Download CM Gastro Exam 3 Review Lecture 23-Imaging of the GI Tract Plain

CM Gastro Exam 3 Review
Lecture 23-Imaging of the GI Tract
 Plain Film Radiography
o Inexpensive and readily available
o KUB (Kidney, ureter and bladder), Acute abdominal series (upright cxr,
supine and erect abd films) and Left lateral decubitus.
o Good to diagnose obstruction, ileus and free air
o Poor tissue contrast
o May see gallstones, urinary tract stones, organomegaly.
 Fluoroscopy-dynamic studies
o Barium swallow-esophagram
 Indicated for problems swallowing
o UGI (stomach and duodenum)
 Indicated to check for PUD
o Small Bowel follow-through
 Suspect small bowel disease, upper and lower tract studies are normal
o Barium enema, single or double contrast (barium and air)
 Evaluate bleeding and screening for colon cancer
o Modified barium swallow-used with a speech pathologist
 Used in pts with feeding difficulty.
o Contrast-barium, water soluble iodine, and air and barium for double
contrast exams.
 Ultrasound: transabdominal/endoscopic
o Uses sound waves
o Doppler techniques to check blood flow
o Useful in eval of liver, gallbladder, and biliary tree
o Cannot evaluate GI tract well, due to air
o No radiation, ideal for pregnant and pediatric pts.
 CT
o Axial slices through the abd with and without oral and IV contrast
o CT enterography of the small bowel
o Virtual colonoscopy-high res images of colon through special reconstruction
from CT slices to visualize colonic lumen.
 MRI
o Increased sensitivity and specificity vs CT because of the best soft tissue
contrast.
o Good visualizations of solid organs and retroperitoneal structures.
o MR cholangiopancreatography-able to visualize entire biliary tree.
o Disadvantage: expensive, no pacemakers or old intracranial aneurysm clips
or any other electronic implants
 Radionuclide Imaging (Nuc Med)
o Labeling radioactive isotope, ex. Technetium 99 labeled red blood cells can
be used to detect GI bleeding.
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o Labeling to iminodiacetic acid analog can be used to study dynamics of bile
flow: a HIDA scan.
o Labeling to food (scrambled eggs) can study dynamics of gastric emptying
o Technetium 99 pertectnetate can be used to localize Meckel’s diverticulum
due to affinity to gastric mucosa.
o Molecular imaging: fusion scan PET/CT
Plain Film Abd Series
o Able to Identify gas patterns:
 Normal-almost always gas in stomach, several small bowel loops and
colon and rectum.
 Free air-best seen on CXR or upright abd, less obvious on lateral
decubitus or supine films.
 Pneumoperitoneum-free air under the diaphragm!
 A continuous diaphragm sign is evidence of free air, able to see
diaphragm all the way across the abdomen.
 Free air on both sides of the bowel, can make bowel wall
visible.
 Gas visualized over the heart is indicative of a hiatal hernia.
 Dilated loops-small and large bowel appeared dilated-possible ileus,
‘sentinel loop’ may be seen.
 Multiple dilated small bowel loops, >2.5 cm and little colonic gas then
small bowel obstruction should be suspected.
 The most common cause of SBO is a hernia.
 Dilated colon-indicative of colonic obstruction
 Cecal volvulus
 Sigmoid volvulus
o Calcifications
 May see phleboliths, gallstones, urinary tract stones, calcified masses
such as uterine leiomyomas, and lymph nodes.
Fluoroscopy-Dynamic Studies
o Barium Swallow
 Identify Zenker’s diverticulum-a pouch off of the esophagus that food
gets caught in.
 Hiatal Hernia-may see a ‘corkscrew pattern’ with esophageal spasms.
o Small bowel follow-through
 Normal transit time is 5 min to 6 hrs.
 Identify strictures or obstructions.
o Barium Enema, single or double
 Identify small mucosal lesions, possibly identify cancerous lesions
Ultrasound
o Can visualize gallstones, much better than CT.
CT
o Abdominal CT with or without contrast
 Appendicitis appears very dilated, >7cm
 IV contrast can help identify carcinomas
Gas seen in portal veins is very bad, indicates bacterial infection in the
liver. Pt probably doesn’t have long to live.
 Identify bowel wall thickening
o Enterography of small bowel
 Ordered when trying to identify stricture or problem with small
bowel.
o Virtual Colonoscopy
 Good screening exam, fewer complications and fewer biopsies than
conventional colonoscopy.
 Cost is much less than colonoscopy, however radiation exposure.
MRI
o No radiation, can slowly heat up the body though. Very expensive!
o Often a problem solving technique
o Primary staging of rectal carcinoma.
o MRCP-visualize gallbladder, common bile duct and pancreatic duct
Radionuclide Imaging
o HIDA scan to check for gallbladder disease. After IV nucleotide is
administered, CCK is given and the gallbladder is observed for ejection and
an ejection fraction is measured.
o Nuclear medicine Hepatobiliary study is the best test for detecting a postoperative bile leak!
o Meckel’s Scan-Technetium 99 pertechnetate scans for ectopic gastric mucosa
over the mid pelvic level.
o PET/CT scan-very time consuming. Pt must rest in a quite room with warm
blankets and eyes closed because an muscle activity shows up on PET scan.
 Staging for documented malignancy
 Expensive
Angiography
o Diagnostic conventional angiography has been largely replaced by
noninvasive CT and MR techniques, but direct catheter angiography remains
an important procedure for directing various therapies.
