1) Need lipases to break down fat into 2 monoglycerides and FA’s, so you need a functioning pancreas.
2) Need villi of the small intestine b/c if we didn’t, the small intestine would have to be a mile long. Villi increase the overall absorptive surface without increasing the length. So, if you don’t have them, you decrease the absorptive surface, and will lose the monoglycerides and FA’s. Therefore, you need a functioning SI with villi.
3) Need bile salts to emulsify the fat and break it down to micelles (tiny particles that are 1 micron in diameter) and chymlomicrons. Emulsifying agents are many times in dishwashers b/c need to get fat off plates. Fat will come to the surface and break up into micelles, which are easier to absorb.
So, need functioning pancreas, bile salts, small intestine that has villi in order to reabsorb fat.
Bile salts are made in the liver from cholesterol. Cholesterol cannot be degraded; it either solubilized in bile (therefore run the risk of cholesterol stones) or is converted to bile acids.
Cannot break down cholesterol. \
Bile salt deficiency is seen in: a) liver dz; b) anything that obstructs bile flow will produce bile salt def; c) bacterial overgrowth can eat and breakdown bile; d) terminal ileal dz, ex.
Crohn’s dz cannot recycle; and e) Cholestyramine: resins – used for treatment of
hyperlipidemia, can produce bile salt def. This is the MOA of resins, by binding and then excreting them, b/c if you are not recycling them, you will make more. What’s happening in the liver? Upregulation of LDL receptors synthesis, b/c need to make more bile salts,
therefore need to suck more out of the blood and will make more LDL receptors. These drugs will eventually take more cholesterol out of the blood and lower it, so you can make more bile salts. It also takes drugs with it, so it’s not good for people taking meds, b/c you will lose these meds in the stool, along with bile salts.
Dz’s: screening test is looking for fat in stool (steatorrhea) – let’s say it is positive. So, we have to figure which if the 3 areas is the cause of the malabsorption – pancreatic def, bile salt def, or something wrong with the small bowel (MC).
B. Celiac Dz (sprue)
Pic of small bowel lesion and a skin zit that has an association with it. This is celiac dz (autoimmune dz), and the skin zit is dermatitis herpetiformis. Celiac dz is an
autoimmune dz against gluten wheat, esp. gliadin. It is very common and is the MCC of malabsorption in this country. So, when you eat wheat products, the gluten is reabsorbed into the villi and there are Ab’s against gliadin, and leads to destruction of the villi (just like Ab’s against parietal cells or intrinsic factors, which destroy everything around it). So, the Ab’s attack gluten that has just been reabsorbed by the food, which will cause destruction of the villus. And there are no villi here – it is flat; blunting of villus – so you are not able to reabsorb fat, proteins, or carbs. There is no villus surface. The glands underneath are fine, however. The villi are absent. There is a 100% chance of dermatitis herpetiformis association with underlying celiac dz. Dermatitis herpetiformis is an autoimmune dz, and it is a vesicular lesion of the skin –looks like herpes of the skin. They will show pic of a dermatitis herpetiformis, and will ask what the cause of diarrhea is? Ab’s against gluten (gliadin).
C. Whipple’s dz
An infection of the small infection due to an organism that you cannot gram stain. T.
whippelii only seen with EM; cannot be cultured. See flat blunted villi and foamy
macrophages (look like Niemann pic bubbly macrophages; can also be from an HIV “+” b/c it looks like Whipple’s, but isn’t). The macrophages have distinctive PAS-positive stains.
HIV positive pt and acid fast stain – pt with helper T cell count of 100. Have an acid fast stain with the foamy macrophages – due to MAI (this is more common that TB), and can cause Whipple like dz with malabsorption.
Whipple’s, being an infection, has systemic signs and symptoms: fever, lymphadenopathy, polyarthritis, generalized pain. It’s an infection therefore can be treated with antibiotics.
So, there are 2 dz’s that cause malabsorption: celiac dz and Whipple’s dz. Other dz’s are dz’s of the pancreas – chronic pancreatitis (MC in alcoholics – 2 reasons for
malabsorption in alcoholics – a lipase def related to chronic pancreatitis, or bile salt def due to cirrhosis, or both in an alcoholic).
