Gastroenterology: Clinical Cases Uncovered

By Satish Keshav and Emma Culver

Gastroenterology is a critically important specialty in medicine, encompassing the GI tract and two vital organs - the pancreas and the liver. Gastroenterology: Clinical Cases Uncovered includes reference to the new JCHMT curriculum for acute and internal medicine concerning gastroenterology and hepatology and presents real-life patient cases and outcomes as seen on the wards and in exams leading students through a practical approach to recognize, understand, investigate and manage gastroenterological and hepatological disorders and conditions.

Following a question-answer approach, with self-assessment MCQs, EMQs and SAQs, and a 'refresher' section on basic science, Gastroenterology: Clinical Cases Uncovered features investigations and the treatment options available for patients with upper and lower GI disorders, liver disease, biliary and pancreatic disease, and problems of nutrition.

Gastroenterology: Clinical Cases Uncovered is ideal for medical students, junior doctors on the Foundation Programme, GP trainees, specialist nurses and nurse practitioners and gastroenterology trainees on the specialty training programme.

• Language: English
• Publisher: Wiley
• Release date: Nov 28, 2011
• ISBN: 9781118293911

Book preview

Preface

Clinical gastroenterology is both simple and complex. The simplicity comes from the finite number of diagnoses that are commonly encountered, and the relatively limited number of symptoms that typically indicate disease of the gastrointestinal system. However, there are hidden depths to the practice of the speciality. Gastroenterologists deal with disease affecting many separate organs that all form part of the same system – the liver, pancreas, stomach, etc. The clinical consequences of some diseases can be dramatic and complex, particularly, for instance, dysfunction of the liver. Symptoms such as abdominal pain, altered bowel function and changes in weight can be combined in myriad ways to pose true clinical puzzles. This book aims to guide the reader through this complexity by offering real case studies and showing how, in practice, clinicians can achieve some degree of clarity, and offer to patients a reasonable diagnostic and therapeutic plan.

In the first section, the book offers a basic and brief overview of anatomical, physiological and pharmacological facts that inform our thinking about gastroenterological problems, and suggests how best to approach the patient in the second chapter. Thereafter, in the second section, each chapter deals with presenting symptoms and signs and the subsequent chapters are arranged in six sections to cover disease processes affecting the upper gastrointestinal tract, lower gastrointestinal tract, liver, pancreas and biliary tract, nutrition, and so-called functional bowel disorders. These are important and often overlooked because there is a profound lack of understanding about their pathogenesis. However, there are many patients with irritable bowel syndrome and the like, and a robust and reliable clinical approach to treating them is essential.

In each of the symptom- or sign-based chapters, the emphasis is on clinical reasoning and strategy, and the reader will have an opportunity to examine how the many possible paths are in practice negotiated to reach a diagnosis and formulate a plan for managing the situation. Exact doses and tests are de-emphasised, while strategies, categories and context are highlighted, all within the framework of dealing with the particular human patient whose predicament is being examined.

Boxes and lists are strategically placed to aid memory and recall, and to emphasise key facts. The last section, which comprises a set of questions to test understanding, is based on the contents of each chapter, and the emphasis in these is on core knowledge rather than the esoteric or arcane.

Writing this book has proved to be an education as well being hugely enjoyable, and our hope is that the reader too will gain knowledge and understanding of the complexity of gastroenterological medicine, whilst acquiring some practical understanding of how to approach the patient with gastrointestinal problems, and some sense of satisfaction and fun. The typical reader might be a medical or nursing student in their clinical years, or a doctor in training, either in their foundation years or in early speciality training. The book will be useful as preparatory reading before joining the gastroenterology firm in a clinical rotation, or as an aid to revision before written and clinical examinations.

Satish Keshav

Emma Culver

How to use this book

Clinical Cases Uncovered (CCU) books are carefully designed to help supplement your clinical experience and assist with refreshing your memory when revising. Each book is divided into three sections: Part 1, Basics; Part 2, Cases; and Part 3, Self-assessment.

Part 1 gives you a quick reminder of the basic science, history and examination, and key diagnoses in the area. Part 2 contains many of the clinical presentations you would expect to see on the wards or to crop up in exams, with questions and answers leading you through each case. New information, such as test results, is revealed as events unfold and each case concludes with a handy case summary explaining the key points. Part 3 allows you to test your learning with several question styles (MCQs, EMQs and SAQs), each with a strong clinical focus.

