9: Cutaneous Vasculature

Question 1

What are the two main divisions of the cutaneous vasculature?

Answer 1

The cutaneous vasculature is divided into:

1. Superficial vascular plexus (SVP)
   
   • Composed of paired, interconnecting arterioles and venules parallel to and just beneath the epidermis.
   • Capillaries arise from the arterioles, extend upward within the papillary dermis, and loop back down to the venules, forming arcade-like structures.
2. Deep vascular plexus (DVP)
   
   • Deeper, anastomosing arterioles and venules connected to the SVP.
   • The plane of the DVP is parallel to that of the SVP and courses above the boundary between the reticular dermis and the underlying subcutis.

Question 2

What is the role of endothelial cells in the blood vascular system?

Answer 2

Endothelial cells (ECs) in the blood vascular system:
- Form a one-cell-thick layer of epithelium-like mesenchymal cells lining the blood vessels.
- Share common features and functions that are crucial for maintaining vascular integrity and function.

Question 3

How do the venules of the deep vascular plexus (DVP) function in relation to inflammation?

Answer 3

The venules of the deep vascular plexus (DVP) are drained by valve-containing veins that return to the subcutaneous fat, serving as portals of entry for leukocytes associated with inflammation.

Question 4

Describe the structural organization of the superficial vascular plexus (SVP) and its functional significance.

Answer 4

The SVP is composed of paired, interconnecting arterioles and venules located just beneath the epidermis. Capillaries arise from the arterioles, extend upward within the papillary dermis, and loop back down to the venules, forming arcade-like structures. This organization facilitates nutrient and oxygen delivery to the epidermis.

Question 5

How do smooth muscle cells (SMCs) and pericytes (PCs) differ in their roles within the dermal vasculature?

Answer 5

Smooth muscle cells (SMCs) are found in larger arterioles and regulate vascular tone, while pericytes (PCs) are associated with microvessels and contribute to vascular stability and endothelial cell interactions.

Question 6

What are the main components of the cutaneous vascular system and their roles?

Answer 6

The cutaneous vascular system is divided into two main components:

1. Superficial Vascular Plexus (SVP)
   
   • Composed of paired, interconnecting arterioles and venules located just beneath the epidermis.
   • Capillaries arise from arterioles, extending upward within the papillary dermis and looping back to venules, forming arcade-like structures.
2. Deep Vascular Plexus (DVP)
   
   • Composed of deeper, anastomosing arterioles and venules connected to the SVP.
   • The DVP runs parallel to the SVP and is located above the boundary between the reticular dermis and the subcutis.
   • Arterioles are fed by penetrating vessels from the subcutis, while venules are drained by valve-containing veins that return to subcutaneous fat, serving as portals for leukocytes associated with inflammation.

Question 7

How do the superficial and deep vascular plexuses interact within the skin?

Answer 7

The Superficial Vascular Plexus (SVP) and Deep Vascular Plexus (DVP) interact as follows:

• The SVP is located just beneath the epidermis and consists of paired arterioles and venules that interconnect and form capillary loops in the papillary dermis.
• The DVP is deeper and connects to the SVP, running parallel to it and situated above the reticular dermis and subcutis.
• Arterioles of the DVP are supplied by penetrating vessels from the subcutis, while venules of the DVP drain into veins that return to the subcutaneous fat, facilitating blood flow and immune response in the skin.

Question 8

What is the significance of the endothelial cells in the blood vascular system of the skin?

Answer 8

Endothelial cells (ECs) in the blood vascular system of the skin are significant because:

• They form a one-cell-thick layer lining the hollow tubes of blood vessels, which is crucial for maintaining vascular integrity and function.
• ECs share common features and functions with mesenchymal cells, contributing to the overall structure and regulation of blood flow.
• They play a vital role in processes such as inflammation, angiogenesis, and the regulation of permeability, impacting how the skin responds to injury and disease.

Question 9

What are the three layers of dermal arterioles and their compositions?

Answer 9

The three layers of dermal arterioles are:

1. Intima - composed of endothelial cells (ECs)
2. Media - composed of smooth muscle cells (SMCs)
   
   • In terminal arterioles, SMCs may be replaced by pericytes (PCs) within the basement membrane of the ECs.
3. Adventitia - composed of connective tissue-type cells.

Question 10

What is the role of postcapillary venules in the skin vasculature?

