phys 56- lipid digestion and absorption

celiac disease

Antibodies against gluten in wheat, oats, rye, barley Attack villi & strip them flat from duodenum to terminal ileum Fat malabsorption- loss of intestinal lining Increased bowel wall lymphoma Anti-endomyseal antibody Anti-Tissue transglutaminase Biopsy most accurate Stop gluten Resolves in a few weeks

fat digestion in the small intestines

Bile Salt secretion Emulsification of lipids Pancreatic Lipase and co-lipase Cholesterol Ester Hydrolase- takes FA off cholesterol Phospholipase A2- cuts @ position A2 on phospholipid

lipid digestion in the stomach

Churn/Mix/Emulsify Lingual and Gastric Lipases 10% Digested Slowly empties Lingual Lipase removes all three Fatty Acids from

bacterial overgrowth effects

Liver conjugates bile acid to salt with taurine or glycine Bacteria DE-conjugate back to an acid Bile acids are re-absorbed too early because when deconjugated they are lipid soluble Similarly, decreased pH in the intestinal lumen promotes "early" absorption of bile acids by converting them to nonionic form

cholesterol ester hydrolase

Pulls the fatty acid off cholesterol Makes it small enough to be absorbed Secreted active Cholesterol ester hydrolase is secreted as an active enzyme and hydrolyzes cholesterol ester to free cho- lesterol and fatty acids. It also hydrolyzes ester link- ages of triglycerides, yielding glycerol.

case

case

Q6. Which of the following decreases the sense of hunger? a. Amylase b. Enterostatin c. Bile reabsorption at terminal ileum d. Acid neutralization by bicarbonate in duodenum e. Lysolecithin

enterostatin

does gallbladder remove effect fat absorption

Gallbladder removal does NOT cause fat malabsorption because the bile recirculates

Q4. What is the site of re-esterification of fats? Micelles Lacteals Villous Capillaries Thoracic Duct Intestinal Epithelial Cells

Intestinal Epithelial Cells They are reesterified in the intestinal epitheleal cells and then moved into the lacteals

where are lipids absorbed

Lipids go into the lacteal not the blood like carbs and proteins do.

Q1 A patient comes with oily, greasy, floating, foul smelling diarrheal stool. They have multiple ulcers in the distal duodenum, a high acid level and a high gastrin level. What is the reason for the diarrhea? Decreased Amylase production Decreased Trypsinogen activation Increased secretion of lipids Acid inactivation of lipase Increased secretion of water

Acid inactivation of lipase Zollinger ellison syndrome Making so much acid that you inactivate lipase

colipase

Co-Lipase pushes bile off the fat so lipase can touch dissolves bile salts Colipase is secreted in pancreatic juices in an inactive form, procolipase, which is activated in the intestinal lumen by trypsin which cleaves off enterostatin . Colipase then displaces bile salts at the lipid-water interface and binds to pancreatic lipase. With the inhibitory bile salts displaced, pancreatic lipase can proceed with its digestive functions.

chylomicron transport

Huge fat balls No Apo B, No absorption Apo B made in intestinal epithelial cells Golgi packs them into vesicles Too large to get into blood capillaries Huge fat drops squeeze in lacteal cells

tropical sprue

Infection of small intestine Found on biopsy Fat malabsorption Treated with antibiotics

structure of a bile salt

The glycine is the water soluble part

2 reasons there might be more H+ delivered from the stomach

There are two reasons that all of the H+ delivered from the stomach might not be neutralized: (1) Gastric parietal cells may be secreting excessive quantities of H+, causing an overload to the duo- denum; or (2) the pancreas may fail to secrete sufficient quantities of HCO3− in pancreatic juice. The first reason is illustrated by Zollinger-Ellison syndrome.

how are fat soluble vitamins absorbed

They are processed in the same manner as dietary lipids. In the intestinal lumen, fat- soluble vitamins are incorporated into micelles and transported to the apical membrane of the intestinal cells. They diffuse across the apical membrane into the cells, are incorporated in chylomicrons, and then are extruded into lymph, which delivers them to the general circulation.

