1
Q
Describe the two leading theories for the cause of inflammatory bowel disease
A
The cause of IBD is not well-established. It is thought to result from immune-mediated and cytokine-mediated bowel injury triggered by environmental factors in a genetically-predisposed individual. This person may not be able to “down-regulate” after inflammation of the colon. Two theories are:
- An inflammatory response may destroy the intestine’s barrier properties leading to increased uptake of bacterial products or dietary antigens. Circulating immune complexes produce a systemic inflammatory response with extraintestinal manifestations.
- An autoimmune response to antigens common to intestine, skin, synovium, eye and biliary tree.
2
Q
What is ulcerative colitis?
A
It is a chronic inflammatory disease that causes ulceration of the colonic mucosa and extends proximally from the rectum into the colon
3
Q
Describe the pathophysiology of ulcerative colitis & what causes it?
A
- UC results in ulcers that start at the rectum and move along the large intestine. The ulcers extend from the mucosa to the submucosal lining leading to colonic epithelial inflammation
- It is usually limited to the rectum and sigmoid colon.
- The ulcers that form are circumferential & continuous with no skip lesions & form crypt abscesses
- Cause of UC is unknown, dietary, infectious, genetic, and immunologic are suggested causes.
4
Q
What are some symptoms associated with ulcerative colitis?
A
- Ulcerations → Anal Bleeding
- Edema & swelling from the inflammation → Cramping & abdominal pain
- Anal irritation stimulates the autonomic and somatic nerves → the urge to defecate
- Damaged colonic epithelial cells are unable to reabsorb sodium & water → Frequent watery diarrhea, Small amounts of blood and purulent material may also be present
- Intermittent periods of exacerbation and remission
- Severe bouts may be associated with fever, 10-20 bowel movements/day, dehydration, anemia
5
Q
What is crohn’s disease?
A
Is an idiopathic inflammatory disorder that affects any part of the GI tract from the mouth to the anus.
6
Q
Describe the pathophysiology of Crohn’s disease & what causes it?
A
- There is transmural (full-thickness) inflammation of the small and/or large intestine leading to characteristic “skip lesions” (discontinuous areas of inflamed bowel with areas of healthy bowel in between)
- The inflammation leads to thickened mucosa with cobblestoning caused by submucosal edema
- The ulcerations can also lead to fistulae
7
Q
What are some symptoms associated with crohn’s disease?
A
- Diarrhea with or without blood
- Post prandial RLQ pain
- Anal pain resulting from perianal abscesses, skin tags, fissures or fistulae
- Fever, vomiting, fatigue, weight loss
- Anorexia
- Palpable intestinal mass resulting from ileal involvement
- Severe flare can lead to electrolyte imbalance, hypoalbuminemia, vitamin B12 deficiency
- Extraintestinal manifestations: oxalate stones, gallstones, aphthous ulcers, clubbing of fingers, uveitis, conjunctivitis, erythema nodosum (red, painful nodules on anterior legs), stunted growth in children, delayed puberty
8
Q
What is fulminant hepatitis (acute liver failure)?
A
- It is a rare syndrome resulting in massive impairment or necrosis of liver cells and a decrease in liver size (acute yellow atrophy) that usually occurs after infection with certain hepatitis viruses, exposure to toxic agents, or drug-induced injury
- Acetaminophen overdose is the leading case of acute liver failure in the U.S.
- Hepatitis B virus is sometimes responsible for fulminant hepatitis, and up to 50% of cases of fulminant hepatitis B involve hepatitis D virus coinfection.
9
Q
What is acute pancreatitis?
A
An acute inflammation of the pancreases caused by an obstruction to the outflow of pancreatic digestive enzymes caused by bile duct or pancreatic duct obstruction
10
Q
Describe the pathophysiology of acute pancreatitis
A
If caused by an obstruction:
- The backup of pancreatic secretions causes activation and release of enzymes within the pancreatic acinar cells →
- The activated enzymes cause autodigestion of pancreatic cells and tissues resulting in inflammation →
- The autodigestion causes vascular damage, coagulative necrosis, fat necrosis, and formation of pseudocysts →
- Edema within the pancreatic capsule leads to ischemia and necrosis
11
Q
Describe what causes the systemic effects associated with acute pancreatitis
A
- Proinflammatory cytokines and vasoactive peptides are released into the bloodstream from the acute inflammation →
- This activates leukocytes, causes injury to blood vessel walls, and coagulation abnormalities with the development of vasodilation, hypotension, and shock →
- ARDS, HF, renal failure, SIRS, & sepsis may develop from the flood of cytokines and peptides released into the blood
12
Q
What are the clinical manifestations associated with acute pancreatitis?