Whether reading individually or working as part of a group, we hope you will enjoy using your CCU book. If you have any recommendations on how we could improve the series, please do let us know by contacting us at: [e-mail].

Disclaimer

CCU patients are designed to reflect real life, with their own reports of symptoms and concerns. Please note that all names used are entirely fictitious and any similarity to patients, alive or dead, is coincidental.

List of abbreviations

Part 1 Basics

Basic science

Introduction

The intestinal tract is essential for maintaining nutrition by appropriate intake of macronutrients, micronutrients, fluid and electrolytes. Intestinal failure can lead to nutritional catastrophe and imbalances in fluid and electrolytes.

The pancreas is the main producer of digestive enzymes that facilitate the extraction of nutrients from food. Pancreatic dysfunction can cause malabsorption of food.

The liver has an essential and central role in metabolism, critical functions in detoxifying and excreting endogenous and exogenous molecules in bile, and in synthesising essential serum proteins such as albumin and clotting factors. Liver failure is rapidly fatal.

Embryology

The entire intestinal tract is derived embryologically from the endoderm, and can be conceptualized as a hollow tube stretching from the mouth to the anus, with the liver and pancreas as gland-like specialised appendages, connected to the main tract by ducts.

Structure

The main intestinal tract has a basic structure that is preserved throughout:

The innermost layer, facing the hollow lumen, is lined by a specialised layer of epithelial cells that vary from region to region.

The epithelium is supported by a layer of connective tissue, the lamina propria.

The lamina propria is surrounded by a layer of smooth muscle, the muscularis mucosae.

The muscularis is surrounded by the submucosal connective tissue.

Outside of this are strong layers of muscle, the muscularis propria. This is generally organised in an inner circular layer with fibres running at right angles to the long axis of the tube, and an outer longitudinal layer with fibres running along the long axis.

The outermost layer of much of the intestinal tract is the visceral peritoneum, which is an epithelial layer.

Most lengths of the small and large intestine are attached to the posterior wall of the abdominal cavity by a length of mesentery, which is comprised of connective tissue covered by a continuation of the visceral peritoneal layer, and through which blood and lymphatic vessels and nerves run.

Blood supply

The arterial blood supply to the intra-abdominal intestinal organs, from stomach to rectum, and including the liver and pancreas, is derived from the coeliac, superior mesenteric and inferior mesenteric arteries, which are direct branches of the abdominal aorta.

The venous drainage of most of the intra-abdominal organs is via the hepatic portal vein, which enters the liver, and provides 75% of the hepatic blood supply. This hepatic portal flow system means that absorbed nutrients first enter the liver, before reaching the systemic circulation.

Nerve supply

Most of the gastrointestinal tract is innervated by the autonomic nervous system with parasympathetic and sympathetic branches. The intestine also contains an intrinsic nervous system organised into interconnected plexuses in the submucosa and the muscularis propria, which is termed the enteric nervous system. This provides isolated segments of intestine with the ability to coordinate secretion and motility without external innervation.

Immune system

The intestinal tract encounters food particles, antigens and potentially harmful microorganisms constantly. Arguably, it must contend with the greatest challenge in defending the organism against infection and other danger, as unlike other areas exposed to the external world, such as the skin and lungs, it also has to make fine distinctions between substances that could be either essential food or lethal foe – ‘salmon or Salmonella?’.

As a consequence, the immune system of the gastrointestinal tract is highly developed and specialised, and contains approximately 70% of all the immune cells in the body.

Anatomy and function

The intestinal tract

Mouth, pharynx and oesophagus

The mouth with teeth, tongue and salivary glands is essential for ingestion of food and nutrition. The senses of taste and smell serve to identify healthy food, and coordinated activity of the muscles of mastication, the tongue and pharynx allow food to be processed and swallowed safely.

The mouth, pharynx and oesophagus are all lined by a stratified squamous epithelium. The muscle layers of the

Fig A Overview of gastrointestinal function.

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Fig B Organisation of the hollow organs.

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upper oesophagus are striated skeletal-type muscle, while the muscle layers of the distal oesophagus, like the rest of the intestinal tract, comprise smooth, non-striated fibres.

Stomach

The stomach is J-shaped, wider at the proximal, upper end, known as the body, and narrowing distally to form the antrum, from which the pylorus leads to the duodenum. This shape means that the stomach can act as a reservoir for food after a meal. Strong churning movements of the stomach convert solid food boluses from the oesophagus into slurry called chyme, which passes easily into the duodenum.

