Review of Pathology and Genetics Gobind Rai Garg, Sparsh Gupta
INDEX
×
Chapter Notes

Save Clear


1Review of Pathology and Genetics
Eighth Edition
Gobind Rai Garg MBBS MD (Gold Medalist) Ex-Assistant Professor (Pharmacology) MAMC, Delhi, India Director Ayush Institute of Medical Sciences Delhi, India Sparsh Gupta MBBS MD (Gold Medalist) Assistant Professor (Pharmacology) VMMC and Safdarjung Hospital, Delhi, India
2
Jaypee Brothers Medical Publishers (P) Ltd
Headquarters
Jaypee Brothers Medical Publishers (P) Ltd
4838/24, Ansari Road, Daryaganj
New Delhi 110 002, India
Phone: +91-11-43574357
Fax: +91-11-43574314
Overseas Offices
J.P. Medical Ltd
83, Victoria Street, London
SW1H 0HW (UK)
Phone: +44-20 3170 8910
Fax: +44 (0)20 3008 6180
Jaypee-Highlights Medical Publishers Inc
City of Knowledge, Bld. 237, Clayton
Panama City, Panama
Phone: +1 507-301-0496
Fax: +1 507-301-0499
Jaypee Medical Inc.
325 Chestnut Street
Suite 412
Philadelphia, PA 19106, USA
Phone: +1 267-519-9789
Jaypee Brothers Medical Publishers (P) Ltd
17/1-B, Babar Road, Block-B, Shaymali
Mohammadpur, Dhaka-1207
Bangladesh
Mobile: +08801912003485
Jaypee Brothers Medical Publishers (P) Ltd
Bhotahity, Kathmandu, Nepal
Phone: +977-9741283608
© 2016, Gobind Rai Garg, Sparsh Gupta
The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book.
All rights reserved. No part of this publication maybe reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers.
All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book.
Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book.
This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought.
Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity.
Inquiries for bulk sales may be solicited at: jaypee@jaypeebrothers.com
Assistant Editors: Mrs Praveen Kumari, Mrs Krishna Gupta
Review of Pathology and Genetics
First Edition: 2009
Second Edition: 2010
Third Edition: 2011
Fourth Edition: 2012
Fifth Edition: 2013
Sixth Edition: 2014
Seventh Edition: 2015
Eighth Edition: 2016
9789385999482
Printed at
3Dedicated to
My parents, wife Praveen,
son Ayush and other family members
—Gobind Rai Garg
My family members and
my teachers (Shri SK Suri and Mrs V Gopalan)
—Sparsh Gupta4
5Preface to the Eighth Edition
We acknowledge the support shown by each of our esteemed readers (present and past) for placing the book at the numero uno position amongst the pathology books for PGMEE. To meet the expectations of students, we have tried to further improve this eighth edition.
The book has been fully colored to increase its appeal to the esteemed readers. We have intentionally chosen the topic of ‘Immunology’ because apart from being very important, it is considered as one of the most difficult chapters of Pathology.
Dear friends, the apprehension regarding the National Eligibility Cum Entrance Test (NEET) has now been taken care of as the examination pattern has not been modified drastically. Cracking the NEET exam and other important PG examinations require a thorough knowledge and understanding of the subject. Readers of this book have got an edge over others in the National Eligibility Cum Entrance Test (NEET) because of the strong theory and conceptual questions. This along with the key points given under the heading of various boxes in the chapters has helped many of you to get extremely good ranks in NEET 2013, 2014, 2015 and 2016.
It is a humble request from our side that all the chapters (and not only general pathology) of this book has to be read by the student so as to maximize the benefit. This is because many additional concepts and questions asked frequently in the exam have been explained in systemic pathology chapters. This is one important point which came as a gist differentiating the people getting a good rank in NEET versus those who did not.
In our constant endeavor to improvise the book, there has been incorporation of important additions in almost all chapters along with the new section of Most recent questions. The question bank of the every chapter has been subdivided into smaller portions. It will help students to solve MCQs after reading the theory of a particular topic of a chapter.
For getting a grasp on the NEET questions in a better way, a new section in the end comprising of Image Based Questions has also been added.
In this eighth edition, we have added a lot of diagrams and flow charts to make learning interesting and easier. Another salient feature of this edition is the updating of appropriate authentic references from standard textbooks particularly in regard to the controversial questions so that reader gets all the relevant information under one roof. Other salient features of the current edition are:
We have fully revised the book and corrected the typographical and some other errors present in the previous editions. We have also added plenty of vital information under the heading of ‘Concept’, ‘Info’ and ‘Subject Links’ at multiple places in almost all the chapters in the book. Further, we have also expanded some of the old topics.
Questions from latest entrance examinations of AIIMS have been added. Several other questions have been incorporated from PGI, DNB and other state PG entrance examinations. In some topics, there are contradictions between different books. In such a situation, we have quoted the text from Harrison's Principles of Internal Medicine, 18th edition.
To help the students to understand the subject better, Dr Gobind has started Ayush Institute of Medical Sciences. Any query regarding the admission in the same maybe addressed to Dr Gobind at the under mentioned e-mail ID.
We must admit hereby that despite keeping an eagle's eye for any inaccuracy regarding factual information or typographical errors, some mistakes must have crept in inadvertently. You are requested to communicate these errors and send your valuable suggestions for the improvement of this book. Your suggestions, appreciation and criticism are most welcome.
March 2016
Gobind Rai Garg
Sparsh Gupta
6Preface to the First Edition
Pathology is one of the most difficult and at the same time most important subject in various postgraduate entrance examinations.
