Cardio 2 Flashcards
Vasculitis
Inflammation of vessels
Clinical vascultis
Depends on vascular bed affected (CNS vs heart vs small bowel)
-constitutional sx: fever, malaise, arthralgias, myalgia
Any vessel may have vascultis. Which are affect most
Arterioles, capillaries and venues (a few vasculitides tend to affect only one vessel type or location)
Form of vascultis
Immune mediated
Infectious
Physical and chemical
Immune mediated inflammation
Immunosuppressive Tx for immune mediated vascultis
Infectious vascultis
Direct or indirect induced a noninfectious vascultis
-generating immune complexes or trigggering cross reactive immune response
Physical and chemical injury vascultis
Injury can also cause vascultis
-irradiation, mechanical trauma, toxins
Non infectious vascultis major cause
Immune response (local or systemic)
- immune complex associated vasculitis
- antineutrophil cytoplasmic antiboeise
- antiendothelial cell antibodies
- gaint cell antibodies
- giant cell temporal arteritis
- takayasu arteritis
- polyarthritis nodose
- kawasaki disease
- microscopic poly angiitis
- churg Strauss syndrome
- behcet disease
- granulomatous is with poly angiitis
- thrombi angiitis obliterates
- vascultis associated with other NONINFECIOUS DOS
The granulomas of giant cell arteritis are found with int he vessel wall as part of the inflammation comprising the vasculitis, but need not be preset to render the diagnosis. The granulomas if granulomatous with polyangitis are longer, spanning between vessels and associated with areas of tissue necrosis
Ok
Giant cell arteritis
Aorta Rare Lymphocytes and macrophages Sometimes giant cells Over forty and polymyalgia rheumatica
Granulomatous is with polyangitis
Granulomas
Churg Strauss syndrome
Eosinophils *, lymphocytes, macrophages, neutrophils
Asthma atopy
Polyarthritis nodosa
Ok
Leukocytociastic vascultis
Ok
Burger disease
Thrombosis
Young male smoker
Bechet disease
Neutrophils
Orogenital ulcers
Noninfectious vascultis immune complex vascultis
Autoantibody production and formation of immune complexes
Deposition of antigen antibody complexes in vascular walls
- incites an inflammatory reaction within the wall
- antigen is often unidentified
Who has immune complex vascultis
SLE
Drug hypersensitivity
-PCN acts as a hapten binding to serum proteins of vessel wall
—streptokinase acts as a foreign protein
Cl
Clinical immune complex vasculitis
Mild to fatal; skin lesions most common
What always consider with immune complex vascultis
Drug hypersensitivity. Stop drug! Get resolution of vascultisi
Secondary immune complex vascultisi
Secondary to exposure of infectious agent
-ab to microbial constituents form immune complexes that deposit in vascular lesions
Polyarthritis nodose: 30% associated with HBsAg and anti-HBsAg
Antineutrophil cytoplasmic antibodies ANCA
A heterozygous group of antibodies reactant with cytoplasmic enzymes found in neutrophil granules, monocytes and endothelial cells
PR3-ANCA
Anti-proteinase 3 associated with polyangitis
Previously c-ANCA
MPO-ANCA
Anti-myeloperoxidase
Previously pANCA
Induced by Rex: propylthiouracil
Assoc with microscopic polyangitis and churg Strauss syndrome
ANCA titres generally follow disease __
Severity
What do ANCA activate
Neutrophils, which then renease ROS
Pauci immune
Due to ANCA Ab directed against cellular constituents and do not form circulating immune complexes
-vascular lesions do not typically contain Ab and cimplement
Non infectious vascultis * Giant cell (temporal arteritis and aortitis
Most common vascultis among older patients, may present with constitutional symptoms (fever, fatigue, weight loss); facial pain, headache
Chronic (T cell mediated CD4>CD8) inflammation of arteries int he head espicially the temporal arteries
Giant cell (temporal arteritis and aortitis
Medial granulomatous inflammation, often with multinucleated giant cells
Fragmentation of the elastic lamina and intima thickening
Sites of involvement within an artery may be patchy and focal (at least 1 cm)
Healed sites of inflammation show scarring of the media and intima thickening
Double vision of involvement of the ophthalmic artery may lead to vision loss
Giant cell temporal arteritis and aortitis
Rare before 50
If. Granulomas,have to have macrophages
Medical emergency due to possible loss of vision when ophthalmic artery is involved
Temporal artery may be painful to palpating
Non infectious vascultis: takayasu arteritis
Characterized by ocular disturbances and marked weakening of pulses of the UE (pulseless disease)
-may present with weak pulse and low blood pressure in the UE
Granulomatous vascultis of medium and larger arteries
Takayasu has similar histological findings to giant cell arteritis except
Involves the aortic arch (aortitis) and major branch vessels
-occ aortitis causes dilation and aortic valve insuffiency
Pulmonary artery (involved 1/2 of cases), coronary and renal arteries may be involved
Younger age group <50
Takayasu arteritis
Transmural fibrous thickening of the aorta, espicially aortic arch and great vessels; producing narrowing of the major branch vessels
Historically associated with Japanese population, now global distribution
Marked intima thickening in takayasu arteritis
Due to intima thickening
Takayasu arteritis morph
Narrowing of brachiocephalic, carotid and subclavian arts
Increase intima thickening
Decrease lumen
Giant cells
Destruction and fibrosis of the arterial media associated with mononuclear infiltrates and inflammatory giant cells
Non infectious vasculitis : polyarthritis nodosa
Systemic vascultis, likely immune complex mediated
Involves
Renal vessels, heart, liver, GI tract
Pulsars vessels are spared
Who gest PAn
Any age group, but classically young adult
Almost 1/3 have chronic hepatitis B
-HBsAg-HBsAb complexes are found in the involved vessels
Treat PAN
Immunosuppressive therapy is usually effective
Morph PAN
Segmental transmural necrotizing inflammation (neutrophils , eosinophils, lymphocytes and macrophages) predilection for branch points
Ulcerations, infarcts, ischemic atrophy or hemorrhage may be first sign of dz
Sites of inflammation are typically not circumferential
Inflamed vessel wall susceptible to..