Answer 10

Postcapillary venules have several key features:
- They have a larger lumen and a thinner muscular wall.
- They contain valves at sites where small vessels connect to larger ones.
- They are lined by more than one endothelial cell (EC), have looser connections between neighboring ECs, and possess a multilayered basement membrane.
- They are associated with various resident populations of leukocytic cells, including T cells, macrophages, dendritic cells, and mast cells.

Question 11

How do capillaries in the skin differ in structure compared to larger blood vessels?

Answer 11

Capillaries in the skin are typically:
- Lined by a single file of highly curved endothelial cells (ECs) that enclose the lumen.
- Tightly connected to adjacent ECs, forming a tube with a lumen that is typically less than 10 μm in diameter.
- The fenestrae of dermal capillary ECs are primarily formed by a protein called plasmalemmal vesicle protein (PV)-1, which is a marker of microvascular ECs.

Question 12

What are the types of anastomosing connections found in the veins of the dermis?

Answer 12

The veins of the dermis have three types of anastomosing connections:
1. Large anastomoses of main trunks of the ascending veins.
2. Small anastomoses in the ascending sections of the small veins.
3. Very small anastomoses from the small ascending veins reaching the papillary dermis.

Question 13

What is the significance of the subcutaneous vascular plexus in skin microvasculature?

Answer 13

The subcutaneous vascular plexus is significant because it:
- Connects the vessels of the dermal vascular plexus (DVP) and provides nourishment for the adnexa within the reticular dermis.
- Serves as a segment of the vasculature through which circulating leukocytes can be recruited into the dermis.

Question 14

What is the significance of the ‘perivascular extraction unit’ in the dermis?

Answer 14

The perivascular extraction unit, composed of leukocytic cells, pericytes, and endothelial cells, serves as a segment of the vasculature through which circulating leukocytes can be recruited into the dermis, playing a critical role in immune surveillance.

Question 15

How do dermal venules differ from arterioles in terms of permeability and structural features?

Answer 15

Dermal venules have a larger lumen, thinner muscular walls, and looser endothelial cell connections compared to arterioles. They are somewhat leaky to macromolecules under basal conditions, unlike arterioles, which are less permeable due to tight junctions.

Question 16

What are the structural and functional differences between the intima, media, and adventitia layers of dermal arterioles?

Answer 16

The intima is composed of endothelial cells, the media of smooth muscle cells (or pericytes in terminal arterioles), and the adventitia of connective tissue-type cells. These layers collectively regulate blood flow and vessel stability.

Question 17

What is the significance of plasmalemmal vesicle protein (PV-1) in dermal capillaries?

Answer 17

Plasmalemmal vesicle protein (PV-1) forms the fenestrae of dermal capillary endothelial cells, enabling selective molecular exchange. It was previously designated as Pathologische Anatomie Leiden-endothelial (PAL-E) antigen.

Question 18

What is the role of vascular endothelial cells in blood fluidity?

Answer 18

Vascular endothelial cells are the principal cells responsible for maintaining blood fluidity by preventing the formation of thrombus while allowing beneficial clot formation at sites of vessel integrity disruption.

Question 19

What are the key inhibitors of coagulation expressed by endothelial cells?

Answer 19

The key inhibitors of coagulation expressed by endothelial cells include:

A. Tissue Factor Pathway Inhibitor - prevents dramatic increases of enzymatic activity of factor 7a on factors 9 and 10.
B. Thrombomodulin - redirects thrombin to activate protein C instead of cleaving fibrinogen.
C. Anticoagulant Heparan Sulfates - activate antithrombin 3 to inhibit thrombin and factor 10a.

Question 20

How do endothelial cells limit platelet activation?

Answer 20

Endothelial cells limit platelet activation by:
1. Producing NO and prostacyclin (PGI2).
2. Expressing ectoenzymes that degrade platelet-activating ATP and ADP to AMP.
3. Minimizing thrombin activation.
4. Masking basement membrane collagen.

Question 21

What is permselectivity in the context of dermal endothelial cells?

Answer 21

Permselectivity refers to the ability of dermal endothelial cells to permit the passage of water and solutes while restricting the passage of macromolecules, thus forming a barrier that allows blood to nourish tissues.

Question 22

What distinguishes tight junctions from adherens junctions in endothelial cells?

