Lecture 24: Digestion and Absorption in GI tract Flashcards
What are the 2 main paths of absorption in the GI?
1) Cellular: lumen –> Apical membrane –> Intestinal epithelial cell –> basolateral membrane –> blood (transporters in membranes)
2) Paracellular: intestinal epithelial cell –> lateral intercellular space –> intestinal epithelial cell (tight junctions)
What are the enzymes secreted for CHO digestion from the saliva, stomach, pancreas, and intestinal mucosa?
Saliva: Amylase
Stomach: none
Pancreas: Amylase
Intestinal mucosa: Sucrase, maltase, lactase, trehalase, α-dextrinase
What are the enzymes secreted for protein digestion from the saliva, stomach, pancreas, and intestinal mucosa?
Saliva: none
Stomach: pepsin
Pancreas: trypsin, chymotrypsin, carboxypeptidase, elastase
Intestinal mucosa: amino-oligopeptidase, dipeptidase, enterokinase
What are the enzymes secreted for lipid digestion from the saliva, stomach, pancreas, and intestinal mucosa?
Saliva: Lingual lipase
Stomach: Gastric lipase
Pancreas: Lipase-colipase, Phospholipase A2, Cholesterol ester hydrolase
What is cavital (luminal) and membrane (contact) digestive activity?
Cavital (luminal): digestion resulting from the action of enzymes secreted by the salivary glands, stomach, and pancreas
Membrane (contact): hydrolysis by enzymes within the brush border that are synthesize by epithelial cells
What makes the structure of the intestinal mucosa ideal for absorption of large amounts of nutrients?
- Arranged in longitudinal folds (folds of Kerckring)
- Villi and mircovilli increase SA of the small intestine (villi longest in duodenum and shorter in the terminal ileum)
What is the function of enterocytes, turnover rate, and what kind of damage are they susceptible to?
- Digestion, absorption, and secretion
- Turnover rate: cells are replaced every 3-6 days
- Susceptible to irradiation and chemotherapy
What are Goblet cells and what is their function?
- Mucus-secreting cells
- Physical, chemical, and immunologic protection
What is the function of Paneth cells within the intestinal epithelium?
- Part of mucosal defense against pathogens
- Secrete agents that destroy bacteria or produce inflammatory responses
What are the 4 transport mechanisms that the enterocyte membrane uses to control the flux or solutes and fluid between the lumen and blood?
Pinocytosis - at the base of microvilli, major mechanism for uptake of protein
Passive diffusion - particles move through pores in the cell membrane or through intracellular spaces
Facilitated diffusion
Active transport
What are the layers from the luminal side through the enterocyte and then blood that a solute must traverse?
- Unstirred layer of fluid
- Glycocalyx
- Apical membrane
- Cytoplasm of the cell
- Basolateral membrane
- Basement membrane
- Wall of the blood capillary or wall of the capillar of the lymph vessel
What is the site of activity for a numbr of digestive enzymes?
Microvillar surface
The capacity of the intestine to adapt is key in which clinical scenarios?
- Small bowel resection
- Bypass
Adaption is limited in some instances, what will occur if the terminal ileum is resected?
Absroption of vitamin B12 and bile salts in abolished
What do CHO’s need to be broken into for absorbtion; what occurs to the disaccharides trehalose, lactose, and sucrose?
- Monosaccharides (glucose, galactose, fructose)
- Trehalose –(Trehalase)–> glucose + glucose
- Lactose –(Lactase)–> glucose + galactose
- Sucrose –(Sucrase)–> fructose + glucose
How is starch broken down?
- Starch is broken down first by α-amylase into α-dextrins, maltose, or maltotriose.
- α-dextrinase, maltase, and sucrase will further break products down to glucose
How are CHO’s transported from the lumen/apical side into the enterocyte; what type of transport is each?
- Glucose and galactose use SGLT1, Na+ dependent (co-transport)
- Fructose used GLUT 5 (facilitated diffusion)
What are the transporters on the blood/basolateral side for monosaccharides?
- Glucose, fructose, and galactose all use GLUT 2 (faciliated diffusion)
- Also a Na+/K+ ATPase
Where is lactase found and what does a deficiency in this enzyme lead to?
- Brush-border enzyme
- Undigested lactose remains in the lumen and holds H2O, causing osmotic diarrhea
- Undigested/unabsorbed lactose is fermented into methane and gas causing excess flatulence
Where does the digestion of proteins begin w/ the action of what enzyme?
In the stomach with the action of pepsinogen which is secreted by Chief cells and converted to pepsin at low gastric pH
What are the 2 classes of proteases, which enzymes are found within each class, and how are they functionally different?
Endopeptidase - hydrolyze the interior peptide bonds of proteins (pepsin, trypsin, chymotrypsin, and elastase)
Exopeptidase - hydrolyze one AA at a time from the C-terminal ends of proteins and peptides (carboxypeptidases A and B)
How does protein digestion continue in the small intestine?
