5. ECCRINE GLANDS
Merocrine glands
Total number-2 to 5 million
LOCATION-located everywhere on the human skin
and are especially dense on the palms,soles,
forehead, and upper limbs but not on the lips,nail
bed,external auditory canal ,clitoris and labia
minora
Eccrine sweat glands are present in densities of
100–600/cm
weight of the eccrine glands totals 100 g.
They play a major role in THERMOREGULATION and
produce approximately 1 litre of sweat per hour
during moderate exercise
5
6. DEVELOPMENT
Atrichial
Embryologically, sweat glands are derived
from a specialized down‐growth of the
epidermis at about the third month of
intrauterine life on the palms and soles and in
the axillary skin in the fifth fetal month, and
finally develop over the entire body by the
sixth fetal month
6
7. Sweat glands are morphologically normal at
birth but may not function fully until about 2
years of age.
No new eccrine glands develop after birth.
7
10. The secretory coil is about 60–80 μm in
diameter and 2–5 mm in length
Single layered with 3 distinct cell types
1.clear cells(secretory)
-large, pyramidal
-apical aspect bears numerous irregular
microvilli
- base rests on basal lamina or on
myoepithelial cells. Highly folded(basal
labyrinth), show marked Na,K-ATPase
activity.
10
11. contents: lipofuscin
granules, glycogen,
mitochondria. Apical
region has glycogen
free and lipid free
vacuoles.
-nucleus is rounded
and moderately
euchromatic.
-basolateral
membrane: site of Na
pump and active
transport of ions during
sweat secretion.
11
12. 12
2.Mucoid cells
-small dark cells
-cuboidal or inverted pyramidal
-occupy all luminal surface
-secrete PAS positive glycoprotiens
3.Myoepithelial cells
-lie on basement membrane, wedged
between the bases of clear cells
-filled with mass of myofilaments
-functions: mechanical support,
propelling the sweat towards the surface.
-respond to cholinergic stimuli
13. 4)Hyaline basement membrane
-present peripheral to myoepithelial cells
-contain collagen fibres
-separate the glandular epithelium from
connective tissue of periadnexal dermis.
13
15. Intradermal sweat duct
Two layers of cells
1.Inner ring of luminal cells
2.Outer ring of basal cells- rich in mitochondria,
strong Na,K-ATPase activity, ductal Na absorption
3These cells are Small, cuboidal and basophillic cells.
4.Pseudocuticle- dense layer of tonofilaments near
luminal membrane gives rigidity to periluminal
region, assures patency
5. unlike the secretory portion, the ductal portion has
no peripheral hyaline basement membrane zone.
The proximal(coiled) intradermal duct appears to be
functionally more active than the distal (straight)
portion.
15
17. Runs spirally from base of rete ridge to the
surface.
Single layered inner luminal cells and 2 to 3
rows of outer basal cells.
Has desmosomes and occasionally
melanocytes.
Keratohyaline granules become apparent in
the ductal cells in the mid epidermis . Prior to
keratinization, the acrosyringeal lumen is lined
by an eosinophilic cuticle.
17
18. 1)Thermoregulation-Each sweat gland
during peak secretory activity may produce as
much as 20 nL per minute . One litre of
evaporated sweat removes about 585
kilocalories of heat from the body.
During heat stress, a maximum sweat rate of
3–4 L/hour can be attained, and a rate of 1–1.5
L/hour can be maintained
18
19. 2)Moisten skin of palms and soles- Improves Grip
3)Organs of excretion-This function of the sweat
gland is instrumental in delivering such drugs as
griseofulvin and ketoconazole to the stratum
corneum by passing the slow diffusion pathways
across the epidermal cell layers
4)Regulation of desquamation-lactate in sweat
regulate desquamation of stratum corneum.so
lactic acid preparation is beneficial in retension
hyperkeratotic disorder
19
20. 5)Produce biological active substances
-proinflammatory
-mitogenic effect
-epidermal immune response
The presence in sweat of various biologically active
compounds such as interleukins and proteolytic
enzymes raises the possibility that eccrine sweat can
be potentially proinflammatory and is capable of
modifying various dermatosis
Eccrine sweat may also possibly have mitogenic
effects for diseases such as psoriasis.
The demonstration of HLA-DR on the human
acrosyringium has led to the suggestion that the
eccrine epithelium, through its interaction with certain
molecules, might play an active role in epidermal
immune responses.
20
21. It has been shown that the sweat of patients with atopic
dermatitis contains specific IgE antibodies to inhalant
allergens, the levels of which correlate with the severity of the
dermatitis.
