fall chem week 2

coronary artery disease CAD/ heart disease CHD

atherosclerosis narrowing the arteries feeding the heart

cerebrovascular disease

interrupted blood flow (ischemia) to the brain transient ischemic attack TIA or lasting (stroke)

peripheral arterial disease PAD

atherosclerosis narrowing arteries of the limbs, usually legs

aortic atherosclerotic disease

plaque buildup weakening/narrowing the aorta, aneurysm or dissection risk

coronary heart disease presentation

angina pectoris (chest pain), myocardial infarction MI (heart muscle death necrosis from blood flow loss ischemia), heart failure (cannot pump enough for body)

other vascular sites CVD presentation

stroke or mini stroke TIA, deep vein thrombosis DVT (blood clot in deep vein in leg), pulmonary embolism PE (clot from DVT lodging in lung arteries), aneurysm (abnormal bulging of weakened vessel wall), aortic dissection (inner wall tear lets blood split vessel layers apart)

Which event most directly converts a stable atherosclerotic plaque into acute coronary syndrome?

A fibrous cap ruptures and exposes thrombogenic material

atherosclerosis

chronic inflammation disease of medium and large arteries, endothelial dysfunction> lipid retention> plaque (gradually marrow artery, reduce blood flow, rupture/erode causing thrombus)

causes of endothelium damage

turbulent flow, hypertension, hyperlipidemia (high LDL), hyperhomocycteinemia (AAs breakdown product, auto oxidizes to free radicals), tobacco smoke, hyperglycemia (glycation and oxidation)

lumen

space blood flows through in vessels

tunica intima

endothelium plus subendothelial space in vessel

internal elastic lamina

divides intima from media in vessel

tunica media

smooth muscle and elastic tissue

atherosclerosis step 1- vascular injury and lipoprotein migration

damaged endothelium is more permeable to lipoproteins causing them to accumulate in intima space and be glycated and oxidized

atherosclerosis step 2- cytokines released

oxidative stress from modified LDL induces local inflammatory cytokines

atherosclerosis step 3-4- wbc recruited and migrate

cytokines raise adhestion molecule expression, monocytes attah and migrate into intima space becoming macrophages with scavenger receptors for oxidized LDL

atherosclerosis step 5 foam cells form

lipid-laden macrophages become foam cells with no shut off (overload) releasing proinflam cytokines, overloaded cells fail spilling contents recruiting more cells creating self sustaining inflam lesion

atherosclerosis step 6-7- smooth muscle cell migration

smooth muscle cells move from media into intima, multiply and secrete collagen and elastin, fibrous tissue builds up strengthening the plaque

atherosclerosis step 8- mature plaque

fibrosis continues, calcification, smooth muscle cells die, fibrous cap left with few living cells surrounds lipid rich core unable to repair itself and ruptures

atherosclerosis outcomes

symptoms at 75% obstruction, stable plaque exertional symptoms resolved with rest, coronary ACD, cerebral (stroke), peripheral (limp ischemia) due to ruptured cap

acute coronary syndrome ACS

unstable ischemic heart disease, angina- without cell death, acute MI- with cell death, chest pain

acute coronary syndrome ACS initial evaluation

physical exam and history, 12-lead electrocardiogram ECG, chest x ray, cardiac biomarkers

STEMI vs NSTEMI

ECG splits MI into 2 types: ST-elevation MI full thickness damage and non-ST-elevation MI inner layer damage (farthest from blood supply hit first)

ruling out MI

normal cardiac biomarkers, normal ECG does not rule out

myocardial injury

no ischemic symptoms required, elevated cardiac marker present

myocardial infarction

injury plus cardiac marker rising and/or falling, plus ischemic symptoms, ECG change, or imaging evidence

apoptosis

programmed, requires energy, dna degraded purposefully, cleared properly by macrophages

necrosis

energy (blood) supply fails, happens rapidly in the heart (huge energy demand, die within min), busted cell contents (drive local imfam response and spill biomarkers into blood stream)

cardiomyopathies

genetic or stress related myocyte injury

abnormal muscle structure/function

chronic myocyte stress, decompensated heart failure due to volume overload

mechanical wall stress from stretch

myocarditis from viruses and bacteria

direct infection and immune attack on myocytes

bacterial toxins in sepsis, certain drugs

ideal cardiac markers

released rapidly into circulation, specific and sensitive, persists several days for late presenters, detectable at low concentration

AST and LDH for cardiac injury

enzymatic, abundant in heart muscle, increase within hours to couple days, long elevation window (A several days, L week), but slow to rise and also in liver and skeletal muscle

