BOOK
Medical Sciences E-Book
Jeannette Naish | Denise Syndercombe Court | Jeannette Naish | Denise Syndercombe Court
(2014)
Additional Information
Book Details
Abstract
An integrated approach to teaching basic sciences and clinical medicine has meant that medical students have been driven to a range of basic science textbooks to find relevant information. Medical Sciences is designed to do the integration for you. In just one book, the diverse branches of medical science are synthesised into the appropriate systems of the human body, making this an invaluable aid to approaching the basics of medicine within in a clinical context.
.An integrated approach to teaching basic sciences and clinical medicine has meant that medical students have been driven to a range of basic science textbooks to find relevant information. Medical Sciences does the integration for you. In just one book, the diverse branches of medical science are synthesised into the appropriate systems of the human body, making this an invaluable aid to approaching the basics of medicine within in a clinical context.
- Eleven new contributors.
- Completely new chapters on Biochemistry and cell biology, Genetics, The nervous system, Bones, muscle and skin, Endocrine and reproductive systems, The cardiovascular system, The renal system and Diet and nutrition.
- Completely revised and updated throughout with over 35 new illustrations .
- Expanded embryology sections with several new illustrations.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Medical Sciences | iii | ||
| Dedication | ii | ||
| Copyright | iv | ||
| Contents | v | ||
| Contributors | vii | ||
| Preface | ix | ||
| Acknowledgements | xi | ||
| Chapter 1: Introduction and homeostasis | 1 | ||
| CHAPTER 2 BIOCHEMISTRY AND CELL BIOLOGY | 1 | ||
| CHAPTER 3 ENERGY METABOLISM | 1 | ||
| CHAPTER 4 PHARMACOLOGY | 1 | ||
| CHAPTER 5 HUMAN GENETICS | 2 | ||
| CHAPTER 6 PATHOLOGY AND IMMUNOLOGY | 2 | ||
| CHAPTER 7 EPIDEMIOLOGY | 2 | ||
| SYSTEMS OF THE BODY | 2 | ||
| CHAPTER 16 DIET AND NUTRITION | 3 | ||
| HOMEOSTASIS | 3 | ||
| HOMEOSTATIC REGULATION MECHANISMS | 3 | ||
| Negative feedback | 4 | ||
| Homeostatic control of glucose metabolism | 4 | ||
| Thermoregulation | 4 | ||
| Human body temperature ( Clinical box 1.1) | 5 | ||
| Heat loss mechanisms | 5 | ||
| Heat gain mechanisms | 5 | ||
| Thermoneutral zones | 6 | ||
| Positive feedback ( Clinical box 1.2) | 6 | ||
| Feedforward ( Information box 1.1) | 6 | ||
| WATER AND ELECTROLYTES: HOMEOSTATIC CONTROL OF BODY FLUIDS | 7 | ||
| Fluid compartments | 7 | ||
| Movement of fluids between compartments | 8 | ||
| Properties of forces that drive fluid movement between compartments | 8 | ||
| Osmolarity | 8 | ||
| Tonicity ( Clinical box 1.3) | 8 | ||
| Effect of solutes on body fluids | 8 | ||
| Homeostatic control of fluid balance | 9 | ||
| Hormonal control of fluid balance ( Clinical box 1.4) | 9 | ||
| Behavioural control of fluid balance ( Clinical box 1.5) | 9 | ||
| Thirst | 9 | ||
| ACID–BASE BALANCE: HOMEOSTATIC CONTROL OF HYDROGEN IONS ( Clinical box 1.8) | 10 | ||
| Partial pressure of hydrogen ions | 10 | ||
| Physiological range of pH | 11 | ||
| Effect of pH on physiological processes | 11 | ||
| Sources of acid and alkali | 11 | ||
| Buffer systems | 11 | ||
| Bicarbonate/carbon dioxide | 11 | ||
| Protein buffers | 12 | ||
| Haemoglobin buffer system | 12 | ||
| Phosphate buffer system | 12 | ||
| Control of acid–base balance | 12 | ||
| Respiratory control of pH ( Clinical box 1.9) | 12 | ||
| Renal control of pH ( Clinical box 1.10) | 13 | ||
| Renal H + excretion | 13 | ||
| Renal bicarbonate reabsorption | 13 | ||
| Chapter 2: Biochemistry and cell biology | 15 | ||
| PRINCIPLES OF MOLECULAR INTERACTIONS | 16 | ||
| ATOMS | 16 | ||
| IONS | 16 | ||
| ACIDS AND BASES | 16 | ||
| CHEMICAL BONDS | 16 | ||
| Ionic bonds | 16 | ||
| Covalent bonds | 17 | ||
| Polar covalent bonds | 17 | ||
| Hydrogen bonds | 17 | ||
| Non-polar molecular interactions | 17 | ||
| ORGANIC COMPOUNDS | 17 | ||
| Spatial arrangement of organic molecules | 18 | ||
| CHEMICAL REACTIONS | 18 | ||
| Electrophiles and nucleophiles | 18 | ||
| Oxidation–reduction (redox) reactions | 18 | ||
| THE ENERGY CYCLE IN BIOLOGY | 18 | ||
| Potential energy of chemical bonds | 18 | ||
| Energy flow in chemical reactions | 19 | ||
| Activation energy | 19 | ||
| Metabolic energy generation | 19 | ||
| Anabolic and catabolic pathways | 19 | ||
| CHEMICAL ELEMENTS THAT FORM THE HUMAN BODY | 20 | ||
| WATER CONTENT AND THE MAIN FLUID COMPARTMENTS | 20 | ||
| ORGANIC BIOMOLECULES | 20 | ||
| CARBOHYDRATES | 21 | ||
| MONOSACCHARIDES, DISACCHARIDES AND POLYSACCHARIDES | 21 | ||
| Monosaccharides | 21 | ||
| The five-carbon sugars (pentoses) | 21 | ||
| The six-carbon sugars (hexoses) | 21 | ||
| Amino sugars and sugar-derived acids | 21 | ||
| Disaccharides | 21 | ||
| Polysaccharides | 21 | ||
| COMPLEX CARBOHYDRATES | 23 | ||
| LIPIDS ( Clinical box 2.2) | 23 | ||
| FATTY ACIDS | 23 | ||
| Triacylglycerols | 23 | ||
| Dietary fats | 24 | ||
| Essential fatty acids | 24 | ||
| Eicosanoids | 24 | ||
| CHOLESTEROL AND OTHER STEROIDS | 24 | ||
| Bile acids | 25 | ||
| Vitamin D | 25 | ||
| Steroid hormones | 25 | ||
| COMPLEX LIPIDS | 26 | ||
| Phospholipids | 26 | ||
| Sphingolipids | 26 | ||
| PURINES AND PYRIMIDINES | 26 | ||
| Synthesis and degradation of nucleotides | 27 | ||
| Nucleotide recycling: the salvage pathways | 28 | ||
| NUCLEIC ACIDS | 28 | ||
| DEOXYRIBONUCLEIC ACID | 28 | ||
| The primary structure of the nucleic acids | 29 | ||
| Secondary structure of DNA | 29 | ||
| The double helix | 29 | ||
| Complementarity of the DNA strands | 30 | ||
| Tertiary structure of DNA: chromatin and the nucleosomes | 30 | ||
| Mitochondrial DNA | 30 | ||
| DNA replication | 31 | ||
| DNA proofing and repair | 31 | ||
| Damage to DNA | 31 | ||
| RIBONUCLEIC ACIDS | 31 | ||
| Secondary structure of RNA | 31 | ||
| AMINO ACIDS | 32 | ||
| Structure of the amino acids | 32 | ||
| Dissociation of amino acids | 32 | ||
| Classification of amino acids | 32 | ||
| PROTEINS | 33 | ||
| The peptide bond | 34 | ||
| STRUCTURE OF PROTEINS | 34 | ||
| Primary structure | 34 | ||
| Secondary structure | 34 | ||
| Tertiary structure | 34 | ||
| Protein denaturation | 34 | ||
| Quaternary structure | 34 | ||
| Cooperativity between protein subunits | 34 | ||
| PROTEIN SYNTHESIS AND PROCESSING | 36 | ||
| Ribosomes | 36 | ||
| Transcription | 36 | ||
| Post-transcriptional modification of mRNA: splicing | 36 | ||
| Translation | 37 | ||
| Elongation of the polypeptide chain | 37 | ||
| Post-translational modification of proteins | 38 | ||
| Cellular protein targeting | 38 | ||
| Protein processing in the endoplasmic reticulum | 38 | ||
| Protein processing in the Golgi apparatus | 39 | ||
| Protein secretion | 39 | ||
| FUNCTIONS OF PROTEINS | 39 | ||
| STRUCTURAL PROTEINS | 39 | ||
| Collagens and proteins present in the extracellular matrix | 39 | ||
| Muscle | 40 | ||
| Cytoskeletal proteins | 40 | ||
| Immunoglobulins | 40 | ||
| Transport (binding) proteins | 40 | ||
| CATALYTIC PROTEINS: ENZYMES | 40 | ||
| Enzyme kinetics | 40 | ||
| Enzyme inhibition | 42 | ||
| Regulation of enzyme activity | 42 | ||
| Enzyme cofactors | 42 | ||
| Cell membranes | 43 | ||
| Proteins in cell membranes | 44 | ||
| CYTOPLASM | 44 | ||
| CYTOSKELETON | 44 | ||
| NUCLEUS | 45 | ||
| ENDOPLASMIC RETICULUM | 45 | ||
| GOLGI APPARATUS (GOLGI COMPLEX) | 45 | ||
| MITOCHONDRIA | 45 | ||
| LYSOSOMES | 45 | ||
| PROTEASOMES | 46 | ||
| PEROXISOMES | 46 | ||
| CELL JUNCTIONS | 46 | ||
| Tight junctions | 46 | ||
| Adhering junctions | 46 | ||
| Gap junctions | 46 | ||
| CELL ADHESION AND RECOGNITION | 46 | ||
| SIGNAL TRANSDUCTION IN CELLS | 46 | ||
| Hormones | 47 | ||
| Neurotransmitters | 47 | ||
| RECEPTORS | 47 | ||
| Cell surface (membrane) receptors | 47 | ||
| Signal transduction cascades | 47 | ||
| Intracellular receptors | 48 | ||
| MEMBRANE TRANSPORT | 48 | ||
| PASSIVE DIFFUSION | 48 | ||
| CARRIER MEDIATED TRANSPORT | 48 | ||
| Facilitated diffusion | 48 | ||
| Ion channels | 49 | ||
| Active transport | 49 | ||
| Na + /K + -ATPase | 49 | ||
| Other ATPases | 49 | ||
| Secondary active transport | 49 | ||
| COORDINATED ACTION OF TRANSPORTERS | 50 | ||
| ENDOCYTOSIS | 50 | ||
| EXOCYTOSIS | 51 | ||
| TRANSCYTOSIS | 51 | ||
| RECEPTOR-MEDIATED ENDOCYTOSIS | 51 | ||
| TRANSPORT OF SUBSTANCES IN THE BLOOD | 51 | ||
| ORGANS AND TISSUES | 51 | ||
| EPITHELIAL TISSUES | 51 | ||
| CONNECTIVE TISSUE | 53 | ||
| Fibrocollagenous tissues | 53 | ||
| Extracellular matrix | 53 | ||
| Cartilage, teeth and bone | 53 | ||
| Fat (adipose) tissue | 54 | ||
| Blood | 54 | ||
| MUSCLE | 54 | ||
| NERVOUS TISSUE | 55 | ||
| INTEGRATED LEARNING: THE SYSTEMIC APPROACH | 56 | ||
| Chapter 3: Energy metabolism | 57 | ||
| INTRODUCTION TO METABOLISM | 57 | ||
| ENERGY IS RELEASED BY CATABOLISM AND CONSUMED BY ANABOLISM | 57 | ||
| TRICARBOXYLIC ACID CYCLE | 59 | ||
| Control of the TCA cycle | 59 | ||
| ELECTRON TRANSPORT CHAIN AND OXIDATIVE PHOSPHORYLATION | 59 | ||
| Electron transport chain | 59 | ||
| Oxidative phosphorylation | 60 | ||
| Coupling of the electron transport chain and oxidative phosphorylation | 60 | ||
| Electron transport chain inhibition | 61 | ||
| Energy output | 61 | ||
| REGULATION OF FUEL METABOLISM | 61 | ||
| Binding of allosteric effectors to an enzyme to alter its affinity for substrate | 61 | ||
| Reversible activation and deactivation by covalent modification | 62 | ||
| Regulation of gene expression and transcription in response to changing metabolic demands | 62 | ||
| Action of hormones | 62 | ||
| When nutrients are plentiful | 62 | ||
| Metabolic adaptation to changes in energy requirement | 62 | ||
| FURTHER CONSIDERATIONS IN FUEL METABOLISM | 62 | ||
| Different tissues metabolise different energy substrates | 63 | ||
| How fuel is stored and transported between tissues | 63 | ||
| CARBOHYDRATE METABOLISM | 63 | ||
| REGULATION OF BLOOD GLUCOSE (GLYCAEMIA) | 63 | ||
| SOURCES OF BLOOD GLUCOSE | 63 | ||
| FOUR KEY PATHWAYS MAINTAIN AND UTILISE BLOOD GLUCOSE | 64 | ||
| GLUCOSE TRANSPORT | 64 | ||
| GLUT1 | 64 | ||
| GLUT2 | 64 | ||
| GLUT3 | 64 | ||
| GLUT4 | 64 | ||
| GLYCOLYSIS – THE ANAEROBIC CATABOLISM OF GLUCOSE | 65 | ||
| Importance of the anaerobic nature of glycolysis | 65 | ||
| For red blood cells | 65 | ||
| When a tissue’s oxygen supply is cut off | 65 | ||
| Energy-using reactions in glycolysis – glucose phosphorylation | 66 | ||
| Hexokinase | 66 | ||
| Glucokinase | 67 | ||
| One of the intermediate metabolites of glycolysis is G6P and at this point the pentose phosphate pathway branches off | 67 | ||
| Phosphofructokinase-1 (PFK-1) | 67 | ||
| PFK-1 activity is highly sensitive to the energy status of the cell | 67 | ||
| Regulation of PFK-1 | 68 | ||
