Vascular Disease with a focus on Atherosclerosis and Ischemic Heart Disease (IHD)
Blood vessels-
1. Arteries
A. Relationships between wall thickness, lumen size, diameter and resistance
B. Aging changes and consequences
a. loss of elastic to increased pulse pressure
b. dilation
2. Arterioles
A. Distribution
B. Flow: pulsatile to steady
C. Carry pressure loads
3. Capillaries- 700 sq.meters
A. Highly regulated transport: muscle, lung, skin, heart,CNS
(continuous)
B. Fenestrated: glomerulus, endocrine, ciliary body, some GI,
choroid plexus-secretory/filtering
C. Sinusoidal (discontinuous): liver, spleen, bone marrow
Endothelium:
1. prothrombotic: low flow; vWf(F VIIIa), TF, PA inhibitor, PGA2
2. antithrombotic: PGI2, thrombomodulin, plasminogen activator, heparins, high flow
Vasoconstrictors: endothelin, ACE, thromboxane
Vasodilators: NO, prostacyclin
Regulators:
Inflammation: IL-1, IL-6, IL-8, adhesion molecules
Cell proliferation: PDGF, CSF, FGF, heparin, TGFß
CONGENITAL
1. Pattern variations: arteries vs veins, important to surgeon
2. Developmental aneurysms (berry)
3. Arteriovenous fistulas
a. physiology
b. congenital, inflammatory, ruptured aneurysm, trauma
ARTERIOSCLEROSIS
I. Atherosclerosis- lipid to intima
II. Monckeberg's sclerosis- limited to media, non-occlusive
III. Endarteritis obliterans- gonadal vessels; a disuse phenomenon
IV. Arteriolosclerosis- hypertension, aging, diabetes
ATHEROSCLEROSIS
Very important; leading cause of death in Western world
1. Sites of importance: aorta, peripheral lower extremities, coronary, cerebral
2. Manifestations: ischemic atrophy, infarction, gangrene, dysfunction
3. Begins early in life
4. Hall mark is the plaque
a. within intima at start
b. lipid, mainly cholesterol and its esters
c. develops fibrous cap
d. obstructive in small arteries
e. destructive in large arteries
Query #1: when can a vein show atherosclerosis?
5. Recent decline due to: lifestyle changes, dietary changes, control of hypertension and possibly diabetes, treatment of consequences. Note sex predisposition; menopause
6. MAJOR PREDISPOSITIONS MINOR PREDISPOSITIONS
Diet/hyperlipidemia Obesity
Diabetes Inactivity
Hypertension Sex
Smoking Family history
Stress
Oral contraceptives
High carbohydrate diet
High homocysteine
High uric acid
Not in rank order
Ed. comment: risk of intermittent claudication is >twofold higher for smokers! It increases progression to severe limb ischemia as well.
Query #2- Why do we believe omega-3 fatty acids are important? Epidemiology and biochemistry please.
7. Morphology: the basic process is intimal thickening with lipid accumulation (atheroma = gruel)
1. near ostia (Query #3 Why?) in frequency: lower aorta, coronaries, popliteals, descending thoracic aorta, internal carotid, circle of Willis (Query #4 Under what circumstances is the pulmonary circuit involved?)
2. eccentric: cells, CT+ECM, lipids
3. what can you tell me about fatty streaks
4. pathogenesis- uncertain but in response to injury both cell proliferation and thrombosis may contribute, however, endothelial dysfunction seems to be a critical early step. This allows platelet adhesion and monocyte transmigration with release of mediators that result in collagen synthesis, altered permeability and lipid accumulation. Alternatively the initial step may be altered endothelial permeability with monocyte adhesion in response scavenger receptor for oxidized LDL- note that lesions occur at location of apparently intact endothelium.
8. Lipid metabolism- briefly reviewed in Robbins but not covered specifically in Path lecture. Keep in mind premature atherosclerosis linked to increased lipoproteins in circulation. Know neutral lipids vs polar lipids {both in plaques}; know role of LDL receptor; have an idea of the different types of lipid disorders, e.g. dysbetalipoproteinemia is associated with elevated cholesterol and hyperlipidemia, xanthomas, and premature coronary artery disease. Role of thrombosis.
