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SELECTED GASTROINTESTINAL (GI) LABORATORY DIAGNOSTICS: serum studies (LFTs – chemistries, serologies, immune) hematology (CBC, coagulation profiles) biopsies (histology, special stains) stool studiess

o cultures & sensitivity studies o stool heme (guiaic)

direct endoscopic & video capsule endoscopy & virtual endoscopy imaging

o radiographic (plain and contrast Xrays) o nuclear medicine scans o ultrasound

LABORATORY OVERVIEW: OVERVIEW of Liver Function Tests (LFTs):

Hepatitis – obstructive, infectious (e.g. HBV, HCV) Cirrhosis – toxic (e.g. alcohol), hereditary (biliary sclerosis) Neoplasm (cancer) Acute hepatitis may progress to chronic active hepatitis, high mortality Complications include ascites, loss of synthetic function (clotting factors, albumin, bile

salts) and biotransformation function (toxicity) Liver Panel typically contains at minimum the following tests:

albumin total bilirubin (direct, indirect) liver enzymes (ALP, AST, ALT)

Comprehensive Metabolic Panel (CMP) contains liver tests plus other tests: albumin total bilirubin (direct, indirect) calcium liver enzymes (ALP, AST, ALT, GGT) total protein electrolytes (Cl-, Na+, K+), Renal (BUN/Cr), glucose

OVERVIEW of Special GI laboratory tests: ammonia (liver failure) hepatitis antigen and antibodies (infectious viral hepatitis) alpha-feto protein (hepatoma) amylase, lipase and trypsinogen (pancreatitis) special antibody tests (e.g. celiac disease) stool tests (methylene blue, cultures, guiaic, other staining) Helicobacter pylori testing (ulcer patients) NALFD fibrosis score (for NASH/NALFD) Child-Pugh Score (residual liver function in cirrhosis patients)

Example: Endoscopic view of stomach with rugae

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Liver Function Tests (LFTs) in detail: Measuring the following liver functions:

o Synthetic (makes globulins, albumin, clotting factors) o Detoxification (drugs, endogenous hormones & chemicals) o Makes bile salts o LFTs determine if the liver is damaged or functionally impaired

Transaminase enzymes: o Alanine aminotransferase (ALT, older name SGPT)

aminotransferases mostly elevated in liver cell (hepatocellular) disease and so an excellent test for detecting hepatitis

Increase in hepatitis, cirrhosis, liver mets, obstructive jaundice, infectious mono, hepatic congestion (CHF), pancreatitis, renal disease, EtOH ingestion.

Decrease in Pyridoxine (Vitamin B6) deficiency. Mostly liver in most presentations, although other visceral organs.

o Aspartate aminotransferase (AST, older name SGOT) aminotransferases mostly elevated in liver cell (hepatocellular) disease note that fractions of this substance produced by both heart & liver, as well as

other visceral organs. However, usually primarily considered an LFT (if any question as to origin of this

enzyme, do isoenzyme fractionation) Increased in: MI (late in course of MI), CHF, myocarditis, pericarditis, myositis,

muscular dystrophy, trauma, hepatic disease, pancreatitis, renal infarct, eclampsia/toxemia, neoplasia, cerebral damage, seizures, hemolysis, EtOH.

Decrease in pyridoxine (Vitamin B6) deficiency, terminal liver disease. o Alkaline Phosphatase (ALP)

elevated mostly from intrahepatic obstructive disease examples: drug effects, biliary cirrhosis, any bile duct blockage remember (review) that this enzymes comes from many sources many need to do isoenzyme fractionation to determine organ system

o Gamma-glutamyl transferase (GGT)(older name GGTP): increased: often due to drugs (alcohol, phenytoin, phenobarbital) decreased: with some drugs (e.g. oral contraceptives)

o Lactate dehydrogenase (LDH): may be elevated in liver disease mostly used in cardiac testing – this enzyme has 5 isoforms and fractionation is

needed to determine body site LDH-1 (heart muscle, RBC); LDH-2 (WBC); LDH-3 (lung); LDH-4 (kidney,

placenta, pancreas); LDH-5 (liver, skeletal muscle).