- thrombus formation/occlusion
- aneurysm
- rupture
All stages of PAN may coexist in different vessels of even same vessel, suggesting what
Ongoing or recurrent insults
Kawasaki disease
Acute arteritis of infants and small children (80% <4 years)
Often involves the coronary arteries
-affected sites may form aneurysms->thrombus or rupture->acute MI
Presentation Kawasaki disease
Erythema of the conjunctiva, oral mucosa, palms and soles, desquamative rash
-cervical lymphnode enlargement “mucocutaneous lymph node syndrome”
Treat Kawasaki
Usually self limited but IVIg ANS asprin are indicated to lower the risk of a coronary event
What causes Kawasaki disesase
Infectious agents (mainly viral) have been implicated in triggering the disease in genetically susceptible individuals. The vascular damage is primary mediated by activated T cells and monocytes/macrophages
Microscopic polyangitis
Necrotizing vasculitis involving arterioles capillaries and venues
-henoch-schonlein purpura, essential mixed cryoglobinemia, vascultis Association with CT DOS
Affect vessels of many organ systems
-renal glomeruli and lung capillaries most common (90% necrotizing glomerulonephritis)
Most cases associated with MPO-ANCA
Segmental necrotizing inflammation with fibrinoid necrosis
- many apoptotic neutrophils are usually sen
- leukocytoclastic vascultiis or hypersensitivity vascultiis
Immunosuppression induces remission, markedly improves long term survival
Churg Strauss syndrome non infectious vascultisi
Small vessel necrotizing vascultiis , associated with
-asthma, allergic rhinitis, hypereosinophihlia, lung infiltrates, extravascular granulomas
The inflammation may resemble PAN or microscopic polyangitis, with the addition of eosinophils and granulomas
Less than 1/2 show ANCA positivity (MPO-ANCA mostly)
May organ systems may be involved
-multisystem diseases with cutaneous involvement (palpable purpura), GI tract bleeding, and renal disease (primarily as focal and segmental glomerulosclerosis)
Myocardial involvement may give rise to cardiomyopathy; heart involved in 605 of patients and accounts for almost half of the deaths in the syndrome
Bechet disease
Vascultiis of small-medium vessels with classic triad
Aphthous ulcers of the oral cavity
Genital ulcers
Uveitis
-also GI pulmonary manifestations
Bechet disease gene
HLA-B51
Morph bechet disease
Vessel inflammation is neutrophilic and morpholgically nonspecific, may involve visceral organ systems with subsequent aneurysm formation
Prognosis bechet disease
Mortality related to severe neurologic involvement or rupture of aneurysms
Treat bechet
Immunosuppression with steroid or TNF antagonists tax effective
*granulomatosis with polyangitis: non infectious polyangitis
Necrotizing vascultis featuring:
- necrotizing granulomas of the upper and/or lower respiratory tracts
- necrotizing or granulomatous vasculitis , most prominently in the respiratory tract
- focal necrotizing, often cresenteric glomerulonephritis
Granulomatosis with polyangitis (formerly wegener granulomatosis) associated
PR3-ANCA (up to 95%)
A form of T cell mediated hypersensitivity response to normally innocuous inhaled microbial or other environmental agents
Clinical features granulomatosis with polyangitis (wegener)
M>F, avg age 40
Most patients have persistent pneumonitis and sinusitis, renal disease, and nasopharyngeal ulceration
-rashes, myalgias , articular involvement, neural inflammation and fever
What happens if granulomatosis with polyangitis is not treated
Rapidly fatal, 80% mortality at one year
Treat granulomatosis with polyangitis
Steroids, cyclophosphamide, TNF antagonists
Once fatal, now chronic relapsing and remitting
Morphology granulomatosis with polyangitis
Upper respiratory tract: sinonasal and pharyngeal inflammation with granulomas and vascultiis (granulomas with geographic patterns of central encrosis* and accompanying vascultisi)
Lower respiratory tract: multiple necrotizing granulomas, which may coalesce and cavitation
Thrombi angiitis obliterates (Berger disease)
Segmental thrombosis , acute chronic vascultis of small and medium vessels, espicially
—tibial arteries and radial arteries
—occ secondary extension to veins and nerves of extremities (leading to pain
What does thrombi angiitis obliterates lead to
Vascular insuffiency of the extremities
Who gets thrombi angiitis obliterates (Berger)
Heavy smoker<35
-most have hypersensitivity to intraderamlly injected tobacco products
—associated with HLA HaplotypE of certain ethnic groups: Israeli, Indian subcontinent and Japanese
Chronic ulcerations, which may lead to gangrene
The strong relationship between Berger and smoking
May stem from either a direct idiosyncratic endothelial cell toxicity caused by some component of tobacco, or an immune response to components of tobacco smoke that modify host vascular wall proteins . Most patients have hypersensitivity to intradermally injected tobacco extracts, and their vessel exhibit impaired endothelium dependent vasodilation when challenged with acetylcholine
Histology Berger
Acute and chronic inflammation, accompanied by luminal thrombosis. Thrombus can contain small microabscesses composed of neutrophils surrounded by granulomatous inflammation
The thrombus in buerger
May eventually organize and recanalize. The inflammatory process extends into contiguous veins and nerves (rare with other forms of vascultiis) and with time all three structures can be encased in fibrous tissue
Infectious vascultisi
Direct invasion of infectious agents
What agents cause infectious vascultiis
Pseudomonas
Aspergilllus
Mucor
Vascular invasion of infectious vascultiis
As part of a localized tissue infection, or less commonly hematogenous spread
-septicemia or embolization from infective endocarditis
Mycotic aneurysms
Vascular infections weaken arterial walls
