Flashcards in Week 3 Deck (37):
Mutation that causes sickle cell anemia
point mutation of the beta globin gene (HbS) - 6th B-globin codon goes from GAG (glutamic acid) to GTG (valine)
Mode of inheritance of sick cell anemia
Typical clinical presentation of sickle cell disease in an infant
Fatigue, activity intolerance, exertional dyspnea, hypersplenism, pain from vaso-occlusive crisis
Factors that contribute to anemia in patient with sickle cell
-sickling of cells cause the membrane to get broken down which then causes hemolysis of that RBC resulting in anemia
Your reticulocyte count is low. That tells your doctor your bone marrow isn’t making red blood cells fast enough.
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.
Iron deficiency anemia
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
Your body doesn’t get enough vitamin B12, also producing a low reticulocyte count.
RBC's not equal size
Variation in cell shape
more staining of RBC in histo slide
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 the heart: also referred to as the apical impulse. However, in certain conditions, the apex of the heart does not cause the PMI.
vibratory tremors that can be felt through the chest by palpation. To assess for tactile fremitus, ask the patient to say “99” or “blue moon”. While the patient is speaking, palpate the chest from one side to the other.
Different forms of Hgb found in an infant
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
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.
Describe how sickled red blood cells cause vaso-occlusive pain
Hemoglobin S molecules tend to stick together and form aggregates. These aggregates distort the shape of red blood cells, resulting in so-called sickle-shaped red blood cells. Hemoglobin S also damages the membrane of 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
role of supplemental oxygen in treatment of sickle cell disease
Increase O2 level in body
role of packed red blood cells in the treatment of sickle cell disease
Increase normal RBC level in body
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.
structure/function relationship of the plasma membrane in erythrocytes
-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.
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
role of folic acid in erythropoies
Folate and vitamin B12 are 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.
mechanism by which hemolysis results in elevations in indirect (unconjugated) bilirubin and jaundice
Intravascular destruction of RBCs increases the amount of unconjugated bilirubin that is transported to the liver.
role of direct antiglobulin testing in the assessment of hemolytic anemia
DAT reveals antibody-coated RBCs is central to the diagnosis of autoimmune hemolytic anemia.
Autoimmune hemolytic anemia
acquired autoimmune disease in which autoantibodies directed against autologous RBC membrane antigens lead to their accelerated destruction.
Dx of Autoimmune hemolytic anemia
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.
clinical presentation of hereditary spherocytosis
anemia, splenomegaly, and jaundice
CBC values associated with anemia
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
What occurs with RBC lysis?
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
clinical utility of serum lactate dehydrogenase
-increased due to hemolysis and release of LDH from degraded cells
osmotic fragility test
-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
-used to separate different types of hemoglobin
peripheral blood smear from a patient with hereditary spherocytosis
-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
role of folic acid supplementation in the treatment of hereditary spherocytosis.
required to sustain erythropoiesis. Patients with HS are instructed to take supplementary folic acid for life in order to prevent a megaloblastic crisis.
indications for splenectomy in hereditary spherocytosis
-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.