Answer 22

The distinctions are as follows:
| Feature | Tight Junctions | Adherens Junctions |
|———|—————-|——————–|
| Expression | Expressed in arterioles, capillaries | Expressed in postcapillary venules |
| Passage | Allow passage of water and solutes | Dynamically regulated to allow some macromolecules to enter during inflammation |
| Function | Prevent paracellular passage of macromolecules | Control which molecules may pass through fenestrae or vesicular transport |

Question 23

What role do endothelial cells (ECs) play in maintaining blood fluidity, and what are the key inhibitors of coagulation they express?

Answer 23

Endothelial cells maintain blood fluidity by expressing inhibitors of coagulation such as Tissue Factor Pathway Inhibitor, Thrombomodulin, and Anticoagulant Heparan Sulfates. These inhibitors prevent excessive enzymatic activity, redirect thrombin activity, and activate antithrombin 3, respectively.

Question 24

What are the primary mechanisms by which endothelial cells limit platelet activation?

Answer 24

Endothelial cells limit platelet activation by producing nitric oxide (NO) and prostacyclin (PGI2), expressing ectoenzymes that degrade platelet-activating ATP and ADP to AMP, and masking basement membrane collagen.

Question 25

What role do vascular endothelial cells play in maintaining blood fluidity and preventing thrombus formation?

Answer 25

Vascular endothelial cells are responsible for maintaining blood fluidity by producing anticoagulant factors such as Tissue Factor Pathway Inhibitor, Thrombomodulin, and Anticoagulant Heparan Sulfates. These factors help prevent excessive coagulation and thrombus formation by regulating the activity of clotting factors and inhibiting platelet activation.

Question 26

How does the concept of permselectivity relate to the function of dermal endothelial cells?

Answer 26

Permselectivity refers to the ability of dermal endothelial cells to allow the passage of water and solutes while restricting macromolecules. This selective permeability is crucial for nutrient exchange and maintaining tissue homeostasis, as it prevents unwanted substances from entering the tissue while still allowing essential fluids and nutrients to pass through.

Question 27

What are the differences between tight junctions and adherens junctions in endothelial cells regarding their permeability and function?

Answer 27

| Feature | Tight Junctions | Adherens Junctions | |---------|----------------|--------------------| | Expression | Arterioles, capillaries | Postcapillary venules | | Passage | Allow passage of water and solutes | Dynamically regulated to allow some macromolecules during inflammation | | Function | Prevent paracellular passage of macromolecules, limiting their crossing to fenestrae or vesicular transport | Enable control of which molecules may pass into the tissue during inflammatory responses |

Question 28

What is the role of hydrostatic and oncotic pressure in capillaries regarding fluid exchange?

Answer 28

Hydrostatic pressure gradients near the arteriolar side of the capillary loop drive fluid and solutes into the tissue, while the oncotic gradient draws them back into the bloodstream on the venular side, allowing dermal vascular endothelial cells to regulate molecular exchange between blood and tissues.

Question 29

How do endothelial cells (ECs) regulate blood flow in terms of smooth muscle cell (SMC) tone?

Answer 29

ECs regulate blood flow by controlling SMC tone, which affects the vessel lumen size and resistance to dilation. They synthesize both vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin), and the balance between these.

Question 30

How do endothelial cells (ECs) regulate blood flow in terms of smooth muscle cell (SMC) tone?

Answer 30

ECs regulate blood flow by controlling SMC tone, which affects the vessel lumen size and resistance to dilation. They synthesize both vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin), and the balance between these is regulated by neural or hormonal signals.

Question 31

What mechanisms are involved in thermoregulation of skin blood flow?

Answer 31

Skin blood flow is modified through sympathetic vasodilation or vasoconstriction. The noradrenergic vasoconstrictor system is activated by cold exposure, while initial vasodilation occurs through reflex removal of vasoconstrictor tone, and further heating leads to active vasodilation via parasympathetic cholinergic nerves releasing acetylcholine.

Question 32

What neurotransmitters are involved in the vasodilation process in the skin?

Answer 32

Neurotransmitters that induce vasodilation include: 1. Substance P 2. Calcitonin gene-related peptide 3. Vasoactive intestinal peptide 4. Pituitary adenylate cyclase activating polypeptide

Question 33

What pathological response is associated with postmenopausal hot flushes and its underlying mechanism?

Answer 33

Postmenopausal hot flushes are associated with estrogen's vasodilator functions, which can cause dysregulation in skin thermoregulation, leading to increased heat sensation and flushing.

