Cardiovascular pt 2 Flashcards
Atherosclerosis
thickening and hardening of vessel wall
-accumulation of lipid-filled macrophages and formation of plaque on vessel wall
-not a dx, a pathologic process
-inflammatory
atherosclerosis is the leading cause of____
coronary artery dx and cerebrovascular dx
Risk factors of atherosclerosis
-genetics
- male/ post-meno women
-inflammation from bacterial infection(chlamydia, periodontal dx)
Causes of atherosclerosis
anything tht causes endothelial injury:
-smoking
-hypertension
-high blood glucose (dm)
obesity
high LDL, low HDL
lipoproteins
fats packaged together with proteins, used to deliver cholesterol to cells
Pathogenesis of atherosclerosis
-damaged endothelial cells
-LDL infiltration –> oxidation
-immune response; macrophages engulf and t cells activate (release cytokines)
-further damage to vessel wall
-further activation of immune cells
fibrous cap forms- can remain stable or rupture
vicious cycle of inflammation and necrosis
-further damage to vessel wall
-further activation of immune cells
Endothelial dysfunction
-injured ECs become inflamed, cant make normal amts of anti-thrombotics and vasodilators (NO and PGI2)
-local mo release inflammatory cytokines (TNF-a, IFN-y, IL-1)
-damages cells + inflammation =oxidative stress
LDL infiltration
-LDLs from plasma infiltrate the vessel wall, and become oxidized by: oxidative stress, inflammation, activated mo
-oxidized LDLs are toxic to ECs:more damage, infiltration and mo
-Mo engluf ox-LDLs–>foam cell
-fatty streak
-T-cells activate mo
-SMCS begin proliferation
Fatty streaks
for some ppl:
-appear in the aorta (1st decade of life)
-in coronary arteries ( 2nd decade)
-in cerebral arteries (3th and 4th)
SMCs begin proliferation
-contractile –> epithelial phenotype
-make collagen, stiffen vessel wall
-also take up ox-LDLs
fatty streak –> lesion
-fatty streaks turn into lesions (plaques)
-fibrous plaque is stable
-complicated lesion is one where cap is ruptured
necrotic cells
dead, lipid-filled mo (foam cells) and SMCs
Factors contributing to plaque rupture
-shear forces
-enzyme degradation (remodeling)
-physical trauma
____of plaques determines what organ affected by vessel occlusion and ischemia
Location
Plaque in coronary arteries
Myocardial ischemia
Plaque in cerebral arteries
Stroke
Plaque in renal arteries
Reno-vascular hypertension
_____underlying cause of 50% of all deaths
Atherosclerosis
Atherosclerosis treatments-reducing risk factors
-smoking cessation
-reducing serum levels of LDL -> statins
-increasing HDL (can reverse pathogenesis)
-managing HTN and DM
-reducing body weight (obesity leads to low grade inflammation TNF-a and IL-6)
detecting pre-clinical lesions
-CAD- Coronary calcium scan
-PAD- Ankle-brachial index
If a lesion has ruptured or obstructed blood flow___
Primary goal is to restore blood flow before too much ischemic damage occurs
Atherosclerosis treatments under investigation
-gene editing
-antioxidants
Effective in animal models
Three conditions form a pathophysiologic continuum
CAD-Coronary artery disease, Myocardial ischemia, and myocardial infract
The three diseases
-are caused by limiting the hearts supply of oxygenated blood by damaging endothelium, causing inflammation, formation of fibrotic plaque
-are the progressive impairment in pumping ability in the heart
CAD, MI and Myocardial ischemia conventional, non-modifiable risk factors
-advanced age (lots of EC damage, poor repair)
-males, post-menopausal females
-fam hx (genetic factors, shared environmental exposures)
CAD, MI and Myocardial ischemia conventional modifiable risk factors
-dyslipidemia (abnormal concentrations of serum lipoproteins)
-smoking
-DM, insulin resistance
-obesity
-HTN
-sedentary lifestyle
-atherogenic diet
CAD, MI and Myocardial ischemia non-traditional risk factors
-increased serum markers for inflammation and thrombosis
-hyperhomocysteinemia
-adipokines
-coronary artery calcification and carotid wall thickness-degree of structural change incr risk
