9: Cutaneous Vasculature Flashcards
What are the two main divisions of the cutaneous vasculature?
The cutaneous vasculature is divided into:
-
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.
-
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.
What is the role of endothelial cells in the blood vascular system?
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.
How do the venules of the deep vascular plexus (DVP) function in relation to inflammation?
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.
Describe the structural organization of the superficial vascular plexus (SVP) and its functional significance.
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.
How do smooth muscle cells (SMCs) and pericytes (PCs) differ in their roles within the dermal vasculature?
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.
What are the main components of the cutaneous vascular system and their roles?
The cutaneous vascular system is divided into two main components:
-
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.
-
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.
How do the superficial and deep vascular plexuses interact within the skin?
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.
What is the significance of the endothelial cells in the blood vascular system of the skin?
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.
What are the three layers of dermal arterioles and their compositions?
The three layers of dermal arterioles are:
- Intima - composed of endothelial cells (ECs)
-
Media - composed of smooth muscle cells (SMCs)
- In terminal arterioles, SMCs may be replaced by pericytes (PCs) within the basement membrane of the ECs.
- Adventitia - composed of connective tissue-type cells.
What is the role of postcapillary venules in the skin vasculature?
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.
How do capillaries in the skin differ in structure compared to larger blood vessels?
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.
What are the types of anastomosing connections found in the veins of the dermis?
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.
What is the significance of the subcutaneous vascular plexus in skin microvasculature?
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.
What is the significance of the ‘perivascular extraction unit’ in the dermis?
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.
How do dermal venules differ from arterioles in terms of permeability and structural features?
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.
What are the structural and functional differences between the intima, media, and adventitia layers of dermal arterioles?
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.
What is the significance of plasmalemmal vesicle protein (PV-1) in dermal capillaries?
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.
What is the role of vascular endothelial cells in blood fluidity?
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.
What are the key inhibitors of coagulation expressed by endothelial cells?
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.
How do endothelial cells limit platelet activation?
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.
What is permselectivity in the context of dermal endothelial cells?
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.
What distinguishes tight junctions from adherens junctions in endothelial cells?
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 |
What role do endothelial cells (ECs) play in maintaining blood fluidity, and what are the key inhibitors of coagulation they express?
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.
What are the primary mechanisms by which endothelial cells limit platelet activation?
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.
What role do vascular endothelial cells play in maintaining blood fluidity and preventing thrombus formation?
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.
How does the concept of permselectivity relate to the function of dermal endothelial cells?
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.
What are the differences between tight junctions and adherens junctions in endothelial cells regarding their permeability and function?
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 |
What is the role of hydrostatic and oncotic pressure in capillaries regarding fluid exchange?
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.
How do endothelial cells (ECs) regulate blood flow in terms of smooth muscle cell (SMC) tone?
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.
How do endothelial cells (ECs) regulate blood flow in terms of smooth muscle cell (SMC) tone?
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.
What mechanisms are involved in thermoregulation of skin blood flow?
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.
What neurotransmitters are involved in the vasodilation process in the skin?
Neurotransmitters that induce vasodilation include:
1. Substance P
2. Calcitonin gene-related peptide
3. Vasoactive intestinal peptide
4. Pituitary adenylate cyclase activating polypeptide
What pathological response is associated with postmenopausal hot flushes and its underlying mechanism?
Postmenopausal hot flushes are associated with estrogen’s vasodilator functions, which can cause dysregulation in skin thermoregulation, leading to increased heat sensation and flushing.
How does the skin vasculature contribute to thermoregulation during exposure to heat?
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.
How do dermal capillaries regulate molecular exchange between blood and tissues?
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).
How does the balance between vasodilators and vasoconstrictors regulate blood flow in the skin?
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.
How do hydrostatic and oncotic pressure gradients in dermal capillaries influence fluid exchange?
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.
What is the role of endothelial nitric oxide synthase (eNOS) in vascular tone regulation?
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.
What are the effects of estrogen dysregulation on skin thermoregulation in postmenopausal women?
Estrogen has vasodilator functions. Its dysregulation in postmenopausal women leads to impaired skin thermoregulation, contributing to hot flushes.
What is the role of interleukin (IL)-17A in vascular tone regulation?
Interleukin (IL)-17A, produced by resident perivascular memory T cells, induces vasoconstriction by influencing smooth muscle cell tone.
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?
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.