CK for cardiac injury

enzymatic, larger increase earlier (few hrs) but found in all tissue and quick return to normal (few days)

CK-MB for cardiac injury

immunoassay, mainly in cardiac tissue, larger increase earlier (few hrs), but some in brain and skeletal muscle and quick return to normal (few days)

MYO for cardiac injury

immunoassay, early rise after MI (couple hrs), tested very quickly, paired well with CK-MB, but not specific in all muscle cells, return to normal too quickly (1 day)

cTn-T or cTn-I for cardiac injury troponin

immunoassay, reg protein of myofibril, highly specific for cardiac muscle, elevated for long time (1-3 weeks), low in pt without CVD, rise in couple hrs peaks in 1 day, but testing to early can miss AMI

early generation cTrop

chronic cardiac damage until passing rule in 0.1 becoming acute cardiac damage (myocardial necrosis), limit of detection 0.01

high sensitivity cTrop

normal levels then chronic cardiac damage until passing rule in 100 becoming acute cardiac damage (myocardial necrosis), limit of detection 6, detects low cTn concentrations, requires clinical interpretation

A patient with chronic kidney disease has hs-cTn results persistently above the reference interval with no meaningful serial change. Which interpretation is most appropriate?

Chronic myocardial injury is more likely than acute injury

cTn of AMI vs cTn of chronic cardiac condition

peak vs no peak using baseline measurement and 2nd measurement

HS Trop baseline- females under 15 and males under 23

pan onset after 2 hrs= acute myocardial injury less likely evaluate clinically

pain onset under 2 hrs= indeterminate 2 hr test recommended

HS Trop baseline- females 15-100 and males 23-100

indeterminate 2 hr test recommended (delta)

HS Trop baseline- greater than 100

acute myocardial injury ruled in, critical result

HS Trop 2 hr delta less than 4

not changing= acute myocardial injury less likely, evaluate clinically

HS Trop 2 hr delta 4-9

indeterminate= 6 hr test rec

HS Trop 2 hr delta more than 9

changing= acute myocardial injury ruled in, critical result

troponin complex

regulates calcium dependent muscle contraction in all striated muscle, reg protiens= tropon C T and I, T and I (cardiac specific isoforms detected by immunoassay)

CHF congestive heart failure

fluid buildup, shortness of breath, fatigue, leg edema

CHF cbc

low hgb/hct or high wbc due to anemia or infection

CHF electrolytes

low sodium due to dilution from fluid

CHF BUN/creatinine

high due to reduced kidney perfusion

CHF glucose

high due to stress, diabetes risk

CHF liver enzymes

high due to hepatic congestion (right sided HF)

CHF TSH

variable due to thyroid disease

CHF natruretic peptides

ANP atrial, BNP b-type, high released due to stretch from pressure and vol overload, most direct marker of HF severity, natriuresis (Na in urine), diuresis (lots of urine), vasodilation, separates cardiac from lung cause of dyspnea (shortness of breath)

BNP vs NT-proBNP

precursor pro-BNP peptide splits into 2 pieces= active BNP and inactive (N-terminal) NT-proBNP longer half life prefered

troponin in HF

elevated without any ACS, reflects wall stress and ongoing cell death, prognostic (2.6-fold higher in hospital mortality) not diagnostic, strongest predictor paired with BNP

congenital heart disease

structural defect at birth, BNP tracks stain or severity, not diagnostic

hypertensive heart disease

chronic pressure overload thickens heart muscle, BNP and Trop reflect ongoing stain

myocarditis

infec/inflamm of heart muscle, Trop rises from direct injury, can mimic MI

endocarditis

infection of heart valves, diagnosed by cultures/echp, Trop/BNP if complicated by heart failure

hs-CRP

high sensitivity c-reactive protein, 0.15-10, less than 1 low risk, 1-3 moderate, over 3 high risk, better predictor than LDL, not routine bc not specific

Lp(a) lipoprotein(a)

genetically determined, non modifiable, pro-atherogenic, predicts premature CVD, 30-20 cutoff, assay standardization difficult

homocysteine

byproduct of methionine metabolism (auto oxidizes to free radicals), associated with atherosclerosis and thrombosis, elevated due to B6, B12, folate def, renal impairment, genetic enzyme defects

D-dimer

product of plasmin mediated fibrin degration, indirect marker of clotting/fibrinolysis, abnormal in 90% of PE pts, raised by malignancy, surgery, age (poor ppv), good npv best to exclude PE not diagnose it

PE risk stratification

Trop and NT-proBNP for severity, elevates= high risk of adverse outcome monitor closely, normal levels= low risk uneverntful course