Mechanical & Chemical Breakdown of Food

Gastrointestinal A&P

Function:

Mechanical & chemical breakdown of food

Absorption of nutrients

GI tract:

Hollow tube from mouth to anus

Mouth:

Breakdown begins w/chewing + salivation (α-amylase→CHO digestion)

Esophagus:

Transports bolus via swallowing

Oropharyngeal (voluntary)

Esophageal (involuntary)

Lower esophageal sphincter (opens to allow food into stomach; closes to prevent regurgitation into esophagus)

Stomach:

Secretes digestive juices + HCL + pepsin

Mixes/stores food; propels chyme into duodenum via peristalsis

Gastrointestinal A&P

Small intestine: (5 meters long!)

Duodenum→Receiveschyme through pyloric sphincter→bile (fats) + pancreatic enzymes (proteins, CHOs, fats) + intestinal enzymes (proteins, CHOs, fats)

Jejunum→Sugars & proteins absorbed

Ileum→Bile salts, Vit B12, chloride absorbed

Large intestine: (“leftovers” enter via ileocecal valve)

Cecum, appendix, colon (ascending, transverse, descending, sigmoid), rectum

When Things Go Wrong—GI Disorders

Motility disorders

Gastritis

Peptic ulcer disease

Malabsorption syndromes

Inflammatory bowel disease

Appendicitis

Vascular insufficiency

Disorders of nutrition

•

Motility Disorders

A)Dysphagia

Difficulty swallowing

Causes:

Mechanical obstruction of esophagus (tumors inside or outside, strictures, diverticularherniations)

Impairment of esophageal motility (CVA, Parkinson disease, achalasia)

Achalasia: nerve dysfunction→failure of muscular ring at end of esophagus to relax→lower esophagus becomes distended

In a condition calledachalasia, the lower esophageal sphincter fails to relax; food that has been swallowed has difficulty passing into the stomach, and the esophagus above the lower esophageal sphincter becomes enlarged. One or several meals may lodge in the esophagus and pass slowly into the stomach over time. There is danger of aspiration of esophageal contents into the lungs when the person lies down

•B) Gastroesophageal Reflux

Reflux of chyme into esophagus from the stomach

Common symptom: “Heartburn”

If long term→esophageal inflammation & erosion→fibrosis & thickening

Causes: Obesity, smoking, delayed gastric emptying (ulcers, pyloric stricture, hiatal hernia)

•C) Hiatal Hernia

Potrusion of ↑ stomach thru diaphragm

Sliding (congenital, short esophagus, trauma, weak diaphragm muscles)

S/S: GER, esophagitis

Paraesophageal(curvature of stomach herniates alongside of esophagus)

S/S: Discomfort after eating, dysphagia

•D) Pyloric Obstruction

Narrowing / blocking of pyloric sphincter

Congenital

Acquired (PUD, carcinoma of pylorus)

S/S: (early) vague epigastric fullness—worse after meals & late in day; nausea; epigastric pain

S/S: (late) gastric distention; vomiting; infrequent, small stools

•E) Intestinal Obstruction

Simple: mechanical blockage

Acute: Torsion, intussusception, herniation

Chronic: Tumor, inflammatory disorder

Functional: ↓ motility (Ex—paralytic ileus)

S/S: “Colicky” pain + vomiting

May become necrotic, perforate → peritonitis (infection)

2) Gastritis

Inflammation of gastric mucosa

Acute: Erosions usually superficial. Acute gastritis refers to a transient inflammation of the gastric mucosa. It’s most commonly associated with local irritants such as bacterial endotoxins, alcohol, and aspirin.

Cause: Chemicals, drugs (NSAIDS)

S/S: Vague abdominal discomfort; epigastric tenderness; BLEEDING (bleeding and hematemesis are associated with alcohol consumption, vauge s/s associated with NSAID use)

Chronic: Age=thinning/degeneration of stomach wall=loss of chief & parietal cells→ ↓ acid→ ↑ gastrin in plasma→ pernicious anemia (↓Vit. B12 absorbed). It’s characterized by the absence of grossly visible erosions and the presence of chronic inflammatory changes leading eventually to atrophy of the glandular epithelium of the stomach.

