Gastrointestinal Week 3 Flashcards
Describe the gross anatomy of the duodenum:
- ~25cm long in total
- C shaped, 4 parts (superior 5cm, descending 7.5cm, inferior 10cm and ascending 2.5cm)
- extends from neck of GB to lower border of L3
- starts at pyloric sphincter
- diameter of 2.5-4cm
- superior part anterior to IVS and bile duct
- > connected to liver by hepatoduodenal ligament
- > last 2cm of superior part onwards = retroperitoneal
- descending part anterior to right kidney
- > curves around head of pancreas
- inferior part anterior to aorta and vena cava (superior mesenteric vessels pass anterior to intestine here)
- at end of ascending part is duodenal-jejunal flexure
- suspensory muscle of the duodenum is found at this flexure and alters the angle of the flexure to control movement of food into the jejunum
- Arteries from coeliac trunk and superior mesenteric artery.
- Above point of bile duct entrance = gastroduodenal artery - branch of coeliac trunk
- Below point of entry of bile duct = inferior pancreoduodenal artery - branch of SMA
- All duodenum veins follow arteries and drain into hepatic portal vein
- Para. supply from vagus
- Symp. supply from thoracic splanchnic nerves relayed through coeliac and superior mesenteric plexus’
- Drained by para-aortic nodes
Describe the gross anatomy of the jejunum and ileum:
Attached to posterior abdominal wall by mesentery
- supplied by superior mesenteric artery and drained by superior mesenteric vein
Jejunum = 2.5m
Ileum = 3.6m
Jejunum:
- > upper L quadrant
- > red
- > long vasa recta (straight arteries) and few arcades
- > thick walled
Ileum:
- > lower R quadrant
- > pink
- > short vasa recta and many arcades
- > thin walled
Describe the histology of the small intestine:
3 features to increase SA:
- > villi
- > microvilli (only seen with electron microscope)
- > plicae circulares (1cm tall circular folds, cause chyme to spiral as it moves through lumen, slows transit for more nutrient absorption)
General structure:
- villi and intestinal glands (Crypts of Lieberkühn)
- microvilli covered by protein coating called glycocalyx
- muscularis mucosa
- submucosa containing venules, arterioles and lymphatic vessels
- circular and longitudinal muscle layers with myenteric plexus inbetween
6 cell types:
- Absorptive enterocyte cells (cover the villi)
- Mucous secreting goblet cells (between enterocytes)
- Entero-endocrine cells (cover villi and produce secretin and CCK)
- Intestinal cells (line the glands and release juice)
- Stem cells (in glands for regeneration)
- Paneth cells (in glands, release lysosyme to destroy unwanted bacteria)
2 surface features of small intestine:
- Brunners glands: in submucosa of DUODENUM and secrete bicarbonate rich mucous
- Peyer’s patches: aggregates of lymphoid tissue
Describe the gross anatomy of the pancreas:
- Head -> uncinate process -> neck -> body -> tail
- 15cm long, endocrine and exocrine function
- uncinate process acts as hook, passing behind superior mesenteric artery and vein
- tail of pancreas overlies hilum of L kidney
- duodenal-jejunal flexure of SI is tucked up below body of pancreas at left edge of uncinate process
- produced 1.5L pancreatic juice per day (pH8) to neutralise acidic chyme
- splenic vein runs behind body of pancreas to join superior mesenteric vein behind neck and they join forming hepatic portal vein
- contains part of biliary tree
- blood supply from splenic artery
- > head also supplied by branches of superior and inferior pancreoduodenal arteries
Describe the histology of the pancreas:
- covered by thin fibrocartilaginous connective tissue capsule, with septa extending into the gland dividing it into lobules
- exocrine component made of cluster of acini cells
- acini contain RER and zymogen granules as they produce and contain manufactured digestive enzymes
- clusters of acini cells are connected by ducts:
intercalated ducts -> intralobular ducts -> main pancreatic duct
How is the hepatic portal vein formed?