| Regulation by energy status and allosteric effectors | 68 | ||
| Fructose-2,6-bisphosphate | 68 | ||
| In the liver | 68 | ||
| In muscle | 68 | ||
| Citrate and pH | 68 | ||
| Energy-producing stage of glycolysis – production of pyruvate and lactate | 69 | ||
| Reactions yielding ATP | 69 | ||
| Pyruvate kinase | 70 | ||
| Fate of pyruvate | 70 | ||
| In mitochondria-containing cells | 70 | ||
| Fed state | 70 | ||
| Fasted state | 70 | ||
| In cells that lack mitochondria, when oxygen is limited, and in starvation | 70 | ||
| Lactate dehydrogenase | 70 | ||
| OXIDATIVE GLUCOSE METABOLISM – AEROBIC GLYCOLYSIS | 71 | ||
| Pyruvate dehydrogenase complex | 71 | ||
| Regulation of PDC activity | 71 | ||
| GLYCOGEN – THE STORAGE FORM OF GLUCOSE | 72 | ||
| In the liver | 72 | ||
| In skeletal muscle | 72 | ||
| SYNTHESIS OF GLYCOGEN | 72 | ||
| Glycogenin, the glycogen primer | 73 | ||
| Glycogen synthase (GS) | 73 | ||
| Structure of glycogen | 73 | ||
| Control of glycogen synthesis | 73 | ||
| Allosteric activation of glycogen synthesis | 74 | ||
| Covalent mechanisms regulating glycogen synthesis | 74 | ||
| Glycogen synthesis in the liver | 74 | ||
| Direct versus indirect pathway of hepatic glycogen synthesis | 74 | ||
| Glycogen synthesis in skeletal muscle | 74 | ||
| GLYCOGENOLYSIS – THE BREAKDOWN OF GLYCOGEN | 75 | ||
| Glycogenolysis in liver | 75 | ||
| Glycogenolysis in muscle | 75 | ||
| REGULATION OF GLYCOGENOLYSIS | 75 | ||
| Regulation of hepatic glycogenolysis | 76 | ||
| Hormone regulation of hepatic glycogenolysis | 76 | ||
| MECHANISM OF GLUCAGON REGULATION OF GLYCOGENOLYSIS – HORMONE SIGNALLING | 76 | ||
| SYMPATHETIC STIMULATION | 76 | ||
| Enzyme regulation of hepatic glycogenolysis | 76 | ||
| REGULATION OF HEPATIC GLYCOGEN PHOSPHORYLASE | 77 | ||
| Regulation of phosphorylase kinase by covalent modification – phosphorylation | 77 | ||
| Amplification of the signalling cascade | 77 | ||
| Ca 2 + as a second messenger | 77 | ||
| Regulation of muscle and brain glycogenolysis | 77 | ||
| Genetic defects in glycogenolysis | 78 | ||
| GLUCONEOGENESIS – GLUCOSE SYNTHESIS | 78 | ||
| Precursors of gluconeogenesis | 78 | ||
| Gluconeogenesis from lactate | 78 | ||
| Gluconeogenesis from protein | 79 | ||
| Gluconeogenesis from glycerol | 80 | ||
| Peroxisome proliferator-activated receptors in energy homeostasis | 80 | ||
| Energy for gluconeogenesis | 80 | ||
| Cori and glucose–alanine cycles | 81 | ||
| Gluconeogenesis from sugars | 81 | ||
| Regulation of gluconeogenesis | 81 | ||
| AMINO ACID METABOLISM | 83 | ||
| METABOLIC CLASSES OF AMINO ACIDS ( Clinical box 3.13) | 83 | ||
| ABSORPTION OF AMINO ACIDS | 83 | ||
| NITROGEN IN AMINO ACID METABOLISM | 84 | ||
| Transamination | 84 | ||
| Amino acid release by skeletal muscle in the post-absorptive state | 84 | ||
| Deamination | 85 | ||
| Glutamine in acid–base homeostasis | 85 | ||
| Ammonia | 86 | ||
| Urea cycle ( Clinical box 3.16) | 86 | ||
| Regulation of the urea cycle | 86 | ||
| Nitrogen balance | 87 | ||
| AMINO ACIDS IN GLUCONEOGENESIS | 87 | ||
| ESSENTIAL AMINO ACIDS (See also Clinical box 3.17) | 87 | ||
| AMINO ACIDS AND SIGNALLING MOLECULES | 88 | ||
| Amino acids as neurotransmitters ( Clinical boxes 3.17 and 3.18) | 88 | ||
| Amino acids as precursors of neurotransmitters and hormones | 88 | ||
| LIPID METABOLISM ( Clinical box 3.19) | 88 | ||
| SOURCES OF FATTY ACIDS | 88 | ||
| Dietary fatty acids | 89 | ||
| Endogenously synthesised fatty acids | 89 | ||
| STORAGE OF LIPIDS | 90 | ||
| FATTY ACIDS | 90 | ||
| Protein-bound fatty acids | 90 | ||
| TRIACYLGLYCEROLS (TRIGLYCERIDES) | 91 | ||
| Regulation of triacylglycerol breakdown | 91 | ||
| LIPOPROTEINS | 91 | ||
| Apolipoproteins | 92 | ||
| Lipoprotein classes and functions | 92 | ||
| Chylomicrons | 92 | ||
| Very-low-density lipoprotein | 92 | ||
| Intermediate-density lipoprotein | 92 | ||
| Low-density lipoprotein | 92 | ||
| High-density lipoprotein | 92 | ||
| Lipoprotein receptors | 93 | ||
| Scavenger receptors | 93 | ||
| Lipoprotein metabolism | 93 | ||
| Reverse cholesterol transport | 93 | ||
| Lipoprotein fuel transport and overflow pathways | 93 | ||
| FATTY ACID OXIDATION | 93 | ||
| Fatty acid activation and transport into mitochondria | 93 | ||
| Carnitine shuttle | 94 | ||
| Carnitine shuttle in the regulation of fatty acid oxidation | 94 | ||
| β-Oxidation of fatty acids in mitochondria | 94 | ||
| Oxidation of acetyl-CoA in the TCA cycle | 94 | ||
| Inhibition of the β -oxidation spiral by excess CoA | 95 | ||
| Ketogenesis in the liver | 95 | ||
| Oxidation of acetyl-CoA in the ketogenic pathway | 95 | ||
| Role of ketone bodies in fuel homeostasis | 96 | ||
| Ketone body utilisation | 96 | ||
| LIPOGENESIS – FATTY ACID SYNTHESIS | 96 | ||
| Stage 1: ACC – the committed step of lipogenesis | 96 | ||
| Regulation of ACC activity | 98 | ||
| Acetyl-CoA contains an allosteric site for the binding of citrate or palmitoyl-CoA | 98 | ||
| ACC control by hormone-dependent covalent modification | 98 | ||
| The rate of ACC synthesis is highly regulated | 98 | ||
| Stage 2: fatty acid synthase (FAS) | 98 | ||
| Chain elongation | 98 | ||
| Desaturation | 98 | ||
| Regulation of fatty acid synthase and rate of lipogenesis | 98 | ||
| Malate shuttle – production of acetyl-CoA for lipogenesis | 98 | ||
| FINE-TUNING OF FATTY ACID SYNTHESIS, OXIDATION AND KETOGENESIS | 99 | ||
| REGULATION OF FAT METABOLISM | 100 | ||
| In the fasting (post-absorptive) state | 100 | ||
| In the fed (absorptive) state | 100 | ||
| Chapter 4: Pharmacology | 101 | ||
| INTRODUCTION | 101 | ||
| DIGOXIN – AN EXAMPLE IN CLINICAL PHARMACOLOGY | 102 | ||
| Pharmacodynamics – how digoxin works | 102 | ||
| Pharmacokinetics – how the body handles digoxin | 102 | ||
| Unwanted effects | 102 | ||
| Factors that contribute to digoxin toxicity | 102 | ||
| ABSORPTION – TRANSFER OF DRUGS ACROSS CELL MEMBRANES | 103 | ||
| PASSIVE DIFFUSION THROUGH LIPID MEMBRANES | 103 | ||
| Lipid solubility | 103 | ||
| Ionised and non-ionised forms of a drug | 104 | ||
| Degree of ionisation of a drug | 104 | ||
| Passive diffusion across cell membranes | 104 | ||
| Ion trapping | 104 | ||
| Effects of acidosis or alkalosis on absorption and distribution | 104 | ||
| CARRIER-MEDIATED TRANSPORT | 104 | ||
| Transporters (carrier proteins) | 105 | ||
| Ion channel proteins | 106 | ||
| ENDOCYTOSIS AND EXOCYTOSIS | 106 | ||
| DIFFUSION THROUGH AQUEOUS AND INTERCELLULAR PORES | 106 | ||
| Gap junctions | 106 | ||
| DRUG DISTRIBUTION | 106 | ||
| BLOOD FLOW | 106 | ||
| CAPILLARY PERMEABILITY AND GAP JUNCTIONS | 106 | ||
| Drug distribution to special organs | 107 | ||
| Central nervous system | 107 | ||
| Foetus | 107 | ||
| ACCUMULATION OF DRUG IN FAT AND REDISTRIBUTION IN OTHER TISSUES | 107 | ||
| BINDING OF DRUGS TO PROTEINS | 107 | ||
| Competitive protein binding | 108 | ||
| Hypoproteinaemia | 108 | ||
| Sequestration of drugs in tissues | 108 | ||
| DISTRIBUTION OF DRUGS IN THE BODY | 108 | ||
| Extent of drug distribution into aqueous compartments | 109 | ||
| Apparent volume of distribution | 109 | ||
| DRUG METABOLISM | 109 | ||
| PHASE I METABOLIC REACTIONS (PRE-CONJUGATION REACTIONS) | 110 | ||
| Oxidation | 110 | ||
| Microsomal oxidation reactions | 110 | ||
| Cytochrome P450 system | 110 | ||
| Non-microsomal oxidative reactions | 110 | ||
| Reduction | 111 | ||
| Hydrolysis – hydroxylation | 111 | ||
| PHASE II METABOLIC REACTIONS (CONJUGATION REACTIONS) | 112 | ||
| Conjugation by glucuronidation | 112 | ||
| Other conjugation reactions | 112 | ||
| Drug detoxification | 112 | ||
| FACTORS AFFECTING DRUG METABOLISM | 112 | ||
| Genetic factors | 112 | ||
| Environmental contaminants and drugs | 112 | ||
| Enzyme induction | 113 | ||
| Enzyme inhibition | 113 | ||
| Enzyme inhibition by metabolites | 113 | ||
| CONVERSION OF INACTIVE PRO-DRUG TO ACTIVE METABOLITE | 113 | ||
| EXCRETION OF DRUGS AND METABOLITES | 113 | ||
| RENAL SYSTEM | 113 | ||
| Glomerular filtration | 114 | ||
| Tubular secretion | 114 | ||
| Tubular reabsorption | 114 | ||
| Diuretic drugs | 115 | ||
| Diuretics acting on the loop of Henle | 115 | ||
| Chapter 5: Human genetics | 155 | ||
| INTRODUCTION | 155 | ||
| HISTORICAL BACKGROUND | 155 | ||
| BASIS OF MODERN GENETICS | 156 | ||
| THE HUMAN GENOME | 157 | ||
| DNA AND CHROMOSOMES | 157 | ||
| Chromosome karyotypes ( Fig. 5.2) | 157 | ||
| Mitochondrial DNA | 157 | ||
| Cell division | 158 | ||
| The cell cycle | 159 | ||
| Interphase | 159 | ||
| Mitosis ( Fig. 5.4) | 160 | ||
| Meiosis | 161 | ||
| Chromosome abnormalities | 163 | ||
| Abnormalities in number | 163 | ||
| Abnormalities in structure | 163 | ||
| DNA AND GENES | 166 | ||
| Homeobox (HOX) genes | 166 | ||
| Non-coding DNA (see Ch. 2) | 166 | ||
| Transcription ( Fig. 5.12) | 166 | ||
| Regulation of transcription | 167 | ||
| Translation | 167 | ||
| DNA DAMAGE | 168 | ||
| DNA damage from environmental factors | 168 | ||
| Spontaneous damage (DNA replication mistakes) | 168 | ||
| Repair mechanisms | 168 | ||
| Direct reversal of base damage | 168 | ||
| Breakage repair | 168 | ||
| Single-strand breaks | 168 | ||
| Double-strand breaks (DSBs) | 169 | ||
| GENES AND DEVELOPMENT | 169 | ||
| MEDIATORS OF DEVELOPMENT | 169 | ||
| Signalling molecules | 169 | ||
| Fibroblast growth factor and fibroblast growth factor receptor | 169 | ||
| Sonic hedgehog | 170 | ||
| Wingless (Wnt) | 170 | ||
| Transforming growth factor β | 170 | ||
| DNA transcription factors | 170 | ||
| SOX family genes | 170 | ||
| Extracellular matrix proteins | 170 | ||
| PATTERNING | 170 | ||
| Anterior/posterior axis formation | 170 | ||
| Left/right axis formation | 170 | ||
| Dorsal/ventral axis development | 170 | ||
| ORGANOGENESIS | 171 | ||
| Neuronal development | 171 | ||
| The asymmetrical heart | 171 | ||
| Organ formation | 171 | ||
| Limb development | 171 | ||
| HUMAN GENETIC VARIATION | 172 | ||
| POLYMORPHISMS | 172 | ||
| Mutation or polymorphism? | 172 | ||
| Types of mutational events leading to polymorphisms | 172 | ||
| Single nucleotide polymorphisms | 172 | ||
| Deletions and insertions ( Clinical box 5.6) | 172 | ||
| Gene duplications | 173 | ||
| Consequences of genetic mutation | 173 | ||
| Founder effects | 173 | ||
| Genghis Khan and the founder effect | 173 | ||
| Bottlenecks | 174 | ||
| Population drift | 174 | ||
| Genotypes, phenotypes and genetic penetrance | 176 | ||
| MODES OF INHERITANCE | 177 | ||
| MENDELIAN DISORDERS | 177 | ||
| Autosomal dominant inheritance ( Figs 5.22 and 5.23) | 177 | ||
| Autosomal recessive inheritance ( Figs 5.24 and 5.25) | 178 | ||
| Consanguinity and recessive disorders | 178 | ||
| Coefficient of relationship | 178 | ||
| Rare disorders and consanguinity | 179 | ||
| X-linked inheritance | 179 | ||
| Lyonisation | 179 | ||
| Dominant X-linked inheritance ( Figs 5.26 and 5.27) | 179 | ||