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Lecture 24 & 25-Acute and Chronic Hepatitis
 Infectious Hepatitis
o Usually caused by one of the major hepatitis viruses (A-E)
o Other viruses are seen including cytomegalovirus, HIV, Herpes, and EbsteinBarr virus
o General Features
 Necroinflammation of the hepatocytes from immune reaction
 T-cell mediated reaction
 Incubation period can last for a long time, non-specific symptoms
 Fatigue
 Nausea
 Right upper quadrant pain
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Pre-icteric stage-note some flu-like symptoms and viral load begins to
increase.
Icteric phase-flu-like symptoms increase and full onset of disease
continues, either eliminated or becomes chronic.
Hepatitis A
o Introduction
 Caused by Hepatitis A virus, RNA virus
 Incubation period of approximately 28 days, must ask pts where they
have eaten or where they have been for the last month.
 Replicates in the liver and is shed in high concentrations in feces from
2 weeks before to 1 week after onset of clinical illness
 Self-limited disease-no chronic infection or chronic liver disease
o Incidence
 Peak in the 1980s
 Sharp decline after introduction of virus in 1996
o Transmission
 Fecal-oral route
 Person-to-person
 Contaminated food or water
 Can be sexually transmitted
o Risk Factors
 Travelers to countries with endemic HAV
 Men who have sex with men
 Users of IV and non-IV illegal drugs
 Person with clotting factor disorders
 Persons working with nonhuman primates, susceptible to HAV
infection
o Signs and Symptoms
 Young children (less than 6yo) can be asymptomatic
 Approximately 1 in 7 pts will require hospitalization
 Abrupt onset of
 Jaundice (>70% of adults)
 Fever
 Fatigue
 Nausea
 Dark urine
 Abd pain
 Joint pain
 Symptoms usually last about 2 months or less
 Can have relapsing symptoms for up to 6 months
 No chronic state noted
 Disease state confers immunity (IgG antibodies)
o Complications
 Fulminant hepatic failure is extremely rare
 Rare cases of autoimmune hepatitis have been reported
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 Arthralgia and rash due to activated immune components.
o Diagnosis
 Clinical symptoms with:
 Serum IgM HAV (acute)-disappear within a year
 Serum IgG HAV (lifelong immunity)
 Elevated liver enzymes are non-specific-ALT
o Treatment
 No specific treatments, supportive treatment if necessary
 Prevention is key
 Avoid contaminated foods, heating to >185 degrees for one
minute will kill virus
 Chlorination of water
 Vaccination
o 2 dose series (0 then 6-12 months later)
o Confers 90-95% immunity after two doses
o Inactivated vaccine
o HAVRIX or VAQTA
o Recommended for:
 All children at age 1
 Persons with travel risks
 Occupational risk factors
 Pts with chronic liver disease
 Men who have sex with men
Hepatitis B
o Introduction
 Hepatitis B, caused by infection with Hepatitis B virus, DNA virus
 Incubation period of approximately 6 weeks to 6 months
 Can present as acute, chronic or perinatal HBV
o Incidence
 Peak in the mid 1980s
 Has begun to decline since development of vaccine, and
improvements to vaccine.
o Transmission
 HBV is transmitted through activities that involve percutaneous or
mucosal contact with infectious blood or body fluids including:
 Sex with infected partner or IV drug use sharing needles (two
most common causes)
 Needle stick injuries for healthcare workers
 Not transmitted through food or water, sharing eating utensils,
breastfeeding, hugging, kissing, hand holding, coughing, or sneezing.
o Risk Factors
 Sex partners of infected persons
 Sexually active persons non in a long-term, monogamous relationship
 Men who have sex with men
 IV drug users
 Travelers to countries with intermediate or high prevalence of HBV
o Signs and Symptoms
 Vague, flu-like symptoms
 Dark urine and clay-colored BMs are common to all hepatitis
o Complications
 Hepatocellular carcinoma with chronic infections
 Fulminant hepatitis (acute)
o Diagnosis
 Signs and Symptoms
 Serological testing
 HBsAg
 Anti-HBs
 Remaining screenings are to determine whether infection is
chronic or acute.
o Treatment
 Prevention
 Vaccine
 Avoid contact or use universal precautions
 Acute infection-symptomatic treatment
 Chronic
 Medications
 Monitoring
 Pts with HBV should be checked for the other hepatitis viruses, and
should be vaccinated against HAV if they haven’t been.
o Vaccine
 Everyone should be vaccinated, cancer preventing and just really good
for everyone to have!
 Post vaccine testing
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Healthcare workers and public safety workers at high risk for
continued exposure.
 Infants born to HBsAg-positive mothers
 Chronic hemodialysis pts, HIV pts
 Sex partners of persons with chronic HBV infection
 Non-responders
 5-8% of vaccine recipients do not achieve detectable anti-HBs
levels
 Suggested that IM injections are better than intradermal
 Doses vary between children and adults, and there are combination
vaccines out there.
o Medication treatment
 Pegylated Interferon alpha-injected, finite treatment regimen
 Nucleoside analog-oral administration, long term treatment,
resistance noted.