Superior mesenteric vein joins with splenic vein at the neck of the pancreas forming the hepatic portal vein
What is the pathway of the biliary tree?
- R and L hepatic ducts from liver
- Join forming common hepatic duct
- Cystic duct joins common hepatic duct forming common bile duct
- Common BD enters pancreas and joins with main pancreatic duct at major duodenal papilla
- May be an accessory pancreatic duct which branches off the main duct and will open at minor duodenal papilla just a few cm proximally to the major papilla
How are carbohydrates digested?
- salivary amylase breaks down small % of starch
- pancreatic amylase breaks down majority of starch
- brush border enzymes in intestines break disaccharides into monosaccharides
How are carbohydrates absorbed?
[Glucose] low:
- SGLT moves glucose into cell
- GLUT2 moves glucose out of cell into bloodstream
[Glucose] high:
- SGLT transporters saturated so GLUT2 molecules are transported to the luminal border of enterocytes and take up glucose
- GLUT2 also transport the glucose out at basolateral side into the bloodstream
Fructose:
- GLUT5 moves fructose into cell
- GLUT2 moves fructose out into the bloodstream
How are fats digested?
What are the contents of a micelle?
- Lipase (some lingual but mainly from stomach produced by chief cells) breaks TAG into fatty acids and monoglycerides
- Bile in intestine emulsifies TAG’s into micelles
- Micelles contain FA, MAG, cholesterol and fat-soluble vitamins and have hydrophilic outer and hydrophobic inner
How are fats absorbed?
- Micelles diffuse into jejunal cells and bile left in gut lumen
- in enterocytes chylomicrons are formed (contain TAG’s, cholesterol, phospholipids….)
- chylomicrons are then absorbed by lymphatic system and released into the bloodstream
How are proteins digested?
- pepsin in stomach digests ~20% proteins
- pancreatic enzymes released into duodenum to digest proteins
- trypsin and chymotrypsin: digest proteins -> small polypeptides
- carboxypeptidase: cleaves individual amino acids from carboxyl end of polypeptides
- elastase: digests elastin fibres that are found in meat
How are proteins absorbed?
- all amino acids/dipeptides/tripeptides are carried into enterocytes by Na-dependent co-transporters
- enterocytes contain specific proteases to digest remaining peptide bonds
- single amino acids can then diffuse into the bloodstream
What are the fat soluble vitamins and how are they absorbed?
Vitamins A, D, E and K
They are absorbed the same way as fats, by forming micelles
How are pancreatic enzymes formed and secreted?
Glandular cells in acini produce the enzymes, the cells have lots of RER and zymogen granules. The epithelial cells lining the pancreatic ducts produce bicarbonate:
- the following reaction occurs in the epithelial cells lining the ducts
- CO2 + H2O H2CO3 H+ + HCO3-
- HCO3- is then secreted into the duct lumen
- zymogens are then activated in the duodenum by enterokinase which is produced by the duodenum, preventing autodigestion of the pancreas
How is the production and release of pancreatic secretions regulated?
- increased acid production by stomach for digestion decreases the pH of chyme in the duodenum
- S cells in duodenum produce secretin to inhibit G cells releasing gastrin and to lower HCl production
- plasma levels of secretin increase
- increased bicarbonate production by the pancreas which flows into the SI
- this bicarbonate in the SI (along with digestive enzymes) helps to neutralise the acidic chyme
- also presence of lipids in duodenum causes I cells to release CCK: GB contracts, sphincter of oddi opens and bile is released to emulsify lipids
Outline causes of chronic pancreatitis and clinical features:
- 60-80% of cases are alcohol related in developed countries
- other causes include CF, hereditary, idiopathic, trauma, hypercalcaemia, autoimmune conditions
- acute pancreatitis: self-limiting and reversible
- chronic: from multiple acute attacks, is not reversible
Features:
- diabetes
- jaundice
- dull epigastric pain radiating to the back
- anorexia (due to malabsorption)
- fear of eating (due to the pain)
- steatorrhoea
- pain after eating fatty foods
What is the pathogenesis of chronic pancreatitis?