9. Smooth muscle proliferation- hard to tell migrating muscle cell from emigrating monocyte. Role of cytokines. Issue of mono or polyclonality, or viruses. (Query #5- What is that last sentence about?)
10. Current thoughts: multifactorial process focusing on endothelial dysfunction that begins early in life and which can be modified in its progression. (Query #6- How?)
Ed. comment: The two principal symptoms of peripheral vascular disease are intermittent claudication and rest pain. The most reliable physical finding is decreased or absent pulses. Listen for bruits, look for subcutaneous atrophy, hair loss, pallor, and cyanosis.
*The most common cause of sudden arterial occlusion is ______?
11. Result:
A. Slow occlusion- ischemia
B. Sudden occlusion- infarct
a. Reperfusion effect
C. Aneurysm
Ed. comment: sudden occlusion leads to pain, paresthesias, distal motor weakness.
Minor item: popliteal artery entrapment is caused by a congenital anomaly in which the median head of the gastrocnemius displaces or compresses the artery- could be a great cross-disciplinary question!
12. Other items in Chapter
A. Vasculitis will be covered later- remember the ANCA
B. Raynaud's likewise
C. Aneurysm
a. atherosclerotic
b. dissecting: cystic medial necrosis (Query #7-= Important or not?)
(1): types and consequences
c. berry
d. mycotic
Can you name organisms with predilection for blood vessels?
What is thromboangiitis obliterans? Not so common and not well understood but very strongly related to smoking...
D. Varicose veins: age, sex, weight
E. Phlebothrombosis and thrombophlebitis
a. importance
b. difference
c. site
d. five major causes: CHF, pregnancy, obesity, postop, immobil
ISCHEMIC HEART DISEASE (IHD, CAD, ASHD)
A. 90% due to coronary artery atherosclerosis; leading cause of death(1/3+), and accounts for over 3/4ths of heart disease
I. angina
II. myocardial infarction
III. chronic ischemic disease
IV. sudden death
B. Most (90%) due to fixed obstruction
a. if one, > 75% is the magic number (over 50% certain)
b. 2 or more usual; within 2 cm LAD, LCX, more distal RCA
C. Acute change: hemorrhage into, fissuring or ulceration of plaques lead to thrombosis and/or occlusion
D. slow leads to collaterals
E. thrombosis
F. vasoconstriction
ANGINA = symptom complex secondary to transient myocardial ischemia (15"<15')
I. Stable/typical- ST depressed- endocardial ischemia
II. variant/Prinzmetal- episodic at rest- ST elevated-vasopasm may be important
III. unstable/crescendo-increasing frequency/severity with less effort
suggests (Query #7)
This really isn't pathology' but it is important- I won't ask about this type of material but it likely is more critical than many things we do ask about
Know areas served by coronary arteries
ACUTE MYOCARDIAL INFARCTION
1.5 million/yr; 1/3 hospitalized; 1/3 die
A. Most common is transmural in distribution of a single coronary artery
B. Subendocardial- not usually due to plaque rupture/thrombosis
C. Non Q-wave- What is importance (clinical)
D. Initial event is usually change in plaque; importance of thrombosis is emphasized by effectiveness of thrombolytic therapy: 4 hr 90% better, 12 24 hrs 60%
Ed. comment However, it must be emphasized that acute occlusions occur at sites where pre-existing occlusions of >70% exist. This is based on observations from preinfarction angiograms.
Symptoms:
Diaphoresis is particularly common in inferior infarcts. Dyspnea and syncope are similarly associated. The syncopal episode is attributable to bradycardia, heart block and tachyarrythmias. Elderly patients present with atypical symptoms in many cases and more than 50% have shortness of breath as a presenting complaints. Dizziness is also common.
About 2/3rds of patients describe the onset of angina or a change in their anginal syndrome in the month prior to infarction.
Patients are anxious and in distress. If atrio-ventricular dissociation occurs, cannon A-waves may characterize the jugular pulse (look this up if you have a moment- the physiology is interesting). If a left bundle branch block occurs, the second heart sound splits.
Ed. comment : The physical examination is often more useful in considering other causes of chest pain than in ruling in or out acute MI.
