Professional Documents
Culture Documents
The failure of this system in peptic ulcer disease typically involves the disruption of
mucosal protective factors (NSAIDs, which inhibit prostaglandin production, and H. pylori,
which can directly damage the mucosa and mucus layer) and/or the production of amounts
of acid that can overwhelm the protective factors (Zollinger-Ellison syndrome, in which
unregulated gastrin production leads to uncontrolled acid secretion, and H. pylori, which
can also promote hypersecretion of gastric acid).
5. Be able to describe and differentiate the various etiologies of hypergastrinemia (to
include and understanding of the pathophysiology of gastrinoma and retained
gastric antrum).
Hypergastrinemia may be due to:
Achlorhydia or hypochlorhydia: abnormally absent or reduced gastric acid stimulates
the production of excessive gastrin, and feedback inhibition does not occur
o Gastric atrophy
o Pernicious anemia
o Chronic gastritis
o Omeprazole therapy
o Vagotomy
Retained gastric antrum: an improperly performed antrectomy & Billroth II
gastrectomy procedure, in which the antrum has not been adequately resected.
Gastrin producing G-cells in the retained antrum are not exposed to acid from the
reconnected stomach and thus sense a paucity of acid and produce high levels of
gastrin.
Gastrinoma: a gastrin-secreting tumor that is not subject to feedback inhibition, as in
Zollinger-Ellison syndrome. In Zollinger-Ellison, hypergastrinemia is associated
with severe peptic ulcer disease, large gastric folds, and diarrhea (due to massive
gastric volume output, direct injury to the GI mucosa, and the inactivation of
pancreatic lipase by gastric acid)
G-cell hyperplasia: unclear if this actually exists
Massive small bowel resection
Gastric outlet obstruction
Renal failure: gastrin is not cleared from the circulation
6. Understand the relationship of NSAIDs to ulcer disease.
NSAIDs are designed to inhibit the inflammatory enzyme COX-2, but also inhibit the
constitutively expressed enzyme COX-1, which is responsible for the synthesis of
prostaglandins in the gastric mucosa. Chronic and heavy NSAID use can inhibit
prostaglandin production to the extent that gastric mucosal defenses are overwhelmed
(decreased mucosal blood flow, impaired epithelial renewal, unrestricted gastrin & acid
production), causing peptic ulceration. Patients especially at risk for this complication
include the elderly, females, and those with prior peptic ulcer disease. The treatment is
withdrawal of NSAIDs, if feasible.
Disorders of the skeletal muscle region present with oropharyngeal dysphagia and
sometimes nasal regurgitation and/or aspiration. Diagnosis involves a modified
barium swallow, manometry, and neurological evaluation if indicated. Management
involves instruction in safe swallow techniques.
Achalasia typically presents with dysphagia and regurgitation, and may also involve
chest pain, heartburn, and symptoms of aspiration. It is diagnosed by barium
swallow, endoscopy, and/or esophageal manometry, and management is directed at
reducing LES basal pressure by pharmacological (calcium channel blockers, Botox,
isosorbide dinitrate) or surgical (myotomy, pneumatic dilation) means.
DES and NSSDs typically present with substernal chest pain, and infrequently
regurgitation and/or dysphagia. Symptoms are typically intermittent and nonprogressive. Treatment is directed at reducing pain and inhibiting gut-brain
interaction (e.g. antidepressants).
Esophageal hypomotility presents with symptoms of GERD (heartburn, pyrosis,
dyspepsia), and is diagnosed by manometry. Treatment is exclusively directed at
managing GERD (e.g. PPIs, H2 antagonists, antacids).
Delayed gastric emptying is initially treated by removing any offending medications and
altering the diet to include more liquids & less fat. Prokinetic agents may be used to
accelerate gastric empyting but have limited utility due to the rapid development of
tachyphylaxis.
Rapid gastric emptying and the dumping syndrome are treated with lifestyle changes (small
meals, ingestion of fluids between meals, less carbohydrates & more protein/fat),
anticholinergic agents, octreotide (experimental), and in severe cases surgical maneuvers
such as jejunum loop interposition or reconstruction of the pylorus.
6. Understand the mechanisms responsible for GERD.
GERD may be produced by three mechanisms: physiological alterations of the LES, hiatal
herniation, and impaired esophageal clearance.
Alterations in the LES include relaxation immediately after a swallow (occurs in normal
patients), intermittent inappropriate relaxations of an LES with normal basal tone, and low
LES basal tone. The second alteration (inappropriate relaxation) is the most common LESrelated cause of GERD and physiologic reflux.
Hiatal herniation contributes to GERD by creating a reservoir of gastric contents near the
LES while the patient is supine, contributing to transient LES relaxations, interfering with
distal esophageal clearance, and eliminating the apposition of the LES and diaphragm,
which normally produces inspiration-related constriction of the LES.
7. Be able to describe the presentation, treatment, and potential outcomes of GERD.
GERD typically presents with heartburn and postural regurgitation; less common
symptoms include chest pain, dysphagia, and odynophagia. Atypical GERD can present
with esophageal chest pain, bronchopulmonary symptoms due to aspiration (asthma,
bronchitis, apnea, pneumonia, fibrosis), or ENT symptoms such as hoarseness, cough,
halitosis, and dental enamel loss.
