LFTs Flashcards
Functions of the Liver
- Involved in amino acid, albumin, angiotensinogen, and cholesterol biosynthesis as well as carbohydrate metabolism (Gluconeogenesis; Glycogenolysis; Glycogenesis)
- Produces thrombopoeitin, coag factors (I, II, V, VII, IX, X, and XI) as well as protein C and S and antithrombin
- Main site of RBC production during the first 32 weeks of fetal development (then bone marrow takes over)
- Converts ammonia to urea.
- Stores glycogen, vitamin A (1-2 years supply), vitamin D (1-4 months supply), vitamin B12, iron, and copper
- Contains many immunologically active cells, acting as a “sieve” for antigens carried to it via the portal system.
- Facilitates the catabolism of hemoglobin and excretes bile.
This is the term for the breakdown of glycogen into glucose.
Glycogenolysis
This is the term for the formation of glycogen from glucose.
Glycogenesis
This is the term for the synthesis of glucose from certain amino acids, lactate or glycerol.
Gluconeogenesis
T/F: The pancreas has exocrine and endocrine functions.
True;
Proteases, Amylases, and Lipases allow for exocrine function.
Insulin and Glucagon allow for endocrine function.
What tests check for Synthetic Function of the Liver?
Total Protein
Albumin
Prealbumin
PT-INR
What tests check for Excretory Function of the Liver?
ALP
GGT
Total and Direct Bilirubin
5’-Nucleotidase
What tests check for Hepatocellular Injury of the Liver?
ALT and AST
What tests check for Detoxification of the Liver?
Ammonia
The Comprehensive Metabolic Panel (CMP) is a combination of ______ and ______. What individual tests does this include?
BMP and HFP (LFTs)
- Na
- K
- Cl
- CO2
- BUN
- Cr
- Glucose
- Ca
- Total Protein
- Albumin
- AST
- ALT
- ALP
- Total Bilirubin
**Direct BR and Globulins not typically included in the CMP.
This synthetic product of the liver is a protein that binds free HgB released from RBCs and inhibits its oxidative activity. The complex with HgB is then removed by the spleen.
Haptoglobin
This synthetic product of the liver is used to screen for hemolytic anemia along with LDH.
Haptoglobin
This synthetic product of the liver is a glycoprotein that transports ferric ions (Fe3+). It CAN measure synthetic function BUT is rarely used.
Transferrin
What is the normal range of Albumin?
4.0-5.0 g/dL
_____ grams of albumin are synthesized and excreted daily by the normal liver.
10
As liver damage progresses, albumin synthesis ___________.
Progressively declines
Half life of Albumin is?
18-20 days (with 4% degraded daily)
Albumin levels may be normal in cases of ____________ and ______________.
- Acute Viral Hepatitis
- Drug-Related Hepatotoxicity Jaundice
A patient with chronic liver disease (cirrhosis) will have albumin levels that are _____.
Low (< 4.0) called Hypoalbuminemia
An albumin levels less than 2.5 g/dL gives a ______ prognosis.
Poor
Someone with Hypoalbuminemia could present with…?
- Peripheral Edema
- Ascites
- Pulmonary Edema
Non-hepatic Causes of Hypoalbuminemia
- Protein Malnutrition/Malabsorption
- Loss from the Kidneys or Gut
- Burns
- Trauma
- EtOH Abuse
A patient with dehydration (as noted with BUN and HCt), would have ____ albumin levels.
High (>5.0) called Hyperalbuminemia
Causes of Hyperalbuminemia
- Anabolic Steroids
- False Elevation if pt on Heparin or Ampicillin
Patients with hyperlabuminemia commonly present with what symptom(s)?
None, often asymptomatic.
Normal Range of Prealbumin (Transthyretin)
17.0-34.0 mg/dL
Half life of Prealbumin
~2 days
Prealbumin binds to _________ and _______.
