WEEK 7

External features of the spinal cord, vertebral column and spinal nerve exits

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Epidermal Cells (4 types)

-Keratinocytes -Melanocytes -Langerhans -Merkel

ACNE- inflammation of a ____ gland • Affects 85 - 100% of people at some point in life • Genetic predisposition • Common in _____ (prior to onset of puberty-adrenal androgens): in all age groups • Affects face, back, chest upper arm - areas with increased sebaceous glands

ACNE- inflammation of a sebaceous gland • Affects 85 - 100% of people at some point in life • Genetic predisposition • Common in adolescents (prior to onset of puberty-adrenal androgens): in all age groups • Affects face, back, chest upper arm - areas with increased sebaceous glands

Conditions affecting pigmentation Albinism • Genetic (autosomal ____) • Loss of pigmentation of the ___, ____ & ____ • Lack of _____ • Types: Ocular + Oculocutaneous • Long term implications - ____ cancers - Reduced ____ acuity / ____phobia (macular hypoplasia) - Social stigma

Albinism • Genetic (autosomal recessive) • Loss of pigmentation of the skin, hair and eyes • Lack of tyrosinase • Types: Ocular + Oculocutaneous • Long term implications - Skin cancers - Reduced visual acuity / photophobia (macular hypoplasia) - Social stigma

CERVICAL - ATYPICAL VERTEBRAE ____ (C1) _____ (C2)

Atlas (C1) Axis (C2)

BURNS Rule of _____ -Used to describe burn coverage over the body and indirectly severity First degree -Partial thickness ____ only -Heals ____ Second degree -Partial thickness ____ & ____ -______ disrupted -Heals ______ Third degree burn -Full thickness ____, ____, & _____ -_____ disrupted -___ & _____ destroyed -Does not heal ______ -_____ loss is extensive

BURNS Rule of nine's -Used to describe burn coverage over the body and indirectly severity First degree -Partial thickness epidermis only -Heals spontaneously Second degree -Partial thickness epidermis and dermis -epithelial water barrier disrupted -Heals spontaneously Third degree burn -Full thickness epidermis, dermis and subcutaneous tissue -Water barrier disrupted -nerves and blood vessels destroyed -Does not heal spontaneously -fluid loss is extensive

-May undergo ulceration -Tumor cells infiltrating into the dermis

Basal cell carcinoma

Basal cell carcinoma • UV light • Proliferation of ___ stem cells • ____ nuclei with sparse poorly defined ____ • Cells at the periphery has a characteristic _____ appearance • ___ cells are more randomly arranged • It invades the ____ and deeper lying structures • Does not typically ____

Basal cell carcinoma • UV light • Proliferation of basal stem cells • Dark nuclei with sparse poorly defined cytoplasm • Cells at the periphery has a characteristic palisaded appearance • Central cells are more randomly arranged • It invades the dermis and deeper lying structures • Does not typically metastasize

List the components of the cardiovascular system Cardiovascular System • Consist of the ____, which pumps blood throughout the body, and the _____, which are a network of small tubes that transport the blood. Types of blood vessels: - _____, which transport blood away from the heart. Arteries have relatively thick walls that can withstand the high pressure of blood ejected from the heart. - _____, which transport blood toward the heart. Compared to arteries, veins are thin-walled vessels with large and irregular lumens. - _______, which connect the arteries and veins. It is at this level where oxygen, nutrients and waste are exchanged within the tissues. Walls of blood vessels • Tunica intima - inner ______ lining • Tunica media - middle _____ muscle layer. May contain ____ fibers • Tunica externa (adventitia) - outer _____ _______ layer

Cardiovascular System • Consist of the heart, which pumps blood throughout the body, and the blood vessels, which are a network of small tubes that transport the blood. Types of blood vessels: - Arteries, which transport blood away from the heart. Arteries have relatively thick walls that can withstand the high pressure of blood ejected from the heart. - Veins, which transport blood toward the heart. Compared to arteries, veins are thin-walled vessels with large and irregular lumens. - Capillaries, which connect the arteries and veins. It is at this level where oxygen, nutrients and waste are exchanged within the tissues. Walls of blood vessels • Tunica intima - inner endothelial lining • Tunica media - middle smooth muscle layer. May contain elastic fibers • Tunica externa (adventitia) - outer connective tissue layer

Cartilage ▪ Specialized type of ______: ➢ Unique cells, fiber population and ground substance ▪ 95% of cartilage is _____ ➢ solid and firm but pliable - accounts for its resilience ▪ 5% cells - _____, _____, _____ ▪ Major component of the ground substance is the _______- chondroitin-4-sulphate, chondroitin-6-sulphate, _______ ▪ Functions- -Confers shape, flexibility & elasticity -______ absorber (resistance to compression) -______ strength -Model for _____ formation

