Week 3

Question 1

Mutation that causes sickle cell anemia

Answer 1

point mutation of the beta globin gene (HbS) - 6th B-globin codon goes from GAG (glutamic acid) to GTG (valine)

Question 2

Mode of inheritance of sick cell anemia

Answer 2

Autosomal Recessive

Question 3

Typical clinical presentation of sickle cell disease in an infant

Answer 3

Fatigue, activity intolerance, exertional dyspnea, hypersplenism, pain from vaso-occlusive crisis

Question 4

Factors that contribute to anemia in patient with sickle cell

Answer 4

-sickling of cells cause the membrane to get broken down which then causes hemolysis of that RBC resulting in anemia

Question 5

Aplastic anemia

Answer 5

Your reticulocyte count is low. That tells your doctor your bone marrow isn’t making red blood cells fast enough.

Question 6

Hemolytic anemia

Answer 6

Your reticulocyte count is high. This type of anemia destroys red blood cells before they would normally die, so your bone marrow has to work overtime to replace them.

Question 7

Iron deficiency anemia

Answer 7

A low reticulocyte count also can be a sign of this. It happens when your body doesn’t have enough iron to make red blood cells

Question 8

Pernicious anemia

Answer 8

Your body doesn’t get enough vitamin B12, also producing a low reticulocyte count.

Question 9

Anisocytosis

Answer 9

RBC’s not equal size

Question 10

Poikilocytosis

Answer 10

Variation in cell shape

Question 11

Polychromatophilia

Answer 11

more staining of RBC in histo slide

Question 12

PMI

Answer 12

the point where there is a maximal impulse against the chest that can be felt. Most often, this is from the apex or tip of theheart: also referred to as the apical impulse. However, in certain conditions, the apex of theheartdoes not cause thePMI.

Question 13

Fremitus

Answer 13

vibratory tremors that can be felt through the chest by palpation. To assess for tactilefremitus, ask the patient to say “99” or “blue moon”. While the patient is speaking, palpate the chest from one side to the other.

Question 14

Different forms of Hgb found in an infant

Answer 14

Hemoglobin A1: low levels indicate anemia or blood loss
Hemoglobin A2: high levels may indicate thalassemia
-Hemoglobin F: normally high in infants, long term elevation is indicative of thalasemia
-Hemoglobin S: presence is abnormal, indicative of sickle cell disease

Question 15

hemoglobin electrophoresis

Answer 15

Hemoglobin electrophoresis measures different types of hemoglobin present in the blood. This is useful to identify presence of any abnormal hemoglobin that should not be present.

Question 16

Describe how sickled red blood cells cause vaso-occlusive pain

Answer 16

Hemoglobin S molecules tendto stick together and form aggregates. These aggregates distort the shape of red blood cells, resulting in so-calledsickle-shaped red blood cells. Hemoglobin S alsodamages the membraneof red blood cells, which makes them sticky. As a result, the cells tend to adhere to the inner lining of blood vessels. Sickle red blood cells also are stiffer than normal blood cells. The combination of these two characteristics is thought to promote the blockage of small blood vessels, which prevents oxygen supply to tissues and causes injury, known as VOC. The cell aggregates that because VOC consist not only of red blood cells, but also of inflammatory cells. Inflammation, therefore, seems to play a role in the development of VOC and might be promoted by infections

Question 17

role of supplemental oxygen in treatment of sickle cell disease

Answer 17

Increase O2 level in body

Question 18

role of packed red blood cells in the treatment of sickle cell disease

Answer 18

Increase normal RBC level in body

Question 19

hydroxyurea

Answer 19

converted to a free radical nitroxide (NO) in vivo, and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme. The entire replicase complex, including ribonucleotide reductase, is inactivated and DNA synthesis is selectively inhibited, producing cell death in S phase and synchronization of the fraction of cells that survive.

Question 20

structure/function relationship of the plasma membrane in erythrocytes

Answer 20

• biconcave disc shape facilitates gas exchange across the cell membrane. -membrane proteins that maintain the shape of the RBC allow it to traverse the capillaries with very small luminal diameters to deliver oxygen to the tissues.
• erythrocyte’s deformability lies in its shape and in the organization of the proteins that make up the RBC membrane.

