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Basic Science in Obstetrics and Gynaecology E-Book

Basic Science in Obstetrics and Gynaecology E-Book

Phillip Bennett | Catherine Williamson

(2014)

Additional Information

Book Details

Abstract

A textbook covering the basic sciences relevant to obstetrics and gynaecology at a level suitable for doctors specialising in the field . The chapters match the syllabus of the specialist UK exam – the MRCOG Part 1

  • This new edition completely revised and updated to cover all the basic science required for the new MRCOG Part 1 exam.
  • Genetics covered by two new chapters: Structure and function of the genome; and Clinical genetics.
  • Extensive revision of immunology, statistics and evidence-based health.
  • Many new illustrations, particularly in anatomy and immunology.
  • New editorial team, plus nearly 50% new contributors.
  • New self-assessment section written in the style of the new exam.
  • This new edition completely revised and updated to cover all the basic science required for the new MRCOG Part 1 exam.
  • Genetics covered by two new chapters: Structure and function of the genome; and Clinical genetics.
  • Extensive revision of immunology, statistics and evidence-based health.
  • Many new illustrations, particularly in anatomy and immunology.
  • New editorial team, plus nearly 50% new contributors.
  • New self-assessment section written in the style of the new exam.

Table of Contents

Section Title Page Action Price
Front cover cover
Half title page i
Basic Science in Obstetrics and Gynaecology iii
Table of Contents v
Copyright page iv
Contributors vii
Preface ix
Acknowledgements xi
One Structure and function of the genome 1
CHAPTER CONTENTS 1
Chromosomes 1
Gene structure and function 2
The central dogma of molecular biology 4
Transcription 4
Translation 5
Replication 5
Regulation of gene expression 5
Epigenetics 6
Epigenetic modification of DNA 6
Epigenetic modification of histones 6
Mitochondrial DNA 6
Studying DNA 6
Mendelian genetics and linkage studies 6
The sequencing of the genome 7
Analysis of complex traits 7
Molecular biology techniques 8
Restriction endonucleases 8
The polymerase chain reaction 8
Electrophoresis 9
Blotting 9
Sequencing 9
Cloning vectors and cDNA analysis 9
Expression studies 9
In-silico analysis 9
The ‘post-genomic’ era 10
The molecular basis of inherited disease – DNA mutations 10
Two Clinical genetics 13
CHAPTER CONTENTS 13
Chromosome abnormalities 13
Aneuploidy 14
Polyploidy 14
Trisomy 15
Monosomy 15
Sex chromosome anomalies 15
Mosaicism 16
Structural chromosome abnormalities 16
Chromosome deletions 16
Chromosome duplications 16
Chromosome inversions 16
Isochromosome 17
Translocations 17
Chromosome nomenclature 19
Single gene disorders 19
Autosomal dominant diseases 19
Autosomal recessive diseases 20
Cystic fibrosis 20
Thalassaemias 21
Sickle cell disease 21
Sex-linked inheritance 21
X-linked recessive diseases 21
X-linked dominant diseases 22
Y-linked diseases 22
Mitochondrial inheritance 22
Genomic imprinting 22
Uniparental disomy 23
Multifactorial inheritance 23
Genetic testing and interpretation of a genetic result 24
Chromosome analysis 24
Molecular cytogenetics: FISH 24
Mutation testing 24
Three Embryology 25
CHAPTER CONTENTS 25
Oogenesis, spermatogenesis and organogenesis 25
Oogenesis 25
Spermatogenesis 26
Early embryogenesis: fertilization, transportation and implantation 27
Early development of the embryo 29
Organogenesis 30
Development of the germ layers 30
Pharyngeal region 31
Cardiovascular system 33
Fetal circulation 33
Alimentary system, pulmonary and peritoneal cavities 33
Respiratory organs 34
Central nervous system 34
Skeletal system 34
Muscles, skin and appendages 36
Development of the genital organs 36
Uterus and tubes 36
Vagina 36
External genitalia 36
Gonads 38
Development of the placenta 40
Placental bed 44
Development of membranes and formation of amniotic fluid 44
Membranes 44
Amniotic fluid 45
Composition of amniotic fluid 47
Four Fetal and placental physiology 49
CHAPTER CONTENTS 49
Introduction 49
Fetal growth 49
Maternal smoking and drug use 50
Maternal hypoxia 50