Thryoxine; Retinol
Prealbumin levels respond to nutritional changes ____more/less____ frequently than albumin.
More
Normal Range of Total Protein
6.0 - 8.3 g/dL
Total Protein reflects the sum of ______ and ____.
Albumin and Globulins
How do you find Globulin levels on LFTs?
Total Protein - Albumin = Globulin
What would elevated Globulin Levels cause you to screen for?
Multiple Myeloma (serum urine protein electrophoresis, BM biopsy, etc.)
Normal Range of Serum Globulins
2-3 g/dL
These are larger proteins than albumin and important for immunologic responses (IgA, IgG, IgM, and IgE) but produced by B-lymphocytes.
Globulins
What do Globulins carry?
- Hormones
- Lipids
- Metals
- Antibodies
What would elevated Globulin levels indicate?
- Chronic Infections
- Liver Dz
- Rheumatoid Arthritis
- Myelomas
- Lupus
What would low levels of Globulins indicate?
- Immune Compromised
- Protein Malnutrition/Malabsorption
- Kidney dz
- Protein Losing Enteropathy
The liver must be able to use Vitamin K in the Coagulation Cascade to produce what Factors?
II, VII, IX, and X
This test is used to screen for INTRINSIC pathway factor inhibitors (Factors VIII, IX, XI, and XII) as well as common pathway factors (Factors II, V, and X)
Activated Partial Thromboplastin Time (aPTT)
This test is used to screen for EXTRINSIC pathway of coagulation (Factors I, II, V, VII, and X). It also measures the Vitamin K Status (Factors II, VII, IX, and X)
Prothrombin Time (PT)
Normal Range for PT
12.7-15.4 seconds
This test accounts for variations between different manufacturer lots of tissue factor.
INR
Normal Range for INR
0.9-1.1
Meaning of Prolonged PT-INR
> 80% of liver synthetic capacity is lost
- Clotting Factors made by the liver are low (Factor VII has a half-life of about 6 hours)
In Acute Liver Dz, the PT may be _______ and as the patient recovers, the PT becomes _______.
Prolonged; normal
Causes of Prolonged PT
- Chronic Cholestasis or Fat Malabsorption from Pancreatic or SB Dz
Bilirubin Metabolism Process
- Macrophages break down senescent RBCs in the spleen into globin and heme moieties
- Globin is catabolized to amino acids and the heme (porphyrin) to biliverdin and unconjugated bilirubin, which uses albumin as carriers
- In liver, there are three steps
a. Uptake by the liver hepatocytes after dissociation with albumin
b. Conjugation with glucoronic acid
c. Excretion of conjugated bilirubin into the bile
d. Conjugate bilirubin can be excreted unchaged in the stool
e. It can also be converted to urobilinogen by commensal bacteria in the distal SB and will:
- - be reabsorbed and enter portal circulation
- - be reabsorbed into portal circulation and by the liver and re-excreted into the bile
- - bypass the liver and be excreted by the kidneys as urine.
Normal Range of TBR (Total Bilirubin)
0.3 - 1.3 mg/dL
Two forms of Bilirubin
- Unconjugated (Indirect)
2. Conjugated (Direct)
Normal Range of Unconjugated Bilirubin
0.2 - 0.9 mg/dL
Normal Range of Conjugated Bilirubin
0.1 - 0.4 mg/dL
How do you calculate Indirect/Unconjugated Bilirubin?
***LFTs only show Conjugated/Direct and Total BR
IBR = TBR - DBR
T/F: Hyperbilirubinemia can occur as Indirect or Direct
True
T/F: Only Indirect/Unconjugated Hyperbilirubinemia can cause Jaundice.
False, Indirect or Direct Hyperbilirubinemia can cause Jaundice
When you see someone with Jaundice, what are you thinking?
Hyperbilirubinemia
What are the best places to look for Jaundice?
