YR 2 Medical MCQ Practice

Function: The gastrointestinal tract digests food mechanically and chemically, then absorbs nutrients.
Main regions:
- Oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus.
- The small intestine includes the duodenum, jejunum and ileum.
- The large intestine includes the caecum, colon, rectum and anus.
Gut wall layers:
1. Mucosa.
2. Submucosa.
3. Muscularis externa.
4. Serosa or adventitia.
Mucosa:
- Epithelium: secretion, absorption and protection.
- Lamina propria: loose fibroelastic connective tissue with blood vessels, lymphoid tissue and glands.
- Muscularis mucosae: thin smooth muscle allowing local mucosal movement.
Submucosa: Collagenous and elastic connective tissue containing blood vessels, glands in some regions and Meissner’s nerve plexus.
Muscularis externa:
- Usually inner circular and outer longitudinal smooth muscle.
- Responsible for peristalsis.
- Innervated by Auerbach’s myenteric plexus.
- Inner circular muscle can form sphincters.
Serosa vs adventitia:
- Serosa: present when the gut is suspended by mesentery and covered by peritoneum.
- Adventitia: present when the organ is retroperitoneal and lacks mesentery.
Oesophagus:
- Transports masticated material from pharynx to stomach.
- Has stratified squamous non-keratinising epithelium.
- Upper third contains skeletal muscle, middle third mixed muscle, lower third smooth muscle.
Stomach:
- Acts as a distensible storage tank.
- Rugae are temporary folds that disappear as the stomach distends.
- Mixes food with gastric juices to form chyme.
- Contains three smooth muscle layers in the muscularis externa.
Gastric glands:
- Mucous cells lubricate and protect the stomach wall.
- Parietal cells produce hydrochloric acid.
- Chief cells contain pepsinogen granules.
- Enteroendocrine cells produce gastrin.
Small intestine specialisation:
- Plicae circulares, villi and microvilli greatly increase surface area.
- Crypts of Lieberkühn contain stem cells and epithelial cell types.
- Main functions are final digestion and nutrient absorption.
Duodenum: Receives bile and pancreatic enzymes; Brunner’s glands secrete alkaline mucus to neutralise acidic chyme.
Jejunum: Main site of nutrient absorption with prominent plicae circulares and tall villi.
Ileum: Contains Peyer’s patches for immune surveillance and forms the longest small intestinal segment.
Large intestine:
- Reabsorbs water and electrolytes.
- Absorbs vitamins released by bacterial activity.
- Compacts chyme into faeces.
- Contains colonic crypts with many goblet cells for mucus production.

Surveillance definition: Ongoing, systematic collection, analysis, interpretation and dissemination of health data for public health action.
Core purpose: Surveillance provides “information for action”.
Health surveillance components:
- Systematic collection of relevant data.
- Orderly consolidation and evaluation of data.
- Prompt dissemination to those who need to know.
- Use of information to guide prevention and control.
Levels of prevention:
- Primary prevention: prevents disease or injury occurring.
- Secondary prevention: detects disease early and intervenes promptly.
- Tertiary prevention: limits disability and supports rehabilitation.
Types of surveillance:
- Passive surveillance: uses routine sources such as notifications, laboratory reports and healthcare data.
- Active surveillance: involves special effort to collect data and confirm diagnoses.
- Sentinel surveillance: uses selected reporting sites or high-risk groups as indicators.
Data sources: Clinical services, laboratories, environmental health, emergency services, community services and public utilities.
Purposes of surveillance:
- Define priorities and support planning.
- Characterise disease patterns by time, place and person.
- Measure incidence and track changes.
- Detect outbreaks, epidemics and emerging problems.
- Evaluate prevention and control measures.
Outbreak definition: Disease cases occurring above normal expectancy in a specific area, group and time period.
Outbreak detection:
- Two or more linked cases.
- A single unusual or rare infection.
- A rate higher than the expected background rate.
- Suspected microbial contamination of food or water.
Notifiable disease principle: Certain infectious diseases must be reported so public health authorities can assess and act quickly.
Successful surveillance system features:
- Timeliness.
- Representativeness.
- Consistency.
- Completeness.
- Accuracy.
- Importance of the condition under surveillance.
Outbreak management:
1. Prepare.
2. Detect.
3. Confirm.
4. Investigate.
5. Control.
6. Evaluate.
Outbreak control team: May include public health specialists, epidemiologists, microbiologists, clinicians, environmental health, communications and service managers.
Case investigation:
- Use an appropriate case definition.
- Actively find cases.
- Collect demographic, clinical and exposure information.
- Consider secondary cases.
Descriptive epidemiology: Orient outbreak data by time, place and person.
Epidemic curves:
- Common point source: cases clustered after a single exposure.
- Common persistent source: exposure continues over time.
- Propagated source: person-to-person spread across generations of cases.
Establishing cause: Combine laboratory, clinical, environmental and epidemiological evidence.
Analytical studies: Case-control studies can calculate odds ratios; retrospective cohort studies can calculate relative risk and attack rates.
Final outbreak report: Documents action, legal and medical issues, investigation quality, recommendations and lessons learned.

GI tract functions: Ingestion, motility, secretion, digestion and absorption.
Peristalsis:
- Alternating waves of contraction and relaxation in the organ wall.
- Propels luminal contents forward.
- Can also help mix food with digestive juices.
Neural regulation:
- The enteric nervous system contains around 100 million neurons.
- Intrinsic ENS pathways can mediate local reflexes.
- Extrinsic autonomic input modifies gut activity.
Reflex control:
- Mechanoreceptors and chemoreceptors detect luminal stimuli.
- Long reflexes involve the CNS, such as responses to the sight or smell of food.
- Short reflexes are mediated by the ENS, such as peristalsis.
Hormonal regulation:
- Endocrine signals enter the bloodstream, e.g. gastrin, CCK, secretin, GIP and motilin.
- Paracrine signals act locally, e.g. somatostatin and histamine.
- Neurocrine signals are released from enteric neurons, e.g. VIP, GRP and enkephalins.
Mastication:
- Controlled mainly by the trigeminal nerve.
- Increases food surface area for digestive enzymes.
- Masticated food mixed with saliva forms a bolus.
Swallowing: Also called deglutition; saliva and mucus reduce friction as the bolus passes to the oesophagus.
Phases of deglutition:
1. Voluntary phase: tongue pushes the bolus into the oropharynx.
2. Pharyngeal phase: soft palate and uvula close the nasopharynx; laryngeal closure prevents aspiration; upper oesophageal sphincter relaxes.
3. Oesophageal phase: peristalsis moves bolus toward stomach; lower oesophageal sphincter opens by short reflex.
Gastric mixing waves:
- Mix and soften food with gastric juices to form chyme.
- Begin in the body of the stomach and increase in strength toward the pylorus.
- Force small volumes of chyme through the pyloric sphincter into the duodenum.
Vomiting:
- Also called emesis.
- Can be triggered by chemical, mechanical, sensory, psychological or pathological stimuli.
- Stages include nausea, retching and emesis.
- Controlled by brainstem vomiting centres and the chemoreceptor trigger zone.
Small intestine motility:
- Segmentation mixes contents and supports absorption.
- Peristalsis propels contents onward.
- Migrating motility complexes clear residual material during fasting.
Migrating motility complex: Motilin-driven “housekeeping” contractions that occur after absorption, clearing leftovers, bacteria and exfoliated cells.
Ileocecal valve: Usually closed; relaxes with ileal motility and prevents reflux of colonic contents into the ileum.
Large intestine motility:
- Haustral contractions mix residue and support water absorption.
- Peristalsis moves contents slowly.
- Mass movements occur a few times per day and are enhanced by the gastrocolic reflex.
Defecation reflex: Rectal wall stretch triggers sigmoid and rectal contraction, internal anal sphincter relaxation and voluntary control of the external anal sphincter.
Diarrhoea types:
- Osmotic: excess luminal solute from malabsorption, e.g. lactose intolerance.
- Secretory: altered balance between water secretion and absorption, e.g. cholera toxin.
- Inflammatory/infectious: tissue damage reduces absorption, e.g. Shigella, Salmonella or norovirus.
Clinical consequence: Vomiting and diarrhoea can cause dehydration and electrolyte disturbance, requiring rehydration and electrolyte replacement.

Lecture focus: Fasciae, vessels, nerves, lymphatics, abdominal wall muscles, rectus sheath and inguinal canal.
Cutaneous innervation:
- The anterior abdominal wall is supplied segmentally by thoraco-abdominal nerves.
- Important nerves include T7–T11, subcostal nerve T12, iliohypogastric nerve L1 and ilio-inguinal nerve L1.
Arterial supply:
- Superior supply includes branches related to the internal thoracic and musculophrenic arteries.
- Inferior supply includes superior epigastric, inferior epigastric and superficial epigastric vessels.
- Intercostal and subcostal vessels also contribute to the abdominal wall.
Venous drainage:
- Superficial venous plexuses drain superiorly into internal thoracic and lateral thoracic veins.
- They also drain inferiorly into superficial and inferior epigastric veins.
Lymphatic drainage:
- Above the transumbilical plane: superficial lymph drains to axillary nodes.
- Below the transumbilical plane: superficial lymph drains to superficial inguinal nodes.
External oblique:
- Most superficial flat muscle of the antero-lateral abdominal wall.
- Forms a broad aponeurosis, which is a flattened tendon.
Internal oblique: Located deep to external oblique and contributes to the abdominal wall and inguinal canal boundaries.
Transversus abdominis: Deepest of the three flat abdominal muscles and lies deep to internal oblique.
Rectus abdominis:
- Paired vertical muscle of the anterior abdominal wall.
- Divided into sections by tendinous intersections.
- Enclosed by the rectus sheath for most of its length.
Rectus sheath:
- Has anterior and posterior components.
- The arcuate line marks the point where the posterior rectus sheath terminates.
Inguinal canal: Passage located between the deep internal inguinal ring and superficial external inguinal ring.
Deep inguinal ring:
- Located at the midpoint of the inguinal ligament.
- The inguinal ligament runs from the anterior superior iliac spine to the pubic tubercle.
- Transmits structures including vas deferens/testicular vessels or the round ligament of the uterus.
Superficial inguinal ring:
- Located superior to the pubic tubercle.
- Transmits the spermatic cord or round ligament of the uterus.
Inguinal canal boundaries:
- Anterior wall: external oblique aponeurosis.
- Posterior wall: conjoint tendon medially and transversalis fascia laterally.
- Roof: fibres of internal oblique and transversus abdominis.
- Floor: lower edge of the inguinal ligament.