What role do endothelial cells (ECs) play in regulating blood flow, and how does the balance between vasodilators and vasoconstrictors affect vascular tone?
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.
In thermoregulation, how does the body respond to temperature changes through sympathetic vasodilation and vasoconstriction?
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.
What neurotransmitters are involved in the process of vasodilation, and how do they contribute to skin blood flow regulation?
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.
What pathological responses can occur in skin thermoregulation, particularly in relation to hormonal changes?
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.
What is the relationship between Type 1 Diabetes Mellitus and skin blood flow?
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.
How does Raynaud’s disease affect skin blood flow?
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.
What causes erythromelalgia and how does it affect the skin?
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.
What role do T lymphocytes play in skin immune surveillance?
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.
What is the significance of cutaneous lymphocyte antigen (CLA) in skin immunity?
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.
How does prostacyclin affect dermal vascular alterations during acute inflammation?
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.
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?
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.
Explain the mechanism of action of prostacyclin during acute inflammation.
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.
Describe the pathological mechanism and genetic basis of erythromelalgia.
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.
What is the role of cutaneous lymphocyte antigen (CLA) in immune surveillance?
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.
What is the role of arteriovenous anastomoses in Raynaud disease?
In Raynaud disease, arteriovenous anastomoses in the skin exhibit exaggerated vasospastic responses to cold or emotion, leading to ischemia in the digits.
How does the skin vasculature respond to inflammation in terms of perfusion?
During inflammation, endothelial cells release vasodilators like nitric oxide and prostacyclin, increasing perfusion at local sites to facilitate immune cell recruitment and tissue repair.
What are the implications of increased skin blood flow in patients with Type 1 DM?
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.
How does Raynaud’s disease affect skin blood flow and what are the underlying mechanisms?
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.
What is erythromelalgia and how does it affect skin vascular response?
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.
What role do T lymphocytes play in skin immune surveillance?
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.
How does prostacyclin influence dermal vascular alterations during acute inflammation?
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.
What are the key changes in endothelial cells during acute inflammation?
- 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.
What are the differences in endothelial cell characteristics between acute and chronic skin inflammation?
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 |
What is the ‘Kissing phenomenon’ observed in psoriasis?
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.
What are the characteristics of Lichen Ruber Planus in terms of dermal vascular changes?
- 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.
What are the effects of chronic inflammation on endothelial cell expression of adhesion molecules?
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.
During acute inflammation, what changes occur in postcapillary venules, and how do these changes facilitate leukocyte recruitment?
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.
In the context of chronic inflammation, what vascular changes are observed, and how do they differ from acute inflammation?
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.
What are the key features of the dermal vascular changes observed in psoriasis?
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.
What are the differences in endothelial cell morphology and adhesion molecule expression between acute and chronic skin inflammation?
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.
What is the ‘squirting papillae’ phenomenon in psoriasis, and what does it indicate?
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.
What are the pathological features of lichen ruber planus in terms of vascular changes?
Lichen ruber planus exhibits an enlarged blood microcirculatory bed within the papillary dermis. Oral lichen planus shows tortuous capillaries with enlarged capillary loop diameters.
How does chronic inflammation lead to fibrosis in the skin?
Chronic inflammation causes constant activation of endothelial cells, leading to epidermal hyperproliferation and fibrosis due to sustained expression of adhesion molecules and inflammatory mediators.
What is the significance of the ‘kissing’ phenomenon in psoriatic capillary loops?
The ‘kissing’ phenomenon in psoriatic capillary loops, where loops touch the epidermis, indicates increased endothelial cell proliferation and altered capillary morphology, contributing to inflammation.
What are the vascular characteristics of Lichen Ruber Planus compared to healthy skin?
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.
What is the significance of the ‘kissing’ phenomenon in psoriatic capillary loops?
The ‘kissing’ phenomenon in psoriatic capillary loops signifies morphological changes and elongation of capillaries due to endothelial cell proliferation.
What are the key differences in endothelial cell (EC) behavior during acute versus chronic inflammation?
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.
How does the morphology of capillary loops change in psoriasis, and what is the clinical significance of these changes?
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.
What are the key processes involved in the formation of new blood vessels during chronic inflammation or tissue injury?
The key processes include vasculogenesis, angiogenesis, vascular remodeling, and adult vasculogenesis.
What signals are known to induce new vessel formation in the skin?
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).
What role do pericytes play in endothelial cell interactions?
