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In Celiac disease, the immune system attacks the microvilli in the:
Small intestine
What is Celiac disease?
An auto-immune disease that affects the small intestine by attacking its microvilli and damaging it
As a result, patients are unable to absorb nutrients as well
Can the damaged microvilli in celiac disease repair itself?
Yes, takes 1-2 years
Celiacs cannot have:
Wheat, rye or barley
As a result of malabsorption seen in Celiac patients, what other conditions can they have?
- Osteoporosis
- Iron-deficiency anemia
- Infertility
- Cancer
What are signs and symptoms of celiac disease?
- Bloating, abdominal pain, diarrhea
- Less noticeable symptoms include anemia, joint pain, stomach pain, irritability, dental/bone disorders, weight loss, stunted growth in kids
- Blistery, itchy rash that appears on elbows, knees and buttocks (dermatitis herpetiformis)
What is silent Celiac disease?
No symptoms but damage is still occurring to the small intestine
What is the only treatment for Celiac disease?
Abstain from wheat
What occurs when a patient with Celiac's ingests wheat?
Gluten and gliadin will build up in the intestinal mucosa, causing direct mucosal damage
What immunoglobulins are seen in patients with Celiac disease?
IgA immunoglobulins (antigliadin, antiendomysial, antitissue transglutaminase)
Patients with celiac disease are sensitive to what proteins found in wheat and wheat products?
Gluten and gliadin
What is included in a celiac panel? (know this)
- Gliadin IgA, IgG
- Endomysial IgA
- Tissue transglutaminase IgA
What is the gold standard to diagnose celiac disease?
Intestinal biopsy
Once a patient with celiac disease goes gluten free, will they still have antibodies present in the serum?
May be negative
A patient with lactose intolerance is given a lactose tolerance breath test that tests for:
Hydrogen
The lactose tolerance breath test is used to detect:
- lactose intolerance
- intestinal malabsorption
- bacterial overgrowth of the small intestine
Lactose intolerance patients have absence of:
Lactase (enzyme that digests lactose in the small bowel)
Which patient populations are commonly affected by lactose intolerance?
- Some newborns, Asian population
- Inflammatory bowel disease
- Malabsorption syndromes
- Short gut syndrome
Why do we perform a hydrogen breath test to test for lactose intolerance?
Bacteria in the colon produces hydrogen when exposed to unabsorbed food (particularly the lactose load not absorbed in the small intestine)
If a patient has lactose intolerance, this bacteria will respond to the undigested food by producing hydrogen
What is the procedure for the lactose tolerance breath test?
- Prior to test, must fast for 12 hours
- At start of test, patient blows into hydrogen analyzer and then ingests small amount of test sugar
- Additional samples of breath are collected and analyzed for hydrogen every 15 minutes for 1 to 5 hours
Prior to lactose tolerance test, patients should avoid:
Smoking, strenuous exercise
What can cause false negative results on lactose tolerance breath test?
Antibiotics --> can decrease bacteria in the intestine so less hydrogen produced
What is H. pylori?
Gram negative bacilli found in mucus overlying gastric mucosa
H. pylori is a risk factor for:
- Duodenal ulcers
- Gastric ulcers
- Chronic gastritis
- Ulcerative esophagitis
What is considered to be a class I gastric carcinogen?
H. pylori
Gastric colonization of H. pylori is reported in what percent of patients with duodenal/gastric ulcers?
Duodenal ulcers: 90-95%
Gastric ulcers: 60-70%
The noninvasive test of choice for diagnosis of H. pylori infection is:
Urea breath test
Gastric colonization of H. pylori increases with:
Age
When is an H. pylori breath test indicated?
In patients who have:
- Recurrent or chronic gastric ulceration
- Duodenal ulceration or inflammation
When H. pylori is treated, the ulcer/inflammation will:
Heal
How does the urea breath test for H. pylori work?
Based on capability of H. pylori to metabolize urea to CO2 because of the organism's capability to produce large amounts of urease
What is the procedure for H. pylori urea breath test?
