Gastrointestinal System (GI tract)Is a long tube that consists of the mouth,

esophagus, stomach, small intestine, large intestine, rectum and anus

Several organs empty into the GI tract. These include the liver, pancreas, and the gall bladder with the salivary glands

The main function of the GI tract is digestion and absorption of nutrients

The movement of the smooth muscles in the GI is called peristasis and propels food in the forward direction

Stomach The stomach further processes the food into a

semisolid substance called chymeParietal cells of the stomach also secretes HCL HCL activates pepsinogen into active enzyme called

pepsin.Pepsin begins the breakdown of proteins in the food

into amino acid peptidesParietal cells also secrete intrinsic factor which is

important for absorption of vitamin B12 in the ileumBicarbonate in the mucus in the stomach is present to

protect the lining of the stomach from the low pH of the acid environment

Small IntestineDuodenum is the part of the small intestine where

most of the digestion occursPancreas secretes alkaline pancreatic juice which

contains an amylase which further breaks down sugars, chymotrypsin (which will break down proteins), lipases (which will break down fats)

Additional the liver produces bile acids and the gallbladder stores the acids until needed. When food enters the duodenum CCK is release and the gallbladder pumps bile acids into the duodenum

Bile acids solubilize the fats into micelles to increase the surface area for pancreatic lipase to work.

End products of DigestionCarbohydrates to glucose and/or FructoseProteins to amino acids and same peptidesFats to fatty acids and glycerolThe enterocytes of the small intestine will

absorb these and the mesenteric veins will empty into hepatic portal vein which carries nutrients to the liver (first pass)

Large IntestineThe main function of the large intestine is to

absorb water and electrolytes into the blood stream

If too much water is absorb the result is constipation

If too little is absorbed the result is diarrhea

Disorders of the GI systemGastroesophegeal reflux or GERD

caused by abnormal amounts of acid in stomachor esophageal sphincter functionDefective prostaglandin synthesis and defective

bicarbonate production (NSAIDs, and ASA)Tx: antacids containing calcium carbonate (TUMS®) or

aluminum and magnesium hydroxide (MAALOX®)Alternatives are PPI (proton pump inhibitors)

Nexium ® (esomeprazole) Protonix® (pantaprazole) Aciphex® (rabeprazole) Prilosec® (Omeprazole) Drugs work on the parietal acids to block HCL secretion

Nausea and Vomiting (NV)Common seen in pregnancy, overeating, alcohol

consumption, illness, bacterial or viral gastroenteritis, food poisoning, and post operative states

A common side effect to opiate medicationsA common side to diabetic gastroparesisDrugs that are used to treat NV

5 HT3 agonist : ondansetron (Zofran®), granisetron (Kytril®) the gold standard in NV tx in chemotherapy

Dopamine blockers: Prochlorperazine (Compazine®): classical used in the morning sickness.

Dopamine blockers/GI stimulant: Metoclopramide (Reglan®) used in tx of diabetic gastroparesis

ConstipationResults from:

Inadequate water intakeInadequate fiber intakeChanges in lifestyleLack of exerciseDrugs like opiatesAbuse of laxatives

Therapy of constipationBulk forming laxative commonly include fiber which increases

bulk of stool to stimulate GI tract. Includes: Metamucil (psyllium)

Emollient makes the fecal matter “slippery” includes mineral oil enema (Fleet® mineral oil)

Surfactants makes the feces more soft: Colace ® (docusate sodium)

Saline laxative powerfully draws water into the stool. Includes magnesium citrate (Citroma®), and sodium phosphates (Fleet® Phosho Soda)

Evacuants work similar to saline laxatives: Golytely (PEG with lytes)

Stimulants: triggers the nerve that control bowel movements to work. Includes bisacodyl (Dulcolax®) and Senna (sennakot®)

Therapy of DiarrheaDiarrhea is a loss of water and electrolytes as a

result of infections or inflammation of the large or small intestine.

Bloody diarrhea is sometimes called dysentery and result in infection with salmonella (Typhus fever), shigella, or E. Coli Treated with Abx: fluoroquinolones or Bactrim

Cholera is disease of the third world where a spirochete, called Vibrio Cholerae infects the small intestine and its toxin produce profound loss of water and electrolytes. Potentially fatal if untreated with Abx and IV hydration

Diarrhea can be treated with fiber Absorbs water from the GI and swells to provide bulkExamples are Metamucil® (natural psyllium hulk) or

fiber from fruits and vegetablesCan be treated with narcotics and narcotic derivatives

Opium Tincture® sig: 0.25 ml-0.5 ml bid as needed to limit bowel movements. Caution: tincture as high concentration. Can result in overdose.

