Normocytic Anemia

Question 1

2 main causes of normocytic anemia?

Answer 1

Increased peripheral destruction or underproduction

Question 2

What helps us distinguish between whether a normocytic anemia is due to the bone marrow problems or peripheral destruction and how do we use it?

Answer 2

Reticulocyte count
Normal count is about 1-2% of RBC total. In an anemia, bone marrow can increase production to greater than 3%. However, in an anemia, the R count is falsely evaluated because it is a percentage of total RBC and we have lost some in anemia. So we need to correct by taking the r count * (HCT/45). If the corrected is over 3% then the bone marrow is good and its peripheral hemolysis. If it is under 3%, then it is a bone marrow problem not able to produce.

Question 3

What are the two types of peripheral destruction fo RBCs?

Answer 3

Extra vascular hemolysis due to the RES, which are macrophages in the spleen, lover and LN
Intravascular hemolysis

Question 4

Explain how hemoglobin is broken down by macrophages and how they leads to clinical findings?

Answer 4

Broken down into globin and heme. Heme is broken down iron and proto. Iron is recycled. Proto is broken down to unconjuagted bilirubin and sent to the liver to be conjugated and excreted. In hemolysis, there is too much bilirubin for the liver to conjugate, exceeds its rate, so it spills into the blood and causes jaundice. Also, gall stones.
Marrow hyperplasia because of the anemia

Question 5

When RBCs are destroyed intravascularly, what happens to hemoglobin?

Answer 5

We want to preserve as much hemoglobin as possible, so it is picked up by haptoglobin and sent to the spleen.

Question 6

4 lab values of intravascular hemolysis?

Answer 6

Hemoglobin in the blood
Hemoglobin in the urine
Hemosiderin (renal tubule cell with iron) in urine
Low haptoglobin level

Question 7

Explain whats going on with hereditary spherocytosis, is it intravascular or extravascular?

Answer 7

Inherited defect in the RBC cytoskeleton-membrane tethering proteins (ankyrin and spectrin). These RBCs lose parts of membrane over time and become smaller and spherical, not bi concave. This causes them to not navigate through he spleen very well and the macros end up eating them causing anemia.

Question 8

2 lab values of this?

Answer 8

Increased RDW and MCHC

Question 9

3 clinical signs?

Answer 9

Big spleen, jaundice and risk for gall stones.

Question 10

How do we diagnose and treat this? What still persists after the spleen is removed and what do we call them?

Answer 10

Osmotic fragility test. Normal RBCs are more resilient to hypotonic solution but these sphere guys will explode.
Remove the spleen. Remember the sphere cells are not harmful, its just the spleen destroys them.
Now, the sphere guys still persist and actually we can get something called Howell jolly bodies. The spleen is in charge of making sure RBCs don’t have a nucleus or taking out fragments that were left. Well, after removal of the spleen, that doesn’t happen anymore so we can see spheres with DNA fragments.

Question 11

What is the mutation in sickle cell disease?

Answer 11

Autosomal recessive mutation in the beta chain of hemoglobin. Replaces a normal glutamic acid with valine. Sickle cell disease occurs when two mutated/abnormal genes

Question 12

Explain what 3 things causes the RBCs to actually sickle and what then is the effect?

Answer 12

The risk of suckling occurs in hypoxia, dehydration and acidosis.
Then, under conditions of deoxygenation, the sickle cells polymerize/aggregate causing problems.

Question 13

What is the first big effect of cells sickling and de sickling through the micro vasculature and what 3 things happen?

Answer 13

RBCs membranes get damaged

1. Extravascualr hemolysis, they are eaten/destroyed by RES
2. Intravascular hemolysis
3. Eryhtroid hyperplasia resulting in blood producing in skull and face and liver and spleen making blood.

Question 14

Extensive sickling leads to vaso occlusion throughout the body. The following questions will be the effect on certain parts of the body. Start the bone?

Answer 14

Dactylitis. Swollen hands and feet because of infarction to bone. Common in kids.

Question 15

What happens to the spleen and what is the consequence?

Answer 15

Shrinks and becomes fibrotic. Essentially doesn’t work.
Increased risk of infection by encapsulated pathogens like strep pneumonia and h influenza. This is the most common cause of death in kids.
Increased risk of infection by salmonella osteomyelitis

Question 16

Lungs?

Answer 16

Occlusion of the pulmonary circulation. often leads to pneumonia and this is the most common cause of death in adults.

Question 17

Kidneys?

Answer 17

Renal papillary necrosis resulting in gross hematuria and proteinuria

Question 18

Explain the big difference between sickle cell trait and sickle cell disease?

Answer 18

Most people with sickle cell disease have HbS as 90% of their hemoglobin because both genes are mutated.
People with trait only have one gene that is S, so they still can make normal beta leading to normal hemoglobin.
What is also important is anyone with trait and not disease has less than 50% of sickle hemoglobin for it to be asymptomatic. If it goes over 50% it becomes symptomatic.

Question 19

What is the exception to this 50% rule of being symptomatic vs. asymptomatic? What is the effect and problem with this exception.

Answer 19

In the renal medulla, it is a very hypoxic environment, so sickling can occur even below 50%. This will lead to micro infarctions and hematuria, eventually losing the ability to concentrate the urine.

Question 20

2 ways we can confirm the presence of sickle cell trait?

Answer 20

Metabisulfate causes any cell with any HbS to sickle.

Hb electrophoresis can tell us the presence of HbS

Question 21

What 3 types of hemoglobin are found in sickle cell disease and what 3 types of hemoglobin are found in trait?

Answer 21

HbS, HbF, and HbA

HbA, HbF and HbA2

Question 22

3 things to remember about Hemoglobin C? What is different about it?

Answer 22

The glutamic acid is replaced by lysine
Mild anemia due to extravascular hemolysis
Characteristic HbC crystals seen in RBCs on blood smear.

Question 23

3 diseases that are normocytic anemia with mostly extravascular hemolysis?

Answer 23

Hereditary spherocytosis
Sickle cell
Hemoglobin c