Module 5 Alimentary System Flashcards

Question

Tongue and lingual papillae

Answer 1

Tongue comprised of extrinsic and intrinsic muscles Filiform lingual papillae - no taste bud (CN V trigeminal nerve) Fungiform (CN VII facial nerve chorda tympani) Vallate (CN IX glossopharyngeal nerve) – often called circumvallate Foliate (CN IX glossopharyngeal nerve) – not many on human tongue

Answer 2

Three pairs of major salivary glands in humans – parotid, submandibular and sublingual Plus minor salivary glands in mucosa of lips, tongue, palate and buccal (cheek) surfaces

Answer 3

Overlies mandibular ramus and secretes serous saliva – 25% of salivary volume. Surrounded by parotid fascia Parasympathetic innervation from CN IX glossopharyngeal nerve Increased saliva production NO facial nerve innervation – CN VII fibres only run through parotid to reach muscles of facial expression Parotid duct pierces cheek wall and opens into oral vestibule opposite second upper molar

Answer 4

Located deep to mandible in floor of mouth Saliva produced is mixed serous and mucous in composition – ~70% of salivary volume Saliva drains into submandibular duct CN VII facial nerve parasympathetic preganglionic nerve fibres travel via chorda tympani

Answer 5

Smallest of the major salivary glands – located deep to tongue and supplies ~5% of saliva Secretion is mostly mucous – contributes to dental pellicle Also main source of lipase Similar innervation to submandibular gland (CNVII) Submandibular and sublingual glands both drain into submandibular duct – opens at sublingual caruncle, just lateral to frenulum of tongue Xerostomia: dry mouth due to insufficient salivary production

Answer 6

Pharyngeal tonsil (lymphoid tissue) Other tonsillar tissue present e.g. palatine tonsils, lingual tonsils Waldeyer’s ring Nasopharynx = nasal choanae  soft palate Oropharynx = soft palate  epiglottis Laryngopharynx = epiglottis  oesophagus Epiglottis separates pharynx from larynx e.g. during swallowing

Answer 7

Oral phase: food pushed by tongue to back of mouth after chewing (mastication) Voluntary tongue movements – under conscious control Pharyngeal phase: reflex response by trigeminal, glossopharyngeal and vagus nerves induces swallowing Soft palate elevates to prevent food from entering nasopharynx and nasal cavities Epiglottis prevents food from entering larynx and trachea Involuntary pharyngeal peristalsis Oesophageal phase: upper oesophageal sphincter (cricopharyngeus muscle) relaxes to allow food to enter oesophagus Peristaltic wave pushes bolus of food past the sphincter and down towards the stomach Lower oesophageal sphincter relaxes to allow bolus to enter stomach

Answer 8

Barium swallow used as part of an upper GI series to visualise stomach and duodenum

Answer 9

Muscular tube around 25cm long Upper 1/3 = skeletal muscle, lower 2/3 = smooth muscle Three regions: cervical, thoracic and abdominal Starts at C6 vertebral level – inferior border of cricoid cartilage Thoracic oesophagus descends through superior and posterior mediastinum to oesophageal hiatus of diaphragm (T10 vertebral level) Abdominal oesophagus is ~1.5cm long and ends at oesophagogastric junction (T11 vertebral level) Anterior and posterior trunks of vagus nerve run along external surface

Answer 10

Arterial supply: oesophageal branches of the thoracic aorta, bronchial arteries, left gastric artery (from the coeliac trunk) and the left inferior phrenic artery (from the abdominal aorta) Venous drainage: to the azygos vein, hemiazygos vein, and the left gastric vein in the abdomen Innervation: oesophageal plexus (parasympathetics from vagus nerve, sympathetics e.g. from T6 – T9 spinal nerves for distal oesophagus) Lymphatic drainage: mainly to the posterior mediastinal and coeliac group of pre-aortic lymph nodes

Answer 11

Posteriorly: thoracic duct, thoracic aorta (near the diaphragm – to the left of oesophagus more proximally) Anteriorly: Aortic arch, trachea and tracheal bifurcation. Right pulmonary artery and the left main bronchus (below level of tracheal bifurcation). Left atrium and pericardium.

Answer 12

The junction of the oesophagus with the pharynx The arch of the aorta in superior mediastinum The left main bronchus in the posterior mediastinum The oesophageal hiatus of the diaphragm

Answer 13

Production of gastric acid, enzymes e.g. pepsin 1000 – 1500ml max capacity in adults Cardia – next to upper oesophageal sphincter Fundus Body Antrum (pyloric antrum) Pylorus Greater and lesser curvatures Rugae – internal gastric folds (increased surface area) Intraperitoneal organ

Answer 14

Most inferior part of oesophagus with slight thickening of circular smooth muscle to help prevent gastric reflux. Also reinforced by other structures: Cardial/cardiac notch: angle created when oesophagus enters stomach. Narrows as stomach fills Oesophageal hiatus: oesophagus surrounded by muscle fibres of diaphragm and fat pads in-between Phrenico-oesophageal ligament: connects oesophagus to diaphragm Combination of anatomical and ‘physiological’ factors to help close the sphincter

Answer 15

Anatomical sphincter – distinct enlargement of circular smooth muscle in the muscularis externa. Sphincter is palpably thicker than stomach and duodenum Controls diameter of pyloric orifice and passage of chyme (digested food + stomach acid) into the duodenum

