Hypertensive Vascular Disease
Definition
Hypertension (HTN) is a sustained elevation of diastolic pressure above 89 mm Hg or systolic
pressure above 139 mm Hg.
Normal BP: <120/<80 mm Hg
Prehypertension: 120–139 / 80–89 mm Hg
Hypertension: ≥140 / ≥90 mm Hg
Malignant hypertension: Rapidly rising BP (>200/120 mm Hg) → leads to end-organ
damage (especially kidneys, brain, eyes).
Classification of Hypertension
Type Description Prevalence
Primary (Essential) HTN No identifiable cause 90–95%
Secondary HTN Due to underlying disorder 5–10%
Causes of Secondary HTN
Renal: Renal artery stenosis, chronic renal disease, polycystic kidney disease
Endocrine: Cushing’s syndrome, Conn’s syndrome, pheochromocytoma,
hyperthyroidism
Cardiovascular: Coarctation of the aorta
Neurologic: Increased intracranial pressure
Drugs: Oral contraceptives, NSAIDs
Mechanisms in Essential HTN
Reduced renal sodium excretion (shift in pressure-natriuresis curve)
Vasoconstrictive influences (↑ vasomotor tone)
Genetic factors (e.g., polymorphisms in RAAS, ion transport genes)
Environmental factors: Obesity, stress, salt intake, smoking, inactivity
Vascular Pathology in Hypertension
Two major morphologic types:
Type Description Seen in
Hyaline Homogeneous, pink hyaline thickening of arteriole walls Benign
Arteriolosclerosis with luminal narrowing HTN
“Onion-skin” concentric, laminated wall thickening with
Hyperplastic Severe
luminal narrowing (smooth muscle + basement membrane
Arteriolosclerosis HTN
reduplication)
Malignant HTN
Fibrinoid necrosis of arterioles + necrotizing arteriolitis
Acute kidney injury can occur
Papilledema, encephalopathy, retinal hemorrhages
Arteriosclerosis
Definition
Arteriosclerosis = hardening of arteries
Includes 3 types:
1. Atherosclerosis (most important) – affects large and medium arteries
2. Arteriolosclerosis – affects small arteries and arterioles
3. Monckeberg Medial Calcific Sclerosis – calcification in media of muscular arteries;
usually incidental, not significant
Atherosclerosis
Definition
A progressive, chronic inflammatory disease of large/medium arteries marked by formation
of intimal atheromatous plaques.
Major Arteries Affected
Elastic arteries: aorta, carotid, iliac
Large muscular arteries: coronary, popliteal
Atherosclerotic Plaque Components
1. Fibrous cap: smooth muscle cells, ECM (collagen, elastin)
2. Necrotic core: lipid (cholesterol), debris, foam cells, fibrin
3. Neovascularization: small blood vessels at plaque base
Risk Factors for Atherosclerosis
Major Constitutional (Nonmodifiable)
Age: 40–60 years and above → risk increases with age
Sex: Men > women (premenopausal); risk equalizes postmenopause
Genetics: Family history = strongest risk factor
Major Modifiable Risk Factors
Hyperlipidemia (especially LDL↑, HDL↓)
Hypertension
Cigarette smoking
Diabetes mellitus: Increases risk of MI by 2x
Other Risk Factors
Inflammation (↑CRP)
Hyperhomocysteinemia
Metabolic syndrome
Lipoprotein(a)
Hemostatic factors (↑ fibrinogen)
Sedentary lifestyle
Pathogenesis of Atherosclerosis
Key Concept: Chronic endothelial injury hypothesis
1. Endothelial injury/dysfunction
o Mechanical (shear stress), hyperlipidemia, smoking, immune
2. Accumulation of lipoproteins (especially oxidized LDL, cholesterol crystals)
3. Monocyte adhesion & transformation into foam cells
4. Inflammation – release of cytokines, growth factors
5. SMC migration & ECM deposition
6. Plaque progression – necrotic core, calcification, angiogenesis
Complications of Atherosclerotic Plaques
Rupture → thrombosis
Hemorrhage into plaque
Aneurysm formation (due to media weakening)
