RBC, Anemias, and Polycythemias Flashcards
what percent does blood constitute of the total body weight?
8%
what is the plasma?
aqueous phase of blood
what are the cellular elements?
erythrocytes
leukocytes
thrombocytes
what part of the blood determines oncotic pressure?
albumin and globulin
what comprises the granulocytes?
neutrophils
eosinophils
basophils
what comprises the agranulocytes?
monocytes
lymphocytes
what are neutrophils?
phagocytic; engulf pathogens or debris in tissues; most abundant of the granulocytes
what are eosinophils?
attack anything that is labeled with antibodies; important in fighting parasitic infections and suppressing information
what are the basophils?
enter damaged tissue and release histamines and other chemicals
what are monocytes?
enter tissues to become free macrophages and engulf pathogens or debris
what are lymphocytes?
cells of lymphoid system, providing defense against specific pathogens or toxins
what are platelets?
hemostasis: clump together and stick to vessel wall; activate intrinsic pathway of coagulation phase
what is hemoglobin?
globular protein complex found in red blood cells
what does hemoglobin transport?
oxygen from the lungs to the peripheral tissue, then coming from the peripheral tissues to the lungs it would be CO2 and H+
what else is hemoglobin involved in?
the regulation of acid base status of the body
what gases do cells consume and produce?
consume O2 and produce CO2
what are the gases with low solubility in plasma?
O2 and CO2
what percentage of heme-iron can be found in the oxidized state, what is this iron called?
1%; ferric iron (Fe(III))
what is hemoglobin containing iron in the oxidized form known as? can this bind oxygen?
methemoglobin; no
what two forms does the hemoglobin take on?
T form and the R form
in terms of the two forms of hemoglobin, T and R form what are they?
T form (tense)- ↓O2 affinity
R form (relax)- O2 affinity
what are effectors in relating to hemoglobin?
small molecules that influence the O2 binding capacity of hemoglobin
what are positive effectors in relation to the hemoglobin?
Increase Hb’s affinity to bind oxygen
what are negative effectors in relation to the hemoglobin?
Decrease the Hb’s affinity to bind oxygen
what is the shape of RBC’s?
biconcave discs which have the potential to change shape without bursting
what is RBC count-average in men and women? hemoglobin count in men and women?
M: 5,200,000
W: 4,700,000, goes up with increasing altitude do to lack of oxygen so RBC goes up to supply tissue with oxygen
Hemoglobin count
M: 15 gm/100 ml
W: 14 gm/100 ml
how does RBC production work in the embryo?
First trimester: Yolk sack (nucleated RBC’s)
Middle Trimester: Liver (spleen/ lymph nodes)
Last month- birth: Bone marrow
what is the origin of the RBC’s?
Pluripotent Hematopoietic Stem Cell, which can further divide into RBC’s for example
what is the significance in the function of the kidney in RBC production?
Kidney monitors blood cell count for hypoxia, it senses this and makes more RBC via erthyropoietin and signal for bone marrow to make more rbc
what inducers are involved in the control of hematopoiesis?
growth inducers and differentiation inducers which are initiated to further develop the red blood cells
what are growth inducers?
promote the growth of already differentiated cells
what are differentiation inducers?
promote cell differentiation
do erythrocytes have nucleus?
no
what are the factors that decrease oxygenation? what happens as a result?
low blood volume anemia low hemoglobin poor blood flow pulmonary disease
overall, hypoxia results and so hematopoiesis is stimulated to produce the RBC’s 90% by kidneys and 10% by liver
what is the action of erythropoietin on the bone marrow?
increase conversion of multi-potent stem cells in to the erythroblasts (differentiation)
increase rate of RBC production (growth- up to 10x)
when happens to erythropoietin levels when we have hypoxia/hemolysis?
increased levels of erythropoietin levels, increased hematocrit (HCT) levels
what is MCV?
mean corpuscular volume which is the measurement of the average RBC volume (i.e. size)
how is MCV calculated?
hematocrit(Hct)/RBC number
***normal value of MCV is?
80-100fl, fl-femtoliter is equal to: 1 µm³
MCV is increased in?
polycythemia (increased blood cell) megaloblastic anemia (B12 and folate deficiency), subcomponent pernicious anemia (up to 150 fl, lack of fit B12 binding to proper protein for transport)
MCV is decreased in?
iron deficiency anemia (most common), microcytic anemia
acute and chronic blood loss
hemolytic anemia
what are the hematopoiesis requirement?