First-line treatment of GERD involves lifestyle modifications (head-of-bed elevation, weight
loss, smoking cessation, reduction of meal size, reduction of coffee/fat/chocolate/alcohol,
avoidance of eating before bedtime). Pharmacotherapy involves control of intragastric
acidity with antacids, H2 antagonists, and/or proton pump inhibitors. Surgical therapy, the
final line of treatment, requires reduction of hiatal hernia and Nissen fundoplication.
Intestinal Malabsorption
1. Understand the importance of anatomical factors, particularly those that are ratelimiting in the absorption of carbohydrates and fats.
The stomach produces gastric lipase (which usually contributes to about 10-20% of TG
hydrolysis, but is upregulated in neonates and pancreatic insufficiency), mechanically
disrupts & emulsifies the meal, regulates normal delivery of nutrients to the small bowel,
synthesizes IF (necessary for B12 absorption) and digests cobalamin complexes & binds
them to R-complexes.
The small bowel is responsible for some digestion and most nutrient absorption.
Anatomical and physiologic differences between the segments of the small bowel are very
important in these processes. About 80% of nutrient uptake is usuall completed in the
proximal bowel (proximal to Ligament of Treitz). The duodenum alone absorbs iron, folate,
and calcium, while the ileum alone absorbs bile salts and vitamin B12-IF. The jejunum is a
fairly redundant segment, and its loss is easily accommodated. Carbohydrate digestion in
the duodenum involves breakdown of oligosaccharides at the brush border; the ratelimiting step is transport of monosaccharides across the epithelium, except for lactose
(hydrolysis by lactase is the rate-limiting step). Fat absorption in the small bowel depends
on intraluminal digestion (by pancreatic enzymes), mucosal processing & uptake, and
normal postmucosal processing and transport (e.g. by the lymphatic system).
The pancreas produces the enzymes necessary for digestion of nutrients: amylases,
proteases, lipases, and nucleases. It also produces the bicarbonate-rich fluid necessary for
normal pH maintenance in the duodenum.
The colon reabsorbs fluid and electrolytes, temporarily stores waste products, serves as a
major repository for enteric flora, and generates short-chain fatty acids (a major energy
source for colonocytes).
2. Understand the pathophysiologic mechanisms for carbohydrate and fat
malabsorption.
The most common mechanism for carbohydrate malabsorption is lactose intolerance, which
is actually a normal adult phenotype (except in northern Europeans and their
descendants). Deficiency or absence of the enzyme lactase, which catalyzes the ratelimiting hydrolysis of lactose, allows the passage of undigested lactose into the colon,
where it is broken down by bacteria, producing bloating, gas, and osmotic diarrhea.
Damage to the intestinal mucosa by various diseases may produce intolerance in patients
who previously tolerated lactose well. Other causes of carbohydrate malabsorption include
overconsumption of high fructose corn syrup (which may overwhelm the small bowels
capacity to absorb fructose), overconsumption of sorbitol, and rare genetic deficiencies of
disaccharidases.
Fat malabsorption may be due to maldigestion, impaired fat processing & uptake, and/or
disruption of post-mucosal fat delivery. It can cause steatorrhea, diarrhea, weight loss,
kidney stones (increased luminal fat chelates calcium, leading to increased absorption of
soluble oxalate), and fat-soluble vitamin deficiencies (A night blindness, D osteopenia
& tetany, K easy bruising, E rarely any functional defects).
The small bowel radiologic series (with barium) is useful for detecting and locating mucosal
abnormalities to guide mucosal biopsy, and can also detect anatomic lesions (fistulae and
strictures) and other conditions that predispose to bacterial overgrowth. A normal study
does not rule out the presence of mucosal lesions, and samples for stool cultures & parasite
screens should be obtained beforehand, since barium inhibits the growth or
microorganisms.
Peroral biopsy of the small bowel is the key to diagnosis for many mucosal conditions.
Patients with suspected celiac sprue should be instructed to institute a gluten-free diet;
failure to respond suggests incomplete removal of gluten or the presence of another GI
condition.
Tests for lactose intolerance may involve a trial of withdrawing milk products (not very
reliable), a lactose tolerance test, which involves monitoring blood glucose to check for
absorption, or a hydrogen breath test, in which breath H2 is measured following ingestion
of lactose in water. Many of these tests suffer from poor correlation between symptoms
and results indicating lactose maldigestion.
The hydrogen breath test may also be used with lactulose or glucose administration to
assess for bacterial overgrowth.
Bacterial culture via endoscopy may be necessary to confirm or rule out bacterial
overgrowth.
The Schilling test is a series of procedures done to determine the cause of vitamin B12
deficiency.
In Stage I, an injection of unlabeled B12 is given to saturate all internal B12 binding
sites, then oral radioactive B12 is administered and the urine is assessed for
radiation. A finding of less than 8-10% of the administered dose in the urine
suggests B12 malabsorption.
In Stage II, radiolabeled B12 complexed with intrinsic factor is administered after
the initial injection. A normal urine finding suggests pernicious anemia.
In Stage III, the patient is given a course of antibiotics before the test is repeated. A
normal urine finding suggests bacterial overgrowth. Web says this is III, coursepack
says this is Stage IV. ???
