DD 03-03-14 09-10am Dermal Structures and Diseases - High Flashcards
1
Q
Dermis - structure/position
A
= a tough but elastic support structure that lies beneath the epidermis & above the subcutaneous tissue
= contains blood vessels, nerves, & cutaneous appendages (hairs, sweat glands/ducts, etc.) that are important to the structure & function of skin as an organ
= ranges in thickness from ~1-4 mm, depending upon body location (much thicker than the epidermis, which is paper thin generally)
2
Q
Dermis - functions
A
- provides nutritional support for the avascular epidermis
= provides strength, resiliency & plasticity of skin
3
Q
Dermal zones (2)
A
- Papillary dermis
- located immediately beneath the epidermis - Reticular dermis
- located deeper in the tissue
4
Q
Dermal matrix
A
= term often used to describe the admixture of collagen fibers, elastic fibers & ground substance all of which are synthesized by dermal fibroblasts
5
Q
Adnexal structures
A
- aka skin appendages
= term used by dermatopathologists to refer to the hair follicles, sebaceous glands (oil glands), & sweat glands found in skin that are vital to protection and homeostasis
6
Q
Basic structure of skin
A
- Epidermis = on top, protective
- Dermis = immediately beneath epidermisbut above the fat.
7
Q
Dermoepidermal junction
A
Interlocking dermoepidermal junction
- Epidermal rete (downward projections of epidermis) interdigitate w/ upward projections of dermal papillae
- -> interlocking pattern affords both strength of adherence & increased surface area btwn epidermis & dermis (important as dermis is sole source of nutrients for epidermis)
- -> On hands & feet, interlocking pattern so pronounced that it contributed to epidermal ridges, known better as “fingerprints.”
8
Q
Dermal papillae
A
= taken in total comprise the papillary dermis, while the deeper layer of the dermis is referred to as the reticular dermis
9
Q
Composition of the dermis
A
Composed predominantly of; - collagen fibers - elastic fibers - ground substance All these materials are synthesized by a highly productive, but sparsely populated fibroblasts in the derims
10
Q
Collagen
A
= one of the basic building-blocks of the dermis
= provides essentially all skin’s tensile strength
- Collagen I, III, IV, VII are the main types of collagen important to the skin
= form large eosinophilic (pink) bundles, easily recognized under the light microscope
11
Q
Collagen I
A
- comprises >85 wt.% of adult dermis
- also a major component of bone
12
Q
Collagen III
A
- comprises large part of fetal dermis but is not a major portion of adult dermis
- thought that this difference in expression explains why adult skin forms scars & fetal skin is much more resistant to scar formation
13
Q
Collagen IV
A
- in high concentration in “basement membrane zone,” in the dermoepidermal junction
- also more prominent around vessels, explaining vascular fragility in some forms of Ehlers-Danlos syndrome
14
Q
Collagen VII
A
- found in anchoring fibrils which are used by the body to attach the epidermis to the dermis
15
Q
Structure & Synthesis of Collagen – PROCOLLAGEN
A
- synthesized intracellularly w/in fibroblasts
- consists of 3 separate chains of proteins arranged in an α-helical structure
- –> Under electron microscope, yields characteristic pattern of striations w/ 68 nm intervals
- Chains generally consist of repeated strings of glycine &2 other proteins, forming Gly-X-Y structure (with X & Y usually proline & hydroxyproline)
16
Q
Structure & Synthesis of Collagen – COLLAGEN ASSEMBLY
A
- synthesized collagen proteins are secreted, then assembled into collagen fibrils EXTRA-CELLULARLY
- Several cofactors are required to facilitate this extracellular assembly of collagen fibrils, the most famous of which is vitamin C (ascorbic acid)
17
Q
Vitamin C & Collagen Synthesis
A
- W/out vitamin C, collagen fibers will not attain their final desired strength
Results in: - minor wounds failing to heal
- abnormal hair growth
- blood vessels fragility due to inadequate support from surrounding collagen
- teeth falling out also for lack of surrounding collagen support
Condition used to be common in sailors who went w/out fresh fruits or vegetables on long ocean journeys
= scurvy
= a classic example of an acquired abnormality in collagen production
18
Q
Ehler-Danlos Syndrome (EDS)
A
= a group of related congenital disorders of collagen synthesis
= is a classic example of disordered collagen production due to genetic defects.