-or induce thrombosis or infarction
Raynaud phenomenon
Excessive vasospasm of small arteries and arterioles, espicially fingers and toes
-red white and blue-proximal vasodilation, central vasoconstriction and distal cyanosis
Primary raynaud phenomenon
Induced by cold or emotion; symmetric involvement of the digits
Estimated 3-5% general population; young women
Benign course
Secondary raynaud
A component of another arterial disease such as SLE, *scleroderma, or thrombi angiitis obliterates;asymmetric involvement of digits
Worsens with time
Raynaud fingers
Sharply demarcated pallor of distal fingers resulting from spasm of the digital arteries
and cyanosis
Of fingertips
Myocardial vessel vasospasm
Excessive vasoconstriction of myocardial arteries or arterioles (cardiac raynaud) may cause ischemia or infarct
High levels of vasoactive mediators can precipitate prolonged myocardial vessel contraction
-usually caused by circulation vasoactive agents, which may be endogenous (epinephrine, pheochromocytoma) or exogenous (cocaine)
Outcome of myocardial vessel vasospasm
Sudden cardiac death or
Takotsubo cardiomyopathy: broken heart syndrome associated with emotional duress
Thyroid hormone myocardial vessel vasospasm
Elevated thyroid hormone causes a similar effect by increasing the sensitivity of vessels to circulating catecholamines, while autoantibodies and T cells in scleroderma can cause vascular instability and vasospasm. In some individuals, extreme psychological stress and the attendant release of catecholamines can lead to atholgic vasospasm
Varicose veins*
Abnormal dilation of veins with valvular incompetence, secondary to sustained intraluminal pressure
-stasis, congestion, thrombus, edema, and ischemia of overlying skin (stasis dermatitis)
Embolism from thrombi of superficial lower extremity veins is rare
-as opposed to DVT
Esophageal varices
Portal HTN (often due to cirrhosis) opens portosystemic shunts which direct blood to veins at the gatroesophageal junction
- esophageal varices (clinically important bc they may fatally rupture)
- the rectum (hemorrhoids)
- and periumbilicus (Capet Medusa)
Superior vena cava syndrome *
Neoplasms compress or invade the SVC
-bronchogenic carcinoma, mediastinal lymphoma, or aortic aneurysm
Obstruction produces a characteristic clinical complex
- marked dilation of the veins of the head, neck, and arms with cyanosis
- pulmonary vessels can also be compressed ->respiratory distress
Inferior vena cava syndrome
Neoplasms that compress or invade the IVC ; or thrombosis of the hepatic, renal or lower extremity veins that propagates cephalic
Hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC); tend to grow within veins, can ultimately occlude the IVC and extend into the right atrium
IVC obstruction induces marked lower extremity edema, distention of the superficial collateral veins of the lower abdomen
-renal vein involvement ->massive proteinuria
Hemorrhoids
Dilation of the venous plexus at the anorectal junction
-extremely common, and cause pain, bleeding and may ulcerate
Thrombophlebitis
Venous thrombosis and inflammation
Almost always involves deep veins in the legs, and can be completely asymptomatic
Risk factor for thrombophlebitis
in LE is prolonged inactivity/immobilization
Maybe systemic hypercoagulability
Serious complication of thrombophlebitis
Pulmonary embolism is most serious
Migratory thrombophlebitis (trousseau sign)
Patients with cancer may experience hypercoagulability as a paraneoplastic syndrome
Particularly seen with mucin producing adenocarcinoma (mucin is though to be thrombogenic)
In the classic case, venous thrombosis appear at one site, disappear and reappear at a different site
Associated with adenocarcinoma of the LUNG, OVARY,PANCREAS
Benign neoplasms
Hemangioma
Lymphangioma
Gloms tumors
Vascular ecstasia
Reactive vascular proliferation’s
Hemangioma
Capillary hemangioma
Cavernous hemangioma
Pyogenic granuloma
Lymphangioma
Simple(capillary) lymphangioma
Cavernous lymphangioma (systolic hygrometer)
Vascular ecstasia
Nexus flammeus
Spider telangiectasia (arterial spider)
Hereditary hemorrhagic telangiectasia (Oiler-Weber-tendu disease)
Reactive vascular proliferation’s
Bacillary angiomatosis
Intermediate grade neoplasms
Kaposi sarcoma
Hemangioendothelioma
Malignant neoplasm
Angiosarcoma
Hemangiopericytoma
Hemangioma
Common; localized increase in neoplastic blood vessels
- common in skin and mucosa membranes of the head and neck and in the liver
- congenital (juvenile or strawberry) hemangiomas often regress
Capillary hemangioma
Most common
Thin walled capillaries; tightly packed together
Cavernous hemangioma
Irregular, dilated vascular channels making a lesion with an indistinct border
More likely to involve deep tissue, more likely to bleed
Pyogenic granuloma (lobular capillary hemangioma)
A type of capillary hemangioma (not pyogenic, not a granuloma)
Rapidly growing , often in oral mucosa (where they may ulcerate)
Lymphangioma: simple lymphangioma
Simple lymphangioma
-appear very similar to capillary hemangiomas but without RBC
Subcutis of head/neck and axilla
Lymphangioma: cavernous lymphangioma (cystic hygrometer)
Neck or axilla of kids
Can be large (up to 15 cm)
Large cavernous lymphangiomas of the neck are often seen in Turner syndrome
Glomus tumor (gloms glioma, paraganglioma)
Benign tumors arising from glomus bodies, and most often appear in distal fingers
Of smooth muscle origin rather than endothelial
Painful
Glomus are benign but painful
Arising from modified smooth muscle cells of the glomus bodies, arteriovenous structures involved in thermoregulation. Although they may superficially resemble hemangiomas (may be blue), glioma gliomas arise from smooth msucle cells rather than endothelial cells. They are most commonly found in the distal portion of the digits espicially under the fingernales.
