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Book Details
Abstract
- Clear, integrated approach to contextualising the medical sciences in their clinical application.
- Highly illustrated.
- Accessible, readable writing.
- e-only chapters which animate difficult concepts
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Inside Front Cover | ifc1 | ||
| Medical Sciences | i | ||
| Copyright Page | iv | ||
| Table Of Contents | v | ||
| Videos | v | ||
| Preface | vi | ||
| Contributors | vii | ||
| Acknowledgements | ix | ||
| Dedication | ix | ||
| 1 Introduction and homeostasis | 1 | ||
| Chapter 2 Biochemistry and Cell Biology | 1 | ||
| Chapter 3 Energy and 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 | 3 | ||
| Homeostatic control of glucose metabolism | 3 | ||
| Thermoregulation | 4 | ||
| Human body temperature (Clinical box 1.1) | 4 | ||
| Heat-loss mechanisms | 5 | ||
| Heat-gain mechanisms | 5 | ||
| Thermoneutral zones | 6 | ||
| Positive feedback (Information box 1.1) | 6 | ||
| Feedforward (Information box 1.2) | 6 | ||
| Water and electrolytes: homeostatic control of body fluids | 6 | ||
| Fluid compartments | 6 | ||
| Movement of fluids between compartments | 8 | ||
| Properties of forces that drive fluid movement between compartments | 8 | ||
| Osmolarity | 8 | ||
| Tonicity (Clinical box 1.2) | 8 | ||
| Effect of solutes on body fluids | 9 | ||
| Homeostatic control of fluid balance | 9 | ||
| Hormonal control of fluid balance (Clinical box 1.3) | 9 | ||
| Behavioural control of fluid balance (Clinical box 1.4) | 9 | ||
| Thirst | 10 | ||
| Acid–base balance: homeostatic control of hydrogen ions (Clinical box 1.7) | 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 1.8) | 12 | ||
| Renal control of pH (Clinical box 1.9) | 13 | ||
| Renal H+ excretion | 13 | ||
| Renal bicarbonate reabsorption | 13 | ||
| 2 Biochemistry and cell biology | 15 | ||
| Introduction | 15 | ||
| Principles of Molecular Interactions | 16 | ||
| Atoms | 16 | ||
| Ions | 17 | ||
| Acids and bases | 17 | ||
| Chemical bonds | 17 | ||
| Ionic bonds | 17 | ||
| Covalent bonds | 17 | ||
| Polar covalent bonds | 18 | ||
| Hydrogen bonds | 18 | ||
| Non-polar molecular interactions | 18 | ||
| Organic compounds | 18 | ||
| Spatial arrangement of organic molecules | 18 | ||
| Chemical reactions | 18 | ||
| Electrophiles and nucleophiles | 19 | ||
| Oxidation–reduction (redox) reactions | 19 | ||
| Energy in biological systems | 19 | ||
| Energy cycle in biology | 19 | ||
| Potential energy of chemical bonds | 19 | ||
| Energy flow in chemical reactions | 20 | ||
| Anabolic and catabolic pathways | 20 | ||
| Generation of metabolic energy | 20 | ||
| Chemical Composition of the Human Body | 20 | ||
| Chemical elements | 20 | ||
| Water content and the main fluid compartments | 21 | ||
| The role of vitamins | 21 | ||
| Organic biomolecules | 22 | ||
| Carbohydrates | 22 | ||
| Monosaccharides | 22 | ||
| The five-carbon sugars (pentoses) | 22 | ||
| The six-carbon sugars (hexoses) | 22 | ||
| Modified monosaccharides: amino sugars and sugar-derived acids | 23 | ||
| Disaccharides | 23 | ||
| Polysaccharides | 23 | ||
| Complex Carbohydrates | 24 | ||
| Lipids | 24 | ||
| Fatty acids | 24 | ||
| Triacylglycerols | 25 | ||
| Dietary fats | 25 | ||
| Essential fatty acids | 25 | ||
| Eicosanoids | 25 | ||
| Cholesterol and steroids | 25 | ||
| Bile acids | 25 | ||
| Steroid hormones | 26 | ||
| Vitamin D | 26 | ||
| 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 | 29 | ||
| Deoxyribonucleic acid | 29 | ||
| Primary structure of the nucleic acids | 29 | ||
| Secondary structure of DNA | 29 | ||
| The double helix | 30 | ||
| Complementarity of the DNA strands | 30 | ||
| Tertiary structure of DNA: chromatin and the nucleosomes | 30 | ||
| Mitochondrial DNA | 30 | ||
| DNA replication | 30 | ||
| DNA proofing and repair | 31 | ||
| Damage to DNA | 31 | ||
| Ribonucleic acids | 31 | ||
| Secondary structure of RNA | 32 | ||
| Amino acids | 32 | ||
| Structure of the amino acids | 32 | ||
| Classification of amino acids | 33 | ||
| Dissociation of amino acids | 34 | ||
| Proteins | 34 | ||
| The peptide bond | 34 | ||
| Structure of proteins | 34 | ||
| Primary structure | 34 | ||
| Secondary structure | 34 | ||
| Tertiary structure | 34 | ||
| Protein denaturation | 35 | ||
| Quaternary structure | 36 | ||
| Cooperativity between protein subunits | 36 | ||
| Protein synthesis and processing | 36 | ||
| Ribosomes | 36 | ||
| Transcription | 37 | ||
| Post-transcriptional modification of mRNA: splicing | 37 | ||
| Translation | 37 | ||
| Initiation of protein synthesis | 37 | ||
| Elongation of the polypeptide chain | 37 | ||
| Termination of protein synthesis | 37 | ||
| Post-translational modification of proteins | 38 | ||
| Cellular protein targeting | 38 | ||
| Protein secretion | 39 | ||
| Functions of proteins | 39 | ||
| Structural proteins | 39 | ||
| Collagens and proteins present in the extracellular matrix | 39 | ||
| Muscle proteins | 39 | ||
| Cytoskeletal proteins | 39 | ||
| Proteins that participate in immunity | 39 | ||
| Transport proteins | 39 | ||
| Procoagulant and anticoagulant proteins | 39 | ||
| DNA-binding proteins: histones and transcription factors | 40 | ||
| Catalytic proteins: enzymes | 40 | ||
| Enzyme kinetics | 40 | ||
| Enzyme inhibition | 41 | ||
| Regulation of enzyme activity | 41 | ||
| Enzyme cofactors | 42 | ||
| Enzymes as biomarkers | 42 | ||
| Signalling proteins and cell signalling systems | 42 | ||
| Hormones | 42 | ||
| Neurotransmitters | 43 | ||
| Hormone receptors | 43 | ||
| Proteins involved in cell adhesion and recognition | 44 | ||
| Membrane transport proteins and membrane transport systems | 44 | ||
| Passive diffusion | 44 | ||
| Carrier-mediated transport | 44 | ||
| Facilitated diffusion | 44 | ||
| Ion channels | 44 | ||
| Active transport | 45 | ||
| Na+/K+-ATPase | 45 | ||
| Other ATPases | 45 | ||
| Secondary active transport | 45 | ||
| Coordinated action of cellular transport systems | 45 | ||
| The Cell | 46 | ||
| Cell walls and cell membranes | 46 | ||
| Proteins in cell membranes | 47 | ||
| Cytoplasm | 47 | ||
| Cytoskeleton | 48 | ||
| Nucleus | 48 | ||
| Endoplasmic reticulum | 48 | ||
| Golgi apparatus (Golgi complex) | 49 | ||
| Mitochondria | 49 | ||
| Lysosomes | 49 | ||
| Proteasomes | 49 | ||
| Peroxisomes | 49 | ||
| Cell junctions | 49 | ||
| Tight junctions | 49 | ||
| Anchoring junctions | 50 | ||
| Gap junctions | 50 | ||
| Cell adhesion and recognition | 50 | ||
| Transport Within Cells | 50 | ||
| Endocytosis | 50 | ||
| Intracellular and Transcellular Transport | 51 | ||
| Exocytosis | 51 | ||
| Transcytosis | 51 | ||
| Receptor-mediated endocytosis | 51 | ||
| Organs and Tissues | 51 | ||
| Epithelial tissues | 52 | ||
| Connective tissue | 52 | ||
| Fibrocollagenous tissues | 52 | ||
| Extracellular matrix | 52 | ||
| Cartilage, teeth and bone | 52 | ||
| Fat (adipose) tissue | 54 | ||
| Blood | 54 | ||
| Muscle | 54 | ||
| Nervous tissue | 55 | ||
| Integrated learning: the systemic approach | 56 | ||
| 3 Energy metabolism | 57 | ||
| Introduction to Metabolism | 57 | ||
| Energy is released by catabolism and consumed by anabolism | 57 | ||
| Tricarboxylic acid cycle | 58 | ||
| Control of the TCA cycle | 59 | ||
| Electron transport chain and oxidative phosphorylation | 60 | ||
| Electron transport chain | 60 | ||
| Oxidative phosphorylation | 61 | ||
| Coupling of the electron transport chain and oxidative phosphorylation | 61 | ||
| Electron transport chain inhibition | 61 | ||
| Energy output | 61 | ||
| Regulation of fuel metabolism | 62 | ||
| Binding of allosteric effectors to an enzyme to alter its affinity for substrate | 62 | ||
| 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 | 63 | ||
| Different tissues metabolise different energy substrates | 63 | ||
| How fuel is stored and transported between tissues | 64 | ||
| Carbohydrate Metabolism | 64 | ||
| Regulation of blood glucose (glycaemia) | 64 | ||
| Sources of blood glucose | 64 | ||
| Four key pathways maintain and utilise blood glucose | 64 | ||
| Glucose transport | 64 | ||
| GLUT1 | 64 | ||
| GLUT2 | 65 | ||
| GLUT3 | 65 | ||
| GLUT4 | 65 | ||
| Glycolysis – the anaerobic catabolism of glucose | 65 | ||
| Importance of the anaerobic nature of glycolysis | 65 | ||
| For erythrocytes | 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) | 68 | ||
| PFK-1 activity is highly sensitive to the energy status of the cell | 68 | ||
| Regulation of PFK-1 | 68 | ||
| Regulation by energy status and allosteric effectors | 68 | ||
| Fructose-2,6-bisphosphate | 69 | ||
| In the liver | 69 | ||
| In muscle | 69 | ||
| Citrate and pH | 69 | ||
| Energy-producing stage of glycolysis – production of pyruvate and lactate | 69 | ||
| Reactions yielding ATP | 69 | ||
| Pyruvate kinase | 70 | ||
| Fate of pyruvate | 71 | ||
| In most cells which contain mitochondria | 71 | ||
| In the fasting state | 71 | ||
| In cells that lack mitochondria or when oxygen supply is limited | 71 | ||
| Lactate dehydrogenase | 71 | ||
| Oxidative glucose metabolism – aerobic glycolysis | 72 | ||
| Pyruvate dehydrogenase complex | 72 | ||
| Regulation of PDC activity | 72 | ||
| Glycogen – the storage form of glucose | 73 | ||
| In the liver | 73 | ||
| In skeletal muscle | 73 | ||
| Synthesis of glycogen | 73 | ||
| Glycogenin, the glycogen primer | 73 | ||
| Glycogen synthase | 73 | ||
| Structure of glycogen | 74 | ||
| Control of glycogen synthesis | 74 | ||
| Allosteric control | 74 | ||
| Covalent mechanisms regulating glycogen synthesis | 74 | ||
| Control of glycogen synthesis in the liver | 74 | ||
| Control of glycogen synthesis in muscle | 75 | ||
| Glycogenolysis – the breakdown of glycogen | 75 | ||
| Glycogenolysis in liver | 75 | ||
| Glycogenolysis in muscle | 76 | ||
| Regulation of glycogenolysis | 76 | ||
| Regulation of hepatic glycogenolysis | 76 | ||
| Hormonal regulation of hepatic glycogenolysis | 76 | ||
| Mechanism of glucagon regulation of glycogenolysis – hormone signalling | 76 | ||
| Sympathetic stimulation | 77 | ||
| Enzyme regulation of hepatic glycogenolysis | 77 | ||
| Regulation of hepatic glycogen phosphorylase | 77 | ||
| Regulation of phosphorylase kinase by covalent modification – phosphorylation | 77 | ||
| Amplification of the signalling cascade | 78 | ||
| Ca2 + as a second messenger | 78 | ||
| Regulation of muscle and brain glycogenolysis | 78 | ||
| Genetic defects in glycogenolysis | 78 | ||
| Gluconeogenesis – glucose synthesis | 78 | ||
| Precursors of gluconeogenesis | 78 | ||
| Gluconeogenesis from lactate | 79 | ||
| Gluconeogenesis from protein | 80 | ||
| Gluconeogenesis from glycerol | 80 | ||
| Peroxisome proliferator-activated receptors in energy homeostasis | 80 | ||
| Energy for gluconeogenesis | 80 | ||
| Cori and glucose–alanine cycles | 81 | ||
| Gluconeogenesis from other sugars | 81 | ||
| Regulation of gluconeogenesis | 81 | ||
| Amino Acid Metabolism | 82 | ||
| Metabolic classes of amino acids (Clinical box 3.13) | 82 | ||
| Essential and non-essential | 82 | ||
| Glucogenic and ketogenic | 82 | ||
| Absorption of amino acids | 82 | ||
| Nitrogen in amino acid metabolism | 84 | ||
| Transamination | 85 | ||
| Amino acid release by skeletal muscle in the post-absorptive state | 85 | ||
| Deamination | 86 | ||