Cartilage ▪ Specialized type of connective tissue: ➢ Unique cells, fiber population and ground substance ▪ 95% of cartilage is extra cellular matrix (ECM) ➢ solid and firm but pliable - accounts for its resilience ▪ 5% cells - chondrocytes and chondroblasts, chondroclast ▪ Major component of the ground substance is the glycosaminoglycans (GAGs)- chondroitin-4-sulphate, chondroitin-6-sulphate, proteoglycans ▪ Functions- -Confers shape, flexibility & elasticity -Shock absorber (resistance to compression) -Tensile strength -Model for long bone formation

Cartilage cells Chondrocytes • Are matured _____ located in the _____ and surrounded by _____ • Located deeper to the chondroblasts and are more spherical • Divide by mitosis to form groups of __-___ chondrocytes, referred to as _____ groups or cell ____ - suggestive of internal growth Chondroclast - • originate from _____. Role is to ____ the cartilage

Cartilage cells Chondrocytes • Are matured chondroblasts located in the lacunae and surrounded by matrix • Located deeper to the chondroblasts and are more spherical • Divide by mitosis to form groups of 4 -8 chondrocytes, referred to as Isogenous groups or cell nest - suggestive of internal growth Chondroclast - • originate from monocytes. Role is to remodel the cartilage

Cartilage cells Chondrocytes • As chondrocytes in isogenous groups mature, they move apart by their own synthesis of ____. -This results in the growth of ____.

Cartilage cells Chondrocytes • As chondrocytes in isogenous groups mature, they move apart by their own synthesis of ECM. -This results in the growth of cartilage.

Cartilage cells • Cell constitute only 3-5% of total cartilage mass Chondroblasts • _____ cells give rise to chondroblasts • Location: just below chondrogenic layer of ______ • Chondroblasts are ovoid and positioned so that their longitudinal axes lie ____ to the cartilage surface • The space occupied by a chondroblast is called a _____ • They synthesize cartilage _____

Cartilage cells • Cell constitute only 3-5% of total cartilage mass Chondroblasts • Chondrogenic cells give rise to chondroblasts • Location: just below chondrogenic layer of perichondrium (P) • Chondroblasts are ovoid and positioned so that their longitudinal axes lie parallel to the cartilage surface • The space occupied by a chondroblast is called a lacuna • They synthesize cartilage matrix

Cell Populations of the Integumentary System ▪ _____ - largest cell population • ______ - pigment producing cells of the epidermis. Makes up about 5% of the cell population • ______ cells - mechanoreceptors/associated with sensory nerve endings/constitutes 6%- 10% of cells in the epidermis • Antigen presenting cells - ______cells - plays a role in the immunological function of skin. Accounts for 2%-5% of cells

Cell Populations of the Integumentary System ▪ Keratinocytes - largest cell population • Melanocytes - pigment producing cells of the epidermis. Makes up about 5% of the cell population • Merkel cells - mechanoreceptors/associated with sensory nerve endings/constitutes 6%- 10% of cells in the epidermis • Antigen presenting cells - Langerhan's cells - plays a role in the immunological function of skin. Accounts for 2%-5% of cells

Describe the flow of blood in the cardiovascular system Circulatory Routes >_____ shunt • Artery directly flows into a vein • Found in fingers, toes, ears; decreases ____ loss, allows blood to bypass exposed areas during _____ > ________: the union of branches of two or more vessels • Venous - Allows for alternative drainage of organs • Arterial - _______ circulation - alternatives routes for blood to reach a tissue or organ

Circulatory Routes >Arteriovenous shunt • Artery directly flows into a vein • Found in fingers, toes, ears; decreases heat loss, allows blood to bypass exposed areas during cold > Anastomosis: the union of branches of two or more vessels • Venous - Allows for alternative drainage of organs • Arterial - Collateral circulation - alternatives routes for blood to reach a tissue or organ

Composition of matrix: • Sulphated groups present in _____, make it hydro______, enabling easy diffusion of nutrition to the cells • Also provides resilience • Presence of ____ provide immense strength to the matrix so that cartilage can function as a model for bone formation.

Composition of matrix: • Sulphated groups present in GAGs, make it hydrophilic, enabling easy diffusion of nutrition to the cells • Also provides resilience • Presence of proteoglycans provide immense strength to the matrix so that cartilage can function as a model for bone formation.

