CAD and ACS Patho Flashcards
Arterioscelerosis
Definition
Disease of arteries where injury/inflammation results in :
1. thickening/narrowing
2. loss of elasticity
Occurs in
1. intima layer (endothelial)
2. medial layer (muscular)
Example:
Atheroscelerosis
Atheroscelerosis
Definition
A type of arterioscelerosis
1. narrowing/thickening
2. loss of elasticity
Results from injury, inflammation, and deposition of cholesterol/lipids in the endothelial/intimal layer of the artery
Arteries involved:
Aorta
Coronary arteries
Carotid arteries
iliac
mesenteric
femoral
Coronary Arteries
Physiology
Coronary ostia
- site where coronary arteries originate
- off of the aorta
- 2 branches
- LCA
- left coronary artery (Left atrium, ventricle)
- Left anterior descending coronary artery (anterior, septum, apical)
- Left circumflex artery (lateral, posterior) - RCA
- right coronary artery (right atrium, ventricle, SA, AV node)
- right posterior descending artery (back of right side of heart)
- right marginal artery (lateral side of heart)
Physiological Function of the Endothelium
Endothelium
- intima
- inner lining of the blood vessels
Functions (homeostasis: vascular tone, coagulation, immune response)
- Anti-platelet (prostaglandins inhibit platelet activation)
- Vasodilation (production NO)
- Anti-coagulation(activate protein C anti-coagulation, produce heparin)
- inflammation (P-Selectin, attachment for platelets and WBC diapedesis)
- angiogenesis (new blood vessels)
Pathophysiology CAD
Step 1
- Endothelial injury and dysfunction
Injury
- virus, toxins, smoking
- inflammatory cytokines
- hypertension
- hyperglycemia, dyslipidemia, hyperuricemia
Endothelial dysfunction
- Narrowing
- cannot produce NO - Clotting
- cannot produce anti-platelet (heparin, C protein)
- cannot produce anti-coagulation (PGE)
Pathophysiology CAD
Step 2
- Formation Fatty Streak (earliest lesion)
- endothelial cell injury
- inflammatory response
- expression P selectins
- recruitment of WBC (neutrophils, macrophages)
- deposition LDL (lipids deposit)
- Neutrophils release ROS which oxidize lipids
- oxidized lipids increase endothelial expression of adhesion molecules (diapedesis WBC)
- macrophages phagocytose the oxidized LDL
- Foam cell = macrophage + oxidized LDL
- signal cytokines to recruit T cells
- cytokines TNF alpha, IFN gamma, IL1 stimualte expression adhesion molecules and procoagulation activity
- formation fatty streak = T cells (WBC) + foam cells (Macropahges + oxidized lipids)
Pathophysiology CAD
Step 3
- Formation fibrous plaque
- Pro-inflammatory cytokines recruit vascular smooth muscle cells and fibroblasts
- proliferation, hypertrophy, increase deposition ECM
- thickening of the intima layer / narrowing
- loss of elasticity
- (aterioscelerosis)
- Formation of the thin fibrous plaque over the foam cell core (proinflammatory)
Unstable plaque
- thin fibrous cap
- large foam cell core (proinflammatory)
- NEW
- Prone to rupture
Pathophysiology CAD
Step 4
- Complicated lesion = ruptured fibrous cap = hemorrhage + thrombi + emboli
- Thin fibrous cap ruptures
- hemorrhage (bleed)
- exposure of ECM results in platelet activation (collagen activates platelet IIb/IIIa receptors)
- thrombus formation
- narrow lumen (thrombi)
- Ischemia at site
- Formation emboli
Diseases that lead to endothelial injury and dysfunction
- hypertension
- diabetes
- chronic kidney disease
- gout
- dyslipidemia
- hyperglycemia/hypoglycemia
- viruses
- inflammatory cytokines
- toxins
- obesity
- injury
- inflammation
- oxidization lipids, fatty streaks
- fibrous cap/scelerosis/thikening/narrowing VSM
- unstable lesion/complicated lesion
Acute Coronary Syndrome
- Unstable Angina
- NSTEMI
- STEMI
*medical emergency
Stable Angina
Definition
Pain < 5 minutes
reversible with rest, medication
Trigger (vasoconstriction): emotions, exercise
Pathphysiology
- atheroscelerosis of the coronary arteries
- Thickening/narrowing intima
- Decreased elasticity