Answer 16

Herniation of the abdominal oesophagus, cardia and/or other parts of the stomach through oesophageal hiatus Common – genetic, increased prevalence with age and body mass index Gastrooesophageal reflux disease (GORD) is main symptom – dyspepsia, heartburn Three types: sliding, paraoesophageal or mixed Sliding (type I, 90% of cases): abdominal oesophagus and cardia displaced into thoracic cavity Paraoesophageal (type II): phrenico-oesophageal ligament intact, proximal stomach displaced. Other organs may herniate through diaphragm e.g. spleen Mixed (type III): combination

Answer 17

Branches from the coeliac trunk (abdominal aorta) Left and right gastric, left and right gastro-omental, short gastric arteries Venous: To the hepatic portal vein via tributaries draining into the splenic and superior mesenteric veins

Answer 18

Most lymph from stomach will ultimately drain to the coeliac group of pre-aortic lymph nodes (via other groups of lymph nodes e.g. left gastric nodes) Coeliac nodes drain directly into cisterna chyli + thoracic duct Virchow’s node: enlarged left supraclavicular node, potential sign of gastric cancer

Answer 19

Protective: Oral cavity and pharynx, oesophagus, anal canal Stratified squamous non-keratinising Secretory: Stomach Simple/branched tubular glands for acid secretion. Absorptive: Small intestine Projections (villi) and glands (crypts), lined by columnar cells (enterocytes) specialised for absorption (microvilli). Goblet cells produce mucus for lubrication and protection Absorptive/protective: Large intestine Lots of goblet cells for lubrication of faeces. Enterocytes absorb water.

Answer 20

1. Epithelium (various types) Site of absorption and/or secretion Exocrine glands 2. Lamina propria (LP) Blood & lymph 3. Muscularis mucosae (MM)

Answer 21

Submucosa (SM) Connective tissue, blood vessels, lymphatics & nerves Submucosal (Meissner’s) plexus – supplies glands and muscularis mucosae Myenteric (Auerbach’s) plexus - autonomic nerves between muscle layers modulates peristalsis Muscularis externa/ propria (MP) Inner circular & outer longitudinal muscle coats help propel food

Answer 22

A feature of the ileum of the small intestine: ‘Peyer’s patches’ overlain by antigen sampling cuboidal cells

Answer 23

Normally closed (highly folded mucosa), stretches on swallowing food bolus Lined by stratified squamous epithelium – resists friction Submucosa: blood vessels, lymphatics, nerves, lymphoid tissue and mucus glands Muscularis externa layer: skeletal in first third (voluntary), smooth in last third (involuntary), mixed in middle third Outer layer is mostly adventitia - fixed to adjacent structures by connective tissue. Last part beyond the diaphragm covered with serosa

Answer 24

Final 1-1.5cm of oesophagus (below the diaphragm) Lining changes from squamous to columnar epithelium (glandular) Barratt’s oesophagus - change of epithelium from stratified squamous to gastric due to repeated damage from gastric reflux (exposure to acid and digestive enzymes) Scarring as a result of healed ulcers can narrow the lumen (oesophageal stricture) – impeding swallowing

Answer 25

Mucous cells (surface & neck): secrete mucus & bicarbonate Parietal cells: secrete gastric acid (HCl) & intrinsic factor (required for vit B12 absorption in ileum) Stem cells – present in small numbers, increase with epithelium damage Chief (peptic) cells: near base, secrete pepsinogen & gastric lipase Endocrine cells: hormone-producing e.g. gastrin (G cells), somatostatin, cholecystokinin (CCK)

Answer 26

Mucosa and submucosa are thrown into folds: plicae circularis Mucosa is folded to form finger like projections: villi Villi are lined with several cell types-the most numerous is the enterocyte: apical surface has a brush border of microvilli. Crypts are tubular glands at the base of villi

Answer 27

Villi Fingerlike projections extending into lumen of small intestine Increase surface area x600 Continues into crypts of Lieberkuhn: short glands between villi extending to muscularis mucosa. Brush border Collective name for microvilli Enzymes – maltase, sucrase, lactase, Aminopeptidase Lacteal Single blind ended lymphatic vessel at centre of each intestinal villus Involved in fat absorption

Answer 28

Duodenum Receives digestive secretions from the gall bladder & pancreas through the ‘hepatopancreatic ampulla’ Brunner’s glands neutralise gastric acid i.e. balance the stomach acid and allow the pH to be at the correct level for pancreatic secretions to work. Absorptive site for iron Jejunum Main absorptive site (amino acids, monosaccharides, fatty acids) Well developed plicae and prominent finger-like villi Ileum Peyer’s patches Villi and crypts smaller and more poorly developed By the terminal ileum, no plicae circulares Absorbs bile salts Vitamin B12 (intrinsic factor) Water Electrolytes Majority of chyme is digested & absorbed in 1st ¼ of small intestine – duodenum & jejunum – implications for resection surgery

Answer 29

Rhythmical contraction & relaxation Produces continuous division & subdivision of intestinal contents Major role = MIXING Rhythm varies along length of intestine Duodenum – 12 contractions/min Ileum – 9 contractions/min Will push contents in both directions, unlike peristalsis which forces in only one direction

Answer 30

Specialised for water & salt absorption Arranged as tubular glands i.e. Has crypts but no villi Large surface area not necessary Tall columnar absorptive cells Large numbers of mucous cells - more friction = needs more mucus Circular & teniae coli muscle

