The Digestive System: From Basic Sciences to Clinical Practice

Preface
Acknowledgments
Introduction
Contents
Contributors
Abbreviations
Warning
I: The Digestive Organs
1: The Esophagus
1.1 Macroscopic Anatomy
1.1.1 Shape and Structure
1.1.2 Vascular Supply
1.1.3 Innervation
1.2 Microscopic Anatomy
1.2.1 Esophageal Mucosa
1.2.2 Muscularis
1.2.3 Serosa
1.3 Embryology/Development
1.3.1 Normal Development
1.3.2 Atresias of the Esophagus
1.3.3 Esophageal Stenosis/Strictures
1.3.4 Duplications and Cysts
1.3.5 Rings and Webs
1.4 Secretion/Absorption
1.5 Motility/Sensitivity
1.5.1 Oropharyngeal (Transfer) Motility
1.5.2 Esophageal (Transport) Motility
1.5.3 Sphincters: Upper and Lower
1.5.4 Sensory Function
1.6 Inflammation Disorders
1.6.1 Peptic Esophagitis
1.6.2 Infectious Esophagitis
1.6.3 Eosinophilic Esophagitis
1.6.4 Caustic Esophagitis
1.6.5 Drug-Induced Esophagitis
1.6.6 Radiation Esophagitis
1.7 Tumor Disorders
1.7.1 Types of Esophageal Neoplasia
1.7.2 Clinical
1.7.3 Diagnosis of Esophageal Cancer
1.7.4 Treatment of Esophageal Cancer
1.8 Function Disorders
1.8.1 Gastroesophageal Reflux Disease (GERD)
1.8.2 Oropharyngeal (Transfer) Dysmotility
1.8.3 Esophageal (Transport) Dysmotility
1.8.4 Sensitivity Disorders
1.9 Miscellaneous
1.9.1 Hiatal Hernia
1.9.2 Diverticulum
1.9.3 Esophageal Rupture
1.9.4 Esophageal Bleeding
1.9.5 Mallory-Weiss
1.9.6 Schatzki’s Ring
2: The Stomach
2.1 Macroscopic Anatomy
2.1.1 Shape and Structure
2.1.2 Vascular Supply
2.1.3 Innervation
2.2 Microscopic Anatomy
2.3 Embryology
2.3.1 Development
2.3.2 Developmental Abnormalities
2.4 Absorption/Secretion
2.4.1 Absorption
2.4.2 Secretion/HCl, Pepsin, and Intrinsic Factor
2.4.2.1 Parietal Cell
2.4.2.2 Chief Cell
2.4.2.3 Mucous Cell
2.4.2.4 Endocrine Cells
2.4.3 Regulation of Gastric Acid Secretion
2.5 Motility/Sensitivity
2.5.1 Motility of the Stomach
2.5.2 Sensitivity of the Stomach
2.6 Inflammation Disorders
2.6.1 Peptic Ulcer Disease
2.6.2 Gastritis and Gastropathies
2.7 Tumor Disorders
2.7.1 Adenocarcinoma
2.7.2 Lymphoma
2.7.3 Neuroendocrine Tumors (NET)
2.7.4 Stromal Tumors
2.7.5 Polyps
2.8 Function Disorders
2.8.1 Motor Disorders
2.8.1.1 Hypomotility/Gastroparesis
2.8.1.2 Hypermotility Disorders
2.8.2 Sensory Disorders/Functional Dyspepsia
