CM- Approach to Intestinal Disease Flashcards
What cells make up the villi of all three regions of the small intestine?
- Goblet cells - secrete mucin to make mucus
- enterocytes- microvilli to absorb/digest
- APUD cells- (endocrine cells)
The epithelium is simple columnar epithelium
What runs in the opposite direction to the villi of the small intestines? What cells make this up?
The Crypts of Lieberkuhn made of simple columnar and regenerative cells.
Paneth cells are basal crypt cells that secrete lysozyme granules
Describe the difference between the fed and fasting motility of the small intestine.
- Fed- segmentation with non-propogated focal contractions simultaneously at multiple levels (4-6hours post meal)
- Fasting- MMC (migratory motor complex)
- Phase1= motor inactivity (15-30min)
- Phase 2 = intermittent, phasic, non-propagating
- Phase 3 = intense contractions
How are carbohydrates absorbed from the intestine?
Enterocytes can only absorb monosaccharides.
- Starch is broken down by salivary and pancreatic amylase to oligosaccharides.
- oligo [maltose, trehalose, lactose, sucrose] get broken down by microvillus enzymes into glucose, galactose, and fructose.
Glucose and galactose have a sodium co-transporter into the enterocyte. Fructose diffuses across the apical membrane.
Sugar enters the lamina propria into the capillary plexus and feeds to the portal vein
Describe the process by which proteins are digested,
- Acidic stomach converts pepsinogen to pepsin which cleaves peptide bonds –> polypeptides
- Alkaline duodenum inactivates pepsin
- Enterokinase/enteropeptidase found in the brush border cleave trypsinogen to trypsin which activates the other pancreatic proteases [typsin, chymotrypsin, elastase, carboxypeptidase A&B]
- Polypeptides –> oligopeptides or single AA
- oligopeptides are broken down further by endopeptidases and exopeptidases in the microvilli of enterocytes then enter cell via active transport
- AA enter cell via cotransport with sodium
- Protein enters circulation via diffusion through basolateral membrane down the conc gradient AND via symporter/transporters
What are the 4 major organs involved in fat absorption?
- Stomach
- Pancreas
- Intestines
- Liver
Where does fat digestion start? What occurs in this organ?
Fat digestion begins in the stomach where:
- gastric lipase hyprolyzes triglycerides into diglycerides and FA
- Forceful contractions and lipolysis turn fat into a fine emulsion of fat droplets anchored with phospholipids
After fat is emulsified in the stomach into fat droplets anchored with phospholipids, what is the next step in fat absorption?
- Pancreatic lipase (with colipase @ pH 6) hydrolyzes the emulsion into FA and monoglycerides in the intestinal lumen.
- pancreatic esterases hydrolyze FA ester bonds of cholesterol and fat-soluble vitamins in the presence of bile salt
- Bile acids form mixed micelles with the FA, monoglycerides and cholesterol
After pancreatic lipase made FA and monoglycerides and pancreatic esterases made mixed micelles, what is the next step of fat digestion?
FA, cholesterol and monoglycerides in micelles enter the enterocyte by passive diffusion.
A surface protein on the enterocyte facilitates the uptake of LCFAs.
In the cell LCFA and cholesterol are taken to the ER for further processing.
FASTING: form TAG in RER
FED: form TAG in SER
Cholesterol is re-esterified by acyl-CoA(cholesterol acyltransferase)
In the enterocyte, cholesterol is re-esterified and triglycerides and licithin are resynthesized. What happens next?
The cholesterol ester, TAG and lecithin join with apolipoproteins are are transported out of the cell.
Where are bile salts reabsorbed?
90% are reabsorbed in the terminal ileum to reenter portal circulation where they are extracted by the liver and re-secreted in bile.
What are the best tests for a patient with malabsorption and why?
- ferritin - iron stores
- RBC folate
- B12
- Prothrombin time (dependent on vit. K which is a fat soluble vitamin)
What are the 2 forms iron is found in?
Where are they both absorbed?
What is used to measure the efficiency of iron absorption?
- Heme iron from meat- duodenum, prox. jejunum [more efficient]
- non-heme iron from vegetables (ingested as ferric, converted to ferrous by stomach acid so that it can be absorbed)– duodenum
Duodenal enterocytes have high affinity for Fe.
Ferritin is iron stores in tissue. Circulating serum ferritin is an estimate of body stores and indirectly duodenal absorption
Where is folate primarily absorbed?
What is folate important for?
How is it measured?
Folate is in fruits and green vegetables. It is absorbed in the jejunum.
Folate –> tetrahydrofolate–> synthesis of nucleic acid/protein precursors
Folate and RBC folate are both used. RBC is better, but used less
Where are vit ADEK absorbed?