Key bony landmarks: Xiphoid process, costal margin, iliac crest, anterior superior iliac spine, pubic symphysis, pubic tubercle and pubic crest.
Abdominal surface anatomy:
- The abdomen can be divided into 9 regions.
- It can also be divided into 4 quadrants.
- The transpyloric plane lies midway between the jugular notch and pubic symphysis, or midway between the xiphoid process and umbilicus.
Peritoneum: A serous membrane that produces a small amount of peritoneal fluid.
Types of peritoneum:
- Parietal peritoneum lines the abdominopelvic cavity.
- Visceral peritoneum covers abdominal and pelvic organs.
Peritoneal cavity: Potential space between parietal and visceral peritoneum containing lubricating fluid with white blood cells and antibodies.
Greater and lesser sacs:
- Greater sac accounts for most of the peritoneal cavity.
- Lesser sac, or omental bursa, lies posterior to the stomach.
Omenta:
- Double-layered folds of peritoneum.
- Lesser omentum attaches the lesser curvature of the stomach to the liver.
- Greater omentum attaches to the greater curvature of the stomach and folds back to the transverse colon.
Mesenteries: Double-layered peritoneal folds that suspend organs and carry vessels, nerves and lymphatics.
Examples of mesenteries:
- Mesentery of the small intestine.
- Transverse mesocolon.
- Sigmoid mesocolon.
Retroperitoneal structures: Organs or structures not suspended by mesentery and located between peritoneum and posterior abdominal wall.
Embryological gut divisions:
- Foregut: oesophagus, stomach, liver, gall bladder, pancreas and proximal duodenum.
- Midgut: distal duodenum, jejunum, ileum, caecum, appendix, ascending colon and proximal two thirds of transverse colon.
- Hindgut: distal one third of transverse colon, descending colon, sigmoid colon, rectum and upper anal canal.
Arterial supply by embryological origin:
- Foregut: coeliac trunk.
- Midgut: superior mesenteric artery.
- Hindgut: inferior mesenteric artery.
Lymphatic drainage:
- Foregut drains to pre-aortic nodes near the coeliac trunk.
- Midgut drains to pre-aortic nodes near the superior mesenteric artery.
- Hindgut drains to pre-aortic nodes near the inferior mesenteric artery.
- Lymph from these nodes drains to the cisterna chyli.

Accessory organs: Salivary glands, liver, pancreas and gallbladder support digestion through secretions.
Liver overview:
- Largest gland in the body.
- Mostly epithelial tissue with very little connective tissue in normal liver.
- Receives dual blood supply from hepatic artery and hepatic portal vein.
Liver blood supply:
- Hepatic artery provides about 30% of blood and is oxygen-rich.
- Hepatic portal vein provides about 70% of blood and carries nutrient-rich blood from abdominal organs.
- Blood exits via hepatic veins into the inferior vena cava.
Liver functions:
- Exocrine function: bile production.
- Endocrine function: plasma protein production.
- Processes and stores absorbed nutrients, such as glycogen.
- Detoxifies drugs, toxins and alcohol.
- Destroys worn-out red blood cells.
Classical liver lobule:
- Based on histological organisation.
- Contains peripheral portal areas, vascular sinusoids, rows of hepatocytes and a central vein.
- Blood flows from portal areas through sinusoids toward the central vein.
Portal area contents:
- Branch of hepatic portal vein.
- Branch of hepatic artery.
- Bile duct.
- Lymphatic vessels.
Liver acinus:
- Based on liver function rather than purely histological appearance.
- Spans two adjoining classical lobules.
- Explains oxygen gradients, drug metabolism patterns and zones of injury.
Acinar zones:
- Zone 1: closest to portal area; receives oxygen- and nutrient-rich blood; active in glycogen and plasma protein synthesis.
- Zone 2: intermediate region receiving second-class blood.
- Zone 3: closest to central vein; low oxygen and nutrient blood; major site of alcohol and drug detoxification; most vulnerable to hypoxia and toxic damage.
Blood and bile flow:
- Blood flows from portal area to central vein through sinusoids.
- Bile flows in the opposite direction through bile canaliculi toward bile ducts.
Hepatocyte-sinusoid boundary:
- Fenestrated endothelial cells line sinusoids.
- Space of Disse allows plasma to contact hepatocyte microvilli.
- Kupffer cells are macrophages located on sinusoid walls.
- Bile canaliculi are sealed intercellular channels between hepatocytes.
Pancreas:
- Divided into lobules by connective tissue septa.
- Has both exocrine and endocrine components.
Exocrine pancreas: Serous acini and branched ducts produce digestive enzymes such as trypsinogen, lipase and amylase, often in inactive form to prevent self-digestion.
Endocrine pancreas:
- Islets of Langerhans are compact endocrine cell clusters with capillaries.
- Alpha cells secrete glucagon.
- Beta cells secrete insulin.
- Delta cells secrete somatostatin.
- F cells secrete pancreatic polypeptide.

Regulation of digestion:
- Digestive activity is controlled by neural reflexes, endocrine hormones, paracrine signals and neurocrine signals.
- Long reflexes involve the CNS.
- Short reflexes are mediated by the enteric nervous system.
GI hormones and signals:
- Endocrine: gastrin, CCK, secretin, GIP and motilin.
- Paracrine: somatostatin and histamine.
- Neurocrine: VIP, GRP and enkephalins.
Salivary glands:
- Produce around 1–1.5 L of saliva per day.
- Major glands are parotid, submandibular and sublingual glands.
- Parotid glands produce mainly serous watery secretion.
- Submandibular glands produce mixed serous and mucous secretion.
- Sublingual glands produce mainly mucous secretion.
Saliva composition:
- Mostly water.
- Contains mucus, ions, growth factors and enzymes.
- Amylase begins starch digestion.
- Lysozyme and IgA provide antibacterial protection.
- Bicarbonate and phosphate help maintain pH around 6.35–6.85.
- EGF helps maintain tissue integrity.
Salivation control:
- Parasympathetic input supports normal salivation.
- Sight, smell or thought of food can stimulate salivation.
- Stress and sympathetic activity reduce salivation.
- Taste signals reach salivary nuclei in the brainstem via facial and glossopharyngeal nerves.
Gastric secretion phases:
- Cephalic phase: triggered by smell, taste or thought of food.
- Gastric phase: stomach distension and food peptides stimulate acetylcholine and gastrin release.
- Intestinal phase: duodenal signals regulate secretion; enterogastric reflex and hormones can inhibit gastric activity.
Gastric digestion:
- Food and gases are stored in the fundus.
- Mixing waves combine food with gastric secretions to form chyme.
- Acidity inactivates amylase.
- HCl activates pepsinogen to pepsin, beginning protein digestion.
- Carbohydrate-rich meals empty fastest; fatty meals empty slowest.
Stomach mucosal barrier:
- Bicarbonate-rich mucus protects against acid.
- Tight junctions seal epithelial cells.
- Stem cells in gastric pits rapidly replace damaged cells.
- The gastric surface is replaced every 3–6 days.
Stomach hormones:
- Gastrin stimulates gastric gland secretion and promotes motility.
- Ghrelin is mainly produced in the fundus and stimulates hunger.
- Histamine stimulates parietal cells to release HCl.
- Serotonin contributes to stomach muscle contraction.
Duodenal secretions: Brunner’s glands secrete bicarbonate-rich mucus to neutralise acidic gastric chyme.
Pancreatic secretion:
- Contains bicarbonate-rich fluid to neutralise acid.
- Contains enzymes including proteases, pancreatic lipase, nucleases and amylase.
- Secretin stimulates duct cells to release bicarbonate-rich juice.
- CCK stimulates acinar cells to release enzyme-rich juice.
Bile:
- Produced in the liver at about 1 L/day.
- Contains water, bile salts, bile pigments, phospholipids, electrolytes, cholesterol and triglycerides.
- Emulsifies lipids.
- Stored and concentrated in the gallbladder between meals.
- Gallbladder contraction is stimulated by CCK.
Bilirubin:
- Main bile pigment.
- Produced from haem degradation after old red cells are removed.
- Converted by intestinal bacteria into stercobilin, giving faeces its brown colour.
- Accumulation can cause jaundice.
Absorption:
- Most electrolytes and water are absorbed in the small intestine.
- Most carbohydrate and protein absorption occurs in the jejunum.
- Bile salts and vitamin B12 are absorbed in the terminal ileum.
- Carbohydrates use sodium-linked transporters.
- Fats form micelles, are reassembled into triglycerides and travel as chylomicrons via lacteals.
Gut microbiome: Large intestinal commensals help digest fibre, synthesize vitamins such as vitamin K and provide colonisation resistance against pathogens.

Energy sources:
- ATP is the universal energy currency.
- Carbohydrate and protein provide approximately 4 kcal/g.
- Fat provides approximately 9 kcal/g.
Central role of glucose:
- In the fed state, glucose is the main energy source.
- Fructose and galactose are converted to glucose in the liver.
- Glucose is the predominant circulating monosaccharide.
Glucose transport:
- Glucose is too large to diffuse freely across membranes.
- Most tissues use facilitated diffusion through GLUT transporters.
- Intestinal absorption uses active sodium-glucose co-transporters.
GLUT transporters:
- GLUT1: basal uptake in most tissues, including brain and red cells.
- GLUT2: liver, kidney and pancreatic beta cells; helps remove excess glucose and regulate insulin release.
- GLUT3: basal uptake in CNS and other tissues.
- GLUT4: skeletal muscle and adipose tissue; increased at the membrane by insulin and exercise.
Insulin:
- Polypeptide hormone made by pancreatic beta cells in islets of Langerhans.
- Secretion is mainly stimulated by increased blood glucose.
- Short circulating half-life of around 6 minutes.
- Mainly degraded in the liver by insulinase.
Regulation of insulin secretion:
- Rapid rise occurs after a meal from preformed insulin.
- New insulin synthesis supports a sustained rise over 2–3 hours.
- Low blood glucose rapidly switches off secretion.
- Amino acids and GI hormones such as gastrin, CCK and GIP can potentiate secretion.
Insulin in muscle:
- Increases GLUT4-mediated glucose uptake 15–20 fold.
- Active muscle uses glucose for energy.
- Inactive muscle stores post-meal glucose as glycogen.
- Exercise increases glucose uptake independently of insulin.
Insulin in liver:
- High insulin increases glucokinase and glycogen synthase activity.
- Promotes glucose uptake and glycogen storage.
- Low insulin increases glycogen phosphorylase and glucose-6-phosphatase.
- Promotes glycogen breakdown and glucose release.
Brain glucose use: Insulin has minimal effect on brain glucose uptake; hypoglycaemia can cause nervous irritability, fainting, convulsions and coma.
Glucagon:
- Produced by pancreatic alpha cells.
- Stimulated mainly by low blood glucose.
- Counter-regulates insulin.
- Promotes hepatic glycogenolysis and glucose release.
Other counter-regulatory hormones:
- Adrenaline and noradrenaline promote glycogenolysis and lipolysis.
- Cortisol and growth hormone promote gluconeogenesis, reduce tissue glucose uptake and increase lipolysis.
Diabetes mellitus:
- Type 1 diabetes: insulin-dependent, beta-cell dysfunction, often autoimmune or juvenile onset.
- Type 2 diabetes: non-insulin dependent, insulin resistance, obesity-related and usually adult onset.
Hyperglycaemia effects:
- Causes glycosuria once renal glucose reabsorption is overwhelmed.
- Raises extracellular osmolarity, causing cellular water loss.
- Leads to polyuria, polydipsia and dehydration.
- Causes glucotoxicity through protein glycation, ROS formation, inflammation, beta-cell dysfunction and endothelial dysfunction.
Ketoacidosis:
- Low insulin increases lipolysis.
- Fatty acids undergo beta-oxidation in liver.
- Keto acids such as acetoacetate and beta-hydroxybutyrate reduce blood pH.
- Diabetic ketoacidosis is a medical emergency.
Diagnosis of diabetes: May involve urinary glucose, fasting blood glucose, fasting plasma insulin, glucose tolerance testing and assessment for ketoacidosis.