A
- Epigastric or midabdominal pain is the cardinal symptom of acute pancreatitis. The pain may radiate to the back because of the retroperitoneal location of the pancreas
- N/V can occur and are caused by the hypermotility or paralytic ileus secondary to pancreatitis or peritonitis.
- Hypotension and hypovolemia can lead to shock → decreased renal profession leads to renal failure
13
Q
What causes chronic pancreatitis?
A
- Chronic alcohol abuse is the most common cause of chronic pancreatitis
- Obstruction from gallstones, autoimmune disease, gene mutations, smoking, and obesity are associated w/ chronic pancreatitis.
- The pancreatic parenchyma is destroyed and replaced by fibrous tissues, strictures, calcification, ductal obstruction, and pancreatic cysts.
- Continuous or intermittent abdominal pain is the classic symptom
14
Q
What is gastroesophageal reflux disease?
A
The persistent return of acid and pepsin into the esophagus and results in complications such as mucosal erosion & bleeding
15
Q
Describe the pathophysiology of GERD
A
- There is a decreased resting tone of the lower esophageal sphincter
- Vomiting, coughing, lifting, bending, or obesity increases abdominal pressure contributing to the development of reflux esophagitis
- GERD causes inflammatory responses in the esophageal wall leading to hyperemia, edema, tissue fragility, erosion, and ulcerations
16
Q
What are the risk factors for peptic ulcer disease?
A
- Genetic predisposition, H. pylori infection of the gastric mucosa, and habitual use of NSAIDS can cause a break in the protective lining of the lower esophagus, stomach, or duodenum.
- Other factors include excessive alcohol use, smoking, acute pancreatitis, COPD, and cirrhosis
17
Q
How does chronic use of NSAIDs contribute to peptic ulcer formation?
A
- Chronic use of NSAIDs suppresses mucosal prostaglandin synthesis, resulting in decreased bicarbonate secretion and mucin production and increased secretion of hydrochloric acid
- Disruption of the mucosa exposes submucosal areas to gastric secretions and autodigestion causing erosion and ulceration
18
Q
How does H. Pylori contribute to peptic ulcer formation?
A
- H. pylori causes inflammation and immune responses that promote mucosal ulcerations or prevent healing of the injured mucosal tissue.
19
Q
What are gastric ulcers and what causes them?
A
Gastric ulcers are ulcers of the stomach and they develop in the antral region, adjacent to the acid-secreting mucosa of the body and are frequently caused by H. Pylori
20
Q
How do gastric ulcers form?
A
Can be caused by H. Pylori OR:
- Primary defect in gastric ulcer formation involves an abnormality that increases the mucosal barrier’s permeability to H+ ions leading to damage of the mucosa → ulcer formation
- Gastric secretion may be normal or less than normal and there may be a decreased mass of parietal cells → limited mucus secreted from the mucosal cells → gastric ulcer formation
- Pyloric sphincter fails to respond to normal stimuli (entry of acid, protein, and fat into the duodenum) to increase resting tone, allowing reflux bile and pancreatic enzymes to damage the gastric mucosa
21
Q
What is the most common composition of gallstones?
A
- The most common type of gallstones are cholesterol gallstones and they are formed in bile that is supersaturated which cholesterol produced by the liver.
- PIgmented gallstones are either black or brown. Black stones are formed of calcium bilirubinate, whereas brown stones are composed of calcium soaps, unconjugated bilirubin, cholesterol,, fatty acids, and mucin and are associated w/ bacterial infections
22
Q
How is Hepatitis A spread?
A
Hepatitis A is spread via the feces, bile, and sera of infected individuals and is usually transmitted via the fecal-oral route, but can also be transmitted via infected blood.
23
Q
What are the clinical manifestations of Hepatitis A?
A
- nonspecific prodrome with anorexia, fever, fatigue, arthralgias, myalgias
- Flu-like symptoms usually resolve when jaundice becomes evident. There may also be clay-colored stools, a skin rash, weight loss and an aversion to cigarette smoke. Hepatomegaly is common. Splenomegaly is occasionally seen.
24
Q
What are the serologic markers for HepA?