Two main hypothesis:
- increased/early activation of trypsinogen -> trypsin in the pancreas
- impaired activation/clearance of the activated enzymes from the pancreas = autodigestion
- prolonged intrapancretic enzyme activity leads to the formation of proteins in the duct lumens, plugs and calcifications form
- alcohol-related pancreatitis -> the alcohol impairs calcium regulation in the pancreas leading to increased calcium levels which promote increased trypsinogen activation
- various genes are also linked to trypsin activation which can be dysfunctional:
- > SPINK-1 gene (a trypsin inhibitor gene that if mutated can cause chronic pancreatitis development)
How would you investigate/diagnose chronic pancreatitis?
1) serum amylase and lipase (levels elevated initially, but then low in severe disease once mass of pancreatic tissue has been lost)
2) faecal elastase - abnormal/reduced levels
3) transabdominal ultrasound scan - to look for duct irregularities or calcifications
4) CT scan and contrast - for detailed assessment of ducts and calcifications
5) MRI and MRCP - to define subtle abnormalities of the pancreatic ducts
How would you treat chronic pancreatitis?
1) Lifestyle
- alcohol and smoking cessation
- enteral feeding to lower CCK levels
2) Diet - reduced fat and enzyme supplementation (especially lipase)
3) Medications
- opioid analgesics e.g. tramadol, for abdomen pain
- PPI’s to increase enzyme activity
4) Surgery
- relieve/remove any obstruction present
- insert a self-expandable metal stent for cholangitis
What is pancreatic insufficiency?
Reduced digestive enzyme levels (therefore reduced effectiveness of digestion and absorption)
What dietary advice would you give someone with chronic pancreatitis?
- avoid alcohol
- avoid high fat content meals (they can increase frequency and intensity of pain)
- monitor blood glucose to prevent hyperglycaemia
- supplementation of fat soluble vitamins
- take supplementary pancreatic enzymes with all meals (quantities adjusted according to quantity of food eaten and its fat content)
What is patient adherence?
The extend to which a patient’s actions match the agreed recommendation
What is unintentional non-adherence and causes of it?
- patient wants to follow medical advice but there are barriers out with their control preventing them
- > poor recall
- > difficulty understanding instructions
- > cost
- > memory issues
- > lack of education
- > controlling family/friends
What is intentional non-adherence and causes of it?
- patient deliberately/meaningfully decides not to follow the agreed treatment
- > beliefs
- > religion
- > previous bad experience
- > heard stigmas/rumours about the drug
- > media
Why is it important that patients adhere?
- so that they get the best medicinal benefits
- so that a patients health improves, not deteriorates
- to avoid costs of:
- > wasted medicines
- > knock-on costs from increased healthcare demands if the patients health deteriorates
What are strategies doctors can use to increase adherence?
- good explanations to remove stigmas
- address any patient concerns
- take ‘no blame’ approach so patient is comfortable with you and has faith in you to follow your advice
- identify potential barriers at the time of prescribing/at regular reviews
- get family and friends involved and educated (with patients permission) so that the patient has support
- make drug regimes are simple and straightforward and easy to understand as possible
What is coeliac disease and its aetiology?
- a gluten sensitive enteropathy
- genetically susceptible individuals get a T-cell mediated immune response
- genetically susceptible individuals get infected with adenovirus 12
- there are similar structures between a portion of the virus and peptides on alpha-gliadin and so CROSS REACTIVITY OCCURS
What is the pathophysiology of coeliac disease?
