Lecture 9: GI (Exocrine Pancreas, Liver/Gallbladder, LI) Flashcards
Which peptide enhances insulin secretion?
Oral Glucose-stimulates Insulinotrophic Peptide
What stimulates GIP release at a larger magnitude? Intravenous glucose or oral glucose
GIP (gastrin inhibitor of peptide) aka K cells
Oral glucose
Intravenously not as stimulatory to GIP b/c not directly in the duodenum but in blood vessels
How much enzymes are produced and secreted by the exocrine pancreas?
Excess, altough prodcution decreases progressively as we age (~30-50 decrease @ ge 75 years)
When do nutrition problems arise?
- If production of pancreatic enzyme falls by as little as 10%
- Outflow of pancreatic juice is obstructed (ex. sphincter of oddi obstructed)
Review: List the sphincters that are present in the Gastrointenstinal Tract
- Upper and lower esophageal sphincters
- Pylorus
- Sphincter of Oddi
- Internal and external anal sphincter
- Illeocecal valve
Know location and function
Which ducts drain to the Duodenum (in duodenal papilla)?
Common bile duct and Pancreatic Duct
What are the major pancreatic enzymes? (8)
- Trypsin
- Chymotrypsin
- Elastase
- Carboxypeptidase
- Lipase
- Amylase
- Ribonuclease
- Deoxyribonuclease
For the Enzyme(s): Trypsin, Chymotrypsin, & Elastase, what is the
- Substrate
- Action
- Substrate: Proteins
- Action: Breaks peptide bonds in proteins to form peptide fragments
For the Enzyme(s): Carboxypeptide, what is the
- Substrate
- Action
- Substrate: Proteins
- Action: Splits off terminal amino acid from carboxyl end of protein
For the Enzyme(s): Lipase, what is the
- Substrate
- Action
- Substrate: Fats
- Action: Splits off two fatty acids from triacylgcerols, forming free fatty acids and monoglycerides
For the Enzyme(s): Amylase, what is the
- Substrate
- Action
- Substrate: Polysaccharides
- Splits polysaccharieds into glucose and maltose
For the Enzyme(s): Ribonuclease, Deoxyribonuclease, what is the
- Substrate
- Action
- Substrate: Nucleic Acids
- Action: Splits muclei acids into free mononucleotides
The Exocrine Pancreas is a two-stage model utilizing _________ and ________.
Acinar cells; Ductal cells
List the cell types that play a part in pancreatic acinar cell regualtion and explain their functions
- Vasointestinal peptide (VIP) and secretin
- Both regulate the activation of cAMP
- GRP, ACh, CCK
- All regulate the presence of intracelluar [Ca2+]
Both cAMP & Ca2+ play a role in the phosphorylation of structural and regulatory proteins→Fusion of granules w/ apical membrane and discharge of contents
What cell dectects low pH in the duodenum?
HIGH yield
Acid sensing S-cells (aka ductal cells)
What hormone acts in the pancreatic duct when S-cells detect low pH?Explain it’s function
S-cells: Ductal cells
HIGH yield
Secretin stimulatese HCO3- secretion to raise duodenum pH
Overall goal: ↑ pH of environment so that enzymes can fucntion properly
How are secretin receptors expressed?
HIGH yield
Densely expressed on Pancreatic Ductular Cells in Humans
What action(s) liberate free fatty acids?
Gastric mixing and triglyceride digestion
Gastric lipase ↑ liberation of TAG
What are fatty acids a potent stimulate for?
CCK release
Which cells in the duodenum releases CCK and how is it activated?
- I-cells
- Free fatty acids(high protein or high carb meal)
What are the roles of CCK?
- Relaxes Stomach
- Can influence eating behavior (satiating effect)
Satiation: Process that causes on to stop eating
How much of TAGs are digested in the stomach?
TAG: Triglycerides
Approx. 10%
Which enzymes are required for the activation of some pancreatic digestive enzymes?
HIGH yield
- Brush Border Entrokinase (aka. Entropeptidase)
- Luminal Tyrsin
What does CCK stimulate and by which methods?
- Stimulates Gallbladder contraction & Sphincter of Oddi Relaxation
- Neural and Humoral Pathways
The sphincter of Oddi is __________ by the hormone___________ via ____________
HIGH yield
The sphincter of Oddi is relaxed by the hormone cholecystokinin (CCK) via vasoactive intestinal peptide (VIP)
What materials is the Large Intenstine (Colon) an entry for?
HIGH yield
- Entry of undigestible/unabsorbed material through the ileocecal sphincter
Unabsorbed material= soluble (ex. pectin)/unsoluble (ex.cellulose) fibers
What the the Colon (LI) a final site for?
HIGH yield
- FInal site for absorption of water and ions (many under hormonal control)
What happens to undigested nutrients (fibers) in the colon?
HIGH yield
Are metabolized by intestinal flora(bacteria) and converted to short chain fatty acids (SCFAs), neurotransmitters (ex. 5HT-3, dopamine) and vitamins
Fiver→colonic bacteria→SCFAs→feed colonocytes
What triggers Peptide YY production and release in the Colon?
Also in Ileum
YY=tyrosine-tyrosine
Protein and Fat
What does the release of PYY cause in the Colon?
