection—urethritis i. Hepatitis B B. Caruncle ii. Haemorrhagic fevers C. Calculus iii. Subacute bacterial endocarditis, and hydatid disease D. Tunours like angioma iv. Parasitic: Malaria, filariasis, schistosomiasis and hydatid E. Injury disease The prostatic causes are c. Malignant hyprtension and Toxaemia of pregnancy A. Prostatitis d. Diabetes mellitus B. Benign hypertrophy e. Collagen disease C. Carcinoma i. Lupus erythematosus ii. Polyarteritis nodosa 2. End of Micturition: Blood in the urine at this stage is of vesical f. Scurvy origin. The causes are g. Drugs A. Cystitis i. Anticoagulants a. Acute cystitis ii. Sulphonamides b. Chronic interstitial cystitis iii. Analgesics c. Radiation cystitis iv. Cyclophosphamide d. Haemorrhagic cystitis h. Neighbouring visceral diseases involving urinary tract B. Calculus i. Carcinoma of the uterus, vagina or colon C. Tumours ii. Inflammatory intestinal ulcerations a. Papilloma • Microscopic haematuria per se occurs in: b. Haemangioma 1. Focal glomerulitis (Berger’s disease); c. Carcinoma 2. Subacute bacterial endocarditis; D. Trauma 3. Malignant hypertension; E. Foreign body 4. Renal calculi; 3. Intimately Mixed Throughout: It is probably from any part of 5. Prostatitis; urinary tract except urethra (usually renal) or general systemic 6. Malignancy and disease (prerenal). 7. Drugs like anticoagulants. The causes are In practice most of the cases of haematuria are due to A. Renal lesion Brothers 1. Infections of the parenchyma and pelvis of the kidney a. Acute pyelonephritis 2. Glomerulonephritis; b. Glomerulopathies: Acute glomerulonephritis and other 3. Renal calculi; glomerular disease 4. Tumours of the kidney or bladder; and c. Interstitial nephritis 5. Prostatic hyperplasia or malignancy. i. Acute ii. Chronic d. Nephrolithiasis e. Neoplasms Calculus: A calculus may stuck up in the urethra resulting i. Benign: Angioma, papilloma in sudden cessation of micturition associated with penile ii. Malignant: Carcinoma (Hypernephroma or Grawitz pain and due to consequent injury of the urethral mucous tumour), nephroblastoma membrane, haematuria may occur. A previous history of f. Renovascular i. Renal arterial occlusion renal colic or palpation of the urethra from outside revealing ii. Renal artery aneurysm impacted stone, offers the clue. iii. Renal vein thrombosis Tumours like angioma: Angioma of the mucous membrane g. Hereditary i. Polycystic kidney of the urethra causes recurrent haematuria. Bleeding may ii. Medullary sponge kidney be spontaneous and unrelated to micturition. There may iii. Alport’sJaypee syndrome (Hereditary nephritis) be no other presenting features except anaemia. It is rare h. Trauma and diagnosed only by urethroscopy. i. Movable kidney (Nephroptosis) Papilloma of the urethra may cause haematuria or j. Oxaluria bleeding may be unrelated to micturition. It is diagnosed by B. Ureteric lesions inspection if it is around external meatus or by urethroscopy. a. Calculi b. Tumours Injury: Membranous urethral injury is usually associated c. Ureterocele with fracture of the pelvis. Injury to bulbous urethra occurs d. Trauma due to a fall. Instruments may injure either the bulbous or Haematuria 255 pendulous urethra. The cause of haematuria is self-evident. prostate specific antigen levels are increased. Needle biopsy Sometimes extravasation of blood and urine may result. establishes the diagnosis.

Prostatic Causes End of Micturition Prostatitis: In acute prostatitis, low back pain, perineal or testicular discomfort, urethral discharge, dysuria Vesical Causes and pyrexia are the presenting symptoms and it is most commonly encountered in youngsters. It follows ascending Cystitis urethral infection or occassionally haematogenous • Acute cystitis: Fever with pain and tenderness in infection. Rectal examination reveals tense tender enlarged the hypogastrium, dysuria, or burning micturition, prostate or fluctuation if there is an abscess formation. Urine frequency, urgency and haematuria are the cardinal examination shows bacteria and pyuria or haematuria. features of acute cystitis. Urethritis is always associated. In chronic prostatitis symptoms are less striking. The The urine may be cloudy or bloody and microscopic prostate is enlarged and firm. A crepitus may be elicited examination may show numerous pus cells, red cells if prostatic calculi are present. Bacteria and pus cells are and bacteria. Infection of bladder is rarely primary and present in the urethral discharge or prostatic smear or commonly secondary to infections of adjacent organs. in the first sample of urine. Prostatic massage (which is The causative organisms are E coil, Pseudomonas, indicated only in chronic prostatitis but not acute) yields Proteus vulgaris, Mycobacterium tuberculosis and copious discharge. Schistosoma haematobium. Predisposing factors are Benign hypertrophy: (Irritative and obstructive symptoms): prostatic stone, tumour or use of infected instruments. Hyperplasia of the prostatic lobes and thickened anatomic Cystoscopy is however contraindicated. capsule result in increased outflow resistance and • Chronic cystitis: In chronic cystitis, the symptoms are functional obstruction at vesical neck and intravesicular usually milder. Cystoscopy may show mucosal irritation ureter. The hypertrophy is possibly related to oestrogen or multiple patches of submucous haemorrhage. androgen imbalance. The typical presentation is prostatism Chronic interstitial cystitis (Hurler’s ulcer) is accom (hesistancy, diminished force of the stream, terminal panied by painful haematuria and increased frequency dribling, frequency) or acute urinary retention. Gradually, of micturition. The bladder is contracted. increasing frequency of micturition and terminal dribbling • BrothersRadiation cystitis: Multiple telangiectases or necrotic may be disturbing. Residual urine (which is appreciated by areas may develop in the vesical mucosa after radiation catheterisation immediately after voiding) and associated for malignant bladder or uterus, even after the original infection may cause burning micturition and accelerate pathology is controlled. the obstructive symptoms. Renal insufficiency may • Haemorrhagic cystitis: Adenovirus types 11 and 12 are occur if the obstruction is prolonged. Rectal examination associated with haemorrhagic cystitis which occur more reveals enlarged prostate. The ultrasound examination commonly in boys unlike bacterial cystitis in girls. Gross confirms the enlargement. Excretory urogram may show haematuria may persist for 10 to 15 days. Cyclophos indentation into the inferior surface of the bladder or phamide is yet another cause documented. hydroureteronephrosis. Cystoscopy may reveal secondary Calculus: Vesical calculus may cause few drops of blood changes in bladder and bleeding may be seen from the in the terminal urine, frequency of micturition during the prostatic surface where the distended veins may be visible day, history of sudden interruption of the stream associated (prostatic varices). Urine examination clinches the evidence with urethral pain and a history of previous renal colic are of infection. the presenting features. Pyuria and nocturnal urination Carcinoma: Prostatic enlargement due to carcinomatous are additional features, if there is associated infection. The or adenomatous type may cause haematuria. Symptoms stones are usually radio-opaque. Excretory urogram reveals due to obstructionJaypee at vesical neck or infection or both are residual urine in the post-voiding film. The calculi can be common clinical features. Sometimes symptoms due to visualised by cystoscopy. metastases (like low back pain down to one or both legs, vertebral collapse, pathological fractures or oedema due to Tumours compression of iliac veins by the enlarged lymph glands) may be the presenting features. Rectal examination reveals • Papilloma: Papilloma may cause profuse gross hard nodule in the lateral sulcus of one lobe or the whole haemorrhage and is usually seen in subjects above 25 gland may appear stony hard. Serum acid phosphatase and years. 256 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

