Control of sweat and sebum

• 1. SHUMEZ . H

2. Sebum is an oily substance secreted by the sebaceous gland. Sebaceous glands form part of the pilosebaceous unit. They open at the junction of the infundibulum and isthumus of the hair follicle. 3. Structure of Sebaceous Gland The sebaceous gland consists of lobes or acini, each with a duct. These ducts converge on the main sebaceous duct which opens into the pilary canal. The pilary canal opens onto the surface of the skin by widely dilated follicular orifices. 4. Each sebaceous lobule consists of an outer layer of undifferentiated germinative cell with a large nuclei. Sebaceous gland is Holocrine. Its secretion is formed by the complete disintegration of the glandular cells. 5. Sebogenesis Cells differentiate towards the centre. Lipid accumulate. The cells increase in size. The cytoplasm becomes pale andvacuolated. Finally the cells disintegrate. The mass of lipid along with cellular debrisis discharged into sebaceous duct as sebum. 6. Receptors Androgen receptors are present in both thegland and the duct. Peroxisome proliferators activated receptors(PPARs) All 3 subtypes (, , ) of PPAR receptorsare expressed by the sebocytes. PPAR 1 is expressed more in the ductal cellsof normal skin. 7. These receptors help in lipid droplet formation. Sebocytes also express Melanocortin receptors - MC1 and MC5. They are target cells for melanocyte stimulating hormone ( MSH) 8. Distribution of Sebaceous glands Present everywhere in the body except onthe palms and soles. More on the face, scalp, uppertrunk, external auditory meatus andanogenital surfaces. Face and scalp - 400/cm to 900/cm. Elsewhere there are < 100 glands/cm 9. Modified Sebaceous glands Meibomian glands of eyelids. Tyson glands of prepuce. Margins of lip (Fordyces spots) . Montgomerys tubercules on areola ofnipples. On the mucocutaneous surfaces of femalegenitalia. Ectopic glands in cervix uteri and tongue. 10. Composition of Sebum Glycerides &Free fatty acids - 57.5% Wax Esters - 26% Squalene - 12% Cholesterol Esters - 3% Cholesterol- 1.5% 11. Lipid production varies according to site. 5 - 10 g/cm on the limbs. 150 - 300 g/cm on the face. Free fatty acids are produced by breakdown of Triglycerides by lipases secreted by bacteria ( Propionibacterium acnes and P. granulosum) . 12. Sebum is present at birth - vernixcaseosa. Present for few postnatal months maternal androgens Enlarge at puberty , due to androgeninfluence. Peak sebum secretion during adolescence. Unchanged during adulthood . Become larger in old age, because cellturn over is decreased 13. ENDOCRINE CONTROLOF SEBACEOUS ACTIVITY 14. ANDROGENS Androgens are the most important hormonescontrolling sebaceous activity in both sexes. This is the reason for enlargement ofsebaceous glands at puberty. The most effective endogenous androgens are Testosterone 5 Dihydrotestosterone (5 DHT) 5 Androsterone - 3 -17 - diol 15. 5 DHT is 5-10 times more potent than testosterone. Testosterone is converted to 5 DHT by the action of 5 reductase. This enzyme has 2 isoforms of which type II is more important for androgenic control. 16. Other enzymes responsible for interconversion of androgens are: 3 Hydroxysteroid dehydrogenase (3 HSD) 17 Hydroxysteroid dehydrogenase (17 HSD) 17. OESTROGENS Larger doses oppose the endogenous stimulation of androgens. Site of action - is at androgen synthesis and not at the level of sebaceous gland. The major active oestrogen is Oestrodiol. 18. PROGESTERONE Progesterone is acompetitive inhibitor of 5 reductaseand is expected to reduce sebaceous gland activity. But itssebosuppressive effect is minimal. 19. Pituitary Hormones Pituitary hormones can directly or indirectly cause increase in sebaceous secretion. These include: ACTH Growth hormone Gonadotrophins MSH 20. Sebaceous activity is also increased in Pregnancy and Lactation. The sebaceous glands are not innervated. Unresponsive to administration of neurotransmitters like Acetylcholine and epinephrine. 21. Functions of sebum Barrier Function Emulsification Antifungal activity Anti bacterial action Protection against Sunburn Vitamin D Precursor Vitamin E production 22. Sebum in Dermatological conditions Sebum production is decreased in disorders which manifest as dry skin Atopic dermatitisContact dermatitisIchthyosis. 23. In Acne Vulgaris Sebaceous secretion is increased in acne. The composition of sebum in acne also changes:Higher levels of Squalene and wax esters.Lower levels of fatty acids. 24. But the principal role of Sebum in Pathogenesis of Acne is - Its capacity of evoking inflammation. Its provision of substrate for the growth of intrafollicular anaerobic bacteria. Inducing faulty follicular keratinisation resulting in comedone formation. 