Term
| What are the 4 major structural components of the small intestine and what are their functions? |
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Definition
1) Plicae circulares
- Folds of mucosa that increase SA and provide mechanical mixing
- Most extensive in jejunum
2) Villi
- Folds of epithelium into the lumen with core of lamina propria (tallest in jejunum and shortest in illeum)
- Epithelium composed of Enterocytes (absorption and bacterial defense) and Goblet cells (Mucins that protect glycocalyx digestive enzymes)
3) Crypts
- Epithelial folds that invaginate into lamina propria containing precursor cells for enterocytes and goblet cells, paneth cells and enteroendocrine cells.
- Crypt enterocytes secrete Cl- and HCO3- (dragging Na+ and water out into the lumen)
- Paneth cells at base of crypts secrete lysozyme, defensins and TNFa
4) Microvilli
- Folds of apical plasma membrane of individual enterocytes coated in glycocalyx (hydrolytic enzymes protected by mucin) and nutrient symporters |
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Term
| What are the important cell types (and their functions) found in the Villi and Crypts of the small intestine? |
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Definition
1) Villi (neighboring cells connected by tight junctions)
- Enterocytes (absorption and bacterial defense, expressing TLRs)
- Goblet cells (Secrete mucins to protect glycocalyx enzymes on microvilli)
2) Crypts
- Precurosors for enterocytes and goblet cells of villi
- Crypt enterocytes secrete Cl- and HCO3-, which pull Na+ and water into the (reabsorbed Na+ facilitates co-transport of nutrients).
- Paneth cells at base of crypts are large, acidophilic cells that secrete lysozyme, defensins and TNF-a (gut flora control)
- Enteroendocrine cells (VIP, Somatostatin, CCK, Secretin, GIP, Gut-type glucagon, Motilin) |
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Term
| What are the major factors produced by Enteroendocrine cells of the small intestinal crypts? |
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Definition
A Bunch!
1) VIP
- Increase HCO3- and water secretion from pancreas and small intestine, and relaxes smooth muscle.
2) Somatostatin (D1 cell)
- Feedback to stomach, inhibiting G cells, ECL cells and Parietal cells.
3) CCK (I cell)
- Secreted from duodenum by fats or proteins in the lumen, indirectly stimulating digestive enzyme release from pancreas and gall bladder contraction
4) Secretin (S cell)
- Released in presence of acid in duodenum; resulting in pancreatic secretion of HCO3- and water
5) Glucose dependent Insulinotropic peptide (GIP)
- Induces insulin secretion in response to glucose in lumen and stimulates lipoprotein lipase (lipid deposits increase).
- Also inhibits gastric acid production
6) Gut-type Glucagon (L cell)
- Stimulates hepatic glycogenolysis
7) Motilin (Mo cell)
- GI motility during fasting state at intervals of 100 min (MMC and "housekeeping") |
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Term
| What are the major functional characteristics of the small intestinal microvilli? |
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Definition
1) Glycocalyx with hydrolytic enzymes; enterokinase (enteropeptidase), dipeptidases and disaccharidases.
- Enterokinase activates pancreatic trypsinogen to trypsin, which activates other pancreatic enzymes.
2) Nutrient symports that use Na+ secreted into lumen on the tail of Cl- and HCO3- secreted by crypt enterocytes. |
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Term
| What is the GALT? What are the afferent and efferent limbs of the system? |
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Definition
One component of Mucosal immune system containing lymph cells other than PMNs.
Aggregated nodules called Peyer's Patches in the ILLEUM with absent villi (covered in follicle associating epithelium M cells)
M cells and IgA are the players!
1) Afferent sensory limb
- M cells sample antigens by transcyctosis and present them to APCs on basolateral surface.
- APCs activate T cells, which cause B cell rearrangements - B and T cells migrate to LN and proliferate into Th, Tc and plasma cells, which leave LN and follow lymphatic drainage to right heart.
- Once cells enter systemic circulation, they express integrin that leads to them MadCAM-1-expressing endothelial cells and allows them to extravasate into these mucosal organs (GI, respiratory, reproductive).
- Once in lamina propria of organs, they produce a lot of IgA
2) Efferent
- Basolateral membrane of enterocytes express poly-IgA receptor (Pig-4) with a secretory component (SC) that binds IgA, leading to complex endocytosis.
- SC remains complexed with IgA and is transcytosed to apical surface of enterocyte, where fusion and IgA secretion occurs
- IgA binds antigens and enterotoxins. |
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Term
| What is the most important immunoglobulin of the GALT and how does it prevent unwanted antigens from breeching the wall of the GI tract? |
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Definition
IgA
1) IgA is produced by plasma cells in lymph nodes after being stimulated by T cells that have been activated by APCs at M cells in Peyer's patches
2) In systemic circulation (after plasma cells return to right heart and are released into circulation), plasma cells enter lamina propria of mucosal organs via extravasation through MadCAM-1 expressing endothelial cells
3) In lamina propria, IgA binds to SC of poly-IgA receptor complex (Pig-r) on basolateral membrane of enterocytes in villi, is endocytosed, and then SC-IgA complex is transcytosed to apical membrane, where fusion occurs and IgA is released into lumen. |
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Term
What are the 3 primary sections of the small intestine?
