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GLANDS
Glands are an aggregation of cells specialized to

secrete or excrete materials . Glands are divided into two main groups, endocrine and exocrine. ENDOCRINE GLANDS:- ductless glands, discharge their secretions (hormones) directly into the blood.
EXOCRINE GLANDS :-Discharge their secretions

through ducts opening on an external or internal surface of the body.

TYPE OF GLANDS ACCORDING TO THEIR SHAPE

GLANDS OF SKIN
Holocrine :- secretory cells are destroyed during the process of

secretion, eg sebaceous glands. Merocrine :-cells are not destroyed during secretion eg sweat glands.
Three subtypes:

Eccrine- no breakdown of any cellular material. Apocrine- secretion involves decapitation of apical cytoplasm. Apoeccrine- mixed.

SWEAT GLANDS

Sweat glands are small tubular structures situated within and under the skin(in the subcutaneous tissue). They discharge a fluid by tiny openings in the surface of skin called as sweat. Sweat is a transparent colorless acidic fluid. It contain some fatty acids and mineral matter . Sweat is also called as perspiration.

ECCRINE SWEAT GLANDS


Distribution Whole skin surface except lips, ext. ear canal, labia minora and clitoris. Total number 2-5 millions. Number varies with sites- active sweat glands are present most densely on the sole, forehead and palm .
620/cm2-soles 120/cm2-thighs & 64/cm2- back Total weight 100gms

EMBRYOLOGY
Derived as specialized down-growth of basal layer of

epidermis, at about 3rd month of IU Life on palms and soles, 5 months elsewhere . By 12 week anlage of the eccrine sweat gland develops from the epidermal ridge as a cord of epithelial cells growing downward. By 1415 weeks, the tips of the eccrine sweat gland rudiments have penetrated deeply into the dermis, and have begun to form the coils. Morphologically normal at birth but fully functioning unit about 2 yrs of life. No new sweat gland develop after birth.

STRUCTURE OF ECCRINE SWEAT GLAND


Eccrine glands are atrichial simple tubular structure . Each consists of a single tube, the deep part of which is

rolled into an oval or spherical ball, named the body of the gland or secretory coil. The superficial part, or duct, traverses the dermis and cuticle and opens on the surface of the skin by a funnelshaped aperture. The uncoiled dimension of the secretory portion of the gland is approximately 3050 m in diameter and 2

5 mm in length.

The size of the glands varies, large in those regions where

the amount of perspiration is great, as in the axillae and groin.

dermis

epidermis
Secretory duct

Subcutaneous fat

Secretory coil

Basal coil or Secretory coil


Situated in the lower 1/3rd of dermis or border b/w

dermis and subcutaneous tissue, surrounded by fatty tissue. Microscopically the secretoy coil consist of a pseudostratified epithelium enclosing a lumen. About half of basal coil formed by secretory portion and another half by coiled ductal portion.

Secretory portion contains 3 types of cells


Large clear cells (secretory

cells) Small dark cells (mucoid cells) Myoepithelial cells

CLEAR CELLS
Rest either directly on the

basement membrane or on the myoepithelial cells.


Pyramidal cells, with

abundance of membrane villi, membrane infoldings.

CLEAR CELLS
Where two or more clear cells adjoin, intercellular

canaliculi are formed. Canaliculi emerge immediately above the BM or the myoepithelial cells and open directly into the lumen of the gland. Basolateral plasma membranes are highly folded & interdigitating with apposed clear cells. Basal infoldings typical of clear cells involved in fluid & ion transport

CLEAR CELLS
Nucleus is round and moderately euchromatc. Cytoplasm contains autofluorescent, PAS positive,

diastase liable granules called lipofuscin granules. Also contains glycogen granules, mitochondria, rough endoplasmic reticulum, and small Golgi complex but few other organelles. This is responsible for secretion of water and electrolytes.

DARK CELLS
Columnar cells, borders nearly all the apical (luminal)

surfaces of the secretory tubules. Function unknown Cytoplasm contains basophilic granules which are PAS positive , diastase resistant, a well developed Golgi complex , numerous vacuoles and vesicles and dense glycoprotein granules. They secret sialomucin.