Answer 31

Mixing Haustration/Segmentation Contraction of the circular muscle in each haustra to mix contents and increase mucosal contact Propulsion Mass peristalsis Intense contraction 1-3 times a day Contents propelled 20cm+ towards anus

Answer 32

Columnar epithelium of rectum gives way to stratified squamous epithelium (squamocolumnar junction). This becomes keratinised when it meets the skin Anal glands lubricate the passage of faeces Venous supply is the haemorrhoidal plexi which can become distended: haemorrhoids Muscular canal controlled by 2 sphincters (internal & external)

Answer 33

Gastric acid Mucus and HCO3 – ‘pre-epithelial defence’ Epithelial layer Prostaglandins

Answer 34

HCl Mucus Enzymes Pepsinogen Early hydrolysis of proteins Liberates B12 from proteins At least 8 types Lipase Early hydrolysis of triglycerides Intrinsic factor

Answer 35

Secretes a large amount of Bicarbonate

Answer 36

Gram negative Microaerophilic Flagellated and highly motile High affinity urease 20% adhere to gastric epithelium Vacuolating cytotoxin Phospholipase A2 Mucinases

Answer 37

Duodenal ulcer Gastric ulcer Gastric adenocarcinoma MALT lymphoma Chronic gastritis Possible associations Non-ulcer dyspepsia Iron deficiency anaemia

Answer 38

Membrane destabilisation Reduced HCO3 Reduced mucus Tight junction loosening

Answer 39

‘pain or discomfort related to eating or drinking that can be attributed to the upper gastro-intestinal tract’

Answer 40

Gastro-oesophageal reflux (GORD) Gastric ulceration (GU) NSAID, H pylori Duodenal ulceration (DU) H pylori, NSAID Biliary colic Chronic pancreatitis Upper GI cancer Functional (non-ulcer dyspepsia) Rare ischaemia

Answer 41

NSAIDS Bisphosphonates Steroids Metformin Calcium antagonists Theophyllines Nitrates

Answer 42

Lifestyle advice Acid Inhibition Antacids H2 receptor antagonists Cimetidine, Ranitidine, Nizatidine Proton Pump Inhibitors (PPI) Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole Surgery Laparoscopic Open Endoscopic

Answer 43

Omeprazole 20 mg bd + Clarithromycin 500 mg bd + Metronidazole 400 mg bd

Answer 44

Consider referral to a specialist service for people: - of any age with gastro-oesophageal symptoms that are non- responsive to treatment or unexplained - with suspected gastro-oesophageal reflux disease who are thinking about surgery - with H. pylori and persistent symptoms that have not responded to second-line eradication therapy In people needing referral, suspend NSAID use. If people have had a previous endoscopy and do not have any new alarm signs, consider continuing management according to previous endoscopic findings.

Answer 45

Macrocytic anaemia Morphological changes in bone marrow Inhibition of DNA synthesis in marrow Commonly due to: B12 deficiency Folate deficiency Rarely due to : Myelodysplasia Inherited defects of DNA synthesis Drugs (e.g. methotrexate)

Answer 46

Diet Vegans Malabsorption Pernicious anaemia Gastrectomy Pancreatic insufficiency Coeliac Disease Ileal surgery Crohn’s disease Bacterial overgrowth*

Answer 47

B12 deficiency may take 5 years to develop

Answer 48

Lemon-yellow skin Glossitis Hepatosplenomegaly Bruising, bleeding Neurological signs Peripheral paraesthesia Loss of proprioception Loss of vibration sense Weakness Ataxia

Answer 49

Investigation B12 levels (<160-180 ng/L) Intrinsic factor, Parietal cell antibodies Coeliac serology Hydrogen breath test Small bowel radiology Treatment i.m. hydroxycobalamin 1mg daily for 5 days Repeat injection every 2-3 months

Answer 50

Blood transfusion of patients with anaemia secondary to B12 deficiency can precipitate subacute combined degeneration of the cord and render the patient disabled.

Answer 51

Nutritional Deficiency Old age Alcoholism Deprivation Anorexia (cancer, GI disease) Pregnancy and lactation Haematological disease Haemolysis Malignancy Dialysis Malabsorption (rare) Antifolate drugs Phenytoin, methotrexate, trimethoprim

Answer 52

Retroperitoneal organ e.g. kidney, between posterior body wall and peritoneum Intraperitoneal organ e.g. small intestine or transverse colon, suspended in peritoneal sac via mesentery

Answer 53

Large apron-like fold of peritoneum with lots of fat Contains leucocytes e.g. macrophages Protects viscera and can wrap around damaged or infected bowel Attaches to greater curvature of stomach and first part of duodenum Drapes over transverse colon, jejunum and ileum Turns to adhere to the transverse colon and transverse mesocolon before attaching to posterior abdominal wall Gastrophrenic, gastrosplenic and gastrocolic ligaments

Answer 54

Hepatogastric ligament Hepatoduodenal ligament Free edge of lesser omentum contains portal triad: Proper hepatic artery Common bile duct Hepatic portal vein Pringle manouevre: clamping the portal triad at the hepatoduodenal ligament during liver surgery to control bleeding

Answer 55

Supracolic compartment, containing the stomach, liver, and spleen Infracolic compartment, containing the small intestine and ascending and descending colon. This compartment lies posterior to the greater omentum