Lomotil® (Diphenoxylate/Atropine) CVImodium ®(Loperamide, a meperidine derivative)Attapulgite (Kaopectate)Bismuth subsalicylate (Pepto Bismol) Note: Black Tongue

Liver DiseaseLiver pathology includes hepatitis, cirrhosis,

and cancerDamage to the liver can also occur from

drugs. Drugs that can cause liver damage are: acetaminophen (Tylenol®), amiodarone (Cordarone®), anabolic steroids, isoniazid, oral contraceptive agents, methotrexate, allopurinol (Zyloprim®)

HepatitisInflammation of the liverCaused by viruses in most cases. Hepatitis B and C is

life long and can lead to hepatocellular carcinoma and cirrhosis of the liver. CMV can also cause hepatitis

Can be caused by drugsAlcoholHepatitis A virus (HAV)

Transmitted by oral-fecal route in endemic areaSymptomic therapy; not life longPrevented by vaccination: Havrix® (GSK) and Vaqta®

(Merck)

Hepatitis B (HBV)“serum hepatitis”Transmitted by blood or infected bodily fluid contact

with mucus membranes or by blood transfusions or by poorly sterilized medical devices (needles)

Can be transmitted to a fetus by an infected motherNew born babies are vaccinated at birth

Recombivax ® 0.5 ml IM or Energix ® 0.5 ml IM hepatitis B surface antigen (HBsAg) produced in yeast cells

Acute infection causes vomiting, abdominal pain, jaundice and sometimes hepatic failure and death

Chronic infection leads to cancer and cirrhosis

Therapy of HepatitisTherapy is complex and involved drug, antibody

level and viral load monitoringAntiviral drugs (similar to HIV drugs)

Lamivudine (Epivir®) Adefovir (Hepsera®) Tenofovir (Viread®) Entacavir (Baraclude®)

Interferons are drugs that modify the immune response to the viral infection Interferon alpha (Intron A®, Roferon®) Interferon alpha (peglyated): Pegasys® give weekly These drugs cool the immune reaction to viral does not clear

the infection

CirrhosisEnd stage liver diseaseFibrosis of the sinusoids of the liverComplications: bleeding, CNS edema, renal

dysfunction, ascites, hypoglycemia, hepatic bone disease (osteodystrophy), bleeding into the GI tract from varices

Terminal conditionChronic hepatitis and carcinoma leads to cirrhosisExtreme alcohol consumptionLiver Transplant is only cure

Vitamin DHelps with the absorption of calcium from

the intestine to make stronger bones and teeth

Deficiency causes metabolic bone softening:Called rickets in childrenCalled osteomalacia in adults

DRI is 5 µg/day (ages 19–50) for both males and females

DRI is 10 µg/day (ages 51–70) for both males and females

17

Vitamin KControls formation of coagulation factors II,

VII, IX, and X in the liverAlso needed for calcium uptake in bonesDeficiency is rareAntidote for coumadin (Warfarin) overdose

Given as 10 mg IVPB or subcutaneously for 3 days

18

Vitamin B3 (niacin)Vital in protein metabolismDeficiency leads to the disease pellagra:

Affects skin, mucous membranes, GI, and brain/CNS systems

Causes photosensitive rash, scarlet stomatitis, glossitis, diarrhea, and mental aberrations

High doses 1 gram and higher used to treat hyperlipidemia and low HDLNiaspan ®

19

Vitamin B6 (pyridoxine)Needed for:

Red blood cell formation - Antibody productionCell respiration - Cell growthConversion of tryptophan to niacinHelps convert stored carbohydrate to glucose to maintain normal

blood sugar levelsSynthesis of neurotransmitters such as serotonin and dopamine

Deficiency can cause:Anemia similar to iron-deficiency anemiaDecreased antibody productionSuppressed immune responseSymptoms such as dermatitis, a sore tongue, depression,

confusion, and convulsionsUsed in high doses for isoniazid toxicity

20

Vitamin B12 (cyanocobalamin)Needed for healthy nerve cells, to make DNA,

and for the formation of RBCsDeficiency leads to irreversible nerve damageIV dose form is given for perniceous anemia

21