Lectures 5-7: Small Intestine Flashcards
Where are new cells born in the small intestine? What is there pathway?
Born near crypt, differentiate and mature as they migrate up the villus
How much fluid is presented to the SI? How much is drank? How much of this gets to the colon? How much excreted fecally?
8000 mL, 2000 mL, 1500 mL, 150 mL
Max abs capacity of SI and colon
12 L, 5 L
What solute drives absorption through the mucosa?
Na+
What are the sodium channels in the intestine? (4, 1 basolateral)
- Apical Na+ channel; 2. Basolateral Na-K ATPase (balances Na+ in); 3. Solute-coupled Na+ transport; 4. Na/H exchanger (w/ HCO3/Cl exchanger as well)
What does aldosterone do?
Increases function of apical Na+ channel
What is the mechanism of oral rehydration therapy?
Requires glucose and Na+ to bring water into cell via solute-coupled Na+ transport, meaning that Na+ can be absorbed in the lumen (hence, ORAL rehydration)
Describe the Na/H Exchanger (what in, what out)
Na+ AND Cl- in, H+ AND HCO3- out
What enhances sodium absorption?
Mineralcorticoids (aldosterone), glucocorticoids, somatostatin, adrenergic agonists (epinephrine)
What slows the intestinal transit? How does this affect Na+ absorption?
Opiates and somatostatin; increases sodium absorption
What is the key ion that drives secretion?
Cl-
How does Cl- get into the body?
Via the Na/H exchanger
How does Cl- enter the cell to drive secretion? How is it secreted?
Basolaterally (Na/K/2Cl transporter); apically (Cl channel = CFTR)
Cl- secretion becomes increased by any factor that activates what?
cAMP, cGMP, intracellular calcium
What four hormones/NTs increase cAMP leading to diarrhea?
VIP, secretin, PGE1, bradykinin
What three hormones/NTs increase calcium leading to diarrhea?
ACh, 5-HT, histamine
What four bacteria increase cAMP leading to diarrhea?
V. cholera, E. coli (heat labile), campylobacter, salmoneella
What two bacteria increase cGMP leading to diarrhea?
Yersinia enterocolitica, E. coli (heat stable)
What are some laxatives that act on the cAMP/calcium pathways?
Bile acids, long chain fatty acids, castor oil, senokot
What factors increase colonic transport?
Cholinergics, anxiety, feeding, laxatives/hormones, distention
What factors slow colonic transit?
Anti-cholinergics, depression, colonic wall inflammation, opiates, electrolyte disturbances
Which will cause more water in the stool: small intestinal or colonic dysfunction?
Small intestinal (does the majority of the water absorption, about 7 L)
Sx of small bowel/colonic diarrhea
Large amount of stool, moderate increase in number, minimal urgency, no tenesmus, little mucus
Sx of recto-sigmoid diarrhea
Small amount of stool, frequency, urgency, tenesmus, mucus, blood
Bile acid-induced diarrhea results from _______ dysfunction. Why?
Ileal; ileum is the ONLY site of active bile acid absorption
Mechanisms of osmotic diarrhea. What is intact?
Nonabsorbable solute in bowel lumen –> water enters lumen –> solute/water load exceeds colonic absorptive capacity; mucosal transport processes intact
What are some examples of osmols that will not be absorbed and will increase secretion?
Carbohydrates: lactose (if lactase deficiency), sorbital; Minerals: Na Sulfate lavage, Mg Citrate
Osmotic diarrhea: what is depleted? What is not depleted?
Water (NOT Na+ depletion) = not life threatening
Osmotic diarrhea: stool volume __________ with fasting
Decreases
Osmotic diarrhea: what can you detect in fecal fluid (osmolality and pH)
Osmotic gap = unmeasured osmolality due to nonabsorbed solute; acidic stool pH due to bacterial fermentation of solute
Mechanism of secretory diarrhea. What is intact?
Stimulation of normal secretory processes; absorptive processes intact but overwhelmed
What 2nd transporters cause secretory diarrhea?
cAMP, cGMP, Ca2+
What is the mechanism of cholera toxin?
Increases intracellular cAMP via AC, driving Cl- out of cell and decreasing Cl- reabsorption (via Na/H transporter), keeping water out of the cell. NOTE the Na/Glucose transporter is spared, hence oral rehydration
Secretory diarrhea: what is depleted?
Salt and water (life-threatening)
Secretory diarrhea: stool volume while fasting
Persists despite fasting
Secretory diarrhea: osmotic gap? pH?
NOPE: all osmolality accounted for by electrolytes; neutral pH
Describe two types of motility diarrhea
Hypermotility: insufficient contact time for absorption (laxatives, anxiety); Hypomotility: altered peristalsis –> stasis (water can flow aound stool and cause both diarrhea and constipation)
What is preferentially absorbed in the duodenum?
Iron and other minerals
What is preferentially absorbed in the ileum?
Cobalamin and bile acids
Secretin
Released by duodenum in response to low pH, increase pancreatic bicarbonate secretion
CCK (cholecystokinin)
Released by duodenum in response to FAs and AAs, causes gallbladder emptying (bile acids) and increases pancreatic enzyme secretion
Starch digestion
Amylase (saliva, pancreas) –> maltose, maltase (BBM) –> glucose
Sucrose digestion
Sucrase-isomaltase (BBM) –> glucose, fructose
Lactose digestion
Lactase (BBM) –> glucose, galactose
How are monosaccharides absorbed?