- Sclera (first)
- Skin
- Mucous Membranes (under tongue, hard palate)
TBR in Jaundice is about
2.0 - 3.0 mg/dL (2-3 x nl)
What is the first step in approaching jaundice?
Determine whether the hyperbilirubinemia is primarily unconjugated (indirect) or conjugated (direct).
Possible Causes of Indirect (Unconjugated) Hyperbilirubinemia
- Increased production of unconjugated bilirubin:
- - Hemolytic Anemia
- - Diserythropoiesis
- - Internal Hemorrhage - Decreased Bilirubin Uptake:
- - HF
- - Sepsis
- - Meds (Rifampin, Probenecid)
- - Fasting - Impaired Bilirubin Conjugation
a. Hereditary
- - Gilbert Syndrome
- - Crigler-Najjar Syndrome
b. Acquired
- - Neonates
- - Hyperthyroidism
- - Ethinyl Estradiol
- - Sepsis
This is a rare disorder affecting the metabolism of bilirubin. It causes a non-hemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in infants.
Crigler-Najjar Syndrome
Presentation of Hemolytic Anemia
Increased Production of Unconjugated BR
- Symptoms of Anemia
- Jaundice
- Splenomegaly
- Gallstones
- Dark Urine
Lab Findings of Hemolytic Anemia
- Elevated serum unconjugated BR
- Elevated serum reticulocyte count
- Dec. haptoglobin and elevated LDH
Possible Causes of Direct (Conjugated) Hyperbilirubinemia
**Elevated Liver Enzymes
- Hepatocellular Injury (Transaminase > ALP)
- - Acute Viral, Alcoholic and Non-Alcoholic Hepatitis
- - Chronic Hepatitis
- - Cirrhosis
- - Drug/Toxins - Extrahepatic and Intrahepatic Obstruction (ALP > Transaminases) – Cholestasic Problems
- - Extrahepatic = Biliary obstruction
- - Intrahepatic = Impaired excretion - Defects in Canalicular Excretion
- - Dubin-Johnson Syndrome
- – Rotor Syndrome
Causes of Intrahepatic Obstruction causing Direct/Conjugated Hyperbilirubinemia
- Viral and Alcoholic hepatitis
- Drugs and Toxins (Steroids)
- Sepsis
- TPN
- Post-liver transplant
- Granulomatous/Infiltrative diseases (sarcoidosis, TB, amyloidosis, lymphoma)
- PSC (associated with UC)
- PBC
Causes of Extrahepatic Obstruction causing Direct/Conjugated Hyperbilirubinemia
- Choledocholithiasis (stones)
- Tumors – benign & malignant
a) Intrinsic to the biliary system (ie: cholangiocarcinoma)
b) Extrinsic to the biliary system (ie: pancreatic head cancer)
- - Primary sclerosing cholangitis (PBC – also fits here too)
- - Strictures (post-procedure)
- - Parasitic infections
- - Ascaris lumbricoides
- - Liver flukes
- - AIDS cholangiopathy
This is an autosomal recessive disorder that causes an increase of conjugated BR in the serum without elevation of liver enzymes (ALT, AST). It is assc with a defect in the ability of hepatocytes to secrete conjugated BR int the bile. It is usually asymptomatic but may be diagnosed in early infancy based on laboratory tests.
- Has dark pigmented liver cells
- GB not visualized
- Normal Total Urine Coproporhyrin Content with 80+% being isomer 1
Dubin-Johnson Syndrome
This is a rare, relatively benign autosomal recessive BR disorder. The main symptom is non-itching jaundice. Mainly elevation of conjugated BR.
- Normal Histology and Appearance
- GB can be visualized by oral cholecystogram
- High Total Urine Coproporhyrin Content with 70+% being isomer 1
Rotor Syndrome
Labs to check for Hyperbilirubinemia
- CBC (Hgb and Hct)
- BMP (BUN)
- LFTs (all)
- GGT
- Coag Study (PT)
- UA (RBCs and everything else)
Two broad categories of Liver Disease
- Hepatocellular (Hepatocytes are inflamed or damaged)
- Cholestatic (Primary interference with metabolism or secretion of BR any from conversion to conjugated form to secretion into duodenum
What lab tests measures Hepatocellular Injury?