| Glutamine in acid–base homeostasis | 86 | ||
| Ammonia | 86 | ||
| Urea cycle | 87 | ||
| Regulation of the urea cycle | 87 | ||
| 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 | 89 | ||
| Dietary fatty acids | 89 | ||
| Endogenously synthesised fatty acids | 90 | ||
| Storage of lipids | 90 | ||
| Fatty acids | 90 | ||
| Protein-bound fatty acids | 91 | ||
| Triacylglycerols (triglycerides) | 91 | ||
| Regulation of triacylglycerol degradation | 91 | ||
| Lipoproteins | 92 | ||
| Apolipoproteins | 92 | ||
| Lipoprotein classes and functions | 92 | ||
| Chylomicrons | 93 | ||
| Very-low-density lipoprotein | 93 | ||
| Intermediate-density lipoprotein | 93 | ||
| Low-density lipoprotein | 93 | ||
| High-density lipoprotein | 93 | ||
| Lipoprotein receptors | 93 | ||
| Scavenger receptors | 93 | ||
| Lipoprotein metabolism | 93 | ||
| Reverse cholesterol transport | 93 | ||
| Lipoprotein fuel transport and overflow pathways | 94 | ||
| Fatty acid oxidation | 94 | ||
| Fatty acid activation and transport into mitochondria | 94 | ||
| 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 | 95 | ||
| Inhibition of the β-oxidation spiral by excessive CoA | 95 | ||
| Ketogenesis in the liver | 95 | ||
| Oxidation of acetyl-CoA in the ketogenic pathway | 95 | ||
| Role of ketone bodies in fuel homeostasis | 95 | ||
| Ketone body utilisation | 96 | ||
| Lipogenesis – fatty acid synthesis | 97 | ||
| Stage 1: ACC – the committed step of lipogenesis | 97 | ||
| Regulation of ACC activity | 97 | ||
| Acetyl-CoA contains an allosteric site for the binding of citrate or palmitoyl-CoA | 97 | ||
| ACC control by hormone-dependent covalent modification | 97 | ||
| The rate of ACC synthesis is highly regulated | 97 | ||
| Stage 2: FAS | 97 | ||
| Chain elongation | 97 | ||
| Desaturation | 97 | ||
| Regulation of fatty acid synthase and rate of lipogenesis | 99 | ||
| Malate shuttle – production of acetyl-CoA for lipogenesis | 99 | ||
| Fine-tuning of fatty acid synthesis, oxidation and ketogenesis | 100 | ||
| Regulation of fat metabolism | 100 | ||
| In the fasting (post-absorptive) state | 100 | ||
| In the fed (absorptive) state | 100 | ||
| Summary | 100 | ||
| 4 Pharmacology | 103 | ||
| Introduction | 103 | ||
| Terms used in pharmacology | 103 | ||
| Routes of Administration of Drugs | 103 | ||
| Oral administration | 104 | ||
| Factors affecting gastrointestinal absorption of a drug | 104 | ||
| Physicochemical properties of the drug, the medium and surface area | 104 | ||
| Drug solubility | 104 | ||
| Acid–base considerations | 104 | ||
| Surface area for absorption | 104 | ||
| Fate of drugs in the stomach | 104 | ||
| Metabolism of drugs in the gastrointestinal tract | 104 | ||
| Bioavailability and bioequivalence | 105 | ||
| First pass metabolism | 105 | ||
| Impact of liver disease on first pass metabolism | 105 | ||
| Parenteral administration | 105 | ||
| Intravenous | 105 | ||
| Subcutaneous | 105 | ||
| Intramuscular | 105 | ||
| Other forms of injection | 105 | ||
| Intrathecal | 105 | ||
| Epidural | 105 | ||
| Local injections into tendons/bursae | 106 | ||
| Buccal/sublingual administration | 106 | ||
| Rectal | 106 | ||
| Topical/transdermal | 106 | ||
| Intranasal administration | 106 | ||
| Inhalation | 106 | ||
| Pharmacokinetics | 106 | ||
| Absorption – transfer of drugs across cell membranes | 107 | ||
| Passive diffusion through lipid membranes | 107 | ||
| Lipid solubility | 107 | ||
| Ionised and non-ionised forms of a drug | 107 | ||
| Degree of ionisation of a drug | 107 | ||
| Passive diffusion across cell membranes | 108 | ||
| Ion trapping | 108 | ||
| Effects of acidosis or alkalosis on absorption and distribution | 108 | ||
| Carrier-mediated transport | 109 | ||
| Transporters (carrier proteins) | 109 | ||
| Ion channel proteins | 109 | ||
| Endocytosis and exocytosis | 109 | ||
| Diffusion through aqueous and intercellular pores | 110 | ||
| Gap junctions | 110 | ||
| Drug distribution | 110 | ||
| Blood flow | 110 | ||
| Capillary permeability and gap junctions | 110 | ||
| Drug distribution to special organs | 110 | ||
| Central nervous system | 110 | ||
| Foetus | 110 | ||
| Accumulation of drugs in fat and redistribution in other tissues | 110 | ||
| Binding of drugs to proteins | 111 | ||
| Competitive protein binding | 111 | ||
| Hypoproteinaemia | 111 | ||
| Sequestration of drugs in tissues | 111 | ||
| Distribution of drugs in the body | 111 | ||
| Extent of drug distribution into aqueous compartments | 112 | ||
| Apparent volume of distribution | 112 | ||
| Drug metabolism | 113 | ||
| Phase I metabolic reactions (pre-conjugation reactions) | 113 | ||
| Oxidation | 113 | ||
| Microsomal oxidation reactions | 113 | ||
| Cytochrome P450 system | 113 | ||
| Non-microsomal oxidative reactions | 113 | ||
| Reduction | 114 | ||
| Hydrolysis – hydroxylation | 114 | ||
| Phase II metabolic reactions (conjugation reactions) | 115 | ||
| Conjugation by glucuronidation | 115 | ||
| Other conjugation reactions | 115 | ||
| Drug detoxification | 115 | ||
| Factors affecting drug metabolism | 115 | ||
| Genetic factors | 115 | ||
| Environmental contaminants and drugs | 116 | ||
| Enzyme induction | 116 | ||
| Enzyme inhibition | 116 | ||
| Enzyme inhibition by metabolites | 116 | ||
| Conversion of inactive pro-drug to an active metabolite | 116 | ||
| Excretion of drugs and metabolites | 116 | ||
| Renal system | 117 | ||
| Glomerular filtration | 117 | ||
| Tubular secretion | 117 | ||
| Tubular reabsorption | 117 | ||
| Diuretic drugs | 118 | ||
| Diuretics acting on the loop of Henle | 118 | ||
| Pharmacodynamics | 118 | ||
| Pharmacokinetics of loop diuretics | 118 | ||
| 5 Human genetics | 153 | ||
| Introduction | 153 | ||
| Historical background | 153 | ||
| Basis of modern genetics | 153 | ||
| The Human Genome | 155 | ||
| DNA and chromosomes | 155 | ||
| Chromosome karyotypes (see Fig. 5.2) | 155 | ||
| Mitochondrial DNA | 155 | ||
| Cell division | 155 | ||
| The cell cycle | 157 | ||
| Interphase | 157 | ||
| Mitosis (Fig. 5.4) | 158 | ||
| Meiosis (Fig. 5.6) | 158 | ||
| Chromosome abnormalities | 161 | ||
| Abnormalities in number | 161 | ||
| Abnormalities in structure | 162 | ||
| DNA and genes | 162 | ||
| Homeobox (and HOX) genes | 162 | ||
| Non-coding DNA | 164 | ||
| Transcription (Fig. 5.12) | 164 | ||
| Regulation of transcription | 165 | ||
| Translation | 165 | ||
| DNA damage | 166 | ||
| DNA damage from environmental factors | 166 | ||
| Spontaneous damage (DNA replication mistakes) | 166 | ||
| Repair mechanisms | 166 | ||
| Direct reversal of base damage | 166 | ||
| Breakage repair | 167 | ||
| Excision repair | 167 | ||
| Non-homologous end joining | 167 | ||
| Microhomology-mediated end joining | 167 | ||
| Homologous recombination | 167 | ||
| Genes and development | 167 | ||
| Mediators of development | 167 | ||
| Signalling molecules | 167 | ||
| Fibroblast growth factor and fibroblast growth factor receptor | 167 | ||
| Sonic hedgehog | 168 | ||
| Wingless (Wnt) | 168 | ||
| Transforming growth factor-β | 168 | ||
| DNA transcription factors | 168 | ||
| SOX family genes | 168 | ||
| Extracellular matrix proteins | 168 | ||
| Patterning | 168 | ||
| Anterior/posterior axis formation | 168 | ||
| Left/right axis formation | 168 | ||
| Dorsal/ventral axis development | 168 | ||
| Organogenesis | 169 | ||
| Neuronal development | 169 | ||
| The asymmetrical heart | 169 | ||
| Organ formation | 169 | ||
| Limb development | 169 | ||
| Epigenetic mechanisms | 170 | ||
| Human Genetic Variation | 170 | ||
| Polymorphisms | 170 | ||
| Mutation or polymorphism? | 170 | ||
| Types of mutational events leading to polymorphisms | 170 | ||
| Single nucleotide polymorphisms | 170 | ||
| Deletions and insertions (Clinical box 5.6) | 171 | ||
| Gene duplications | 171 | ||
| Consequences of genetic mutation | 171 | ||
| Founder effects | 172 | ||
| Genghis Khan and the founder effect | 172 | ||
| Bottlenecks | 172 | ||
| Population drift | 173 | ||
| Genotypes, phenotypes and genetic penetrance | 173 | ||
| Modes of Inheritance | 175 | ||
| Mendelian disorders | 175 | ||
| Autosomal dominant inheritance (Figs 5.22 and 5.23) | 175 | ||
| Autosomal recessive inheritance (Figs 5.24 and 5.25) | 176 | ||
| Consanguinity and recessive disorders | 177 | ||
| Coefficient of relationship | 177 | ||
| Rare disorders and consanguinity | 177 | ||
| X-Linked inheritance | 177 | ||
| Lyonisation | 177 | ||
| Dominant X-linked inheritance (Figs 5.26 and 5.27) | 178 | ||
| Recessive X-linked inheritance (Figs 5.28 and 5.29) | 178 | ||
| Haemophilia – the royal disease | 178 | ||
| Other modes of inheritance | 179 | ||
| Genomic imprinting | 179 | ||
| Mitochondrial disorders | 180 | ||
| Mosaicism | 180 | ||
| Inborn errors of metabolism (see Ch. 3) | 181 | ||
| Polygenic or Complex Disease | 182 | ||
| Continuous effects models | 182 | ||
| Threshold effects models | 182 | ||
| Characteristics of multifactorial diseases | 182 | ||
| Heritability | 183 | ||
| Genetic epidemiology | 183 | ||
| Twin studies | 183 | ||
| Biases in twin studies | 184 | ||
| Adoption studies | 184 | ||
| Association studies | 184 | ||
| Tools to Investigate Polygenic Diseases | 184 | ||
| Information from single gene disorders | 184 | ||
| Animal models | 184 | ||
| Linkage studies | 185 | ||
| Expression profiles | 185 | ||
| Whole-genome association studies (WGAS) | 185 | ||
| Cancer Genetics | 185 | ||
| Models of carcinogenesis | 185 | ||
| Inheritance of cancer genes | 186 | ||
| Colon cancer | 186 | ||
| Cancer Genes | 186 | ||
| Tumour suppressor genes | 187 | ||
| Retinoblastoma and the two-hit theory of carcinogenesis | 187 | ||
| Loss of heterozygosity | 187 | ||
| Oncogenes | 187 | ||
| Retroviruses | 187 | ||
| Transfection | 187 | ||
| DNA repair genes | 187 | ||
| Identifying Disease Genes | 188 | ||
| Genome mapping | 188 | ||
| Physical maps | 189 | ||
| Low-resolution mapping | 189 | ||
| Karyotyping | 189 | ||
| Dosage mapping | 189 | ||
| Fluorescence in situ hybridisation (FISH) | 189 | ||
| Chromosomal comparative genomic hybridisation (CGH) arrays | 190 | ||
| High-resolution mapping | 190 | ||
| Sanger sequencing | 190 | ||
| Cloning | 190 | ||
| Genetic linkage and monogenic disease | 190 | ||
| Linkage disequilibrium | 191 | ||
| LOD scores | 191 | ||
| Genetic linkage – a clinical example | 191 | ||
| Calculating the recombination frequency | 192 | ||
| Calculating the LOD score | 193 | ||
| LOD problems encountered in linkage studies | 193 | ||
| Locus heterogeneity | 193 | ||
| Incomplete penetrance | 193 | ||
| Phenocopies | 193 | ||
| Genetic linkage and polygenic disease | 194 | ||
| Restriction fragment length polymorphism | 194 | ||
| Variable number of tandem repeats | 194 | ||
| Single nucleotide polymorphisms | 194 | ||
| Genome microarrays | 196 | ||
| Massively parallel sequencing (MPS) | 196 | ||
| Bioinformatic tools | 197 | ||
| Personal genomics | 198 | ||
| The Human Genome Project | 198 | ||
| Can a DNA sequence be patented? | 198 | ||
| Beyond the sequence | 198 | ||
| What did the HGP tell us? | 199 | ||
| Statistics | 199 | ||
| Functions | 199 | ||
| Structure | 199 | ||
| Variation | 199 | ||
| Comparison with other species | 199 | ||
| Using data from the HGP | 199 | ||
| 1000 Genomes project | 199 | ||
| 100 000 Genomes project | 199 | ||