A
Serologic testing for hepatitis antibodies confirms the diagnosis.
- IgM anti-HAV is detectable 3-6 months after infection
- IgG anti-HAV by itself indicates past infection with recovery. These individuals are immune to re-infection.
- Liver enzymes ALT and AST are elevated. Bilirubin may also be elevated.
25
How is Hepatitis B spread?
* HBV is transmitted through blood-blood contact and via sex.
* Can also be transmitted from mother to infant
26
What are the clinical manifestations of HepB?
* fatigue, nausea, vomiting, jaundice, abdominal pain, RUQ tenderness, may be asymptomatic until chronic disease develops
27
What are the serologic markers for HepB?
Serologic testing for hepatitis antibodies confirms the diagnosis.
* Hepatitis B surface antigen (HGsAg) is the initial marker of infection. It continues in the acute state and into early convalescence. Presence after 6 months indicates chronic infection.
* Hepatitis B core antigen antibodies (anti-HBc) appear at illness onset and persist indefinitely. Their presence indicates current or past infection.
* Hepatitis B e antibody (anti-HBe) appears when infection is resolving.
* Serum bilirubin, ALT and AST levels are usually elevated during the acute disease state, but normal in chronic infection.
28
What serologic markers would be present in a patient who is susceptible to hepatitis b?
No markers would be found since the patient has not yet been exposed to the virus
29
What serologic markers would be present in a patient who is immune due to natural infection to hepatitis b?
* **HBsAg** would be **negative** because the patient is no longer in an infectious state
* **anti-HBc** would be **positive** because it indicates that the patient has previously been infected w/ the hepatitis B virus
* **anti-HBs** would be **positive** because it means the patient has developed immunity to HepB
30
What serologic markers would be present for a patient who is immune to hepatitis B from vaccination?
* **HBsAg** would be negative because the patient is not in an infectious state
* **anti-HBc** would be negative because the individual was never infected w/ the hepatitis B virus
* **anti-HBs** would be positive because it means the patient has developed immunity to HepB
31
What serologic markers would be present for a patient who is acutely infected with hepatitis b?
* **HBsAg** would be **positive** because the patient is actively being infected by the virus **and is infectious**
* **anti-HBc** would be **positive** because the individual is actively being infected w/ the virus
* **IgM anti-HBC** would be **positive** because the patient is being acutely infected (\<6months)
* **anti-HBs** would be **negative** because the patient has not yet recovered or gained immunity to hepatitis B
32
What serologic markers would be present in a patient who is chronically infected with hepatitis b?
* **HBsAg** would be **positive** because the patient is continually being infected by the virus and is infectious
* **anti-HBc** would be **positive** because the individual is actively being infected w/ the virus
* **IgM anti-HBC** would be **negative** because the patient is being chronically infected (IgM only persists for 6 months)
* **anti-HBs** would be **negative** because the patient has not yet recovered or gained immunity to hepatitis B
33
What is the diagnostic criteria for chronic hepatitis b infection?
* Occurs when there is persistent clinical manifestations of hepatitis and liver inflammation after more than 6 months.
* HBsAg persists in serology tests
34
How is Hepatitis C spread?
* Spread parenterally, via contaminated blood, or sex
35
What are the clinical manifestations of HepC?
* fatigue, nausea, vomiting, fever, mild RUQ discomfort beginning about 6 weeks after exposure, jaundice in 20-30% of patients
* Symptoms are often absent until liver disease is advanced.
* An infected mother may transmit the infection to her child at birth. Transmission through breast milk has not been documented.
36
What are the serologic markers for hepatitis C infection?
* **Anti-HCV antibodies will confirm the exposure to the virus,** but will not help determine whether the infection is active, resolved, or chronic. Some persons will not have antibodies until 6-9 months after illness onset.
* Polymerase chain reaction (PCR) technique detection using gene amplification can detect HCV within 1-3 weeks of exposure. But this test may not be as reliable as antibody testing.
* Serum ALT and AST may be elevated in acute disease, but only mildly elevated in chronic disease.
* Enzyme-linked immunosorbent assay for anti-HCV antibodies (HCV RNA) allow one to differentiate between active disease, convalescence, and carrier state.
37
Describe the pathophysiology associated with viral hepatitis
* The virus infects the hepatocytes in the liver, leads to their death, and causes hepatic cell necrosis, scarring, kupffer cell hyperplasia, and infiltration of mononuclear phagocytes.