Epidermal turnover time Time line: Days 1 - 2: cells in stratum basale -Divide _____ Days 3 - 31: remain in the stratum spinosum -And move to _____ Days 32 - 46 : keratinocytes become Keratinized and enter _____

Days 1 - 2: cells in stratum basale -Divide mitotically Days 3 - 31: remain in the stratum spinosum -And move to granulosum Days 32 - 46 : keratinocytes become Keratinized and enter corneum

Deep wound healing Inflammatory Phase: -______ is formed and loosely attaches the cut edges. -Vaso____ and increased permeability helps ____ & _____ (which become macrophages) to enter the area and eliminate microbes, foreign material and dying tissue. -_____ cells develop into fibroblasts. Migratory Phase: -As the clot becomes a ____, _____ cells migrate beneath it to bridge the wound. -____ synthesize scar tissue (collagen and glycoprotein) and damaged vessels regrow. -This now constitutes the _____ tissue. Proliferative Phase: -_____ of the epithelial tissue at random. -Continued growth of vessels. Maturation Phase: -_____ sloughs off. -_____ restored to normal thickness. -______ is more organized. -_____ decrease and blood vessels stabilize. -This type of scar - ____

Deep wound healing Inflammatory Phase: -Blood clot is formed and loosely attaches the cut edges. -Vasodilatation and increased permeability helps neutrophils and monocytes (which become macrophages) to enter the area and eliminate microbes, foreign material and dying tissue. -Mesenchymal cells develop into fibroblasts. Migratory Phase: -As the clot becomes a scab, epithelial cells migrate beneath it to bridge the wound. -Fibroblasts synthesize scar tissue (collagen and glycoprotein) and damaged vessels regrow. -This now constitutes the granulation tissue. Proliferative Phase: -Growth of the epithelial tissue at random. -Continued growth of vessels. Maturation Phase: -Scab sloughs off. -Epidermis restored to normal thickness. -Collagen is more organized. -Fibroblasts decrease and blood vessels stabilize. -This type of scar - fibrosis.

Dermis: Papillary layer • _____ layer • _____ connective tissue (more cells) • Contains ____ vessels • Predominately ___ & ____ collagen fibers • The elastic fibers are threadlike and form an ____ network • Relatively thin and includes the substance of the dermal papillae and dermal ridges • Contains _____

Dermis: Papillary layer • Superficial layer • Loose connective tissue (more cells) • Contains blood vessels • Predominately type I and III collagen fibers • The elastic fibers are threadlike and form an irregular network • Relatively thin and includes the substance of the dermal papillae and dermal ridges • Contains Meissner corpuscles

Dermis: Reticular layer • Considerably thicker than and deep to the papillary layer • _____ connective tissue (less cells) • It is characterized by _____ bundles of mostly ____ collagen and courser elastic fibers

Dermis: Reticular layer • Considerably thicker than and deep to the papillary layer • Dense irregular connective tissue (less cells) • It is characterized by thick irregular bundles of mostly type I collagen and courser elastic fibers

Eccrine sweat glands • The duct passes through the ___ & ___ to open onto the surface - Takes gentle spiral course to the epidermis which becomes ____ toward the surface - Composed of _____ epithelium consisting of a ____ layer and a ____ layer

Eccrine sweat glands • The duct passes through the dermis and epidermis to open onto the surface - Takes gentle spiral course to the epidermis which becomes tighter toward the surface - Composed of stratified cuboidal epithelium consisting of a basal layer and a luminal layer

Epidermal Appendages: Apocrine glands ▪ Found only in ___ & _____ ▪ _____ glands - Secretory portion located in the _____ > Secretory ____ larger than eccrine sweat glands ▪ Secrete ______ ▪ Secretion mode is ____ ▪ Ducts are ____ and lined by _____ epithelium - Has a ___ lumen ▪ Opens into the _____ ▪ Innervation: sympathetic via ____ neurotransmitters

Epidermal Appendages: Apocrine glands ▪ Found only in armpit and perineum ▪ Coiled tubular glands - Secretory portion located in the dermis/hypodermis > Secretory lumen larger than eccrine sweat glands ▪ Secrete pheromones ▪ Secretion mode is merocrine ▪ Ducts are straight and lined by stratified cuboidal epithelium - Has a narrow lumen ▪ Opens into the hair follicle ▪ Innervation: sympathetic via catecholamines neurotransmitters

Epidermal Appendages: Eccrine sweat glands ▪ Thick and thin skin ▪ _____ glands ▪ Innervation: ____ via cholinergic neurotransmitters ▪ Secretory portion is in the ____, _____ secretion Contains: - ____ cells - abundant glycogen stains well with PAS - ____ cells - rER and secretory granules are abundant - _____ cells - basal aspect of the secretory segment

