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Common Non-communicable Diseases - ME2366 > L6 - Endothelium > Flashcards

L6 - Endothelium Flashcards

1
Q

What is the purpose of vasodilation in acute inflammation?

A

Vasodilation increases blood flow to the affected area, causing redness and warmth and facilitating immune cell delivery.

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2
Q

Which inflammatory mediators are responsible for vasodilation?

A

Histamine
Serotonin
Cytokines (e.g., IL-1, TNF-α)
Eicosanoids (e.g., prostaglandins)

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3
Q

How does histamine induce vasodilation?

A

Histamine acts on H1 receptors on vascular smooth muscle, causing relaxation and increased vessel diameter.

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4
Q

What is the role of serotonin in vasodilation?

A

Serotonin, released from platelets during activation, induces vasodilation and enhances vascular permeability.

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5
Q

Which eicosanoids contribute to vasodilation, and how?

A

Prostaglandins (e.g., PGE2, PGI2) relax vascular smooth muscle, leading to increased blood flow and vasodilation.

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6
Q

How do cytokines like IL-1 and TNF-α influence vasodilation?

A

They indirectly promote vasodilation by stimulating endothelial cells to release nitric oxide (NO), a potent vasodilator.

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7
Q

What role do arterioles play in vasodilation during acute inflammation?

A

rterioles are the primary site of vasodilation, increasing blood flow to capillaries in the affected tissue.

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8
Q

What visible clinical signs are associated with vasodilation?

A

Redness (erythema) and warmth due to increased blood flow.

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9
Q

What is the effect of vasodilation on immune cell recruitment?

A

Vasodilation enhances immune cell delivery by increasing blood flow to the site of injury or infection.

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10
Q

What is endothelial retraction in acute inflammation?

A

It is the temporary separation of endothelial cells, increasing vascular permeability to allow leukocytes, proteins, and fluid to move into the injured tissue.

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11
Q

Which inflammatory mediators trigger endothelial retraction?

A

Histamine
Bradykinin
Nitric Oxide (NO)
Complement components

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12
Q

How long does normal endothelial cell retraction last?

A

15–30 minutes.

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13
Q

What is the difference between endothelial retraction and endothelial injury?

A

Endothelial Retraction: Caused by chemical mediators, temporary and reversible.
Endothelial Injury: Caused by severe physical damage (e.g., burns), rapid onset, and long-lasting (hours to days).

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14
Q

How does endothelial retraction contribute to inflammation?

A

t increases vascular permeability, allowing immune cells (leukocytes), proteins (e.g., fibrinogen), and fluid to exit blood vessels and reach the site of injury.

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15
Q

What is the role of leukocytes in endothelial retraction?

A

Leukocytes migrate through the widened endothelial gaps to reach the inflamed tissue and combat infection or repair damage.

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16
Q

What role do proteins play in endothelial retraction?

A

Plasma proteins, such as fibrinogen and complement components, move into the tissue to help with clot formation and immune defence.

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17
Q

How does severe injury (e.g., thermal burns) affect the endothelium?

A

Severe injury causes direct endothelial damage, leading to sustained permeability and prolonged leakage of fluid and proteins into tissues.

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18
Q

What clinical signs result from endothelial retraction?

A

Swelling (oedema) and pain due to fluid accumulation and protein leakage into the interstitial space.

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19
Q

What is leukocyte adhesion in acute inflammation?

A

It is the process by which leukocytes attach to and migrate across the endothelium to reach inflamed tissues.

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20
Q

What are the four key steps of leukocyte adhesion?

A

Rolling
Integrin activation
Firm adhesion/spreading
Migration

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21
Q

What mediators are involved in leukocyte rolling?

A

P-selectin and E-selectin on endothelial cells bind to Sialyl-Lewis X-modified glycoproteins on leukocytes.

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22
Q

What activates integrins during leukocyte adhesion?

A

Cytokines and chemokines secreted by macrophages and endothelial cells activate integrins on leukocytes, increasing their affinity for endothelial ligands.

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23
Q

What is the difference between low-affinity and high-affinity integrins?

A

Low-affinity integrins: Allow leukocytes to roll along the endothelium.
High-affinity integrins: Enable firm adhesion and spreading on the endothelium.