- unable to vasodilate under stress
- ishemia (demand for oxygen > supply)
Laboratory findings
- normal troponin
- normal ECG (unless stress ECG / exercise ECG)
Unstable Angina
Definition
Pain > 5 minutes and < 20 minutes
reversible if < 20 minutes
Occurs at rest (no trigger)
Pathophysiology
- Unstable, complicated plaque
- rupture, thrombus formation
- blocks blood flow at rest
- ischemia at rest
*high risk of MI
Laboratory findings
- Normal or slightly elevated troponin
- normal or ST depression, T wave inversion ECG (when in pain)
NSTEMI
Definition
Non ST elevated MI
> 20 minutes cardiac ischemia -> Necrosis
Troponin elevated
ECG changes (ST depression, T wave inversion)
*endocardium
STEMI
Definition
ST elevated MI
> 20 minutes cardiac ischemia -> necrosis
troponin elevated
ECG changes (ST elevation)
*transmural necrosis (more serious than NSTEMI)
Interventions ACS
- Reperfusion of cardiac muscle (time is muscle)
MONA
- morphine
- oxygen
- nitroglycerin
- anti-platelet therapy (ASA)
PCI
- percutaneous coronary intervention
Anti-fibrinolytic therapy
- TNK or Tissue plasminogen activator
- dissolve the clot if PCI is not available
Unstable Angina
Clinical Signs and Symptoms
- crushing substernal chest pain
- increase frequency and severity of the angina pain
- lasts > 5 minutes
- unprovoked (occuring at rest when calm)
STEMI/NSTEMI
Typical Clinical Signs and Symptoms
Ischemia:
Crushing substernal chest pain
pain in back
referred pain back, shoulder, arm, neck, jaw
nausea, vomiting
arrhythmias
SNS activation:
pale
diaphoresis
tremor
anxiety
tachycardia
Decreased CO:
fatigue
confusion
hypotension
syncope
pulmonary edema (SOB), dyspnea
Atypical
STEMI and NSTEMI
Older > 85 years
DM
female
*neuropathy results in no SNS signals
Decrease CO:
Hypotension
fatigue
weakness
confusion
shortness of breath
Referred pain:
abdominal indegestion like pain
neck, back
*Higher mortality as it is missed
Pathophysiology
Acute Coronary Syndromes
CAD leads to decrease blood flow (ischemia)
- Stable angina
- trigger: vasoconstriction
- < 5 minutes pain
- reversible - Unstable angina
- No trigger: at rest
- ruptured plaque: complicated lesion, thrombosis ischemia
- < 20 minutes
- reversible
- no death of cardiomyocytes - MI
- ischemia > 20 mintues, infarct
- Change in 1. function 2. structure of the heart
- cardiomyocyte stunning (loss of contraction due to anaerobic metabolism, low pH, electrolyte imbalance, activation SNS, change in contractility/HR/conduction)
- cardiomyocyte hibernation (change in metabolism to survive, occurs if frequent ischemia, adaptive)
- cardiomyocyte remodelling (inflammation, myofibroblasts/VSM proliferation/hypertrophy/ECM; SNS, RAAS, cytokines) - Change conduction pathways
- dysrhythmias - change in size, shape, function
- hypertrophy
- heart failure
- dissections
CVD
Modifiable risk factors
CVD = injury/inflammation (endothelial dysfunction)
- virus
- toxins (smoking, alcohol)
- obesity (pro-inflammatory)
- diabetes (hyperglycemia)
- dyslipidemia
- hyperuricemia (gout)
- HTN
- stress/depression (pro-inflammatory)
- diet
- exercise
CVD
Non-modifiable risk factors
- Age
- older
- women > 65 years
- men > 55 years
- before this is premature CVD - gender
- males > females (early in life) - family history
Social Determinants of Health
CVD
- housing
- food
- stress
- employment
- racisim/sexism/discrimination
- environment pollution
Influences endothelial injury, dysfunction, CVD development and disease progression
Indigenous Peoples
CVD
- Higher HTN
- Higher DM
- Higher CVD
*discrimination, racism, SDOH -> CVD
- poor access to care, cost of care
- bias in assessment, not screened
- emergency PCI vs. planned
- higher morbidity and mortality post operatively
PQRSTUAAA
Chest Pain
Provokes: at rest? trigger?
Quality: crushing? heavy?
Radiation: jaw, neck, back, shoulder, arm
Region: substernal
Severity: Severe
Timing: with exercise? in morning? with stress? all the time? with movement? without movement? > 5 mintues?
