Lecture 6: Hemostasis, coronary artery disease, myocardial infarction, hypertension, heart failure

list out steps of what happens after blood vessel is damaged

1. blood vessel damaged

2. altered endothelial surface (collagen exposure)

3. platelets activation and aggregation

4. activated platelet factors

5. leads to vasoconstriction of vascular smooth muscle and platelet plug (from aggregation of platelets)

clotting cascade

1. 2 clotting factors (XII and VII) activated by exposure of blood to collagen or subendothelial tissue

2. activation of a cascade of factors which culminates in activation of Factor X (Xa)

3. Cleaves prothrombin to thrombin (enzyme)

4. Thrombin cleaves fibrinogen to fibrin (loose white meshwork). Thrombin also activates factor XIII → stabilizes clot → positively feeds back to activate 3 earlier sterps in the cascade

5. Fibrin forms the clot

why don’t clots occur all the time/stick around forever?

1. healthy endothelial cells secrete factors to inhibit platelet activation

2. proteins that inactivate multiple clotting factors are expressed on healthy endothelial cell membranes

3. circulating plasminogen is activated to plasmin after clot formation, which breaks down existing clots (a process called fibrinolysis)

what is produced by liver in clotting cascade

clotting factors and fibrinogen

coronary artery disease

• caused by atherosclerosis = thickening of vessel wall with “plaque” which narrows the lumen

• can lead to insufficient blood flow (ischemia) to an area of the heart muscle

myocardial infarction (MI)

• heart attack

• area of cell damage or death in the heart due to O2 deprivation

• can be caused by:

  • plaque rupture and clot formation (thrombosis) → total occlusion

  • embolism lodging in narrowed artery → total or partial occlusion

  • coronary artery spasm → temporary occlusion

  • mismatch between demand and delivery due to significantly narrowed artery, but not due to one of the previous 3

what happens to CO in myocardial infarction

• if muscle cells are affected, may reduce the ability of a ventricle to adequately eject blood (decreased SV → decreased CO)

• if conduction system is affected, problem with HR (decreased HR → decreased CO, or sometimes chaotic or huge increase in HR → decrease SV → decrease CO)

STEMI myocardial infarction

ST elevation, which indicates complete blockage of flow (total occlusion)

NSTEMI myocardial infarction

either ST depression or T inversion. limited flow but not total occlusion

immediate HR, CO, MAP, TPR changes that occur when heart attack begins (damage to LV → significant decrease in SV)

• no change in HR (SV and HR are unrelated to one another)

• CO decreases (CO = HR x SV)

• MAP decreases (MAP = HR x SV x TPR)

• no change in TPR

compensatory responses to HR, CO, MAP, TPR, VR after heart attack (damage to LV → significant decrease in SV)

• decreased SV → decreased MAP → decreased baroreceptor firing to medulla →

  • decreased PS to SA/AV nodes → increased HR

  • increased symp → arterioles → vasoconstriction → increased TPR

  • increased symp → veins → venoconstriction → increased VR

  • CO increases b/c HR increases (CO = HR x SV)

  • MAP increases (MAP = HR x SV x TPR)

hypertension and its effect

• chronically increased systemic arterial pressure. typically caused by increased TPR

• increases afterload on the heart

why does hypertension lead to heart failure

hypertension → increased afterload → left ventricular hypertrophy → decreased compliance → decrease filling (diastolic dysfunction) → decreased EDV → decreased SV → decreased CO → heart failure

heart failure and cause

• heart fails to pump adequate CO

• causes

  • heart attack causes systolic dysfunction

  • chronic hypertension causes diastolic dysfunction

When left heart failure is occurring (left ventricle’s CO is too low), where would edema FIRST become evident?

• lungs (pulmonary circulation)

• flow into lungs > flow out of lungs

  • LV (low CO) → RA (systemic organs)

  • RV → LA (lungs)

• Pc increases → filtration increases

When right heart failure is occurring (right ventricle’s CO is too low), where would edema FIRST become evident?

• periphery (systemic circulation) = abdomen, lower extremities

• Flow into systemic circulation > flow out of systemic circulation

explain physiologic changes of chest pain (or jaw, neck, arm, shoulder, back pain) symptom in MI

• lack of blood flow to regions → cell death

• chemicals released activate nociceptors (pain receptors)

• “referred pain” = a brain interpretation issue

explain physiologic changes of lightheadedness symptom in MI

decrease CO → decrease MAP → blood flow to brain decreases

explain physiologic changes of weak but rapid pulse symptom in MI

• pulse pressure decreased due to decrease SV = weak pulse

• rapid pulse due to increase HR due to baroreceptor response to low MAP

explain physiologic changes of pale skin symptom in MI

decrease MAP → increase symp to arterioles → vasoconstriction → increase TPR → blood flow to skin is reduced

explain physiologic changes of cold hand/feet symptom in MI

decrease MAP → increase symp to arterioles → vasoconstriction → increased TPR → decrease blood flow to extremities