Liver and Pancreatic Labs

Question 1

AST

Answer 1

An aminotransferase enzyme

Present in the liver, cardiac and skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, and RBCs

Reflects damage to hepatocytes, but is less specific than ALT

Question 2

ALT

Answer 2

An aminotransferase enzyme

Primarily present in the liver

Reflects damage to hepatocytes, and is more specific than AST

ALT>AST in most acute hepatocellular damage

Question 3

Normal aminotransferase levels

Answer 3

10-40 U/L

Question 4

Elevated aminotransferase levels

Answer 4

Ranked mild-severe

Mild: <80 (2x ULN)
Moderate: <600 (15x ULN)
Severe: >600 U/L
>1000 U/L indicates EXTENSIVE hepatocellular injury

Question 5

Viruses causing elevated aminotransferases

Answer 5

Viral hepatitis A, B or C

Question 6

NAFLD causing elevated aminotransferases

Answer 6

Associated with metabolic syndrome

Should be strongly considered in individuals with mild elevations of AST/ALT (levels rarely >300)

Question 7

Alcoholic liver disease causing elevated aminotransferases

Answer 7

An AST:ALT > 2:1 is suggestive, and >3:1 is highly suggestive, of alcoholic liver disease (ALD) with history of alcohol use

Elevated GGT supports the diagnosis of alcoholism or alcohol abuse (but unhelpful by itself)

Question 8

Autoimmune conditions that can elevate aminotransferases

Answer 8

□ Hypothyroidism
□ Rheumatoid arthritis
□ Ulcerative colitis
□ Synovitis
□ Sjogren’s

Question 9

Drugs/supplements that can elevate aminotransferases

Answer 9

□ Statins
□ Antiepileptics
□ NSAIDS
□ Cocaine
□ Certain herbal remedies

Question 10

Metabolic/genetic conditions that can elevate aminotransferases

Answer 10

Hemochromatosis:
Autosomal recessive genetic defect of the HFE leading to a multi-organ iron deposition disorder

Wilson’s disease:
A genetic disorder of biliary copper excretion, leading to copper deposition in the liver and other organs

Alpha-1 antitrypsin deficiency (rare):
Causes cirrhosis/emphysema in young patients

Question 11

Elevated aminotransferase workup

Answer 11

1. Do they have s/sx that suggest a certain condition?
2. Is this finding new, stable, improving, or worsening?
3. Is the elevation mild, moderate, or severe?

EtOH, meds, or NAFLD? Implement lifestyle changes and recheck

Hepatitis screening:
◊ HepB: HBSAG
◊ HepC: HCV antibody
◊ HepA: IgM anti-HAV antibodies (usually only screened if symptomatic [diarrhea, illness, acute onset, recent travel])

Iron studies: to evaluate for hemochromatosis
Liver U/S

Continue to occasionally monitor if no identifiable causes, annually or biannually

Question 12

ALP

Answer 12

Associated with cholestasis (impairment of flow of bile from the liver to the duodenum)

Indicative of cholestatic injury (biliary tree, bile duct, gallbladder)

Question 13

Elevated ALP

Answer 13

<3 fold increase seen in almost any type of liver disease and not specific for cholestasis

> 4 fold increase can indicate a cholestatic liver disorder, infiltrative liver disease (cancer), or bone conditions with rapid turnover of bone (Paget’s disease)

Question 14

Normal total bilirubin level

Answer 14

<1-1.5 mg/dl

Question 15

More detailed bilirubin testing

Answer 15

Van der Bergh assay: determination of total, conjugated (direct) and unconjugated (indirect) bilirubin levels

May or may not see rise in cholestatic inury

Question 16

Serum albumin to assess liver function

Answer 16

Synthesized exclusively by the hepatocytes

NOT a good indicator of acute or mild hepatic dysfunction

Question 17

Coagulation factors to assess liver function

Answer 17

Blood clotting factors (except Factor VIII) are exclusively synthesized in hepatocytes

The single best acute measure of hepatic synthetic function in acute parenchymal liver disease due to their rapid turnover rates

Question 18

Amylase

Answer 18

A digestive enzyme that is predominantly secreted by the pancreas (also produced by the salivary glands)

Aids in the hydrolysis of starch into sugars

Can indicate pancreatic dysfunction, salivary disease, appendicitis, perforated bowel, celiac disease, ruptured ectopic pregnancy, PID, etc.

Question 19

Lipase

Answer 19

A digestive enzyme predominantly secreted by the pancreas

Main function is to hydrolyze triglycerides into glycerol and FFAs

Can indicate pancreatic dysfunction, HIV, HCV, IBD, T2DM, etc.