| Investigating the human genome | 199 | ||
| Gene families | 200 | ||
| Molecular phylogenetics | 200 | ||
| Protein modelling | 201 | ||
| X-ray crystallography | 201 | ||
| Nuclear magnetic resonance | 201 | ||
| Homology modelling | 201 | ||
| Model organisms | 201 | ||
| Mammals as model organisms | 201 | ||
| The mouse | 201 | ||
| Non-mammals as model organisms | 202 | ||
| Retroviruses | 202 | ||
| Bacteria and other microbes | 202 | ||
| Saccharomyces cerevisiae (baker’s yeast) | 203 | ||
| Archaea | 203 | ||
| Caenorhabditis elegans (round worm) | 203 | ||
| Drosophila (fruit fly) | 203 | ||
| Danio rerio (zebrafish) | 203 | ||
| Genetic Disease, Diagnosis and Therapy | 203 | ||
| Gene testing | 203 | ||
| Ethics | 203 | ||
| Genetic counselling | 203 | ||
| Congenital disease | 204 | ||
| Teratogens | 204 | ||
| Pharmacogenomics | 204 | ||
| Antibiotics and pharmacogenomics | 206 | ||
| Evidence-based treatment (see also Ch. 7) | 206 | ||
| Genetic medicine | 206 | ||
| Metabolic manipulation | 206 | ||
| Protein augmentation | 206 | ||
| Stem cell therapies | 206 | ||
| Embryonic stem cell transplantation | 207 | ||
| Haematopoietic stem cell transplantation | 207 | ||
| Non-haematopoietic stem cell transplantation | 207 | ||
| Gene transfer | 207 | ||
| Ex vivo approach | 207 | ||
| In vivo approach | 207 | ||
| RNA modification | 207 | ||
| Future of genetic therapy | 208 | ||
| 6 Infection, immunology and pathology | 209 | ||
| Introduction | 210 | ||
| Infection | 210 | ||
| Biological Agents | 210 | ||
| The burden of infectious disease | 210 | ||
| The variety of biological infectious agents | 210 | ||
| Bacteria | 211 | ||
| Structure | 211 | ||
| Cytoplasm | 211 | ||
| Cell membrane (plasma membrane) | 211 | ||
| Cell wall | 212 | ||
| Bacterial classification | 212 | ||
| Other bacterial surface features | 212 | ||
| Unusual types of bacteria | 213 | ||
| Replication | 213 | ||
| Viruses | 213 | ||
| Nucleocapsid structure | 213 | ||
| Genomic material | 213 | ||
| Capsid | 213 | ||
| Host cell infection | 214 | ||
| Virus classification | 215 | ||
| Viruses and cancer | 215 | ||
| Fungi | 216 | ||
| Structure | 216 | ||
| Classification | 216 | ||
| Protozoa | 216 | ||
| Characteristics | 217 | ||
| Classification | 217 | ||
| Structure | 217 | ||
| Reproduction | 217 | ||
| Helminths | 219 | ||
| Classification | 219 | ||
| Replication | 219 | ||
| Prions | 220 | ||
| The Symbiotic Relationship Between Infectious Agents and Humans | 220 | ||
| Normal flora | 221 | ||
| Pathogens: Successful Biological Infectious Agents | 222 | ||
| How pathogens enter the host | 222 | ||
| Skin | 223 | ||
| Respiratory tract | 223 | ||
| Gastrointestinal tract | 223 | ||
| Urogenital tract | 223 | ||
| The eyes | 223 | ||
| Placenta | 224 | ||
| Childbirth | 224 | ||
| How pathogens exploit their environments | 224 | ||
| The progress of a pathogenic infection | 224 | ||
| Adhesion | 224 | ||
| Invasion | 224 | ||
| Host organ dissemination | 224 | ||
| Survival within the host | 225 | ||
| Attacking the host | 226 | ||
| Exit | 226 | ||
| Transmission | 226 | ||
| The Pattern of Disease | 227 | ||
| Local versus general infections | 228 | ||
| Persistence | 228 | ||
| Incubation period | 228 | ||
| Disease manifestation | 228 | ||
| Pandemics and epidemics | 228 | ||
| Prevention of infection by vaccination | 228 | ||
| History | 228 | ||
| Aim of vaccination | 228 | ||
| Types of vaccines | 229 | ||
| Immunity | 229 | ||
| The Non-Immunological Defence System | 229 | ||
| Physical and functional barriers | 229 | ||
| Simple chemical and biological barriers | 229 | ||
| The Immunological Defence System | 229 | ||
| Detection and destruction of the invading immunogen | 230 | ||
| Receptors | 230 | ||
| Antigens | 230 | ||
| Agents of destruction | 230 | ||
| The innate immune system | 231 | ||
| The adaptive immune system | 231 | ||
| T lymphocytes | 231 | ||
| Terminology | 232 | ||
| CD nomenclature | 232 | ||
| Major histocompatibility complex (MHC) | 232 | ||
| Human leucocyte antigen (HLA) | 232 | ||
| Interactions with T lymphocytes | 232 | ||
| Antigen recognition | 234 | ||
| A mnemonic | 234 | ||
| T cell activation and killing | 234 | ||
| Switching off activated T cells | 234 | ||
| B lymphocytes | 234 | ||
| B cell activation | 235 | ||
| B cell response | 236 | ||
| Switching off B cells | 236 | ||
| Null lymphocytes | 236 | ||
| Antibodies | 236 | ||
| Antibody complexes | 237 | ||
| Antibody functions | 237 | ||
| Complement | 237 | ||
| The classical and lectin pathways (Fig. 6.16) | 238 | ||
| The alternative pathway (see Fig. 6.16) | 238 | ||
| Factors that inhibit the alternative pathway | 238 | ||
| Factors that encourage positive feedback of the alternative pathway | 238 | ||
| The central role of C3 | 238 | ||
| The lytic sequence (see Fig. 6.16) | 239 | ||
| The cellular defences | 240 | ||
| Basophils and mast cells | 240 | ||
| Mast cell activation | 240 | ||
| Substances released by mast cells | 240 | ||
| Neutrophils | 240 | ||
| Role of neutrophils in inflammation | 241 | ||
| Movement to site of damage | 241 | ||
| Phagocytosis | 241 | ||
| Monocytes and macrophages | 241 | ||
| Role of macrophages in inflammation | 241 | ||
| A functioning macrophage | 241 | ||
| A struggling macrophage | 241 | ||
| Eosinophils | 241 | ||
| Role of eosinophils in inflammation | 242 | ||
| Red cells | 242 | ||
| Platelets | 242 | ||
| Hypersensitivity | 242 | ||
| Type 1 hypersensitivity | 242 | ||
| Type 2 hypersensitivity (Clinical box 6.15) | 242 | ||
| Type 3 hypersensitivity | 242 | ||
| Type 4 hypersensitivity | 244 | ||
| Type 5 hypersensitivity | 244 | ||
| Tolerance | 244 | ||
| Tolerance mechanisms | 244 | ||
| Clonal deletion (central tolerance) | 244 | ||
| Anergy | 244 | ||
| Acquired tolerance | 244 | ||
| Autoimmune disease | 244 | ||
| B cell self-tolerance breakdown | 245 | ||
| T cell self-tolerance breakdown | 245 | ||
| Other substances important to the immune system | 245 | ||
| Interferons | 245 | ||
| Tumour necrosis factor | 245 | ||
| Acute phase proteins | 245 | ||
| Transforming growth factor-β (TGF-β) | 245 | ||
| Inflammation and Repair | 246 | ||
| Acute inflammation | 246 | ||
| Vascular events | 246 | ||
| Cellular events | 246 | ||
| Phagocytosis and killing of microbes | 246 | ||
| Initiation of the inflammatory response | 246 | ||
| Systemic effects of acute inflammation | 247 | ||
| Outcome of acute inflammation | 247 | ||
| Chronic inflammation | 247 | ||
| Initiation of chronic inflammation | 247 | ||
| Manifestation of chronic infection | 247 | ||
| Granulomas | 248 | ||
| Stimulants of granulomas | 248 | ||
| Tuberculosis | 248 | ||
| Schistosomiasis | 248 | ||
| Other granulomatous conditions | 248 | ||
| Granulomas and granulation tissue | 248 | ||
| Complications of chronic inflammation | 249 | ||
| Outcomes of chronic inflammation | 249 | ||
| Repair | 249 | ||
| Regeneration | 249 | ||
| Liver | 250 | ||
| Bone | 250 | ||
| Bone marrow | 250 | ||
| Repair | 250 | ||
| Inflammation | 250 | ||
| Proliferation | 251 | ||
| Remodelling | 251 | ||
| Repair complications | 251 | ||
| Factors that hamper tissue repair (Clinical box 6.22) | 251 | ||
| Lymphoid Organs | 252 | ||
| Lymph nodes | 252 | ||
| Structure | 252 | ||
| Afferent and efferent lymph vessels | 253 | ||
| Cortex | 253 | ||
| Medulla | 253 | ||
| Reticular network and sinuses | 253 | ||
| The spleen | 253 | ||
| Neoplasia | 253 | ||
| Introduction | 253 | ||
| Growth, differentiation and development | 253 | ||
| The cell cycle | 254 | ||
| Control of cell proliferation | 254 | ||
| Cell death | 254 | ||
| Variation in cell growth and differentiation (see Clinical box 6.23) | 254 | ||
| Increased growth | 254 | ||
| Decreased growth | 254 | ||
| Abnormal differentiation (see Clinical Box 6.24 and Fig 6.22) | 254 | ||
| Metaplasia | 254 | ||
| Epithelial metaplasia | 255 | ||
| Connective tissue metaplasia | 255 | ||
| Dysplasia | 255 | ||
| Defects of development | 256 | ||
| Anomalies of organ development | 257 | ||
| Tumour-like developmental lesions | 257 | ||
| Pathology of Neoplasia | 257 | ||
| Epidemiology of neoplasia | 257 | ||
| Nomenclature and classification of neoplasms | 258 | ||
| Epithelial neoplasms | 258 | ||
| Mesenchymal neoplasms | 258 | ||
| Haemopoietic neoplasms | 258 | ||
| Nervous system neoplasms | 258 | ||
| Primitive embryonal neoplasms | 260 | ||
| Germ cell neoplasms | 260 | ||
| Characteristics of benign and malignant neoplasms | 260 | ||
| Macroscopic features and growth pattern | 260 | ||
| Histological features | 261 | ||
| Differentiation and grade of malignant neoplasms | 261 | ||
| Behaviour of malignant neoplasms | 262 | ||
| Local invasion | 262 | ||
| Metastasis | 262 | ||
| Patterns and sites of metastasis (see Clinical box 6.29 and Fig 6.35) | 262 | ||
| Clonal evolution | 263 | ||
| Effects of a Neoplasm on the Host | 263 | ||
| Local effects | 263 | ||
| Immunological effects | 263 | ||
| Metabolic effects | 264 | ||
| Specific metabolic effects | 264 | ||
| General metabolic effects | 264 | ||
| Paraneoplastic Syndromes | 264 | ||
| Paraneoplastic endocrinopathies | 264 | ||
| Other types of paraneoplastic syndrome | 264 | ||
| Diagnosis, Staging and Prognosis of Neoplasms | 264 | ||
| Diagnosis of neoplasms | 265 | ||
| Tumour markers | 265 | ||
| Staging of neoplasms | 265 | ||
| Prognosis of neoplasms | 266 | ||
| Prognostic factors in pathology reports | 266 | ||
| Screening for malignancy | 267 | ||
| Why do patients die from neoplasia? | 267 | ||
| Carcinogenesis | 267 | ||
| Biology of neoplastic cells | 267 | ||
| Genes associated with cancer and oncogenesis | 268 | ||
| Chemical carcinogens | 268 | ||
| Infective carcinogens | 268 | ||
| Effects of radiation | 268 | ||
| Effects of hormones | 268 | ||
| Genes and inherited cancer syndromes | 268 | ||
| Host factors | 268 | ||
| Multihit theory of carcinogenesis (see also Ch. 5, Cancer Genetics) | 268 | ||
| 7 Epidemiology: science for the art of medicine | 271 | ||
| Introduction | 271 | ||
| The Epidemiological Approach | 271 | ||
| Epidemiology as the detective | 271 | ||
| The Broad Street pump | 271 | ||
| Causal association by inference | 274 | ||
| Patterns of life and death | 274 | ||
| Descriptive studies | 274 | ||
| Measuring disease occurrence | 275 | ||
| Disease incidence | 275 | ||
| Disease prevalence | 275 | ||
| Rates and relationship between incidence and prevalence | 275 | ||
| Measuring disease outcome | 276 | ||
| Births and deaths | 276 | ||
| Confidential enquiries | 276 | ||
| Disease surveillance | 277 | ||
| Cancer registration | 277 | ||
| Congenital anomalies notification | 277 | ||
| Communicable disease surveillance | 277 | ||
| Notification of infectious diseases | 277 | ||
| Examining data from different sources | 277 | ||
| International infectious disease surveillance and information sources | 277 | ||
| Global infectious disease surveillance | 278 | ||
| Special surveillance systems | 278 | ||
| Monitoring adverse reaction to drugs | 278 | ||
| Measures for health of populations | 278 | ||
| Mortality and life expectancy | 278 | ||
| Morbidity | 279 | ||
| The population census and health surveys | 279 | ||
| Measures for quality of life (QALYs) | 279 | ||
| Health inequalities | 279 | ||
| Health inequalities in the UK | 279 | ||
