participants had increases in HDL cholesterol averaging about 2.5 mg/dL. This increase in HDL cholesterol was only modest, but was statistically significant. Furthermore, since cardiac risk is thought to drop by two to three percent for each 1 mg/dL increase in HDL, a 2.5 mg/dL rise in HDL amounts to a substantial reduction in risk.
Exercise is involved in increasing the production and action of several enzymes that function to enhance the reverse cholesterol transport system (Durstine & Haskell 1994). The precise mechanisms are unclear, but evidence indicates that other factors including diet, body fat, weight loss, and hormone and enzyme activity interact with exercise to alter the rates of synthesis, transport and clearance of cholesterol from the blood (Durstine & Haskell 1994).
CARDIOVASCULAR SYSTEMPATHOGENESIS:“response to injury hypothesis”A disease of intimaChronic inflammation of arterial wall inresponse to injury to endothelium
CARDIOVASCULAR SYSTEMMacrophages toxic oxygen species oxidation of lipids GF smooth muscle cell proliferationT lymphocytes cellular & humoral3. Lipids: cholesterol & its esters in atheromas Oxidized LDL in macrophages
CARDIOVASCULAR SYSTEM genetic defects hypercholesterolemia AS MI at young age with ↑ cholesterol DM, hypothyroidism ↑ cholesterolAS high cholesterol diet AS severity of AS levels of cholesterol ↓ing cholesterol levels risk of AS ↓
CARDIOVASCULAR SYSTEM“ Structure of hypertrophied heart is not normal. It is a tight balance between adaptation and deleterious alterations ( ↓ capillary-to- myocyte ratio, ↑ fibrous tissue & synthesis of abnormal proteins). Thus sustained cardiac hypertrophy evolves into cardiac failure.”
CARDIOVASCULAR SYSTEMMolecular & cellular changes that initially mediate enhanced function later contributes to heart failure.Physiologic hypertrophy.Pathologic hypertrophy.
CARDIOVASCULAR SYSTEMLeft sided heart failure:Causes: IHD HTN Aortic, mitral valvular disease non ischemic MC disease
CARDIOVASCULAR SYSTEMMorphology: Evidence of cause enlarged size ↑ left vent wall thickness secondary effects on atria
CARDIOVASCULAR SYSTEMExtracardiac effects:1. Pulmonary congestion & edema heavy, wet lungs interstitial transudate Kerly’s B lines widening of alveolar septa edema in alveolar spaces heart failure cells
CARDIOVASCULAR SYSTEM dyspnea orthopnea paroxysmal nocturnal dyspnea2. Kidneys ↓ renal perfusion pre renal azotemia
CARDIOVASCULAR SYSTEM3. Brain hypoxic encephalopathyRight sided heart failure:Causes left sided heart failure chronic severe pulmonary HTN (cor pulmonale)
CARDIOVASCULAR SYSTEMRole of inflammation:All stages of ASMacrophages & T lymphocytesIL-1, IL-6, TNF, INF gMetalloproteinses weaken plaqueInflammation destabilizes plaque
CARDIOVASCULAR SYSTEMRole of coronary thrombus:Partial / total acute coronary syndromesMural branch thrombus embolize MicroinfarctsRole of vasoconstriction:Potentiate plaque change
CARDIOVASCULAR SYSTEMANGINA PECTORIS:“A symptom complex of IHD cahracaterized by recurrent attacks of substernal/precordial chest discomfort caused by transient MC ischemia that falls short of inducing infarction.”
CARDIOVASCULAR SYSTEMMYOCARDIAL INFARCTION: “Heart attack”Death of cardiac muscle due to ischemia.Transmural infarctionSubendocardial infarction
CARDIOVASCULAR SYSTEMTRANSMURAL SUBENDOCARDIALFull thickness of MC Inner 1/3rd or halfAS plaque change As plaque change thrombosis thrombosis recanalized Hypotension / shock on chronic stenosing ASLimited to area of supply Can extend beyond
CARDIOVASCULAR SYSTEM FEATURE TIMEATP depletion SecondsLoss of contractility < 2 minATP reduced to 50% 10 min 10% 40 minIrreversible cell injury 20 – 40 minMicrovascular injury > 1 hr
CARDIOVASCULAR SYSTEMEarly identificationReperfusion30 min reversible injuryMC ischemia subendocardial zoneWavefront progression transmuralNecrosis within 6 hrsGrossly visible after 12 hrs
CARDIOVASCULAR SYSTEMFactors influencing MI:1. Site, size, rate of development of AS2. Size of vascular bed3. Duration4. Mc demands5. Collateral circulation6. Coronary artery spasm7. BP, HR, cardiac rhythm
CARDIOVASCULAR SYSTEM Morphology: Left ventricle > right ventricle Rim of subendocardium preservedLAD 40 – 50% Ant wall left vent, apex, ant septumRCA 30 – 40% Inf-post wall lt vent, post septum, post right ventLCA 15 – 20% Lat wall left vent
CARDIOVASCULAR SYSTEMTIME GROSS MICROSCOPIC0 – ½ hr ----- myofibril relaxation, swelling of mitochondria½ - 4 hr ----- Wavy fibers4 – 12 h Occ dark mottling Coag necrosis, edema, hge12-24 h Dark mottling Necrosis, pyknosis,myocyte eosinophilia, contraction bands, neutrophils
CARDIOVASCULAR SYSTEM1 -3 days Mottling + yellow Loss of nuclei & striations, centre PMNs ++3 – 7 days Red border, Disintegration, phagocytosis yellow tan center7 – 10 Max yellow soft Phagocytosis ++, granulationdays center, red borders tissue at margins10-14 Red-gray Granulation tissue ++,days depressed collagen +2 – 8 wks Grey white scar ↑ collagen, ↓ cellularity> 2 month Complete scar Dense collagenous scar