• Haemangioma: Haemangioma may occur as a spider Recurrent urinary tract infections may lead to chronic naevus of the mucous membrane or as a solid tumour. pyelonephritis, hypertension and impaired renal function. • Carcinoma: Carcinoma of the bladder may cause Urine examination reveals many pus cells, some RBCs haematuria, increased frequency of micturition or and epithelial cells. Pyuria with no obvious organisms penile pain after micturition or symptoms of cystitis is suggestive of tuberculosis or analgesic nephropathy due to secondary infection. Ureteral orifice occlusion or urethral syndrome (urethritis and cystitis usually in leads to renal pain. Extravesicular extension may women). cause suprapubic pain and involvement of the vesical Urinary tract infections include not only acute neck results in urinary obstruction. Bimanual pelvic pyelonephritis but cystitis, prostatitis and urethritis. examination may reveal a palpable mass at the base of the bladder. Cystoscopy and biopsy clinch the diagnosis, though excretory urograms are usually normal. CT scan Glomerulopathies may detect invasion. Glomerulopathies: (The glomerulus consists of epithelium— Trauma: Low abdominal pain with suprapubic tenderness podocytes; basement membrane; capillary endothelium or with or without shock and a history of local trauma are mesangium). invariably present. Peritonitis results if the injury is The glomerular diseases are grouped as: (1) Primary and intraperitoneal and a mass develops in the suprapubic area (2) Secondary to multisystem diseases. if it is extraperitoneal. If the patient can void, haematuria is Microscopy (both light and electron); immuno- detectable. X-ray may reveal fracture of the pelvis. A large fluorescence help the analysis of glomerulopathies. gray area in the vesical region is seen in extraperitoneal Either of this group can evoke a nephritic or nephrotic collection of blood and urine. Retrograde cystogram reveals response. The clinical picture in the nephritic spectrum either intraperitoneal extravasation or extraperitoneal is associated with oedema, proteinuria (less than 3 g/d), rupture. haematuria (dysmorphic RBC), RBC casts, and renal insufficiency; whereas the clinical picture in the nephrotic spectrum is insidious oedema, proteinuria (more than Intimately Mixed Throughout Micturition 3 g/d) hypoalbuminaemia, hyperlipidaemia, rarely haematuria or hypertension. Renal Causes All glomerular diseases may ultimately progress to chronicBrothers stage (chronic glomerulonephritis). Renal lesions Acute Pyelonephritis Nephritic It may of primary or secondary origin. Acute pyelonephritis: It may herald with fever, chills, pain Primary nephritic spectrum: in the flanks and loins radiating to the iliac fossae, dysuria, 1. IgA nephropathy stranguary, frequency and burning on urination. There may 2. Pauci-immune ANCA (Antineutrophil cytoplasmic be tenderness over costovertebral angle. The diagnosis is antibodies) associated crescentic glomerulonephritis confirmed by examining the urine which is of fishy odour (rapidly progressive) and cloudy in appearance and acidic in reaction. Albumin 3. Antiglomerular basement membrane glomerulon uria and microscopic deposits containing pus cells, red ephritis: (rapidly progressive glomerulonephritis or cells, bacilli with a count of > 105 organisms per mL of urine, cresenteric). Good pasture’s syndrome, with or without are cardinal features. It is usually due to lung haemorrhage. a. Infections (E. coli or tuberculosis, predominantly 4. Membranoproliferative glomerulonephritis (vide infra). associated with diabetes mellitus) b. Obstruction of the passages (due to calculus or prostate) Secondary nephritic spectrum: c. Congenital malformation.Jaypee 1. Postinfectious diffuse glomerulonephritis (Acute GN) The risk of infection is increased during pregnancy or 2. Focal or segmental glomerulonephritis vesicoureteral reflux. In women, it is much more common 3. Lupus nephritis because of the anatomical relationship of the short 4. Pauci-immune ANCA associated cresentric glome urethra with the rectum, and much more so in pregnancy rulonephritis: Granulomatosis with; mircoscopic due to atonia of the ureters caused by progesterone and polyangitis; polyarteritis nodosa/Churg-Strauss obstruction by the uterus. The diagnosis is confirmed by syndrome; Wegener’s granulomatosis identifying the organisms from culture of the urine, before 5. Cryoglobulin associated glomerulonephritis administration of antibiotics. 6. Henoch-Schonlein purpura. Haematuria 257

Nephrotic or segmental proliferative glomerulonephritis, and (d) Immunofluorescence microscopy showing diffuse • It may be of primary or secondary origin. deposition of IgA in the mesangium. Prognosis is good. Primary nephrotic spectrum Pauci-immnune ANCA associated. 1. Minimal change disease ii. Crescentic glomerulonephritis and rapidly progressive 2. Membranous nephropathy GN: It is a form of proliferative GN and may be idiopathic 3. Membranoproliferative glomerulonephritis in origin or associated with infections or multisystem (Proliferative Mesangio capillary Glomerulonephritis)— diseases. Haematuria, hypertension and oliguria are Nephritic features may also be present. presenting features. It occurs in adults and presents as 4. Mesangial proliferative glomerulonephritis acute GN or acute renal failure. Histology shows large 5. Focal segmental glomerulosclerosis. cellular epithelial cresents in > 60% of the glomeruli. iii. Anti-glomerular basement membrane glomerulo Secondary nephrotic spectrum: nephritis: (Good pasture’s syndrome). 1. Diabetic nephropathy Good pasture’s syndrome: It usually affects young men and 2. Deposition disorders (Dysproteinaemias): Amyloidosis; consists of pulmonary as well as renal involvement due Light chain deposition disease; Heavy chain deposition to antibasement membrane antibodies (Antiglomerular disease; fibrillary/immunotactoid glomerulonephritis. basement membrane glomerulonephritis) (glomerular 3. Membranoproliferative glomerulonephritis (Nephritic and alveolar). Consequently, haemoptysis and features of features may also be present with nephrotic syndrome) cresentic proliferative glomerulonephritis (haematuria, 4. Infections associated: HIV, Malaria, Hepatitis-B proteinuria and red cell casts and acute renal failure) are 5. Focal Segmental glomerulosclerosis the presenting features. Haemoptysis may be recurrent. 6. Others: Sickle cell anaemia, drugs (gold, penicillamine), Chest X-ray may show infiltrations in the lower zones. neoplasia. Renal vein thrombosis. Renal biopsy shows cresentic glomerulonephritis. 7. Heredofamilial. Immunofluorescence of the renal biopsy material reveals Thus, glomerulopathies may be immunologically induced. linear deposits of the antibody (IgG) along the glomerular A. Antigen antibody complexes in the circulation getting capillary walls. A recent history of viral infection or trapped in glomerular capillaries, for example, primary inhalation of volatile hydrocarbons may be forthcoming. IgA nephropathy, MPGN; secondary-postinfectious, iv. Membrano proliferative glomerulonephritis (vide infra). lupus, cryoglobulin associated) B. Formation of antibody to some fraction of glomerular Brothers basement membrane and deposition of antibasement Nephritic: (Secondary) membrane immunoglobulin (Vide supra) i. Acute Postinfectious Glomerulonephritis (Diffuse C. Pauci-immune (Vide supra). Proliferative GN): It usually follows one to three weeks The granular deposits of immunoglobulins may be after infections with nephritogenic strains of group-A associated with or without complement deposition. The haemolytic streptococci. It may also follow other antigens involved in the immune complex glomeru bacterial, viral and parasitic infections. It is probably lonephritis are predominantly infections, occasionally due to circulating immune complexes. colonic carcinoma or associated with multisystemic disease The onset of the disease is recognised by the appearance like SLE. of subcutaneous oedema of the eyelids, legs and back. History of sore throat or impetigo or fever with chills 1 to 3 weeks earlier may be forthcoming. Hypertension with Nephritic: (Primary) or without encephalopathy and evidence of reduced i. IgA nephropathy (Berger’s disease): Few symptoms glomerular filtration rate (transient) may be present. or asymptomatic, persistent or recurrent haematuria Urine is scanty and smoky with high specific gravity with or without proteinuria seen. Recurrent episodes albuminuria and contains blood cells, renal epithelial of haematuriaJaypee may be macroscopic or microscopic. It is cells, RBC casts, and other casts (epithelial and hyaline idiopathic in origin and a common cause in young men. casts). Blood chemistry may show azotaemia and Vague constitutional symptoms may be complained. hyperkalaemia. Serum antistreptolysin titres may be Since focal and segmental proliferation of mesangial cells increased and the serum complement especially C4 is low. is seen, this is regarded as one type of focal proliferative Renal biopsy shows diffuse (all glomeruli) endocapillary GN. Predominant immunoglobulin deposited in proliferative glomerulonephritis. IgG is deposited. mesangium is IgA. The diagnosis is established by Most of these subjects (a) May recover uneventfully, (a) Increased serum IgA levels, (b) Biopsy of the skin of especially children; or (b) A Small number may develop the forearm (volar surface showing capillary deposits of rapidly progressive glomerulonephritis in the course of IgA in the dermis, (c) Renal biopsy which shows focal weeks to months with progressive onset of renal failure, 258 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