- ALT (Alanine Aminotransferase)
- AST (Aspartate Aminotransferase)
- GGT (Gamma-Glutamyl Transpeptidase)
Normal Range of ALT
7 - 41 units/L
Men usually < 30
Women usually < 20
Function of ALT
Catalyzes the transfer of an amino group from alanine to alpha-ketoglutarate (transamination)
Glutamate + Pyruvate alpha-ketoglutarate + Alanine
Half life of ALT
17 - 47 hours
Why is ALT a measure of Hepatocellular Injury?
ALT leaks into bloodstream as hepatocytes are damaged. So it correlates with the degree of cell death or inflammation.
T/F: ALTs can give us an accurate estimate of inflammatory activity or the amount of cell death.
False, only Liver Biopsy can do that.
Normal Range of AST
12 - 38 units/L
Men: < 30
Women: < 20
Function of AST
Catalyzes the transfer of an amino group from aspartate to alpha-ketoglutarate (transamination)
Glutamate + Pyruvate alpha-ketoglutarate + Aspartate
T/F: AST is similar to ALT but ALT is less specific for Liver Dz because it is also produced in Skeletal and Cardiac Muscle
False.
AST is similar to ALT but AST is less specific for Liver Dz because it is also produced in Skeletal and Cardiac Muscle
T/F: In many cases of liver inflammation, the ALT and AST activities are elevated roughly in a 1:1 ratio.
True
In some conditions, such as _________, the elevation in the serum AST level may higher than the elevation in the serum ALT level (> 2-3:1and AST < 400).
Alcoholic Hepatitis
Drug Sources of Hepatocellular Injury
- Acteominophen
- Allopurinol
- Amiodarone
- Cisplatin
- Dapsone
- Ketoconazole
- Isoniazid
- NSAIDs
- Methotrexate
- Lovastatin
Non-Drug Sources of Hepatocellular Injury
- Alcoholic Liver Dz
- Autoimmune Hepatitis
- Celiac Sprue
- CHF
- NAFLD
- Hemochromatosis
- Wilson’s Dz
Viral Sources of Hepatocellular Injury
- Hep A
- Hep B
- Hep C
- Hep D
- Hep E
- EBV
- CMV
What lab tests measures Cholestasis?
- Alkaline Phosphatase
- GGT
- 5’-Nucleotidase
Normal Range of Alkaline Phosphatase
33 - 96 units/L
What is Alkaline Phosphatase?
A family of related enzymes (isoenzymes), produced in the bile ducts, small intestine, kidney, placenta and bone (usually ~80% in liver & bone).
Variability with Alkaline Phosphatase
- Adolescents may have 3X adult levels
- May be increased late in pregnancy due to placental ALP
- Bile accumulation increases hepatic ALP by hepatocytes
- Generally associated with cholestatic D/Os (though cannot distinguish this with ALP alone.
Hepatic Sources of ALP Elevation
- Bile Duct Obstruction
- Primary Biliary Cirrhosis
- Primary Sclerosing Cholangitis
Non-Hepatic Sources of ALP Elevation
- Bone (Healing Fractures, Osteomalacia, Tumors)
- Metabolic (Hyperthyroidism, Renal Failure, Acromegaly)
- Drug Related (Anticonvulsants, Lithium, OCP)
Normal Range of GGT
9 - 58 Units/L
Where does GGT come from?
Bile Ducts (just like ALP)
T/F: Elevations of GGT with ALP suggests Bile Duct Disease
True
T/F: GGT maybe be elevated in virutally any liver dz and sometimes in normal individuals.