As we experienced it ourselves, most of the students preparing for postgraduate entrance examinations are in a dilemma, whether to study antegrade or retrograde. Antegrade study takes a lot of time and due to bulky textbooks, some important questions are likely to be missed. In a retrograde study, the students are likely to answer the frequently asked MCQs but new questions are not covered. We have tried to overcome the shortcomings of both of the methods while keeping the advantages intact.
In this book, we have given a concise and enriched text in each chapter followed by MCQs from various postgraduate entrance examinations and other important questions likely to come. The text provides the advantage of antegrade study in a short span of time.
After going through the book, it will be easier for the student to solve the questions of most recent examinations, which are given at the end of the book.
Eighth edition of Robbins is just to strike the Indian market. We have arranged this edition directly from US and added the references from its text. Further, important differences between 7th and 8th edition of Robbins have been mentioned with the relevant questions.
It is very difficult and at times very confusing to remember large number of pathological features. To make learning easy, several easy to grasp MNEMONICS have been given throughout the text.
Despite our best efforts, some mistakes might have crept in, which we request all our readers to kindly bring to our notice. Your suggestions, appreciation and criticism are most welcome.
Gobind Rai Garg
Sparsh Gupta
7Acknowledgments
When emotions are profound, words sometimes are not sufficient to express our thanks and gratitude. With these few words, we would like to thank our teachers at University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, for the foundation they helped to lay in shaping our careers.
We are especially thankful to Dr KK Sharma, Ex-Professor and Head, Department of Pharmacology, UCMS, Delhi who has been a father-figure to whole of the department.
We would also like to acknowledge the encouragement and guidance of Prof CD Tripathi, (Director Professor and Head, Pharmacology, VMMC and Safdarjung Hospital), Dr SK Bhattacharya (Professor and Head, Hindu Rao Hospital), Dr Uma Tekur (Director Professor, MAMC), Col (Dr) AG Mathur (Professor, ACMS), Dr Vandana Roy (MAMC) and Dr Shalini Chawla (MAMC), all professors in the department of Pharmacology, in the completion of this book.
We feel immense pleasure in conveying our sincere thanks to all the residents of department of Pharmacology at VMMC, MAMC and ACMS for their indispensable help and support.
No words can describe the immense contribution of our parents, Ms Praveen Garg, Ms Ruhee, Mr Nitin Misra, Ms Dhwani Gupta, Mr Rohit Singla and Mrs Komal Singla, without whose support this book could not have seen the light of the day.
We want to extend our special thanks to Dr Sonal Aggarwal (ESI Hospital, Delhi) and Dr Raina SG (AIIMS, Delhi) for their unconditional support in the making of this edition.
We would also like to extend our special thanks to Dr Sonal Pruthi (UCMS, Delhi), Dr Smiley M Gupta (Kerala), Dr Ashita (Punjab), Dr Saurabh Jain (TSMA, Tver, Russia), Dr Amrita Talwar (ACMS, Delhi), Dr Avinash A, Dr Nikita Mary Baby, Dr Mamta Nikhurpa, Dr Rihas Mohammed, Dr Anuradha Tiwari (ACMS, Delhi) and Dr Sandeep Goel (MD Radiodiagnosis, AIIMS).
Although it is impossible to acknowledge the contribution of all individually, we extend our heartfelt thanks to:
  • Dr Bhupinder Singh Kalra, Assistant Professor (Pharmacology), MAMC, Delhi
  • Lt Col (Dr) Dick BS Brashier, Associate Professor (Pharmacology), AFMC, Pune
  • Lt Col (Dr) Sushil Sharma, Associate Professor (Pharmacology), AFMC, Pune
  • Lt Col (Dr) Dahiya, Associate Professor (Pharmacology), AFMC, Pune
  • Dr Nitin Jain, DCH, DNB (Pediatrics, Std), Delhi
  • Dr Sushant Verma, MS (General Surgery), MAMC, Delhi
  • Dr Kapil Dev Mehta, MD (Pharmacology), UCMS, Delhi
  • Dr Saurabh Arya, MD (Pharmacology), UCMS, Delhi
  • Dr Deepak Marwah, MD (Pediatrics), MAMC, Delhi
  • Dr Shubh Vatsya, MD (Medicine), MAMC, Delhi
  • Mr Rajesh Sharma, MBA
  • Dr Puneet Dwivedi DA (Std), Hindu Rao Hospital, Delhi
  • Dr Sandeep Agnihotri, DVD, Safdarjung Hospital, Delhi
  • Dr Harsh Vardhan Gupta MD, Pediatrics (Std), Patiala
  • Mr Tarsem Garg, LLB, DM, SBOP
  • Dr Pardeep Bansal, MD (Radiodiagnosis), UCMS, Delhi
  • Dr Pankaj Bansal, MS (Orthopedics), RML Hospital, Delhi
  • Dr Pradeep Goyal, MD (Radiodiagnosis), LHMC, Delhi
  • Dr Rakesh Mittal, MS (Surgery), Safdarjung Hospital, Delhi
  • Dr Amit Miglani, DM (Gastroenterology), PGI, Chandigarh
  • Dr Sachin Gupta DA, DMC (Ludhiana)
  • Dr Reenu Gupta DGO BMC (Bangalore)
  • Dr Shiv Narayan Goel, MCh (Urology), KEM, Mumbai
  • 8Dr Kamal Jindal, Assistant Professor (Physiology), LHMC, Delhi
  • Dr Gaurav Jindal, MD, Radiodiagnosis Resident, Boston, USA
  • Dr Saket Kant, MD (Medicine UCMS), DM (Endocrinology, BHU)
  • Dr Mukesh Kr Joon, DM (Cardiology), Udaipur, Rajasthan
  • Dr Amit Garg, Assistant Professor (Psychiatry), IHBAS, Delhi
  • Dr Garima Mahajan, MD (Pathology), UCMS, Delhi
  • Dr Ravi Gupta, MD (Psychiatry), Jolly Grants Medical College, Dehradun, Uttarakhand
  • Dr Shashank Mohanty, MD (Medicine), Udaipur, Rajasthan
  • Dr Amit Shersia, MS (Orthopedics), MAMC, Delhi
  • Dr Mohit Gupta, DCP, DNB (Pathology), Delhi
  • Dr Mayank Dhamija, DCH, DNB (Pediatrics), DNB (Hemato-oncology), Delhi
Last but not the least, we would like to thank Shri Jitendar P Vij (Group Chairman), M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India, publishers of this book and the entire PGMEE team, for their keen interest, innovative suggestions and hardwork in bringing out this edition.
March 2016
Gobind Rai Garg
Sparsh Gupta
9Advisory Editorial Board
  • Dr Swapnil Aggarwal, MBBS (LHMC), MD (MAMC)
  • Dr Mohit Gupta, DCP, DNB (JJ Medical College, Davangere)
  • Dr Garima Mahajan, MD, DNB (UCMS)
  • Dr Amandeep Kaur, MD, (PGI Chandigarh)
  • Dr Paritosh Garg, MD (UCMS)
  • Dr Ashish K DM (AIIMS)
  • Dr INI Nair, MD Kochi
References
  • Robbin's Pathological basis of diseases, 9th edition
  • Harsh Mohan's Textbook of Pathology, 7th edition
  • Harrison's Principles of Internal Medicine, 18th edition
  • Current Medical Diagnosis and Treatment 2015
  • Wintrobe's Clinical Hematology, 12th edition
  • Ackerman's Surgical Pathology, 10th edition
  • Sternberg's Diagnostic Surgical Pathology, 5th edition
 