Cause: ?Autoimmune, H. pylori

3) Peptic Ulcer Disease

Break / ulceration in protective mucosal lining of stomach, duodenum

Submucosa exposed to gastric secretions → autodigestion

↑ Risk: Smoking, ↑ age, NSAIDS, alcohol, H. pylori, chronic diseases

•Gastric/Duodenal Ulcers

Causes:

NSAIDS→ inhibits prostaglandins + ↓mucus production

H. pylori→ stimulates gastrin production→ ↑acid production/ulcer formation

S/S: Chronic intermittent pain relieved by food intake/antacid use; 1st clinical manifestation may be hemorrhage / perforation

4) Malabsorption Syndromes

Interfere with nutrient absorption in small intestine

Pancreatic insufficiency→ Deficient production of pancreatic enzymes (affects digestion of proteins, CHO, fats)

Lactase deficiency→ Lactose not broken down

Bile salt deficiency→ Fats not digested / absorbed

5) Inflammatory Bowel Disease

Ulcerative colitis—chronic, inflammatory→ulceration of mucosa in colon (usually in sigmoid & rectum)

Crohn disease—inflammatory, affects both small & large intestine (rectum is seldom involved)

Diverticular disease—herniations / saclike outpouchings of mucosa thru muscle layers (usually wall of sigmoid colon)



6) Appendicitis

Inflammation of vermiform appendix

Most common surgical emergency of abdomen

Generally 20-30 years of age (can happen at any age

Cause: ?obstruction of lumen w/stool, foreign bodies, tumors → bacterial infection

Obstruction → appendix can’t drain → ↑pressure → appendix becomes hypoxic → mucosa ulcerates → bacteria invasion → inflammation → gangrene → perforation

7) Vascular Insufficiency

Gastrointestinal system extremely vascular

Atherosclerotic lesions, emboli, thrombi can occlude blood flow anywhere

Chronic mesentary insufficiency can develop as result of cardiovascular disorders—cardinal s/s: Colicky abdominal pain after eating

8) Disorders of Nutrition

Obesity

Complex disorder

Numerous theories

Increases risk for CAD, DM, gallstones, HTN, CVD; breast/cervical/endometrial/ liver CA in women; prostate/colon/rectal CA in men

Anorexia nervosa / bulimia nervosa

Psychologic syndromes

Starvation—short-term vs long-term

Liver, GB, Pancreas A&P Review

•Contribute enzymes, bile, hormones

•All three organs vital to digestion

•Deliver secretions to the duodenum through duct system

Liver Structure

•Large

•Highly Vascular

•Enclosed in upper right abdomen

Liver has blood supply from the heart and from the GI tract. GI tract blood supply provides the nutrients and low oxygenated blood

•Glisson capsule covers liver (blood vessels, lymphatics, nerves) When the liver is diseased or swollen, distention of the capsule causes pain et the lymphatics may ooze fluid into the peritoneal space

•Hepatic artery (oxygenated blood)from the heart

•Portal vein (some oxygen + nutrients)from the GI tract

•Liver lobules – smaller anatomic units

•Metabolic functions of the liver require a large amount of blood. The liver receives blood from both arterial and venous sources. The hepatic artery branches from the abdominal aorta and provides oxygenated blood (400-500ml/min). The hepatic portal vein, which receives blood from the inferior and superior mesenteric veins and the splenic vein, delivers about 1000-1200ml/min to the liver. Portal venous blood constitutes 70% of the blood supply to the liver. This blood carries some oxygen and is rich in nutrients that have been absorbed from the digestive tract.