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.
What are the stages involved in the healing of full-thickness wounds?
The stages involved in the healing of full-thickness wounds include coagulation, inflammation, proliferation, and remodeling.
Which factors are considered main contributors in the angiogenic response during wound healing?
The main contributors in the angiogenic response during wound healing include VEGF, FGF-2, PDGF, and members of the TGF-β family.
What are the primary signals that induce new vessel formation in the skin, and what processes do they regulate?
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.
What is the role of pericytes in endothelial cell-pericyte interactions, and how do they influence vascular stability?
Pericytes directly contact endothelial cells, forming adherens junctions and secreting ANGPT1, which maintains vascular stability and prevents capillary leak.
How does the coagulation cascade contribute to wound healing after vascular injury?
The coagulation cascade activates, leading to platelet clot and fibrin clot formation, stopping bleeding and providing a scaffold for cell migration and tissue repair.
What is the role of VEGF in the angiogenic response during wound healing?
VEGF promotes rapid formation of blood vessels during the inflammatory and proliferative stages, facilitating tissue repair and regeneration.
What are the key differences between angiogenesis and vasculogenesis in the context of skin vasculature?
Angiogenesis involves the formation of new blood vessels from existing ones, while vasculogenesis refers to the formation of primitive blood vessels from angioblasts.
How does the activation of the coagulation cascade lead to inflammation during wound healing?
The coagulation cascade activates platelets, leading to fibrin clot formation and the release of CXC chemokines that recruit neutrophils, initiating the inflammatory response.
What is the role of Tie receptors in vascular remodeling?
Tie receptors, specifically Tie1 and Tie2, are required for vascular remodeling, with Tie2 interacting with ANGPT1 to maintain endothelial cell junctions.
What are the key stages involved in the healing of full-thickness wounds, and how do they interconnect?
The key stages are coagulation, inflammation, proliferation, and remodeling. These stages overlap and are interconnected, influencing each other in the healing process.
How do endothelial progenitor cells contribute to new vessel formation in chronic inflammation or tissue injury?
Endothelial progenitor cells migrate to sites of injury or inflammation, responding to stimuli to differentiate and form new blood vessels.
What role do pericytes play in endothelial cell interactions and vascular remodeling?
Pericytes contact ECs to form adherens junctions and secrete ANGPT1, influencing capillary integrity and vascular stability.
What are the main signals that induce new vessel formation in the skin, and what are their roles?
Main signals include VEGF, FGF, EGF, heparin-binding EGF-like growth factor, and HGF, which regulate angiogenesis and vascular remodeling.
What is the role of hypoxia in tumor angiogenesis?
Hypoxia leads to the expression of hypoxia-inducible factor (HIF) family of transcription factors, stimulating secretion of TGF-β, PDGF, CXCL2, and endothelin.
What are the mechanisms by which skin tumors acquire their blood supply?
Skin tumors acquire their blood supply through neighboring blood capillaries, intussusceptive angiogenesis, vasculogenic mimicry, vessel co-option, and vasculogenesis.
What factors do tumors produce that are involved in angiogenesis?
Tumors produce factors such as VEGF, FGF-2, EGF, and HGF or SF.
How do endothelial cells (ECs) of the subcutaneous vascular plexus (SVP) interact with keratinocyte-derived factors?
Endothelial cells (ECs) of the SVP may directly respond to keratinocyte-derived factors, indicating a potential interaction that influences vascular behavior.
What role do endothelial cells play in antigen presentation?
Endothelial cells (ECs) play a role in antigen presentation due to their constitutive expression of HLA class II.
How does the skin vasculature respond to hypoxia during tumor growth?
During tumor growth, hypoxia induces the expression of hypoxia-inducible factors (HIFs), stimulating secretion of TGF-β, PDGF, CXCL2, and endothelin.
How do tumors acquire their blood supply through vasculogenic mimicry?
In vasculogenic mimicry, tumor cells form fluid-conducting channels that mimic blood vessels, enabling nutrient supply.
How do endothelial cells contribute to antigen presentation in the skin?
Endothelial cells contribute to antigen presentation by constitutively expressing HLA class II molecules.
What is the role of hypoxia in tumor angiogenesis and which factors are stimulated as a result?
Hypoxia leads to the expression of hypoxia-inducible factor (HIF) family of transcription factors, stimulating secretion of TGF-β, PDGF, CXCL2, and endothelin.