Question 34

How does the skin vasculature contribute to thermoregulation during exposure to heat?

Answer 34

During heat exposure, the parasympathetic cholinergic nerves release acetylcholine, causing active vasodilation. This is preceded by reflex removal of active vasoconstrictor tone. Autonomic and sensory nerve fibers also release neurotransmitters like substance P and vasoactive intestinal peptide to induce vasodilation.

Question 35

How do dermal capillaries regulate molecular exchange between blood and tissues?

Answer 35

Dermal capillaries regulate molecular exchange by allowing fluid and solutes to cross the endothelial cell lining via paracellular routes while preventing macromolecules from doing so. This is achieved through tight junctions, adherens junctions, and fenestrae formed by plasmalemmal vesicle protein (PV-1).

Question 36

How does the balance between vasodilators and vasoconstrictors regulate blood flow in the skin?

Answer 36

Endothelial cells synthesize vasodilators like nitric oxide and prostacyclin, and vasoconstrictors like endothelin. The balance between these molecules, influenced by neural or hormonal signals, regulates blood flow by controlling smooth muscle cell tone and vessel lumen size.

Question 37

How do hydrostatic and oncotic pressure gradients in dermal capillaries influence fluid exchange?

Answer 37

Hydrostatic pressure gradients near the arteriolar side of the capillary loop drive fluid and solutes into the tissue, while oncotic gradients on the venular side draw them back into the bloodstream, maintaining fluid balance.

Question 38

What is the role of endothelial nitric oxide synthase (eNOS) in vascular tone regulation?

Answer 38

Endothelial nitric oxide synthase (eNOS) produces nitric oxide, a vasodilator that reduces smooth muscle cell tone. Inhibition of eNOS causes vasoconstriction and increased vascular resistance.

Question 39

What are the effects of estrogen dysregulation on skin thermoregulation in postmenopausal women?

Answer 39

Estrogen has vasodilator functions. Its dysregulation in postmenopausal women leads to impaired skin thermoregulation, contributing to hot flushes.

Question 40

What is the role of interleukin (IL)-17A in vascular tone regulation?

Answer 40

Interleukin (IL)-17A, produced by resident perivascular memory T cells, induces vasoconstriction by influencing smooth muscle cell tone.

Question 41

How do dermal vascular endothelial cells (ECs) regulate molecular exchange between blood and tissues, and what is the significance of hydrostatic and oncotic pressure in this process?

Answer 41

Dermal vascular ECs regulate molecular exchange by allowing fluid and solutes to cross the endothelial lining via the paracellular route. Hydrostatic pressure gradients near the arteriolar side drive fluid and solutes into the tissue, while the oncotic gradient draws them back into the bloodstream on the venular side, maintaining homeostasis between blood and tissues.

Question 42

What role do endothelial cells (ECs) play in regulating blood flow, and how does the balance between vasodilators and vasoconstrictors affect vascular tone?

Answer 42

ECs regulate blood flow by controlling smooth muscle cell (SMC) tone, which affects vessel lumen size and resistance to dilation. They synthesize vasodilators (e.g., nitric oxide) that reduce SMC tone and vasoconstrictors (e.g., endothelin) that increase it. The balance between these factors is influenced by neural or hormonal signals, impacting overall vascular tone.

Question 43

In thermoregulation, how does the body respond to temperature changes through sympathetic vasodilation and vasoconstriction?

Answer 43

The body responds to temperature changes by modifying skin blood flow through sympathetic vasodilation or vasoconstriction. Cold exposure activates the noradrenergic vasoconstrictor system, while body heating initiates vasodilation through reflex removal of vasoconstrictor tone, followed by parasympathetic release of acetylcholine for active vasodilation.

Question 44

What neurotransmitters are involved in the process of vasodilation, and how do they contribute to skin blood flow regulation?

Answer 44

Neurotransmitters involved in vasodilation include Substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and pituitary adenylate cyclase activating polypeptide. These substances directly or indirectly induce vasodilation, contributing to the regulation of skin blood flow and thermoregulation.

Question 45

What pathological responses can occur in skin thermoregulation, particularly in relation to hormonal changes?

Answer 45

Pathological responses in skin thermoregulation can include postmenopausal hot flushes, where estrogen, which has vasodilator functions, leads to dysregulation in thermoregulation, causing abnormal temperature regulation and discomfort.

