Cardiac Physiology: Clotting and Resolution Flashcards
What is the #1 cause of death?
Cardiovascular Disease
What is the major underlying cause of CVD?
Ischemia due to: - Atherosclerosis (plaque buildup) Artery Spasm
High blood cholesterol is linked to what physiological process?
Atherogenesis
Inflammatory mechanisms couple dyslipidemia with the formation of what?
Atheroma formation
Early Atherogenesis is characterized by?
Leukocyte recruitment and expression of pro-inflammatory cytokines
What system modulates inflammation?
Nervous System
Thrombosis is promoted by what physiological pathway and is responsible for MI and most strokes?
Inflammatory pathways
Prevention of blood loss
Hemostasis
What are the mechanisms of hemostasis? (4)
Vascular spasm, formation of a platelet plug, blood coagulation, and fibrous tissue growth
What happens during vascular constriction associated with trauma? (3)
-Neural reflexes (SNS induced constriction from pain) -Local myogenic spasm (responsible for most constriction) -Local humoral factors (thromboxane A2 from platelets and is especially important in smaller vessels)
The degree of spasm is directly proportional to what?
Severity of the trauma
T/F? Platelets function as whole cells but cannot divide.
True
Platelets contain:
Contractile proteins, enzymes, Calcium, ADP/ATP, Thromboxane A2, serotonin, growth factors
What does the platelet cell membrane contain?
Glycoproteins and phospholipids
T/F? Glycoproteins avoid normal epithelium but adhere to damaged area?
True
What platelet factor do phospholipids contain?
Platelet factor 3 (AKA thromboplastin which initiates clotting)
Describe the steps of platelet activation.
- Swell 2. Irregular form w/ radiating processes protruding from surface 3. contractile proteins activated causing granule release 4. Secrete ADP, Thromboxane A2 and serotonin
Thromboxane A2
Vasoconstrictor; potentiates the release of granule contents
Platelets have a half life of ___ and are eliminated by ___?
8-12 days; macrophage
What is the role of endothelium?
-Prevents platelet aggregation, produces PGI2 (prostacyclin), and produces factor VIII (clotting)
Describe Prostaglandin synthesis
-Insert picture
Describe Thromboxane synthesis
-Insert picture
Why take aspirin to prevent heart attacks?
Low dose aspirin inhibits primarily COX1 associated with the platelet which inhibits production of thromboxane A2
Aspirin and ibuprofen block thromboxane A2 and prostacyclin. What is the mechanism?
Blocks fatty acid COX which converts arachidonic acid to PGG2 and PGH2
Inhibition of COX 1 has its primary affect on which synthesis pathway?
Platelets and the formation of Thromboxane A2
Inhibition of COX 2 has its primary affect on which synthesis pathway?
Endothelial pathway and formation of PGI2
What is the function of anticoagulants?
Prevents clots from forming
What is the function of chelators?
Tie up calcium
Complexes with anti-thrombin III?
Heparin
What inhibits Vitamin K dependent factors?
Dicumarol
What factors are synthesized by hepatocytes?
Factors II, VII, IX, X
What is the difference between anticoagulants and lysis of clots?
Anticoagulants PREVENT clots from forming while lysis dissolves clots that have already formed.
Endogenous activators of plasminogen are found where?
Tissues, plasma and urine
Exogenous activators of plasminogen?
Streptokinase and tissue plasminogen activator (tPA)
Most tissue damage associated with infarction occurs upon reperfusion. Why?
There is formation of highly reactive oxygen species (free radicals)
The ability to open up alternate routes of blood flow to compensate for a blocked vessel
Collateralization – requires angiogenesis and vasodilation
What system may impede collateralization via vasoconstriction?
SNS
the extrinsic mechanism of blood coagulation is initiated by?
Chemical factors released by damaged tissues
The intrinsic mechanism of blood coagulation is initiated by?
Components found in blood or from damaged vessels upon exposure to collagen or foreign substances
What is hepatocyte’s (liver’s) role in clotting?
The liver synthesis 5 clotting factors: I: fibrinogen II: prothrombin VII: SPCA IX: AHF B X: Stuart factor
Coumarin (warfarin or Coumadin) depresses liver formation of II, VII, IX, X by blocking what?
Vitamin K
Describe hemophilia
Sex linked (X chromosome) therefore occurs almost exclusively in males. 85% of cases have a defect in factor VIII and 15% have defect in factor IX; varying degree in severity
What is the key step in clotting?
Conversion of fibrinogen to fibrin which requires thrombin
Describe the intrinsic pathway of clotting
~~~~Insert picture~~~
Describe the extrinsic pathway of clotting
~~~Insert picture~~~
Describe anti-phospholipid antibody syndrome
Autoimmune disorder where body makes antibodies against phospholipids in cell membranes; causes abnormal clots to form
What are risk factors in heart disease
Increasing age, males, hereditary, tobacco smoke, high blood cholesterol, high BP, physical inactivity, obesity, diabetes mellitus and high blood homocysteine
Amino acid in the blood that may irritate blood vessels promoting atherosclerosis
Homocysteine; can also cause cholesterol to change into oxidized LDL
high levels of Homocysteine in the blood can reduced by supplementing what?
Folic acid, B6 and B12
Which two antigen sets are likely to cause blood transfusion reactions if mismatched?
ABO and Rh
Which antibodies cause lysis of RBCs by activating the compliment system?
Primarily IgM; lysis releases proteolytic enzymes rupturing cell membrane
Which blood type is the universal donor?
O negative
Which blood type is the universal recipient?
AB positive
Hemolysis due to mismatched transfusions tend to be immediate or delayed? What is the most lethal effect?
Delayed (hemolysis to donor’s RBCs not recipient); Kidney failure
What is the mechanism of kidney failure?
Toxic substances are released from lysed RBCs, circulatory shock, and hemoglobin from lysed RBC precipitate and blocks renal tubules
What is the most common and most antigenic Rh blood type?
D Antigen (Rh + 85%)
What is another name for Erthroblastosis Fetalis?
Hemolytic disease of the newborn
Describe hemolytic disease of the newborn.
Characterized by agglutination and hemolysis of the fetus’ RBC by the mother’s anti Rh agglutinins
How can erythroblastosis fetalis present and what is the mechanism?
Jaundice; Agglutination of fetal blood release Hgb which is converted by macrophages to bilirubin
If a neonate (1-2 months) presents with anemia, enlarged liver and spleen, and has precipitation of bilirubin in neurons of the brain, what is a possible cause?
Erythroblastosis fetalis; mother’s anti agglutins from can circulate for 1-2 months causing RBCs to be destroyed and anemia results.
What is the prevention and treatment of Erythroblastosis Fetralis?
Treatment: replace neonate’s blood with Rh - blood
Prevention: administration of RhoGAM to mother at 28-30 weeks
