GI Topic 3 - Small Intestine, Exocrine Pancreas, Pancreatitis Flashcards
Where do pancreatic juices drain?
- Pancreatic duct runs the full length of the pancreas, unites with the common bile duct to form the pancreatic ampulla of Vater
- The ampulla opens into the 2nd part of the duodenum via the major duodenal papilla, controlled by the sphincter of Oddi
List the risk factors for chronic pancreatitis
- Male
- Middle aged
- Afro-carribean
Describe the epidemiology of Haemachromatosis
- Males affected more severely than females - lose iron through menstruation/pregnancy
- Most prevelant in celtic (Northern Europe) population
Describe the functional adaptations of the walls of the duodenum
- Submucosal Brunner’s glands - produce alkaline mucous in the crypts of Leiberkuhn to neutralise acidic chyme
- Villi and microvilli increase the surface area for absorption
Describe movement of fluid in the jejunum and ileum
- Enterocytes responsible for fluid movement - pump sodium into the intestinal lumen, water follows - aids digestion
- Enterocytes are CFTR dependents and cAMP modulated
- Cl-, Na+ and K+ move in, CFTR pumps Cl- out, Na+ follows
- Water also moves by passive diffusion - there is increasing osmotic activity with advancing digestion
What is the normal daily iron requirement? Is this usually fulfilled?
1-2mg/day, western diet is 15-20mg/day
How are Ferroportin and Hepcidin involved in iron balance?
- Ferroportin - transmembrane protein, essential for release of iron from macrophages
- Hepcidin - responsible for iron homeostasis
- Decreases GI absorption of iron, decreases RES release of iron - decreases iron levels
- Binds to and degrades ferroportin
Describe the structure of the exocrine pancreas
- Lobulated, serous gland
- Composed of approx 1 milion clusters called acini, connected by short intercalated ducts (1 per lobe)
- Intercalated ducts drain to intralobular collecting ducts which drain to the main pancreatic duct
Describe the parts of the duodenum
4 parts - superior/1st part, descending/2nd part, transverse/horizontal/3rd part, ascending/4th part
- 1st part - intraperitoneal, level L1, attached to liver by hepatoduodenal ligament
- 2nd - 4th - retroperitoneal
- 2nd part has major duodenal papilla - bile and pancreatic secretions enter from ampulla of Vater
- 3rd crosses vena cava and aorta, posterior to superior mesenteric artery and vein
- 4th - joins jejunum at duodenojejunal flexure
Describe carbohydrate absorption in the jejunum and ileum
- Carbohydrates broken down from polysaccharides to monosaccharides
- Glucose and galactose - absorbed by active transport if concentration is low, facilitated transport if concentration is high
- Fructose - limited absorption, co-absorption with glucose
- Protein - amino acids absorbed by sodium-gradient facilitated diffusion, small amount of di/tripeptides by active transport
List the symptoms of chronic intestinal pseudo-obstruction
Abdominal pain, constipation, vomiting, weight loss
What are plicae circularis?
Folds circling the lumen of the jejunum - increase surface area
List the enzymes which contain iron
- Cytochromes
- Perioxidases
- Xanthine oxidase
- Catalases
- RNA reductase
Describe the gross structure of the small intestine
- Duodenum
- Jejunum
- Ileum
What is the function of Gastrin?
Increases stomach motility and gastric acid/enzyme secretion
Describe the histological changes which occur in coeliac disease and the affect this has
- Loss of villous height
- Elongation of crypts of Leiberkuhn
- Increased proinflammatory cells
- Decreased surface area of intestine walls
- Decreased absorptive capacity
List the endocrine secretions of the jejunum and ileum
- VIP
- GLP-1 and 2
- GHRF
- Neuropeptide Y
- Peptide YY
- Substance P
- Bombesin
- Serotonin (from enterochromaffin cells)
What are arcades?