The gastric epithelial lining is comprised of a single layer of columnar cells, which is also the case for the rest of the intestinal tract distal to the stomach. In the stomach this epithelial layer is specialised to produce hydrochloric acid from parietal cells, via a specialized K+/H+ transporter, popularly known as the proton pump. This initiates the process of digestion by activating the enzyme pepsinogen, produced by oxyntic cells in the gastric epithelim.

Duodenum

Anatomy

The epithelium of the duodenum is specialised for absorption, comprising a single layer of columnar cells that are lined with microscopic microvilli to increase the surface area for absorption. Furthermore, specialised molecules on the cell surface, including transporters and enzymes, are critically important for this digestive and absorptive function.

The lining of the duodenum, like the rest of the small intestine, is arranged into finger-like projections into the lumen, called villi, which serve to increase the surface area, and indentations into the wall of the intestine, called crypts. The stem cells, from which the entire epithelial lining is renewed, approximately every 7 days, are located in the crypts. The stem cells provide, by division and differentiation, all the major cells of the intestinal lining; these include:

Absorptive enterocytes.

Goblet cells, which produce mucus.

Paneth cells, which have a role in antibacterial defence.

Neuroendocrine cells, which produce a variety of enteric hormones such as somatostatin, cholecystokinin, gastrin, vasoactive intestinal peptide (VIP) and glucacon-like peptides.

Function

Bile from the gallbladder, and pancreatic secretions enter the duodenum through the ampulla of Vater, providing bicarbonate-rich alkaline secretions, bile salts to emulsify fats, and carbohydrate, protein and fat-digesting enzymes, which neutralise acid chyme from the stomach, and begin the major work of digestion. Thus the duodenum is a crucial region for digestion and absorption.

Jejunum and ileum

Anatomy

The basic structure of the distal small intestine is identical to the duodenum, with villi, crypts, submucosa and circular and longitudinal muscle layers.

Blood and lymphatic supply

The blood supply is from the superior mesenteric artery. The venous drainage is via the superior mesenteric vein, joining the splenic vein to form the hepatic portal vein, which enters the liver carrying nutrients from the small intestine.

The lymphatic drainage of the small intestine, which carries fat-rich particles absorbed from food, enters the thoracic duct, emptying into the systemic venous circulation. The smallest lymph channels, called lacteals, are found in the central core of each villus, strategically placed to absorb triglyceride-rich chylomicrons.

Function

These segments of the small intestine are essential for absorbing food. The minimum length of small intestine necessary to sustain life is approximately 100 cm, and the function of this minimum length is enhanced if the ile-ocaecal valve is intact.

There is some regional specialisation – the jejunum is the main site of absorption of folic acid, and the ileum is essential for the absorption of vitamin B12 and of bile salts, which are recycled via an enterohepatic circulation.

Box A Specialisation in the small bowel

Ileum: absorption of vitamin B 12 and bile salts

Jejunum: absorption of folic acid

Constant peristaltic activity of the small intestine, including a daily migrating motor complex wave that clears the intestine, together with many antibacterial substances secreted into the intestine, keep the number of bacteria in the small intestine relatively low, certainly compared to the large intestine. This may be important for optimum absorption of nutrients, and, in certain pathological conditions, bacterial overgrowth in the small intestine can cause diarrhoea and malabsorption.

The large intestine

Anatomy

The basic structure of the large intestine is similar to the small intestine. The differences are:

The external longitudinal layer of smooth muscle in the large intestine is collected into bands called taenia.

There are no villi in the large intestine.

The ileum enters the caecum, which is the most proximal part of the large intestine, via the ileocaecal valve, which partially prevents the reflux of bacteria into the small intestine. Distal to the caecum is the ascending colon, situated along the right flank, the transverse colon extending from just below the liver to just below the spleen, the descending colon situated along the left flank, the sigmoid colon curving over the pelvic brim, and the rectum which is situated in front of the sacrum and ends at the junction of rectum and anus.

The anus is the muscular sphincter that maintains the continence of faeces and flatus in the rectum, and is comprised of an inner layer of smooth muscle, the internal sphincter, and an outer layer of voluntary muscle, the external sphincter. The lining of the anus is a stratified squamous epithelium that blends into the skin at the anal verge.

Box B Structural components of the large intestine (proximal to distal)

Ileocaecal valve

Caecum

Ascending colon

Hepatic flexure

Transverse colon

Splenic flexure

Descending colon

Sigmoid colon

Rectum

Anus

Blood supply

The vascular supply of the colon is derived from the superior and inferior mesenteric arteries, and the venous drainage is via the superior and inferior mesenteric veins. The venous return from the rectum is into the systemic circulation so that portosystemic shunts can form in this region, as they can in the distal oesophagus.