In Stage IV, the patient is given pancreatic enzymes along with the B12. A normal
urine finding suggests pancreatic insufficiency. Web says this is IV, coursepack says
this is III.
Diarrhea is defined as a stool volume >200 mL/day or stool weight greater than 200 g/day.
Clinical complaints associated with diarrhea may include increase in stool frequency,
increase in stool volume, and decrease in stool consistency.
2. Understand the major features of fluid and electrolyte absorption in the small
intestine and colon.
Intestinal fluid & electrolyte absorption involves both passive and active transport across a
polarized epithelium with tight junctions. Transport is both active and passive, and may
involve specialized membrane proteins. Na, K, Cl, and HCO3 are the main ions whose active
transport is involved in controlling fluid movement, which follows electrolyte movement.
Solute-coupled sodium absorption is important in the jejunum, especially following a meal.
Electroneutral NaCl absorption is relatively more important in the ileum & proximal colon,
and involves the secretion of bicarbonate and H+. Electrogenic Na transport plays a more
important role in the distal colon.
Most ingested potassium is absorbed in the small intestine via diffusion; active absorption
of K+ occurs in the distal colon. The colon is aldosterone-responsive, and can actively
secrete K+ in exchange for Na+. Chloride is secreted via special channels throughout the
intestine. Bicarbonate secretion is an important cytoprotective mechanism in the
duodenum and elsewhere, and may be uncoupled or coupled to Cl cycling.
3. Identify the major pathophysiologic mechanisms of diarrhea.
A simple approach to diarrhea divides pathogenic mechanisms into two categories:
enhanced secretion and impaired absorption. A more detailed approach identifies five main
categories:
Osmotic diarrhea: defined as diarrhea that stops when the patient fasts and has an
osmotic gap >100 on stool analysis. Osmotic diarrhea is caused by the presence in
the intestines of poorly absorbed solutes that drag water and salt into the lumen.
This may be due to ingestion of poorly absorbed solutes (sorbitol, mannitol,
lactulose, various salts), deficiencies of nutrient absorption (disaccharidase
deficiencies, generalized malabsorption), or other causes.
Secretory diarrhea: caused by enhanced secretion by the proximal GI tract, which
overloads the absorptive mechanisms of the colon. Usually involves the production
of large volumes of water stool with no osmotic gap, blood, pus, or significant
steatorrhea. Causes include infection (acute cases), tumors, celiac sprue, congenital
defects, portal hypertension, and Zollinger-Ellison syndrome (chronic cases).
Impaired net colonic absorption of fluid: due to impaired colonic absorption (diffuse
colitis, colon resection) or enhanced colonic secretion (fatty acid diarrhea, bile salt
diarrhea, villous adenoma).
Motility disorders: rapid transit through the GI tract does not allow for sufficient
absorption of fluid/electrolytes (except in scleroderma). Almost always cause
chronic diarrhea. Examples include acute stress-related diarrhea, IBS, post-
Epidemiology: third most common cause of cancer & cancer-related death in both
men and women. Increased risk is associated with hereditary syndromes (FAP,
HNPCC), personal history of colorectal cancer or adenomas; first-degree family
history of colorectal cancer or adenomas; personal history of ovarian cancer,
endometrial cancer, breast cancer, ulcerative colitis.
Pathogenesis: alterations in tumor suppressors and proto-oncogenes in the stem
cells of the colonic epithelium lead to the development of adenomas (polyps)
which acquire further mutations and develop into malignant lesions.
Clinical presentation: may be asymptomatic, or present with iron deficiency anemia,
occult GI blood loss, hematochezia, alterations in bowel frequency or stool caliber,
or obstructive symptoms. Small lesions are often asymptomatic, so most patients
present with advanced disease. Right-sided cancers are more likely to present with
occult stool blood, iron-deficiency anemia, and fatigue; left-side cancers are more
likely to present with frank blood in the stool and changes in bowel habits.
2. Understand screening and preventive strategies concerning colorectal cancer.
Since cancers of the colon are usually asymptomatic when small and potentially curable,
screening programs for asymptomatic individuals are very clinically important. High-risk
individuals (family or personal history of polyps/cancer, personal history of IBD/breast
cancer/gynecologic cancer, known familial colorectal cancer syndrome) need earlier, more
frequent, more aggressive screening than average-risk individuals (over 50, no family or
personal history of colorectal cancer or polyps, no personal history of IBD, breast cancer, or
gynecologic cancer).
Colonoscopy is the gold standard; it allows for concurrent screening & treatment of small
lesions and screens the entire colon. It is, however, uncomfortable (and requires colonic
lavage) and expensive. Sigmoidoscopy uses a flexible scope to examine the distal colon, and
is more acceptable to patients. Fecal occult blood testing is inexpensive and easy, but nonspecific and susceptible to false positives due to various foods. CT colonography, or virtual
colonoscopy is expensive, requires colonic lavage, and does not allow for immediate
removal of detected lesions, but it does not require sedation. Fecal immunochemical tests
are more specific versions of the occult blood test that detect only human globin. Fecal DNA
tests detect DNA shed by neoplasms; they are costly and require the collection of an entire
bowel movement.