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Serum Total Protein & Albumin: either albumin or globulins

o We are not considering the lipoproteins here (HDL-C, LDL-C, etc.) o Lab gives you a Total Protein (TP) value & an Albumin value

subtract albumin value from the TP to get the remaining globulin portion o Albumin (major fraction) made in the liver o Immunoglobulins (gamma globulins, Ig) made by plasma cells (activated B-

lymphocytes) o Other globulins are made by the liver (e.g. sex-binding globulin, SBG; clotting factors) o Normally, globulin < albumin

Pathological: globulin portion > albumin decreased albumin OR increased globulin first thing to do – evaluate which fraction is GREATEST

o Total Protein (TP): very nonspecific Increased (could be globulin): multiple myeloma, myxedema, lupus,

sarcoidosis, DI, dehydration (volume contraction), collagen disease. Decreased (usually due to reduced albumin): burns (transudation protein

loss), cirrhosis, malnutrition, nephrosis, malabsorption, overhydration (dilutional), GI protein loss (inflammatory bowel).

o Albumin: made in liver. Increase in volume contracted states (dehydration & DI) Decrease in overhydration (water intoxication), malnutrition, malabsorption,

nephrosis, hepatic failure, burns, multiple myeloma, metastatic carcinoma. o Globulin:

Immunoglobulins (gamma-globulins): made in plasma cells (activated B-lymphocytes).

Other (liver) globulins: clotting factors, carrier proteins (TBG, SBG, etc.) o SPEP – Serum Protein Electrophoresis: review this material, remember we can further

differentiate the proteins by this procedure (protein broken down into component parts) – might order this test if abnormal protein component on CMP

Total Bilirubin AND direct bilirubin OR indirect bilirubin:

o Bilirubin: composed of indirect (unconjugated) & direct (conjugated) bilirubin Lab gives you a total bilirubin and also a value for direct or indirect Subtract the direct/indirect from the total to determine all three values

o Discussion of bilirubin in the jaundice section o Need to understand WHAT portion of the total bilirubin is elevated o Is it direct? indirect? o Is there urinary bilirubin? urobilinogen? o Answers to these questions point at the etiology of the elevated bilirubin

Increase in hepatic disease, obstructive jaundice, hemolytic anemia, pulmonary infarct, Gilbert's disease, Dubin-Johnson syndrome, neonatal jaundice.

Secondary events in overt liver failure: altered mental status from elevated ammonia Symptoms: nausea, anorexia & fatigue, encephalopathy (sleepy, confused), coma Findings: jaundice and brownish urine (bilirubinemia), bleeding (liver not making coagulation

factors), asterixis (hand tremor), hyperammonemia

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SPECIAL GI lab tests in detail: Alpha-feto-protein (AFP): prenatal screening test for fetal abnormalities such as Down Syndrome (screening test for

fetal spinal cord defects (test maternal serum prenatally, then confirmed with amniotic fluid testing), but it is also for GI

increase in hepatoma, testicular tumor, chronic hepatitis B. Amylase & Lipase: enzymes released by damaged tissues or inflamed tissues Testing for pancreatitis, but also found elevated in salpingitis (PID), GI obstruction Always order these two tests together if you want to confirm pancreatitis, since just amylase

elevation alone can be due to multiple other abdominal/pelvic organ inflammation Lipase: more specific test for pancreatitis.

o Always order both the amylase and the lipase -- try to differentiate from PID (salpingitis) and pancreatitis. Lipase is also increased also in macroamylasemia

Amylase: o Increase: pancreatitis, GI obstruction, mesenteric thrombosis/infarction,

parotitis/mumps, renal disease, ruptured tubal pregnancy, PID (salpingitis), lung Ca++, acute EtOHism, postop abdominal surgery.

o Decrease: in significant pancreatic destruction. Note that point-of-care (bedside) urine trypsinogen (UT) testing compares favorably with

these lab tests for pancreatitis, and may be used more frequently in the future. Magnesium (Mg+2): Renal function test and cardiac testing (often decreased in acute MI) However, decrease also seen in diarrhea and malabsorption (stool losses)

o Increase: renal disease, excess Mg (IV -- toxemia, or PO -- MI & EtOHism). o Decrease: diarrhea, malabsorption, renal tubular acidosis, acute tubular necrosis

(kidney), chronic glomerulonephritis, drugs (diuretics, antibiotics), EtOHism, aldosteronism, hyperthyroidism, hypercalcemia, uncontrolled DM, acute myocardial infarction (MI)

TENDS TO FOLLOW THE OTHER DIVALENT CATION (Ca+2) & the POTASSIUM (K+). Remember: always order Calcium & Potassium levels if Mg dysregulation is suspected

Celiac Disease (GI non-tropical sprue):