Hepatitis D
o RNA virus which requires HBV infection to replicate
o Only seen in pts with HBV
o Transmitted the same way as HBV.
o Coprimary infection seen in IV drug users
o Increases risk of fulminant hepatitis from HBV
o Can be prevented with HBV vaccine
o Superinfection
 Previously infected with HBV, and then infected with HDV and
progresses to cirrhosis
o Coinfection
 Infection at the same time, most cases are resolved.
o No commercial test in the US for HDV
Hepatitis C
o Introduction
 Hepatitis C, caused by infection with HCV
 Incubation period of approximately 8 weeks
 Acute and chronic illness seen
o Incidence
 Declined rapidly until 2002 and has remained stable since then.
o Transmission
 Percutaneous exposure
 IV drug users, most common in the US
 Recipient of donated blood
 Needlestick injuries
 Birth to a HCV positive mother
 Infrequently in sex or sharing contaminated items.
o Risk Factors
 Current IV drug users
Recipients of blood transfusions before 1992, when better testing
became available
 Chronic hemodialysis pts
 Persons with known exposures to HCV, such as healthcare workers,
recipients of blood or organs from a donor with HCV, persons with
HIV
Screening Recommendations
 Persons born from 1945-1965
 Persons who have ever used IV drugs
 Persons with known exposure to HCV
 All persons with HIV
 Pts with signs or symptoms of elevated LFTs
Signs and Symptoms
 About 2% develop acute symptoms
 Abrupt onset of jaundice, fever, general flu-like symptoms
Complications
 Of every 100 persons infected:
 75-85% will develop chronic infection
 60-70% will go on to develop chronic liver disease
 5-20% will develop cirrhosis over a period of 20-40 yrs
 1-5% will die from consequences of chronic infection
 Diabetes occurs 3x more frequently
 Renal insufficiency
 Essential mixed cryoglobulinemia
 Prophyria cutanea tarda
 Non-Hodgkins lymphoma
Diagnosis
 Elevated liver enzymes (non-specific)
 Serum Testing
 Anti-HCV is the screening test of choice
o If negative then pt is not at risk for exposure.
o If positive then should be followed up with RIBA or RNA
testing
 HCV RNA
 RIBA for anti-HCV
Treatment
 Prevention is key
 No vaccine available
 Assess for chronic liver disease
 Medications
 Combination therapy: pegylated interferon and Ribavirin
 Genotyping is important for treatment, determines the length of
treatment and the response rate of treatment.
 Genotype 1-treatment is much longer, up to 48 weeks
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Genotype 2 and 3-treatment response is much better, and
shorter treatment given
o Treatment Counseling
 Avoid alcohol
 Avoid meds metabolized in the liver
 Sexual transmission is low, but can occur. Pts should use condom
 No occupational restrictions noted
Hepatitis E
o Acute, self-limited viral hepatitis, RNA virus
o First officially recognized in 1980s
o Epidemiology
 Usually seen in developing countries
 Fecal-oral transmission
 High rates among young adults, with relative sparing of children
 High rates in pregnant women
 Can result in fulminant hepatitis and death in the mother,
especially in 3rd trimester.
 Highly endemic in Asian countries, eastern Africa and Mexico.
o Symptoms
 Many asymptomatic cases (50-90%)
 Pregnant women have more severe symptoms
 Symptoms mimic other viral hepatitis cases
 Symptoms develop 15-60 days after exposure
o Complications
 Fatality rate in pregnant women is 10-30%
 Extremely rare chronicity
o Diagnosis and Treatment
 No serological test in the US
 Look for travel to endemic areas
 Sanitation is the key to prevention
 No vaccine available in the US
Lecture 26-Noninfectious Hepatitis and Hepatic Obstruction
 Anatomy and Physiology of Bile
o When hemoglobin is broken down, bilirubin is produced.
o Unconjugated bilirubin is then transported to the liver where it is
transported into the hepatocyte and conjugated.
o Then secreted into bile and the gut
o In the ileum and colon, it is converted to urobilinogen.
 Pathophysiology of Jaundice
o Increased production of bilirubin
o Decreased conjugation
o Cholestasis (obstruction)
 Measuring Bilirubin
o Total serum bilirubin and direct (conjugated) are both directly measured.
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o Indirect (unconjugated) bilirubin is calculated.
 TB-DB=IB
o Normal TB is <1
Increased Production of Bilirubin
o Increased Unconjugated bilirubin is either from decreased uptake or
increased production.
 Increased production causes include anything that causes
extravascular hemolysis of blood into the tissues or intravascular
hemolysis that allows extravasation of blood into the tissues.
 Increased unconjugated bilirubin in the tissues may also be from
decreased uptake of or decreased ability to conjugate bilirubin.
 Causes of Decreased uptake:
o CHF
o Certain drugs (Rifampin and probenecid)
 Causes of inability to conjugate bilirubin:
o Gilbert’s disease
o Crigler-Najarr syndrome
o Neonatal jaundice (physiologic)
o Hyperthyroidism
o Estrogens
o Liver disease-chronic hepatitis, cirrhosis and Wilson’s
disease.
o Increased Conjugated Bilirubin
 Increased conjugated bilirubin from cholestasis due to:
 Impaired Excretion caused by:
o Hepatitis
o Hepatocellular injury-toxic exposures or other damage
o Primary biliary cirrhosis
o End-stage liver disease
o Sepsis and hypoperfusion states
o Diseases that infiltrate the liver: TB, amyloid, sarcoid,
lymphoma
o Liver or hepatic crisis in sickle cell disease
 Obstruction caused by:
o Choledocholithiasis or Cholestasis
o Tumors and Cancer
o Strictures after invasive procedures
o Acute and chronic pancreatitis
o Primary sclerosisn cholangitis
o Parasitic infections-Ascaris and liver flukes.