Patients
Timing
If you block coronary circulation ATP is used up in seconds and ischemic pain begins with change to aerobic glycolysis and increase in lactic acid. Within a minute contractility falls off and coagulative necrosis is established by 20-40' and reaches completion by 3-6 hours. Microvascular injury occurs within the first hour and this is reflected in reperfusion change (How?).
Your text details the frequency of sites of injury from post sept/free wall to atrial to isolated right ventricle- not important but follows logically.
For those who care there is a classic clinical presentation of a patient with hemodynamically significant right ventricular infarction: hypotension with clear lung fields and an elevated jugular pressure.
Note: preservation of 0.1 mm of endocardium in infarction...why?
Query#8 What do we mean by 'extension'
Ultrastructural change by 20-40'
Irreversible by 1-2 hours
Wavy fibers 1-3 hours
Microscopic necrosis 4-12 hours
Gross changes 12-14 hours- What would you see?
Acute inflammation (What leads to it?)- 2-3 d
Macrophages 5-10 d
Granulation tissue 2-4 wk
Complete 8 wks
Query #9. Dr. Miller has decided to give individual oral exams to assess competence. He presents you with a slide taken from the posterior septum of and shows you a picture. A 44 year old, otherwise healthy female, died suddenly. She had an isolated plaque 4 cm from the ostium of the left anterior descending artery that occluded 60% of the lumen. The myocardium showed a transmural yellowish area within which the fibers appeared to be opaque and lacking in distinctness. The slide revealed an area of dense fibrous tissue without vascularity or inflammation. Surrounding muscle was hypertrophied. Dr. Miller tells you he has dated the histology as 4 year in age. He asks for your comments.
INFARCT MORPHOLOGY IN THE FACE OF THROMBOLYTIC THERAPY- Either enzymatic or mechanical
1. 70% effective if given in time. Query#9- How soon if necrosis is to be prevented
2. salvage after necrosis begins
3. reperfusion
a. hemorrhage- why? necrosis accentuated- why?
b. contraction bands- not specific- why do they occur?
Ed. comment: In some patients the artery supplying the infract may open and close sporadically over a 12 hour period giving pain and pain-free periods. This has obvious implications for therapy.
Note: The use of direct coronary angioplasty without thrombolytic therapy has been shown to offer a slight but definite improvement in mortality, reinfarction rate and frequency of stroke. Why would it be the universally preferred treatment?
What is abciximab?
4. recovery
DIAGNOSIS:
Critique the use of: EKG, echocardiography, angiography, scanning
(not for pathology but to keep in mid for the future)
Benefits and drawback of the following
LDH
CK
CK-MB
Myoglobin
Troponin
Ed. comment: Rapid analysis provides results in 30 minutes or less. Creatine kinase usually requires 3 hours of ischemia to rise significantly. A clinical 'pearl': In a patient with typical chest pain but no electrocardiographic changes, a white count with differential may be helpful since a lymphopenia (<20%WBC) is an independent predictor of acute MI in such patients.
CONSEQUENCES/COMPLICATIONS
Hospitalized cases
Sudden death 20% in first two hours accounts for half the deaths
Uncomplicated 10-20%
Complicated 80-90%
Arrhythmia in over 3/4ths
Atrial fibrillation is most commonVentricular fibrillation, though less common, is a much more frequent cause of death.
Sinus bradycardia, as noted, is common in inferior infarcts but commonly does not need treatment
Cardiogenic shock in large infarcts (40% ventricular mass- dysfunction proportional to mass)-2/3rds of hospital deaths- Compare to arrhythmia- what does this mean?
Pericarditis
Extension
Aneurysm
Rupture (relatively rare; end of week one)Ed. comment: As salvage rates have improved during the acute episode, the importance of rupture has increased!
Mitral regurgitation (Query (extra credit)- why?)Stroke- extensive infarction of the apex and anterior wall leads to mural thrombus in 30% of patients with embolization occurring in 15% of this group
Query #10 Discuss the sites at which rupture occurs and the consequences of each. Why am I asking you this if rupture is uncommon?
Outlook after an infarct?
CHRONIC ISCHEMIA
I. Clinical presentation
II. Pathology
SUDDEN DEATH
I. Cardiac- what is it due to?
II. Basic mechanism ?