Inhibits meal-stimulated GI functions
- ↓ Gastric acid secretion
- ↓ Gastric emptying
- ↓ Pancreatic secretion
- ↓ decreased transit rate
- ↓ Colonic motility
PYY has very strong anti appetite effet
List the parts of the Colon
- Terminal Ileum
- Ileocecal valve
- Cecum
- Ascending colon (site of most colon cancers)
- Transverse colon
- Descending colon (↑ [microbome])
- Sigmoid colon
- Rectum
What is the main difference in the right and left colon and why?
Function and Slow Wave Propagation differ to help ↑ H2O reabsorption
What is the function of the right and left colon?
- Right colon: Absorption of water and electrolytes
- Left colon: Formation and storage of feces
What are the three contraction pattern displayed by the colon?
- Mixing Movements
- Haustral Migration
- Mass Movement
Explain the three contraction patterns
- Mixing Movements
- Haustral Migration
- Mass Movements
- Mixing Movements: Strong contraction of circular muscles to ↑ SA→to help main absorption
- Haustral Migration: Back and forth contraction to ↑ H2O extraction
- Mass Movements: Stimulated by eating, laxatives, exercise by enteric NS to ↑ contraction
What occurs with sympathetic nerve stimulation in the colon?
Sympathetic nerve stimulation decreases spike frequency and inhibits colonic contractions
Mainly a parasympathetic process
What are Interstital Cells of Cajal (ICC)?
- “Pacemakers” and generate slow waves
- aka: BER; basal electrical rhythm
How is the colonic response to a meal initated?
By signals from the stomach, intestines and brain
Gastrocolonic Reflex: neural and hormonal controlled
What role does Aldosterone play in the colon?
HIGH yield
- Promotes expression of transporters required for sodium absorption
- Water follows sodium concentration
List the main functions of SCFAs from gut microbiome (5)
SCFAs= Short Chain Fatty Acids
HIGH yield
- Main fuel for coloncytes
- Tumor supressor effect
- Crosesses Blood Brain Barrier (BBB)
- HDAC activity
- Downregulates VEGF and has other epigentic effects
What enhances the production of SCFAs?
Prebiotics and Probiotics that influence colonic bacteria
What mediates the transport of SCFA in the gut?
HIGH yield
Sodium coupled monocarboxylate transporters (SMCT1)
What are the different causes of constipation?
- Usually d/t diet
- Drugs
- Diseases
List the dietary aspects that cause constipation (3)
HIGH yield
- Not enough dietary fiber
- High Calcium + Diary
- Dehydration
List the drugs the cause constipation (2)
- Opiates
- Calcium antacids
List the diseases that cause constipation (5)
- Irritable Bowel Disease
- Hirchsprung’s Disease: lack of ENS in distal colon
- Physiological Stress
- Hypothyroid
- GI cancers
List the causes of Diarrhea (5)
- Viral, bacterial, or parasitic infection in the colon (most common). Drugs too (Antibiotics, PPIs, Chemo, etc)
- Inflammatory bowel syndrome/Crohn’s disease
- Food intolerances: Wheat and diary products, sugar
- Ischemic bowel disease (older individuals)
- Colon
NOTE: Diarrhea kills more children than malaria, measles, and AIDs combined
List the four types of Diarrhea (4)
HIGH yield
- Secretory diarrhea: e.g. Cholera toxin
- Osmotic diarrhea: maldigestion, hyperosomtic
- Motilty-related diarrhea: vagotomy, neuropathy
- Inflammatory: Brush border damage from infection
What are treatments for Diarrhea?
- Antimotility agents (Immodium=Loperamide)
- Nonspecific agents (Pepto-Bismol=bismuth subsalicylate) buffer and anti-inflammatory effects
Loperamide=opioid receptor agonist that remains in stomach
How do you treat Traveler’s Diarrhea?
CDC recommends antibiotics (3 day regimen) or Pepto Bismol (8 doses over 4 hours)
What is Gastritis (inflammatory) and how do you treat?
HIGH yield
- Serious diarrhea combined with vomiting and retching over several hours
- The fluid loss from the colon will cause metabolic acidosis
- Treatment: Go to ER for anti-emetic, IV fluids, and anti-diarrheal
Anti-emetic: anti-vomiting
What is Irritable Bowel Disease (IBD)
NOT IBS and Celiac
HIGH yield
- Chronic inflammation of bowel; unkown reasons
- Include Crohn’s Disease and Ulcerative Colitis
List the abnormalities found in IBD (4)
Irritable Bowel Disease (IBD)
HIGH yield
- Inapproriate immune response to normally innocuous gut flora
- Damage to intestinal: maldigestion/malabsorption; defects in barrier function
- Malabsorption of bile acids in terminal ileum impacts colonic electrolyte transport, leading to diarrhea
List the abnormalities reported in Irritable Bowel Syndrome (IBS) (6)
- ↑ incidence of 3/min slow waves (↑ motility=diarrhea)
- ↓ myoelectric response to feeding (↓ motility=constipation)
- ↑ response to CCK and cholinergic agents (↑ pancreatic secretions)
- ↓ stressed-related small bowel dysmotility (slowed digestion)
- ↓ threshold for pain caused by distension (hypersensitve b/c cytokine & chemokine receptors increase)
- ↑ psychophsiologic scores