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Clinical Chemistry 2 > 10 Liver Function > Flashcards

10 Liver Function Flashcards

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1
Q

What is the function of the liver? What happens if you no longer have a functioning liver?

A

Liver: Responsible for metabolism, detoxification, storage, secretion and excretion.

Liver can regenerate but total loss of the liver results in death from hypoglycemia within 24 hours.

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2
Q

How much blood goes through the liver per minutes & the % distribution through the hepatic artery and portal vein?

A

Liver Blow Flow Rate: ~1500 mL/min

25% of blood is provided by the hepatic artery (branch of the aorta, supplies oxygen)

75% of blood provided by portal vein, nutrient rich blood from digestive tract.

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3
Q

What are the bile canaliculi and the intrahepatic ducts? Describe the path to the duodenum?

A

Small spaces between the hepatocytes that form intrahepatic ducts.

Intrahepatic ducts - join to form the right and left hepatic ducts, which then merge to form the common hepatic duct.

Common hepatic duct joins w/ the cystic duct of the gallbladder to form the common bile duct. Finally digestive secretions are expelled into the duodenum.

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4
Q

What do the sinusoids do?

A

Sinusoids - mix O2 and nutrient rich blood. Sinusoidal capillary larger than usual capillaries.

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5
Q

Where is heme waste excreted into and what is it?

A

Heme waste is breakdown product from RBCs and is processed into bilirubin and excreted by the liver into bile. Bile is comprised of bile acids or salts, bile pigments and cholesterol.

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6
Q

What does bile do?

A

Bile is concentrated in the gallbladder and gets released after meals for digestion and absorption of lipids.

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7
Q

What all can the liver do with carbohydrates?

A 
The liver with carbs can:
Use - glycolysis
Store - glycogenesis
Degrade - glycogenolysis
Create - gluconeogenesis
Circulate carbs to peripheral cells.
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8
Q

Where does 70% of cholesterol production occur?

A

Occurs in liver.

Also metabolizes lipids and lipoproteins.

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9
Q

What does the liver do with proteins?

A

The liver:

  1. Synthesizes proteins (other than immunoglobulins).
  2. Transamination & deamination of proteins.
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10
Q

How does your liver protect you from toxic substances?

A

Liver does detoxification of drugs, poisons, bilirubin, ammonia, etc.

  1. Every substance is absorbed in the GI and passes through the liver “first pass”.
  2. Inactivates substances (makes them less toxic) & soluble for excretion in bile or urine.
  3. Processes them through oxidation, reduction, hydrolysis, hydroxylation, carboxylation and demethylation reactions.
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11
Q

What does unconjugated bilirubin consist of and why?

A

Bilirubin bound to albumin to transport it to the liver.

Unconjugated bilirubin is an insoluble non-polar substance and would not be able to go through the blood without being made soluble by a transport protein.

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12
Q

What happens to unconjugated bilirubin in the liver?

A

The liver takes up unconjugated bilirubin by its hepatocytes and conjugates it with glucoronic acid by uridine disphosphate glucuronosyltransferase (UDPGT) to make in soluble conjugated bilirubin.

Also referred to as bilirubin diglucoronide.

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13
Q

What happens to conjugated bilirubin after it is excreted from the common bile duct into the intestines?

A

Intestinal bacteria will eventually turn conjugated bilirubin into urobilinogen.

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14
Q

What are the 3 outcomes to urobilinogen after intestinal bacteria is done with it?

A
  1. 80% of urobilinogen is oxidized to urobilin (stercobilin –> orange colour) and excreted in feces.
  2. 20% of urobilinogen is absorbed by extrahepatic circulation, recycled through liver and re-excreted.
  3. Very Small% of urobilinogen is filtered & excreted by kidneys; referred to as systemic circulation.
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15
Q

What is jaundice? What does it become clinically apparent?

A

Yellow discoloration of the skin, eyes, and mucous membranes caused by the retention of bilirubin.

Not clinically apparent until total bilirubin is > 34 umol/L.
(Usually well tolerated except in infants).

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16
Q

What is a serum or plasma sample that is yellow in colour referred to as?

A

Serum or plasma that is yellow –> ICTERIC sample

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17
Q

What are the classification of jaundice based on?

A

Jaundice classification based on:

 1. Pre-hepatic jaundice
 2. Hepatic jaundice
 3. Post-hepatic jaundice
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18
Q

What is pre-hepatic jaundice and what is its characteristics for unconj. bilirubin, conj. bilirubin & total bilirubin in blood/serum & urine & urobilinogen?

