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Clinical Chemistry > Heme Derivatives > Flashcards

Heme Derivatives Flashcards

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1
Q

Is Heme a protein?

A

Heme is not a protein; it is a prosthetic group found in hemoglobin, myoglobin, chlorophyll, cytochromes, and several other enzymes

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2
Q

Where is Heme most concentrated in?

A

Most concentrated in RBCs and Liver cells

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3
Q

Porphyrins

A

Intermediates of the enzymatic pathway of heme synthesis

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4
Q

Elevated porphyrins (porphyria) are either _________ or ________

A

Erythropoietic or hepatic

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5
Q

Synthesis of heme is regulated by _______ feedback of heme (something happens to throw the body out of regulation, your body tries to counteract it to get it back to “balance”…….. Ex: Low on heme, sends biosignals to make more RBCs to make more heme)

A

Negative

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6
Q

Porphyrias

A

Are rare inherited metabolic disorders caused by loss/gain of function enzymes responsible for heme biosynthesis

Porphyrias may also be classified based on their associated symptoms as acute or cutaneous (non-acute).

Can also be caused by liver diseases or and heavy metal poisoning as well

Cutaneous (non-acute) Porphyrias:
- Chronic conditions
- Photosensitivity
- Blistering lesions

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7
Q

Testing used to monitor and diagnose Porphyrias

A

Genetic assays

Function/quantitative assays for enzymes responsible for heme synthesis

Identify/quantify porphyrins and other precursor compounds

(Must be protected from light to prevent degradation)

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8
Q

Urine Porphyrin Testing

A

Stable for 48 hours refrigerated and several weeks frozen

Dilute samples (creatinine <25 mg/dL) inadequate for testing

Porphyrin in urine causes it to have a Port wine color

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9
Q

Stool Porphyrin Testing

A

Must be stored frozen

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10
Q

Blood Porphyrin testing

A

EDTA whole blood samples

Stored in the dark refrigerated

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11
Q

What is Hemoglobin?

A

Is classified as a transport protein.

Its role is to transport oxygen from the lungs to the tissues, and transport carbon dioxide back to the lungs.

Heme synthesis occurs in plasma and mitochondria

The steps catalyzed by ALA dehydratase and ferrochelatase are inhibited by LEAD (how heavy metals inhibit the synthesis of heme)

Hemoglobin synthesis occurs in the immature RBCs located in the bone marrow

2 α-like chains and 2 β-like chains that surround a heme molecule

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12
Q

Synthesis of hemoglobin

A

Synthesized in RBCs located in bone marrow

Iron is inserted into heme to help bind Oxygen

After RBC lysis hemoglobin is transported to the liver to be recycled
- Iron is stored (ferritin)
- Globin chains broken down into amino acids
- Heme converted to bilirubin and urobilinogen

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13
Q

Testing of hemoglobin

A

Hemoglobin concentration is part of CBC

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14
Q

Sickle Cell Anemia

A

HbA mutated to HbS

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15
Q

Thalassemia

A

Mutation reduce the amounts of normal hemoglobin produced

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16
Q

Hemoglobinopathies

A

Mutations globin chain that produce structurally different hemoglobin decreasing RBC survival

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17
Q

How can Hemoglobinopathies be evaluated?

A

Evaluated via electrophoresis

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18
Q

What is myoglobin?

A

Myoglobin is the primary oxygen-carrying protein found in striated skeletal and cardiac muscle, accounting for approximately 2% of total muscle protein.

When striated/cardiac muscle is damaged myoglobin is released

Is a nephrotoxin, severe muscle damage (muscle torn or separated from tendon) can cause harm to the kidneys

Heart attack, muscle injury

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19
Q

Liver

A

Liver is an extremely vascular organ that receives its blood supply from two major sources: the hepatic artery and the portal vein.

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20
Q

Excretory and Secretory Functions (Liver)

A

Processing and excretion of endogenous and exogenous substances into the bile or urine such as the major heme waste product bilirubin

The liver is the only organ that has the capacity to rid the body of heme waste products.

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21
Q

Unconjugated bilirubin

A

(indirect and has not had glucuronic acid attached to bilirubin) is insoluble in water and cannot be removed from the body until it has been conjugated by the liver.

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22
Q

Conjugated bilirubin

A

(glucuronic acid attached to bilirubin) is water soluble and can be secreted from the hepatocyte into the bile canaliculi.

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23
Q

_______ mg of bilirubin is produced per day

A

200-300 mg

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24
Q

Key Points of Bilirubin Metabolism

A

After RBC destruction hemoglobin is broken down into heme and globin

Heme is further broken down into unconjugated bilirubin to be transferred to the liver by albumin

In the liver converts unconjugated bilirubin to conjugated bilirubin

In the intestines conjugated bilirubin is converted to urobilinogen

50-250 mg of urobilinogen is excreted in feces per day

1-4 mg of urobilinogen is excreted in the urine per day

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25
Q

Metabolism and how they can process carbs

A

Second major function of the liver is the metabolic processes.