Question 20

Serum amylase in pancreatitis

Answer 20

Acute threefold elevation

Rises within 6-12 hours and returns to normal within 3-5 days

Elevation of >3x the ULN has a sensitivity for dx acute pancreatitis of 67-83% and a specificity of 85-98%

Extra-pancreatic causes of elevations are not associated with a greater than threefold elevation

Question 21

Serum lipase in pancreatitis

Answer 21

Acute threefold elevation

Rises within 4-8 hours (peaking at 24) and returns to normal within 8-14 days

Elevations occur earlier and last longer than amylase

Sensitivity for acute pancreatitis ranges from 82-100% (*more sensitive than amylase)

Extra-pancreatic causes of elevations are not associated with a greater than threefold elevation

Question 22

Vitamin D functions

Answer 22

Serum calcium and phosphate homeostasis

1. Increases intestinal absorption of calcium and phosphate
2. Increases renal reabsorption of calcium and phosphate
3. Increases bone resorption to release calcium

Question 23

Vitamin D pathway

Answer 23

80% from sun & 20% from diet –> LIVER calcitriol –> KIDNEY calcitriol active form

VDBP (vitamin D binding protein): transports in blood

Question 24

Vitamin D deficiency outcomes

Answer 24

Hypocalcemia &/or hypophosphatemia

Developing countries: causes rickets and osteomalacia (no longer observed in developed countries)

Developed countries: subclinical deficiency is increasing, with an estimated prevalence as high as 40%, causing osteoporosis, fractures, and reduction in immune/CV health

Question 25

Vitamin D level

Answer 25

serum 25-hydroxyvitamin D (25[OH]D) -- calcidiol Sufficiency: > 20 ng/mL (50 nmol/L) Insufficiency: 12-20 ng/mL (30-50 nmol/L) (levels <20 ng/mL are suboptimal for skeletal health) Deficiency: <12 ng/mL

Question 26

Vitamin D deficiency screening

Answer 26

Universal screening is not currently recommended High-risk groups include individuals with: -Medications that accelerate Vitamin D metabolism (phenytoin) Increased skin pigmentation Obesity Limited sun exposure Osteoporosis Chronic illness with malabsorption (IBD, celiac, etc.)

Question 27

HgbA1C

Answer 27

The average BGL over the previous 2-3 months Used to monitor chronic glycemic control/efficacy of treatment and dx DM

Question 28

HgbA1C targets for patients with DM

Answer 28

Individualized with the goal of avoiding hypoglycemic episodes with too stringent of control Healthy adult: <7.5% Older adults with comorbid conditions: 8-8.5% Children: <7% Children who cannot verbalize s/sx of hypoglycemia: <7.5% Pregnant women: <6%

Question 29

DM ADA screening criteria

Answer 29

Fasting plasma glucose >/= 126 mg/dL Hemoglobin A1C >/= 6.5% Two-hour plasma glucose >/= 200 mg/dL 75 g oral glucose tolerance test (OGTT) Classic symptoms and a random BGL of >/= 200 mg/dL

Question 30

Population screening recommendations

Answer 30

Overweight or obese adults (BMI >/= 25 kg/m2 or >/= 23 kg/m2 in Asian Americans) who have 1+ of the following risk factors: □ First-degree relative with DM □ High-risk race/ethnicity (African American, Latino, Native American, Asian American, Pacific Islander ) □ Hx of CVD □ HTN □ HDL cholesterol <35 mg/dL &/or triglyceride level >250 mg/dL □ Women with PCOS □ Physical inactivity □ Clinical conditions associated with insulin resistance (Obesity, acanthosis nigricans, etc.) -Patients with prediabetes should be tested yearly (A1C >/= 5.7%, IGT, or IFG) -Women who were dx with GDM should have lifelong testing at least q3 years -All patients (even without meeting screening criteria) should begin at age 45 years If results are normal, testing should be repeated at a minimum of 3-year intervals, with considerations of more frequent testing depending on initial results and risk status

Question 31

DM BGL monitoring

Answer 31

□ T1DM: qid Postprandially Before exercise 0300 □ T2DM: generally unnecessary and treated with diet alone as agents do not cause hypoglycemia □ Pregnancy: Fasting Before and 1-2 hours after each meal Bedtime ® Goals: ◊ Fasting, pre-prandial, and nocturnal BGL: 70-90 mg/dl ◊ One hour postprandial: 110-140 mg/dl ◊ Two hour postprandial: 100-120 mg/dl