03- Gastrointestinal Flashcards
What is the fundamental role of the GI tract?
Extract nutrients from the external environment to provide energy and building blocks
What are the four functions of the GI tract?
Digestion, absorption, secretion, and motility
What is receptive relaxation?
Making space in the stomach in response to swallowing
What is gastrica ccomodation?
The vagovagal reflex triggers further relaxation in the stomach
What are the three phases of acid secretion in the stomach?
Cephalic, gastric, and intestinal
What is the postprandial phase?
Digestion period after eating
What is the interdigestive phase?
The period where we are not fed or digestion is complete
How small must food be to pass through the pyloric sphincter in the various phases?
Less than 2mm during the postprandial phase
More than 2mm in the interdigestive phase
What moves material through the small intestine during the interdigestive phase?
The migrating motor complex
Which nerve innervates the majority of the GI tract?
The vagus nerve
Which nerve innervates the distal colon?
The pelvic nerve
What does calcium do in the body?
Modulates hormone secretion, muscle contraction, nerve conduction, exocytosis, and the activity of many metabolic enzymes
What does phosphate do in the body?
Acts as a key component in ATP
How do calcium and phosphate regulation coordinate?
Together they are the principal components of hydroxyapatite crystals (mineral component of bone) and they are regulated by the same hormone
What is parathyroid hormone?
A peptide hormone synthesized and stored in the parathyroid glands
What does parathyroid hormone do?
Promotes Ca reabsorption and inhibits PO4 reabsorption
How do calcium levels influence PTH?
PTH synthesis is inhibited by high Ca and activated by low Ca
What does vitamin D do?
Binds to nuclear receptors to suppress PTH production
How does excess PO4 influence PTH?
PTH levels rise to balance the Ca-PO4 ratio
What do epithelial cells secrete?
Bicarbonate and mucus
What do parietal cells secrete?
HCl
What do chief cells secrete?
Pepsinogen and gastric lipase
What cells are in the corpus and what do they secrete?
Enterochromaffin-like cells secrete histamine
D cells secrete somatostatin
What cells are in the antrum and what do they secrete?
G cells secrete gastrin
D cells secrete somatostatin
What does the low pH of the stomach do to proteins?
Causes their denaturation to expose proteolytic sites
What two pH values are important for pepsinogen?
Pepsinogen is cleaved at a pH of 3.5 and activated at a pH of 3
Why do H and Cl move to the lumen?
H is exchanged for K which enters due to a concentration gradient
Cl follows a concentration gradient
How is the stomach protected from the low pH and pepsin?
Epithelial cells secreting bicarbonate and mucins
How does acetylcholine increase gastric acid secretion?
It stimulates histamine release which acts on histamine receptors, gastrin release which acts on CCK receptors, and the acetylcholine acts directly on M3 receptors
What factors stimulate acid secretion in the intestinal phase?
Gastrin, entero-oxyntin, and absorbed amino acids
How does somatostatin cause negative feedback?
Inhibition of histamine, gastrin, and acid secretion
What are the basic functions of salivary exocrine glands?
Lubricate ingested food, initiate starch digestion, and prevent dehydration of oral mucosa
What are the basic functions of pancreatic exocrine glands?
Produce a pancreatic juice that neutralizes chyme as it enters the duodenum and is rich in zymogens which facilitate digestion
What are acinar cells?
Polarized epithelial cells specialized for the production and export of protein
What are duct cells?
Polarized epithelial cells specialized for the export of electrolytes
What is the primary function of duct cells?
Fluid and electrolyte transport
What do serous-type acinar cells secrete?
Amylase
What do mucous-type acinar cells secrete?
Mucin and proline-rich proteins
What is sjorgen syndrome?
An autoimmune disease that can destroy salivary glands
What controls salivary secretions?
The parasympathetic nervous system
What do bicarbonate and isotonic fluid secreted from the duct cells do in the duodenum?
Provide hydration to the mucous layer and neutralize the pH
What prevents premature activation of zymogens?
Enterokinase is only found in the duodenum, zymogens are condensed in granules, and inhibitors of digestive enzymes are co-packed in the secretory granules
What absorption occurs in the small intestine?
Nutrients, Na, K, Cl, and water
What absorption occurs in the large intestine?
Electrolytes and water
What cells cause absorption in the large and small intestine?
Villous absorptive cells in the small intestine
Surface absorptive cells in the large intestine
What cells perform secretion?
Crypt cells
Why are tight junctions important?
Prevention of unwanted material in the intestinal lumen from entering
What is solvent drag?
When fluid movement takes ions with it
What is the most significant contributor to Na absorption in the post-prandial phase?
Na/glucose or Na/amino acid cotransporters
What is the main function of the Na/H exchanger?
Neutralize pH when it becomes too high
What is the primary mechanism of Na absorption between meals?
Na/H and Cl/HCO3 coexchanger
How do epithelial Na channels work?
Na moves down its concentraton gradient
How does passive Cl absorption work?
Cl moves down its electrochemical gradient in a paracellular or transcellular method
What is unique about the Cl/HCO3 coexchanger when discussing chloride movement?