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Differential Diagnosis of Jaundice
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Reasons for Jaundice and Unconjugated Hyperbilirubinemia
o Physiologic Reasons
 Newborn
 Pregnancy
o Non Physiologic Reasons
 Burns, crush injuries
 Recent transfusion
 Prior known blood disorder
 Drugs pt may be on
 Infection
 EtOH abuse or other reason for cirrhosis
 History of chronic hepatitis
 CBC, peripheral smear, and liver enzymes
o If the above are not present then begin to rule out inherited disorders
 Additional exams may include liver biopsy, and urine corporphyrins
o Crigler-Najjar Syndrome
 Type 1 is a rare autosomal recessive disorder.
 These pts have no ability to conjugate bilirubin at all, no
enzymes present
 Phototherapy may be beneficial, but phenobarbital does not
help!
 Exchange transfusions can also be used to treat, to help remove
bilirubin from circulation
 Type II-rare autosomal recessive disorder
 Have some enzyme activity, but very low.
 Bilirubin levels are slightly lower than type 1, but still elevated.
 Phenobarbitol and phototherapy can be used to treat.
o Gilberts Disease
Most common disorder causing about 10% of cases of jaundice
Affects processing of unconjugated bilirubin causing unconjugated
hyperbilirubinemia.
 Reduced activity of enzyme.
 Made worse by stress, exertion, infection or EtOH
 Treatment is generally not required, just reassurance for pts.
Conjugated Bile Disorders and Jaundice
o Caused by impaired secretion or obstruction, or the below disorders
o Dubin-Johnsons Syndrome
 Autosomal recessive-rare
 Increase in conjugated (direct) bilirubin
 Made worse by alcohol, hepatitis, drugs excreted through liver, birth
control, pregnancy and infection
 No treatment required
 Black pigmentation of liver on biopsy
 Gallbladder cannot be visualized
o Rotor Syndrome
 Autosomal recessive-rare
 Increase in conjugated bilirubin with lifelong jaundice
 Made worse by the same as above
 No treatment required, just avoid stressors of the liver
 Normal histologic appearance on biopsy
 Gallbladder can be visualized
Cirrhosis of the Liver
o Cirrhosis is a complication of liver diseases. Damage leads to cirrhosis
because the inflammation and repair causes scar tissue to form and does not
allow regeneration of tissue.
o May be caused by:
 EtOH
 Toxic chemicals or toxic levels of medication
 Chronic viruses
 Toxic metals that accumulate in the liver from certain disease
 Autoimmune disease or autoimmune disorders
o Signs and Symptoms of Cirrhosis
 Jaundice
 Fatigue
 Weakness
 Loss of appetite
 Itching
 Easy bruising from decreased production of clotting factors by the
liver
 Non-specific symptoms until late
 Splenomegaly
o Complications
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Scarring in the liver obstructs flow of blood through the liver and to
the liver cells, as a result the blood backs up causing portal
hypertension.
 Spontaneous bacterial peritonitis-can occur in the fluid in the abd
cavity, serves as a good growth medium for bacteria that would
normally be eliminated by the liver. This is a life-threatening
complication
 Esophageal varices-Blood flow bypasses liver and goes through
esophagus, enlarging the veins and can result in bleeding which is lifethreatening
 Hepatic encephalopathy-toxic substances from GI accumulate in
blood, like ammonia causing hepatic encephalopathy resulting in
memory loss, confusion, coma and even death.
 Drug toxicities-toxic substances make the brains of pts with cirrhosis
very sensitive to drugs
 Hypersplenism-blood draining from spleen backs up causing the
spleen to swell
 Hepatorenal syndrome-late stage and normally a progressive failure
of kidneys, which results in toxic accumulations in the blood.
 Increased risk of liver cancer
o Diagnosis & Treatment
 Diagnosed by elevated liver enzymes early in the disease, liver biopsy
demonstrating scarring and by CT.
 Treatment focuses on minimizing any further damage and removing
what the causative agent is when possible.
Primary Sclerosing Cholangitis
o Progressive liver disease caused by inflammation and scarring of the bile
ducts of the liver. This impedes blood flow of bile to gut and leads to
cirrhosis, liver failure, and is associated with liver cancer.
o Autoimmune disorder
o Diagnosis made by using ERCP and imaging of bile ducts or MRI.
o 80% of pts with have autoantibodies (p-ANCA)
o Disease progresses slowly and may take time to diagnose.
o Liver transplant is the definitive treatment
Primary Ascending Cholangitis
o Ascending cholangitis is caused by bacterial infection usually from a
gallstone or from stricture, tumor or following an ERCP
o Bacteria is usually aerobic including E. coli, Klebsiella or Pseudomonas
o Symptoms include pain, jaundice and fever (Charcot’s triad)
o Requires surgical correction or it is fatal.
o Treatment
 IV fluids and borad spectrum antibiotics
 Pt should be NPO
 If mild, surgery may be avoided
 Medical therapy can be complimentary to surgery
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o Diagnosis
 CBC shows leukocytosis
 LFTs show hyperbilirubinemia and increased alkaline phosphatase
levels
 CRP and ESR are elevated
o Imaging
 Ultrasound is helpful in early diagnosis however CT or MRI may be
needed.
