Lab 4.4 Histology and Pathology of Blood Vessels

Question 1

Blood vessel walls

Answer 1

All blood vessels except capillaries have walls that contain smooth m., CT, and endothelium. The amount & arrangement of each depends on mechanical (e.g. BP) and metabolic factors.

Question 2

Functions of endothelium

Answer 2

• Semipermeable barrier → metabolite exchange between blood and tissues
• Nonthrombogenic surface on which blood cannot clot
  
  • but also secretion of agents that control clot formation (heparin, tPA, vWF)
• Regulate local vascular tone and blood flow by secreting factors that stimulate smooth m. contraction (endothelin-1, ACE) or relaxation (NO)
• Roles in inflammation and immune responses
• Secretes growth factors for vasculogenesis and angiogenesis

Question 3

Three concentric layers of vessels

Answer 3

• Tunica intima
  
  • endothelium
  • subendothelial loose CT layer
  • Arteries and large veins also contain an internal elastic lamina layer
    
    • consists of elastin
    • has holes that allow better diffusion
• Tunica media
  
  • concentric helically arranged smooth m. cells
  • variable amounts of elastic fibers, elastic lamellae, reticular fibers, & proteoglycans
• Tunica externa (adventitia)
  
  • type I collagen and elastic fibers
  • Continous with and bound to the stromal CT of the organ the vessel runs through

Question 4

Three layers in aa. versus vv.

Answer 4

• Arteries typically have
  
  • ​a thicker tunica media w/ more elastin (to expand with blood when the heart contracts)
  • a narrow lumen
• ​Veins typically have
  
  • ​a larger lumen
  • a thicker tunica externa or adventitia
  • tunica intima of veins is often folded to form valves
• Remember, capillaries only have an endothelium with none of the other layers or components

Question 5

Elastic arteries

Answer 5

• Aorta, pulmonary artery, and their largest branches (aka conducting arteries) [carotids, iliacs]
  
  • “Conduct blood from heart and with elastic recoil help move blood forward under steady pressure”
• Well-developed intima (often w/ folds)
• Thick media
  
  • elastic lamellae alternate w/ smooth m. fibers
    
    • during systole elastin is stretched to distend the wall to limit set by collagen
    • during diastole elastin passively rebounds and the wall recoils to maintain arterial pressure
• Thinner adventitia

Question 6

Muscular arteries

Answer 6

• Coronary, renal, and popliteal aa.
  
  • “Distribute blood to all organs and maintain steady blood pressure and flow with vasodilation and constriction”
• Tunica intima
  
  • thin subendothelial CT layer
  • prominent internal elastic lamina
• Tunica media
  
  • many smooth m. layers with fewer elastic lamellae
  • external elastic lamina present in larger aa.
• Adventitia
  
  • CT tissue
  • thinner than media
  • vasa vasorum may be present

Question 7

Arterioles

Answer 7

• Microvasculature
  
  • “Resist and control blood flow to capillaries; major determinant of systemic blood pressure”
• Tunica intima
  
  • Endothelium
  • No smooth m. or CT
  • absent elastic lamina
• Tunica media
  
  • Only one or two smooth m. layers
• Tunica externa/adventitia
  
  • thin and inconspicuous

Question 8

Capillaries

Answer 8

• “Exchange metabolites by diffusion to and from cells”
• Function in groups called capillary beds
• Tunica intima
  
  • endothelium only
• Tunica media
  
  • pericytes only (perivascular contractile cells)
• No tunica externa/adventitia

Question 9

Venules

Answer 9

• “Drain capillary beds; site of leukocyte exit from vasculature”
• Large diameter of the lumen compared to the overall thickness of the wall.
• Tunica intima
  
  • endothelium
  • no valves
• Tunica media
  
  • Scattered smooth m. cells
• Tunica externa/adventitia
  
  • none

Question 10

Small Veins

Answer 10

• “Collect blood from venules”
• Tunica intima
  
  • endothelium
  • scattered smooth m. fibers
• Tunica media
  
  • thin
  • 2-3 layers of smooth m. cells
• Tunica externa/adventitia
  
  • CT
  • Thicker than media

Question 11

Medium Veins

Answer 11

• “Carry blood to larger veins, with no backflow.”
• Tunica intima
  
  • endothelium
  • CT with valves
• Tunica media
  
  • 3-5 more distinct layers of smooth m. cells
• Tunica externa/adventitia
  
  • Thicker than media
  • longitudinal smooth m. may be present

Question 12

Large veins

Answer 12

• “Return blood to heart”
• Tunica intima
  
  • endothelium
  • CT
  • Smooth m. cells
  • Prominent valves
• Tunica media
  
  • Greater than 5 layers of smooth m. cells
  • Much collagen
• Tunica externa/adventitia
  
  • Thickest layer
  • Bundled longitidunal smooth muscle

Question 13

Pathogenesis of Atherosclerosis: Endothelial injury

Answer 13

• Hypothesis: Atherosclerosis is a chronic inflammatory response of the arterial wall to endothelial injury.
  