Metabolism of carbohydrates is one of the most important functions of the liver.

Can process them in one of three ways:
(1) use the glucose for its own cellular energy requirements
(2) circulate the glucose for use at the peripheral tissues
(3) store glucose as glycogen (principal storage form of glucose) within the liver itself or within other tissues

Is responsible for metabolizing both lipids and the lipoproteins and is responsible for gathering free fatty acids from the diet, and those produced by the liver itself, and breaking them down to produce acetyl-CoA

Almost all proteins are synthesized by the liver except for the immunoglobulins (produced by WBCs) and adult hemoglobin (produced mainly in the bone marrow).

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26
Q

Detoxification and Drug Metabolism

A

Serves as a gatekeeper between substances absorbed by the gastrointestinal tract and those released into systemic circulation

System is responsible for the detoxification of many drugs through oxidation, reduction, hydrolysis, hydroxylation, carboxylation, and demethylation

To get rid of drugs, your body will have to get rid of it by using the liver. Abusing drugs impacts your liver.

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27
Q

Jaundice

A

Describes the yellow discoloration of the skin, eyes, and mucous membranes, most often resulting from the retention of bilirubin

Comes from the French word jaune, which means “yellow”

One of the oldest known pathologic conditions reported

Icterus: Yellow discoloration of serum/plasma due to bilirubin concentration

Jaundice is classified based on the site of the disorder:
- Prehepatic jaundice (somethings occurring before bilirubin reaches liver to cause jaundice…ex: hemolytic anemia)
- Hepatic jaundice
- Posthepatic jaundice

28
Q

Prehepatic jaundice

A

Occurs when the problem causing the jaundice occurs prior to liver metabolism.

29
Q

Hepatic jaundice

A

Occurs when the primary problem causing the jaundice resides in the liver.

30
Q

Posthepatic jaundice

A

Results from biliary obstructive disease, usually from physical obstructions.

31
Q

Cirrhosis

A

Clinical condition in which scar tissue replaces normal, healthy liver tissue

Rarely causes signs and symptoms in its early stages, but as liver function deteriorates, signs and symptoms appear including fatigue, nausea, unintended weight loss, jaundice

In the United States, the most common cause of cirrhosis is chronic alcoholism.

Other causes of cirrhosis include chronic infection with the hepatitis B (HBV), C (HCV), and D (HDV) viruses; autoimmune hepatitis; inherited disorders; nonalcoholic steatohepatitis; blocked bile ducts; drugs; toxins; and infections.

32
Q

Tumors

A

Are classified as primary or metastatic. Primary liver cancer is cancer that begins in the liver cells, while metastatic cancer occurs when tumors from other parts of the body spread (metastasize) to the liver.

Malignant tumors of the liver include hepatocellular carcinoma (HCC) (also known as hepatocarcinoma, and hepatoma) and bile duct carcinoma.

Chronic liver failure and cirrhosis are important risk factors for HCC

33
Q

Reye’s Syndrome

A

A group of disorders caused by infectious, metabolic, toxic, or drug-induced disease found almost exclusively in children

Acute illness of noninflammatory encephalopathy, fatty degeneration of the liver, profuse vomiting, and varying degrees of neurological impairment.

Seen with hyperbilirubinemia, & 3x increases in ammonia, ALT, and AST (liver enzymes)

34
Q

Drug- and Alcohol-Related Disorders

A

Primary target organ for adverse drug reactions because it plays a central role in drug metabolism

Many drugs are known to cause liver damage, ranging from very mild transient forms to fulminant liver failure.

 - The most important is ethanol. In very small amounts, ethanol causes very mild, transient, and unnoticed injury to the liver; however, with heavier and prolonged consumption, it can lead to alcoholic cirrhosis.

 - It can also lead to alcoholic fatty liver with inflammation (steatohepatitis) or fatty liver disease
35
Q

Common signs and symptoms of alcoholic hepatitis

A

Fever
Ascites
Proximal muscle loss
Elevated AST, ALT, GGT, and ALP
Total Bilirubin (both direct and indirect) > 5 mg/dL

36
Q

Diazo reaction

A

In old times diazo reaction was used to calculate bilirubin from urine testing to also calculate serum bilirubin

All common bilirubin testing methodologies use a modification of the diazo reaction

37
Q

Bilirubinometry used for testing ______ population

A

Neonatal population

Uses microspectrophotometers to quantify optical density of bilirubin, Hgb, and melanin in subcutaneous layer of infant skin

Not used on adults because carotenoid compounds in adult serum interfere

38
Q

Three fractions of bilirubin are measured to make up Total Bilirubin….