Question 46

What is the relationship between Type 1 Diabetes Mellitus and skin blood flow?

Answer 46

Patients with Type 1 DM have greater skin blood flow, potentially related to moderate vasodilation induced by hyperinsulinemia and an impaired thermoregulatory response of skin vessels.

Question 47

How does Raynaud's disease affect skin blood flow?

Answer 47

Raynaud's disease leads to exaggerated vasospastic responses to cold or emotion, resulting in ischemia of the digits. Attacks are restricted to cutaneous arteries supplying skin sites with a rich density of arteriovenous anastomosis, and patients exhibit increased sympathetic vasoconstrictive activity, resulting in increased blood flow through these anastomoses.

Question 48

What causes erythromelalgia and how does it affect the skin?

Answer 48

Erythromelalgia is caused by mutations affecting the SCN9A gene, leading to channelopathies. It most severely affects the palms and soles, and arterioles and venules show abnormal innervation or response.

Question 49

What role do T lymphocytes play in skin immune surveillance?

Answer 49

T lymphocytes display special affinity for the skin, determined by signals received from resident cutaneous cells. After an immune response, a subset of memory T cells develops, contributing to the skin's immunologic barrier.

Question 50

What is the significance of cutaneous lymphocyte antigen (CLA) in skin immunity?

Answer 50

CLA is the first skin-associated protein expressed on a population of memory T lymphocytes, binding to E-selectin expressed on activated endothelium, facilitating skin-specific immune responses.

Question 51

How does prostacyclin affect dermal vascular alterations during acute inflammation?

Answer 51

Prostacyclin results from cytokine-induced increases in cyclooxygenase (COX)-2 expression, causing a shift in the balance of vasodilatory molecules released by endothelial cells, contributing to higher perfusion at local sites of inflammation.

Question 52

A patient presents with ischemia in their digits triggered by cold exposure. What pathological mechanism is likely involved, and which vascular structures are primarily affected?

Answer 52

The patient likely has Raynaud disease, characterized by an exaggerated vasospastic response to cold or emotion. The pathological mechanism involves increased sympathetic vasoconstrictive activity, primarily affecting cutaneous arteries supplying skin sites with a rich density of arteriovenous anastomoses.

Question 53

Explain the mechanism of action of prostacyclin during acute inflammation.

Answer 53

Prostacyclin is produced due to cytokine-induced expression of cyclooxygenase (COX)-2. It shifts the balance of vasodilatory molecules released by endothelial cells, contributing to higher perfusion at local sites of inflammation.

Question 54

Describe the pathological mechanism and genetic basis of erythromelalgia.

Answer 54

Erythromelalgia is caused by mutations in the SCN9A gene, leading to channelopathies. It most severely affects the palms and soles, with arteriole-venule shunts showing abnormal innervation or responses.

Question 55

What is the role of cutaneous lymphocyte antigen (CLA) in immune surveillance?

Answer 55

Cutaneous lymphocyte antigen (CLA) binds to E-selectin expressed on activated endothelium, facilitating skin-specific leukocyte homing. It is expressed on memory T cells that develop after an immune response in the skin.

Question 56

What is the role of arteriovenous anastomoses in Raynaud disease?

Answer 56

In Raynaud disease, arteriovenous anastomoses in the skin exhibit exaggerated vasospastic responses to cold or emotion, leading to ischemia in the digits.

Question 57

How does the skin vasculature respond to inflammation in terms of perfusion?

Answer 57

During inflammation, endothelial cells release vasodilators like nitric oxide and prostacyclin, increasing perfusion at local sites to facilitate immune cell recruitment and tissue repair.

Question 58

What are the implications of increased skin blood flow in patients with Type 1 DM?

Answer 58

Patients with Type 1 DM experience greater skin blood flow due to moderate vasodilation induced by hyperinsulinemia and an impaired thermoregulatory response of skin vessels. This can lead to altered skin temperature regulation and potential complications in skin health.

Question 59

How does Raynaud's disease affect skin blood flow and what are the underlying mechanisms?

Answer 59

Raynaud's disease leads to exaggerated vasospastic responses to cold or emotion, resulting in ischemia of the digits. The attacks are restricted to cutaneous arteries with a rich density of arteriovenous anastomosis, and patients exhibit increased sympathetic vasoconstrictive activity, which enhances blood flow through these anastomoses.

