this presentation is about the blood supply and nerve supply of skin with clinical aspects

1. Vasculature and innervation of
skin
PRESENTER : DR ANSHUL AGRAWAL
1

2. VASCULATURE OF SKIN
• Blood vessels of the skin are formed embyrologically by an intricate
network of mesenchymal cells that come to surround arbonizing spaces.
BLOOD VESSELS
superficial
plexus
deep plexus
venules
ALL OF WHICH ARE CONNECTED BY
COMMUNICATED BLOOD VESSELS
2

3. • Communicating vessels arise from and lead back to arteries and veins that
lie within the septa of the subcutaneous fat.
• Deep plexus: lower part of reticular dermis
• Superficial plexus: upper part of reticular dermis , just beneath the papillary
dermis (sub papillary plexus)
• Superficial and deep plexus lie parallel to the skin surface
• Communicating vessels lie perpendicular to it
3

4. • Superficial plexus: arcade of capillary loop upward into each dermal
papillae.
• Endothelium of those capillary stain well for alkaline phosphatase.
• Capillary loop consists of ascending arterial component ----hairpin turn---descending venous limb.
4

5. VENOUS PORTION EMPTIES INTO
Postcapillary venules of superficial plexus
Dermal communicating venules
Large venules of deep plexus
Small veins of subcutaneous fat.
5

6. 6

7. 7

8. • Superficial and deep plexus anastomose richly thoughout the dermis
• Anastomoses is developed most highly at upper part of dermis and around
folliculo-sebaceous-apocrine units and eccrine glands.
• This arrangement permits development of alternative channels for
preferential blood flow if other routes become blocked.
8

9. Vascular development
• During embryogenesis, the first blood vessels are formed through
Vasculogenesis.
9

10. EXTRAEMBRYONIC MESODERM OF YOLK SAC
BLOOD ISLANDS OF HEMANGIOBLASTS
(CLUSTERS OF EPITHELIOID CELLS)
OUTER CELLS
ANGIOBLAST
INNER CELLS
PRIMITIVE
HEMATOPOETIC CELLS
10

11. 11

12. ANGIOGENESIS
• Sprouting of the new blood vessels from existing primordial vessels,
represents a major mechanism of new blood vessel formation.
• The Tie- 2 receptor tyrosine kinase , expressed on vascular endothelial cells
,plays a crucial role in sprouting and remodeling during early embryonic
angiogenesis.
• Pericyte derived angiopoieten 1 (Ang-1) activates the Tie-2 receptor ,
whereas Angiopoietin 2 acts as inhibitor of Ang-1
12

13. 13

14. • Angiogenesis occurs as :
1. The sprouting outgrowth of new capillaries from pre-existing
post capillary venules
2. Non-sprouting remodling of pre-existing vessels either through
circumferential growth/vascular enlargement or through the
formation of intravascular endothelail cell pillars
14

15. • Stepwise induction of angiogenesis:
1. Induction of microvascular hyperpermeability
2. Enzymatic degradation of vascular basement membrane and interstitial
matrix
3. Endothelial cell migration via integrin receptors on activated endothelial
cells interacting with native or degraded matrix molecules.
4. Endothelial cells proliferation
5. Formation of mature blood vessels
15

16. 16

17. Histology of blood vessels
Arteries in the subcutaneous fat and larger arterioles in the deep part of the
dermis consist of:
1. INITIMA: composed of endothelial cells
and internal elastic membrane.
2. MEDIA: contains collagen , non layered
elastic fibers, and several concentric layers
of smooth muscles which in arteries
are bound by external elastic membrane .
3. ADVENTITIA: constitutes fibrocytes,
type III collagen and elastic fibers.
17

18. •
Arterioles in the superficial dermis do not posses an internal or external elastic
membrane and their wall contains discontinuos layers of elastic fibers and
smooth muscle cells.
• Ascending segment of capillary loop consist of single layer of endothelial
cells that line a narrow lumen and in turn is surrounded by discontinuous
layer of pericytes.
• Endothelial cells and pericytes are enveloped by continuous homogeneous
appearing basal lamina.
18

