Blood Flashcards
What is hemoglobin?
A molecule consisting of 2 alpha and 2 beta polypeptide chains
4 Heme groups which contain an Iron ion that binds O2
How is the majority of the oxygen transported in the blood?
98.4% of O2 is transported bound to Hemoglobin
What does oxygenated blood look like?
Bright red
What does deoxygenated blood look like?
Dark red
What does Hemoglobin also bind to?
Carbon dioxide
Hydrogen ions
Carbon monoxide
Where are erythrocytes produced?
In the bone marrow
Derived from hemopoietic stem cells
What stimulates the production of erythrocytes?
Erythropoietin secreted from the kidneys under conditions of hypoxia (low oxygen level in the blood flowing through the kidneys)
Simple description of erythrocyte differentiation
- Erythropoietin triggers hematopoietic stem cells to differentiate into erythrocytes
- Cells begin to produce hemoglobin gradually becoming redder
- Developing erythrocytes lose nuclei and organelles
What three vitamins/ compounds are needed for erythrocyte production?
Iron
Folic acid
Vitamin B12
What is folic acid AND Vitamin B12 needed for in erythrocyte production?
Necessary for DNA replication and thus cell proliferation
What organ filters old erythrocytes?
SPLEEN
Spleen macrophages filter blood by phagocytosis of old, fragile RBCs
Hemoglobin is catabolized by removing heme from iron creating bilirubin
What organ destroys old erythrocytes?
LIVER
Metabolizes by-products from brreakdown of erythrocytes
Describe Hemoglobin catabolism
- Heme is removed from the globin part (protein)
- Globin (alpha and beta polypeptides) broken down into amino acids and recycled
- Iron is removed from the hemoglobin leaving heme which is now called biliverdin
- Biliverdin is broken down into bilirubin is released into the bloodstream bound to albumin
- Travels to the liver for further metabolism into bile
How is iron recycled?
Heme molecules are toxic to the body and must be broken down
Heme oxygenase breaks heme into biliverdin and Fe2+
Fe2+ leaves the macrophage and is converted to Fe3+
Fe3+ binds to transferrin and is transported into through the blood as T-iron
Transferrin goes from the GI tract to the bone marrow or from the liver to the bone marrow
Name three places where ferritin is stored
Liver (Ferritin iron (F-iron))
Spleen
Small intestine
Where is bilirubin converted to bile?
Liver
How is some bile secreted?
In the form of feces and in the urine
What are the two types of stem cells produced from hemopoietic stem cells?
Myeloid stem cells
Lymphoid stem cells
What leukocytes develop from myeloid stem cells?
Neutrophil
Basophil
Eosinophil
Macrophage/ Monocyte
Platelets/Megakaryocytes
Erythrocytes
What leukocytes develop from Lymphoid stem cells?
Lymphocytes
B cells/ plasma cells
Cytotoxic T cells
Natural killer cells
Helper T cells
What are the clinical causes of dietary anemia?
Low iron
Low Vitamin B12 (pernicious anemia
What is the cause of hemolytic anemia?
Hemolytic =destruction of RBCs
Malaria
Sickle cell anemia
What is the cause of aplastic anemia?
Aplastic= bone marrow does not produce new cells, body susceptible to infection and bleeding
Bone marrow defect
What is the cause of renal anemia?
Kidney disease
Kidneys produce erythropoietin to trigger RBC production
Diseased kidneys = little to no erythropoietin
What is the cause of hemorrhagic anemia?
YOU ARE BLEEDING MY GUY
How do we prevent the blood from clotting?
Healthy endothelial cells produce Nitric oxide and Prostacyclin (PGI2) which inactivate platelets
This prevents the spread of a platelet plug (platelet aggregation)
List the 5 steps in hemostasis
Vascular spasm
Platelet plug formation
Coagulation
Clot retraction and repair
Fibrinolysis
`Vascular spasm
Damage to the endothelium can lead to blood loss
To prevent blood loss the vessel contracts to minimize blood loss by decreasing the diameter of the vessel (⇑⇑⇑⇑ Resistance & ⇓⇓⇓⇓ Flow)
Sympathetic innervation and Intrinsic vascular response
What is the intrinsic vascular response in vascular spasm?