Understanding:
Associated S&S: SNS (diaphoresis, tremors, anxiety, pale, tachycardia), CO (fatigue, confusion, dizziness, syncope, hypotension, bradycardia)
Alleviation: rest?
Aggrevation: exercise?
Typical Angina
Classification
3/3 Typical symptoms
- substernal chest pain
- crushing
- < 5 minutes - provoked by
- stress
- exercise - relieved by
- rest
- nitroglycerin medicaiton
Atypical Angina
Classification
2/3 classical signs and symptoms
SILENT
- women, > 85 years, DM can present with atypical angina
- fatigue, confusion, N/V, abdominal discomfort
1. provoked
2. relieved with rest
Meet 2/3
Non-cardiac
classification
1/3 classical signs and symptoms
investigate other cause
- heart
- lungs
- MSK
- mind
Canadian Cardiovascular Society (1976)
Angina Classification
I-IV
Class I-III
- stable angina
- Class I: strenuous exercise
- Class II: exercise
- Class III: normal activities
Class IV
- unstable angina
- provoked at rest
Diagnostic and Laboratory Tests
CAD
CBC
Lytes (Na, K, Mg, Ca, Phosphate)
Lipid pannel (TC, TG, LDL, HDL)
A1C and FPG
Creatinine
INR and PTT (preparation for PCI)
ECG (12 lead)
Troponin I and T
Hs-cTN
Troponin I vs. T vs. hs-cTN
Troponin
- Actin (thin filament) = actin, tropomyosin (covers myosin binding site), troponin (I, T, C)
- indicators of MI (or muscle breakdown)
cTnI
- Cardiac troponin I
- one isoform, only expressed in cardiomyocytes
- most specific marker for MI
- rises 2-4 hours post MI
- can take up to 12 hours to appear
- remains elevate for 10-14 days
TnT
- not specific to cardiac muscle damage
- however can be used to indicate MI
hs-cTn
- high sensitivity cardiac troponin
- can be elevated in unstable angina
Disorders with elevated troponin
- MI
- Unstable angina
- atrial fibrillation
- myocarditis
- heart failure
- structural heart disease (cardiomyopathy)
- depression
- rhabdomyolysis
- sepsis
- renal failure
*inflammation and muscle damage
leads to the release of troponin from the muscle cell
Information obtained from ECG
- rate
- rhythm
- conduction (Bundle branch block = MI)
- ischemia / infarct (ST elevation, depression, T wave inversion)
- necrosis (Q waves)
ST:
time from ventricular contraction (depolarization) to ventricular relaxation (repolarization)
- isoelectric to PR
- not isoelectric = ischemia
NSTEMI: ST depression, T wave inversion
STEMI: ST elevation
Alterations ECG with ACS
- unstable angina
- ischemia present then ECG changes present
- ST depresison, T wave inversion - NSTEMI
- ST depression
- T wave inversion
- * No Q wave
- *clot dissolves, only subendothelial - STEMI
- ST elevation
- Q wave (ncrosis)
*Transmural infarct
Diagnostic work up pathways
Angina
1. typical 2. atypical 3. non-cardiac
STABLE chest pain syndrome
- typical 3/3
- atypical 2/3
- non-cardiac 1/3
- substernal chest pain< 5 mintutes
- provoked by stress/activity
- relieved by rest
Not emergency, perform labs:
- CBC, lytes, lipid pannel, A1C, FPG, Cr
- ECG
- Typical (3/3) or atypical (2/3)
- non invasive testing
- choice of test dependent on ECG - non-cardiac 1/3
- males > 40 years, females > 60 years, CVRF present: non-invasive testing
- males < 40 years, females < 60 years, no CVRF present: watch and wait
Non invasive CAD testing
Questions:
Is your ECG normal?
Can you exercise? (no HTN > 200mmHg SBP; MI; HF; electrolyte imbalances; PE; arrhythmias)
- Exercise stress test
- ECG while exercising (vasoconstriction induced) - Exercise echocardiography (ECG abnormal, can excercise)
- echocardiography: wall motion, LV ejection fraction, and ECG - Exercise perfusion imaging (ECG abnormal, can exercise)
- Vasodilator echocardiography (cannot exercise)
- pharmacological induced ischemia - Vasodilator perfusion imaging (branch blocks, ventricular paced rhythm)
- pharmacological induced ischemia - cardiac computed tomography (branch blocks, ventricular paced rhythm)
Information obtained from cardiac CT
- extent and area of the block
Gold standard diagnosis CAD
Coronary angiography
- contrast dye
SE:
- 1/1000 MI, CVA, death
Physiological Function
Cholesterol
- Cell/organelle membranes (fluidity, rigidity)
- Bile salts (absorption/digestion fat, GI, Liver)
- prevent water loss skin
- Steroid hormones (estrogen, progesterone, testosterone)
*LDL delivers cholesterol to non-hepatic cells
Cholesterol
Endogenous vs. Exogenous
Majority of cholesterol is ENDOGENOUS
- made by liver
- HMG CoA reductase (3 hydroxy 3 methyl glutaryl co enzyme A)
- rate limiting step
Minority cholesterol is DIET
- dietary intake
- liver stops synthesis
What type of fat intake increases endogenous cholesterol synthesis?
