Year GEP 1 GEP/DGM: Digestion, Growth and Metabolism

Introduction to Metabolism

Lecture: Biological Energy

1. Explain chemically how energy is stored in PMF and ATP.
2. Describe in overview where biological energy comes from and how it is turned into stores.
3. Describe biological stores of energy.
4. Describe in overview the uses of biological energy.
5. Explain how energy is transferred between these stores.

Lecture: The Anterior Abdominal Wall and Inguinal Anatomy

1. Understand the origins of the layers of the spermatic cord.
2. Idenify different types of hernia.
3. Describe the basic anatomy of the inguinal ligament.
4. Explain where inguinal hernias commonly form and why.
5. Understand the anatomy of the anterior abdominal wall.
6. To be able to identify the surface anatomy of the anterior abdominal wall.

Lecture: Digestion and Absorption

1. Causes of general malabsorption.
2. Specific malabsorptive states.
3. Anatomical features of the midgut.
4. Absorption of nutrients.
5. Understand the 3 phases of digestion and absorption.

Lecture: Gut Health

1. Understand and describe common upper and lower GI conditions.
2. Describe role of gut brain axis and microbiota in IBS.
3. Describe the role of microbiota, prebiotics and probiotics in GI functions.
4. Describe the gut brain axis and its role in normal GI function.
5. Understand the anatomy and key roles of the gastrointestinal tract.
6. Define intrinsic and extrinsic nervous system of the gut.

Lecture: Mouth to Oesophagus

1. To be able to identify the major anatomical features of the mouth.
2. To understand the sensory nerve supply to the face, teeth, tongue and pharynx.
3. To understand the motor nervous supply to the muscles of mastication, facial expression, soft palate, tongue, pharynx and oesophagus.

Gastrointestinal Motility

1. Basic elements of control
2. Movements of esophagus, stomach and intensite both during hunger and after eating.
3. Introduction to reflex control and feedback regulation.
4. The peristaltic reflex.
5. Different movements of the colon.

Lecture: Glycolysis and Glucose Oxidation

1. Outline the potential metabolic fates of glucose 6-phosphate.
2. Describe the mechanisms of glucose uptake into cells and distinguish between facilitative glucose transporters (GLUTS) with respect to their tissue distribution and kinetic properties.
3. Explain the significance of the regulatory and kinetic properties of glucokinase and hexokinsase with respect to their tissue locations and physiologic roles.
4. Discuss how PFK responds to intracellular messages.
5. Describe how glycolysis produces ATP by substrate-level phosphorylation.
6. Relate glycolysis to the metabolism of glycerol, fructose and pentose sugars.

Lecture: Glycogen Synthesis and Utilisation

1. Explain the different roles of glycogen storage in muscle and liver in relation to the metabolic fate of glucose 1-phosphate.
2. Discuss how the key enzymes glycogen synthase and glycogen phosphorylase are controlled by reversible phosphorylation influenced by hormonal action.
3. Outline the role of liver glycogen as a source of blood glucose during a normal feeding cycle.
4. Describe the structure of glycogen.
5. Outline the circumstances under which glycogen synthesis and degradation will occur.

Lecture: Blood supply to the gut

1. Explain the anatomy and the distribution of the 3 unpaired arteries of the abdominal aorta
2. Describe the blood supply to the liver. Explain the formation of the hepatic portal vein

Lecture: Gut as an Immune Organ

1. Know the main types of harmful organisms that can colonize the gut
2. Understand the role of the gut in the interphase between the outside world and the body .
3. Understand how antigens are sampled in the gut and the main types of immune cells involved in the gut immune response.
4. Understand by which mechanism T cells are primed and home to the gut to deliver the immune response
5. Understand gut Immunoglobulins production and secretion.
6. Examples

Lecture: Gastric Secretions

1. Secretory function of the stomach (different secretions of the stomach and how they control the chemical environment, control by nerves and hormones and pathophysiology of peptic ulcer disease and gastro-oesophageal reflux disease).
2. Gastric secretions in health (neurohumoral control).
3. Gastric secretions in disease (reflux disease (GORD) and peptic ulcer disease)

Lecture: Gluconeogenesis

1. Discuss the control of gluconeogenesis.
2. Describe the role of gluconeogenesis in maintaining blood glucose concentrations.
3. Discuss the significance of gluconeogenesis in fasting and in exercise.
4. Discuss the interactions between gluconeogenesis and fatty acid metabolism.
5. Discuss how the metabolism of pyruvate, glycerol and amino acids contributes to gluconeogensis.