2.8.3 Cyclic Vomiting Syndrome
2.8.4 Aerophagia/Belching/Excessive Belching Syndrome
2.8.5 Rumination Syndrome
Table 2.2 Ulceration in stomach or duodenum: causes
Table 2.3 Peptic ulcer: acute complications and their treatments
Table 2.7 H. pylori eradication: indications and benefits
Table 2.8 NSAID/ASA ulcers: therapeutic strategies
Table 2.9 PPIs: potential side effects
Table 2.10 Gastritis and gastropathies
Table 2.11 Gastroparesis: causes
Table 2.12 Functional dyspepsia: therapeutic options
2.9 Miscellaneous
2.9.1 Gastrinoma (Zollinger-Ellison Syndrome)
2.9.2 Ménétrier’s Hypertrophic Gastritis
2.9.3 Volvulus
2.9.4 Bezoars
2.9.5 Perforations
2.9.6 Gastric Bleeding
2.9.7 Dieulafoy’s Lesion
2.9.8 Gastric Surgery
3: The Small Intestine
3.1 Macroscopic Anatomy
3.1.1 Shape and Structure
3.1.2 Vascular Supply
3.1.3 Innervation
3.2 Microscopic Anatomy
3.2.1 Mucosa
3.2.2 Submucosa
3.2.3 Muscularis
3.2.4 Serosa
3.2.5 Summary
3.3 Embryology/Developmental Abnormalities
3.4 Absorption/Secretion
3.4.1 Absorption by the Small Intestine
3.4.1.1 General Mechanisms
3.4.1.2 Water and Electrolyte Uptake
3.4.1.3 Absorption of Macronutrients
3.4.1.4 Vitamin Absorption
3.4.1.5 Mineral Absorption
3.4.1.6 Distal Small Intestine
3.4.1.7 Vitamin B12 Absorption
3.4.1.8 Bile Salt Absorption
3.4.1.9 Drug Absorption/Biotransformation
3.4.2 Secretion by the Small Intestine
3.4.2.1 Water and Electrolyte Secretion
3.4.2.2 Bicarbonate Secretion
3.4.2.3 Mucus Secretion
3.4.2.4 “Endocrine” Secretions
3.4.2.5 Chloride Secretion and Pathological Conditions
3.4.2.6 Miscellaneous
3.4.3 Other Functions of the Small Intestine
3.4.3.1 Protection
3.4.3.2 Digestive Regulation
3.5 Motor/Sensory Functions
3.5.1 Intestinal Muscle
3.5.2 Peristaltic Reflex
3.5.3 Enteric Nervous System
3.5.4 Interdigestive Motility/MMC
3.5.5 Postprandial or Digestive Motility
3.5.6 Sensitivity
3.6 Inflammation Disorders
3.6.1 Celiac Disease/Gluten Enteropathy
3.6.2 Crohn’s Disease
3.6.3 Infections
3.6.4 “Special” Infections of the Small Intestine
3.6.5 Small Intestinal Bacterial Overgrowth (SIBO)
Table 3.8 Crohn’s disease diarrhea = multifactorial and often related to the length and severity of intestinal inflammation and of concomitant colon involve ment