Treat glomus
Excision is curative
Turner
Missing X on 23 pair
Results from complete or partial monosomy of the X chromosome and is characterized primarily by hypogonadism in phenotypic females. Bilateral neck webbing and persistent looseness of skin not he back of the neck. Congenital heart disease is also common. Left sided cardiovascular abnormalities , particularly predictable coarctation of the aorta and bicuspid aortic valve, are seen most frequently. Cardiovascular abnormalities are the most important cause of increased mortality in children with turner
*bacillary angiomatosis
A vascular proliferation in response to gram negative bartonella bacilla
Who gets bacillary angiomatosis
Skin of immunocompromised patients
Describe lesions of bacillary angiomatosis
Localized, forming red papules
Micro: proliferation of capillaries with plump endothelial cells
The bacteria can be identified with PCR or visualized with a warthin starry stain*
Treat bacillary angiomatosis
Macrolides antibiotics effective
Epithelial hemangioendothelioma
Neoplastic endothelial cells are plump and cuboidal , resembling epithelium. Vascular channels may be difficult to recognize
Variable clinical behavior with metastasis in 20-30%
Kaposi sarcoma cause by what
HHV8
What are the four forms of kaposi sarcoma
AIDS associated KS
Classic KS
Endemic african KS
Transplant associated KS
AIDS associated KS
The most common form seen int he US. Most common AIDS related malignant tumor. May spread to lymph nodes and viscera
Classic kaposi sarcoma
Older men from middle eastern, Mediterranean or Eastern European descent, NOT associated with HIV,
Tumors localized to skin
Endemic african kaposi
Not associated with HIV, patients <40. Can involve lymph nodes
Transplant associated KS
Not associate with HIV
But with T cell immunosuppression. Can spread to lymph nodes and viscera
Kaposi sarcoma morph
Sheets of plump, proliferating spindle cells
Coalescent red purple macules and plaques of the skin
Angiosarcoma
Malignant endothelial tumor
M=F
What causes angiosarcoma
Can be induced by radiation exposure can arise ins eating of lymphedema (UE after radical mastectomy)
-hepatic angiosarcoma associated with arsenic, pesticides, thorotrast (contrast agent), polyvinyl chloride)
Where get angiosarcoma
Skin
Soft tissue
Breast
Liver
Angiosarcoma prognosis
Locally invasive and may metastasize
5 year survival around 30%
Pathology of vascular intervention
Therapeutic intervention that injures the endothelium also tends to induce intima thickening by recruiting smooth msucle cells promoting extracellular matrix deposition, analogous to atherosclerosis
Endovascular stenting
Balloon angioplasty
Coronary stents
Drug elating stents
Balloon angioplasty
Rupture of occluding plaque and limited dissection produced
-abrupt reclosure can result frmoextensive dissection thus 90% angioplasties followed by stent placement
Coronary stents
Expandable tubes of metallic mesh
- due to endothelial injury may induce thrombosis
- long term: proliferative in stent restenosis (1/3 of patients within 6-12 mo)
Drug elating stents: leach antiproliferative drugs to block sm m activation
Decrease restensois at 1 year by 50-80%
Paclitaxel sorilimus
Vascular replacement
- synthetic or autologous vascular grafts
- synthetic large bore works for aorta, but small bore fail due to thrombosis or intima hyperplasia at junction of the graft with the native vasculature
Thus utilize saphenous vein or left internal mammary arteries for small bore grafts (coronary arteries)
Saphenous vein 50% potency at 10 years
Internal mammary arteries: 90% at 10 years
Intima hyperplasia histology
Angiogram constriction
Gore Tex graft
Photomicrograph demonstrating gore Tex graft with prominent intima proliferation and very small residual lumen
28 yo male presented to ED because of repeated episodes of acute vertigo that occurred after chiropractic neck manipulations for chronic neck pain. The first PE was normal and the patient was discharged. However, the following day, besides vertigo the patient also had loss of balance , blurred vision and mild numbness and weakness of the left extremities, with cerebellar signs on the right side. Angiography revealed dissection of the vertebral artery
Vertebral artery dissection
What are the three concentric layers of vascular
Intima
Media
Adventitia
Intima
Single layer of endothelial cells
-internal elastic lamina demarcates intima from media
Media
Arteries well organized concentric layers of smooth muscle, veins haphazard
Different in elastic arteries, muscular arteries and arterioles
Media elastic arteries
High elastin content allows expansion during systole, recoil during diastole
- propels blood towards organs
- less compliant with increased age-> increased systolic BO
Media muscular arteries
Circumferential oriented smooth msucle
-arteriolar sm m contraction=vasoconstriction, or relaxation=vasodilation
Arterioles media
Principal point of physiologic resistance to blood flow
- resistance to fluid flow is inversely proportional to the fourth power of the diameter
- halving the diameter increases resistance 16 fold (small changes in vasoconstriction has profound effects on BP_
Adventitia
External to media , often separated from media by wide external elastic lamina
Vasa vasorum=vessels of hte vessels, small arterioles supply I2 to outer media or large arteries
Three types of arteries
Large elastic arteries-aorta and its major branches (common carotid, iliac pulm art)
Medium sized muscular arteries-smaller branches of the aorta (coronary and renal)
Arterioles-within tissues and organs
Capillaries
Diameter of an RBC, no media, pericytes (resembles sm m cells)
Veins
Most inflammatory reactions, vascular leakage and leukocyte exudation
-large lumens, thinner less organized walls; contains about 2/3 of the total blood vol
- less rigid-susceptible to dilation and compression, as well as infiltration by tumors and inflammatory process
- reverse flow dueto gravity prevented in extremities by venous valves
Lymphatics
Thin walled, lined by specialized endothelium
-return intestinal tissue and fluid and inflammatory cells too the blood stream
-transplant bacteria and tumor cells-pathway for disease dissemination