True
Normal Range of 5’-Nucleotidase
0 - 11 units/L
Where is 5’-Nucleotidase found?
Many Tissues (Liver, Brain, Heart, Vessels)
But most elevated in hepatic dzs.
Can also be elevated in RA and some cancers
T/F: 5’-Nucleotidase responds similar to ALP.
True
With the following Lab Results, what should be in your DDx?
ALP: Mildy Elevated
GGTP: Normal
ALT & AST: Normal
- Preggo
- Non-Hepatic Causes
With the following Lab Results, what should be in your DDx?
ALP: Moderately Elevated
GGTP: Markedly Elevated
ALT & AST: Normal
Cholestatic Syndromes
With the following Lab Results, what should be in your DDx?
ALP: Mildy Elevated
GGTP: Mildly Elevated
ALT & AST: Markedly Elevated
Hepatocellular Dz
This is produced by the breakdown of amino acides that are converted to urea by the liver. It is able to measure the liver’s ability to detoxify.
Ammonia
In severe liver disease, what happens to serum ammonia levels? BUN levels?
Increase; Decrease
Increasing ammonia may signal _____ with a high risk of hepatic encephalopathy or coma.
ESLD
T/F: Measures of Ammonia are best in venous blood.
False, Arterial Blood
Venous blood levels may be elevated as a result of the metabolism of AAs in the muscles.
When are ammonia levels most useful?
In patients with stupor or coma of unknown origin.
Normal Range of Ammonia
10-80 microg/dL
Urea is formed in the _____ and Eliminated in the _______.
Liver; Kidneys
Facts about Hep A
Source: Feces
Route of Transmission: Fecal-Oral
Chronic Infection? No
Prevention: Pre-Exposure Immuization
Facts about Hep B
Source: Blood/Blood-Derived Body Fluids
Route of Transmission: Percutaneous, Permucosal
Chronic Infection? Yes
Prevention: Pre-/Post-exposure Immunization
Facts about Hep C
Source: Blood/Blood-Derived Body Fluids
Route of Transmission: Percutaneous, Permucosal
Chronic Infection? Yes
Prevention: Blood Donor Screening
Facts about Hep D
Source: Blood/Blood-Derived Body Fluids
Route of Transmission: Percutaneous, Permucosal
Chronic Infection? Yes
Prevention: Pre-/Post-exposure Immunization
Facts about Hep E
Source: Feces
Route of Transmission: Fecal-Oral
Chronic Infection? No
Prevention: Ensure safe drinking water
Hepatitis A Antibody Testing for:
Acute Hep A
Anti HAV Total (IgG, IgM): Positive
IgM Anti-HAV: Positive
Hepatitis A Antibody Testing for:
Resolved Hep A
Anti HAV Total (IgG, IgM): Positive
IgM Anti-HAV: Negative
Hepatitis A Antibody Testing for:
Immunized Hep A
Anti HAV Total (IgG, IgM): Positive
IgM Anti-HAV: Negative
Where is Hep B e antigen located?
Inside the first capsule.
Where is Hep B surface antigen (HBsAg) located?
Outside the first capsule.
Where is Hep B core antigen (HBcAg) located?
Inner capsule (Core capsule?)
Hepatitis B Antibody Testing for:
Immunized Hep B
HBsAg: Negative
anti-HBc: Positive (or neg if long time ago)
Anti-HBs: Positive
Anti-HBc: Negative
HBsaAg: Negative
Hepatitis B Antibody Testing for:
Acute Hep B
HBsAg: Positive
IgM anti-HBc: Positive
Anti-HBs: Negative
HBV DNA: Positive
HBeAg: May be either.
Hepatitis B Antibody Testing for:
Chronic Hep B
HBsAg: Positive
IgG anti-HBc: Positive
Anti-HBs: Negative
HBV DNA: Positive
Therapeutic Regimens for HBV
- lamivudine (Epivir)
- adefovir (Hepsera)
- tenofovir (Viread)
- telbivudine (Tyzeka)
- entecavir (Baraclude)
– Two Immune System Modulators = Interferon Alpha-2a and PEGylated Interferon Alpha-2A (Pegasys)
T/F: Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage.
