Flashcards in Day 6.3 Cardio Deck (133):
Types of lipids in cholesterol (?)
4 signs of hyperlipidemia
1. Atheromas (plaq in bld vessel walls)
2. Xanthomas (plaqs/nodules md of lipid-laden histiocytes in the skin, esp eyelids- xanthelasma)
3. Tendinous xanthoma (lipid deposit in tendon, esp achilles)
4. Corneal arcus (lipid deposit in cornea, non-specific- aka arcus senilis)
What are the 3 kinds of arteriosclerosis?
Calcification in the media (only) of the arteries, esp radial or ulnar arteries.
Intima is NOT involved, so does not obstruct flow.
Hyaline thickening of sml arteries
In essential HTN or in DM
Hyperplastic "onion skinning" in malignant HTN
Fibrous plaqs and atheromas form in the intima of arteries - bad bc restricts flow.
Dz of elastic arteries and M/Lg muscular arteries.
Risk factors for atherosclerosis
Pathway of progression for atherosclerosis
Endothelial cell dysfn leads to macrophg and LDL accumulation. Foam cells form, cause fatty streaks. There is smooth musc cell migration (involving PDGF and FGF-beta), resulting in a fibrous plaq. This leads to complex atheromas.
Where is atherosclerosis usually located?
From most common to least:
Abd aorta (can lead to AAA)
What is an aneurysm? What is AAA?
Aneurysm - widening of blood vessel bc it's weak.
AAA - abd aortic aneurysm. monitor closely and when it gets to 5cm, surgery. If it ruptures will have massive bleed in belly.
Symptoms of atherosclerosis
Can have angina, claudication (angina in legs)
Complications of atherosclerosis
Aneurysms, ischemia, infarct, peripheral vascular dz, thrombus, emboli
What drugs are used to treat atherosclerosis?
The lipid lowering agents:
HMG coA reductase inhibitors
Bile acid resins (not common)
Cholesterol absorption blockers
Omega 3 FA (fish oil, flaxseed)
HMG-coA reductase inhibitors
Effect, MoA, Side effects
Lovastatin, Pravistatin, Simvastatin, Atorvastatin, Rosuvastatin
Main effect is to decrease LDL
(Also raise HDL slightly and lower TG slightly)
MoA: inhibit cholesterol precusor mevalonate
SEff: hepatotoxicity, rhabdomyolysis
Effect, MoA, Side effects
Drug of choice to increase HDL
also lowers LDL and TG
Inhibits lypolysis in adipose tsu and reduces hepatic VLDL secretion into circulation
SEff: red flushed face (decreases w longterm use or w aspirin), Hyperglycemia (acanthosis nigricans skin hyperpigmt), Hyper uricemia (worsens gout)
Bile acid resins
Effect, MoA, side effects
Cholestyramine, coestipol, colesevelam
also slightly increases HDL and slightly (bad) increases TG
Prevents intestinal reabs of bile acids, so liver must use up cholesterol to make more
Side eff: pts hate it- tastes bad, GI discomfort. decreased abs of fat-sol vit (ADEK). cholesterol gall stones.
What can Cholestyramine be used for?
To bind C. diff toxin and reduce toxin load.
Chlosterol absorption blockers
Effect, MoA, Side eff
Prevents cholesterol reabs at sml intest brush border.
Side eff: can actually mk plaq thicker. not really used.
Effect, MoA, Side eff
gemfibrozil, clofibrate, bezafibrate, fenofibrate
Decrease triglycerides (a lot)
Also decrs LDL, incrs HDL
They upregulate LPL to increase TG clearance.
Side eff: myositis + hepatotoxicity (so DON"T combo w statins usu), cholesterol gallstones
Omega 3 FA
Effect, side eff
Can also reduce severity of rheumatic dz; decreases risk of arrhythmias in pts w heart dz
Side eff: smells. need to give a LOT to get effect.