Epidermal Appendages: Eccrine sweat glands ▪ Thick and thin skin ▪ Simple coiled tubular glands ▪ Innervation: sympathetic via cholinergic neurotransmitters ▪ Secretory portion is in the deep dermis, merocrine secretion Contains: - Clear cells - abundant glycogen stains well with PAS - Dark cells - rER and secretory granules are abundant - Myoepithelial cells - basal aspect of the secretory segment

Epidermal Appendages: Sebaceous glands ▪ ______ gland ▪ Secretory portion - Located _____ ▪ Opens into ____ ▪ Secretion is ____ ▪ Product is _____ - Poor staining with H&E - Prevents the hair from becoming ___ & _____ -Clinical correlate: _____

Epidermal Appendages: Sebaceous glands ▪ Simple branched acinar gland ▪ Secretory portion - Located deeper dermis ▪ Opens into hair follicle ▪ Secretion is holocrine ▪ Product is sebum - Poor staining with H&E - Prevents the hair from becoming dry and brittle -Clinical correlate: Acne

Epidermal ridge, dermal ridge, dermal papillae Areas of increased mechanical stress has ______ epidermal ridges and ____, more ____ spaced dermal papillae Responsible for ____

Epidermal ridge, dermal ridge, dermal papillae Areas of increased mechanical stress has deeper epidermal ridges and longer, more closely spaced dermal papillae Responsible for fingerprinting

Epithelial Appendages: Hair Follicle • Hair: _____ shafts composed of ____ • Extends into the ____dermis • Produced in ____ • Associated with _____ gland - Hair follicle plus gland and smooth muscle (_____) = _____ organ/unit • Found in ____ skin only • Consists of - Infundibulum - Isthmus - Inferior segment • Bulb contains the matrix cells for hair formation - _____ stem cells are found in the bulb

Epithelial Appendages: Hair Follicle • Hair: Cylindrical shafts composed of keratin • Extends into the hypodermis • Produced in follicles • Associated with sebaceous gland - Hair follicle plus gland and smooth muscle (arrector pili) = pilosebaceous organ/unit • Found in thin skin only • Consists of - Infundibulum - Isthmus - Inferior segment • Bulb contains the matrix cells for hair formation - Melanocyte stem cells are found in the bulb

Extra Cellular Matrix (ECM) • Constitutes >95% of ____ volume • Composed of amorphous ____ and ____ fibrils • Collagen constitutes about 15% of the total mass with Type ____ being most abundant. Elastic fibers and Type ____ collagen also present depending on the type of cartilage • It is not readily discernible in histological sections because some of the fibrils (type II collagen) are very fine and have the same refractive index as the ground substance as seen in hyaline cartilage.

Extra Cellular Matrix (ECM) • Constitutes >95% of cartilage volume • Composed of amorphous ground substance and collagen fibrils • Collagen constitutes about 15% of the total mass with Type II being most abundant. Elastic fibers and Type 1 collagen also present depending on the type of cartilage • It is not readily discernible in histological sections because some of the fibrils (type II collagen) are very fine and have the same refractive index as the ground substance as seen in hyaline cartilage.

Free Nerve Endings • Occupy _____ and send twigs into the ____ (terminate in the stratum ____) • ____ numerous • Do not possess any ____ or ____ • Subserve multiple sensory modalities -Pain, fine touch, itching, temperature (heat and cold) • Networks of free dermal endings surround most ____ - Attach to their ____ - Very sensitive to hair movement and serve as mechanoreceptors

Free Nerve Endings • Occupy papillary dermis and send twigs into the epidermis (terminate in the stratum granulosum) • Most numerous • Do not possess any myelin or connective tissue • Subserve multiple sensory modalities -Pain, fine touch, itching, temperature (heat and cold) • Networks of free dermal endings surround most hair follicles - Attach to their outer root sheath - Very sensitive to hair movement and serve as mechanoreceptors

Functions of Skin • Barrier • Immunological role - presents ____ to the lymphatic tissue • Homeostasis - regulation of body temperature and ____ loss • Sensory information - samples the external environment and relays this information to the nervous system • Endocrine functions - secretes hormones, cytokines and growth factors, converts vitamin D into its hormonally active form ____ • Excretion - secretes ____ and other products from the body

Functions of Skin • Barrier • Immunological role - presents antigens to the lymphatic tissue • Homeostasis - regulation of body temperature and water loss • Sensory information - samples the external environment and relays this information to the nervous system • Endocrine functions - secretes hormones, cytokines and growth factors, converts vitamin D into its hormonally active form D3 • Excretion - secretes sweat and other products from the body

Melanocytes Functions: • Produce melanin that is transferred to surrounding keratinocytes (_____ secretion) - UV protection • Skin color - amount and ratio of melanin types present - Lighter skinned individuals have increased melanin ______ • Oxidation of _____ to 3,4- dihydroxyphenylalanine (DOPA) and subsequent transformation of DOPA into _____

