The Digestive System Part 2

Bowel Infections

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Bowel Infections•Clostridium difficile: An opportunistic infection associated with broad-spectrum antibiotic use (a suprainfection).

•E. coli O157:H7: A strain of E. coli that produces a toxin that can make some humans very sick. This strain of E. coli is carried by cattle and is transmitted to humans through fecal contamination.

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E. coli O157:H7

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E. coli O157:H7• Not everyone infected with E. coli O157:H7 gets diarrhea or any other symptoms.• Ex. people who work around cattle their entire

lives may be immune to the strain• Some people get very sick or even die.• Some may develop hemolytic-uremic syndrome.• Some may develop thrombotic thrombocytopenic purpura (TTP).

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Bowel Infections Appendicitis

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Bowel Infections Appendicitis

• Appendicitis is a localized infection of the appendix, which is a blind outpouching from the cecum.

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AppendicitisSigns and Symptoms

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AppendicitisSigns and Symptoms

• Manifests as ill-defined pain starting in the area of the umbilicus and later progressing to the lower right quadrant.• Fever is an undependable sign. •A feeling of abdominal fullness and wanting to defecate is common.• The bowel is shut down because of inflammation.• Bowel sounds will be absent and the patient may think

he/she is constipated.• Vomiting or loss of appetite is common.• If the appendix ruptures, pain may abate to return later with signs of an acute abdomen.

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Diverticulitis

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Diverticulitis

• Diverticuli are outpouchings that have developed throughout the intestine, although they are most common in the large bowel.

• Most adults have them to some degree, some more than others

• They can get infected and rupture, similar to the appendix.

• Signs and symptoms are similar to appendicitis except they may not necessarily be on the right lower quadrant 11

Duodenal Diverticuli

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Duodenal Diverticuli

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Irritable Bowel SyndromeDiagram

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An 80-year-old man with a history of irritable bowel syndrome presented with a 5-day history of abdominal pain in the left lower quadrant, without aggravating or relieving

factors

Fisher R and Doma S. N Engl J Med 2009;361:28615

Stages of Diverticulitis

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Jacobs D. N Engl J Med 2007;357:2057-2066

Stages of Diverticulitis•Antibiotics are prescribed to treat the infection.

•Abscesses may be drained percutaneously.

•In about 10% of cases, surgery is necessary to remove a section of the colon or even to remove the entire colon (total colectomy)

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Colorectal CancerPolyps

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Colorectal CancerPolyps

• Third cause of death from cancer for both men and women

•Most colorectal cancer starts out as a benign polyp which progresses to carcinoma in situ and finally to invasive cancer.

• Not all polyps progress to cancer.

• Most polyps bleed sporadically.

• Bleeding can be detected by the fecal occult blood test (FOBT).

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Colorectal CancerTreatment

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Colorectal CancerTreatment

• We can prevent the development of most colorectal cancer by removing all polyps.

• Do not know which, if any, will become cancer but just to be safe all of them should be removed

• Polyps, and therefore colorectal cancer, develop in the lumen of the colon. In order to become metastatic, the cancer has to invade the smooth muscle of the intestine and gain access to blood vessels and/or the peritoneal cavity.

• If the cancer has not invaded very far, the prognosis is very good.

• If it has metastasized, colorectal cancer always metastasizes to the liver and sometimes elsewhere.

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ColonoscopyDiagram

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23Fu K and Sano Y. N Engl J Med 2006;355:1912

A 56-year-old man underwent a colonoscopy after a positive fecal occult-blood test

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The GallbladderDiagram

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The GallbladderDiagram

Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 632 25

Components of Bile

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Components of Bile

1. Bile salts are detergents which emulsify fat for digestion.

2. Bile pigments are mainly conjugated bilirubin.

3. Cholesterol.

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Function of the Gallbladder

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Function of the Gallbladder

• The gallbladder also concentrates the bile by removing water– If it removes too much water, it can precipitate the

bile (which is usually made of cholesterol)

• Many people have gallstones and do not even know it– The problems come when the gallstones leave the

gallbladder and get stuck somewhere

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Causes of Gallstones

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Guyton & Hall, Textbook of Medical Physiology, 9th ed., Saunders, 1996, p.830.

Causes of Gallstones

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GallstonesDiagram

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Yekeler & Akyol, NEJM 351:2318, 200433

34Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 653 34

Treatment of Gallstones

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Treatment of Gallstones• Since it is felt that new stones will probably re-form if we just remove the stones, the gall bladder is usually removed.

• When the gall bladder is no longer present, the bile will not be as concentrated and precipitation of the components probably will not occur.

• Gall bladder surgery is typically done endoscopically through the abdominal wall.

• In patients who are not candidates for surgery, stones can be fragmented with lithotripsy. If they are in the duct, they can be crushed endoscopically from the stomach. There are drugs that dissolve gallstones, but they are not used very much.

