Unit 1: Cardiac Physiology- Physiology III Pt. 1 Flashcards
What is the #1 cause of death in U.S.? What is the main underlying cause?
cardiovascular disease
due to ischemia
What causes ischemia?
- atherosclerosis (plaque buildup)
- white thrombus
- red thrombus - artery spasm
What has been linked to causing atherogenesis?
- high blood cholesterol
- leukocyte recruitment and expression of pro-inflammatory cytokines
Inflammatory mechanisms has coupled what to artheroma formation?
dyslipidemia (aborm. amounts of lipids)
Inflammatory pathways promote __________, which is responsible for ____ and ____.
thrombosis; myocardial infarctions and most strokes
What can aid in modulating inflammation?
the nervous system. primarily the vagus nerve
What is hemostasis and what is the mechanisms of it?
= prevention of blood loss Mechanism: - vascular spasm (limits and prevents blood movement) - formation of platelet plug - blood coagulation - fibrous tissue growth to seal (Ca2++ is important in clotting)
What is first to occur when there is trauma to a vessel wall? And what three aspect aid in it?
vasoconstriction
- Neural reflexes – SNS induced constriction from pain
- Local myogenic spam— responsible for most of the constriction
- Local humoral factors– thromboaxane A2 from platelets, esp. important in smaller vessels
T/F. The degree of spasm is proportional to severity of the trauma.
True
Are platelets whole cells? Can platelets divide?
Yes, they are whole cells
No, they cannot divide
What three things do platelets contain that are our focus?
ADP, Thromboxane A2, and serotonin
Describe the appearance of an inactive vs active platelet.
Inactive = smooth Active = spiky and will degenerate and release substances to promote clotting
What two things does a platelet’s cell membrane contain?
- glycoproteins that avoid normal endothelium, but adhere to damaged area
- Phospholipids containing platelet factor 3—AKA thromboplastin
What does thromboplastin do?
initiates clotting
What four steps occur when a Platelet contacts damaged area and becomes activated?
- swell
- irregular form w/ irradiating processes protruding form surface
- contractile proteins contract causing granule release
- secrete ADP, Thromboxane A2, and Serotonin
What does Thromboxane A2 cause?
- vasoconstrictior
2. Potentiates the release of granule contents
T/F. Thromboxane A2 is essential for release of granule contents to occur.
False– if block Thromboxane A2, granule contents can still be release, it is not essential for release to occur
What primarily eliminates platelets and where are they located?
macrophages–greater than 1/2 are all in spleen
What are two roles of the endothelium?
Prevents platelet aggregation
- produces PG12 (prostacyclin) (inhibits platelet aggregation)
Produces factor VII (clotting)
What are three effecs of PG12 (prostacyclin) produced by endothelium?
- vasodilator
- stimulates platelet adenyl cyclase, which suppresses release of granules
- limits platelet extension
What is the precursor for all prostaglandins (PGG2 and PGH2)? And what enzyme is used?
Arachidonic acid
Enzyme: Fatty Acid cyclooxygenase (COX)
What enzyme is used in platelets to produce Thromboxane A2? And what are the effects of Thromboxane A2?
COX1 (cyclooxygenase)
Effects:
- vasoconstriction
- potentiates platelet degranulation
What enzyme is used in Endothelium to produce Prostacyclin? And what are the effects of Prostacyclin?
COX2
Effects:
- vasodilator
- inhibits platelet degranulation
- Cardioprotective
What do Aspirin and Ibuprofen block?
Fatty acid cyclooxygenase (COX)– which converts Arachidonic acid into prostaglandins–PGG2 and PGH2 (intermediates)
- therefore blocking production of thromboxane A2 and prostacyclin
Why do individuals take aspirin to prevent heart attacks?
low dose aspirin targets (inhibits) primarily COX1, ass. with platelets, which inhibits production of thromboxane A2
What are NSAID and what are they used for?
Nonsteroidal anti-inflammatory drug, used to control pain and inflammation
- COX inhibitors are a type of NSAIDs
What is the primary effect of inhibition of COX 1? COX 2? Examples of each.
inhibit COX 1–>effect on platelet and decrease Thromboxane A2 (Ex: Aspirin)
inhibit COX2–> effect on endothelium and decrease PGI2 (Ex: Celebrex, Vioxx)
–has less GI risk (bleeding ulcers) than COX 1 inhibitors
Compare anticoagulants vs lysis of clots.
What enzyme is used in lysis of clots?
Anticoagulants –> prevents clots from forming
Lysis of Clots–> dissolves clots that have already formed, use Plasmin (from plasminogen)
These are types of Anticoagulants. Tell me what they do.
- chelators
- heparin
- dicumarol
all prevent clots from forming…
1. tye up calcium (ex: citrate, oxylate)
- complexes with Antithrobin III
- inhibition of Vit. K dependent factors (Ex: cumadin, warfarin)
What is the inactive form of plasmin that circulates in the blood?
plasminogen
Where are Endogenous Activators of Plasminogen found?
tissues, plasma, urine
recall plasminogen = inactive form of plasmin, and plasmin is involved in lysis clots
What are Exogenous Activators of plasminogen?
(aka drugs)
- streptokinase
- *tPA (tissue plasminogen activator)–> 3 hr window for MI and stroke
What causes most of the frank tissue damage associated with infarctions? Why?
reperfusion; b/c ass. with formation of highly reactive oxygen species with unpaired electrons = “free radicals” –> which are generated when pressure on tissues is relieved
What is collateralization?
the ability to open up alternate routes of blood flow to compensate for a blocked vessel
- Angiogenesis
- Vasodilation
- Role of SNS–> vasoconstriction
What is the role of the SNS in relation to collateralization?