If positive, definitive diagnosis is with a jejunal biopsy on endoscopy Pathology: tissue transglutaminase is the autoantigen that elicits endomysial antibodies Lab: immunochromatographic assay detects both IgA and IgG antibodies to

transglutaminase in human serum or plasma. Stool tests:

methylene blue culture and parasite (ova & parasite) evaluation Clostridium dificile test Testing for occult blood along with DRE (digital rectal exam) in colon cancer screening;

most providers perform in all adults > 50 yo annually and earlier in high risk

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Serum Ammonia (elevated): elevation seen in liver failure, many different syndromes Physiology & Pathophysiology:

o normally, ammonia comes from the breakdown of protein in the GI tract – this is done by intestinal bacteria

o there is entero-hepatic circulation, which absorbs the ammonia from the gut to the liver via the hepatic portal vein, and the liver converts the ammonia to urea

o urea then is absorbed into the bloodstream, and excreted by the kidney via urine o if the liver is unable to convert ammonia to urea, levels of ammonia will rise in the

bloodstream, and indicate that there is a problem with the liver Reye Syndrome:

o This is encephalitis + liver failure. o Presentation is usually change of mental status (or coma) in a febrile child who may

have taken aspirin or even NSAIDs (rare) for the fever o Lab: serum ammonia levels are high, along with hypoglycemia. o Life saving administration of IV glucose immediately with suspicion of this illness. o Perform serum ammonia level in ALL children with change in mental status

NOTE that elevated ammonia levels also found in other liver failure conditions o Examples:

inborn errors of metabolism (such as urea cycle disorders) hepatitis with advanced liver damage (chronic active liver disease) cirrhosis – inflammation of the liver results in scarring – most likely etiology in

USA is alcohol abuse and chronic viral hepatitis (HBV, HCV), less commonly from drugs or hemochromatosis

Ammonia levels often obtained (along with LFTs, glucose) in any presentation of atraumatic altered mental status

Other reasons to order serum ammonia: o monitor high-calorie intravenous feedings o part of TPN (Total Parenteral Nutrition) management to insure liver function

Cobalt-albumin binding assay (CABA): Test is elevated in bowel ischemia (mesenteric ischemia) Often difficult to evaluate now with existing tests, so this is an advance in clinical diagnostics Fecal calprotectin: Intracellular protein shed by neutrophils inside gut lumen in response to inflammation Negative test can exclude inflammatory GI process CPG for use of test (2013) from NICE: http://www.guideline.gov/content.aspx?id=48534 Special tests for NASH/NALFD: most common cause of abnormal LFTs in developed countries

LFT elevation is mildly raised alanine aminotransferase levels (ALT) ALT levels drop as hepatic fibrosis progresses – later stages may have normal ALT Other tests are the NASH FibroSURE uses 10 biomarkers & the ELF (enhanced liver

fibrosis score) uses 3 biomarkers – both then use an algorithm to determine if steatosis is present

The NALFD Fibrosis score is easily calculated: http://www.nafldscore.com/ (from age, AST, ALT, platelet count, albumin level, and if prediabetes/diabetes present)

Confirming diagnosis: Ultrasound and MRI and then a liver biopsy

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Evaluation for liver transplant in hepatic cirrhosis: liver transplant scoring:

o MELD score online calculator – prognosis: http://www.hepatitisc.uw.edu/page/clinical-calculators/meld

o Child-Pugh score for cirrhosis mortality and liver transplant decision making: https://www.mdcalc.com/child-pugh-score-cirrhosis-mortality/

Child-Pugh Score is used to assess residual liver function and injury severity in cirrhosis patients.

CHILD-PUGH SCORE

Criteria 1 point 2 points 3 points

Total serum bilirubin (mg/dL)

<2 2−3 >3

Serum albumin (g/dL) >3.5 2.8−3.5 <2.8

INR <1.70 1.71−2.20 >2.20

Ascites No ascites Ascites controlled Ascites not controlled

Encephalopathy No encephalopathy Encephalopathy controlled

Encephalopathy not controlled

INTERPRETATION OF CHILD-PUGH SCORES

Class A Class B Class C

Points 5−6 7−9 10−15

Life expectancy 15−20 years Candidate for liver transplant

1−3 years

Perioperative mortality 10% 30% 82%

3-Month Mortality Based on MELD Scores

The estimated 3-month mortality is based on the MELD score highlighted in yellow above.

MELD Score Mortality Probability

40 71.3% mortality

30-39 52.6% mortality

20-29 19.6% mortality

10-19 6.0% mortality

9 or less 1.9% mortality

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Hepatic encephalopathy:

somnolence, confusion, coma acute liver failure causes the brain to swell due to ammonia crossing the BBB evaluate using West Haven OR the “FOUR” score

Table below from: Widjicks, E.F.M. (2016) Hepatic Encephalopathy. N Eng J Med, 375(17), 1660-1670. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMra1600561

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EVALUATION OF JAUNDICE: (jaune is French for “yellow”) usually also pruritic (itchy) icterus is yellowing of skin, mucous membranes, sclera due to hyperbilirubinemia usually, bilirubin is > 2-3 mg/dL to cause visible jaundice Bilirubin metabolism:

o RBC degraded in spleen (also in liver & bones) heme biliverdin o unconjugated bilirubin (insoluble) binds to albumin for transport ot liver o In liver, dissociates from albumin and liver enzymes conjugate the bilirubin (attach it to

glucuronate) (now it is water soluble) o Conjugated bilirubin stored in gall bladder, released during gall bladder contraction o Once in intestine converted by bacteria to urobilinogen

half excreted (becomes stercoblinin in intestine normal brown stool) half reabsorbed (entero-hepatic circulation) a little goes into the systemic bloodstream and is filtered/excreted by the kidneys