Table 3.10 Traveler’s diarrhea
Table 3.11 Stool examination for pathogens
3.7 Tumor Disorders
3.7.1 Malignant and Benign Tumors
3.7.2 Neuroendocrine Tumors (NETs)
3.8 Function Disorders
3.8.1 Intestinal Pseudo-obstruction
3.8.2 Rapid Transit
3.8.3 Slow Transit/Ileus
3.8.4 Irritable Bowel Syndrome (IBS)
Table 3.14 Small intestine: transit variations
3.9 Miscellaneous
3.9.1 Ulcerations
3.9.2 Vascular Abnormalities (Angiectasias, Etc.)
3.9.3 Intestinal Ischemia
3.9.4 Bile Salt Diarrhea
3.9.5 Lactose Intolerance
3.9.6 Meckel’s Diverticulum
3.9.7 Short Bowel Syndrome/Intestinal Failure
3.9.8 Congenital Diarrhea
3.9.9 Diarrhea in Children
4: The Colon
4.1 Macroscopic Anatomy
4.1.1 Shape and Structure
4.1.2 Vascular Supply
4.1.3 Innervation
4.2 Microscopic Anatomy
4.2.1 Mucosa
4.2.2 Muscularis
4.2.3 Serosa
4.3 Embryology/Development
4.4 Absorption/Secretion
4.4.1 Water Absorption
4.4.2 Sodium Absorption
4.4.3 Potassium Movements
4.4.4 Chloride Movements
4.4.5 Nutrient Uptake
4.4.6 Secretions
4.4.7 Intestinal Flora (Microbiota)
4.4.8 Intestinal Gas
4.4.9 Summary
4.5 Motility/Sensitivity
4.5.1 Motility
4.5.2 Sensitivity
4.6 Inflammation Disorders
4.6.1 Infectious Colitis
Table 4.1 Management of Clostridioides difficile infection
4.6.2 Ischemic Colitis and Colonic Ischemia
4.6.3 Microscopic Colitis
4.6.4 Radiation Colitis
4.6.5 Colitis in Oncology
4.6.6 Inflammatory Bowel Diseases (IBD): Ulcerative Colitis and Crohn’s Disease
4.7 Tumor Disorders
4.7.1 Benign Neoplasms: Polyps
4.7.2 Malignant Neoplasm: Adenocarcinoma
4.7.3 Other Colon Tumors
4.7.4 Tropical Specificity
4.8 Function Disorders
4.8.1 Irritable Bowel Syndrome (IBS)
4.8.2 Colon Transit Disorders
Table 4.16 Rapid colon transit: causes
Table 4.17 Slow colon transit: causes
4.8.3 Bile Acid Diarrhea
4.9 Miscellaneous
4.9.1 Diverticular Disease
Table 4.18 Medical treatment of diverticulitis
4.9.2 Acute Appendicitis
4.9.3 Colonic Bleeding
Table 4.20 Management of lower GI bleeding
4.9.4 Epiploic Appendix/Appendagitis
4.9.5 Volvulus
4.9.6 Melanosis Coli
4.9.7 Bristol Stool Chart
5: The Pancreas
5.1 Macroscopic Anatomy
5.1.1 Shape and Structure
5.1.2 Vascular Supply
5.1.3 Innervation
5.2 Microscopic Anatomy
5.2.1 Acini
5.2.2 Ducts
5.2.3 Islets of Langerhans
5.3 Embryology
5.3.1 Normal Development
5.3.2 Developmental Abnormalities
5.4 Secretion
5.4.1 Acinar Cell
5.4.2 Ductal Cell
5.4.3 Regulation of Pancreatic Secretion
5.4.4 Activation of Pancreatic Proenzymes
5.5 Motility/Sensitivity
5.6 Inflammation Disorders
5.6.1 Acute Pancreatitis
5.6.2 Chronic Pancreatitis
5.7 Tumor Disorders
. Table 5.8 Primary tumors of the exocrine pancreas according to the World Health Organization
5.7.1 Pancreatic Cancer/Adenocarcinoma
5.7.2 Cystic Tumors/Cysts
5.7.3 Neuroendocrine Tumors (NETs)
5.8 Function Disorders
5.9 Miscellaneous
5.9.1 Cystic Fibrosis
6: The Biliary Tree
6.1 Macroscopic Anatomy
6.1.1 Shape and Structure
6.1.2 Vascular Supply
6.1.3 Innervation
6.2 Microscopic Anatomy
6.2.1 Bile Ducts
6.2.2 Gallbladder
6.3 Embryology
6.3.1 Normal Development
6.3.2 Developmental Malformations
6.4 Secretion/Absorption
6.4.1 General Considerations
6.4.2 Bile
6.4.3 Bile Acids and Bile Salts
6.4.4 Bilirubin/Icterus