- Carbon labeled urea is administered orally
- Urea is then absorbed through the gastric mucosa
- If H. pylori is present, the urea will be converted to CO2
- The CO is then taken up by the capillaries in the stomach wall and delivered to the lungs when it is exhaled
- The labeled carbon can be measured by gas chromatography
How are ulcers formed in H. pylori infection?
H. pylori causes excess production of HCl by cells of the stomach lining --> the excess acid removes the mucosal layer and the stomach cells are then attacked, resulting in an ulcer
What is identified in exhaled air during the H. pylori urea test?
Ammonia
What are pancreatic enzymes most commonly used for?
To assess for pancreatitis in acute abdominal pain cases
What are the two pancreatic enzymes we typically check for?
- Amylase
- Lipase
Which is more specific for pancreatic disorders: amylase or lipase?
Lipase
Why is amylase not very specific for pancreatic disorders?
It also rises in disorders of the salivary gland or intestines
What is the normal level of amylase?
60-120 Somogyi units/dL
or 30-220 units/L
What is the normal value for lipase?
0-160 units/L
What is a critical value of amylase?
More than 3 times the upper limit of normal (which is 120 units/dL)
When is amylase secreted from pancreatic acinar cells?
When there is damage to the pancreas
Sensitive, but not specific
When does amylase rise and fall after disease onset?
Rises within 12 hours of disease onset and is cleared rapidly by the kidneys --> back to normal in 48-72 hours
Rises first, but gone quicker
What is the most common cause of elevated lipase?
Acute pancreatitis
When is lipase secreted by the pancreas?
To break down TGDs into fatty acids
When does lipase rise and fall after disease onset?
Rises later than amylase (28-28 hours), remains elevated for 5-7 days
Which is more useful in the diagnosis of acute pancreatitis later in the disease: amylase or lipase?
Lipase --> peaks later and remains elevated longer than serum amylase
What is in a comprehensive metabolic panel?
- Glucose
- BUN
- Creatinine
- BUN
- Sodium
- Chloride
- Potassium
- CO2
- Calcium
- Protein, total
- Albumin
- Bilirubin
- Alkaline phosphatase
- AST
- ALT
What is part of the hepatic function panel?
- Albumin
- Bilirubin, total
- Bilirubin, direct
- Protein
- ALT
- AST
- Alkaline phosphatase
What are liver function tests? Why is this name not totally correct?
Measurement of hepatic enzymes
Do not measure liver function, they measure liver damage
Full work-up of liver conditions should also include true LFTs which are:
- PT and PTT (liver makes clotting factors)
- Albumin (also manufactured by the liver)
What is the normal value of ALT?
10-40 U/L
What is the preferred enzyme for evaluation of liver injury?
ALT
What is the normal value of AST?
0-35 U/L
AST is present in which organs/cells?
- Muscle
- Brain
- Kidneys
- Pancreas
- Lungs
- Blood cells
- Liver
What is the normal value of gamma-glutamyl transferase (GGT)?
0-30 U/L
In acute hepatocellular injury that occurred less than 24 hours ago, which is higher: AST or ALT?
AST > ALT
In acute hepatocellular injury that occurred more than 24 hours ago, which is higher: AST or ALT?
AST < ALT (bc ALT has longer half-life!)
Which is higher in alcoholic hepatitis: AST or ALT?
AST > ALT
Which is more elevated in chronic liver injury: AST or ALT?
ALT > AST
Which is more elevated in end stage liver cirrhosis: ALT or AST?
NEITHER!! They are not elevated
There is so much tissue damage in end-stage liver cirrhosis that these cannot be elevated
Which is more elevated in acute fulminant hepatic failure?
Both are increased
AST:ALT > 1
What is alkaline phosphatase?
Enzyme present in liver and bone
If elevated along with other liver enzymes, suggests obstructive liver disease
If elevated alone, consider bone pathology such as metastatic disease
If alkaline phosphatase is elevated along with other liver enzymes, this suggests:
Obstructive liver disease
If alkaline phosphatase is elevated in isolation, consider:
Bone pathology such as metastatic disease
Alkaline phosphatase is normally elevated in:
Children
Their bones are still actively developing
If you get a high alkaline phosphatase level, you can then order:
Fractionated alkaline phosphatase
This tells you if it is from bone or liver
What is gamma glutamyl transferase (GGT)?