Answer 56

Lateral to the ascending colon and descending colon Allow for communication between the supracolic and infracolic compartments e.g. movement of peritoneal fluid, blood, metastases, infection

Answer 57

Part of supracolic compartment Subphrenic recess separates the diaphragmatic surface of the liver from the diaphragm Divided into right and left subphrenic spaces by the falciform ligament Subhepatic (hepatorenal) recess lies inferior to the liver, adjacent to stomach and right kidney Infections and metastases in the peritoneal cavity can spread into these spaces via the right paracolic gutter and cause abscesses e.g. peritonitis due to a ruptured appendix

Answer 58

Foregut Oesophagus to duodenum (D2) Arterial supply = coeliac trunk Lymphatics = coeliac (group of pre-aortic) nodes Midgut Duodenum (D2) to distal 1/3 transverse colon. Arterial supply = superior mesenteric artery Lymphatics = superior mesenteric nodes Hindgut Distal 1/3 transverse colon to mid anal canal. Arterial supply = inferior mesenteric artery Lymphatics = inferior mesenteric nodes

Answer 59

Bile produced in liver enters left and right hepatic ducts Form common hepatic duct Bile stored in gallbladder Enters via cystic duct Gallbladder has a neck, body and fundus Bile duct joins main pancreatic duct to form hepatopancreatic ampulla (ampulla of Vater) controlled by hepatopancreatic sphincter (sphincter of Oddi) Gallstones: blockage of biliary tree causes colic pain in right hypochondrium

Answer 60

Intraperitoneal organ derived from embryonic mesoderm (not embryonic foregut) Inferior to diaphragm, deep to ribs 9 and 10 on the left. LUQ / left hypochondrium Gastrosplenic ligament (contains short gastric and gastro-omental vessels) Splenorenal ligament (contains splenic vessels) Splenomegaly – spleen can enlarge in an anterior, medial and inferior direction

Answer 61

Arterial supply = superior rectal artery Venous drainage = internal rectal venous plexus  superior rectal vein (inferior mesenteric vein) Lymphatic drainage = internal iliac lymph nodes

Answer 62

Arterial supply = inferior rectal artery Venous drainage = internal rectal venous plexus  inferior rectal vein (internal iliac vein) Lymphatic drainage = superficial inguinal lymph nodes (for perineum)

Answer 63

Usually small intestine. Due to mechanical obstruction or impairment of peristalsis (due to nerve or muscle damage e.g. after abdominal surgery) Results in distension and loss of fluids and electrolytes. Can lead to interruption of blood flow (strangulation due to increased pressure), necrosis and rapid bacterial growth, gangrene and perforation Symptoms: pain, absolute constipation, abdominal distension and vomiting

Answer 64

Idiopathic and chronic relapsing inflammatory diseases Abnormal local immune response to normal gut flora/self antigens Both more common in white population in developed nations and rising in incidence Both have systemic effects

Answer 65

Can affect anywhere from oesophagus to anus but commonly terminal ileum Granulomatous inflammation ulcerates mucosa and deep into submucosa – entire wall thickness Symptoms: diarrhoea, crampy pain, fever Skip lesions – lengths of diseased bowel separated by apparently normal tissue Fissures – deep ulcers that involve the full wall thickness Thickened GI wall due to inflammation: oedema, fibrosis, muscle hypertrophy. Leads to a narrow lumen – strictures Cobblestoning – appearance of oedematous (fluid-filled) mucosal folds and fissures Sequelae: Strictures may lead to obstruction Fistulae may lead to adhesions of bowel loops or to other abdominal structures Fistulae may lead to perforation and abscess/peritonitis Sufferers have remission and relapses of inflammation, punctuated by complications Surgery is often required to relieve intestinal obstruction & repair fistulas No cure, but treatment improves the symptoms and maintains remission

Answer 66

A disease of the large intestine Starts at the rectum and is continuous and can affect the whole colon Extensive inflammatory damage to the mucosa (and submucosa) - ulceration Watery stools are common (may contain blood) Severe damage causes replacement of the straight glands with branched short glands Recovering ulcers protrude into lumen as pseudopolyps Lack of absorptive = watery stools (may contain blood) High risk of bowel cancer

Answer 67

Insufficient pancreatic enzymes (CF) Insufficient bile (gallstones) Loss of small intestinal surface area (coeliac) Lack of mucosal brush border enzymes

Answer 68

Diarrhoea and steatorrhoea Haemopoietic: Anaemia due to deficiency in iron, folate and B12 Bleeding due to vitamin K deficiency (fat soluble) Skeletal: Osteopenia due to Ca, Mg, vit D and protein deficiency Endocrine: Impotence, infertility, amenorrhea, due to malnutrition Hyperparathyroidism due to low Ca and Vit D Skin: oedema (protein deficiency) and dermatitis (vitamin A) Nervous system: peripheral neuropathy (Vits A and B12)