Lecture focus: Abdominal aorta, inferior vena cava, coeliac trunk and superior mesenteric artery.
Abdominal aorta:
- Enters the abdomen through the aortic hiatus at T12.
- Descends against the vertebral bodies.
- Terminates at L4.
- Normal diameter is about 1–1.5 cm.
Unpaired anterior branches:
- Coeliac trunk.
- Superior mesenteric artery.
- Inferior mesenteric artery.
Paired branches:
- Supply paired abdominal organs and body wall structures.
- Examples include renal, suprarenal, gonadal, lumbar and inferior phrenic branches.
Terminal branches: The abdominal aorta terminates by dividing into right and left common iliac arteries.
Inferior vena cava:
- Begins at L5 from the union of right and left common iliac veins.
- Ascends to the right of the abdominal aorta.
- Passes through the diaphragm at T8.
Coeliac trunk:
- Short unpaired branch of the abdominal aorta.
- Usually arises at T12.
- Supplies foregut-derived structures.
Main coeliac trunk branches:
1. Left gastric artery.
2. Splenic artery.
3. Common hepatic artery.
Important coeliac-derived vessels:
- Short gastric arteries.
- Left gastro-omental artery.
- Right gastro-omental artery.
- Gastroduodenal artery.
- Right gastric artery.
Superior mesenteric artery:
- Branch of the abdominal aorta.
- Usually arises at L1.
- Supplies midgut-derived structures.
SMA branches:
- Inferior pancreaticoduodenal artery.
- Jejunal arteries.
- Ileal arteries.
- Ileo-colic artery.
- Right colic artery.
- Middle colic artery.
Jejunal arterial pattern: Jejunal branches form arterial arcades and long vasa recta.
Ileal arterial pattern: Ileal branches usually form more arcades and shorter vasa recta than the jejunum.
Clinical anatomy principle: Arterial supply broadly follows embryological origin: foregut by coeliac trunk, midgut by SMA and hindgut by IMA.

Lecture focus: Anatomy of the liver, gallbladder, biliary tree, hepatic portal system and porto-systemic anastomoses.
Liver surface anatomy:
- Right side extends from the 5th intercostal space in the mid-clavicular line to the 10th rib in the mid-clavicular line.
- Left side extends to the 5th intercostal space in the mid-clavicular line.
Liver surfaces:
- Diaphragmatic surface faces the diaphragm.
- Visceral surface contacts abdominal organs.
- Important recesses include the subphrenic recess and hepatorenal recess.
Lobes and ligaments:
- Right and left anatomical lobes are separated by the falciform ligament.
- The round ligament runs in the falciform ligament.
- The round ligament is the obliterated umbilical vein.
- Coronary and triangular ligaments help attach the liver to the diaphragm.
Visceral surface features:
- Caudate lobe.
- Quadrate lobe.
- Bare area.
- Porta hepatis.
Porta hepatis contents:
- Hepatic portal vein.
- Hepatic artery proper.
- Bile duct.
Hepatic veins: Three hepatic veins drain directly into the inferior vena cava.
Gallbladder:
- Pear-shaped organ that stores bile.
- Regions are fundus, body and neck.
- Cystic duct is continuous with the neck.
- Fundus is normally located near the tip of the 9th costal cartilage.
Biliary tree:
- Right and left hepatic ducts join to form the common hepatic duct.
- Cystic duct joins common hepatic duct to form the bile duct.
- Bile duct usually joins pancreatic duct before opening into the second part of the duodenum.
Hepatopancreatic ampulla: The bile duct and main pancreatic duct usually join at the ampulla of Vater in the wall of the second part of the duodenum.
Sphincter of Oddi: Surrounds the terminal bile duct and pancreatic duct region, regulating flow into the duodenum.
Duodenal papillae:
- Major duodenal papilla receives the main biliary and pancreatic drainage.
- Minor duodenal papilla is also located in the second part of the duodenum.
Hepatic portal system:
- Carries nutrient-rich blood from gastrointestinal organs to the liver.
- Splenic vein and superior mesenteric vein unite posterior to the neck of the pancreas to form the hepatic portal vein.
- Hepatic portal vein enters the liver at the porta hepatis.
Porto-systemic anastomoses: Connections between portal venous drainage and systemic venous drainage.
Portal hypertension: Raised portal pressure can force blood through collateral channels instead of normal hepatic recovery.
Sites of porto-systemic anastomosis:
- Gastro-oesophageal junction: left gastric vein to azygos tributaries.
- Umbilicus: para-umbilical veins to anterior abdominal wall veins.
- Ano-rectal junction: superior rectal vein to middle and inferior rectal veins.
Clinical relevance:
- Gastro-oesophageal varices may develop at the gastro-oesophageal junction.
- Caput medusae may develop around the umbilicus.
- Anorectal varices may develop at the ano-rectal junction.

Key roles of proteins:
- Structural support, e.g. collagen.
- Enzymes that catalyse chemical reactions.
- Transport proteins, e.g. albumin and transferrin.
- Protection through immune proteins such as antibodies.
- Hormones, receptors, storage proteins and contractile proteins.
Amino acids:
- There are 20 amino acids used in the human body.
- All contain an amino group and an acidic carboxyl group.
- 10 amino acids are essential and must come from the diet.
- Non-essential amino acids are still required for protein formation but can be synthesised by the body.
Peptide bonds: Amino acids are joined by covalent peptide bonds, releasing water and forming polypeptide chains.
Absorption and transport:
- Proteins are largely absorbed in the ileum as amino acids via secondary active transport.
- Normal blood amino acid levels are approximately 35–65 mg/dL.
- Excess circulating amino acids are rapidly taken up by cells.
- Amino acids are reabsorbed in proximal renal tubules, but excess can be lost in urine.
Amino acid storage:
- Free amino acids cannot be stored like glucose or fatty acids.
- They rapidly form peptides and intracellular proteins.
- The liver has a large capacity for storing proteins, with kidney and intestinal mucosa also contributing.
Protein turnover: Body proteins are constantly broken down and rebuilt, allowing amino acids to be redistributed between tissues.
Plasma proteins:
- Albumin maintains plasma oncotic pressure.
- Globulins support innate and acquired immunity.
- Transferrin transports iron.
- Fibrinogen supports clot formation.
Liver protein metabolism:
- Transamination: synthesis of non-essential amino acids.
- Deamination: amino acid degradation and energy generation.
- Oxidation: conversion into energy via gluconeogenesis or ketogenesis.
- Excretion: nitrogen disposal through the urea cycle.
Transamination: An amino group is transferred from an amino acid to an alpha-keto acid using aminotransferases, with vitamin B6 as an important cofactor.
Deamination: Removes amino groups from amino acids; excess amino acids can then be used for energy or converted into glucose, ketone bodies or fat.
Urea formation:
- Ammonia released during amino acid catabolism is toxic.
- Ammonia is converted into urea in the liver.
- Urea is excreted mainly by the kidneys.
Urea cycle mnemonic: Orange Coloured Cats Always Ask For Awesome Umbrellas.
Inborn errors:
- Citrullinaemia: urea cycle defect causing ammonia accumulation.
- Tyrosinaemia: tyrosine metabolism defect causing liver and neurological disease.
- Phenylketonuria: phenylalanine hydroxylase defect causing CNS damage if untreated.
Hormonal control:
- Growth hormone promotes protein synthesis and amino acid transport.
- Insulin promotes amino acid uptake and inhibits protein breakdown.
- Glucocorticoids increase protein breakdown and circulating amino acids.
- Thyroxine increases metabolic activity and can promote either protein synthesis or breakdown depending on energy availability.
Nitrogen balance:
- Positive nitrogen balance: intake exceeds loss; seen in growth, pregnancy and recovery.
- Negative nitrogen balance: loss exceeds intake; seen in starvation, cachexia, burns, trauma and sepsis.
Measurement: Nitrogen balance is estimated using dietary protein intake and 24-hour urinary nitrogen measurement.
Energy relationship: During starvation, carbohydrate stores are used first, then fat stores; protein is increasingly depleted during chronic starvation.

Purpose of allocations: The clinical allocation system creates a three-year clinical placement journey across Years 3, 4 and 5.
Core principles:
- Fairness in distance from QUB.
- Fairness in exposure to different hospitals and Trusts.
- Fair geographical variety of placements.
How schedules are generated:
- An algorithm creates schedules covering groups, locations and timings.
- Schedules are assigned according to venue capacity.
- Each schedule is scored year-by-year to support fairness across the full clinical journey.
- Year 2 students are randomly assigned a generated schedule.
Swapping system:
- Students may swap after allocations are released.
- Whole schedules can be swapped.
- Students cannot normally swap individual specialties or individual years.
Year 3 placements:
- Students undertake two Longitudinal Integrated Clerkships.
- One LIC takes place in Belfast Trust.
- One LIC takes place in a peripheral Trust.
- Students also attend GP teaching and cardiac simulation training.
Year 4 placements:
- Students are assigned to a timetable group and base Trust or hospital.
- Rotations include specialties such as Ageing and Health, Child Health, Emergency Medicine, General Practice, Mental Health and Reproductive Health.
- Students return to QUB for mandatory face-to-face teaching during pillar weeks.
Year 5 placements:
- Students rotate through GP, Medicine, Surgery and Assistantship.
- Medicine and Surgery are usually linked to one Trust.
- Assistantship may be allocated to another Trust.
- Palliative care, Hospital at Home and eALS experiences may occur across the province.
Trust responsibilities: Trust Sub-Deaneries produce detailed daily timetables and provide information about hospital sites and accommodation.
Accommodation:
- Accommodation is usually available at most peripheral hospital sites.
- Students normally still need a Belfast base.
- Students may be able to claim a travel bursary instead of accommodation.
Self-directed learning weeks:
- SDL weeks are scheduled to support teaching delivery.
- They cannot normally be moved.
- They may help accommodate remedial teaching or catch-up opportunities where possible.
Pre-allocation principle: Most students follow the standard system, but a small number with exceptional circumstances may be considered for pre-allocation to specific Trust areas.
Pre-allocation locations:
- Year 3: one LIC in Belfast Trust and one LIC in the pre-allocated Trust.
- Year 4: all year in the pre-allocated Trust.
- Year 5: one clinical period or assistantship in the pre-allocated Trust and one period in another Trust.
Important limits:
- Travel, accommodation and employment are not covered by pre-allocation.
- Allocation is to a Trust area, not a guaranteed hospital.
- General Practice attachments are not currently covered.
- Allocations depend on available placement capacity.
Possible pre-allocation categories:
- Parental or caring responsibilities.
- Health-related issues.
- Disability-related circumstances recorded through accessible learning support.
- Elite athlete status supported by Queen’s Sport evidence.
Key takeaway: Students should consider their circumstances early because clinical years involve multiple Trust sites, travel and changing placement patterns.