which may be associated with haematuria, proteinuria, cold in the glomerulo capillaries (reversible) besides oliguria, hypertension and characteristic histological purpura necrotising dermal lesions, arthralgias and appearance of epithelial cells accumulating into hepatosplenomegaly and neuropathy. (Refer to Chapter crescents; or may develop into (c) Nephrotic syndrome titled ‘Bleeding disorders’). with heavy proteinuria (> 3.5 G/24 hours) and reduced vi. Henoch-Schönlein purpura (HSP): Glomerulonephritis GFR; or (d) Chronic renal failure in the course of years is another component besides nonthrombocytopenic resulting in hypertension with small kidneys and end- purpura which presents essentially as protenuria and stage renal failure. haematuria, within four weeks of onset. Evidence of ii. Focal or segmental glomerulonephritis: This is vasculitis may be present. Renal failure may occur. Mild characterised by painless haematuria or clinical picture diffuse mesangial cell proliferation (crescents) may be of acute glomerulonephritis syndrome. Proliferative seen depending on the severity of involvement. Since, and necrotic changes in only some glomeruli (focal) IgA or IgG deposits are found in the mesangium and and in only a segment of the glomerulus (segmental) is dermal capillaries, HSP is attributed to circulating IgA the typical histology picture. Some of these cases may containing immune complexes. It is a systemic version show immunoglobulin deposits in the mesangium. Such of IgA nephropathy. Prognosis is good in the majority focal changes are associated with subacute bacterial of cases. (Refer to Chapter titled ‘Bleeding Disorders’). endocarditis or multisystem involvement as in SLE or So acute GN is due to (1) postinfections (with immune periarteritis nodosa (Vide infra) or of unknown origin. mechanism) (2) SLE (3) Vasculititis (4) Henoch- Most often prognosis is good. Schonlcin purpura (5) Good pasture’s syndrome (6) iii. Lupus Nephritis: In about 70 per cent of SLE cases, Berger’s disease. the kidney is involved. The clinical features of renal involvement may vary from asymptomatic to massive proteinuria with microscopic haematuria. Hypertension Nephrotic: (Primary) and renal failure (even ESRD) may be present. Renal i. Minimal change disease: It usually presents as overt pathology may be diffuse mesangial cell proliferation nephrotic syndrome (marked proteinuria more (mesangial lupus glomerulonephritis), or focal cellular than 3 g in 24 hours, hypoalbuminaemia, hyper proliferation (focal lupus GN), or diffuse mesangial cholesterolaemia with more LDL and oedema) and endothelial cell proliferation (diffuse lupus GN), frequently in children (80%) and uncommonly in or proteinaceous deposits over the outer aspect of the adults (20%). It is the most frequent form of idiopathic glomerular capillary wall (membranous lupus GN) or Brothersnephrotic syndrome encountered in practice, as obliterative sclerosing lesions of portions of glomeruli compared to other forms of nephrotic syndrome. (young stage lupus GN) (Refer to Chapter titled Proteinuria is usually selective (small albumin ‘Polyarthritis’). molecules present and selectivity index is less than iv. Pauci-immune ANCA associated crescentic GN: 0.2). Hypertension and microscopic haematuria (Disseminated vasculitise: renal involvement of the are rare. Light microscopic examination is normal. blood vessels may include). Electron microscopy shows fusion of foot processes. a. Inflammatory lesions of small blood vessels Immunocomplexes are not implicated. Tendency (Microscopic polyangitis) of the kidney and other to relapse is its hallmark. Renal function is usually viscera (hypersensitivity angitis) normal. Acute renal failure may occur but rarely. b. Inflammatory lesions of the larger vessels ii. Membranous GN: It accounts for 50 per cent of (polyarteritis nodosa) idiopathic nephrotic syndrome in adults or present as c. Granulomatous necrotising vasculitis in the kidney isolated proteinuria. Microscopic haematuria may be and other organs (Wegener’s granulomatosis and present in some cases. Half of these cases develop renal allergic granulomatous arteritis). failure and 25 per cent recover spontaneously. Renal d. Churg-Strauss is a small vessel vasculitis with biopsy shows thick leaky glomerular wall, with IgG and eosinophiliaJaypee and pulmonary infiltrates associated complement deposition along its subepithelial aspect with asthma. Other manifestations may be sinusitis, on immunofluorescence. This glomerulopathy can also polyneuropathy and rash. develop secondary to infections (malaria or Hepatitis The presenting features are haematuria, proleinuria B), SLE, malignancy or drugs (gold or penicillamine) or and renal failure. Hypertension may be usually sickle cell disease. associated. The other features are related to the iii. Membranoproliferative glomerulonephritis: It is involvement of different organs (Refer to Chapter immune complex depostion glomeurlonephritis. titled ‘Polyarthrits’) It occurs in children or young adults. The clinical v. Cryoglobulin associated glomerulonephritis: presentation is asymptomatic proteinuria with Diffuse proliferative glomerulonephritis may be haematuria or acute GN or nephrotic syndrome in over seen due to precipitation of cryoimmunoglobulins in 50 per cent of cases. Hypertension may or may not be Haematuria 259

present. Renal function is impaired in 50 per cent of vii. Others: Sickle cell anaemia (Refer to Chapter titled cases. Two different types of lesions are described. ‘Jaundice’); (a) The deposition is either in the subendothelial layer Neoplasia; drugs; and renal vein thrombosis. of the capillary wall (b) or the deposition is dense within Note: Short duration of diabetes, proteinuria and the glomerular basement membrane itself. IgG in Type I haematuria, absence of retinopathy is suggestive of

and IgM in Type II besides C3 are deposited. Persistent non-diabetic renal disease. low serum C3 is diagnostic marker in type II and low viii. Dysproteinaemias (Idiopathic mixed cryoimmuno C4 in Type I. If the GFR is decreased at the onset of the globulinaemia): Diffuse proliferative GN may be disease or associated with hypertension, prognosis is seen due to precipitation of cryoimmunoglobulins in poor. (Other name is proliferative mesangio capillary glomerulocapillaries, besides purpura and necrotising GN). dermal lesions, arthralgias and hepatosplenomegaly. iv. Proliferative mesangial glomerulonephritis: Clinically, It may also cause vasculitis (Refer to Chapter titled it is difficult to differentiate from minimal change ‘Bleeding Disorders’). glomerulonephritis. Pure mesangial proliferative So causes of nephrotic syndrome are (1) Minimal glomerulonephritis is a primary glomerular disease, change disease (2) Membranous nephropathy (3) identified by renal biopsy. It may present as nephrotic Membrano- proliferative GN (4) Proliferative mesangial syndrome. Heavy proteinuria is characteristic GN (5) Focal glomeurulosclerosis (6) Secondary to DM, with haematuria in the majority of cases. Usually, infs, SLE, etc. serum C levels are normal. 1gM deposits in the 3 Note: mesangium are found by immunofluorescence • Diffuse connotes all glomeruli involvement of both microscopy. Spontaneous remissions occur. Prognosis kidneys. is comparatively favourable. • Focal indicates some of the glomeruli involvement v. Focal and segmental glomerulosclerosis: Clinically, it is • Segmental indicates only part of each glomerulus. difficult to distinguish between this and minimal change Causes of rapidly progressive GN are (i) Cresentic GN; or mesangial proliferative GN. Patients principally (ii) Good pasture’s syndrome; (iii) Pauci-immune ANCA present as nephrotic syndrome and others with associated crescentic GN; (iv) Membranoproliferative asymptomatic isolated proteinuria, or accompanied by haematuria. Proteinuria is usually nonselective. GN. Hypertension and progressive decline in renal function occur later. Sclerosis and hylanisation of some of the InterstitialBrothers Nephritis glomeruli (initially juxtamedullary glomeruli) is the • The tubules and the interstitium are predominantly characteristic lesion (focal) and only a portion of the involved than glomeruli and renal vasculature. Only a glomerular tuft is affected (segmental). Progressive small proportion of these lesions result from infection tubulointerstitial damage may be present. It does not per se (pyelonephritis Vide supra). Exogenous toxins respond to steroids unlike minimal change GN. (drugs and chemicals) and endogenous toxins like metabolites account for the majority of cases. i. Acute interstitial nephritis: Usually occurs from Nephrotic (Secondary) drugs and chemicals or bacterial infections. The i. Diabetic Nephropathy: (Refer to Chapter titled drugs include (a) Analgesics (phenacetin, NSAIDs, ‘Polyuria’) aspirin); (b) Antibiotics (methicillin and other ii. Deposition Disorders: (Refer to Chapter titled ‘Chronic penicillins, aminoglycosides, and amphotericin B); Diarrhoea’, ‘Bleeding Disorders’ and ‘Low Backache’) and (c) Radiographic contrast media. The clinical and Dysproteinaemas (vide infra). manifestations include acute oliguria and sometimes iii. Membranoproliferative glomerulonephritis: allergic reactions like fever, arthralgia and rash, if it is (Proliferative mesangiocapillary glomerulonephritis) due to drugs. Urine examination shows microscopic Secondary Jaypeeto Hepatitis C infection, SLE and chronic haematuria, pyuria and eosinophiluria. The renal infections (vide supra). failure usually responds readily to withdrawal of the iv. Infections Associated: HIV; Hepatitis B; Quartan offending drug. malaria. (Refer to Chapter titled ‘Jaundice’ and ii. Chronic interstitial nephritis (analgesic nephropathy): Appendix AIDS). Results from v. Focal segmental Glomerulosclerosis: 1. Drugs and chemicals Secondary forms are associated with IV drug abuse; a. Consumption of analgesics over a long period and some forms of HIV. b. Cytotoxic drugs (cisplatin and methyl-CCNU) vi. Heredofamilial diseases (Vide infra) c. Lithium 260 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

d. Heavy metals (lead) may be due to gout or treatment with uricosuric agents. e. Radiation Struvite stones are due to urinary tract infection with 2. Metabolites (hyperuricaemia, hypercalcaemia, urea splitting organisms like proteus which possess hypokalaemia) urease. Struvite, which develops in the alkaline urine 3. Bacterial infections is the commonest cause of staghorn calculi (Triple 4. Neoplasia (myeloma). phosphate big and horny) which causes obstruction. Functional abnormalities like diminished GFR Cystine calculi are due to cystinuria consequent to may occur in most of these cases sooner or later inherited tubular transport defects. Supersaturation due to glomerular injury and changes in renal of urine with crystalloids (due to their excessive microcirculation (Ischaemia) leading to renal excretion or factors which diminish solubility) leads failure. Occasionally, acute papillary necrosis to precipitation. Infection may predispose, to stone in nondiabetics with haematuria or even renal formation or may result from calculi as an effect. The colic, severe anaemia and sterile pyuria are other necrotic tissue or clots of blood may serve as a nidus for manifestations of analgesic nephropathy. Urine stone formation. Obtained stones may appear colourless shows red cells and pus cells without any organisms. or coloured (Brown and soft with uric acid or lemon Appearance of ring shadow in IVP is characteristic. yellow with cystine stones).