3. Be able to describe the pathophysiology, clinical presentation, and treatment
approaches to diverticular disease.
Causes: narcotics, recent surgery with resumption of normal diet, other medications
that cause hypomotility, idiopathic
Clinical presentation: abdominal distension, tympany to percussion, absent or
hypoactive bowel sounds; gaseous distension & dilated cecum on X-ray
Both ulcerative colitis and Crohns present with diarrhea, abdominal pain, fever, and
weight loss, and occur at any age (peak 10-35). Fever, severe pain, and severe
weight loss are more common in Crohns, but these are usually not useful ways to
distinguish between the two.
Ulcerative colitis typically presents with rectal bleeding and rectal involvement in
the disease process. It rarely involves anal fissures, anal fistulae, or abdominal
masses. Inflammation is mucosal, crypt abscesses are common, and the disease is
continuous and confined to the colon.
Crohns disease typically presents with anal fissures & fistulae and abdominal mass.
It typically does not involves the rectum or present with rectal bleeding.
Inflammation is transmural, granulomas & fissures are common, and the disease is
discontinuous and may occur anywhere in the GI tract.
The etiology of IBD is still unknown. Genetic factors are known to play a role, especially in
Crohns. IBD involves prolonged immune activation with infiltration by lymphocytes &
macrophages and increased IgG production. Neutrophil infiltration is also involved. The
prolonged response eventually causes tissue damage via proteases and reactive oxygen
species. Suggested mechanisms for this prolonged immune response are a) an appropriate
response to an unknown persistent antigen, and b) an inappropriately prolonged and
intense response to a normal dietary or microbial antigen, resulting from an antigenspecific defect in immune regulation. Various factors are known to precipitate or flare
IBD, including antibiotics, enteric infections, NSAIDs, and smoking cessation (UC only).
4. Be able to describe the current medical therapy for IBD based on our
understanding of its pathogenesis.
Current medical therapy for IBD involves anti-inflammatory drugs of various classes,
intended to suppress the inappropriately prolonged and intense immune reaction that
causes tissue damage in IBD.
Ulcerative colitis is usually treated with 5-ASA compounds, azathioprine, or anti-TNF
antibodies (e.g. infliximab). Crohns disease is treated with azathioprine or anti-TNF
antibodies.
Acute flares of either disease require different treatment. Acute UC should be treated
with topical 5-ASA or steroids for distal disease, oral 5-ASA or steroids for extensive
disease, azathioprine for steroid-dependent disease, and anti-TNF antibodies is
azathioprine fails. Trials of oral 5-ASA and steroids are underway. Surgical therapy
(colectomy) is required if medical therapy fails. Actue Crohns is treated with oral steroids
or antibiotics, or azathioprine or anti-TNF antibody for steroid dependent or steroid
refractory disease. Surgical therapy is required for failure of medical therapy or
complications (obstruction, perforation, bleeding).
Viral Hepatitis
1. Differentiate the salient features of the main hepatotropic viruses (A,B,C,D,E).
Hepatitis A
Organism: Non-enveloped RNA virus
Epidemiology: Leading cause of acute viral hepatitis worldwide; spread is fecal-oral
& person-person, and related to poor sanitation, bad hygiene, and overcrowding.
Water-borne and food-borne outbreaks common.
Risk groups: residents of and travelers to endemic regions, children and caregivers
in daycare centers
Pathogenesis: Liver injury is mediated by cellular immune response to infected
hepatocytes
Clinical Course: mild to severe illness following incubation of 2-6 weeks: malaise,
fatigue, headache, abdominal pain, arthalgias, nausea/vomiting, anorexia, fever;
followed by jaundice, dark urine, pruritus, pale stools. Recovery within 6-12 weeks;
fulminant cases very rare (<1/1000)
Chronic Sequelae: no chronic hepatitis, low acute fatality rate, no cirrhosis, no carrier
state
Diagnosis: acute = IgM anti-HAV; recovered/latent = IgG anti-HAV; vaccinated = IgG
anti-HAV
Treatment: symptomatic; hospitalization rarely required
Prevention: HAV vaccine (pre-exposure), immune globulin (post-exposure)
Hepatitis B
Organism: double-shelled DNA virus. Outer envelope = HBsAg; inner core = HBcAg
Epidemiology: in the US & Europe, disease of adulthood A/W IV drug use,
transfusions, needle-sticks, nosocomial spread, promiscuity. In Africa & Asia,
endemic and largely transmitted by maternal-infant or child-child spread
Risk Groups: IV drug users, multiple sexual partners, MSM, infants born to infected
mothers, HCW, transfusion recipients
Pathogenesis: immune-mediated (apoptotic, humoral, cellular)
Clinical Course: acute form is stereotypical hepatitis with 40-180 day incubation
period; chronic form may be silent or present with fatigue and intermittent
exacerbations resembling acute form
Chronic Sequelae: chronic hepatitis (2-10% adults, 90% children <5 y), cirrhosis, low
acute fatality rate, carrier state exists
Diagnosis: see below under objective 4
Treatment: interferons, nucleoside analogs, nucleotide analogs to suppress or
eradicate HBV
Prevention: HBV vaccine (pre-exposure), HBIg + HBV vaccine (post-exposure)
Hepatitis C
Organism: RNA virus
Epidemiology: worldwide distribution; recreational injection drug use is the
dominant mode of transmission. Other routes include hemodialysis, high-risk sexual
behaviors, sexual & household contacts, HCW.