What are the important characteristics of each section? |
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Definition
1) Duodenum
- curves around head of pancreas
- leaf-like villi with few goblet cells in epithelium and Brunner's glands in submucosa (alkaline mucous secretion to neutralize chyme)
2) Jejunum
- Best developed plicae circulares with long, finger-like villi (medium number of goblet cells)
- Major area for final digestion and absorption.
3) Illeum
- Longest portion (3.5 m) with Peyer's patches and short, club-like villi.
- Shallow crypts and low plicae circulares.
- Many goblet cells
- Terminal illeum is site for absorption of B12/intrinsic factor complex and reabsorption of bile acids and secretory-IgA |
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Term
| What is so important about the terminal Illeum? |
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Definition
| Terminal illeum is site for absorption of B12/intrinsic factor complex and reabsorption of bile acids and secretory-IgA |
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Term
| What are "Brunner's glands" and where are they found? |
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Definition
| Jejunal submucosal glands that secrete alkaline mucus to neutralize chyme. |
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Term
| What are the major anatomical sections of the Large intestine? |
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Definition
Re-abospriton of water and salts and excretion of undigested feces.
1) Cecum
2) Appendix
3) Colon
4) Rectum
5) Anus |
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Term
| What are the major similarities/differences between the mucosa of the small intestine and large intestine? |
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Definition
Differences
- Small intestine has plicase circulares and villi, while Large intestine has neither (only crypts)
- LI has no paneth cells or hydrolytic enzymes on glycocalyx
- LI lamina propria lacks lymphatic capillaries
Similarities
- Epithelium of BOTH large intestine and small intestinal villi have enterocytes and goblet cells. |
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Term
| How does the large intestinal Muscularis Externa/Serosis differ from the small intestine? |
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Definition
1) Large intestine has 3 longitudinal bands called taeniae coli, which contract and create sacculations called haustra.
2) Ascending and descending colon are retroperitoneal with adventitia covering (like small intestine), but rest of colon is covered in fat. |
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Term
| How can you tell histologically that you have exited the rectum and entered the anus? What are the critical features of the anus? |
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Definition
1) Epithelium becomes stratified cuboidal or squamous (no absorption)
2) Submucosa is well vascularized, with nerves (Pacinian corpuscles for deep pressure).
3) Thickened circular muscularis externa to form internal anal sphincter (smooth muscle).
4) External sphincter is skeletal muscle. |
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Term
| How can the appendix be most easily distinguished from the colon histologically? |
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Definition
Low power view reveals SMALL LUMEN!
You MIGHT notice thinning of the muscular layer.
You still see crypts without villi, and a predominance of goblet cells like in the colon. |
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Term
| How do enterocytes migrate from the base of a crypt to their final destination in the villus? What molecular changes take place? |
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Definition
Migration takes 4-7 days.
Cells divide in base of crypt and characteristics change from secretory (Cl- and HCO3- release) to absorptive along the crypt-vollous axis |
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Term
| What changes in the epithelium take place moving proximal-distal along the long-axis of the small intestine? |
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Definition
1) Proximally, cells are more permeable, with more uptake of glucose, folate, calcium and iron are taken up proximally
2) Distally, cells have higher transepithelial resistance, and B12 and bile acids are taken up
**Vitamin C is taken up the whole way |
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Term
| What is the "pump-leak sequence" of transepithelial transport in the small intestine? |
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Definition
1) Anion/Cation flux occurs through channels on apical membrane (electrochemical gradient)
2) On basolateral side of cell, active (ATP-driven) transport processes take place to generate an ionic gradient |
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Term
| What Antiporter/exchangers are found in the small intestinal epithelium? |
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Definition
1) Na/K exchanger responsible for sodium uptake
**Decrease results in diarrhea, since less water is absorbed**
2) Cl/HCO3 exchanger transports Cl-in and HCO3- out
**Decrease also produces diarrhea, because less H+ is exchanged for Na+ to balance HCO3-** |
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Term
| Describe 2 molecular mechanisms for how inflammation causes diarrhea. |
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Definition
1) Down-regulation of Na/K pump in basolateral membrane of intestinal epithelial cells results in loss of driving force for Cl/HCO3 exchanger.
2) Increased permeability, with decreased tight junction protein expression (less contractile protein) |
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Term
| Why would you expect diarrhea from a Cholera infection to be less severe in a CF patient? |
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Definition
In general, Hormonal activation of GPCR (VIP) increases cAMP and leads to phosphorylation/activation of the CFTR, which leads to Cloride secretion and inhibition of ENaC.