| Recessive X-linked inheritance ( Figs 5.28 and 5.29) | 180 | ||
| Haemophilia – the royal disease | 181 | ||
| Other modes of inheritance | 181 | ||
| Genomic imprinting | 181 | ||
| Mitochondrial disorders | 182 | ||
| Mosaicism | 182 | ||
| Inborn errors of metabolism (see Ch. 3) | 182 | ||
| POLYGENIC OR COMPLEX DISEASE | 183 | ||
| CONTINUOUS EFFECTS MODELS | 184 | ||
| THRESHOLD EFFECTS MODELS | 184 | ||
| CHARACTERISTICS OF MULTIFACTORIAL DISEASES | 184 | ||
| Heritability | 185 | ||
| Genetic epidemiology | 185 | ||
| Twin studies | 185 | ||
| Biases in twin studies | 186 | ||
| Adoption studies | 186 | ||
| Association studies | 186 | ||
| TOOLS TO INVESTIGATE POLYGENIC DISEASES | 186 | ||
| Information from single gene disorders | 186 | ||
| Animal models | 186 | ||
| Linkage studies | 186 | ||
| Expression profiles | 187 | ||
| Whole-genome association studies (WGAS) | 187 | ||
| CANCER GENETICS | 187 | ||
| CANCER AS A MULTI-STEP GENETIC DISEASE | 187 | ||
| INHERITANCE OF CANCER GENES | 187 | ||
| Colon cancer | 187 | ||
| CANCER GENES | 188 | ||
| Tumour suppressor genes | 188 | ||
| Retinoblastoma and the two-hit theory of carcinogenesis | 188 | ||
| Loss of heterozygosity | 188 | ||
| Oncogenes | 189 | ||
| Retroviruses | 189 | ||
| Transfection | 189 | ||
| DNA repair genes | 190 | ||
| IDENTIFYING DISEASE GENES | 190 | ||
| GENOME MAPPING | 190 | ||
| Physical maps | 191 | ||
| Low-resolution mapping | 191 | ||
| Karyotyping | 191 | ||
| Dosage mapping | 191 | ||
| Fluorescence in situ hybridisation (FISH) | 191 | ||
| High-resolution mapping | 191 | ||
| Sanger sequencing | 191 | ||
| Sequence tagged sites | 191 | ||
| Cloning | 192 | ||
| Chromosomal comparative genomic hybridization (CGH) arrays | 194 | ||
| Genetic linkage and monogenic disease | 194 | ||
| Linkage disequilibrium | 194 | ||
| LOD scores | 194 | ||
| Genetic linkage – a clinical example | 195 | ||
| Calculating the recombination frequency | 195 | ||
| Calculating the LOD score | 195 | ||
| LOD problems encountered in linkage studies | 195 | ||
| Locus heterogeneity | 195 | ||
| Incomplete penetrance | 196 | ||
| Phenocopies | 196 | ||
| Genetic linkage and polygenic disease | 196 | ||
| Restriction fragment length polymorphism | 196 | ||
| Variable number of tandem repeats | 196 | ||
| Single nucleotide polymorphisms | 196 | ||
| Genome microarrays | 197 | ||
| Personal genomics | 198 | ||
| Next generation sequencing (NGS) | 198 | ||
| Bioinformatic tools | 198 | ||
| THE HUMAN GENOME PROJECT | 199 | ||
| Can a DNA sequence be patented? | 199 | ||
| Beyond the sequence | 199 | ||
| What the HGP has already told us | 200 | ||
| Statistics | 200 | ||
| Functions | 200 | ||
| Structure | 200 | ||
| Variation | 200 | ||
| Comparison with other species | 200 | ||
| Using data from the HGP | 200 | ||
| Investigating the human genome | 200 | ||
| Gene families | 200 | ||
| Molecular phylogenetics | 201 | ||
| Protein modelling | 202 | ||
| X-ray crystallography | 202 | ||
| Nuclear magnetic resonance | 202 | ||
| Homology modelling | 202 | ||
| Model organisms | 202 | ||
| Mammals as model organisms | 202 | ||
| The mouse | 202 | ||
| Non-mammals as model organisms | 203 | ||
| Retroviruses | 203 | ||
| Bacteria and other microbes | 204 | ||
| Saccharomyces cerevisiae (baker’s yeast) | 204 | ||
| Archaea | 204 | ||
| Caenorhabditis elegans (round worm) | 204 | ||
| Drosophila (fruit fly) | 204 | ||
| Danio rerio (zebrafish) | 204 | ||
| GENETIC DISEASE, DIAGNOSIS AND THERAPY | 204 | ||
| GENE TESTING | 204 | ||
| Ethics | 204 | ||
| Genetic counselling | 204 | ||
| CONGENITAL DISEASE | 205 | ||
| Teratogens | 205 | ||
| PHARMACOGENOMICS | 205 | ||
| Antibiotics and pharmacogenomics ( Clinical boxes 5.15 and 5.16) | 207 | ||
| Evidence-based treatment (see also Ch. 7) | 207 | ||
| GENETIC MEDICINE | 207 | ||
| Metabolic manipulation | 207 | ||
| Protein augmentation | 208 | ||
| Stem cell therapies | 208 | ||
| Embryonic stem cell transplantation | 208 | ||
| Haematopoietic stem cell transplantation | 208 | ||
| Non-haematopoietic stem cell transplantation | 208 | ||
| Gene transfer | 208 | ||
| Ex vivo approach | 208 | ||
| In vivo approach | 209 | ||
| RNA modification | 209 | ||
| Future of genetic therapy | 209 | ||
| Chapter 6: Pathology and immunology | 211 | ||
| INTRODUCTION | 212 | ||
| INFECTION | 213 | ||
| BIOLOGICAL AGENTS | 213 | ||
| The burden of infectious disease | 213 | ||
| The variety of biological infectious agents | 213 | ||
| BACTERIA | 213 | ||
| STRUCTURE | 214 | ||
| Cytoplasm | 214 | ||
| Cell membrane (plasma membrane) | 214 | ||
| Cell wall | 214 | ||
| BACTERIAL CLASSIFICATION | 215 | ||
| OTHER BACTERIAL SURFACE FEATURES | 215 | ||
| UNUSUAL TYPES OF BACTERIA | 215 | ||
| REPLICATION | 215 | ||
| VIRUSES (see Information box 6.2) | 216 | ||
| NUCLEOCAPSID STRUCTURE | 216 | ||
| Genomic material | 216 | ||
| Capsid | 216 | ||
| HOST CELL INFECTION | 216 | ||
| VIRUS CLASSIFICATION | 217 | ||
| VIRUSES AND CANCER | 218 | ||
| FUNGI (see Information box 6.3) | 218 | ||
| STRUCTURE | 218 | ||
| Chapter 7: Epidemiology: science for the art of medicine | 277 | ||
| INTRODUCTION | 277 | ||
| THE EPIDEMIOLOGICAL APPROACH | 277 | ||
| EPIDEMIOLOGY AS THE DETECTIVE | 277 | ||
| The Broad Street pump | 277 | ||
| PATTERNS OF LIFE AND DEATH | 280 | ||
| Descriptive studies | 280 | ||
| Measuring disease occurrence | 280 | ||
| Disease incidence | 280 | ||
| Disease prevalence | 281 | ||
| Rates and relationship between incidence and prevalence | 281 | ||
| Measuring disease outcome | 281 | ||
| Births and deaths | 282 | ||
| Confidential enquiries | 282 | ||
| Disease surveillance | 282 | ||
| Cancer registration | 283 | ||
| Congenital anomalies notification | 283 | ||
| Communicable disease surveillance | 283 | ||
| Notification of infectious diseases | 283 | ||
| Examining data from different sources | 283 | ||
| Infectious disease surveillance and information sources | 283 | ||
| Global infectious disease surveillance | 284 | ||
| Special surveillance systems | 284 | ||
| Monitoring adverse reaction to drugs | 284 | ||
| Measures for health of populations | 284 | ||
| Mortality and life expectancy | 284 | ||
| Morbidity | 285 | ||
| The population census and health surveys | 285 | ||
| Measures for quality of life (QALYs) | 285 | ||
| Health inequalities | 285 | ||
| Health inequalities in the UK | 286 | ||
| Changes in health outcomes over time | 286 | ||
| Interpretation of data | 286 | ||
| Data inadequacies | 286 | ||
| Clustering | 288 | ||
| Socio-economic factors | 288 | ||
| Health-related behaviours | 288 | ||
| Healthcare facilities | 288 | ||
| Environmental factors | 288 | ||
| Migration | 289 | ||
| Standardisation of rates | 289 | ||
| Direct method of standardisation | 290 | ||
| Indirect method of standardisation | 290 | ||
| Choice of method for standardisation | 291 | ||
| EPIDEMIOLOGICAL ENQUIRY | 291 | ||
| SOME BASIC CONCEPTS IN EPIDEMIOLOGY | 291 | ||
| The distribution of data | 291 | ||
| The normal or Gaussian distribution curve | 292 | ||
| Measures of centre | 292 | ||
| The mean | 292 | ||
| The median | 292 | ||
| The mode | 292 | ||
| Measures of spread: standard deviation from the mean | 292 | ||
| Outliers | 292 | ||
| Ordered data and the interquartile range | 292 | ||
| How accurate is the distribution summary? | 293 | ||
| Contingency tables | 293 | ||
| Some statistical concepts used in epidemiological enquiry (hypothesis tests and p values) | 293 | ||
| Hypothesis tests | 294 | ||
| Tests of probability: p values and confidence intervals | 294 | ||
| AN OVERVIEW OF EPIDEMIOLOGICAL ENQUIRY | 296 | ||
| Investigation by observation: causation or association? | 296 | ||
| Observational studies | 296 | ||
| Cross-sectional studies | 297 | ||
| Sampling for cross-sectional studies | 297 | ||
| Interpreting the data from cross-sectional studies | 297 | ||
| Case–control studies | 297 | ||
| Selecting the sample for case–control studies | 298 | ||
| Analysing and interpreting data from case–control studies | 299 | ||
| Strength of the association | 299 | ||
| Consistency of findings | 300 | ||
| Specificity of the association | 300 | ||
| Relationship in time | 301 | ||
| The biological gradient | 301 | ||
| Demonstration of reversibility | 301 | ||
| Biological plausibility | 302 | ||
| Coherence of the evidence | 302 | ||
| Cohort studies | 302 | ||
| Selecting the sample for cohort studies | 302 | ||
| The Whitehall studies | 302 | ||
| Assembling the cohort | 303 | ||
| The prospective follow-up | 303 | ||
| Whitehall II | 303 | ||
| Analysing and interpreting data from cohort studies | 303 | ||
| The role of genetics in observational studies | 304 | ||
| Association between genotype and risk factor | 304 | ||
| Interaction with environmental factors | 305 | ||
| Investigation by experiment | 305 | ||
| Evaluation of clinical effectiveness: RCTs | 305 | ||
| Selecting the sample: experimental and control groups | 305 | ||
| Ethical considerations during the planning stage of clinical trials | 306 | ||
| The CRASH trial | 306 | ||
| Achieving similar groups for comparison: randomisation to minimise bias | 306 | ||
| Selecting the sample for the 4S trial | 306 | ||
| Calculating sample size | 307 | ||
| Power calculations | 307 | ||
| Measuring the outcomes during a trial | 307 | ||
| 'Blinding’ to avoid bias during a trial | 307 | ||
| Outcomes of interest: end-point definition | 308 | ||
| Ethical principles during a trial: stopping a trial and interim analyses | 308 | ||
| Interim analyses | 310 | ||
| What outcomes should be considered in an interim analysis? | 310 | ||
| How should the information be obtained? | 310 | ||
| How should the information be treated? | 310 | ||
| How should the decision be made to stop a trial? | 310 | ||
| Measuring outcomes: follow-up | 310 | ||
| Analysing and interpreting the results | 310 | ||
| Analysis by intention-to-treat | 310 | ||
| Sensitivity analysis | 311 | ||
| Measures of treatment effect | 311 | ||
| Statistical significance | 311 | ||
| Clinical significance: the number needed to treat | 311 | ||
| Interpreting the results | 312 | ||
| Tests of significance | 312 | ||
| Presenting the results | 313 | ||
| Dissemination | 313 | ||
| Statistical assessment of data | 313 | ||
| Choosing a statistical test | 313 | ||
| Looking for differences in quantitative data ( Fig. 7.18) | 313 | ||
| Looking for differences in categorical data ( Fig. 7.19) | 314 | ||
| Looking for patterns in data ( Fig. 7.20) | 314 | ||
| Degrees of freedom | 314 | ||
| The t-test | 315 | ||
| Evaluating probability for t -values | 315 | ||
| Criteria for applying the t-test | 316 | ||
| The χ 2 test | 316 | ||
| Evaluating probability for χ 2 values | 316 | ||
| Criteria for applying the χ 2 test | 317 | ||
| Linear association: correlation and regression | 317 | ||
