Clinical Hematology: Chapter 1 (RBC Catabolism & Hemolysis)

What is the normal amount of RBC's that breakdown in a single day?

1% RBC's breakdown in a single day.

During the breakdown of RBC's what happens to each component of Hemoglobin?

-Fe is recycled, either directly used or stored

-Amino acids are used for other functions, can't be stored

-Protoporphyrin is recycled into bile salts, stored in the gallbladder, and eventually excreted.

During Extracellular Hemolysis what are the two organs mostly responsible for RBC breakdown?

-Spleen (mostly takes care of old RBC's)

-Liver (mostly takes care of damaged/distored RBC's)

How do phagocytes in the liver (kupffer cell) Breakdown RBC's

- Kupffer cell exhibits a receptor specifically for C3B compliment fragment that's attached to an RBC which starts the breakdown, during which the kupffer cell engulfs the spill.

How does intravascular hemolysis occur?

RBC breakdown can happen in the blood vessel when a complement fragment is large enough to create a hole in the cell.

What component of the complement system can lead to RBC breakdown in intravascular hemolysis at non-normal rates?

C5b6789 (membrane attack complex)

What condition could complement system C5b6789 be associated with?

Autoimmune hemolytic anemia

Please list the two types of recycling that attribute to the 1% RBC breakdown that occurs in a day, and list how much each attributes to cell breakdown.

-intravascular hemolysis: attributes 10%

-extravascular hemolysis: attributes 90%

What are some ways that intravascular hemolysis can be exacerbated?

-heinz bodies (precipitants on red cell membrane)

-intercellular parasites such as malaria and babesia

What are the two carriers involved in extravascular hemolysis?

-transferrin

-albumin

What is the role of transferrin during extravascular hemolysis?

transferrin is a carrier for Fe, more specially it carries iron as Fe3+ (this is the ferric state) to bone marrow for erythroblast.

During extravascular hemolysis hemeoxygenase takes off a CO molecule from protoporphyrin (nitrogenous ring of rings) to form what?

-Bilrubin (indirect bilrubin; unconjugated)

(can be described as a string of rings)

Name the enzyme that breaks down heme in extravascular hemolysis.

hemeoxygenase

list the oxidation states of heme as its broken down in extravascular hemolysis

-1st oxidation state:

biliverdin (green)

-2nd oxidation state

Bilirubin (yellow)

What is the role of albumin during extravascular hemolysis?

albumin is a carrier for the fat soluble, indirect bilirubin. albumin will bring bilirubin to the liver so it can be changed into a water soluble form.

where is most of our Fe kept in the body?

In Hgb. Approximately 2/3 of the total Fe in the human body is used in Hgb.

After indirect bilirubin gets to the liver via an albumin carrier what is the next step in the process of hemolysis

glucuronyl transferase adds a water soluble group to bilirubin transforming it into its conjugated state called direct bilirubin.

The name of the enzyme responsible for making indirect bilirubin water soluble

glucuronyl transferase

Name the enzyme that breaks down the nitrogenous ring of rings in Hgb

hemeoxygenase

What is considered to be the first breakdown product from heme in extravascular hemolysis?

indirect bilirubin or unconjugated bilirubin

A measurable product of heme breakdown in its final oxidation states after bacterial enzymes have been added is called?

Urobilinogen

It can become stercobilin when leaving in stool or it can pass through kidneys if not reabsorbed.

bilirubin found in stool is called?

stercobilin

what are the products in extravascular hemolysis that can be used to indicate hemolytic anemia or liver function problems?

increased levels/measurement of:

-indirect bili

-direct bili

-urobilnogen

in intravascular hemolysis what are the two routes that ultimately cause RBC breakdown?

-alpha and beta dimers are separated in solution

-Fe is oxidized

A carrier seen in intravascular hemolysis that is responsible for carrying dimers that have been separated in solution to the liver is called?

Haptoglobin

A decrease in haptoglobin could indicate what?

hemolytic anemia or increase red cell breakup

what is methemoglobin?

is Hgb but the iron is in Fe+3 state

What carrier is responsible for carrying methemoglobin to liver in intravascular hemolysis

hemopexin

A decrease in hemopexin or haptoglobin mean could mean?

Increased RBC breakdown or hemolytic anemia

in intravascular hemolysis this carrier binds to methemoglobin when hemopexin is unavailable.

albumin

why is the binding of methemoglobin to albumin important when hemopexin is unable?

to prevent loss of Fe by the kidneys.

In hemolytic anemia due to increase intravascular RBC death passed the normal limit where might Hbg travel?

Hgb passes through the kidneys

in intravascular hemolysis what happens when the kidney attempts to break down Hgb?

Hgb goes to the parenchyma of the kidney where Hgb get trapped in the tubular cells and are partially broken down, these tubular cells slough off into the urine with the trapped precipitated Fe+3 (iron). This is called hemosiderinuria.

What stain is used to observe hemosiderin (Fe+3)

Prussian blue stain

The presence of what two compounds is a sign that intravascular hemolysis is happening extensively, is too much for the body to handle, and is a good sign of hemolytic anemia?

(hint kidneys are involved)

Hemosiderinuria and Hemoglobinuria

In the liver glucuronyl transferase oxidizes indirect bilirubin by adding a polar group what is this group called and why is it an important step?

The polar group that is added is glucuronic acid and its essential to make bilirubin water soluble so that It can reabsorb and excreted.

What is it called when you have an excess of Hgb in the plasma because RBC breakup is so great?

Hemoglobinemia

What substance appears in the urine when Hgb goes through the kidneys and the kidney can't break it down at all (the hgb is unadulterated)?

Hgb ends up in the urine and is called hemoglobinuria

What carrier takes unconjugated bilirubin (indirect bilirubin) to the liver?

albumin

What is normal value of WBC count?

4.5-11.0 x 10^3/uL

(4,500-11,000uL)

What is the normal value of RBC count for both male and female?

Male: 4.50-6.00 x 10^6uL (4,500,000-6,000,00uL)

Female: 4.00-5.50 x 10^6uL (4,000,000-5,500,000uL)

What is normal level of Hemoglobin for both men and women?

Male: 13.5-18.0 g/dL

Female: 12.0-16.0 g/dL

Normal Hematocrit level for both males and Females?

Male: 40-54%

Female: 36-48%

What is Normal MCV value?

80-98 um3

What is Normal MCH value?

27-32 pg

What is normal MCHC range?

32-36 g/dL

Normal RDW range?

11.5-14.5%

Normal Platelet count?

140-415 x 10^3/uL

(140,000-415,000ul)

MPV range?

7.4-10.4 fL

What are the tests you could preform to check whether a patient might be suffering from hemolytic anemia or liver disease? What results would indicate this clinical diagnosis?

-haptoglobin (decreased levels)

-Hemopexin (decreased levels)

-Urobilinogen (increased levels)

-direct and indirect bilirubin

(increased levels)

-Hemoglobinuria (increased levels)

-Hemosiderinuria (increased levels)

-Liver function test (LFT) [increased levels, enzymes]

What are symptoms that could indicate hemolytic anemia or liver disease?

-Jaundice

-Fatigue

-chills and fever

-skin pallor

-increased heart rate, pulse and Blood pressure.

-Dark/brown urine