Embolism
Calcification
Aneurysms and Dissection
Aneurysm: Definition
Localized abnormal dilation of a blood vessel or heart chamber
Type Morphology
Bounded by complete vessel wall; may be saccular or
True aneurysm
fusiform
False aneurysm Defect in wall → extravascular hematoma with fibrous
(pseudoaneurysm) capsule
Blood enters wall through tear and dissects between
Dissection
layers
Abdominal Aortic Aneurysm (AAA)
Common Site: Infrarenal abdominal aorta
Risk Factors
Atherosclerosis (primary cause)
Smoking
Male gender
Age >50
Complications
Rupture → fatal hemorrhage
Obstruction of branch vessels
Embolism
Compression of adjacent structures
Thoracic Aortic Aneurysm
Causes
Hypertension (most common)
Marfan syndrome (fibrillin-1 mutation)
Syphilis (tertiary, rare now)
Symptoms
Respiratory issues
Dysphagia
Persistent cough (recurrent laryngeal nerve compression)
Aortic regurgitation
Rupture
Aortic Dissection
Definition: Tear in intima → blood dissects between intima and media
Risk Factors
Hypertension (90%)
Connective tissue disorders: Marfan, Ehlers-Danlos
Bicuspid aortic valve
Classification
Stanford A: Involves ascending aorta ± descending (more common, dangerous)
Stanford B: Descending aorta only
Complications
Cardiac tamponade
Aortic rupture
End-organ ischemia
🩸 VASCULITIS
Inflammation of blood vessel walls leading to damage and potential ischemia
Classification of Vasculitis
Type Vessel Size Common Diseases
Large vessel Aorta and major branches Giant cell arteritis, Takayasu arteritis
Main visceral arteries &
Medium vessel Polyarteritis nodosa, Kawasaki disease
branches
Microscopic polyangiitis, GPA, Churg-
Small vessel Arterioles, capillaries, venules
Strauss
Noninfectious Vasculitis
Immune-mediated vessel injury, typically from immune complexes or autoantibodies.
Immune Complex–Associated Vasculitis
Pathogenesis: Deposition of immune complexes activates complement → neutrophil
recruitment → vessel wall injury.
Examples:
o Hypersensitivity vasculitis (drug or infection induced)
o Henoch-Schönlein purpura (IgA complexes)
o Cryoglobulinemic vasculitis
Antineutrophil Cytoplasmic Antibodies (ANCA)
Two main types:
c-ANCA (cytoplasmic pattern): Directed against proteinase 3 (PR3); associated with
Granulomatosis with polyangiitis (GPA)
p-ANCA (perinuclear pattern): Directed against myeloperoxidase (MPO); seen in
Microscopic polyangiitis and Churg-Strauss syndrome
Anti–Endothelial Cell Antibodies
Found in some vasculitis cases; role unclear.
Associated with Kawasaki disease and transplant vasculopathy.
Large Vessel Vasculitis
Giant Cell (Temporal) Arteritis
Most common vasculitis in adults >50 years.
Affects branches of the carotid artery, especially temporal artery.
Pathogenesis: T-cell mediated granulomatous inflammation with multinucleated
giant cells.
Clinical Features:
o Headache (temporal artery)
o Jaw claudication
o Visual loss (due to ophthalmic artery involvement)
o Elevated ESR
Morphology:
o Intimal thickening → luminal narrowing
o Granulomatous inflammation of media
Treatment: High-dose corticosteroids immediately (to prevent blindness).
Takayasu Arteritis
Granulomatous inflammation of the aortic arch and its branches.
Affects young women <40 years (“pulseless disease”).
Clinical: Weak/absent pulses in upper limbs, fever, night sweats.
Morphology similar to giant cell arteritis but in younger patients.
Complications: Stenosis, aneurysm.
Medium Vessel Vasculitis
Polyarteritis Nodosa (PAN)
Necrotizing vasculitis of medium-sized muscular arteries.
Often renal and visceral arteries involved; spares pulmonary arteries.