It is also suggested that sweating may possibly facilitate
percutaneous sensitization of atopic individuals to specific
antigens.Acrosyringeal keratinocytes have been shown to
express S100 protein26 and major histocompatibility class II
antigens.
Eccrine glandular and ductal epithelium also express epithelial
membrane antigen and carcinoembryonic antigen.
The acrosyringium and the cells of the intradermal sweat duct
show positive staining for angiotensin 1.
21
22. INNERVATION OF ECCRINE
SWEAT GLAND
Postganglionic sympathetic fibers which are
the slow conducting nonmyelinated C fibers.
Acetylcholine is the principal neurotransmitter.
VIP and Norepinephrine promote glandular
growth and protect the cells from an abnormal
increase in intracellular Ca concentration by
maximizing intracellular cAMP accumulation
during cholinergic stimulation.
22
23. SYMPATHETIC SUDOMOTOR
PATHWAY
Central Autonomic network preganglionic effector
pathways , sympathetic ganglia, postganglionic
sympathetic fibers, periglandular neurotransmitters ,
glandular receptors.
Centrally there is Nucleus Tractus Solitarius which is
controlled by neocortical regions, nuclei of the forebrain,
higher brainstem, diencephalon,and the cerebellum.
Axons from NTS form reticular formation in ventral
medullary region interomedial neurons in the lateral
horn of spinal cord preganglionic sympathetic white
ramus communicantes synapse in the sympathetic
ganglia postganglionic fibers gray rami
communicantes peripheral mixed nerve trunks sweat
glands.
Face is supplied by T1- T4, upper limbs by T2 - T8 , trunk
by T4 – T12, and lower limbs by T10 – L2.
23
24. Types of sweating
Thermoregulatory-hypothalamus. Mostly involves the
upper trunk and face
Emotional-frontal or premotor area. Mostly involves
palms and soles
Gustatory-medullary nuclei.Mostly involves lips forehead
and nose
Other factors that may modify the quality and quantity of
sweat in the presence of an intact sympathetic nerve
supply include local temperature changes, glandular
size, periglandular vascular activity, axon and spinal
reflexes, plasma electrolyte concentrations, and
hormones
24
25. 25
CENTRAL CONTROL OF
THERMOREGULATORY SWEATING
Thermosensitive neurons of hypothalamus sense both
internal as well as peripheral temperatures and initiate
appropriate thermoregulatory responses.
The effect of a rise in core temperature is nine
times more efficient than the same rise in skin temperature in
stimulating sweating. An increase in core temperature
activates cooling
mechanisms including sweating, panting and vasodilatation.
Conversely,
cooling promotes heat‐preservation mechanisms such as
vasoconstriction and shivering
Heat sensitive neurons -preoptic and anterior hypothalamus
,activated by rise in central and skin temperature.
26. Cold sensitive neurons -posterior
hypothalamus,activated by extrahypothalamic cooling or
warming.
When the body temperature is increased, sweating
occurs at and above a certain core temperature called
Temperature Set Point(TSE).
If the skin temperature is constant ,the rate of sweating is
linearly related to core temperature above TSE.
If the skin temperature also rises, sweating is induced at
a lower temperature as though TSE has been lowered.
TSE is also influenced by alterations in blood osmolarity
Efferent pathway from the hypothalamus includes the
medulla, lateral horn of the spinal cord and sympathetic
ganglia
26
27. LOCAL CONTROL
From the sympathetic ganglia non‐myelinated
C fibres pass to eccrine sweat glands ending
at many cholinergic terminals and a few
adrenergic terminals. vasoactive intestinal
polypeptide, calcitonin gene‐related peptide
and nitric oxide play some role in the control
of eccrine sweating.
Sweat coils contain androgen receptors , and
androgens may be at least partly responsible
for the increase in sweating around puberty
and for the greater sweat activity in males.
Other factors may modify the quantity and
quality of sweat in the presence of an intact
sympathetic nerve supply
27
30. Stimulation of sympathetic neuronal outflow
↓
Release of Ach which binds to receptors on secretory cell
membrane
↓
Increase in cytosolic calcium
↓
Activation of K and Cl channels and efflux of KCl
↓
Decreased cytosolic ionic concentration
↓
activation of Na K Cl cotransporters
↓
Increase in cellular Na concentration
↓
activation of Na+K+ATPase
30
31. ↓
For each ATP hydrolysed, 3Na ions are pumped out in
exchange for 2K ions
↓
After each cycle, 5K ions diffuse out of the cell generating a
membrane potential
↓
Na and K recycle across the basolateral membrane but all 6 Cl ions
which moved into the cell pass through the Cl channels into the
lumen generating a lumen negative potential
↓
Attracts six Na ions and water across the intercellular junctions
↓
Primary sweat
↓
Ductal reabsorption of Na, Cl and HCO3 through Na+K+ATPase
↓
Na passively enters the cell from the ductal lumen through the Na
channels on the luminal membrane
31
32. ↓
pumped out across the basal membrane by the sodium
pump in exchange for K
↓
Cellular K leaks out passively through K channels,
generating a membrane potential, and K then recycles
↓
Cl follows passively down the gradient through Cl
channels at both the luminal and basal membranes and
across the intercellular junctions. The sweat duct may
also reabsorb HCO3 either directly or via H ion secretion
↓
Final sweat
32
33. Sweat is a colorless, odourless hypotonic solution
with a specific gravity of about 1.005 and basic
similiarity to plasma .The composition of sweat
varies greatly from person to person, time to time
and site to site.