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24
Q

What endothelial adhesion molecules bind to integrins on leukocytes?
A:

A

ICAM-1 (Intercellular Adhesion Molecule-1)
PECAM-1 (CD31)

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25
Q

What role does PECAM-1 (CD31) play in leukocyte migration?

A

PECAM-1 facilitates leukocyte transmigration (diapedesis) through the endothelial junctions into the tissue.

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26
Q

What triggers the expression of P-selectin, E-selectin, and ICAM-1 on endothelial cells?

A

Inflammatory signals like cytokines and microbes stimulate their upregulation on endothelial surfaces.

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27
Q

How do macrophages contribute to leukocyte adhesion?

A

Macrophages release cytokines and chemokines that activate endothelial cells and leukocytes, promoting adhesion and migration.

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28
Q

What happens after leukocytes migrate into the tissue?

A

: They phagocytose microbes, secrete inflammatory mediators, and assist in tissue repair.

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29
Q

What are vasoactive amines?

A

Vasoactive amines, like histamine, are molecules released during inflammation that alter vascular tone and permeability.

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30
Q

Where is histamine stored in the body?

A

Histamine is stored in mast cells, basophils, and platelets.

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31
Q

What triggers histamine release from mast cells?

A

Physical injury (e.g., trauma or heat)
IgE binding during allergic reactions
Complement proteins (C3a and C5a - anaphylatoxins)
Cytokines and neuropeptides

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32
Q

What are the primary effects of histamine during inflammation?

A

Vasodilation of arterioles
Increased vascular permeability in venules
Smooth muscle contraction in some tissues (e.g., bronchi)

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33
Q

What histamine receptor mediates its pro-inflammatory effects?

A

The H1 receptor mediates vasodilation, increased permeability, and smooth muscle contraction.

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34
Q

What is the role of histamine in vascular changes?

A

Causes endothelial retraction, leading to leakage of plasma and proteins.
Promotes redness (erythema) and swelling (oedema).

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35
Q

How long does histamine activity last in acute inflammation?

A

Histamine acts rapidly but is short-lived, as it is quickly degraded by enzymes like histaminase.

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36
Q

What is the systemic effect of histamine in severe allergic reactions?

A

Histamine release can cause anaphylaxis, characterised by widespread vasodilation, bronchoconstriction, and hypotension.

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37
Q

What pharmacological agents block histamine effects?

A

H1-receptor antagonists (e.g., loratadine) block inflammation and allergic symptoms.
H2-receptor antagonists (e.g., ranitidine) reduce gastric acid secretion.

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38
Q

Why is histamine considered a key mediator of acute inflammation?

A

Its rapid release and potent effects on blood vessels initiate early vascular changes essential for inflammation.

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39
Q

What is serotonin (5-HT), and where is it found?

A

Serotonin is a vasoactive amine primarily stored in enterochromaffin cells of the gut, platelets, and the CNS.

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40
Q

How is serotonin taken up into platelets?

A

: Serotonin is taken up by platelets via the serotonin transporter (SERT).

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41
Q

What is the role of serotonin in the gastrointestinal (GI) tract?

A

Regulates gut motility by acting on smooth muscle.
Released into the gut lumen by enterochromaffin cells in response to stimuli.

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42
Q

What is serotonin’s function during inflammation?

A

Causes vasoconstriction or vasodilation depending on the vascular bed.
Enhances vascular permeability.
Promotes platelet aggregation during haemostasis.

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43
Q

How does serotonin contribute to platelet aggregation?

A

Serotonin is released from activated platelets, amplifying the aggregation response and contributing to clot formation.

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44
Q

What receptors mediate serotonin’s effects in inflammation?

A

Serotonin acts via 5-HT receptors, particularly 5-HT2 receptors, to modulate vascular tone and permeability.

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45
Q

What is serotonin’s role in capillary dynamics?

A

It influences capillary tone by inducing either constriction or relaxation, depending on the receptor subtype and local conditions.

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46
Q

How does serotonin act as a mediator of acute inflammation?