Overall role: The liver acts as a major metabolic, storage, detoxification and excretory organ.
Functional anatomy:
- The liver is the largest internal organ.
- It receives a large blood supply, around 25% of resting cardiac output.
- The hepatic portal vein supplies nutrient-rich “food soup” blood from the gut.
- The hepatic artery supplies oxygenated blood.
Blood flow:
- Portal venous flow increases after meals.
- The hepatic circulation is low resistance.
- The liver can act as a capacitance vessel.
Classical lobule:
- Arranged like a bicycle wheel.
- Central vein forms the hub.
- Portal triads form the rim.
- Blood flows from portal triads toward the central vein.
- Bile flows in the opposite direction, from hepatocytes toward portal triads.
Acinus concept:
- More physiologically useful than the classical lobule.
- Places the portal triad at the centre of function.
- Divides liver tissue into zones 1, 2 and 3 based on oxygen and nutrient exposure.
Metabolic functions:
- Carbohydrate metabolism.
- Fat metabolism.
- Protein metabolism.
- Detoxification.
- Pathogen clearance.
- Bile production.
Glucose buffer:
- The liver stores approximately 100 g of glycogen.
- After meals, it removes excess glucose from blood and stores it.
- Between meals and during starvation, it releases glucose to maintain blood glucose levels.
Fat metabolism:
- Handles triglycerides, phospholipids and cholesterol.
- Forms lipoprotein complexes such as LDL and HDL for lipid transport.
- Supports cholesterol handling and fat-soluble molecule transport.
Protein metabolism:
- The liver synthesises plasma proteins such as albumin and clotting factors.
- It deaminates amino acids.
- It converts toxic ammonia into urea for renal excretion.
Vitamin storage and activation:
- Stores fat-soluble vitamins A, D, E and K.
- Stores vitamin B12.
- Hydroxylates vitamin D to 25-hydroxycholecalciferol before kidney activation.
Detoxification:
- Kupffer cells phagocytose material from blood.
- The liver detoxifies cholesterol, drugs, alcohol, poisons, trace metals, steroids and ammonia.
- Fat-soluble compounds can be converted into more water-soluble forms for excretion.
Bile composition:
- Bile pigments.
- Bile acids.
- Other solutes in an alkaline medium.
Bile functions:
- Excretes haemoglobin degradation products.
- Aids fat digestion by promoting micelle formation.
- Provides a route for waste excretion.
Enterohepatic circulation: Most bile and bile salts are recycled between intestine and liver.
Gallstones:
- May consist of cholesterol crystals or calcium bilirubinate.
- Gallbladder concentrates bile.
- Micelle composition helps determine whether cholesterol precipitates.
Jaundice:
- Caused by excess free or conjugated bilirubin in blood.
- Pre-hepatic: excess bilirubin production.
- Hepatic: impaired uptake, conjugation or canalicular transport.
- Post-hepatic: bile duct or gallbladder obstruction.

Functional reserve: The liver has a large reserve; around 80–90% of hepatic function may be lost before clinical liver failure becomes apparent.
Regeneration: Hepatocytes are conditionally renewing cells and can divide when needed, allowing liver regeneration after partial hepatectomy.
Portal tract structures:
- Portal vein branch.
- Hepatic artery branch.
- Bile duct.
- Adjacent hepatocytes and sinusoids.
Steatosis:
- Fatty change within hepatocytes.
- Can be microvesicular or macrovesicular.
- Represents reversible cell injury.
Steatohepatitis:
- Fat accumulation with accompanying inflammatory change.
- May occur with alcohol-related disease, metabolic dysfunction-associated steatotic liver disease or drug-related injury.
- Repeated injury and chronic inflammation can lead to fibrosis.
- Mallory bodies or Mallory hyaline may be seen histologically.
Fibrosis assessment: FibroScan measures liver stiffness as a surrogate marker of fibrosis and can also estimate steatosis.
Cirrhosis:
- Diffuse liver process defined by fibrous septa and structurally abnormal nodules.
- End-stage result of many progressive liver diseases.
- Distorts hepatic architecture and impairs liver function.
Complications of decompensated liver disease:
- Jaundice due to impaired bilirubin handling.
- Coagulopathy due to impaired clotting factor synthesis.
- Encephalopathy due to hyperammonaemia.
- Ascites due to low albumin and portal hypertension.
- Splenomegaly due to portal hypertension.
- Gastrointestinal bleeding from oesophageal varices.
Stigmata of chronic liver disease:
- Caput medusae.
- Splenomegaly.
- Ascites.
- Leukonychia.
- Flapping tremor.
Viral hepatitis:
- Many viruses can infect liver cells, including HSV, EBV and CMV.
- Hepatotropic viruses specifically target hepatocytes.
- Most acute viral hepatitis reflects liver cell inflammation and death.
- Hepatitis B and C can also cause chronic hepatitis.
Hepatitis A:
- Self-limiting disease with 2–6 week incubation.
- Spread faecal-orally.
- Not associated with chronic hepatitis, cirrhosis or carrier state.
Hepatitis B:
- Spread through blood and sexual transmission.
- May cause acute hepatitis, fulminant hepatitis, chronic hepatitis, cirrhosis and hepatocellular carcinoma.
- Carrier state can occur.
- Vaccination and screening are important prevention tools.
Hepatitis C:
- Spread through contaminated blood, tattoos, injecting drug use and historical blood products.
- Initial infection may be asymptomatic.
- Can progress to chronic hepatitis and cirrhosis.
Autoimmune liver diseases:
- Autoimmune hepatitis: chronic hepatitis, often female predominance, raised IgG and autoantibodies such as anti-smooth muscle antibodies.
- Primary biliary cholangitis: autoimmune destruction of intrahepatic bile ducts, often anti-mitochondrial antibody positive.
- Primary sclerosing cholangitis: inflammatory destruction of intrahepatic and extrahepatic ducts with beading on MRCP or ERCP.
Inherited/metabolic liver disease:
- Haemochromatosis: iron overload causing liver damage, pancreatic injury, cardiomyopathy, pigmentation and loss of libido.
- Wilson’s disease: copper metabolism defect causing copper accumulation in liver, basal ganglia and eye with low caeruloplasmin.
Liver tumours:
- Hepatocellular carcinoma is a primary malignant tumour of hepatocytes and may raise alpha-fetoprotein.
- Cholangiocarcinoma arises from bile duct epithelium and may be intrahepatic or extrahepatic.
- Perihilar cholangiocarcinomas at the duct bifurcation are called Klatskin tumours.

Main topic: Infectious causes of jaundice include viral hepatitis, biliary tract infection, liver abscesses and zoonotic or vector-borne infections.
Common hepatitis viruses:
- Hepatitis A and E are commonly faecal-orally transmitted.
- Hepatitis B, C and D are mainly blood-borne or vertically transmitted.
- Other viruses, especially EBV and CMV, can also cause hepatitis.
Hepatitis A:
- Endemic worldwide.
- Usually food-borne, but person-to-person spread can occur.
- Vaccine preventable.
- Diagnosed by serology.
Hepatitis E:
- Often water-borne.
- Classically associated with Asia.
- Carrier state is possible.
- Diagnosed by serology.
Hepatitis C:
- Classically spread through blood or blood-contaminated equipment.
- Different serotypes affect prognosis and treatment.
- Long-term complications include cirrhosis, liver failure and liver cancer.
- Diagnosed using serology and RNA PCR.
- No vaccine; treated with direct-acting antivirals.
Hepatitis B:
- DNA virus with reverse polymerase.
- Spread by mother-to-child transmission, blood and sexual contact.
- Acute jaundiced infection usually resolves in adults.
- Chronic infection is more likely when acquired young.
- Surface, core and e antigens are used in serological diagnosis.
- Preventable through vaccination, blood screening and antenatal screening.
Hepatitis D: Defective virus that requires hepatitis B surface antigen to bud from hepatocytes.
Biliary tract infection pathophysiology:
- Static bile provides a good medium for bacterial growth.
- Obstruction may arise from inside or outside the bile ducts.
- Acute stress responses can slow bile flow.
Biliary tract infection presentation:
- Cholecystitis or cholangitis.
- Pain and tenderness.
- Jaundice.
- Signs of sepsis.
Biliary tract infection management:
- Source control.
- ERCP where appropriate.
- Samples before antibiotics.
- Broad-spectrum antibiotics such as beta-lactam/beta-lactamase inhibitor combinations.
Liver abscess pathogenesis:
- Bacteria may reach the liver from the GI tract through portal circulation.
- Can involve Gram-positive, Gram-negative and anaerobic organisms.
- Entamoeba histolytica can cause dysentery and amoebic liver abscess.
- Echinococcus granulosus can cause hydatid cysts.
Liver abscess management:
- Consider the aetiology.
- Achieve source control.
- Consider drainage.
- Use prolonged high-dose broad-spectrum antibiotics if polymicrobial infection is not drained.
- Amoebic disease is treated with anti-amoebic therapy.
Vector-borne infection: Infection transmitted by an arthropod, such as a mosquito.
Zoonosis: Infection with a non-human animal source; humans are often dead-end hosts.
Examples causing jaundice:
- Malaria.
- Dengue and other arboviruses.
- Q fever.
- Leptospirosis.
- Brucellosis.
- Viral haemorrhagic fevers.
Leptospirosis:
- Caused by Leptospira interrogans.
- Zoonotic and classically associated with rat urine contamination.
- Risk groups include sewerage workers and triathletes.
- Can cause a biphasic flu-like illness followed by jaundice, thrombocytopenia and renal failure.
Disease notification:
- A fundamental pillar of public health medicine.
- Supports recognition of epidemic potential, food-borne threats, rare serious infections and imported infections.
- Allows public health action, contact tracing and prevention of spread.