D. Diarrhea
Best way to classify is to subdivide into 3 types:
1. Invasive: bacteria invades
2. Secretory: the bacteria produces toxins and that will stimulate cAMP (or other
mechanisms) causing the small bowel to secrete small amounts of ISOTONIC fluid, which is NaCl.
3. Osmotic: lactase deficiency. Also produced by laxatives, and other inborn errors of metabolism.
Secretory and osmotic diarrheas are high volume diarrheas and you go frequently, whereas invasive diarrhea is a small volume diarrhea. Best/cheapest test to get in a pt with diarrhea
= fecal smear for leukocytes. If there are NOT any neutrophil don’t worry because not invasive. If there are inflammatory cells then you must do fecal smear test for
campylobacter or shigella.
a) Osmotic diarrhea (fits in with osmotic water movement) is when there is some osmotically active substance in the bowel lumen that is sucking water out of the bowel, causing a high volume, hypotonic loss of fluid. Example: lactase def. = brush border or disaccharidase deficiency, a brush border enzyme. In a classic case but they will not tell you it’s a lactase def, instead will tell you it’s a disaccharidase def or even a brush border enzyme def. So if you’re lactase def, it means that any dairy products which contains lactose (which breaks down into glucose and galactose) can’t be indigested. So it will go to the colon, and act as desserts to the anaerobic bacteria which will eat the lactose and produces hydrogen gas, and other gases, and acids, and get acidic stools. The hydrogen gases causes the bloating, distention, and incredible explosive diarrhea.
b) Secretory diarrhea: two things to know, Vibrio cholerae and ETEC (traveler’s diarrhea).
These are not invasive diarrhea, therefore when you do a bowel biopsy there will not be one iota of inflammation, it’s perfectly normal. It’s purely a toxin that activates a pump either cAMP (Vibrio) or some other pump: guanylate cyclase (E. coli). Treatment: when you give fluid replacement to patients with v. cholerae, you need to give glucose along with the fluids.
This is b/c you need glucose to co-transport Na that was in the fluids. Side note: Need to know the other E. coli related toxins: EHEC: O157:H7; EIEV; and EaggEC.
c) Invasive diarrhea: the MC in US is caused by campylobacter jejuni, and shigella is a close second. Classic case: a person with low vine(?) diarrhea, with some blood in it, and on gram stain there were comma shaped or S-shaped organisms that’s campylobacter jejuni.
Both of these organisms can produce pseudomembranes. Therefore all pseudomembranes does not necessarily mean you will see C. difficile.
d) Parasites that causes diarrhea:
Giardia: owl eyes that move. This is the MCC of diarrhea due to a parasite in the US.
Treatment: metronidazole.
Cryptosporidium parvi: MCC of AIDS diarrhea is a partially acid-fast organism. It sticks to the wall of the colon. Classic case: there is a pt that has AIDS and has diarrhea, and when they stain it, there are oocysts that are partially acid-fast. It will kill if you are immunocompromised. The treatment is almost worthless. It comes at the end when the helper T-cells are near 50 or 75, and that’s when all the organisms that will kill you: MAI, cryptosporidium, toxoplasmosis, and CMV all comes in at the end. P. carinii comes in around 200 helper T-cells.
Clostridium difficile: This is an autopsy pic of an older woman who was in the hospital with pneumonia, and she developed diarrhea. What was found on autopsy? Well, it is safe to say that if she had pneumonia, then she was taking antibiotics. So this is pseudomembranous colitis, caused by clostridium difficile. This occurs when taking antibiotics that wipe off the good organisms, leaving behind c. difficile.
Everybody has c. difficile in their stools, but E. coli, enterobacter fragilis are keeping it in check. But when taking antibiotics such as ampicillin (MC), clindomycin (2nd MC) for a period of time, you knock off the good guys, giving c. difficile a chance to proliferate and make toxins that damage the superficial layers of the colon. The bacteria doesn’t invade, it’s the toxins that do. This is analogous to c. diphtheria, which also has a toxin that damages and produces pseudomembranes but the organism does not invade. The ribosylation thing, and the Elongation factor 2 (EF-2 allows for protein elongation) are messed up, therefore cannot elongate proteins.