Detects cholestasis, biliary obstruction, cholangitis, or cholecystitis
Most sensitive liver enzyme to detect biliary obstruction
What is the most sensitive liver enzyme to detect biliary obstruction?
Gamma glutamyl transferase GGT
What is a normal value for GGT?
Males and females 45 and older --> 8-38 units/L
Gamma glutamyl transferase is in highest concentration in:
Liver and biliary tract --> detects liver cell dysfunction
Gamma glutamyl transferase increases with:
EtOH ingestion
75% of people who chronically ingest EtOH have elevated GGT
What is bilirubin?
Breakdown product of hemoglobin
Exists in two forms: unconjugated and conjugated
Unconjugated bilirubin is:
Conjugated bilirubin is:
Unconjugated = indirect
Conjugated = direct
Unconjugated bilirubin gets conjugated in the _______.
liver
Yellow discoloration occurs when total serum bilirubin exceeds:
2.5 mg/dL
What are normal values of total bilirubin?
0-1.0 mg/dL
What are normal values of indirect (unconjugated bilirubin)?
0-1.0 mg/dL
What are normal values of direct (conjugated) bilirubin?
0-0.2 mg/dL
What is jaundice?
Discoloration of the body tissues caused by abnormally high bilirubin
Why does neonatal jaundice occur?
Newborn's liver is immature and does not have enough conjugating enzymes
Results in high levels of unconjugated bilirubin
What is a potential complication of neonatal jaundice?
Kernicterus --> bilirubin crosses BBB and causes encephalopathy
Elevated conjugated bilirubin can indicate:
- Liver mets
- Gallstones
- Cholestasis from meds
Elevated unconjugated bilirubin indicates:
- Hemolytic disease of newborn
- Hemolytic jaundice
- Hepatitis
- Sepsis
- Hemolytic anemia
- Cirrhosis
- Sickle cell
- Transfusion reaction
Conjugated bilirubin is elevated from:
Extrahepatic obstruction of ducts (gallstones, tumor blocking bile duct)
Unconjugated bilirubin elevation results from:
Hepatocellular process (ex. hepatitis)
What is the normal level of albumin?
4-6 g/dL
Why is albumin considered to be a liver function test?
It is manufactured by the liver (liver is sole source of albumin production)
What can cause elevated albumin?
Dehydration
What can cause decreased albumin?
- Manufacturing problems (liver disease)
- Loss of albumin through kidney
What is the normal value of ammonia?
10-80 mcg/dL or 6-47 umol/L
What is ammonia?
Product of metabolism in the body, liver is responsible for neutralizing it
If liver is not working properly --> will not be able to neutralize ammonia
As the liver fails, ammonia levels:
Rise
If ammonia rises high enough, _______________ will develop.
hepatic encephalopathy
Which patients need hepatic enzymes/bilirubin/amylase/lipase checked?
- Suspicious of hepatitis (infectious or toxic)
- Hepatotoxic medications
- Upper abdominal pain
- Jaundice
- Annual screening of healthy, asx patients for liver disease using ALT and AST
What is ceruloplasmin?
Protein that is most helpful in diagnosing a patient presenting with jaundice, abdominal pain, behavioral changes, tremors or other symptoms related to Wilson's disease
What is most helpful in diagnosing a patient presenting with jaundice, abdominal pain, behavioral changes, tremors or other symptoms related to Wilson's disease?
Ceruloplasmin
What is a normal value of ceruloplasmin?
20-60 mg/dL
Wilson's disease can present with:
- Jaundice
- Fatigue
- Abdominal pain
- Behavioral changes
- Tremors
What is anti-smooth muscle antibody (ASMA)?
Anti-cytoplasmic antibody directed against actin (cytoskeletal protein)