A

Released rapidly by platelets at sites of injury.
Initiates vascular changes and platelet aggregation.
Plays a secondary role compared to histamine.

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47
Q

Why is serotonin less studied as an inflammatory mediator compared to histamine?

A

Its effects are more localised and variable, and its primary role is in the GI tract and CNS rather than systemic inflammation.

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48
Q

What drugs affect serotonin pathways?

A

Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine) block SERT in the CNS.
Antiplatelet agents (e.g., aspirin) reduce serotonin release from platelets.

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49
Q

What are eicosanoids, and what are they derived from?

A

: Eicosanoids are lipid mediators derived from arachidonic acid, a polyunsaturated fatty acid found in cell membranes.

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50
Q

How is arachidonic acid released from cell membranes?

A

It is released by the enzyme phospholipase A2 (PLA2) in response to inflammatory stimuli.

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51
Q

What are the two main pathways for eicosanoid synthesis?
A:

A

Cyclooxygenase (COX) pathway
5-Lipoxygenase (5-LOX) pathway

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52
Q

What does the COX pathway produce?

A

Produces prostaglandins, prostacyclins, and thromboxanes.

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53
Q

What are the functions of prostaglandins (PGs)?

A

PGE2: Vasodilation, fever, and pain sensitisation.
PGI2 (prostacyclin): Vasodilation, inhibition of platelet aggregation.
PGF2α: Smooth muscle contraction.

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54
Q

What is the role of thromboxane (TXA2)?

A

Promotes platelet aggregation and vasoconstriction.

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55
Q

What does the 5-LOX pathway produce?

A

Produces leukotrienes (LTs) and lipoxins.

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56
Q

What are the functions of leukotrienes?

A

LTB4: Chemotaxis and activation of neutrophils.
LTC4, LTD4, LTE4: Bronchoconstriction, increased vascular permeability (important in asthma and allergies).

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57
Q

What are the functions of lipoxins?

A

Anti-inflammatory mediators that promote the resolution of inflammation.

58
Q

How do NSAIDs affect eicosanoid synthesis?

A

NSAIDs inhibit the COX enzymes (COX-1 and COX-2), reducing the production of prostaglandins and thromboxanes.

59
Q

What are the differences between COX-1 and COX-2?

A

COX-1: Constitutive, involved in maintaining homeostasis (e.g., gastric mucosal protection, renal blood flow).
COX-2: Inducible, upregulated during inflammation.

60
Q

What are the side effects of COX inhibition by NSAIDs?

A

COX-1 inhibition: Gastric ulcers, impaired platelet function.
COX-2 inhibition: Increased cardiovascular risk.

61
Q

What drugs target the 5-LOX pathway?

A

Zileuton: A 5-LOX inhibitor used in asthma treatment.
Leukotriene receptor antagonists (e.g., montelukast): Block the effects of LTC4, LTD4, LTE4.

62
Q

Why are eicosanoids important in inflammation?

A

They mediate key processes such as vasodilation, vascular permeability, leukocyte recruitment, pain, and fever.

63
Q

What are leukotrienes, and how are they synthesised?

A

Leukotrienes are eicosanoids produced via the 5-lipoxygenase (5-LOX) pathway from arachidonic acid.

64
Q

Which cells produce leukotrienes?

A

LTB4: Produced mainly by neutrophils.
Cysteinyl leukotrienes (LTC4, LTD4, LTE4, LTF4): Produced by mast cells, macrophages, eosinophils, and basophils.

65
Q

What is the primary function of LTB4?

A

Acts as a potent chemoattractant, recruiting neutrophils to sites of inflammation.
Enhances neutrophil adhesion and activation.

66
Q

What are the roles of cysteinyl leukotrienes (LTC4, LTD4, LTE4)?

A

Cause bronchoconstriction.
Increase vascular permeability.
Contribute to mucus secretion.
Involved in asthma and allergic responses.

67
Q

What are the receptors for leukotrienes, and what do they mediate?
A:

A

BLT1 and BLT2: Receptors for LTB4, mediate neutrophil recruitment.
CysLT1 and CysLT2: Receptors for cysteinyl leukotrienes, mediate bronchoconstriction and inflammation.

68
Q

What are the therapeutic targets for leukotrienes?

