Lecture 3: CV Pathophysiology I Flashcards
abnormally high hematocrit
polycythemia vera
What causes polycythemia vera?
- overproduction of blood cell cursors by bone marrow
- genetic mutation
How is polycythemia vera treated? What are the complications?
- regular phlebotomy
- increases risk of abnormal clotting, enlargement of spleen, and damage to bone marrow
fraction of blood volume that is erythrocytes (normal = 42-45%)
hematocrit
lower than normal hematocrit
anemia
What can cause anemia?
- blood loss (heavy menstrual periods, hemorrhage, internal bleeding)
- hemolysis (via infectious/autoimmune disease)
- nutritional deficiencies (iron, vitamin B12)
- defects in regulation of blood cell production
rupturing of red blood cells
hemolysis
too many white blood cells
leukemia
Why is leukemia damaging?
- tends to go hand in hand with anemia
- immune defense does not function well; vulnerable to infection
too few white blood cells
AIDS, immune deficiency, chemotherapy
Why are low levels of leukocytes dangerous?
prone to infection
What happens during primary hemostasis?
- vasoconstriction and formation of a platelet plug
- tissue damage exposes collagen
- platelets adhere to collagen via von Willebrand factor (vWF)
- fibrinogen links aggregating platelets –> plug
released from platelets; causes vasoconstriction
thromboxane A2
What happens during secondary hemostasis?
- transforms blood into a solid gel (clot/thrombus)
- clot surrounds and reinforces platelet plug
- blood solidifies at site of wound
How is the extrinsic pathway of hemostasis activated?
- triggered by exposure of blood to sub-endothelial cells that produce tissue factor
- some cells only produce tissue factor in response to damage
- monocytes/macrophages produce tissue factor in response to inflammation
- TF can also be found in circulating blood and endothelial cells even in the absence of damage
How is the intrinsic pathway of hemostasis activated?
activated by exposure to collagen
irreversibly binds to thrombin, preventing it from catalyzing the formation of fibrin
antithrombin
What about endothelial cells increases the effectiveness of antithrombin?
surface of endothelial cells contains heparin sulfate which enhances antithrombin 1000 fold
inactivates key acceleration factors in the coagulation pathway; second protein enhances the first
Protein C and Protein S
an endothelial receptor that binds thrombin and activates protein C
thrombomodulin
inactivates the complex of tissue factor
TFPI (Tissue Factor Protein Inhibitor)
What inhibits thrombin via negative feedback to limit clotting?
fibrin
a protein that cleaves the protein plasminogen to plasmin, which in turn enzymatically breaks down fibrin clots
tPA (tissue plasminogen activator)
inhibits platelet activation and aggravation; causes vasodilation
prostacyclin
inhibits platelet activation and causes vasodilation
nitric oxide
3 factors that help resolve blood clots:
- tPA
- prostacyclin
- nitric oxide
Factors that inhibit clotting:
- Antithrombin
- Protein C/Protein S
- Thrombomodulin
- TFPI
- Fibrin
rare genetic disorder; sex-linked; inability to produce vWF
hemophilia
lack of vWF, cannot form platelet plug
von Willebrand Disease
when a piece of a thrombus breaks off and lodges in a blood vessel down stream
embolism
thrombus associated with the rupture of an atherosclerotic plaque (ofter in coronary artery or brain) or atria fibrillation
arterial thrombosis
thrombus that occurs in legs of a person who has been immobilized and leads to pulmonary embolism
venous (deep vein thrombosis)
occurs in patients with heat stroke, sepsis, or other conditions that strongly activate the immune system
disseminated intravascular coagulation (DIC)
an anti-clotting drug that interferes with the actions of vitamin K (necessary for certain clotting factors)
Coumadin (warfarin)
caused by blood pressure in the capliaries; favors filtration
capillary hydrostatic pressure
due to the osmotic force of proteins in the plasma, tending to draw fluid back into the capillary; favors reabsorption
capillary oncotic pressure
generally very low; can increase with swelling; favors absorption
tissue hydrostatic pressure
generally low; favors filtration
tissue oncotic pressure
non-permeating substances that create the osmotic pressure that favors reabsorption
colloids
the colloid osmotic pressure due to the presence of proteins in a solution
oncotic pressure
a disease of protein malnutrition
Kwashiorkor
What can alter fluid balance?
- Kwashiorkor
- liver disease (decrease production of plasma protein)
- inflammation –> vasodilation –> increased capillary hydrostatic pressure –> increase permeability –> causes proteins to leak out –> decreased plasma oncotic pressure
How does the lymphatic system resolve fluid imbalance due to inflammation?
returns leaked proteins to circulation; more permeable than tissue capillaries
How does the lymphatic system fight against infection?
lymph carries pathogens to lymph nodes where white blood cells can trap them
Which organs can temporarily withstand severe reductions in blood flow?
kidneys, skin, GI tract, liver
Which organs are most vulnerable to interruptions in blood flow?
brain, heart, skeletal muscle
Characteristics or arteries?
- low resistance
- highly elastic
Characteristics of arterioles?
- control TPR
- control blood flow to organs and tissues (vasodilation and constriction)
Characteristics of capillaries and venues?
- site of nutrient exchange
- largest area
- slowest flow
- largest drop in BP
Characteristics of veins?
- low resistance
- holds >60% of blood volume at rest
- one-way valves
- skeletal muscle pump
a weakness in the wall of an artery that can progress to dissection ff the inner layer or the artery begins to tear; eventually will rupture
aneurysm
excessive pressure distends veins and damages valves; blood unable to return to heart and alternate pathways develop
varicose veins
heart valve does not close completely
valve insufficiency
valve does not open completely
valve stenosis
Characteristics of cardiac muscle?
- striated
- gap junctions
- longer action potentials due to prolonged opening of Ca+ channels (prevents summation of action potentials)
Why is the conduction through the AV node slower?
gives atria time to completely depolarize before the ventricles start to depolarize
cardiac muscle fibers that are specialized for rapid conduction of electrical impulse in the ventricle
Purkinje fibers
Name all the stages of an ECG wave.
P wave - atrial depolarization
QRS complex - ventricular depolarization
T wave - ventricular repolarization
only about half of the signal from SA node/atria is transmitted to the ventricles
partial AV block
none of the signal from SA node/atria is transmitted to ventricles; no synchrony –> ventricles beat slower than the atria
complete AV block
What are the complications of atrial fibrillation?
- decreased cardiac output
- increased risk of blood clot (arterial thrombosis)
Where do the abnormal signals of atrial fibrillation arise?
pulmonary vein
How can atrial fibrillation be treated?
- anti-arrythmics
- anti-coagulants
- ablation of a region of the pulmonary vein
- surgical removal of the atrial appendage to prevent pooling of blood
What can cause changes in extracellular concentration of Na+, K+, or Ca+ that can interfere with cardiac rhythm?
- eating disorders (hypokalemia)
- hyponaturemia (can results from overconsumption of water)
- antidiuretic drugs (can lead to hyper or hypokalemia)
phase of ventricular contraction
systole
phase of ventricular relaxation
diastole
What causes the first heart sound – “lub”?
closing of the AV valves (mitral and tricuspid)
What causes the second heart sound – “dub”?
closing of the semilunar valves (aortic and pulmonic)
When do the heart sounds occur?
at the end of systole
What does a murmur during systole indicate?
insufficient AV valve or a stenotic semilunar valve
What does a murmur during diastole indicate?
insufficient semilunar valve or stenotic AV valve