| Changes in health outcomes over time | 280 | ||
| Interpretation of data | 281 | ||
| Data inadequacies | 281 | ||
| Clustering | 281 | ||
| Socio-economic factors | 281 | ||
| Health-related behaviours | 281 | ||
| Healthcare facilities | 281 | ||
| Environmental factors | 282 | ||
| Migration | 282 | ||
| Standardisation of rates | 282 | ||
| Direct method of standardisation | 282 | ||
| Indirect method of standardisation | 283 | ||
| Choice of method for standardisation | 283 | ||
| Epidemiological Enquiry | 284 | ||
| Some basic concepts in epidemiology | 284 | ||
| The distribution of data | 284 | ||
| The normal or Gaussian distribution curve | 285 | ||
| Measures of centre | 285 | ||
| The mean | 285 | ||
| The median | 285 | ||
| The mode | 285 | ||
| Measures of spread: standard deviation from the mean | 285 | ||
| Outliers | 286 | ||
| Ordered data and the interquartile range | 286 | ||
| How accurate is the distribution summary? | 286 | ||
| Contingency tables | 287 | ||
| Some statistical concepts used in epidemiological enquiry (hypothesis tests and p values) | 288 | ||
| Hypothesis tests | 288 | ||
| Tests of probability: p values and confidence intervals | 288 | ||
| An overview of epidemiological enquiry | 289 | ||
| Investigation by observation: causation or association? | 289 | ||
| Observational studies | 290 | ||
| Cross-sectional studies | 290 | ||
| Sampling for cross-sectional studies | 290 | ||
| Interpreting the data from cross-sectional studies | 291 | ||
| Case–control studies | 291 | ||
| Selecting the sample for case–control studies | 292 | ||
| Analysing and interpreting data from case–control studies | 292 | ||
| Strength of the association | 292 | ||
| Consistency of findings | 293 | ||
| Specificity of the association | 294 | ||
| Relationship in time | 294 | ||
| The biological gradient | 294 | ||
| Demonstration of reversibility | 294 | ||
| Biological plausibility | 295 | ||
| Coherence of the evidence | 295 | ||
| Cohort studies | 295 | ||
| Selecting the sample for cohort studies | 295 | ||
| The Whitehall studies | 296 | ||
| Assembling the cohort | 296 | ||
| The prospective follow-up | 297 | ||
| Whitehall II | 297 | ||
| Analysing and interpreting data from cohort studies | 297 | ||
| The role of genetics in observational studies | 297 | ||
| Association between genotype and risk factor | 297 | ||
| Interaction with environmental factors | 297 | ||
| Investigation by experiment | 298 | ||
| Evaluation of clinical effectiveness: randomised controlled trials (RCTs) | 298 | ||
| Selecting the sample: experimental and control groups | 298 | ||
| Ethical considerations during the planning stage of clinical trials | 298 | ||
| The CRASH trial | 299 | ||
| Achieving similar groups for comparison: randomisation to minimise bias | 299 | ||
| Selecting the sample for the 4S trial | 299 | ||
| Calculating sample size | 300 | ||
| Power calculations | 300 | ||
| Measuring the outcomes during a trial | 301 | ||
| ‘Blinding’ to avoid bias during a trial | 301 | ||
| Outcomes of interest: end-point definition | 301 | ||
| Ethical principles during a trial: stopping a trial and interim analyses | 302 | ||
| Interim analyses | 302 | ||
| Measuring outcomes: follow-up | 303 | ||
| Analysing and interpreting the results | 303 | ||
| Analysis by intention-to-treat | 303 | ||
| Sensitivity analysis | 303 | ||
| Measures of treatment effect | 303 | ||
| Statistical significance | 304 | ||
| Clinical significance: the number needed to treat | 304 | ||
| Interpreting the results | 305 | ||
| Tests of significance | 305 | ||
| Presenting the results | 305 | ||
| Dissemination | 305 | ||
| Investigation by Review | 306 | ||
| Meta-analysis | 306 | ||
| Cumulative meta-analysis | 306 | ||
| Experiment or review? | 307 | ||
| Differences between reviews and RCTs | 307 | ||
| What best evidence is | 307 | ||
| Statistical assessment of data | 307 | ||
| Choosing a statistical test | 308 | ||
| Looking for differences in quantitative data (Fig. 7.20) | 308 | ||
| Looking for differences in categorical data (Fig. 7.21) | 308 | ||
| Looking for patterns in data (Fig. 7.22) | 308 | ||
| Degrees of freedom | 308 | ||
| The t-test | 308 | ||
| Evaluating probability for t values | 309 | ||
| One- and two-tailed tests of significance | 310 | ||
| Criteria for applying the t-test | 310 | ||
| The χ2 test | 310 | ||
| Evaluating probability for χ2 values | 311 | ||
| Criteria for applying the χ2 test | 311 | ||
| Linear association: correlation and regression | 311 | ||
| Multivariate analysis | 312 | ||
| Health Education and Promotion | 313 | ||
| Health education | 313 | ||
| Approaches to health education | 313 | ||
| Strategies for disease prevention and health promotion | 314 | ||
| Population strategies | 314 | ||
| High-risk strategy | 314 | ||
| Two concepts of ‘risk’ | 314 | ||
| Essentials for effective health education | 314 | ||
| Ethical considerations in prevention and health promotion | 315 | ||
| Case scenario: a new diagnosis of diabetes | 315 | ||
| Elicit the person’s health beliefs | 315 | ||
| Information phase | 315 | ||
| Explanation of the diagnosis | 315 | ||
| 8 The nervous system | 327 | ||
| Introduction | 327 | ||
| Embryology | 327 | ||
| Neurulation | 328 | ||
| Brain development | 328 | ||
| Ventricles | 328 | ||
| Spinal cord development | 329 | ||
| Developmental disorders of the nervous system | 330 | ||
| Gross Anatomy | 330 | ||
| Central nervous system | 330 | ||
| Brain | 330 | ||
| Cerebrum (telencephalon) | 330 | ||
| Cerebral cortex | 330 | ||
| Basal ganglia | 331 | ||
| Limbic system | 332 | ||
| Diencephalon | 332 | ||
| Brainstem | 333 | ||
| Midbrain | 334 | ||
| Pons and medulla | 334 | ||
| Cerebellum | 335 | ||
| Spinal cord | 335 | ||
| Grey matter | 335 | ||
| White matter | 335 | ||
| Peripheral nervous system | 336 | ||
| Somatic nervous system | 336 | ||
| Cranial nerves | 336 | ||
| Olfactory (I) nerve | 336 | ||
| Optic (II) nerve | 336 | ||
| Oculomotor (III) nerve | 336 | ||
| Trochlear (IV) nerve | 336 | ||
| Trigeminal (V) nerve | 337 | ||
| Sensory division | 337 | ||
| Motor division | 337 | ||
| Abducens (VI) nerve | 337 | ||
| Facial (VII) nerve | 337 | ||
| Vestibulocochlear (VIII) nerve | 337 | ||
| Glossopharyngeal (IX) nerve | 338 | ||
| Vagus (X) nerve | 338 | ||
| Accessory (XI) nerve | 338 | ||
| Hypoglossal (XII) nerve | 338 | ||
| Spinal nerves | 338 | ||
| Structure of peripheral nerves | 338 | ||
| Nerve fibre classification | 338 | ||
| Meninges | 339 | ||
| Dura mater | 339 | ||
| Arachnoid mater | 339 | ||
| Pia mater | 340 | ||
| The Ventricular System | 341 | ||
| Secretion and circulation of CSF | 341 | ||
| Absorption of CSF | 341 | ||
| Functions of CSF | 341 | ||
| Metabolic functions | 341 | ||
| Mechanical functions | 342 | ||
| Cells of the Nervous System | 342 | ||
| Size | 342 | ||
| Morphology | 342 | ||
| Connectivity | 342 | ||
| Chemistry | 343 | ||
| Blood Supply to the Brain and Brain Metabolism | 343 | ||
| Arterial blood supply | 343 | ||
| Anterior cerebral circulation | 344 | ||
| Posterior cerebral circulation | 345 | ||
| Arterial blood supply to the spinal cord | 345 | ||
| Venous drainage | 345 | ||
| Blood–brain barrier | 345 | ||
| Metabolic requirements of the brain | 346 | ||
| Transmission of Neural Signals | 346 | ||
| Action potentials | 347 | ||
| Equilibrium potentials | 347 | ||
| Depolarisation and hyperpolarisation | 347 | ||
| Generation of action potentials | 347 | ||
| Initiation | 348 | ||
| Upstroke | 348 | ||
| Repolarisation | 348 | ||
| Refractory period | 348 | ||
| Conduction of action potentials | 348 | ||
| Synapses | 348 | ||
| Electrical synapses | 349 | ||
| Chemical synapses | 349 | ||
| Neurotransmission | 349 | ||
| Neurotransmitters | 350 | ||
| Neurotransmitter release | 350 | ||
| Neurotransmitter receptors | 350 | ||
| Summation | 350 | ||
| Neurotransmitter inactivation | 350 | ||
| Presynaptic receptors | 351 | ||
| Types of neurotransmitters | 351 | ||
| Amino acids | 351 | ||
| Excitatory amino acids | 351 | ||
| Inhibitory amino acids | 352 | ||
| Acetylcholine | 353 | ||
| Monoamines | 353 | ||
| Purines | 354 | ||
| Peptides | 354 | ||
| Motor Control and Pathways | 354 | ||
| Motor cortex | 355 | ||
| Primary motor cortex | 355 | ||
| Premotor and supplementary motor cortices | 355 | ||
| Lateral motor pathways | 355 | ||
| Brainstem | 356 | ||
| Medial motor pathways | 356 | ||
| Upper and lower motor neurons | 357 | ||
| Spinal cord | 357 | ||
| Motor reflexes | 357 | ||
| Stretch reflex | 357 | ||
| Muscle spindles | 358 | ||
| Golgi tendon organ reflex | 358 | ||
| Cutaneous reflexes | 358 | ||
| Locomotion | 358 | ||
| Muscle tone | 358 | ||
| Spinal cord injury | 359 | ||
| Cranial nerve reflexes | 359 | ||
| Cerebellum | 360 | ||
| Anatomy | 360 | ||
| Functional subdivisions | 360 | ||
| Cerebellar cortex and circuitry | 361 | ||
| Basal ganglia | 362 | ||
| Eye movements | 364 | ||
| Control of eye movements | 364 | ||
| Gaze stabilisation | 364 | ||
| Gaze shift | 365 | ||
| Sensory Systems | 365 | ||
| Sensory receptor transduction | 365 | ||
| Receptive field structure | 366 | ||
| Touch and proprioception | 366 | ||
| Touch and conscious proprioception pathway | 366 | ||
| Somatosensory cortex | 366 | ||
| Other proprioception pathways | 367 | ||
| Pain and temperature | 367 | ||
| Thermoreceptors | 367 | ||
| Nociceptors | 368 | ||
| Pain and temperature pathways | 368 | ||
| Summary of the ascending sensory pathways | 369 | ||
| Pain regulation | 369 | ||
| Analgesic agents | 370 | ||
| Placebo effect | 370 | ||
| Visceral sensation | 370 | ||
| Referred pain | 370 | ||
| Phantom pain | 371 | ||
| Special Senses | 371 | ||
| Vision | 371 | ||
| The anatomy of the eyeball | 371 | ||
| Optics of the eye | 372 | ||
| Pupillary reflexes | 372 | ||
| Retina | 372 | ||
| Photoreceptors | 373 | ||
| Retinal processing | 374 | ||
| Central visual pathways | 375 | ||
| Visual perception | 376 | ||
| Vestibular system | 376 | ||
| Anatomy | 376 | ||
| Central vestibular pathways | 378 | ||
| Auditory system | 379 | ||
| Sound | 379 | ||
| External and middle ear | 379 | ||
| Inner ear (cochlea) | 380 | ||
| Central auditory pathways | 380 | ||
| Sound frequency coding | 381 | ||
| Sound localisation | 382 | ||
| Smell | 382 | ||
| Taste | 382 | ||
| Central pathways of taste | 382 | ||
| Central Autonomic Networks | 382 | ||
| Examples of central autonomic control | 384 | ||
| Thermoregulation | 384 | ||
| Regulation of feeding and satiety | 384 | ||
| Orexigenic pathway | 384 | ||
| Anorexigenic pathway | 384 | ||
| Regulation of thirst and drinking | 384 | ||
| Regulation of sexual function | 385 | ||
| Consciousness | 385 | ||
| Sleep and Wakefulness | 385 | ||
| Arousal system | 385 | ||
| NREM sleep | 386 | ||
| REM sleep | 386 | ||
| Emotion | 386 | ||
| Limbic system | 386 | ||
| The pathways of fear | 387 | ||
| Emotion recognition | 387 | ||
| Emotional expression | 387 | ||
| Prefrontal cortex and emotion | 388 | ||
| Motivation and Goal-Directed Behaviours | 388 | ||
| The brain reward system | 388 | ||
| Drugs and the brain reward system | 388 | ||
| Higher Cortical Functions | 389 | ||
| Cognition | 389 | ||
| Memory | 389 | ||
| Declarative memory | 390 | ||
| Anatomical structures and declarative (explicit) memory | 390 | ||