Answer 69

Diagnosis: serology for IgAs: anti-TtG (tissue transglutaminase) and anti EMA (endomyseal antibody); endoscopy + biopsy of small bowel mucosa; check for nutritional disorders e.g. iron deficiency anaemia Sensitivity to gluten- immune response (T cell) to gliadin, a protein in gluten (from wheat, barley and rye-not oats) Treatment: complete removal of gluten from the diet. Leads to recovery Infant symptoms: failure to thrive, diarrhoea, abdominal distension and malnutrition. Less obvious in adults Adult symptoms (less obvious): anaemia, constipation (dermatitis herpetiformis) Most severe in proximal small intestine (maximal exposure to gluten) Loss of villous architecture (blunting or flattening) due to inflammation Lymphocytic infiltration of mucosa and lamina propria Various stages dependant on extent of loss of surface area and number of lymphocytes Increased cancer risk for non-Hodgkin’s lymphoma

Answer 70

Affects 5-10% of over-45s in western society Seen in 80% of over 85yrs. Lack of fibre, aging and poor bowel habit. Often asymptomatic. Treat by increasing bulk to decrease intraluminal pressure Outpouches of the sigmoid colon: mucosa herniates through muscularis - due to arrangement of wall of colon-teniae coli x3 Diverticulitis: inflammation/perforation of diverticulae. Lower left quadrant pain and tenderness, bloody stool, and mild fever. Treat with antibiotics and liquid food.

Answer 71

Salivary α-amylase begins break down of CHO in the mouth. Pancreatic amylase continues digestion in the small intestine (SI). Brush border enzymes dextrinase and glucoamylase continue to digest compounds of 3+ simple sugars. Brush border enzymes maltase, sucrase, and lactase break down maltose, sucrose, and lactose into monosaccharides.

Answer 72

Glucose entry is via a coupled transport process. Sodium-Glucose cotransporter (SLGT1) provides entry at the apical membrane (2 molecules of Na+ per 1 molecule of glucose). Na+ moves down a concentration and electrochemical gradient. Na+,K+ ATPase pumps Na+ out of the basolateral membrane, coupled to K+ transport in to maintain the gradient. Secondary active transport. Fructose movement via facilitated diffusion.

Answer 73

Glucose-galactose malabsorption (GGM) syndrome (rare), autosomal recessive, mutations in the SGLT1 transporter. Characterized by severe diarrhoea and dehydration as early as Day 1 of life due to the effect of glucose and galactose that draw water out of the body into the intestinal lumen, resulting in diarrhoea. Symptoms (diarrhoea) controlled by removing lactose, sucrose, and glucose from diet. Infants can still will thrive on a fructose-based replacement formula. Pancreatic insufficiency: Cystic fibrosis or Shwachman-Diamond syndrome both result in reduced pancreatic amylase.

Answer 74

Acinar cells grouped to form lobules and a ductal system that flows into the main pancreatic duct. Pancreatic zymogens produced to prevent autodigestion. Zymogen definition: an inactive substance which is converted into an enzyme when activated by another enzyme. Pancreas receives neural and peptide stimulation e.g secretin, gastrin, cholecystokinin (CCK).

Answer 75

Free amino acids transported into enterocytes by 4 active, carrier-mediated Na+-dependent mechanisms. Carriers for: Neutral amino acids Basic amino acids and cystine Acidic amino acids Glycine and imino acids

Answer 76

Cystic Fibrosis or Shwachman-Diamond syndrome, patients with limited pancreatic proteases. Enterokinase Deficiency (very rare), results in protein malabsorption, poor growth and development. Hartnup disease, autosomal recessive, lack of transport of neutral amino acids, results in a range of physical, neuronal, emotional/mood changes. Treatment: high protein content (+supplements).

Answer 77

emulsification of fats and then digestion

Answer 78

From week 5, the midgut and dorsal mesentery undergo rapid elongation to form the primary intestinal loop which communicates with the yolk sac through the vitelline duct The primary intestinal loop has cranial and caudal limbs The cranial limb will form: distal duodenum, jejunum and proximal ileum The caudal limb will form: distal ileum, caecum, appendix, ascending colon and proximal 2/3 transverse colon From week 6, there is rapid elongation of the midgut and growth of the liver Not enough room in the abdominal cavity Primary intestinal loop herniates into the umbilical cord As herniation occurs, the midgut also rotates 90° anti-clockwise bringing the cranial limb to the right and the caudal limb to the left Jejuno-ileal loops form From week 10, the midgut returns to the abdomen and rotates a further 180° anti-clockwise This brings the proximal jejunal loops to the left side and the caecum lies inferior to the liver The caecum develops a wormlike diverticulum: vermiform appendix The vitelline duct is also obliterated during this process The midgut has re-entered the abdominal cavity by week 11 and has undergone 270° anti-clockwise rotation in total Once the midgut has returned, the caecum descends from the liver to the right iliac fossa This pulls the ascending and transverse colon into place resulting in the final arrangement of the midgut The dorsal mesentery of the ascending and descending colon now shortens and degenerates pulling them against the posterior abdominal wall: secondarily retroperitoneal

Answer 79

A remnant of the vitelline duct (vitellointestinal duct) that creates an outpouching of the ileal wall Most common gastrointestinal malformation affects approx. 2% population Often asymptomatic but may contain ectopic pancreatic or gastric tissue, causing inflammation, ulceration and bleeding Rule of 2s: Affects 2% population 2 times more common in males 2 feet (50 cm) from ileocaecal junction 2 inches (3-6 cm) long Symptomatic in 2% cases

Answer 80

Failed midgut retraction – midgut does not fully return to the abdominal cavity Associated with an increased risk of mortality and other malformation e.g. cardiac or neural tube defects Diagnosed prenatally using ultrasound Varies in size - may only contain intestines or may include other organs e.g. liver