The most important constituents are sodium,
chloride, potassium, urea and lactate. Sweat is
hypotonic and this is largely due to reabsorption of
sodium in the duct from which it is derived.
Aldosterone can increase ductal sodium
reabsorption and in Addison disease high sweat
sodium can be demonstrated (70–80 mmol/L).
Antidiuretic hormone may reduce sweat rates in
humans, but it also induces local vasoconstriction.
33
34. Sweat contains:
1.SODIUM- concn is lower than plasma and
directly proportional to sweat rate. sweat Na
concentration is low (10–20 m mol) but increases
with increasing sweat rates to plateau at around 100
m mol
2.POTASSIUM -The sweat K concentration in the
primary sweat is 5–6 m mol but the concentration is
slightly higher in the final sweat.The sweat
potassium are higher than plasma and is inversely
proportional to sweat rate.
3.CHLORIDE- as sodium.
34
35. 4.BICARBONATE-When measured under a constant
CO2 pressure (5% pCO2),sweat pH is approximately
7.2–7.3 in the primary sweat with an HCO3
concentration of 14 m mol. The pH of the final
sweat,however, is about 5.0 at lower sweat rates with
the HCO3 concentration close to zero and at higher
sweat rates, the pH is 6.5–7.0, indicating that the duct
is capable of acidifying sweat.
5.LACTATE-The sweat lactate concentration usually
depends on the sweat rate and varies from 30–40 m
mol at low sweat rates and 10–15 m mol at higher
sweat rates. This is in contrast to a plasma lactate
concentration of 2 m mol implying that the sweat
lactate is derived mainly from the sweat gland as an
end product of glycolysis.
35
36. 6.UREA-same or slightly higher than plasma
7.AMMONIA-20 to 50 times more than plasma
8.AMINO ACID-same or slightly lower than
plasma.
9.PROTEINS-glycoproteins and
mucopolysaccharides
10.PROTEOLYTIC ENZYMES-Glandular
kallikrein, kininase, C1 esterase, urokinase,
cysteine proteinases and their endogenous
inhibitors
11.Epidermal Growth Factors
12.GLUCOSE
13.OTHERS-HISTAMINE, PROSTAGLANDIN
36
37. Other Ingredients in Sweat
Normoglycemic individuals excrete only small
amounts of glucose in the sweat (0.2–1.5 mg/dl).
But uncontrolled diabetics may excrete more
glucose in the sweat.
The pyruvate concentration in sweat ranges from
0.2–1.6 m mol.
organic compounds reported to be excreted in
sweat include histamine, prostaglandins,
amphetamine-like compounds, and
various chemicals such as clofazimine,
griseofulvin,ketoconazole, other azoles, sulfa
drugs, iodides, phenytoin,phenobarbitone,
carbamazepine, cytotoxic agents, and,ethanol
37
38. To test the distal sympathetic axonal integrity and to
determine the cholinergic receptor function of sweat
glands in a test site, a local pharmacological sweat
test (intradermal injection or iontophoretic
application of 0.01% pilocarpine or methacholine) is
most useful.
A highly quantitative and reproducible but
technically complex test is QSART (Quantitative
sudomotor axon reflex testing).A 10% solution of
acetylcholine is iontophoresed into the skin using a
2 mA current for five minutes. Sweat output is
recorded in the test site by “circular cells” that
detect sweat. A galvanic skin resistance test is an
easy but not a dependable method of sweat testing. 38
39. Visualization of individual sweat droplets induced by
pharmacological agents or by other measures can be achieved
in several ways.
The one step iodine starch method is the most simple and
suitable test for a clinical setting. This involves spraying
iodinated starch powder (prepared by adding 0.5–1 g of iodine
crystals to 500 g of soluble starch in a tightly capped bottle and
letting it stand for a week) with large cotton balls or a powder
puff or an atomizer in the test skin site.
