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. Mouth and oral cavity • Teeth normally masticate food which increases the surface area for digestive enzymes to work • Salivary amylase is secreted and begins the digestion of starch and complex carbohydrates into disaccharides and trisaccharides • The oral cavity is also called the pharanyx • Esophagus delivers the food to the stomach

3. 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

4. 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.

5. End products of Digestion • Carbohydrates to glucose and/or Fructose • Proteins to amino acids and same peptides • Fats to fatty acids and glycerol • Fats are transported via chylomicrons to the liver where VLDL, and LDL are secreted • 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)

6. 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

7. 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

8. 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

9. Malabsorption diseases • Celiac disease: autoimmune disease of the small intestine where there is a senstivity to gluten • Tropical Sprue: a disease causing the villi of the small intestine to stop absorbing nutrients • Pancreatic disease including pancreatic cancer, pancreatitis and cystic fibrosis • Cholestatic jaundice

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

11. 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®)

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 • Drugs used in the therapy: • Interferons: are protein that modulate the immune system and help in viral infections. Includes interferon alpha 2 alpha (Roferon®) and interferon alpah 2 beta (Intron A®) and Peginterferon alpha 2 alpha (Pegasys®) • Antiviral agents: Ribavirin • Protease Inhibitors for HCV: Telaprevir (Incivek®)

14. 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