Usually in middle-aged adults.
Associated with HBV infection in ~30% cases.
Clinical: Hypertension, abdominal pain, renal infarcts, skin nodules.
Morphology: Segmental transmural necrotizing inflammation → aneurysms and
thrombosis → ischemia.
Treatment: Corticosteroids + immunosuppressants.
Kawasaki Disease
Acute febrile illness of infants/young children.
Medium vessel vasculitis involving coronary arteries.
Clinical: Fever, conjunctivitis, mucosal erythema, lymphadenopathy, rash.
Major concern: Coronary artery aneurysms → thrombosis or rupture.
Treatment: IVIG and aspirin.
Small Vessel Vasculitis
Microscopic Polyangiitis
Necrotizing vasculitis affecting capillaries, arterioles, venules.
c-ANCA negative, p-ANCA positive.
Clinical: Pulmonary hemorrhage, rapidly progressive glomerulonephritis.
No granulomas.
Granulomatosis with Polyangiitis (GPA, Wegener)
Necrotizing granulomatous inflammation of respiratory tract + necrotizing vasculitis
of small vessels.
c-ANCA positive (anti-PR3).
Clinical triad:
o Upper respiratory tract: sinusitis, nasal ulceration
o Lower respiratory tract: lung nodules/cavities
o Renal: pauci-immune glomerulonephritis
Morphology: Granulomas with necrosis and vasculitis.
Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis)
Necrotizing granulomatous vasculitis with eosinophilia.
Asthma, allergic rhinitis common.
p-ANCA positive in ~40%.
Clinical: Asthma, peripheral eosinophilia, vasculitis.
Thromboangiitis Obliterans (Buerger Disease)
Segmental, thrombosing inflammation of small and medium arteries, mainly in young
male smokers.
Clinical: Claudication, ulceration, gangrene of fingers/toes.
Pathology: Highly cellular inflammatory thrombus with sparing of vessel wall.
Vasculitis Associated With Other Noninfectious Disorders
Systemic lupus erythematosus (SLE) vasculitis: Immune complex deposition in
vessels.
Rheumatoid vasculitis: Medium and small vessel involvement.
Henoch-Schönlein purpura: IgA immune complex vasculitis, often pediatric.
Others: Cryoglobulinemic vasculitis, Behçet disease.
Infectious Vasculitis
Due to direct invasion of vessel wall by bacteria, fungi, viruses.
Examples:
o Mycotic aneurysms (infected arterial aneurysms)
o Septic emboli causing vascular thrombosis and infarcts
o Syphilitic aortitis (tertiary syphilis)
Absolutely! Here are ultra-detailed, topper-style notes on Disorders of Blood Vessel
Hyperreactivity from Robbins & Cotran 10th edition, pages 516-517:
Disorders of Blood Vessel Hyperreactivity
Functional abnormalities of vascular tone causing intermittent vasospasm and ischemia
Raynaud Phenomenon
Definition:
A paroxysmal vasospasm of small arteries and arterioles, especially in fingers and toes,
triggered by cold or emotional stress, leading to color changes in the skin.
Types
Type Description Clinical Features
Primary Raynaud Idiopathic, usually young Symmetric attacks; triphasic color
Phenomenon women changes:
White (ischemia)
Blue (deoxygenation)
Red (reperfusion) |
| Secondary Raynaud Phenomenon | Due to an underlying disease | More severe;
asymmetric; may lead to ulcers or gangrene; associated with:
Systemic sclerosis
SLE
Buerger disease
Atherosclerosis |
Pathogenesis
Exaggerated vasoconstriction mediated by α2-adrenergic receptors on vascular
smooth muscle
Structural vascular abnormalities in secondary form (intimal thickening, fibrosis)
Morphology
Usually normal vessel histology in primary form
Secondary: fibrosis, lumen narrowing, thrombosis in small arteries
Clinical Manifestations
Episodic pallor, cyanosis, and rubor of digits
Numbness, pain during attacks
Chronic cases: skin atrophy, ulceration
Myocardial Vessel Vasospasm
Also known as: Prinzmetal angina or variant angina
Definition
Transient spasm of the coronary arteries causing myocardial ischemia without fixed
atherosclerotic obstruction.
