UTHSC Fall 2022 D2 Par 4 Pathology
__________ __________________ is responsible for more morbidity andmortality
than any other category of human disease
Vascular pathology
Weakening of vessel walls leads to
dilation or rupture
stenosis
Narrowing or complete obstruction of vessel lumens
The general architecture and cellular composition of blood vessels (are/are not)
similar throughout the cardiovascular system
are
what do structural specilizations in the cardiovascular system reflect?
distinct functional roles characterize specific kinds of vessels
All vessels except capillaries share a three-layered architecture consisting of?
endothelium lined intima, a surrounding smooth muscle media, and supportive
adventitia, admixed with extracellular matrix.
Intima
endothelial cells, basal lamina, pericytes, subendothelial connective tissue, and the
internal elastic lamina; in the heart
Media
smooth muscle cells and elastic laminas including the external elastic lamina
Adventitia
collagenous connective tissue; in the heart called epicardium
what two factors influence the sequential differentiation of the blood vessels?
- Mechanical factors or hemodynamic forces (esp., blood pressure)
- metabolic factors or tissue requirements
veins are (low/high) pressure
low
arteries are (low/high) pressure
high
The smooth muscle cell and matrix content of arteries, veins, and capillaries vary
according to what?
hemodynamic demands (e.g., pressure, pulsatility) and functional requirements
The specific composition of the vessel wall at any given site within the vascular
tree influences what about pathologic injuries?
the nature and consequences
Vasculogenesis
De novo formation of blood vessels during embryogenesis
Angiogenesis
• The process of new vessel formation in the mature organism.
• Neovascularization
Arteriogenesis
Remodeling of existing arteries in response to chronic changes in pressure or flow.
Endothelial cells Inflammatory Response
,- capture and Rolling (E-selectin)
- Adhesion and Arrest 9ICAM-1, VCAM-1, PECAM-1)
- Diapedesis
Endothelial cells Vessel Remodeling (wall Growth, development and
differentiation)
- vasculogenesis
- angiogenesis
- arteriogenesis
Endothelial cells Barrier/Endocrine/Paracrine/Autocrine Functions
- solute flux & fluid permeability (barrier)
- EC derived NO, PGI2 (autocrine and paracrine)
- EC derivedd CNP and ET-1 (Endocrine)
Endothelial cells Regulation of Blood Homeostasis
- Blood homeostasis
- blood fluidity
- fibrinolysis (tPA, PAI-1)
what is critical for maintaining vessel wall homeostasis and circulatory function?
endothelial cells
what are the functions of endothelial cells?
- Maintenance of permeability barrier
- Elaboration of anticoagulant, antithrombotic, fibrinolytic regulators
- Elaboration of prothrombotic molecules
- Extracellular matrix production
- Modulation of blood flow and vascular reactivity
- Regulation of inflammation and immunity
- Regulation of cell growth
- Oxidation of LDL
what causes endothelial activation in vascular endothelial cells?
- Normotension
-Laminar flow
-Growth factors (e.g., VEGF)
-Cytokines
-Hypoxia, acidosis
what is the result of endothelial activation in vascular endothelial cells?
- Growth factors
- Vasoactive mediators
- Adhesion molecules
- Anti-coagulants
what causes endothelial dysfunction in vascular endothelial cells?
Turbulent flow, Hypertension, Cytokines, Complement, Bacterial products, Lipid
products, Advanced glycation end-products, Hypoxia, acidosis, Viruses, Cigarette
smoke
what is the result of endothelial dysfunction in vascular endothelial cells?
Growth factors, Chemokines, Cytokines, Pro-coagulants proteins, Adhesion molecules,
Vasoactive mediators
what is the predominant cellular element in the vascular media?
,Vascular Smooth Muscle Cells
Vascular Smooth Muscle Cells
- The predominant cellular element in the vascular media
- Important roles in normal vascular repair and atherosclerosis
- Capacity to proliferate when stimulated
- Synthesize extracellular matrix proteins
- Elaboration of growth factors and cytokines
- Responsible for vasoconstriction in response to physiologic or pharmacologic stimuli
what is the process of Intimal Thickening?
Vascular injury → endothelial cell loss/dysfunction → muscle cells growth and matrix
synthesis → intimal thickening (neointima)
Intimal Thickening: A Stereotypic Response to Vascular Injury
- Distinct phenotype of neointimal smooth muscle cells from that of medial smooth
muscle cells: no contractile, but able to divide
- Age-related intimal change
long summary of Response of Vascular Wall Cells to Injury
- All vessels are lined by endothelium; although all endothelial cells share certain
homeostatic properties, endothelial cells in specific vascular beds have special features
that allow for tissue-specific functions (e.g., fenestrated endothelial cells in renal
glomeruli).
- Endothelial cell function is tightly regulated in both the basal and activated states.
Various physiologic and pathophysiologic stimuli induce endothelial activation and
dysfunction that alter the endothelial cell phenotype (e.g., procoagulative vs.
anticoagulative, proinflammatory vs. anti-inflammatory, and nonadhesive vs. adhesive).