It works independent of the Na/H coexchanger
What is the primary mechanism of Cl absorption between meals?
Na/H and Cl/HCO3 exchanger
Where does Cl secretion occur?
In the large and small intestine via crypt cells
Where and how does passive K absorption occur?
In the small intestine via solvent drag
Where and how does active K absorption occur?
The distal end of the colon in exchange for a hydrogen
Where and how does passive K secretion occur?
Occurs in the large intestine via solvent drag
What can stimulate secretion?
Secretagogues such as the enteric nervous system and immune cells
What can stimulate absorption?
Aldosterone, angiotensin, and somatostatin
Where are macronutrients absorbed?
The duodenum and jejunum
Where are iron and folate absorbed?
Duodenum
Where is calcium absorbed?
Throughout the small intestine
Where are bile acids absorbed?
Distal jejunum, ileum, and ascending colon
Where is B12 absorbed?
Ileum
What does amylase do in digestion?
Reduces polysaccharides to oligosaccharides
What do brush border enzymes do in carbohydrate digestion?
Digest oligosaccharides into monosaccharides
What is lactase?
The only enzyme which can digest lactose
What can maltase, sucrase, and isomaltase all digest?
Alpha1-4 linkages of maltose, maltotriose, and alpha-limit dextrins
What can maltase digest?
Straight chain oligosaccharides 9 monomers long
What can sucrase digest?
Sucrose
What can isomaltase digest?
Alpha1-6 linkages
How is the absorption of glucose and galactose mediated on the apical surface?
Sodium-glucose co-transporter
What mediates the absorption of fructose on the apical surface?
Glut5
What mediates the transport of monosaccharides into the blood stream on the basolateral surface?
Glut2
What causes lactose intolerance?
Lactase deficiency
What causes glucose-galactose malabsorption?
SGLT1 deficiency
What reduces proteins into oligopeptides?
Pepsin and pancreatic proteases
What breaks oligopeptides into absorbable sizes?
Brush border peptidases
How are amino acids in the intestinal lumen absorbed?
Sodium/amino acid co-transporter
How are tetra, tri, and di-peptides absorbed?
H/oligopeptide co-transporter called PepT1
When does hartnup disease occur?
Absorption of neutral amino acids is defective
When does cystinuria occur?
When absorption of cationic amino acids is defecctive
When does lysinuric protein intolerance occur?
When there is impaired basolateral transport of cationic amino acids
What is key to lipid digestion?
Emulsification in the duodenum to form a microenvironment in which digested lipids become accessible
What makes up mixed micelles?
Bile salts, fatty acids, monoacylglycerols, lysophospolipids, and cholesterol
Which proteins mediate fatty acid uptake?
Fatty acid translocase, intestinal fatty acid binding protein, and fatty acid transport protein
What happens if bile acids are absorbed?
They are secreted into the lumen using ABCG1/ABCG8 transporter
How is cholesterol absorption mediated?
Niemann-pick C-1 like 1 protein
What happens to lipids once they have been absorbed?
They are packaged into chylomicrons and enter the lymphatic system
How is folate absorbed?
PteGlu7 is deconjugated by folate conjugase which converts it to PteGlu1. This is absorbed by SLC46A1
How is cobalamin absorbed?
It binds to intrinsic factor and is carried into enterocytes through receptor mediated uptake
How is non-heme iron absorbed?
Ferric iron is converted to ferrous iron by ferric reductase Dcytb, and then ferrous iron is absorbed via the divalent metal co-transporter DMT1
What are the functions of the liver?
Enhance lipid absorption, detoxify compounds, produce substances, and store, metabolize, and distribute nutrients
What side of hepatocytes are microvilli present on?
Basolateral
Which side of hepatocytes are canaliculi on?
Apical
Where does the blood flowing through the liver come from?
75% portal vein, 25% hepatic artery
What makes up the portal triad?
Hepatic artery, portal vein, and bile duct
What are the main primary bile acids present in humans?
Cholic acid and chenodeoxycholic acid
What is used to uptake bile salts?
Sodium/taurocholate cotransporting polypeptide
What is the main exporter of bile acids?
Bile salt export protein
What mediates conjugated bilirubin uptake?
OATP1B1 and OATP1B3
What mediates the uptake and excretion of organic cations?
Uptake occurs via the organic cation transporter and excretion occurs via MDR1
What is the major component of bile?
Phosphatidylcholine
What occurs in phase one of hepatocyte detoxification?
Oxidation-reduction reactions performed by cytochrome p450 enzymes to make the compound more polar
What occurs in phase two of hepatocyte detoxification?
Conjugation with agents such as sulfate, glucuronate, or glutathione to make the compound more water soluble.
What occurs in phase three of hepatocyte detoxification?
Modified compound is recognized and delivered to transporters for excretion
What is canalicular bile flow?
The sum of a constant bile acid independent flow, and a flow that is dependent on the amount of bile being excreted
What is total bile flow?
The sum of canalicular bile flow and ductular secretions from cholangiocytes
What is the second major source of fluid in bile?
Cholangiocytes
What stimulates gallbladder emptying?