MYOEPITHELIAL CELLS
Spindle-shaped, lie on the BM and adjoin the clear

cells. Contractile with abundant actin filaments Principal function is to provide structural support for the secretory epithelium. It propels the eccrine sweat towards the surface. They respond only to cholinergic stimulation.

Eccrine sweat duct


Divided into 2 parts Intraepidermal duct (acrosyringium) Intradermal duct

Intraepidermal duct is spiral structure, cells are

derived from dermal duct cells. Dermal duct has an upper straight and lower coiled part. It has 2 layers of cells but no BM.

Eccrine units consist of three portions: (1) the acrosyringium or intraepidermal spiralled duct; (2) the coiled and straight intradermal duct; and (3) the secretory coiled gland

Schematic illustration of the ultrastructures of the eccrine duct and secretory coil and the localization of Na+, K+-ATPase. D, dark cells; C,clear cell; M, myoepithelial cell; Mc, mitochondria; BM, basement membrane. The thick lines indicate the localization of Na+, K+-ATPase.

Sweat Duct
Eccrine sweat duct Consists of mainly two layers of

small cuboidal deeply basophilic cells. An outer ring of Basal ductal cells and inner ring of Luminal ductal cells Proximal (coiled) duct is functionally more active than the distal (straight) portion. Luminal cytoplasm of the ductal cells forms a border consisting of a dense layer of tonofilaments called cuticular border. Cuticle is homogeneous, eosinophilic, PAS positive and diastase resistant.

Basal ductal cells have numerous mitochondria and rich in

Na-K+-ATPase activity. Involved in ductal Na+ absorption. Cuticular border of luminal cells provides structural resilience to the ductal lumen, which may dilate whenever ductal flow of sweat is blocked. Lumen and duct contain -defensin, an antimicrobial peptide.

Histology
Sweat glands typically

appear as clusters of several round or oval profiles. tubule consists of cuboidal epithelium . Duct Cells, are usually stained more intensely than those comprising the secretory portion of the tubule. Secretory portion appears to be single layered with clear and darkly stained cells.

STAINING OF ECCRINE GLANDS


Glands and their products can be identified by special

histochemical, enzymatic & immunohistochemical methods. Demonstration of :1. CK7 (cytokeratin 7) 2. CK34E12 3. P63 4. CEA- carcinoembryonic antigen. 5. EMA- epithelial membrane antigen. 6. S100-acidic protein binds Ca++ & Zn++ ions, soluble in 100% ammonium sulfate at neutral pH, found in cytoplasm and nucleus.

CK7-secretory+ve& duct-ve

CK34E12-basal secretory & ductal +ve

P63- basal ductal & scattered secretory +ve

CEA- classical luminal expression pattern

EMA- canalicular pattern

S100- some secretory cells & stromal nerves

INNERVATION OF ECCRINE SWEAT GLANDS


Sympathetic nerve supply which is muscarinic

cholinergic, unlike other sympathetic fibers. Glands influence the nerves to secrete appropriate NT, during development. Also stimulated by and -adrenergic stimulation . Ratio of maximal secretory rates for human sweat glands is 5 : 1 : 1 for cholinergic, -adrenergic and adrenergic stimulation, respectively.

AFFERENT PATHWAY FOR THERMAL STIMULI FROM SKIN


Thermal senses discriminated by 3 types of receptors-cold,

warmth and pain receptors, situated in dermis. Warmth receptors are mainly free nerve endings, called Ruffinis corpuscles. Warmth sensations transmitted by non-myelinated Cfibers. Cold receptors known as Krauses end bulb. Cold sensations transmitted by myelinated A nerve fibers.

Sensory nerve fibers arising from

receptors reach to dorsal root ganglion cells through related sensory nerves. They terminate in laminae I, II and III of dorsal horn. After processing, signals enter in long ascending fibers that cross to opposite anterolateral sensory tract (Lateral STT) and runs parallel to pain fibers. They terminates in both (1)reticular areas of brain stem and (2)ventral-lateral and ventral-posterior complex of thalamus . Few signals also relayed to somatosensory areas of cortex.

