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Pathology 2 Block 1 Notes

Intima- single layer of endothelial cells


Media- consists of smooth muscle cells
o Nutrients for the inner of the media get there through
diffusion from the blood vessel
o The outer gets it from the adventitias vasa vasorum
o Capillaries have no media
Adventitia- connective tissue with nerves and vasa vasorum
Weakening and outpouching of the
o Arterial wall= aneurysm
o GI- diverticulum
o Airways- bronchipasis
o Venous- vacosity of vein
Sarcomas travel through veins,
o Exception, Renal cell carcinoma, hepatic cell carcinoma,
one other
Carcinomas travel though the lymphatics
Histamine causes the arterial side of the capillary to vasodilate
but causes contraction of the endothelial cells
Atheriosclerosis- hardening of the arteries- loss of elasticity
o Hyaline arteriosclerosis- pink/glassy appearance
Protein deposited in the walls
Likely caused by Diabetes Mellitus Nonenzymatic glycosylation of protein renders
the basement membrane permeable to plasma
proteins
Or hypertension
Increased pressure pushes protein into the
lumen
Benign hypertension- 140-160
Malignant is over 200
Protein accumulation causes narrowing of lumen
which can cause ischemic damage to the organs
Kidneys become smaller and scared. (explains
why patients with DM or hypertension have
chronic renal failure)
o Hyperplastic arteriosclerosis
Commonly found in malignant hypertension and
scleroderma
Smooth muscle proliferation resulting in thickening
and luminal narrowing
The narrowing of the blood vessel can cause
ischemic damage

o Disease of large elastic and medium sized arteries


characterized by the formations of artheromas (fibrous
plaque) deposited in the intima
These arteromas can obstruct blood flow or weaken
the underlying media which can cause aneurysms
Abdominal aorta is the MC vessel
o The first step in an artheroma is the formation of a fatty
streak. The fatty streak doesnt disrupt blood flow because
it isnt raised
It is compased of macrophages filled with lipids
(cholesterol)
Not all fatty streaks progess to atheromas
o The atheroma is a raised focal lesion in the intima of a
blood vessel.
Soft necrotic core and hard outer fibrous cap.
The blood vessels in the plaque can cause the plaque
to rupture or swell
o Reaction to injury theory
Endothelial dysfunction leads to permeability to lipids
within the intima.
Adhesion molecules also are expressed.
Blood monocytes migrate into the intima and
transform into macrophages where they accumulate
lipids and become foam cells. They also oxidize the
LDL
PDGF is also expressed which activates platelets
cause migration of smooth muscle cells (from the
media) to the intima and they proliferate in the
intima
Ongoing inflammation occurs because cytokines and
growth factors are released.
o Over 70% occluded coronary artery occluded can cause
angina or MI
o Rupture or ulceration of the plaque normally comes from
the shoulder of the turbulent blood flow on the plaque at
that point.
o Hemorrhage into the plaque can cause plaque rupture
o A stable plaque has a large fibrous cap and small lipid core
and an unstable plaque is the opposite
o Aneurysm formation occurs when the weakening of the
underlying media causes an outpouching
The tension and radius of the aneurysm are directly
related so when the tension icreases the radius
increases as well.

o Acute occlusion due to thrombus formation can occur when


blood is cut off to the vessel.
Acute MI can occur when the coronary artery is cut
off
Stroke can occur when the internal carotid or middle
cerebral is cut off
Small bowel infarction can occur when the superior
mesenteric artery is cut off
Gangrene of lower extremities can occur with the
cutoff from the popliteal artery
o Chronic narrowing of the vessel can cause chronic ischemia
This can cause renal atrophy- if its the renal artery
Can also cause skin atrophy- in DM and peripheral
vessel
o The narrowing of the renal artery in atherosclerosis can
also cause secondary hypertension because the lower
blood flow can cause the activation of the renin
angiotensin aldosterone system.
o Peripheral vascular disease can be caused due to the
narrowing of lower limb vessels
If its the popliteal artery gangrene of the lower legs
is seen
Leriche syndrome- impotence in men, atrophy of calf
muscles and pain in buttocks is seen
o Atheroemboli can cause a renal infarction
o Cerebral atrophy is caused when AS is in the circle of willis
o Major risk factors
Nonmodifiable
Age- male over 45, female over 55
Male gender
Family history
Modifiable
Hyperlipidemia
o Over 160 mg/dl of LDL enhances (70-75
is safe)
Transports cholesterol to peripheral
tissues
o HDL less and 35 mg/dl (Over 60 is
considered very good)
Exercise and moderate ethanol
raise HDL levels
Obesity and smoking lower it
Hypertension- over 169/95

