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Questions and Answers
What is the primary role of the cellular components in the structure of a blood vessel?
Which of the following best describes the concept of vascular diameter modulation?
What are vasodilators primarily responsible for in the context of blood flow regulation?
Which mechanism is primarily implicated in the progression of atherosclerosis?
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Which current pharmacological strategy is typically employed to improve vascular reactivity?
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What is the primary function of Endothelial Derived Hyperpolarizing Factor (EDHF)?
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Which of the following is NOT a component of the diagnostic criteria for Metabolic Syndrome?
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What stage of atherosclerosis involves the accumulation of immune cells?
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According to the WHO diagnostic criteria, which of the following only partially contributes to the Metabolic Syndrome?
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Which factor is assessed for dyslipidaemia in the context of Metabolic Syndrome?
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What is the primary role of systemic arteries?
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How does vessel diameter influence blood pressure?
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What is the order of blood pressure across different vessel types?
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Which layer of an artery is primarily responsible for regulating its diameter?
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What structural feature is unique to veins and venules?
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Which of the following functions is NOT associated with endothelial cells?
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What structural characteristic allows arteries and arterioles to modulate their diameter?
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Why is tight regulation of blood pressure essential?
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What is the primary difference in the structure of veins compared to arteries?
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What is the function of the vaso vasorum?
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What is the primary function of Nitric Oxide in vascular regulation?
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Which factor is primarily responsible for stimulating potassium efflux in smooth muscle cells?
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Which hormone is known to inhibit endothelial Nitric Oxide Synthase (eNOS)?
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What is the major effect of Angiotensin II on vascular tone?
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What is the source of Nitric Oxide production in the vasculature?
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What role does Guanylyl cyclase play in the action of Nitric Oxide?
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In what condition is the production of Endothelial Derived Hyperpolarizing Factor (EDHF) most crucial?
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What effect does Endothelin-1 have on blood vessels?
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How does Nitric Oxide cause relaxation of muscle fibers?
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Which signaling mechanism is primarily engaged by Angiotensin II to exert its effects on smooth muscle?
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What effect does a 5% weight loss have in relation to insulin sensitivity?
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Which statement best describes the role of hyperinflammatory adipocytes in metabolic syndrome?
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What is one of the functions of GLP1 receptor agonists in the treatment of metabolic syndrome?
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Which of the following is NOT a therapeutic approach for treating components of metabolic syndrome?
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What is the effect of increased angiotensin II (ANGII) levels in metabolic syndrome?
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Which statement about endothelin-1 (ET-1) in metabolic syndrome is true?
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How do thiazolidinediones (TZDs) affect cholesterol levels?
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What is the primary action of AMPK activators like metformin in metabolic syndrome management?
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Which of the following processes is impaired due to the decreased production of endothelial-derived hyperpolarizing factors (EDHFs) in metabolic syndrome?
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What effect do dietary antioxidants have in relation to metabolic syndrome?
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Study Notes
The Structure of the Vasculature- Blood Flow
- Blood vessels carry blood around the body towards target organs and tissues
- Systemic Arteries, arterioles, and capillaries carry oxygenated blood and nutrients from the left ventricle towards systemic organs
- Systemic Veins, venules, and capillaries carry deoxygenated blood and waste from the periphery towards the right atria
- The heart pumps blood to and from the lungs and the rest of the body
- Pulmonary blood vessels are responsible for reoxygenation of blood at the lungs and then returned to the heart for circulation
The Structure of the Vasculature- Blood Pressure
- Blood pressure is the pressure exerted by the blood on the vessel wall
- Tight regulation of blood pressure is essential for optimal delivery of oxygen and nutrients to target tissues
- Vessel diameter regulates blood flow and blood pressure:
- Wider diameter = lower pressure exerted on vessel wall, Greater blood flow through wider vessel
- Narrow diameter = higher pressure exerted on vessel wall, Less blood flow through narrow vessel
- Blood pressure differs between vessel types
- Greatest pressure in larger systemic arteries
- Pressure reduces with increasing number of vessels (e.g., fewer arteries than arterioles and capillaries)
- Lowest pressure in larger systemic veins
The Structure of Arteries and Arterioles
- Arteries and arterioles are comprised of three main layers
- Intima
- Endothelial cells + subendothelial space
- Single-cell layer
- First barrier to pathogens in the blood
- Communicates with vascular smooth muscle to regulate diameter
- Media
- Vascular smooth muscles
- Relaxation/constriction dictates vessel diameter
- Adventitia/externa
- Collagen rich (where sympathetic nerves embed)
- External elastic lamina
- Vaso vasorum (small blood vessels supplying the larger vessel in some larger vessels)
- Intima
The Structure of Veins and Venules
- Veins and Venules contain three main layers (tunics)
- Intima
- Endothelial cells
- Media
- Small amount of vascular smooth muscle
- Externa
- Usually thicker than in arteries/arterioles
- Intima
- Veins and venules have valves
- Prevent backflow of blood
- Veins and venules lack elastic layers
The Structure of the Vasculature
- Arteries and arterioles are specially designed to modulate their diameter
- Communication between endothelial cells and vascular smooth muscle cells
- Relaxation/Contraction = Vasodilation/Vasoconstriction
- Endothelial cells possess specific functions depending on tissue and organ:
- Fluid filtration
- Hormone trafficking
- Immune cell recruitment and signaling
- Thrombolysis
- Lipolysis
- Vascular tone
- And more!