 Endoscopic retrograde cholangiopancreatography (ERCP) is both
diagnostic and therapeutic
Lecture 27-Benign Pancreatic Tumors and Pancreatic Cancer
 Periampullary Cancers-group of similar tumors with similar presentation,
preoperative assessment and similar treatment
o Pancreatic Adenocarcinoma, Cholangiocarcinoma, Primary Ampulla
Adenocarcinoma, and Duodenal adenocarcinoma
 10th most commonly diagnosed cancer, and #4 cause of cancer death
 Risk Factors
 Presents in elderly population
 Smoking, alcoholism and diabetes are increased risk
 Chronic pancreatitis
 Inherited cancer syndromes
 Presentation
 Most common presentation is painless jaundice from
extrahepatic biliary obstruction
 Abdominal or back pain
 Weight loss
 Other symptoms include itching, early satiety, GI bleeding and
malaise
 Evidence of metastatic disease
 New onset diabetes
 Courvoisier sign-non-tender, palpable gallbladder. Associated
with biliary obstruction
 Laboratory Studies
 CA 19-9
o Serum tumor marker
o Elevation is associated with pancrease cancer
o Level may correlate to T & N stage
 Bilirubin
o Elevated conjugated bilirubin due to biliary duct
obstruction
 Alkaline Phosphatase
o Elevated higher than the other liver enzymes.
 Imaging and Peroperative Staging
 Important things to visualize
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o Pancreatic mass
o Peritoneal or hepatic metastases
o Patency and invasion of the SMV or Portal vein
 CT & MRI-both can be used to visualize tumors.
o Pancreas protocol CT involves narrow cuts through the
pancreas during arterial and venous contrast phases
with concurrent imaging of the remainder of the
abd/pelvis.
 Good at determining resectability
 Endoscopic ultrasound is very operator dependent but can
image relationship to visceral vessels
 ERCP
o Diagnostically difficult to differentiate between benign
and malignant tumors, able to directly visualize
ampullary or duodenal tumors.
o Can be used therapeutically for stenting if tumor is
unresectable or pt cannot have resection immediately.
 PET-CT-Incompletely defined, able to visualize mets.
 Laparoscopy-useful prior to resection for detecting occult
metastasis
Resectability
 Resectable-no encasement of celiac or SMA, patent SMV and
PV, no extrapancreatic disease
 Unresectable-Encasement of SMA or celiac axis or
extrapancreatic disease
Surgical Treatment
 Whipple procedure-pancreaticoduodenectomy
o Includes removing head of pancreas, distal stomach,
and proximal duodenum.
o Takes at least 4-6 hrs to perform, major surgery!
 Best chance for cure is R0 surgical resection (negative
microscopic margins)
 Outcome
o Mortality is 1-4%
o Morbidity is 30-40%
o Pancreatic Fistula
 Leaking of pancreatic fluids, which can digest
surrounding organs.
o Delayed Gastric Emptying
 Inability to eat or take tube feedings after 10
days postop
Adjuvant Therapy
 Chemotherapy or chemotherapy followed by chemoradiation
postop
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30% of pts do not receive treatment due to inability to
withstand therapy.
 Neoadjuvant Therapy-administer chemo and XRT prior to surgery
 High local recurrence rates
 High rates of incomplete adjuvant therapy
 Improves chance of R0 resection
 Borderline resectable tumors
 Selection of favorable biology
Cystic Neoplasms
o Serous Cystadenoma
 1/3 of cystic neoplasms of pancreas
 Occur throughout the gland
 Symptoms from mass effect, they compress due to size
 Benign, true epithelium
 Do NOT communicate with pancreatic duct
 Fluid Analysis
 Serous
 Low CEA and low mucin
 Natural History-growth is 0.5-2cm/year
 If the pt is asymptomatic then they can be observed, completely
benign with no risk of cancer
 Appears honeycombed or has a central scar seen on CT.
o Mucinous Cystadenoma
 ¼ of cystic neoplasms
 Occurs predominantly in body and tail of pancreas
 Does NOT communicate with pancreatic duct
 Large single, or multioculated cyst
 Fluid Analysis
 String like mucin with elevated CEA levels
 Significant risk of developing cancer, up to 50%
 Symptoms are very similar to serous cystadenoma
 Surgical resection is indicated due to risk of cancer
 Often confused with pseudocyst on imaging, but is a true cyst because
of epithelial lining.
 Lobulations seen on CT.
o IPMN (intraductal papillary mucinous neoplasm)
 Communicate with the pancreatic duct, must differentiate between
association with branch duct or main duct.
 Visualized with MRCP
 Fluid is high in amylase and CEA
 High rate of becoming neoplasm, more common in main duct variety.
 Becomes either colloid adenocarcinoma or tubular
adenocarcinoma.
 Up to 60% are asymptomatic
Symptoms include pancreatitis and/or exocrine insufficiency with
bloating, steatorrhea, weight loss or malnutrition.
 Up to 1/3 may have associated GI malignancy
 Imaging
 MRCP is more accurate for determining duct involvement
 Can be visualized with CT
 ERCP is good for seeing main duct involvement, but lessens in
distal pancreas
 PET-CT may indicate progression to malignancy.
 Surgical Resection is offered to all patients
Neuroendocrine Tumors
o Very, very rare tumors!!
o Insulinoma
 Most common NET
 Whipple’s triad: hypoglycemia, neuroglycopenic symptoms (fatigue,
confusion, blurry vision, weakness, seizure) and relief with glucose
administration.
 Preferred diagnosis is supervised fast with insulin level, pro-insulin, cpeptide and BGL checks every 6 hrs.
 Evenly distributed throughout pancreas.