Pathogenesis
Hyperreactivity of vascular smooth muscle → intense vasospasm
Endothelial dysfunction may play a role
Clinical Features
Episodes of chest pain at rest
Transient ST-segment elevation on ECG during pain
Symptoms relieved by nitrates or calcium channel blockers
Morphology
No permanent damage in pure vasospasm
Can cause myocardial infarction if prolonged
Importance in Clinical Practice
Differentiates from typical exertional angina caused by fixed obstruction
Treatment focuses on relieving vasospasm
VEINS AND LYMPHATICS
Structure, function, and pathology of veins and lymphatic vessels
Varicose Veins
Definition
Dilated, tortuous superficial veins caused by increased intraluminal pressure and valve
incompetence.
Etiology and Risk Factors
Prolonged standing or increased intra-abdominal pressure (pregnancy, obesity)
Familial predisposition
Age and female sex
Pathogenesis
Valve incompetence → venous reflux
Venous dilation → wall remodeling and further valve damage
Venous hypertension → vein wall thickening and varicosities
Common Sites
Superficial veins of lower extremities (great and small saphenous veins)
Esophageal varices (due to portal hypertension)
Hemorrhoids (anal canal veins)
Morphology
Dilated, elongated, and tortuous veins with thickened walls
Intimal fibrosis
Sometimes thrombosis and inflammation (superficial thrombophlebitis)
Clinical Features
Aching pain, swelling, fatigue in affected limbs
Risk of thrombophlebitis and skin ulceration
Thrombophlebitis and Phlebothrombosis
Definitions
Thrombophlebitis: Inflammation of a vein with associated thrombosis, usually in
superficial veins
Phlebothrombosis: Thrombosis without obvious inflammation, usually in deep veins
Etiology
Stasis of blood flow
Endothelial injury
Hypercoagulability (Virchow’s triad)
Sites
Deep leg veins (deep vein thrombosis, DVT) are clinically important because of risk of
embolism.
Complications
Pulmonary embolism (from DVT)
Post-thrombotic syndrome (chronic venous insufficiency)
Local inflammation and pain
Superior and Inferior Vena Caval Syndromes
Superior Vena Caval (SVC) Syndrome
Obstruction of SVC → venous congestion of head, neck, and upper limbs
Causes: Lung cancer (esp. small cell), lymphoma, thrombosis from catheters
Clinical: Facial swelling, plethora, cyanosis, distended veins
Inferior Vena Caval (IVC) Syndrome
Obstruction of IVC → lower limb edema, venous collaterals on abdomen
Causes: Tumors, thrombosis
Lymphangitis and Lymphedema
Lymphangitis
Acute inflammation of lymphatic vessels
Usually bacterial infection (Group A Streptococcus) spreading from skin wound
Clinical: Red streaks along lymphatic vessels, fever, chills
Lymphedema
Chronic swelling due to lymphatic obstruction or malformation
Causes:
o Primary: Congenital hypoplasia or aplasia of lymphatics
o Secondary: Surgery, radiation, infection (filariasis), tumors
Morphology: Interstitial fluid accumulation with fibrosis and chronic inflammation
Clinical: Non-pitting edema, skin thickening (“elephantiasis” in filariasis)
VASCULAR TUMORS
Neoplasms derived from blood vessels or lymphatics with a spectrum from benign to
malignant
Benign Tumors and Tumor-Like Conditions
1. Hemangiomas
Definition: Benign tumors of blood vessel endothelial cells.
Types:
o Capillary hemangioma: Most common; small, closely packed capillaries; often
in skin, mucous membranes; “strawberry” hemangioma in infants.
o Cavernous hemangioma: Large dilated vascular channels; may involve deeper
structures like liver, brain.
Clinical: Usually present at birth or early childhood; may regress spontaneously.
Morphology: Lobulated mass of vascular channels lined by flattened endothelium,
with minimal atypia.