| Multivariate analysis | 318 | ||
| INVESTIGATION BY REVIEW | 319 | ||
| META-ANALYSIS | 319 | ||
| Cumulative meta-analysis | 319 | ||
| Experiment or review? | 320 | ||
| Differences between reviews and RCTs | 320 | ||
| Definition of best evidence | 321 | ||
| HEALTH EDUCATION AND PROMOTION | 321 | ||
| HEALTH EDUCATION | 321 | ||
| Approaches to health education | 321 | ||
| Strategies for disease prevention and health promotion | 321 | ||
| Population strategies | 321 | ||
| High-risk strategy | 322 | ||
| Two concepts of ‘risk’ | 322 | ||
| Essentials for effective health education | 322 | ||
| Ethical considerations in prevention and health promotion | 322 | ||
| Case scenario: a new diagnosis of diabetes | 322 | ||
| Elicit the person’s health beliefs | 323 | ||
| Information phase | 323 | ||
| Explanation of the diagnosis | 323 | ||
| Chapter 8: The nervous system | 337 | ||
| INTRODUCTION | 337 | ||
| EMBRYOLOGY | 337 | ||
| Neurulation | 338 | ||
| Brain development | 338 | ||
| Ventricles | 338 | ||
| Spinal cord development | 338 | ||
| Developmental disorders of the nervous system | 339 | ||
| GROSS ANATOMY | 339 | ||
| CENTRAL NERVOUS SYSTEM | 339 | ||
| Brain | 339 | ||
| Cerebrum (telencephalon) | 339 | ||
| Cerebral cortex | 340 | ||
| Basal ganglia | 341 | ||
| Limbic system | 341 | ||
| Diencephalon | 341 | ||
| Brainstem | 341 | ||
| Midbrain | 343 | ||
| Pons and medulla | 344 | ||
| Cerebellum | 344 | ||
| Spinal cord | 344 | ||
| Grey matter | 345 | ||
| White matter | 345 | ||
| PERIPHERAL NERVOUS SYSTEM | 345 | ||
| Somatic nervous system | 346 | ||
| Cranial nerves | 346 | ||
| Olfactory (I) nerve | 346 | ||
| Optic (II) nerve | 346 | ||
| Oculomotor (III) nerve | 346 | ||
| Trochlear (IV) nerve | 346 | ||
| Trigeminal (V) nerve | 346 | ||
| Sensory division | 346 | ||
| Motor division | 346 | ||
| Abducens (VI) nerve | 346 | ||
| Facial (VII) nerve | 347 | ||
| Vestibulocochlear (VIII) nerve | 347 | ||
| Glossopharyngeal (IX) nerve | 347 | ||
| Vagus (X) nerve | 347 | ||
| Accessory (XI) nerve | 348 | ||
| Hypoglossal (XII) nerve | 348 | ||
| Spinal nerves | 348 | ||
| Structure of peripheral nerves | 348 | ||
| Nerve fibre classification | 349 | ||
| MENINGES | 349 | ||
| Dura mater | 349 | ||
| Arachnoid mater | 350 | ||
| Pia mater | 351 | ||
| THE VENTRICULAR SYSTEM | 351 | ||
| Secretion and circulation of CSF | 351 | ||
| Absorption of CSF | 352 | ||
| Functions of CSF | 352 | ||
| Metabolic functions | 352 | ||
| Mechanical functions | 352 | ||
| CELLS OF THE NERVOUS SYSTEM | 352 | ||
| Size | 352 | ||
| Morphology | 352 | ||
| Connectivity | 353 | ||
| Chemistry | 353 | ||
| BLOOD SUPPLY TO THE BRAIN AND BRAIN METABOLISM | 353 | ||
| ARTERIAL BLOOD SUPPLY | 353 | ||
| Anterior cerebral circulation | 353 | ||
| Posterior cerebral circulation | 354 | ||
| Arterial blood supply to the spinal cord | 354 | ||
| Venous drainage | 355 | ||
| BLOOD–BRAIN BARRIER | 355 | ||
| METABOLIC REQUIREMENTS OF THE BRAIN | 356 | ||
| TRANSMISSION OF NEURAL SIGNALS | 356 | ||
| ACTION POTENTIALS | 356 | ||
| Equilibrium potentials | 356 | ||
| Depolarisation and hyperpolarisation | 357 | ||
| Generation of action potentials | 357 | ||
| Initiation | 357 | ||
| Upstroke | 357 | ||
| Repolarisation | 357 | ||
| Refractory period | 358 | ||
| Conduction of action potentials | 358 | ||
| SYNAPSES | 358 | ||
| Electrical synapses | 358 | ||
| Chemical synapses | 358 | ||
| NEUROTRANSMISSION | 359 | ||
| Neurotransmitters | 359 | ||
| Neurotransmitter release | 359 | ||
| Neurotransmitter receptors | 359 | ||
| Summation | 360 | ||
| Neurotransmitter inactivation | 360 | ||
| Presynaptic receptors | 360 | ||
| Types of neurotransmitters | 360 | ||
| Amino acids | 360 | ||
| Excitatory amino acids | 360 | ||
| Inhibitory amino acids | 362 | ||
| Acetylcholine | 362 | ||
| Monoamines | 362 | ||
| Purines | 363 | ||
| Peptides | 364 | ||
| MOTOR CONTROL AND PATHWAYS | 364 | ||
| MOTOR CORTEX | 365 | ||
| Primary motor cortex | 365 | ||
| Premotor and supplementary motor cortices | 365 | ||
| Lateral motor pathways | 365 | ||
| BRAINSTEM | 365 | ||
| Medial motor pathways | 365 | ||
| Upper and lower motor neurons | 366 | ||
| SPINAL CORD | 367 | ||
| Motor reflexes | 367 | ||
| Stretch reflex | 367 | ||
| Muscle spindles | 367 | ||
| Golgi tendon organ reflex | 368 | ||
| Cutaneous reflexes | 368 | ||
| Locomotion | 368 | ||
| Muscle tone | 368 | ||
| Spinal cord injury | 368 | ||
| CRANIAL NERVE REFLEXES | 369 | ||
| CEREBELLUM | 369 | ||
| Anatomy | 369 | ||
| Functional subdivisions | 370 | ||
| Cerebellar cortex and circuitry | 371 | ||
| BASAL GANGLIA | 372 | ||
| EYE MOVEMENTS | 373 | ||
| Control of eye movements | 374 | ||
| Gaze stabilisation | 374 | ||
| Gaze shift | 374 | ||
| SENSORY SYSTEMS | 375 | ||
| Sensory receptor transduction | 375 | ||
| Receptive field structure | 376 | ||
| Touch and proprioception | 376 | ||
| Touch and conscious proprioception pathway | 376 | ||
| Somatosensory cortex | 377 | ||
| Other proprioception pathways | 378 | ||
| Pain and temperature | 378 | ||
| Thermoreceptors | 378 | ||
| Nociceptors | 378 | ||
| Pain and temperature pathways | 378 | ||
| Summary of the ascending sensory pathways | 379 | ||
| Pain regulation | 379 | ||
| Analgesic agents | 380 | ||
| Placebo effect | 380 | ||
| Visceral sensation | 381 | ||
| Referred pain | 381 | ||
| Phantom pain | 381 | ||
| SPECIAL SENSES | 381 | ||
| VISION | 381 | ||
| The anatomy of the eyeball | 381 | ||
| Optics of the eye | 381 | ||
| Pupillary reflexes | 382 | ||
| Retina | 383 | ||
| Photoreceptors | 383 | ||
| Retinal processing | 385 | ||
| Central visual pathways | 386 | ||
| Visual perception | 386 | ||
| VESTIBULAR SYSTEM | 386 | ||
| Anatomy | 386 | ||
| Central vestibular pathways | 388 | ||
| AUDITORY SYSTEM | 388 | ||
| Sound | 388 | ||
| External and middle ear | 389 | ||
| Inner ear (cochlea) | 389 | ||
| Central auditory pathways | 390 | ||
| Sound frequency coding | 392 | ||
| Sound localisation | 392 | ||
| SMELL | 392 | ||
| TASTE | 392 | ||
| Central pathways of taste | 392 | ||
| CENTRAL AUTONOMIC NETWORKS | 392 | ||
| Examples of central autonomic control | 394 | ||
| Thermoregulation | 394 | ||
| Regulation of feeding and satiety | 394 | ||
| Orexigenic pathway | 394 | ||
| Anorexigenic pathway | 394 | ||
| Regulation of thirst and drinking | 395 | ||
| Regulation of sexual function | 395 | ||
| CONSCIOUSNESS | 395 | ||
| SLEEP AND WAKEFULNESS | 395 | ||
| Arousal system | 396 | ||
| NREM sleep | 396 | ||
| REM sleep | 396 | ||
| EMOTION | 396 | ||
| Limbic system | 396 | ||
| The pathways of fear | 397 | ||
| Emotion recognition | 397 | ||
| Emotional expression | 397 | ||
| Prefrontal cortex and emotion | 398 | ||
| MOTIVATION AND GOAL-DIRECTED BEHAVIOURS | 398 | ||
| The brain reward system | 398 | ||
| Drugs and the brain reward system | 398 | ||
| HIGHER CORTICAL FUNCTIONS | 399 | ||
| COGNITION | 399 | ||
| MEMORY | 399 | ||
| Declarative memory | 399 | ||
| Anatomical structures and declarative (explicit) memory | 400 | ||
| Long-term potentiation and depression | 400 | ||
| ATTENTION | 401 | ||
| AGNOSIAS | 401 | ||
| APRAXIAS | 401 | ||
| LANGUAGE | 401 | ||
| BRAIN DEATH | 402 | ||
| Chapter 9: Bone, muscle, skin and connective tissue | 403 | ||
| INTRODUCTION | 403 | ||
| IMAGING IN MEDICINE | 403 | ||
| THE SKELETAL SYSTEM | 404 | ||
| CARTILAGE | 404 | ||
| BONE MICROANATOMY | 405 | ||
| Bone matrix | 405 | ||
| Cellular content of bone | 405 | ||
| BONE FORMATION | 406 | ||
| SKELETAL COMPONENTS | 406 | ||
| STRUCTURE OF BONE | 406 | ||
| Compact bone | 410 | ||
| Spongy bone | 411 | ||
| Blood and nerve supply to bone | 411 | ||
| BONE DEVELOPMENT | 411 | ||
| Endochondral ossification | 411 | ||
| Intramembranous ossification | 412 | ||
| BONE GROWTH | 412 | ||
| Bone growth in length | 412 | ||
| Growth in bone thickness | 414 | ||
| Factors affecting bone growth | 414 | ||
| Bone remodelling | 414 | ||
| BONE’S ROLE IN CALCIUM HOMEOSTASIS | 415 | ||
| Parathyroid hormone | 415 | ||
| Vitamin D | 416 | ||
| Calcitonin | 416 | ||
| Other factors affecting bone mass | 416 | ||
| Oestrogen | 416 | ||
| Exercise | 416 | ||
| Diet and bone mass | 417 | ||
| BONE HEALING | 417 | ||
| JOINTS | 418 | ||
| BONY JOINTS | 418 | ||
| FIBROUS JOINTS | 418 | ||
| Suture | 418 | ||
| Syndesmosis | 418 | ||
| Gomphosis | 419 | ||
| Schindylesis | 419 | ||
| CARTILAGINOUS JOINTS | 419 | ||
| SYNOVIAL JOINTS | 419 | ||
| Synovial joint structure | 419 | ||
| Articular cartilage | 420 | ||
| Articular capsule | 420 | ||
| The synovium | 420 | ||
| The synovial fluid | 421 | ||
| Accessory ligaments | 422 | ||
| Articular discs | 422 | ||
| Blood and nerve supply to the joint | 422 | ||
| Types of synovial joints | 422 | ||
| Planar or gliding synovial joint | 422 | ||
| Hinge joint | 423 | ||
| Pivot joints | 424 | ||
| Condyloid or ellipsoidal joint | 424 | ||
| Saddle joint | 425 | ||
| Ball and socket joint | 425 | ||
| A complex joint | 428 | ||
| TENDONS AND LIGAMENTS | 428 | ||
| Bursae and tendon sheaths | 431 | ||
| ANATOMICAL RELATIONSHIPS | 432 | ||
| SKELETAL MUSCLE | 432 | ||
| THE NEUROMUSCULAR JUNCTION AND MUSCLE INNERVATION | 432 | ||
| Neurotransmitter release | 433 | ||
| Acetylcholine receptors | 433 | ||
| Neuromuscular blockade | 434 | ||
| Breakdown of acetylcholine | 434 | ||
| Motor units | 434 | ||
| Development of sustained tension | 435 | ||
| Muscle tone | 435 | ||
| Sensory innervation of muscle | 435 | ||
| ISOTONIC VERSUS ISOMETRIC CONTRACTION | 435 | ||
| THE SKELETAL MUSCLE FIBRE | 435 | ||
| The contractile proteins | 436 | ||
| Thin filaments | 437 | ||
| Thick filaments | 437 | ||
| The sliding filament model of muscle contraction | 438 | ||
| THE CONTRACTILE PROCESS | 438 | ||
| Excitation–contraction coupling | 438 | ||
| Intracellular calcium release ( Fig. 9.17A) | 438 | ||
| Cross-bridge formation and muscle contraction ( Fig. 9.17B) | 440 | ||
| Calcium removal and muscle relaxation | 440 | ||
| Muscle length and tension | 440 | ||
| MUSCLE METABOLISM | 440 | ||
| Creatine phosphate | 441 | ||
| Creatine supplementation | 441 | ||
| Muscle fatigue | 441 | ||
| TYPES OF MUSCLE FIBRES | 441 | ||
| THE CONNECTIVE TISSUE OF MUSCLE | 441 | ||
| MUSCLE GROWTH AND REPAIR | 442 | ||
| MUSCLE NOMENCLATURE | 442 | ||
| Muscle shape | 442 | ||
| Muscle names | 443 | ||
| POSTURE AND LOCOMOTION | 443 | ||
| STANDING | 444 | ||
| WALKING | 444 | ||
| Stance phase | 444 | ||
| Swing phase | 444 | ||
| Stabilisation | 444 | ||
| Gait analysis | 444 | ||
| SPECIALISED CONNECTIVE TISSUES: SKIN, HAIR AND NAILS | 444 | ||
| STRUCTURE OF SKIN | 444 | ||
| Epidermis | 445 | ||
| Melanocytes | 445 | ||
| Dermis | 446 | ||
| Sweat glands | 447 | ||
| Sebaceous glands | 447 | ||
| Subcutaneous layer | 447 | ||
| HAIR | 447 | ||
| Structure of hair | 447 | ||