 Treatment is surgical resection or enucleation
o VIPoma
 Vasoactive intestinal peptide
 WDHA or Verner Morrison Syndrome
 Watery diarrhea
 Hypokalemia
 Achlorhydria
 Usually found in pancreas or duodenum, usually >3 cm
 Somatostatin analogs (octreotide) can be used to treat and control
symptoms.
 Somatostatin can also be tagged and studied with a nuclear medicine
study to see distribution of tumor
o Glucagonoma
 Characterized by necrolytic migratory erythema-scaly rash affection
pretibial, perioral, and intertriginous areas!
 Found in tail of pancreas
 Symptoms include rash, diabetes, hypoaminoacidemia, weight loss
and acacheixia
 Highly malignant
 Often advanced at time of diagnosis
 High DVT and PE risk
o Ectopic hormone secreting tumors
o Somatostatinoma
 Somatostatin shuts off secretion of other GI hormones
 Diagnosed with serum fasting somatostatin assy


Associated with Von Recklinghausen Disease
Symptoms include cholelithiasis, steatorrhea, DM and
Hypochlorhydria
o Surgical resection is the best treatment, either complete resection or
debulking.


Lecture 28-Fluid Replacement Therapy in Adults and Children
 Pediatric Fluid and Electrolyte Management
o Water Content
 Water is largest constituent of the human body
 Relative water volume in the body changes with age:
 TBW Fetus-85%
 TBW newborn-75%
 TBW Adult 55-60%
 TBW Elderly 50%
 Water found in extracellular and intracellular space, cell membrane
separates these spaces and plays critical role in fluid and electrolyte
physiology
 Extracellular fluid:
o Predominates early in fetal life
o Equivalent to intracellular at birth
o Postnatal diuresis causes further reduction
 Intacellular fluid:
o Rises with cellular proliferation
 Blood Volume
 Fetus-90 ml/kg
 Toddlers-80ml/kg
 School aged-75ml/kg
 Adolescents-65ml/kg
 ECF vs ICF: baseline Differences
Plasma Osmolality = (Na x 2) + (Glu/18) + (BUN/2.8)
 Normal osmolality is 280-300 mOsm/kg
o Functional Differences between Children and Adults
 1. Increased fluid flux relative to size
 2. Greater surface area relative to size  increased insensible water
losses

o
o
o
o
 3. Increased metabolic rate up to 2 yrs
 4. Immature kidney function (0-2 yrs)
Kidney Function in the Infant (0-2 yrs)
 Decreased renal blood flow
 Increased renovascular resistance
 Decreased concentrating capacity
 Decreased tubular sensitivity to ADH
 Sodium retention
 Term infant conserves sodium effectively, less effective sodium
excretion
 Pre-term infant-‘salt waster,’ unable to conserve
sodiumhighly susceptible to changes in intravascular and
extravascular volume
 FEna: fractional excretion of sodium
o FENA= (UNa)(PCr)/(UCr)(PNa)
o Determines if renal tubular function indicates sodium
resorption.
o Less than 1% indicates that sodium retention and
suggests prerenal cause due to renal hypoperfusion
(hypovolemia, CHF)
o Greater than 3% implies poor sodium retention and
suggest an intraparenchymal cause
Fluid Requirements
 Requires understanding of:
 Preexisting fluid imbalance (dehydration)
 Maintenance requirements
 Ongoing losses
 Goals
 Reversal of symptoms and signs of dehydration
 Correction of electrolyte or acid-base abnormalities
 Normalization of urine output
Normal Urine Output
 No ‘normal’ urine output for neonates
 Ideal output estimated by measuring serum osmolar load and
calculating amount of urine necessary to clear this load if urine
is maintained at an isotonic level of 280mOsm/dL
 General Rules of Thumb
 Preterm infants 3-4mL/kg/hr
 Neonates and infants 2mL/kg/hr
 Toddlers and school-age children: 1mL/kg/hr
 Adults: 0.5mL/kg/hr
 Elderly: 0.25 mL/kg/hr
Remember than neonates and young children are very sensitive to small
changes in body chemistry and do not have mechanisms to compensate for
rapid changes in fluid and electrolyte flux!
o Fluid Replacement Strategies
 Maintenance Requirements
 Replaces the ongoing losses of water and electrolytes via
normal physiologic processes
o Excretion-urine and stool
o Evaporative-transepithelial (fever, radiant warmers,
phototherapy, premature infants) and respiration
(tachypnea and mechanical ventilation)
o Metabolic-1ml/cal metabolized/day at rest
 Delivered at constant rate over 24 hrs
 Holliday-Segar Method
o Based on weight:
o 0-10 kg receives 100ml/kg/day
o 11-20kg receives 1,000ml + 50ml/kg over 10kg
o >20kg receives 1500ml + 20ml/kg over 20kg
 4-2-1 Rule
o 0-10kg receives 4ml/kg/hr
o 11-20kg receives 2ml/kg/hr
o >20kg receives 1ml/kg/hr
 Electrolyte Requirements-replenish losses based on baseline
caloric expenditures
o Na+ is 3mEq/kg/day
o K+ is 2mEq/kg/day
o Glucose requirements are based on individual pt, must
provide sufficient support to meet needs of glucoseobligate tissues
 Preexisting Fluid Imbalance
 Replaces water and electrolytes lost during disturbance in
normal processes (dehydration)
 Stable pts: half of calculated volume usually replaced in 1st 8
hrs, the other half over next 16 hrs
 Unstable pts: Isotonic crystalloid boluses initially in all pts,
blood next in trauma pts, other therapies based upon disease
process
 Extravascular Fluid Imbalances (mild-mod dehydration)
characterized by:
o Poor skin turgor
o Recessed eyes
o Sunken or soft fontanel
o Dry mucous membranes
o Absence of tears
o Orthostatic hypotension/tachycardia
 Intravascular Fluid Imbalances (severe dehydration)
characterized by:
o Resting tachycardia



o Resting hypotension
o Oliguria-is urine output appropriate
o Delayed cap refill
o Reduced extremity temperature
o Diminished peripheral pulses
o Altered mental status
Types of Fluid Loss
o Isonatremic problems
 Fluid lost has similar sodium concentration as
serum and/or kidney is able to compensate
 Most common!!