Arterial loops of the small intestines
Compare sources of haem and non-haem iron
Haem iron - red meat
Non-haem iron - white meat, green vegetables, cereals
Compare normal RBCs to anaemic RBCs
- Normal - healthy outer rim of haemoglobin, paler in the middle
- Anaemic - paler (hypochromic), smaller (microcytic), pencil-like
Describe small intestinal motility when fasting
Migrating motor complex
Describe the dietary changes which are made in the management of chronic pancreatitis
- Low fat, high protein, high calorie diet
- Fat soluble vitamin supplementation
- Pancreatic enzyme supplementation for steatorrhoea or poor nutritional status
How does the pancreas produce bicarbonate?
Secreted by centracinar cells and the epithelial lining of intercalated ducts, supply maintained by cystic fibrosis transmembrane conductance regulator (CFTR)
Describe the gross structure of the pancreas
Head, neck, body and tail
Describe the iron content of the body
- Total body = 4g
- RBC = 3g
- Reticuloendothelial system = 200-500mg
- Myoglobin = 200-300mg
- Enzymes = 100mg
What are the consequences of iron overload in haemochromatosis?
Extra 20g of iron - distributed to other tissues:
- Liver - causes cirrhosis, nodules and fibrosis
- Pancreas - causes diabetes
- Skin - causes bronzing
- Joints - causes arthritis, especially of metacarpophalangeal joint of middle finger
Where is the spleen in relation to the pancreas?
Hilum of the spleen sits on the tail of the pancreas
Describe the risk of infection associated with coeliac disease
- Increased risk of infection from encapsulated organisms
- Pneumoccocal
- Haemophilus influenzae
- Meningoccocus
- Vaccination important
What causes haemochromatosis?
- Autosomal recessive disorder, causes iron overload
- Abnormalities of HFE gene (needed for Hepcidin production) usually cause - homozygous C282Y most common
What is the function of secretin?
- Increases bile secretion
- Increases buffer secretion by the pancreas
- Decreases gastric motility and secretion
What is refractory coeliac disease?
- Persistance malabsorption/villous atrophy after 6-12 months gluten-free diet
- Type 1 - normal immunophenotype
- 96% 5 year survival
- Treatment - steroids, immunosuppressants
- Type 2 - abnormal immunophenotype
- Ulcerative jejunitis, ulceration in jejunum/ileum
- 58% 5 year survival
- 60-80% progression to enteropathy-associated T-cell lymphoma
What is the exocrine function of the pancreas?
Produces pancreatic juices - aid digestion
Describe the venous drainage of the pancreas
- Head - superior mesenteric vein, drains to HPV
- Rest - pancreatic veins which drain to the splenic vein (joins the superior mesenteric vein to form the HPV)
How do erythroblasts use iron?
- Transferrin-iron complex binds to Tf receptor on cell surface
- RBC precursor mitochondria use Iron to produce Haem using ALA-S2
List the differences between the jejunum and ileum
- Jejunum
- Upper L quadrant
- Thick intestinal wall
- Longer vasa recta
- Less arcades
- Red in colour
- Inner mucosal lining has plicae circularis
- Ileum
- Lower R quadrant
- Thin intestinal wall
- Short vasa recta
- More arcades
- Pink in colour
- No plicae circularis
What causes bile acid malabsorption and how is it treated?
- Caused by ileal resection/malabsorption
- Treat with bile acid sequestrants
Define chronic pancreatitis
Continuing inflammatory disease of the pancreas characterised by morphological changes - pain and loss of exocrine and endocrine functions
Describe the location of the jejunum and ileum
- Intraperitoneal
- Attached to posterior abdominal wall by mesentery
- Jejunum begins at duodenojejunal flexure
- No clear demarcation between the jejunum and ileum
- Ileum ends at the ileocaecal valve
List the diseases associated with coeliac disease
- Dermatitis herpetiformis
- Itchy rash on extensor surfaces, occurs after 90% villous atrophy
- Other AI diseases - Type 1 diabetes, thyrotoxicosis, Addison’s disease
How can the risk of coeliac-related malignancy be reduced?
Adherance to a gluten-free diet
Describe the innervation of the pancreas
- Parasympathetic - vagus
- Sympathetic - thoracic splanchnic nerves from superior mesenteric and coeliac plexuses
How is iron balance regulated?