Maternal inflammatory conditions 50
The placenta and fetal growth 50
The IGF (insulin-like growth factors) axis 50
Fetal circulation 50
Development 50
Distribution and pattern of the fetal circulation 51
Changes at birth 51
Response to stress 52
Renal function and amniotic fluid dynamics 52
Amniotic fluid 52
Fetal lung development 53
Surfactants 53
Changes at birth 54
Fetal brain development 54
The placenta 54
Nutrient transport across the placenta 55
Endocrine function of the placenta 55
The placenta in perinatal disease 55
Fetal origins of adult disease 55
References 55
Five Applied anatomy 57
CHAPTER CONTENTS 57
Introduction 58
Body tissues and cells 58
The nervous system 58
The somatic nervous system 58
The autonomic nervous system 59
Clinical application 59
Sympathetic (thoracolumbar) nervous system 60
Sympathetic effects 60
The adrenal medulla 60
Parasympathetic (craniosacral) nervous system 61
Cranial: III, VII, IX, X 61
Sacral: S2 and S3 61
Parasympathetic effects 61
The spinal cord and meninges 61
Spinal nerve roots and their plexuses 62
Clinical application 62
Anatomy of the brain 62
The thalami 62
The hypothalamus 62
The pineal gland 62
The pituitary gland 62
Clinical application 63
The lymphatic system 63
Lymphatic vessels 63
Lymphatic tissue 63
The vascular system 63
Fetal circulation and changes after birth 63
Oxygenated blood 63
Deoxygenated blood 63
Changes at and after birth 63
The arterial system 64
The aorta 64
Three ventral branches 64
Three terminal branches 64
Four pairs of branches 64
Four lateral pairs 64
The common iliac arteries 65
The venous system 65
The inferior vena cava 65
Collateral venous drainage pathways 65
Six Pathology 97
CHAPTER CONTENTS 97
General pathological principles 97
Cellular injury and death 97
Response to tissue injury 98
Acute inflammation 98
Tissue repair and wound healing 98
Chronic inflammation 99
Control of cell and tissue growth or differentiation 99
Pathology of gynaecological tumours 100
Vulva 100
Vagina 100
Cervix 101
Endometrium 101
Myometrium 101
Ovary 101
Pathology of miscarriage and gestational trophoblastic disease 102
Chromosomal abnormalities 102
Infection 102
Maternal disease 102
Other factors 102
Gestational trophoblastic neoplasia 103
Pathology of common congenital abnormalities 103
Pathology of the placenta 104
Intrauterine growth restriction and pre-eclampsia 104
Ascending genital tract infection 105
Seven Microbiology and virology 107
CHAPTER CONTENTS 107
Bacteriology, mycology and parasitology 107
Introduction 107
Morphology and structure 107
Classification and typing 108
Pathogenesis 110
Laboratory identification 110
Specimen collection 110
Culture 111
Antigen detection 111
Nucleic acid detection 111
Antibody detection 112
Bacteria and disease 112
Normal flora 112
Normal genital tract flora of women 112
Gram-positive and Gram-negative bacteria 112
Spirochaetes, mycoplasmas, chlamydiae and other bacteria 116
Killing bacteria 117
Action of antibiotics 117
Physical methods 118
Sterilization/disinfection 118
Heat 118
Chemicals 119
Other 119
Mycology 119
Pathogenic fungi 119
Moulds 119
True yeasts 119
Yeast-like fungi 120
Dimorphic fungi 120
Parasites 120
Protozoa 120
Helminths (worms) 121
Virology 121
Introduction 121
Viral nucleic acid 121
Replication 121
Structure of viruses 122
Diagnosis of viral infections 124
Viruses of importance in obstetrics and gynaecology 124
Viruses which may induce severe infection in pregnancy 124
SARS and other coronaviruses 126
Intrauterine infections 126
Rubella 127
CMV 127
Varicella 127
Parvovirus B19 128
HIV-1 and -2 128
Enteroviruses (polioviruses, coxsackie A and B viruses, echoviruses) 128
Perinatal infections 128
HSV 128
Hepatitis B 129
Hepatitis C 129
Human papillomavirus (HPV) 129
Human T cell lymphotrophic virus type 1 (HTLV-1) 129
References 130
Eight Immunology 131
CHAPTER CONTENTS 131
Introduction 131
The immune system 131
Adaptive immune systems 132
Antibody molecules 132
B cells 134
T cells 135
Antigen recognition 135
Function of T cells 135
Cells of the innate immune system 137
NK cells 137
Macrophages 138
Granulocytes 138
The dendritic cell 138
Regulation of the immune system 138