(urobilin causes the normal yellow urine) Laboratory:

o conjugated = direct o unconjugated = indirect

Clinically: o pre-hepatic (usually hemolytic): (usually hemolysis with excess RBC destruction)

examples: malaria, G6PD deficiency (genetic drug reactions), sickle cell crisis, transfusion reaction

can also be inborn errors (defects) in bilirubin metabolism usually an increase in indirect (unconjugated) bilirubin since there is so much

bilirubin created by the pre-hepatic process, that the conjugation systems of the liver are overwhelmed

o hepatic: Adults: hepatocellular damage – such as hepatitis, hepatotoxicity (drugs),

alcoholic hepatitis, primary biliary cirrhosis, Gilbert’s syndrome, metastatic cancer to liver

Infants: neonatal jaundice (immature liver) Usually see increase in total bilirubin (mostly unconjugated, indirect

bilirubin) o post-hepatic (obstructive):

cholestasis – bile cannot drain due to obstruction of the common bile duct (CBD) examples: gallstones, cancer of the head of the pancreas (obstructs bile duct –

think of “painless jaundice”), strictures of CBD, ductal cancer, pancreatitis, pancreatic pseudocyst

since bile can’t reach the intestine, stools are pale since bile can’t reach the intestine, direct bilirubin builds up and enters

bloostream, where it is cleared by the kidney into urine (remember, direct bilirubin is water soluble) and shows up on urine testing

therefore, usually see an increase in the direct (conjugated) bilirubin since the liver is able to conjute bilirubin normally, but it is unable to excrete it via biliary tree

A good little internet discussion with “instant feedback” mini-quiz online: http://www.rnceus.com/lf/lfbili.html

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Neonatal jaundice: (mostly a benign, self-limited) Pathophysiology:

o breakdown of fetal hemoglobin (shorter lifespan of fetal RBC, also relative erythrocytosis in newborn) combined with immature liver hyperbilirubinemia

o occurs from day 2 through day 8 in term birth, up to day 14 in premature birth o may be worsened by breast milk (some unknown factor increases entero-hepatic

circulation time, increasing reabsorption of bilirubin that has become “deconjugated” if it stays too long in the intestine)

o neonatal jaundice never occurs on day 1 of life (this is pathologic!!) o neonatal jaundice is unconjugated bilirubin (indirect) o any conjugated (direct) hyperbilirubinemia is pathologic!! o usually benign, unless level reaches so high as to cause kernicterus (CNS damage

due to neurotoxicity of unconjugated bilirubin) o if infant is anemic, appears ill, if jaundice persists more than 2 weeks, if jaundice

begins on day 1 or after day 3 of life consider other pathologic processes How to monitor:

o heelstick testing with blood to lab for total bilirubin o transcutaneous bilirubinometry (meter that checks skin jaundice and uses computer

to correlate with blood bilirubin levels) o danger of kernicterus at level of 20 mcg/dL in term infants (lower level in

premature) – phototherapy started, possibility of exchange transfusion Possible additional workup:

o blood type & Rh (mother & infant), direct Coombs, Hct & Hb o serum albumin, LFTs, ABGs to look for acidosis, TFTs o end-tidal CO2 breath test (ETCO) as a measure of bilirubin production o reticulocyte count, CBC & peripheral smear for RBC morphology o total, conjugated (direct) and unconjugated (indirect) bilirubin o reducing substance in urine to screen for galactosemia

Treatment: o Phototherapy (different types) converts bilirubin to harmless isomers o danger of kernicterus at level of 20 mcg/dL in term infants (lower level in

premature) – phototherapy started, possibility of exchange transfusion AAP Guidelines for Neonatal Jaundice:

o Main (2010) http://www.aafp.org/afp/2010/0815/p408.html o Update (2009) for infants 35 weeks gestation or greater:

https://www.med.unc.edu/ai/pedclerk/schedules/clerkship-at-moses-cone/readings-and-resources/supplemental-readings/newborn-issues/10-Hyperbilirubin%20for%20Newborns.pdf

For the layperson: https://www.healthychildren.org/English/ages-stages/baby/Pages/Jaundice.aspx and http://kidshealth.org/en/parents/jaundice.html

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The Bhutani Nomogram for neonatal jaundice: Online calculator: http://www.bilitool.org Phototherapy nomogram from AAP: http://pediatrics.aappublications.org/content/114/1/297/F3.large.jpg