Actively transported into cell –> portal vein
What happens to unabsorbed CHO?
Converted to short chain fatty acids in colon
Stomach’s role in protein digestion
HCl denatures, pepsin hydrolyzes into polypeptides
Duodenum and pancreas role in protein digestion
Pancreas releases pro-proteases, enterokinase in duodenal BBM activates trypsin which then activates other pro-enzymes
Small intestine’s role in protein digestion
BBM oligopeptidases hydrolyze oligopeptides into smaller peptides
How are AAs and oligopeptides absorbed?
They are transported into the cell –> portal vein
Stomach’s role in lipid digestion
Churns fat (mostly TGs) into unstable emulsion
Duodenum and small intestine’s role in lipid digestion
Emulsion stabilized by phospholipids (diet) and bile salts (liver), dietary fat –> CCK –> lipase (pancrease) and bile salts, micelles form
What does lipase do?
Lipase + co-lipase break down TGs into MGs and FFAs
Describe a micelle
MGs and FFAs inside with bile salts outside
How are MGs and FFAs absorbed?
Micelles bring them to the BBM and then they are released and passively diffuse into cell, then they are resynthesized into chylomicrons and VLDL, exported into lymphatics (lacteal)
What is different about medium chain TGs?
Bypass lymphatics and are absorbed into portal vein
What are the four stages of chylomicron formation?
Esterification, surface stabilization, addition of lipoprotein, and secretion via intracellular spaces into lacteals
How is B12 absorbed?
Ingested in food –> binds to R factor in saliva –> intrinsic factor (IF) made by parietal cells –> pancreatic proteases breaks up B12*R –> B12 binds with IF –> absorbed in ileum
What could go wrong with B12 levels?
Not enough B12 in diet, no IF (autoimmune gastritis), no R factor (salivary glands), no proteases (pancreatic insufficiency), no absorption (ileal disease), and bacterial overgrowth
Malabsorbed: protein
Edema
Malabsorbed: fats
Weight loss and steatorrhea
Malabsorbed: carbs
Diarrhea, bloat, gas
Malabsorbed: vit A
Hyperkeratosis, night blindness
Malabsorbed: vit D, Ca2+
Tetany, osteomalacia
Malabsorbed: vitamin E
Neuropathy (pins and needles); deficiency = hemolytic anemia, acanthocytosis, weakness, posterior column/spinocerebellar tract demyelination
Malabsorbed: vit K
Bruising (made by intestinal bacteria)
Malabsorbed: vit B12
Megaloblastic anemia, glossitis, cheilosis, neuropathy
Malabsorbed: folate
Megaloblastic anemia, glossitis
Malabsorbed: iron
Microcytic anemia, dyspnea, fatigue, glossitis
Lactase deficiency can be what two types?
Primary (genetic) and secondary (loss of enterocytes due to infection, resection, radiation)
How much pancreas must be lost before you have pancreatic exocrine insufficiency?
90-95%
What can cause pancreatic exocrine insufficiency?
CF, chronic pancreatitis, pancreatic resection
How do you treat pancreatic exocrine insufficiency?
Oral pancreatic enzyme replacement (enteric coated)
How does bile salt deficiency cause maldigestion?
Low bile salt pool = maldigestion of fat/fat-soluble vitamins
What can cause bile salt deficiency?
Severe cholestasis, distal ileal resection or disease (Crohn’s), bacterial overgrowth
How do you treat bile salt deficiency?
Treat underlying condition and give medium chain triglycerides
What prevents bacterial overgrowth?
Gastric acids, small bowel motility, ileocecal valve, secreted immunoglobulins
What conditions are associated with the development of bacterial overgrowth? (2 classes)
Motility disorders (stasis) and anatomic disorders (fistula, diverticulitis, blind loop)
Consequences of bacterial overgrowth
Deconjugate the bile salts –> fat malabsorption and B12/iron deficiency due to bacterial consumption
How can bacterial overgrowth be dx?
Breath tests
How can bacterial overgrowth be treated?
Correct underlying problem and give antibiotics
What two broad categories of disease cause malabsorption?
Loss of absorptive surface and impaired mucosal/lymphatic transport
Three examples of loss of absorptive surface
Short bowel syndrome, celiac sprue, tropical sprue
Three examples of impaired mucosal/lymphatic transport
Abetalipoproteinemia, Whiple’s disease, intestinal lymphangiectasia
How could one get short bowel syndrome?
Caused by resection or bypass
Celiac disease is an inappropriate response to…where does it favor in the bowel?
Gliadin (in gluten); proximal > distal
What is tropical sprue? Tx?
Infection seen after Central America, Caribbean, SE Asia that is histologically similar to celiac sprue but is PANenteric (not just duodenum); tx = antibiotics
What is abetalipoproteinemia? Tx?
AR disease in which epithelial cells CANNOT assemble chylomicros, so lipids accumulate in cells, causes fat malabsorption; tx = fat restriction and MCT oil
What des the D-Xylose test test? Describe.
Tests functioning of SI absorption; under normal conditions, 25% of ingested amount of D-Xylose should be in urine, if less, than not enough absorbed
There is fat malabsorption. D-Xylose normal =
Pancreatic disease
There is fat malabsorption. D-Xylose abnormal =
Small bowel disease
