Flashcards in GI Deck (62):
VASOACTIVE INTESTINAL PEPTIDE
Relaxation of smooth muscle; increased intestinal and pancreatic secretion
Co-secreted with Ach
Contraction of smooth muscle; increased salivary secretion
Gastroesophageal Reflux Disease
Increased Intra-abdominal pressure. LES unable to prevent gastric acids from refluxing. Can degrade esophageal lining.
- H2 receptor antagonists to reduce gastric acid secretion
- Proton pump inhibitors
Upper portion of stomach is sticking through the diaphragm, into the chest cavity.
Causes pain and acid-reflux. LES no longer functions properly.
Smooth muscle layer of esophagus lacks normal peristalsis and LES does not relax normally in response to swallowing,
Treatment is surgical. Pt's also treated with Ca2+ channel blockers, botox to the LES, and other muscle relaxants.
6 type of secretory cells of the fundus/antrum AND what they secrete
(1) Parietal/oxyntic cells: hcl and intrinsic factor
(2) Mucous Neck cells: mucus
(3) Peptic/Chief cells: pepsinogens
(4) ECL cells: histamine
(5) D cells: somatostatin
(6) G cells: gastrin
Required for normal absorption of vitamin B12 in the ileum.
ONLY ESSENTIAL COMPONENT OF GASTRIC JUICE in a healthy human
3 substances which stimulate H+ secretion by parietal cells:
The rate of H+ secretion can be regulated by each His, Ach, and Gastrin independently, as well as by interactions among the three.
Inhibition of Gastric Acid Secretion by Parietal Cells
Negative Feedback Loop
Acidic chime in the distal stomach inhibits acid secretion via direct and indirect somatostatin effects + effects of prostaglandins
Process in which much of the chyme which does not empty into the duodenum is propelled back to the stomach for further mixing and breakdown. This allows them to be small enough to enter duodenum.
The lining of the stomach contains columnar epithelium folded into these gastric pits.
Each gastric pit is the OPENING WHERE GASTRIC GLANDS EMPTY
Usually a tumor (or gastrinoma)located in the pancreas secretes high quantities of gastrin. Increases H+ secretion by parietal cells and parietal cell mass.
Produces duodenal ulcer and leads to fatty stool (steatorrhea).
Gastric emptying happens after what 4 conditions?
(1) An increase in tone (intraluminal pressure) in the proximal portion of stomach
(2) Increased strength of antral contractions
(3) Opening of the pylorus so the contents can move
(4) Simultaneous inhibition of duodenal segmental contractions
Function of pancreatic secretions
2 main components:
(1) Aqueous component, high in HCO3-.
- functions to neutralize the H+ delivered to the duodenum from incoming chyme
(2) Enzymatic component
- enriched with enzymes that digest carbohydrates, proteins and lipids into absorbable molecules.
Control of Pancreatic Ductal Secretion
When the luminal pH is below 4.5, S-cells are triggered to release secretin.
This triggers bicarb release from ducts. It is ultimately shut off via a negative feedback loop.
How does Secretin function?
(1) Increases cAMP in duct cells
(2) Opens CFTR Cl- channels, causing outflow of Cl- into lumen of duct
(3) High Cl- levels trigger Cl- - HCO3- anti-porter, causing HCO3- to be pumped into lumen (in exchange for Cl-)
What secretes CCK?
I cells (in the small intestinal epithelium)
2 methods by which CCK stimulates acinar secretion.
(1) As an endocrine factor which binds to acinar cell CCK1 receptor
(2)stimulation of neural reflexes which activate vagovagal reflex, leading to secretion of ACh, GRP and VIP
Mechanism of Acinar Enzyme Secretion
CCK, ACh and GRP acts via mobilizing intracellular Ca2+ to cause the release of granules into lumen.
Granular contents = pre-synthesized and stored secretory products.
Premature activation of proteases (by TRYPSIN) before they reach the appropriate site of action.
CCK and Bile
CCK stimulates the contraction of the Gallbladder and relaxation of the Sphincter of Oddi. This allows for Bile release into the small intestine.
Secretes mucus and Bicarb
Secrete Peptidases and Enzymes that digest carbohydrates
Small Intestine (reside at bottom of villi)
Secrete antimicrobial peptides and enzymes.
What type of carbohydrates are absorbed through intestinal epithelial cells?
ONLY MONOSACCHARIDES. Thus, all ingested carbohydrates must be digested into monosaccharides to be absorbed.
What is most significant for the breakdown of starch?
Where does protein digestion begin? When is it completed?
-It starts in the stomach (with the action of pepsin)
-It is completed in the small intestine with pancreatic and brush-border proteases
Describe the 2 classes of proteases.
Endopeptidases: Hydrolyze the interior peptide bonds of proteins
Exopeptidases: Hydrolyze one amino acid at a time from the C-terminal ends of proteins and peptides
First step in intestinal protein digestion
Activation of inactive trypsinogen to active trypsin by brush border enzyme ENTEROKINASE.
Function of Trypsin
Trypsin catalyzes the conversion of all other inactive precursors used for intestinal protein digestion, into their active enzyme forms (even autocatalyzing some trypsinogen into trypsin)
Disorders of Protein Digestion and Absorption.
(1) Single AA Absorption Diseases- can't absorb single AA so must be di- or tri-
(2) Trypsinogen deficiency
(3) Cystinuria- one of the AA transporters is absent in small intestine and kidneys. This causes increased AA secretion in feces and urine.
The mixing action of the stomach churns the dietary lipids into a suspension of fine droplets- this greatly increases the surface area for digestive enzymes,
In the stomach --> dietary proteins facilitate emulsification
In the small intestine --> bile acids facilitate emulsification
Components of pancreatic juice
(1) Pancreatic lipase: hydrolyzes triglycerides to monoglycerides
Phospholipase A2: (activated by trypsin). Hydrolyzes phospholipids to lysolecithin and fatty acids.