The iodine starch reaction is also used for obtaining sweat
imprint papers,although such imprints can be obtained only
from flat body surfaces or on small areas of skin.
Thermal sweating may be induced by appropriate heating
devices or in a sauna. The body core temperature must rise by
at least 1°C to induce a moderate amount of sweating for
visualization
39
40. Some methods useful for determining the maximal
sweat rate include water vapor analyzer
(applicable only to local pharmacological
sweating),the filter paper method, collection of
sweat droplets under mineral oil, and the
anaerobic bag method.
A skin biopsy may be helpful to determine the
absence or atrophy of sweat glands in diseases
such as anhidrotic ectodermal dysplasia or
scleroderma and in disease like congenital
sensory neuropathy.
In vitro sweat induction from isolated sweat gland
and microcanulization of sweat ducts or secretory
cells are the other procedures that give valuable
information about sweat glandular function under
different test conditions
40
41. 41
ADRENOCORTICAL DISORDERS
Cushing’s syndrome and hyperaldosteronism
the concentration of sodium and chloride in
sweat decreases and that of potassium
increases.
Addison’s disease and hypopituitarism the
sweat sodium concentration may be as high as
70–80 m mol due to reduced sodium
reabsorption
42. Cystic Fibrosis-An elevated sweat sodium concentration
is the most reliable diagnostic test for cystic fibrosis. Sweat
potassium concentration also increases.
Other disorders-A)Increased Electrolytes
bronchiectasis , emphysema,diabetes mellitus, nephrogenic
diabetes insipidus, glycogen storage disease (type I),
adrenogenital syndrome, familial ectodermal dysplasia with
sensorineural deafness, myxedema,miliaria, and in
unacclimatized individuals exposed to heat. An increase in
sweat potassium has been observed in infants with
apparent life threatening events like “near miss sudden
infant death syndrome”
B)DECREASED ELECTROLYTES-Decreased electrolyte
levels are observed in thyrotoxicosis, nephrosis, cirrhosis,
aldosteronism, and Cushing’s syndrome
42
43. INCREASED UREA EXCRETION (URHIDROSIS)-The urea
concentration of sweat increases with increasing serum
levels of urea
Increased Calcium Excretion-Interstitial calcinosis
without evidence of any parathyroid dysfunction may
result in increased excretion of calcium in sweat
Abnormal Amino Acid Excretion- Excretion of phenyl
pyruvic acid and phenyl acetic acid in sweat produces a
characteristic musty or sweaty “locker room towel” odor
in phenylketonuria. Branched chain amino acids, valine,
leucine, isoleucine, and their alpha keto analogs
accumulate in the urine and sweat of patients with
maple syrup urine disease and produce a malty, caramel-
like, or maple syrup-like odor.
43
44. Accumulation of alpha hydroxybutyric acid and
phenylpyruvic acids as well as
methionine,phenylalanine, and tyrosine in sweat
and urine carry an odor that is suggestive of
decayed malt or hops, in oasthouse syndrome.
Excretion of 1 keto alpha methyl butyric acid in
sweat and urine produces a strong, fishy, fruity
or rancid butter-like odor in patients of
hypermethioninemia.
High levels of isovaleric acid in the sweat and
urine induce a cheesy or sweaty feet odor in
patients of isovaleric acidemia.
44
46. epitrichial
Small amount of cytoplasm is pinched off during
secretion.
Location-axillae, areola, periumbilical, perianal and
cicumoral areas, prepuce, mons pubis and labia minora.
modified apocrine galnds-ceruminous glands of
external ear canal, moll’s glands of eyelid and the
mammary glands.
Development-from primary epithelial germ cells or hair
germs, together with hair and sebaceous glands.
Dormant postnatally, become functional around
puberty.
Development is dependent on sex hormones.
46
48. Secretory coil
Simple convoluted tubular structures.
Situated in lower dermis or in subcutaneous fat.
Secretory cells-single layered, cuboidal or columnar
cells, eosinophillic cytoplasm, contains large PAS
positive and diastase resistant granules around
nucleus.
Myoepithelial cells
Hyaline basement membrane zone
Ductal portion
Straight and short.
Double layered basophillic cuboidal cells and
perluminal eosinophillic cuticle.
Empties into the infundibulum of hair follicle above
the entrance of sebaceous duct.
48
51. APOCRINE SECRETION
Human apocrine sweat is a protein rich, milky,
or viscid, colourless secretion when it is first
formed composed of cholesterol,triglycerides
and fatty acids.
Bacterial decomposition is responsible for the
characteristic odour.
Mechanism-an apical cap and a dividing
membrane are formed initially. The apical cap
is then detached and discharged into the
lumen of the gland(Apocopation)
Apocrine glands respond to emotional stimuli
that promote sympathetic discharge.