EFFERENT PATHWAY
Efferent sudomotor pathway consists of the cerebral

cortex to Hypothalamus >brainstem and medulla-> intermediolateral cell columns of spinal cord>preganglionic sympathetic ganglia------------>postganglionic nonmyelinated C fibers-joins the major peripheral nerves and end around the sweat glands . Supply to the skin of upper limbs is commonly comes from T2 to T8, face & eyelids from T1 to T4,trunk from T4 toT12 and lower limb T10 to L2 .

Cerebral cortex-----Hypothalamus----medulla (mostly crossed) ----spinal cord

FUNCTIONS OF SWEAT GLANDS


Thermoregulation- Heat can

be lost through the skin surface by radiation, convection, conduction and evaporation. When skin temp. is greater than the temp. of surroundings heat can be lost by radiation, convection ,conduction and evaporation. But when temp. of surroundings becomes greater than skin, instead of losing heat body gains heat by both radiation and conduction. Under these conditions the only means by which the body can loose the heat is by evaporation.

1 gm of water evaporation leads to loss of 0.58 kcal.

Heat. Body loses about 6oo ml-700 ml water per day insensibly from the skin and lungs, this causes continuous heat loss at rate of 16-19 Kcal per hour. Sweat cools the surface of the skin and reduces body temperature. This cooling is the primary function of sensible perspiration.

An increase in local skin

temperature of 10 C (50 F) triples the local sweating rate until the sweat rate plateaus. The effect of core temperature rise is about nine times more efficient than skin temperature in stimulating sweating.

Sweat moisten the thick stratum corneum of palms and

soles which improves the pliability, grip and fine tactile skills. Protection- Merocrine sweat gland secretion provides protection from environmental hazards by :1. Diluting harmful chemicals. 2. Discouraging growth of microorganisms by means of some immunoglobulins and antimicrobial peptides present in sweat.

Excretion- provide a significant excretory route for

water and electrolytes. Sweat may contain a trace amount of metabolic wastes. Sweat can be potentially proinflammatory and may modify various dermatoses, suggested by presence of ILs, proteolytic enzymes and antibodies in sweat. Lactate and urea in sweat may regulate desquamation. Active excretion or secretion of drugs such as sulfaguanidine, sulfadiazine, amphetamines, iodides, phenytoin, phenobarbital, carbamazepine, griseofulvin, ketoconazole, fluconazole, ciprofloxacin, diamorphine, cocaine and nicotine may contribute to their efficacy.

CONTROL OF ECCRINE SWEATING

Alteration of activity occurs in response to


Thermal stimulation

Osmotic changes
Mental and emotional activity Gustatory factors

THERMAL SWEATING
Play an important role in keeping the body

temperature constant. Occur especially on upper trunk and face with some generalized increase. Heat regulating centre situated in the hypothalamus preoptic area and anterior hypothalamic. Activated by
Change in temperature & osmotic pressure of the blood

perfusing it . By afferent stimuli from the skin . Deep thermal receptors situated in spinal cord, in or around visceras and great vessels in abdomen and thorax .

Signals generated by the temp. receptors of

hypothalamus are extremely powerful. When core temp. of body rises above a certain level (thermal set point), eccrine sweating is initiated. Thermal set point is a critical body core temp. of about 37 c (98.4 F), body attempt to bring body temp. back to this set point when body core temp. increases above or decreases below this set point. Hypothalamic thermal set point also influenced by alterations of blood osmotic pressure.

Receptors in other parts of body play additional role

in temp. regulation. Receptors in skin and visceras are more sensitive to cold rather than warmth. Signals from hypothalamic and other receptors transmitted to posterior hypothalamic area. Here, the signals received from all area are combined and integrated, to control the heat-producing and heat conserving reactions of body.