- at least 10 subtypes, but all of subtypes share varying degrees of the 4 major clinical features including:
— skin hyperextensibility
— joint hypermobility
— tissue fragility
— poor wound healing
- hyperextensible skin in EDS NOT due to disorder in elastic fibers, but due to abnormally formed collagen
19
Q
Elastic Fibers
A
= provide skin with resiliency (ability of skin to be distorted but then return to original shape)
= much smaller than collagen fibers
= difficult to ID w/ standard staining techniques
= BUT argyrophilic (silver-loving) & can use special silver stains (Verhoff-Van Gieson stain) that will not stain collagen fibers
20
Q
Solar elastosis
A
= most common acquired disorder of elastic fibers
- Over a lifetime, a person accumulates significant sunlight exposure –> degeneration of elastic fibers
- -> These collagen bundles become dystrophic & tend to “clump” and aggregate
21
Q
Solar elastosis & microscopy
A
The abnormal, sun-damaged collagen bundles which aggregate are easy to appreciate on routine microscopy
= basophilic (blue) staining material w/in superficial portions of dermis
IMPORTANT CLUE UNDER THE MICROSCOPE that informs you instantaneously that the tissue:
- is from a middle-aged or older person
- was taken from a sun-exposed skin site
- –> helpful in study of sun-induced neoplasms
22
Q
Pseudoxanthoma elasticum (PXE) - pverview
A
Classic example of inherited elastic disorder
Caused by mutation in gene encoding part of the “multidrug resistance complex”
- this complex is responsible for pumping compounds out of cells
- when mutated in cancerous cell, may result in resistance to certain forms of chemo
- not well-understood how this MDR defect leads to disease
23
Q
Pseudoxanthoma elasticum (PXE) - pathogenesis
A
Gene mutation in “multidrug resistance complex”
Elastic fibers of dermis become enlarged, tangled, & calcified
—> characteristic purple-blue color upon routine histological examination
Clinically, skin of flexural areas of body maintains “plucked chicken” appearance
= clue to Dx
Elastic fibers of blood vessels are also damaged
—> HTN, bleeding disorders (esp. in eye)
24
Q
Ground Substance defn.
A
= general term for a gelatinous material intercalated between & amongst collagen bundles, elastic fibers, and appendageal structures of the dermis
= “pie filling” made of long chains of sugar molecules (glycosaminoglycans)
25
Ground Substance - components
Consists principally of 2 glycosaminoglycans:
- hyaluronic acid
- dermatan sulphate
Also, fibronectins
= serve as "glue"
26
Glycosaminoglycans
= complex molecules made up of proteins & sugars
| - capable of absorbing >10,000x their weight in water
27
Ground substance - action
Glycosaminoglycans + Fibronectins = gel-like mass functions like a sponge
= under pressure it can expel bound water
= then it can take it up again
---> helps to facilitate nourishment of overlying epidermis by easily allowing a water-based environment for diffusion
28
Ground substance - destruction / renewal
- In contrast to collagen fibers, which are renewed mostly when necessary (injury), ground substance is constantly being destroyed and then renewed
- destroyed by enzymes like hyaluronidase
- renewed via production from fibroblasts
29
Restylane
= an excellent example of ground substance
= cosmetic filler product
= simply pure hyaluronic acid produced via recombinant (yeast + plasmid) technology
Cosmetic dermatologists place this material under skin to augment the tissue & remove lines/wrinkles
Well-suited for this for two reasons:
1. It is a natural substance that is already present in skin & it does not engender immune response
2. It absorbs a tremendous amount of water & amplifies the augmentation
Just like endogenously produced hyaluronic acid, Restylane is broken down by tissue hyaluronidases and it is not a permanent augmentation.