19. • Descending venous loop is wider, pericytes are more numerous and basal
lamina becomes multilayered.
• Post capillary venules resemble capillaries, their walls consisting only of
endothelial cells ,pericyte and basal lamina surrounded by thin zones of
type III collagen fibers. Walls of larger venules posses variable amount of
smooth muscle and elastic fibers , but no elastic membrane .
• All arterioles , capillaries and venules in dermis are encircled by flat
adventitial cells: Veil cells whose exact nature is unclear and is situated
entirely outside the wall of a vessel, demarcating it from surrounding dermis.
They are seen infrequently around vessels of subcutaneous fat.
19

20. Capillaries of the skin are continuous type and when viewed through
electron microscope , adjacent endothelial cells that constitute them appear
to be connected to one another by specialized intercellular junctions
Endothelial cells contain mostly of
• cytoplasmic filaments: diameter 7.5 and 10 nm
• Pinocytotic vesicles that measure 50 – 70 nm in diameter
20

21. Exchange of fluid and small water soluble molecules from lumina of
continuous capillaries to pericapillary tissue occurs mainly through
pinocytotic vesicles .
These vesicles form at the luminal membrane of an endothelial cell, pass through
the cytoplasm ,and discharge their contents in contraluminal membrane .
21

22. In contrast, fenestrated venous capillaries situated within the adventitial dermis
adjacent to eccrine glands and follicular bulbs, allow passage of larger molecules
through gaps between adjacent endothelial cells.Intercellular gaps may be widened
by contraction of actin filaments 7.5nm in diameter , within cytoplasm of
endothelial cells
Hence, continuous capillaries are permeable to small, water soluble molecules
mainly by way of micropinocytic route, whereas fenestrated capillaries also allow
interendothelial transport of larger molecules such as plasma proteins.
22

23. • Postcapillary venules, the predominant type of vessel within the upper part
of dermis, are most permeable of the cutaneous blood vessels and
frequently are sites of pathologic changes of inflammatory skin diseases.
• In post capillary venule, pericytes and endothelial cells make contact with
one another at many points over their entire surfaces.
23

24. •
Single pericyte forms tight junction with 2-4 subadjacent endothelial cells through
breaks in multilaminated basement membrane.This contact is rich in fibronectin .
24

25. • The presence in pericyte of contractile protein isomyosins, coupled with
complex cytoplasmic interdigitations , supports the concept that pericytes
are major contractile cells for effecting interendothelial cell gaps in post
capillary venular segments where the inflammatory events take place
• In addition vaso active substance such as prostaglandins and histamine
released by leucocytes , mast cells or platelets increase venullar
permeability by inducing contraction of endothelial cells and pericytes with
resultant widening of intercellular spaces .
• This process favors deposition of immune comlpexes within the walls of
post capillary venules in conditions such as leuckocytoclastic vasculitis
and allows extravasation of fluids and inflammatory cells in the
surrounding connective tissue
25

26. Glomus bodies
• Specialized arteriovenous shunts
• Allow blood to be shunted from arteriole to venule , thereby bypassing the
capillary bed and increasing the rate and volume of regional blood flow
• They are most abundant in the dermis of acral skin i.e nail beds, finger
toes,ears and nose
26

27. •
•
•
Arterial segment of glomus body termed as Sucquet-Hoyer canal,has narrow lumen
and thick wall that consists of endothelium surrounded by 3-6 contractile glomus
cells
Venous segment is thin walled and has wide lumen that drains into subpapillary
venule
These are modified smooth muscle cells that possess uniform ovoid nuclie and pale
staining cytoplasm with rindistinct cell margins
27

28. • The total volume of the blood that flows through the skin exceeds by far
the metabolic requirement
• Primary functions of cutaneous vessel is related to control of temperature
and to regulation of blood pressure.
• In an thermally neural environment, the skin receives 5-10% of cardiac
output and this may increase to upto sevenfold under conditions of severe
heat stress or decrease to zero in extremely cold environments
28