CCK secreted from I cells
What provides negative feedback to the gallbladder?
Fibroblast growth factor 19 which is secreted when bile reaches the ileum
What does the sphincter of oddi do?
Controls bile flow
What are the mechanisms of bile recycling?
Passive intestinal absorption, active intestinal absorption, feedback via FGF19, and hepatic regulation
What does microsomal triglyceride transfer protein do?
Catalyzes the lipidation of apolipoprotein B-48 and the lipid droplet
What is a lacteal?
A single, blind-ended, lymphatic vessel at the centre of each intestinal villus
What are lipoproteins?
Structures of lipids and proteins used to transport lipids through the body
What does GPIHBP1 do?
Tethers the lipoprotein to the lipase to encourage breakdown
Where does the liver get cholesterol?
Chylomicron remnant, LDL, HDL remnant, and synthesis
Where does cholesterol from the liver get sent?
Bile acids, direct secretion, and out in VLDL
What is TG-CE exchange?
HDL gives other lipoproteins cholesterol ester in exchange for TAG
What are VLDLs made of?
TAG. phospholipids, cholesterol, cholesterol esters, and proteins
Where do triacylglycerol’s in the liver come from?
Fatty acid flux, de novo lipogenesis, and liver stores
Where does the liver send TAGs?
VLDL synthesis and secretion, oxidation, and liver stores
What exchange occurs between the liver and the muscle?
Liver produces glucose and ketone bodies
Muscle provides lactate and amino acids
How does adipose tissue regulate the liver?
Liver metabolism is regulated by adipokines and hormones secreted from the adipose tissue
What characteristics do white adipocytes have?
They are spherical, contain a single lipid droplet, and expand for larger lipid storage capacity
What characteristics do brown adipocytes have?
They are ellipsoidal, have dispersed lipid droplets, and numerous mitochondria
How do beige adipocytes come to be?
Arise from beiging of white adipocyte tissue induced by cold, diet, and exercise
Where are pink adipocytes found and why?
Animal mammary glands because they are needed for milk fat production
What occurs in white adipocytes during the post-prandial phase?
Fatty acid uptake, TAG synthesis, and lipid storage
What occurs in white adipocyte tissue during the fasting phase?
Fatty acid release
What is ectopic lipid accumulation?
Insufficient lipid retention in white adipose tissue leading to lipid accumulation in other tissues
What does leptin do?
Suppress appetite, promote energy expenditure, and regulate heat loss
What is leptin resistance?
The inability to respond to leptin despite sufficient or excess levels in circulation
What are lipokines?
Lipid hormones which are produced by adipocytes
What are microRNAs?
Small noncoding RNAs produced by all cells of the body
What is proglucagon cleaved to in pancreatic alpha cells?
Glucagon-related polypeptide, glucagon, and a C-terminal fragment
What is proglucagon cleaved into in neuroendocrine cells?
Glicentin, intervening peptide-1, glucagon-like peptide-1, and glucagon-like peptide-2
How do GIP, CCK, GLP2, and 5-HT impact glucose absorption in enterocytes?
GIP and GLP2 stimulate absorption
CCK and 5-HT decrease absorption
How do GIP, GLP2, and 5-HT impact amino acid absorption in enterocytes?
GIP and GLP2 increase amino acid absorption
5-HT reduces amino acid absorption
How do NTS, SCT, PYY, GLP1, and GLP2 impact lipid absorption in the enterocytes?
NTS, SCT, and GLP2 increase lipid absorption
PYY and GLP1 decrease lipid absorption
What is the incretin effect?
There is higher insulin secretory response with oral glucose administration as compared to intravenous insulin
What does DPP4 do?
Cleaves proteins which reduces their bioactivity
What impacts energy homeostasis?
Food intake and energy expenditure
What impacts glucose homeostasis?
Glucose production and utilization
Which neurons sense the body’s energy state?
Neuropeptide Y, agouti-related protein, and proopiomelanocortin producing neurons
What does the NTS do in response to signals of increased food intake?
Activates vagal afferents to reduce food intake
What is activated by the preoptic area to promote thermogenesis?
The preoptic area dorsomedial hypothalamus rastral raphe pallidus pathway
What does the autonomic nervous system do when it is signaled of increased food intake?
Modulates pancreatic insulin/glucagon secretion, hepatic glucose production, and skeletal muscle glucose uptake
What do central glucoregulatory circuits neurons do?
Respond to input from afferent glucose-sensing neurons and project onto and regulate the output from neuroendocrine and autonomic control systems
What is type 1 diabetes?
An autoimmune disease in which pancreatic islet beta-cells are destroyed
What is type 2 diabetes?
Insulin resistance and beta-cell dysfunction
What is the most effective treatment for people with severe obesity?
Bariatric surgery
What is dyslipidemia?
Disrupted lipid homeostasis leading to high LDL levels
What is atherogenic dyslipidemia?
Increased fasting triglycerides, low HDL, and small dense LDL
What is metabolic syndrome?
The co-occurrence of several known cardiovascular risk factors, such as insulin resistance, obesity, atherogenic dyslipidemia, and hypertension
