What is intestinal failure and what causes it?

- its when the SMALL INTESTINE fails to absorb nutrients

Causes:

- major resection of small intestine, aka short bowel syndrome (due to intestinal infarction, Chron's therapy by resection)

- diffuse disease of small intestine (Chron's, radiation, amyloid)

- motility abnormality (diffuse scleroderma)

*Chron's disease is a major one.

Who resorbes more fluid, the small or large intestine?

- acutally the small intestine can do 12L max, and the large intestine 5 L max.

- You resorb almost all the fluid that enters the bowel every day (either from ducts or the outside)

- ileum is the major water absorber of the small intestine.

Where do vitamin B12 and bile salts get absorbed? What does the large gut absorb?

- in the ileum.

- water, electrolytes and short chain fatty acids get absorbed in the large gut

How much bowel do you need to live without parenteral nutrition? What's the threshold for getting symptoms?

- It's the 100cm rule!

- For ileum, if you loose > 100cm, you loose a lot of bile acids into the stool cause your ileum cannot reabsorb it enough. In that case you get steatorrea due to unabsorbed fats (the liver cannot compensate for the loss of the bile absorbing power of the ileum). If you loose <100cm, then you have enough bile, but you don't absorb as much as you should, so you still get too much bile in the stool and that causes irritation and diarrhea.

- For duodenum, you'd loose your iron, folate and calcium absorbing power

- if you have less than 100 cm left of bowel, you most likely will need parenteral nutrition.

COLON, whaaaat is it good for?

- absorbing back water and electrolytes but also taking in small chain fatty acids which can provide quite a bit of E! Like 500 kcal!

- however, this has a downside too!

- if a person with short bowel syndrome still has their colon, then can get oxalate nephropathy!

Explained: Oxalate is in veggies and stuff, and we want to excrete it, otherwise it can go to the kidney and cause stones. Normally Ca binds to oxalate in the gut, and fatty acids are absorbed by the large colon and ileum so they don't get in the way. But if there is a lack of bile salts (which happens in short bowel people) then those fatty acids do not get absorbed as well, and THEY will go and bind up all that Ca2+. The dumb old unbound oxalate then gets absorbed!

- Tx: Give Ca2+, low fat diet, or low oxalate diet.

What's the diff between starvation and catabolic state?

- in starvation you're not sick, you're just not eating. Your metabolism slows down to compensate and that's not a problem cause it's not fighting anything off. In this case nutrition leads to anabolism and increase in lean body mass. Some causes may be esophageal mass, CNS problem, anorexia nervosa.

- catabolic state is when you have physiologic injury (ex; pneumonia, resp failure, inf, surgery, pancreatitis, BURN), so you have increase in catabolic hormones, inflammatory cytokines... They are breaking down stuff, so when you feed then there will not be weight gain. They will break down muscle to get aas, which means that even their heart can get weak. They will develop hyperglycemia and hyperTGemia which is bad long term. Infections, impaired wound healing, weakness, fatigue, organ dysfunction,

Describe enteral feeding

- always preferred if possible. This could be necessary in like, someone with ileus (non-motility), or with MS. Or head and neck cancer. 

- NG tubes are used for short term, G tubes (so from the skin to the stomach) for long term.

Describe total parenteral nutrition

- it's got dextrose, lipis, aas, electrolytes and minerals, vitamins and trace elements. Usually infused over 24 hours if in hospital, over 8-10 hours while they sleep for home parenteral nutrition.

- can be central or peripheral (but it's really always just central, so like right ot the heart, cause it's thrombogenic), It can be implanted, tunneld or a PICC (peripherally inserted catheter). They all have threads that go right to the SVC.

What are potential complications of nutrition support?

- Refeeding syndrome (CHO stimulates insulin release which causes a rapid shift of K, PO4 and Mg intracellularly)

- cardiac muscle mass is reduced so don't give a big bolus.

- overfeeding

- liver or bone disease

- catheters can crimp, cause thrombosis, break, cause infection...

- So you've got to start slow

- if you've got deteriorating liver function, or loss of vascular access, then you would look to intestinal transplant, but that's pretty uncommonly done it seems.

Why could giving medium chain fatty acids be good for someone?

- those fatty acids are absorbed into the portal system, not the lymph system! So say you have lymphoma or something, and you can't get fats through to the systemic circulation that way, then you give people medium chain fatty acids so they can get their fats!

- glycerol also goes right through to the portal circulation.

How do TGs get broken down?

- they go into emulsification droplets

- those droplets are surrounded by amphymorphic molecules (phospholips, bile salts or both), and those molecules attract colipase, which attracts lipase, and that will break the 1st and 3rd bond on the TG, forming 2 fatty acids and one monoglyceride.

- those 3 products can then be taken up by micelles which are formed by colipase, and then in micelles they can be absorbed by the intestinal cells.