Altering GI iron absorption/excretion is the only mechanism for regulating iron balance
Describe the treatment of chronic pancreatitis
- Lifestyle - quit smoking and drinking alcohol
- Endoscopic removal of stones/dilate strictures
- Coeliac axis block - manage pain
- Screen for diabetes mellitus
- Analgesia - paracetamol, NSAIDs, opiods
What is acute post-operative ileus?
- Constipation and intolerance of oral intake (no mechanical obstruction) after surgery
- Physiological ileus:
- Small intestine - 0-24 hours
- Stomach - 24-68 hours
- Colon - 48-72 hours
List disorders of iron metabolism
- Iron deficiency anaemia
- Iron malabsorption e.g. coeliac disease
- Haemochromatosis
- Sideroblast anaemia
What is the function of VIP?
Reduces acid secretion in the stomach
Describe the venous drainage of the jejunum and ileum
- Superior mesenteric vein
- splenic vein at neck of pancreas - drains to hepatic portal vein
How does recurrent acute pancreatitis cause chronic pancreatitis?
- Inflammatory changes and necrosis - scarring in periductular areas
- Ductules become obstructed - stone formation
Describe the functional adaptations of the ileum
- Lymphoid follicles (Peyer’s patches) in submucosa, extends to lamina propria - produce lymphocytes in response to ingested foreign molecules
- Enteroendocrine cells especially in crypts
- Paneth cells deep in crypts - immune granules to destroy microorganisms
Describe the arterial supply of the jejunum and ileum
- Superior mesenteric artery
- Arises from aorta at level of L1, immediately inferior to coeliac trunk
- Moves between layers of mesentery, splits into approximately 20 branches
- Branches anastomose to form loops - arcades
- Arcades form long, straight vasa recta
Describe the innervation of the duodenum
- Sympathetic - intestinal plexuses along pancreaticoduodenal arteries
- Parasympathetic - coeliac and superior mesenteric plexuses (vagus nerve)
Describe the anatomical position of the pancreas
- Mostly posterior to stomach, retroperitoneal
- Extends across posterior abdominal wall from duodenum to spleen
- Epigastric and L hypochondrium regions
- Head is in the ‘C’ of the duodenum
Describe steatorrhoea
Fatty stool - loose, pale, floating
Describe the presentation of coeliac disease in adults
- Symptomatic - diarrhoea, bloating, flatulence, abdominal pain/discomfort (may be constipated)
- Chronic/recurrent iron deficiency anaemia
- Nutritional deficiency
- Reduced fertility/amenorrhoea
- Osteoporosis
- Elevated AST/ALT
- Neurological/psychiatric symptoms
How is iron absorbed in the small intestines?
- Ferrous iron absorbed by mucosal cells into the blood/ECM bound to ferritin
- Low pH aids absorption
- Only absorbed in duodenum and jejunum
- Rate of absorption proportional to requirement
How is iron transported in plasma?
- Transferrin - glycoprotein, made in hepatocytes
- High concentration when iron concentration is low
- Low concentration when iron concentration is high
- Two iron atoms per molecule of ferritin
- Normally - 30% saturated with iron, 70% free
How is iron stored within cells?
Ferritin (soluble) or Haemosiderin (insoluble)
List the zymogens produced by the pancreas and describe their activation
- Trypsinogen, activated to trypsin by enterkinase
- Chymotrypsin, activated to chymotrypsin by trypsin
- Lipase/co-lipase/phospholipase
- Amylase - digests alpha 1-4 glucose to glucose bonds only
- Lipase - digests triglycerides to free fatty acids and monoglycerides
What is the consequence of bile acid malabsorption?
Unable to absorb fat soluble vitamins - A, D, E, K
Describe the presentation of coeliac disease in infants
- 4-24 months - introduction of cereals
- Impaired growth, diarrhoea, vomiting, abdominal distention
How does hereditary pancreatitis develop?