Lecture: The Tricarboxylic acid (TCA) cycle

1. Discuss the control of the TCA cycle.
2. Discuss the TCA cycle with respect to oxidative metabolism and ATP synthesis.
3. Explain the significance of the biosynthetic role of the TCA cycle.
4. Describe the reciprocal interaction between the metabolism of glucose and fatty acids.
5. Discuss how cells adapt metabolically to hypoxia.

Lecture: Peritoneum

1. Describe the location and the function of the visceral and parietal peritoneum.
2. Outline the embryology of the foregut, the midgut and the hindgut and the formation of the peritoneal cavity.
3. Outline the extent and the subdivisions of the peritoneal cavity.
4. Describe the difference between retroperitoneal organs and intraperitoneal organs.

Lecture: Body fluid compartments & water balance

1. State typical values (and normal ranges) for the osmolality of urine and daily urine production
2. Distinguish between the terms ‘osmolarity’ and ‘osmolality’ State a normal value for plasma osmolality.
3. Understand how water and solutes are transported across the cellular membrane.
4. Name the main fluid compartments of the body, commenting on their volumes and predominant cations.
5. Explain how total body water and total body sodium are regulated by mechanisms that are sensitive to plasma volume and plasma osmolality.

Lecture: Fat Metabolism

1. Outline the role of lipids as metabolic fuels.
2. Discuss lipolysis and its regulation.
3. Describe how fatty acids are transported into the mitochondrial matrix and oxidised there.
4. Describe how fatty acids are synthesized and how this is controlled with respect to fatty acid breakdown.
5. Discuss the significance of ketone body metabolism under normal conditions and in disease states.

Lecture: Imaging of Gut

1. Understand the challenges of imaging the GI tract
2. Know the techniques available for imaging the GI tract
3. Know which technique is best for which part of the GI tract
4. Recognise examples of GI tract conditions that can be imaged

Lecture: Excercise and Metabolism

Lecture: Insulin Secretion & Action

1. Describe the structure of the pancreatic islet of Langerhans; list the major cell types and the hormones that they secrete.
2. Describe the main structural features of the insulin molecule.
3. Outline how insulin secretion is regulated.
4. List the major metabolic actions of insulin on the metabolism of the major energy fuels, glucose and lipid, in the postprandial state.
5. Describe the main features of the insulin receptor.
6. Describe the main features of the intracellular insulin signalling pathway.
7. Define insulin resistance.
8. Describe the molecular basis of insulin resistance at the level of the insulin receptor.

Practical: Abdominal Wall Anatomy

Practical: Mouth to Oesophagus

Lecture: Insulin Counter-Regulatory Hormones

1. List the symptoms, causes and consequences of hypoglycaemia.
2. Describe the actions of glucagon on glucose and lipid metabolism in the post absorptive and fasting states.
3. Describe the hepatic glucoregulatory actions of glucagon.
4. Outline how glucagon opposes insulin action as glucose levels fall.
5. Outline the action of glucagon on hepatic lipid homeostasis during fasting.
6. Understand the regulation of thyroid pathophysiology.
7. Outline the metabolic effects of thyroid hormones.
8. Describe the acute metabolic actions of adrenaline and noradrenaline.
9. Summarise the physiological actions of the glucocorticoids on metabolism.

Practical: Peritoneum and Foregut

Practical: Hepatobiliary and Spleen

Practical: Midgut and Hindgut

Practical: Retroperitoneal Anatomy

Lecture: Diabetes Mellitus

1. The effects of persistent hyperglycaemia
2. The long-term complications of diabetes mellitus
3. HbA1C Test
4. Advanced glycation end products (AGEs) and AGE receptors (RAGEs)
5. The macrovascular complications of diabetes mellitus
6. How glucose tolerance can be maintained by the balance between insulin secretion and action
7. How beta-cell mass changes in type 2 diabetes
8. The effects of inadequate insulin secretion or action upon carbohydrate and fat metabolism, including the etiology of diabetic ketoacidosis
9. Oral glucose tolerance test in normal, insulin resistant and diabetic subjects
10. Outline the potential abnormalities of glucose homeostasis in diabetes mellitus.
11. Describe the principal forms of diabetes mellitus.