SYMBOLS USED IN BOXES ON ‘HIGH YIELD POINTS’
  • Key points
  • Definition
  • Mnemonic
  • Concept
  • Questions asked in most recent exam
101112
13IMPORTANT NOTES OF NEW CHAPTER ADDED IN ROBBINS 9TH EDITION  
CELL AS A UNIT OF HEALTH AND DISEASE
  • Virchow coined the term ‘cellular pathology’
  • The human genome contains roughly 3.2 billion DNA base pairs and only about 2% is used for coding of proteins.
  • 80% of the human genome either binds proteins, implying it is involved in regulating gene expression, or can be assigned some functional activity, mostly related to the regulation of gene expression, often in a cell-type specific fashion.
  • The two most common forms of DNA variation in the huxivxiiiman genome are single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs).
  • SNPs are variants at single nucleotide positions and are almost always biallelic (i.e., only two choices exist at a given site within the population, such as A or T).
  • CNVs are a more recently identified form of genetic variation consisting of different numbers of large contiguous stretches of DNA from 1000 base pairs to millions of base pairs.
  • Epigenetics is defined as heritable changes in gene expression that are not caused by alterations in DNA sequence.
  • Nuclear chromatin exists in two basic forms:
  • Different histone modifications are generically called as marks. The modifications include methylation, acetylation, or phosphorylation of specific amino acid residues on the histones.
Gene regulation can also be done through noncoding RNAs which can be of the following subtypes:
  1. MicroRNAs (miRNA): The miRNAs are small RNA molecules 22 nucleotides in length which do not encode proteins. They function primarily to modulate the translation of target mRNAs into their corresponding proteins.
  2. Long noncoding RNAs (lncRNA): RNAs are >200 nucleotides in length. Its example includes XIST, which is transcribed from the X chromosome and plays an essential role in physiologic X chromosome inactivation.
MiRNA associated with cancers are called oncomiRs. They act by increasing the number of cancer causing genes and suppress the tumor suppressor genes.
The non coding RNAs fall into several classes:
  • Piwi-interacting RNAs (piRNAs), the most common type of small noncoding RNA, which (like miRs) are believed to have a role in post-transcriptional gene silencing;
  • Sno RNAs, which are important in maturation of rRNA and the assembly of ribosomes; and
  • Long intervening noncoding RNAs (lincRNAs), some of which regulate the activity of chromatin “writers,” the factors that modify histones and thereby control gene expression
 