o Hyponatremic problems
 Fluid lost has greater sodium concentration than
serum, kidney unable to compensate and results
in serum sodium levels
o Hypernatremic
 Fluid lost has lower sodium concentration than
serum, results in sodium levels higher than
normal range
Estimating Fluid Deficit
o Fluid deficit (L) = (pre-illness weight (kg) – illness
weight (kg)) x 1000 mL/kg
o Estimating Na+ deficit
 Na+ deficit = ECF deficit (L) x 140 mEq/L
o Estimating K+ deficit
 K+ deficit = ICF deficit (L) x 150 mEq/L
o ECF Deficit = 0.6 x total fluid deficit
o ICF Deficit = 0.4 x total fluid deficit
Route of Administration
o Enteral (by mouth) recommended in pts with mildmoderate dehydration. Safer than parenteral when
appropriate, but inadequate in pts with sign/symptoms
of intravascular volume depletion.
 Gatorade is a good option
 WHO’s oral rehydration solution-right balance of
glucose and sodium to replenish
o Parenteral recommended with signs of intravascular
volume depletion in severe dehydration!
o
Resuscitation
o Stable medical hypovolemia
 Isotonic crystalloid (NS) in 10-20mL/kg in
judicious boluses
o Unstable medical hypovolemia (sever dehydration)
 Isotonic crystalloid in 10-20 mL/kg in serial
boluses
o Unstable traumatic hypovolemia
 Isotonic crystalloid20 mL/kg bolus x2
 Packed red blood cells  10 mL/kg initially
o Boluses are followed by careful assessment of response
to therapy!
 Ongoing Losses
 Due to body secretions
o GI losses-NG suction, enterostomal, diarrhea,
pancreatic/biliary.
 Different electrolyte profiles from various levels
of the GI tract. Most secretions are replaced mL
per mL of similar composition of fluid to that
lost.
o Lymph-chylous ascites or chylothorax
 Replacement usually requires addition of
albumin to replace lost serum oncotic pressure
rd
o 3 space-sequestration of extracellular fluids in
interstitial space, result of surgical, inflammatory, and
traumatic injury
 Replacement best administered by intermittent
bolus, exact rate of fluid loss is not measurable.
 Judge adequacy of resuscitation by physiologic
response
Fluid and Electrolyte Replacement in Adults
o Fluid Replacement Strategies
 Maintenance Requirements-fluid lost in normal physiologic processes
 Preexisting fluid Imbalance
 Ongoing Losses
o Clinical Manifestations


Physical exam in general is not sensitive or specific because of the
associated comorbidities in adults
 Physical findings
 Decreased skin turgor
 Dry skin, particularly axilla
 Dry mucous membrane
 Low arterial blood pressure
 Orthostatic hypotesion
 Tachycardia
 Narrowed pulse pressure
 Lab Values
 Renal
o BUN/Cr ration normally around 10
o Increased above 20 suggests prerenal state
o Rise in BUN without rise in Cr called prerenal azotemia
o Urine more concentrated
o FENa to help determine problem
 Hematologic
o Hgb/Hct increased with dehydration secondary to
hemoconcentration
o Most common cause of Na and H20 excretion are administration of diuretics
and nonreabsorbed solutes in urine.

Lecture 29-Endocrine Autoimmune Diseases (Type 1 Diabetes)
 Type 1 Diabetes symptoms are caused by hyperglycemia, by loss of insulin
production.
 Loss of Insulin-Producing Beta cells
o Seems to be a T-cell mediated event that results in selective destruction of
insulin-producing cells.
o There are insulin-specific T cells found in circulation.
 History of Autoimmune Diabetes
o Begins with genetic susceptibility
o There are also thought to be environmental factors involved.
o Immune cells become activated and begin to destroy beta cells, these are T
cells.
o Autoantibodies are also being produced that recognize insulin. These are
produced early on.
o Oscillation in loss of beta cells due to some replacement by new beta cells,
but overall loss in beta cells.
o Eventually a threshold level is reached and there is not enough insulin being
produced to regulate glucose levels and symptoms begin.
 Mechanism of Beta Cell Destruction
o T cells specific for beta cells destroy the beta cells.
 Central and Peripheral Tolerance Mechanisms
o Central Tolerance is focused mainly on T and B cells, purpose is to eliminate
self-reactive cells in the generative organs.
 B cells
 In the bone marrow, stromal cells present self antigens to
developing B cells.
 If the BCR (IgM) recognizes the antigen being presented by the
stromal cells, and strong binding occurs then apoptosis is
induced.