MENTAL ( EMOTIONAL ) SWEATING


Consequence of higher cerebral centres (frontal

region) acting on the thermoregulatory centres in the anterior hypothalamus. Emotions such as fear and anxiety prompt eccrine gland sweating, predominantly of the palms, soles and axillae. Emotional sweating on the palms and soles ceases during sleep, whereas thermal sweating occurs even during sleep if the body temperature rises.

GUSTATORY SWEATING
Physiological gustatory sweating is symmetrical, and it

is confined to the forehead & nose and exceptionally the neck. Hot spicy foods are the most likely cause. Gustatory sweating is accompanied by flushing of the face and the upper part of the body, salivation, lacrimation and nasal secretion. Sensory receptors mediating gustatory sweating are probably pain fibres. Substances which stimulate the taste fibres without causing pain do not give rise to gustatory sweating.

MECHANISM OF SWEAT SECRETION


Eccrine sweat forms in two steps.
First, the secretory coil secretes

isotonic fluid in lumen, rich in Na+ and Cl+. In the ductal portion, Na+ reabsorbed and H+ secreted to produce hypotonic and acidic fluid.

Sweat forms in sequential steps:-

(1) Stimulation of the eccrine sweat gland by ACh via increased intracellular Ca2+ (2) Ca2+-stimulated loss of cellular K+, Cl-, and H2O, which leads to eccrine gland cell shrinkage; (3) Volume-activated transcellular plus paracellular fluxes of Na-, CI-, and H2O, which results in net flux of largely isotonic NaCl solution into the glandular lumen.

Cholinergic stimulation -Release of ACh cytosolic Ca2+ Opening of Ca-sensitive Cl and K channels Leads to luminal and basolateral secretion of Cl and K, water moves osmotically Cell shrinkage Activation of Na/K/2Cl cotransporter and Na-K ATPase 1.Recycling of K+ along basolateral membrane 2.Secretion of Cl- into lumen 3.Paracellular flux of Na+

Final product of glandular secretion is therefore the

net movement of Na+, Cl- and H2O into the glandular lumen to form the isotonic NaCl precursor of sweat. by increased intracellular cyclic adenosine monophosphate.

Adrenergic-induced sweating appears to be mediated

MECHANISM OF DUCTAL REABSORPTION


Ductal portion of sweat gland not only reabsorb

electrolytes but also acidify the sweat, which results in a final sweat product that is hypotonic and acidic. Na+ enters the duct cells through the apical membrane via amiloride-sensitive epithelial Na+ channels (ENaC) and is transported across the basolateral membrane by Na-K ATPase pumps. Cl- transport appears to be both transcellular and paracellular with the cystic fibrosis transmembrane regulator (CFTR) Cl- channels playing an important role in transcellular fluxes.

Na+ enters the apical (luminal) membrane through epithelial sodium channel (ENaC) and is transported across the basolateral membrane by Na+ K+ ATPase. Cl- transported via CFTR and paracellularly. Sweat acidification by carbonic anhydrase mediated reaction.

REGULATION OF SWEAT GLANDS


Sweat glands respond to cholinergic agents, and

adrenergic stimulants, and other periglandular neurotransmitters as VIP and ATP. Sweat rate in a given area of the skin is determined by the number of active glands and the average sweat rate per gland. Aldosterone increases Na+ reabsorption. Vasopressin may increase water reabsorption in response to osmotic changes. Other factors as local temp , hormones, circulatory changes, spinal reflexes and androgens may modify quantity and quality of sweat.

EFFECT OF CERTAIN PHYSIOLOGICAL CONDITIONS ON SWEATING


1.

In old ageSpontaneous sweating on the fingertips declines, as a result of a combination of a reduction in the number of glands and of the output per gland. 2. Glands tend to display both disarray and shrinkage of secretory cells and lumen . 3. Sweating response to dry heat is diminished ,making prone to heat stress in old age. In pregnancy1. Eccrine activity may be noticeably increased . 2. This may be responsible for the recognized increased frequency of miliaria.