Microanatomy: Renal

Lecture 17: Acid-Base Regulation

1. Learn how to calculate the anion gap and what type of metabolic disorders it is associated with.
2. Learn the four forms of acid base disturbance.
3. Learn how cell metabolism and environment are constantly challenging the pH of the human body.
4. Understand why Acid-Base homeostasis is essential for human physiology.
5. Learn the relationship between pH, [HCO3-] and PaCO2
6. Learn which organs are involved in pH regulation and by which mechanisms.

Lecture: Metabolic Insights from Genetic Disease

1. Define inherited metabolic disorders and list common inherited metabolic disorders.
2. Outline the metabolic impact of Von Gierke's disease.
3. Outline the biochemical basis and consequences of galactosaemia.
4. Outline the biochemical basis and consequences of McArdle's disease
5. Describe the consequences of a deficiency of liver fructokinase or fructose 1-phosphate aldolase.
6. Outline the inherited metabolic disorders of amino acid metabolism
7. Describe the consequences of phenylketonuria.
8. List the genetic causes of dyslipidaemia.
9. Describe the consequences of familial hypercholesterolaemia.

Lecture: Appetite Regulation

1. Demonstrate how nutrients in the GI tract stimulate GI function.
2. Use of endocrine knowledge to treat dietary disturbance.
3. Outline the control of food intake by the arcuate nucleus including the role of malonyl-CoA in the hypothalamus.
4. Summarise how hormones modulate food intake.
5. Define the terms anorexigen and orexigen.
6. Outline the role of serotonin in the regulation of appetite.

Lecture: Obesity : Prevalence, Pathophysiology and Treatment

1. Discuss the pathological consequences of obesity (links between obesity, insulin resistance and diabetes).
2. Describe the treatments for obesity.
3. Understand the generic underpinning of obesity.
4. Describe its relationship with the population's intake of fat and carbohydrates and trends in physical exercise.
5. Describe the prevalence of obesity in the world and the UK.

Lecture: Defecation & Anal Anatomy

1. Understand the anatomy the embryology of the anorectum
2. Understand the role of the colon
3. Understand the mechanisms/physiology of defaecation
4. Outline the investigations available to investigate GI disorders
5. Understand how stools analysis can be a powerful non-invasive method to assess various metabolism issues

Lecutre: Endocrine Anatomy

1. Discuss the anatomy and list the structures that pass through cavernous sinus.
2. Describe the blood supply and venous drainage of the pituitary gland.
3. Describe the position, the anatomical relations, and the blood supply of the adrenal glands.
4. Describe the position, the anatomical relations, and the blood supply of the thyroid and parathyroid glands.
5. Describe the position, the anatomical relations, and the blood supply of the pancreas.
6. Describe the structural and functional relationships between the hypothalamus and both the anterior and posterior lobes of the pituitary gland.

Lecture: Urinary Anatomy

1. Describe the anatomy of the bladder, prostate and urethra
2. Outline the general organisation of the urinary system including the kidney, ureter, bladder and urethra
3. Identify the parts of the nephron and describe the role of each component in the physiologic processes involved in urine production
4. Describe the vasculature of the kidney, relating its unique features to the physiology of urine production and nourishment of the nephron
5. Understand the descent of the ureters through the pelvis and the position of the bladder and urethra in the male and female

Lecture: The Thyroid

1. Describe the general organisation of endocrine tissues in the thyroid and parathyroid glands.
2. Outline the synthesis, storage and release of thyroid hormones
3. Describe the effects of thyroid stimulating hormone on the thyroid gland
4. Outline the actions of thyroid hormones
5. Briefly explain the pathophysiology of hypo- and hyperthyroidism.
6. List the effects of excess and deficiency of thyroid hormones
7. Describe the detection and treatment of hyperthyroidism and hypothyroidism

Lecture: Adrenals

1. Describe the structure of the adrenal gland and relate the zones to production of hormones.
2. Describe the regulation of hormone secretion by each zone
3. Describe the physiological actions of the adrenal hormones
4. Explain the effects of both excess and deficiency of adrenal hormones

Lecture: Kidney Microanatomy

1. Outline the general organisation of the urinary system including the kidney, ureter, bladder and urethra.
2. Identify the parts of the nephron and describe the role of each component in the physiologic processes involved in urine production.
3. Describe the vasculature of the kidney, relating its unique features to the physiology of urine production and nourishment of the nephron.
4. Identify the components of the juxtaglomerular apparatus and describe its role in regulation of blood and urine volumes and renal homeostasis.
5. Outline the structural components of the urinary passageways and bladder and describe how micturition is controlled.