True
This is a chronic disease involving progressive destruction of small intrahepatic bile ducts leading to cholestatis and progressive fibrosis over decades. It can necessitate transplantation.
- Etiology is unknown, but may be autoimmune.
- Occurs in F>M 9:1
- Onset: Early 20 - late 80s
Clinical Presentation:
- Inc. ALP, GGT, and BR
Primary Biliary Cirrhosis (PBC)
What is the most useful test for PBC?
AMA (AntiMitochondrial Antibody)
85% Sensitive
Clinical Presentation of PBC
- Fatigue
- Cholestasic Symptoms (Jaundice, Generalized Pruritius, etc)
- Fat-Soluble Vitamin Deficiencies
- Xerostoma
Sibling Dz of PBC
- RA
- Sjorgen Syndrome
- Systemic Scleroderma
Managements of PBC
- Prednisone and Ursodiol
- Liver Transplant
Tests to Assess Pancreatic Inflammation:
- Amylase
- Lipase
- Trypsin and Tysinogen
- CT or MRI
Where does Amylase come from?
Originates from Pancreas and Salivary Glands
How soon does Amylase rise after onset of pancreatitis?
2-6 Hours
Peaks: 12-30 hours
3-5x normal = Diagnostic for Pancreatitis
How soon do Amylase levels return to normal?
3-5 days
Half life of Amylase in blood
1-2 hours
How soon does Lipase rise after onset of pancreatitis?
2-6 hours
Peaks: 12-3- hours
3-5x normal = Diagnostic for Pancreatitis
How soon do Lipase levels return to normal?
8-14 days
Half life of Lipase in blood
7-14 hours
Pathogen causing Ulcer Dz
H. pylori
Transmission of H. Pylori
- Gram-negative, microaerophilic bacillus that is contracted via oral-fecal transmission during childhood.
- Prevalence increases with age; most are asymptomatic but >90% of patients with duodenal ulcers and 80% with gastric ulcers is caused by H. pylori.
H. pylori can cause
MALT (Lymphoma) that is cured when the pathogen is destroyed.
How do you dx H. pylori?
- Urea Breath Test and Fecal Ag
- EGD with bx
Treatment of H. pylori
14 day:
- concomitant (PPI + 1 gram of Amoxicillin + 500 mg of Metronidazole or Tinidazole bid
- Bismuth quadruple (PPI bid + bismuth subsalicylate qid + tetracycline 500 mg qid + Metronidazole 500 mg tid
- hybrid-concomitant (PPI + Amoxicillin 1g for 14 days with Amoxicillin 1 gram + 500 mg Clarithromycin + 500 mg Metronidazole or Tinidazole for the last 7 days).
This condition can be acute or chronic and often presents with profound bloody diarrhea, urgency and abdominal cramping. It is distinguished from non-inflammatory on the basis of physical signs (fever, abdomen, leukocytosis).
Colitis
Causes of Colitis
- Infectious (C. jejuni, Shigella, Samonella, Hemorrhagic E. coli O157:H7)
- CMV, Herpes = immunocompromised
- Ischemic = Mesenteric colitis
- Drug-induced = NSAIDs
- IBD = CD, UC, Indeterminate
This is a toxin-induced dz caused by facultative gram positive anaerobe with evolving antibiotic-resistant strains. It is most commonly assc. with fluoroquinolones, clindamycin, cephalosporins, and beta-lactams.
Depending on the carrier state would determine if it was chronic diarrhea or life-threatening Colitis with sepsis.
C. Difficile
Dx of C. Diff
- PCR
- Toxins A and B
Management of C. Diff
- Flagyl –> PO Vanc
- Fidaxomycin –> Fecal Transplant