6.4.5 Solubility of Bile Constituents/Biliary Stones
6.5 Motility/Sensitivity
6.6 Inflammation Disorders
6.6.1 Cholecystitis/Lithiasis
6.6.2 Cholangitis
6.6.3 Primary Sclerosing Cholangitis
6.6.4 Autoimmune Cholangitis
6.6.5 “Atypical” Infectious Cholangitis
Table 6.3 Treatment of gallstone(s) disease
6.7 Tumor Disorders
6.7.1 Cholangiocarcinoma
6.7.2 Gallbladder Cancer
6.7.3 Benign Tumors/Polyps
6.8 Function Disorders
6.8.1 Functional Gallbladder Disorders
6.8.2 Functional Oddi Disorders
6.9 Miscellaneous
6.9.1 Chronic Cholecystitis
6.9.2 Porcelain Gallbladder
6.9.3 Acute Acalculous Cholecystitis
6.9.4 Emphysematous Cholecystitis
6.9.5 Mirizzi’s Syndrome
6.9.6 Isolated Bile Duct Dilatation
6.9.7 Adenomyomatosis-Cholesterolosis
7: The Anorectum
7.1 Macroscopic Anatomy
7.1.1 Rectum and Anus
7.1.2 Vascular Supply
7.1.3 Innervation
7.2 Microscopic Anatomy
7.2.1 Mucosa
7.2.2 Muscularis
7.2.3 Serosa
7.3 Embryology
7.3.1 Normal Development
7.3.2 Atresias
7.3.3 Hirschsprung’s Disease
7.4 Secretion/Absorption
7.5 Motility/Sensitivity
7.5.1 Anorectal Physiology
7.5.2 Defecation
7.6 Inflammation Disorders
7.6.1 Rectal Inflammation (Proctitis, Rectal Ulcers)
7.6.2 Anal and Perineal Inflammation (Abscess, Fistulas, Anal Pruritus)
7.7 Tumor Disorders
7.7.1 Rectum Cancer
7.7.2 Anus Cancer
7.8 Function Disorders
7.8.1 Proctalgia Fugax
7.8.2 Levator Ani Syndrome
7.8.3 Anorectal Dyssynergia/Anismus
7.8.4 Hirschsprung’s Disease
7.8.5 Fecal Incontinence
7.9 Miscellaneous
7.9.1 Vascular Diseases: Hemorrhoids/Varices
7.9.2 Anal fissure
7.9.3 Neurological Diseases with Anorectal Impact
7.9.4 Pelvic Floor Disorders
7.9.5 Fecaloma
8: The Liver
8.1 Macroscopic Anatomy
8.1.1 Shape and Structure
8.1.2 Vascular Supply
8.1.3 Innervation
8.2 Microscopic Anatomy
8.2.1 Organization of Hepatocytes: Lobules and Acini
8.2.2 Sinusoids
8.2.3 Bile Ducts
8.2.4 Hepatocytes
8.2.5 Kupffer Cells
8.2.6 Hepatic Stellate Cells
8.2.7 Liver-Associated Lymphocytes (LAL)
8.3 Embryology/Development
8.4 Hepatic Catabolism
8.4.1 Heme-Bilirubin
8.4.2 Urea-NH4+
8.4.3 Drugs
8.4.4 Hormones
8.4.5 Lactic Acid
8.5 Hepatic Synthesis
8.5.1 Proteins
8.5.2 Hormones and Pro-hormones
8.5.3 Bile Salts
8.5.4 Cholesterol
8.5.5 Glucose, Lipids, and Amino Acids
8.6 Inflammation Disorders
8.6.1 Acute Hepatitis
8.6.1.1 Viral Hepatitis (A, B, C, D, E, and Other Viruses)
8.6.1.2 Toxic Hepatitis (Drugs, Acetaminophen)
8.6.1.3 Autoimmune/Metabolic Hepatitis
8.6.1.4 Vascular Hepatitis
Table 8.4 Acute hepatitis: paraclinical evaluation
8.6.2 Chronic Hepatitis
8.6.2.1 Viral Hepatitis (B, D, C, E)
8.6.2.2 Toxic Alcoholic Hepatitis
8.6.2.3 Chronic Autoimmune Liver Diseases (AIH, PBC, Sclerosing Cholangitis)
8.6.2.4 Metabolic Liver Diseases (NAFLD, Hemochromatosis, Wilson’s)
8.6.3 Cirrhosis
8.6.3.1 Pathology
8.6.3.2 Etiology of Cirrhosis
Table 8.7 Causes of cirrhosis
8.6.3.3 Clinical Manifestations of Cirrhosis
Table 8.8 Clinical signs suggestive of cirrhosis
Table 8.9 Classification of portal hypertension
Table 8.10 Treatment of variceal bleeding in  cirrhotic patients
Table 8.11 Treatment of ascites
Table 8.13 Treatment of hepatic encephalopathy
8.6.3.4 Prognosis of Cirrhosis
8.7 Tumor Disorders
8.7.1 Primary Neoplasms