Question 60

What is erythromelalgia and how does it affect skin vascular response?

Answer 60

Erythromelalgia is caused by mutations in the SCN9A gene, leading to channelopathies that most severely affect the palms and soles. It is characterized by abnormal innervation of arterioles and venules, resulting in altered vascular responses and potential pain or discomfort in affected areas.

Question 61

What role do T lymphocytes play in skin immune surveillance?

Answer 61

T lymphocytes form an immunologic barrier in the skin by displaying special affinity for skin, determined by signals from resident cutaneous cells. After an immune response, a subset of memory T cells develops, which is crucial for long-term immunity and skin health.

Question 62

How does prostacyclin influence dermal vascular alterations during acute inflammation?

Answer 62

Prostacyclin results from cytokine-induced increases in cyclooxygenase (COX)-2 expression, leading to a shift in the balance of vasodilatory molecules released by endothelial cells of arterioles and capillaries. This shift contributes to higher perfusion at local sites of inflammation, enhancing the inflammatory response.

Question 63

What are the key changes in endothelial cells during acute inflammation?

Answer 63

- **Selectins** expressed by endothelial cells (ECs) cause tethering and rolling of leukocytes. - **IL-8 (CXCL8)** is important for neutrophils, while **MCP-1** (CCL2) aids monocyte attachment. - **ICAM-1** mediates leukocyte crawling. - **VCAM-1** may assist in capture, rolling, and crawling of leukocytes. - **TNF-alpha** and **IL-1** induce proinflammatory changes in ECs.

Question 64

What are the differences in endothelial cell characteristics between acute and chronic skin inflammation?

Answer 64

| Feature | Acute Inflammation | Chronic Inflammation | |-----------------------|----------------------------------|-----------------------------------| | E and P selectin | ↑ E and P selectin | Moderate E selectin | | VCAM-1, ICAM-1 | Moderate VCAM-1, ICAM-1 | ↑ VCAM-1 | | Appearance | Flat appearance | Cuboidal appearance |

Question 65

What is the 'Kissing phenomenon' observed in psoriasis?

Answer 65

The 'Kissing phenomenon' refers to the capillary loops at the turnaround point touching the epidermis, leading to elongation and an increase in diameter of the capillary loops due to endothelial cell proliferation.

Question 66

What are the characteristics of Lichen Ruber Planus in terms of dermal vascular changes?

Answer 66

- Lichen Ruber Planus has an **enlarged blood microcirculatory bed** within the papillary dermis compared to healthy skin. - Oral lichen planus features **tortuous capillaries** with an enlarged capillary loop diameter.

Question 67

What are the effects of chronic inflammation on endothelial cell expression of adhesion molecules?

Answer 67

In chronic inflammation, there is: - Continuous and high expression of **ICAM-1** and **VCAM-1**. - **E-selectin** is absent and cannot be reinduced by additional TNF stimulation. - **CXCL5** and **MCP-3** are overexpressed. - Sustained expression of **E-selectin** is a skin-specific feature of chronic inflammation, with slower internalization and degradation of the E-selectin protein.

Question 68

During acute inflammation, what changes occur in postcapillary venules, and how do these changes facilitate leukocyte recruitment?

Answer 68

In acute inflammation, postcapillary venules become leaky and display IL-8, E- and P-selectins, VCAM-1, and ICAM-1. These changes facilitate leukocyte recruitment by enabling tethering, rolling, and firm attachment of leukocytes to the endothelium.

Question 69

In the context of chronic inflammation, what vascular changes are observed, and how do they differ from acute inflammation?

Answer 69

In chronic inflammation, endothelial cells exhibit continuous activation, leading to epidermal hyperproliferation and fibrosis. ICAM-1 and VCAM-1 expression is high, while E-selectin is absent. In contrast, acute inflammation involves transient expression of E- and P-selectins and moderate ICAM-1 and VCAM-1 expression.

Question 70

What are the key features of the dermal vascular changes observed in psoriasis?

Answer 70

In psoriasis, capillary loops elongate and change morphology, with the 'kissing' phenomenon where loops touch the epidermis. Endothelial cells within the loops proliferate, increasing diameter and expressing adhesion molecules that support leukocyte tethering, rolling, and extravasation.

Question 71

What are the differences in endothelial cell morphology and adhesion molecule expression between acute and chronic skin inflammation?