| Long-term potentiation and depression | 390 | ||
| Attention | 390 | ||
| Agnosias | 391 | ||
| Apraxias | 391 | ||
| Language | 391 | ||
| Brain Death | 392 | ||
| 9 Bone, muscle, skin and connective tissue | 393 | ||
| Introduction | 393 | ||
| Imaging in medicine | 393 | ||
| The Skeletal System | 394 | ||
| Cartilage | 394 | ||
| Bone microanatomy | 395 | ||
| Bone matrix | 395 | ||
| Cellular content of bone | 395 | ||
| Bone formation | 396 | ||
| Skeletal components | 396 | ||
| Structure of bone | 396 | ||
| Compact bone | 400 | ||
| Spongy bone | 400 | ||
| Blood and nerve supply to bone | 401 | ||
| Bone development | 401 | ||
| Endochondral ossification | 401 | ||
| Intramembranous ossification | 402 | ||
| Bone growth | 402 | ||
| Bone growth in length | 403 | ||
| Growth in bone thickness | 404 | ||
| Factors affecting bone growth | 404 | ||
| Bone remodelling | 404 | ||
| Bone’s role in calcium homeostasis | 405 | ||
| Parathyroid hormone | 405 | ||
| Vitamin D | 406 | ||
| Calcitonin | 406 | ||
| Other factors affecting bone mass | 406 | ||
| Oestrogen | 406 | ||
| Exercise | 406 | ||
| Diet and bone mass | 406 | ||
| Bone healing | 407 | ||
| Joints | 408 | ||
| Bony joints | 408 | ||
| Fibrous joints | 408 | ||
| Suture | 408 | ||
| Syndesmosis | 408 | ||
| Gomphosis | 409 | ||
| Schindylesis | 409 | ||
| Cartilaginous joints | 409 | ||
| Synovial joints | 409 | ||
| Synovial joint structure | 409 | ||
| Articular cartilage | 410 | ||
| Articular capsule | 410 | ||
| The synovium | 410 | ||
| The synovial fluid | 411 | ||
| Accessory ligaments | 412 | ||
| Articular discs | 412 | ||
| Blood and nerve supply to the joint | 412 | ||
| Types of synovial joints | 412 | ||
| Planar or gliding synovial joint | 412 | ||
| Hinge joint | 413 | ||
| Pivot joints | 413 | ||
| Condyloid or ellipsoidal joint | 415 | ||
| Saddle joint | 417 | ||
| Ball and socket joint | 417 | ||
| A complex joint | 417 | ||
| Tendons and ligaments | 417 | ||
| Bursae and tendon sheaths | 421 | ||
| Anatomical relationships | 422 | ||
| Skeletal Muscle | 422 | ||
| The neuromuscular junction and muscle innervation | 422 | ||
| Neurotransmitter release | 422 | ||
| Acetylcholine receptors | 422 | ||
| Neuromuscular blockade | 424 | ||
| Breakdown of acetylcholine | 425 | ||
| Motor units | 425 | ||
| Development of sustained tension | 425 | ||
| Muscle tone | 425 | ||
| Sensory innervation of muscle | 425 | ||
| Isotonic versus isometric contraction | 425 | ||
| The skeletal muscle fibre | 426 | ||
| The contractile proteins | 426 | ||
| Thin filaments | 426 | ||
| Thick filaments | 426 | ||
| The sliding filament model of muscle contraction | 427 | ||
| The contractile process | 428 | ||
| Excitation–contraction coupling | 428 | ||
| Intracellular calcium release (Fig. 9.17A) | 428 | ||
| Cross-bridge formation and muscle contraction (see Fig. 9.17B) | 429 | ||
| Calcium removal and muscle relaxation | 429 | ||
| Muscle length and tension | 431 | ||
| Muscle metabolism | 431 | ||
| Creatine phosphate | 431 | ||
| Creatine supplementation | 431 | ||
| Muscle fatigue | 431 | ||
| Types of muscle fibres | 431 | ||
| The connective tissue of muscle | 431 | ||
| Muscle growth and repair | 432 | ||
| Muscle nomenclature | 432 | ||
| Muscle shape | 432 | ||
| Muscle names | 432 | ||
| Posture and Locomotion | 433 | ||
| Standing | 433 | ||
| Walking | 433 | ||
| Stance phase | 433 | ||
| Swing phase | 434 | ||
| Stabilisation | 434 | ||
| Gait analysis | 434 | ||
| Specialised Connective Tissues: Skin, Hair and Nails | 435 | ||
| Structure of skin | 435 | ||
| Epidermis | 435 | ||
| Melanocytes | 436 | ||
| Dermis | 436 | ||
| Sweat glands | 436 | ||
| Sebaceous glands | 436 | ||
| Subcutaneous layer | 437 | ||
| Hair | 437 | ||
| Structure of hair | 437 | ||
| Structure of hair follicle | 437 | ||
| Types of hair | 438 | ||
| Nails | 438 | ||
| Generalised Connective Tissue | 438 | ||
| 10 Endocrinology and the reproductive system | 441 | ||
| Introduction | 441 | ||
| The Endocrine System | 441 | ||
| Peptide hormones: secretion and mechanisms of action | 442 | ||
| Steroid hormones: synthesis, actions and metabolism | 443 | ||
| Modified amino acids: thyroid hormones and catecholamines | 444 | ||
| Neuroendocrinology | 445 | ||
| Important concepts in endocrinology | 445 | ||
| Patterns of hormone secretion | 445 | ||
| Negative feedback | 445 | ||
| Endocrine disease | 445 | ||
| Endocrine testing | 446 | ||
| Measuring hormones in blood | 447 | ||
| Endocrine regulation – the role of the hypothalamus and pituitary | 448 | ||
| Functional anatomy of the hypothalamus and pituitary | 448 | ||
| The posterior pituitary | 448 | ||
| The hypothalamus controls hormone secretion by the anterior pituitary | 449 | ||
| Prolactin secretion is under inhibitory regulation (Fig. 10.12) | 451 | ||
| Growth hormone | 451 | ||
| Growth | 451 | ||
| The regulation of growth hormone | 452 | ||
| Actions of growth hormone | 453 | ||
| Endocrine Homeostasis | 454 | ||
| Thyroid gland and the regulation of metabolism | 454 | ||
| The structure and location of the thyroid | 454 | ||
| Iodine – an important trace element | 455 | ||
| Hormone synthesis in the thyroid gland | 455 | ||
| Control of thyroid function | 455 | ||
| Thyroid hormones in blood | 455 | ||
| Peripheral metabolism of thyroxine | 456 | ||
| Functions of thyroxine (Table 10.5) | 456 | ||
| Hormones and ‘stress’ | 457 | ||
| Adrenal cortex and medulla | 457 | ||
| Structure of the adrenals | 457 | ||
| Stress: the adrenal medulla | 458 | ||
| Stress: the adrenal cortex | 458 | ||
| Actions of cortisol | 459 | ||
| Endocrine control of glucose metabolism (details of biochemistry in Chs 2 and 3) | 460 | ||
| Regulation of plasma glucose concentration | 460 | ||
| Endocrine pancreas | 462 | ||
| Insulin synthesis | 462 | ||
| Control of insulin secretion (Fig. 10.27) | 462 | ||
| Glucagon | 462 | ||
| Diabetes mellitus | 463 | ||
| Glycosuria | 463 | ||
| Type 1 diabetes | 464 | ||
| Type 2 diabetes | 464 | ||
| Obesity | 464 | ||
| Complications of poorly controlled blood glucose 1: diabetic ketoacidosis | 464 | ||
| Complications of poorly controlled blood glucose 2: HONK | 465 | ||
| Complications of poorly controlled blood glucose 3: hypoglycaemia | 465 | ||
| Endocrine control of blood calcium (details of bone in Ch. 9) | 465 | ||
| Calcium homeostasis | 465 | ||
| Control of blood calcium and phosphate concentrations | 466 | ||
| Reproductive Physiology | 468 | ||
| Male reproductive endocrinology | 468 | ||
| Male reproductive tract (Fig. 10.35) | 468 | ||
| Hypothalamic–pituitary–testicular axis | 469 | ||
| Spermatogenesis | 470 | ||
| Female reproductive endocrinology | 471 | ||
| Female reproductive tract | 471 | ||
| Follicular development | 471 | ||
| Hormonal control of the ovary and menstrual cycle | 472 | ||
| The menstrual and ovarian cycles | 472 | ||
| Puberty | 473 | ||
| Pregnancy | 474 | ||
| Fertilisation | 475 | ||
| The establishment of pregnancy | 475 | ||
| Hormone production by the placenta | 477 | ||
| Pregnancy tests | 478 | ||
| Foetal development | 478 | ||
| Parturition – labour | 478 | ||
| Lactation | 481 | ||
| Infertility (subfertility) | 481 | ||
| The endocrinology of ageing (including menopause) | 481 | ||
| 11 The cardiovascular system | 483 | ||
| Introduction | 483 | ||
| Clinical Anatomy of the Cardiovascular System | 483 | ||
| The heart | 483 | ||
| The pericardium | 483 | ||
| The heart chambers | 483 | ||
| The apex of the heart | 484 | ||
| The heart valves | 484 | ||
| Heart sounds and murmurs | 484 | ||
| The human circulation | 486 | ||
| The pulmonary circulation | 486 | ||
| The systemic circulation | 489 | ||
| The arterial system | 490 | ||
| Aortic arch | 490 | ||
| Thoracic aorta | 491 | ||
| Abdominal aorta | 491 | ||
| Common iliac arteries | 492 | ||
| Peripheral arterial pulses | 492 | ||
| The venous system | 493 | ||
| Jugular venous pulse | 493 | ||
| Regional circulations | 493 | ||
| The coronary circulation | 493 | ||
| Coronary blood flow | 493 | ||
| The cerebral circulation | 494 | ||
| The hepatic circulation | 494 | ||
| The skeletal muscle circulation | 495 | ||
| The cutaneous circulation | 495 | ||
| Embryology | 495 | ||
| Development of the heart | 496 | ||
| The chambers of the heart | 496 | ||
| The atria | 497 | ||
| The ventricles | 497 | ||
| The great arteries | 498 | ||
| Development of the vasculature | 498 | ||
| The foetal circulation | 498 | ||
| The neonatal circulation | 498 | ||
| Cellular Structure and Function of the Heart | 500 | ||
| Structure of heart muscle | 500 | ||
| Cardiomyocytes | 500 | ||
| Intercalated discs | 500 | ||
| T-tubules and sarcoplasmic reticulum | 500 | ||
| The contractile process | 500 | ||
| Cardiac muscle contraction | 500 | ||
| Cardiac muscle relaxation | 501 | ||
| Cardiac muscle metabolism | 502 | ||
| Electrical activation of the heart | 502 | ||
| Pacemaker cells | 502 | ||
| The cardiac conduction system | 503 | ||
| Nerve supply to the heart | 503 | ||
| Parasympathetic supply | 503 | ||
| Sympathetic supply | 504 | ||
| Adrenal medulla | 504 | ||
| Electrocardiography | 505 | ||
| The ECG | 505 | ||
| The normal ECG | 506 | ||
| The electrical axis of the heart | 507 | ||
| Cardiac arrhythmias | 507 | ||
| Anti-arrhythmic drugs | 511 | ||
| Therapeutic ablation | 511 | ||
| Conduction disorders | 511 | ||
| The cardiac cycle | 511 | ||
| Atrial systole | 515 | ||
| Ventricular systole | 515 | ||
| Ventricular diastole | 515 | ||
| The pressure–volume loop | 515 | ||
| Cardiac output | 516 | ||
| Preload | 516 | ||
| Myocardial contractility | 517 | ||
| Afterload | 517 | ||
| Ventricular hypertrophy | 517 | ||
| Heart failure | 517 | ||
| Classification of heart failure | 517 | ||
| Low-output and high-output heart failure | 517 | ||
| Acute and chronic heart failure | 517 | ||
| Systolic and diastolic heart failure | 518 | ||
| Causes of heart failure | 518 | ||
| Pathophysiological mechanisms activated by heart failure | 518 | ||
| Natriuretic peptides | 518 | ||
| Treatment of heart failure | 519 | ||
| Blood Vessels | 519 | ||
| The vessel wall | 519 | ||
| Arteries | 520 | ||
| Veins | 521 | ||
| Atherosclerosis | 521 | ||
| Evolution of the atherosclerotic plaque | 522 | ||
| Endothelial damage | 522 | ||
| Uptake of modified LDL particles, adhesion and infiltration of macrophages | 522 | ||
| Smooth muscle proliferation and formation of fibrous cap | 523 | ||
| Plaque rupture | 523 | ||
| Risk factors for atherosclerosis | 523 | ||
| Non-modifiable risk factors | 523 | ||
| Modifiable risk factors | 523 | ||
| Markers of risk | 524 | ||
| Prevention and treatment of atherosclerosis | 524 | ||
| Non-atherosclerotic arteriosclerosis | 525 | ||
| Ischaemic heart disease | 525 | ||
| Angina | 526 | ||
| Stable angina | 526 | ||
| Variant angina | 526 | ||
| Treatment of angina | 527 | ||
| Acute coronary syndromes | 527 | ||
| Unstable angina | 527 | ||
| Myocardial infarction | 528 | ||
| Non-ST elevation MI | 528 | ||
| ST elevation MI | 528 | ||
| Complications of MI | 528 | ||
| Thromboembolism | 530 | ||
| Thrombus formation | 530 | ||
| Deep vein thrombosis | 531 | ||
| Pulmonary embolism | 532 | ||
| Non-thrombotic emboli | 532 | ||
| The microcirculation | 533 | ||
| Capillary structure | 533 | ||
| The capillary bed | 533 | ||