8.7.2 Secondary Neoplasms
8.7.3 Benign Tumors
8.7.4 Other Lesions (Cysts, Abscesses)
8.8 Function Disorders
8.8.1 Porphyria
8.8.2 Disorders of the Urea Cycle
8.8.3 Glycogen Storage Diseases
8.8.4 Tyrosinemia
8.8.5 Galactosemia and Fructosemia
8.8.6 α1-Antitrypsin Deficiency
8.9 Miscellaneous
8.9.1 Liver Transplantation
Table 8.16 Contraindications to hepatic transplantation
Table 8.17 Liver transplant indications
8.9.2 Pregnancy and Liver
II: Digestive Symptoms, Signs and Other
9: Esophageal Symptoms: Heartburn, Dysphagia, and Chest Pain
9.1 Digestive Symptoms
9.1.1 Heartburns
9.1.2 Odynophagia
9.1.3 Dysphagia
9.2 Extra-digestive Symptoms
9.2.1 “Respiratory” Symptoms
9.2.2 “Cardiac” Symptoms
10: Nausea and Vomiting
10.1 Definition
10.2 Physiology
10.3 Causes
Table 10.1 Nausea/vomiting: causes
10.4 Complications
10.5 Treatment
11: Upper Gastrointestinal Bleeding (UGIB)
11.1 Definition
11.2 Clinical Presentation
11.3 Causes of UGIB
11.4 Treatment of UGIB
Table 11.2 UGIB: initial clinical assessment and emergency management
11.5 Special Topic: GI Bleeding and Altered Coagulation
12: Dyspepsia
12.1 Definition
12.2 Symptoms
12.3 Differential Diagnosis
12.4 Investigation
12.5 Treatment
13: Diarrhea
13.1 Definition
13.2 Simplified Pathophysiology
13.3 Differential Diagnosis
Table 13.2 Diarrhea: diagnostic tests
13.4 Treatment
13.5 Summary
14: Abdominal Distension and Bloating
14.1 Abdominal Distension
Table 14.1 Abdominal distension: causes
14.2 Abdominal Bloating
14.3 Treatment
Table 14.2 Treatment of intestinal gases
15: Constipation
15.1 Definition
15.2 Pathophysiology
15.3 Investigation
15.4 Treatment
15.5 Miscellaneous
15.6 Constipation in Children
16: Abdominal Pain
16.1 General Considerations
16.2 Clinical Approach to Abdominal Pain
16.3 Diagnostic Strategies in Abdominal Pain
16.4 Therapeutic Strategies for Abdominal Pain
16.5 Miscellaneous
Table 16.4 Non-visceral/nonsurgical abdominal pain
16.6 Abdominal Pain in Children
17: Abdominal Hernias
17.1 Definition
17.2 Diaphragmatic Hernias
17.3 Ventral Hernias
17.4 Groin Hernias
17.5 Pelvic Hernias
17.6 Flank Hernias
18: Fecal Incontinence
18.1 General Considerations
18.2 Physiology and Pathophysiology
18.3 Investigation
18.4 Treatment
Table 18.2 Treatment of incontinent patients
19: Anorectal Pain
19.1 Thrombosed Hemorrhoid
19.2 Acute Anal Fissure
19.3 Perianal Abscess
19.4 Proctalgia Fugax
19.5 Levator Ani Syndrome
20: Rectal Bleeding
20.1 Common Causes of Chronic Intermittent Rectal Bleeding
20.2 Investigation
21: Lower GI Bleeding
21.1 Step One
21.2 Step Two
21.3 Step Three
21.4 Step Four
21.5 Step Five
21.6 Step Six
21.7 Special Topic: GI Bleeding and Altered Coagulation
22: Food Allergies
22.1 IgE-Mediated Manifestations
22.2 Non-IgE-Mediated Manifestations
22.3 Mixed, IgE- and Non-IgE-Mediated Manifestations
23: Undernutrition and Nutritional Support
23.1 Types of Undernutrition
23.2 Pathophysiology of Fasting
23.3 Nutritional Assessment
Table 23.2 Nutritional assessment: clues to look for
23.4 Indications for Nutritional Support
23.5 Assessment of Energy and Protein Needs
23.6 Nutritional Support: Enteral Versus Parenteral
23.7 Enteral Nutrition
Table 23.4 Gastric or jejunal tube feeding (?)