CELLULAR HOUSEKEEPING (as per 9th edition of Robbins)
Organelles
Key points
Mitochondria
Oxidative phosphorylation
Intermediates for heme synthesis
Intrinsic pathway of Apoptosis (programmed cell death)
Smooth endoplasmic reticulum (SER)
Abundant in gonads and liver
Used for lipoprotein and steroid hormone synthesis,
Required for converting the hydrophobic compounds like drugs into water-soluble molecules
Sequestration of calcium
Proteasomes
Required for selectively chewing of denatured proteins using ubiquitin.
Also needed for presentation of peptides in context of the class I major histocompatibility molecules
Peroxisomes
Breakdown of fatty acids
14
Plasma membrane proteins
Phosphatidylinositol serves as scaffold for intracellular proteins as well as for the generation of intracellular second signals like diacylglycerol and inositol trisphosphate.
Phosphatidylserine is required for apoptosis (programmed cell death) and on platelets, it serves as a cofactor in the clotting of blood.
Glycolipids are important in cell-cell and cell-matrix interactions, including inflammatory cell recruitment and sperm-egg interactions.
Lysosomes
Most cytosolic enzymes prefer to work at pH 7.4 whereas lysosomal enzymes function best at pH 5 or less.
Golgi apparatus
Mannose 6 phosphateQ is the marker
  • Exocytosis is the process by which large molecules are exported from cells. In this process, proteins synthesized and packaged within the RER and Golgi apparatus are concentrated in secretory vesicles, which then fuse with the plasma membrane and expel their contents.
  • Transcytosis is the movement of endocytosed vesicles between the apical and basolateral compartments of cells. It is a mechanism for transferring large amounts of intact proteins across epithelial barriers.
  • Potocytosis is literally “cellular sipping.” whereas pinocytosis is “cellular drinking
  • Endocytosis is the uptake of fluids or macromolecules by the cell. It could be of the following types:
    1. Caveolae-mediated endocytosis: CaveolinQ is the major structural protein of caveole. Internalization of caveolae with any bound molecules and associated extracellular fluid is sometimes called potocytosis—literally “cellular sipping.”
    2. Pinocytosis and receptor mediated endocytosis: Pinocytosis (“cellular drinking”) describes a fluid-phase process during which the plasma membrane invaginates and is pinched off to form a cytoplasmic vesicle. Receptor-mediated endocytosis is the major uptake mechanism for certain macromolecules like transferrin and low-density lipoprotein (LDL).
  • Most cytosolic enzymes prefer to work at pH 7.4 whereas lysosomal enzymes function best at pH 5 or less.
 