A

5-LOX inhibitors (e.g., zileuton): Block leukotriene synthesis.
CysLT1 receptor antagonists (e.g., montelukast): Used in asthma to prevent bronchoconstriction and inflammation.

69
Q

What clinical conditions are leukotrienes most implicated in?

A

Asthma.
Allergic rhinitis.
Chronic obstructive pulmonary disease (COPD).

70
Q

What is LTB4, and what are its primary functions?

A

LTB4 is a leukotriene produced by neutrophils that acts as a potent chemoattractant, recruiting leukocytes to inflammation sites and enhancing their adhesion and activation.

71
Q

What are the two receptors for LTB4?

A

The two receptors for LTB4 are BLT1 and BLT2.

72
Q

What are the characteristics and functions of BLT1?

A

Expressed: Predominantly on leukocytes.
Function: Facilitates chemotaxis and immune cell recruitment.
Affinity: High-affinity receptor for LTB4.
Signalling: Coupled to Gi/o proteins, leading to ↓cAMP and enhanced immune responses.

73
Q

What are the characteristics and functions of BLT2?

A

Expressed: Broadly in several tissues, including the gastrointestinal (GI) tract.
Function: Supports GI barrier integrity and function.
Affinity: Low-affinity receptor for LTB4.
Signalling: Coupled to Gi/q proteins, leading to ↓cAMP and ↑PLC activity.

74
Q

How does LTB4 affect intracellular signalling through BLT receptors?
A:

A

BLT1: Activation decreases cAMP levels (↓cAMP) via Gi/o proteins, promoting immune cell activity.
BLT2: Activation involves decreased cAMP (↓cAMP) and increased phospholipase C (↑PLC) activity, contributing to tissue-specific responses.

75
Q

What roles do BLT1 and BLT2 play in health and disease?

A

BLT1: Critical in immune responses and inflammation, such as neutrophil recruitment in infections and autoimmune conditions.
BLT2: Plays a role in maintaining the GI barrier, potentially protecting against intestinal damage.

76
Q

Why is LTB4 a target for anti-inflammatory therapies?

A

LTB4 contributes to chronic inflammation and immune cell recruitment, making its receptors (BLT1/BLT2) potential targets for conditions like asthma, rheumatoid arthritis, and inflammatory bowel disease (IBD).

77
Q

What are the two cysteinyl leukotriene receptors, and what do they bind?

A

The two receptors are CysLT1 and CysLT2, which bind cysteinyl leukotrienes (LTC4, LTD4, LTE4).

78
Q

Where is CysLT1 expressed, and what are its primary functions?

A

Expressed on: Leukocytes and airway smooth muscle.
Functions:
Bronchoconstriction: Contributes to airway narrowing in asthma.
Leukocyte activation: Promotes immune cell recruitment and activity.

79
Q

Where is CysLT2 expressed, and what are its primary functions?

A

Expressed on: Leukocytes and vascular smooth muscle.
Functions:
Leukocyte activation: Enhances inflammatory responses.
Vasoconstriction: Constricts blood vessels, affecting blood flow and pressure.

80
Q

What role do cysteinyl leukotrienes (via CysLT1 and CysLT2) play in respiratory conditions?

A

They contribute to asthma and allergic rhinitis by promoting bronchoconstriction, mucus secretion, and immune cell recruitment to the airways.

81
Q

Why are CysLT1 receptors a therapeutic target in asthma?

A

Blocking CysLT1 receptors with leukotriene receptor antagonists (e.g., montelukast) reduces bronchoconstriction, airway inflammation, and symptoms of asthma and allergies.

82
Q

What is the difference in vascular effects between CysLT1 and CysLT2?

A

CysLT1: Primarily involved in bronchoconstriction.
CysLT2: Contributes to vasoconstriction, affecting blood vessel dynamics.

83
Q

What is the role of cyclooxygenase (COX) enzymes in prostaglandin synthesis?

A

Cyclooxygenase (COX) enzymes convert arachidonic acid into PGG2 and then into PGH2, which are precursors for various prostaglandins, thromboxanes, and prostacyclins.