29. Vascular tone and its regulation
• In acral regions vessels are controlled predominantly by unmyeilinated
adrenergic sympatatic nerves.
• These tonically active vasoconstrictor nerve fibers are the efferent arm of
1 . Baroreflexes that originate in both arterial and cardiopulmonary
baroreceptors
2. Reflex baro responses to operate posture and exercise
3. Chemoreceptor reflexes
4. Thermo regualtory reflexes
• Non acral skin: also possess a neurogenic vasodilator system that is an a
efferent arm of reflexes originating in hypothalamic thermo receptors
29

30. FACTORS AFFECTING THE CALIBER OF ARTERIOLES
Vasoconstrictors:
Vasodilators:
Increased adrenergic discharge
Circulating catecholamines (expect
epinephrine in skeletal muscles)
Circulating Angiotgensin II,
Locally released Serotonin
Decreased local temperature
Increased carbon dioxide
tension
Decreased adrenergic discharge
Activation of cholenergic dilators
Ethanol
Histamines
Kinins
Decreased oxygen
Prostaglandins of E- series
Local heating of the skin.
30

31. Lymphatics
•
•
•
•
•
Lymphatic vessels were first described in the seventeenth century by gasparo aselli
as ‘’lacteae venae ‘’i.e milky veins
The cutaneous lymphatic system develops in parallel with blood vascular system
through a process termed lymphangiogenesis.
The lymphatic system is composed of vascular network of thin walled capillaries
that drain protein rich lymph from extra- cellular space and maintain a crucial role
in maintenance of normal tissue pressure
lymphatic vessels also play a vital role in mediating the trafficking of immune cells
from the skin to regional lymph nodes , and in metastatic spread of cutaneous
malignancies
Histopathology: lympahtic capillaries are lined by continuous single layer of
overlapping endothelial cells and lack continuous basement membrane
31

32. •
•
The lymphatic vessels of skin form two horizontal plexuses.
Superficial collects lymph from lymphatic capillaries that can extend into the
dermal papilaae and is located in close vicinity to superficial cutaneous arterial
plexus
•
Vertical lymphatic vessels connect superficial vessels with larger collecting vessels
in lower dermis and upper sub cutis
the deep lymphatic vessels are located below the deep arterial system and
contain valves to ensure unidirectional fluid transport
•
•
Finger tips, palms and soles,the scrotum and foreskin appear to have more
abundant lymphatic network.
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33. Clinical aspect
33

34. Cutaneous vascular responses
•
•
•
Erythema
Flushing
Blushing
34

35. •
•
Erythema anuulare centrifugum
Erythema chronicum migrans
Erythema marginatum rheumaticum
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36. Telangiectases
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37. Erythema multiforme
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38. Urticaria
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39. Angioedema
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40. Idiopathic thrombocytopenic purpura
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41. Disseminated intravascular coagulation (DIC)
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42. Acroangiodermatitis
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43. •
•
•
•
Purpura’s:
Pigmented purpura dermatoses
Painful bruising syndrome
Contact pupura
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44. Vasculitis
1. Large vessel vascultis
2. Medium vesssel vascultis
3. Small vessel vasculitis
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45. •
•
•
•
Thromboangitis obliterans
Erythromelalgia
Venous ulcers
Deep vein thrombosis
•
1.
2.
3.
4.
Disorders of lymphatics:
Lymphedema
Lymphangioma circumscriptum
Cavernous lymphangioma
Lymphangiectases
45

46. NERVES
Skin is innervated by a dense, three dimentional network of highly specialized
afferent sensory and efferent autonomic nerve branches.
Part of 2 major systems:
• somatic sensory
• Autonomic motor
46

47. Somatic sensory
•
Sensory innervation follows well-defined dermatomes with some overlap between
adjacent dermatomes
47

48. 48

49. Somatic sensory
•
The afferent sensory neurons are unipolar and branch off with a single axon
travelling towards the skin.
•
Sensory nerves not only function as an afferent system to conduct stimuli back
from the skin to the CNS, but also act in an efferent neurosecretory fashion,
releasing neuropeptides with important visceromotor, infl ammatory and trophic
effects on skin
•
Somatic sensory system mediates the sensations of pain ,itch, temperature, light
touch, pressure, and vibration, proprioception and epicritical or discriminative
sensations of touch
50