| Structure of hair follicle | 447 | ||
| Types of hair | 448 | ||
| NAILS | 448 | ||
| GENERALISED CONNECTIVE TISSUE | 448 | ||
| Chapter 10: Endocrinology | 451 | ||
| INTRODUCTION | 451 | ||
| THE ENDOCRINE SYSTEM | 451 | ||
| Peptide hormones: secretion and mechanisms of action | 452 | ||
| Steroid hormones: synthesis, actions and metabolism | 453 | ||
| Modified amino acids: thyroid hormones and catecholamines | 454 | ||
| NEUROENDOCRINOLOGY | 455 | ||
| IMPORTANT CONCEPTS IN ENDOCRINOLOGY | 455 | ||
| Patterns of hormone secretion | 455 | ||
| Negative feedback | 455 | ||
| Endocrine disease | 455 | ||
| Endocrine testing | 456 | ||
| Measuring hormones in blood | 458 | ||
| ENDOCRINE REGULATION – THE ROLE OF THE HYPOTHALAMUS AND PITUITARY | 458 | ||
| Functional anatomy of the hypothalamus and pituitary | 458 | ||
| The hypothalamus controls hormone secretion by the anterior pituitary | 458 | ||
| Prolactin secretion is under inhibitory regulation ( Fig. 10.12) | 461 | ||
| GROWTH HORMONE | 461 | ||
| Growth | 461 | ||
| The regulation of growth hormone | 461 | ||
| Actions of growth hormone | 462 | ||
| THYROID GLAND AND THE REGULATION OF METABOLISM | 464 | ||
| THE STRUCTURE AND LOCATION OF THE THYROID | 464 | ||
| Iodine – an important trace element | 464 | ||
| HORMONE SYNTHESIS IN THE THYROID GLAND | 465 | ||
| CONTROL OF THYROID FUNCTION | 466 | ||
| Thyroid hormones in blood | 466 | ||
| Peripheral metabolism of thyroxine | 466 | ||
| Functions of thyroxine ( Table 10.5) | 466 | ||
| HORMONES AND ‘STRESS’ | 467 | ||
| Adrenal cortex and medulla | 468 | ||
| Structure of adrenals | 468 | ||
| Stress: the adrenal medulla | 468 | ||
| Stress: the adrenal cortex | 469 | ||
| Actions of cortisol | 469 | ||
| ENDOCRINE CONTROL OF GLUCOSE METABOLISM (details of biochemistry in Chs 2 and 3) | 471 | ||
| Regulation of plasma glucose concentration | 471 | ||
| ENDOCRINE PANCREAS | 471 | ||
| Insulin synthesis | 471 | ||
| Control of insulin secretion ( Fig. 10.27) | 471 | ||
| Glucagon | 472 | ||
| Diabetes mellitus | 472 | ||
| Glycosuria | 472 | ||
| Type 1 diabetes | 473 | ||
| Type 2 diabetes | 473 | ||
| Obesity | 473 | ||
| Complications of poorly controlled blood glucose 1: diabetic ketoacidosis | 474 | ||
| Complications of poorly controlled blood glucose 2: HONK | 474 | ||
| Complications of poorly controlled blood glucose 3: hypoglycaemia | 474 | ||
| ENDOCRINE CONTROL OF BLOOD CALCIUM (details of bone in Ch. 9) | 475 | ||
| CALCIUM HOMEOSTASIS | 475 | ||
| CONTROL OF BLOOD CALCIUM AND PHOSPHATE CONCENTRATIONS | 475 | ||
| MALE REPRODUCTIVE ENDOCRINOLOGY | 478 | ||
| Male reproductive tract ( Fig. 10.35) | 478 | ||
| Hypothalamic–pituitary–testicular axis | 479 | ||
| Spermatogenesis | 480 | ||
| FEMALE REPRODUCTIVE ENDOCRINOLOGY | 481 | ||
| Female reproductive tract | 481 | ||
| Follicular development | 481 | ||
| HORMONAL CONTROL OF THE OVARY AND MENSTRUAL CYCLE | 481 | ||
| The menstrual and ovarian cycles | 482 | ||
| PUBERTY | 484 | ||
| PREGNANCY | 486 | ||
| FERTILISATION | 486 | ||
| The establishment of pregnancy | 486 | ||
| Hormone production by the placenta | 487 | ||
| Pregnancy tests | 488 | ||
| FOETAL DEVELOPMENT | 488 | ||
| PARTURITION – LABOUR | 488 | ||
| Lactation | 489 | ||
| INFERTILITY (SUBFERTILITY) | 491 | ||
| THE ENDOCRINOLOGY OF AGEING (INCLUDING MENOPAUSE) | 491 | ||
| Chapter 11: The cardiovascular system | 493 | ||
| INTRODUCTION | 493 | ||
| CLINICAL ANATOMY OF THE CARDIOVASCULAR SYSTEM | 493 | ||
| THE HEART | 493 | ||
| The pericardium | 493 | ||
| The heart chambers | 494 | ||
| The apex of the heart | 494 | ||
| The heart valves | 494 | ||
| Heart sounds and murmurs | 495 | ||
| THE HUMAN CIRCULATION | 497 | ||
| The pulmonary circulation | 499 | ||
| The systemic circulation | 500 | ||
| The arterial system | 500 | ||
| Aortic arch | 501 | ||
| Thoracic aorta | 501 | ||
| Abdominal aorta | 501 | ||
| Common iliac arteries | 502 | ||
| Peripheral arterial pulses | 502 | ||
| The venous system | 503 | ||
| Jugular venous pulse | 503 | ||
| Regional circulations | 503 | ||
| The coronary circulation | 503 | ||
| Coronary blood flow | 504 | ||
| The cerebral circulation | 504 | ||
| The hepatic circulation | 504 | ||
| The skeletal muscle circulation | 505 | ||
| The cutaneous circulation | 505 | ||
| EMBRYOLOGY | 505 | ||
| DEVELOPMENT OF THE HEART | 506 | ||
| The chambers of the heart | 506 | ||
| The atria | 507 | ||
| The ventricles | 507 | ||
| The great arteries | 508 | ||
| DEVELOPMENT OF THE VASCULATURE | 508 | ||
| The foetal circulation | 508 | ||
| The neonatal circulation | 510 | ||
| CELLULAR STRUCTURE AND FUNCTION OF THE HEART | 510 | ||
| STRUCTURE OF HEART MUSCLE | 510 | ||
| Cardiomyocytes | 510 | ||
| Intercalated discs | 510 | ||
| T-tubules and sarcoplasmic reticulum | 510 | ||
| THE CONTRACTILE PROCESS | 510 | ||
| Cardiac muscle contraction | 510 | ||
| Cardiac muscle relaxation | 511 | ||
| Cardiac muscle metabolism | 512 | ||
| ELECTRICAL ACTIVATION OF THE HEART | 512 | ||
| Pacemaker cells | 512 | ||
| The cardiac conduction system | 513 | ||
| Nerve supply to the heart | 513 | ||
| Parasympathetic supply | 513 | ||
| Sympathetic supply | 514 | ||
| Adrenal medulla | 515 | ||
| Electrocardiography | 515 | ||
| The ECG | 515 | ||
| The normal ECG | 516 | ||
| The electrical axis of the heart | 517 | ||
| Cardiac arrhythmias | 518 | ||
| Anti-arrhythmic drugs | 520 | ||
| Conduction disorders | 520 | ||
| THE CARDIAC CYCLE | 522 | ||
| Atrial systole | 524 | ||
| Ventricular systole | 524 | ||
| Ventricular diastole | 524 | ||
| The pressure–volume loop | 524 | ||
| CARDIAC OUTPUT AND HEART FAILURE | 525 | ||
| Preload | 525 | ||
| Myocardial contractility | 525 | ||
| Afterload | 526 | ||
| Ventricular hypertrophy | 526 | ||
| Causes of heart failure | 526 | ||
| Pathophysiological mechanisms activated by heart failure | 526 | ||
| Treatment of heart failure | 527 | ||
| BLOOD VESSELS | 528 | ||
| THE VESSEL WALL | 528 | ||
| Arteries | 529 | ||
| Veins | 529 | ||
| ATHEROSCLEROSIS | 530 | ||
| Evolution of the atherosclerotic plaque | 530 | ||
| Endothelial damage | 530 | ||
| Uptake of modified LDL particles, adhesion and infiltration of macrophages | 530 | ||
| Smooth muscle proliferation and formation of fibrous cap | 531 | ||
| Plaque rupture | 531 | ||
| Risk factors for atherosclerosis | 532 | ||
| Non-modifiable risk factors | 532 | ||
| Modifiable risk factors | 532 | ||
| Markers of risk | 532 | ||
| Prevention and treatment of atherosclerosis | 533 | ||
| Non-atherosclerotic arteriosclerosis | 533 | ||
| ISCHAEMIC HEART DISEASE | 534 | ||
| Angina | 534 | ||
| Stable angina | 534 | ||
| Variant angina | 534 | ||
| Treatment of angina | 534 | ||
| Acute coronary syndromes | 534 | ||
| Unstable angina | 534 | ||
| Myocardial infarction | 534 | ||
| Non-ST elevation myocardial infarction | 535 | ||
| ST elevation myocardial infarction | 537 | ||
| Complications of myocardial infarction | 537 | ||
| THROMBOEMBOLISM | 539 | ||
| Thrombus formation | 539 | ||
| Deep vein thrombosis | 540 | ||
| Pulmonary embolism | 540 | ||
| Non-thrombotic emboli | 541 | ||
| THE MICROCIRCULATION | 541 | ||
| Capillary structure | 541 | ||
| The capillary bed | 542 | ||
| Capillary exchange | 542 | ||
| Diffusion | 543 | ||
| Free diffusion | 543 | ||
| Channel-based diffusion | 543 | ||
| Active membrane transport | 543 | ||
| Influence of blood flow on capillary exchange | 543 | ||
| Water exchange | 543 | ||
| Starling forces | 543 | ||
| Filtration and resorption | 544 | ||
| Oedema | 545 | ||
| Increased capillary hydrostatic pressure | 545 | ||
| Decreased plasma oncotic pressure | 545 | ||
| Increased capillary permeability | 545 | ||
| Reduced lymphatic drainage | 545 | ||
| MECHANICS OF BLOOD FLOW | 546 | ||
| Pressure and vascular resistance | 546 | ||
| Velocity of blood flow | 546 | ||
| Types of blood flow | 547 | ||
| Laminar blood flow | 547 | ||
| Turbulent blood flow | 547 | ||
| Bolus flow | 547 | ||
| Control of blood flow | 547 | ||
| Structure of vascular smooth muscle | 547 | ||
| Vascular smooth muscle contraction | 548 | ||
| Excitation-contraction coupling of smooth muscle | 548 | ||
| Regulation of flow in small arteries and arterioles | 549 | ||
| Sympathetic nervous system mediated vasoconstriction | 550 | ||
| Hormone-mediated vasoconstriction and vasodilatation | 550 | ||
| Non-adrenergic autonomic nervous system mediated vasodilatation | 551 | ||
| Receptor-mediated differential effects of catecholamines | 551 | ||
| Vasoconstriction by catecholamines | 551 | ||
| Vasodilatation by catecholamines | 552 | ||
| Regulation of flow in the microcirculation | 552 | ||
| Autoregulation of blood flow | 552 | ||
| Metabolic byproduct vasodilatation | 553 | ||
| Local vasoactive hormones | 553 | ||
| SYSTEMIC ARTERIAL BLOOD PRESSURE | 554 | ||
| REGULATION OF ARTERIAL BLOOD PRESSURE | 554 | ||
| Baroreceptor reflex | 554 | ||
| Chemoreceptor reflexes | 555 | ||
| Cardiopulmonary reflexes | 555 | ||
| Central regulation of cardiovascular reflexes | 555 | ||
| Regulation of the baroreceptor reflex | 555 | ||
| Long-term control of blood pressure | 556 | ||
| Vasopressin | 556 | ||
| Angiotensin II | 556 | ||
| Aldosterone | 556 | ||
| Atrial natriuretic peptide | 556 | ||
| Orthostasis | 556 | ||
| SHOCK | 556 | ||
| Hypovolaemic shock | 557 | ||
| Cardiogenic shock | 558 | ||
| Vasodilatory (septic) shock | 559 | ||
| Anaphylactic shock | 559 | ||
| Neurogenic shock | 559 | ||
| Homeostatic mechanisms activated by shock | 559 | ||
| Clinical signs of shock | 560 | ||
| Decompensated shock and multi-organ failure | 560 | ||
| Cellular damage in shock | 560 | ||
| Treatment of shock | 560 | ||
| Supportive therapy | 561 | ||
| Fluid replacement | 561 | ||
| Sympathomimetic drug treatment | 561 | ||
| Prognosis in shock | 562 | ||
| HYPERTENSION | 562 | ||
| Diagnosis of hypertension | 562 | ||
| Aetiology of hypertension | 562 | ||
| Pathophysiology of hypertension | 562 | ||
| Secondary hypertension | 563 | ||
| Hypertension due to chronic kidney disease | 563 | ||
| Renovascular hypertension | 563 | ||
| Endocrine causes of hypertension | 563 | ||
| Drug-induced hypertension | 564 | ||
| Coarctation of the aorta | 564 | ||
| Pregnancy-induced hypertension | 564 | ||
| Malignant hypertension | 564 | ||
| Treatment of hypertension | 565 | ||
| Resistant hypertension | 565 | ||
| Chapter 12: Haematology | 567 | ||
| THE HAEMOPOIETIC SYSTEM | 567 | ||
| BLOOD AND ITS CONSTITUENTS | 567 | ||
| Blood plasma | 567 | ||
| Blood cells | 567 | ||
| Red cells (erythrocytes) | 567 | ||
| White blood cells (leucocytes) | 568 | ||
| Neutrophils | 568 | ||
| Monocytes and macrophages | 569 | ||
| Eosinophils | 569 | ||
| Basophils | 569 | ||
| Lymphocytes | 569 | ||
| Platelets | 569 | ||
| STEM CELLS AND THEIR ROLE IN HAEMOPOIESIS | 570 | ||