| Capillary exchange | 534 | ||
| Diffusion | 534 | ||
| Free diffusion | 534 | ||
| Channel-based diffusion | 534 | ||
| Active membrane transport | 534 | ||
| Influence of blood flow on capillary exchange | 535 | ||
| Water exchange | 535 | ||
| Starling forces | 535 | ||
| Filtration and resorption | 536 | ||
| Oedema | 536 | ||
| Increased capillary hydrostatic pressure | 536 | ||
| Decreased plasma oncotic pressure | 536 | ||
| Increased capillary permeability | 536 | ||
| Reduced lymphatic drainage | 536 | ||
| Mechanics of blood flow | 537 | ||
| Pressure and vascular resistance | 537 | ||
| Velocity of blood flow | 537 | ||
| Types of blood flow | 538 | ||
| Laminar blood flow | 538 | ||
| Turbulent blood flow | 538 | ||
| Bolus flow | 538 | ||
| Control of blood flow | 539 | ||
| Structure of vascular smooth muscle | 539 | ||
| Vascular smooth muscle contraction | 539 | ||
| Excitation-contraction coupling of smooth muscle | 539 | ||
| Regulation of flow in small arteries and arterioles | 541 | ||
| Sympathetic nervous system mediated vasoconstriction | 541 | ||
| Hormone-mediated vasoconstriction and vasodilatation | 541 | ||
| Non-adrenergic autonomic nervous system-mediated vasodilatation | 542 | ||
| Receptor-mediated differential effects of catecholamines | 542 | ||
| Vasoconstriction by catecholamines | 542 | ||
| Vasodilatation by catecholamines | 543 | ||
| Regulation of flow in the microcirculation | 543 | ||
| Autoregulation of blood flow | 544 | ||
| Metabolic byproduct vasodilatation | 544 | ||
| Local vasoactive hormones | 544 | ||
| Systemic Arterial Blood Pressure | 545 | ||
| Regulation of arterial blood pressure | 545 | ||
| Baroreceptor reflex | 545 | ||
| Chemoreceptor reflexes | 546 | ||
| Cardiopulmonary reflexes | 546 | ||
| Central regulation of cardiovascular reflexes | 546 | ||
| Regulation of the baroreceptor reflex | 546 | ||
| Long-term control of blood pressure | 546 | ||
| Vasopressin | 547 | ||
| Angiotensin II | 547 | ||
| Aldosterone | 547 | ||
| Atrial natriuretic peptides | 547 | ||
| Orthostasis | 547 | ||
| Shock | 547 | ||
| Hypovolaemic shock | 547 | ||
| Cardiogenic shock | 548 | ||
| Vasodilatory (septic) shock | 548 | ||
| Anaphylactic shock | 550 | ||
| Neurogenic shock | 550 | ||
| Homeostatic mechanisms activated by shock | 550 | ||
| Clinical signs of shock | 550 | ||
| Decompensated shock and multi-organ failure | 550 | ||
| Cellular damage in shock | 551 | ||
| Treatment of shock | 551 | ||
| Supportive therapy | 551 | ||
| Fluid replacement | 551 | ||
| Sympathomimetic drug treatment | 552 | ||
| Prognosis in shock | 552 | ||
| Hypertension | 552 | ||
| Diagnosis of hypertension | 552 | ||
| Aetiology of hypertension | 553 | ||
| Pathophysiology of hypertension | 553 | ||
| Secondary hypertension | 553 | ||
| Hypertension due to chronic kidney disease | 554 | ||
| Renovascular hypertension | 554 | ||
| Endocrine causes of hypertension | 554 | ||
| Drug-induced hypertension | 554 | ||
| Coarctation of the aorta | 555 | ||
| Pregnancy-induced hypertension | 555 | ||
| Malignant hypertension | 555 | ||
| Treatment of hypertension | 555 | ||
| Resistant hypertension | 555 | ||
| 12 Haematology | 557 | ||
| The Haemopoietic System | 557 | ||
| Blood and its constituents | 557 | ||
| Blood plasma | 557 | ||
| Blood cells | 557 | ||
| Red cells (erythrocytes) | 557 | ||
| White blood cells (leucocytes) | 558 | ||
| Neutrophils | 558 | ||
| Monocytes and macrophages | 559 | ||
| Eosinophils | 559 | ||
| Basophils | 559 | ||
| Lymphocytes | 559 | ||
| Platelets | 559 | ||
| Stem cells and their role in haemopoiesis | 560 | ||
| Stem cells are multipotent | 560 | ||
| Blood cell production and the bone marrow microenvironment | 560 | ||
| Regulation of haemopoiesis | 560 | ||
| The bone marrow stroma | 560 | ||
| Growth factors | 560 | ||
| Haemopoietic receptors | 561 | ||
| Red Cells | 561 | ||
| Transcription factors in erythropoiesis | 561 | ||
| Tal-1/SCL | 561 | ||
| Rbtn2/LMO2 | 561 | ||
| GATA-2 | 561 | ||
| GATA-1 | 561 | ||
| Growth factors in erythropoiesis | 561 | ||
| Erythropoietin controls the red cell mass | 562 | ||
| Epo production involves a negative feedback loop | 562 | ||
| Stromal molecules in erythropoiesis | 562 | ||
| Other hormones that influence haemoglobin production | 563 | ||
| Red cell production during life | 563 | ||
| Transport of oxygen by haemoglobin | 563 | ||
| The oxygen dissociation curve | 563 | ||
| Role of acid in oxygen release | 564 | ||
| Role of 2,3-DPG in oxygen release from haemoglobin | 564 | ||
| Transport of carbon dioxide | 564 | ||
| The red cell membrane | 565 | ||
| Spectrin | 565 | ||
| Haemoglobin | 565 | ||
| Coordinating haemoglobin production throughout life | 565 | ||
| Red cell enzymes are required to maintain red cell components | 565 | ||
| Glucose is the main source of red cell energy | 566 | ||
| Maintenance and recycling of red cells | 566 | ||
| Fate of old red cells | 566 | ||
| Recycling of red cell components | 566 | ||
| Anaemias | 567 | ||
| General features of anaemia | 567 | ||
| Physiological adaptations to anaemia | 567 | ||
| Tissues and perfusion | 567 | ||
| Cardiovascular system | 567 | ||
| Classification of anaemia | 567 | ||
| (1) Using the mean cell volume (MCV) | 567 | ||
| (2) Acquired or inherited | 568 | ||
| Acquired anaemias due to deficiencies | 568 | ||
| Iron deficiency | 568 | ||
| Iron metabolism | 568 | ||
| Iron loss | 568 | ||
| Iron homeostasis: regulation of ferritin and transferrin receptor levels | 569 | ||
| Causes of iron deficiency | 569 | ||
| Laboratory findings in iron deficiency | 569 | ||
| Megaloblastic anaemia | 570 | ||
| Why are vitamins B12 and folate important? | 570 | ||
| Vitamin B12 (cobalamin, Cbl) | 570 | ||
| Causes of vitamin B12 deficiency | 571 | ||
| Folate | 572 | ||
| Causes of folate deficiency | 572 | ||
| Laboratory findings in B12 and folate deficiency | 572 | ||
| Acquired anaemias due to blood loss | 572 | ||
| Acute blood loss | 572 | ||
| Chronic blood loss | 573 | ||
| Acquired anaemias due to chronic disease | 573 | ||
| Anaemia of chronic disease (ACD) | 573 | ||
| Mechanism of ACD | 573 | ||
| Diagnosis of ACD | 573 | ||
| Anaemias due to haemolysis | 573 | ||
| Acquired autoimmune haemolytic anaemia (AIHA) | 573 | ||
| Laboratory findings in AIHA | 573 | ||
| Other acquired anaemias | 573 | ||
| Non-immune haemolytic anaemias | 573 | ||
| Mechanical red cell fragmentation | 573 | ||
| Marrow infiltration | 575 | ||
| Marrow failure | 575 | ||
| Rare inherited anaemias | 575 | ||
| Inherited anaemias | 575 | ||
| Red cell membrane disorders | 575 | ||
| Hereditary spherocytosis | 576 | ||
| Red cell enzyme disorders | 576 | ||
| Glucose-6-phosphate dehydrogenase deficiency | 576 | ||
| Haemoglobin disorders | 576 | ||
| Sickle cell disease | 577 | ||
| Elevated foetal haemoglobin levels are beneficial | 577 | ||
| Precipitants of sickle cell disease | 577 | ||
| Laboratory findings in sickle cell disease | 577 | ||
| The thalassaemias | 578 | ||
| α Thalassaemia | 578 | ||
| β Thalassaemia | 579 | ||
| Laboratory findings in the thalassaemias | 579 | ||
| Oncogenesis and Disorders of Blood Cell Production | 579 | ||
| Normal blood production relies on coordinated gene expression | 579 | ||
| Oncogenesis | 579 | ||
| The search for oncogenes in human blood disease | 579 | ||
| Oncogenes and tumour suppressor genes | 579 | ||
| Oncogenes | 580 | ||
| Mutations | 580 | ||
| Chromosome translocations | 580 | ||
| Viral activation | 580 | ||
| Tumour suppressor genes | 580 | ||
| The lymphoid system | 580 | ||
| Primary lymphoid tissues | 581 | ||
| Secondary lymphoid tissues | 581 | ||
| Myeloproliferative disorders (MPDs) | 581 | ||
| Subtypes of MPDs | 581 | ||
| Polycythaemia | 581 | ||
| Polycythaemia rubra vera | 581 | ||
| Essential thrombocythaemia | 581 | ||
| Myelofibrosis | 581 | ||
| Molecular pathogenesis of myeloproliferative disorders | 581 | ||
| Myelodysplastic syndromes | 582 | ||
| Leukaemias | 582 | ||
| The acute leukaemias | 582 | ||
| Incidence and causes | 582 | ||
| Laboratory findings | 582 | ||
| Importance of underlying genetic lesions in acute leukaemia | 583 | ||
| Chronic leukaemias | 583 | ||
| Chronic myeloid leukaemia | 583 | ||
| Chronic lymphocytic leukaemia | 583 | ||
| Laboratory findings | 583 | ||
| Lymphomas | 583 | ||
| Non-Hodgkin lymphoma (NHL) | 583 | ||
| Chromosome translocations | 585 | ||
| Viral infection | 585 | ||
| Other implicated factors | 585 | ||
| Hodgkin lymphoma | 585 | ||
| Plasma cell disorders | 585 | ||
| Multiple myeloma | 585 | ||
| Clinical feature of multiple myeloma | 585 | ||
| Laboratory features of multiple myeloma | 586 | ||
| Haemostasis and Thrombosis | 586 | ||
| Normal haemostatic mechanisms | 586 | ||
| The role of the endothelium and platelets in the maintenance of haemostasis | 587 | ||
| Coagulation cascade | 587 | ||
| The intrinsic pathway | 588 | ||
| The extrinsic pathway | 588 | ||
| The common pathway | 588 | ||
| Natural anticoagulants are required to maintain the balance | 588 | ||
| The fibrinolytic system | 589 | ||
| Clinical consequences of fibrin degradation products | 589 | ||
| Plasminogen activators: tissue and urinary plasminogen activator (tPA and uPA) | 589 | ||
| Fibrinolysis inhibitors | 589 | ||
| Assessment of the coagulation system | 589 | ||
| Full blood count and film | 590 | ||
| The bleeding time | 590 | ||
| Coagulation tests | 590 | ||
| Disorders of the haemostatic system | 591 | ||
| Inherited disorders | 591 | ||
| Haemophilia A | 591 | ||
| Haemophilia B (Christmas disease) | 591 | ||
| Clinical and diagnostic features of haemophilia | 591 | ||
| Von Willebrand disease | 591 | ||
| Inherited platelet disorders | 592 | ||
| Acquired disorders | 592 | ||
| The thrombocytopenias | 592 | ||
| Thrombocytopenia caused by impaired platelet production | 592 | ||
| Thrombocytopenia caused by increased platelet destruction | 592 | ||
| Non-immune causes of thrombocytopenia | 592 | ||
| Disseminated intravascular coagulation | 592 | ||
| Thrombocytopenia due to an altered distribution or dilution | 592 | ||
| Immune causes of thrombocytopenia | 592 | ||
| Immune thrombocytopenia (ITP) | 592 | ||
| Heparin-induced thrombocytopenia (HIT) | 593 | ||
| The thrombophilias | 593 | ||
| The inherited thrombophilias | 593 | ||
| Deficiencies of the naturally occurring anticoagulants | 593 | ||
| Antithrombin deficiency | 593 | ||
| Protein C deficiency | 593 | ||
| Protein S deficiency | 593 | ||
| Gain-of-function mutations | 593 | ||
| Factor V Leiden | 593 | ||
| Prothrombin gene mutation | 594 | ||
| Acquired prothrombotic states | 594 | ||
| Antiphospholipid syndrome | 594 | ||
| Lupus anticoagulant | 594 | ||
| Anticardiolipin and β2-glycoprotein 1 antibodies | 594 | ||
| Blood Groups and Transfusion Medicine | 594 | ||
| Definition of a blood group | 594 | ||
| Blood group antigens | 594 | ||
| Antibody production | 594 | ||
| Blood group systems in transfusion medicine | 595 | ||
| The ABO system | 595 | ||
| ABO antigens | 595 | ||
| Changes in blood groups | 596 | ||
| The Rhesus system | 596 | ||
| Production of antibodies to blood group antigens | 597 | ||
| ABO blood group system antibodies | 597 | ||
| Rh blood group antibodies | 597 | ||
| Other blood group systems | 597 | ||
| Kell | 597 | ||