Although the basic organization of the vasculature is constant, the thickness and composition of the various layers differ according to hemodynamics forces and tissue requirements. The aorta has substantial elastic tissue to accommodate high pulsating forces, with the capacity to recoil and transmit energy into forward blood flow. The muscular arteries and arterioles have concentric rings of medial smooth muscle cells whose contractile state regulates vessel caliber and, thereby, blood flow and blood pressure. The venous system has relatively poorly developed medial layers that permit greater capacitance. The capillary wall permits ready diffusion of oxygen and nutrients bc it is comprised only of an ndothelial cell and spares encircling pericytes. The differing structural and functional attributes leave the various parts of the vascular tree vulnerable to particular disorders. This , loss of aortic elastic tissue in a large artery may result in aneurysm, while statsis in a dilated venous bed may produce a thrombus
Ok
Vascular anomalies
Berry aneurysms
Arteriovenous malformations
Fibromuscular dysplasia
Berry aneurysm
Circle of Willis, ADPKD
Arteriovenous malformations
Reviewed in CNS (artery->vein, no capillaries)
- usually developmental defect, but can arise from trauma etc
- large or multiple AVMs may shunt blood from arterial to venous circulation, forces heart to pump additional volume leading to high output cardiac failure
Fibromusclar dysplasia
Focal irregular thickening in medium and large muscular arteries (renal, carotid, splanchnic, and vertebral vessels)
What causes fibromuscular dysplasia
Unknown, probably developmental
First degree relatives have increased incidence; young women*
Medial and intima hyperplasia->
Luminal stenosis
Renovascular HTN
Due to fibromuscular dysplasia of renal arteries
Fibromuscular dysplasia morphology
String of beads on angiography due to making attenuation of adjacent media
Problem with fibromuscular dysplasia
Can develop aneurysms that may rupture
Is fibromuscular dysplasia asssoacited with oral contraception or increased estrogen
No
Endothelial cells
Distinct gene expression profiles, behaviors and morph in different portions of the vascular tree
- nonthrombogenic surface=maintains blood in a fluid state
- modulate medial sm m tone (influence vasc resistance)
- metabolize hormones (angiotensin), regulate inflammation, affect growth of other cells ypes (esp sm m cells)
Endothelial activation figure 11-2
Ok
Endothelial dysfunction
Alteration in phenotype->proinflammatory and prothrombogenic
-initiation of thrombus formation, atherosclerosis and vascular lesions of HTN
Vascular smooth muscle cells
NL vasc repair and atherosclerosis
- ability to proliferate
- synthesize collagen , elastin and proteoglycans
- elaborate growth factors and cytokines
- vasoconstriction and/or dilation
Intima thickening
Stereotypical responses of a vessel wall to any insult
- associated with endothelial cell dysfunction or loss , stimulates sm m cell recruitment and proliferationa nd associated matric synthesis->intima thickening
- neointimal response
Neointimal sm m cells are motile, undergo cell division, acquire new biosynthetic capabilities
- sm m cells can return to nonproliferative state with normalization of endothelial layer
- however, the healing response results in intima thickening that may impede blood flow
Basal and activated endothelial cell states. Normal blood pressure, laminar flow, and low growth factor levels promotes a basal endothelial cell state that maintains a nonthrombotic, nonadhesive surface with appropriate vascular wall smooth msucle tone. Injury or exposure to certain mediators results in endothelial activaiton, a state where endothelial cells develop a procoagulatn surface that can be adhesive for inflammatory cells, and also express factors that cause smooth muscle contraction and/or proliferation and matrix synthetisis. VEGF, vascular endothelial growth factor
Ok
Basal endothelial state
normotension, laminar flow and growth factors (VEGF)
->Non adhesive, non thrombogenic surface
Initial event following vascular injury ?
Endothelial cell activation
Activated state
Turbulent flow, HTN, cytokines, complement, bacterial products, lipid products, lipid products, advanced glycation end products, hypoxia, acidosis, viruses, cigarette smoke
->
Increased expression of *procoagulants, *adhesion molecules, and proinflammatory factors
Altered expression of chemokine, cytokines, and *growth factors
Response to vascular injury
Intima thickening, emphasizing intima smooth msucle cell migrationa Nd proliferationa ssociated with extracellular matrix synthesis. The new intima cells are shown in a different color to emphasize that they have a proliferative, synthetic, and noncontractile phenotype distinct from medial smooth msucle cells
Response to vascular injury steps
- Recruitment of smooth msucle cells or smooth msucle precursor cells to the intima
- Smooth msucle cell mitosis
- Elaboration of extracellular matrix
Hypertensive vascular disease
High BP->end organ damage and major risk factor in atherosclerosis
Sustained diastolic >89mmHg or sustained systolic >139 mmHg associated with what
Increased risk of atherosclerosis
-295 OF POPULATIONA RE HYPERTENSIVE BASED ONT HESE NUMBERS
Secondary HTN
Underlying renal or adrenal disease 5% of pop
Primary aldosteronism, Cushing, pheochromacytoma
Hypertension secondary to renal artery stenosis is caused by increased production of renin from the ischemic kidney; a bruit can be heard on auscultation of the affected kidneys
Essential HTN
Idiopathic 90-95% of population
Prevelance and vulnerability increase with age: african American high risk
Cardiac hypertrophy and heart failure (hypertensive heart disease), multi infarct failure, another third die of stroke
Malignant htn
5% rapid increase BP lead to death in 1-2 years
Systolic>200, diastolic >120 mmHg
Severe HTN, renal failure, reitinal hemorrhages and exudates with or without papilledema
Often superimposed on pre existing benign HTN
Cause of HTN in most individuals is
Unknown
Multifactorial genetic, environmental
Essential HTN
95% of cases
Secondary HTN renal
Acute glomerulonephritis
Chronic renal disease
Polycystic disease
Renal artery stenosis
Renal vasculitis
Renin producing tumors
Secondary htn endocrine
Adrenocortical hyperfunction (Cushing, aldosteronism, congenital adrenal hyperplasia)
-exogenous hormones
Pheochromacytoma
Acromegaly
Cardiovascular cause of secondary htn
Coarctation of aorta
Polyarthritis nodosa
Increased intravascular volume
Neurologic causes secondary htn