Lecture: Nutrition in Medicine

1. Understand the difference between malnutrition and undernutrition.
2. Understand the different methods of delivery of nutrition support.
3. Explain the prevalence and causes of malnutrition in UK
4. Describe how to identify those at risk of malnutrition
5. Describe the physical and psychological consequences of under-nutrition.
6. Describe the different methods of nutritional assessment
7. Describe briefly the ethical and medico-legal aspects of artificial nutrition support

Lecture: Functional Histology of the Gut

1. Outline the basic components that make up the wall of the alimentary tract.
2. Define the acronyms MALT and GALT.
3. Describe variations in the basic wall plan at particular sites (i.e. junctions, retroperitoneal regions).
4. Describe the changing nature and function of the mucosae in the alimentary tract.
5. Explain how the mucosa of the small intestine is adapted to increase its surface area for absorption.
6. Outline the cellular composition of the epithelia in each part of the alimentary tract.

Lecture: Hypothalamus and Pituitary

1. Describe the structure and origins of the pituitary gland and explain the relationship between the hypothalamus and both the anterior and posterior pituitary.
2. List the hormones secreted by both the anterior and posterior pituitary and in each case explain the role of the hypothalamus in regulating their secretion
3. Use the concept of negative feedback to explain the principles underlying clinical tests for pituitary hormone secretion
4. Briefly outline the actions of the hormones of the posterior and anterior pituitary.

Lecture: Liver and Gall Bladder

1. Give an overview of the role of the liver in carbohydrate, lipid and protein metabolism
2. Describe the role of the liver in glucose homeostasis
3. Describe how the liver acts as an organ of detoxification
4. Discuss the role of the liver in protein synthesis
5. Describe the storage functions of the liver
6. Describe the components of the biliary tree (including the sphincter of Oddi)
7. Outline the formation and functions of bile
8. Describe the function of the gallbladder and its control
9. Describe the enterhepatic circulation of bile
10. Describe the origin, metabolism and excretion of bilirubin

Lecture: Liver Disease

1. To understand the link between structure and function of the hepato-biliary tract and link this to clinical presentation
2. To identify the important causes of acute and chronic liver disease.
3. To appreciate the difference between liver failure, portal hypertension and cirrhosis.
4. To understand the different effects of alcohol on the liver.
5. To understand the natural history of Hepatitis B and C viruses and their presentation with acute and chronic liver disease
6. To recognise the features of biliary tract obstruction.

Lecture: The Gut

1. Overview of the GI tract.
2. Understand link between anatomy/physiology and clinical presentations.
3. General understanding of mechanisms.
4. A general introduction to the gastrointestinal tract.

Lecture: Nausea & Vomiting

1. Emesis (nausea + vomiting) is a normal defensive reflex which becomes a medical issue if induced by drugs or disease
2. Many different causes (pregnancy, motion, drugs, gastrointestinal/ painful conditions, surgery). Can be especially severe during cancer chemotherapy and palliative medicine
3. There are different classes of anti-emetic drugs with different actions; no drug is effective against all types of emesis
4. Old, 'established' anti-emetic drugs are commonly used, often with a 'mixed pharmacology' (antagonise at M1, H1 and/ or D2 receptors) and side-effects
5. Antagonists at 5-HT3 and NK1 receptors are used to inhibit severe emesis often in combination with the steroid, dexamethasone
6. Nausea is not the same as vomiting and is more difficult to treat

Lecture: Lipoprotein Handling

1. Outline the process of lipogenesis and its control.
2. Describe the structure and composition of the main classes of lipoprotein, including very-low density lipoproteins (VLDL).
3. Describe the role of low-density proteins (LDL).
4. Describe the contribution of LDL to atherogenesis and clinical treatments to lower serum LDL-cholesterol levels.
5. Discuss the significance of high-density lipoproteins (HDL).

Lecture: Nitrogen Metabolism

1. Discuss nitrogen homeostasis and nitrogen balance.
2. Outline the metabolic fates of amino acids.
3. Describe the metabolic classification of amino acids.
4. Discuss, with examples, the metabolic significance of glutamate, glutamine, and ?-ketoglutarate.
5. Describe the role of urea as the excretory form of surplus nitrogen in humans.