A

Pre-hepatic Jaundice:
1. Occurs when the problem causing the jaundice occurs prior to liver metabolism. Most commonly caused by excessive amount of bilirubin presented to the liver (seen in Acute & Chronic Hemolytic Anemia, also in neonatal jaundice)
2. Increased unconjugated bilirubin (bound to albumin & can’t be filtered out by kidneys).
3 Normal conjugated bilirubin.
4. Increase Total Bilirubin.
5. Negative for urine bilirubin.
5. Greater output of urine and fecal urobilinogen.

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19
Q

What is hepatic jaundice and its characteristics (similar to the last question)?

A

Hepatic Jaundice - most common type, from damaged liver (i.e. Hepatitis, Cirrhosis, Defective Conjugation, etc.)

  1. Increased conjugated bilirubin
  2. Increased unconjugated bilirubin
  3. Increased total bilirubin
  4. Positive for urine bilirubin
  5. Normal or Elevated for Urine Urobilinogen.
20
Q

What is post-hepatic jaundice and its characteristics?

A

Post-hepatic Jaundice: Biliary obstructive disease (gallstones or tumours) that prevents conjugated bilirubin from being excreted from the body leading to build-up.

  1. Increased conjugated bilirubin.
  2. Normal unconjugated bilirubin.
  3. Increased total bilirubin
  4. Positive for urine bilirubin
  5. Clay coloured stool due to low urobilinogen levels.
  6. Low stool and normal to low urine urobilinogen levels (no bile).
21
Q

What causes jaundice in infants and what is the concern?

A

Jaundice in infants –> Caused by deficiency of uridine disphosphate glucuronosyltransferase (UDPGT), previously handled by Mom.

Concern is the rapid build-up of unconjugated bilirubin which is life threatening.

22
Q

What is Kernicterus (which can occur in infants) and what damage can it cause? What is the therapy to prevent damage?

A

Kernicterus results when unconjugated bilirubin spreads into brain tissue causing permanent brain damage and death.

Occurs with levels > 350umol/L of unconjugated bilirubin.

Phototherapy breaks down unconjugated bilirubin through photo-oxidation (inexpensive and non-invasive).
In extreme cases, exchange transfusion is required.

23
Q

What occurs in cirrhosis and what are some of the causes?

A

Cirrhosis:
Irreversible condition in which scar tissue replaces healthy tissue in the liver.
–> Results in blockage of blood flow and prevents normal functioning of the liver (i.e.. it cannot produce clotting factors, which can lead to hemorrhage).

Causes: Chronic alcoholism, hepatitis B infection, hepatitis C infection, autoimmune diseases, hemochromatosis, etc.

24
Q

How can cirrhosis be treated?

A

Treat by preventing further progression of scar tissue

e.g. abstain from alcohol.

25
Q

Where is a common place for metastatic cancers to metastasize to?

A

90-95% of liver cancers start in other locations and metastasize to the liver.

26
Q

What type of tumours can occur in the liver?

A

Primary liver cancer starts in the liver:

  1. Hepatocellular carcinoma (HCC)
    a) Malignant tumour in the liver.
    b) Cirrhosis can progress to HCC.
27
Q

What disease states can be found in the liver (other than cancer)?

A
  1. Drug and Alcohol Related Disorders –> mild or even liver failure. Discontinue drug and liver function may return to normal.
  2. Ethanol and hepatoxicity –> A functioning liver metabolism uses two enzymes to convert alcohol to acetaldehyde and acetate. Acetate is oxidized to water and carbon dioxide or enters the citric acid cycle for elimination.
    Chronic alcoholism can lead to Alcoholic fatty liver, Alcoholic hepatitis, and Alcoholic cirrhosis.
28
Q

What are the liver function tests for Bilirubin, Enzymes and Synthetic Assessment?

A

Liver Function Tests:
Bilirubin: Total, Conjugated & Urine Bilirubin.
Enzymes: ALT, AST, ALP, GGT, and LDH.
Synthetic Assessment: Serum Proteins (albumin), Coag Factors, & Ammonia. (This tests how well the liver is making proteins).

29
Q

What is another name for conjugated bilirubin?

A

Conjugated bilirubin is also called: Direct Bilirubin.

Also unconjugated bilirubin is called Indirect Bilirubin.