Intrinsic vascular response: Endothelial cells will release endothelin which binds to receptors on the smooth muscle below and cause it to contract
Platelet plug formation
Blood vessel damage
Exposure of subendothelium
Von Willebrand factor secreted by endothelial cells bind to collagen fibers
Injured endothelial cells cannot secrete nitric oxide and prostacyclin so platelets become activated and clotting factors are activated
Platelets bind to Von Willebrand factor
Platelets secrete ADP, Thromboxane A2, Seratonin
What is the function of ADP and Thromboxane A2 in Platelet plug formation
ADP and Thromboxane A 2 increase the stickiness of the platelets in circulation and activate them drawing them to the site of injury.
Causes = Platelet aggregation
Use a Positive feedback loop
What specific protein causes the platelets to stick together?
Fibrinogen
Describe the Coagulation cascade
(Intrinsic)
- Factor 12 comes in contact with the platelets or collagen and becomes factor 12a
- Factor 12a activates factor 11 → Factor 11 a
- Factor 11 a activates factor 9 → factor 9a
- Factor 9 a and factor 8 will come together with platelet factor 3 and Ca2+ forming a complex that converts factor 10 to 10 a
- Factor 10 a will react with factor 5, platelet factor 3, and Ca 2+ to activate Prothrombin activator
- Prothrombin activator will convert Factor 2 (prothrombin) into factor 2a (thrombin)
- Thrombin will cause soluble fibrinogen to polymerize into fibrin (insoluble) causing blood to become jelly-like to slow blood flow
- Factor 13 (fibrin stabilizing factor) will cross-link the fibrin to form a fibrin mesh to hold down the platelet plug to prevent it from dislodging and traveling (embolism)
How do the intrinsic and extrinsic coagulation pathways differ?
Intrinsic pathway is activated through exposed endothelial collagen
Extrinsic pathway is activated through tissue factor (Factor 3) released into the blood by endothelial cells after external damage.
Extrinsic coagulation cascade
Tissue damage causes the release of tissue factor (Factor 3)
Factor 3 will interact with factor 7 which will stimulate the activation of factor9
Factor 7 converges on the common pathway where facto 10 is activated
Factor 10a binds to factor 5, platelet factor 3 and Ca2+ to activate the prothrombin activator
What is the common factor between the intrinsic and extrinsic pathways?
Conversion of Factor 10 into 10a
Write of the coagulation cascade shortcut
Clot retraction and repair
Platelets contain actin and myosin that allows them to contract and pull the edges of the endothelial cells closer together
Platelets will secrete platelet-derived growth factors to help renew damaged smooth muscle
Platelets secret vascular endothelial growth factor replenishes the endothelial lining
Fibrinolysis
Tissue plasminogen activator (tPA) on endothelial cells which converts/ cleaves plasminogen into plasmin
Plasmin begins to digest/ cut up the fibrin mesh and busts up the clot to prevent the blood vessel from becoming occluded
What 3 factors limit the formation of clots to prevent occlusions of blood vessels?
Anticoagulants
Tissue Factor pathway inhibitor (Extrinsic pathway inhibitor)
Thrombomodulin
How do anticoagulants limit clot formation in low doses?
Anticoagulants are chemicals that inhibit blood clotting or coagulation.
Low doses of aspirin acts by inhibiting the formation of Thromboxane A 2 (produced by activated plateletes to increase aggregation) thereby decreasing platelet aggregation and platelet plug formation
How do anticoagulants limit clot formation in high doses?
Aspirin decreases the formation of prostacyclin (inactivates platelets) which increases the likelihood of clot formation
How do tissue factor pathway inhibitor limit clot formation?
Secreted during the initial phase of clotting by healthy endothelial cells
Inhibits the extrinsic pathway so that not so much factor 10 is activated and ultimately fibrin mesh formed
Clot size does not occlude the blood vessel
How do Thrombomodulin limit clot formation?
Thrombomodulin binds to thrombin forming the thrombomodulin-thrombin complex
Thrombin cannot convert fibrinogen into fibrin
Complex activates protein C (anticoagulant) that inhibits both intrinsic and extrinsic pathways
Explain hemophila and clot formation disorders
Genetic disorder caused by a deficiency of gene for specific coagulation factor
Most commonly Factor 8 or 9 is deficient
Explain how von Willebrand’s disease affects clotting
Genetic bleeding disorder where there is a deficiency in vWf making it hard to form a platelet plug due to reduced levels
vWf is also a plasma carrier for factor 8 so its absence makes factor 8 more unstable and quick to break down
Low factor 8 levels
How does Vitamin K affect clotting?
Clotting factors are made in the liver and vitamin K is needed for the synthesis of many of the proteins necessary in blood clotting