Answer 81

Abnormal rotation of the midgut can cause parts that would normally be retroperitoneal (e.g. duodenum) to remain suspended by dorsal mesentery This can lead to volvulus (twisting) of the midgut Volvulus causes acute obstruction of the bowel and bilious vomiting Volvulus may also constrict arterial supply to the gut causing ischaemia

Answer 82

Caudal foregut has both ventral and dorsal mesenteries Ventral mesentery critical for development of liver and pancreas Midgut and hindgut have a dorsal mesentery – not all of it persists into later development Retroperitoneal structures e.g. ascending/descending colon Dorsal mesentery permits development of neurovascular structures associated with gut Dorsal mesentery: from distal/abdominal oesophagus to cloaca Ventral mesentery: from distal/abdominal oesophagus to first part of duodenum (D1) Forms lesser omentum and falciform ligament (umbilical vein) Mesenteries carry blood supply, lymphatics and nerve supply to and from organs

Answer 83

The stomach appears in week 4 as a dilation of the foregut It is suspended in the abdomen by the dorsal and ventral mesenteries Differential growth in week 5 forms greater curvature (the dorsal wall grows faster) In weeks 4 – 8, the stomach undergoes rotation around 2 axes 90° clockwise rotation around the craniocaudal (longitudinal) axis causes the lesser curvature to move to the right The greater curvature moves from dorsal position to the left The vagus nerves are initially on left and right sides of the gut tube but also rotate so the left vagus trunk becomes anterior and the right becomes posterior There is also some rotation around the ventrodorsal (anteroposterior) axis so that: the greater curvature faces caudally (inferior) the lesser curvature cranially (superior)

Answer 84

As the stomach rotates around the craniocaudal axis, it creates a space behind it The lesser sac (omental bursa) The rest of the peritoneal cavity is now the greater sac The epiploic foramen is the narrow opening that connects greater and lesser sacs

Answer 85

The hindgut forms distal 1/3 of transverse colon, descending colon, sigmoid colon, rectum and proximal 2/3 of anal canal The distal end of the hindgut enters the dorsal part of the cloaca – anorectal canal The ventral part of the cloaca (urogenital sinus) will form some pelvic organs e.g. bladder During weeks 4 – 6 a layer of mesoderm extends caudally to separate the urogenital sinus and anorectal canal Urorectal septum The urorectal septum approaches near to the cloacal membrane (ectoderm derivative) Week 7: cloacal membrane ruptures Creates the anal opening and a ventral opening for the urogenital sinus The tip of the urorectal septum lies between them and forms the perineal body

Answer 86

The upper 2/3 is derived from hindgut (endoderm) The lower 1/3 is derived from proctodeum / anal pit (ectoderm) Join together when cloacal (anal) membrane degenerates Junction between endoderm and ectoderm derivatives is marked in adult by the pectinate line Different epithelial linings, lymphatic drainage and blood supply

Answer 87

Uncommon: affects 1 in 5,000 births Caused by abnormal cloaca e.g. too small or failure of urorectal septum to extend caudally Opening of hindgut is shifted ventrally to the urethra in males and the vagina in females

Answer 88

Failure of anal membrane to degenerate Skin covers site of anal opening Usually requires immediate surgery to allow evacuation of faeces Good long term prognosis in the majority of cases

Answer 89

PRE-HEPATIC Excess production of bilirubin Examples: haemolysis, sickle cell, thalassaemia, hereditary spherocytosis, elliptocytosis, autoimmune hereditary haemolysis. HEPATIC Liver (conjugation) failure (usually due to inflammation) Examples: hepatitis, sepsis, drugs, pregnancy, primary biliary cirrhosis, sclerosing cholangitis, hereditary. POST-HEPATIC Biliary obstruction Examples: calculus (gallstone), tumour, chronic pancreatitis.

Answer 90

Bilirubin: a product mainly of catabolism of the haem moiety of haemoglobin from effete rbcs. Haem, oxidised via microsomal haem-oxygenase to biliverdin. Biliverdin reduced to bilirubin by cytosolic reductase. Plasma bilirubin associated with albumin, termed unconjugated. Bilirubin taken up by hepatocyte as protein ‘bound’ to albumin. Bilirubin then undergoes conjugation and is water soluble, and enters bile canaliculi. Enters gut via duodenal papilla. Bacteria form urobilinogen, absorbed into urine and colours stools brown.

Answer 91

Cords of cells separated by sinusoids as leaky ‘capillaries’ lined by endothelial cells and Kupffer cells. Kupffer cells: phagocytic cells (recticulo-endothelial system) - capture and breakdown of bacteria and aged/damaged rbcs) – filtering action. Stellate cells within the Space of Disse, store vitamin A in lipid droplets. Myofibroblasts participate in collagen production and repair and fibrosis.