50. • Cutaneous sensory receptors are classified into 2 groups :
1. Specialized receptors :possess terminal nerve endings that are surrounded
by distinct lamellar condensations of connective tissue and shwann cells
( e.g pacini corpuscles , meissners corpuscles and mucocutaneous end
organs )
2. Unspecialised receptors: do not possess distinct structural features.
51

51. 52

52. Pacini corpuscles
• Situated chiefly on weight bearing surfaces in the deep portion of the
dermis and the subcutaneous fat
• Numerous in the oral lips, penis,clitoris,nipples
• Each corpuscle measures about 0.8 x 1.5 mm and is supplied by myelinated
axon that makes several turns before it enters the concentrically layers
connective tissue capsule that envelops the sensory terminal.
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53. • The concentric lamellae consist of flattened cells( laminar cells) that
probably are modified shwann cells
• Spaces filled with fluid separate thin layers of adjacent laminar cells with
their associated connective tissue, in the outer portion of pacini corpuscle
• In central core bulbous terminal nerve ending, now devoid of its mylein
sheath is in direct contact with the innermost laminar cells
54

54. •
The lamillar organization of corpuscle may enable it to act as a primary receptor
that gives rise to action potentials when its architecture is destorted
•
Pacini corpuscle are mechano receptors that primarily detect the sensation of
pressure
55

55. Meissner’s corpuscle
• Present at tips of dermal papillae on volar skin and are most plentlyful over
fingertips
• Each corpuscle measures about 50 x 150 microns and consists of layers of
flattened laminar cells among which some ramify axon terminals derived
from myelinated nerves
56

56. •
•
•
Typically the axons weave back and forth between stacks of lamillae
Under elecron microscope, laminar cells posses basal lamina and at the periphery of
the corpuscle are separated by collgen fibers, elastic fibers and fibrillary
intercellular material
Function: rapidly adapting mechanoreceptors that detect the senstaion of light touch
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57. Mucocutaneous end organs
• Located in subpapillary connective tissue of the glans penis,prepuce
,clitoris ,labia minora , perianal area ,eyelids and oral lips
• In contrast to pacini and meissner corpuscle these cannot be visualized in
sections stained by hematoxylin and eosin .
• Measure about 50 microns in diameter and contain loops of loosely wound,
branching axons that form irregular oval masses .
58

58. •
There is no ture capsule around a mucocutaneous end organ.
•
By ultrastructural examination, seen to be divided into lobullar units that contain
axon terminals surrounded by concentric lamellar processess originating from
lamellar cells.
•
Interlamellar substance at the periphery of a mucocutaneous end organ contains
collagen fibers, elastic fibers and other cross banded structures.
•
Act as touch receptors
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59. Unspecialized receptors
• The millions of unspecialzed sensory receptors that supply the skin maybe
categorised as follows:
1. Associated with hair follicles
2. Unassociated with hair follicles
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60. •
These fine nerve endings are visualized by light microscope with specialized stains
of silver salts, methylene blue or cholinesterase
•
Hair follicles are supplied by myelinated sensory nerves that branch extensively
•
One ,myelinated axon may supply many hair follicles and each follicle may in turn
be supplied by several different axons
•
•
These sensory endings are most numerous just below the level of a sebaceous duct.
Free nerve endings are particularly abundant in the glans penis where they are
found in almost every dermal papillae as well as scattered throughout the deeper
dermis .
61