When using this nomogram, remember that "risk" refers to the risk of a subsequent bilirubin level in that infant >95%ile for age. From: http://med.stanford.edu/newborns.html (MANY neonatal testing guidelines here)

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Bilirubin/Urobilinogen Pathology Summary: Pre-hepatic, such as hemolytic anemia: increased total bili and unconjugated (indirect) bilirubin liver is healthy, there is some other process causing the problem excretion of bilirubin to intestine creates more urobilinogen, urine may have more

urobilinogen Hepatic, such as any intrinsic liver disease (hepatitis, even heart failure): increase in total bilirubin (mostly unconjugated) (indirect) diseased liver is unable to reabsorb urobilinogen from the entero-hepatic circulation urobilinogen stays in the portal blood systemic blood kidneys urine urobilinogen Post-hepatic (obstructive): increased total bili & conjugated (direct) bilirubin conditions such as cholelithiasis, neoplasm urobilinogen amounts decrease, and urinary urobilinogen amounts decrease in urine bilirubin increases in urine (conjugated bilirubin into systemic bloodstream)

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EVALUATION OF HEPATITIS: elevated transaminases (LDH, ALP, AST, GGTP, AST) elevated bilirubin, mostly unconjugated (direct) (hepatocellular damage) viral hepatitis has an incubation period of 4-20+ weeks, then jaundice is seen this is a serologic diagnosis hepatitis panel includes antigen and antibody studes hepatitis viruses are A (HAV), B (HBV), C (HCV), D, E, G (delta) & Epstein-Barr (EBV)

SEROLOGIES in HBV:

o IgM = acute phase titers of immunoglobulin (recent exposure to virus) o IgG = convalescent phase titers of immunoglobulin (immune titers) o Surface Antigen in HBV (HBsAg) first detectable lab test in early hepatitis, converts to

negative when enter inactive (carrier) state o Envelope Antigen in HBV (HBeAg) is chronic active infection and highly contagious

state o Envelope Antibody (HBeAb IgM & IgG) predict resolution

SEROLOGIES in HCV: o Anti-HCV Antibody, present in 70% of those with symptoms; 90% at 3 months

SEROLOGIES in HAV: o Fecal HAV antigen in stool (2-6 weeks post exposure) o IgM acute infection (4 – 12 weeks post exposure) o IgG convalescent titer (present 4 weeks post exposure)

Chronic (active) HBV (no recovery): o remain surface antigen positive (HBsAG) and envelope antigen positive (HBeAg) o remain envelope antibody negative (HBeAb IgM & IgG) o LFTs elevated, viral load HBV DNA hybridization positive, albumin decreased o will need liver biopsy, at risk for complications of disease (bleeding, infection)

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CYSTIC FIBROSIS (CF): autosomal recessive, most common lethal genetic disease of Caucasions (1:2,500 live births) abnormal gene encodes multiple types of a protein "polypeptide cystic fibrosis transmembrane

regulator" (CFTR) that results in abnormal chloride channel transport (dysfunction of secretory epithelium)

Clinical: o mucosal surface dehydration o inspissated mucous plugs o abnormal cilia action o eventual airway and other luminal obstruction

Exocrine function disrupted – reduced GI enzymes & secretions o “cystic fibrosis of pancreas" was original name o pancreatic insufficiency with steatorrhea, malabsorption, vitamin deficiencies, intestinal

obstruction o eventual endocrine pancreas insufficiency (insulin deficient DM)

Pulmonary effects o mucus plugging o recurrent infection with ventilatory impairment

GU tract – infertility in both males and females At risk for:

o heat exhaustion o hypochloremic alkalosis due to salt/water metabolism dysfunction o vitamin deficiencies (fat soluble) o Caloric deficiencies

LABORATORY: sweat test & Delta F508 o Sweat test (quantitative pilocarpine iontophoresis)

stimulate sweat production using parasympathetic drug and move the drug into the skin using iontophoresis (electrical conduction)

sweat collected (need 50 mg minimum) and analyzed for Na+ and Cl+ Normal: sweat has < 60 meq/L sodium & chloride CF sweat: > 70 meq/L sodium & chloride all sweat tests must be repeated at least once for confirmation False positive tests due to many reasons (G6PD deficiency, hypothyroidism,

glycogen storage disease, adrenal insufficiency, malnutrition) Diagnosis: if using the sweat test, need two positive sweat tests AND positive

CXR or positive family history or exocrine pancreas insufficiency. Newer tests now becoming the standard.

o Delta F508 chromosome analysis to identify chromosome 7 mutation (70% of CF) and other

mutations (G551D) uses cheek epithelial cells

o Tag-It Cystic Fibrosis Kit Blood test to look for CTFR gene mutation

o Other: starch intolerance test electrolyes (BMP), KUB (abdominal Xray) showing dilated loops of small bowel CXR showing evidence of COPD