Nephrolithiasis Neoplasms • Big stones may be asymptomatic and small stones • Benign papilloma: Angioma or papilloma are may result in intermittent pain depending on the uncommon and may give rise to haematuria which anatomical location of the calculi. The pain may be dull may be profuse and intermittent. Pyelography shows or excruciating type, or colicky in nature. Pain varies filling defect in a papilloma of the renal pelvis. according to the position of the calculus. Loin pain • Malignant carcinoma—Nephroblastoma (Wilms’ suggests calculi in the kidneys; pain radiating from the tumour): Papillary carcinoma or squamous cell loin to the groin and into the genitalia is indicative of carcinoma of the renal pelvis, or adenocarcinoma of the ureteral calculi (renal colic); strangury or frequency of kidney (hypernephroma) may give rise to haematuria, micturition by day point towards vesical calculi; and flank pain and systemic symptoms. A mass per abdomen interruption to the urinary flow with penile pain suggests may be detected which can be differentiated from stone in the urethra. Nausea and vomiting occur Brothersbenign cysts or hydronephrosis by CT and ultrasound. often. The affected subjects present with haematuria Renal tumours can be demonstrated by contrast (gross or microscopic), with recurrent urinary tract radiography. Diagnosis is confirmed by percutaneous infections or features of urinary tract obstruction. needle aspiration for cytology. Rarely acute renal failure occurs when associated with Embryoma of the kidney (nephroblastoma or Wilms’ obstruction to a solitary kidney or bilateral ureters. On tumour) is usually seen in children. Painful haematuria, examination tenderness may be elicited in the region weight loss, abdominal mass (sometimes bilateral) are of kidney-ureter-bladder. Numerous RBCs in urinary the clinical features. An intravenous urogram shows sediment with or without evidence of infection is highly distortion of calyces and kidney. This tumour contains suggestive. Crystals which combine to form stones may both epithelial and sarcomatous cell type including also be found in the urinary sediment. Urine of 24 hours abortive tubules and glomeruli, muscle, bone and may show hypercalciuria (> 300 mg), hyperuricaemia (> cartilage. 750 mg), oxaluria (> 50 mg) and cystinuria (> 200 mg). The calculi are identified by radiographic techniques Renovascular (plain X-ray of the abdomen or IVP) or by ultrasound examination of KUB area. • Renal arterial occlusion: Vascular occlusion of the renal Renal Jaypeecalculi consists of crystals and small artery causes haematuria and proteinuria besides flank quantities of protein and glycoprotein. Most of the or upper abdominal pain, nausea, vomiting, fever and stones are composed of calcium oxalate (spiky) or hypertension. It is due to thromboembolic episodes phosphate (Big) (75%) which are radiodense. Oxalate consequent to vascular disese, atrial fibrillation, or stones form in the acidic urine like uric acid or cystine. endocarditis or mural thrombi. Renal arteriography Others include struvite (MG NH4 PO4), uric acid and confirms the diagnosis. Ultrasound examination is cystine. (Uric acid stones only are radiolucent, i.e. no noncontributory. Renal impairment depends on the radiological shadow, whereas calcium, struvite and function of contralateral kidney. cystine are radiopaque). The calcium stones may be • Renal artery aneurysm: It is rare. Haematuria may occur due to hyperparathyroidism or excess of vitamin-D or due to renal congestion or even before the swelling calcium intake (nephrocalcinosis). Uric acid stones becomes palpable. It may be associated with hyperten Haematuria 261

sion and a bruit. Plain X-ray of abdomen may show a ring shadow. Renal arteriography is diagnostic. • Renal vein thrombosis: The sudden thrombosis of a renal vein may cause haematuria and lumbar pain with loss of renal function. If this is gradual, renal function is not impaired and nephrotic syndrome may result.

Hereditary • Polycystic kidney: Infantile type is rare than the adult type. The cysts are filled with fluid (clear or straw coloured). The inheritance is autosomal recessive in the infantile and dominant in the adult type. It may be asymptomatic or present as abdominal lump (unilateral or bilateral commonly) pain in the renal angles, slowly developing hypertension or renal insufficiency. Urinary abnormalities in early stages are polyuria with low specific gravity and later haematuria with proteinuria. Fig. 17.1: CT scan of abdomen showing adult polycystic disease of the The nontender palpable polycystic mass differs from kidney associated with cysts in the liver and pancreas hydronephrosis where fluctuation is rarely present. as severe pain radiating downwards and backwards, Urinary infection is common in the third decade. accompanied by nausea, vomiting, collapse and Progressive renal failure occurs in the majority. IVP is haematuria. characteristic which shows large kidneys with elongated and bent or distorted calyces reflecting as ring shadows. Ultrasound and CT examination demonstrate the cysts. Oxaluria Sometimes polycystic liver and pancreas may also be • This term refers to presence of calcium-oxalate crystals associated (Fig. 17.1). in the acid urine. It may account for haematuria and • Medullary sponge kidney: Dilatation of renal collecting pain in the loin, apart from frequency of micturition tubules is the essential feature. Medullary sponge kidney and nocturnal enuresis. Dietary articles like spinach, presents as gross or microscopic haematuria, nephro Brotherstomatoes, gooseberries and strawberries influence lithiasis (calcium stones) or urinary infection. There oxaluria. It may be associated with oxalate calculus may be family history forthcoming. It is confirmed by (Vide supra). IVP which demonstrates the dilated tubules. • Alport’s syndrome (Hereditary nephritis): It is charac terised by glomerulonephritis (with proteinuria and Ureteric lesions haematuria) and extrarenal manifestations like nerve Ureteric calculus: It is associated with painful haematuria deafness, ocular disorders like cataract or myopia or (abrupt ureterorenal colic). They are usually obstructive retinitis pigmentosa. (partial or complete) and may pose a threat to renal function and infection. Cystoscopic examination may reveal ecchymosis of one ureteric orifice, if it is near the bladder. Trauma Tumours of the ureter: They are usually associated with • It is uncommon and the injury may range from bruising transitional cell tumours of either the renal pelvis or to laceration. Gross haematuria, flank pain or a mass bladder. Haematuria is the most common symptom which in the flank due to extravasation of blood and/or urine, may be gross or microscopic. There may be pain if the may be present. Oliguria and shock may be present. tumour is obstructive. A large hydronephrotic kidney may Renal biopsyJaypee may also cause haematuria (transient) in be palpable. Excretory urograms may show filling defect of a few cases. History of trauma is diagnostic. the ureter with proximal dilatation. Urine sediment shows cancer cells. Movable Kidney (Nephroptosis) Ureterocele: It connotes ballooning of the submucosal • This term is applied when the kidney can be moved ureter into the bladder. It may obstruct the vesical neck by external manipulation or when there is excessive and result in hydronephrosis or pyelonephritis. Excretory respiratory excursion. It may be asymptomatic or urogram may show space occupying lesion on the affected present as dragging pain or Dietl’s crises (which is due side of the bladder. A cystogram may reveal reflux usually to kinking and partial obstruction of ureter) presenting into the second ureter and rarely in the ureterocele ureter. 262 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

Ureteric trauma: Ureteric trauma is usually iatrogenic. If a positive culture for Streptococcus viridans are confir it goes unrecognised at surgery, there may be a complaint matory. of pain in the flank and/or lower abdomen on the affected Parasitic side. Ileus may be conspicuous. Leakage of urine into the • Malaria: Quartan malarial nephropathy is associated peritoneal cavity may cause rebound tenderness. Oliguria with Plasmodium malariae and affects children or anuria occurs in bilateral ureteral injury. Retrograde and young adults. Nephrotic syndrome develops urography reveals the site of injury. several weeks after the onset of quartan fever. A small proportion of patients may develop glomerulopathy. Oedema, albuminuria and haematuria may appear. General (Systemic) Diseases Diagnosis is confirmed by demonstrating the parasitised RBCs (may appear in “band” form and merozoites Haematological arranged in a rosette) in the peripheral blood smear. Bleeding disorders: (Refer to Chapter titled ‘Bleeding Falciparum malarial glomerulopathy may occur Disorders’) soon after the onset of fever. Proteinuria, microscopic Sickle cell disease: Though the renal injury in sickle cell haematuria and cylinduria may be seen in about 1/3rd disease is predominantly tubulointerstitial, glomeruloneph of cases. This is transient as against quartan which may ritis is also documented. Circulating iron bound protein lead to progressive renal failure. Diagnosis is established complexes which appear during sickle cell crisis may by demonstrating RBCs containing rings (more than be responsible for the glomerular damage. The normal one) or presence of gametocytes (banana shaped) in renal circulation may be impeded due to increased blood the peripheral smear. (Refer to Chapter titled ‘Rashes’) viscosity. Gross painless haematuria and proteinuria are • Filariasis: Filarial glomerulopathy (proliferative GN in the manifestations in sickle cell nephropathy. The source of some and nephrotic syndrome relatively common) with bleeding may be from vasocclusive macro or micro infarcts deposits of IgM, IgG and C3 are reported. Urine may in the kidney (Refer to Chapter titled ‘Jaundice’). show haematuria and albuminuria (Refer to Chapter titled ‘Rashes’). • Schistosomiasis: It is caused after contact with water Infections containing cercariae (infective stage) which penetrate the skin and migrate to the lungs and mature in the : It is associated with membranous nephropathy Hepatitis B portal vein S. haematobium affects the genitourinary in children and mesengiocapillary GN in adults. Brotherstract and causes dysuria and haematuria. S. mansoni Presenting features may be nephrotic syndrome or non- though known to produce dysentery due to ulcers in nephrotic proteinuria with haematuria. Clinical evidence of the lower gastrointestinal tract and liver fibrosis, may associated liver disease is more common in adults than in also cause overt glomerulopathy in a small percentage children. Other features like arthritis, rash, polyneuropathy of cases. Diagnosis is confirmed by identification of may also be present. Humoral immune mechanisms are ova in the stool (S. mansoni) or ova in the urine (S. incriminated. HBSAg and anti-HBSAg are demonstrable haematobium) (Refer to Chapter titled ‘Pruritus’). (Refer to Chapter titled ‘Jaundice’). • Echinococcus granulosus (Hydatid disease): Eggs are Haemorrhagic fevers: Haemorrhagic fevers like arbovirus swallowed after contact with infected dogs or vegetables. infections may present with haemorrhagic manifestations The larvae migrate through the duodenum and settle probably due to coagulation defects (prolonged prothrombin in any of the organs. When the kidney is affected renal time and partial thromboplastin time), thrombocytopenia colic with haematuria and hydatid hooklets in the or disseminated intravascular coagulation or vascular urine are the presenting features. Renal swelling may factors (toxic capillary endothelial damage associated be appreciated before the cyst ruptures. Casoni’s test with increased vascular permeability). The renal damage is diagnostic. in the form of renal interstitial haemorrhages may occur due to obstructionJaypee of the vasa recta from oedema. The toxic haemorrhagic phase with oliguria may be preceded by a Malignant Hypertension febrile phase and a hypotensive phase. Refer to Chapter titled ‘Oliguria’. Subacute bacterial (Infective) endocarditis: Haematuria accompanied by embolism of renal vessel is not uncommon in subacute bacterial endocarditis which may manifest as Toxaemia of Pregnancy sudden pain in the loin with microscopic haematuria. This a. Pre-elampsia: Characterised by hypertension, oedema is to be suspected specially if there is fever in a subject with and proteinuria (nonconvulsive form). a known cardiac disease. Olser’s nodes (red tender nodules b. Eclampsia in which hypertension is fairly severe with on fingers), changing cardiac murmurs, splenomegaly and convulsions and coma. Usually toxaemia of pregnancy Haematuria 263