Cigarette smoking enhances AS by damaging


endothelial cells
Diabetes mellitus- induces
hypercholesterolemia
o Incidence of MI twice as high
o MC cause of death in DM is acute MI
o Minor risk factors
Hyperhomocystinemia- over 100 umole/L
Insufficient folate or B12 intake
Increased C reactive protein
Obesity
Induces hypertension, DM,
hypertriglyceridemia and decreased HDL
Physical inactivity, stress, high carb intake,
chlamydia
Mockeberg medial calcific sclerosis- age dependent with no
clinical significanceo Doesnt compromise the blood vessel
o Calcium deposits in the walls of muscular arteries
Aneurysms
o Localized dilations of arteries due to the weakening of the
wall
o Law of laplace- as the diameter increases so does the
pressure which means enlargement is inevitable
True aneurysm- walls are the layers of blood vessels
False- blood leaked inot surrounding CT which is just
containing the hematoma
o Abdominal aortic aneurysm
Over 50 years old, MC men over 55
Complication of atherosclerosis
Located below renal artery but above the bifurcation
because each heartbeat beats that section against
the vertebral bodies causing injuries
Also theres no vasa vasorum under there
Mostly are asymptomatic but symptoms are pulsatile
mass, severe back pain which is followed by
hypotension
Abdominal ultrasound for diagnosis
o Syphilitic aneurysm- in aortic arch
Tertiary syphilis in men 40-55 years old
Inflammation of vasa vasorum by T. Pallidum
Endarteritis obliterans
Focal necrosis and scarring of media

Roughened intimal surface gives a tree bark


appearance
Dilation of the aorta causes improper closing of the
aortic valve which results in aortic regurgitation
This regurgitation causes increased SV which
causes left ventricular hypertrophy and
hyperdynamic circulation
o Bounding pulse, uvula pulsating, brassy
cough, respiratory difficulty and bouncing
pulse seen
o Die by rupture of heart failure
o Mycotic aneurysm- weakening of the vessel wall due to
microbial infection
Septic embolism because of infective endocarditis
Thrombosis with or without infarction rupture and
hemorrhage
o Berry aneurysm
Occurs at the bifurcation of the circle of willis
because the there is a gap in the circular muscle
layer there
Increased intravascular pressure can cause them
Rupture can lead to fatal subarachnoid hemorrhage
Worst headache of my life and nuchal rigidity
neurological defects can be seen
aortic dissection- intimal tear that dissects a path along the
length of the vessel
o Causes a Tearing pain and pain to the back
An MI would have a squeezing pain and pain in the
jaw and arm
o In men between 40-60 with hypertension
in younger patients with marfans or EDS
MCC of death in EDS
Change in these diseases are known as cystic
medial necrosis/degeneration
o Cystic spaces filled with myxoid material
Pregnancy can cause this because of increased blood
volume
Copper deficiency can cause this because it is a
cofactor of lysl oxidase which is used for collagen
crosslinking
Aging is also a factor
o Weakening of the aortic media
Normally in the first 10 cms because pressure is the
highest at this point.

Can progress proximal or distally to the heart


If the tear continues it can effect coronary, carotid,
subclavin, renal and mesenteric arteries
Most common and more dangerous type starts at the
decending aorta
Other type starts after the subclavin artery
o AV regurgitation is due to a aortic valve dilation
o The subclavin artery is compressed which has a loss of the
upper extremity pulse
o It can rupture in the pericardial sac (tamponade MC)
pleural cavity, peritoneal cavity
o Diagnosis by chest x ray, CT or MRI but confirmed by Transesophageal echocardiography
Vascular tumors
o Hemangiomas
Capillary hemangiomas- benign tumor of small
mature capillary channels
Located on the skin, mucous membrane and
liver spleen or kidney
Strawberry hemangioma Commonly seen on the face of new borns
Raised lobulated vascular tumors
Grows for a few months and regresses at age
1-3 years
80% regress by 8 years
no treatment needed
cavernous hemangiomas
large vascular channels
MC benign tumor of the liver/spleen,
cholangioma
o Can rupture spleen/liver
Associated with von-hippel landau disease
Cherry hemangioma
MC benign blood vessel tumor in adults
3rd or 4th decade of life
do not regress and number increases with age
(senile hemangioma)
bright red popular lesion
Glomus tumor
Benign extremely painful tumor which arises
from a sensitive neuromyoarterial receptor that
regulates arterial flow
Beneath nail beds and are less than 1 cm

Bacillary angiomatosis
Potentially fatal infectious disease caused by
bartonella henselae and bartonella Quintana
o Bacteria induces proliferation of small
blood vessels
o Occurs as opportunistic infection
The lesions are red nodular masses composed
of capillary proliferations
o Numerous neutrophils nuclear dust and
purplish granular material
o The lesions look like Kaposi sarcoma but
dont have the above features
o Malignant tumors
Kaposi sarcoma
Derviced from endothelial cells
Transplant associated KS, European KS, African
KS, AIDS associated KS
o MC cancer in AIDS due to HHSV-8
Begins as painful purple or brown lesions which
progresses from a flat lesions to a plaque to a
nodule and then it may ulcerate
Sheets of spindle cells creating slit like vacular
channels
Areas of microhemorrhages and hemosiderin
deposits
Angiosarcoma
Highly malignant tumor derived for the vessel
endothelium
o Anaplastic cells without vascular
channels
Liver is associated with vinyl chloride (plastic
manufacturer), arsenic (pesticides), throtrast
(radio contrast material)
Positive for CD 31 and factor 8
o Tumors of lymphatics
Simple lymphangioma- composed of lymphatic
channgels
Cavernous lymphangioma( cystic hygroma)- neck or
axilla in children
Composed of dilated lymphatic channels
Turners syndrome develops from this
Lymphangiosarcoma
Associated with chronic lymphedema