The danger theory 138
Tolerance 138
The fetus as an allograft 139
Systemic control mechanisms 140
Local immunomodulation 140
Antibodies and pregnancy 140
Other immunological interactions with the fetus 141
Conclusion 142
Nine Biochemistry 143
CHAPTER CONTENTS 143
Structure and function of the normal cell 143
Cells 143
Nucleus 143
Cytoplasm 144
Cell types 145
Intercellular matrix 145
Proteins, peptides and amino acids 145
Amino acids 146
Structure of proteins 149
Purification and analysis of proteins 151
Modification of protein structure 151
Metabolism 152
Overall energy metabolism 152
Glycolysis 153
Citric acid cycle 153
Respiratory chain 155
Fatty acid oxidation 155
Regulation of metabolic pathways 156
Catabolism 158
Haemoglobin 158
Urea cycle 158
Enzymes 159
Enzyme kinetics 160
Vitamins 160
Role of enzymes in digestion 161
Protein 161
Carbohydrate 161
Fat 161
Cell signalling and second messaging 162
General overview 162
Eicosanoid synthesis 163
Gap junctions 164
Nitric oxide is an important signalling molecule 164
Calcium as an intracellular messenger 165
Signals acting on intracellular receptors 165
Ion channels 166
G-protein-linked receptors which increase cyclic AMP 166
Inhibitory G-proteins 167
cAMP-dependent protein kinase (protein kinase A) 169
Inositol phosphate and diacylglycerol second messengers 169
Enzyme-linked receptors 169
Vascular endothelial growth factors 170
Ten Physiology 173
CHAPTER CONTENTS 173
Biophysical definitions 174
Molecular weight 174
Distribution of water and electrolytes 174
Anion gap 174
Transport mechanisms 175
Acid–base balance 177
Normal acid–base balance 177
pH 178
Partial pressure of carbon dioxide (Pco2) 178
Henderson–Hasselbalch equation 178
Control of pH 178
Buffers 179
Buffer base and base excess 180
Standard bicarbonate 180
Abnormalities of acid–base balance 180
Respiratory acidosis 180
Respiratory alkalosis 180
Metabolic acidosis 180
Metabolic alkalosis 180
Cardiovascular system 181
Conduction system of the heart 181
Factors affecting heart rate 181
Cardiac chambers 181
Electrocardiogram (ECG) 181
Pressure and saturation in the cardiac chambers 183
Haemodynamic events in the cardiac cycle and their clinical correlates 183
Control of cardiac output 184
Changes in blood volume and cardiac output during pregnancy 186
Blood pressure control 186
Autonomic nervous system and blood pressure control 187
Local control of blood flow 187
Blood pressure changes in pregnancy 188
Endothelium in pregnancy 188
Endothelium as a barrier 188
Endothelium as a modulator of vascular tone 189
Endothelium-derived vasodilators 189
Nitric oxide 189
Prostacyclin 190
Endothelium-derived hyperpolarizing factor 190
Vascular endothelial growth factor 190
Placental growth factor 190
Thromboxane 191
Endothelin 191
Angiotensin II 191
Oestrogen and the endothelium 191
Endothelium and haemostasis 191
Endothelium and inflammation 192
Pre-eclampsia 192
Endothelial dysfunction in pre-eclampsia 192
Nitric oxide in pre-eclampsia 192
Prostanoids in pre-eclampsia 193
Prothrombotic states 193
Aetiology of maternal endothelial dysfunction in pre-eclampsia 193
Conclusion 193
Respiration 193
The lungs, ventilation and its control 193
Gas composition 193
Dead space 194
Oxygen consumption 194
Lung volumes 194
Mechanics of ventilation 194
Resistance to air flow 195
Oxygen transfer 195
Effect of pregnancy 195
Control of respiration 195
Response to hypercapnia 196
Response to hypoxia 196
Effect of changes in hydrogen ion concentration 196
Oxygen and carbon dioxide transport 197
Oxygen transport 197
Carbon monoxide 198
Carbon dioxide transport 199
Urinary system 199
Microanatomy 199
Renal clearance 200
Glomerular filtration rate 200
Renal blood flow 201
Handling of individual substances 201
Glucose and amino acids 201
Sodium and chloride 201
Bicarbonate 201
Potassium 202
Hydrogen ions 202
Water 202
Urea 202
Endocrine functions of the kidney 202
Effects of pregnancy 203
Renal glomerular function during pregnancy 203
Renal tubular function during pregnancy 203
Renal endocrine function during pregnancy 204
Physiology of micturition 205
Passive phase 205
Active phase 205
Urodynamic data in the normal adult female 205