hyperhomocysteinemia
- lack of enzyme that breaks down homocysteine, associated with pathogenic events of atherosclerosis
hs-CRP
(acute phase reactant made in the liver)—>plauque related inflammation
Adipokines
-hormones -leptin and adiponectin released by adipose cells
-have pro-inflammatory effects
Myocardial ischemia
Supply of coronary blood cannot meet demand of myocardium for O2 and nutrients
Myocardial ischemia caused by:
-HTN, cocaine abuse, excessive/excertion, thyrotoxicosis
-atherosclerotic plaques in coronary vessels
Role of atherosclerosis for myocardial ischemia
-plaques can grow in size
-ruptures plaque causes thrombosis
-occluding vessel lumen—> ischemia
Myocardium becomes ischemic within_______of coronary occlusion. If ischemia persists longer than _____infarction will occur
10 seconds , 20 mins
Myocardial infraction
Result of prolonged disruption in blood flow; myocytes dies
Myocardial infraction- cell injury effects
-oxygen deprived
-anaerobic respiration -accumulation of H+ and lactic acid
-damaged myocytes trigger release of Epi and NE—> further stress on heart
-reperfusion injury (ROS damage)
-loss of contractility
Myocardial infraction- cell death
-after 20 min of ischemia, irreversible hypoxic injury
-necrosis of dead myocytes-intracellular molecules relapsed into blood and lymph
-troponin-can be measured clinically
Myocardial infraction- heart remodeling
-damaged cells are degraded and removed
-fibroblasts proliferate —. Scar tissue
-scar tissue is strong but lack contractility f healthy myocardium
Function changes in heart
Level of impairment depends in severity of damages
-decreases cardiac contractility
-altered LV compliance
-decr stoke volume and dejection fraction
-SA or AV node malfunction
Ischemia/infarct manifestations
-chest pain (angina pectoris) -70-80% of ischemia episodes asymptomatic
-shock-if primary coronary vessels occluded, assc with septum damage, rupture of chamber wall
-nausea/vomitting- due to activation of vagus nerve
-trachycardia-increase Epi and NE to maintain stroke volume
Infarct diagnosed by___
ECG and alteration in serum biomarkers (troponin)
Half of all infarcts are_____ by any symptoms
NOT preceded
Infarct treatment
Initial: supplemental O2, aspirin (antithrombotic)
Long-term:lifestyle, manage/treat co-existing condition (ACE inhibitors, beta-blockers, statins)
-thrombolytic/ antithrombotic
Cardiomyopathies
-group of conditions that affect wall of heart
-tissue remodeling due to ischemia or hypertension (usually)
-often leads to heart failure
Dilated cardiopathy
-chambers stretched out, heart is globe-shaped
-ventricular dilation leads in increase in intracranial volume
-increase in preload (affects SV and CO)
Dilated cardiomyopathy causes
Genetic
Infectious
Starvation
Alcohol
Most common cause of sudden death in athletes
Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy
-characterized by thickening of heart walls
-response to increased afterload
-loss of compliance, cannot adequate fill with blood (affects SV, and CO)
Hypertrophic cardiomyopathy CAUSES
HTN
Genetic
Myocardial remodeling , Body compensates by activating_____
Symph NS and RAAS.
-Dysfunction decreases CO, MAP
-Myocardial cells remodel to adapt to extra stress
Heart failure
Inability of the heart to generate adequate cardiac output
Cmon risk factors for heart failure are____and ______
Ischemia and hypertension
Other risk factors for heart failure
-age, obesity, renal failure, myocarditis, alcoholism, congenital heart dx, cardiomyopathies
Types of heart failure
-systolic-heart cannot generate enough force to pump blood
-diastolic-heart cannot dilate enough to fill with blood
-left-sided-left side of heart most common
-right-sided: affecting right side of heart - can be causes by pulmonary dx
Heart failure manifestations
-dyspnea or excertion
-increases venous pressure, lung edema
-insufficient CO, blood begins “backing up”
-tissue edema, lower extremities, increase in capillary hydrostatic pressure prevents reabsorption of fluid