occurs in the last trimester of pregnancy, or within seven Neighbouring Visceral Disease Involving days after delivery. The glomeruloendotheliosis and uteroplacental ischaemia Urinary Tract account for the clinical manifestations. Normally, the blood Diseases of the pelvic organs like (i) Carcinoma of pressure in pregnancy falls and any pressure raising upwards the uterus, vagina, pelvic colon or rectum, and (ii) should be taken as abnormal. Urine shows proteinuria, Inflammatory intestinal ulcerations may cause haematuria haematuria infrequently and elevated levels of blood uric acid due to direct spread to the bladder wall by the disease will be more conclusive than blood urea or creatinin (Refer to process. Carcinoma of the genitalia, as it progresses may Chapter titled ‘Vomiting and Epileptic Seizures’). involve the bladder, which usually results in ulceration and haematuria. Similarly, carcinoma of the colon or any other infective intestinal ulceration may cause haematuria due Diabetes Mellitus to inflamed mucous membrane, consequent to adherence of the bowel to the fundus of the bladder. Cystoscopic Refer to Chapter titled ‘Polyuria’. examination may show localised congestion at the fundus Renal involvement in diabetes mellitus is a common without any other pathology. complication. The term diabetic nephropathy connotes Note: Microscopic haematuria causes and in practice the renal lesions occurring in diabetic subjects which common causes of Haematuria (Rafer Table 17.1 Vide supra). include glomerulosclerosis. Arterionephrosclerosis, chronic interstitial nephritis, papillary necrosis and peritubular deposits may also be present. Consequently the clinical CLINICAL APPROACH presentations may vary, ranging from asymptomatic proteinuria, nephrotic syndrome, hypertension to Haematuria is a definite indicator of the presence of an progressive renal failure. Stages of diabetic nephropathy are abnormality anywhere in the urinary tract or bleeding increased kidney size; clinical latency; microalbuminuria: diathesis. It may be asymptomatic or symptomatic Macroalbuminuria and renal failure. Though haematuria (associated with pain, frequency of micturition, etc). When is not a significant finding per se in diabetic nephropathy, it is gross, it is observed by the patient; when present in small the ascending pyelonephritis leading to acute medullary amounts, microscopic examination enables the clinician necrosis (acute suppurative pyelonephritis or necrotising to detect it. papillitis) or papillary necrosis (characterised by flank or The initial step is to determine whether the gross abdominal pain, haematuria and fever with chills) may haematuriaBrothers is due to the presence of blood or the red colour account for it. (Refer Chapter ‘Polyuria’) of the urine is due to conditions simulating haematuria (like haemoglobinuria, myoglobinuria, porphyria, consumption of certain drugs and large quantities of beetroot which Collagen Diseases colour urine red). Pitfalls like menstrual blood getting mixed Systemic Lupus Erythematosus with urine during micturition (most often microscopic (Vide supra) Polyarteritis Nodosa } haematuria) and other physiological causes like microscopic haematuria after exercise or lordosis should be eliminated. If microscopic haematuria is persistent even in small Scurvy number, it is all the more significant. The second step is to confirm the presence of blood by Scurvy (Avitaminosis C) associated with subcutaneous guaiac test or occult test tablets or more conveniently by ecchymoses, swollen haemorrhagic gums and delayed the use of dipstick (orthotolidine). A positive orthotolidine healing of wounds may be accompanied by haematuria test may indicate not only presence of blood but also which may go unrecognised. haemoglobin or myoglobin in the urine. In haematuria, the dipstick is positive along with presence of RBCs in the spun sediment of urine whereas in haemoglobinuria and Drugs Jaypee myoglobinuria dipstick is positive with no RBCs in sediment The administration of anticoagulants may account for of urine. However, chemical test is negative when foods or microscopic haematuria which may be taken as an index drugs are implicated to colour urine red. of prolonged prothrombin time particularly with oral The third step is to determine the site of bleeding in the anticoagulants. Sulphonamides are known to produce urinary tract. haematuria if the urine is not maintained alkaline. The fourth step is to identify the cause of bleeding Analgesics (interstitial nephritis) and cyclophosphamide whether it is due to a disease localised to the urinary tract (haemorrhagic cystitis) (Vide supra) oral contraceptives or systemic disease or trauma per se. cause recurrent haematuria with dull loin pain in young Such an approach demands for a diligent enquiry into women due to narrowing of the intrarenal vessels. the history and meticulous physical examination apart from 264 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine a thorough detailed physical, chemical, microscopic and i. Placing one hand posteriorly over the angle just microbiological examination of urine supported by other below the last rib and erector spinae and the other relevant investigations. hand anteriorly below the costal margin. ii. Asking the patient to breathe deeply. iii. Applying gentle pressure by both hands when an History enlarged kidney may be felt during deep inspiration as it descends. The points to be focussed are as follows: b. Palpation over 1. Age and Sex: In children, acute nephritis or haemorrhagic i. Suprapubic region for evidence of a distended disorders and in young adults, calculus or tuberculosis bladder or tenderness and generally occur. In the 40 years and above age ii. For any hepatosplenomegaly. group, renal neoplasms or hypertension or prostatic c. Auscultation for any arterial bruit. hypertrophy and in women, urinary tract infection, d. Pelvic examination cancer of cervix, are usually encountered. i. Examination of genitalia for local causes like urethral 2. Occupation: Common in the workers of dye industry. caruncle or any nodule or swelling of the epididymis 3. Any history of trauma preceding haematuria? or genital ulcers. 4. Any relation to exercise like jogging, since it may suggest ii. Vaginal examination for any evidence of disease a tumour or calculus, or may be physiological? (neoplasms) in the pelvic organs. 5. Any history of intake of drugs like anticoagulants? iii. Rectal examination for any enlarged prostate. 6. Any recent history of fever with chills or lymphangitis or passing cloudy urine or any chronic illness like diabetes mellitus? Other Systems 7. Any previous episode of haematuria (recurrent)? 8. Is it accompanied by other symptoms (like frequency of Chest examination for any evidence of cardiac lesions and micturition, dysuria) or an isolated complaint? subacute bacterial endocarditis. 9. Is it painless or painful? If there is pain define its location, as pain in the loin radiating to the groin suggests calculus; pain in the perineal region indicates malignant Investigations prostate; and pain during micturition points towards urethral caruncle or vesical malignancy. Painless UrineBrothers Examination haematuria may be due to renal neoplasms, polycystic kidney, systemic diseases like hypertension, sickle cell Physical Examination disease and bleeding disorders. a. Colour 10. Timing of the appearance of blood during micturition— i. Bright red suggests origin from lower urinary tract. Initial, terminal or throughout uniformly mixed (Vide ii. Dark red coloured (reddish brown) suggestive of supra). large amount of blood present in the urine or due to retention of blood in the bladder over a time. Physical Examination iii. “Smoky” suggests the presence of small amount of blood. iv. Clear red or brown colour is suggestive of General Examination haemogobinuria. It includes, looking particularly for v. Colour may be normal with small number of RBCs a. Baggy eyelids especially in the morning hours or (microscopic haematuria) or even traces of blood. puffiness of the face or any oedema of the legs vi. Sediment may be red or brown when RBCs settle at b. Anaemia the bottom in the container. c. Purpura Jaypee b. Three glass test: When urine is collected in three glasses d. High blood pressure at a time, haematuria in the first glass indicates source e. Temperature (UTI, endocarditis or hypernephroma). either from the urethra or prostate; if present in the second glass mixed evenly, it suggests the source either from renal (kidney or ureter) or prerenal, or bladder Systemic Examination sometimes and if present in the third glass usually points towards the bladder. Abdomen c. Examination of urine collected in a tray filled with water. a. Each kidney should be palpated bimanually to detect i. Look for clots and their shape: If triangular shaped enlargement or tenderness over renal angle or lumbar (suggestive of renal pelvis origin), worm shaped quadrants. (ureter) and disc-shaped (bladder). Haematuria 265

ii. Any other tissue like renal papillary tissue or neoplastic pieces or mucopus plugs. d. Specific gravity: Valuable test to assess renal (tubular) function. If it is 1020 or more, tubular damage is unlikely (Refer to Chapter titled ‘Polyuria’).