Gastrointestinal tract 205
Mouth 205
Mechanics 205
Digestive processes 205
Oesophagus 206
Eleven Endocrinology 231
CHAPTER CONTENTS 231
Introduction 232
Mechanisms of hormone action and second messenger systems 232
Cell surface receptors 232
Nuclear receptors 233
Hormone types 233
Peptide hormones 233
Steroid hormones 234
Ovary 234
Adrenal 234
Testis 234
Placenta 236
Steroid binding and metabolism 236
Amino acid hormones 236
Prostaglandins and leukotrienes 236
Hypothalamus and pituitary 236
Embryology 238
Anatomy 238
Boundaries 238
Blood supply 239
Structure 239
Hypothalamic products 239
Pituitary gland products 240
Pineal gland 240
Reproductive hormones 240
Function 240
Oestrogen and progesterone 241
Androgens 242
Sex differentiation in utero 242
Puberty 242
Female 242
Male 243
Endocrinology of puberty 243
Leptin 243
Menstrual cycle 243
Inhibin and activin 245
Pregnancy 245
Biochemistry of human labour 246
Pro-pregnancy factors 246
Placental clock 247
Labour: an inflammatory reaction 247
A unified hypothesis of the onset of labour in humans 247
Lactation 247
Menopause 247
Growth 248
Physiology 248
Dysfunction 248
Pancreas 248
Embryology 248
Anatomy 248
Function 249
Dysfunction 249
Thyroid 249
Embryology 249
Anatomy 249
Thyroid hormone synthesis 249
Function 252
Dysfunction 253
Therapy of thyroid disease 253
Adrenal gland 253
Embryology 253
Anatomy 253
Adrenal cortisol synthesis 253
Function 253
Metabolism 254
Connective tissue 254
Haematology and immunology 254
Cardiovascular and renal effects 254
Miscellaneous effects 254
Dysfunction 254
Adrenal androgens 254
Adrenal medulla 254
Calcium homeostasis 255
Parathyroid hormone (PTH) 255
PTH anatomy and embryology 255
PTH synthesis 255
PTH function 255
PTH dysfunction 255
Vitamin D 256
Vitamin D synthesis 256
Vitamin D function 256
Vitamin D dysfunction 256
Calcitonin 256
Calcitonin synthesis 256
Calcitonin function 256
Calcitonin dysfunction 256
Osteoporosis 256
Twelve Drugs and drug therapy 259
CHAPTER CONTENTS 259
Introduction 259
Language of clinical pharmacy 260
Teratogenesis 261
Organogenesis 261
Pharmacokinetics 261
Drugs can undergo different types of transport 262
Pharmacodynamics 263
Factors that influence drug action 263
Drug metabolism 263
Drug interactions 263
Impaired liver function 264
Physiological changes that affect drug metabolism in pregnancy 264
The placental barrier 264
Some commonly used drugs 265
Selective β2 agonists 265
Vasodilators 265
α2-Adrenergic agonists 265
b-Adrenoceptor antagonists 265
Calcium channel blockers 265
Ergot alkaloids 266
General anaesthetics 266
Mechanism of action 266
Intravenous anaesthetics 266
Inhalational anaesthetics 266
Neuromuscular blocking agents 266
Local anaesthetics 267
Drugs affecting uterine activity 267
Prostaglandins 267
Oxytocin 267
Tocolytics 267
Diuretics 267
Opioids 268
Retinoids 269
Cytotoxic drugs 269
Anticoagulants 269
Warfarin 269
Heparin 269
Anticonvulsants 270
Anti-inflammatory drugs 270
Non-steroidal anti-inflammatory drugs (NSAIDs) 270
COX-2 inhibitors 270
Colchicine 270
Antimicrobials 270
Antibiotics 270
Macrolides 271
Antiviral agents 272
Antifungals 272
Antithyroid drugs 272
Sulphonylureas 272
Adrenocortical steroids 272
Antineoplastic drugs 273
Alkylating agents 273
Antimetabolites 274
Antibiotics 274
Platinum-based drugs 274
α-Cisplatin 274
Vinca alkaloids 274
Taxanes 274
Psychotropic drugs 275
Lithium 275
Antidepressants 275
Selective serotonin re-uptake inhibitors (SSRIs) 275
Tricyclic antidepressants 275
Oral contraceptives 275
Mechanism of action of the combined pill 275
Mechanism of action of the progestogen-only pill and depot injections of progestogen 275
Metabolic effects of the combined oral contraceptive pill 275
The combined oral contraceptive pill and cancer 276
Drugs of choice in breastfeeding 276
Conclusion 276
Thirteen Physics 279
CHAPTER CONTENTS 279
Diagnostic ultrasound 279
Intensity 279
Characteristic impedance and reflections 279
Absorption 280
Diffraction 280
Focusing 280
Ultrasound reception 281
Doppler effect 281
Radioactivity and X-rays 281
Ionization and excitation 283
Quantity of radioactive material 284
Radiation exposure and dose 284
