Gastroenterology Flashcards
Where is most water reabsorbed
90% in jejunum and ileum
10% in the colon
Where is bicarbonate secreted and resorbed
Secreted by Pancreatic fluid to neutralise gastric acid
Reabsorbed in the jejunum
what is the function of the following cells
-parietal cells
-endochromaffin cells
-chief cells
-G-cells
-D-cells
-Mucus cells
-parietal cells: secrete HCl
-Endochromaffin cells: secrete histamine which promotes HCl production by parietal cells
-Chief cells; secrete pepsinogen- needed for protein digestion
-G-cells: secrete gastrin which promotes the parietal cells to secrete HCl
-D-Cells: secretes somatostatin- inhibits G-cells, endocromaffin cells and parietal cells to reduce gastric acid secretion
What 3 things stimulate HCl secretion
-Vagal nerve- releases EACh to activate ECE and parietal cells
-Endochromaffin cells- secrete histamine which binds to H2 receptors on parietal cells to increase HCl secretion
-Gastrin- released into blood stream and binds to ECE cells to stimulate histamine release
How does ibuprofen causes ulcers
COX inhibitor
COX 1 + 2 enzymes result in the synthesis of prostaglandins E2 and I2. These bind to parietal cells to reduce HCl secretion.
Prostaglandins also activate the mucus cells to secrete more protective mucus and bicarbonate
Blockage = increased stomach acid, reduced mucus, reduced bicarbonate which can result in ulceration
How does the sympathetic NS reduce stomach acid production
Inhibits G-cells (reduced gastrin = reduced parietal and ECE cell stimulation) and stimulates D-cells to make more somatostatin
Net effect = inhibition of HCl production
What affect do CCK and secretin have on gastric acid
Reduce it
What is absorbed at
-the duodenum and jejunum
-ileum
-most proteins/fat/water/salts
-ileum= bile salts and B12
Describe the process of fat absorption
-Fat enters mouth
-broken down by lingular lipase secreted by Ebner’s gland
-enters stomach; acid breaks down further
-In duodenum, fat entering triggers the release of CCK from the pancreas. CCK stimulates gallbladder contraction
-Pancreas releases lipase which breaks down the fat to Free fatty acids and monoglycerides.
-Bile salts then coat the fat and make a MICELLE which is absorbed directly into the enterocyte
-In the enterocyte, micelle breaks down
-Short and medium chain fatty acids are taken up directly into portal blood
-Long chain fatty acids travel to the endoplasmic reticulum; made into triglycerides which conjugate to make lipoproteins. Many lipoproteins= chylomicron
-Chylomicron is absorbed into the lymphatic system and empties into the thoracic duct
What is the role of CCK in fat absorption
stimulates the gallbladder to release bilesalts into the duodenum.
Stimulated on arrival of fat into the duodenum. Secreted by the pancreas
Describe the digestion of carbohydrates
Salivary parotid amylase breaks down
In the duodenum, amylase is secreted by pancreas, which helps further break down polysaccharides to disaccharides
Enterocytes have a brush boarder with enzymes
-sucrase: breaks down sucrose -> fructose and glucose
-lactase: breaks down lactose –> glucose and galactose
-maltase: breaks down maltose to 2x glucose
Na/K ATPase pump on enterocyte basomembrane pumps sodium out of cell to make sodium gradient
-Glucose or Galactose/Na co-transporter absorbed into the enterocyte
-Exits into blood stream via GLUT-2 transporter
Fructose absorbed by GLUT-5 transporter on apical membrane. Can exit via GLUT-5 transporter OR be phosphorylated in the cell to glucose and exit via GLUT-2 transporter
What are features of a glucose/galactose malabsorption and why do they occur
What is the management
Severe diarrhoea, hypoglycaemia, glucosuria
AR defect in sodium/glucose transporter (SGLT1). Result = inability to absorb glucose and galactose.
Manage- fructose as this uses GLUT 5 transporter
How is Fructose absorbed
GLUT-5 transporter on apical membrane
If you have a sucrase/isomalatase deficiency what won’t you absorb and how will you present
Sucrose ==> glucose + fructose
Maltose= 2x glucose
Main symptom is severe toddlers diarrhoea when fruit is introduced as increased fructose is present and not absorbed
What percentage of fat is not absorbed for there to be ‘malabsorption’
> 6%
Describe protein digestion
Amino acids broken down in stomach acid.
Enter duodenum. Enzymes from pancreas release- chymotripsinogen, trypsinogen and elastase.
Brush boarder enzyme enterokinase activates typsinogen –> trypsin which in turn activates chymotripsinogen to chymotrypsin. Enzymes break the protein down to dipeptides and tripeptides
Enzymes on the brush boarder break down the protein further
Absorbed into the cell using hydrogen/peptide transporter.