Functions: • Produce melanin that is transferred to surrounding keratinocytes (Cytocrine secretion) - UV protection • Skin color - amount and ratio of melanin types present - Lighter skinned individuals have increased melanin degradation • Oxidation of tyrosine to 3,4- dihydroxyphenylalanine (DOPA) and subsequent transformation of DOPA into melanin

Hair follicle and hair formation • Matrix cells contribute to formation of the _____ and the ____ • Keratogenous zone: matrix cells undergo _____ as soon as they pass through this zone • The fully keratinized hair consisting of ____ keratin is not followed by the internal root sheath • It is separated from the underlying dermis via a _____ (glassy membrane)

Hair follicle and hair formation • Matrix cells contribute to formation of the internal root sheath and the hair shaft • Keratogenous zone: matrix cells undergo keratinization as soon as they pass through this zone • The fully keratinized hair consisting of hard keratin is not followed by the internal root sheath • It is separated from the underlying dermis via a thick basal laminal (glassy membrane)

Describe the flow of blood in the cardiovascular system Circulatory Routes >Most common • _______ > Portal system • Blood flows through to consecutive _______ before returning to the heart - Between the _____ - Anterior _____

Heart - arteries - arterioles - capillary bed - venules - veins - heart capillary beds intestines & liver pituitary

Hypodermis • Found deep to (beneath) the _____ • Often referred to as the subcutaneous fascia in gross anatomy • Contains variable amounts of _____ tissue (panniculus adiposus) arranged in lobules and separated by connective tissue septa • Can be very _____ in cold countries • Can find _____, _____, and ______ in this layer

Hypodermis • Found deep to (beneath) the dermis • Often referred to as the subcutaneous fascia in gross anatomy • Contains variable amounts of adipose tissue (panniculus adiposus) arranged in lobules and separated by connective tissue septa • Can be very thick in cold countries • Can find hair follicles, glands and mechanoreceptors in this layer

In older cells... Electron micrographs: • Irregular chondrocyte surfaces • Extensive ____ • Abundant ______ • __chromatic nucleus • _____ droplets and _____ deposits

In older cells... Electron micrographs: • Irregular chondrocyte surfaces • Extensive Golgi apparatus • Abundant rough ER • Euchromatic nucleus • Lipid droplets and glycogen deposits

Integument System Two layers of skin: 1. _______ (Epithelium + cells) -Keratinized stratified squamous epithelium -Derived from ______ 2. _____ -Dense connective tissue -Derived from _____

Integument System Two layers of skin: 1. Epidermis (Epithelium + cells) -Keratinized stratified squamous epithelium -Derived from ectoderm 2. Dermis -Dense connective tissue -Derived from mesoderm

Keratinization - a summary • The process via which cells accumulate _____ in their cytoplasm • Cells lose their ____, ___ & ____ • More ______ are formed • arranged into ____ by _____ • When it reaches the upper layers of the stratum _____ the _____ are broken apart • Cells sloughed off • Total epidermal turnover time +/- ___ days

Keratinization - a summary • The process via which cells accumulate keratin in their cytoplasm • Cells lose their organelles, cytoplasm and nuclei • More tonofilaments are formed • arranged into fibrils by filaggrin • When it reaches the upper layers of the stratum corneum the desmosomes are broken apart • Cells sloughed off • Total epidermal turnover time +/- 47 days

Keratinocytes • Keratinocytes in the stratum basale contain: 1. Organelles: • Numerous free _____ (giving them a basophilic appearance) - Responsible for the _____ of keratin • Small Golgi apparatus • Mitochondria • rER 2. Cytoskeletal Elements: - Keratin filaments > Later gets assembled into _____ - stratum ____ (hence more eosinophilic staining)

Keratinocytes • Keratinocytes in the stratum basale contain: Organelles: • Numerous free ribosomes (giving them a basophilic appearance) - Responsible for the synthesis of keratin • Small Golgi apparatus • Mitochondria • rER Cytoskeletal Elements: - Keratin filaments > Later gets assembled into tonofibrils - stratum spinosum (hence more eosinophilic staining)

Keratinocytes • Constitutes most of the cell types (85%) of the epidermis • Differentiates from ____ layer, and continues throughout all layers of the epidermis Functions: • Produces ____ (_____)- mainly the keratinocytes of stratum ____ • Produce kerato_____ granules - cells in ____ and _____ layers • Contributes to the formation of the epidermal ______ barrier

Keratinocytes • Constitutes most of the cell types (85%) of the epidermis • Differentiates from basal layer, and continues throughout all layers of the epidermis Functions: • Produces keratin (cytokeratin)- mainly the keratinocytes of stratum basale • Produce keratohyalin granules - cells in spinosum and granulosum layers • Contributes to the formation of the epidermal water barrier