Lecture focus: Drug treatment of dyspepsia, peptic ulcer disease, Helicobacter pylori infection and constipation.
Peptic ulcer definition: A defect in gastric or duodenal mucosa caused by imbalance between peptic acid secretion and mucosal defence.
Principles of PUD therapy:
- Relieve pain.
- Promote ulcer healing.
- Prevent relapse and complications.
- Investigate those at increased risk of gastric carcinoma because treatment may mask early symptoms.
Aetiological factors:
- Helicobacter pylori infection.
- NSAIDs.
- Aspirin, corticosteroids and bisphosphonates.
- Smoking, alcohol and caffeine.
- Severe physiological stress.
- Rare hypersecretory states.
General treatment approach:
- Remove irritants, especially NSAIDs.
- Eradicate H. pylori if present.
- Use antacids, proton pump inhibitors, H2 receptor antagonists and antibiotics where appropriate.
Antacids:
- Provide symptomatic relief by raising gastric pH.
- Reduce proteolytic activity.
- Often contain aluminium and magnesium salts.
- Sodium bicarbonate acts quickly but may cause metabolic alkalosis, sodium/water retention and renal stones.
Proton pump inhibitors:
- Examples: omeprazole, lansoprazole, pantoprazole and esomeprazole.
- Irreversibly inhibit the H⁺/K⁺-ATPase proton pump.
- Used for dyspepsia, PUD and reflux oesophagitis/GORD.
- Very effective and generally well tolerated.
PPI cautions:
- May mask gastric cancer symptoms.
- Common adverse effects include GI disturbance and headache.
- Important adverse effects include C. difficile risk, hyponatraemia, hypomagnesaemia, hepatitis, interstitial nephritis and blood disorders.
- Omeprazole and esomeprazole can interact with warfarin and clopidogrel through CYP450 effects.
- Stopping after prolonged use may cause rebound acid hypersecretion.
H2 receptor antagonists:
- Examples include cimetidine, famotidine and nizatidine.
- Competitively antagonise H2 receptors on parietal cells.
- Reduce basal and stimulated acid output.
- Used as second-line agents for PUD and reflux oesophagitis.
Cimetidine:
- Can cause diarrhoea, confusion and gynaecomastia.
- Potent inhibitor of cytochrome P450 metabolism.
H. pylori:
- Gram-negative bacillus associated with most duodenal ulcers and many gastric ulcers.
- Can be associated with gastric cancer and MALT lymphoma.
- Produces urease, converting urea to ammonia and carbon dioxide, weakening mucosal protection.
H. pylori testing:
- Urea breath test.
- Stool antigen test.
- Validated serology.
- Endoscopy with biopsy and rapid urease test.
- PPIs and antibiotics should be withheld before testing to reduce false negatives.
H. pylori eradication:
- PPI or H2RA plus amoxicillin and clarithromycin or metronidazole.
- Triple therapy is usually given for 7 days.
- Large or complicated ulcers may need prolonged acid suppression.
- Second-line therapy should use different antibiotics.
NSAID-induced ulcers:
- Withdraw NSAID if bleeding occurs.
- High-risk patients needing NSAIDs should receive PPI or H2RA protection.
- H. pylori positive patients should receive eradication before starting NSAIDs.
Urgent upper GI endoscopy:
- Acute bleeding.
- Chronic bleeding or iron deficiency anaemia.
- Weight loss.
- Dysphagia.
- Persistent vomiting.
- Unexplained persistent dyspepsia, especially age 55+.
Constipation management:
- Increase fluid intake, mobility and dietary fibre unless opioid-related.
- Stop or adjust constipating drugs where possible.
- Exclude underlying pathology.
Laxative types:
- Bulk-forming laxatives, e.g. fibre/Fybogel: swell and distend the colon.
- Osmotic laxatives, e.g. macrogols, lactulose and magnesium salts: draw water into bowel.
- Stimulant laxatives, e.g. bisacodyl, senna and glycerol: stimulate the enteric nervous system.
- Faecal softeners, e.g. docusate: soften stools and can have stimulant effects.
Opioid-induced constipation: Avoid bulk-forming laxatives; use an osmotic laxative plus a stimulant laxative or docusate where appropriate.

Lecture focus: How liver disease affects drug handling, prescribing safety, hepatotoxic drugs and pharmacological treatment of liver failure complications.
LFTs are a misnomer:
- ALP and GGT suggest obstructive or cholestatic patterns.
- AST and ALT suggest hepatitic patterns.
- Bilirubin may also be measured.
- True liver synthetic function is better assessed using PT/INR and albumin.
First-pass metabolism: Oral drugs may be metabolised in gut wall and liver before reaching systemic circulation, affecting bioavailability.
Phase 1 metabolism:
- Uses cytochrome P450 monooxygenase enzymes.
- Involves oxidation, reduction and hydrolysis.
- Creates more chemically reactive metabolites.
- Products may be active, inactive, toxic or carcinogenic.
- Prepares molecules for Phase 2 conjugation.
Phase 2 metabolism:
- Conjugation usually makes drugs inactive and more water soluble.
- Substituent groups include glucuronyl, sulphate, methyl, acetyl, glycyl and others.
- Products are excreted in urine or bile.
Enzyme induction:
- Increases CYP isoenzyme activity by increased synthesis or reduced breakdown.
- Mnemonic: PC BRAGS.
- Examples include phenytoin, carbamazepine, smoking, barbiturates, rifampicin, alcohol, griseofulvin and St John’s wort.
Enzyme inhibition:
- Can increase levels of drugs metabolised by the inhibited pathway.
- Examples include ciprofloxacin, amiodarone, fluoxetine, azole antifungals and erythromycin.
Hepatotoxic drugs:
- Alcohol.
- Excess paracetamol.
- Isoniazid.
- Statins.
- Methotrexate.
- Amiodarone.
- Chlorpromazine.
- Halothane.
Paracetamol toxicity:
- Normally safe at therapeutic doses.
- Overdose overwhelms conjugation pathways.
- Excess is oxidised to toxic NAPQI.
- NAPQI can cause severe hepatic injury and liver failure.
Manifestations of cirrhosis:
- Ascites.
- Encephalopathy.
- Coagulopathy.
- Hepatorenal syndrome.
- Varices and portal hypertension.
Severity scoring: Child-Turcotte-Pugh classification grades cirrhosis severity from class A to C.
Ascites management:
- Non-pharmacological: sodium restriction, paracentesis, catheter drainage and TIPS.
- Pharmacological: diuretics.
- Spironolactone blocks aldosterone receptors in the distal tubule.
- Furosemide inhibits the Na/K/2Cl transporter in the loop of Henle.
Hepatic encephalopathy:
- May involve excess ammonia not converted to urea.
- May also involve excess GABA or neurosteroids.
- Treat precipitants such as infection, GI bleeding, constipation and metabolic disturbance.
Encephalopathy drug treatment:
- Lactulose promotes movement of ammonia into the gut lumen and reduces intestinal ammonia production.
- Rifaximin reduces gut bacterial ammonia generation and may reduce recurrent encephalopathy.
- Thiamine replacement may be needed in malnutrition or alcohol-related disease.
Coagulopathy:
- Increased prothrombin time reflects impaired clotting factor production.
- Vitamin K may be used but may fail if absorption or synthetic function is poor.
- Clotting factors may need replacement during active bleeding.
Hepatorenal syndrome:
- Multifactorial renal failure in advanced liver disease.
- Partly related to splanchnic vasodilation and altered vascular resistance.
- Terlipressin, a vasopressin analogue, may be used and is also relevant in variceal bleeding.
Prescribing caution:
- Low albumin increases free active drug levels for highly protein-bound drugs.
- Reduced metabolism causes accumulation of parent drugs and active metabolites.
- Diazepam is generally avoided in liver failure because it is protein-bound, long-acting and has active metabolites that can precipitate encephalopathy.

Case scenario: Alex, a 25-year-old university student, returned from Malawi and developed jaundice four weeks later.
Session plan:
- Review the case.
- Highlight key consultation elements.
- Classify jaundice and consider causes.
- Review viral hepatitis types and transmission.
- Apply GCAT theme considerations.
Consultation themes:
- Lay referral and how patients seek advice.
- Risk history for jaundice.
- Signs to look for on abdominal examination.
- Safe and clear delivery of results.
- Managing catastrophising and information from “Dr Google”.
Relationship-centred care:
- Consider the doctor-patient relationship.
- Recognise unconscious bias.
- Recognise LGBTQIA+ barriers and health inequalities.
Jaundice classification:
- Pre-hepatic: increased bilirubin production before liver processing.
- Hepatic: liver cell dysfunction or impaired bilirubin processing.
- Post-hepatic: obstruction of bile flow after bilirubin conjugation.
Clinical approach to jaundice:
- Use history, examination and investigations together.
- Interpret liver blood test patterns.
- Consider travel, sexual, drug, transfusion and exposure history.
- Assess for abdominal signs and systemic illness.
Bilirubin metabolism:
- Haemoglobin breakdown produces bilirubin.
- The liver conjugates bilirubin.
- Bile excretes conjugated bilirubin into the gut.
- Patterns of bilirubin abnormality help classify jaundice.
Viral hepatitis overview:
- Main types are A, B, C, D and E.
- Transmission routes differ by virus.
- Some cause acute self-limiting illness; others can cause chronic disease.
- Chronic hepatitis can lead to cirrhosis and hepatocellular carcinoma.
Hepatitis B markers:
- HBsAg and HBeAg suggest active infection.
- Persistent HBsAg suggests chronic infection.
- Anti-HBc suggests recent or previous infection.
- Anti-HBs indicates immunity.
- HBV DNA PCR measures viral load.
Global and population health:
- Notifiable diseases and the role of Public Health.
- Contact tracing and its importance.
- Impact of international borders and differing legality.
- Providing information and advice to patients and close contacts.
- Diagnostic approach to infection in the returning traveller.
Clinical science and practice:
- Use of Electronic Care Record or Encompass.
- History, examination and investigation planning.
- Consideration of drug prescribing in liver impairment.
Achieving good medical practice:
- Maintain confidentiality.
- Support patient wellbeing and resilience.
- Provide reliable information and signposting.
Teamwork for safe care:
- Communicate clearly with the wider team.
- Label infectious bodily fluid samples safely.
- Coordinate referrals between primary and secondary care.
- Liaise with Public Health teams when required.
Psychological considerations:
- Sex and gender can influence healthcare experiences.
- LGBTQIA+ people may experience barriers, inequities and reluctance to disclose full histories.
- Patients may fear liver cancer due to incomplete or misunderstood online information.
- Anxiety, hypervigilance and catastrophising should be addressed empathetically.
Essential learning: Define jaundice, classify causes, explain haemoglobin-bilirubin metabolism, recognise infective hepatic jaundice and interpret hepatitic versus cholestatic blood test patterns.