They are absorbed in the jejunum like dietary lipids. They are absorbed passively as chylomicrons and enter lymphatics.
What is vit A necessary for?
What do deficiencies cause?
It is necessary for cell growth and differentiation as well as rhodopsin (visual pigment).
Deficiency leads to xerophthalmia and night blindness.
What is vit D necessary for?
What do deficiencies cause?
It is necessary for calcium absorption by the small intestine.
Deficiency leads to osteomalacia, rickets, and delays in bone mineralization
What is vit E used for ?
What do deficiencies cause?
It is used in cell membranes and is an antioxidant (esp. in neuronal tissue)
Deficiency = progressive neurologic dysfunction
What is vit K used for? What would a deficiency cause?
Vit K is a cofactor in the liver for coagulation factors: 2,7,9,10 and protein C and S.
Deficiency causes clotting dysfunction and long PT
Symptoms of malabsorption generally depend on the nutrient not absorbed, however, what are some general presentations of malaborption?
- weight loss
- steattorhea (floating stool that smells)
- diarrhea
- vit deficiencies
Steatorrhea is a generalized sign of malabsorption. What are 4 places things can go wrong that would cause fat malaborption?
- decreased pancreatic secretions
- decreased biliary secretions
- abnormal enterocyte processing
- lymphatic obstruction
What malabsorption problems does pancreatic insufficiency from chronic pancreatitis cause?
- Protein malabsorption - decreased secretion of trypsinogen, chymotrypsin, carboxypeptidase, proelastase
- Fat malabsorption (steatorrhea) - decreased lipase/colipase
(carb malabsorption is rare because of the large reserves of amylase)
What will patients with liver disease malabsorb?
- Lipid malabsorption- Damage to hepatocytes (cirrhosis, PBC, etc) will decrease bile formation.
Bile is only necessary for lipid absorption
What malabsorption is associated with gastric disorders?
Surgical alterations will impair mixing and the ingested food will precede the arrival of pancreatic enzymes and bile salts.
This leads to:
1. protein malabsorption
2. fat malabsorption
What is “blind loop syndrome”?
The small intestine usually has less than 10^5 bacteria (lactobacilli, enterococci, G+aerobes, facultative anaerobes). Bacterial overgrowth occurs when:
- hypomotility
- partial intestinal obstructon
- diverticuli
- decreased gastric acid secretion
How do bacteria in the lumen disrupt digestion?
- inactivating bile acids
- catabolizing disaccharides in microvilli
- reducing effectiveness of enterokinase
How can you differentiate bacterial overgrowth from tropical sprue?
In bacterial overgrowth there will be:
- B12/fat soluble vitamin deficiency
- normal folate
In sprue there will be:
- folate deficiency
- B12 deficiency
What is a non-invasive test for the presence of intestinal bacterial overgrowth?
What is the treatment for bacterial overgrowth?
Test: Give patient glucose and test breath for hydrogen production.
H- = all the glucose was absorbed in the prox. small intestine (normal)
H+ = bacterial fermentation of glucose–>increased
antibiotics
What are the five main categories for malabsorption in the small intestine? What is the mechanism of all five?
The mechanism of all 5 is that there is a decrease in surface area for absorptioin.
- Intestinal inflammation and villus flattening
- Ischemia
- Ulceration
- Infiltration (amyloid, collagenous sprue)
- extensive small bowel resection
What is celiac sprue? What part of the intestine is most affected? What is the first thing malabsorbed?
Celiac sprue is inflammation of the proximal small intestine in response to the gliadin component of gluten.
Most celiac sprue has no evidence of malabsorption but if there is any, it will be Fe (followed very distantly by folate).
Despite the destroyed villus, carbs, fat and proteins are still absorbed
What is the histologic appearance of celiac sprue?
Celiac sprue has:
- flattened intestinal villi
- intraepithelial lyphocytes
- hyperplastic crypts
How is diagnosis made for celiac sprue?
- intestinal biopsy
- serologic tests for anti-tTg (tissue transglutaminase) IgA
[in negative tests, the IgA total titer must be normal or else it may be a false neg due to IgA deficiency and NOT celiac sprue]
What is treatment for celiac sprue and why is it important that patients adhere?
It is a gluten free diet.
The diet can reverse the villi flattening and normalize the TTG antibody.
Patients should adhere because celiac sprue can lead to:
lymphomas
adenocarcinomas
What is the genetic test for celiac sprue? Why is the test not necessarily useful?
HLA for DQ2 and DQ8.
It is not that useful however because the majority of people with a positive test have IBS and NOT sprue
What are the three things required for diagnosis of tropical sprue?