84
Q

What are the key prostanoids derived from PGH2, and their synthesising enzymes?
A:

A

Prostacyclin (PGI2): Synthesised by prostacyclin synthase.
Thromboxane A2 (TXA2): Synthesised by thromboxane synthase.
Prostaglandins (PGD2, PGE2): Synthesised by specific prostaglandin synthases.

85
Q

hat are the primary effects of prostacyclin (PGI2)?

A

Vasodilation: Expands blood vessels.
↓ Platelet aggregation: Prevents blood clot formation.

86
Q

What are the primary effects of thromboxane A2 (TXA2)?

A

Vasoconstriction: Narrows blood vessels.
↑ Platelet aggregation: Promotes blood clot formation.

87
Q

What are the effects of PGD2 and PGE2 in inflammation?

A

PGD2:
Vasodilation: Expands blood vessels.
Increased vascular permeability: Facilitates immune cell migration.
PGE2:
Vasodilation: Enhances blood flow to inflamed areas.
Vascular permeability: Contributes to redness and swelling.

88
Q

How do COX inhibitors (e.g., NSAIDs) affect this pathway?

A

They block COX enzymes, reducing the production of prostanoids (e.g., PGI2, TXA2), thereby decreasing inflammation, pain, and fever.

89
Q

What is the functional difference between PGI2 and TXA2 in vascular homeostasis?

A

PGI2: Promotes vasodilation and inhibits platelet aggregation (anti-thrombotic).
TXA2: Promotes vasoconstriction and enhances platelet aggregation (pro-thrombotic).

90
Q

What are the primary functions of COX-1 (constitutive COX)?

A

Gastric protection: Helps maintain the stomach lining.
Vascular homeostasis: Regulates blood flow and vessel function.
Platelet aggregation: Promotes blood clot formation.
Renal function: Supports kidney function, including maintaining blood flow.
Reproductive functions: Involved in processes like uterine contractions.

91
Q

What is the primary role of COX-2 (inducible COX)?

A

Site of Inflammation: Primarily expressed at sites of inflammation, where it is responsible for the production of prostaglandins that promote pain, fever, and swelling.

92
Q

Where are COX-1 enzymes constitutively expressed?

A

Brain: Involved in normal brain function.
Kidneys: Important for renal blood flow and function.
Bone: Plays a role in bone health and remodeling.

93
Q

How do COX inhibitors (NSAIDs) affect COX-1 and COX-2?

A

COX-1 inhibitors reduce protective functions like gastric protection and renal blood flow.
COX-2 inhibitors primarily target inflammation but may carry a lower risk of gastric irritation.

94
Q

What is the role of Phospholipase A2 (PLA2) in the production of arachidonic acid?

A

PLA2 is the most common enzyme that generates arachidonic acid.
It cleaves the phospholipid at the sn2 position, releasing arachidonic acid from membrane phospholipids.

95
Q

How does the alternate pathway generate arachidonic acid?

A

The alternate pathway involves Phospholipase C (PLC), which generates diacylglycerol (DAG).
DAG is then cleaved by DAG-lipase, releasing arachidonic acid by cutting at the sn2 position.

96
Q

What is the significance of arachidonic acid in eicosanoid biosynthesis?

A

Arachidonic acid is a precursor to important eicosanoids like prostaglandins, thromboxanes, and leukotrienes, which are key mediators of inflammation and immune responses.

97
Q

What is the function of Tumour Necrosis Factor (TNF)?

A

TNF is a pro-inflammatory cytokine that plays a key role in systemic inflammation.
It is involved in fever induction, apoptosis, and the activation of immune cells such as macrophages and neutrophils.

98
Q

What are the major roles of Interleukin-1 (IL-1)?

A

IL-1 is a pro-inflammatory cytokine that helps in the regulation of immune and inflammatory responses.
It induces fever, endothelial activation, and stimulates the production of other cytokines, contributing to the acute phase response during inflammation.

99
Q

What are chemokines and how do they function?

A

Chemokines are a subgroup of cytokines that function as chemoattractants, guiding the movement of leukocytes to sites of infection or injury.
They bind to specific receptors on immune cells to mediate chemotaxis.

100
Q

What are the key functions of Tumour Necrosis Factor (TNF)?