| Duffy | 597 | ||
| I/i | 597 | ||
| Platelet antigens | 598 | ||
| Blood transfusion | 598 | ||
| Guidelines for safe transfusion | 598 | ||
| Management of the blood transfusion process | 598 | ||
| Transfusion reactions | 599 | ||
| Tests used in transfusion medicine | 599 | ||
| Blood grouping | 599 | ||
| The antibody screen | 600 | ||
| The antiglobulin test | 600 | ||
| The cross-match (compatibility test) | 600 | ||
| Non-red cell transfusion | 601 | ||
| Platelet transfusion | 601 | ||
| White cell transfusion | 601 | ||
| Frozen plasma and plasma concentrate transfusion | 601 | ||
| Immunoglobulin | 602 | ||
| 13 The respiratory system | 603 | ||
| Introduction | 603 | ||
| Epidemiology of Respiratory Disease and Its Social Impact | 604 | ||
| Smoke and respiratory disease | 604 | ||
| Classification of Common Respiratory Diseases | 604 | ||
| Obstructive pulmonary disease | 605 | ||
| Restrictive pulmonary disease | 605 | ||
| Anatomy of the Respiratory System | 605 | ||
| Anatomy of the upper airways (Clinical box 13.4 and Information box 13.2) | 606 | ||
| Nasal cavity | 606 | ||
| Pharynx | 606 | ||
| Larynx | 606 | ||
| Trachea | 607 | ||
| Gross anatomy of the lungs | 607 | ||
| The tracheobronchial tree | 607 | ||
| Breath sounds | 608 | ||
| Vocal resonance | 608 | ||
| Specialised tracheobronchial cells | 608 | ||
| Cilia and macrophages | 608 | ||
| Goblet cells and the mucociliary escalator | 609 | ||
| Clara cells | 609 | ||
| The alveoli | 609 | ||
| The gas–blood barrier | 609 | ||
| Cell types at the alveolar level | 610 | ||
| Capillary endothelial cells | 610 | ||
| Type I alveolar cells | 611 | ||
| Type II alveolar cells | 611 | ||
| Macrophages | 611 | ||
| Collateral ventilation | 611 | ||
| The pleura | 611 | ||
| Pleurisy and other pleural conditions | 611 | ||
| Pulmonary lymphatics | 611 | ||
| Pulmonary oedema | 612 | ||
| Anatomy of the pulmonary circulation | 612 | ||
| Arteries | 613 | ||
| Veins | 613 | ||
| Right-to-left (arteriovenous) shunts | 613 | ||
| Pulmonary blood flow | 613 | ||
| Volume of blood in lungs | 614 | ||
| Pulmonary arterial and venous pressure | 614 | ||
| Pulmonary blood vessels | 615 | ||
| Variations in pulmonary blood flow | 615 | ||
| Effect of gravity on pulmonary blood flow | 615 | ||
| Surface anatomy of the respiratory system | 615 | ||
| Larynx and trachea | 615 | ||
| Surface markings of the thorax | 615 | ||
| Anterior surface of the chest | 615 | ||
| Lateral surface of the chest | 616 | ||
| Posterior surface of the chest | 616 | ||
| The lungs and pleural cavity | 616 | ||
| Mechanics of Breathing | 617 | ||
| The diaphragm and other muscles used in breathing | 617 | ||
| Inspiration | 617 | ||
| Expiration | 618 | ||
| Pulmonary pressure changes during ventilation | 618 | ||
| Intrapulmonary pressure | 618 | ||
| Intrapleural pressure | 618 | ||
| Maximal respiratory pressures | 618 | ||
| Pulmonary ventilation | 618 | ||
| Lung volumes and capacities | 618 | ||
| Dead space | 619 | ||
| Functional residual capacity | 619 | ||
| Measuring rates of airflow | 620 | ||
| Forced expiratory volume | 620 | ||
| Peak expiratory flow rate | 621 | ||
| Reversibility of airflow limitation | 621 | ||
| Work of breathing | 622 | ||
| Airway resistance | 622 | ||
| Asthma | 623 | ||
| Bronchoconstriction | 623 | ||
| Inflammation and secretion | 623 | ||
| Lung inflation and deflation | 623 | ||
| Pressure–volume relationship | 623 | ||
| Compliance | 623 | ||
| Surface tension | 625 | ||
| Flow-related airway collapse | 625 | ||
| Closing capacity and posture | 625 | ||
| Dyspnoea in early disease | 625 | ||
| Principles of Gas Exchange | 626 | ||
| Diffusion | 626 | ||
| Pulmonary diffusion capacity | 626 | ||
| Measuring lung diffusion capacity – single breath CO testing (DLCO) | 626 | ||
| Partial pressures of gases in air | 626 | ||
| Partial pressures of gases in alveoli and blood | 627 | ||
| Carriage of Oxygen by the Blood | 627 | ||
| Respiratory pigments | 627 | ||
| Oxygen dissociation curve | 627 | ||
| Haemoglobin | 627 | ||
| Myoglobin | 628 | ||
| Carriage of Carbon Dioxide by the Blood | 628 | ||
| Carbon dioxide dissociation curve | 629 | ||
| Disturbances of acid–base balance | 629 | ||
| The four classes of acid–base disorder | 630 | ||
| Respiratory acidosis | 630 | ||
| Respiratory alkalosis | 630 | ||
| Metabolic acidosis | 630 | ||
| Metabolic alkalosis | 630 | ||
| Matching Lung Ventilation to Lung Perfusion | 630 | ||
| Ventilation–perfusion ratio | 630 | ||
| Uneven perfusion | 630 | ||
| Uneven ventilation | 631 | ||
| Ventilation–perfusion mismatch | 631 | ||
| Control of Breathing | 631 | ||
| The respiratory centre | 631 | ||
| Respiratory receptors (Clinical box 13.21) | 631 | ||
| Respiratory chemoreceptors | 632 | ||
| Central chemoreceptors | 632 | ||
| Peripheral chemoreceptors | 633 | ||
| Lung receptors | 633 | ||
| Pulmonary stretch receptors | 633 | ||
| Cough or lung-irritant receptors | 633 | ||
| Haemoptysis | 633 | ||
| J-receptors | 634 | ||
| Other receptors | 634 | ||
| Muscle stretch receptors | 634 | ||
| Joint proprioceptors | 634 | ||
| Baroreceptors | 634 | ||
| Higher-centre control of breathing | 634 | ||
| Energy Production and Oxygen Consumption | 634 | ||
| Respiratory quotient as an indication of metabolic fuel | 634 | ||
| Methods for estimating energy consumption | 635 | ||
| Basal metabolic rate | 635 | ||
| Challenges to Normal Respiration | 635 | ||
| Exercise | 635 | ||
| Altitude | 635 | ||
| Physiological responses to high altitude | 635 | ||
| Acclimatisation to altitude | 636 | ||
| Mountain sickness | 636 | ||
| Breath-holding | 636 | ||
| Prolonging the held breath | 636 | ||
| Diving | 636 | ||
| Effects of pressure in free diving | 636 | ||
| Effects of pressure during ascent from depth | 636 | ||
| Effects of pressure in deep diving | 636 | ||
| Diving reflex | 637 | ||
| Drowning | 637 | ||
| High oxygen levels | 637 | ||
| Neurological oxygen toxicity | 637 | ||
| Cellular oxygen toxicity | 637 | ||
| Carbon monoxide poisoning | 637 | ||
| Respiratory Failure | 637 | ||
| Causes of respiratory failure | 637 | ||
| Type I respiratory failure | 638 | ||
| Type II respiratory failure | 638 | ||
| Asthma | 638 | ||
| COPD | 638 | ||
| Emphysema | 638 | ||
| Clinical effects of respiratory failure | 639 | ||
| Lung Defences Against Infection | 639 | ||
| The upper airways | 639 | ||
| Conducting airways | 639 | ||
| Mucins and ciliary action | 639 | ||
| Other factors | 639 | ||
| Innate immunity | 639 | ||
| Destroying the invading organism | 639 | ||
| Defensins | 640 | ||
| Surfactant proteins | 640 | ||
| Inflammatory responses | 640 | ||
| Respiratory microbiome | 640 | ||
| Development of the Lungs and Changes in the Newborn | 640 | ||
| Early lung development | 640 | ||
| Embryonic phase | 640 | ||
| Stages in lung maturation | 640 | ||
| Pseudoglandular phase (6–16 weeks in utero) | 640 | ||
| Canalicular phase (16–24 weeks in utero) | 640 | ||
| Saccular phase (24 weeks in utero to birth) | 640 | ||
| Alveolar phase (32 weeks to 8 years) | 641 | ||
| Respiratory system changes at normal delivery | 642 | ||
| Respiratory distress syndrome of the newborn | 642 | ||
| 14 The renal system | 643 | ||
| Introduction | 643 | ||
| Functions of the kidney | 643 | ||
| Urine volume and composition | 643 | ||
| Balance of fluid intake and loss | 644 | ||
| Renal failure | 644 | ||
| Anatomy of the Kidney | 645 | ||
| Gross structure | 645 | ||
| Renal pyramids | 645 | ||
| The nephron | 645 | ||
| The renal corpuscle (renal glomerulus) | 645 | ||
| The renal tubule | 646 | ||
| Proximal convoluted tubule | 646 | ||
| Loop of Henle | 646 | ||
| Distal convoluted tubule | 646 | ||
| Collecting ducts | 646 | ||
| Renal vasculature | 646 | ||
| Renal microvasculature | 647 | ||
| Peritubular capillaries | 647 | ||
| Glomerular filtration barrier | 647 | ||
| Nerve supply to the renal tract | 649 | ||
| Development of the Kidney | 650 | ||
| Pronephros | 650 | ||
| Mesonephros | 650 | ||
| Metanephros | 650 | ||
| Permanent kidney | 650 | ||
| Congenital renal agenesis | 650 | ||
| Polycystic kidney disease | 650 | ||
| Renal Function | 650 | ||
| Glomerular filtration and the production of primary urine | 651 | ||
| Pore size and macromolecules | 652 | ||
| Filtration forces | 653 | ||
| Proteins | 653 | ||
| Functions of the proximal convoluted tubule | 653 | ||
| Tight junctions | 653 | ||
| The sodium pump | 653 | ||
| Carrier proteins | 655 | ||
| Ion channels | 655 | ||
| Recovery of bicarbonate by the PCT | 655 | ||
| Water | 655 | ||
| Aquaporins | 655 | ||
| Peritubular capillaries | 655 | ||
| Sugars, amino acids and other small organic molecules | 655 | ||
| Facilitated carriers | 656 | ||
| Sodium and chloride | 656 | ||
| Secretion of organic anions and cations | 656 | ||
| Organic anion transport | 656 | ||
| Para-aminohippuric acid | 657 | ||
| PAH and drug dosage | 657 | ||
| Efflux transporters and drugs | 657 | ||
| Nephrotoxicity | 657 | ||
| Organic cation transport | 657 | ||
| Renal function tests | 657 | ||
| Blood and urine tests | 657 | ||
| Relative density of urine | 657 | ||
| Osmolality | 657 | ||
| Specific gravity | 657 | ||
| Refractometry | 658 | ||
| Dry chemistry | 658 | ||
| Analysing urine | 658 | ||
| Proteinuria | 658 | ||
| Renal handling of molecules | 658 | ||
| Renal clearance | 658 | ||
| Clearance of molecules that are only filtered | 659 | ||
| ‘Inulin’ clearance as an index of GFR | 659 | ||
| Creatinine clearance | 659 | ||
| Urea clearance | 660 | ||
| Current methods for measuring renal clearance (half-life) | 660 | ||
| Clearance of molecules that are filtered and reabsorbed | 660 | ||
| Clearance of molecules that are filtered and secreted | 661 | ||
| Use of clearance methods to assess renal function | 661 | ||
| Advanced clinical tests | 661 | ||
| Renal control of fluid balance | 661 | ||
| Vasopressin | 661 | ||
| Vasopressin release | 664 | ||
| Vasopressin receptors | 664 | ||
| Calculation of renal water excretion | 664 | ||
| Mechanism of urine concentration and dilution | 665 | ||
| Osmolarity gradient | 665 | ||
| Vasa recta and counter-current hypothesis | 665 | ||
| Transport properties of the loop of Henle | 665 | ||
| Water | 665 | ||
| Sodium and chloride | 665 | ||
| Counter-current mechanism | 665 | ||
| Urea | 665 | ||
| Vasa recta | 665 | ||
| The diluting segment and the DCT | 665 | ||
| Cortical collecting duct | 666 | ||
| Renal control of sodium balance | 666 | ||
| Renal sodium handling | 668 | ||
| Sodium recovery | 668 | ||
| The PCT | 668 | ||
| The loop of Henle | 668 | ||
| The DCT | 668 | ||
| The collecting ducts | 668 | ||
| Control of GFR by the renal capillaries | 669 | ||
| Autoregulation | 669 | ||
| Glomerular–tubular balance | 669 | ||
| Receptors involved with sodium balance | 669 | ||
| Baroreceptors | 669 | ||
| The juxtaglomerular apparatus | 669 | ||
| Renin–angiotensin–aldosterone system | 670 | ||
| Role of angiotensin II and Na+ control | 670 | ||
| Aldosterone | 670 | ||
| Potassium | 671 | ||
| Autoregulation and the DCT | 671 | ||
| Tubulo-glomerular feedback | 671 | ||
| Na+ balance summary | 671 | ||
| Diuretics | 671 | ||
| Osmotic diuresis | 671 | ||
| Carbonic anhydrase inhibitors | 671 | ||
| The thiazide diuretics | 672 | ||
| Loop diuretics | 672 | ||