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The LiverDiagram

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Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 633

The LiverDiagram

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Functions of the Liver

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Functions of the Liver

A. Carbohydrate metabolism

B. Lipid metabolism.

C. Protein and energy metabolism.

1. Enzymes important in energy metabolism: ALT, AST, GGT- Used as tests for liver necrosis

2. Synthesis of plasma proteins: albumin, coagulation factors, etc.

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Blood Flow of the Liver

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Blood Flow of the Liver

1. Hepatic artery: 350 ml/min

2. Portal vein: 1100 ml/min

3. Total blood flow: 1450 ml/min, 29% of resting cardiac output.

4. The liver is drained by the hepatic vein, which enters the inferior vena cava.

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Detoxification

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Detoxification• The liver binds polar molecules to drugs and other molecules. This is called conjugation. Conjugating drugs and other molecules makes them easier to excrete, either by the kidney or in the bile.

• Bilirubin is detoxified by conjugation (addition) of a glucuronic acid molecule.

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Bilirubin Formation, Circulation, and EliminationDiagram

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Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 636

•The process of bilirubin formation, circulation and elimination

•Urobilinogen is responsible for the brown color of the stool

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Excretion by the Liver

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Excretion by the Liver

• Bile is the vehicle for excretion

• What is excreted?

1. Some drugs—most are conjugated before excretion

2. Bilirubin

3. Cholesterol

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Hepatitis

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Hepatitis• Means “inflammation of the liver.” Stating hepatitis does

not indicate what the cause is, just that there is inflammation. There are several different etiologies:

1. Toxic Hepatitis is caused by drugs/chemicals like halothane or isoniazid.

2. Bacterial hepatitis is caused by such organisms as TB, Staph, or Pseudomonas

3. Parasitic hepatitis is caused by a variety of parasites

4. Viral hepatitis is caused by such viruses as Epstein Barr, and Hepatitis A, B, or C- This is usually what the person means 50

Hepatitis A: Viral

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Hepatitis A: Viral

• Sort of a mild disease• May feel sick, but most people do not die from hepatitis A

•Vaccine available

• No carrier state• You have it and then you get over it and do not have it

anymore

• Caused by oral ingestion of contaminated water or food (fecal-oral route).

• Lifetime protection against re-infection if you get either the vaccine or the infection 52

Hepatitis B: Viral

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Hepatitis B: Viral

• Vaccine available

• Carrier (chronic active) state

• Spread by parenteral routes and exchange of body fluids• For the majority of hepatitis B patients, it is unknown

how they got it because there is a long incubation period and the person does not remember

• Long incubation period

• Acute disease can last weeks or months • Afterward may get rid of the disease or may go into

an active chronic hepatitis and have it forever 54

Hepatitis B: ViralDiagram

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Hepatitis B: ViralDiagram

Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 640 56

Progression/Outcomes of Hepatitis B Infection

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Kumar et al, 2010, Robbins & Cotran, Pathologic Basis of Disease, 8th ed. Elsevier,

Progression/Outcomes of Hepatitis B Infection

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Blood Markers of Acute Hepatitis B Infection and Recovery

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Blood Markers of Acute Hepatitis B Infection and Recovery

Kumar et al, 2010, Robbins & Cotran, Pathologic Basis of Disease, 8th ed. Elsevier, 60

Blood Markers of Chronic Active Hepatitis B Infection

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Blood Markers of Chronic Active Hepatitis B Infection

Kumar et al, 2010, Robbins & Cotran, Pathologic Basis of Disease, 8th ed. Elsevier,

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Hepatitis C

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Hepatitis C• Parenteral routes of transmission.

• Carrier (chronic active) state is more frequent with hepatitis C than with hepatitis B.

• Blood tests are available for the virus itself or for antibodies.

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Progression/Outcomes for Hepatitis C

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Kumar et al, 2005, Robbins & Cotran, Pathologic Basis of Disease, Elsevier, p.894

Progression/Outcomes for Hepatitis C

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A patient has the following lab tests: Hepatitis B viral DNA is negative; IgG-anti-HBc is positive. IgM-anti-

HBc is negative. What can we say about this patient?

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A patient has the following lab tests: Hepatitis B viral DNA is negative; IgG-anti-HBc is positive. IgM-anti-HBc is negative. What can we say about this patient?

