Treatment of Myocardial Infarction. If an area of the heart is ischemic due to vascular occlusion, the goal is to reperfuse the heart. Thrombolytic drugs such as streptokinase and tissue plasminogen activator (t PA) or procedures such as angioplasty with coronary stenting can accomplish this goal. In addition to the treatments discussed above for angina (lifestyle mod ifications, nitrates, cholesterol-lowering agents, beta blockers, calcium channel blockers, aspirin), ACE in hibitors and anticoagulants (e.g., heparin) are compo nents of treatment for myocardial infarction as well as prevention of a subsequent myocardial infarction. #201 | | |
VA SC ULA R DISEASEOUTSIDE TH E HEART: PERIPHERAL ARTERIES AND AO RTA #202 | | |
| | |
An embolus can be a clot (thrombus), cholesterol plaque, fat, tumor fragment, amniotic fluid, or an air bubble that #204 | | |
travels from somewhere to somewhere else. For example, a clot (thrombus) that forms in a fibrillating atrium and travels through the arterial system (as an embolus) can affect the cerebral vasculature (causing stroke), the vas cular supply of the gut (causing mesenteric ischemia), or the renal vasculature (causing renal ischemia). These are examples of arterial emboli. #205 | | |
A common site for venous clot formation is in a deep vein, known as deep venous thrombosis (DVT). This most commonly occurs in deep leg veins. One cause of pulmonary embolus can be deep venous thrombosis (DVT) in the leg. Thrombus from the DVT can travel to the right heart and then to the pulmonary artery. Venous thrombosis can occur in any hypercoagulable state (see hematology Chapter 6). #206 | | |
Consider the case of a young patient who has a stroke but is not in atrial fibrillation and has no atheroscle rotic disease. One possible cause would be a hypercoag ulable state. What if the patient is found to have recurrent DVTs and strokes? Hopefully you are saying, ''Wait! The patient has venous thrombosis and is ending up with strokes?! How can that be if the venous return is to the right heart? Shouldn't the patient have pul monary emboli instead of strokes?" What could account for this? If the patient has an atrial or ventricular sep tal defect, a clot from the venous side can cross through this defect from right atrium to left atrium and lead to a stroke (paradoxical embolus). One cause of paradoxi cal embolus is a patent fo ramen ovale, a congenital de fect leaving a hole that connects the atria. #207 | | |
Peripheral Vascular Disease #208 | | |
Atherosclerosis can occur in any artery, which can cause symptoms and signs related to the ischemia of the affected organ, such as mesenteric ischemia, stroke, renal ischemia, retinal ischemia, etc. The same risk factors and pathophysiological circumstances that lead to coronary arterial atherosclerosis can also cause atherosclerosis of peripheral arteries with sim ilar consequences. #209 | | |
Atherosclerotic lesions of peripheral vasculature can cause claudication, which is analogous to angina in the heart: exertion involving the muscles supplied by the compromised vessels leads to pain and weakness, which is relieved by rest. Further occlusion of the arter ies can lead to symptoms even at rest (rest pain), anal ogous to unstable angina in the heart. The symptoms and signs of peripheral vascular disease are often referred to as "the 6 Ps": pallor, pulselessness, pain, pares thesias (uncomfortable sensory disturbances), paraly sis, and poikilothermia (cold temperature). Changes in hair, nail, and skin can also occur in the affected re gion(s). Commonly affected sites include the buttocks/thighs (caused by disease of the distal aorta and/or iliac arteries; ischemia here can also cause impo tence in men) and the calves (caused by disease of the popliteal and femoral arteries). Less commonly, the arms (supplied by the subclavian arteries) may be af fe cted. #210 | | |
Diagnosis can be confirmed by Doppler ultrasound, angiography, and/or ankle-brachial index of blood pressure (ABI). The ABI compares the blood pressure at the ankle with that in the arm. Normally, these should be equivalent, yielding a ratio of 1. A lesser ra tio demonstrates decreased blood pressure at the an kle as compared to the upper extremity and indicates peripheral vascular disease of the lower extremity. #211 | | |
Like treatment of atherosclerotic heart disease, treatment of peripheral vascular disease involves di etary and lifestyle modifications (exercise, cholesterol reduction, smoking cessation, etc.) as well as angio plasty and/or surgical bypass. #212 | | |
Atherosclerosis of the Aorta #213 | | |
| | |
Atherosclerosis is one cause of aortic aneurysm (dila #215 | | |
tation of the aorta). Atherosclerosis-induced aortic aneurysm occurs more commonly in the abdominal portion of the aorta. Other causes of aortic aneurysm in either the thoracic or abdominal portions include connective tissue diseases (such as Marfan Syndrome and Ehler's-Danlos Syndrome), infections (e.g., syph ilis), and vasculitis. Aortic aneurysms may be asymp tomatic or may cause symptoms related to pressure on nearby structures, especially in the case of thoracic #216 | | |
aortic aneurysms (e.g., compression of esophagus or trachea leading to dysphagia or cough). An abdominal aortic aneurysm may be palpable as a pulsating mass on abdominal exam. Depending on size and rate of expansion, surgical repair is often necessary to prevent rupture. #217 | | |