Endocrine organs:
- Collections of glands widely separated from each other.
- Essential for homeostasis, growth and development.
- Consist of secretory epithelial cells surrounded by capillary networks.
- Release hormones into the bloodstream to act on target tissues.
Development of endocrine glands:
- Begin as down-growing epithelial buds.
- Develop by separating from surface epithelium.
- The isolated cell mass then acquires its own blood supply.
Pituitary gland:
- Also called the hypophysis or “master gland”.
- Small ovoid organ attached to the hypothalamus by the infundibular stalk.
- Located in the sella turcica of the sphenoid bone.
- Enclosed by a connective tissue capsule.
Pituitary parts:
- Anterior pituitary: adenohypophysis.
- Posterior pituitary: neurohypophysis.
- These regions are histologically distinct.
Pituitary development:
- Anterior pituitary develops from Rathke’s pouch from buccal ectoderm.
- Posterior pituitary develops from neuroectoderm.
Anterior pituitary cells:
- Somatotrophs produce growth hormone.
- Mammotrophs produce prolactin.
- Corticotrophs produce ACTH.
- Thyrotrophs produce TSH.
- Gonadotrophs produce FSH and LH.
Posterior pituitary:
- Pale staining region made of unmyelinated axons.
- Axons arise from supraoptic and paraventricular nuclei of the hypothalamus.
- Stores and releases hypothalamic neurosecretory products.
Hypothalamo-pituitary link:
- The hypothalamus links the nervous and endocrine systems.
- The anterior pituitary is regulated via the hypophyseal portal system.
- The posterior pituitary is directly connected by hypothalamic axons.
Thyroid gland:
- Bilobed gland on the anterior and lateral surface of the upper trachea.
- Highly vascular.
- Parathyroid glands sit posteriorly and regulate calcium levels.
- Goitre is thyroid enlargement and may be associated with hypo- or hyperthyroidism, cancer, iodine deficiency or autoimmune disease.
Thyroid histology:
- Composed of spherical follicles.
- Follicles are lined by simple cuboidal epithelium.
- Colloid stores thyroglobulin.
- C cells produce calcitonin.
Thyroid hormone production:
- Follicular cells produce thyroglobulin.
- Thyroglobulin is stored as colloid.
- TSH stimulates reabsorption and breakdown of thyroglobulin into T3 and T4.
- T3 and T4 are released into the bloodstream.
Colloid patterns:
- Hyperthyroidism is associated with reduced colloid.
- Hypothyroidism is associated with increased colloid.
Adrenal glands:
- Also called suprarenal glands.
- Highly vascular and surrounded by connective tissue capsule.
- Located in perirenal fat at the superior poles of the kidneys.
- Contain cortex and medulla.
Adrenal cortex:
- Zona glomerulosa: produces mineralocorticoids such as aldosterone.
- Zona fasciculata: produces glucocorticoids such as cortisol under ACTH control.
- Zona reticularis: produces androgens.
Adrenal medulla: Produces catecholamines, including adrenaline and noradrenaline, for “fight or flight” responses.
Endocrine pancreas:
- Islets of Langerhans form the endocrine component of the pancreas.
- Alpha cells secrete glucagon.
- Beta cells secrete insulin.
- Delta cells secrete somatostatin.
- F cells secrete pancreatic polypeptide.
GEP system:
- Gastro-entero-pancreatic endocrine system includes islets and enteroendocrine cells.
- Enteroendocrine cells are diffusely arranged in GI epithelium.
- They secrete peptide hormones controlling gut function.
Examples of GEP hormones:
- Gastrin stimulates gastric acid secretion.
- CCK stimulates gallbladder contraction.
- Motilin stimulates gastric and intestinal motility.
- Secretin stimulates pancreatic secretion and inhibits gastric acid secretion.

Reflux oesophagitis:
- Caused by regurgitation of gastric contents into the lower oesophagus.
- Associated with lower oesophageal sphincter incompetence and increased intra-abdominal pressure.
- Symptoms include heartburn, waterbrash and odynophagia.
Barrett’s oesophagus:
- Metaplastic replacement of normal squamous oesophageal epithelium by columnar or glandular epithelium.
- Usually intestinal type with goblet cells.
- Associated with chronic gastro-oesophageal reflux.
- Increases risk of oesophageal adenocarcinoma.
Oesophageal adenocarcinoma:
- Commonest in the distal third of the oesophagus.
- Incidence is increasing in Western countries.
- Risk factors include obesity, high BMI, reflux disease and Barrett’s oesophagus.
Oesophageal squamous cell carcinoma:
- Commonest in the middle third of the oesophagus.
- Commonest oesophageal cancer type globally, especially in parts of Asia and Iran.
- Risk factors include alcohol, tobacco, betel nuts, achalasia and tylosis.
Helicobacter pylori and gastritis:
- H. pylori induces gastric mucosal inflammation.
- In duodenal ulcer disease, inflammation is often most pronounced in the antrum.
- H. pylori is linked to chronic gastritis, peptic ulcer disease and gastric cancer risk.
Gastric cancer symptoms:
- Persistent indigestion.
- Stomach pain.
- Early satiety.
- Weight loss.
- Loss of appetite.
Intestinal-type gastric adenocarcinoma:
- Often forms gland-like structures.
- More likely to be associated with environmental risk factors and chronic gastritis pathways.
- May present as a mass lesion.
Diffuse-type gastric adenocarcinoma:
- Less cohesive tumour cells infiltrate the stomach wall.
- Can produce linitis plastica.
- May present with reduced stomach distensibility and early satiety.
Coeliac disease:
- Immune-driven enteropathy due to dietary gluten.
- Has widespread extra-gastrointestinal effects.
- Diagnosed using high anti-transglutaminase titres and positive anti-endomysial antibodies.
- Biopsy shows villous atrophy and lymphocytic infiltrates.
- Lifelong gluten-free diet can normalise small bowel histology and function.
Small bowel tumours:
- Carcinoid, now called well-differentiated neuroendocrine tumour, is the commonest small bowel tumour.
- Neuroendocrine tumours may cause carcinoid syndrome through hormonally active peptides.
- Small bowel adenocarcinoma is rare compared with colorectal adenocarcinoma.
- Small bowel can be a site of metastatic carcinoma.
- Small bowel lymphomas can occur as a complication of coeliac disease.
GIST:
- Gastrointestinal stromal tumours are spindle cell or mesenchymal tumours.
- Can occur throughout the GI tract.
- Behaviour ranges from indolent to aggressive depending on site, size and mitotic activity.
- Small bowel GISTs are often more aggressive than small incidental gastric GISTs.
- Can metastasise through the peritoneal cavity and liver.
Inflammatory bowel disease:
- Chronic idiopathic inflammatory bowel disease has multifactorial aetiology.
- Common in Western and developed populations.
- Diagnosis requires exclusion of infections and medication reactions.
Crohn’s disease:
- Can affect any part of the GI tract.
- Typically causes transmural inflammation.
- May produce skip lesions, strictures, fistulae and granulomas.
Ulcerative colitis:
- Limited to colon and rectum.
- Typically involves continuous mucosal inflammation starting at the rectum.
- Can cause bloody diarrhoea and increased colorectal cancer risk in long-standing disease.
Diverticular disease:
- Diverticulum: an outpouching.
- Diverticulosis: presence of diverticula.
- Diverticulitis: inflammation of diverticula.
- Complications include perforation, abscess and fistula formation.
Colorectal adenocarcinoma:
- Fourth commonest cancer in the UK.
- More common in Northern Europe and North America than some low-incidence regions.
- Many cases are linked to preventable lifestyle and environmental factors.
- Risk factors include processed meat, obesity, smoking, alcohol, diabetes, low physical activity and inflammatory bowel disease.
Inherited colorectal cancer risk:
- Lynch syndrome: germline mismatch repair mutation causing microsatellite instability.
- FAP: germline APC mutation causing hundreds of adenomatous polyps and high cancer risk by age 50.
Right-sided colorectal cancer:
- Wide lumen and liquid faeces make obstruction less common.
- Polypoid tumours may ulcerate and cause iron deficiency anaemia or melaena.
- Can spread to abdominal wall, peritoneum, lymph nodes and liver.
Left-sided colorectal cancer:
- Smaller lumen and more solid faeces make obstruction more common.
- Stricturing tumours can cause constipation, diarrhoea, rectal bleeding and tenesmus.
- Can spread locally and metastasise to lymph nodes and liver.

Core concept: The hypothalamus and pituitary form a major neuroendocrine control axis linking the nervous system to endocrine function.
Pituitary anatomy:
- The pituitary sits in the hypophyseal fossa of the sphenoid bone.
- It is connected to the hypothalamus by the infundibulum.
- It has two functionally distinct lobes: posterior pituitary and anterior pituitary.
Posterior pituitary connection:
- Connected to the hypothalamus by a neural pathway.
- Hypothalamic neurons release hormones from their axon terminals in the posterior pituitary.
- Main hormones released are ADH and oxytocin.
Anterior pituitary connection:
- Connected to the hypothalamus by a vascular pathway.
- Hypothalamic hormones enter the hypophyseal portal system.
- These regulate secretion of anterior pituitary hormones.
Oxytocin:
- Stimulates uterine contraction.
- Stimulates milk ejection during lactation.
Antidiuretic hormone:
- Also called vasopressin.
- Increases water permeability and water reabsorption in renal collecting ducts.
- Can act as a vasoconstrictor.
Anterior pituitary hormones:
- GH: growth hormone.
- TSH: thyroid-stimulating hormone.
- ACTH: adrenocorticotrophic hormone.
- FSH and LH: gonadotrophins.
- Prolactin: supports lactation.
Hypothalamic releasing and inhibiting hormones:
- GHRH stimulates GH release.
- Somatostatin inhibits GH release.
- TRH stimulates TSH release.
- CRH stimulates ACTH release.
- GnRH stimulates FSH and LH release.
- Dopamine inhibits prolactin release.
Feedback control:
- Target gland hormones regulate pituitary and hypothalamic output.
- Negative feedback prevents excessive hormone secretion.
- Trophic hormones are modulated by circulating target hormone levels.
Regulatory rhythms: Pituitary hormone secretion may show pulsatile, diurnal or circadian patterns.
Hyposecretion: Low pituitary hormone output causes reduced target gland stimulation and symptoms related to the deficient hormone pathway.
Hypersecretion: Excess pituitary hormone output overstimulates target tissues, producing disease patterns such as growth hormone excess or excess ACTH drive.

Thyroid structure:
- The thyroid gland is made of lobules of spherical follicles.
- Follicles are filled with colloid.
- The primary component of colloid is thyroglobulin.
Basic ingredients: Thyroid hormone synthesis requires tyrosine and iodine.
Hormone synthesis:
- Iodine plus tyrosine forms monoiodotyrosine, or MIT.
- MIT plus iodine forms diiodotyrosine, or DIT.
- DIT plus DIT forms thyroxine, or T4.
- DIT plus MIT forms triiodothyronine, or T3.
T3 vs T4:
- T4 is produced in greater quantity.
- T4 must be converted to T3 for full biological activity.
- T3 is the more biologically active thyroid hormone.
Transport in plasma:
- Thyroid hormones are mostly protein-bound in blood.
- T4 is mainly bound to thyroid-binding globulin, transthyretin and albumin.
- T3 is less tightly bound than T4 and has more free hormone available.
Cellular mechanism:
- Thyroid hormones act mainly through intracellular nuclear receptors.
- T3 binds thyroid hormone receptors and alters gene transcription.
- This changes protein synthesis and cellular metabolic activity.
Metabolic effects:
- Increase oxygen consumption.
- Increase basal metabolic rate.
- Produce a calorigenic effect.
- Increase glucose absorption, glycogenolysis and gluconeogenesis.
- Increase lipolysis and fatty acid oxidation.
- Decrease cholesterol and increase LDL receptor number.
Systemic effects:
- Heart: increases heart rate, cardiac output and systolic blood pressure.
- Lungs: increases ventilation rate.
- GIT: increases appetite, digestive juice secretion and motility.
- Reproductive system: supports normal reproduction and lactation.
- Musculoskeletal system: supports growth, skeletal maturation and muscle function.
- Nervous system: supports neuronal development and adult synaptic activity.
Regulation:
- Hypothalamus releases TRH.
- Anterior pituitary releases TSH.
- TSH stimulates the thyroid gland to produce T3 and T4.
- T3 and T4 provide negative feedback to hypothalamus and pituitary.
TSH actions:
- Increases iodide trapping and binding.
- Promotes thyroglobulin synthesis and secretion into colloid.
- Stimulates thyroid peroxidase synthesis.
- Stimulates T3 and T4 synthesis.
- Promotes colloid endocytosis.
- Increases thyroid follicular cell size, number and blood flow.
Primary thyroid defect: Problem is within the thyroid gland itself.
Secondary thyroid defect: Problem is due to abnormal pituitary TSH production.
Tertiary thyroid defect: Problem is due to abnormal hypothalamic TRH secretion.
Hypothyroidism:
- Low thyroid hormone output reduces metabolic and systemic activity.
- Primary causes include Hashimoto’s thyroiditis, iodine deficiency, enzyme defects or thyroid removal/destruction.
- Congenital hypothyroidism must be diagnosed early because brain and skeletal development can be seriously impaired.
Hyperthyroidism: Excess thyroid hormone causes exaggerated metabolic and sympathetic-like effects.