| BLOOD CELL PRODUCTION AND THE BONE MARROW MICROENVIRONMENT | 570 | ||
| Regulation of haemopoiesis | 570 | ||
| The bone marrow stroma | 570 | ||
| Growth factors | 570 | ||
| Haemopoietic receptors | 571 | ||
| RED CELLS | 571 | ||
| TRANSCRIPTION FACTORS IN ERYTHROPOIESIS | 571 | ||
| Tal-1/SCL | 571 | ||
| Rbtn2/LMO2 | 571 | ||
| GATA-2 | 571 | ||
| GATA-1 | 571 | ||
| GROWTH FACTORS IN ERYTHROPOIESIS | 571 | ||
| Erythropoietin controls the red cell mass | 571 | ||
| Epo production involves a negative feedback loop | 572 | ||
| STROMAL MOLECULES IN ERYTHROPOIESIS | 572 | ||
| Other hormones that influence haemoglobin production | 572 | ||
| Red cell production during life | 572 | ||
| TRANSPORT OF OXYGEN BY HAEMOGLOBIN | 573 | ||
| The oxygen dissociation curve | 573 | ||
| Role of acid in oxygen release | 574 | ||
| Role of 2,3-DPG in oxygen release from haemoglobin | 574 | ||
| TRANSPORT OF CARBON DIOXIDE | 574 | ||
| THE RED CELL MEMBRANE | 575 | ||
| Spectrin | 575 | ||
| HAEMOGLOBIN | 575 | ||
| Coordinating haemoglobin production throughout life | 575 | ||
| RED CELL ENZYMES ARE REQUIRED TO MAINTAIN RED CELL COMPONENTS | 576 | ||
| Glucose is the main source of red cell energy | 576 | ||
| MAINTENANCE AND RECYCLING OF RED CELLS | 576 | ||
| Fate of old red cells | 576 | ||
| Recycling of red cell components | 576 | ||
| ANAEMIAS | 576 | ||
| General features of anaemia | 576 | ||
| Physiological adaptations to anaemia | 577 | ||
| Tissues and perfusion | 577 | ||
| Cardiovascular system | 577 | ||
| Classification of anaemia | 578 | ||
| 1) Using the mean cell volume (MCV) | 578 | ||
| 2) Acquired or inherited | 578 | ||
| Acquired anaemias due to deficiencies | 578 | ||
| Iron deficiency | 578 | ||
| Iron metabolism | 578 | ||
| Iron loss | 579 | ||
| Iron homeostasis: regulation of ferritin and transferrin receptor levels | 579 | ||
| Causes of iron deficiency | 580 | ||
| Laboratory findings in iron deficiency | 580 | ||
| Megaloblastic anaemia | 580 | ||
| Why are vitamins B 12 and folate important? | 580 | ||
| Vitamin B 12 (cobalamin, Cbl) | 581 | ||
| Causes of vitamin B 12 deficiency | 581 | ||
| Folate | 581 | ||
| Causes of folate deficiency | 581 | ||
| Laboratory findings in B 12 and folate deficiency | 581 | ||
| Acquired anaemias due to blood loss | 582 | ||
| Acute blood loss | 582 | ||
| Chronic blood loss | 582 | ||
| Acquired anaemias due to chronic disease | 582 | ||
| Anaemia of chronic disease (ACD) | 582 | ||
| Mechanism of ACD | 582 | ||
| Diagnosis of ACD | 583 | ||
| Anaemias due to haemolysis | 583 | ||
| Acquired autoimmune haemolytic anaemia (AIHA) | 583 | ||
| Laboratory findings in AIHA | 585 | ||
| Other acquired anaemias | 585 | ||
| Non-immune haemolytic anaemias | 585 | ||
| Mechanical red cell fragmentation | 585 | ||
| Marrow infiltration | 585 | ||
| Marrow failure | 585 | ||
| Rare inherited anaemias | 585 | ||
| Inherited anaemias | 586 | ||
| Red cell membrane disorders | 586 | ||
| Hereditary spherocytosis | 586 | ||
| Red cell enzyme disorders | 586 | ||
| Glucose-6-phosphate dehydrogenase deficiency | 586 | ||
| Haemoglobin disorders | 587 | ||
| Sickle cell disease | 587 | ||
| Elevated foetal haemoglobin levels are beneficial | 587 | ||
| Precipitants of sickle cell disease | 587 | ||
| Laboratory findings in sickle cell disease | 587 | ||
| The thalassaemias | 587 | ||
| α Thalassaemia | 588 | ||
| β Thalassaemia | 588 | ||
| Laboratory findings in the thalassaemias | 589 | ||
| ONCOGENESIS AND DISORDERS OF BLOOD CELL PRODUCTION | 589 | ||
| NORMAL BLOOD PRODUCTION RELIES ON COORDINATED GENE EXPRESSION | 590 | ||
| ONCOGENESIS | 590 | ||
| The search for oncogenes in human blood disease | 590 | ||
| Oncogenes and tumour suppressor genes | 590 | ||
| Oncogenes | 590 | ||
| Mutations | 590 | ||
| Chromosome translocations | 590 | ||
| Viral activation | 590 | ||
| Tumour suppressor genes | 590 | ||
| THE LYMPHOID SYSTEM | 590 | ||
| Primary lymphoid tissues | 591 | ||
| Secondary lymphoid tissues | 591 | ||
| MYELOPROLIFERATIVE DISEASES | 591 | ||
| The myeloproliferative diseases | 591 | ||
| Polycythaemia | 591 | ||
| Polycythaemia rubra vera | 592 | ||
| Essential thrombocythaemia | 592 | ||
| Myelofibrosis | 592 | ||
| MYELODYSPLASTIC SYNDROMES | 592 | ||
| LEUKAEMIAS | 592 | ||
| The acute leukaemias | 592 | ||
| Incidence and causes | 593 | ||
| Laboratory findings | 593 | ||
| Chronic leukaemias | 593 | ||
| Chronic myeloid leukaemia | 593 | ||
| Chronic lymphocytic leukaemia (CLL) | 593 | ||
| Laboratory findings | 595 | ||
| LYMPHOMAS | 595 | ||
| Non-Hodgkin lymphoma (NHL) | 595 | ||
| Chromosome translocations | 595 | ||
| Viral infection | 595 | ||
| Other implicated factors | 595 | ||
| Hodgkin disease | 595 | ||
| PLASMA CELL DISORDERS | 596 | ||
| Multiple myeloma | 596 | ||
| Clinical feature of multiple myeloma | 596 | ||
| Laboratory features of multiple myeloma | 596 | ||
| HAEMOSTASIS AND THROMBOSIS | 596 | ||
| NORMAL HAEMOSTATIC MECHANISMS | 596 | ||
| The role of the endothelium and platelets in the maintenance of haemostasis | 597 | ||
| Coagulation cascade | 598 | ||
| The intrinsic pathway | 598 | ||
| The extrinsic pathway | 598 | ||
| The common pathway | 598 | ||
| Natural anticoagulants are required to maintain the balance | 599 | ||
| The fibrinolytic system | 599 | ||
| Clinical consequences of fibrin degradation products | 599 | ||
| Plasminogen activators: tissue and urinary plasminogen activator | 599 | ||
| Fibrinolysis inhibitors | 600 | ||
| Assessment of the coagulation system | 600 | ||
| Full blood count and film | 600 | ||
| The bleeding time | 600 | ||
| Coagulation tests | 600 | ||
| COAGULATION FACTOR DISORDERS | 601 | ||
| Inherited disorders | 601 | ||
| Haemophilia A | 601 | ||
| Haemophilia B (Christmas disease) | 601 | ||
| Clinical and diagnostic features of haemophilia | 601 | ||
| Von Willebrand disease | 601 | ||
| Inherited platelet disorders | 602 | ||
| Acquired disorders | 602 | ||
| THE THROMBOCYTOPENIAS | 602 | ||
| Thrombocytopenia caused by impaired platelet production | 602 | ||
| Thrombocytopenia caused by increased platelet destruction | 602 | ||
| Non-immune causes of thrombocytopenia | 602 | ||
| Disseminated intravascular coagulation | 602 | ||
| Thrombocytopenia due to an altered distribution, or dilution | 602 | ||
| Immune causes of thrombocytopenia | 602 | ||
| Immune thrombocytopenic purpura | 603 | ||
| Heparin-induced thrombocytopenia | 603 | ||
| THE THROMBOPHILIAS | 603 | ||
| The inherited thrombophilias | 603 | ||
| Protein C deficiency | 603 | ||
| Protein S deficiency | 603 | ||
| Activated protein C resistance | 603 | ||
| The acquired thrombophilias | 603 | ||
| Anti-phospholipid syndrome | 604 | ||
| Lupus anticoagulant | 604 | ||
| Anti-cardiolipin antibody | 604 | ||
| BLOOD GROUPS AND TRANSFUSION MEDICINE | 604 | ||
| DEFINITION OF A BLOOD GROUP | 604 | ||
| BLOOD GROUP ANTIGENS | 604 | ||
| ANTIBODY PRODUCTION | 604 | ||
| BLOOD GROUP SYSTEMS IN TRANSFUSION MEDICINE | 604 | ||
| The ABO system | 604 | ||
| ABO antigens | 604 | ||
| Changes in blood groups | 606 | ||
| The Rhesus system | 606 | ||
| Production of antibodies to blood group antigens | 606 | ||
| ABO blood group system antibodies | 606 | ||
| Rh blood group antibodies | 607 | ||
| Other blood group systems | 607 | ||
| Kell | 607 | ||
| Duffy | 608 | ||
| I/i | 608 | ||
| Platelet antigens | 608 | ||
| BLOOD TRANSFUSION | 608 | ||
| Guidelines for safe transfusion | 608 | ||
| Management of the blood transfusion process | 608 | ||
| Transfusion reactions | 609 | ||
| Tests used in transfusion medicine | 609 | ||
| Blood grouping | 609 | ||
| The antibody screen | 609 | ||
| The antiglobulin test | 610 | ||
| The cross-match (compatibility test) | 610 | ||
| NON-RED-CELL TRANSFUSION | 610 | ||
| Platelet transfusion | 610 | ||
| White cell transfusion | 611 | ||
| Frozen plasma and plasma concentrate transfusion | 611 | ||
| Chapter 13: The respiratory system | 613 | ||
| INTRODUCTION | 613 | ||
| EPIDEMIOLOGY OF RESPIRATORY DISEASE AND ITS SOCIAL IMPACT | 614 | ||
| SMOKE AND RESPIRATORY DISEASE | 614 | ||
| CLASSIFICATION OF COMMON RESPIRATORY DISEASES | 614 | ||
| OBSTRUCTIVE PULMONARY DISEASE | 615 | ||
| RESTRICTIVE PULMONARY DISEASE | 615 | ||
| ANATOMY OF THE RESPIRATORY SYSTEM | 615 | ||
| ANATOMY OF THE UPPER AIRWAYS ( Clinical box 13.4 and Information box 13.2) | 616 | ||
| Nasal cavity | 616 | ||
| Pharynx | 617 | ||
| Larynx | 617 | ||
| Trachea | 617 | ||
| GROSS ANATOMY OF THE LUNGS | 617 | ||
| The tracheobronchial tree | 617 | ||
| Breath sounds | 618 | ||
| Vocal resonance | 619 | ||
| Specialised tracheobronchial cells | 619 | ||
| Cilia and macrophages | 619 | ||
| Goblet cells and the mucociliary escalator | 619 | ||
| Clara cells | 619 | ||
| The alveoli | 619 | ||
| The gas–blood barrier | 620 | ||
| Cell types at the alveolar level | 621 | ||
| Capillary endothelial cells | 621 | ||
| Type I alveolar cells | 621 | ||
| Type II alveolar cells | 621 | ||
| Macrophages | 621 | ||
| Collateral ventilation | 621 | ||
| The pleura | 621 | ||
| Pleurisy and other pleural conditions | 621 | ||
| Pulmonary lymphatics | 622 | ||
| Pulmonary oedema | 622 | ||
| ANATOMY OF THE PULMONARY CIRCULATION | 623 | ||
| Arteries | 623 | ||
| Veins | 623 | ||
| Right-to-left (arteriovenous) shunts | 624 | ||
| Pulmonary blood flow | 624 | ||
| Volume of blood in lungs | 624 | ||
| Pulmonary arterial and venous pressure | 624 | ||
| Pulmonary blood vessels | 624 | ||
| Variations in pulmonary blood flow | 625 | ||
| Effect of gravity on pulmonary blood flow | 625 | ||
| SURFACE ANATOMY OF THE RESPIRATORY SYSTEM | 626 | ||
| Larynx and trachea | 626 | ||
| Surface markings of the thorax | 626 | ||
| Anterior surface of the chest | 626 | ||
| Lateral surface of the chest | 626 | ||
| Posterior surface of the chest | 626 | ||
| The lungs and pleural cavity | 627 | ||
| MECHANICS OF BREATHING | 627 | ||
| THE DIAPHRAGM AND OTHER MUSCLES USED IN BREATHING | 627 | ||
| Inspiration | 627 | ||
| Expiration | 628 | ||
| PULMONARY PRESSURE CHANGES DURING VENTILATION | 628 | ||
| Intrapulmonary pressure | 628 | ||
| Intrapleural pressure | 628 | ||
| Maximal respiratory pressures | 628 | ||
| PULMONARY VENTILATION | 629 | ||
| Lung volumes and capacities | 629 | ||
| Dead space | 629 | ||
| Functional residual capacity | 630 | ||
| Measuring rates of airflow | 630 | ||
| Forced expiratory volume | 630 | ||
| Peak expiratory flow rate | 631 | ||
| Reversibility of airflow limitation | 631 | ||
| WORK OF BREATHING | 631 | ||
| Airway resistance | 631 | ||
| Asthma | 633 | ||
| Bronchoconstriction | 633 | ||
| Inflammation and secretion | 634 | ||
| Lung inflation and deflation | 634 | ||
| Pressure–volume relationship | 634 | ||
| Compliance | 634 | ||
| Surface tension | 635 | ||
| Flow-related airway collapse | 635 | ||