Absorbed across the basomembrane using sodium-peptide cotransporter
Travel to liver in portal blood
What is the role of gastrin
“GO” hormone of digestion
-stimulates parietal cells to secrete gastric acid
-stimulates pancreas
-stimulates Intrinsic factor release
-Stimulates Chief cells to release pepsinogen
What is the role of secretin
“STOP” hormone of digestion- stimulated by intra-luminal acid secretion
-stimulate pancreatic bicarb secretion
-reduces stomach acid
-prevents gastric emptying
What is the role of CCK
Cholecystokinin pancreozymin
-stimulated by intraluminal food
-stimulates gallbladder contraction
-stimulates pancreatic release of enzymes and bicarbonate
-reduces gastric emptying
What affect does increased GIP have on insulin
Stimulates insulin production
What is the role of GIP
Gastric inhibitory protein
-inhibits gastric emptying
-induces insulin secretion
Stimulated by glucose/protein/fats
What is the role of VIP
Vasoactive Inhibitory Protein
“FIGHT OR FLIGHT” protein
-sympathetic neural stimulation = reduced HCl and Pepsin secretion by parietal and chief cells
-reduced gastric motility
-increased secretion of insulin
What affect do both VIP and GIP have on insulin
increase the secretion insulin
How many calories / kg/ day does an infant need vs a child
100 vs 55
What vitamin is B1 and what sx do you get in deficiency
B1= Thiamine- get Beri Beri
Wet beriberi = CHF causing shortness of breath and oedema
Dry Beri Beri= demyelination and axonal degeneration peripheral to proximal. Get tingling, loss of reflexes, weakness, cramping of muscles.
Eventually can get aphonia (laryngeal nerve), ptosis (optic nerve)
Late stage- wernickes encephalopathy, coma, death
What is vitamin B2 and what sx do you get in deficiency
Riboflavin
Photophobia, blurred vision
Magenta glottis
Stomatitis
What is vitamin B3 deficiency and what does it cause when deficiency
Niacin
Pellegra- diarrhoea, dementia, dermatitis
What is Vitamin B6 and what do you get in deficiency
Pyridoxine
Enzyme for decarboxylation and transamination so get diffuse breakdown
e.g. peripheral neuritis, stomatitis, glossitis
What is vitamin B12 and what do you get in deficiency
Cobalamin
Important in DNA /RNA repair and synthesis, RBC synthesis and lipid synthesis
-Lipid: degeneration of myelin sheath = spinal cord degerneration
-DNA/RNA:Beefy red tongue / glossitis
-RBC: macroblastic anaemia
Causes:
-diet
-stomach fundoscopy (where Intrinsic factor secreted from parietal cells)
-ileum resection (absorbed via enterocytes)
-pernicious anaemia
What is the name of Vitamin C deficiency and what are the symptoms
Scurvy
-Glossitis, gum hypertrophy, poor wound healing, gingivitis, weakness, jaundice, neuropathy
What are symptoms of vitamin A deficiency
Retinal - blindness from keratomalacia (cornea softens and goes cloudy)
Teeth- faulty enamel
Bones- faulty epiphyseal plate
Poor growth
What are is the syndrome of vitamin D deficiency and the signs
Rickets
Bony signs: frontal bossing, wide open fontanelle, bowed legs, swelling of ankles and wrist, rachitic rosary, minimal trauma fracture
Non-bony: delayed gross motor development, poor linear growth
What are the symptoms of Vitamin E deficiency
Cerebellar ataxia
Posterior column dysfunction
Peripheral neuropathy
What co-factors if Vitamin K involved in
Factor 2, 7, 9, 10
Protein C + S
what would you see in iron deficiency on iron studies
low serum iron
low ferritin
high transferrin
What is congenital zinc deficiency called and what are the features
Acrodermatitis enteropathica
-perioral and perianal dermatitis
-alopecia
-anaemia
-recurrent infections especially candida
-anaemia
-poor wound healing
What are the signs of hypercalcaemia
What is the relationship of calcium and magnesium
-Bony pain, renal stones, abdomen pain/constipation, confusion
Low Mg drives low calcium- can result in Vitamin D resistant rickets
What is the condition of congenital copper deficiency called and its features
Menkes Kinky hair
Disorder of copper transport
Result = kinky hair, demyelination of nervous tissue and facility of large blood vessels.