Stable isotopes 284
Lasers 285
Magnetic resonance imaging (MRI) 286
Fourteen Statistics and evidence-based healthcare 289
CHAPTER CONTENTS 289
Introduction 289
Some basic statistical principles 290
Sampling and inference to the population at large 290
Type 1 error 290
Type 2 error 291
The null and active hypotheses 291
Bias and generalizability 291
Confidence intervals, accuracy and precision 291
Independence and matched data 291
Data types, distribution assumptions and parametric tests 292
Quantitative or continuous 292
Ordinal 292
Categorical 292
Binary 292
Time-dependent data 292
The normal distribution 292
Parametric and non-parametric tests 293
Deciding whether to use parametric or non-parametric tests 293
Data collection and presentation 294
Example 295
Mean 295
Variance 295
Standard deviation (SD) 295
Standard error of the mean (SEM) 296
Confidence interval for the mean 296
Mode 296
Median 296
Range 296
Interquartile range 296
Proportion and risk 296
Odds 297
Rate 297
Measures of outcome, exposure and effect 297
Prevalence 297
Incidence 297
Question 1 – Is there any difference in the use of hypertensive therapy between men and women? 297
Question 2 – Is there any difference in mortality between men and women? 298
Confounding and interaction 298
Types of study and experimental design 299
Types of bias 300
Selection bias 300
Responder or observer bias 300
Types of study 301
Ecological studies 301
Cross-sectional studies 301
Cohort studies 301
Case–control studies 301
Randomized controlled trials (RCTs) 302
The intention-to-treat principle 302
Diagnostic testing studies 302
Equations for basic power calculations 304
For continuous outcomes 304
For categorical outcomes 304
Acknowledgement 304
Recommended statistics texts 304
Fifteen Clinical research methodology 305
CHAPTER CONTENTS 305
Introduction 305
Types of clinical investigation 306
Types of study 306
What is audit? 306
The clinical research process 307
Integrated Research Application System (IRAS) 307
Research and development approval 307
International Conference on Harmonisation guideline on Good Clinical Practice (ICH GCP) 308
The European Union (EU) Clinical Trials Directive 308
Investigational medicinal products 308
Medical devices 308
Responsibilities of an investigator 308
When are studies not covered by the EU directive? 309
The Medicines and Healthcare products Regulatory Agency 310
Registration of trials 310
EudraCT 310
International Standard Randomised Controlled Trial Number (ISRCTN) 310
metaRegister of Controlled Trials (mRCT) 310
Data 311
Data security 312
Consent, information and sponsors 313
Patient information sheet 313
Informed consent form 313
Sponsorship 313
Trial Steering Committees (TSC) and Data Monitoring and Ethics Committees (DMEC) 313
Review of the literature 313
Amendments and reports 314
Substantial amendments 314
Non-substantial amendments 314
Reporting adverse reactions 314
Serious adverse events and serious unexpected adverse events 315
The end of the trial 315
Promoting and maintaining a trial 315
Common statistical terms used in clinical trials 315
Power 315
Incidence 315
Intention to treat 315
Likelihood ratio (LR) 315
Sensitivity 315
Specificity 315
Positive predictive value 316
Negative predictive value 316
Numbers needed to treat (NNT) 316
Numbers needed to harm (NNH) 316
Relative risk reduction (RRR) 316
Odds ratio (OR) 316
Risk 316
Risk ratio (can be referred to as relative risk) 316
P values 316
Type I and type II errors 316
References 316
Useful sources of information 316
Sixteen Multiple choice questions 317
CHAPTER CONTENTS 317
The cell, chromosomes and molecular genetics 317
Questions 317
Answers 320
Clinical genetics 321
Questions 321
Answers 322
Embryology 322
Questions 322
Answers 325
The fetus 326
Questions 326
Answers 328
Anatomy 328
Questions 328
Answers 336
Pathology 338
Questions 338
Answers 341
Microbiology and virology 342
Questions 342
Answers 345
Immunology 346
Questions 346
Answers 348
Biochemistry 349
Question 349
Answers 351
Physiology 352
Questions 352
Answers 359
Endocrinology 361
Questions 361
Answers 362
Drugs and drug therapy 363
Questions 363
Answers 365
Index 367