| | |
Aortic aneurysm/rupture is distinct from aortic dissec tion. Aortic dissection is a tear in the intima of the aorta into which blood can flow, furthering the tear. Trauma, hypertension, syphilis, and connective tissue diseases such as Marfan Syndrome and Ehler's Danlos Syndrome can predispose to aortic dissection. Dissection presents as "tearing/ripping'' chest and/or back pain. On physical exam, loss of pulses and differ ent blood pressures between the two arms may be present. Other consequences of dissection can include stroke (leading to neurological deficits), myocardial in farction, aortic regurgitation (leading to a diastolic #219 | | |
murmur), and/or tamponade (leading to hypotension, muffled heart sounds, and elevated JVP). Chest X-ray may demonstrate a widened mediastinum. Emer gency surgical repair is often necessary, and beta blockers can be used to reduce blood pressure while awaiting surgery. #220 | | |
Lipids and Lipid-Lowering Drugs #221 | | |
Since elevated lipids are a risk factor for developing atherosclerosis, maintaining low serum lipids is one goal of prevention of atherosclerotic disease. #222 | | |
Fig. 1-21. Lipid processing pathways and lipid-low ering drugs. Lipids are processed in the body via two pathways: the exogenous pathway, which absorbs fats from the digestive tract into the circulation, and the endogenous pathway, which transports fats synthe sized in the liver between the liver and the peripheral tissues. LDL (low density lipoprotein) is often re ferred to as "bad cholesterol" and HDL (high density lipoprotein) as "good cholesterol," because LDL largely transports cholesterol to the periphery (where it may be incorporated into atherosclerotic lesions), and HDL mostly transports cholesterol back to the liver from the periphery. #223 | | |
Aside from dietary modification to decrease lipid intake, what sites of pharmacologic intervention are possible? #224 | | |
Treatments affecting the exogenous pathway: #225 | | |
| | |
Lipid absorption can be inhibited (e.g., ezetimibe). #227 | | |
| | |
Bilemotingacidstheircanlossbe andsequesteredhence increasingin the GIconversiontract, pro #229 | | |
of hepatic cholesterol to bile acids for secretion (bile acid sequestrants, also known as resins, e.g., cholestyramine). #230 | | |
Treatments affecting the endogenous pathway: #231 | | |
| | |
HDL(e.g., gemfibrozil).can be increased by nicotinic acid or fibrates #233 | | |
| | |
Hepaticthe followingcholesterolmechanisms:production can be decreased by #235 | | |
-Inhibiting the enzyme HMG Co-A reductase, a #236 | | |
rate-limiting step in cholesterol synthesis (e.g., statins) #237 | | |
- LDL can be decreased (nicotinic acid decreases #238 | | |
hepatic production of VLDL; it also raises HDL by mechanisms less well understood). #239 | | |
Fibrates and nicotinic acid also lower triglycerides #240 | | |
| | |
Vasculitis is an inflammation of blood vessels that can be caused by infection (Hepatitis B or C, Epstein Barr virus, cytomegalovirus), drugs (penicillin, sulfon amides, quinolones), autoimmune disease (systemic lupus erythematosis, rheumatoid arthritis), or inde pendent vasculitic syndromes. #242 | | |
Fig. 1-22. Vasculitis syndromes. The vasculitic syn dromes are classified by the size of vessels that they affect (small vs. medium vs. large). #243 | | |
Symptoms/signs of any vasculitis can include consti tutional symptoms (weight loss, fatigue, fever) as well as consequences of ischemia including skin rashes/ ulcers, renal dysfunction, neuropathy, and/or bowel infarction. Other features are specific to specific vas culitis syndromes. Lab fe atures used in diagnosis are included in the table. Infectious causes, drugs, and underlying systemic diseases must be ruled out before diagnosis of a vasculitic syndrome can be made. Arterial biopsy and/or angiogram is necessary for definitive diagnosis, and treatment involves immuno suppressive drugs, most commonly steroids. #244 | | |
| | |
Most cases of hypertension have no identifiable cause (essential hypertension). Before making the di agnosis of essential hypertension, causes of second ary hypertension must be ruled out. Secondary hypertension can be caused by any process that in creases arterial resistance, blood volume, and/or car diac output. Thus, potential culprits are the kidneys, hormonal changes, changes in the blood vessels themselves, or drugs. #246 | | |
Renal disease can cause failure to adequately excrete sodium and water, increasing intravascular volume. Additionally, stenosis of one or both renal arteries can lead to hypertension. This stenosis decreases blood flow to the kidney(s), causing increased renin secretion. This activates the renin-angiotensin aldosterone axis, leading to increased blood volume (secondary to aldosterone increase) and increased ar terial resistance (secondary to angiotensin increase). See Fig. 1-6. Renal artery stenosis can be caused by atherosclerosis or fibromuscular dysplasia of one or both renal arteries. #247 | | |
Hormonal changes that can cause hypertension in clude: #248 | | |
| | |
creasedHyperaldosteronismsodium reabsorption(increased aldosterone ----? in #250 | | |