A

TNF is a pro-inflammatory cytokine involved in the systemic inflammatory response.
It stimulates the activation of immune cells (macrophages, neutrophils).
Plays a role in fever induction and apoptosis of infected or damaged cells.
Involved in vascular permeability and endothelial activation.
Contributes to cachexia (wasting syndrome) in chronic inflammation.

101
Q

What are the two types of Tumour Necrosis Factor (TNF) receptors?

A

TNFR1: Predominantly involved in inflammation, cell survival, and apoptosis.
TNFR2: Primarily involved in immune regulation and cell growth.

102
Q

What are the primary functions of Interleukin-1 (IL-1)?

A

IL-1 is a pro-inflammatory cytokine that contributes to the acute-phase response in inflammation.
Induces fever by acting on the hypothalamus.
Promotes the activation of endothelial cells and leukocyte adhesion to blood vessels.
Stimulates the production of other pro-inflammatory cytokines, such as IL-6 and TNF.
Plays a significant role in tissue repair and immune cell activation.

103
Q

What are the two types of Interleukin-1 (IL-1)?

A

IL-1α: Primarily expressed in tissue cells, particularly in response to cell damage or stress.
IL-1β: Secreted by macrophages and monocytes during inflammation.

104
Q

What are the main receptors for IL-1?

A

IL-1R1: The primary receptor that mediates the majority of IL-1’s pro-inflammatory effects.
IL-1R2: Acts as a decoy receptor that inhibits IL-1 activity.

105
Q

What are the key features of acute inflammation?

A

Infiltration of immune cells such as neutrophils.
Tissue destruction due to the inflammatory response.
Healing attempts: The body tries to repair the damaged tissue.
Cuboidal epithelium may appear in damaged tissues as part of tissue repair.
Lung tissue may show signs of oedema, congestion, and infiltration of immune cells.

106
Q

What are the key features of chronic inflammation?

A

Infiltration of immune cells: Chronic inflammation involves predominantly macrophages, lymphocytes, and plasma cells.
Fibrosis: Excessive collagen deposition leading to scar tissue formation.
Tissue destruction: Ongoing damage to tissues from prolonged inflammation.
Healing attempts: Ongoing attempts to repair the tissue, but this process may be impaired or incomplete, leading to chronic scarring and functional loss.

107
Q

How does chronic inflammation affect lung tissue?

A

Infiltration of immune cells such as macrophages and lymphocytes.
Fibrosis: Thickening and scarring of the lung tissue, which can impair lung function.
Tissue destruction: Continuous damage to alveolar structures.
Chronic lung diseases like chronic obstructive pulmonary disease (COPD) or pulmonary fibrosis may result from prolonged inflammation.

108
Q

What is the primary role of macrophages in inflammation?

A

Phagocytosis: Macrophages engulf and digest pathogens, dead cells, and debris.
Cytokine production: They release inflammatory cytokines like TNF-α, IL-1, and IL-6, which modulate immune responses.
Tissue repair: Macrophages help in tissue repair by secreting growth factors and collagen.
Antigen presentation: They present antigens to T-cells, initiating adaptive immunity.

109
Q

How do macrophages contribute to acute inflammation?

A

Early response: Macrophages are among the first immune cells to respond to infection or injury.
Cytokine release: They release pro-inflammatory cytokines, such as TNF-α and IL-1, which promote vasodilation, recruit other immune cells, and amplify the inflammatory response.
Phagocytosis: Macrophages clear pathogens, dead cells, and debris from the inflamed tissue.

110
Q

How do macrophages contribute to chronic inflammation?

A

Persistent activation: In chronic inflammation, macrophages are continuously activated and release pro-inflammatory cytokines, contributing to the cycle of ongoing inflammation.
Tissue damage: Prolonged macrophage activity leads to tissue damage and fibrosis through the release of matrix metalloproteinases (MMPs) and other damaging factors.
Macrophage polarization: In chronic inflammation, macrophages can become alternatively activated (M2), promoting tissue repair and fibrosis, but this can also lead to scar formation and impaired tissue function.

111
Q

What is the role of macrophages in tissue repair?