Chemical Examination a. Reaction: Urinary pH ranges from 4.3 to 8. Normal urine is usually acidic and may be alkaline if tubular function is impaired to excrete acid (without taking either acids or alkalies). Haematuria in acidic urine may be from kidney or due to beetroot. A pH greater than 8 indicates vesicle pathology or urinary tract infections (with organisms likely to form ammonia from urea) or a phosphatic renal calculi. The red colour of the urine due to beetroots disappears on alkanisation and reappears on reacidification. b. Protein: If proteinuria is associated with haematuria, it may be due to primary renal disease like glomerulo nephritis. The functional severity of the glomerular damage can be assessed by the amount of protein lost in the urine. Proteinuria occurs as leakage from glomeruli or tubules (normal protein consists of plasma proteins). In glomerular proteinuria like albumin pass through glomerular basement membrane in larger quantities. Tubular protein consists of more globulins (Tamm- Fig. 17.2: Urine microscopy showing crystals, cells and casts

horsfall protein) and albumin: b2 microglobulin ratio 100–1 unlike glommerular quantitative excretion of, i.e. acetic acid, granules disappear and nuclei are seen. > 1000:1 Quantitative excretion of protein is usually < 2 BrothersMore than four pus cells per HPF indicates infection. g/d in tubular wheras it is > 3 g/d in glomerular lesions. iii. Epithelial cells: They are larger in size and variable c. Sugar: For evidence of diabetes mellitus. in shape and their presence in excessive numbers d. Chemical test for blood (Vide supra). indicate renal disease. Renal epithelial cells remain e. Porphobilinogen (Watson Schwartz test)—It reacts unaltered or appear crowded with fat globules in with Ehrlich’s aldehyde reagent to form a red complex glomerulonephritis, depending on its duration. (confirmed by chromatography). Epithelial cells derived from the pelvis of the kidney f. Estimation of 24 hours urine calcium, urate, oxalate, appear tailed. Prostatic epithelial cells appear cystine phosphates and citrate helps to determine the identical. Bladder or vaginal epithelial cells are cause of stone. seen as collection of squamous cells. Normal urine g. Urine protein electrophoresis. contains occasional epithelial cells. iv. Malignant cells (Vide infra): It is not a part of routine urinalysis. Microscopic Examination of Centrifuged Urinary b. Tube casts: Fresh urine sample is essential to detect Sediment (Fig. 17.2) casts which are cylindrical in shape with rounded ends or ragged at one end and formed in the renal tubules a. Cells Jaypee by coagulation of protein. If the cells are impressed on i. RBCs: Biconcave forms or outlines showing double this matrix, which consists mainly of Tamm-Horsfall contour in fresh urine; circular with sharp outline in glycoprotein, cellular casts result and if they are not dilute urine; crenated deformed and of unequal size impressed hyaline casts occur. If the cells impressed in haematuria of glomerular origin. (Phase contrast undergo degeneration granular casts result. microscopy differentiates glomerular bleeding from i. Red cell casts are seen in acute glomerulonephritis, other genitourinary bleeding). More than two RBCs malignant hypertension and may appear greenish per high power field (HPF) is abnormal. (they are demonstrated only in fresh urine or acid ii. Pus cells or leucocytes: The diameter is more than urine; alkaline urine destroys them). RBCs and contains granules. When treated with ii. Epithelial casts—Indicate early stage of acute GN. 266 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

iii. WBC casts—Indicate acute pyelonephritis. c. Arterial pH; HCO3; and PaCO2 iv. Hyaline casts—Which are transparent may be d. Spectrometry—Methaemoglobin gives an absorption found in glomerulonephritis and occasionally in the band in the red (if haemoglobin is converted to normal urine especially after exercise. methaemoglobin) in addition to the two bands in the v. Granular casts—Present in any chronic renal disease green characteristic of oxyhaemoglobin. or acute tubular necrosis and rapidly progressive e. Calcium phosphorus, uric acid and parathyroid GN. harmone Add a few drops of methylene blue to the urine Other biochemical tests (Refer to Chapter titled before centrifugation; the cells in the casts shows ‘Oliguria’) nuclei stain. More than one cast per 20 HPF is significant. Certain objects like cotton or prostatic threads and Special Blood Tests so called cylindroids, which are of no significance, a. Complement—Hypocomplementaemia indicates resemble tube casts but they are differentiated by glomerulonephritis their shape, and sharp outline (Cylindroids are very b. LE cell for collagen disorders long, narrow and tapered). c. Antinuclear factors for collagen disorders especially for c. Crystals: Presence of crystals in acid urine points SLE. towards renal calculi. They are chiefly urates, uric acid, d. Blood culture for evidence of subacute bacterial oxalates and cystine. In alkaline or neutral urine, triple endocarditis. phosphates are common. They combine to form stones. d. Bacteria: Cocci or rods may be present in freshly collected urine, which correlates usually with counts Renal Function Tests more than 100,000 organisms per mL of urine (Vide a. Creatinine clearance test (Refer to Chapter titled infra). ‘Polyuria’) e. Parasites: Ova of Bilharzia haematobium are the only b. Specific gravity test (Refer to Chapter titled ‘Polyuria’) helminthic ova seen in the urine to cause haematuria. c. Phenol-Sulphon-Phthalein (PSP) test: For renal f. Malignant cells: Cells in the spun sediment are stained efficiency. After parenteral administration of 6 mg of by Papanicolaou method. Transitional cell tumours the dye, over 60 per cent is excreted in two hours. It also of renal pelvis or ureter are better appreciable by serves as a clinical measurement of renal blood flow. Wright’s stain. Exfoliative cytology enables recognition d.Brothers Acidification test: When oral ammonium chloride 0.1 of malignant cells. g per kg body weight is administered the urine pH falls below 5.3. In distal renal tubular acidosis, urine Microbiological examination: Midstream specimen of pH cannot be reduced below 5.3 which may be due to urine must be cultured within two hours for identifying failure of acidification of urine in the distal tubule, i.e. the incriminating organism. Gram’s stain may be helpful. ability to form acid urine is lost. This test may be useful in determining the underlying cause of renal calculi since it is associated with hypercalciuria, hyperphosphaturia Blood Tests and nephrocalcinosis. Haematological a. Full blood counts (like red blood cell count, haemo Radiological Investigations globin, white blood cell count, differential count, platelet a. Plain X-ray of abdomen for any radiopaque stones. count, ESR) b. Plain X-ray of chest for evidence of any tuberculosis. b. Parasites (microfilaria) c. Intravenous pyelogram—Useful to determine the level c. Sickling of obstruction and its probable cause. Radiolucent uric d. Test for integrityJaypee of platelet and coagulation components acid calculi can be outlined. (Refer to Chapters titled (if indicated) ‘Polyuria’ and ‘Oliguria’) e. Anticoagulated blood centrifuged shows reddish brown d. Post-voiding film—For detecting bladder abnormalities. plasma in haemoglobinuria whereas in haematuria or e. Retrograde pyelography (Vide infra). myoglobinuria, it is normal. f. Nephrotomography—45 per cent of sodium diatrizoate is injected rapidly and a series of tomograms taken. This test is useful in differentiating renal tumour from Biochemical Tests a cyst. A tumour is densely opacified whereas a cyst a. Blood urea and serum creatinine is radiolucent with no vessels. This test is replaced by b. Serum protein—A/G ratio imaging techniques. Haematuria 267

g. Renal arteriography—Valuable to diagnose renal artery TREATMENT OF HAEMATURIA stenosis and to differentiate abnormal vascular supply from any renal mass (Refer to Chapter titled ‘Oliguria’). The therapeutic approach of haematuria depends essentially h. DMSA scan, for evaluating scarring. on detection of the source of bleeding which may be due to disease of the urinary tract or disorder of haemostasis. Imaging Techniques Its mode of presentation in relation to micturition (initial, throughout or terminal) and microscopic findings of urinary a. Ultrasound examination (sonography)—Useful for sediment (RBCs and RBC casts with proteinuria point differentiating solid tumours from cysts apart from towards glomerulus to urethra wheres RBCs alone towards assessing the renal size and stones and associated renal pelvis to urethra including prostate) are of immense dilatation of pelvicalyceal system (Refer to Chapter titled diagnostic value. If the morphology of RBC is deformed, ‘Oliguria’). the bleeding is from upper urinary tract whereas presence b. CT scan—Useful to diagnose renal masses and their of RBC of normal morphology indicates lower urinary tract extension. pathology. Further, haematuria associated with renal colic offers clue that the bleeding is of renal or ureteric origin. Radionuclide Studies a. Isotope renogram—After IV injection of diethylenetria mine pentacetic-acid labelled with technetium Symptomatic Relief 99m ( TcDTPA) provides information about arterial 1. Anxiety: Reassurance relieves apprehension. Alprazolam perfusion of each kidney, and arterial obstruction which (0.5–1 mg) may be necessary in highly anxious patients. affects any of the three classical phases, i.e. transit time, 2. Pain: Bed rest and physical therapy (hot application over peak activity and excretion. the site of the pain) are the initial measures. High fluid b. Isotope scan—Following injection of Dimercapto intake is advised so as to produce a daily urine output 99m succinic acid labelled with technetium ( TcDMSA) of 2–3 litres (provided the renal function is normal). images of the kidney can be obtained with a gamma Antispasmodic-analgesics are administered if the camera, which can be compared, to assess the function pain is intolerable. Buprenorphin (0.3 mg IM) or of each kidney. pethidine (100 mg IM) given. Diclofenac (100 mg IM) is an alternative. Antispasmodics like atropine sulphate Brothers(1 mg IM) or dicyclomine orally (10 mg) hyoscine butyl Instrumental Investigations (Invasive) bromide (10 mg QID or 20 mg IM/IV) or drotaverine a. Cystoscopy: Ureteric catheterisation permits direct (40 mg tds orally or paremerally) may be given. These visualisation of the bladder and ureteric orifices thereby drugs may be repeated if necessary. Diclofenac and/ revealing any bladder lesion or blood dribbling from or drotaverine are preferred. Ketorolac is another non- one of the ureters especially during the attack. Ureteric opioid analgesic recommended. catheters can be inserted during cystoscopy and contrast 3. Bleeding: Haemostatics may be given as in haemoptysis. medium is injected to outline the ureters and renal pelvis If the bleeding is severe, blood transfusion may be (retrograde pyelography). necessary. b. Urethroscopy: To detect strictures and stones. 4. Fever: Appropriate antibiotics are to be considered, if c. Antegrade pyelography: A fine catheter is inserted indicated (Vide infra). Antipyretics may be necessary, percutaneously into the pelvicalyceal system under if the fever is high. ultrasound control and contrast medium is injected, 5. Urinary alkalisers like disodium hydorgen citrate or which procedure sheds light about the details of the potassium citrate may be considered. pelvi-calyceal and ureteric pathology. d. Renal biopsy: This percutaneous technique enables the Specific Treatment for Specific Diseases clinician to Jaypeeobtain precise information by microscopic and immunohistological examination of the biopsied tissue. Though histological diagnosis is forthcoming, Initial Haematuria (Urethral and Prostate) the clinician should weigh the pros and cons of this procedure, while investigating a case of haematuria. Urethral Nevertheless, it is imperative to appreciate that the • Urethritis: Nonspecific urethritis usually responds to tests providing the data base to establish the diagnosis, tetracycline (0.5 g 6 hourly; given for 7 days). should be suitably tailored as per the relevance of Specific urethritis may be treated accordingly. clinical picture. Amoxycillin (1.5 g/d to 3 g/d) or cephalosporin or 268 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