Which is more imp to treat first: high LDL or high TG?
Treat high TG first, bc they can cause acute pancreatitis, which can be fatal
Longitudinal intraluminal tear forming a false lumen.
Assoc w HTN or cystic medial necrosis (Marfan's)
Tearing chest pain radiates to scapula/back
CXR shows mediastinal widening
False lumen occupies most of the descending aorta.
Can result in aortic rupture and death.
Rx for aortic dissection
Type A (before subclavian)- more dangerous, prob need surgery
Type B (after subclavian): give B-blockers (reduces overall BP, plus reduces slope of rise of BP)
4 manifestations of ischemic heart dz
Angina (stbl, unstbl, prinzmetal)
Sudden cardiac death
Chronic ischemic heart dz
CAD narrowing more than 75% (is less usu don't have sympt)
Stable: mostly 2ndary to atherosclerosis
ST depression on EKG (retrosternal chest pain w exertion)
Unstable/Crescendo: Thrombosis but no necrosis. ST deprsn on EKG (worsening pain at rest, w v little exertion)
Prinzmetal angina: occurs at rest, but secondary to coronary artery spasm.
see ST elevation (!!) on EKG- means severe ischemia.
Rx for Prinzmetal angina
Ca2+ chnl blocker- dihydropyridine (aka works at vessles) like nifedipine
usu acute thrombosis d/t coronary artery atherosclerosis
results in myocyte necrosis
if complicated, leads to sudden cardiac death
Sudden cardiac death
Death from cardiac causes w/in one hour of onset of sympt
Most often d/t lethal arrhythmia (e.g. V-fib)
Chronic ischemic heart dz
Progressive onset of CHF over many years d/t chronic ischemic myocardial dmg
5 deadly causes of chest pain
Most common cause of non-cardiac chest pain?
also esophageal spasm, msk, costochondritis
Acute onset of dyspnea, tachycardia, and confusion in a hospitalized pt
(classic for hospitalized pts)
What is costrochondritis?
Chest pain where ribs insert into sternum, often d/t coughing.
Sharp pain lasting hrs-days that is kinda helped by sitting fwd
Goal of anti-anginal therapy
Reduce myocardial O2 consumption (MVO2) by decreasing one or more determinants of MVO2. They are:
What are the drugs used in anti-anginal therapy?
Nitrates, Beta-blockers, or the two in combination.
Nifedipine has similar effects as Nitrates
Verapamil has similar effects as Beta-blockers
Do nitrates and beta-blockers affect preload or afterload?
Nitrates- decrease preload (decrs EDV)
Beta-blockers- decrease afterload (decrs BP)
How is EDV affected by nitrates and b-blockers?
Nitrates decrease preload, so they decrs EDV
B-blockers decrease afterload, so they increase EDV
N+BB has no effect or decreases EDV
How is BP affected by nitrates and b-blockers?
Nitrates decrs preload so they decrs BP
B-blockers decrs afterload so they decrs BP
Together they decrs BP a lot
How is contractility affected by nitrates and b-blockers?
Nitrates decrease preload, but there is a reflexive response to the decrs in BP, so contractility is increased.
B-blockers decrease contractility
N+BB has no effect
How is HR affected by nitrates and b-blockers?
Nitrates decrease preload, but there is a reflexive response to the decrs in BP, so HR is increased.
B-blockers decrease HR
N+BB has decreases HR
How is ejection time affected by nitrates and b-blockers?
Nitrates decrease preload, so they decrs ejection time.
B-blockers decrease afterload, so they increase ejection time.
N+BB has no effect
How is overall MVO2 affected by nitrates and b-blockers?
Nitrates decrease preload, so they decrs MVO2.
B-blockers decrease afterload, so they decrs MVO2.
N+BB acts to very much decrease MVO2 - this is the goal.
If you add an ACE inhibitor, it will reduce it even more!
What 3 drugs are given together to reduce MVO2?