Question 21

membrane-associated cytoskeleton

Answer 21

chief protein component, spectrin, consists of two polypeptide chains, α and β, which form intertwined (helical) flexible heterodimers. The “head” regions of spectrin dimers self-associate to form tetramers, while the “tails” associate with actin oligomers. Each actin oligomer can bind multiple spectrin tetramers, thus creating a two-dimensional spectrin-actin skeleton that is connected to the cell membrane by two distinct interactions. The first, involving the proteins ankyrin and band 4.2, binds spectrin to the transmembrane ion transporter, band 3. The second, involving protein 4.1, binds the “tail” of spectrin to another

Question 22

role of folic acid in erythropoies

Answer 22

Folate and vitamin B12are required for DNA synthesis. When these vitamins are deficient, DNA replication and nuclear division do not keep pace with the maturation of the cytoplasm. Consequently, the nucleus is extruded before the requisite number of cell divisions has taken place, and the cell volume is greater than it should be, and fewer blood cells are produced.

Question 23

mechanism by which hemolysis results in elevations in indirect (unconjugated) bilirubin and jaundice

Answer 23

Intravascular destruction of RBCs increases the amount of unconjugated bilirubin that is transported to the liver.

Question 24

role of direct antiglobulin testing in the assessment of hemolytic anemia

Answer 24

DAT reveals antibody-coated RBCs is central to the diagnosis of autoimmune hemolytic anemia.

Question 25

Autoimmune hemolytic anemia

Answer 25

acquired autoimmune disease in which autoantibodies directed against autologous RBC membrane antigens lead to their accelerated destruction.

Question 26

Dx of Autoimmune hemolytic anemia

Answer 26

The diagnosis of AIHA is thus based on the presence of a positive result on the direct antiglobulin test (DAT), also known as the direct Coombs test, and on the absence of any other hereditary of acquired cause of hemolysis.

Question 27

clinical presentation of hereditary spherocytosis

Answer 27

anemia, splenomegaly, and jaundice

Question 28

CBC values associated with anemia

Answer 28

Hgb: protein that carries oxygen, will be decreased
Hematocrit: amount of space in blood that is occupied by RBC’s, will be low
MCV: average size of RBC, increased

Question 29

Heme catabolism

Answer 29

Heme–bilirubin–bilirubin-albumin–bilirubin diglucouronide–bile-bacteria–urobilinogen–excreted

Question 30

What occurs with RBC lysis?

Answer 30

free hemoglobin–hgb dimers–hgb and haptoglobin complex

• -to macrophage-heme–unconjugated bili–unconj bili to liver–unconj to conju bili
• -to liver–heme to porphyrin–to uncoj bili–to conj bili

Question 31

clinical utility of serum lactate dehydrogenase

Answer 31

-increased due to hemolysis and release of LDH from degraded cells

Question 32

osmotic fragility test

Answer 32

• measures RBC resistance to hemolysis when exposed to inreasingly dilute saline solutions
• sooner hemolysis occurs, the greater the osmotic fragility
• increased in: hereditary spherocytosis, acquired spherocytosis
• decreased in: thalassemia, iron deficiency anemia, sickle cell anemia

Question 33

hemoglobin electrophoresis

Answer 33

-used to separate different types of hemoglobin

Question 34

peripheral blood smear from a patient with hereditary spherocytosis

Answer 34

• RBC morphology in HS is distinctive yet not diagnostic. Anisocytosis is prominent, and the smaller cells are spherocytes.
• spherocytes are fairly uniform in size and density and characterized by lack of central pallor, decreased mean corpuscular diameter, increased density

Question 35

role of folic acid supplementation in the treatment of hereditary spherocytosis.

Answer 35

required to sustain erythropoiesis. Patients with HS are instructed to take supplementary folic acid for life in order to prevent a megaloblastic crisis.

Question 36

indications for splenectomy in hereditary spherocytosis

Answer 36

• Appropriate vaccination required against encapsulated organisms
• Children who are candidates include those with severe HS requiring red cell transfusions and those with moderate HS who manifest growth failure or other signs and symptoms of anemia. Splenectomy for children with HS should not be performed until the child is older than 6 years, to reduce the risk of infections with encapsulated bacteria.

Question 37

role of the spleen in the maintenance of the erythrocyte population

Answer 37

-Micro filter for red blood cells: disposes of altered or aged blood cells in structures called the interendothelial slits. Red blood cells are squeezed through the slits and rigid or misshapen blood cells might not be able to pass through these narrow passages.