how do the contents of a chylomicron compare to that of VLDL, LDL and HDL

This is the CONTENTS of the chylomicron The COVERING is 80% phospholipid and 20% apoprotein Formation within intestinal epithelial cell

dietary lipids

Triglycerides Cholesterol Phospholipids

failure to synthesize apoproteins

Failure to synthesize Apo B (β-lipoprotein) causes abetalipopro- teinemia. In this disease, chylomicrons either do not form or are unable to be transported out of intestinal cells into lymph. In either case, there is decreased absorption of lipids into blood and a buildup of lipid within the intestinal cells.

does ileal resection effect fat absorption

Ileal resection (removal of the ileum) interrupts the enterohepatic circulation of bile salts, which then are excreted in feces rather than being returned to the liver. Because the synthe- sis of new bile salts cannot keep pace with the fecal loss, the total bile salt pool is reduced.

really long mechanism of lipid digestion/ absorption

1. The products of lipid digestion (cholesterol, mono- glycerides, lysolecithin, and free fatty acids) are solubilized in the intestinal lumen in mixed micelles, except glycerol, which is water soluble. Mixed micelles are cylindrically shaped disks with an average diameter of 50 Å. As discussed earlier, the core of a micelle contains products of lipid digestion and the exterior is lined with bile salts, which are amphipathic. The hydrophilic portion of the bile salt molecules dissolves in the aqueous solution of the intestinal lumen, thus solubilizing the lipids in the micellar core. 2. The micelles diffuse to the apical (brush-border) membrane of the intestinal epithelial cells. At the apical membrane, the lipids are released from the micelle and diffuse down their concentration gradi- ents into the cell. The micelles per se do not enter the cell, however, and the bile salts are left behind in the intestinal lumen to be absorbed downstream in the ileum. Because most ingested lipid is absorbed by the midjejunum, the "work" of the bile salts is completed long before they are returned to the liver via the enterohepatic circulation. 3. Inside the intestinal epithelial cells, the products of lipid digestion are reesterified with free fatty acids on the smooth endoplasmic reticulum to form the original ingested lipids, triglycerides, cholesterol ester, and phospholipids. 4. Inside the cells, the reesterified lipids are pack- aged with apoproteins in lipid-carrying particles called chylomicrons. The chylomicrons, with an average diameter of 1000 Å, are composed of triglycerides and cholesterol at the core and phospholipids and apoproteins on the outside. Phospholipids cover 80% of the outside of the chylomicron surface, and the remaining 20% of the surface is covered with apoproteins. Apopro- teins, which are synthesized by the intestinal epi- thelial cells, are essential for the absorption of chylomicrons. Failure to synthesize Apo B (or β-lipoprotein) results in abetalipoproteinemia, a condition in which a person is unable to absorb chylomicrons and, therefore, is also unable to absorb dietary lipids. 5. Thechylomicronsarepackagedinsecretoryvesicles on the Golgi apparatus. The secretory vesicles migrate to the basolateral membranes, and there is exocytosis of the chylomicrons. The chylomicrons are too large to enter vascular capillaries, but they can enter the lymphatic capillaries (lacteals) by moving between the endothelial cells that line the lacteals. The lymphatic circulation carries the chy- lomicrons to the thoracic duct, which empties into the bloodstream.

Q7. Why doesn't removal of the gallbladder lead to weight loss? Bile not essential for caloric intake Fats are absorbed in the colon Active transport mechanisms take over vitamin ADEK absorption Bile continuously recirculates without loss Increased lingual lipase to compensate

Bile continuously recirculates without loss

Q5. Which of the following is most specific diagnostic test for tropical sprue? Sudan black stain for extra fecal fat Hypocalcemia Bone densitometry low Elevated prothrombin time from coagulaopathy Biopsy

Biopsy All forms of fat absorption will show: Positive sudan black Hypocalcemia due to malabsorption of vitD Low bone density because of low Ca Elevated prothrombin time because low in vit K Biopsy detects bacteria in tissue

Deficiency of bile salts.

