Pathoma: Red Blood Cell Disorders

Question 1

What does hemoglobin made of?Explain the 4 reasons that cause microcytic anemia.

Answer 1

Heme + globin, heme itself consists of iron and protoporhyrin.Iron deficiency anemia is when there is not enough iron to make heme, Thalessemia is when the globin chains are defective, third cause is when there is lack of production of protoporphyrin which causes Sideroblastic Anemia and finally the last cause is when heme is locked away in ferritin in macrophages so its not available to be used, this is called Anemia of Chronic Disease

Question 2

Explain iron absorption and storage.What is the key regulatory step in iron absorption that determines if the body will absorb it?

Answer 2

Absorbed in the duodenum by enterocyte
Enterocyte transfer iron into the blood via surface membrane transporter called ferroportin
In the blood iron is carried while bound to transferrin
Stored in liver and bone marrow while bound to ferritin

Transfer of iron into the blood via ferroportin is the key regulatory step in iron absorption. Physiologically the human body has no way of getting rid of iron.

Question 3

What does the following measure?

• Serum iron
• TIBC
• % sat
• Serum ferritin

Answer 3

Serum iron measures how much iron is there in the blood, TIBC measures transferrin levels in the blood, % sat measures how many transferrin are actually bound to iron and serum ferritin measures how much iron is stored in the liver and bone marrow

Question 4

How can gastrectomy lead to iron deficiency?

Answer 4

Iron can only be absorbed in the body when its oxidation state is 2+, this is promoted by HCl in the stomach, gastrectomy leads to poor absorption of iron since it stays in its 3+ oxidation state”Fe 2 goes in 2 the body”

Question 5

What are the stages of iron deficiency?

Answer 5

• Storage iron is depleted
• Serum iron is depleted
• Normocytic anemia
• Microcytic, hypochromic anemia
  It is very important to know that normocytic anemia precedes microcytic anemia in iron deficiency.

Question 6

Clinical findings of iron deficiency?

Answer 6

• Anemia
• Koilonychia = spoon shaped nails
• Pica = Ingesting inedible things

Question 7

Lab findings of iron deficiency anemia?

Answer 7

FEP is free erythrocyte proptoporhyrin

Question 8

Plummer Vinson Syndrome

Question 9

Explain the pathophysiology of anemia of chronic disease?

Answer 9

In chronic disease or cancer inflammatory cytokines are released for a long period of time, once such inflammatory molecules is hepcidin, it limits iron transfer from macrophages to erythroid precursors and suppressed EPO production, leading to anemia

Question 10

What are the lab findings of anemia of chronic disease?

Answer 10

High ferritinTIBC is lowSerum iron is low% sat is lowFEP is high.(This all should make sense due to the etiology of the disease)

Question 11

What classic cell do we see in H&E in sideroblastic anemia? Where does that cell arise from?

Answer 11

Nucleus of a erythroblast is surrounded by mitochondria, when protoporphyrin cannot be made iron is stuck inside the mitochondria (recall that this reaction takes place inside the mitochondria) and hence all these iron loaded mitochondria accumulate to form a ringed sideroblast.

Question 12

Lab findings of sideroblastic anemia?

Answer 12

“Iron overloaded state” - hemachromatosis and sideroblastic anemia share the same lab findings as far as the iron panel is concerned.

Question 13

What patients are classically seen as vitamin B6 deficient?

Answer 13

Those who are treated with isoniazid.

Question 14

What is the hallmark finding in beta thalessemia minor?

Answer 14

Increased HbA2 on Hb electrophoresis, usually its 2% but in this case it can be as high as 5%

Question 15

Explain how does cobalamin interacts with THF?

Answer 15

THF is methylated and passes on its methyl group to vitamin B12, this then passes the methyl group on to homocyteine to become methionine

Question 16

Where is folate absorbed?

Answer 16

Jejunum

Question 17

What are the findings of folate deficiency macrocytic anemia?

Answer 17

Folate serum levels are low, RBCs are macrocytic, hypersegmented neutrophils, glossitis.Homocysteins is high and methylmalonic acid is normal

Question 18

What is more common, folate or vitamin B12 deficiency?

Answer 18

Folate deficiency as B12 stores can last for years as opposed to folate stores that last for 6 months

Question 19

What is the most common cause of B12 deficiency?

Answer 19

Pernicious anemia, antibodies are made against parietal cells of the stomach and intrinsic factor is not made anymore

Question 20

What are other reasons for B12 deficiency?