Psychogenic
Increased intracranial pressure
Sleep apnea
Acute stress, including surgery
BP is a function of what
Cardiac output and peripheral vascular resistance, both are influenced by multiple genetic and environmental factors
Cardiac output
Heart rate and stroke volume (which is strongly influenced by blood volume which is regulated by renal sodium excretion or resorption)
Vascular resistance
Regulated at level of arterioles; influenced by neural and hormonal inputs
Cardiac output is a function of what
Stroke volume and heart rate
Blood pressure=
COx peripheral resistance
What effects CO
Blood volume-Na, mineralocorticoids, ANP
Cardiac features-HR and contractility
What effects peripheral resistance
Humoral constrictors-angiotensin II, catecholamines, thromboxane, leukotrienes, endothelin1
Humoral dilators-prostagladin, kinins, NO
Constricting -a adrenergic
Dilators -b adrenergic
Autoregulaton pH , hypoxia
A and b adrenergic systems
Regulate fill pressure and heart rate/contractility (also vascular tone)
Filling pressure
Most impt determinate of stroke vol
Heart rate and myocardial contractility (2nd factor affecting stroke volume)
Ok
CO
A and b adrenergic
Filling pressure
Heart and myocardial contractility (2nd factor affecting stroke vol)
Peripheral resistance
Neural and hormonal input regulates at arterioles
Vascular tone=balance between vasoconstrictors and vasodilator
Vasoconstriction-angiotensin II, catecholamines, endothelin1
Vasodilator: kinin, prostagladin, nitric acid
Resistance vessels also exhibit autoregulation; increased blood flow->vasoconstriction to protect tissue against hyperperfusion BP fine tuned by tissue pH and hypoxia to accommodate local metabolic demands
Blood volume and vascular tone modified and maintained by
Renin angiotensin aldosterone system
In states of low volume or low peripheral resistance, or a decreased glomerular filtration rate, __ is released by juxtaglomerular cells in the afferent arterioles in the kidney
Renin
What does renin do
Cleaves circulationg angiotensinogen from angiotensin I
Angiotensin I is cleaved to form angiotensin II by ACE
Angiotensin II
Potent but short lived vasoconstrictor
Stimulated adrenal cortex to release aldosterone, causing renal reabsorption of Na and water
Resistance and voincreased raising bp
The volume expansion induces myocardial release of ___, leading to Na excretiona dn diuresis as well as vasodilation thus lowering bp
ANP
ANP and RAAS
Maintains bp homeostasis
HTN
30% adults
Major risk factor for atherosclerosis, CHF and renal failure
Essential HTN
90-95% of cases see figures 11-4 11-5
Sustained HTN
Requires participation of the kidney
HTN controlled by
A single gene DO or is secondary to renal disease, adrenal disease or other endocrine DO
What does HTN cause
Degenerative vegetative changes in the walls of large and medium arteries, that can lead to aortic dissection and/or cerebrovascular hemorrhage
What are two forms of blood vessel disease
Hyaline arteriosclerosis
Hyperplastic arteriosclerosis
Hyaline arteriosclerosis
Increased smooth muscles matric synthesis
Plasma protein leakage across damaged endothelium
HOMOGENOUS PINK HYALINE THICKENING of the vessel wall, with associated luminal narrowing
Hyperplastic arteriosclerosis
Occurs in SEVERE HTN
Smooth msucle cells form CONCENTRIC LAMELLATIONS (INION SKINNING) with resultant luminal narrowing
Morphology vascular HTN
Hyalinized vessel wall-> narrow lumen
-the arteriolar wall is thickened with increased protein deposition (hyalinized) and the lumen is markedly narrowed
Hyperplastic arteriosclerosis
-onion skinning causing luminal obliteration PAS stain
Benign HTN
Mild to moderate increase of bp and an asymptomatic period of several years before the inevitable onset of symptoms and end organ damage (hence the condition is not truly benign)
Malignant HTN
Marked increase of bp and rapid progression over a few weeks to end organ failure. Most patients with essential HTN follow the benign pattern, although it may accelerate to malignant HTN. The characteristic vascular lesion of benign essential HTN is widespread hyaline arteriosclerosis manifest by thickening of the walls of the smalla rteries and arterioles by amorphous eosinophilic material composed of degenerated smooth cells and deposited plasma proteins
Hyaline arteriosclerosis
With associated small cortical scare (hyaline arteriolonephrosclerosis) is commonly seen in the kidneys . Hyperplastic arteriosclerosis, marked luminal narrowing by cellular intima proliferation in a lamellar, onionskin pattern , is the characteristic lesion of malignant HTN. In severe malignant HTN, fibrinoid necrosis of the glomerular arterioles occur. As associated ischemic injury develops rapidly, leading to petechial hemorrhages in multiple organs, including the kidneys (hyperplastic arteriolonephrosclerosis)
Arteriosclerosis
Hardening of the arteries, generic term
-arterial wall thickening and loss of elasticity
Arteriosclerosis
Sm arterioles and arterioles, may cause downstream ischemic injury (see previous hyaline vs hyperplastic_
Monckenberg medial sclerosis
> 50
Calcification of muscular arteries, internal elastic membrane involved, NO narrowing of lumen, NO clinical significance
Atherosclerosis
Gruel and hardening , most frequent and clinically important pattern
Atherosclerosisunderlies pathogensis of what
Coronary, cerebral and peripheral vascular disease
Atherosclerosis demographics
Common espicially in the developed world
- causes more morbidity and mortality (roughly half of all deaths) in the western world than any other disorder
- myocardial infarction responsible for almost 1/4 of all deaths in US
- soviet union highest ischemic heart disease mortality 3-5x US 7-12 x japan
Atheroma=atheromatous-atherosclerotic plaque
Raised lesion with a soft rumors core of lipid covered by a fibrous cap
Describe atherosclerotic plaque. INTIMAL BASED PROCESS**
Fibrous cap-smooth msucle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovasculaturization)
Necrotic center -cell debris, cholesterol crystals, foam cells, calcium
Media
What is prevelance and extend or atherosclerosis related to
Multiple risk factors, which have synergistic (rather than additive) effect
40-60yo incidence up 5x
Death rates from ischemic heart disease increase each __
Decade
Premenopausal women are somewhat protected from atherosclerosis