* Cellular injury is caused by cell-mediated immune mechanisms (cytotoxic t-cells, NK cells)
* The inflammation caused by the infection damages and obstructs bile canaliculi, leading to cholestasis and obstructive jaundice.
38
What are some possible complications of chronic hepatitis?
* Fibrosis
* cirrhosis
* hepatic failure
* hepatocellular carcinoma
39
What is and what causes liver cirrhosis?
* It is an irreversible inflammatory, fibrotic liver disease
* Structural changes in the liver occurs due to injury (alcohol, viruses, chemicals) and fibrosis.
* Fibrosis is a consequence of Kupffer cell activation w/ release of inflammatory mediators, ROS, and activation of fibrogenic fibroblasts →
* Chaotic fibrosis alters/obstructs biliary channels & blood flow → jaundice and portal hypertension
* Portal hypertension → blood shunting away from the liver → metabolic alterations & toxin accumulation
* Liver regeneration is disrupted by hypoxia, necrosis, atrophy, and liver failure
* Chrrosis develops slowly over several years
40
What is and what causes portal hypertension?
* It is an abnormally high BP in the portal venous system caused by resistance to portal blood flow
* It is caused by disorders that obstruct or impede blood flow through any component of the hepatic portal system
* Prehepatic causes occur from thrombosis or narrowing of the hepatic portal vein
* Intrahepatic causes are from vascular remodeling with intrahepatic shunts, thrombosis, inflammation or fibrosis
* Posthepatic causes occur from hepatic vein thrombosis or R. heart failure
41
How does alcoholic cirrhosis develop?
* It is caused by the toxic effects of alcohol metabolism on the liver, immunologic alterations, oxidative stress from lipid peroxidation, and malnutrition
* ETOH → converts to acetaldehyde → Excessive amounts of acetaldehyde are toxic and induce lipid peroxidation & oxidative stress, & disrupt cytoskeletal and membrane function → persistent inflammation leads to fibrosis & scarring & necrosis of the liver → hepatocytes lose their ability to regenerate
* Acetaldehyde inhibits export of proteins from the liver, alters metabolism of vitamins and minerals, promotes liver fibrosis, and contributes to malnutrition
*
42
What complications can result from alcohol-induced liver cirrhosis?
Liver cirrhosis can cause hepatomegaly, splenomegaly, ascites, gastrointestinal hemorrhage, portal hypertension, hepatic encephalopathy, and esophageal varices.
43
What is and what causes diverticulitis?
* It is the inflammation of the saclike outpouchings of mucosa through the muscle layers of the colon wall
* Diverticula can occur anywhere in the GI tract, but commonly occur in the L. colon in the sigmoid colon
* They form at weak points in the colon wall leading to out pouches of the mucosa
44
What are the clinical manifestations associated with diverticulitis?
* Cramping pain of the lower abdomen
* Diarrhea, constipation, distension, or flatulence may occur.
45
What is the function of leptin?
* It is a product of the obesity gene and is expressed primarily by adipocytes, acts on the hypothalamus to suppress appetite and regulates body weight within a narrow range.
* Low levels during fasting stimulate food intake and reduce energy expenditure
* High levels in the fed state inhibit food intake and increase energy expenditure
* Leptin secretion increases as adipocytes increase in size or number
46
What causes leptin resistance?
* High levels of leptin in obesity become ineffective at decreasing appetite and increasing energy expenditure.
* Leptin resistance disrupts hypothalamic satiety signaling, promotes overeating and excessive weight gain, and is a factor in the development of obesity
47
Describe the role of hormones in obesity
* **Adiponectin -** produced by visceral adipose tissue and has insulin-sensitizing properties contributing to insulin resistance and type II DM. Decreased lvls leads to increased hepatic gluconeogenesis, decreased skeletal muscle glucose uptake, and increased inflammation
* **Ghrelin -** produced by the stomach in response to hunger and stimulates food intake. It stimulates metabolic changes leading to an increase in body weight and body fat mass & stimulates the release of GH, and pancreatic functions
* **Glucose-like Peptide 1 (GLP-1) -** stimulates pancreatic glucose-dependent insulin secretion, delays gastric emptying, and suppresses appetite.
* **Peptide YY (PYY) -** Released from intestinal endocrine cells in response to nutrients entering the intestine and inhibits gastric motility and decreases appetite. PYY lvls decrease with increases in adiposity, leading to obesity.
*
Patho Exam 4
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