- Cholera constitutively activates G-alpha, increasing cAMp and activating CFTR (more inhibition of ENaC leads to less sodium reabsorption and diarrhea.
- In CF, ENaC is not inhibited because of defective CFTR, so sodium is over-absorbed and so is water (leading dehydrated stool). So CF is protective against diarhea in this case |
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Term
| What is the importance of epithelial K+ and Cl- channels in the intestine? |
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Definition
1) K+ channels lead to K+ efflux and membrane polarization, driving sodium influx and water absorption and nutrient absorption.
**Defective K+ channel might cause diarrhea**
2) Cl- channels like CFTR are important for secreting cloride and leading to sodium reabsorption. |
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Term
| Describe the basic digestive process leading to nutrient reabsorption in the small intestine? |
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Definition
1) Mastication and digestive enzymes in saliva (amylase)
2) In stomach, mechanical and chemical fragmentation occurs with pepsin (protein) and lipase (fat) from Chief cells.
3) In proximal small intestine (duodenum), bile emulsifies fat and smaller droplets undergo lipolysis by pancreatic enzymes (protein and carb also occur here) |
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Term
| What factors are responsible for chemical fragmentation of carbohydrates, proteins and fats, respectively? |
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Definition
1) Carbs
- Salivary amylase
- Pancreatic amylase
2) Proteins
- Gastric pepsin
- rypsin.endopeptidases
3) Fat
- Micelle formation (bile acids)
- Lipase (gastric/pancreatic) |
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Term
| How are carbohydrates digested and absorbed? |
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Definition
1) Chemical (amylase) and mechanical fragmentation in mouth, followed by further fragmentation by pancreatic amylase (generating dextrins and ultimately maltose)
2) Maltose and disaccharides (lactose) are broken down by brush-border enzymes (disaccharidases), freeing glucose, fructose and/or galactose.
**lactase normally decreases with age, leading to intolerance (except in US and UK)**
3) Monosacharides are taken up by enterocytes via co-tranport in small intestine (SGLT1 is example of sodium/glucose co-transporter)
4) Glucose exits enterocyte via facilitated diffusion through basolateral channels (using Na/K pump gradient) |
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Term
| What is the importance of SGLT1 in carbohydrate digestion? |
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Definition
Na-Glucose co-transporter involved in uptake of monosacharides into intestinal enterocytes (Glucose then exits basolateral side via facilitated diffusion from gradient created by Na/K ATPase)
**experiments with this channel show that glucose drags water into cells, making it a good option for children with dehydration from diarrheal disease** |
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Term
Why give a child with severe diarrheal disease glucose?
Why not fructose? |
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Definition
1) Glucose will be taken up by intestinal enterocytes via SGLT1 channel and drag water with it.
2) Fructose over-saturated GLUT5 channel capacity, leading to luminal buildup and worsening bloating and diarrhea |
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Term
| What is the etiology of congenital sodium diarrhea (CSD)? |
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Definition
| Defective Na/H exchanger in apical membrane of enterocyte prevents Na "water pull" and leads to diarrhea |
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Term
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Definition
1) Starts in stomach with gastric pepsinogen from chief cells, that is activated () to pepsin
2) Chyme enters duodenum and pancreatic enzymes are added until protein is ultimately broken to single AA and di or tripeptides.
3) AA taken up by specialized transporters (more than one type for each transporter) |
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Term
| What is the importance of luminal glutamine? |
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Definition
| It decreases "leakiness" of enterocyte epithelium |
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Term
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Definition
1) Amphipathic bile acids emulsify fats to form micelles (lipid droplet surrounded by bile acid heads (hydrophillic)
2) Micelles are targeted by gastric/pancreatic enzymes that cleave ester bonds and enable cellular uptake
3) In cells, lipids are re-esterified and packaged with apolipoproteins and realeased as chylomicrons or VLDL into lymphatics |
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Term
| What are the secretory and anti-secretory neural factors that regulate intestinal function? |
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Definition
1) Secretory
- Peptides (VIP, SubP, NT)
- 5-HT
- ACh
- ATP
2) Anti-secretory
- Peptides (NPY, SOM, Enk)
- NE |
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Term
How do each of the following enteric hormones alter intestinal function?
1) CCK
2) PYY
3) Grehlin |
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Definition
Released by APUD cells and also effect nerves!
1) Release triggered by fat/protein within duodenum, stimulating gall bladder contraction, pancreatic secretion, intestinal motility and decreased gastric emptying.
2) Release also triggered by nutrients, and slows down movement into colon ("ileal break")
3) Increases prior to eating and regulated food intake. |
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Term
| How can immune cells regulate intestinal function? |
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Definition
1) 5-HT, PGE/LCT, Histamine and Bradykinin can all cause secretion
2) TNF and IFN-y and ILs can all cause changes in gene expression. |
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