Answer 71

In acute inflammation, endothelial cells have a flat appearance and express E- and P-selectins. In chronic inflammation, they exhibit a cuboidal appearance, with high ICAM-1 and VCAM-1 expression and sustained E-selectin expression.

Question 72

What is the 'squirting papillae' phenomenon in psoriasis, and what does it indicate?

Answer 72

The 'squirting papillae' phenomenon in psoriasis refers to lymphocytes and neutrophils histologically extravasating within the papillae tips. It indicates active inflammation and immune cell recruitment in the affected skin.

Question 73

What are the pathological features of lichen ruber planus in terms of vascular changes?

Answer 73

Lichen ruber planus exhibits an enlarged blood microcirculatory bed within the papillary dermis. Oral lichen planus shows tortuous capillaries with enlarged capillary loop diameters.

Question 74

How does chronic inflammation lead to fibrosis in the skin?

Answer 74

Chronic inflammation causes constant activation of endothelial cells, leading to epidermal hyperproliferation and fibrosis due to sustained expression of adhesion molecules and inflammatory mediators.

Question 75

What is the significance of the 'kissing' phenomenon in psoriatic capillary loops?

Answer 75

The 'kissing' phenomenon in psoriatic capillary loops, where loops touch the epidermis, indicates increased endothelial cell proliferation and altered capillary morphology, contributing to inflammation.

Question 76

What are the vascular characteristics of Lichen Ruber Planus compared to healthy skin?

Answer 76

Lichen Ruber Planus has an enlarged blood microcirculatory bed within the papillary dermis compared to healthy skin and exhibits tortuous capillaries with an enlarged capillary loop diameter.

Question 77

What is the significance of the 'kissing' phenomenon in psoriatic capillary loops?

Answer 77

The 'kissing' phenomenon in psoriatic capillary loops signifies morphological changes and elongation of capillaries due to endothelial cell proliferation.

Question 78

What are the key differences in endothelial cell (EC) behavior during acute versus chronic inflammation?

Answer 78

**Acute Inflammation:** Increased expression of E and P selectins, moderate expression of VCAM-1 and ICAM-1, TNF-alpha and IL-1 induce proinflammatory changes in ECs. **Chronic Inflammation:** Sustained high expression of ICAM-1 and VCAM-1, E-selectin is absent and cannot be reinduced by TNF stimulation, overexpression of CXCL5 and MCP-3, slower internalization and degradation of E-selectin protein.

Question 79

How does the morphology of capillary loops change in psoriasis, and what is the clinical significance of these changes?

Answer 79

In psoriasis, the capillary loops undergo significant morphological changes: elongation and diameter increase due to endothelial cell proliferation, kissing phenomenon indicating altered vascular architecture, and squirting papillae indicative of inflammation and immune response.

Question 80

What are the key processes involved in the formation of new blood vessels during chronic inflammation or tissue injury?

Answer 80

The key processes include vasculogenesis, angiogenesis, vascular remodeling, and adult vasculogenesis.

Question 81

What signals are known to induce new vessel formation in the skin?

Answer 81

The signals that induce new vessel formation in the skin include VEGF, FGF, EGF, heparin-binding EGF-like growth factor, and hepatocyte growth factor (HGF).

Question 82

What role do pericytes play in endothelial cell interactions?

Answer 82

Pericytes play a crucial role in endothelial cell interactions by directly contacting ECs and forming adherens junctions, and secreting angiopoietin 1 (ANGPT1) to maintain endothelial cell junction integrity.

Question 83

What are the stages involved in the healing of full-thickness wounds?

Answer 83

The stages involved in the healing of full-thickness wounds include coagulation, inflammation, proliferation, and remodeling.

Question 84

Which factors are considered main contributors in the angiogenic response during wound healing?

Answer 84

The main contributors in the angiogenic response during wound healing include VEGF, FGF-2, PDGF, and members of the TGF-β family.

Question 85

What are the primary signals that induce new vessel formation in the skin, and what processes do they regulate?

Answer 85

Primary signals include VEGF, FGF, EGF, heparin-binding EGF-like growth factor, and hepatocyte growth factor (HGF). These signals regulate angiogenesis, vasculogenesis, and vascular remodeling.

Question 86

What is the role of pericytes in endothelial cell-pericyte interactions, and how do they influence vascular stability?