- Gene coding for trypsin overactive, cannot be inactivated
- Autodigestion of pancreatic tissue
- Acute pancreatitis leading to chronic pancreatitis
Describe the functional adaptations of the jejunum
- Tallest villi
- No Brunner’s glands
How does HFE gene mutation cause iron overload in haemochromatosis?
Mutation causes decreased hepcidin production, increased GI absorption of iron
How is coeliac disease diagnosed?
- Serology
- High IgA tTG - sensitive
- High IgA EMA (antiendomysial antibody) - specific
- Endoscopy
- Scalloping, lack of folds
- Mosaic pattern
- Prominent submucosal BVs
- Nodular muscoa
- Biopsy
- Distal duodenum - 4x, must be on gluten-rich diet
List the risks factors for coeliac disease
- Female
- 1st degree relative with coeliac
- HLA-DQ2/DQ8 gene
What is the function of GIP?
Decreases gastric activity
List the symptoms and treatment of enteropathy-associated T-cell lymphoma
- Weight loss, night sweats, itch, GI bleeding
- Often advanced and incurable
What is chronic intestinal pseudo-obstruction?
Signs of mechanical obstruction of the intestines without actual occlusion
List the risk factors for acute post-operative ileus
- Open surgery
- Prolonged abdominal/pelvic surgery
- Delayed enteral nutrition
- Peri-operative complications
- Peri-operative opiates
Describe the treatment of coeliac disease
Gluten-free diet - avoid wheat, barley, rye
How are haem and non-haem iron absorbed?
- Haem iron is easily absorbed
- Non-haem
- Released by acidic digestion and proteolytic gastric enzymes
- Converted from ferric to ferrous form by duodenal cytochrome b1
- Influenced by Vitamin C
- Absorbed into enterocytes by divalent metal transporter 1 (DMT1)
How long are the jejunum and ileum?
Jejunum = 2.5m
Ileum = 3.5m
What happens if an individual with Haemochromatosis is treated with a blood transfusion?
Causes iron overload - bone marrow failure
Define coeliac disease and describe its cause
- Gluten-sensitive enteropathy
- Small intestinal villous atrophy - resolves when gluten is withdrawn from diet
- Innappropriate T-cell mediated immune response in the genetically susceptible
- Alpha-gliadin is the most toxic moiety
How is Vitamin B12 absorbed in the small intestines?
- Dependent on B12 from diet although intestinal microflora produce B12
- Need low pH, gastric enzymes and intrinsic factor from parietal cells for absorption
- IF-B12 complex is absorbed in the terminal ileum
Describe the morphological changes which occur in chronic pancreatitis
- Dilated pancreatic ducts, filled with protein plugs (may be calcified)
- Atrophy of acini and fibrosis - relative preservation of islets
- Increasing concentration of pancreatic proteins and increasing duct pressure = formation of protein plugs with calcium carbonate, leading to calculi formation
- Lack of lipases in advanced disease - malabsorption of fat, reduced absorption of vitamins A, D, E and K, steatorrhoea
- Islets can be lost in advanced disease leading to diabetes mellitus
How do contractions of the small intestine change after a meal?
Entry of chyme to duodenum stimulates the gastroenteric reflex - along with vagal stimulation, myenteric plexus action, gastrin, CCK, insulin and serotonin release causes increased intestinal motility
List diseases of malabsorption
- Coeliac disease
- Pancreatic exocrine insufficiency
- Steatorrhoea (post-hepatic jaundice)
- Bile acid malabsorption
- Zollinger-Ellison Syndrome
Describe the histology of the exocrine pancreas
- Functional unit - acinus
- Lined by pyramidal cells joined by apical junction complexes
- centroacinar cells, continuous with low cudoidal epithelium of intercalated duct
What is the function of CCK?
- Increases pancreatic secretions
- Increases bile and pancreatic secretions release into the duodenum
- Reduces gastric activity
- Reduces hunger
Describe the arterial supply of the duodenum
- Before ampulla of Vater - gastroduodenal artery (from coeliac trunk)
- After ampulla of Vater - inferior pancreaticoduodenal artery (branch of super mesenteric artery)
- Change marks the transition from foregut to midgut
What is a peristaltic rush and why does it occur?