30
Blood vessels in skin (cutaneous vascular system)
Epidermis has no blood supply
- derives its nourishment via diffusion of materials through ground substance of dermis
Important also for:
- Wound healing
- Control of homeostasis
- Modulation of inflammation/leukocyte trafficking
31
Blood vessels of the dermis
Divided into superficial & deep vascular plexi
32
Wound healing & Cutaneous Blood System
<–- the endothelium (single-cell lining on innermost surface of vessels) elaborates important cytokines including endothelial growth factor
33
Control of homeostasis & Cutaneous Blood System
<-- via structure called Sucquet-Hoyer canal
= smooth muscle derived valve-like structure
- blood may be directed toward skin during overheating, or away from skin in hypothermia
34
Modulation of inflammation/leukocyte trafficking & Cutaneous Blood System
may exit vasculature to fight infection in skin & soft tissue
35
Capillary structures of the skin
- Contained in uppermost portion of papillary dermis (suprapapillary plate)
- involved in Auspitz sign & Verruca
36
Auspitz sign
- when thickened scales of psoriasis are forcefully removed, pinpoint bleeding is noted at area of removal
- In truth, sudden removal of epidermal scale leads trauma to capillaries of uppermost papillary dermis
- --> pin-point bleeding observed
* Please note the scale of psoriasis is entirely w/in the epidermis, and Auspitz sign does not violate the rule that there are no blood vessels in the epidermis!
37
Verruca
= aka warts
= benign, virally induced neoplasms (growth) that require increased blood supply to support virally-proliferating cells
- These proliferating vessels may be IDed as brownish, thrombosed capillary structures in the center of the verruca
- Presence of central thombosed capillary loops is a reassuring sign that the lesion is in fact a wart
38
Leukocytoclastic vasculitis - overview
= common disease involving post-capillary venules
Some type of insult --> immune complexes form & deposit in vessel walls, causing inflammation (Type III immunopathology)
- Most common cause is Strep infection, but may be medicine allergies, cryoglobulin production from hepatitis C, or a myriad of other conditions
39
Inflammation in leukocytoclastic vasculitis
Neutrophils attach to vessel wall & degranulate
---> damage & extravasation of RBCs into dermis
Leukocytoclasia = this process of fibrinoid deposition in vessel walls, w/ infiltrating neutrophils & neutrophil debris
40
Clinical manifestation of leukocytoclastic vasculitis
“Palpable purpura”
- palpable b/c of the inflammation
- purpuric (& non-blanchable) due to extravasation of RBCs into dermis
(if vessels were simply dilated, but still intact, pressure applied to skin would redness go away)
41
Disruption to dermal vascular plexi --->
---> necrosis and sloughing of the epidermis
B/c epidermis is completely dependent upon dermis for nutrition & support
<--- may be caused by any process which corrupts the dermal vascular plexi, whether vasculitis (inflammation), vasculopathy (mechanical occlusion) or otherwise, if prolonged and/or severe
42
Nervous tissue of the dermis
```
= function similar to nervous tissue in other areas of the body, specifically to inform & protect
Most important structure:
- Meissner's corpuscles
- Free nerve endings
- Pacinian corpuscles
```
43
Free nerve endings
- pass through upper dermis to terminate at dermoepidermal junction
- thought to be involved in sensation both of pain & of itch (pruritus)
44
Pruritus - sensation's travels to the brain
- originates in free nerve endings near dermoepidermal junction
--> conducted centripetally by afferent nerves entering spinal cord via dorsal roots
(small, unmyelinated C fibers w/ slow conduction)
After entering spinal cord, primary neurons synapse w/ secondary neurons
- --> axons cross to opposite side of body
- --> travel cephalad
Sensations arrive at cerebral cortex
- --> body can ID location, nature, intensity, etc.