nitrofurantoin. Oestrogen cream is beneficial for senile Apart from treating recurrent cystitis with appropriate urethritis. Surgical dilatation and drainage of infected antibiotics a prophylactic course of nitrofurantoin or periurethral ducts done if indicated. co-trimoxazole or norfloxacin for 6 weeks to 6 months • Caruncle: Treated by local excision. (depending on the number of recurrences) immediately • Calculus: Small stones can be removed or crushed after the regular course of treatment, is beneficial. transurethrally. In chronic cystitis, bladder washes with suitable urinary • Tumours: Require resection with or without radio antiseptics may be necessary in addition to the therapy therapy. Urethrocystectomy indicated for proximal mentiond above. tumours. Factors predisposing to infection like calculi, etc. or associated infections of genitalia must be corrected, if present. Prostatic Interestial cystitis (Hurner’s ulcer) is treated with • Prostatitis: Specific antibiotics according to culture and dimethyl sulfoxide (50 mL of 50% solution instilled into sensitivity tests. Cotrimoxazole (two tablets twice daily) bladder and retained for 15 minutes. This is to be repeated or ciprofloxacin or ofloxacin for four weeks advocated. after two weeks or pentosan polysulphate sodium (100 mg • Benign hypertrophy: Conservative treatment usually TDS.) is advocated. suffices. Prostatic congestion should be removed. Vesical calculi: Small calculi require transurethral Voiding urine as the urge develops, protects vesical tone. approach whereas large calculi require suprapubic Flavoxate (100–200 mg tds orally) offers symptomatic transvesical removal. Installation of hemiacidrin through a relief. Darifenacin (7.5–15 mg) or solifenacin (5–10 mg) cathether which is clamped for one hour may be beneficial. are also beneficial. Finasteride (5 mg/day/orally) and/ Analgesics and antibiotics administered, if indicated (vide or alpha adrenoreceptor blockers may be benecificial infra). (Prazosin, terazosin and tamsulosin) for better urinary Tumours: Total cystectomy and prostatectomy indicated flow. Recently Silodosin (8 mg) is introduced which for papilloma and invasive tumours with urinary diversion appear effective. In acute retention, an indwelling measures. Radiation therapy (6000 rads given for 6 weeks is catheter for 3 or 4 days restores detrusor tone. If the useful) is supplemented. Chemotherapy is not encouraging. symptoms are disturbing or renal impairment is likely, However, 60 mg of thiotepa is dissolved in 60 ml of normal surgery is the alternative. Transurethral prostatectomy is saline and instilled by catheter weekly. favoured. Cryosurgery considered in poor risk patients. • Carcinoma: Nodular lesions treated by radical ImmunotherapyBrothers with BCG vaccine is being favoured. prostatectomy with or without pelvic lymphadenectomy. Trauma: The site of the trauma is drained and a cystostomy Suprapubic implantation of radioactive gold appears to tube is inserted for extraperitoneal ruptures. The rent is be effective in advanced lesions. closed transperitoneally and the bladder is drained by Radiation therapy and/or antiandrogen therapy cystostomy in cases of intraperitoneal ruptures. (orchidectomy with or without oestrogens like stilbestrol 1–3 mg/d or gonadorelin analogues like buserelin 500 mg 8 hourly SC for one week followed by 100 µg Total (Throughout) Haematuria intranasally 4 hourly or antiandrogenic like cyproterone (Renal Lesions) 100 mg tds) bicalutamide (50 mg/day orally) are palliative measures. Pain from metastatic bone lesions may be relieved by corticosteroids. Acute Pyelonephritis Transurethral resection is a surgical palliative It is treated with appropriate antimicrobial agents initially procedure to relieve obstruction. and may be changed based on culture reports if necessary. Norfloxacin or ciprofloxacin or other quinolones are Terminal Haematuria (Vesical Lesions) acceptable in most of the cases. Therapy should last for Jaypee at least two weeks and better extended up to 4–6 weeks in Cystitis patients with recurrent infections. Optimum amounts of fluids (at least 2 L/d) are administered to induce adequate It is treated with cotrimoxazole or nitrofurantoin or output. A follow-up of the response to treatment is gentamicin or ciprofloxacin for 10 days depending on mandatory. Prompt evaluation and correction of structural the culture and sensitivity tests. Fosfomycin (400 mg as abnormalities are indicated in relapses and reinfections. single dose) is recommended for cystitis. Dicyclomine (10 Single dose of the suitable antimicrobials at bed time is mg TDS.) or pyridium (200 mg TDS.) may be useful for rewarding. Amikacin parenterally is useful in some cases suprapubic pain and dysuria. Copious fluids are indicated. and dose is adjusted as per serum creatnine. Haematuria 269

Glomerulopathies addition to cyclophosphamide (1 g/m2 i.v. monthly) recommended. • Nephritic: In stage V, short course of Prednisolone or a. IgA nephropathy: Treatment consists of angioten- mycophenolate (1 g t.d.s.) for 6 months advocated. sion converting enzyme inhibitors or ARBs are given ` If necessary, rituximab weekly 375 mg/m2 IV to reduce the intraglomerular pressure, and omega-3 recommended for 4 weeks like other immune fatty acids (fish oil) may prevent further renal mediated disorders. deterioration. If the disease is progressive, prednisi- g. Pauci-immune ANCA associated gesentic lone (1 mg/kg/d) with or without cytotoxic drugs. glomerulonephritis Vasculitis: Prednisolone b. Rapidly progressive (cresentic) GN: High dose of (60 mg/d tapered over 1–3 months) and oral steroids considered. Methyl prednisolone 30 mg/kg cyclophosphamide (1–3 mg/kg/d for three months IV over few hours, every alternate day for three doses or till the disease becomes quiescent) are effective. followed by oral prednisolone 60 mg/d tapered over The offending drug leading to hypersensitivity several weeks. vasculitis may be withdrawn. Cyclophosphamide (2 mg/kg daily for three We gener’s granulomatosis treated with prednisolone months) and plasma exchange (2–4 L exchanged and cyclophosphamide for 3 months, then steroids daily for couple of days and then fortnightly till for one year to prevent relapses. Double strength improvement occurs) are advocated. sulfamethoxazole with trimethoprim given twice Heparin and dipyridamole may be considered. daily, to reduce extrarenal relapses. Dialysis, if c. Antiglomerular basement membrance GN (Good necessary, undertaken. pasture’s syndrome): Methyl prednisolone 1 g IV h. Cryoglobulin associated glomerulonephritis: Target on three consecutive days followed by predni causative factor. Pulse corticosteroids, plasma solone 60 mg/d for six weeks and then taper. exchange, cytotoxics are used. (Refer to Chapter Cyclophosphamide 2 mg/kg/d may be added. titled ‘Bleeding disorders’). Plasmapheresis and the above immunosuppressive i. Henoch-Schönlein purpura: Treatment is sympto therapy is effective if the renal function is not matic. Some may have to be treated as for crescentric impaired and in pulmonary haemorrhage. If the renal glomerulonephritis. function is impaired, dialysis and transplantation are • Nephrotic: considered. Nephrotic syndrome d. Poststreptococcal glomerulonephritis: Conservative Brothers a. Minimal change disease: Symptomatic treatment treatment is advised. is with bed rest, salt and fluid restriction; high ◊ Bed rest protein diet; diuretics and IV infusions of albumin. ◊ Salt restriction (1–2 g/d) Specific treatment with prednisolone 60 mg/d for ◊ Fluid restriction (maintaining optimum fluid four weeks or until remission of proteinuria occurs, intake and output chart). which should be tapered over four weeks. If relapses ◊ Diet: Adequate calories from carbohydrates and are frequent, or if no response to prednisolone fats with less proteins. cyclophosphamide (2 mg/kg body weight given ◊ Loop diuretics may be necessitated for oedema for six weeks or continued for two weeks after at times. remission) or cyclosporin (< 4 mg/kg/d) considered ◊ Hypertension should be controlled with loop chlorambucil (0.15 to 0.2 mg/kg/d for six weeks) with diuretics or enalapril (in case seizures occur, prednisolone effective. parenteral diazepam may be given). b. Membranous nephritis: Spontaneous remission may ◊ Penicillin or erythromycin (alternative) may be occur. Alternate day high dose prednisolone (120 helpful, though it does not influence the course mg for 8 weeks and tapered), if given, prior to renal of the disease (Glomerulonephritis associated insufficiency, may reduce further renal impairment. withJaypee other infections usually resolves with Prednisolone for 4 weeks and alternating with suitable antibiotics). chlorambucil (0.2 mg/kg for 4 weeks) for a period e. Focal and segmental glomerulonephritis: Treatment of six months is an alternative. Cyclophosphamide is symptomatic. The underlying systemic disease (1.5 mg/kg/d given for 1–2 years) is known to may be treated appropriately. delay the end stage disease. Associated blood f. Lupus Nephritis: First and second stages, no specific pressure and oedema must be treated. Prophylactic treatment is necessary. In the third stage, short anticoagulation useful in severe cases. Rituximab course of steroids is administered. Fourth stage can be considered like for SLE. is treated with methyl prednisolone (7–15 mg/ c. Membranoproliferative glomerulonephritis: In kg/d) given iv for 3 days followed by oral therapy in primary cases treatment with corticosteroids useful 270 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