51
52. 52
Stimulated humorally by circulating catecholamines.
With ageing apocrine glands tend to accumulate
lipofuscin and undergo attenuation. Reduced body
odour in aged.
53. FUNCTION:
Concerned with human behavioral and sexual
interaction by pheromones- androstenone and
androsterol
Innervation
Post ganglionic sympathetic fibres that have
adrenalin
Apocrine sweat is clear and odourless
Bacterial decomposition leads to a specific odour
(bromhidrosis)
Secretion of pigmented sweat(yellow , green or black)is
known as chromohidrosis
53
54. Mixed sweat glands-share some
morphological and functional features of both
eccrine and apocrine sweat gland.
Location-adult human axilla.
Constitute less than 10% of all glands found in
adult human axilla.
larger than eccrine and smaller than apocrine
glands.
Development-from eccrine glands or eccrine
like precussor glands.
54
55. Structure-
Secretory portion-irregularly dialated with some
cells resembling clear cells of eccrine glands and
some like cuboidal or columnar cells of apocrine
glands.
Ductal portion-long, opens on to the skin surface.
Functions- like eccrine glands yields copious
serous sweat in response to both cholinergic and
adrenergic stimulus. Significantly contribute to
the overall axillary sweating in adults.
55
57. Sebaceous glands, functional
from their formation are small
sacculated glands lodged in the
substance of the dermis,
usually opening into hair
follicles and secreting an oily
or greasy material composed in
great part of fat which softens
and lubricates the hair and skin.
57
58. 10-12th week- Hair germs develop
In the following weeks- follicles extend downward into dermis
and develop 3 bulges(epithelial placodes) on their
undersurface
The middle bulge forms the sebaceous gland
58
59. Sebaceous glands form part of
pilosebaceous unit and development
begins with of development hair follicle
Upper bulge involutes or forms an
apocrine gland
Lower bulge –attachment of arrecor pili
muscle
59
60. The bulge region contains epidermal stem cells that generate
multiple cell lineages, including epidermal and follicular
keratinocytes and sebaceous glands
Changes in the expression pattern of numerous transcription
factors determine their final cell lineage
60
STEM CELL
Tcf3
Sebocy
te
Hair
cell
Wnt
Lef1
Shh
Myc
Wnt
SHH-sonic hedgehog
Myc- myelocytomatosis oncogene
Wnt- wingless signalling pathway
Lef1- lymphoid enhancer binding
factor
62. 13-15 wks- sebaceous glands are clearly distinguishable
These at first contain glycogen which lingers at the periphery
of the gland, but is quickly lost at the centre, where large lipid
drops are visible at 17 weeks
The cells around the neck of the bud keratinize and form the
sebaceous duct.
At the point of their origin from the follicle, centrally positioned
cells degenerate to form a lumen, and surrounding cells
keratinize to form the sebaceous duct
Glands reach peak activity during 3rd trimester.
At birth its secretion forms a part of vernix caseosa.
Their activity declines by the end of one year and remains low
until puberty, at which time it increases again, now under the
influence of its own androgens, in particular 5α-
dihydrotestesterone (DHT). Sebum is the first demonstrable
glandular product of the human body
62
63. Sebaceous glands are present everywhere except for the palms
and soles. They are sparse over the dorsa of the feet and hand,
but are numerous on the scalp, face, external auditory
meatus,mid chest, back, and anogenital surface. Larger glands
are found on the face and scalp, where their number varies
from 400/cm2 to 900/cm2. They are smaller on extremities,
where their number is 100/cm2 or less. Smaller glands are
more superficial than larger ones
It is the large sebaceous glands with widely dilated plugged
follicular orifices that are involved in the development of
lesions of acne vulgaris. While the size of sebaceous glands
does not always correlate with the size of the hair follicle,
generally larger glands are seen in association with thin vellus
hair, especially on the face. The ducts of the larger glands join
the canal about 0.5 mm below the skin surface.
63
64. In a number of sites, sebaceous glands are
modified and open directly on to the surface.
These are:
1. Meibomian glands of eyelids.
2. Tyson glands of prepuce.
3. Free sebaceous glands on the
mucocutaneous surfaces of
female genitalia.
4. Montgomery’s tubercles on areola of nipples.
5. Ectopic glands in cervix uteri, tongue, and
parotid glands.