Deficiency of bile salts interferes with the ability to form micelles, which are necessary for solubilization of the products of lipid digestion. No bile = Minimal Fat absorbed

Q3. Which of the following is the most important mechanism for absorption of lipids? Secondary active transport Exchange for H+ Diffusion SGLT 1 GLUT 2

Diffusion Side note: Di and tri peptides are co transported with H+ not exchanged for H+

enterostatin

Enterostatin - signals satisfaction to the brain produced by conversion of procolipase to colipase Breaks off of pro-colipase Decreases hunger and fat intake Effective peripherally or into the brain Yells at it to stop eating

Q2. A patient with colon cancer has the entire colon including the terminal ileum resected. What do you expect to occur? Increased fat absorption Increased synthesis of bile acid Decreased synthesis of bile salt Decreased cholesterol synthesis Vitamin A toxicity

Increased synthesis of bile acid Malabsorption of B12 and bile So you will make more bile acids

mechanism of lipid absorption

Micelles form from lipid products: Monoglyceride Cholesterol Free Fatty Acids (FFA) Lysolecithin (phospholipid- 1FA) Covered with bile salts Enter apical brush border by diffusion Bile salts NOT absorbed- if they are then that is a disease Lipid products re-esterify with FFA

fat soluble vitamins

No fat absorption, no ADEK absorption Celiac, Tropical sprue, bile insufficiency ALL decrease ADEK absorption No Lipase, No ADEK

effect of pancreas on lipids

No lipase, No lipid absorption No bicarbonate, lipase is inactivated at acid pH (<5) Acid "cooks", or "deep fries" digestive enzymes such as lipase

pancreatic insufficiency

Pancreatic insufficiency. Diseases of the exocrine pancreas (e.g., chronic pancreatitis and cystic fi- brosis) result in failure to secrete adequate amounts of pancreatic enzymes including those involved in lipid digestion, pancreatic lipase and colipase, cho- lesterol ester hydrolase, and phospholipase A2. For example, in the absence of pancreatic lipase, triglyc- erides cannot be digested to monoglycerides and free fatty acids. Undigested triglycerides are not absorbable and are excreted in feces.

phospholipase A2

Phospholipase A2 is secreted as a proenzyme and, like many other pancreatic enzymes, is activated by trypsin. Phospholipase A2 hydrolyzes phospholipids to lysolecithin and fatty acids. Cholesterol, Phospholipids and triglycerides are all too BIG to be absorbed Pancreatic enzymes remove fatty acids to make them small enough to come into the body Phospholipase A2 is the name of the FFA remover from position A2 Note that the digestion of phospholipids produces the precursors for leukotrienes and prostaglandins

chylomicrons

Re-esterified lipids Covered with apoproteins Enter lacteals Return to circulation at thoracic duct Everything is in it, but it can't be used 1,000 Angstroms Triglycerides 85-92% Phospholipids 6-12% Cholesterol 1-3% Proteins 1-2%

pancreatic lipase

Secreted in active form Removes 2 of 3 fatty acids Leave a position 2-Monoglyceride Pancreatic lipase is secreted as the active enzyme. It hydrolyzes triglyceride molecules to one molecule of monoglyceride and two molecules of fatty acid. A potential problem in the action of pancreatic lipase is that it is inactivated by bile salts. Bile salts displace pancreatic lipase at the lipid-water interface of the emulsified lipid droplets. This "problem" is solved by colipase.

why is the rate of gastric emptying important

The rate of gastric emptying, which is so critical for subsequent intestinal digestive and absorptive steps, is slowed by CCK. CCK is secreted when dietary lipids first appear in the small intestine.