Adrenal overview:
- The adrenal glands sit superior to the kidneys.
- They have an outer cortex and inner medulla.
- The cortex produces corticosteroids.
- The medulla produces catecholamines.
Adrenal cortex zones:
- Zona glomerulosa: produces mineralocorticoids.
- Zona fasciculata: produces glucocorticoids.
- Zona reticularis: produces adrenal androgens.
Mineralocorticoids:
- Main example is aldosterone.
- Promotes sodium retention and potassium excretion.
- Important for extracellular fluid volume and blood pressure regulation.
Glucocorticoids:
- Main example is cortisol.
- Supports metabolic responses to stress.
- Influences glucose metabolism, protein metabolism, fat metabolism and immune activity.
Adrenal androgens:
- Include DHEA-S and androstenedione.
- Contribute to androgenic effects, especially in females.
Transport in blood:
- Cortisol is mostly bound to corticosteroid-binding globulin, also called transcortin.
- Cortisol is partly albumin-bound and a small fraction is unbound.
- Aldosterone is mainly albumin-bound.
- DHEA-S and androstenedione are highly albumin-bound.
Steroid synthesis:
- All adrenal steroids are derived from cholesterol.
- Enzyme expression differs between adrenal cortical zones.
- Aldosterone synthase supports aldosterone production in the zona glomerulosa.
Regulation of secretion:
- ACTH stimulates cortisol production, mainly in the zona fasciculata.
- Angiotensin II stimulates aldosterone production, mainly in the zona glomerulosa.
- Potassium levels also influence aldosterone secretion.
Intracellular steroid action:
- Steroid hormones are lipid-soluble.
- They cross cell membranes and bind intracellular receptors.
- The hormone-receptor complex alters gene transcription.
- Effects are generally slower onset but longer lasting than many peptide hormone effects.
Clinical relevance:
- Excess cortisol causes Cushing’s syndrome.
- Deficient cortisol production contributes to adrenal insufficiency.
- Excess aldosterone can cause hypertension and hypokalaemia.

Adrenal medulla:
- The inner region of the adrenal gland.
- Functionally related to the sympathetic nervous system.
- Produces catecholamine hormones.
Main catecholamines:
- Adrenaline.
- Noradrenaline.
Physiological role:
- Supports acute “fight or flight” responses.
- Rapidly prepares the body for stress, danger or exertion.
- Acts through target tissue receptors rather than direct neural synapses alone.
Systemic effects:
- Increases heart rate and cardiac contractility.
- Supports redistribution of blood flow during stress.
- Mobilises metabolic fuels.
- Can increase blood glucose availability.
Cellular mechanism:
- Catecholamines are water-soluble signalling molecules.
- They bind to cell surface adrenergic receptors.
- They activate intracellular second messenger pathways.
- Responses are usually rapid compared with steroid hormone effects.
Contrast with adrenal cortex:
- Cortex produces steroid hormones from cholesterol.
- Medulla produces catecholamines.
- Cortical hormones act mainly through intracellular receptors.
- Medullary hormones act mainly through membrane receptors.
Integrated adrenal function:
- The cortex supports longer-term metabolic and volume-regulating responses.
- The medulla supports immediate sympathetic stress responses.
- Together, the adrenal gland coordinates endocrine responses to stress.

Lecture focus: Thyroid hormone synthesis, drug targets, hyperthyroidism treatment, hypothyroidism treatment and drug effects on thyroid function.
Thyroid hormone synthesis targets:
- Iodide uptake into follicular cells.
- Thyroglobulin iodination.
- Coupling reactions forming T3 and T4.
- Endocytosis and secretion of thyroid hormones.
- Peripheral conversion of T4 to T3.
Mechanism of thyroid hormone action:
- Mainly through thyroid nuclear receptors.
- These are part of the superfamily 4 intracellular receptor group.
- Other examples include oestrogen, androgen, vitamin D, glucocorticoid and mineralocorticoid receptors.
Hyperthyroidism treatment principles:
- Treatment choice depends on clinical context and shared decision making.
- Options include anti-thyroid drugs, radioactive iodine and surgery.
- Beta blockers treat early adrenergic symptoms.
Anti-thyroid drugs:
- Carbimazole and propylthiouracil block thyroglobulin iodination.
- They act quickly at the biochemical target, but clinical effects may take weeks because stored hormone remains in colloid.
- Carbimazole is commonly used as “block” or “block and replace” therapy.
- Maintenance treatment may continue for 12–18 months before stopping and monitoring for relapse.
Important anti-thyroid drug warning:
- Patients must be warned about agranulocytosis.
- Sore throat, fever or infection symptoms during treatment require urgent medical review and blood count testing.
Propranolol:
- Controls early symptoms such as tremor, palpitations and anxiety.
- Does not correct the underlying thyroid hormone excess.
Radioactive iodine:
- Radioactive iodine-131 can be used as definitive treatment.
- Often used first-line in some contexts or after relapse.
- Can lead to hypothyroidism requiring replacement therapy.
Surgery:
- May be considered depending on goitre size, malignancy suspicion, relapse or patient preference.
- Requires careful pre-operative control of thyroid status.
Hypothyroidism treatment:
- Treated with levothyroxine replacement.
- Principle is “low and slow”, especially in older patients or those with cardiac disease.
- Dose is adjusted using symptoms and thyroid function monitoring.
Monitoring:
- TSH is the key test in most primary thyroid disease monitoring.
- Free T4 may also guide treatment depending on context.
- Over-replacement can cause symptoms of hyperthyroidism and increase risk of atrial fibrillation or bone loss.
Drugs affecting thyroid function:
- Some drugs affect thyroid hormone synthesis.
- Some affect conversion of T4 to T3.
- Some affect thyroid hormone binding, metabolism or assay interpretation.

Core concept: Calcium homeostasis is maintained by tightly regulated ion transport between the gastrointestinal tract, bone and kidneys.
Calcium input and output:
- Calcium enters through diet and supplements.
- Calcium is stored mainly in bone.
- Calcium is lost primarily through renal excretion.
Total body calcium:
- Total body calcium is approximately 1–2 kg.
- About 99% is stored in the skeleton.
- About 1% is intracellular.
- About 0.1% is extracellular.
Plasma calcium:
- Typical plasma calcium is about 2.5 mmol/L.
- Normal plasma calcium range is approximately 2.35–2.55 mmol/L.
- Only a fraction of plasma calcium is free ionised calcium.
Important variables:
- Albumin concentration affects measured total calcium.
- pH affects ionised calcium availability.
Ionised calcium:
- Ionised calcium is the biologically active form.
- Changes in albumin can alter total calcium without necessarily changing ionised calcium.
- Clinical interpretation must consider protein binding.
Effect of pH:
- As pH decreases, hydrogen ions displace calcium from albumin binding sites.
- This increases the amount of free ionised calcium.
- Alkalosis has the opposite effect and can reduce ionised calcium.
Physiological functions of calcium:
- Formation and maintenance of bones and teeth.
- Glycogen metabolism.
- Protein secretion.
- Plasma membrane integrity.
- Blood coagulation.
Homeostatic organs:
- Gut controls calcium absorption.
- Bone acts as the major calcium reservoir.
- Kidneys control calcium excretion and reabsorption.
Clinical relevance:
- Calcium abnormalities can reflect changes in albumin, pH, renal handling, bone turnover or endocrine regulation.
- Interpreting calcium requires distinguishing total calcium from ionised calcium.

Diabetes mellitus: Abnormal metabolic state characterised by glucose intolerance due to inadequate insulin action.
Type 1 diabetes pathogenesis:
- Often occurs in genetically susceptible children.
- May be triggered by viral infection or immune dysregulation.
- Autoreactive T cells infiltrate pancreatic islets, causing insulitis.
- Beta cells are destroyed, leading to insulin deficiency.
- Autoantibodies may be detectable against beta-cell antigens.
- Clinical onset occurs when beta-cell loss becomes critical, causing hyperglycaemia with or without ketoacidosis.
Type 2 diabetes pathogenesis:
- Complex, multifactorial and polygenic.
- Insulin resistance reduces peripheral tissue response to insulin.
- Beta-cell dysfunction causes inadequate insulin secretion in the face of insulin resistance and hyperglycaemia.
Diabetic complications:
- Macrovascular disease: accelerated atherosclerosis and cardiovascular disease.
- Renal disease: diabetic nephropathy.
- Ophthalmic disease: diabetic retinopathy.
- Neuropathy and infection susceptibility.
- Microangiopathy affecting multiple organs.
Glycation injury:
- Advanced glycation end products contribute to diabetic complications.
- HbA1c acts as a surrogate marker of glycaemic control.
- Better glycaemic control reduces complication risk.
Pituitary adenomas:
- May cause hormone excess syndromes.
- May compress surrounding structures.
- Growth hormone adenomas in adults cause acromegaly.
- Growth hormone excess before epiphyseal fusion causes gigantism.
Hypopituitarism:
- Anterior pituitary hypofunction may cause amenorrhoea, infertility, hypothyroidism and hypoadrenalism.
- Posterior pituitary syndromes are often hypothalamic in origin.
- Loss of ADH production can cause diabetes insipidus.
Hashimoto’s thyroiditis:
- Common cause of hypothyroidism.
- Shows lymphocytic infiltration with reactive lymphoid follicles.
- Follicular epithelial cells may show Hurthle cell change.
Hyperthyroid pathology:
- Includes Graves’ disease and toxic nodular disease.
- May cause goitre and systemic features of excess thyroid hormone.
Thyroid cancer:
- Main types include papillary, follicular, medullary and anaplastic carcinoma.
- Behaviour varies from indolent to highly aggressive.
- Histological type strongly affects prognosis.
Cushing’s syndrome:
- Clinical syndrome due to hypercortisolism.
- Most often due to an ACTH-producing pituitary microadenoma, called Cushing’s disease.
- Can also result from adrenal cortical neoplasms, adrenal cortical hyperplasia or ectopic ACTH-like peptide production.
Conn’s syndrome:
- Primary hyperaldosteronism.
- Associated with bilateral nodular adrenal hyperplasia or adrenal adenoma.
- Causes hypertension and hypokalaemia.
Addison’s disease:
- Primary adrenal insufficiency.
- Causes deficient adrenal cortical hormone production.
- Can present with fatigue, hypotension, electrolyte disturbance and pigmentation depending on cause.
Secondary hypoadrenalism:
- Results from deficient ACTH stimulation of the adrenal cortex.
- Adrenal gland itself may be structurally intact.
Hyperparathyroidism:
- Important cause of hypercalcaemia.
- Approximately 90% is associated with parathyroid adenoma.
- A smaller proportion is associated with parathyroid hyperplasia.
- May occur with Multiple Endocrine Neoplasia syndromes.
- Secondary hyperplasia can occur in chronic renal failure.