- micelles then contain lysolecithin, ffas, glycerol, cholesterol and fat soluble vitamins.

What happens to the lipids when they get absorbed into the intestinal epithelial cell?

- protein facilitates diffusion accross the membrane.

- then we have to re-make the TGs in the ER, then they'll go to the golgi body and get packed up into chylomicrons. Those have TGs, phospholipids and cholesterol

- Chylomicrons get taken out into the lymph vessels by vesicle fusion with the epithelial membrane then they sneak into the lymphatics through holes in their intercellular junctions

- Goes to cisterna chyli, then to the left thoracid duct, then to the left subclavian vein.

What would be  good ddx for fat malabsorption?

- bile salt deficiency (like from cholestatic liver disease, bacterial overgrowth causing deconjugation of bile salts)

- lack of pancreatic lipase

- intesinal mucosal problem (loss of mucosa from intestinal resections) or intestinal disease (ex; celiac)

- obstruction to lymphatic flow (lymphangiectasia)

Name the steps of B12 absorption

- B12 gets eaten, and it gets separated from the protein that it's bound to (acid in the stomach does that)

- R protein binds it in the stomach

- IF is produced form gastric parietal cells

- dissociation of R-cobalcumin and degredation of R protein happens in the duodenum by Trypsin from the pancreas

- then B12 binds IF

- B12-IF receptors take up that complec in the ileum.

*A very small amount of B12 can be absorbed passively, so even in pernicious anemia we can give daily high dose (1000ug) oral vit B12.

What are the fat soluble vitamins?

A - Retinoic acid (normal immune function, vision, antioxidant)

D - Cholecalciferol (Ca2+ absorption)

E - Tocopherol (antioxidant) *def results in neuro deficiency and myopathy

K - Phylloquine (syn of coag factors II, VII, IX and X) *deficiency results in bleeding

What are water soluble vitamins?

- Thiamin (B1): deficiency: Wernicke-Korsakoff syndrome, Beri Beri

- Vitamin C (ascorbic acid): scurvy

- Folic acid: megaloblastic anemia

- Niacin: Pellagra (DDD! Diarrhea, dermatitis, dementia)

Why is it better to have your green leafy veggies with acid on them?

- normal stores is 4 g, normal losses is 1-2mg/day, and we eat about 20mg/day

- Fe2+ is easier to absorb than Fe 3+

- H+ and vit C will convert Fe3 to Fe2!

- mostly it's absorbed in the upper duodenum and ileum.

What does Zinc deficiency do?

- caused by malabsorption and diarrhea

- you get like, perioral vesiculobullous rash, groin and distal extremities

- allopecia

- impaired taste

- depression

- delayed wound healing

- You can test Zinc levels in serology.

Dark skin rash in sun exposed areas, desquamating rash or scaling... what is it?

- Pellagrra (niacin deficiency)

- inadequate diet, malabsorption,

- skin lesions in sun exposed areas, scaling, blistering, red brow color, sore tongue, atrophic glossitis

- DDD: Dementia, dermatitis, depression ( I think ti was)

Folliculitis, easy bruising, bad gums, what is it?

- scurvy

- causes also coiled hair, weakness, lassitude, depression

- tests is plasma vit C level

Essential fatty acid deficiency

- omega 3 and 6 def

- In the liver they would normally get elongated and desaturated

- if there's less o3 and 6, then the liver will work on omega 9 instead. So what we want to do is compete the triene (o9 product) to tetraene (o6 product) metabolite levels in the blood

- growth retardation

- decreased wound healing

- sparse hair growth

- susceptability to infection

Talk about celiac disease girl

- wheat, barley and rye have these gliadins that cause a problem

- there's a protein fragment that makes it through the mucosal barrier, then tissuetransglutaminase de-aminases it, and then that creates affinity to antigen presenting cells

- then there's a cascade of immune activation.

- affects the upper small intestine (d and jej), cause that's where the protein interacts with the intestine more there.

- dx: there have been development of Abs (ex; IgA against the transglutaminase enzyme)

- celiac screen: they do a TTG IgA test, and then they will also run an IgA endomeysial. If both are +, 95% chance you have celiac. You have to ingest gluten to be positive! After the + blood test, you should do a duodenal biopsy. (Even you might find early lymphoma or collagenous sprue or something else).

- you see scalloping and sortof a mosaic pattern on endoscopy

- villi is gone, lots of lymphocytes, crypt hypertrophy.

- genetic association with DQ2 and DQ8 HLAs, but a lot of normal people have these, but a negative test would mean that you don't have this. (not common in primary care though)

- 1:150 people.

What are the symptoms of celiac disease?

- abdominal pain and bloating

- diarrhea

- weight loss

- fatigue

- anemia (Fe def)

- constipation

*but a lot of these are similar to IBS!

What are the disease assocations of ppl with celiac?

- type I DM

- Down's

- IgA def

- Infertility (unexplained)

- osteoporosis