30
Q

What is the Jendrassick-Grof Method to measure total bilirubin? How does it work?

A

Jendrassik-Grof Method:
Bilirubin pigments in serum or plasma are reacted with a diazo reagent (diazotized sulfanic acid), resulting in the production of a purple product azobilirubin. If an accelerator such as Caffeine-benzoate-acetate is added it will solubilize the water-insoluble fraction of bilirubin & yield TOTAL Bilirubin value (all fractions). The reaction can be done without the accelerator to yield only conjugated bilirubin (because it is soluble).

  1. Bilirubin + diazotized sulfanic acid + accelerator (Caffeine-benzoate-acetate) –> 2 azobilirubin (TOTAL Bilirubin)
  2. Bilirubin + diazotized sulfanic acid –> 2 azobilirubin (Unconjugated Bilirubin)

Measure blue colour at 600 nm using a spectrophotometer.

31
Q

How do you determine the unconjugated bilirubin form the Jendrassik-Grof Method?

A

Subject the results from the two reactions as follows:

Unconjugated Bilirubin = Total Bilirubin - Conjugated Bilirubin

32
Q

What are the advantages of the Jendrassick-Grof Method?

A

The Pros of the J-G method are:

  1. Unaffected by sample pH
  2. Unaffected by protein concentration
  3. Sensitive even at low bilirubin concentrations, and
  4. Relatively constant sample blank.
33
Q

What is liver function bilirubinometry?

A

Liver Function Bilirubinometry is the measurement of reflected light from skin using two wavelengths:

  1. 454 nm –> Absorption max for bilirubin & oxyhemoglobin.
  2. 540 nm –> Absorption max for oxyhemoglobin.

Subtract the two values and you get bilirubin result. Done automatically by bilirubinometer.

34
Q

What is application for liver function bilirubinometry?

A

For neonatal population.
Can’t use in adults because presence of cacotenoids interferes with test results.

Can possibly save the baby a poke!!

35
Q

What is the reference range for bilirubin in urine?

A

Negative, should not be present normally.

36
Q

What is the reference range for urobilinogen in urine?

A

Urobilinogen (Urine) –> 3-16 umol/L (measured w/ Ehrlich method)

37
Q

What is the reference range for bilirubin in CSF?

A

Bilirubin in CSF –> < 0.008 absorbance units.

Xanthrochromia from subarachnoid hemorrhage.

38
Q

What is the reference range for direct bilirubin (plasma)?

A

Direct bilirubin (plasma): < 7umol/L

Provides an estimate of the amount of conjugated bilirubin present.

39
Q

What is the reference range for Total Bilirubin (Plasma)?

A

Total Bilirubin (Plasma): 5 - 21 umol/L (6 days old to 60 years)

40
Q

What is important to remember about sample collection for bilirubin analysis? Preferences?

A

All samples must be protected from light.

Prefer fasting plasma samples that are not hemolysed (interferes with diazo reagent) or lipemic.

41
Q

What enzyme is most “liver-specific”?

A

Alanine Transaminase (ALT) –> most “liver specific” and remains elevated longer than AST.

42
Q

Why are enzymes analyzed in regards to liver function?

A

Damage to hepatocytes results in the release of enzymes, therefore enzyme analysis is important in assessing liver function.

43
Q

What is AST, ALP, GGT, and LDH stand for and what conditions are they elevated in?

A 
Aspartate Transaminase (AST) - liver disease (monitoring & diagnosing), also elevated in heart , skeletal muscle & kidney diseases.
Alkaline Phosphatase (ALP) - Used for diagnosing & monitoring treatment of liver, bone, intestinal & parathyroid diseases.
Gamma-glutamyl transferase (GGT) - Diagnosis & monitoring of hepatobiliary diseases.  Screening test for chronic alcoholism.
Lactate Dehydrogenase (LDH)  - non specific. elevate in various disease states.
44
Q

If ALP is increased alone what is the mostly likely diseased organ? And if ALP and GGT are both increased?

A

ALP is increased alone –> Bone
ALP and GGT increased –> Liver

Study more table in slide 24.

45
Q

What tests are done (proteins measured, etc.) to assess hepatic synthesis ability?

A

Hepatic Synthesis Ability Tests:

  1. Measuring serum proteins in liver disease:
    a) Albumins decreased
    b) Globulins decreased
    c) Prothrombin time increased (no clotting factors)
    d) Ammonia increased.

Clinical Chemistry 2 (13 decks)

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