61. • Apocrine and eccrine glands are supplied by unmyelinated
adrenergic and cholenergic nerves
• Apocrine secretion is mainly due to adrenergic activity .
• Cholinergic stimulation is responsible for widespread eccrine
sweating that occurs as a consequence of attempts to regulate high
temperature , whereas adrenergic stimulation eccrine secretion
causes perspiration localized to palms and soles , axillae and
forehead during emotional stress
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62. •
Three principal fiber groups are recognized in cutaneous nerves and are
designated A,B and C. this sequence represents the order of increasing threshold
of sensation and decreasing conduction velocity
Fiber type
A-α
Proprioception
A-β(10 an 14 microns)
sensations of touch vibration and
proprioception
A- γ
sensations of light touch and
pressure
A- δ
sensations of pain, temprature and
physiologic itching
B
Preganglianic
C(less than 5 microns )
•
function
sensations of pain , temprature
and pathologic itching
Type A fibers are myeilinated and C are unmyeilinated
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63. Autonomic nervous system
•
The autonomic nervous system innervates the skin through postganglionic fibres
originating in sympathetic ganglia, and terminating in autonomic plexuses that
supply sweat glands, blood vessels and arrector pili muscles.
•
Histochemically there are two main groups of post-ganglionic nerve fibre in the
skin.
1. Firstly, adrenergic fibres synthesize and store catecholamines and norepinephrine
(noradrenaline).
2. The second major group consists of the cholinergic Fibres containing acetylcholine.
Co-localizing with acetylcholine are ‘secretory’ neuropeptides such as vasoactive
intestinal peptide (VIP) and peptide histidine methionine (PHM).
64

64. •
Autonomic motor nerves control cutaneous vascular tone , pilomotor responses and
pseudomtor activity.
•
The secretory portion of the eccrine sweat glands, myoepithelial cells and nearby
blood vessels are innervated by a basket-weave pattern of nerves, containing
predominantly acetylcholine but also significant numbers of fibres containing
‘secretory neuropeptides’ including VIP ,PHM, neuropeptide Y (NPY), calcitonin
gene related peptide (CGRP), galanin, atrial natriuretic peptide (ANP) and
norepinephrine.
•
Adrenergic fibres mediate strong vasoconstriction and arrector pili muscle activity,
thus diverting blood from the skin, and pulling hairs into the upright position, in
the classical ‘fight or flight’ reaction.
65

65. Merkel cells
• Dicovered by friedrich merkel in 1875
• Also called as tastzellen or touch cells
• Appear in fetal skin by 16th week of gestation
• Cannot be differentiated by melanocyte or langerhan cells by conventional
microscope
• According to histochemical techniques Similar to other end organs of
nerves due to presence of esterases, peptidases, phosphidases and
cholinestrases
• With immuno flouroscence stain merkel cells do not react with anti sera 2
neurofilaments or glial acidic fibrillary protein but react with monoclonal
antibodies to keratin, neural specific enolase
66

66. • Distinctive features under electron microscope :
elecron lucent cytoplasm rich in organelles,
peripheral cytoplasmic processes that interdigitate
with surrounding keratinocytes,
poorly developed desmosomes ,
delicate cytoplasmic microfilaments ,
many membrane bound granules,with dense core,
lobulated nuclei and intra nuclear rodlets
composed of parallel filaments
surrounded by chromatin free zone
67

67. • Supplied by myelinated nerves that , as they near the epidermis loose their
myelin sheaths and continue as unmyelinated axons
• Nerve fibers terminate in flat, miniscus like contacts that are studded along
the base of merkel cells
• The basement membrane of axons fused with basal lamina of epidermis
• Apposition between merkel cells and axon terminals of specialized
membranes creates a zone that exhibits the typical components of chemical
synapse
68

68. 69

69. •
Functions as slow adapting, low threashold touch receptor,
•
Detects mechanical deformities of epidermis via cytoplasmic processes and
desmosomal attachments to neighboring keratinocytes
•
May act to regulate epithelial prolifertaion throught their cytoplasmic contacts with
keratinocytes
70

70. Clinical aspect
•
•
•
•
•
•
•
•
•
•
•
Post- herpetic neuralgia
Neruopathic ulcers
Peripheral neuropathy
Trigeminal trophic syndrome
Heriditary sensory and autonomic neuropathies (type I-V)
Complex regional pain syndrome
Honer’s syndrome
Gustatory hyperhidrosis
Scalp dysaesthesia
Notalgia paraesthetica
Brachioradial pruritis
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71. THANK YOU
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