Cholesterol ester hydrolase: hydrolyzes cholesterol ester to free cholesterol and fatty acids. Also produces glycerol.
Inside the cell, lipid digestion products are re-esterified with free fatty acids and packaged with apoproteins, to form these CHYLOMICRONS.
These are then packaged in secretory vesicles and go through exocytosis. They go through the lymphatic system to the thoracic duct, where they empty into the bloodstream.
Disorders of Lipid Digestion and Absorption
(1) Pancreatic Insufficiency- chronic pancreatitis and cystic fibrosis --> steatorrhea
(2) Acidity of Duodenal Contents- pancreatic enzymes cannot function optimally at acidic pH
(3) Deficiency of Bile Salts- no micelle formation or loss of bile in feces
(4) Abetalipoproteinemia- failure to synthesize Apoprotein and form chylomicrons or to transport fat via lymph.
Major site of Na+ absorption in the small intestine.
Epithelium cells of intestinal crypts vs those lining the villi
Intestinal crypts: secrete fluid and electrolytes
Lining villi: mostly absorb fluid and electrolytes.
What happens in cholera
Adenylyl cyclase is highly activated. Fluid secretion by the crypt overwhelms the absorptive capacity of villus cells, causing major diarrhea.
Osmotic vs Secretory Diarrhea
OSMOTIC- caused by the presence of non-absorbable solutes in the intestinal lumen (ex. lactase deficiency)
SECRETORY- caused by excessive secretion of fluid by crypt cells (ex. cholera)
Absorption of Vitamin B12 (cobalamin) is dependent on...
Its ability to bind to intrinsic factor (IF). IF is secreted by gastric parietal cells.
In gastrectomy, parietal cells are lost and this leads to pernicious anemia, because Vitamin B12 is needed for RBC formation.
What separates the ileum from the cecum?
The Ileocecal sphincter. It normally is closed and separates the ileum from the cecum.
Secrete Peptide YY (Ileal brake), in response to lipid in the lumen.
It decreases gastric emptying and overall intestinal motility. Also reduces fluidity of intestinal contents and propulsion of chyme. This allows for MORE TIME FOR DIGESTION AND ABSORPTION IN THE SMALL INTESTINE.
Short duration contractions which mix and circulate contents.
Na+-dependent symporter used for absorption of short-chain fatty acids in the colon.
Channel used to absorb Na+ in distal colon. Causes sodium reabsorption as a result of neurotransmitters or hormones.
Improper functioning --> diarrhea.
Used to cure intestinal infections caused by dangerous type of bacteria which antibiotics cannot control. Usually diluted with salt water first.
Segment of colon is permanently contracted due to improper enteric nervous system development. This causes obstruction. Surgical excision of affected area is needed.
Hepatic Triad and associated zones
TRIAD: Hepatic artery, portal vein and bile duct
(1) periportal cells. closest to triad. most sensitive to oxidative injury
(2) intermediate cells
(3) pericentral cells. closest to hepatic vein. most sensitive to ischemia.
Channel which is formed by hepatocytes and serves to drain bile from liver and transport it the biliary ductules.
Metabolic Function of the Liver
CARBOHYDRATE(gluconeogenesis and glycogen storage), LIPID (fatty acid oxidation, conversion of cholesterol to bile acids), and PROTEIN METABOLISM (synthesis of all non-essential amino acids, synthesis of plasma proteins and clotting factors and converts ammonia to urea).
Phase I and Phase II reactions of liver detox function
Phase I: oxidation, hydroxylation etc. Catalyzed by cytochrome P-450 enzymes
Phase II: conjugate the substances with other substances, to be excreted
Main components of bile
Bile acids = 65%
Also cholesterol, bile pigments, proteins, phospholipids etc.
Reabsorption of bile acids
It is unconjugated so is unable to passively cross the intestinal epithelial. Once chyme reaches the terminal ileum, conjugated bile is REABSORBED VIA A SYMPORTER KNOWN AS APICAL NA+-DEPENDENT BILE ACID TRANSPORTER (ASBT).
The fraction of bile acid which enters the colon becomes deconjugated and is reabsorbed PASSIVELY.
Precipitated bile constituents which accumulate in the gallbladder or elsewhere in the biliary tree.
Composed predominantly of CHOLESTEROL OR Ca2+ BILIRUBINATE (PIGMENT) STONES.
Picks up unconjugated bile and brings it into liver
Increase in unconjugated bilirubin in plasma reflects:
-loss or absence of UGT (enzyme which conjugates)
-sudden oversupply of heme (e.g. in transfusion reactions)
In conjugated bilirubinemia, there is high bilirubin in urine (dark color) due to:
-defect in transporter that secretes conjugated bilirubin in bile
-blockage of bile flow due to a gall stone (most common)
When does jaundice become clinically manifested?
When total plasma bilirubin is > 2 mg/dl (2 mg per 100mL of plasma)
Urea cycle and liver function
UREA CYCLE --> Conversion of ammonia (which is very toxic to CNS) to urea for excretion. Occurs in liver.
The urea cycle is usually preserved as long as the liver has some function. Once the urea cycle stops functioning, you know the damage is VERY serious.
Main Pathologies of Liver
(1) Hepatic Encephalopathy- decreased liver function which leads to ammonia and other toxins not being cleared by the liver. Results in decline in mental function
(2) Liver Cirrhosis- irreversible destruction of the functional anatomy of the liver. Drugs, poisons and hepatitis are the major causes.
(3) Portal Hypertension- increased vascular resistance in the liver.