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GI ULCERS AND H. pylori: Bacterial infection with H. pylori – a CARCINOGEN: H. pylori infection raises risk of ulceration and BLEEDING – so a lot of the rationales of

testing recommendations is to PREVENT bleeding by treating H. pylori if found H. pylori is classified as a stomach carcinogen (gastric cancer) American College of Gastroenterology CPG 2007:

http://gi.org/clinical-guidelines/clinical-guidelines-sortable-list/ and http://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdf

Current opinion regarding H. pylori:

o The cause of most PUD (especially recurrent PUD) is this infection o a paradigm shift (way of thinking about something) – no longer do we consider the

“acid” as the etiology but instead focus on the infection o Ulceration risk is higher in those infected with H. pylori, especially if they are on NSAID

therapy or taking PPIs (proton pump inhibitors) o longterm infection also confers increased stomach cancer risk

When to test for H. Pylori and treat to eradication:

o All patients with active peptic ulcer disease (PUD) or a past history of PUD (unless previous cure of H. pylori infection has been documented)

o Those with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma o Those with a history of endoscopic resection of early gastric cancer (EGC) o Prior to long-term treatment for the infection o Prior to starting long-term NSAID therapy, including low-dose aspirin o Any patients with GERD symptoms that do not respond to routine, time-limited therapy o Those with persistent breakthrough symptoms o Those who are being committed to long-term PPI therapy o ALSO those with severe gastric atrophy, corpus-predominant gastritis, or intestinal

metaplasia o Those with pernicious anemia patient with achlorhydric gastritis of long standing is

especially prone to this complication o Those with iron-deficiency anemia o Those with idiopathic thrombocytopenic purpura (ITP)

Those not at risk: duodenal ulcers are not usually at risk

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Non-endoscopic testing for H. pylori: Antibody blood test is a serology test that can leave a “serologic scar” (once positive, may

remain always positive) – thus if you get a positive blood test, ASK the patient if they’ve been treated already in the past

Urea breath test – no serologic scar – if positive you have active disease – this is the “gold standard” for outpatient noninvasive testing

o patient drinks a urea solution, H. pylori breaks down the urea, carbon is exhaled (carbon is labeled)

Fecal antigen test (the Helicobacter pylori stool antigen, HpSA test) is accurate, but to determine if infection eradicated, must wait 6-8 weeks after antibiotic treatment to test

Endoscopic testing for H. pylori: histology from biopsy (tissue tests) from endoscopy include the rapid urease test, histology,

and culture rapid urease testing culture PCR

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Testing for acid secretion: looking for acid reflux to diagnose GER (gastroesophageal reflux disease, also called GERD) continuous 24-hour ambulatory probe is done mostly in children patient has nasogastric tube placed connected to probe which records the pH patient can push buttons on the outside unit corresponding with activity (eating, sleeping,etc.)

similar to a Holter monitor for cardiac recording an upper GI (barium swallow) can also see reflux, but only evaluates for reflux over a few

minutes under fluoroscopy while the study is being done a negative pH probe in a child who is symptomatic might need to be repeated this test is highly specific – a positive result rules in GER but that means that a negative test DOESN’T rule it out Testing for neoplasm in peptic ulcer disease: done by endoscopy tissue biopsy of suspicious sites is sent to pathology for histology evaluation could also do gastric washes and cytology 2013 American College of Gastroenterology GERD CPG: http://d2j7fjepcxuj0a.cloudfront.net/wp-content/uploads/2013/10/ACG_Guideline_GERD_March_2013_plus_corrigendum.pdf

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CLINICAL BIOMARKERS IN ALCOHOL EXPOSURE: Many serum tests for alcoholism (biomarkers for alcohol use disorder, AUD) A free publication can be requested from SAMHSA:

http://store.samhsa.gov/shin/content/SMA12-4686/SMA12-4686.pdf Note the National Center for Alcohol and Drug Information (NCADI) is part of the Substance

Abuse and Mental Health Services Administration (SAMSHA) http://www.samhsa.gov/ From SAMHSA publication above:

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Liver enzymes and proteins: Gamma glutamyl transferase (GGT) Aspartate amino transferase (AST) and alanine amino transferase (ALT) Carbohydrate-deficient transferrin (CDT)

CBC:

Mean corpuscular volume (MCV) (unknown why this occurs) Direct markers: (the result of alcohol metabolism)

Phosphatidyl ethanol (PEth) Urine ethyl glucoruonide (EtG) Urine ethyl sulfate (EtS)

All of these biomarkers vary according to their ability to test for recent exposure, heavy or binge drinking, and chronic alcohol use – see below (from SAMHSA publication above):