- travel to Caribbean, India, SE Asia
- consistent biopsy with sprue
- B12 and folate deficiency [megaloblastic anemia]
What is shown on biopsy for tropical sprue?
It looks very similar to celiac sprue:
- flattened villi
- intraepithelial lymphocytes
- crypt hyperplasia
however, it is more patchy villus atrophy and affects proximal AND distal areas of the small intestine
What is the cause of Whipple Disease? What are the symptoms ?
Whipple disease is caused by a gram postive actinomycete called Tropheryma whippelii
Symptoms:
- GI symptoms
- fever
- joint pain
- neurological symptoms .
What does small intestinal biopsy of Whipple disease show?
It will show:
- blunted villi
- infiltration in the lamina propria with PAS + macrophages filled with organism
What is treatment for tropical sprue?
- antibiotics for a year
2. B12 and folate supplements
What is treatment for Whipple disease?
antibiotics
What is blood supply to the bowels?
SMA- duodenum, small intestine, first half of the colon
IMA- rest of colon and rectum
marginal arteries and arc of Riolan = collateral circulation
What causes chronic mesenteric ischemia?
Which part of the GI tract is more likely to become chronically ischemic?
When 2 of the 3 major vessels to the bowels is obstructed.
The small intestine is likely to become chronically ischemic whereas the colon will be acutely ischemic and self-limiting
What is the most vulnerable layer to ischemic injury? What is the likely cause if it is transmural infarction? Partial?
The most vulnerable layer is the mucosa.
Transmural = embolism or thrombi
Partial = hypoperfusion
What are the 5 main reasons why the small intestine is the least common site for primary cancers?
- alkaline –> stops activation of carcinogens
- lymphatics and IgA protecting mucosa
- transit time is fast so less exposure to carcinogens
- higher cell turnover and robust genetic protection
- colon has products of bacterial metabolism [carcinogenic]
What are the 4 most common tumors in the small intestine?
adenocarcinomas
carcinoid
lymphoma
sarcoma
What are the 5 most common metastases to the small intestine in order of most to least common?
- melanoma
- ovarian
- bladder
- breast
- lung
What are the major risk factors for small bowel tumors?
- age
- men
- diet (animal product and smoked/cured meats)
- Crohn’s (adenocarcinoma)
- celiac (T cell lymphoma)
What is diagnosis for small bowel tumors?
- enteroscopy
- barium studies
- CT
- capsule endoscopy
What is the pathophysiological definition of diarrhea?
- volume >200g/24 hours
- loose consistency
- frequency
- water content over 60-85% of stool weight
Solute concentration in the stool is always equal to what?
Solute concentration in the stool is always equal to serum concentration because the stomach, intestines and colon are incapable of maintaining a water gradient
What is the principle anion of the small intestine? What happens to it as it moves through the small intestine and colon?
Cl- is the principle anion of the small intestine.
as it moves down the small intestine chloride absorption concentrations decrease and bicarb is exchanged for it.
Cl- decreases and HCO3 increases down the intestines and into the colon
What are the 4 main etiologies of diarrhea?
- secretory- when excess water and electrolytes are transported into the lumen [cholera]
- osmotic- water is retained in the lumen by osmotically active agents [milk of magnesia, poorly absorbed carbs, or ions]
- inflammatory- bowel is inflamed and normal function is impaired
- motility- abnormally rapid transit due to increased bowel motor activity (hyperthyroidism, IBS) so the colon doesnt have time to dry the stool
What are 4 situations when diarrhea would need further evaluation?
- blood/pus
- weight loss
- > 3 days
- evidence of malabsorption
In general, how is inflammatory diarrhea recognized?
Blood or pus in the stool.
Test for occult and microscopic blood. If + then do a culture and biopsy for diagnosis of IBD.
What does the absence of blood and WBC in the stool after microscopic examination suggest?
What is the key exception?
It suggests that the diarrhea is not inflammatory.
Lymphocytic colitis however, has normal appearing right colon mucosa
How can you further evaluate watery diarrhea that is not inflammatory?
Stool osmotic gap:
280- 2(Na+K)
the diarrhea by secretory and osmotic types are usually watery enough to measure electrolytes
Secretory: less than 50
Osmotic : greater than 50 (presence of an unmeasured osmol)
What are the 5 main causes of secretory diarrhea?
- pathogens that secrete toxins
- reduction of mucousal SA (less nutrients absorbed, more water goes out)
- absence of ion transporter
- inflammation (Crohn’s, microscopic colitis)
- circulating secretagogues (NE tumors)
What does stool nitrogen tell you?
It quantifies protein malabsorption
What does stool xylose tell you?
It quantifies carb malabsorption