  • Endothelial injury: early lesions begin at sites of intact, but dysfunctional endothelium w/
    
    • increased permeability
    • enhanced leukocyte adhesion
    • altered gene expression
  • Triggers of endothelial injury are:
    
    • HTN, hyperlipidemia, hemodynamic disturbances (turbulent blood flow), and toxins from smoking, homocysteine, and infectious agents.

Question 14

Pathogenesis of Atherosclerosis: Inflammation

Answer 14

• Contributes to the initiation, progression, and complications of atherosclerotic lesions
• Dysfunctional endothelial cells express adhesion molecules that promote leukocyte binding (VCAMI binds monocytes and T cells)
• Adhesion of leukocytes to the endothelium allows their migration into the arterial wall intima
  
  • monocytes differentiate into macrophages and engulf lipoproteins (oxidized LDL, cholesterol crystals). They also produce ROS that drive LDL oxidation
  • activated T cells elaborate inflammatory cytokines (IFNgamma), which stimulate macrophages, endothelial cells, and smooth muscle cells.
• The chronic inflammatory state → growth factor release → smooth muscle cell proliferation and matrix synthesis

Question 15

Pathogenesis of Atherosclerosis: Smooth Muscle Cell Proliferation

Answer 15

• Contributes to the progressive growth of atherosclerotic lesions
  
  • Smooth muscle cell proliferation and ECM deposition convert fatty streaks (earliest lesions) into mature atheromas (plaques)
  • These smooth m. cells can originate from the media or circulating precursors, but they have a proliferative & synthetic phenotype different from other medial smooth m. cells.
  • Smooth m. cells synthesize the ECM
  • ECM stabilizes the plaques

Question 16

Histologic Features of Atherosclerotic Plaques

Answer 16

• Superficial fibrous cap composed of smooth muscle cells and dense collagen
• “Shoulder” (where caps meets vessel wall) composed of macrophages, T cells, and smooth muscle cells
• Necrotic core composed of lipids, necrotic debris, lipid-laden macrophages (foam cells), smooth m. cells, fibrin, thrombin, and other plasma proteins

Question 17

Stable vs. Unstable Plaques

Answer 17

• Stable plaques have:
  
  • densely collagenized and thickened fibrous caps
  • negligible necrotic cores
  • minimal inflammation
• Unstable plaques have:
  
  • thin fibrous caps
  • large lipid cores
  • ⇡ inflammation
  • More likely to rupture

Question 18

Aneurysm

Answer 18

• Pathogenesis
  
  • Structure or fxn of CT is compromised by:
    
    • Inadequate/abnormal CT synthesis (TGF)
    • Excessive CT degradation (MMP)
    • Loss of smooth m. cells (or synthesis)
      
      • ischemia of inner or outer media (atherosclerosis or HTN, respectively)
• Gross
  
  • Dilation of vessel due to change within all 3 layers of the wall
  • Thrombus usually fills dilated segment
  • Inflammatory AAAs - dense periaortic fibrosis
  • Mycotic AAAs - suppuration
• Histologic
  
  • Cystic medial degeneration (areas devoid of elastin)
• Radiologic
  
  • Widened aortic arch (on CXR) or other aortic dilation
  • Clots on CT
• Clinical Features - AAA (atherosclerosis)
  
  • Obstruction of a vessel branching off aorta → ischemia of distal organs (kidneys, legs, etc.)
  • Embolism from atheroma or mural thrombus
  • Compression of adjacent structures (e.g. ureter) or erosion of vertebrae
  • Abdominal mass that simulates a tumor
  • Rupture
    
    • risk ⇡ with ⇡ size
• Clinical Features - TAAs (HTN, Marfan Syndrome)
  
  • Respiratory or feeding difficulties due to airway or esophageal compression
  • persistent cough from irritation of recurrent laryngeal nerves
  • pain caused by erosion of bone
  • cardiac disease due to valvular insufficiency or narrowing of coronary ostia
  • Rupture

Question 19

Aortic Dissection

Answer 19

• Pathogenesis
  
  • Major risk factor: HTN
  • Intimal tear → blood under systemic pressure dissects through the media along laminar planes to form a blood filled channel within the aortic wall
• Gross
  
  • Intimal tear in a region w/o atherosclerosis
  • Intramural hematoma
• Histologic
  
  • cystic medial degeneration characterized by smooth muscle layer dropout and necrosis, elastic tissue fragmentation, and accumulations of amorphous proteoglycan-rich ECM.
• Radiologic
  
  • Aortogram - Contrast is also seen in a false lumen produced by the channel in the wall of the aorta (looks like a second large vessel)
  • CT: see intimal flap b/w true lumen and false lumen
• Clinical Features
  
  • Sudden onset of excruciating tearing or stabbing pain usually beginning in the anterior chest
    
    • radiating to the back b/w the scapulae
    • moves downward as dissection progresses
  • MCC of death is rupture in pericardial, pleural, or peritoneal cavity.
  • Type A (proximal w/ or w/o distal)
  • Type B (distal-beyond subclavian a.)