Answer 92

Metabolism: carbohydrate, protein, lipid, nucleic acid. Vitamin storage (A, D, E, K, B12), and copper and iron. Bile synthesis and secretion. Detoxification: conjugation and elimination of metabolites and toxins: Phase I – eg CytP450 catalysed hydrolysis/Ox and then Phase II conjugation to make more water soluble for excretion. Carbohydrate metabolism - Glycogen storage and release as glucose on requirement (glycogenolysis) including overnight fasting. ‘Surplus’ glucose utilisation for glycerol production with fatty acids for TG production and storage. Starvation: initiation of gluconeogenesis. Protein metabolism - Synthesis: albumin (required for maintenance of colloid osmotic pressure and major transport protein for endogenous proteins and exogenous drugs). globulins, clotting factors, fibrinogen, plasminogen, prothrombin etc. non-essential amino acid production via transamination. innate immunity proteins e.g. complement proteins, CRP, and proteins for the acute phase response. Degradation: Transamination: removal of an amino group from amino acids to make non-essential amino acids and C-skeletons used for gluconeogenesis. Deamination: removal of an amino group making ketoacids and ammonia, which is toxic and so is rapidly converted to urea via the urea cycle.

Answer 93

Metabolism: carbohydrate, protein, lipid, nucleic acid. Vitamin storage (A, D, E, K, B12), and copper and iron. Bile synthesis and secretion. Detoxification: conjugation and elimination of metabolites and toxins: Phase I – eg CytP450 catalysed hydrolysis/Ox and then Phase II conjugation to make more water soluble for excretion. Carbohydrate metabolism - Glycogen storage and release as glucose on requirement (glycogenolysis) including overnight fasting. ‘Surplus’ glucose utilisation for glycerol production with fatty acids for TG production and storage. Starvation: initiation of gluconeogenesis. Protein metabolism - Synthesis: albumin (required for maintenance of colloid osmotic pressure and major transport protein for endogenous proteins and exogenous drugs). globulins, clotting factors, fibrinogen, plasminogen, prothrombin etc. non-essential amino acid production via transamination. innate immunity proteins e.g. complement proteins, CRP, and proteins for the acute phase response. Degradation: Transamination: removal of an amino group from amino acids to make non-essential amino acids and C-skeletons used for gluconeogenesis. Deamination: removal of an amino group making ketoacids and ammonia, which is toxic and so is rapidly converted to urea via the urea cycle. Lipid metabolism - Main site of lipogenesis (cholesterol, phospholipid, and lipoprotein production). Free fatty acids can be oxidised to ketones as an energy source, particularly utilized during starvation. Trigyceride production as a fat storage product.

Answer 94

Stored in the liver and exported with majority (~80%) converted to produce bile salts. Biosynthesis of cholesterol is limited by the enzyme HMG-CoA reductase, which is a target for statins.

Answer 95

Hepatocytes make bile (~1 L/day) which flows via bile canaliculi, through bile ductules into portal tracts and then into the common hepatic duct. Gall bladder (GB) is a site of concentrated bile (~50 mL). Muscular-walled sac, pear-shaped, under surface of RL of liver. Epithelium adapted for salt and water absorption, highly folded with microvilli, Na+/K+ ATPase pumps out Na+ and Cl-. Concentrated bile exits the GB via the cystic duct into the common bile duct and then into the duodenum

Answer 96

Essential for fat digestion via emulsification and absorption of fats (via micelles). Contains water, bile salts (Na+, Cl-, K+ and HCO3-), bilirubin (colour) and cholesterol. Released into the duodenum via the CBD, majority absorbed in the intestine, passes through the portal system and recycled up to 20x and then excreted in the faeces. Duodenal release (FAs stimulate) cholecystokinin (CCK) release that stimulates contraction of GB & relaxation of sphincter of Oddi at the Ampulla of Vater.

Answer 97

Alkaline phosphatase (ALP) Mainly in cell membrane between canaliculi and hepatocyte (also cells lining bile ducts) – often increased in disorders affecting bile duct (biliary system). But, also used as a marker of bone turnover/metabolism/damage. Gamma glutamyl transpeptidase (GGT) Involved in transport of amino acids and peptides to the liver. Transport increases with recent alcohol exposure. Sensitive to hepatobiliary disease, if changes mirror ALP, often indicates biliary system damage. Albumin – blood levels measured. Blood clotting time measured as prothrombin time (PT) (typically 10-14 sec) also considered as International Normalization Ratio (INR). Reduced liver synthetic function results in reduced production of clotting factors and increased PT time. Transaminases within the hepatocytes – released due to cell injury e.g. ischaemia/hypoxia/hepatitis/toxic drugs/xenobiotic exposures. AST (aspartate transaminase) – blood levels quantified. ALT (alanine aminotransferase) – blood levels quantified. high AST:ALT ratio sometimes used, indicative of cirrhotic liver damage typically in alcoholism. Lactate dehydrogenase (LDH) measures hepatocyte integrity/death since it is released after a loss of cell membrane integrity.

Answer 98

+ve single stranded RNA genome, like the enteroviruses Faecal-oral route of transmission Entry via contaminated food or water Excreted in faeces Asymptomatic infection Acute icteric hepatitis Fulminant hepatitis (rare) Prevention of hepatitis A: Avoidance of uncooked foods, unboiled water, when travelling Passive immunisation – normal human immunoglobulin – contains IgG anti-HAV Active immunisation – HAV vaccine – killed whole virus vaccine

Answer 99

Hepadnavirus (DNA) Perinatal (mother to baby – at birth) Sexual Parenteral (unsafe injections and transfusion) Chronic if: Defined as persistence of HBsAg for > 6 months (i) HBeAg positive High infectivity eg needlestick Increased risk of inflammatory liver disease (ii) Anti-HBe positive Lower infectivity Lower risk of inflammatory liver disease Prevention of HBV infection: Simple precautions and education of carriers Passive immunisation – HBIg Active immunisation Sub-unit vaccine HBsAg, induces anti-HBs response

Answer 100

RNA virus classified as hepeviridae Faecal-oral spread No chronic sequelae in immunocompetent host Higher mortality than HAV – espec in pregnancy Usually associated with travel abroad, but endogenous infection increasingly recognised In UK, zoonosis – genotype 3 virus found in pigs

Answer 101

+ve ss RNA Bloodborne 75% chronic

Answer 102

Heam is a complex organic molecule that contains Iron at the center of a porphyrin ring. It contains a single ferrous (Fe2+) or ferric (Fe3+) ion, able to bond with diatomic oxygen and transport it around the body.