- --> secondary activation of pre-motor areas of brain
- --> probably synaptic connections to motor area of cortex (which prepare for scratching)
45
Pruritis & Pain
- For a long time it was thought that itch represents a weak pain
- Debated whether same nerves conduct itch & pain
- Now recognized that itch & pain are different & independent sensory modalities, even if local anesthesia or cutting of sensitive nerves may abolish both
46
Observations that led to belief that receptors / transmission apparatus for itch & pain differ:
- itch elicits scratching, while pain yields withdrawal
- morphine relieves pain but can produce pruritus
- heating of skin to 41°C relieves itch but not pain
- removal of epidermis & upper dermis abolishes pruritus, but not pain
47
Pacinian corpuscles
= resemble an onion in cross-section (see pic in notes)
- involved in pressure & vibratory sensation
- most concentrated in genital area
48
Meissner’s corpuscles
= resemble pine-cone (see pic in notes)
- involved in fine touch & tactile discrimination
- in highest concentration on distal aspects of digits, esp. pulps of the fingers
49
Insensitivity to pain
- rarely congenital; usually w/ co-exisiting anhidrosis (inability to sweat)
Caused by mutations in neurotrophic tyrosine receptor kinase 1 (NTRK1) gene
--> encodes for nerve growth factor receptor (NGFR)
- Such children suffer from enormous number of injuries to skin & integument, including corneal erosions in >70%
- cannot feel common danger signs which normally lead to protective responses
- must be examined several times a day for cuts, scrapes, sand stuck in the eye, materials in the skin & other perils common to small children
50
Areas & Types of hair
- Nearly entire body surface is covered by hair
- Areas specifically NOT covered w/ hair include palms, soles, glans penis, and labia minora
Two different types of hair:
- Terminal Hairs
- Vellus Hairs
51
Terminal Hairs
- large, thick, coarse, pigmented
- on scalp, a man’s beard area & possibly chest / back, pubic area
- begin deep in dermis at/near dermal-subcutaneous junction
52
Vellus Hairs
- small, fine, apigmented
- located diffusely on body
- represented the types of hairs often on the ear, the lateral face of women, and the body in general
53
Anatomy of the average hair follicle
Arrector pili muscle
Sebaceous gland
Common to divide hair follicle into thirds
1. Infundibulum = upper third
2. Isthmus = middle third (from sebaceous duct to insertion of arrector pili)
3. Matrical area = lower third
(see pic in notes)
54
Arrector pili muscle
= small, smooth-muscle
| - when activated by autonomic nervous system, brings hair into more erect position (“goose bumps”)
55
Sebaceous glands
- secrete oily substance called sebum onto hair & indirectly onto skin surface
- more prominent in oily” areas of body (face, neck, chest, upper back)
56
Basic embryology of dermal structures
Follicular unit is derived from primitive ectodermal germ (PEG), whose development is an excellent examnple of embryonic induction
57
Development of PEG via embryologic induction
Induction
= means underlying mesenchyme (which will become dermal papillae of hair) induces formation of PEG in overlying fetal skin
Several bulges of PEG are significant:
- Lower bulge – attachment for arrector pili
- Middle bulge – sebaceous gland
- Upper bulge – apocrine gland (axillae, groin, or other areas with apocrine glands)
58
Androgenic alopecia overview
- aka androgenetic alopecia, or pattern baldness
= common “illness” which illustrates some of the important properties of hair growth
Scalp hairs are terminal hairs (thick, pigmented, deep in dermis/subcutis)
In androgenic alopecia, hairs become miniaturized, finer & lie higher in the dermis
---> Ultimately, resemble vellus hairs
59
Normal adult scalp - growth/rest phases of hair
Scalp of adult contains >100,000 hairs
- ~85% are in anagen (growth phase)
- ~10-15% in telogen (resting phase)
- remainder (1-5%) in catagen (transition phase btwn anagen & telogen)
60
Androgenic alopecia - men vs. women patterns