- stomach digests proteins including alpha-gliadin
- alpha gliadin passes into SI and binds to secretory IgA antibodies and this IgA-gliadin complex is normally targetted by the immune system and destroyed
- in coeliacs, the IgA-gliadin complex binds to Tf receptors on enterocytes and is transported into enterocyte
- then the enzyme TTG (tissue transglutaminase enzyme) deaminates the gliadin
- gliadin is the phagocytosed by macrophages and expressed on their MHCII receptors
- the HLA type that someone is determines what complex is expressed on their MHCII receptors
- in coeliac disease, HLA DQ2 and DQ8 cause this
- T helper (CD4) cells then recognise the gliadin and release pro-inflammatory factors e.g. TNF and IF-gamma
- these inflammatory factors destroy epithelial cells and the villi structure in the small intestine
What are clinical features of coeliac disease?
- vomiting
- impaired growth
- flatulence
- bloating
- diarrhoea
- unexplained increase in ALT and AST
Why do you get malabsorption in coeliac disease and what chemical imbalances occur?
Changes to the structure of the villi and mucosa in the duodenum and ileum cause reduced nutrient absorption in coeliac disease.
- loss of villi height
- short and broad villi
- mucosal inflammation and patchy mucosal damage
- NO CHANGE IN TOTAL MUCOSAL THICKNESS as the crypts of lieberkühn become elongated as the villi shorten
- increased number of intraepithelial lymphocytes and plasma cells
- electrolyte imbalances due to the malabsorption:
- > folate deficiency
- > calcium/vit D deficiency = osteoporosis
- > low vitamin K (coagulation issues)
- > low Mg
- > low vitamin B12
How does coeliac disease affect iron homeostasis is the body?
- makes individuals more prone to IDA (iron deficiency anaemia)
- in IDA various RBC changes are seen:
- > hypochromic cells (pale staining)
- > pencil shaped cells (elongated on smear)
- > microcytic cells (smaller and have a lower MCV)
How do you diagnose coeliac disease?
Endoscopy
- scalloped mucosal folds
- patchy mucosal damage
- damage is in mosaic pattern like cracked mud
- prominent sub-mucosal blood vessels
Serological tests
- look for 3 common antibodies: tTG, EMA, DGP (tissue transglutaminase antibodies, endomysial antibodies, deaminated gliadin peptide antibodies)
Biopsy - minimum of 4 taken from distal duodenum due to patchy mucosal damage
Marsh classification
What other diseases are associated with coeliac disease?
Associated with other autoimmune diseases:
- T1DM
- hyperthyroidism
- Addison’s disease (adrenal insufficiency)
- dermatitis herpetiformis (itchy rash on extensor surfaces - occurs with 90% villous atrophy)
What are the different types of marsh classifications?
Marsh type No. intraepithelial lymphocytes per 100 enterocytes crypt hyperplasia villi
0 <40 normal normal
1 >40 normal normal
2 >40 increased increased
3a >40 increased mild atrophy
3b >40 increased marked atrophy
3c >40 increased absent villi
How do you treat coeliac disease?
- Gluten free diet (avoid wheat, barley, rye, oats are OK BUT RISK OF FACTORY CONTAMINATION)
What are complications of coeliac disease? (Name 6 and describe):
1 - Infection (coeliacs get defective spleen and poor immune responses)
2 - osteoporosis
3 - refractory coeliac disease where you have recurrent malabsorptive symptoms and villous atrophy after adherence to GFD for 6-12months.
-> type 1 = villous strophy and normal immunophenotype
-> type 2 = villous atrophy and ABNORMAL immunophenotype
4 - progression of type 2 RCD to EATL (enteropathy associated T-cell lymphoma)
- EATL = night sweats, itching, weight loss, thromboembolism, treat with chemotherapy or stem cell transplant
5 - small bowel adenocarcinoma
6 - oesophageal and colonic adenocarcinoma
Describe the anatomy of the gallbladder:
Fundus -> body -> neck -> cystic duct
Hartmann’s pouch = an outpouching of the gallbladder wall forming a mucosal fold where stones commonly get stuck
Can hold 30-50ml bile
Concentrated bile removing H2O
Lies in the gallbladder fossa on the inferior surface of the livers right lobe
What does cholecystitis?
Inflammation of the GB
What does cholelithiasis?
Gallstone in GB