o 10 years after radical mastectomy for


breast cancer
o Vascular Ectasias
Localized dilations of preexisting vessels
Telangiectasia- dilation of preformed vessels creating
a focal red lesion
Nevus flammeus- ordinary birth mark
MC vascular ectasias
Pink to blue flat lesions
Sturge Weber Syndrome
Port wine stain in the distribution of the
ophthalmic branch of the trigeminal nerve
CNS vascular abnormalities located in the
leptomeninges
Calcification and bleeding and mental
retardation
Hereditary hemorrhagic telangiectasia (osler-weberrendu disease)
MC genetic vascular disorder
Dilated vessels on the skin and mucous
membranes in the mouth and GI
Epitaxis, hematemesis or GI bleed
o Iron deficiency anemia can result
Spider angioma
Spider angioma
o Red dot in the center with redish
extensions
Compression of the body causes
the tentacle sto blanch and
disappear
o Associated with hyperestrinism
Pregnancy and cirrhosis
Vasculitis
o Inflammation of a blood vessel wall
o Immunologic hypersensitivity reactions
Type 2- complement dependent
Type 3- immune complex mediated
Deposition of immune complex which activates
complement which releases C5a (chemotactic)
Inflammation can cause healing by fibrosis
which can cause stenosis of the lumen of the
blood vessel

Endothelial damage can also occur following


inflammation which can cause release of
coagulation factors which can cause
thrombosis and ischemic damage to tissues
Type 4: cell mediated
Delayed hypersensitivity due to the presence
of granulomas in the vessel wall.
Healing by laying down of fibrous tissues which
causes the thickened blood vessel wall which
narrows the lumen and causes decreased blood
supply
Direct invasion
Rickettsiae- rocky mountain spotted fever
Meningococcus- only cause of meningitis that
invades the blood vessel- purpuric hemorrhage
Fungus
Labs
Antineutrophil cytoplasmic antibodies- ANCA
Activate neutrophils which causes a release of
enzymes and free radicals resulting in vessel
damage
C-ANCAAb dierected against proteinase 3 in
cytoplasmic granules
o Cytoplasmic staining pattern
o Wegeners granulomatosis
P-ANCAs
o Perinuclear staining pattern
o Ab against myeloperoxidase
o Churg-Strauss syndrome, microscopic
polyangiitis
ESRs
Biopsy of the blood vessel is the gold standard
Giant cell arteritis (Temporal arthritis)- large blood vessels
Commonly in women over 50 years old
Type 4 hypersensitivity and involves the temporal
artery and ophthalamic branch of the carotid
Palpable
Granulomatous inflammation of vessel with giant
cells
Temporal headache, painful and enlarged temporal
artery
Temporary and permanent blindness
Elevated ESR which indicates corticosteroid use
Takayasus arteritis (pulseless disease)- large blood vessels

Asain women under 50


Absent pulses and decreased BP
Aorta and the aortic arch vessels have type 4
hypersensitivity
Granulomatous vasculitis with fibrosis and stenosis of
the lumen of the blood vessels which decreases
blood flow
Causes claudication of upper extremity which
can cause visual disturbances and dizziness
Angiography for diagnosis and corticosteroids for
treatment
o Polyarteritis nodas- medium sized blood vessels
Medium sized blood vessels of the kidney, liver, GIT,
and skin are affected
Type 3 hypersensitivity
Transmural inflammation- fibroid necrosis
Young to middle aged males with symptoms due to
ischemic damage
Infarction, hypertension and hematuria
albuminuria
Abdominal pain, melena
Aneurysms and MI
Renal failure is the MC COD
HBSAG in 30% of cases
Diagnose with a biopsy of the palpable nodulations
Untreated can be fatal but good response to
immunesuppressents
Churg-strauss syndrome (allergic granulomatous
angitis)
Variant of PAN with asthma
Involves small vessels of the respiratory tract,
heart, spleen skin
Peripheral eosinophilia, high serum IgE, p-ANCA
o Kawasakis disease
Japanese and Hawaiian infants
Cornary thrombosis or aneurysm formation and its
rupture
Erythematous rash of trunk and extremities
Cracked lips and oral erythema
Swelling of hands and feet
MCC of acute MI in children
AVOID corticosteroids and give aspirin
Abnormal ECG

o Buergers disease (thromboangitis obliterans)


Young to middle age smoking males
Tibial, popliteal and radial arteries
Inflammation of the vessel, thrombus formation,
ischemia nd gangrene of the extremities
Claudication of hands and feet
Biopsy for diagnosis and discontinuation of smoking
for treatment