Answer 103

Haem has a very complex biosynthesis pathway and can be generated in most tissues. However, the main types are erythroid cells (immature red blood cells) in the bone marrow and hepatocytes, in the liver. a) most cells: cytochrome C (oxidative phosphorylation) b) liver: cytochrome P450 (steroid / drug metabolism) c) bone marrow: haemoglobin (transport oxygen)

Answer 104

The first step involves the enzyme aminolevulinic acid (ALA) synthase that catalyses the condensation of glycine with succinyl-CoA to form ALA in the mitochondrial matrix.

Answer 105

General nutritional deficit Reduced Succinyl-CoA from TCA cycle Iron poor diet Haem needs Iron to form the core Vitamin deficiency, especially the vitamin B group cofactors, can also impair the production of haem. These include but is not exhaustive: B6 Pyridoxine B9 Folic acid B2 Riboflavin B12 Cyanocobalamin B3 Niacin B5 Pantothenic acid These either work directly as cofactors, as in vitamin B6 affecting the first step in the synthesis pathway, or indirectly by disrupting erythroid progenitor cells

Answer 106

There are two general categories of porphyria: The acute porphyria's which mainly affect the nervous system (also called acute hepatic porphyria's – AHP) The cutaneous porphyria's, which mainly affect the skin. There are two types of porphyria that have both acute and skin symptoms Variegate Porphyria (VP) and Hereditary Coproporphyria (HCP) Acute porphyrias: Acute Intermittent Porphyria (AIP) Variegate Porphyria (VP) Hereditary Coproporphyria (HCP) Aminolevulinate Dehydratase (ALAD) Deficiency Porphyria (ADP) Cutaneous (skin) porphyrias: Porphyria Cutanea Tarda (PCT) Erythropoietic Protoporphyria (EPP) X-linked Dominant Erythropoietic Protoporphyria (XLDPP) Congenital Erythropoietic Porphyria (CEp) For some of the most common Porphyria Hepatic and Erythropoietic Uroporphyrin accumulates in Urine Red-Brown in natural light Photosensitivity

Answer 107

A polyp is a macroscopic protrusion of the colonic mucosa into the bowel lumen. Colonic polyps can be classified according to their malignant potential. Neoplastic polyps can become malignant while non-neoplastic polyps cannot. Certain characteristics are associated with higher cancer risk. These include: Multiple adenomas Size > 1.0 cm Advanced histology (villous, tubulovillous, high grade dysplasia) Proximal location of adenoma Older age at diagnosis of adenoma(s) Family history of colon cancer in a parent

Answer 108

HNPCC is an autosomal dominant syndrome caused by a germline mutation in one of the DNA mismatch repair (MMR) genes. It is associated with 2% - 3% of all colon cancer cases. The lifetime risk of a developing colon cancer can be as high as 70%. In recent report, median age of colon cancer diagnosis in patients with Lynch Syndrome (HNPCC) was 54 years in men and 70 years in women. This syndrome is also associated with tumors of other organs such as the uterus, ovaries, stomach, pancreas, ureters, kidneys, small bowel, biliary tract, and brain.

Answer 109

FAP is an autosomal dominant syndrome caused by germline mutation in the APC gene. It accounts for < 1% of all colon cancer cases. Approximately 50% of affected patients develop adenomatous polyps by age 15 and 95% by age 35. The average age at diagnosis of colon cancer is about 35-40 years. The lifetime risk of developing colon cancer in a patient with FAP approaches 100%.

Answer 110

Tend to be polypoid or fungating or ulcerating Unlikely to obstruct Tends to present with weakness & anemia May have melena. Advanced lesions can cause change in bowel habits and bowel obstruction

Answer 111

Tend to be annular or constricting lesions Likely to obstruct Produce an "apple-core" Or "napkin-ring" appearance on Ba enema Tends to present with change in bowel habits & Gross bleeding

Answer 112

Most common symptom of rectal cancer is hematochezia Unfortunately, this is often attributed to hemorrhoids (by patient & physician), hence correct diagnosis is consequently delayed until the cancer has reached an advanced stage. Other symptoms include: – mucus discharge – tenesmus – change in bowel habit – pain (usually with locally advanced rectal cancer

Answer 113

Stage 0 or CIS = early stage of bowel cancer. Cancer cells in the bowel lining (completely contained). There is little risk of any cancer cells having spread. Stage 1 - cancer has grown through the inner lining of the bowel, or into the muscle wall, but no further. Stage 2 - 2A means that the cancer has grown into the outer covering of the bowel , 2B - plus into the tissues and organs next to it. Stage 3 - + LN involvement ; Stage 4 - + Metastasised to other parts of the body