- Trypsinogen secreted by the pancreas is activated to trypsin by the brush border enzyme enterokinase.
- Initially a small amount of trypsin is produced, which then catalyzes the conversion of all the other inactive precursors to their active enzymes (trypsin, chymotrypsin, elastase, carboxypeptidase A and B)
- Trypsin catalyzes the hydrolysis of trypsinogen (autocatalysis) to more trypsin
Protein in the stomach is broken down by pepsin into what?
- AA’s
- Oligopeptides
Protein in the small intestine is broken down by trypsin, chymotrypsin, elastase, carboxypeptidase A/B, and peptidase into what products?
- AA’s, Dipeptides, and Tripeptides by trypsin, chymotrypsin, elastase, carboxypeptidase A and B (lumen)
- Oligopeptides which are further broken down by peptidase (brush border) into AA’s, Dipeptides, and Tripeptides
What are the transporters on the luminal/apical side of the enterocyte for proteins?
- 4 separate cotransporters: one each for neutral, acidic, basic, and imino AA’s
- AA’s use co-transport w/ Na+
- Di- and tripeptides use co-transport w/ H+
- There is also a Na+/H+ exchanger
Once inside the enterocyte what methods of transport exist for proteins to the blood/basolateral side?
- Di- and Tripeptides can cross via facilitated diffusion or be further broken down by peptidase into AA’s
- AA’s use facilitated diffusion via 4 separate mechanisms: one each for neutral, acidic, basic, and imino AA’s
- There is also a Na+/K+ ATPase
Chronic pancreatitis and cystic fibrosis can lead to protein absorption disorders how?
Deficiency of pancreatic enzymes
The absence of trypsin alone makes it appear as if all of the pancreatic enzymes are missing, why?
Trypsin is necessary for the activation of all precursor enzymes (including trypsin itself) to their active forms
What is Cystinuria?
- Genetic disorder in which the Na+-amino acid cotransporter for the dibasic AA’s cystine, lysine, arginine, and ornithine is absent in both the small intestine and kidney
- AA’s are not absorbed and are excreted in the feces and urine
What is Hartnup disease, what do the symptoms resemble, and what will be seen in urine samples of these patients?
- Recessive genetic disorder where you cannot absorb neutral AA’s
- Sx’s resemble those caused by pellagra (niacin deficiency): red, scaly skin rash, photosensitivity, neurological problems
- Urine samples reveal abnormally high excretion of neutral AA (tryptophan) and their by-products (i.e., serotonin)
Why is lipid assimilation complicated and what must occur?
- They need to be solubilized in micelles and transported to the apical membrane of intestinal epithelial cells for absorption
TAG’s are broken down by what enzymes and into what products?
- Lingual, gastric, and pancreatic lipases
- Monoglycerides + 2 FA’s
Cholesterol esters are broken down by what enzyme into what products?
- Cholesterol ester hydrolase (pancreas)
- Cholesterol + FA
Phospholipids are broken down by what enzyme into what products?
- Phospholipase A2 (pancrease)
- Lysolecithin + FA
Where does lipid digestion begin, using what enzymes, and what must occur?
- Lipids are broken down into smaller droplets in the stomach by gastric and lingual lipase
- No bile acids in stomach, so dietary proteins perform the emulsifying action
In order for sufficient time for lipids to get digested properly what is released and what is the outcome?
- CCK is released when dietary lipids first appear in small intestine
- Slows the rate of gastric emptying
What form is pancreatic lipase secreted in, what inactivates it, and how is this problem solved?
- Active form, but is inactivated by bile salts
- Colipase is secreted as inactive form (procolipase), but is activated by trypsin, and once activated binds to pancreatic lipase displacing bile salts
What are the actions of cholesterol ester hydrolase?
- Catalyes the production of cholesterol from cholesterol esters
- Hydrolyzes TAG’s to produce glycerol
What activates Phospholipase A2?
Secreted as a proenzyme and is activated by trypsin
What is the optimum pH for the activity of pancreatic lipase?
pH = 6
What are the 5 steps involved in getting lipids from the lumen into the enterocyte and then into the blood?
- Solubilized by micelles
- At apical membrane lipids are released from micelles and diffuse into the cell
- Inside cell the products of lipid digestion are re-esterified w/ FFA’s on the smooth ER to form the original ingested lipids, TAG’s, cholesterol esters, and phospholipids
- Packaged w/ apoproteins (Apo B) in chylomicrons
- Exocytosis of chylomicron into lymphatic capillaries (lacteals)
What occurs if there is a lack of ApoB?
- Abetalipoproteinemia
- No lipid absorption will occur
What abnormalities can result in steatorrhea?