Nitrates, B-blockers, ACE inhibitors
What B-blockers are contraindicated in angina?
Pindolol and acebutolol- they are partial Beta-agonists.
MI: which coronary arteries are most likely to be occluded?
LAD > RCA > CFX
Sympt of MI
diaphoresis, naus/vom, severe retrosternal pain, pain in L arm and/or jaw, SoB, fatigue, adrenergic sympt (tachycardia)
During what time period is myocardial ischemia reversible?
Up to 20-40 min. After that, dmg is permanent.
MI Day 1
Artery is occluded, infarct occurs.
Dark mottling of infarcted tsu; pale w tetrazolium stain
Risk for arrhythmia
No visible chg by light microscopy in first 2-4 hrs
Contraction bands visible after 1-2 hrs
Early coag necrosis after 4 hrs
Rls of contents of necrotic cells into bloodstream (CK-MB, Troponin I, CPK, myoglobin) and beginning of neutrophil emigration
MI 2-4 Days
Hyperemia in infarcted tsu
Risk for arrhythmia (Arrhythmia is most common complication! Keep K+ >4 and Mg2+ >2)
Tsu surrounding infarct show acute inflam (see neutrophils)
Dilated vessels (hyperemia- redness)
Musc shows extensive coag necrosis
MI 5-10 days
Hyperemic (red) border w central yellow/brown softening. Max yellow and soft at by 10 days
Risk for free wall rupture; tamponade; papillary musc rupture; IVseptal rupture (all d/t macrophgs having degraded imp structural components)
Outer zone (See ingrowth of granulation tissue)
MI >10 days
Artery recanalized (at 7 wks)
Infarcted tsu is grey/white
Risk for ventricular aneurysm- the scar tsu doesn't contract. Over time it starts to bulge.
Contracted scar is complete
LAD occlusion results in which type of MI?
Anterior wall MI
What can reduce the risk for arrhythmia?
K+ > 4
Mg2+ > 2
Which pt populations don't have classic chest pain w an MI?
Older women and diabetics
Dx'g MI in first 6 hrs
EKG is gold standard
Cardiac troponin I
Rises 4 hrs post-MI
Elevated for 7-10 days
More specific than other protein markers
Mainly found in myocardium but can also be rlsd from skel musc, so less specific.
Peaks at 1 day post-MI, gone by 3 days
non-specific, can be found in cardiac, liver, skel musc
Peaks at 1-2 days post-MI
EKG chgs in MI
ST elevation: transmural infarct (affects both superficial and deep layers)
ST depression: subendocardial infarct
Pathologic Q waves (transmural infarct, old infarction)
T wave inversion
Affects entire wall (superficial and deep layers)
See ST elevation on EKG
Subendocardium = myocardium (bt endocardium and pericardium)
D/t ischemic necrosis of <50% of ventricle wall
Subendocardium is esp vulnerable to ischemia bc there are fewer collaterals, higher prs
ST depression on EKG
Complications of MI (7)
1. Cardia arrhythmia (imp cause of death before reaching hosptial; common in first few days)
2. LV failure and pulm edema
3. Cardiogenic shock (large infarct = high mortality)
4. Rupture: ventricular free wall rupture leading to cardiac tamponade. or rupture of papillary musc leading to severe mitral regurg. or IVseptum rupture leading to VSD.
5. Aneurysm formation (decreased CO, risk of arrhythmia, embolism from mural thrombus
6. Post-infarct pericarditis- friction rub 3-5 days post-MI
7. Dressler's syndrome (auto-im fibrinous pericarditis several wks post-MI)
When can you see ST elevation on EKG?
STEMI (transmural MI)
List the thrombolytics
How do thrombolytics work?
Directly/indirectly cause plasminogen to be converted to plasmin.
Plasmin cleaves fibrin clots
What is the fibrinogen pathway?