2. Lymphangiomas
Benign tumors of lymphatic vessels.
Types:
o Simple (capillary) lymphangioma: Small lymphatic channels.
o Cystic hygroma: Large cystic lymphatic spaces; often in neck region.
Associated with: Turner syndrome, Down syndrome.
Morphology: Thin-walled lymphatic channels lined by endothelium, often filled with
proteinaceous fluid.
3. Glomus Tumor
Tumor of modified smooth muscle cells of the glomus body.
Common under fingernails; painful.
Well-circumscribed, reddish-blue nodule.
4. Reactive Vascular Proliferations
Pyogenic granuloma (Lobular capillary hemangioma): Rapidly growing red polypoid
lesion, often after trauma.
Not true neoplasms but reactive proliferation.
Intermediate-Grade (Borderline) Tumors
1. Kaposiform Hemangioendothelioma
Occurs in infancy and childhood.
Locally aggressive but no metastasis.
Histology: Nodules of spindle cells with slit-like vascular spaces.
2. Epithelioid Hemangioendothelioma
Low-grade malignant vascular tumor.
Occurs in soft tissue, liver, lungs.
Histology: Epithelioid endothelial cells in myxohyaline stroma.
Clinical course is variable, often indolent.
Malignant Tumors
1. Angiosarcoma
Malignant endothelial cell tumor.
Occurs in skin, soft tissues, breast (post-radiation), liver (especially with vinyl chloride
exposure).
Highly aggressive with early metastasis.
Morphology:
o Poorly formed vascular channels or solid sheets of malignant endothelial
cells.
o Cells show marked atypia, mitoses, and multilayering.
Clinical: Rapidly enlarging, infiltrative mass, often ulcerated.
2. Kaposi Sarcoma
Vascular tumor associated with HHV-8 infection.
Types:
o Classic: Mediterranean elderly men, indolent.
o Endemic (African): More aggressive.
o AIDS-associated (epidemic): Aggressive, widespread.
o Iatrogenic (transplant-related).
Pathogenesis: HHV-8 latent infection causes proliferation of spindle endothelial cells.
Morphology:
o Early: Patch and plaque stages with thin, jagged vascular channels.
o Nodular stage: Spindle cell proliferation, slit-like vascular spaces, extravasated
RBCs, hemosiderin.
Clinical: Purple macules/nodules on skin; can involve mucosa, lymph nodes, viscera.
PATHOLOGY OF VASCULAR INTERVENTION
Endovascular Stenting
Definition
Placement of a metal mesh (stent) into a blood vessel to restore patency in stenotic or
occluded arteries, commonly used in coronary and peripheral arteries.
Indications
Atherosclerotic arterial stenosis (e.g., coronary artery disease)
Restenosis after angioplasty
Dissection or aneurysms needing reinforcement
Pathologic Changes Post-Stenting
1. Intimal Hyperplasia
Proliferation of smooth muscle cells and extracellular matrix deposition in the intima
as a healing response.
May lead to in-stent restenosis (re-narrowing).
2. Inflammation
Foreign body reaction to stent material.
Chronic inflammatory infiltrate can promote neointimal proliferation.
3. Endothelialization
Healing involves regrowth of endothelium over stent struts to reduce thrombosis
risk.
4. Thrombosis
Early or late stent thrombosis may occur if endothelialization is incomplete or
platelet activation occurs.
Vascular Replacement
Definition
Surgical replacement of diseased vascular segments with grafts—autologous vein grafts or
synthetic prostheses (e.g., Dacron, PTFE).
Pathologic Considerations
1. Graft Patency
Dependent on graft type, location, and host factors.
2. Vein Graft Disease
Intimal hyperplasia and atherosclerosis can cause graft failure over time.
3. Synthetic Graft Complications
Thrombosis, infection, anastomotic aneurysm formation.
4. Healing and Remodeling
Endothelialization and incorporation into host tissue critical for long-term success.
Complications
Infection of prosthetic grafts → sepsis, graft failure.
Anastomotic intimal hyperplasia → stenosis.
Pseudoaneurysm formation at anastomosis.