Langerhan's Cell: Structure • Originates from _____ Function • _____ role • Encounters, processes and expresses antigens (_____ cell (_____)) • Migrates to the lymph node to present the antigen to _____-lymphocytes • Involved in delayed type _____ reactions • Express both ____ and ____ and receptors for IgG Under light microscopy: Nucleus stain with hematoxylin (blue) Cytoplasm is clear

Langerhan's Cell: Structure • Originates from common lymphoid progenitor (CLP) Function • Immunological role • Encounters, processes and expresses antigens (Antigen presenting cell (APC)) • Migrates to the lymph node to present the antigen to T-lymphocytes • Involved in delayed type hypersensitivity reactions • Express both MHC 1 and MHC II and receptors for IgG Under light microscopy: Nucleus stain with hematoxylin (blue) Cytoplasm is clear

Langerhan's Cell: TEM Structure • Nucleus is _____ making the nuclear profile uneven (see arrows) • Possesses tennis racquet shaped granules (_____ granules) - small vesicles which appear as rods with a bulbous expansion (function unclear)

Langerhan's Cell: TEM Structure • Nucleus is indented making the nuclear profile uneven (see arrows) • Possesses tennis racquet shaped granules (Birbeck granules) - small vesicles which appear as rods with a bulbous expansion (function unclear)

Describe the flow of lymph Lymphatic system • Consists of lymphatic ____, lymph _____ and lymphatic _____ • Drains excessive ______ • Excessive ^^ flows into lymphatic ______ located amongst the tissues. • Lymph eventually drains into lymphatic ______. • Located alongside lymphatic vessels are lymph _____. Larger groups are found near the ___,___, & ____. Lymph nodes function as a ______ for the fluid flowing through them. • Eventually all lymphatic fluid drains back into the cardiovascular system via the ______ duct and _____ duct.

Lymphatic system • Consists of lymphatic vessels, lymph nodes and lymphatic organs • Drains excessive interstitial fluid • Excessive ^^ flows into lymphatic capillaries located amongst the tissues. • Lymph eventually drains into lymphatic vessels. • Located alongside lymphatic vessels are lymph nodes. Larger groups are found near the mammary glands, axilla and groin. Lymph nodes function as a filter for the fluid flowing through them. • Eventually all lymphatic fluid drains back into the cardiovascular system via the right lymphatic duct and thoracic duct.

Malignant Melanoma • Malignant transformation of _____ • Causes highest # of skin cancer related deaths in US • More common in whites, Australia / S. Africa • Etiology-exposure to sunlight (UV): (typesacute, intermittent, blistering) • Increased number of melanocytes with large atypical morphology --arranged at the _____ junction • May invade the _____ - metastases - fatal

Malignant Melanoma • Malignant transformation of melanocytes • Causes highest # of skin cancer related deaths in US • More common in whites, Australia / S. Africa • Etiology-exposure to sunlight (UV): (typesacute, intermittent, blistering) • Increased number of melanocytes with large atypical morphology --arranged at the dermo-epidermal junction • May invade the dermis - metastases - fatal

Meissner's Corpuscle ▪ Touch receptors particularly responsive to ____ frequency stimuli - ____ cylinders . - 150 microns along their long axis - Perpendicular to the skin surface ▪ ___ papillae just beneath the epidermal ____ ▪ Appears as twisted skein of wool ▪ There are one or two unmyelinated nerve endings of myelinated nerve fibers follow spiral paths in the corpuscle ▪ The cellular component consist of flattened _____ cells that form several _____ lamellae through which the axons course to the pole of the corpuscle

Meissner's Corpuscle ▪ Touch receptors particularly responsive to low frequency stimuli - Tapered cylinders . - 150 microns along their long axis - Perpendicular to the skin surface ▪ Dermal papillae just beneath the epidermal basal lamina ▪ Appears as twisted skein of wool ▪ There are one or two unmyelinated nerve endings of myelinated nerve fibers follow spiral paths in the corpuscle ▪ The cellular component consist of flattened Schwann cells that form several irregular lamellae through which the axons course to the pole of the corpuscle

Melanocytes • Found in the _____ layer (stratum ___) - Appear clear with large ___ nuclei - Cytoplasmic processes extend between _____ - 1 melanocyte can communicate with up to ______ - No desmosomal connections but are attached to the basal lamina via ______ like structures • Melanocyte to _____ ratio 1:4 to 1:10 - Varies according to the region of the body