 Stromal cells can release a soluble self-antigen. If strong
binding to this antigen occurs without crosslinking of BCR, it
results in B cell anergy, which means that B cells cannot
proliferate and reduces expression of BCR.
 No recognition of self-antigen results in survival of the B cell.
 Some B cells that recognize self-antigens can undergo receptor
editing to change BCR recognition. If the new BCR still
recognizes self-antigen then tolerance is induced with
apoptosis or anergy….if it does not recognize self-antigen then
it survives and enters circulation.
 Naïve mature B cells reside in the follicles of lymph nodes,
however anergic B cells cannot enter the follicle and remains in
the T cell zone of the lymph node.
 T cells
 The only antigens that are in the thymus are self-antigens, all
others are removed by macrophages in the epithelium of the
thymus. These macs also destroy the remnants of T cells that
are lysed.
 MTEC cells produce self-antigen for display to T cells
 Dendritic cells in the thymus present the self-antigen to T cells.
 Negative Selection
o Strong or no binding of TCR results in apoptosis
o Weak MHC-pep-TCR binding results in survival of T cell.
o Naïve mature T cells reside in T cell zones in the lymph
node/spleen.
 Central tolerance removes a large portion of potentially self-reactive
lymphocytes it is NOT foolproof.
o Peripheral Tolerance Mechanisms-deficiencies in any of these mechanisms
can result in an overt inflammatory response.
 Within the 3 signals for T cell activation:
 If only signal one occurs
o With no costimulation by an immature antigenpresenting cell (has not been stimulated by a TLR ligand
or an innate cytokine) then anergy results and the selfreactive T cell will become inactivated.
o This would occur at the spleen/lymph node level.
 Inhibition by CTLA-4

o With an infection present a mature APC can activate a T
cell at the spleen/lymph node level. Once in the tissue
though, the activated T cell will begin to express CTLA4.
o While in the tissue this T cell will encounter other APCs
and instead of the normal costimulation by the binding
of CD28, the CTLA-4 molecule will outcompete CD29
and bind to CD80/CD86 on the APC.
o This produces an inhibitory signal to the activated T cell
and turns itself off.
o CTLA-4 is produced about 72 hrs after initial T cell
activation and is one of the control mechanisms for
effector T cell populations
 Apoptosis by Fas-FasL
o Comes up slowly like CTLA-4 and limits expansion of
immune response. Fas binding to Fas L results in
apoptosis. Binds to Fas Ligand on other activated T
cells.
o Limits expansion of the immune response.
 Immunosuppression
 Controlled by Treg system. Tregs are made in the Thymus and
can turn off APCs and activated T cells through contact
inhibition.
 Tregs also produce soluble cytokines like IL-10 and TGF-beta
to turn off APCs, Tcells and B cells.
 All Tregs have a TCR for self-antigen, so when a self-reactive T
cell is activated a Treg is also activated in the lymph node and
often results in inactivation of the T cell before it leaves the
lymph node.
 Level of action is at level of lymph node. CTLA-4 and Fas-FasL
is a back up of the Treg system.
T Cells Cause Beta Cell Death
o T cells and B cells must escape central tolerance to gain access to draining
lymph node of pancreas.
 Occurs due to genetics:
 HLA connection, specifically MHC class II affecting CD4 T cells.
 HLA defect results in an incomplete MHC residue when binding
to T cell in the thymus. This allows self-reactive T cells to
survive due to a lack of strong binding.
o T cells must also be activated by APC expressing beta cell antigen with all 3
signals
 APCs present beta cell antigen to T cell, and microbes can provide
signals 2 & 3 to activate T cell.
 Microbes can provide antigens (Molecular mimicry) which results in
an antigen similar to beta cells, thereby activating self-reactive T Cells.


It is thought that this occurs with Coxsackievirus in type 1
diabetes.
o T cells must overcome peripheral tolerance to acquire the capacity to
damage/kill beta cells
 There is a noted deficiency in CTLA-4 expression or signaling, which
allows T cell proliferation, which results in CTLA-4 not being
expressed and the APCs continue to provide the 3 signals for
activation in the tissues.
 Deficiencies in T reg cell numbers or function due to a loss of IL-2,
which stimulates T reg cell development in the thymus. May also have
an issue with FoxP3 gene resulting in reduced function.
 Normally T reg cells bind to APC, which causes a decreased
production in CD80/CD86, IL-12 and increased IL-10. The
APCs then lose ability to induce effector T cells. Tregs also shut
down effector T cells completely
 Without T regs shutting APCs down then effector T cells are
allowed to proliferate.
Anergic Self-Reactive B Cell Peripheral Control
o Follicular Exclusion
 The anergic B cells cannot enter follicular zone because they lack
CXCR5 signal.
 Anergic B cells may encounter activated T cells that express Fas-L and
can induce apoptosis of the anergic B cells by binding to Fas on the
surface of the cell.
o Activated self-reactive CD4+ T Cells can rescue anergic B cells through CD40
ligand signaling.
 CD40 Ligand signaling reverses anergy and induces CXCR5 Expression
for migration into follicle. BCR also begins to be expressed.
 Once back in the follicle the B cell develops into the centroblast. Once
the BCR interacts with the follicular dendritic cell that is presenting its
antigen, and receives a survival signal.
 A helper T cell also interacts and signals B cell to begin antibody
production, which results in plasma and memory B cells being
produced.
 Ultimately results in autoantibody production.
o Autoantibody production does not cause IDDM type 1, but can cause other
autoimmune diseases.