- Injury (of almost any type) to the vessel wall results in a stereotyped healing response
involving smooth muscle cell proliferation, extracellular matrix deposition, and intimal
expansion.
- The recruitment and activation of the smooth muscle cell involves signals from cells
(e.g., endothelial cells, platelets, and macrophages), as well as mediators derived from
coagulation and complement cascades.
- Excessive thickening of the intima may result in luminal stenosis and vascular
obstruction
Hypertension
- Blood pressure is a function of cardiac output and peripheral vascular resistance, both
of which are influenced by multiple genetic and environmental factors
- Hypertension can cause vessel and end-organ damage.
- A clinically significant hypertension considered sustained diastolic pressure > 89 mm
Hg and systolic pressure > 139 mm Hg, associated with increased risk of
atherosclerosis
- Accelerated or malignant hypertension, > 200/120
- Resulting in cardiac hypertrophy, heart failure, multi-infarct dementia, aortic dissection,
and renal failure
Hypertension Complications of the eyes
Retinopathy/blindness
Hypertension Complications of the Blood vessel damage
Atherosclerosis
, Hypertension Complications of the Brain
Cerebral hemorrhage
Stroke
Encephalopathy
Dementia
Hypertension Complications of the Heart
Left ventricular hypertrophy
Congestive heart failure
Aortic dissection
Coronary insufficiency
Myocardial infarction
Hypertension Complications of the Kidneys
Hyperplastic arteriosclerosis
Chronic renal disease
HBP as the second-leading cause of kidney failure
Idiopathic/primary/essential hypertension
• Hereditary- familial/genetic factors ; blacks>whites
• Reduced renal sodium excretion
• Vasoconstrictive influences
• Environmental factors; stress, obesity, smoking, physical inactivity, and heavy
consumption of salt
Secondary hypertension
• Chronic renal disease
• Endocrine lesions
• Cardiovascular diseases
• Neurologic causes
what are the environmental factors that lead to hypertension?
inactivity
stress
obesity
tobacco
age
salt
alcohol
what are the gene/environment interactions that lead to hypertension?
Race
Gender
Hypertension in Walls of large and medium arteries
Degenerative changes -> Aortic dissection, Cerebrovascular hemorrhage
Hypertension in Small blood vessel disease
Arteriolosclerosis -> Hyaline arteriolosclerosis, Hyperplastic arteriolosclerosis
Arteriosclerosis
• "Hardening of the arteries" and loss of elasticity.
• Three general patterns: Hypertension-related arteriolosclerosis affecting small arteries
and arterioles (hyaline and hyperplasic variants), Monckeberg medial sclerosis, and
atherosclerosis
__________ __________________ is responsible for more morbidity andmortality
than any other category of human disease
Vascular pathology
Weakening of vessel walls leads to
dilation or rupture
stenosis
Narrowing or complete obstruction of vessel lumens
The general architecture and cellular composition of blood vessels (are/are not)
similar throughout the cardiovascular system
are
what do structural specilizations in the cardiovascular system reflect?
distinct functional roles characterize specific kinds of vessels
All vessels except capillaries share a three-layered architecture consisting of?
endothelium lined intima, a surrounding smooth muscle media, and supportive
adventitia, admixed with extracellular matrix.
Intima
endothelial cells, basal lamina, pericytes, subendothelial connective tissue, and the
internal elastic lamina; in the heart
Media
smooth muscle cells and elastic laminas including the external elastic lamina
Adventitia
collagenous connective tissue; in the heart called epicardium
what two factors influence the sequential differentiation of the blood vessels?
- Mechanical factors or hemodynamic forces (esp., blood pressure)
- metabolic factors or tissue requirements
veins are (low/high) pressure
low
arteries are (low/high) pressure
high
The smooth muscle cell and matrix content of arteries, veins, and capillaries vary
according to what?
hemodynamic demands (e.g., pressure, pulsatility) and functional requirements
The specific composition of the vessel wall at any given site within the vascular
tree influences what about pathologic injuries?
the nature and consequences
Vasculogenesis
De novo formation of blood vessels during embryogenesis
Angiogenesis
• The process of new vessel formation in the mature organism.
• Neovascularization
Arteriogenesis
Remodeling of existing arteries in response to chronic changes in pressure or flow.
Endothelial cells Inflammatory Response
,- capture and Rolling (E-selectin)
- Adhesion and Arrest 9ICAM-1, VCAM-1, PECAM-1)
- Diapedesis
Endothelial cells Vessel Remodeling (wall Growth, development and
differentiation)
- vasculogenesis
- angiogenesis
- arteriogenesis
Endothelial cells Barrier/Endocrine/Paracrine/Autocrine Functions
- solute flux & fluid permeability (barrier)
- EC derived NO, PGI2 (autocrine and paracrine)
- EC derivedd CNP and ET-1 (Endocrine)
Endothelial cells Regulation of Blood Homeostasis
- Blood homeostasis
- blood fluidity
- fibrinolysis (tPA, PAI-1)
what is critical for maintaining vessel wall homeostasis and circulatory function?
endothelial cells
what are the functions of endothelial cells?