6. Margins of lip (Fordyce’s spots).
64
66. 66
STRUCTURE
The Sebacious gland consist of lobes or acini each
with a duct converging on the main sebacious duct
which opens in to the pilary canal.The pilary canal
opens into the skin by wide dilated follicullar orifice
Each sebacious lobule consist of an outer layer of
undifferentiated deeply basophilic,flattened
germinative cells with large nuclei analogous to the
basal cells of the epidermis
They lie on the pas positive basement membrane
zone,surrounded by periadnexal dermis
67. Outer basophilic cells are mitotically active and
replenish the gland, rest on the PAS +ve basement
membrane and have large nucleus
Connected to each other by desmosomes.
All cells have numerous mitochondria.
Contain no lipid droplets, but rich in ribonucleioproteins
As cells move toward the centre of lobe, they become
progressively acidophilic and their lipid content rises
During lipid synthesis, cytoplasm becomes packed
with smooth endoplasmic reticulum and golgi zone
becomes apparent.
Golgi body is the centre where lipid aggregates to form
sebum vacuoles.
67
69. The sebaceous duct is lined
by keratinizing squamous
epithelium, which is
compactly arranged. At one
end, these cells are
continuous with lipid
producing cells of the
lobules, and at other end with
stratified squamous
epithelium of follicular
endothelium
A mite, Demodex folliculorum,
is commonly present within
the infundibulum and the
sebaceous ducts of face as a
normal inhabitant.
69
70. Electron microscope studies reveal that undifferentiated cells
at the periphery of the glands rest upon a basement membrane,
and are connected to each other by desmosomes. These cells
contain tonofilaments, abundant smooth endoplasmic
reticulum (SER), Golgi apparatus, many mitochondria, and
stain with basic dyes. The lipid droplets arise in SER and in the
region of the Golgi apparatus. As differentiation occurs, more
fat accumulates, the cells become acidophilic and organelles
disintegrate before the cell membrane disorganizes and
ruptures.
The physiologic autolysis in the disintegrating cells is brought
about by lysosomal enzymes, of which, acid phosphatase and
aryl sulphatase activity is most pronounced in preductal region
It takes 7 to 25 days from the formation of the cell to its rupture
70
71. 3 TYPES OF PSILOSEBACEOUS
UNIT
VELLOUS HAIR FOLLICLE:SHORT THIN
HAIR AND SMALL SEBACEOUS GLAND
SEBACEOUS FOLLICLES:MIDSIZED HAIR
AND LARGE SEBACEOUS GLAND
TERMINAL HAIR FOLLICLES:LONG THICK
HAIR AND LARGE SEBACEOUS GLAND
71
72. Sebum is a complex mixture of lipids. Its
exact chemical nature cannot be
determined since the analysis of its
composition is complicated by two factors.
1) The sebum on the surface of the skin
includes not only sebum from sebaceous
glands but also the material from
keratinizing epidermis and secretions
from apocrine and eccrine glands.
2) on reaching the skin surface the sebum
undergoes enzymatic degradation due to
decomposition by bacteria.
It is estimated that each sebaceous gland
contains 10 micrograms of lipid. Human
skin surface lipid film composition
includes the following: 72
73. 1. Triglycerides and free fatty acids (57.5%).
2. Wax esters (26%).
3. Squalene (12%).
4. Cholesteryl esters (3%).
5. Cholesterol (1.5%).
Of these lipids, only squalene and wax esters are
derived from sebaceous glands alone. Free fatty
acids are not found in the sebum within the
sebaceous glands, but in the infundibulum due to
esterase activity of P. acnes and P. granulosum on
acyl glycerols. These free fatty acids provoke
inflammation and are important in the pathogenesis
of acne vulgaris
73
74. In areas with low sebaceous gland density,surface lipid is low
and contains no wax esters and squalene, and this lipid
represents that contributed by the epidermis (glycerides,
cholesterol esters and cholesterol
Thus, wax esters and squalene are produced by sebaceous
glands only and sebaceous glands do not convert squalene to
sterols,
whereas in the epidermis squalene synthesized in the lower
layers is rapidly and totally converted to sterols, either to
precursors of vitamin D or to cholesterol
Squalene is unique to sebum and is virtually unique to
humans
74
75. o The patterns of unsaturation of fatty acids in
TGLs,wax esters and cholesterol esters also
distinguish sebum from other lipid secretion :
o The predominant pattern of desaturation is
insertion of a Δ6 double bond into palmitic
acid(16:0) resulting in sapienic acid(16:1Δ6), the
major fatty acid in human sebum
o Elongation of chain by 2 carbons and insertion of
another double bond gives sebaleic acid
(18:2Δ5,8), unique to human sebum.
75
76. The rate of secretion of sebum depends upon the
rate of production of sebaceous cells and the
synthesizing capacity of each cell. The production of
sebum appears to be entirely under hormonal
control and is not affected by the temperature,
amount of skin surface, lipid film, or by innervation
of glands.