•Hepatocytes “plates” (functional cells of liver) – can regenerate, therefore damaged or resected liver tissue can regrow

•Sinusoids (capillaries between plates of hepatocytes) – located between the plates of hepatocytes, receive mixture of arterial and venous blood from branches of the hepatic artery and portal vein. Blood from the sinusoids drains to a central vein in the middle of each lobule. Venous blood from all the lobules then flows into the hepatic vein, which empties into the IVC

•Kupffer cells (mononuclear phagocyte system) immunity cells

The sinusoids of the liver lobules are lined withhighly permeable endothelium. This permeability

enhances the transport of nutrients from thesinusoids into the hepatocytes, where they are

metabolized. The sinusoids are also lined withphagocyticKupffer cells, which are part of the

mononuclear phagocyte system.

These Kupffer cells remove foreign substances fromthe blood and trap bacteria.

•Disse space (hepatic lymph system) drainage Between the endothelial lining of the sinusoid and the hepatocyte is the Disse space, which drains interstitial fluid into the hepatic lymph system.

•Bile canaliculi (channels that conduct bile to bile ducts)

•Common bile duct >Sphincter of Oddi

Liver Function

•Performs numerous complex & important functions

•Many related to digestion & nutrition

A large, highly vascular organ, the liveris enclosed in a fibrous capsule in theupper right area of the abd. The liverperforms numerous complex andimportant functions, many of which arerelated to digestion and nutrition

Liver Function #1

•Filters/detoxifies blood

–Metabolic detoxification / biotransformation (cuts down reabsorption of potentially toxic substances, then facilitates their excretions through the intestines or kidneys

–Alchohol, barbiturates, amphetamines, steroids and hormones (estrogens, aldosterone, ADH, testosterone) are metabolized, preventing excessive accumulation and AE

–Alters chemicals to make less toxic, or biologically active

–*****However, sometimes the end products of this process themselves can become toxins. For example, end products of alcohol metabolism are acetaldehyde and hydrogen. Excessive alcohol intake over a prolonged period causes these end products to damage hepatocytes. Acetaldehyde (poison) damages cellular mitochondria, and the excess hydrogen promotes fat accumulation. This is how alcohol impairs the liver’s ability to function.

–Diminishes intestinal reabsorption

–Diminishes renal tubular reabsorption

Liver Function #2

•Removes ammonia from body fluids

–Process called deamination (amino acids converted to carbohydrates, or ketoacids, by removal of ammonia)

–Converts to urea, then passes into the blood

–Excreted in urine

Liver Function #3

•Produces bile

–Contains bile salts, bilirubin, etc.

–Emulsifies fats

–Helps in absorption of fats

•The liver secretes 700 to 1200 ml of bile per day. Bile contains bile salts, cholesterol, bilirubin, electrolytes, water.

•It is formed by hepatocytes & secreted into the canaliculi. Bile salts (conjugated bile acids), are needed for emulsifying and absorption of fats. After this work is done, most bile salts are actively absorbed in the terminal ileum and returned to the liver through the portal circulation for resecretion.

•This recycling of bile salts is called the enterohepatic circulation.

•Conjugation, or binding of bile acids with amino acids, makes the bile acids more water soluble, thus keeping them from being diffused in the duodenum & ileum.

•Intestinal bacteria will deconjugate some bile salts back into bile acids (secondary bile acids). These acids diffuse passively into the portal blood from both small & large intestines. An increase in the plasma concentration of bile acids accelerates the uptake and resecretion of bile acids and salts by the hepatocytes. The cycle of hepatic secretion, intestinal absorption, and hepatic resecretion of bile acids completes the enterohepatic circulation.

•Bile secretion is called choleresis. A choleretic agent stimulates the liver to secrete bile. One strong stimulus is a high concentration of bile salts. Other choleretics include secretin, which increases the rate of bile flow by promoting the secretion of bicarbonate from canaliculi and other intrahepatic bile ducts; cholecystokinin; and vagal stimulation.