| Diuretics acting on the late distal tubule and the collecting ducts (K+ sparing) | 672 | ||
| Amiloride and triamterene | 672 | ||
| Spironolactone | 673 | ||
| Renal control of acid–base balance | 673 | ||
| Hydrogen ions | 673 | ||
| Sources of H+ ions | 673 | ||
| Cell metabolism produces ‘volatile’ H+ ions | 673 | ||
| ‘Fixed’ H+ ions | 673 | ||
| Sources of non-respiratory H+ ions | 673 | ||
| Disease states | 674 | ||
| Acid–base balance is vital for life | 674 | ||
| Renal mechanisms of control | 674 | ||
| ions and pCO2 | 674 | ||
| Loop of Henle and ions | 675 | ||
| The distal nephron | 675 | ||
| Renal buffers | 675 | ||
| Phosphate buffering | 675 | ||
| Ammonium synthesis | 675 | ||
| Abnormalities of acid–base balance (Clinical box 14.14) | 675 | ||
| The Urinary Tract | 676 | ||
| Ureters | 676 | ||
| Urinary tract obstruction | 677 | ||
| Congenital problems | 677 | ||
| Gross structure of the bladder | 678 | ||
| Maintenance of continence | 678 | ||
| Nerve supply | 678 | ||
| Bladder filling and tone | 678 | ||
| Control of micturition | 678 | ||
| The micturition reflex | 678 | ||
| Renal tumours | 679 | ||
| Benign | 679 | ||
| Malignant | 679 | ||
| Renal Diseases | 679 | ||
| General classification of renal disease | 679 | ||
| Onset of renal disease | 680 | ||
| Acute kidney injury | 680 | ||
| Acute tubular necrosis | 680 | ||
| Nephrotoxic agents | 681 | ||
| Pre-renal | 681 | ||
| Intrinsic renal | 681 | ||
| Antibiotics | 681 | ||
| Antifungals | 681 | ||
| Proton pump inhibitors | 681 | ||
| Metformin | 682 | ||
| Drugs and the elderly | 682 | ||
| Chronic kidney disease | 682 | ||
| Causes of chronic kidney disease | 682 | ||
| Progression of chronic kidney disease | 682 | ||
| Chronic kidney disease and hypertension | 682 | ||
| Erythropoietin | 682 | ||
| Pharmacological renal damage and chronic renal failure | 683 | ||
| Renal replacement therapy | 683 | ||
| 15 The alimentary system | 687 | ||
| Introduction | 687 | ||
| Basic functions and structure of the alimentary system | 687 | ||
| Blood supply to the gastrointestinal tract | 688 | ||
| Overview of Digestion and Absorption | 689 | ||
| Physical digestion | 689 | ||
| Chemical digestion | 689 | ||
| Carbohydrate digestion | 689 | ||
| Protein digestion | 690 | ||
| Protein digestion in the stomach | 690 | ||
| Protein digestion in the small intestine | 690 | ||
| Fat digestion | 690 | ||
| Absorption | 692 | ||
| General principles of absorption | 692 | ||
| Carbohydrate absorption | 693 | ||
| Glucose and galactose absorption | 693 | ||
| Fructose absorption | 694 | ||
| Protein absorption | 694 | ||
| Di- and tripeptide absorption | 694 | ||
| Amino acid absorption | 694 | ||
| Fat absorption | 694 | ||
| Bile salt absorption | 695 | ||
| Vitamins | 695 | ||
| Water-soluble vitamins | 695 | ||
| Vitamin B12 | 695 | ||
| Fat-soluble vitamins | 695 | ||
| Absorption of electrolytes and water | 695 | ||
| Pathways for electrolyte and water absorption | 695 | ||
| Calcium absorption | 695 | ||
| Iron absorption | 696 | ||
| Regulation of iron absorption | 697 | ||
| Surface Anatomy of the Abdomen | 697 | ||
| Abdominal regions | 698 | ||
| Epigastric region | 698 | ||
| Umbilical region | 698 | ||
| Suprapubic (hypogastric) region | 698 | ||
| Left and right hypochondrium | 698 | ||
| Left and right lumbar region | 699 | ||
| Left and right iliac fossa (inguinal region) | 699 | ||
| Quadrants | 699 | ||
| Microanatomy of the Gastrointestinal Tract | 699 | ||
| Innervation of the alimentary canal | 701 | ||
| Mouth | 701 | ||
| Teeth | 701 | ||
| Tongue | 701 | ||
| Mastication | 701 | ||
| Salivary Glands | 701 | ||
| Functions of saliva | 703 | ||
| Lubrication | 703 | ||
| Protection | 703 | ||
| Digestion | 703 | ||
| Composition of saliva | 703 | ||
| Organic constituents | 703 | ||
| Inorganic constituents | 703 | ||
| Secretory mechanisms | 703 | ||
| The salivon | 704 | ||
| Mechanisms of secretion of saliva | 704 | ||
| Stage one – the primary secretion | 704 | ||
| Stage two – modification of the primary secretion | 705 | ||
| Secretion of organic constituents | 705 | ||
| Control of salivary secretion | 705 | ||
| Parasympathetic nervous system | 705 | ||
| Sympathetic nervous system | 705 | ||
| Intracellular messengers producing salivary secretion | 705 | ||
| Pharynx and Oesophagus | 706 | ||
| Swallowing | 706 | ||
| Oral or voluntary phase | 706 | ||
| Pharyngeal phase | 706 | ||
| Oesophageal phase | 707 | ||
| Stomach and Duodenum | 707 | ||
| Anatomy of the stomach | 707 | ||
| Gastric and duodenal musculature | 708 | ||
| The gastric mucosa | 709 | ||
| Control of Gastric Secretions | 710 | ||
| Stimulation of gastric acid secretion | 710 | ||
| 16 Diet and nutrition | 737 | ||
| Introduction | 737 | ||
| Diet | 737 | ||
| Worldwide dietary patterns and food guides | 737 | ||
| Food guides | 737 | ||
| Food labelling | 737 | ||
| Dietary reference values | 738 | ||
| Nutritional requirements | 739 | ||
| Variations in nutritional requirements | 739 | ||
| Preconception | 739 | ||
| Pregnancy | 739 | ||
| Lactation | 739 | ||
| Infancy | 740 | ||
| Nutritional Status | 740 | ||
| Clinical assessment of nutritional status | 740 | ||
| Food intake | 740 | ||
| Detailed dietary assessment | 741 | ||
| ‘Usual weight’ and weight loss/gain | 741 | ||
| Body mass index | 741 | ||
| Children | 741 | ||
| Measures of body composition: adults | 742 | ||
| Estimating body fat | 742 | ||
| Skinfold thickness | 742 | ||
| Arm circumference | 742 | ||
| Waist circumference and waist/hip ratio | 742 | ||
| Other measurements of nutritional status | 742 | ||
| Plasma proteins | 742 | ||
| Vitamin status | 742 | ||
| Muscle strength | 742 | ||
| Immunological skin testing | 743 | ||
| Malnutrition screening tools | 743 | ||
| Energy and nitrogen balance | 743 | ||
| Conversion of macronutrients to energy | 743 | ||
| Energy balance | 743 | ||
| Basal metabolic rate (BMR) and resting energy expenditure | 743 | ||
| Total energy expenditure | 743 | ||
| Measuring energy expenditure | 744 | ||
| Total energy expenditure and the effect of physical activity | 744 | ||
| Energy expenditure during daily living | 744 | ||
| Estimates of energy consumption for different types of activity | 744 | ||
| Energy expenditure during exercise | 744 | ||
| Anaerobic carbohydrate metabolism | 744 | ||
| Aerobic carbohydrate metabolism | 745 | ||
| Nitrogen balance and protein requirements | 745 | ||
| Dietary nitrogen | 745 | ||
| Protein requirements | 745 | ||
| Essential and non-essential amino acids | 745 | ||
| Obligatory nitrogen loss | 745 | ||
| Minimum nitrogen requirement | 745 | ||
| Nitrogen excretion | 746 | ||
| Energy and protein metabolism during fasting and feeding | 746 | ||
| Fed state | 747 | ||
| Absorbed carbohydrate in the fed state | 747 | ||
| Absorbed fat in the fed state | 747 | ||
| Protein in the fed state | 748 | ||
| Fasted state | 748 | ||
| The need for glucose in the fasted state | 748 | ||
| Decreased insulin – fasting state | 748 | ||
| Fat in the fasted state | 748 | ||
| Prolonged fasting/starvation | 749 | ||
| Metabolic response to stress: sepsis and trauma | 749 | ||
| Energy metabolism during illness | 749 | ||
| Insulin and the inflammatory response | 750 | ||
| Protein metabolism in illness | 750 | ||
| Protein metabolism and acute phase response in illness | 750 | ||
| Micronutrients and Water | 750 | ||
| Vitamins | 750 | ||
| Vitamins as coenzymes | 750 | ||
| Vitamins as antioxidants | 751 | ||
| Water-soluble vitamins | 751 | ||
| The B vitamins | 751 | ||
| Vitamin B1 (thiamine) | 751 | ||
| Vitamin B2 (riboflavin) | 751 | ||
| Vitamin B3 (niacin) | 751 | ||
| Vitamin B6 (pyridoxine) | 751 | ||
| Biotin | 751 | ||
| Pantothenic acid | 751 | ||
| Folic acid | 751 | ||
| Vitamin B12 (cobalamin) | 751 | ||
| Vitamin C (ascorbic acid) | 752 | ||
| Fat-soluble vitamins | 752 | ||
| Vitamin A | 752 | ||
| Vitamin D (calciferol) | 752 | ||
| Vitamin E (tocopherols) | 752 | ||
| Vitamin K | 753 | ||
| Trace elements: minerals | 753 | ||
| Iron | 753 | ||
| Copper | 753 | ||
| Zinc | 753 | ||
| Selenium | 753 | ||
| Magnesium | 754 | ||
| Calcium | 754 | ||
| Phosphate | 754 | ||
| Iodine | 754 | ||
| Fluoride | 754 | ||
| Water and electrolytes | 754 | ||
| Water | 754 | ||
| Daily water requirements | 754 | ||
| Electrolytes | 754 | ||
| Water and electrolyte depletion | 755 | ||
| Intravenous fluid replacement | 755 | ||
| Water overload | 755 | ||
| The Control of Food Intake | 755 | ||
| Appetite and satiety | 755 | ||
| The physiological control of eating | 755 | ||
| Peripheral satiety signals | 755 | ||
| Gastric distension and emptying | 756 | ||
| Balance of chemical contents in the gut | 756 | ||
| Peptides and hormones | 756 | ||
| Peripheral hunger signals | 756 | ||
| Ghrelin | 757 | ||
| Long-term satiety signals | 757 | ||
| Leptin | 757 | ||
| Insulin | 757 | ||
| Oestrogen | 757 | ||
| Diet and disease | 757 | ||
| Association between diet and disease | 757 | ||
| Reactive oxygen species or free radicals | 758 | ||
| Formation of reactive oxygen species | 758 | ||
| Body defence against cancer or invading bacteria | 758 | ||
| Oxidative stress | 758 | ||
| Defence against reactive oxygen species – antioxidants | 758 | ||
| Diet and carcinogenesis | 758 | ||
| Antioxidants | 759 | ||
| Obesity | 759 | ||
| Nutrition and cancer treatment | 759 | ||
| Diet and cardiovascular disease | 759 | ||
| Dietary prevention of atherosclerosis | 760 | ||
| Atherogenesis | 760 | ||
| Homocysteine | 760 | ||
| Diet and hypertension | 761 | ||
| Dietary approach to hypertension | 761 | ||
| Cardioprotective diets | 761 | ||
| Some therapeutic diets | 761 | ||
| Dietary treatment of coeliac disease | 761 | ||
| Dietary restrictions in renal disease | 761 | ||
| Protein | 761 | ||
| Energy | 761 | ||
| Potassium | 761 | ||
| Phosphate | 761 | ||
| Sodium and fluid | 762 | ||
| Dietary control in diabetes mellitus | 762 | ||
| Exercise in diabetes | 762 | ||
| Lipid lowering | 762 | ||
| Artificial nutrition | 762 | ||
| Enteral nutrition | 762 | ||
| Complications of enteral feeding | 762 | ||
| Parenteral nutrition | 763 | ||
| Malnutrition | 763 | ||
| Malnutrition and disease states | 763 | ||
| Diagnosis of malnutrition | 763 | ||
| Refeeding syndrome | 763 | ||
| Avoidance of refeeding syndrome | 764 | ||
| Obesity | 764 | ||
| Aetiology of obesity | 764 | ||
| Psychogenic factors | 765 | ||
| Environmental factors and exercise | 765 | ||
| Treatment of obesity | 766 | ||
| Dietary management | 766 | ||
| A psychological model for dietary modification | 766 | ||
| Pharmacological management | 767 | ||
| Appetite suppression | 767 | ||
| Inhibition of fat absorption | 767 | ||
| Surgical management | 767 | ||
| Endoscopic management strategies | 767 | ||
| Duodenal jejunal bypass liner | 767 | ||
| Intragastric balloon | 767 | ||
| Increasing physical activity | 768 | ||
| Prevention of obesity | 768 | ||
| Index | 771 | ||
| A | 771 | ||
| B | 772 | ||
| C | 773 | ||
| D | 775 | ||
| E | 776 | ||
| F | 777 | ||
| G | 777 | ||
| H | 778 | ||
| I | 779 | ||
| J | 780 | ||
| K | 780 | ||
| L | 780 | ||
| M | 781 | ||
| N | 782 | ||
| O | 783 | ||
| P | 783 | ||
| Q | 785 | ||
| R | 785 | ||
| S | 786 | ||
| T | 787 | ||
| U | 788 | ||
| V | 788 | ||
| W | 788 | ||
| X | 789 | ||
| Y | 789 | ||
| Z | 789 |