Risk Groups: injection drug users, transfusion recipients
Pathogenesis: unknown; may involve immune-mediated and direct cytopathic injury
Clinical Course: acute form has an indolent course with mild or no symptoms after
an 8 week incubation period; fulminant form is extremely rare; chronic form
presents with malaise, weakness, fatigue, serious consequences later in the infection
(cirrhosis, HCC, lymphoma, membranous glomerulonephritis, vasculitis, etc.)
Chronic Sequelae: very low acute fatality rate, carrier state, high prevalence of
chronic hepatitis (70-85%), cirrhosis
Diagnosis: see below under objective 4
Treatment: subcutaneous pegylated interferon and oral ribavirin, 6-12 months
Prevention: no vaccine or prophylactic treatment exists
Hepatitis D
Organism: defective RNA virus that must get help from HBV to acquire an envelope
and become infective
Epidemiology: occurs worldwide, but prevalence higher in tropical and subtropical
areas of Africa & S. America; direct parenteral and sexual routes are the most
efficient mode of transmission
Risk Groups: any person infected with hep B, injection drug users
Pathogenesis: immune-mediated and direct cytopathic mechanisms
Clinical Course: acute and chronic forms similar to other forms of viral hepatitis;
acute form suggests coinfection and rarely becomes chronic, while the chronic form
suggests superinfection; both forms can precipitate fulminant hepatitis
Chronic Sequelae: moderate (2-10%) acute fatality rate, carrier state, chronic
disease progresses to cirrhosis in 3-5 years in about 40% of patients
Diagnosis: acute = IgM anti-HDV and/or HDV Ag; chronic & recovered/latent = IgG
anti-HDV
Treatment: pegylated interferon alfa
Prevention: no vaccine is available, but can be prevented by timely administrated of
HBV vaccine as it requires HBV to cause disease
Hepatitis E
Organism: non-enveloped RNA virus
Epidemiology: primarily in the developing world; primary mode of transmission is
fecal-oral; zoonotic (pigs are reservoir)
Risk Groups: residents of and travelers to endemic regions
Pathogenesis: appears to involve cytopathic damage & immune-mediated damage
Clinical Course: acute form is stereotypical hepatitis with incubation period of 2-8
weeks; course is usually benign with recovery in 2-6 weeks; progression to chronic
hepatitis is rare; fulminant hepatitis is very rare
Chronic Sequelae: low acute fatality rate, no carrier state, very little progression to
chronic hepatitis, no cirrhosis or HCC
Diagnosis: in the USA, ELISA assays for IgM anti-HEV or HEV-RNA are available only
through the CDC and specialty labs in the
Treatment: supportive and symptomatic
Prevention: vaccine not available but should be soon
2. Understand the natural history of acute and chronic viral hepatitis.
Acute hepatitis, a major public health problem, usually presents with acute-onset malaise,
fatigue, headache, abdominal pain, myalgias, arthalgias, nausea, vomiting, anorexia, and/or
fever. These initial symptoms are usually followed by jaundice, dark urine, pale stools, and
pruritus. It is usually followed by recovery, although rare cases may result in death.
Fulminant hepatitis is a subtype of acute hepatitis which involves the onset of altered
mental status (hepatic encephalopathy) and impaired coagulation within 8 weeks of the
initial symptoms of liver disease in an otherwise healthy individual. Other clinical
Most digestive enzymes are synthesized as zymogens and are not normally
activated until they reach the duodenum, where enterokinase activates trypsin.
Intracellular (just-produced) digestive enzymes are segregated in granules, keeping
them away from lysosomes and other cellular components.
The activating enzyme, enterokinase, is anatomically segregated from the pancreas.
o Iatrogenic
Chronic pancreatitis:
Alcohol toxicity
Idiopathic
Other (minor causes):
o Hereditary pancreatitis
o Cystic fibrosis
o Tropical pancreatitis
5. Understand the clinical presentation, diagnosis, and management of chronic and
acute pancreatitis.
Acute pancreatitis:
Clinical Presentation: steady dull or boring pain in the epigastrium or LUQ, which
may radiate to the back; mild to intense pain on abdominal palpation; other
symptoms may include anorexia, nausea, vomiting, fever, dyspnea (rare), coma
(rare). Signs include Gray-Turner sign, ascites, hypotension, rebound tenderness,
respiratory distress
Diagnosis: serum amylase (faster rise but less specific), serum lipase (slower rise
but very specific), physical exam, CT scan and/or EUS showing enlargement/fluid
collection
Management: hospitalization, aggressive IV fluid & electrolytes with Hct monitoring,
NPO if eating cause worsening pain, antiemetics & narcotic analgesics, antibiotics if
infection detected
Chronic pancreatitis:
Clinical Presentation: abdominal pain, episodes of acute pancreatitis (~50%), weight
loss, malabsorption, upper GI bleed, diabetes mellitus
Diagnosis: plain radiographs (calcification), EUS, CT; exogenous stimulation of
pancreatic secretion with secretin or secretin/CCK, 72-hr fecal fat collection to
determine if fat malabsorption is present
Management: analgesics, enzyme replacement (with H2 antagonist or PPI),
nutritional support, therapy for DM, drainage of pseudocysts and fluid collections,
surgical intervention in extreme cases
6. Know the common complications of acute and chronic pancreatitis and
understand the current theories of the pathophysiology behind those complications.