Atheroprotective effect of estrogen if started early postmenopausal, otherwise no benefit
Hypercholestermia
Major risk factor even in absence of other factors, it is sufficient to initiate lesion development
Metabolic syndrome
Associated with central obesity
Insulin resistance, HTN, dyslipidemia (increase LDL decrease HDL), hypercoagulability, and proinflammatory state may contribute to endothelial dysfunction andor thrombosis
Nonmodifiable factors of atherosclerosis
Genetic abnormalities
Family history
Increasing age
Male gender
Modifiable risk factors of atherosclerosis
Hyperlipidemia
HTN
Cigarette
Diabetes
Inflammation
See table 11-2
Ok
10year rate of coronary artery disease in 55 year old men and women as function of established risk factors (hyperlipidemia, HTN, smoking and diabetes)
Increase
CRP predicts cardiovascular risk
Increase@
Response to injury model for atherosclerosis
Chronic injury and/or dysfunction of endothelium, leading to chronic inflammation and attempts to repair the tissue
Endothelial injury and dysfunction : hemodynamics turbulence
Atherosclerosis does not occur. Randomly in vessels, nor does it occur everywhere uniformly
Mostlesions tend to occur at openings of exciting vessels, branch points, posterior abdominal aorta-due to flow disturbances ormally seen in these locations
Andothelial injury and dysfunctionL Circulating lipids
Lipids in atheromatous plaques are predominantly cholesterol and cholesterol esters
Accumulate in the intima, are taken up by macrophages and partially oxidized
This modified LDL further accumulates within macrophages and smooth msucle cells, forming foam cells and a lesion known as a fatty streak
This stimulates an inflammatory response to accumulation of this toxic form of LDL
Arterial wall response to injury
Chronic endothelial injury
Endothelial dysfunction
Macrophages activation, smooth msucle recruitment
Macrophage and smooth msucle cells engulf lipids
Smooth msucle proliferation, collagen and other extracellular matrix deposition, extracellular lipid
Chronic endothelial injury
Hyperlipidemia HTN Smoking Homocysteine Hemodynamics factors Toxins Viruses Immune reactions
Endothelial dysfunction
Increased permeability leukocyte adhesion
Monocytes adhesion and emigration
Macrophage activation, smooth msucle recruitment
See smooth msucle cells
Macrophages and smooth muscle cells engulf ___
Lipid
See fatty streak and T cells
Smooth msucle proliferation, collagen and other extracellular matrix deposition, extracellular lipid
Lipid debris, T cell and collagen
Evolution of arterial wall changes in the response to injury
- Normal
- Endothelial injury with monocyte and platelet adhesion
- Monocyte and smooth msucle cell migration into the intima with macrophage activation
- Macrophage and smooth muscle cell uptake of modified lipids, with further activation and recruitment of T cells
- INTIMAL smooth msucle cell proliferation with extracellular matrix production, forming a well developed plaque
Inflammation atherosclerosis pathogenesis
Accumulation of cholesterol crystals within macrophages is recognized by the inflammasome which leads to IL1 secretion
More macrophages and T cells are recruited and activated
Inflammatory cytokines further activate endothelial cells, and growth factors stimulate smooth muscle cells to migrate to the intima and proliferate
Smooth muscle proliferation and matrix deposition pathogenesis atherosclerosis
Several growth factors are implicated in smooth msucle cell proliferation, including PDGF as well as macrophages, endothelial cells and smooth msucle cells, fibroblast growth factor and transforming growth factor TGF-a
Proliferating smooth msucle cells synthesize extracellular matric including collagen
Due to the INTIMAL expansion from foam cells and extracellular lipid recruited inflammatory and smooth msucle cells and increased ECM, an atheromatous plaque is formed
Over time a soft fibrofatty plaque becomes covered with a fibrous cap (dense collagen fibers). The center of the plaque is necrotic, containing lipid debris, foam cells and thrombus, surrounded by a zone of inflammatory and smooth msucle cells
What happens when have hyperlipidemia, hyperglycemia, HTN, and endothelial injury
Platelet adhesion and recruitment of circulating monocytes and T cells, with subsequent smooth msucle cell migration and proliferation as well as further macrophage activation. Foam cells in atheromatous plaques derive from macrophages and smooth msucle cells that have accumulated modified lipids via scavenger and LDL receptor related proteins. Extracellular lipid is derived from insulation fromt he vessel lumen, particularly in the presence of hypercholesterolemia, as well as from degenerating foam cells. Cholesterol accumulation inthe plaque reflects an imbalance between influx and EF flux; HDL likely helps clear cholesterol fromthese accumulations. In response to the elaborated cytokines and chemokine, smooth msucle cells migrate to the intima, proliferate and produce extracellular matrix, including collagena dn proteoglycans
Common sites of atherosclerosis
Abdominal aorta Coronary arteries Popliteal arteries Internal carotid arteries Circle of Willis
Complications of atherosclerotic plaques
Rupture and ulceration
-may lead to thrombosis
Hemorrhage
-may follow plaque rupture
Embolism
- may follow plaque rupture
- aneurysm formation
Histology fatty streak
Collection of foamy macrophages in the intima
Mild vs severe atherosclerosis aorta histology
Mild-fibrous plaques
Severe-diffuse and complicated lesions including an ulcerated plaque and lesion overlying thrombus
Stenosis of the atrial lumen from atherosclerosis
Plaques tend to continually grow bc of repeated cycling through the injury healing process
The lumen of the affected vessel gradually shrinks, eventually leading to ischemia downstream (a point known as critical stenosis-approximately 70% occluded)
This may lead to chronic ischemia of myocardium, bowel and brain , the extremities
Acute plaque change atherosclerosis
An acute Thrombus may form over the plaque, occluding the artery. This may occur secondary to:
- Rupture of the plaque
- erosion or ulceration of the plaque surface
Hemorrhage into the plaque may acutely expand its volume
Some plaques are more prone to rupture than others
The fibrous cap is continually being degraded and resynthesized (remodeled
Increased inflammation int he plaque can accelerate fibrous cap degradation and inhibit its resynthesis, Thur reducing the amount of collagen in the cap and weakening it
