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
I. 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 common
Ventricular
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 ?