MEN: --> classic fronto-temporal or postero-occipital balding
WOMEN: --> thinning of hair on crown area
Nearly 50% of both sexes are affected to some degree, though not as widely discussed in women
61
Androgenic alopecia - process & treatment
= not understood completely, but known that conversion of testosterone to 5-dihydrotestosterone is important in promoting this change
- Finasteride (5-α-reductase inhibitor) blocks this conversion & is used in treatment of male pattern baldness
- Both men & women also treated w/ minoxidil, a drug known to promote anagen phase of hair growth
Neither treatment is entirely satisfactory
62
Sebaceous glands - overview
= oil-secreting glands located predominantly in oily” areas of the body including scalp, face, neck, upper chest, and upper back
= the classic example of a holocrine gland
- persons vary widely with respect to basal level of sebum (oil) production
- sebum secretion is dependent on sex hormone
- these glands do not appear to be innervated by the autonomic nervous system, but exact mechanism governing sebum production is poorly understood
63
Holocrine gland
= method of secretion involved entire sebocytes (sebaceous gland cells) being secreted & in the process breaking-down to extrude the contents
64
Sebaceous gland disorders - timing
As sex hormones are requisite to sebum secretion, disorders associated w/ the sebaceous glands (like acne) are not prevalent until after adrenarche (puberty)
65
Medication to decrease sebum production
Isotretinoin (Accutane)
= one of the only meds to significantly decrease sebum production
= rather toxic
= decreases sebum production by up to 90%, often permanently
= mechanism largely unknown
66
Acne
= ubiquitious disorder of the pilosebaceous unit
- multifactorial (no single cause)
Plugging of ostia of pilosebaceous unit by hyperkeratotic debris
--> accumulation of oil w/in
Propionibacterium acnes (normal commensal bacteria) then begins to multiply
--> converts sebum to pro-inflammatory fatty acids
Pilosebaceous unit ruptures
---> characteristic inflammatory “zit”
67
Pilosebaceous unit
the combined hair follicle and oil glands
68
Blocked pores
Blocked pores themselves constitute comedones, that are further classified to be:
- open - “black heads”
- closed - “white heads”
69
Eccrine glands - overview
= aka “general sweat glands”
- Primary function is thermoregulation
- --> accomplished through cooling effects of evaporation of this sweat on skin surface
- classic example of merocrine secretion
70
Location of eccrine glands
- located throughout the body b/c so important in temperature regulation
- most numerous on forehead, upper cutaneous lip, and palms/soles
71
Merocrine glands
secrete WITHOUT either the apocrine blebbing, or holocrine shedding
72
Embryologic development of Eccrine glands
Develop from an eccrine germ
| - DISTINCTLY different from primitive ectodermal germ of the follicular unit
73
Three main components to the eccrine gland
- Coiled secretory portion deep in the dermis
- Intradermal duct (coiled & straight duct)
- Intraepidermal portion (called the acrosyringium)
(see pic in notes)
74
Eccrine sweat - composition
- water
- sodium
- potassium lactate
- urea
- ammonia
- serine
- ornithine
- citrulline
- aspartic acid
- heavy metals
- organic compounds
- proteolytic enzymes
75
Regulation / Initiation of Sweating
CRITICAL TO RECOGNIZE that
- even though sweating is mediated by sympathetic portion of autonomic nervous system
- it is triggered via acetylcholine secretion
Acetylcholine
= chemical otherwise associated w/ the parasympathetic nervous system
76
Results of Sympathetic vs. ACh control of sweating
Control by sympathetic nervous system:
- explains sweating under stress
Mediation via acetylcholine (NT often associated w/ parasympathetic responses)
- explains why certain drugs that increase acetylcholine levels result in increased sweating despite parasympathetic response systemically
Furthermore, this is why atropine poisoning (a drug which has anticholinergic activity) results in a warm, flushed, but anhidrotic (non-sweating) patient.