Physical stresses can cause plaque rupture
-changes in blood pressure
Vasoconstriction
Aneurysms
Localized abnormal dilation of a blood vessel, or the heart, that may be congenital or acquired
True aneurysm
An intact (but thinned) muscular wall at the site of dilation
False aneurysm
Defect through the wall of the vessel, or heart, communicating with an extravascular hematoma
An aneurysm can occur whenever the connective tissue of the vascular wall is weakened, whether by acquired or congenital conditions
Defective vascular wall CT
-marfan (defective fibrillin synthesis)
Net degradation of vascular wall CT
-inflammatory conditions (such as atherosclerosis)->increased matric metalloprotease
Weakening of the vascular wall by ischemia
- atherosclerosis->ischemia of inner media
- HTN->ischemia of outer media
- tertiary syphilis->ischemia of outer media (thoracic aorta)
Tertiary syphilic and aneurysm
Obliterating endarteritis (characteristic of late stage syphilic) shows a predilection for small vessels, including those of the vasa vasorum of the thoaracic aorta. This elads to ischemic injury of the aortic media and aneurysmal dilation. Which sometimes involves the aortic valve annulus (aortic valve regurgitation)
Cystic medial degeneration aneurysm
Loss of vascular wall elastic tissue, or ineffective elastin synthesis, leads to cystic medial degeneration, which disrupted and disorganized elastin filaments and increased ground substance (proteoglycans)
Final common result of different conditions, including ischemic medial damage and marfans
Two most important causes of aortic aneurysms are
Atherosclerosis and HTN
Mycotic aneurysms
Can originate from:
Septic emboli (usually complication of infective endocarditis)
Extension of an adjacent suppurative process
Circulating organisms directly infecting the arterial wall
Cystic medial degeneration
Marfan
Elastin fragmentation and areas devoid of elastin that resemble cystic spaces but are actually filled with proteoglycans
Normal media for comparison, showing the regular layered pattern of elastic tissue
AAA
Abdominal aortic aneurysm
Usually from atherosclerosis
Occur in abdominal area, usually below the renal arteries, and often involve the common iliac arteries
Who gets aaa
Men smokers 6th decade
Characterization aaa
Severe atherosclerosis of the aorta, covered with mural thrombus
May be detected as a pulsating mass in the abdomen
Complications aaa
Rupture and hemorrhage
Occlusion of branching arteries and downstream ischemia
Embolism
Impingement on another structure
Morph aaa
Lines of Shan-alternating light pink bands (fibrin and platelets) with dark pink bands RBC
Thoracic aortic aneurysm
Often due to HTN or less commonly congenital defect in CT Marfan
Marfan
AD genetic disorder resulting in defective synthesis of fibrillin that leads to aberrant TGF-B activity that weakens elastic tissue
Clinical presentation thoracic aortic aneurysm
Impingement
- lower respiratory tree
- esophagus
- recurrent laryngeal nerves
Aortic valvular insuffiency
Rupture
Aortic dissection
Occurs when blood enters a defect in the intima and travels through a tissue plane within layers of the aortic media
Who gets aortic dissection
HTN males 40-60
Younger patents with disorders of vessel CT (marfan)
Primary risk factor aortic dissection
HTN
Classic presentation of aortic dissection
Sudden onset of severe chest pain (usually beginning in anterior chest) radiating to the back between the scapulae, and moving downward as the dissection progresses
-can be confused with AMI
Aortic dissection pathogensis
Blood enters aortic wall via an INTIMAL tear forming an intramural hematoma
Usually in hypertensive patients, there is some degree of cystic medial degeneration
Where are most aortic dissection
Most dissections arise in the ascending aorta, within 10cm of the aortic valve
What happens when dissections rupture through the adventitia
Massive hemorrhage (into the thoracic or abdominal cavities) or cardiac tamponade (hemorrhage into the pericardial sac)
If the dissecting hematoma renters the lumen of the aorta through a second distal INTIMAL tear
A new false vascular channel (double barreled aorta) is created
-this averts a fatal extraaortic hemorrhage, and over time, such false channels can be enotheliazed to become recognizable chronic dissections
Type A dissection (involving the ascending aorta)
Are more common and associated with higher morbidity and mortality
Most common cause of death in both dissections
Rupture
Dissection may also extend along arterial branches of the aorta, causing potential occlusion of those vessels
Treat type a dissection
Antihypertensive therapy and an attempt to surgically reprair the INTIMAL tear
Type B
Distal debarked III arise after the take off of the great vessels
What dissection has most serious complications and mortality
Type A
The effects of HTN with excessive hemodynamics trauma on a weakened aortic wall can lead to the formation of a ___ in the media
Hematoma
The hematoma dissects longitudinally to split the media, which creates a dissecting hematoma or a __ __, a double barreled aorta with true and false lumens. In most cases, a proximal INTIMAL tear allows blood to enter the false lumen under systemic pressure
Dissecting aneurysmtype A dissections
The proximal INTIMAL tear is inthe ascending thoracic aorta
Type a
Type b dissection
The proximal INTIMAL tear is int he aortic arch or the descending thoracic aorta
What are type a dissections prone to
External rupture intothe mediastunmin or pericardial cavity, necessitate surgical intervention. Some dissections develop distal tears and become chronic with the potential for late rupture. Blood pressure control is key in the treatment of any aortic dissection
Severe diseases give rise to annuloaortic ecstasia
A progressive aneurysmal dilation of the aortic root with accompanying aortic valvular incompetence.
Atherosclerotic aneurysms of the iliofemoral arteries
Fills with unorganized mural thrombus and the expanding aneurysms become susceptible to rupture
Aortic root and ascending aorta atherosclerotic aneurysms
Secondary to end arterioles is of the vasa vasorum produced years previously by systemic infection of trep pallidumm=
The entire abdominal aorta and the descending thoracic aorta form a
Thoracoabdominal atherosclerotic aortic aneurysm