The first step in management is to do a toxin assay of stools, not gram stain b/c there are lots of gram stain organisms in the stools, not blood culture b/c it’s not in the blood. The screening test of choice is toxin assay of stool! The treatment is to give metronidazole, used to give vancomycin b/c c. difficile became resistant to it. Metronidazole itself can produce pseudomembranous colitis but you take that chance.
VI. Diseases of the Small Intestine
A. Small bowel obstruction: See classic step ladder appearance of air-fluid levels: air, fluid, air, fluid (step ladder appearance). When you have a hollow viscous that peristalsis, you get a certain characteristically pain, called COLIC pain. It isn’t like a crampy pain with no painfree intervals; colicky pain is when you have pain, a painfree interval, pain, and then a painfree interval. The intervals are not consistent, sometimes you have a 15 min painfree interval, and other times if may be longer or shorter. This is colicky pain; it means TOTAL
small bowel obstruction. By the way, the bile duct does not have peristalsis, therefore you do not get colicky pain, and instead you get crampy pain. You have to have peristalsis to get colicky pain, it has to move. And what’s it doing is trying to move against that
obstruction and that’s causing the pain. B/c you cannot perstalse you get stagnation of the food proximal to wherever the obstruction is, and get air-fluid levels. Distal to the area of obstruction there is no air. In obstruction, there are two things that can happen:
constipation or obstipation. Constipation is where you have a problem with stooling, which does not necessarily mean obstruction. Obstipation means that not only do you have constipation you also have a problem passing gas, that means you have complete
obstruction. So you have to ask the pt whether they have passed any stools or gas. MCC of obstruction: adhesions from previous surgeries. Slide: those are watermelon pits, with a narrow lumen. But if the case read that this pt did not have pervious surgeries and had colicky pain, this is due to the bowel being trapped in the indirect inguinal hernia.
Example: there was a weight lifter who developed colicky pain in the RLQ area, had no previous surgery, the most likely cause is indirect inguinal hernia. Weight lifters often times create indirect inguinal hernias.
Side note: there was a pic of Down’s syndrome kid. Trisomy 21 (abnormal number of
chromosomes) is due to nondisjunction (unequal separation during the first stage of meiosis I) but not all down’s have trisomy 21. But if the kid had normal 46 chromosomes, this is due to
Robertsonian translocation. In this case, they would have 46 chromosomes but on one of those chromosomes 21, will be another chromosome attached to it. They will have three functional chromosome 21. The two GI diseases that are MC’ly seen in Down’s are duodenal atresia (double bubble sign) and Hirschsprung dz.
B. Hirschsprung dz: the nerves are there but the ganglionic cells are missing. So, what happens if it’s missing in the rectum, the stools cannot get by, even when there is an opening, b/c there is no peristalsis. So the stools just stay there. So, the dilation of the proximal colon has ganglionic cells, and there peristalsis occurring and you can’t get the stools thru the rectal area. So this means that the rectal ampulla has no stools in it.
Example: if you have a child that didn’t pass the meconium in 24 hours and a rectal exam was performed. If there was NO stools that came out on exam it means
Hirschsprung dz. If on exam, there was stools on the finger, it means tight sphincter.
This is a dz of the colon.
C. Intussusception: most occur in children, and it’s when the terminal ileum intussuscepts goes into the cecum. There will be colicky pain b/c you are obstructing, and not only that, you are compromising blood flow, so you get the bleeding. They will say: a 2 y/o kid, with colicky pain and bloody stools. They might way there is an oblong mass in the RUQ. In some kids, it spontaneously comes out, but if not, then the radiologists will do barium enema, and put a little pressure there, and he reverts it. So you get complete bowel obstruction and infarctions.
D. Volvulus: Twisting of the colon around the mesentery b/c there’s too much of it causing