Answer 86

Pericytes directly contact endothelial cells, forming adherens junctions and secreting ANGPT1, which maintains vascular stability and prevents capillary leak.

Question 87

How does the coagulation cascade contribute to wound healing after vascular injury?

Answer 87

The coagulation cascade activates, leading to platelet clot and fibrin clot formation, stopping bleeding and providing a scaffold for cell migration and tissue repair.

Question 88

What is the role of VEGF in the angiogenic response during wound healing?

Answer 88

VEGF promotes rapid formation of blood vessels during the inflammatory and proliferative stages, facilitating tissue repair and regeneration.

Question 89

What are the key differences between angiogenesis and vasculogenesis in the context of skin vasculature?

Answer 89

Angiogenesis involves the formation of new blood vessels from existing ones, while vasculogenesis refers to the formation of primitive blood vessels from angioblasts.

Question 90

How does the activation of the coagulation cascade lead to inflammation during wound healing?

Answer 90

The coagulation cascade activates platelets, leading to fibrin clot formation and the release of CXC chemokines that recruit neutrophils, initiating the inflammatory response.

Question 91

What is the role of Tie receptors in vascular remodeling?

Answer 91

Tie receptors, specifically Tie1 and Tie2, are required for vascular remodeling, with Tie2 interacting with ANGPT1 to maintain endothelial cell junctions.

Question 92

What are the key stages involved in the healing of full-thickness wounds, and how do they interconnect?

Answer 92

The key stages are coagulation, inflammation, proliferation, and remodeling. These stages overlap and are interconnected, influencing each other in the healing process.

Question 93

How do endothelial progenitor cells contribute to new vessel formation in chronic inflammation or tissue injury?

Answer 93

Endothelial progenitor cells migrate to sites of injury or inflammation, responding to stimuli to differentiate and form new blood vessels.

Question 94

What role do pericytes play in endothelial cell interactions and vascular remodeling?

Answer 94

Pericytes contact ECs to form adherens junctions and secrete ANGPT1, influencing capillary integrity and vascular stability.

Question 95

What are the main signals that induce new vessel formation in the skin, and what are their roles?

Answer 95

Main signals include VEGF, FGF, EGF, heparin-binding EGF-like growth factor, and HGF, which regulate angiogenesis and vascular remodeling.

Question 96

What is the role of hypoxia in tumor angiogenesis?

Answer 96

Hypoxia leads to the expression of hypoxia-inducible factor (HIF) family of transcription factors, stimulating secretion of TGF-β, PDGF, CXCL2, and endothelin.

Question 97

What are the mechanisms by which skin tumors acquire their blood supply?

Answer 97

Skin tumors acquire their blood supply through neighboring blood capillaries, intussusceptive angiogenesis, vasculogenic mimicry, vessel co-option, and vasculogenesis.

Question 98

What factors do tumors produce that are involved in angiogenesis?

Answer 98

Tumors produce factors such as VEGF, FGF-2, EGF, and HGF or SF.

Question 99

How do endothelial cells (ECs) of the subcutaneous vascular plexus (SVP) interact with keratinocyte-derived factors?

Answer 99

Endothelial cells (ECs) of the SVP may directly respond to keratinocyte-derived factors, indicating a potential interaction that influences vascular behavior.

Question 100

What role do endothelial cells play in antigen presentation?

Answer 100

Endothelial cells (ECs) play a role in antigen presentation due to their constitutive expression of HLA class II.

Question 101

How does the skin vasculature respond to hypoxia during tumor growth?

Answer 101

During tumor growth, hypoxia induces the expression of hypoxia-inducible factors (HIFs), stimulating secretion of TGF-β, PDGF, CXCL2, and endothelin.

Question 102

How do tumors acquire their blood supply through vasculogenic mimicry?

Answer 102

In vasculogenic mimicry, tumor cells form fluid-conducting channels that mimic blood vessels, enabling nutrient supply.

Question 103

How do endothelial cells contribute to antigen presentation in the skin?

Answer 103

Endothelial cells contribute to antigen presentation by constitutively expressing HLA class II molecules.

Question 104

What is the role of hypoxia in tumor angiogenesis and which factors are stimulated as a result?

Answer 104

Hypoxia leads to the expression of hypoxia-inducible factor (HIF) family of transcription factors, stimulating secretion of TGF-β, PDGF, CXCL2, and endothelin.