Fibrinogen + thrombin = fibrin (clot)
Fibrinogen can be degraded (plasmin can do this)
Or, it can be converted to fibrin (thrombin does this)
The fibrin can then be degraded (by plasmin) into D-dimers.
How do thrombolytics chg the PT, PTT, platelet count?
No chg in platlet count.
Clinical use for Thrombolytics
Early MI (STEMI only, don't use for N-STEMI
Early ischemic stroke
Toxicity/Contraindication for thrombolytics
Contraindic in pts w active bleeding, hx of intracranial bldg, recent surg, known bleeding diathesis (eg hemophilia), or severe HTN.
How do you treat thrombolytic toxicity/OD?
Aminocaproic acid (it inhibits fibrinolysis)
How do you treat a STEMI?
1. Cardiac catheterization
if that's not available,
Acetylates and irrev inhibits COX-1 and COX-2 to prevent conversion of arachnidonic acid to TxA2.
Increases bleeding time
No effect on PT, PTT
Clinical use for aspirin
Anti-platelet. Give to pts w chest pain.
If a pt arrives to the hospital w chest pain and probable MI, what do you give them?
Statins (HMG-coA reductase inhibitors)
Side effects of aspirin
Peptic ulcer (bc lose protective effect of prostaglandins)
Reye's syndrome (don't give aspirin to kids)
Idiosyncratic rxn (unusu/unpredictable rxn)
Noise (Tinnitus- CN VIII)
What are the ADP receptor blockers?
How do Clopidogrel and Ticlopidine work?
Inhibit platelet aggregation by irreversibly blocking ADP receptors.
Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa expression
(Toxicity of ticlopidine is neutropenia- sml # of neutrophils)
Clincal use for ADP receptor blockers
Acute coronary syndrome
Reduces incidence or recurrence of thrombotic stroke.
What are the Glycoprotein IIb/IIIa inhibitors?
How do the IIb/IIIa inhibitors work?
They are monoclonal Ab's- they bind to the glycoprotein IIb/IIIa receptor on activated platelets, and prevent aggregation.
Toxicity - bleeding, thrombocytopenia
Clinical use of IIb/IIIa inhibitors
NSTEMI, Acute coronary syndromes, PTCA (percutaneous transluminal coronary angioplasty (balloon dilation of arteries w cardiac catheterization)
What is used to treat STEMI vs NSTEMI
STEMI = thrombolytics
NSTEMI = IIb/IIIa inhibitors (abciximab, tirofiban, eptifibatide)
What are the major categories of cardiomyopathy?
Dilated (congestive)- most common (90% of cases)
Reasons for dilated cardiomyopathy
chronic Alcohol abuse
wet Beriberi (vit B1/thiamine deficiency)
Coxsackie B virus-induced myocarditis
chronic Cocaine use
Chagas dz (T. cruzi)
Doxorubicin toxicity (chemo drug)
Hemochromatosis (iron overload)
Systolic dysfn occurs as a result of dilated cardiomyopathy. There is also eccentric hypertrophy (sarcomeres are added in series)
Findings in dilated (congestive) cardiomyopathy
S3 heart sound
dilated heart on US
balloon appearance on CXR
laterally displaced apical pulse
"globular heart" - almost spherical
What is hypertrophic cardiomyopathy?
Occurs when hypertrophied IVseptum is too close to mitral valve leaflet, leading to outflow obstruction.
Causes sudden death in young athletes bc they can't perfuse that thick of a myocardium
See myocyte disarray, disoriented, tangled hypertrophied myocardial fibers.