Answer 20

Pancreas make the proteases so that B12 can dissociate from heptocorrin, a transport molecule made by salive, he called it B-binder

Question 21

Clinical lab findings of B12 deficiency?

Question 22

How are RBCs cleared in extravascular hemolysis?

Answer 22

Cleared by the reticuloendothelial system which involves macrophages in the spleen, liver and lymph nodes

Question 23

Explain the RBC clearence process during intravascular hemolysis. What is a clinical and lab finding of this?

Answer 23

As Hb is released during intravscular hemolysis, the free Hb will bind to haptolgobin found in the serum which will take it to spleen for recycling. As a result, we get the following clinical lab findings:

• Decreased haptoglobin serum levels
• Hemaglobinuria
• Hemaglobinemia
• Hemosiderinuria (Hb goes into the renal tubular cells which convert it and store it as hemosiderin, these cells are eventually sloughed off and we get hemosiderin in urine as a result)

Question 24

What are some of the lab findings that we see in hereditary spherocytosis?What proteins are responsible for this?What are the clinical features?

Answer 24

Proteins involved in maintaining the cytoskeleton structure of RBCs are mutated, these proteins are spectrin, ankyrin and band 3.1Lab findings are:
* High RDW
* High MCHC
Clinical features are: anemia. jaundice, increased risk of gallstones, increased risk of aplastic crisis with parvovirus infection.

Question 25

How is hereditary sperocytosis diagnosed?

Answer 25

Diagnosed via osmotic fragility test, spherocytes are increasing fragile in hypotonic solution due to defective cytoskeleton

Question 26

What is a classic presentation of sickle cell anemia in a 6 month old?

Question 27

What is the most common death in adults with sickle cell disease?What is it precipitated by?

Answer 27

Vaso occlusion in the pulmonary microcirculation is called acute chest syndrome. Presents with chest pain, shortness of breath and lung infilterates.These patients develop acute chest syndrome due to pneumonia, pneumonia often preicipitates veno occlusion in pulmonary circulation in patients with sickle cell disease.This is the most common cause of death in adults with SCD.

Question 28

What are the renal findings in sickle cell disease?

Answer 28

Renal papillary necrosis which leads to gross hematouria and proteinuria

Question 29

Explain sickle cell trait.

Answer 29

• Presence of one mutated and one normal beta chain
• Results in less than 50% HbS in RBCs, so the cells dont sickle since for sickling we need to more than half HbS.
• Generally asymptomatic, can have mild anemia However it has renal medulla complications:
• Extreme hypoxia and hypertonicity causes the cells to sickle
• Initially presents with microinfarctions
• Later causes microscopic hematouria and eventually decreased ability to concentrate the urine

Question 30

How is SCD dx?

Answer 30

Metabisulfate screen: causes cells with any amount of HbS to sickle, so its positive in trait and disease.Hb electrophoresis is done to confirm the diagnosis.

Question 31

Hemaglobin C disease

Question 32

Explain paroxysmal nocturnal hemaglobinuria

Answer 32

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
Acquired (not inherited) defect in myeloid stem cells resulting in absent glycosy 1 phosphatidyl inositol (GPI); renders cells susceptible to destruction by complement
* Blood cells coexist with complement.
* Decay accelerating factor (DAF) on the surface of blood cells protects against complement-mediated damage by inhibiting C3 convertase.
* DAF is secured to the cell membrane by GPI (an anchoring protein).
* Absence of GPI leads to absence of DAF, rendering cells susceptible to complement-mediated damage. Intravascular hemolysis occurs episodically, often at night during sleep,
* Mild respiratory acidosis develops with shallowbreathing during sleep and activates complement.
* RBCs, WBCs, and platelets are lysed,
* Intravascular hemolysis leads to hemoglobinemia and hemoglobinuria (especially in the morning); hemosiderinuria is seen days after hemolysis.
* Sucrose test is used to screen for disease (sucrose activates complement); confirmatory test is the acidified serum test or flow cytometry to detect lack of CD55 (DAF) on blood cells, Main cause of death is thrombosis of the hepalic, portal, or cerebral veins.
* Destroyed platelets release cytoplasmic contents into circulation, inducing th rombosis.
* Complications include iron deficiency anemia (due to chronic loss of hemoglobin in the urine) and acute myeloid leukemia (AML), which develops in 10% of patients.