COMPOSITION OF SWEAT
Varies from person to person, time to time & site to site. Constituents
NaCl - 10 to 20 mmol/L at low rates, upto

100 mmol/L at high rates K -5 to 10 mmol/L HCO3 - < 1 mmol/L Urea Lactate- 4 to 40 mmol/L Glucose- 0 to 3 mg/dl Ammonia and Amino acids -0.5 to 8 mmol/l Pr0teins

Ph 4 to 6.8 Specific gravity 1.005

ALTERATION IN SWEAT COMPOSITION


In hyperaldosteronism, concentration of Na and Cl

decreases while K increases. In Additions Ds, concentration of Na may increase to 7080 mmol/L . Increase in sweat electrolytes occurs in Cystic Fibrosis High sweat glucose found in uncontrolled DM. Other substances like Antigen and antibodies may be found in sweat.

IgE level increased in atopic dermatitis. In uremia, the evaporation of sweat with high urea concentrations results in the deposition of urea on the skin, referred to as uremic frost. Abnormal amino acids or their breakdown products excreted into sweat results in abnormal body odor .

Musty or sweaty or locker room towel odor in

PKU. Malty, caramel-like or maple syrup-like odor in maple syrup urine disease . Decayed malt or hops like odor in oasthouse syndrome. Strong, fishy, fruity or rancid butter-like odor in hypermethioninemia. Cheesy or sweaty feet odor in isovaleric acidemia.

APOCRINE SWEAT GLANDS


Develops from upper bulge of hair follicle at 4th month

of intrauterine life. Initially, solid epithelial cord projects at right angle to long axis of hair follicle, later, it turns downward. Survive to become functional only in axillae, genital area & areolae just before puberty.

STRUCTURE
Apocrine gland also has 3 segments- basal coil,

intraepidermal and dermal duct. Basal coil situated in subcutaneous fat. Basal coil forms only by secretory portion. Have single layer of tall columnar cells, resting on BM. Duct opens in the pilosebaceous follicle above the entrance of the sebaceous duct or sometimes directly on surface. Intraepidermal portion of duct is straight. Duct consists of double layer of cuboidal cells .

HISTOLOGY
Diameter of the

tubular lumen of apocrine sweat glands is much greater than that of eccrine sweat glands, and the epithelium is typically taller. Cells contain larger granules than eccrine dark cells. Luminal surface has dome-shaped apical cap.

SECRETION
Milky or viscid, colorless & odorless when first secreted.

Subsequent bacterial action is responsible for odor production which produces ammonia and short chain fatty acids( e-3-methy-2-hexenoic acid). Decomposition on the skin surface modified the secreted substances.
Decomposition results in the typical penetrating rancid

(by corynebact. sp.) or sweaty (by micrococcus sp.) body odor.

Secretion consist of the release of portion of

cytoplasm. An apical cap and dividing tubule are formed initially. Apical cap is then detached and discharged into lumen, it is called decapitation.

Mode of secretion- pulsatile due to contraction of myoepithelial cells. Secretion is controlled by adrenergic nerve. Also stimulated by Circulating epinephrine. Modified apocrine glands
In the external ear canal-ceruminous glands. In the eyelid molls glands. In the breast mammary glands.

FUNCTION
No thermoregulatory function.
Because the apocrine glands of humans do not begin

to function until puberty and are odor producing, have 5-reductase activity. May have some sexual function by olfactory communication, which may now be vestigial.

APOECCRINE SWEAT GLANDS


Have features of both apocrine and eccrine. Develops during puberty from eccrine glands. Consistently present in the adult axillae, forms <10% of axillary glands. Larger than eccrine and smaller than apocrine. Found in all levels in dermis .

Larger duct opens nonfollicular skin surface like

eccrine. Secretory coil- irregularly dilated. Reponds to cholinergic & also to epinephrine. Persistent secretion of clear fluid in the presence of Ach. Sweat rate is variable but higher than eccrine gland In axillary hyperhidrosis, apoeccrine glands may be 50% of axillary glands.