Nerve supply

Defecation is controlled by both autonomic and somatic nerves, and the nerve supply of the rectum is from the sacral plexus.

Function

The main function of the large intestine is to reabsorb water from the small intestinal effluent. When patients undergo a colectomy and are left with an ileostomy, fluid losses from the stoma can be of the order of litres per day; this is in contrast to the normal volume of faecal output, which is approximately 200 mL.

Specialised cells

The main epithelial cells, colonocytes, are specialised for the absorption of electrolytes and water, and there are many goblet cells and few or no Paneth cells in the crypts of the colon.

Hepatobiliary system and pancreas

Liver

Anatomy

The liver is the largest single organ in the body at approximately 1.5 kg in weight. It is located in the right upper quadrant of the abdomen, directly under the right hemi-diaphragm. The arterial supply is via the hepatic branch of the celiac artery, and the portal vein. The venous drainage via the hepatic veins is into the inferior vena cava.

The secretory product of the liver, bile, is excreted via biliary canaliculi that coalesce to form bile ducts. The bile ducts in turn form the main intrahepatic bile ducts, which form the hepatic duct. This is joined by the cystic duct from the gallbladder, which has the capacity to store and concentrate bile, to form the common bile duct. This exits the liver, and is joined by the main pancreatic duct before entering the duodenum at the ampulla of Vater.

Box C Functions of the liver

Amino acid synthesis

Carbohydrate metabolism (gluconeogenesis, glycogenosis, glycogenesis)

Protein metabolism, synthesis and degradation

Lipid metabolism, cholesterol synthesis and lipogenesis

Coagulation factor production (fibrinogen, prothrombin) and protein C, protein S and antithrombin

Albumin production

Angiotensinogen synthesis (hormone raising blood pressure if activated by renin)

Bile production and excretion

Immunological effects via the reticuloendothelial system

Storage of glucose (as glycogen) and vitamins

Detoxification, converting ammonia to urea

Breakdown of toxic substances

Breakdown of haemoglobin, insulin and other hormones

Excretion of waste products

Function

The liver is the main organ of metabolic control, maintaining circulating levels of glucose and fats, and providing essential circulating proteins such as albumin, carrier proteins and a number of clotting factors and complement components. The liver also receives almost the entire venous drainage of the intestinal tract, performing an essential regulatory and detoxifying role. When this circulation is disrupted, patients suffer consequences such as severe neurological dysfunction, which can lead to coma and death, known as hepatic encephalopathy. In addition, the liver metabolises and is essential for the excretion of endogenous and exogenous waste products such as bilirubin derived from the breakdown of haem, and of ammonia from the breakdown of amino acids, which is excreted in the form of urea.

Without the liver, life cannot be sustained for more than a few hours, and there is as yet no adequate artificial liver substitute.

Specialised cells

The liver is composed of a huge number of hepatocytes, which are arranged in columns and sheets with intervening channels through which blood courses, known as sinusoids; between adjacent hepatocytes are the microscopic biliary canaliculi into which bile is secreted. The sinusoids are lined by an endothelial cell layer that, unlike vascular endothelia in other organs, is relatively loosely organised, with many gaps in the lining.

Between the vascular endothelium and the hepatocytes is the space of Disse in which specialised stellate cells of the liver are located. These cells store retinoic acid and have a critical function in repairing liver injury and forming scar tissue that can lead to hepatic cirrhosis. Immune cells including lymphocytes and resident hepatic macrophages known as Kupffer cells reside in the sinusoidal and peri-sinusoidal spaces.

Hepatocytes are specialised to process, store and export sugars, fats and proteins, and to metabolise and detoxify endogenous and exogenous organic compounds. Typical ultrastructural features of hepatocytes include numerous mitochondria, extensive rough and smooth endoplasmic reticulum, Golgi apparatus, fat-filled vacuoles and glycogen-storage granules.

Pancreas

Anatomy

The pancreas is a large exocrine secretory organ located in the epigastrium, inferior to the stomach and to the left of the duodenum. The pancreas also contains endocrine islets that produce the essential hormones insulin and glucagon, which maintain glucose homeostasis.

The exocrine pancreas comprises secretory epithelial cells organised into acini, with the secretions draining into ducts. These ducts coalesce to form the main pancreatic duct; this drains into the duodenum at the ampulla of Vater.