Melanocytes • Found in the basal layer (stratum basale) - Appear clear with large enlongated nuclei - Cytoplasmic processes extend between keratinocytes - 1 melanocyte can communicate with up to 40 keratinocytes - No desmosomal connections but are attached to the basal lamina via hemidesmosome like structures • Melanocyte to keratinocyte ratio 1:4 to 1:10 - Varies according to the region of the body

Merkel's Corpuscle ▪ Merkel's cell in communication with expanded terminal bulb of afferent myelinated nerve fibers = Merkel's corpuscle ▪ Detect ___ sensations ▪ Most abundant in ____ where sensory perceptions is ____ (fingertips) ▪ Cytoplasm contains ____ granules ▪ Express _____ markers of both epidermal and neural type

Merkel's Corpuscle ▪ Merkel's cell in communication with expanded terminal bulb of afferent myelinated nerve fibers = Merkel's corpuscle ▪ Detect touch sensations ▪ Most abundant in skin where sensory perceptions is acute (fingertips) ▪ Cytoplasm contains neurosecretory granules ▪ Express antigenic markers of both epidermal and neural type

Pacinian Corpuscle ▪ Large ovoid ▪ Deep ___ & ____ ▪ Have macroscopic dimensions more than 1mm along their long axis ▪ Composed of a ____ nerve ending surrounded by a capsule structure ▪ Nerve looses its myelin sheath after entering capsule ▪ The unmyelinated portion is covered by a series of tightly packed, flattened _____ lamellae that form the inner core of the corpuscle ▪ The remainder is formed by a series of ____ lamella ▪ ____ pressure and ____

Pacinian Corpuscle ▪ Large ovoid ▪ Deep dermis and hypodermis ▪ Have macroscopic dimensions more than 1mm along their long axis ▪ Composed of a myelinated nerve ending surrounded by a capsule structure ▪ Nerve looses its myelin sheath after entering capsule ▪ The unmyelinated portion is covered by a series of tightly packed, flattened Schwann cell lamellae that form the inner core of the corpuscle ▪ The remainder is formed by a series of concentric lamella ▪ Deep pressure and vibration

Process of hair growth • Cyclical process • Occurs in three (3) phases: - Long phase of active growth (anagen) - Short phase of involution (catagen) - Short inactive phase (telogen) • Growth cycle varies from site to site: - Scalp hair follicles have active growth growth phase of 2 years and a short inactive of a few months - Pubic hairs, coarse trunk hair, eyelashes, eyebrows have a short growth phase and a relatively long resting phase hence they are not so long

Process of hair growth • ____ process • Occurs in three (3) phases: - ____ phase of active growth (____) - ____ phase of involution (____) - ____ inactive phase (_____) • Growth cycle varies from site to site: - _____ hair follicles have active growth growth phase of 2 years and a short inactive of a few months - _____ hairs, coarse trunk hair, eyelashes, eyebrows have a short growth phase and a relatively long resting phase hence they are not so long

Ruffini's Corpuscle • Simplest and have an elongated _____ shape - 1-2 microns • Thin connective tissue capsule surrounding a ______ space • ____ fibers from surrounding connective tissue pass through the capsule • _____ myelinated fiber enters the capsule - Looses its myelin sheath - Branches to form a dense _____ of fine axonal endings each terminating in a small knoblike bulb • The axonal endings are dispersed and intertwined inside the capsule • The axonal endings respond to displacement of the collagen fibers induced by sustained or continuous mechanical stress and so to respond to ____ and ____

Ruffini's Corpuscle • Simplest and have an elongated fusiform shape - 1-2 microns • Thin connective tissue capsule surrounding a fluid filled space • Collagen fibers from surrounding connective tissue pass through the capsule • Single myelinated fiber enters the capsule - Looses its myelin sheath - Branches to form a dense arborization of fine axonal endings each terminating in a small knoblike bulb • The axonal endings are dispersed and intertwined inside the capsule • The axonal endings respond to displacement of the collagen fibers induced by sustained or continuous mechanical stress and so to respond to stretch and torque

Dermis deeply infiltrated by islands and sheets of malignant squamous

Squamous Cell Carcinoma

Squamous Cell Carcinoma • Malignant tumor of _____ • Exposure to UV with DNA damage (inactivation of _____ gene) • Loss of orderly maturation with variability in nuclear size and shape • ___keratosis and ____keratosis • Common in _____ people (70thdecade) • _____-skinned > ____-skinned • Predisposing factors : - sunlight (UV) - industrial carcinogens - chronic ulcers - tobacco chewing - Burns - ionizing radiation - betel nut chewing • More common in ___ & _____ region (likely due to sunlight exposure)