- If intestinal mucosa is irritated
- Enteric nervous initiation of contraction
- Sweeps chyme from the small intestines into the colon - relieves irritation of the small intestines
Name the secretions of the duodenum
- CCK
- Secretin
- GIP
- VIP
- Gastrin
- Alkaline mucous from Brunner’s glands
Describe the release of iron from the RES
- Macrophages get iron from breakdown of RBCs
- RES iron stored as ferritin/haemosidin
- Ferroportin/hepcidin control RES macrophage iron release
- If cells don’t require iron - stored as ferritin
- If cells require iron - bound to transferrin, taken to tissues
- RBC recycle iron - released on breakdown, transferrin iron taken up by erythroblasts if they have the transferrin receptor
List the symptoms of chronic pancreatitis
- Chronic/recurrent upper or generalised abdominal pain
- Nausea
- Vomiting
- Bloating
- Weight loss
- Steatorrhoea
- Jaundice
- Chronic liver disease
Describe Sideroblastic anaemia
RBC takes in iron but iron is trapped in ring sideroblast - can’t synthesise haem
Describe the presentation of coeliac in older children
Anaemia, short, pubertal delay, recurrent abdominal pain, behavioural disturbance
How is chronic pancreatitis diagnosed?
- Transabdominal ultrasound - shows inflammation of pancreas and gallstones
- MRCP - radiolabelled isotope injected to show pancreas, gallbladder and the pancreatic/bile ducts
- CT
- Blood tests -
- IgG4 - autoimmune
- Serum amylase, lipase and trypsinogen (will be high in pancreatitis)
Which cells are resposible for iron absorption?
Enterocytes
What causes chronic pancreatitis?
T - toxic and metabolic (alcohol, smoking, hypercalcaemia, hyperlipidaemia)
I - idiopathic
G - genetic (HP, CFTR, SPINK-1)
A - autoimmune
R - Recurrent and severe acute pancreatitis
O - obstructive (gallstones)
Describe the shape and size of the duodenum
- Shortest and widest part - 0.25m long
- C-shaped curve around the head of the pancreas
Where does exocrine secretion occur in the jejunum and ileum?
Crypts of Leiberkuhn
How quickly do liquids and solids pass through the small intestines?
- Transports liquids and solids at same rate
- Liquids reach caecum earlier due to faster gastric emptying
- Liquids - 30 minutes, solid chyme - 150 minutes
How does coeliac disease cause iron malabsorption?
Infiltration of small lymphocytes into the lamina propria of the GI tract causes blunting of villi, causes ineffective absorption
Describe the general function of the small intestines
Majority of digestion/absorption, relatively little secretion
Describe the arterial supply of the pancreas
- Head - superior and inferior pancreaticoduodenal arteries, branches of the gastroduodenal artery (from the coeliac trunk) and superior mesenteric arteries
- Rest - pancreatic branches of splenic artery
Describe the Marsh Classification of Coeliac disease
0 = No changes - <40 lymphocytes per 100 enterocytes, crypts and villi normal
1 = >40 lymphocytes per 100 enterocytes, crypts and villi normal
2 = >40 lymphocytes per 100 enterocytes, crypts elongated, villi normal
3a = >40 lymphocytes per 100 enterocytes, crypts elongated, mild villous atropy
3b = >40 lymphocytes per 100 enterocytes, crypts elongated, marked villous atrophy
3c = >40 lymphocytes per 100 enterocytes, crypts elongated, absent villi
List disorders of small bowel transit
- Chronic intestinal pseudo-obstruction
- Acute post-operative ileus
How is Haemochromatosis treated?
- Venesection (initially up to weekly)
- Monitor ferritin and transferrin saturation
- Prevent/limit organ damage
Describe the layers of the walls of the small intestines
- Mucosa - columnar epithelium, lamina propria, muscularis mucosae
- Submucosa - Brunners glands (produce mucous)
- Muscularis propria - circular and longitudinal smooth muscle
- Serosa - forms visceral peritoneum
What is Zollinger-Ellison disease?
