This page intentionally left blank This is an admirably concise and clear guide to Clinical Physiology fundamental concepts in physiology relevant to clinical practice. It covers all the body systems in an accessible style of presentation. Bulleted checklists and boxed information provide an easy overview and summary of the essentials. By concentrating on the core knowledge of physiology, it will serve as a useful revision aid for all doctors striving to achieve postgraduate qualification, and for anyone needing to refresh their knowledge base in the key elements of clinical physiology. The author’s own experience as an examiner at all levels has been distilled here for the benefit of postgraduate trainees and medical and nursing students. Dr Ashis Banerjee is Consultant in Emergency Medicine and serves as Examiner for those undertaking their MB, BS, MRCS and MFAEM examinations. Clinical Physiology An Examination Primer Ashis Banerjee Consultant in Emergency Medicine, Lewisham University Hospital cambridge university press Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo Cambridge University Press The Edinburgh Building, Cambridge cb2 2ru,UK Published in the United States of America by Cambridge University Press, New York www.cambridge.org Informationonthistitle:www.cambridge.org/9780521542265 © A. Banerjee 2005 This publication is in copyright. Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published in print format 2005 isbn-13 978-0-511-12927-8 eBook (EBL) isbn-10 0-511-12927-0 eBook (EBL) isbn-13 978-0-521-54226-5 paperback isbn-10 0-521-54226-x paperback Cambridge University Press has no responsibility for the persistence or accuracy of urls for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. Every effort has been made in preparing this publication to provide accurate and up-to-date information that is in accord with accepted standards and practice at the time of publication. Nevertheless, the authors, editors and publisher can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The authors, editors and publisher therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use. Contents Preface page vii 1 Cell physiology 1 2 Water and electrolyte balance 19 3 Acid–base balance 31 4 Renal physiology 44 5 Temperature regulation 66 6 Cardiovascular system 71 7 Respiratory system 115 8 Blood 140 9 Neurophysiology 177 10 Endocrine physiology 258 11 Gastrointestinal physiology 316 Index 349 v Preface The teaching of physiology at the undergraduate level often fails to provide its students with any enthusiasm or lasting zeal for the subject. This is regrettable because a good knowledge of normal human physiology is critically important in understanding the effects of organ dysfunction secondary to disease. Adequate treatment of the multiple insults to the body in the seriously ill patient requires a good understanding of the underlying pathophysiological mechanisms. Undoubtedly, the gradual demise of academic physiology in the United Kingdom has contributed to the current state of affairs. This book explains the basic concepts of physiology in a succinct and didactic fashion. Its aim is to aid the medical student and the junior doctor in obtaining a good understanding of the homeostatic mechanisms of the human body so that the effects of dysfunction of these mechanisms can be better understood. It is also designed to aid with the basic science component of the various royal college examinations that are required to be passed prior to entering specialist training in the United Kingdom. Ashis Banerjee vii Cell physiology 1 & Introduction The cell is the structural and functional unit of life. Bounded by a cell mem- brane, which maintains the homeostasis of the cell interior, it contains various membrane-bound compartments or organelles within, which subserve specia- lised functions. These membrane-bound organelles are characteristic of all eukaryotic cells, including those in humans. & Cell membrane The cell membrane bounds all cells in the human body, forming a dynamic interface between the intracellular and extracellular environments. It serves, or facilitates, the following functions: * The maintenance of cell shape and structure. This is achieved by the pre- sence of anchoring sites for cytoskeletal filaments and extracellular matrix components. * A transport function. This is brought about by selective permeability to ions and macromolecules, allowing the maintenance of cytosolic ionic composi- tion, osmotic pressure and pH (around 7.2–7.4). * Intercellular communication, involving signal transduction, i.e. the detec- tion of chemical signals (messengers) from other cells. These signals mediate nerve transmission, hormone release, muscle contraction and the stimulation of growth. This is the result of the binding of signalling molecules by trans- membrane receptors. * Intercellular adhesion. This is brought about by the fusion of the membrane with other cell membranes via specialised junctions. * Directed cell movement. 1 Cell physiology Structure of cell membranes The thickness of cell membranes ranges from 6–10 nm, typically being about 7.5 nm. * One nanometre is equal to 10À9 metre. Cell membranes are composed primarily of lipids and proteins. Lipids are the major components of membranes, including glycerophospholipids (phospho- glycerides), sphingolipids (sphingomyelin) and cholesterol. Cephalin (phospha- tidylethanolamine) and lecithin (phosphatidylcholine) are the most common glycerophospholipids in membranes. Membrane lipids form self-sealing bilayers. They are amphipathic molecules, with hydrophobic and hydrophilic moieties. The hydrophobic groups, the long fatty acyl side chains, form the core, with the polar hydrophilic groups lining both surfaces. Carbohydrates comprise 5%–10% of cell membranes. They consist of glyco- lipids and glycoproteins and form the glycocalyx coat on the surface of the plasma membrane. This layer is responsible for the immunological characteristics of the cell and carries surface receptors that are involved in molecular recognition. According to the fluid mosaic model of Singer and Nicolson cell membranes possess fluid structures, being considered as two-dimensional solutions of oriented globular proteins and lipids. They take the form of a continuous fluid but stable lipid bilayer, studded with an array of membrane-associated or membrane- spanning proteins. The fluidity of the membrane is determined by the degree of unsaturation of the constituent fatty acids. The lipids and proteins can undergo rotational and lateral movement.Membranes are structurally and functionally asymmetrical. This is due to asymmetrical orientation of integral and peripheral membrane proteins, laterally and transversely. Membranes are also electrically polarised, with the inside being negative with respect to the exterior. On electron microscopy, a trilaminar structure is evident. This consists of two dark outer bands, representing the polar heads of the membrane phospholipids and protein molecules on the inner and outer surfaces of the membrane, and an inner lighter band due to the nonpolar tails of the lipid molecules. Membrane proteins Classification of membrane proteins Membrane proteins can be classified according to their structural relationship to the lipid bilayer into: Integral proteins, which penetrate the lipid bilayer; Peripheral or extrinsic proteins, which are located outside the lipid bilayer; 2 Cell membrane Membrane protein functions Transport carriers in facilitated diffusion processes; Ion channels; Pumps involved in active transport; Receptors for hormones and neurotransmitters, e.g. G-proteins, which act as mole- cular switches: signal transduction; Cell to cell recognition and interaction; Junctional proteins in intercellular junctions: cell adhesion molecules; Second messenger enzymes. Lipid-anchored proteins, which lie outside the lipid bilayer but are covalently linked to lipid molecules within the bilayer. Properties of integral membrane proteins Integral membrane proteins demonstrate asymmetrical orientation in the mem- brane. They are amphipathic, with both hydrophobic and hydrophilic regions. If they span the membrane, they are known as transmembrane proteins. Removal from the membrane can be achieved by denaturation of the membrane, using either a detergent, e.g. ionic detergent sodium tetradecyl sulphonate, or the non-ionic detergent Triton X-100, or an organic solvent. Examples of integral membrane proteins include hormone receptors, ion channels, gap junction proteins, Naþ/Kþ-ATPase and histocompatibility antigens. Classification of cell membrane receptors Cell membrane receptors are classified according to the signal transduction mechanism involved into: * Ion channel-linked (ionotropic) receptors, which are coupled directly to ligand-gated ion channels. Examples include nicotinic acetylcholine recep- tors, ionotropic glutamate receptors,