Saturated fats
Reduce intake = reduce cholesterol synthesis by 15-25%
Lipoproteins
Components, Function
Lipoproteins
1. phospholipid
2. Triglyceride and cholesterol core
3. Apolipoprotein
- circular structure
- soluble transport of lipids in the blood
Apolipoprotein function
- structure
- receptor attachment site (uptake)
- activate enzyme for metabolism
Types of lipoproteins
- VLDL
- LDL
- HDL
Structure and Function
VLDL, LDL, HDL
VLDL
- TG core
- *predictive pancreatitis
LDL
- Cholesterol core
- transport cholesterol to non-hepatic tissues
- tissues increase LDL receptors when they need cholesterol
-*predictive CAD and ASCVD
- 1% reduction = 1% reduction
HDL
- Cholesterol core
- Transport cholesterol back to liver
- good cholesterol
- Protective
Role of LDL oxidation in Atheroscelerosis (ASCVD)
LDL deposits in intima (below endothelial cells)
Oxidation LDL
- cytotoxic = inflammation
- signals monocytes
- engulphed by macrophages
- causes vacuolation of macrophages = foam cells
- prevents their mobility
- macrophages signal for WBC
- accumulation = atheroma
- lumpy = turbulent blood flow = pro-coagulation
What is more likely to rupture
Mature or immature plaque?
Immature plaque
Thin fibrous cap
unstable and more likely to rupture
What causes a plaque to rupture?
Accumulation inflammatory cells
Turbulent blood flow
shearing forces
high blood pressure
ASCVD Risk Factors
- age
- black
- hypertension (BP > 130)
- smoking
- HDL, Total cholesterol, LDL
DM is EQUIVALENT to having ASCVD
3 principle presentations of unstable angina
- rest angina > 5 minutes
- new onset class III (regular activities)
- more frequent, more severe, longer duration, lower threshold trigger
Management unstable angina hospital
- hospital
- MONA
- morphine, oxygen, nitrates, anti-coagulation therapy - PCI (reperfusion) or anti-thrombotic therapy or both
- beta blocker + ACEi + statin + hyperglycemic control
Functional impairment Post MI and complications
- contractility & conduction
- end diastolic pressure
- ejection fraction
- dysrhythmias
- 6 weeks for scar tissue to heal
Complications of MI
dysrhythmias; 90% post MI
LV HF
pericarditis
rupture heart wall, vessels
thromboembolism
sudden death (> 65 years, HTN, shock, DM, dysrhythmia, prior MI)
Peripheral Artery DIsease (PAD)
Pathophysiology
Atheroscelerosis of the arteries of the lower extremities
- iliac
- femoral
- acute or 2. gradual ONSET
Clinical S&S
- intermittent claudication
Lipids that predict CVE
Lipoprotein B (structural protein on LDL, allows for deposition into tissue)
non HDL C (atherogenic lipids)
LDL
low HDL
Lipoprotein A (genetically pre-determined at birth)
- predictive for women
Non pharmacological ways to raise HDL
fish oil
exercise
weight loss
moderate alcohol intake
Diagnostic labs for ACS
ECG
Labs:
CBC and WBC diff
ESR, CRP
high sensitivity troponin
other:
lipid pannel
A1C, RPG
Chest x ray
Treatment STEMI and NSTEMI
MONA
morphine
oxygen
nitroglycerine
ASA
ICU orders for MI
Continuous monitoring ECG, oxygen
Blood work trends:
CBC, WBC, high sensitivity troponin, CRP every 24 hours
Bed rest for 14 days
Continuous medicaitons
ACEi/ARB + Beta blocker
Statin
Anti-coagulant (heparin/LMWH, DOAC)
Treatment
glucose
stool softeners
ECG indications
Q wave - necrosis
ST elevation - Injury myocardium
T wave inversion - ischemia