Acute pancreatitis:
Local complications related to autodigestion: fluid collection, pseudocyst, pancreatic
necrosis, vascular issues, mass effect
Shock: 3rd spacing intravascular hypovolemia and hypotension, capillary leak,
possibly inadequate cardiac response due to vasoactive agents (?)
Coagulopathy: destruction of components of the clotting cascade by pancreatic
enzymes
Chronic pancreatitis:
Pain: possibly secondary to obstruction, irritation, inflammation of pancreas
Malabsorption: failure of pancreatic enzyme production (especially lipases)
Malnutrition: secondary to malabsorption
Diabetes mellitus: destruction of pancreatic islets
Pseudocysts & fluid collections
Obstruction of the common bile duct: strictures or fibrosis
Pancreatic cancer
In the hepatocytes, bilirubin is conguated by the enzyme UGT, located in the endoplasmic
reticulum, then transported across the canlicular membrane into the bile, and eventually
excreted into the duodenum. The intestine cannot absorb conjugated bilirubin; in the
terminal ileum and colon, it is converted to unconjugated bilirubin by bacterial enzymes.
The unconjugated bilirubin is then reduced by colonic bacteria to form urobilinogen. Most
urobilinogen is excreted with stool, but some is reabsorbed and excreted in the urine.
3. Understand the definition and potential etiologies of cholestasis.
Cholestasis is decreased or absent bile flow. It may be extrahepatic or intrahepatic.
Extrahepatic cholestasis is usually secondary to bile duct obstruction, e.g. by gallstones,
tumors, strictures, and extrinsic compression. Compression & bile backup cause profound
changes in hepatocytes; pumps and proteins that normally localize to the canalicular
membrane are redistributed to inhibit the accumulation of toxic bile components in the
hepatocyte.
Intrahepatic cholestasis:
Cystic fibrosis: CFTR function is impaired, leading to decreased chloride and
bicarbonate secretion in the intrahepatic bile ducts. The change in pH decreases
ductular bile flow and may cause precipitation of mucus plugs.
Certain drugs may cause a decrease in the activity of Na/K ATPase, which is
necessary to create the sodium gradient that allows for normal bile production
Drugs that interfere with bile acid binding cytosolic proteins and/or microtubule
assembly (which is necessary for normal intracellular transport of bile acids in
vesicles) can decrease bile flow
Alterations of the canaliculus, e.g. decrease in ATP-dependent transport of organic
ions by cMOAT, caused by estrogens
Autoimmune liver diseases; e.g. primary biliary cirrhosis
Viral hepatitis
Infiltrative disease (e.g. AFLD, NAFLD)
The gallbladder modifies the bile while it is being stored: it concentrates bile by absorbing
water and electrolytes, and also secretes mucoprotein (to coat the gallbladder surface) and
acid (to prevent calcium stone formation) into the bile, which consists mainly of a mixture
of cholesterol, phospholipids, and bile salts.
2. Gallstones and their complications
Gallstones are a very common clinical problem: more than 20 million Americans have
gallstones, although 75-80% of these patients have no symptoms. There is a 2:1 female:
male prevalence, risk increases with age, and certain ethnicities have high incidence of
gallstones. Gallstones may present with biliary colic and/or acute cholecystitis.
There are three main types of gallstones: cholesterol, black pigment, and brown pigment.
Cholesterol stones, the most common in the US, form by cholesterol supersaturation, recur
often (35%), and occur preferentially in the gallbladder. Risk factors include age, female
sex, obesity, pregnancy, rapid weight loss, and TPN. Black pigment stones are composed of
calcium carbonate & calcium bilirubinate and are caused by the overproduction of
unconjugated bilirubin; they preferentially occur in the gallbladder and rarely recur. Risks
include hemolysis, ileal disease, and cirrhosis. Brown pigment stones, the least common,
are caused by bacterial infections of the bile, recur quite often, and preferentially occur in
the ducts. Risk factors include bile duct dyskinesia and IgA deficiency.
Gallstone formation requires three principal defects: a) supersaturation of the bile, usually
caused by high cholesterol levels or low bile acid levels; b) nucleation, either homogeneous
or heterogeneous, which is much more important and involves mucus and bacteria; and c)
gallbladder hypomotility or stasis, which may occur in pregnancy, TPN, and starvation or
rapid weight loss.
The complications of gallstones include:
Biliary colic, a colicky pain usually centered in the RUQ caused by sudden and
temporary obstruction of the cystic duct by a stone.
Acute cholecystitis, caused by the impaction of a stone in the cystic duct or neck of
the gallbladder
Mirizzis syndrome, the obstruction of the common bile duct by a gallstone in the
neck of the gallbladder
Choledocholithiasis, the obstruction of the common bile duct by a stone that has
passed through the cystic duct, which can lead to jaundice, ascending cholangitis,
and/or acute pancreatitis
Cholecystoduodenal fistula, caused by the erosion of a stone out of the gallbladder
into the duodenum, which can lead to Bouverets syndrome (the stone becomes
lodged in the duodenal bulb, causing vomiting) or gallstone ileus (the stone
obstructs the ileocecal valve).