- Hyperplasia/tumour - gastrinoma
- Constant hypersecretion of gastrin
- Aggressive recurrent peptic ulcer disease
- Diagnosis - stimulated gastrin level
- Treat with v high doses of PPI, surgery to remove tumour
List the potential complications of coeliac disease
- Infection
- Osteoporosis
- Refractory coeliac disease
- Malignancy
Describe the contractions which occur in the small intestine
- Prolonged propagated contractions move the chyme intermittently from the ileum to the colon in boluses
- Mixing contractions - segmentation, propulsive contractions due to peristalsis
- Peristalsis is weak in the small intestine - contractile ring around gut moves chyme forwards
How does obstruction e.g. due to gallstones cause pancreatitis?
- Uncontrolled activation of trypsin - tissue damage due to autodigestion
- Stones cause scarring, ulceration, obstruction, stasis and atrophy of pancreatic tissue
Describe the management of chronic intestinal pseudo-obstruction
- Nutritional - enteral/parenteral feeding
- Antibiotics for small intestinal bacterial overgrowth
- Refractory - small bowel transplantation
What causes chronic intestinal pseudo-obstruction?
Primary or secondary to other diseases
- Myopathic - scleroderma, amyloidosis
- Neuropathic - Parkinson’s
- Endocrine - Diabetes mellitus, servere hypothyroidism
- Drugs - Phenothiazines, Parkinson’s drugs
What reduces intestinal motility?
Secretin and glucagon
What causes iron deficiency anaemia?
- Young women (20%) - menstruation/pregnancy
- Males + post-menopausal females - due to GI blood loss until proven otherwise
How are fats absorbed in the small intestine?
Bile acid circulation
List the exocrine pancreatic secretions
- Bicarbonate (neutralises chyme)
- Zymogens - enzyme precursors, activated to give functional digestive enzymes
Compare transferrin saturation in iron deficiency anaemia and Haemachromotosis to normal
- Normal = 30% saturation
- IDA - high transferrin, low iron
- Haemochromatosis - low transferrin, high iron - up to 100% saturation
Describe the pathophysiology of coeliac disease
- Genetic susceptibility and adenovirus 12 infection
- Peptide on alpha-gliadin similar to E1b portion of virus
- Cross reactivity = inappropriate immune response to alpha-gliadin
Describe the innervation of the jejunum and ileum
- Sympathetic - T5-9 form the coeliac and superior mesenteric ganglia - gives off greater and lesser splanchnic nerves
- Parasympathetic - preganglionic from posterior vagal trunks, synapse on postganglionic cells in myenteric + submucosal plexus of intestinal wall
Which important vascular structures are associated anatomically with the pancreas?
- Splenic vein and superior mesenteric vein unite behind the neck of the pancreas to form the portal vein
- The inferior mesenteric vein joins the splenic vein behind the body of the pancreas
- The aorta becomes the superior mesenteric artery behind the neck of the pancreas
- The splenic artery and vein follow behind the pancreas to the spleen
What is absorbed in the jejunum and ileum?
- Carbohydrates
- Peptides
- Fat
- Water
- Vitamins
- Electrolytes
- Minerals
Describe the venous drainage of the duodenum
- Follow major arteries, drain into portal vein
- 1st part - prepyloric vein drains into HPV
- 2nd - 4th parts - superior pancreaticoduodenal vein drains into superior mesenteric vein
What causes small bowel adenocarcinoma?
Rare - coeliac or Crohn’s disease
Describe the pathogenesis of Coeliac disease
- Alpha gliadin digested and absorbed
- Exposed to tissue transglutaminase (TTG) which causes deamination, making it more immunogenic
- Enables binding to HLA-DQ2 and activation of pro-inflammatory T cell response
- CD4 T cells cause villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis
- B cellls produce antibodies e.g. antigliadin, antiendomysial and anti-TTG antibodies