results in death before age 3
What is the condition of copper excess, what genetic defect and what are the symptoms
Wilsons disease
Gene: ATP7B
Features
-Eyes; KF rings
-Brain: psychosis
-heart: cardiomyopathy
-liver: hepatitis, portal HTN
-renal: acute tubular acidosis
What is the difference between Kwashiok and Marasmus
Marasmus- muscle wasting and depletion of fat stores
Kwashiok- generalised oedema and flaky peeling skin
What does IFALD stand for and what are the causes/risk factors/symptoms/management
Intestinal failure associated liver disease
-TPN associated liver disease
-Liver disease associated with chronic use of TPN
Risk factors: prolonged TPN use, prematurity, lack of enteral nutrition, bacterial gut overgrowth, CVC infections
Symptoms: cholestasis, hepatic fibrosis, and can develop portal hypertension and liver failure
Management
-prevent: early enteral nutrition, prevent CVC infection
-manage: introduce fish oil fatty acids (SMOF), ursodeoxycholic acid- improves bile acid flow and reduces gallbladder stasis
What is intestinal failure
Inadequate small bowel available to support nutrition and growth
-unable to absorb enough nutrients, water and electrolytes
-require IV nutrition to sustain growth and health
In short gut syndrome, what length is associated with likely need for long term nutritional support
<40cm
What motility disorders cause short gut syndrome
Gastroschisis
High level hirschsprungs
Chronic intestinal pseudo-obstruction
What hormone is elevated in Prada-willi syndrome that stimulates appetite
Gherlin
What is the difference in diarrhoea illness of these E. Coli
-Enterotoxic
-Enterohaemorrhagic
-Enteroinvasive
-Enteropathogenic
Enterotoxic: produces a toxin that results in pores forming in the apical surface. Leak Cl/Na/water into the lumen to cause secretory diarrhoea
Enterhaemorrhagic: produces Shigella toxin- E.Coli 0157:H7 is associated with HUS. Toxin causes inflammation of endothelial cells resulting in microangiopathy, platelet aggregation and AKI
Enteroinvasive E.Coli: uses adhesive proteins to invade enterocytes and uses the cell machinery to multiple. Causes severe mucosal damage and inflammation –> profuse watery diarrhoea and fever
Enteropathogenic” common toddlers diarrhoea
What channel is affected in congenital Chloride diarrhoea and what does it do to the blood gas
Cl/HCO3 exchanger
Results in inability to reabsorb Cl and cannot excrete bicarbonate
Result= metabolic alkalosis with hypochloraemia
What channel defect occurs in congenital sodium diarrhoea
What is the affect on the blood gas
What kind of stool do you get
Na/H channel defect- cannot absorb sodium or excrete hydrogen
Metabolic acidosis
Alkaline stool
What pathology occurs in congenital Microvillus atrophy and tufting enteropathy
have epithelial cell aplasia in the microvillus surface with microvilli atrophy and in tufting enteropathy get tufts of epithelia cells extruding from the epithelia cells on biopsy
Results in severe secretory diarrhoea from birth
Require PN
Require Gut transplant
What malfunctions in fructose malabsorption vs intolerance
Fructose malabsorption- GLUT5 transporter defect
Fructose intolerance- metabolism defect = due to fructose-1-phosphate-aldolase
Gene=ALDOB
what is Zollinger-Ellison syndrome
Gastrin producing tumour. Results in increased parietal stimulation –> increased acid secretion –> gastric ulcers and chronic diarrhoea
Name 4 causes of exocrine pancreatic insufficiency (genetic) and their features
Cystic fibrosis- CFTR mutation
Schwann-Diamond syndrome: SBDS mutation - neutropenia, bone abnormalities, acinar duct aplasia leading to exocrine pancreatic insufficiency
Pearson Syndrome- fibrosis of exocrine gland, sideroblastic anaemia
Johnson-Blizzard syndrome- fibrosis of pancreatic gland, severe nasal hypoplasia
What genes are associated with hereditary pancreatisi
SPINK-1, PRSS
What are the risk of developing coeliac in these people
-HLA matched sibling of a coeliac person
-Monozygotic twin
-1st degree relative
-30-40%
-70-100%
-5-10%
What are drugs in the Calcinerin inhibitor group and what are their MOA and side effect profile
Tacrolimus and Cyclophosphamide
MOA: inhibit IL2 transcription so T-cells cannot proliferate
Side effects:
-Cyclosporin: nephrotoxicity, hairiness, gum hypertrophy, dyslipidaemia
-Tacrolimus: nephrotoxicity, HTN
Describe the metabolism of Azathiopurine and what affects the dosing in various populations
Azathiopurine works to inhibit DNA purine synthesis
Broken to 6-Metacaptopurine.
From there can be metabolised to 6-thioguanine OR to 6-MMP by the enzyme TPMT.
6-MMP= liver toxicity
6-TG= bone marrow suppression
If too little TPMT, get increased 6-TG levels and can cause profuse bone marrow suppression
Avoid in homozygous
What is the MOA of methotrexate and what is the side effect profile
Anti-folate/anti-metabolite
Side effect- liver injury, lung fibrosis, Bone marrow suppression