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SELECTED GI ENDOSCOPIC AND BIOPSY FINDINGS: 1) Video capsule endoscopy: patient swallows disposable capsule with enclosed battery, microchip camera & light source patient wears recorder and camera transmits images over 6 hour battery life (2 images/sec) cannot use if patient has stool impaction or small bowel stricture Capsule picture of normal pylorus Capsule picture of pylorus with erosions 2) Virtual Endoscopy: Isn’t this amazing!! The picture on the right is a 3D computer creation from helical CT

scanning. The picture on the left is direct visualization on conventional colonoscopy. Preparation:

o same colon prep as for BE, colonscopy o air (or CO2) insufflation to distend the colon

Is VIRTUAL colonscopoy as good as DIRECT colonscopy? o Not yet – although newer computer software aided studies are coming close. o Better for larger polyps (> 6 mm)

Possible uses: o screening in low-risk o may cut need for colonoscopy by 2/3

False negatives: flat lesions, polyps < 10 mm, inadequate insufflation

Conventional (left) and virtual (right) colonoscopy images of the same pedunculated polyp in the sigmoid colon.

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4) UPPER ENDOSCOPY: Gastric and esophageal varices (dilated veins) are caused most commonly by cirrhosis with associated portal hypertension. They are categorized by their location in the GI tract; 14-35% bleed (mortality 30-50%); and there is a 30% rebleeding rate. Endoscopic sclerotherapy and/or tamponade is first-line treatment, with medical support (beta-blockers) and surgical approaches (shunts). Bleeding esophatgeal varices Paracentesis: drawing off ascites fluid and subjecting to laboratory evaluation. Useful in determining if portal hypertension exists. Z-track needle entry into abdomen labs ordered

o cytology (is ascites due to cancer?) o cultures (considering spontaneous bacterial peritonitis, SBP) o albumin (determine serum/ascites albumin gradient, SAAG; subtract ascites albumin

from serum albumin, value > 1.1 g/dL implies portal hypertension)

Hemorrhagic gastritis (corpus of stomach)

Helicobacter pylori seen with special stain of biopsied stomach mucosa. Stains include the Warthin-Starry silver stain (this slide), Giemsa stain, acridine orange stain, and Gimenez stain. The bacteria are seen in the lumen of the gastric pits.

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File: advpatho_unit9_8diag.pdf Source: C. DeCristofaro, MD

5) LOWER ENDOSCOPY: Sigmoidoscopy Colonoscopy Anoscopy (flexible) Sigmoidoscopy: misses up to 25% of colonic neoplasms usually able to insert 7-15 cm maximum (rectum only) certain findings (large polyps > 5 mm, suspicion of cancer, adenomatous polyps) still need

colonoscopy recent recommendations are moving away from sigmoidoscopy and towards colonoscopy,

even for screening purposes Colonoscopy: Identifies up 95% of colon cancer, reduces mortality previous rigid scopes had higher incidence of bowel perforation, newer flexible scopes have

mostly eliminated this (perforation incidence 1 in 1,500) preferred screening test for colon cancer in high risk patients Adenocarcinoma of colon Anoscopy: can be done in the office, no sedation only visualizes lower few inches of anorectal insertion Indications:

o rectal bleeding, pain, prolapse o anal pain, hemorrhoids, anal fistula, perianal condyloma o mass palpated on DRE (digital rectal exam)

Procedures: o rubber-band ligation of hemorrhoids (1-2 per visit) o infrared coagulation of hemorrhoids (one quadrant per visit, more likely to cause

prolapse) o evacuation of thrombosed hemorrhoid (needs suture repair with interrupted buried

vicryl sutures to prevent bleeding)

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File: advpatho_unit9_8diag.pdf Source: C. DeCristofaro, MD

SELECTED IMAGING DIAGNOSTICS IN GI: 1) TECHNECHIUM SCANNING: Normally functioning Non-functioning gallbladder gallbladder (seen 30 min (seen 60 min after nuclide injection) after nuclide injection) Also used in evaluation of possible Meckel’s diverticulum (pediatric). 2) ULTRASOUND:

Intraductal ultrasound with hyperechoic defect and associated acoustic shadow seen with common bile duct stone.

Something simple to see -- ultrasound of gallbladder with cholelithiasis (gallstones).