Vit B12 and folic acid, serves as the cofactor for thymidine triphosphate (DNA building blocks)
what happens to the RBCs when you lack any of the cofactors for hematopoiesis?
macrocytic anemia
what is macrocytic anemia?
larger cells, flimsy, less distensible membrane, described as biconcave discs, they have short life spans and break easy.
what is the life span of RBC’s?
120 days
T/F, RBCs do not have nucleus, mitochondria, ER?
T
T/F, RBC’s do not have cytoplasmic enzymes producing ATP?
F, they do
why do RBC’s have enzymes?
To maintain pliability and ion transport capacity of the membrane
To maintain cells hemoglobin in ferrous Fe (II) not ferric form (III)
To prevent oxidation of proteins
what happens to the old erythrocytes?
Become less distensible (oxidative stress membrane damage)
Pass through the spleen (red pulp) - self destruct
How ? Need to squeeze trough the tight space – hemolysis
what is anemia?
deficiency of hemoglobin
what causes anemia?
decrease number of RBC’s and decrease concentration of hemoglobin
how can we classify anemia?
MCV and MCHC
what are the classifications of Anemia according to the MCV (RBC scale)?
<80 fl microcytic
80-100 fl normocytic
>100 fl macrocytic
what are the classifications of anemia according to the MCHC scale (amount of hemoglobin in RBC)?
decreased -> hypochromic
normal -> normochromic
increased + RBC’s misshaped -> spherocytosis
what are the two causes of microcytic anemia we discussed in class?
iron deficiency and thalassemia (alpha and beta), MCV count less than 80
what is iron deficiency anemia also known as?
microcytic, hypochromic anemia
what is the cause for microcytic anemia?
chronic blood loss (GI of GYN bleeding)
dietary deficiency (old and young)
malabsorption of iron (decreased HCI secretion, small bowel resection)
what are the lab values for a patient with microcytic anemia?
↓ Ferritin levels
↓ O2 saturation+ Serum iron levels (transferrin)
↑ Total iron binding capacity (TIBC)
↓ Hemoglobin
what is an early sign of microcytic anemia?
↑ RWD= standard deviation of MCV/MCV, increase work on bone marrow to make up for loss in RBC for imperfectly matured red blood cells, elevated numbers of reticulocytes
how does a patient present with microcytic anemia?
Weakness, pallor, tachycardia, Glossitis, Pica (cravings for iron)
what is folate deficiency anemia also known as?
microcytic anemia
what are sources of folic acid?
green vegetables, some fruits, meats (liver)
what can cause folate deficiency anemia?
disease of the small intestine (Sprue), folate destroyed by cooking
what is the most common cause of folate deficiency anemia?
intestinal sprue
what is intestinal sprue?
an infectious / autoimmune condition that results in an autoimmune destruction of enterocytes
in terms of the folate deficiency anemia, when you have the destruction of enterocytes what is the effect on cell metabolism resulting in intestinal sprue?
impedes the absorption of folate and its intracellular reduction in to tetrahydrofolate
what is Tetrahydrofolate essential for?
the maturation of RBCS
what is the recommended therapy for intestinal sprue, folate deficiency anemia?
Treatment of the underlying cause
Folate supplements
what is pernicious anemia?
Failure of the absorption of vitamin B12 (cobalamin)
Atrophic gastric mucosa does not produce glycoprotein- INTRINSIC FACTOR
so we know that vitamin B12 is high maintenance and that it has to be tied up to another molecule, this is called? and what does it do?
intrinsic factor
Combines with B12 from the food (protection against digestion)
Binds to intrinsic factor receptor in terminal ileum (small bowel), thus separated
Helps import the B12 in to the gut wall cells
what is Vitamin B12 also called?
cobalamin and then called transcobalamin 1 (in saliva), 2(intrinsic factor), 3(terminal ilium-absorbed by the liver)
what is pernicious anemia also called?
macrocytic anemia also called pernicious anemia
what are other types of anemia not covered under the classification system?
aplastic anemia
hemolytic anemia
what is aplastic anemia?
empty spaced and so bone marrow aplasia due to chemotherapy, or irradiated. Autoimmune cases for aplastic anemia can cause this and fight off stem cells. Transfusion to fix, to clear off bone marrow and then it picks up just fine. Drugs help suppress attack on bone marrow.
what is hemolytic anemia?
something is causing the cell to lyse; like in patients who have new valves for heart, so when blood passes by, RBCs are lysed because of mechanical pressure and constant anemia occurs. RBC lifespan is shorter like hereditary spherocytosis
what is an example of hemolytic anemia?