Diabetes definition: Diabetes mellitus is a metabolic disorder characterised by chronic hyperglycaemia with disturbed carbohydrate, fat and protein metabolism due to defects in insulin secretion, insulin action or both.
Late complications:
- Microvascular disease: retinopathy and nephropathy.
- Macrovascular disease: atherosclerosis.
- Neuropathy.
Type 1 vs Type 2 diabetes:
- Type 1 usually begins in childhood or puberty and involves beta-cell destruction and insulin insufficiency.
- Type 2 usually occurs in adulthood and involves insulin resistance plus beta-cell dysfunction.
- Type 1 requires insulin therapy.
Insulin synthesis:
- Insulin is produced by pancreatic beta cells.
- Proinsulin is cleaved into insulin and C-peptide.
- C-peptide can be measured to assess endogenous insulin production.
Insulin secretion:
- Glucose enters beta cells and increases ATP production.
- ATP-sensitive potassium channels close.
- Membrane depolarisation opens calcium channels.
- Calcium influx triggers insulin granule exocytosis.
Insulin action:
- Binds insulin receptor tyrosine kinases.
- Stimulates glucose uptake in insulin-sensitive tissues.
- Promotes glycogen synthesis.
- Inhibits lipolysis and ketogenesis.
- Promotes protein synthesis and anabolic metabolism.
Medical indications for insulin:
- All patients with type 1 diabetes.
- Emergency treatment of ketoacidosis.
- Type 2 diabetes when control is inadequate or during intercurrent illness.
- Pregnancy where required.
- Emergency treatment of hyperkalaemia to shift potassium intracellularly.
Insulin administration:
- Usually given subcutaneously.
- Can be given intravenously or intramuscularly in emergency settings.
- Oral insulin is ineffective because insulin is degraded in the gastrointestinal tract.
Insulin absorption factors:
- Injection site: abdomen absorbs fastest, followed by arm, buttocks and thigh.
- Exercise increases blood flow at the injection site.
- Depth of injection matters.
- Insulin concentration and dose affect absorption.
- Subcutaneous insulin-degrading activity can influence availability.
Insulin preparations:
- Rapid-acting analogues: lispro, aspart and glulisine.
- Short-acting insulin: regular soluble insulin.
- Intermediate-acting insulin: NPH or isophane.
- Long-acting analogues: glargine and detemir.
Type 1 treatment regimes:
- Basal-bolus regimens aim to mimic physiological insulin patterns.
- Basal insulin provides background coverage.
- Bolus insulin covers meals and correction doses.
- Insulin pumps can deliver continuous subcutaneous insulin infusion in selected patients.
Adverse effects of insulin:
- Hypoglycaemia.
- Weight gain.
- Injection site reactions.
- Lipohypertrophy from repeated injections at the same site.
Hypoglycaemia:
- Can cause sweating, tremor, hunger, palpitations, confusion, seizures or coma.
- Requires rapid carbohydrate if conscious and able to swallow.
- Severe cases may need glucagon or intravenous glucose.
Diabetic ketoacidosis:
- Medical emergency caused by insulin deficiency.
- Features include hyperglycaemia, ketonaemia and acidosis.
- Treatment includes ABC assessment, fluids, insulin and electrolyte monitoring.
- Resolution includes venous ketones below 0.3 mmol/L and venous pH above 7.3.
HHS:
- Hyperosmolar hyperglycaemic state is a life-threatening emergency more typical of type 2 diabetes.
- Marked hyperglycaemia and dehydration occur without the same degree of ketoacidosis as DKA.
DKA vs HHS:
- DKA: ketones and acidosis are prominent.
- HHS: hyperosmolarity, profound dehydration and very high glucose are prominent.

WASH overview: Water, sanitation and hygiene are major public health determinants affecting infectious disease, nutrition, child health and development.
Learning focus:
- Global trends and targets for water, sanitation and hygiene.
- Major waterborne pathogens and hazards.
- Wider environment and health links.
Sustainable Development Goal 6:
- Safe and affordable drinking water.
- Ending open defecation and improving sanitation and hygiene.
- Improving water quality, wastewater treatment and safe reuse.
- Increasing water-use efficiency.
- Integrated water resources management.
- Protection and restoration of water-related ecosystems.
Health burden:
- Poor hygiene, poor sanitation and unsafe water contribute substantially to diarrhoeal deaths.
- Diarrhoeal disease contributes to childhood mortality and lost productivity.
- Undernutrition and intestinal infection are closely linked.
Handwashing:
- Handwashing with soap can reduce acute respiratory infections.
- Maternal handwashing can reduce neonatal mortality.
- Hygiene promotion is a key part of sanitation programmes.
Sanitation definition: Collection, transport, treatment and disposal or reuse of human excreta, domestic wastewater and solid waste, with associated hygiene promotion.
Waterborne illness routes:
- Ingestion of contaminated water causing diarrhoea and vomiting.
- Inhalation exposure, such as Legionella.
- Skin contact exposure, such as cyanobacteria or schistosomes.
- Indirect water-related disease, such as malaria.
Bacterial waterborne pathogens:
- Campylobacter.
- Legionella.
- Salmonella species.
- Shigella.
- Vibrio species.
- VTEC.
Viral waterborne pathogens:
- Enterovirus.
- Hepatitis A and E.
- Norovirus.
- Polio.
- Rotavirus.
Protozoal pathogens:
- Cryptosporidium.
- Giardia.
Cryptosporidium:
- Important waterborne protozoan pathogen.
- Can cause diarrhoeal illness.
- Control requires safe water systems and outbreak detection.
Environmental hazards:
- Water contamination can arise from sewage, agriculture, flooding and inadequate treatment.
- Unsafe sanitation increases environmental pathogen load.
- Water stress and climate pressures affect access to safe water.
Public health approach:
- Improve access to safe drinking water.
- Improve sanitation infrastructure.
- Promote hand hygiene.
- Monitor water quality and disease outbreaks.
- Consider wider social determinants of health.
Key message: Treating disease alone is insufficient if people return to the environmental conditions that made them sick.

Lecture focus: Classification, diagnosis and multidisciplinary pharmacological management of diabetes mellitus, especially type 2 diabetes.
Classification:
- Type 1 diabetes: autoimmune beta-cell destruction, often triggered by infection in susceptible individuals.
- Type 2 diabetes: impaired insulin secretion, insulin resistance and increased hepatic glucose production.
- Other types include gestational diabetes, steroid-induced diabetes, LADA and MODY.
LADA:
- Latent autoimmune diabetes in adulthood.
- May resemble type 2 diabetes initially.
- Associated with anti-GAD antibodies and other autoimmune disease.
- Often shows poor control with oral agents.
MODY:
- Rare genetic form of diabetes.
- Often occurs in young people.
- May not require insulin.
- Requires genetic testing and antibody assessment.
Diagnostic criteria:
- Type 1 diabetes: hyperglycaemia with features such as DKA, rapid weight loss, low BMI or autoimmune history.
- Type 2 diabetes: HbA1c ≥48 mmol/mol on two occasions, fasting plasma glucose ≥7.0 mmol/L or random plasma glucose ≥11.1 mmol/L.
HbA1c cautions:
- Do not use HbA1c to diagnose type 1 diabetes.
- HbA1c below 48 mmol/mol does not exclude type 2 diabetes.
- HbA1c is unreliable in increased red cell turnover, pregnancy, anaemia, haemoglobinopathies, acute illness or rapidly rising glucose.
Individualised HbA1c targets:
- Targets should be personalised.
- Any reduction toward the agreed target is beneficial.
- Very intensive control below 48 mmol/mol may not be appropriate for all patients.
Multifactorial management:
- Control blood glucose.
- Control blood pressure.
- Use statins where indicated.
- Support smoking cessation.
- Address lifestyle, weight, education and cardiovascular risk.
Non-pharmacological management:
- Structured education at diagnosis and annual review.
- Individualised nutritional advice.
- Weight loss and exercise support.
- Foot care with podiatry input.
- Retinal photography screening.
Complication mnemonic: KEVIN’S got DM = kidneys, eyes, vascular, infections, neuropathy and skin.
Drug classes:
- Biguanides: metformin.
- Sulfonylureas: gliclazide.
- GLP-1 analogues: liraglutide, exenatide.
- DPP-4 inhibitors: sitagliptin.
- SGLT2 inhibitors: dapagliflozin.
- Thiazolidinediones: pioglitazone.
- Meglitinides: repaglinide.
- Alpha-glucosidase inhibitors: acarbose.
Metformin:
- Mechanism is not fully defined.
- Activates liver AMP-kinase and reduces hepatic glucose output.
- Increases insulin sensitivity in liver, muscle and fat.
- Enhances peripheral glucose uptake and utilisation.
- Unlikely to cause hypoglycaemia alone.
- Often causes weight loss or weight neutrality.
- Common adverse effects include flatulence, nausea and diarrhoea.
- Dose should be increased gradually to reduce GI adverse effects.
- Renal function must be considered when prescribing.
Sulfonylureas:
- Bind sulfonylurea receptors on beta cells.
- Close ATP-sensitive potassium channels.
- Increase calcium influx and stimulate insulin release.
- Require functioning beta cells.
- Can cause prolonged hypoglycaemia and weight gain.
- Other adverse effects include hyponatraemia, oedema, hepatotoxicity, photosensitivity and rash.
Incretin-based therapy:
- GLP-1 receptor agonists enhance glucose-dependent insulin secretion.
- They can reduce appetite and support weight loss.
- DPP-4 inhibitors increase endogenous incretin activity.
- Incretin effect after oral glucose is reduced in type 2 diabetes.
SGLT2 inhibitors:
- Reduce renal glucose reabsorption.
- Promote glycosuria and lower blood glucose.
- Can cause euglycaemic DKA in type 2 diabetes.
- Patients should be counselled about sick-day rules and ketone risk where appropriate.
Pioglitazone:
- Improves insulin sensitivity.
- Can cause weight gain and oedema.
- Requires careful patient selection.
Key treatment principle: Diabetes management is no longer glucose-only; it is personalised, preventative and multidisciplinary, with earlier use of multiple drug classes where appropriate.

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