Gallbladder carcinoma
3. Cholangiopathies
Immune-mediated:
o Primary sclerosing cholangitis: an inflammatory disease of the bile duct of
unknown etiology. It is usually diffuse and associated with IBD, can lead to
cirrhosis, and predisposes to cholangiocarcinoma. Strictures caused by PSC
that involve the extrahepatic bile ducts should be sampled to rule out
carcinoma.
o Primary biliary cirrhosis: inflammatory destruction of the interlobular and
septal bile ducts, thought to be immune-mediated. Typically presents in
middle-aged females, who may be asymptomatic or complain of vague
symptoms like fatigue. The hallmark test is positive AMA.
o Chronic GVHD: seen after bone marrow transplantation due to mismatch of
minor histocompatibility antigens on cholangiocytes
Infectious: ascending cholangitis
o Bacterial: enteral gram-negative bacteria (e.g. E. coli)
o Viral: AIDS cholangiopathy, associated with cryptosporidium infection
o Parasitic and fungal infections are very rare causes
Vascular:
o Post-surgical injuries: post cholecystectomy bile duct injury, post liver
transplant stricture at anastomosis and/or diffuse ischemia
Malignant: cholangiocarcinoma, which presents with painless jaundice
Genetic: various genetic defects leading to absence of ducts (Alagilles), multiple
cysts of the ducts (Carolis) or mucus plugging (cystic fibrosis)
History & physical: jaundice (especially of sclera), pale stools, dark urine, +/- pain
(common in stone disease, not in carcinoma), pruritus
Lab tests: bilirubin (obstruction elevated total & direct), liver transaminases
(elevated in acute obstruction), alkaline phosphatase (biliary obstruction, not
specific), GGT (more specific test of biliary obstruction)
Transabdominal ultrasound: good for cholecystitis, bile duct disease; not sensitive
for common bile duct stones
HIDA scan: uptake and excretion into the bile of a radiolabeled compound; lack of
GB filling after 60 minutes suggests cystic duct obstruction and lack of passage into
the duodenum suggests CBD obstruction
Cross-sectional imaging: CT (cannot detect cholesterol stones), MRI
Endoscopic ultrasound
Surgery: cholecystectomy
o Standard of care for acute cholecystitis and symptomatic cholelithiasis
o Typically laparoscopic
ERCP: combined endoscopic and fluoroscopic procedure that may be used for
diagnosis (brush cytology & stricture visualization) or treatment (stone extraction,
stenting, treatment of leaks, sphincterectomy)
Percutaneous intervention: for gallbladder decompression and stone removal in
patients who are not surgical candidates, or in whom ERCP has been unsuccessful
Medical therapy: ursodiol (synthetic bile acid) for improved bile clearance,
cholestyramine (bile acid binding resin) for pruritus of cholestasis
3. Understand the prognostic indicators and treatments for acute liver failure.
In addition to lab levels like pH, INR, creatinine, and bilirubin levels, the etiology of acute
liver failure is typically a useful prognostic indicator. ALF caused by acetaminophen,
hepatitis A, ischemia/shock, or pregnancy typically has a good prognosis; ALF caused by
drug toxicity, hepatitis B, Wilson disease, or an unknown cause has a bad prognosis.
The mangement of acute liver failure involves both etiology-specific and general
interventions:
Etiology-specific
o Acetaminophen toxicity: administer N-acetylcysteine
o Amanita phalloides: administer PCN or silibinin
o Autoimmune hepatitis: may respond to corticosteroids
o Wilsons disease: may require transplant (?)
General
o Critical care
o Airway protection for high-grade encephalopathy
o Manage cerebral edema: elevate head of bed, administer mannitol, possibly
monitor intracranial pressure
o Liver transplantation if necessary
GI Pharamcology I & II
See Google Doc of required drugs
Definition: cirrhosis is a chronic disease of the liver in which diffuse destruction and
regeneration of hepatic parenchymal cells have occurred and in which a diffuse
increase in connective tissue has resulted in disorganization of the lobular and
vascular architecture
Etiologies: cirrhosis is the final pathway of many types of chronic liver injury. Some
common causes of chronic liver injury that may result in cirrhosis are:
o Alcohol abuse
o Viral hepatitis (B or C)
o Cholestatic disorders (PBC, PSC)
o Autoimmune liver disease
o Metabolic disease (Wilsons, hemochromatosis, alpha-1-antitrypsin
deficiency, NAFLD)
o Drugs & toxins
o Venous outflow obstruction (Budd-Chiari syndrome)
Pathophysiology: activation of stellate cells during hepatic injury leads to
transformation, proliferation, collagen hypersecretion, inflammation, and
contraction. These changes, when chronic, lead to the deposition of fibrous bands,
distortion of normal liver architecture, capillarization of liver sinusoids, and
bizarre patterns of hepatocyte death & regeneration. These processes produce the
fibrotic, disorganized tissue of advanced cirrhosis, which in turn causes vascular
derangement (portal hypertension) and hepatic dysfunction (hypoalbuminemia,
clotting abnormalities, hypoglycemia, excretory problems, and failure of
detoxification).
factors such as alcohol consumption. An ROS should be performed with special attention to
changes in weight & appetite.