77
Anticholinergics / "Parasympathetic" drugs & Sweating
Drugs that increase ACh despite their parasympathetic action
- Neostigmine
- Physostigmine
- Organophosphate-based pesticides
- --> increase sweating despite parasympathetic systemic response
Atropine poisening
= anticholinergic activity
--> results in warm, flushed, but ANHIDROTIC (non-sweating) patient
78
Apocrine Glands - embryological development
= outgrowths of upper bulge of primitive ectodermal germ (fetal structure yielding the follicular unit)
79
Location & timing of apocrine glands
- only in axillary & anogenital area
- present at birth, but remain small & nonfunctional until after puberty
- At puberty, hormonal stimulation causes apocrine glands to become functional
- Glands respond mainly to sympathetic adrenergic stimuli initiated by emotional stress
80
Specialized variants of apocrine glands
- Moll's glands on the eyelids
- Cerumen (ear wax) glands of external auditory canal
- Lactation glands of the breasts
81
Apocrine gland structure
- coiled portion deep in the dermis
- straight duct traversing dermis & emptying into hair follicle
Coiled gland
= one layer of secretory cells around a lumen that is ~10x the diameter of its eccrine counterpart
= surrounded by contractile myoepithelial cells
Straight duct
= runs from coiled gland to hair follicle
82
Predominant mode of apocrine secretion
Decapitation
| = process where apical portion of secretory cell cytoplasm pinches-off & enters lumen
83
Apocrine sweat
Consists mainly of sialomucin
= odorless initially
= as apocrine sweat comes in contact w/ normal bacterial flora on skin surface, odor develops
More viscous & produced in smaller amounts than eccrine sweat
84
Function of apocrine glands
Exact function is unclear
| Likely represent scent glands
85
Chromohidrosis
= a disorder of apocrine glands (exclusively apocrine in origin)
- literally translates into “colored sweat”
- mostly reported on face, axillae, & breast areola (though apocrine glands are also in genital region)
Lipofuscin pigment
= responsible for colored sweat
= produced in apocrine gland
= its various oxidative states account for characteristic yellow, green, blue, or black secretions observed in apocrine chromhidrosis
~10% of people W/OUT true chromohidrosis have colored sweat which is regarded as minor, acceptable, and within the normal range
No fully satisfactory cure or treatment.
86
Apoeccrine Glands
= hybrid sweat glands found chiefly in axilla
- may play role in axillary hyperhidrosis
Apocrine features:
- larger diameter portion, similar to apocrine gland
Eccrine features:
- small diameter portion, similar to eccrine gland
- respond mainly to cholinergic stimuli
- ducts are long & open directly onto skin surface
May constitute up to 45% of sweat glands found in axillary region in some pts
Secrete nearly 10x as much sweat as eccrine glands, making them by far the most productive gland in the dermis.
87
Localized Hyperhidrosis - defn. & source
= focal excessive sweating
| = may be eccrine (esp. w/ "clammy hands” or “sweaty feet) or may apoeccrine (in axilla)
88
Patterns in Localized Hyperhidrosis
- Positive family Hx in 30%–50% of pts
Generally do not sweat during sleep
- therefore, most consider it a disease of autonomic dysfunction
89
Normal vs. Hyper- Hidrosis
Normal (no strict defn.)
- <1 mL/m2 of sweat production per minute by eccrine glands at rest & room temp
Hyperhidrosis
- For practical purposes, any degree of sweating that interferes with ADLs should be investigated
90
Qualitative documentation of perspiration
= for purposes of tracking treatment
1. Apply iodine solution (1%–5%) to dry surface
2. After a few seconds, sprinkle starch over same area.
3. Starch & iodine interact in presence of sweat
- --> purple-black sediment
- Purple area IDes duct of sweat gland
91
Initial treatments for focal hyperhidrosis
Focus on antiperspirant solutions or anticholinergic meds, which decrease eccrine & apoeccrine output
92
Subsequent treatments for focal hyperhidrosis
- Thoractomy w/transaction of sympathetic nerve trunk
| - Botulinum toxin A (Botox)
93
Thoracotomy w/ transaction of sympathetic nerve trunk to treat Focal Hyperhidrosis
- Often wanted by patient, while physicians are often reluctant
- High incidence of mild to severe compensatory hyperhidrosis (new area of increased sweating), usually involving trunk & lower limbs
- -> occurs in up to 86% after thoracotomy
94
Botulinum toxin A (Botox) to treat Focal Hyperhidrosis
- When injected into dermis & subcutis, blocks release of ACh from nerves
- --> thereby blocks stimulus for sweat production
- Effective
- Expensive (generally not covered by insurance)
- Transient
- --> limited use