50% of cases are familial, auto-dom
Assoc w Friedreich's ataxia
Causes diastolic dysfn
Concentric hypertrophy (sarcomeres added in parallel)
Findings in hypertrophic cardiomyopathy
S4 heart sounds
Increased size of apical impulses (not displaced, but bigger area)
The proximity of the hypertrophied IVseptum to the mitral leaflet obstructs the outflow tract, resulting in a systolic murmur and syncopal episodes (fainting)
Rx for hypertrophic cardiomyopathy
Non-dihydropyridine CCB (Verapamil)
Causes of restrictive/obliterative cardiomyopathy
Endocardial fibroelastosis (thick fibroelastic tsu in endocardium of young kids)
Loffler's syndrome (endomyocardial fibrosis w prominent eosinophilic infiltrate)
Hemochromatosis (iron overload- can also cause dilated cardiomyopathy)
Causes diastolic dysfn
Loffler's eosinophillic pneumonitis
not related to restrictive cardiomyopathy.
assoc w ascaris lumbricoides worm
(loffler's syndrom features an eosinophilic infiltrate, but is completely different- causes endomyocardial fibrosis (restrictive cardiomyopathy)
Generally, what do S3 and S4 indicate?
S3 = dilated ventricles (so hear it in dilated cardiomyopathy)
S4 = stiffened ventricle (hear it in hypertrophic cardiomyopathy)
What is Restrictive/obliterative cardiomyopathy?
Things* are deposited in the myocardium, so it becomes thickened and can't fn well
*eg granulomas of sarcoidosis; abn protein from amyloidosis; fibrous tsu; iron from hemochromatosis
Definition of CHF
Clinical syndrome including sympt such as dyspnea, fatigue and signs such as edema, rales.
Occurs in pts w an inherited or acquired abn of cardiac structure/fn
CHF abn: dyspnea on exertion. Cause?
LV output doesn't increase as it should during exercise.
CHF abn: Cardiac dilation. Cause?
Greater ventricular EDV
CHF abn: pulmonary edema and paroxysmla nocturnal dyspnea. Cause?
LV failure leads to increased pulm venous prs, causing pulmonary venous distention and transudation of fluid. (edema)
Presence of macrophages w lots of hemosiderin ("heart failure cells") in the lungs is d/t microhemorrhages from the increased pulmonary capillary prs.
CHF abn: orthopnea (SoB when supine). Cause?
There is increased venous return when supine- this worsens any pulmonary vascular congestion.
CHF abn: hepatomegaly (nutmeg liver). Cause?
Increased central venous prs causes increased resistance to portal blood flow.
This can cause R heart failure.
Rarely, causes "cardiac cirrhosis"
CHF abn: Ankle and sacral edema. Cause?
RV failure leads to increased venous prs, which causes fluid transudation (edema)
CHF abn: Jugular venous distention. Cause?
R heart failure- results in increased venous prs (and so distention)
Isolated R heart failure (not d/t L heart failure) is usu d/t what?
What are the 2 results of a decrease in LV contractility?
1. Pulmonary venous congestion (this causes Pulm edema)
2. Decreased CO- this causes decreased BP
What are the 2 results of decreased CO, leading to decreased BP?
1. Decreased BP activates the renin-ang system, which increases systemic venous prs
2. The renin-ang system also activates aldosterone, which increases renal Na+ and water reabsorption.
What are the 2 results of increased systemic venous prs?
1. Peripheral edema
2. Increased preload and CO
What is myocarditis?
Inflamation of the myocardium (not from ischemia)
Most common cause in US is Cocksackie B virus
Echovirus and Influenza virus can also cause it
Histologically, see a diffuse interstitial infiltrate of lymphocytes and myocyte necrosis.
2 most common causes of decreased LV contractility
Chronic HTN (causes LVH, which causes decreased contractility)
Where do L and R-sided heart failure cause edema?
Left-sided = pulmonary edema
Right-sided = peripheral edema
What 4 drugs are usu used for CHF?