A

M2 polarization: Macrophages can polarize into an anti-inflammatory phenotype (M2) that promotes tissue healing and fibrosis.
Collagen secretion: They secrete growth factors (e.g., VEGF, TGF-β) and collagen to facilitate wound healing and tissue repair.
Resolution of inflammation: Macrophages also help to resolve inflammation by clearing apoptotic cells and initiating repair processes, including reepithelialization and revascularization.

112
Q

How do macrophages influence immune response during infection?

A

Innate immunity: As part of the innate immune system, macrophages act as first responders to pathogens.
Adaptive immunity activation: They present antigens to T-cells, bridging the innate and adaptive immune responses.
Cytokine production: Through cytokine release, they modulate the immune response, promoting either inflammation or resolution based on the context of the infection.

113
Q

What is the primary role of the endothelium in the vascular system?

A

The endothelium regulates vascular tone, blood flow, barrier function, inflammation, and angiogenesis.

114
Q

How does endothelial heterogeneity relate to organ-specific function?

A

Endothelial cells differ in structure and function depending on the organ or tissue, supporting specific physiological roles like nutrient exchange, filtration, or immune response.

115
Q

What is the blood-brain barrier (BBB)?

A

The BBB is a specialised endothelial barrier in the brain that prevents the entry of harmful substances while allowing selective transport of nutrients and essential molecules.

Q

116
Q

What causes dysfunction in the blood-brain barrier?

A

Infections, inflammation, oxidative stress, and neurodegenerative diseases can disrupt BBB integrity, leading to leakage and neuronal damage.

117
Q

What is the role of the endothelium in the lymphatic system?

A

The lymphatic endothelium facilitates the transport of lymph, immune cells, and interstitial fluid while maintaining tissue fluid homeostasis.

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118
Q

What are the consequences of endothelial dysfunction?

A

Endothelial dysfunction can lead to increased vascular permeability, thrombosis, inflammation, and diseases like atherosclerosis, hypertension, and stroke.

Q

119
Q

How is endothelial heterogeneity determined?

A

: It is established during development through arterial/venous specification and microvascular differentiation, tailored to organ-specific needs.

120
Q

What are the three layers (tunics) of blood vessels?

A

Tunica Intima: The innermost layer, consisting of endothelial cells and a thin layer of connective tissue.
Tunica Media: The middle layer, composed of smooth muscle cells and elastic fibres, responsible for vasoconstriction and vasodilation.
Tunica Adventitia: The outermost layer, made up of connective tissue, providing structural support and anchoring vessels to surrounding tissues.

121
Q

What is the role of the endothelium in blood vessels?

A

The endothelium lines the inner surface of blood vessels, regulating vascular tone, blood flow, permeability, and preventing thrombosis by producing anti-coagulant and anti-inflammatory factors.

122
Q

What is the difference between static and pulsatile blood flow?

A

Static Flow: Slow or stagnant blood flow, often occurring in smaller vessels or during vascular obstruction.
Pulsatile Flow: Rhythmic, dynamic flow generated by the heart’s pumping, commonly seen in arteries.

123
Q

How does static and pulsatile flow affect the endothelium?

A

Pulsatile flow promotes healthy endothelial function by generating shear stress, which stimulates protective signalling pathways.
Static flow can lead to endothelial dysfunction, inflammation, and increased risk of atherosclerosis.

124
Q

What is atherosclerosis, and how does it involve the endothelium?

A

Atherosclerosis is a chronic inflammatory condition characterised by the accumulation of lipids, immune cells, and fibrous tissue in the arterial walls, often initiated by endothelial dysfunction.

125
Q

What are the key factors that cause endothelial dysfunction in atherosclerosis?

A

Oxidised LDL cholesterol
Inflammatory cytokines
Mechanical injury (e.g., hypertension)
Reactive oxygen species (ROS)
Shear stress imbalance (low or disturbed flow)

126
Q

How does atherosclerosis progress in relation to endothelial dysfunction?

A

Endothelial damage leads to increased permeability and adhesion of monocytes and platelets.
Monocytes differentiate into macrophages, which engulf lipids to form foam cells.
Smooth muscle cells migrate and proliferate, forming a fibrous cap over the lipid core.
Plaque rupture can result in thrombosis and vascular occlusion.