–See Figure 29-4, p. 636 in Porth

Liver Function #4

•Produces plasma proteins

–Albumins and globulins (synthesized by liver)

–Maintains blood volume & pressure

•Synthesizes nonessential amino acids (tested with liver function test)

–AST, ALT, LDH, alkaline phosphatase

•Can store vitamin A for several years

Liver Function #5

•Plays important role in carbohydrate metabolism

–Releases glucose during hypoglycemia

–Takes up glucose during hyperglycemia

The liver MANAGES (contributes to thestability of blood glucouseleves byreleasing glucose during times of lowblood sugar and taking up glucose duringtime of high blood sugar

Liver Function #6

•Converts glucose to glycogen

•Glyconeogenesis

•Stores it for fuel for muscles

•Or, converts glucose to fat

•Can convert amino acids & glycerol to glucose

•Gluconeogenesis

Liver Function #7

•Stores essential nutrients

•Iron (as ferritin) & copper – released as needed for red blood cell production

•Vitamin B12 & D—stores for several months

•Vitamin A – stores for several years

•Vitamins E & K

•The liver stores these and in times of excessive intake and releases them in times of need

Liver Function #8

•Stores fats – synthesized from carbs and protein

•Fat absorbed by lacteals in the intestinal villi enter the liver through the lympatics, primarily as triglycerides.

Triglycerides can be hydrolyzed to glycerol and free fatty acids and used to produce ATP (for cellular use)

•Converts excess sugars to fats – Stored in adipose tissue

Liver Functions #9, #10, #11

•Storage of large volumes of blood

•Removal of bacteria & foreign particles

•Synthesizes prothrombin, fibrinogen, factors I, II, VII, IX, X

•Because of its extensive vascular network, the liver can store a large volume of blood. The amount stored at any one time depends on pressure relationships in the arteries and veins. The liver also can release blood to maintain systemic circulatory volume in the event of hemorrhage.

•Kupffer cells in the sinusoids of the liver remove bacteria and foreign particles from the portal blood. Because the liver receives all the venous blood from the gut and pancreas, the Kupffer cells play an important role in destroying intestinal bacteria and preventing infections.

•The liver also has hemostatic functions. It synthesizes prothrombin, fibrinogen, and factors I, II, VII, IX, and X, all of which are necessary for effective clotting. Vitamin K, a fat-soluble vitamin, is essential for the synthesis of other clotting factors. Because bile salts are needed for reabsorption of fats, vitamin K absorption depends on adequate bile production in the liver.

Liver Function #12

•Metabolism of bilirubin

•By-product of destruction of old rbc’s

•Gives bile greenish black color

•Produces yellow tinge of jaundice

•See Handouts re: Enterohepatic circulation of bile salts & Bilirubin Metabolism

Liver Disorders

•Viral hepatitis

•Fulminant hepatitis

•Alcoholic cirrhosis

•Biliary cirrhosis

Viral hepatitis

•Relatively common

•Affects primarily the liver

•All five types (A, B, C, D, E) can cause acute, icteric (jaundice) illness

•Pathologic lesions similar to other viral infections (“you’ve seen one…”)

•Hepatic cell necrosis

•Kupffer cell hyperplasia

•Infiltration by mononuclear phagocytes (varying severity)

•An inflammatory process

•Can damage/obstruct bile canaliculi

•Leads to cholestasis & obstructive jaundice

•In milder cases, liver parenchyma (functional tissue) not damaged

•Damage tends to be most severe in Hep B & Hep C

•Hep B can result in acute fulminating hepatitis

•Wide spectrum of manifestations

•Absence of symptoms→fulminating hepatitis with liver failure & coma

•Causes abnormal liver function test results: ↑serum aminotransferase, ↑AST, ↑ALT

•AST = aspartatetransaminase

•ALT = alaninetransaminase

•Clinical course:

•Prodromal phase—begins @ 2 weeks post exposure; ends w/appearance of jaundice

•Clinical (Icteric) phase—begins 1-2 weeks after prodromal phase; lasts 2-6 weeks

•Recovery phase—begins w/resolution of jaundice, @ 6-8 weeks post exposure

Viral hepatitis—Clinical Manifestations

Prodromal phase:

•Appearance of jaundice

•Fatigue / malaise (caused by systemic effects of liver inflammation)

•Anorexia (caused by systemic effects of liver inflammation on the GI system)

•Nausea/vomiting

•Arthralgia / Myalgia

•Headache

•Changes in sense of taste and smell

•Hyperalgia (extreme sensitivity to pain)

•Cough

•Low-grade fever

Clinical phase:(actual phase of illnesss)

–Worsening of all symptoms of the prodromal stage

•Jaundice

•Itching

•Dark urine

•Clay-colored stools

•Enlarged, smoothliver

•Liver tender, painful to percussion

Recovery phase:

•Begins w/resolution of jaundice

•Symptoms diminish

•Liver remains enlarged/tender

•Liver function returns to normal

Viral hepatitis--Complications

•Chronic active hepatitis (if it happens at least twice)

•Cirrhosis

•Hepatic failure & death

•Primary hepatocellular carcinoma

Fulminant hepatitis

•Clinical syndrome

•Results in severe liver impairment / necrosis of liver cells

•High potential for liver failure

•May occur as complication of:

•HCV infection

•HBV infection

•Combination HBV / HDV infection

•Rarely occurs with HAV infections

•May also occur as a result of:

•Toxic reactions to drugs (eg. Tylenol)

•Congenital metabolic disorders

Clinical course:

•Develops 6-8 weeks post initial symptoms

•Many of same symptoms + ascites & GI bleed

•Hepatic encephalopathy

•Hepatic necrosis irreversible, 60% to 90% die

•Acute liver failure usually develops within 6-8 weeks after the initial symptoms of viral hepatitis or a metabolic liver disorder. Anorexia, vomiting abdominal pain, & progressive jaundice are initial signs, followed by ascites & GI bleed. Hepatic encephalopathy is manifested as lethargy, altered motor functions, and coma & is related to cerebral edema, ischemia, & brain stem herniation. Liver function tests show elevations of both direct & indirect serum bilirubin, serum transaminases, & blood ammonia. Prothrombin time (PT) is prolonged. Renal failure & pulmonary distress can occur.

•Antiviral reverse transcriptase inhibitors are available to treat chronic hepatitis B or C. Treatment of acute liver failure is supportive. The hepatic necrosis is irreversible, & 60% to 90% of affected children die. Liver transplantation may be lifesaving & should be considered early.

•It’s amazing, but survivors usually do not develop cirrhosis or chronic liver disease.

Cirrhosis

•Chronic liver disease—develops slowly

•Widespread destruction of hepatic cells + collapse of supporting structure

•Replaced by fibrous cells

•Liver develops “cobbly” appearance

•Cirrhosis is a chronic liver disease. It’s characterized by widespread destruction of hepatic cells, which are replaced by fibrous cells. This process is called fibrotic regeneration. Cirrhosis is a common cause of death in the U.S. It’s twice as common in men as in women, and is especially prevalent among malnourished persons over age 50 with chronic alcoholism. Mortality is high; many patients die within 5 years of onset.

•IT’S INTERESTING TO ME THAT DEATHS FROM ALCOHOL-RELATED LIVER DISEASE HAVE INCREASED OVER THE LAST DECADE. HOWEVER, HIGH ALCOHOL CONSUMPTION AMONG WOMEN LEADS TO EARLIER & MORE SEVERE CIRRHOSIS. ALTHOUGH ALCOHOLIC CIRRHOSIS IS THE MOST PREVALENT OF THE DIFFERENT TYPES OF CIRRHOSIS, THE OCCURRENCE OF CIRRHOSIS AMONG PERSONS WITH ALCOHOLISM IS RELATIVELY LOW (@25%).

Cirrhosis--Types

•Classified by “cause” (See Handout of Cirrhosis of the liver)

•Most common:

•Laennec’s (also called alcoholic, portal, fatty cirrhosis)

•Postnecrotic

•Biliary

•Metabolic