Digoxin (increases contractility and CO)
ACE inhibitors and ARBs (decrease renin-ang-aldo response)
Loop diuretics (decrease water reabs)
B-blockers (decrease symp activity)
Rx for acute(!) CHF exacerbation
Loop diuretics or Lasix (furosemide)
Morphine (for air hunger- help pt relax)
Nitrates (dilate peripheral vasculature)
Positioning (sit so that blood pools in legs, not lungs)
Pressor (eg dobutamine. Remove B-blockers 1st)
Mechanism of cardiac glycosides
directly inhibit Na+/K+ ATPase
this indirectly inhibits the Na+/Ca2+ exchanger, so more Ca2+ stays inside the cell
more Ca2+ = positive inotropy (aka contraction).
Stimulates the vagus nerve
Clinical use for cardiac glycosides
-CHF (chronic, not really in acute. increases contractility)
-A-fib: depresses SA node and decreases conduction at AV node, so decreases HR. (only decreases resting HR tho, doesn't help in exercise)
Toxicity of cardiac glycosides
Cholinergic: naus/vom, diarrhea; blurry yellow vision
Often causes bradycardia on EKG- give atropine (but could also cause tachy)
Antidote for cardiac glycoside toxicity
Normalize K+ (slowly) and Mg2+
Lidocaine (if tachycardic)
Atropine (if bradycardic- more common)
Anti-dig Ab fragments
Know all toxins/antidotes p239
Signs and sympt of lead poisoning
Gums (lead line)
What is the first-line treatment for alcohol toxicity?
It inhibits alcohol dehydrogenase.
How is ethylene glycol broken down?
alcohol dehydrogenase converts it to oxalic acid, this causes metabolic acidosis (elevated anion gap) and/or nephrotoxicity (bc it makes calcium oxidate crystals)
How is methanol (wood alcohol) broken down?
Alcohol dehydrogenase converts it to formaldehyde and formic acid - these cause severe metabolic acidosis (elevated anion gap) and also retinal dmg(!)
How is ethanol broken down?
Alcohol dehydrogenase converts it to acetaldehyde. Acetaldehyde dehydrogenase converts adetaldehyde to acetic acid.
If acetaldehyde builds up either bc a)you drank too much too fast or b) you took disulfiram and blocked acetaldehyde dehydrogenase, then you get naus/vom, headache, hypotension.
What does disulfiram inhibit?
What drugs cause disulfiram-like rxn?
Inhibits acetaldehyde dehydrogenase.
Procarbazine (alkylating agent for Hodgkin's)
1st gen sulfonylurea (anti-DM drug)
What causes metabolic acidosis (compensated by hyperventilating) with increased anion gap
Methanol (formic acid)
Paraldehyde or Phenformin
Iron tablets or Isoniazid
Ethylene glycol (oxalic acid)
Anion gap eqn
Anion gap = Na+ - (Cl- + HCO3-)
Normal is 8-12 mEq/L
What kind of cardiomyopathy is assoc w Friedreich's ataxia? What is FA?
Auto-recessive neuro disorder- degeneration of nerve tsu in SC. Onset usu 5-15yo. Progressive weakness, esp in lower limbs.
Ataxia, speech problems, heart dz and DM
Which spinal tract conveys touch, prs, and vibration?
Dorsal columns (fasciculus cuneatus and fasciculus gracillis)
Lose this in tertiary syphilis
Which spinal tract gives voluntary motor command from motor cortex to body?
Corticospinal tracts (main one is lateral corticospinal tract)
Carries motor info to contralat. limbs.
Which spinal tract carries voluntary motor command from the motor cortex to the head/neck?
Which spinal tract carries alternate routes for the mediation of voluntary mvmt?
Reticulospinal tracts (reticular formation to SC)
Rubrospinal tracts (red nucleus to SC)
Which spinal tract carries P/T sensation
Lateral spinothalamic tract (ascending- brings info from SC up to thalamus)
Which spinal tract is important for postural adjustments and head stabilization?
Vestibulospinal tract (comes from vestibular apparatus aka ear stuff to SC)
Which spinal tract carries proprioceptive info for the cerebellum?
Dorsal and ventral spinocerebellar tracts (from SC to cerebellum)
What causes compression of the anterior commisure?