Lecture: Diet and Cardiovascular Disease

1. List the major risk factors for cardiovascular disease
2. Be aware of key epidemiological studies of risk factors for cardiovascular disease.
3. Review the main dietary factors that influence the development of cardiovascular disease and hypertension.
4. Differentiate between types of lipids in relation to protection from and contribution to cardiovascular disease.
5. Understand how salt and alcohol influence cardiovascular function
6. Outline evidence that the risk of cardiovascular disease may be modified by environmental influences in early life.

Lecture: Retroperitoneal Anatomy

Lecture: Intestine - Gateway To Life

1. Critical role of the intestine in animal/human evolution
2. Normal gastrointestinal tract
3. Diseases of oesophagus - Reflux and cancer
4. Diseases of stomach - acid secretion; cancer and bleeding
5. Small intestine - absorption; immune system, coeliac disease and inflammatory bowel disease
6. Summary - reasons for gastroenterology being an interesting and important area in which to work

Lecture: Steroids

1. Describe the mechanisms of action contributing to anti-inflammatory and immunosuppressive effects of corticosteroids.
2. Clinical uses of corticosteroids
3. Explain how long-term corticosteroid therapy disrupts endogenous corticosteroid secretion
4. Describe other unwanted effects arising from long-term therapy with glucocorticoids.
5. List some synthetic steroids with mainly glucocorticoid activity.
6. Explain the reason for the development of such compounds.

Lecture: Kidney & Adrenals

1. Appreciate the basic anatomy of the intermediate mesoderm, mesonephric and metanephric systems
2. Know that the kidney is composed of the collecting system and excretory system
3. That the embryonic origin of the collecting system is the ureteric bud
4. The origin of the excretory system is the metanephric mesoderm
5. Appreciate during development how these tissue combine to give rise to the fully developed kidney
6. Describe the ascent of the kidney
7. Understand from their knowledge of kidney development how some of the common defects in kidney development can arise
8. Understand the embryonic origin of the adrenal medulla and cortex and how they give rise to the adrenal gland
9. Describe the development of zonation within the adrenal gland

Practical: Alimentary canal

Practical 2: Endocrine System

Microanatomy: Alimentary

1. Outline the changing nature and function of the epithelial lining of the alimentary tract.
2. Draw a diagram of the normal small intestinal mucosa and show what changes occur in enteropathy.
3. Illustrate the structure of the upper small intestinal wall (serosa to mucosa).
4. Describe common pathologies of the gastrointestinal tract.

Microanatomy: The Liver

Microanatomy: Endocrine

1. Describe the blood supply to the adrenal gland and the functional relationship between the adrenal medulla and the nervous system
2. Recognise and describe specific disease processes that affect the glands of the endocrine system

DGM PBL 1: Gastro-oesophageal reflux

DGM PBL 2: One for the road

DGM PBL 3: Reaching New Heights

DGM PBL 4: Understanding your illness

DGM PBL 5: Genes & Jeans

DGM PBL 6: A Slowed-down Teacher

DGM PBL 7: Sarah Taylor

Formative Assessment: The Endocrine System

Lecture: Micturition

1. Describe the anatomy of the bladder, prostate and urethra
2. Distinguish between urge incontinence, stress incontinence, overflow incontinence and leak incontinence
3. Describe the reservoir and emptying functions of the bladder and outline the neurological control of each
4. Explain the most common causes for each of the above.
5. Outline the investigations available to distinguish the cause of incontinence in an individual.
6. Describe treatments available for disorders of micturition.

Lecture: Diuretics

1. Show, by means of a labelled diagram, the proportions of sodium reabsorbed from tubular fluid in: the proximal tubule; the loop of Henle; the distal tubule; the collecting duct.
2. Compare the different mechanisms for sodium re-absorption found in different parts of the nephron.
3. Describe the actions of aldosterone on the distal tubule and collecting duct which maintain the sodium balance of the body. State the fraction of the total sodium re-absorption which is subject to regulation by aldosterone.
4. List the major clinical indications of the uses of a diuretic.
5. Give the primary sites of action of thiazide, loop diuretics, and spironolactone, and rank them in order of their efficacy.
6. Explain why diuretics increase potassium excretion, and how this may be reduced.
7. Explain the use of mannitol as a 'diuretic'.