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File: advpatho_unit9_8diag.pdf Source: C. DeCristofaro, MD

3) PLAIN RADIOGRAPHS (XRAYS):

Ileus on “flat plate” Xray of the abdomen showing “air-fluid” levels due to gravity (obstructive pathology)

A 9-year-old boy ingested 23 magnets (Panel A). Four days later, he had clinical and surgical evidence of intestinal perforation and peritonitis due to pressure necrosis of the bowel. In an unrelated incident, a developmentally delayed 13-year-old boy ingested 15 magnets. Ten days later, volvulus and intestinal occlusion developed (Panel B, arrows). Both patients were operated on without complications, and all magnets were removed. Although ingested nonmagnetic foreign bodies are likely to be passed spontaneously without consequence, ingested magnets may attract each other through the intestinal wall and cause severe damage, such as pressure necrosis, perforation, intestinal fistulas, volvulus, and obstruction. Thus, close observation and early intervention are warranted after ingestion of magnets. (FROM: New England Journal of Medicine, 25 June 2009;360(26):2770. With permission: http://content.nejm.org/cgi/content/full/360/26/2770

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File: advpatho_unit9_8diag.pdf Source: C. DeCristofaro, MD

4) CONTRAST RADIOGRAPH STUDIES: Examples: Barium enema (usually ordered as “double-contrast” or DCBE with air insufflation to

better outline the image) Upper GI series (usually ordered “with small bowel follow through”)

Barium Enema: Contrast media fills lumen of colon and displays haustrae; multiple films are taken in sequence over time to demonstrate the contractile pattern of the colon.

Apple Core Lesion: In colon cancer, the presence of the tumor narrows the lume; this lumen-narrowing causes a narrow image of contrast dye filling; it looks like an “apple core.” Sometimes called a “napkin ring” lesion.

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File: advpatho_unit9_8diag.pdf Source: C. DeCristofaro, MD

Upper GI series (ALSO called a “Barium Swallow): Identifies: esophageal strictures & varices hiatal hernia ulcers tumors polyps GERD Fluoroscopy: real-time visualization of the barium moving through the GI tract via peristalsis especiallyl good for evaluating swallowing problems Risks: constipation after procedure Normal UGI aspiration of barium allergic reaction to contrast

NOTE: most experts will say that the BE & UGI are really no longer first-line tests. If available, upper and/or lower endoscopy are preferred – biopsies can be taken,

instrumentation can be done (coagulate bleeding, etc) and no risk of aspiration, constipation, or contrast reaction.

Also, direct visualization is preferred.

Obstruction due to marked narrowing of first and second parts of the duodenum. Laparotomy demonstrated malignant infiltration of the duodenum caused by adenocarcinoma of the gallbladder. (Blue arrow) (from: http://www.emedicine.com/radio/topic225.htm )

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File: advpatho_unit9_8diag.pdf Source: C. DeCristofaro, MD

5) Computed Tomography (CT):

Diverticular abscess, CT scan shows segment of colon with many diverticula (small arrows). Adjacent abscess with air-fluid level (thick white arrow), showing connection with the colon through the ruptured diverticulum.

“Whirl sign” on CT in small intestine volvulus (black arrows).

From: Hong M, Chi C. Small-intestinal volvulus. N Engl Med 28 July 2011;365(4):358.

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File: advpatho_unit9_8diag.pdf Source: C. DeCristofaro, MD

6) ENDOSCOPIC RETROGRADE CHOLANDIOPANCREATOGRAPHY (ERCP) and MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY (MRCP): ERCP – diagnostic and interventional MRCP – diagnostic only ERCP: minimally invasive technique evaluates pancreas, gallbladder, liver, bile ducts endoscope passed through mouth, esophagus, stomach into duodenum done under mild sedation, outpatient Diagnostic:

o dye injected via endoscope into pancreas and bile ducts & Xray taken o biopsy can also be done using instruments passed through scope

Interventional: o instruments inserted through scope to remove stones, insert drains, biopsy

Indications: o Gallstones trapped in the main bile duct o Blockage of the bile duct o Evaluation of jaundice o Undiagnosed upper-abdominal pain o Cancer of the bile ducts or pancreas o Pancreatitis

Picture shows stones in the bile duct. (from University of Wisconsin Dept. of Surgery, http://www.surgery.wisc.edu/general/patients/uwmhpsercp.shtml

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File: advpatho_unit9_8diag.pdf Source: C. DeCristofaro, MD

MRCP: noninvasive, diagnostic only evaluation of biliary disease, pancreatitis, sclerosing cholangitis, congenital malformations maps biliary tree (ductal structures) extremely well especially useful if anatomy altered from disease or prior surgery How does it work?

o stationary fluid in the ducts allows MRI to “cone down” on very thin slices for computer processing

Don’t use: o if intervention is needed – e.g. stones that could be removed via instrumentation in

ERCP (i.e. endobiliary therapy) ERCP & MRCP: mostly used in evaluation of difficult cases where other diagnostic tests have not helped considered definitive evaluation of biliary tree

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NOTE: images used are public domain unless otherwise cited. Some locations for public domain images in GI are the Visible Human Project, Feldman’s GastroAtlas, GastroSource, MediClicks, and more.

Obstruction of right and left hepatic ducts by a mass as seen on MRCP.