Hereditary spherocytosis: Congenital-Auto-hemolytic
describe Hereditary spherocytosis: Congenital-Auto-hemolytic? what is used to test for it? how does present histologically? therapy?
Mutation of spectrin, ankyrin gene- shape change; Osmotic fragility test; RBC’s spherical and prone to rupture Splenomegaly; Transfusions, Splenectomy (infection prevention)
what are the hemodynamic effects of anemia?
Anemia leads to decrease RBC No. leading to decrease viscosity leading to decrease viscosity leading to decreased resistance in small blood vessels increasing blood flow through the tissues
increasing blood flow and then increasing Cardiac Output (CO) if too much, then hypoxia can set in leading to dilatation of peripheral blood vessels and then increased return of the blood to the heart increasing the return back to the heart increasing the cardiac output
what is the compensatory mechanism observed in the hemodynamic effects of anemia? what could happen to someone with this condition?
increased cardiac output leads to increased oxygen delivery
EXERCISE LEADS TO HYPOXIA AND INCREASED DEMAND ON THE HEART WHICH LEADS TO ACUTE CARDIAC FAILURE
what is unique about G6PD deficiency?
an x-linked recessive disorder in which there is a mutation of the gene encoding the production of glucose 6 phosphate dehydrogenase and rate limited in PPP
this affects more than 10% of the worlds population and results in a decreased half life of the enzyme
what is G6PD deficiency? how is it characterized?
Episodic Hemolytic anemia precipitated by oxidative stress caused by the increase in oxidative stress like:
Infection
Oxidizing drugs (sulfonamides, antimalarials)
Fava beans
Heinz Bodies and Bite Cells
what is Heinz Bodies and what is this associated with?
presence of precipitated denatured oxidized hemoglobin in RBC’s
what are Bite cells and what is this associated with?
Reticuloendothelial cells from the spleen attack the abnormal RBCs resulting in specific damage (Bite cells)
what is warm autoimmune hemolytic anemia (WAIHA)?
Warm reacting IgG autoantibodies (37 C) reactive against RBC surface antigens and then Coated RBCs cleared by the spleen leading to low red blood cell count
what are the causes of Warm Autoimmune Hemolytic Anemia (WAIHA)?
Causes: Idiopathic Autoimmune disease Chronic lymphocytic leukemia Drugs (Penicillin, methyldopa)
how is Warm Autoimmune Hemolytic Anemia (WAIHA) characterized?
Characterized by the presence of microspherocytes (RBCs missing parts of their membrane)
Confirmed by : Coombs’ test- anti-IgG immune globulin
how can we test for Warm Autoimmune hemolytic Anemia (WAIHA)? Lab findings?
Coombs test and Therapy
Laboratory findings:
MCV is elevated
Bilirubin elevated in blood
Therapy:
Transfusions
Corticosteroids
Important Note:
This blood can not be used in transfusions due to cross reactivity with several blood types
are examples of Non-immune hemolytic Anemias?
Fragmentation Hemolytic Anemia
Hypersplenism
Infection
what causes Fragmentation Hemolytic Anemia?
Mechanical trauma and shear stress
due to:
Damaged microvasculature- Microangiopathic hemolytic anemia
Arteriovenous malformations
Cardiac abnormalities (Prosthetic valves)
Drugs (Cyclosporine, Cocaine)
what causes Hypersplenism?
Hyperactivity of splenic tissue (splenomegaly)
leading to decreased life span of RBC’s
what causes infection?
Hyperactivity of splenic tissue (splenomegaly) Due to: Parasites (Malaria) Immune mechanisms Induction of hypersplenism Toxin, Enzymes
what is secondary polycythemia? examples?
decrease O2 delivery to the tissues results in the increase RBC production (up to 5-7 million/mm3)
Physiologic polycythemia: Altitudes above 14000-17000 ft.
Heart Failure polycythemia: heart failure causes ischemia (failure of the pump)
what is Polycythemia Vera (erythemia)? Causes? Clinical Signs?
Production of RBC’s on and above 7-8 million/mm3, Hematocrit 60-70 % (normal: 40-45%); Abnormal division (uncontrolled) of hemocytoblastic cells (neoplasia); Increased number of all blood cells, increased viscosity and volume of blood
what are the effects of Polycythemia?
increase viscosity leading to decrease blood return and thus cardiac output and this also increase blood volume and increases blood return all trying to normalize cardiac output
also blue color of the skin
what is some therapy we can use for Polycythemia?
Phlebotomy
Chemotherapy
Anti-thrombotics