1. He has active hepatitis B 2. He is contagious with

hepatitis B 3. He was exposed to

hepatitis B in the past but has recovered

4. We can't tell whether he has active hepatitis B from these tests

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Characteristics of Hepatitis A, Hepatitis B, and Hepatitis C

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Characteristics of Hepatitis A, Hepatitis B, and Hepatitis CPoint of comparison Hepatitis A Hepatitis B Hepatitis C

Causative agent Hepatitis A virus Hepatitis B virus Hepatitis C virus

Infections that become chronic None 3%-5% >70%

Acute infections each year in the US

179,000 185,000 38,000

US residents with chronic infection

None 1.25 million 2.7 million

Annual deaths in the US from chronic infection

None 6000 8000-10,000

People worldwide with chronic infection

None 350 million 170 million

Method of prevention Hepatitis A vaccine

Hepatitis B vaccine Hepatitis C vaccine (not yet available)

Preferred treatment None Interferon alfa or lamivudine

Interferon alfa plus ribavirin

Adapted from Lehne, 2009, Pharmacology for Nursing Care, 7th ed., Elsevier, p. 107670

Complications of Chronic Active Hepatitis B or C

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Complications of Chronic Active Hepatitis B or C

• Cirrhosis with portal hypertension may manifest as:1. Varices in the GI tract2. Ascites3. Congestive splenomegaly

• Hepatocellular carcinoma

• Liver failure may manifest as: 1. Low coagulation factors/bleeding2. Low serum albumin lowers the serum osmolic

pressure/edema3. Hepatic encephalopathy

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Features of Cirrhosis

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Features of Cirrhosis

1. Fatty liver: reversible, caused by alcohol consumption and many other things.

2. Fibrosis: not reversible; hepatic vasculature is rearranged, causing portal hypertension and varices.

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The Liver and its Venous Vasculature

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Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 633

The Liver and its Venous Vasculature

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Consequences of Cirrhosis/Liver Failure

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Consequences of Cirrhosis/Liver Failure

1. Portal hypertension with varices

2. Ascites- The pressure in the liver vasculature is so great that fluid is squeezed

out of the vasculature and into the portal cavity

3. Portosystemic venous shunts

4. Congestive splenomegaly- Blood backs up out of the liver

5. Hepatic encephalopathy- Brain problems and confusion due to buildup of ammonia because it

cannot be converted into urea and excreted from the body

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Consequences of Liver Failure

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Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 649

Consequences of Liver Failure

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Consequences of Portal Hypertension

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Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 646

Consequences of Portal Hypertension

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Portal Hypertension and the Diversion of Blood Flow

Diagram

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Porth, 2007, Essential of Pathophysiology, 2nd ed., Lippincott, p. 648

Portal Hypertension and the Diversion of Blood FlowDiagram

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Portal Hypertension and the Diversion of Blood Flow

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Portal Hypertension and the Diversion of Blood Flow

• The portal veins drain the lower part of the esophagus and the stomach

• Normally, blood is going through the blood vessels, down the veins, into the liver and the portal vein– Other blood goes through the vessel into the vena cava

• If there is a backup, the blood cannot get through the liver and it results in portal hypertension– The veins enlarge and you get varicosities in the lower esophagus

and throughout the gastrointestinal tract• People can actually bleed to death from lower esophageal

varices

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Porto-systemic Venous Shunts

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Porto-systemic Venous Shunts

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•Caput medusa.

•Esophageal varices.

Yang P and Chen D. N Engl J Med 2005;353:e19

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Varices Caused by Portal Hypertension

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Varices Caused by Portal Hypertension• The varices in the esophagus are typically the most troublesome and bleed, sometimes profusely.

• Bleeding varices can also develop in the stomach or intestinal mesentery.

• Internal hemorrhoids are varices of veins that drain the rectum and are frequently caused by liver disease. (External hemorrhoids are not caused by liver disease and are almost a universal finding in people over about age 30).

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Causes of Ascites Liver Disease

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Causes of Ascites Liver Disease

•Causes:

1. Increased lymph formation by liver with transudation through hepatic capsule. Transudation involves the slow escape of liquids from blood vessels through pores or breaks in cell membranes.

2. Sodium and water retention by kidney.

3. Hypoalbuminemia

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AscitesDiagram

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AscitesDiagram

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Cirrhosis Diagram

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A 52-year-old man with cirrhosis associated with alcohol abuse presented to the emergency department with hematemesis and lightheadedness, which had developed 3 hours earlier, after

binge drinking

Torrazza-Perez E and Carreno N. N Engl J Med 2010;362:e13

Video:http://www.nejm.org/doi/full/10.1056/NEJMicm0807812

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Other Consequences of Liver Failure

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Other Consequences of Liver Failure

• Congestive splenomegaly caused by portal hypertension.

• Hepatic encephalopathy: not sure of cause, but probably ammonia is not the whole story.

• Difficulty in metabolizing particular drugs (acetaminophen).

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Hepatocellular Carcinoma

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Hepatocellular Carcinoma• Associated with cirrhosis, hepatitis B, or hepatitis C

• Environmental toxins can cause it (aflatoxins).

• The liver is a favorite site of metastasis for many different kinds of cancer that arise elsewhere, such as colon, breast, and lung. These cancers are not liver cancers.

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