The physical exam should include careful inspection of hair, skin, eyes, mouth, teeth,
extremities, and fluid status. Temporal muscle wasting, sunken supraclavicular fossae,
and/or decreased adipose stores are important signs of undernutrition. An assessment of
body size and/or composition should be performed and BMI calculated.
Serum protein levels and lymphocyte count are not helpful in nutritional assessment, as
they are more related to inflammation and injury than malnutrition.
4. Memorize how to calculate BMI and be ready to do so on the exam. Know BMI
cutoff points for underweight & obesity.
BMI = weight (in kg) / [height (in m)]2
<18.5 = underweight
30+ = obese
5. Know and understand the components of the Harris-Benedict equation (but you
dont have to memorize the formula).
Total energy expenditure = basal metabolic rate + activity + thermic effect of food
BMR (in kcal/day) = 66.5 + (13.8 x weight in kg) + (5 x height in cm) (6.76 x age) for men
BMR (in kcal/day) = 655 + (9.56 x weight in kg) + (1.85 x height in cm) (4.68 x age) for
women
BMR is multiplied by the Physical Activity Level (PAL) to produce BMR + PAL
Thermic effect of food is added (~6-10% TEE on average)
So components are sex, weight, height, age, physical activity level.
6. Understand how physical activity affects total energy expenditure.
Increased physical activity levels increased total energy expenditure. (Duh?)
7. Nutrition and the life cycle: focus on infant needs (what nutrients are low in breast
milk, why does one add cereal at age 4-6 months). What are the common
vitamin/mineral deficiencies in the elderly?
Infants have a number of special nutrition requirements. Human milk is the best food for
the infant (it provides energy and immunoglobulins), but does not provide enough fluoride,
iron, vitamin K, or vitamin D. Breast milk contains iron, but the babys iron needs increase
rapidly after 4-6 months; it is thus necessary to introduce cereal fortified with iron at 4-6
months of age. Cows milk is not recommended until one year of age due to its low iron
content, high renal solute load, and association with blood loss via the GI tract.
The elderly also have special nutritional requirements. Food intake is often poor or altered,
due to xerostomia, mental status changes, altered dentition, and taste & smell dysfunction.
The elderly also have altered GI motility and poor glucose tolerance & renal function.
Constipation is a common problem due to decreased fluid consumption. Psychosocial and
economic factors also affect food purchase and preparation. Nutrients of particular concern
are calcium, Vitamin D, iron, and B12.
8. Understand the general factors that affect vitamin or mineral deficiency
(beginning of lecture).
General factors and conditions that affect vitamin and/or mineral deficiency include poor
appetite (aged & chronically ill patients), alcoholism and other substance abuse, psychiatric
disease, fad diets, physician-prescribed diets (e.g. for renal failure and genetic conditions),
and malabsorption (gut resection, bowel disease, etc.).
9. Know which of the vitamins are fat-soluble and which are water soluble.
Vitamins A, D, E, and K are fat-soluble.
Thiamine, riboflavin, niacin, pantothenic acid, biotin, vitamin B6, vitamin B12, folic acid,
and vitamin C are water-soluble.
10. Understand how fat-soluble vitamin deficiency is generated (underlying
pathophysiology including pancreatic insufficiency, loss of ileum, etc.)
Fat-soluble vitamin deficiency is typically generated by defects in the absorption, tissue
distribution, and handling of fat. These include disorders affecting the pancreas (which
decrease lipase production), the intestine (generalized malabsorption), the ileum especially
(loss of bile acids, necessary for the digestion of fat), the intestinal lymphatics, and the liver
& biliary tree. In addition, disorders affecting the skin, liver, and/or kidneys may impact
Vitamin D handling, and many antibiotics can cause Vitamin K defects.
11. Focus on vitamin D deficiency as an example of fat soluble vitamin vitamin D
metabolism, sources, underlying causes of deficiency, and role of supplementation.
Active vitamin D is found in dairy products, eggs, and fish. Dietary sterols in the skin are
converted to an inactive form of vitamin D (D3), which is hydroxylated by the liver to
produce 25-OHD3, which is in turn hydroxylated by the kidney to 1,25-(OH)2D3, which is
the more potent form. Deficiency of vitamin D can cause rickets in children and
osteomalacia in adults. Deficiency is common in patients with conditions that affect bile
production and reabsorption (biliary cirrhosis, small-bowel disease or resection), obesity,
renal or liver disease, and chronic antiepileptic use.
20. Know which factors affect predicted energy expenditure in the harris-benedict
equation.
Repeat of #5.
21. Understand the lack of utility of checking plasma protein levels to diagnose
protein malnutrition
OK.
22. Understand that while protein is necessary for optimal organ function that
oversupply is not beneficial
OK.
23. Know that in general overfeeding is more dangerous than underfeeding
OK.
24. Know the nutritional risk factors (i.e. weight loss) that predict in-hospital
mortality
????
25. Understand that nutrition is rarely an acute issue and that waiting for limited
periods of time for the clinical situation to become more clear is the best course.
OK.