A
  1. Direct Bilirubin (conjugated bilirubin)
  2. Indirect Bilirubin (unconjugated bilirubin)
  3. Delta Bilirubin
39
Q

Direct Bilirubin (conjugated bilirubin)

A

Directly measured
Water soluble, reaction does not require accelerator

40
Q

Indirect Bilirubin (unconjugated bilirubin)

A

Calculated by subtracting direct bilirubin from total bilirubin
Water insoluble, reaction requires accelerator

41
Q

Delta Bilirubin

A

Conjugated bilirubin that is covalently bound to albumin

Only seen in significant hepatic obstruction
To big for glomerular filtration

42
Q

How is unconjugated (indirect) bilirubin calculated?

A

Total bilirubin - Conjugated bilirubin

43
Q

What is the preferred reference method or standardization of bilirubin analysis?

A

There is no preferred reference method or standardization of bilirubin analysis; however, the American Association for Clinical Chemistry and the National Bureau of Standards have published a candidate reference method for total bilirubin, a modified Jendrassik-Grof procedure using caffeine–benzoate as a solubilizer.

Adults Total bili = 0.2 - 1.0 mg/dL
Premature total bili = 10 - 12 mg/dL
Full term bili = 4 - 6 mg/dL

On chart: infants have a much higher bilirubin

44
Q

Sample processingfor Liver Function Tests

A

Serum or Plasma used for testing

Fasting sample preferred in the presence of lipemia (false high bilirubin)

Hemolyzed samples should be avoided (false low results)

If left unprotected from light results may reduce 30%-50% per hour

Storage:
- In the dark
- Stable 2 days at room temperature
- Stable 1 week refrigerated
- Stable indefinitely frozen

If left in light, the bilirubin will be converted to biliverdin

45
Q

Urobilinogen - Urine Liver function test storage

A

Increased in hemolytic conditions and defective liver function (hepatitis)

Absent in biliary obstruction

Uses the Ehrlich reaction (P-dimethylamino benzaldehyde)

Fresh 2 hr sample protected from light

Sitting sample will cause falsely low results due to oxidation of urobilinogen to urobilin

Reference Range: 0.1-1.0 Ehrlich units/ mg

46
Q

Urobilinogen - Feces Liver function test storage

A

Usually detected via physical examination

Semiquantitive methods are available

47
Q

Hepatitis

A

Inflammatory condition of the liver

Viral infection account for most cases observed in the clinical setting, symptoms include:

Acute Onset (“sudden”)
Jaundice
Dark Urine
Fatigue
Nausea
Vomiting
Abdominal Pain
Serum transaminase levels elevated more than 6 months in chronic cases

48
Q

Hepatitis B

A

Known previously as serum hepatitis or long-incubation hepatitis, HBV can cause both acute and chronic hepatitis and is the most ubiquitous of the hepatitis viruses. Viable for 7 days on surfaces.

49
Q

Hepatitis B Surface Antigen (HBsAg)

A

Patient infected but not infectious

Only serological marker in weeks 3-5 of infection

50
Q

Hepatitis B Surface Antibody (anti-HBs)

A

Suggest past infection or vaccine immunity

51
Q

Hepatitis B Core Antigen

A

No test available

Only present during acute stage of infection

52
Q

Hepatitis B Core Antibody, Total

A

Test used to differentiate chronic and recent infections

53
Q

Hepatitis B Core Antibody, IgM

A

Second step in differentiating between chronic and recent infections

54
Q

Hepatitis B Envelope Antigen (HBeAg)

A

HBeAg in the presence of HBsAg predicts severe infection and chronic liver disease

Coorelates with the number of infectious virus particles

(“comes later on in the infection”)

55
Q

Hepatitis B Envelope Antibody (Anti-HBe)

A

Indicates low infectivity

56
Q

Hepatitis A

A

HAV, also known as infectious hepatitis or short- incubation hepatitis, is the most common form of viral hepatitis worldwide. Additional symptoms include fever, anorexia, and malaise.

57
Q

Hepatitis C

A

HCV (originally “non-A non-B hepatitis”) is caused by a virus with an RNA genome that is a member of the Flaviviridae family. HCV is transmitted parenterally.

58
Q

Hepatitis D

A

Hepatitis D virus (also known as delta hepatitis) is a unique subviral satellite virus. It is a small, defective RNA-containing virus that cannot replicate independently but rather requires the HBsAg of HBV for replication.
(Needs Hepatitis B to exist)

59
Q

Hepatitis D

A

Hepatitis D virus (also known as delta hepatitis) is a unique subviral satellite virus. It is a small, defective RNA-containing virus that cannot replicate independently but rather requires the HBsAg of HBV for replication.
(Needs Hepatitis B to exist)

60
Q

Hepatitis E

A

A nonenveloped RNA virus & the sole member of the genus Hepevirus in the family Hepeviridae.

61
Q

Hepatitis F

A

Is an enteric agent that may be transmitted to primates.

62
Q

Hepatitis _____ is the only one that has DNA as a nucleotide

A

B

63
Q

Which Types of Hepatitis has vaccines?

A

A & B

64
Q

Which is the only type of Hepatitis that does not cause chronic infection?

A

A

65
Q

Are serological diagnosis available for all Hepatitis?

A

Yes

Clinical Chemistry (6 decks)

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