Anemias of Increased Destruction of RBCs - Hemolytic Anemias

Hemolytic anemia refers to condition in which there is

increased destruction of RBCs

Is erythropoiesis normal in hemolytic anemia?

Yes, its the lifespan of RBCs that are affected

Hemolytic anemias can be classified by type of poikilocyte present on smear. What types are they?

Schistocytes or spherocytes

what are the 2 locations of hemolysis?

Extravascular and intravascular

Where does extravascular hemolysis occur?

Outside the vessels - spleen, liver, BM

Extravascular hemolysis is characterized by which poikilocyte?

spherocytes

Why do spherocytes form during extravascular hemolysis?

splenic macrophages partially phagocytose RBC membrane, reducing the SA while cell volume stays the same

Where does intravascular hemolysis occur?

In the vessels as they circulate

Intravascular hemolysis is characterized by which poikilocyte?

Schistocytes

In normal destruction of aged RBCs, the globin chains in hemoglobin are…

returned to amino acid pool

In normal destruction of aged RBCs, the iron in hemoglobin is…

separated and stored

In normal destruction of aged aged RBCs, the protoporphyrin (heme ring) is…

degraded into bilirubin

What form of bilirubin is it when protoporphyrin is broken down?

unconjugated (indirect)

Is unconjugated bilirubin water-soluble or non-soluble?

non water-soluble

In conjugated bilirubin water-soluble or non-soluble?

water-soluble

After the unconjugated bilirubin enters plasma from the spleen, it binds to … before reaching the liver

albumin

The liver adds 2 glucose molecules on the bilirubin making it…

conjugated (direct)

The conjugated bilirubin leaves the liver as bile and is dumped into GI tract. Here the GI bacteria converts bilirubin into…

urobilinogen

Is urobilinogen secreted and in what?

Yes. majority in stool, some in urine

The path of normal destruction of heme rings

1. heme ring broken into unconjugated bilirubin

2. Bilirubin is secreted into the plasma and binds to albumin

3. reaches the liver and is conjugated with glucose

4. Liver secrets it as bile and is dumped into the GI tract

5. The GI bacteria convert bilirubin into urobilinogen

6. excreted as stool or urine

What is increased in extravascular hemolysis?

• unconjugated bilirubin in serum

• urobilinogen in urine and stool

When RBC is hemolyzed intravascularly, free hemoglobin binds to the protein…

haptoglobin

In severe intravascular hemolysis, not enough protein is produced, so it accumulates in plasma. What is this known as?

Hemoglobinemia (hemoglobin in plasma)

Usually, free hemoglobin can be absorbed in the kidneys and recycled. But when there is excess free hemoglobin from intravascular hemolysis, it will appear in the urine. This is known as…

hemoglobinuria

What is present in the urine that shows that the kidney has filtered a significant amount of hemoglobin?

Hemosiderinuria

What is hemosiderin?

Iron converted to hemosiderin in the renal tubes

What is increased in intravascular hemolysis?

• free hemoglobin in plasma

• hemoglobinuria

• hemosiderinuria

• unconjugated bilirubin

Why do unconjugated bilirubin levels rise during hemolytic anemias?

The rate of hemolysis and bilirubin production exceeds the liver’s ability to conjugate and excrete it

What is a disease of hemolytic anemia?

Jaundice due to deposits of bilirubin

These signs are indicative of?

• Elevated RETIC

• Splenomegaly

• schistocytes or spherocytes

Hemolytic anemia

Why does splenomegaly occur during hemolytic anemias?

The spleen is working overtime to remove defective RBCs

Hereditary hemolytic anemias are intrinsic or extrinsic?

Intrinsic

Intrinsic hemolytic anemias meaning that

defects are within the red cells

Acquired hemolytic anemias are intrinsic or extrinsic?

Extrinsic

Extrinsic hemolytic anemias meaning that

defects are caused by the action of external acts upon the normal RBCs

Hereditary hemolytic anemias are usually destroyed 

extravascularly

Hereditary hemolytic anemias outline

Membrane defects

• hereditary spherocytosis

• hereditary elliptocytosis

Enzyme defects

• G6PD deficiency

• pyruvate kinase deficiency

Globin defects

• hemoglobinopathies

• thalassemias

Among whites, … is the most commonly inherited anemia

Hereditary spherocytosis (HS)

Hereditary spherocytosis and Hereditary elliptocytosis (HE) are due to the deficiency of the cell membrane protein…

spectrin

Spherocytes cannot be filtered in the spleen as easily because of their … They get trapped in the cords and are phagocytized by macrophages.

lack of deformability

What test is increased in HS?

osmotic fragility (decreased stability of RBC)

How is the osmotic fragility test performed?

RBCs are put in hypotonic solns where water enters the cells until equilibrium is achieved. Because spherocytes have dec SA:V ratio, they lyse WAY easier

In HS, patients may experience splenomegaly and require

splenectomy

Is there anemia present in HS?

Yes it may be present

Is there anemia present in hereditary elliptocytosis (HE)?

No, also no hemolysis. Its just a membrane defect

The hereditary hemolytic anemia glucose-6-phosphate dehydrogenase deficiency (G6PD) is due to a … defect

enzyme

What is the most common erythrocyte disorder?

G6PD

What does the G6PD affect?

The hexose monophosphate shunt. NADP is not reduced to NADPH, GSH does not remain reduce, and Hemoglobin is oxidized at a much higher rate

G6PD does not cause problems until exposed to all except

Reductant drugs