127
Q

What are the key roles of the endothelium in vascular regulation?

A

Regulates vascular tone through the release of vasodilators (e.g., nitric oxide, prostacyclin) and vasoconstrictors (e.g., endothelin-1).
Maintains vascular permeability to control fluid and solute exchange.
Modulates platelet aggregation by producing anti-thrombotic and pro-thrombotic factors.
Influences leucocyte function, enabling recruitment during inflammation.
Affects vascular smooth muscle contraction/relaxation and growth.

128
Q

What is the role of the endothelium in regulating vascular permeability?

A

The endothelium acts as a selective barrier, controlling the passage of molecules, ions, and fluids between the bloodstream and tissues. Dysregulated permeability leads to oedema and inflammation.

129
Q

How does the endothelium regulate platelet aggregation?

A

Produces anti-aggregatory substances like nitric oxide (NO) and prostacyclin (PGI2) to prevent clot formation.
Releases pro-thrombotic factors (e.g., von Willebrand factor) when injury occurs to promote clotting.

130
Q

What are the local mechanisms of vascular tone regulation?

A

Myogenic: Vessel wall responds to changes in blood pressure; e.g., vasoconstriction in response to stretch.
Humoral: Release of chemical mediators (e.g., nitric oxide, prostaglandins).
Metabolic: Accumulation of metabolites (e.g., CO2, lactic acid) causes vasodilation to meet tissue oxygen demands.

131
Q

What systemic mechanisms regulate vascular tone?

A

Neural: Sympathetic nervous system influences vasoconstriction (via noradrenaline).
Humoral: Circulating hormones and substances, such as angiotensin II (vasoconstrictor) and atrial natriuretic peptide (vasodilator).

132
Q

How does vascular smooth muscle contribute to tone and growth?

A

Contraction/Relaxation: Smooth muscle contracts in response to vasoconstrictors (e.g., endothelin-1) and relaxes with vasodilators (e.g., NO).
Growth: Stimulated by chronic injury or inflammation, leading to vascular remodelling in conditions like atherosclerosis.

133
Q

How do systemic and local factors influence vascular tone?

A

Systemic Factors: Neural input (e.g., sympathetic activation) and circulating hormones like adrenaline and angiotensin II.
Local Factors: Endothelial-derived mediators (e.g., NO, prostacyclin), myogenic responses, and metabolic by-products (e.g., CO2, lactate).

134
Q

What is the importance of humoral regulation in vascular tone?

A

Humoral factors like hormones (e.g., angiotensin II, vasopressin) and dissolved gases (e.g., oxygen, carbon dioxide) play a critical role in maintaining blood pressure and flow, adapting to physiological demands or stress.

135
Q

Which agents are involved in relaxing vascular tone?

A

Nitric Oxide (NO)
Prostaglandins, such as prostacyclin (PGI2).

136
Q

Which agents are involved in contracting vascular tone?

A

Endothelin-1 (ET-1)
Angiotensin II (Ang II)

137
Q

What are the mechanisms of prostacyclin (PGI2) in vascular regulation?

A

Inhibits platelet aggregation: Through increasing cAMP levels.
Relaxes smooth muscle: Via activation of cAMP-dependent pathways.
Inhibits vascular smooth muscle proliferation: Prevents abnormal vessel remodelling.

138
Q

How is prostacyclin derived?

A

Prostacyclin is produced from arachidonic acid via the cyclooxygenase (COX) pathway.

139
Q

What are the key features of Endothelin-1 (ET-1)?

A

A 21-amino acid peptide and the most potent known vasoconstrictor.
Stimulates proliferation of vascular smooth muscle, contributing to remodelling.
No effect on platelets.
Implicated in pathological states, such as hypertension.

140
Q

What are the physiological roles of nitric oxide in vascular tone?

A

Potent vasodilator, reducing blood pressure.
Inhibits platelet aggregation and smooth muscle proliferation.
Released by endothelial cells in response to shear stress or agonists like acetylcholine.

141
Q
A

Common Non-communicable Diseases - ME2366 (8 decks)

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