| Closing capacity and posture | 636 | ||
| PRINCIPLES OF GAS EXCHANGE | 636 | ||
| DIFFUSION | 636 | ||
| Pulmonary diffusion capacity | 636 | ||
| Measuring lung diffusion capacity – single breath CO testing (D L CO) | 636 | ||
| PARTIAL PRESSURES OF GASES IN AIR | 637 | ||
| PARTIAL PRESSURES OF GASES IN ALVEOLI AND BLOOD | 637 | ||
| CARRIAGE OF OXYGEN BY THE BLOOD | 637 | ||
| RESPIRATORY PIGMENTS | 638 | ||
| Oxygen dissociation curve | 638 | ||
| Haemoglobin | 638 | ||
| Myoglobin | 638 | ||
| CARRIAGE OF CARBON DIOXIDE BY THE BLOOD | 639 | ||
| CARBON DIOXIDE DISSOCIATION CURVE | 639 | ||
| DISTURBANCES OF ACID–BASE BALANCE | 639 | ||
| The four classes of acid–base disorder | 640 | ||
| Respiratory acidosis | 640 | ||
| Respiratory alkalosis | 640 | ||
| Metabolic acidosis | 640 | ||
| Metabolic alkalosis | 640 | ||
| MATCHING LUNG VENTILATION TO LUNG PERFUSION | 640 | ||
| VENTILATION–PERFUSION RATIO | 641 | ||
| Uneven perfusion | 641 | ||
| Uneven ventilation | 641 | ||
| Ventilation–perfusion mismatch | 641 | ||
| CONTROL OF BREATHING | 642 | ||
| THE RESPIRATORY CENTRE | 642 | ||
| RESPIRATORY RECEPTORS ( Clinical box 13.21) | 642 | ||
| Respiratory chemoreceptors | 642 | ||
| Central chemoreceptors | 643 | ||
| Peripheral chemoreceptors | 643 | ||
| Lung receptors | 644 | ||
| Pulmonary stretch receptors | 644 | ||
| Cough or lung-irritant receptors | 644 | ||
| Haemoptysis | 644 | ||
| J-receptors | 644 | ||
| Other receptors | 644 | ||
| Muscle stretch receptors | 644 | ||
| Joint proprioceptors | 644 | ||
| Baroreceptors | 645 | ||
| HIGHER CENTRE CONTROL OF BREATHING | 645 | ||
| ENERGY PRODUCTION AND OXYGEN CONSUMPTION | 645 | ||
| RESPIRATORY QUOTIENT AS AN INDICATION OF METABOLIC FUEL | 645 | ||
| METHODS FOR ESTIMATING ENERGY CONSUMPTION | 645 | ||
| Basal metabolic rate | 645 | ||
| CHALLENGES TO NORMAL RESPIRATION | 646 | ||
| EXERCISE | 646 | ||
| ALTITUDE | 646 | ||
| Physiological responses to high altitude | 646 | ||
| Acclimatisation to altitude | 646 | ||
| Mountain sickness | 647 | ||
| BREATH-HOLDING | 647 | ||
| Prolonging the held breath | 647 | ||
| DIVING | 647 | ||
| Effects of pressure in free diving | 647 | ||
| Effects of pressure during ascent from depth | 647 | ||
| Effects of pressure in deep diving | 647 | ||
| DIVER’S REFLEX | 648 | ||
| DROWNING | 648 | ||
| HIGH OXYGEN LEVELS | 648 | ||
| Neurological oxygen toxicity | 648 | ||
| Cellular oxygen toxicity | 648 | ||
| CARBON MONOXIDE POISONING | 648 | ||
| RESPIRATORY FAILURE | 648 | ||
| CAUSES OF RESPIRATORY FAILURE | 648 | ||
| Type I respiratory failure | 649 | ||
| Type II respiratory failure | 649 | ||
| Asthma | 649 | ||
| COPD | 649 | ||
| Emphysema | 649 | ||
| Clinical effects of respiratory failure | 649 | ||
| LUNG DEFENCES AGAINST INFECTION | 650 | ||
| THE UPPER AIRWAYS | 650 | ||
| CONDUCTING AIRWAYS | 650 | ||
| Mucins and ciliary action | 650 | ||
| Other factors | 650 | ||
| INNATE IMMUNITY | 650 | ||
| Destroying the invading organism | 650 | ||
| Defensins | 651 | ||
| Surfactant proteins | 651 | ||
| INFLAMMATORY RESPONSES | 651 | ||
| DEVELOPMENT OF THE LUNGS AND CHANGES IN THE NEWBORN | 651 | ||
| EARLY LUNG DEVELOPMENT | 651 | ||
| Embryonic phase | 651 | ||
| STAGES IN LUNG MATURATION | 651 | ||
| Pseudoglandular phase (6–16 weeks in utero) | 651 | ||
| Canalicular phase (16–24 weeks in utero) | 651 | ||
| Saccular phase (24 weeks in utero to birth) | 651 | ||
| Alveolar phase (32 weeks–8 years) | 652 | ||
| RESPIRATORY SYSTEM CHANGES AT NORMAL DELIVERY | 653 | ||
| RESPIRATORY DISTRESS SYNDROME OF THE NEWBORN | 653 | ||
| Chapter 14: The renal system | 655 | ||
| INTRODUCTION | 655 | ||
| FUNCTIONS OF THE KIDNEY | 655 | ||
| URINE VOLUME AND COMPOSITION | 655 | ||
| BALANCE OF FLUID INTAKE AND LOSS | 656 | ||
| RENAL FAILURE | 656 | ||
| ANATOMY OF THE KIDNEY | 657 | ||
| GROSS STRUCTURE | 657 | ||
| Renal pyramids | 658 | ||
| THE NEPHRON | 659 | ||
| The renal corpuscle (renal glomerulus) | 659 | ||
| The renal tubule | 659 | ||
| Proximal convoluted tubule | 659 | ||
| Loop of Henle | 659 | ||
| Distal convoluted tubule | 659 | ||
| Collecting ducts | 659 | ||
| RENAL VASCULATURE | 659 | ||
| Renal microvasculature | 659 | ||
| Peritubular capillaries | 661 | ||
| Glomerular filtration barrier | 661 | ||
| NERVE SUPPLY TO THE RENAL TRACT | 662 | ||
| DEVELOPMENT OF THE KIDNEY | 662 | ||
| Mesonephros | 662 | ||
| Metanephros | 662 | ||
| PERMANENT KIDNEY | 662 | ||
| Congenital renal agenesis | 662 | ||
| Polycystic kidney disease | 663 | ||
| RENAL FUNCTION | 663 | ||
| GLOMERULAR FILTRATION AND THE PRODUCTION OF PRIMARY URINE | 664 | ||
| Pore size and macromolecules | 665 | ||
| Filtration forces | 665 | ||
| Proteins | 665 | ||
| FUNCTIONS OF THE PROXIMAL CONVOLUTED TUBULE | 665 | ||
| Tight junctions | 665 | ||
| The sodium pump | 667 | ||
| Carrier proteins | 667 | ||
| Ion channels | 667 | ||
| Recovery of bicarbonate by the PCT | 667 | ||
| Water | 667 | ||
| Aquaporins | 668 | ||
| Peritubular capillaries | 668 | ||
| Sugars, amino acids and other small organic molecules | 668 | ||
| Facilitated carriers | 668 | ||
| Sodium and chloride | 668 | ||
| Secretion of organic anions and cations | 668 | ||
| Organic anion transport | 668 | ||
| Para-aminohippuric acid | 669 | ||
| PAH and drug dosage | 669 | ||
| Efflux transporters and drugs | 669 | ||
| Nephrotoxicity | 670 | ||
| Organic cation transport | 670 | ||
| RENAL FUNCTION TESTS | 670 | ||
| Blood and urine tests | 670 | ||
| Relative density of urine | 670 | ||
| Osmolality | 670 | ||
| Specific gravity | 670 | ||
| Refractometry | 670 | ||
| Dry chemistry | 670 | ||
| Analysing urine | 670 | ||
| Proteinuria | 670 | ||
| Renal handling of molecules | 671 | ||
| Renal clearance | 672 | ||
| Clearance of molecules that are only filtered | 672 | ||
| 'Inulin’ clearance as an index of GFR | 672 | ||
| Creatinine clearance | 672 | ||
| Urea clearance | 673 | ||
| Current methods for measuring renal clearance (half-life) | 673 | ||
| Clearance of molecules that are filtered and reabsorbed | 673 | ||
| Clearance of molecules that are filtered and secreted | 674 | ||
| Use of clearance methods to assess renal function | 674 | ||
| Advanced clinical tests | 674 | ||
| RENAL CONTROL OF FLUID BALANCE | 674 | ||
| Vasopressin | 674 | ||
| Vasopressin release | 674 | ||
| Vasopressin receptors | 674 | ||
| Calculation of renal water excretion | 677 | ||
| Mechanism of urine concentration and dilution | 678 | ||
| Osmolarity gradient | 678 | ||
| Vasa recta and counter-current hypothesis | 678 | ||
| Transport properties of the loop of Henle | 679 | ||
| Water | 679 | ||
| Sodium and chloride | 680 | ||
| Counter-current mechanism | 680 | ||
| Urea | 680 | ||
| Vasa recta | 680 | ||
| The diluting segment and the DCT | 680 | ||
| Cortical collecting duct | 680 | ||
| RENAL CONTROL OF SODIUM BALANCE | 680 | ||
| Renal sodium handling | 681 | ||
| Sodium recovery | 681 | ||
| The PCT | 681 | ||
| The loop of Henle | 681 | ||
| The DCT | 681 | ||
| The collecting ducts | 681 | ||
| Control of GFR by the renal capillaries | 681 | ||
| Autoregulation | 682 | ||
| Glomerular–tubular balance | 682 | ||
| Receptors involved with sodium balance | 682 | ||
| Baroreceptors | 682 | ||
| The juxtaglomerular apparatus | 682 | ||
| Renin–angiotension–aldosterone system | 683 | ||
| Role of angiotensin II and Na + control | 683 | ||
| Aldosterone | 683 | ||
| Potassium | 684 | ||
| Autoregulation and the DCT | 684 | ||
| Tubulo-glomerular feedback | 684 | ||
| Na + balance summary | 684 | ||
| DIURETICS | 684 | ||
| Osmotic diuresis | 684 | ||
| Carbonic anhydrase inhibitors | 684 | ||
| The thiazide diuretics | 685 | ||
| Loop diuretics | 685 | ||
| Diuretics acting on the late distal tubule and the collecting ducts (K + sparing) | 686 | ||
| Amiloride and triamterene | 686 | ||
| Spironolactone | 686 | ||
| RENAL CONTROL OF ACID–BASE BALANCE | 686 | ||
| Hydrogen ions | 686 | ||
| Sources of H + ions | 686 | ||
| Cell metabolism produces ‘volatile’ H + ions | 686 | ||
| 'Fixed’ H + ions | 686 | ||
| Sources of non-respiratory H + ions | 686 | ||
| Disease states | 687 | ||
| Acid–base balance is vital for life | 687 | ||
| Renal mechanisms of HCO3- control | 687 | ||
| HCO3- ions and pCO 2 | 687 | ||
| Loop of Henle and HCO3- ions | 687 | ||
| The distal nephron | 688 | ||
| Renal buffers | 688 | ||
| Phosphate buffering | 688 | ||
| Ammonium synthesis | 688 | ||
| Abnormalities of acid–base balance (also see Clinical box 14.14) | 689 | ||
| THE URINARY TRACT | 690 | ||
| URETERS | 690 | ||
| Urinary tract obstruction | 690 | ||
| Congenital problems | 691 | ||
| GROSS STRUCTURE OF THE BLADDER | 691 | ||
| Maintenance of continence | 691 | ||
| Nerve supply | 691 | ||
| Bladder filling and tone | 692 | ||
| CONTROL OF MICTURITION | 692 | ||
| The micturition reflex | 692 | ||
| Renal tumours | 692 | ||
| Benign | 692 | ||
| Malignant | 692 | ||
| RENAL DISEASES | 692 | ||
| GENERAL CLASSIFICATION OF RENAL DISEASE | 693 | ||
| ONSET OF RENAL DISEASE | 693 | ||
| ACUTE KIDNEY INJURY | 693 | ||
| Acute tubular necrosis | 694 | ||
| Nephrotoxic agents | 694 | ||
| Drugs and the elderly | 694 | ||
| CHRONIC KIDNEY DISEASE | 694 | ||
| Causes of chronic kidney disease | 695 | ||
| Progression of chronic kidney disease | 695 | ||
| Chronic kidney disease and hypertension | 695 | ||
| Erythropoietin | 695 | ||
| Pharmacological renal damage and chronic renal failure | 695 | ||
| RENAL REPLACEMENT THERAPY | 696 | ||
| Chapter 15: The alimentary system | 699 | ||
| INTRODUCTION | 699 | ||
| BASIC FUNCTIONS AND STRUCTURE OF THE ALIMENTARY SYSTEM | 699 | ||
| BLOOD SUPPLY TO THE GASTROINTESTINAL TRACT | 700 | ||
| OVERVIEW OF DIGESTION AND ABSORPTION | 701 | ||
| PHYSICAL DIGESTION | 701 | ||
| CHEMICAL DIGESTION | 701 | ||
| Carbohydrate digestion | 702 | ||
| Protein digestion | 702 | ||
| Protein digestion in the stomach | 702 | ||
| Protein digestion in the small intestine | 702 | ||
| Fat digestion | 702 | ||
| ABSORPTION | 702 | ||
| General principles of absorption | 703 | ||
| Carbohydrate absorption | 704 | ||
| Glucose and galactose absorption | 704 | ||
| Fructose absorption | 705 | ||
| Protein absorption | 705 | ||
| Di- and tripeptide absorption | 706 | ||
| Amino acid absorption | 706 | ||
| Fat absorption | 706 | ||
| Bile salt absorption | 707 | ||
| Vitamins | 707 | ||
| Water-soluble vitamins | 707 | ||
| Vitamin B 12 | 707 | ||
| Fat-soluble vitamins | 707 | ||
| Absorption of electrolytes and water | 707 | ||
| Pathways for electrolyte and water absorption | 707 | ||
| Calcium absorption | 708 | ||
| Iron absorption | 708 | ||
| Regulation of iron absorption | 709 | ||
| SURFACE ANATOMY OF THE ABDOMEN | 709 | ||
| ABDOMINAL REGIONS | 710 | ||
| Epigastric region | 710 | ||
| Umbilical region | 710 | ||
| Suprapubic (hypogastric) region | 710 | ||