23.8 Parenteral Nutrition
Table 23.7 Parenteral nutrition: evaluation of nutrient solutions to be administered
23.9 Re-feeding Syndrome
23.10 Addendum
24: Obesity
24.1 Definition of Obesity
24.2 Complications of Obesity
24.3 Etiology of Obesity
24.4 Treatment of Obesity
24.5 Summary
25: Genes and Digestive Cancers
25.1 Clinical Approach to Families at Risk
25.2 Predisposition Syndromes to Colorectal Cancer
25.2.1 Lynch Syndrome
25.2.2 Hereditary Polyposis
25.2.2.1 Familial Adenomatous Polyposis (FAP)
25.2.2.2 Hamartomatous Polyposis
25.3 Predisposition to Other Digestive Cancers
25.3.1 Pancreatic Cancer
25.3.2 Hereditary Diffuse Gastric Cancer
Table 25.1 When to suspect lynch syndrome?
26: Jaundice
26.1 General Considerations
26.2 Differential Diagnosis
26.2.1 First Question Asked: Is This a Pre-conjugation Disorder?
26.2.2 Second Question: Is the Post-conjugation Disorder Located at the Hepatic or Post-hepatic Level?
26.3 Treatment
27: Abnormal Liver Tests
27.1 Bilirubin Elevation
27.2 Transaminase Elevation
Table 27.1 Causes of abnormal blood liver tests in asymptomatic subjects
Table 27.4 Some drugs and substances whose abuse can increase transaminases
27.3 Alkaline Phosphatase Elevation
28: Ascites
28.1 Causes
28.2 Diagnosis
28.3 Treatment
Table 28.1 Ascites: etiological diagnoses
Table 28.2 Ascites fluid analyses (to be performed according to the clinical context)
29: Diets and Digestive Diseases
29.1 Esophageal Disorders
29.1.1 Oropharyngeal Dysphagia
29.1.2 Obstructive Esophageal Dysphagia
29.1.3 Eosinophilic Esophagitis (EoE)
29.1.4 Gastroesophageal Reflux Disease (GERD)
29.2 Gastric Disorders
29.2.1 Gastroparesis
29.2.2 Dyspepsia
29.2.3 Dumping Syndrome
29.2.4 Post-gastrectomy
29.3 Intestinal Disorders
29.3.1 Celiac Disease
29.3.2 Non-celiac Gluten Sensitivity (NCGS)
29.3.3 Lactose Intolerance
29.3.4 Acute Gastroenteritis
29.4 Colon Disorders
29.4.1 Irritable Bowel Syndrome (IBS)
29.4.2 Chronic Constipation
29.4.3 Diarrhea
29.4.4 Bloating
29.4.5 Diverticular Disease
29.4.6 Inflammatory Bowel Disease (IBD)
29.5 Biliopancreatic Disorders
29.5.1 Acute Pancreatitis
29.5.2 Chronic Pancreatitis
29.5.3 Gallstones
29.6 Liver Disorders
29.6.1 Cirrhosis Malnutrition
29.6.2 Ascites
29.6.3 Encephalopathy
29.6.4 NASH
29.6.5 Metabolic Function Disorders
Index