- Maintenance of permeability barrier
- Elaboration of anticoagulant, antithrombotic, fibrinolytic regulators
- Elaboration of prothrombotic molecules
- Extracellular matrix production
- Modulation of blood flow and vascular reactivity
- Regulation of inflammation and immunity
- Regulation of cell growth
- Oxidation of LDL
what causes endothelial activation in vascular endothelial cells?
- Normotension
-Laminar flow
-Growth factors (e.g., VEGF)
-Cytokines
-Hypoxia, acidosis
what is the result of endothelial activation in vascular endothelial cells?
- Growth factors
- Vasoactive mediators
- Adhesion molecules
- Anti-coagulants
what causes endothelial dysfunction in vascular endothelial cells?
Turbulent flow, Hypertension, Cytokines, Complement, Bacterial products, Lipid
products, Advanced glycation end-products, Hypoxia, acidosis, Viruses, Cigarette
smoke
what is the result of endothelial dysfunction in vascular endothelial cells?
Growth factors, Chemokines, Cytokines, Pro-coagulants proteins, Adhesion molecules,
Vasoactive mediators
what is the predominant cellular element in the vascular media?
,Vascular Smooth Muscle Cells
Vascular Smooth Muscle Cells
- The predominant cellular element in the vascular media
- Important roles in normal vascular repair and atherosclerosis
- Capacity to proliferate when stimulated
- Synthesize extracellular matrix proteins
- Elaboration of growth factors and cytokines
- Responsible for vasoconstriction in response to physiologic or pharmacologic stimuli
what is the process of Intimal Thickening?
Vascular injury → endothelial cell loss/dysfunction → muscle cells growth and matrix
synthesis → intimal thickening (neointima)
Intimal Thickening: A Stereotypic Response to Vascular Injury
- Distinct phenotype of neointimal smooth muscle cells from that of medial smooth
muscle cells: no contractile, but able to divide
- Age-related intimal change
long summary of Response of Vascular Wall Cells to Injury
- All vessels are lined by endothelium; although all endothelial cells share certain
homeostatic properties, endothelial cells in specific vascular beds have special features
that allow for tissue-specific functions (e.g., fenestrated endothelial cells in renal
glomeruli).
- Endothelial cell function is tightly regulated in both the basal and activated states.
Various physiologic and pathophysiologic stimuli induce endothelial activation and
dysfunction that alter the endothelial cell phenotype (e.g., procoagulative vs.
anticoagulative, proinflammatory vs. anti-inflammatory, and nonadhesive vs. adhesive).
- Injury (of almost any type) to the vessel wall results in a stereotyped healing response
involving smooth muscle cell proliferation, extracellular matrix deposition, and intimal
expansion.
- The recruitment and activation of the smooth muscle cell involves signals from cells
(e.g., endothelial cells, platelets, and macrophages), as well as mediators derived from
coagulation and complement cascades.
- Excessive thickening of the intima may result in luminal stenosis and vascular
obstruction
Hypertension
- Blood pressure is a function of cardiac output and peripheral vascular resistance, both
of which are influenced by multiple genetic and environmental factors
- Hypertension can cause vessel and end-organ damage.
- A clinically significant hypertension considered sustained diastolic pressure > 89 mm
Hg and systolic pressure > 139 mm Hg, associated with increased risk of
atherosclerosis
- Accelerated or malignant hypertension, > 200/120
- Resulting in cardiac hypertrophy, heart failure, multi-infarct dementia, aortic dissection,
and renal failure
Hypertension Complications of the eyes
Retinopathy/blindness
Hypertension Complications of the Blood vessel damage
Atherosclerosis
, Hypertension Complications of the Brain
Cerebral hemorrhage
Stroke
Encephalopathy
Dementia
Hypertension Complications of the Heart
Left ventricular hypertrophy
Congestive heart failure
Aortic dissection
Coronary insufficiency
Myocardial infarction
Hypertension Complications of the Kidneys
Hyperplastic arteriosclerosis
Chronic renal disease
HBP as the second-leading cause of kidney failure
Idiopathic/primary/essential hypertension
• Hereditary- familial/genetic factors ; blacks>whites
• Reduced renal sodium excretion
• Vasoconstrictive influences
• Environmental factors; stress, obesity, smoking, physical inactivity, and heavy
consumption of salt
Secondary hypertension
• Chronic renal disease
• Endocrine lesions
• Cardiovascular diseases
• Neurologic causes
what are the environmental factors that lead to hypertension?
inactivity
stress
obesity
tobacco
age
salt
alcohol
what are the gene/environment interactions that lead to hypertension?
Race
Gender
Hypertension in Walls of large and medium arteries
Degenerative changes -> Aortic dissection, Cerebrovascular hemorrhage
Hypertension in Small blood vessel disease
Arteriolosclerosis -> Hyaline arteriolosclerosis, Hyperplastic arteriolosclerosis
Arteriosclerosis
• "Hardening of the arteries" and loss of elasticity.
• Three general patterns: Hypertension-related arteriolosclerosis affecting small arteries
and arterioles (hyaline and hyperplasic variants), Monckeberg medial sclerosis, and
atherosclerosis
