Red Blood Cell Disorders

Question 1

What are the mechanisms of Anemia?

Answer 1

RBC loss
Decreased RBC Survival
Decreased RBC Production

Question 2

What can cause RBC loss?

Answer 2

Hemorrhage

Question 3

What can cause Decreased RBC Survival?

Answer 3

Hemolysis

RBCs usually survive 120 days, but destroying them earlier can cause anemia

Question 4

What can cause Decreased RBC production?

Answer 4

Nutritional deficiencies
Aplastic anemia
Myelophthistic processes

Question 5

How much blood loss can a young, healthy individual tolerate with minimal symptoms?

Answer 5

Up to 1000mL (1L) of rapid blood loss with minimal symptoms

Question 6

Rapid loss of 2000mL (2L) of blood can lead to what?

Answer 6

Shock

Question 7

Loss of RBC stimulates what?

Answer 7

Erythropoeitin, which leads to increased RBC production

Question 8

What causes chronic hemorrhage

Answer 8

Rate of RBC loss exceeds production

It is typically secondary to GI bleeding or increased menstrual bleeding

Question 9

What are the two types of Intravascular hemolysis

Answer 9

Immune

Non-immune

Question 10

What causes immune intravascular hemolysis?

Answer 10

Transfusion reaction

Not seen much anymore

Question 11

What causes non-immune intravascular hemolysis?

Answer 11

Mechanical trauma - turbulence caused by a bad heart valve

Question 12

What is a key feature of intravascular hemolysis?

Answer 12

A decrease in free haptoglobin - haptoglobin binds to hemoglobin released form lysed RBCs and takes it to the liver to be cleared

Question 13

What happens if plasma hemoglobin exceeds the amount of available haptoglobin

Answer 13

Free hemoglobin is excreted to the kidney

Question 14

Free hemoglobin effect on the kidney

Answer 14

Hemoglobin is toxic to the kidney, and iron that accumulates in the proximal tubular cells
That iron can only get excreted if tubular cells are shed and lost
Can lead to hyperbilirubinemia and jaundice

Question 15

Extravascular hemolysis

Answer 15

Destruction of RBCs in reticuloendothelial system (liver and spleen)
Hemoglobin is broken down intracellularly

Question 16

What happens to hemoglobin that is broken down intracellularly (via Extravascular hemolysis)

Answer 16

Free hemoglobin is not released directly into the blood and urine, but hemoglobin products (bilirubin) are increased (hyperbilirubinemia) and jaundice may result

Question 17

What are some clinical complications of extravascular hemolysis?

Answer 17

Spleen and liver may become enlarged

Chronically elevated levels can promote formation of gallstones

Question 18

Extrinsic defects causing Hemolytic Anemia are what?

Answer 18

Immune-related

Question 19

Autoimmune Hemolytic Anemia

Answer 19

Pt makes autoantibodies to his/her own RBCs
The antibody-coated cells can be lysed or removed via the reticuloendothelial system
Phagocytosis of antibody-coated RBCs can lead to partial loss of RBC membrane, creating spherocytes

Question 20

Erythroblastosis fetalis

Answer 20

Caused by blood group incompatibility between the mother and the fetus
An extrinsic hemolytic anemia

Question 21

Intrinsic defects causing Hemolytic anemia are what?

Answer 21

Non-immune related

Question 22

Hereditary Spherocytosis

Answer 22

RBC membrane defect leading to hemolytic anemia
Causes a loss of deformability of the RBC
Can be a qualitative or quantitative deficiency of spectrin (structural protein of the cytoskeleton)
Cells can’t squeeze through the splenic sinusoids, so the effected cells are sequestered and destroyed in the spleen

Question 23

Sickle-Cell Anemia cause

Answer 23

Single b.p. a.a. substitution at the position 6 of the beta-chain
Defect of the globin chain causing hemoglobin to gel upon deoxygenation

Question 24

Sickle-Cell Anemia mechanism

Answer 24

Low oxygen tension induces hemoglobin S polymerization, leading to a sickled shape
The cells are rigid and prone to sequestration
Sickled cells can also be trapped in microcirculation - leading to ischemia

Question 25

Sickle-Cell Anemia Complications

Answer 25

Moderate to severe anemia | Autosplenectomy - spleen fibroses because the over-engorement of macrophages

Question 26

If 8% of all African-Americans in the US are heterozygous, why are they not effected?

Answer 26

It's Autosomal Codominant They're asymptomatic because less than half the hemoglobin is abnormal, and the concentration of HbS is insufficient to cause sickling

Question 27

Thalassemia

Answer 27

Diminished or absent synthesis of the a or B chains of hemoglobin, leading to decreased globin produciton The ineffective RBC produciton in the bone marrow will cause the bone marrow to grow Extravascular RBCs are lysed - leads to hemolytic anemia

Question 28

Glucose-6-Phosphate Dehydrogenase Deficiency

Answer 28

Red cells are susceptible to oxidant injury by drugs or toxins Denaturation of oxidized hemoglobin causes hemoglobin to precipitate and attach to the RBC membrane The RBC becomes less flexible and subject to extravascular hemolysis RBCs look like Bite Cells (looks like Pacman or a bite was taken out) Pts are asymptomatic without a trigger

Question 29

Schistocytes

Answer 29

RBC fragments Indicate that there was a hemolysis due to mechanical trauma They look like a popped balloon

Question 30

What are the settings of Iron Deficiency Anemia

Answer 30

``` Inadequate Intake (seen in infants) Increased demands (pregnancy) Increased loss (due to bleeding) ```

Question 31

What would the blood make up of a Iron deficient patient look like?

Answer 31

Decrease serum iron Decreased serum ferritin Increased serum iron-binding capacity Hypochromatic RBCs

Question 32

What causes Megaloblastic Anemia

Answer 32

Vitamin B12 and Folate deficiencies

Question 33

What is the pathology of Megaloblastic Anemia

Answer 33

B12 and Folate are responsible for the synthesis of thymidine - a base of DNA Without thymidine, mitosis is delayed - and the cell grows but can't divide (hence the name Megaloblastic)

Question 34

Vitamin B12

Answer 34

Present in Animal foods Large body stores In addition to hematologic abnormalities, deficiency can cause neurologic symptoms Deficiency can be due to decreased intake (vegans), malabsorption, pernicious anemia

Question 35

Folic Acid

Answer 35

In fresh veggies Body stores are small Deficiency can be due to increased requirements, decreased dietary intake, malabsorption

Question 36

How can we tell Vitamin B12 deficiency of Folic Acid deficiency apart?

Answer 36

They're indistinguishable clinically, so we have to rely on lab tests

Question 37

Polycythemia

Answer 37

An increase in Red Blood Cell mass

Question 38

Relative Polycythemia

Answer 38

Occurs with hemoconcentration from dehydration or vomitting

Question 39

What are the types of Absolute Polycythemia?

Answer 39

Primary | Secondary

Question 40

Primary Absolute Polycythemia

Answer 40

Neoplastic proliferations of RBCs that are unregulated | Treatment is removal of excess RBCs by phlebotomy

Question 41

Secondary Absolute Polycythemia

Answer 41

``` Increased erythropoeiting production Can be due to: -cyanotic heart disease -pulmonary disease -living at high altitudes -erythropoeitin-producing tumors ```

Question 42

How can you tell if it is primary or secondary polycythemia

Answer 42

If there is elevated erythropoeitin, it is secondary | If not, it's primary