- may impede(delay/prevent) via vasoconstriction (ass. with NT Norepinepherine)
- may augment (make greater by adding to it) via release of neuropeptide Y (NPY)
How is the creation of a thrombosis done by the Extrinsic mechanism?
initiated by chemical factors released by damaged tissues
How is the formation of a thrombosis done by the Intrinsic mechanism?
requires only components in blood and trauma to blood or exposure to collagen (or foreign surface)
What are hepatocytes role in clotting?
hepatocytes = liver cells
Live synthesizes 5 clotting factors:
- I (fibrinogen)
- II (prothrombin)
- VII (SPCA)
- IX (AHF B)
- X (Stuart factor)
What does Coumarin (warfarin or cumadin) due to liver formation of factors II, VII, IX, and X? How?
depresses liver formation of them by blocking action of vitamin K
What is Hemophilia? And what is the defect in 85% of cases, 15% of cases, and <1% of cases?
a sex linked X chromosome disorder (blood doesn’t clot properly)–varies in degree
- 85% cases = defect in factor VII
- 15% of cases = defect in factor IX
- <1% of cases = defect in factor XI
What steps of blood coagulation do not require Ca2++?
first two steps in intrinsic steps, formation of Factor XII and Factor XI
At formation of what factors do the intrinsic and extrinsic blood coagulation pathways come together?
factor V and X
What is the key step in clotting of blood?
conversion of fibrinogen to fibrin, by thrombin
What is Antiphospholipid antibody syndrome?
Autoimmune disorder where body makes antibodies against phospholipids in cell membranes —> causes abnormal clots to form
What is an amino acid in the blood that may irritate blood vessels, promoting atherosclerosis, and can make blood more likely to clot?
homocysteine
What can homocysteine cause cholesterol to change into?
oxidized LDL
How can you reduce high levels of homocysteine in the blood?
by increasing intake of folic acid, B6 and B12
What are the two particular antigen sets likely to cause blood transfusion reactions if mismatched?
O-A-B and Rh
What blood types, O-A-B, cause most blood transfusion reactions and why?
Type A or B. They have A and B antigens on the RBCs known as agglutinogens b/c they can trigger agglutination
(O is essentially functionless)
What are the possible allele combinations of blood types?
OO, OA or AA, OB or BB, and AB
List the blood types in order form most common to least common?
O, A, B, AB
Simply,
What are agglutinogens?
What are agglutinins?
agglutinogens = surface markers agglutinins = soluble anitbodies
Which blood types have agglutinogens and what types do they have?
O = none A = A B = B AB = A and B
Which blood types have agglutinins and what types do they have?
O = Anti-A and Anti-B A = Anti-B B = Anti-A AB = none
T/F. Agglutinins for O-A-B blood types are produced spontaneously after birth (2-8months)
True
When do antibody titers peak?
about 10 years of age and then decline throughout life
T/F. Anti-A titiers are 2x Anti-B titers in respective blood type.
True
In a mismateched transfusion, which is more common, immediate or delayed hemolysis?
immediate (less common)
delayed (more common)
What causes the lysis of RBCs and how?
antibodies (primarily IgM), by activating compliment system which releases proteolytic enzymes rupturing cell membrane
T/F. When hemolysis occurs in mismatched transfusions, it occurs to the recipients blood.
False. It occurs to the donor’s RBCs
What blood type is the universal donor? The universal recipient?
donor = O- recipient = AB+
What is the most lethal effect of a blood transfusion reaction? Why/how does it occur?
Kidney failure:
- toxic substances released form hemolysed RBC’s
- Circulatory shock
- hemoglobin from lysed RBCs precipitates and blocks renal tubules
T/F. Spontaneous agglutinins for Rh factor arises after birth.
False!! spontaneous agglutinins for Rh factor never arises (this is unlike O-A-B system)
What are the 6 common Rh antigens (Rh factors) on RBC’s? And which makes you Rh+ or Rh-?
C D E c d e
D = MC and most antigenic (Rh+) at 85% of population
Lacking the D antigen (Rh-), as in have either C, E, c, d, e
When Rh+ RBCs are infused into a person who is Rh-, what occurs?
it will stimulate production of anti-Rh antibodies, but they develop slowely and will reach max. conc. 2-4 months later—> therefore is exposed again later a strong hemolysis rxn can occur
What is the disease that is charactized by agglutination and hemolysis of the fetus’ RBCs by the mother’s anti Rh agglutinins?
Erythroblastosis Fetalis (AKA “Hemolytic disease of the Newborn”)
What occurs during Erythroblastosis Fetalis
causes agglutination of fetal blood, therefore release Hgb which is converted by macrophages into bilirubin —> cause JAUNDICE (yellow)
Most cases of erythroblastosis fetalis, mother is Rh- and fetus inherits Rh+ from father. What occurs and when does the problem occur?
mother develops anti-Rh agglutinins from exposure to fetus’ Rh+ antigen
symptoms usually don’t occur with initial pregnancy, but will occur whith 2nd (3%) or 3rd (10%) pregnancy where fetus is Rh+
What happens in the fetus when erythroblastosis fetalis occurs?
after birth the anti Rh agglutinins from mother circulate for another 1-2 months destroying more neonate RBCs –> lead to anemia
Neonates liver and spleen enlarge
In erythroblastosis fetalis, the potential for bilirubin to precipitate in neurons of the brain and causing mental impairment could occur. What is that called?
kernicterus
What is the treatment option for Erythroblastosis fetalis?
Prevention?
replace neonate’s blood with Rh- blood
administer Rh immunoglobulin globulin (RhoGAM), an anti-D antibody, to mother at 28-30 weeks of gestation