| Left and right hypochondrium | 710 | ||
| Left and right lumbar region | 711 | ||
| Left and right iliac fossa (inguinal region) | 711 | ||
| QUADRANTS | 711 | ||
| MICROANATOMY OF THE GASTROINTESTINAL TRACT | 711 | ||
| INNERVATION OF THE ALIMENTARY CANAL | 713 | ||
| MOUTH | 714 | ||
| TEETH | 714 | ||
| TONGUE | 714 | ||
| MASTICATION | 714 | ||
| SALIVARY GLANDS | 714 | ||
| FUNCTIONS OF SALIVA | 715 | ||
| Lubrication | 715 | ||
| Protection | 715 | ||
| Digestion | 715 | ||
| COMPOSITION OF SALIVA | 715 | ||
| Organic constituents | 716 | ||
| Inorganic constituents | 716 | ||
| SECRETORY MECHANISMS | 716 | ||
| The salivon | 716 | ||
| Mechanisms of secretion of saliva | 716 | ||
| Stage one – the primary secretion | 716 | ||
| Stage two – modification of the primary secretion | 716 | ||
| Secretion of organic constituents | 717 | ||
| CONTROL OF SALIVARY SECRETION | 717 | ||
| Parasympathetic nervous system | 718 | ||
| Sympathetic nervous system | 718 | ||
| Intracellular messengers producing salivary secretion | 718 | ||
| PHARYNX AND OESOPHAGUS | 718 | ||
| SWALLOWING | 718 | ||
| Oral or voluntary phase | 718 | ||
| Pharyngeal phase | 718 | ||
| Oesophageal phase | 719 | ||
| STOMACH AND DUODENUM | 719 | ||
| ANATOMY OF THE STOMACH | 719 | ||
| Gastric and duodenal musculature | 720 | ||
| The gastric mucosa | 721 | ||
| CONTROL OF GASTRIC SECRETIONS | 722 | ||
| STIMULATION OF GASTRIC ACID SECRETION | 722 | ||
| Cephalic phase | 722 | ||
| Gastric phase | 723 | ||
| Intestinal phase | 723 | ||
| INHIBITION OF GASTRIC ACID SECRETION | 723 | ||
| Cephalic phase | 724 | ||
| Gastric phase | 724 | ||
| Intestinal phase | 724 | ||
| STIMULATION OF PEPSINOGEN SECRETION | 724 | ||
| CELLULAR MECHANISMS OF GASTRIC ACID SECRETION | 724 | ||
| Morphological changes in parietal cells ( Fig. 15.16) | 724 | ||
| Intracellular messenger for the action of acetylcholine, gastrin and histamine | 725 | ||
| Ion movements during acid secretion | 726 | ||
| Proton pump | 726 | ||
| Sodium pump | 726 | ||
| GASTRIC MUCOSAL PROTECTION | 726 | ||
| Peptic ulceration | 727 | ||
| GASTRIC MOTILITY | 727 | ||
| GASTRIC MUSCULATURE | 727 | ||
| ELECTRICAL AND CONTRACTILE ACTIVITY OF GASTRIC SMOOTH MUSCLE | 727 | ||
| GASTRIC MOTILITY DURING THE INTERDIGESTIVE PERIOD | 728 | ||
| GASTRIC MOTILITY DURING A MEAL | 728 | ||
| Receptive relaxation | 728 | ||
| Mixing of gastric contents | 728 | ||
| Gastric emptying | 728 | ||
| Gastric contents | 728 | ||
| Duodenal contents | 729 | ||
| Other factors | 730 | ||
| NAUSEA, RETCHING AND VOMITING | 730 | ||
| EXOCRINE PANCREAS | 730 | ||
| PANCREATIC ENZYMES | 730 | ||
| Mechanisms of enzyme secretion | 731 | ||
| Alkaline secretion | 731 | ||
| CONTROL OF PANCREATIC JUICE SECRETION | 734 | ||
| Cephalic phase | 734 | ||
| Gastric phase | 734 | ||
| Intestinal phase | 734 | ||
| Interactions between acetylcholine, cholecystokinin and secretin | 734 | ||
| Intracellular messengers for acetylcholine, cholecystokinin and secretin | 734 | ||
| Inhibition of pancreatic secretion | 734 | ||
| THE LIVER AND BILIARY SYSTEM | 734 | ||
| ANATOMY OF THE LIVER | 735 | ||
| Gross anatomy of the liver | 735 | ||
| Blood supply to the liver | 735 | ||
| Microanatomy of the liver | 735 | ||
| FUNCTIONS OF THE LIVER | 737 | ||
| The liver and carbohydrate metabolism | 737 | ||
| The liver and protein metabolism | 737 | ||
| The liver and lipid metabolism | 737 | ||
| The liver and red blood cells | 738 | ||
| Metabolism of bilirubin | 738 | ||
| The liver and bile production | 738 | ||
| Bile secretion | 738 | ||
| Cellular mechanisms of bile secretion | 739 | ||
| Bile-salt-dependent secretion | 739 | ||
| Bile-salt-independent flow | 739 | ||
| The liver and drug metabolism | 739 | ||
| Immunological functions of the liver | 740 | ||
| The liver and hormones | 740 | ||
| Storage function of the liver | 740 | ||
| SOME DISEASES OF THE LIVER | 740 | ||
| Hepatocellular disease | 740 | ||
| Some causes of hepatitis | 741 | ||
| Cirrhosis of the liver | 741 | ||
| Portal hypertension | 741 | ||
| Ascites | 742 | ||
| Porto-systemic encephalopathy | 742 | ||
| GALL BLADDER | 742 | ||
| Bile is concentrated in the gall bladder | 743 | ||
| Emptying of the gall bladder | 743 | ||
| Enterohepatic circulation of bile salts | 743 | ||
| SMALL INTESTINE | 743 | ||
| STRUCTURE OF THE SMALL INTESTINE | 744 | ||
| SMALL INTESTINAL FLUID SECRETION | 744 | ||
| SMALL INTESTINAL MOTILITY | 745 | ||
| Intestino-intestinal inhibitory reflex | 745 | ||
| Gastro-ileal reflex | 745 | ||
| LARGE INTESTINE | 746 | ||
| LARGE INTESTINAL FLUID SECRETION | 746 | ||
| MUSCULATURE OF THE LARGE INTESTINE | 746 | ||
| LARGE INTESTINAL MOTILITY | 746 | ||
| MOTILITY OF THE RECTUM AND ANAL CANAL | 747 | ||
| DEFECATION | 747 | ||
| Chapter 16: Diet and nutrition | 749 | ||
| INTRODUCTION | 749 | ||
| WORLDWIDE DIETARY PATTERNS AND FOOD GUIDES | 750 | ||
| FOOD GUIDES | 750 | ||
| FOOD LABELLING | 750 | ||
| DIETARY REFERENCE VALUES | 751 | ||
| NUTRITIONAL REQUIREMENTS | 751 | ||
| VARIATIONS IN NUTRITIONAL REQUIREMENTS | 752 | ||
| Preconception | 752 | ||
| Pregnancy | 752 | ||
| Lactation | 753 | ||
| Infancy | 753 | ||
| NUTRITIONAL STATUS | 754 | ||
| CLINICAL ASSESSMENT OF NUTRITIONAL STATUS | 754 | ||
| FOOD INTAKE | 754 | ||
| Detailed dietary assessment | 754 | ||
| 'USUAL WEIGHT’ AND WEIGHT LOSS/GAIN | 754 | ||
| BODY MASS INDEX | 755 | ||
| CHILDREN | 755 | ||
| MEASURES OF BODY COMPOSITION: ADULTS | 755 | ||
| ESTIMATING BODY FAT | 755 | ||
| Skinfold thickness | 755 | ||
| Arm circumference | 755 | ||
| Waist circumference and waist/hip ratio | 756 | ||
| OTHER MEASUREMENTS OF NUTRITIONAL STATUS | 756 | ||
| PLASMA PROTEINS | 756 | ||
| VITAMIN STATUS | 756 | ||
| MUSCLE STRENGTH | 756 | ||
| IMMUNOLOGICAL SKIN TESTING | 756 | ||
| MALNUTRITION SCREENING TOOLS | 756 | ||
| ENERGY AND NITROGEN BALANCE | 756 | ||
| CONVERSION OF MACRONUTRIENTS TO ENERGY | 756 | ||
| ENERGY BALANCE | 757 | ||
| Basal metabolic rate (BMR) and resting energy expenditure | 757 | ||
| Total energy expenditure | 757 | ||
| Measuring energy expenditure | 757 | ||
| Total energy expenditure and the effect of physical activity | 757 | ||
| Energy expenditure during daily living | 757 | ||
| Estimates of energy consumption for different types of activity | 758 | ||
| Energy expenditure during exercise | 758 | ||
| Anaerobic carbohydrate metabolism | 758 | ||
| Aerobic carbohydrate metabolism | 758 | ||
| NITROGEN BALANCE AND PROTEIN REQUIREMENTS | 759 | ||
| Dietary nitrogen | 759 | ||
| Protein requirements | 759 | ||
| Essential and non-essential amino acids | 759 | ||
| Obligatory nitrogen loss | 759 | ||
| Minimum nitrogen requirement | 759 | ||
| Nitrogen excretion | 759 | ||
| Energy and protein metabolism during fasting and feeding | 760 | ||
| Fed state | 760 | ||
| Absorbed carbohydrate in the fed state | 760 | ||
| Absorbed fat in the fed state | 761 | ||
| Protein in the fed state | 761 | ||
| Fasted state | 761 | ||
| The need for glucose in the fasted state | 761 | ||
| Decreased insulin – fasting state | 762 | ||
| Fat in the fasted state | 762 | ||
| Prolonged fasting/starvation | 762 | ||
| Metabolic response to stress: sepsis and trauma | 763 | ||
| Energy metabolism during illness | 763 | ||
| Insulin and the inflammatory response | 763 | ||
| Protein metabolism in illness | 763 | ||
| Protein metabolism and acute phase response in illness | 764 | ||
| VITAMINS | 765 | ||
| Vitamins as coenzymes | 765 | ||
| Vitamins as antioxidants | 765 | ||
| WATER-SOLUBLE VITAMINS | 765 | ||
| The B vitamins | 765 | ||
| Vitamin B 1 (thiamine) | 765 | ||
| Vitamin B 2 (riboflavin) | 766 | ||
| Vitamin B 3 (niacin) | 766 | ||
| Vitamin B 6 (pyridoxine) | 766 | ||
| Biotin | 766 | ||
| Pantothenic acid | 766 | ||
| Folic acid | 766 | ||
| Vitamin B 12 (cobalamin) | 766 | ||
| Vitamin C (ascorbic acid) | 766 | ||
| FAT-SOLUBLE VITAMINS | 766 | ||
| Vitamin A | 766 | ||
| Vitamin D (calciferol) | 767 | ||
| Vitamin E (tocopherols) | 767 | ||
| Vitamin K | 767 | ||
| TRACE ELEMENTS: MINERALS | 767 | ||
| IRON | 767 | ||
| COPPER | 767 | ||
| ZINC | 768 | ||
| SELENIUM | 768 | ||
| MAGNESIUM | 768 | ||
| CALCIUM | 768 | ||
| PHOSPHATE | 768 | ||
| IODINE | 768 | ||
| FLUORIDE | 769 | ||
| WATER AND ELECTROLYTES | 769 | ||
| WATER | 769 | ||
| Daily water requirements | 769 | ||
| ELECTROLYTES | 769 | ||
| WATER AND ELECTROLYTE DEPLETION | 769 | ||
| Intravenous fluid replacement | 769 | ||
| WATER OVERLOAD | 770 | ||
| THE CONTROL OF FOOD INTAKE | 771 | ||
| APPETITE AND SATIETY | 771 | ||
| THE PHYSIOLOGICAL CONTROL OF EATING | 771 | ||
| PERIPHERAL SATIETY SIGNALS | 771 | ||
| Gastric distension and emptying | 771 | ||
| Balance of chemical contents in the gut | 771 | ||
| Peptides and hormones | 772 | ||
| PERIPHERAL HUNGER SIGNALS | 772 | ||
| Ghrelin | 772 | ||
| LONG-TERM SATIETY SIGNALS | 772 | ||
| Leptin | 772 | ||
| Insulin | 773 | ||
| Oestrogen | 773 | ||
| DIET AND DISEASE | 773 | ||
| ASSOCIATION BETWEEN DIET AND DISEASE | 773 | ||
| Reactive oxygen species or free radicals | 773 | ||
| Formation of reactive oxygen species | 773 | ||
| Body defence against cancer or invading bacteria | 774 | ||
| Oxidative stress | 774 | ||
| Defence against reactive oxygen species – antioxidants | 774 | ||
| DIET AND CARCINOGENESIS | 774 | ||
| Antioxidants | 774 | ||
| Obesity | 775 | ||
| NUTRITION AND CANCER TREATMENT | 775 | ||
| DIET AND CARDIOVASCULAR DISEASE | 775 | ||
| Dietary prevention of atherosclerosis | 775 | ||
| Atherogenesis | 776 | ||
| Homocysteine | 776 | ||
| Diet and hypertension | 776 | ||
| Dietary approach to hypertension | 776 | ||
| Cardioprotective diets | 777 | ||
| Some therapeutic diets | 777 | ||
| Dietary treatment of coeliac disease | 777 | ||
| Dietary restrictions in renal disease | 777 | ||
| Protein | 777 | ||
| Energy | 777 | ||
| Potassium | 777 | ||
| Phosphate | 777 | ||
| Sodium and fluid | 777 | ||
| Dietary control in diabetes mellitus | 777 | ||
| Exercise in diabetes | 778 | ||
| Lipid lowering | 778 | ||
| Artificial nutrition | 778 | ||
| Enteral nutrition | 778 | ||
| Complications of enteral feeding | 778 | ||
| Parenteral nutrition | 778 | ||
| MALNUTRITION | 779 | ||
| Malnutrition and disease states | 779 | ||
| Diagnosis of malnutrition | 779 | ||
| Refeeding syndrome | 779 | ||
| Avoidance of refeeding syndrome | 780 | ||
| OBESITY | 780 | ||
| Aetiology of obesity | 781 | ||
| Psychogenic factors | 781 | ||
| Environmental factors and exercise | 781 | ||
| Treatment of obesity | 782 | ||
| Dietary management | 782 | ||
| A psychological model for dietary modification | 782 | ||
| Pharmacological management | 783 | ||
| Appetite suppression | 783 | ||
| Inhibition of fat absorption | 783 | ||
| Surgical management | 783 | ||
| Increasing physical activity | 784 | ||
| Prevention of obesity | 784 | ||
| Index | 785 |