CHARACTERISTICS OF SWEAT GLANDS


ECCRINE
Localization Entire body except lip, labia minora , and clitoris, external auditory canal .

APOCRINE
Axillae , anogenital area , areolae (ceruminous glands , moll,s glands of eyelids and mammary glands are modified apocrine glands). Short thick duct opens into upper part of follicular canal Secretory coil with wide lumen.

APOECCRINE
Axillae.

Morphology

Long, thin duct opens to skin surface secretory coil with narrow lumen.

Duct comparable to eccrine gland duct secretory coil with dilated and undilated tubular segments.

Cell type of Secretory coil


Main innervation /transmitter

Large secretory clear cells, dark cells, myoepithelial c ells.


Sympathetic fibers / acetylcholine.

Epithelial and myoepithelial cells Cells contain larger granules then eccrine dark cells.
Sympathetic fibers / mainly by adrenergic (epinephrine and norepinephrine).

Eccrine and apocrine morphologic features.


Sympathetic fibers / acetylcholine.

Development

Present at birth No relationship to pilosebaceous follicle.

Present at birth but poorly developed, functional at puberty. related to pilosebaceous follicle.

Probably not present before adolescence. No relationship to pilosebaceous follicle.


Thermoregulation, Role in axillary hyperhydrosis.

Function

Thermoregulation.

Unclear, some role in olfactory communication.

METHODS OF STUDYING SWEAT GLAND FUNCTION


Tests for distal sympathetic axonal integrity and to determine receptor function of sweat gland
1.

2.

3.

Pharmacological sweat test- Sweat induced by intradermal injection of 0.01% pilocarpine or methacholine. Quantitative sweat axon reflex test -A small battery-operated current stimulates the sweat glands directly. Quantitative sudomotor axon reflex test (QSART).

QUANTITATIVE SUD OM OTOR AXON REFLEX TEST (QSART)


Test has three parts and measures resting skin

temperature, resting sweat output, and stimulated sweat output. Measurements are typically taken on arms, legs or both. A small plastic cup is placed on the skin and the temperature and amounts of sweat under the skin are measured. To stimulate sweat pilocarpine 0.01% or Ach 10% is delivered electrically through the skin to a sweat gland. A computer is used to analyze the data to determine how well the nerves and sweat glands are functioning.

DETERMINATION OF MAXIMAL SWEAT RATE


Water- vapour analyzer. Filter paper method. Collection of sweat droplet under mineral oil. Anaerobic bag method. Micro-cannulation of the sweat duct or coil. weighing and analyzing of sweat composition.

TESTS FOR THERMAL SWEATING


Thermoregulatory sweat test- after change into a

disposable bathing suit, apply iodine-starch powder to skin. Patient then go into a warm and humid large glass room (much like a sauna) for 20 to 30 minutes. Orange powder turns purple where sweating occurs, telling which parts of the autonomic nervous system are working, and which are not. Core body temp. must rise at least 1 c.

CHLORIDE SWEAT TEST


Helps diagnose cystic fibrosis (CF), an inherited

disorder characterized by mutation of gene for CFTR. Sweat test measures amount of chloride in sweat Child with cystic fibrosis can have 2 to 5 times the normal amount of chloride in their sweat In a sweat test, the skin is stimulated to produce enough sweat to be absorbed into a special collector and then analyzed. If child has a sweat chloride level of more than 60 mmol/L, its considered abnormal

VISUALIZATION OF INDIVIDUAL SWEAT DROPLETS

By Iodine-starch test or by sodium alizarin sulfonate (alizarin Red S). Iodine-starch test Iodinated starch powder is prepared by adding 0.5 to 1g of iodine crystals to 500 g of soluble starch in a tightly capped bottle. Applied to the skin and undergo a dramatic color change when moistened by the water (sweat) from activated sweat glands. Iodine-starch reaction also used for sweat imprint papers.

A patient with Segmental anhidrosis (Yellow) with

compensatory left-sided hemihyperhidrosis (purple) due to a Upper thoracic spinal cord injury (sodium alizarin sulfate indicator powder)