Cytoskeleton
The ability of cells to adopt a particular shape, maintain polarity, organize the relationship of intracellular organelles, and move about depends on the intracellular scaffolding of proteins called the cytoskeleton. The three major classes of cytoskeletal proteins are:
  1. Actin microfilaments are 5- to 9-nm diameter fibrils formed from the globular protein actin (G-actin), the most abundant cytosolic protein in cells.
  2. Intermediate filaments are 10-nm diameter fibrils that impart tensile strength and allow cells to bear mechanical stress. The examples include:
Clinical significance!
Since they have characteristic tissue-specific patterns of expression, they are useful for assigning a cell of origin for poorly differentiated tumors.
  1. Microtubules: these are 25-nm-thick fibrils composed of non-covalently polymerized dimers of α- and β-tubulin arrayed in constantly elongating or shrinking hollow tubes with a defined polarity. Within cells, microtubules are required to move vesicles, organelles, or other molecules around cells along microtubules. There are two varieties of these motor proteins: kinesins (for anterograde transport) and dyneins (for retrograde transport).
15
 
Mitochondrial function: key points
 
Receptors
Cell-surface receptors are generally transmembrane proteins with extra cellular domains that bind soluble secreted ligands. They can be of the following types:
  1. Ion channels (typically at the synapse between electrically excitable cells)
  2. G protein coupled receptors: activate an associated GTP-binding regulatory protein
  3. Enzymatic receptors: activate an associated enzyme usually tyrosine kinase
  4. Receptors which trigger a proteolytic event or a change in protein binding or stability that activates a latent transcription factor. Examples include Notch, Wnt, and Hedgehog receptors which regulate normal development.
 
Transcription factors
Summary of growth factors and the receptors
The major role of growth factors is to stimulate the activity of genes that are required for cell growth and cell division. They are also involved in the non-growth activities, including migration, differentiation, and synthetic capacity. Some important examples include:
  1. Epidermal Growth Factor and Transforming Growth Factor-α.
  1. Hepatocyte Growth Factor (also known as scatter factor)
  1. Platelet-Derived Growth Factor
    PDGF is stored in platelet granules and is released on platelet activation.
  2. Vascular Endothelial Growth Factor
  1. Fibroblast Growth Factor (FGF-7)
  • FGF-7 is also referred to as keratinocyte growth factor (KGF).
  1. Transforming Growth Factor-β
16TGF-β has multiple and often opposing effects depending on the tissue and concurrent signals. Agents with such multiplicity of effects are called pleiotropic.
 
Extracellular matrix
  • Laminin is the most abundant glycoprotein in basement membrane
  • The major constituents of basement membrane are amorphous nonfibrillar type IV collagen and laminin.
  • Collagens are typically composed of three separate polypeptide chains braided into a ropelike triple helixQ.