Function

Pancreatic secretions provide the great bulk of digestive enzymes, including proteases, lipases and amylases. The pancreas also produces c01ie001_fmt to neutralise stomach acid and create the optimal pH for digestive action.

Pancreatic enzymes have the capacity to cause autodigestion of the gland itself, and of intestinal tissues. Enzymes are therefore produced as larger proteins, known as pro-enzymes that are inactive; they are activated by cleavage after they have been secreted into ducts and the intestine.

Damage to the pancreas, which may release enzymes into the gland itself, can cause severe damage and a life threatening condition – acute pancreatitis. Diseases that damage the pancreatic capacity to produce enzymes, such as chronic pancreatitis, reduce the digestive capacity and cause malabsorption of fats, carbohydrates and proteins.

Digestion and absorption

The intestine is essential for processing and obtaining nutrition from food, regulating metabolism, and maintaining aspects of fluid and electrolyte balance. This is mediated by integrated action of all parts of the gastrointestinal tract, including the luminal organs from oesophagus to colon, and the pancreas and liver.

Digestion

Mechanical dissolution of food after chewing and swallowing is continued by the stomach, producing slurry known as chyme. The smaller the particles of food, the greater the surface area to volume ratio, providing a more tractable target for digestive enzymes including those produced by the pancreas and secreted into the duodenum. Fat is poorly soluble in the aqueous chyme, and bile salts secreted in bile help to disseminate fat from the diet into micelles, allowing greater access for fat-digesting enzymes. Thus obstruction to bile flow compromises the digestion and absorption of fats and fat-soluble vitamins such as D and K.

Digestion is the process of enzyme-mediated hydrolysis of macromolecules such as starch, triglycerides and proteins in food. The products of digestion are the constitutive components of these macromolecules – monosaccharides, free fatty acids, amino acids and short peptides – which are absorbed through the intestinal epithelium into the vascular and lymphatic circulation via specific transporter proteins. These transporters typically have exquisite specificity, for example for glucose coupled with Na + ions, or fructose, or acidic, basic and neutral amino acids.

Fatty acids absorbed from the diet are reconstituted in the epithelial cells into triglycerides and are secreted into lacteals as chylomicrons, for transport into the circulation. Other transport systems are responsible for the transport of micronutrients, that is, mineral

Fig C Hepatobiliary and pancreatic function.

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elements and vitamins. These systems are regionally distributed, so that, for example, most absorption of iron occurs in the duodenum, while absorption of vitamin B12 occurs in the terminal ileum. Damage to the intestinal epithelium in different regions may therefore produce distinct patterns of malabsorption and deficiency.

Reabsorption

Digestive enzymes are secreted in large quantities of fluid and electrolytes, and if all of the secreted electrolytes and fluids were not reabsorbed the body would be depleted. Some reabsorption takes place in the distal small intestine; however the greatest capacity is in the colon, and the ileal effluent of over 1 L of fluid per day is reduced to

Fig D Digestion and absorption.

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approximately 200 mL. Reabsorption of water is accompanied by the reabsorption of salts, particularly Na+, Cl− and c01ie001_fmt .

Diarrhoeal illness

In diarrhoeal illnesses, the overall volume of stool is increased. It is possible to distinguish if this is due to one of the following processes:

Hypersecretion, for example caused by cholera toxin, which activates secretion from intestinal epithelial cells.

Inf ammation, where secretion may be stimulated and the reabsorptive capacity of the intestine is compromised.

Osmotic diarrhoea, whereby osmotically active substances in the intestinal content prevent reabsorption of water by creating a steep osmotic pressure gradient.

Hypermotility, where increased peristalsis results in a rapid transit of intestinal contents through the intestine, exceeding the rate at which fluid can be reabsorbed.

Because absorption of water from the intestine follows electrolytes and osmotically active molecules such as sugars, diarrhoeal losses can be counteracted by providing luminal salt and sugar in the correct proportions. This is the basis of oral rehydration solutions to combat diarrhoea, which typically provide Na+ and glucose to exploit the Na+ /glucose transporter. Hypotonic fluids such as plain water dilute the luminal Na+ and reduce the capacity for absorption of water.

Gastrointestinal pathology

Infection

Gastrointestinal infection accounts for a major part of morbidity and mortality worldwide. Simple enteric infections, food poisoning and gastroenteritis, and specific infections such as cholera, which occur in outbreaks following the ingestion of contaminated food and water, can cause severe illness and death, particularly in