in children unlike in adults. The secondary forms are Nephrolithiasis treated by targeting against the underlying cause like Hepatitis–C. If it progresses rapidly, plasmaperesis • General management: Relieve pain with analgesics and may be helpful. antispasmodic drugs (vide supra). Encourage high fluid d. Proliferative mesangial glomerulonephritis: Treat intake 3–5 litres per day and low salt. Potassium citrate with prednisolone (2 mg/kg/d up to 80 mg/d is given can be instituted in hypocitraturia and in gouty diathesis till remission occurs or for 8 weeks). If ineffective or (20 mEq twice daily). Treat concurrent infection. Watch relapse occurs cyclophosphamide (1–2 mg/kg/d for for any increasing obstruction (if the obstruction is 8 weeks) is given. longer than four weeks, renal damage may result). e. Focal/segmental glomerulosclerosis: Prednisolone Attempt to sieve urine, for any stones passed for analysis (120 mg on alternate days for eight weeks and (calculi < 6 mm) usually pass off within four weeks. tapered over four weeks) is beneficial. If relapses • Pharmacologic intervention occur, cyclophosphamide or chlorambucil with • Specific stone therapy: Any known cause of calculi must prednisolone for eight weeks is useful. Hypertension be corrected. and oedema are to be corrected. Renal failure should a. Uric acid stones: Allopurinol (100 mg tds), xanthine be appropriately managed, if necessary. oxidase inhibitor is beneficial (prophylaxis). f. Diabetic nephropathy: Tight control of blood Alkalinise the urine with sodium bicarbonate, 1–2 glucose may delay diabetic nephropathy (metformin mEq/kg (1 g = 12 mEq), in divided doses. Potassium should not be given. Sulphonylureas which are citrate or acetazolamide can be given. Reduce purine metabolised then excreted like glipizide, must be diet like meat and beans. chosen; dose of insulin must be adjusted daily) b. Calcium stones: Thiazide (Bendrofluazide 5 mg/d) Effective management of hypertension (with ACE decreases calcium excretion. Restrict salt as it inhibitors and/or angiotensin II receptor antagonists negates hypocalciuric effects of thiazide. Neutral or diuretics like loop diuretics and spironolactone) phosphate (1.5 g tds) or sodium cellulose phosphate and dietary restriction of protein (0.5 g/kg/d) may (5 g bd) are the alternatives. Avoid calcium rich diet delay progression to renal failure. If hyperkalaemia like milk and cheese or vitamin D supplements. present control with diet and drugs like calcium c. Oxalate stones: Thiazides, and pyridoxine are gluconate; insulin + glucose; kayexalate + sorbitol beneficial along with alkalinisation. Avoid rhubarb, (Rafer to Chapter ‘Paraplegia’) If renal failure sets in, spinach, tomato, chocolates, tea. Vitamin C (2 g/d) treatment for chronic renal failure must be instituted. Brothersis useful for hyperoxaluria. Continuous ambulatory peritoneal dialysis is better d. Phosphatic stones: Acidify urine, since alkalinisation than haemodialysis. Renal transplantation in favours calculi. selected cases may be successful. (Refer to Chapter e. Cystine stones: Alkalinise the urine. Prescribe low titled ‘Polyuria’). methionine diet. Penicillamine may be advised (start g. Deposition Disorders (Dysproteinaemias): 0.5 g/d and increase to 1 g/d). Mercaptopropionyl Melphalan and prednisolone can improve renal glycine (1–2 mg/day in divided doses) increases function. In secondary forms remission can occure if solubility of cystine by breakage and exchange of causative agent is targeted. (Refer to Chapters titled disulphide bonds. ‘Bleeding Disorders’ ‘Chronic Diarrhoea’ and ‘Low f. Struvite stones: Avoid phosphates and infections with Backache’) urea-splitting organisms. Antibiotics beneficial for h. Infections associated: (Refer to Appendix AIDs and triple phosphate staghorn stones. Acidification of Chapter titled ‘Jaundice’) urine is recommended. Surgery and irrigation with i. Others: Refer to Chapter titled ‘Fatigue’ and hemiacidrin advocated or lithotripsy. ‘Jaundice’. j. HeredofamilialJaypee diseases (Vide infra). Interventional Therapy • Percutaneous nephrolithotomy; Antegrade Neph Interstitial Nephritis rostomy Percutaneous chemolysis (with Trishydroxy (Tubular Predominantly) Methyl Amine Methane (THAM) dissolves uric acid Withdrawal of drugs like analgesics may stabilise the and cystine stones; surgical lithotomy (endourologic renal function. Other causes like bacterial pyelonephritis, stone extraction with Dornier basket or open surgical multiple myeloma, Sjögren’s syndrome or metabolic removal); lithotripsy (Extracorporeal Shock Wave disorders, if incriminated, may be treated. If acute or Lithotripsy [ESWL]), (electrohydraulic lithotripsy or chronic renal failure occurs, treat accordingly. ultrasonic lithotripsy) are indicated when the stones Haematuria 271

Brothers

Jaypee 272 Differential Diagnosis and Medical Therapeutics—A Treatise on Clinical Medicine

cannot be dissolved or stones are associated with to lie on his abdomen or adopt knee-elbow position. Hot obstruction of one month duration. Laser therapy is an fomentations applied over the site. Buprenorphine may be alternative. administered. Nephrectomy is indicated in Dietl’s crises or hydronephrosis. Prophyalxis Oxaluria • Mandelamine may be considered to prevent infection in nephrolithiasis, since it liberates formaldehyde Treatment consists of avoiding diet containing oxalates and and lowers pH of urine, apart from high fluid intake those which facilitate excessive carbohydrate fermentation and appropriate dietary and drug schedule to prevent in the intestine as well as foods with high purine content. nephrolithiasis. Administration of magnesia prevents formation of calcium oxalate crystals. Rendering the urine strongly acidic reduces calculi of oxalates. Neoplasms In hyperoxaluria, cholestyramine (8–16 g per day) Early surgery offers encouraging results for renal carcinoma. helps in binding oxalate or calcium lactate (8–14 g per Radiotherapy and progesterone like hormones are helpful day) precipitates oxalate in the gut. High fluid intake and for metastases. pyridoxine (200 mg/d) are beneficial. Prevention aimed by Wilms’ tumour is radiosensitive and chemotherapy is giving pyridoxine (up to 10 mg) per day. effective. Endoscopic resection and intravesical chemotherapy with thiotepa or epodyl advised for bladder carcinoma. Ureteric Lesions BCG vaccine may be effective. Total cystectomy and Ureteric calculus: Calculi with less than 0.6 cm diameter transplantation of ureters into ileal channel may become may pass off spontaneously. The ureterorenal colic may necessary at times. be trea ted symptomatically and antibiotics administered for control of infection. If progessive hydronephrosis or Renovascular recurrent infections occur the calculus is better removed either by cystoscopic manipulations or surgery or i. Surgical revascularisation and angioplasty yield results lithotripsy. in renal artery stenosis. TumoursBrothers: If benign, local excision may be done. Otherwise, ii. Renal vein thrombosis: Established cases need oral anticoagulant therapy till the symptoms subside. Risks nephroureterectomy and removal of periureteral vesical of pulmonary embolism and impaired renal function area may be considered. may be treated accordingly, if necessary. Ureterocele: If large, transvesical excision and reimplan tation of both ureters into the bladder may be done. Hereditary Nephroureterectomy is indicated, if the kidney is damaged. • Polycystic kidney: Treat promptly urinary infection and Trauma: Ureteral ligation or end to end anastomosis or associated hypertension. Sodium chloride and sodium reimplantation of ureter into the bladder or transuretero bicarbonate may be supplemented in salt losing states. If stomy or nephrectomy considered as the case may be. renal function deteriorates, treat as chronic renal failure. Scanning of family members and genetic counselling may be undertaken. Treatment of Haematuria due to General (Systemic) Diseases Renal Trauma Treated symptomatically in addition to specific therapy for Shock and haemorrhageJaypee are treated with blood transfusion. the underlying systemic cause. Persistent bleeding requires surgical exploration and 1. Haematological (Refer to Chapters titled ‘Bleeding nephrectomy, if necessary. Disorders’ and ‘Fatigue’) 2. I nfections (Refer to Chapters titled ‘PUO’ and ‘Oedema’) 3. Hypertension (Refer to Chapter titled ‘Headache’) Movable kidney and Dietl’s crises 4. Diabetic renal lesions (Refer to Chapter titled ‘Polyuria’) Abdominal support and breathing exercises to improve 5. Collagen diseases (Refer to Chapter titled ‘Polyarthritis’) muscle tone may suffice. In Dietl’s crises, patient is advised 6. Drugs (Withdraw the offending drug).