Hormonal Regulation of Vascular Tone
- Hormones produced within and out with the vasculature can regulate vasomotor tone
- Four key players:
- Nitric Oxide
- Endothelial Derived Hyperpolarizing Factor (EDHF)
- Endothelin-1 (ET-1)
- Angiotensin II (AngII)
The Vascular Endothelium-Vascular tone
- Endothelial cells are capable of producing Nitric oxide (NO)
- ‘Endothelium-Derived Relaxing Factor’
- Vasoactive hormone gas
- Synthesized in the endothelium
- Diffuses sub-endothelial space
- Causes relaxation of vascular smooth muscle
Hormonal Regulation of Vascular Tone- Nitric Oxide
- Production of Nitric Oxide (NO):
- Stimulation of GPCR by ligand (e.g., ACh)
- Multi-protein phosphorylation cascade
- Intracellular calcium release
- Calmodulin activation
- eNOS activation
- Conversion of L-Arginine to L-Citrulline with release of NO
Hormonal Regulation of Vascular Tone- Nitric Oxide
- Nitric oxide causes smooth muscle relaxation:
- NO activates Guanylyl cyclase
- Converts GTP to cyclic GMP
- Activates Protein Kinase G
- Stimulates relaxation of muscle fibres
Hormonal Regulators of Vascular Tone-Vasodilation
- Endothelial Derived Hyperpolarizing Factor (EDHF)
- Another endothelium-derived vasodilatory hormone
- Believed to be substance or electrical signal
- Hyperpolarizes smooth muscle by stimulated K+ efflux
- Muscle relaxation
- Important when NO production is compromised
- Tends to influence organ blood flow more than systemic
Hormonal Regulators of Vascular Tone-Vasoconstriction
- The Endothelium also regulates vasoconstriction via production of Endothelin-1 (ET-1)
- Acts on smooth muscle to induce vasoconstriction via smooth muscle intracellular calcium release
Hormonal Regulators of Vascular Tone-Vasoconstriction
- ET-1 also:
- Inhibits eNOS
- Reduces NO bioavailability
- Promotes vascular inflammation
Hormonal Regulators of Vascular Tone-Vasoconstriction
- Angiotensin II (AngII)
- Produced in the liver as Angiotensinogen
- Multiple target tissues
- Smooth muscle constriction via G-protein coupled receptor signaling and intracellular Ca2+ release
- Excessive levels promote high blood pressure and vascular inflammation
The Metabolic Syndrome
- The metabolic syndrome is:
- A constellation of interconnected physiological, biochemical, clinical, and metabolic factors that directly increases the risk of cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality
- Diagnostic criteria (WHO 1998):
- Insulin resistance
- Impaired glucose tolerance or impaired fasting glucose levels AND any 2 of the following:
- Obesity
- BMI > 30 kg/m2 (recent revision: Waist circumference >40in (M)/ 35in (F))
- Dyslipidaemia
- Raised TGs (≥150 mg/dL) and/or reduced HDL (140:90mmHg)
- Hypercholesterolaemia (LDL>150mg/dl, HDL6,1mmol/l)
- Insulin resistance
- Obesity (BMI>30kg/m2)
- Smoking
- Inactivity
- Age
- Hereditary
- Insulin resistance
Atherosclerosis
- Atherosclerosis development can be broken down into five key stages:
- Endothelial dysfunction
- Immune cell infiltration
- Fatty streak
- Young plaque
- Mature plaque
Metabolic Syndrome and CVD: Summary
- Pathophysiology of CVD and MetS are multifaceted
- Wide array of therapies to treat numerous contributing factors:
- Insulin Resistance
- Inflammation
- Oxidative stress
- Cholesterol
- Hyperglycaemia
- Hypertension
- Or target the vasculature
Common Therapies for MetS and Atherosclerosis
-
Thiazolidinediones (TZDs/Glitazones), e.g., pioglitazone
- PPAR𝛾 agonsists
- Insulin sensitizers
- Increases HDL cholesterol
- Anti-inflammatory effect in vessel wall
-
AMPK activators (Biguanides), e.g., metformin
- Complex I inhibition
- Regulates glucose metabolism
- Increases FA oxidation
- Reduces inflammation
-
GLP1-RAs (e.g., Exenatide and Liraglutide)
- Stimulates Insulin secretion and suppresses appetite
- Reduced blood glucose
- Reduces blood pressure (due to diuretic effect), thereby reducing AngII production and vascular inflammation
-
SGLT inhibitors (dapagliflozin, empagliflozin)
- Inhibits/slows glucose (re)absorption
- Reduces blood glucose and volume
- Reduces blood pressure
- Improves endothelial and VSMC function
Common Therapies for MetS and Atherosclerosis
- HMG-CoA Reductase Inhibitors (Statins), e.g., simvastatin
- Cholesterol biosynthesis inhibitors
- Increases HDL cholesterol levels
- Decreases LDL cholesterol levels and oxidation
- Dietary antioxidants, e.g.
- Vitamin C, E
- Polyphenols
- Beta-carotene
- Flavonoids
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Description
Test your knowledge on the structure and function of blood vessels in the human body. This quiz covers systemic and pulmonary circulation, blood flow, and the regulation of blood pressure. Assess your understanding of how the vasculature plays a crucial role in oxygen and nutrient delivery.