Flashcards in Karius Deck (33):
Erythropoieitin - production location, stimulation, action
1. Produced in kidney and liver
2. Stimulated by tissue hypoxia, resulting in HIF not being destructed and accumulating in cell, then acting as a transcription factor for genes like EPO and increased Fe absorption/transport
3. EPO acts on HSC to increase erythroid lineage and speed RBC maturation.
Granulocyte Colony Stimulating Factor - production location, action
1. Produced by endothelium, macrophages, other mature immune cells. Regulated by TNF-alpha and IL-1alpha
2. Factor acts on HSC to promote differentiation and development of various WBC lineages (also activates mature WBC)
Thrombopoietin - production location and regulation
i. Produced continually by liver and kidney
ii. Regulation via binding to mpl-receptor on circulating platelets, then TPO is internalized and degraded
Correlation between platelet number and free TPO
Inversely proportional to platelets
1. Low platelet number correlates with increased free TPO and increased production of platelets
2. High platelet number correlates with decreased free TPO due to binding, internalization, and consequent TPO destruction.
What protein maintains RBC shape, allowing for what?
spectrin maintains biconcave shape, allowing for deformation through small capillaries and splenic sinusoids
Location of hematopoiesis - childhood v. adulthood
i. Childhood – long bones of legs
ii. Adulthood – sternum and vertebra
First identifiable RBC precursor
Two nutrient/vitamin requirements for maturation of RBC
Vitamin B12 and Folic Acid
Deficiency in Vitamin B12 - usually due to what, and leads to what?
Due to intrinsic factor deficiency=decreased absorption.
B12 deficiency leads to pernicious anemia
Deficiency in Folate - usually due to what
heat, alcohol, intestinal absorption
Steps in hemoglobin production
1. Succinyl-CoA + glycine = pyrrole
2. Four pyrroles = protoporphyrin 9
3. Protoporphyrin 9 + iron = heme
4. Heme + peptide chain (alpha or Beta) = hemoglobin chain
5. Four hemoglobin chains = one hemoglobin molecule
Type of hemoglobin chains in: . a. Adult hemoglobin
b. Fetal hemoglobin
c. Sickle cell hemoglobin
a. Adult hemoglobin: 2 alpha + 2 beta
b. Fetal hemoglobin: 2 alpha + 2 gamma
c. Sickle cell hemoglobin: 2 beta with amino acid substitution, valine replaces glutamic acid
What is the major limitation to hemoglobin production?
What does protein does the liver add to bile to increase iron availability?
apotransferrin added to bile so that hemoglobin can bind (making transferrin), which is released into blood
What is the liver storage protein for iron?
What is excess iron (in the liver?) stored as?
Lifespan of RBC
ATP deficiency results in what happening to RBC?
rupture of RBC, resulting in emglobin release, leading to Fe release
Definition of polycythemia. What change does this result in?
too many blood cells, leading to increased blood viscosity (increased work on heart).
Two categories of polycythemia causes.
A. Primary – mpl or similar receptor abnormality
B. Secondary - Physiologic (normal human hypoxic environment (i.e. altitiude)) or Secondary (kidneys detecting hypoxia because of damage to lungs or heart (i.e. COPD, CHF))
Four steps of hemostasis
1. Vascular spasm
2. Platelet Plug
3. Clotting Cascade
Vascular spasm (first step in hemostasis) is caused by?
Myogenic response (smooth muscle contraction), serotonin and TxA2 (from damaged tissue and platelets), reflex (minor contributor)
Platelet Plug (second step in hemostasis) is caused by?
Activation of platelet by exposure to collagen in vessel wall.
i. Binding to collagen via receptor and von Willebrand factor triggers activation of platelets
1. ADP and TxA2 release triggers platelet to become sticky/adhere to each other to plug the hole
Clotting Cascade (third step in hemostasis) is caused by?
1. Formation of prothrombin activator
2. Prothrombin to thrombin
3. Thrombin to firbongogen to fibring
3. Clot stabilization via polymerization fo fibrin strnads
Repair (fourth step in hemostasis) is caused by?
Platelet-derived Growth Factor – promotes fibroblast differentiations to heal damage that caused bleeding
i. Healing occurs and then clot dissolves (Protein C gets rid of tPA inhibitor, then tPA activated and cleaves plasminogen into plasmin, plasmin cleaves fibrin to remove clot)
Three things that prevent clots
smooth endothelial lining of vessels, glycocalys on endothelium, thrombomodulin
Three anticoagulants in blood
fibrin, antithrombin 3, heparin (from mast cells)
Three things that result in bleeding conditions
i. Vitamin K deficiency - Fat soluble vitamin necessary for clotting
ii. Hemophilia – absence of clotting factors (factor 8 deficiency most common)
iii. Thrombocytopenia – too few platelets
Two things that cause inappropriate clotting
i. Change in blood vessels – loss of endothelial lining, sluggish blood flow
ii. Genetic factors – protein C/Leiden mutation (activated factor 5 resistant to Protein C)
Proteins/antigens in blood v. antibodies people have to these antigens that they do not have.
Proteins/antigens in blood are AGGLUTINIGENS.
Antibodies that people have to antigens the do not have are AGGLUTININS
Agglutinin development is/is not dependent on prior exposure to blood?
Is not dependent on prior exposure.
Rh- person must/does not have to be expsoed to Rh+ to produce antibodies to D protein
Does need to have prior exposure.