No motor nerve supply has been demonstrated in
the human sebaceous glands. The glands are
unresponsive to physiologic neurotransmitters,
norepinephrine, and acetylcholine. Sebum
production is continuous rather than intermittent.
76
77. • Neonatal period : resembles adult sebum
• Thereafter and up to 8 years : wax esters and squalene
remain low, and epidermal lipids, that is cholesterol and
its esters, are high and sebum constitutes less than half
the total surface lipid of the forehead
• 8 to 10 years : wax esters and squalene rise to about
two-thirds of the adult level
• 10 to 15 years : the composition comes to resemble that
of the adult.
• Upto 60 years: remains unchanged
• >60 years: glands become larger but sebum production
declines
77
79. 1)Swabbing by pads soaked in solvent.
2)Washing of circumscribed skin area with lipid solvents &
absorption on paper.
3)Pressing a ground glass plate on the skin followed by
photometric assessment.
4) Absorption into specially devised papers and then weighing
the lipid content absorbed.
Wt of sebum× time of collection = SER
Area of collection
5)Squalene content of skin biopsies
6)Sebum absorbent tape (sebutape)
79
80. o Secretion of sebum is a continuous process.
o Entirely under hormonal control.
o Neural control is absent.
o Diet : 1)There is no evidence that any
components of sebum are directly derived from
ingested fats. In humans, most of the
unsaturated fatty acids in the surface film are Δ6
compounds, whereas dietary lipids are Δ9
compounds
2)Prolonged starvation of human subjects
decreased the rate ofsebum synthesis by about
40%, without any decrease in the actual amount of
squalene
80
81. Androgen receptors- present in basal cells of
lobule and outer root sheath of hair.
PPARs (Peroxisome proliferator activated
receptors)- nuclear receptors and act as
transcriptional regulators
3 subtypes of PPARs- alpha, delta, gamma
PPARs play a role in regulating sebum production
and selective modulation of their activity may lead
to novel therapies for the treatment of acne.
Fibrates(PPAR-alpha) & thiazolidinediones(PPAR-
gamma) ligands increases sebum secretion.
81
82. Melanocortin receptors(MC1 and MC5)- target
for alpha melanocyte stimulating hormone & ACTH
Cytokines - IL-1α and IL-1β, TNF-α. May relate to
development of inflammation.
Fibroblast growth factor receptors- FGFR1 and
FGFR2 expressed in epidermis and skin appendages.
Germ line mutations in FGFR2 lead to Apert
syndrome associated with acne.
82
83. 1. ANDROGENS :
◦ The most important hormones controlling sebaceous gland
activity
◦ Responsible for the development and maintenance of sebum
secretion in both sexes
◦ Causes increased sebocyte differentiation and proliferation
leading to increased sebum secretion
◦ Majority of potent androgens are produced by peripheral
target tissues
◦ Sebaceous gland has got many enzymes (3βhydroxysteroid
dehydrogenase, 17β hydroxysteroid dehydrogenase,
5αreductase type 1) for intracellular conversion of various
androgens. It also has the ability to synthesize testosterone
from adrenal precursors as well as inactivate it.
◦ The biological activity of testosterone on the skin is induced
by its conversion to 5α-DHT by the enzyme 5α-reductase
◦ Testosterone and 5α-DHT stimulate 5α- reductase mRNA and
5α-reductase activity and exert their effects through binding
to androgen receptors.
83
84. ◦ Genetic deficiency of androgen receptors (complete
androgen insensitivity) have no detectable sebum
secretion and do not develop acne.
◦ Sebum secretion starts to increase in children during
adrenarche, a developmental event that precedes puberty
by about 2 years.
◦ Weak adrenal androgen, dehydroepiandrosterone
sulfate (DHEAS) are high in newborns, very low in 2- to 4-
year-old children, and start to rise when sebum secretion
starts to increase.
◦ DHEAS is present in the blood in high concentration. The
enzymes required to convert DHEAS to more potent
androgens are present in sebaceous glands
84
86. ESTROGENS
Estrogen decreases the size of sebaceous
glands and reduces sebum production but
only in high doses. It appears that estrogens
do not act at the level of the sebaceous
glands, but by reducing endogenous
androgen production through the pituitary
gonadal axis.
86
87. Progesterone has been blamed for a
fluctuation of sebum levels in women during
the menstrual cycle and in turn for
premenstrual flare, but this has not been
proved experimentally.It has no effect on the
sebaceous glands in physiological doses in
both sexes.
Cortisone suppresses sebaceous secretion
due to suppression of adrenal androgens.
87
88. ACTH causes hyperplasia of sebaceous glands,
and increases both sebum production and mitosis
of the sebaceous cells.