25. Sebum in systemic disordersIncreased sebum secretion is seen in: Adrenal Hyperplasia Ovarian tumours Polycystic ovarian disease Acromegaly Parkinsonism After phenothiazine drugs 26. Sebum secretion is decreased in: Primary and secondary hypogonadism Adrenal insufficiency Panhypopituitarism Starvation 27. PHARMACOLOGICAL CONTROLOF SEBACEOUS ACTIVITY 28. ANTI ANDROGENS Suppress the generation of androgens. Inhibit peripheral metabolism of androgenin target tissues. But use is limited to women because of thefeminizing effects in men. 29. These include: Oestrogen Cyproterone acetate Spironolactone Ketoconazole Cimetidine 30. Role of Isotretinoin Isotretinoin (13 cis RA) reduces the size of sebaceous glands and markedly suppresses sebum production. Mechanism of action: Prolongation of maturation of basal sebocytes. Inhibition of terminal sebocyte differentiation. Reduction of 5 reductase activity in liver and skin. 31. Types of Sweat glands Eccrine glands Apocrine glands Apoeccrine glands 32. Eccrine glands Primary sweat glands responsible for thermoregulation. Present all over the body Merocrine glands. They open directly onto the surface of the skin. Smaller in size 33. Apocrine glands Present only in axillae, areola and perianalregion. Open into the hair follicle. Larger in size. Not functional until puberty. Decapitation secretion. Apocrine secretion is protein rich, milky whitein colour and odourless when first formed. Alteration by bacteria causes odour. 34. Apoeccrine glands Mixed type of sweat glands. Share morphological and functional featuresof both eccrine and apocrine glands. Develop during puberty. Open directly onto skin surface. Larger than eccrine glands and smaller thanapocrine glands. Constitute about 10 45 % of all glands inaxilla. 35. Control of sweat It is under : Thermal Osmotic Emotional Gustatory 36. Thermal control Thermoregulatory sweating occurs all over thebody, but more on the face and upper trunk. When central core temperature exceedstemperature set point, sweating occurs. Excessive body heat is dissipated byevaporation of sweat. One litre of evaporated sweat removes about585 kilocalories of heat from the body. 37. Thermosensitive receptors are present in preoptic area and anterior hypothalamus. They are also triggered by a rise in skin temperature. But the effect of core temperature rise is 9 times more efficient than skin temperature rise, in stimulating sweating. 38. Osmotic control Hyperosmolarity results in an elevation of the temperature set point and reduced sweating. As sweat is hypotonic, this is a response to conserve further water loss. 39. Emotional control Mental stimuli also produce sweating. Especially on the palms and soles. The responsible centres are within the frontal region of the brain. 40. Gustatory control After eating certain foods, sweating on the lips, forehead and nose occurs physiologically in many people. Hot spicy foods are the most common cause. Gustatory hyperhidrosis also occurs in pathological conditions involving the autonomic nervous system. 41. Innervation of Eccrine gland Sweat glands are innervated by postganglionicsympathetic fibres. These are slow conducting nonmyelinated Cfibres. Acetylcholine is the principalneurotransmitter. Physiological sweating is under cholinergiccontrol and partly adrenergic control. 42. Efferent Sudomotor pathwayCerebral cortex Sweat glandHypothalamusSympathetic ganglionMedullaLateral horn of spinal cord 43. Mechanism of sweat secretion Stimulation of neuronal outflow Release of acetylcholine ACH reacts with receptor in secretory cellmembrane Elaboration of nearly isotonic sweat from thesecretory coil Modification of primary sweat by reabsorbtionof NaCl to produce hypotonic eccrine sweat 44. Composition of sweat Odorless, colorless, hypotonic solution Sp. Gravity 1.005 pH between 4.5 & 5.5 Contents sodium, chloride, Potassium, urea, lactate, bic arbonate, ammonia, calcium, glucose, aminoa cids, proteins. Its composition differs from person to person, from time to time, and from site to 45. Other contents found are : Glandular Kallikrein Kininase C1 esterase Urokinase Cysteine proteinase Epidermal growth factor Drugs like Griseofulvin and Ketoconazole which are excreted. 46. Functions of sweat Thermoregulation Skin moisturisation (urea) Proinflammatory action (kallikrein) Excretion (drugs, toxins) Desquamation of stratum corneum (lactate) 47. Alteration in composition of sweatIncreased excretion of Electrolytes seen in : Cystic Fibrosis - esp. Sodium Addisons disease Diabetes mellitus Nephrogenic Diabetes insipidus Glycogen storage disease (type I) Adrenogenital syndrome Miliaria 48. Decrease electrolyte excretion seen in : Thyrotoxicosis Nephrosis Cirrhosis Aldosteronism Cushings syndrome 49. Excretion of large amounts of amino acids in sweat may occur in -PhenylketonuriaMaple syrup urine diseaseOast house syndromeHypermethioninemia Parathyroid dysfunction - calcium excretion Uremia - urea excretion 50. Hyperhidrosis Generalised hyperhidrosis Palmoplantar, axillary, craniofacial hyperhidrosis Localised or asymmetrical hyperhidrosis 51. Generalised hyperhidrosis Infections -malaria, TB, brucellosis, endocarditis Metabolic diseases -diabetes, hypoglycemia, hyperthyroidism, phaeochromocytoma Parkinsonism Congestive heart failure Malignancies Peripheral neuropathies Drugs - fluoxetine 52. Anhidrosis Leprosy, syringomyelia, diabetes Ross syndrome Icthyosis, scleroderma, myelomatosis Sjogrens syndrome Incontinentia pigmenti Psoriasis, lichen planus, eczemas Botulism Alcoholism 53. Treatment of hyperhidrosis Topical Anticholinergics - 1 % Glycopyrronium bromide 2 % Poldine methosulphate 1% Formaldehyde 10% Glutaraldehyde 20% Aluminium chloride Iontophoresis using tap water orglycopyrronium bromide Botulinum toxin A injection 54. Systemic drugs such as : Propantheline bromide Oxybutinin Diltiazem Amitriptyline Surgical treatment - sympathectomy 55. THANK YOU