Abnormalities in ANY of these steps:
- Pancreatic enzyme secretion
- Bile acid secretion
- Emulsification
- Micelle formation
- Diffusion of lipids into intestinal epithelial cells
- Chylomicron formation
- Transfer of chylomicrons into lymph
What is critical for the integrity of pancreatic enzyme function; what are some of the problems that interrupt this?
- Regulation of the acidity of duodenal content, needs to be adequately neutralized by HCO3 containing pancreatic secretions
- Pancreatic insufficiency: failure to secrete pancreatic enzymes
- Zollinger-Ellison syndrome: increased H+ secretion
- Pancreatitis: impaired HCO3 and enzyme secretions
What factors cause deficits in bile salts?
- Ileal resection: interrupts enterohepatic circulation and the total bile salt pool is reduced
- Small intestine bacterial overgrowth
Why does small intestinal bacterial overgrowth cause problems; what are the 2 main causes?
- Bacteria deconjugate bile salts, impairing micelle formation and fat malabsorption
- Severe overgrowth damages the intestinal mucosa
- 2 main causes: decreased gastric acid secretion and small intestine dysmotility
What is Tropical sprue; leads to?
- Decreased # of intestinal epithelial cells; reduces the microvillar SA
- Lipid absorption is impaired because the SA for absorption is decrease = steatorrhea
- Nutritional deficiencies, especially folate and B12
What is Celiac sprue, what occurs, and what does it lead to?
- Autoimmune disease
- Ab’s develop against a gluten component - Gliadin
- Leads to destruction of small intestine villi (atrophy), as well as hyperplasia of the intestinal crypts
- Malabsorption related to deficiencies in folate, iron, calcium, and vitamins A, B12, and D
What are some of the symptoms of Celiac sprue and best tx option?
Sx: abdominal pain, constipation, diarrhea, weight loss, steatorrhea, tingling/numbness, itchy skin w/ rash, fatigue, seizures, easy brusing, and bone fractures
Tx: Gluten-free diet
How are the fat soluble vitamins (A, D, E, and K) absorbed?
Same mechanism as absorption of lipids
How are most of the water-soluble vitamins (B1, B2, B3, B12, C, biotin, folic acid, nicotinic acid, and pantothenic acid) absorbed?
- Most via a Na+-dependendent cotransport mechanims
What are several of the important functions of Vit B12; and how can deficiency interrupt these processes?
- Coenzyme for reducing ribonucleotides to deoxyribonucleotides during gene replication
- Co-factor in folate co-enzyme recycling and nerve myelination. Demyelination of large nerve fibers of spinal cord may occur w/ B12 deficiency
- Important in DNA synthesis in RBC’s (as well as folate). Pernicious anemia is caused by failure of RBC maturation when B12 deficient
Explain the mechanism for the absorption of Vitamin B12?
1) B12 is released from food by pepsin in stomch
2) B12 is complexed w/ R protein from salivary secretions in stomach
3) B12+ R protein is carried to duodenum and dissociated by pancreatic proteases
4) B12 is attached to IF and carried to the distal ileum where there are receptors for IF
5) B12 is carried into mucosa and attached to TCII to be carried in blood
What are 2 causes of disrutpion in the absorption of vitamin B12?
- Gastrectomy: loss of parietal cells (source of IF)
- Gastric bypass: exclusion of the stomach, duodenum, and proximal jejunum alters absorption of B12
Explain the mechanism for the absorption of calcium using vitamin D?
- Dietary Vit D3 is inactive, but in the liver is converted to 25-hydroxycholecalciferol, which is the prinicple circulating inactive form of Vit D
- In proximal tubules of kidney, 25-hydroxycholecalciferol is converted to a biologically active form, 1,25-dihydroxycholecalciferol,l by 1α-hydroxylase
- 1,25-dihydroxycholecalciferol promotes: increased gut Ca2+ absorption, increased bone calcification, and increased bone resorption
What occurs w/ vitamin D deficiency or failure to convert vitamin D to 1,25-dihydroxycholecalciferol?
- Inadequate absorption of Ca2+ from GI tract
- Rickets (children) and osteomalacia (adults)
Explain the mechanism for iron absorption starting with the liver
- Liver secretes apotransferrin into bile, which flow through the bile duct into the duodenum
- Apotransferrin binds w/ free iron and w/ hemoglobin forming transferrin
- Trasnferrin binds to receptors in the membranes of intestinal epithelial cells, absorbed into these cells via pinocytosis and later released into the blood
- Iron can also be absorbed as free iron (Fe2+)
What is absorbed in the colon?
- H2O and electrolytes
- Medium-chain triglycerides
- Calcium
- AA’s
How do glycerol and MCFA’s become absorbed?
Due to their solubility in the aqueous unstirred layer, they enter the enterocyte WITHOUT micelle solubilization
Some lipids will be broken down in the stomach into what? How are they able to get into the small intestine?
- Glycerol + FFA
- No bile in stomach, so they will be emulsified by dietary proteins
