Gastrointestinal System (GI tract)

1. 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

2. Stomach • The stomach further processes the food into a semisolid substance called chyme • Parietal 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 peptides • Parietal cells also secrete intrinsic factor which is important for absorption of vitamin B12 in the ileum • Bicarbonate in the mucus in the stomach is present to protect the lining of the stomach from the low pH of the acid environment

3. Small Intestine • Duodenum is the part of the small intestine where most of the digestion occurs • Pancreas 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.

4. End products of Digestion • Carbohydrates to glucose and/or Fructose • Proteins to amino acids and same peptides • Fats to fatty acids and glycerol • The 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)

5. Large Intestine • The 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

6. Disorders of the GI system • Gastroesophegeal reflux or GERD • caused by abnormal amounts of acid in stomach • or esophageal sphincter function • Defective 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

7. 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 medications • A common side to diabetic gastroparesis • Drugs 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

8. Constipation • Results from: • Inadequate water intake • Inadequate fiber intake • Changes in lifestyle • Lack of exercise • Drugs like opiates • Abuse of laxatives

9. Therapy of constipation • Bulk 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®)

10. Therapy of Diarrhea • Diarrhea 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

11. Diarrhea can be treated with fiber • Absorbs water from the GI and swells to provide bulk • Examples are Metamucil® (natural psyllium hulk) or fiber from fruits and vegetables • Can 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) CV • Imodium ®(Loperamide, a meperidine derivative) • Attapulgite (Kaopectate) • Bismuth subsalicylate (PeptoBismol) Note: Black Tongue

12. Liver Disease • Liver pathology includes hepatitis, cirrhosis, and cancer • Damage 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®)

13. Hepatitis • Inflammation of the liver • Caused 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 drugs • Alcohol • Hepatitis A virus (HAV) • Transmitted by oral-fecal route in endemic area • Symptomic therapy; not life long • Prevented by vaccination: Havrix® (GSK) and Vaqta® (Merck)

14. 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 mother • New 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

15. Therapy of Hepatitis • Therapy is complex and involved drug, antibody level and viral load monitoring • Antiviral 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

16. Cirrhosis • End stage liver disease • Fibrosis of the sinusoids of the liver • Complications: bleeding, CNS edema, renal dysfunction, ascites, hypoglycemia, hepatic bone disease (osteodystrophy), bleeding into the GI tract from varices • Terminal condition • Chronic hepatitis and carcinoma leads to cirrhosis • Extreme alcohol consumption • Liver Transplant is only cure

17. Vitamin D • Helps with the absorption of calcium from the intestine to make stronger bones and teeth • Deficiency causes metabolic bone softening: • Called rickets in children • Called 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

18. Vitamin K • Controls formation of coagulation factors II, VII, IX, and X in the liver • Also needed for calcium uptake in bones • Deficiency is rare • Antidote for coumadin (Warfarin) overdose • Given as 10 mg IVPB or subcutaneously for 3 days

19. Vitamin B3 (niacin) • Vital in protein metabolism • Deficiency 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 HDL • Niaspan ®

20. Vitamin B6 (pyridoxine) • Needed for: • Red blood cell formation - Antibody production • Cell respiration - Cell growth • Conversion of tryptophan to niacin • Helps convert stored carbohydrate to glucose to maintain normal blood sugar levels • Synthesis of neurotransmitters such as serotonin and dopamine • Deficiency can cause: • Anemia similar to iron-deficiency anemia • Decreased antibody production • Suppressed immune response • Symptoms such as dermatitis, a sore tongue, depression, confusion, and convulsions • Used in high doses for isoniazid toxicity

21. Vitamin B12 (cyanocobalamin) • Needed for healthy nerve cells, to make DNA, and for the formation of RBCs • Deficiency leads to irreversible nerve damage • IV dose form is given for perniceous anemia