There is evidence from animal studies to show
that α-MSH, growth hormone, and prolactin might
have a similar effect. However, the pituitary gland
is important in sebum production, since in
hypopituitarism sebum production is decreased.
The thyroid gland may also influence sebaceous
secretion since thyroidectomy results in a
decrease in sebaceous gland activity, and this can
be reversed by the administration of thyroxine
88
89. The pituitary has a major effect on sebaceous gland
activity.The pituitary acts on sebaceous glands
indirectly through its various target glands, and also
directly by some of its hormones
89
90. Antiandrogens
Sebaceous secretion can be inhibited by some
synthetic nonestrogenic steroids which antagonize
the action of androgens at the target
site.Antiandrogens include α- norprogesterone,17-α
methyl-β nortestosterone, flutamide,
spironolactone,cyproterone acetate (CPA),
chlormadinone acetate, ranitidine,and cimetidine.
The effect of CPA on sebaceous secretion is dose-
dependent and it is a promising agent in the
treatment of acne in women.
Inhibitors of 5α-reductase (which inhibit conversion
of testosterone to 5α-dihydrotestosterone without
blocking attachment to intracellular receptors) also
reduce sebum production. Its activity varies in
different regions of the pilosebaceous units.
90
91. When compared with interfollicular epidermal cells, infra- infundibular
keratinocytes have an increased capacity for producing androgens,
which may play a role in the follicular keratinization seen in acne.
Other Agents
Isotretinoin (13-cis-RA), a vitamin A derivative, given systemically,
reduces the size and secretion of sebaceous glands significantly. It
not only reduces 5 α- reductase activity in human skin and the liver
but also acts by reducing synthesis of DNA and incorporation of lipid
precursor, C14 acetate.
Topical retinoids on the other hand do not have any effect on sebum
production.
Topical antibiotics do not influence sebum secretion or excretion
significantly; however, topical erythromycin along with zinc acetate
has been reported to reduce secretion of sebum.
The mechanism for this is unclear.
91
92. The suggested functions of sebum in human skin
are:
1. Barrier function.
2. Regulation of percutaneous absorption by
preventing the evaporation of water.
3. Antifungal function due to products of
hydrolysis.
4. Antibacterial due to certain surface free fatty
acids.
5. Protects skin surface lipids on the face by
secreting vitamin E.
6. Vitamin D precursor.
92
93. ANTIOXIDANT FUNCTION : Sebum mantles the
epidermis, representing the ultimate barrier of the
body against exogenous oxidative insults.
It is believed to deliver antioxidants to the surface in
the form of vitamin E and CoQ10
Squalene is the 1st human skin surface lipid
targeted by oxidative stresses such as sun light and,
as a consequence, is depleted where a toxic photo-
oxidation product is produced.
The antioxidant function of sebum is important as
the buildup of reactive oxygen species on the skin
surface can cause a breakdown of the skin barrier
and signs of aging.
93
94. ANTI-BACTERIAL AND FUNGISTATIC ACTION
Gram-positive bacteria tested(Staphylococcus
aureus, Streptococcus salivarius) were exceedingly
susceptible to sebum, with a significant decrease in the
number of viable cells.
Suppression of sebaceous gland activity by isotretinoin may
be followed by impetigo towards the end of a 4-month
course.
Fractionation of the human sebum lipids showed that isomer
of palmitoleic acid (cPA) was the most active anti-bacterial
fatty acid component and the most active fraction in blocking
the adherence of a pathogenic strain of Candida albicans to
the porcine stratum corneum
94
95. IMMUNOMODULATORY ROLE
It has been suggested that the capacity to
develop delayed immune hypersensitivity
may be augmented and maintained by the P.
acnes, which colonizes sebaceous glands in
adults.
Enhanced immunoregulatory effect,
producing some protection against cancers
such as leukaemia and melanoma, which
occur less frequently in acne patients.
95
96. Antimicrobial peptides, including cathelicidin, psoriasin, β-
defensin 1, and β- defensin 2 are expressed within the
sebaceous gland.
Functional cathelicidin peptides have direct antimicrobrial
activity against Propionibacterium acnes.
Innate immune Toll like receptors 2 and 4 (TLR2, TLR4),
CD1d and CD14 molecules are also expressed in sebaceous
glands and immortalized human sebocytes
Some components of sebum contributes to body odour
Role in water barrier function is minimal.
96
97. The level of sebaceous gland activity varies
from individual to individual and is probably
genetically determined.
The abnormalities of sebaceous activity
include:
1. Excess production of sebum or seborrhea.
2. Sebaceous gland hyperplasia without
clinical seborrhea.
3. Obstructive disorders of sebaceous duct,
e.g. comedones.
97