Squamous Cell Carcinoma • Malignant tumor of keratinocytes • Exposure to UV with DNA damage (inactivation of P53 gene) • Loss of orderly maturation with variability in nuclear size and shape • Hyperkeratosis and parakeratosis • Common in older people (70thdecade) • Fair-skinned > Dark-skinned • Predisposing factors : - sunlight (UV) - industrial carcinogens - chronic ulcers - tobacco chewing - Burns - ionizing radiation - betel nut chewing • More common in head and neck region (likely due to sunlight exposure)

Stratum Basale • Single layer of cuboidal to low columnar cells • _____ active > Keratinocytes stem cells (stratum _____) - _____ cells - ______cytes - Noticeable ____philia on H&E staining • Small cells with scant basophilic staining cytoplasm - Nuclei ____ spaced - Contains many ____ granules - Synthesize ____ filaments • Rests on the ______ - Attached by _____ • Extensive cell junctions - ______ Clinical correlate: ______

Stratum Basale • Single layer of cuboidal to low columnar cells • Mitotically active > Keratinocytes stem cells (stratum germinativum) - Merkel cells - Melanocytes - Noticeable basophilia on H&E staining • Small cells with scant basophilic staining cytoplasm - Nuclei closely spaced - Contains many melanin granules - Synthesize keratin filaments • Rests on the basal lamina - Attached by hemidesmosomes • Extensive cell junctions - Desmosomes Clinical correlate: Bullous pemphigoid

Stratum Corneum • Several layers of ____ keratinocytes - Variable number of layers > Point of _____ between thick and thin skin - Lack _____ - Thick plasma membranes covered with _____, forming a barrier that is impermeable to _____ • Keratinocytes filled with keratin aggregated into ______ • Abrupt transition from granulosum • Clinical correlates: - bullous pemphigoid - Pemphigoid vulgaris

Stratum Corneum • Several layers of dead keratinocytes - Variable number of layers > Point of differentiation between thick and thin skin - Lack organelles - Thick plasma membranes covered with lipid, forming a barrier that is impermeable to water (WATER BARRIER) • Keratinocytes filled with keratin aggregated into tonofibrils • Abrupt transition from granulosum • Clinical correlates: - bullous pemphigoid - Pemphigoid vulgaris

Stratum Granulosum • Most _____ of the nonkeratinized cells • Averages ____ to ____ cell layers thick • Contains _____ granules which give them a granulated appearance - _____ granules > Irregularly shaped, variably sized, stains intensely basophilic > _____ & ______ rich proteins = precursors for _____ • Responsible for aggregating the keratin filaments within the cornified cells • Keratinization (soft keratin) - Loss of ______, thickened cell membrane, _____ pH • Lamellar bodies • Epidermal ______ barrier

Stratum Granulosum • Most superficial of the nonkeratinized cells • Averages one to three cell layers thick • Contains conspicuous granules which give them a granulated appearance - Keratohyalin granules > Irregularly shaped, variably sized, stains intensely basophilic > Cystine and histidine rich proteins = precursors for fillagrin • Responsible for aggregating the keratin filaments within the cornified cells • Keratinization (soft keratin) - Loss of organelles, thickened cell membrane, decreased pH • Lamellar bodies • Epidermal water barrier

Stratum Lucidum • Only well seen in ____ skin • Some consider it a subdivision of the stratum ______ • In light microscopic view it appears as a light highly refractile eosinophilic band • Appears to contain cells in which the ______ process is well advanced

Stratum Lucidum • Only well seen in thick skin • Some consider it a subdivision of the stratum corneum • In light microscopic view it appears as a light highly refractile eosinophilic band • Appears to contain cells in which the keratinization process is well advanced

Stratum Spinosum (S) • Most noticeable in the most ___ layer of cells - Nuclei become ____ instead of ovoid • Keratinocytes in uppermost part of this layer - begin to produce _____ granules - ______ bodies • ______ cells - Also found predominantly in this layer, but are able to move freely throughout epidermis Clinical correlate: _______

Stratum Spinosum (S) • Most noticeable in the most superficial layer of cells - Nuclei become elongated instead of ovoid • Keratinocytes in uppermost part of this layer - begin to produce keratohyalin granules - lamellar bodies • Langerhans cells - Also found predominantly in this layer, but are able to move freely throughout epidermis Clinical correlate: Pemphigus vulgaris

Stratum Spinosum (S) • Several cell layers thick • _______ are larger than those in the stratum basale • Make _____ filaments • Exhibit numerous _____ or _____ - Prickle cell layer - Processes of neighboring cells are connected to each other via ____ > Appears as a slight thickening and is known as _____ • Gradually change their appearance as they move closer to the surface - Increase in size and become ____ in a plane parallel to the surface

Stratum Spinosum (S) • Several cell layers thick • Keratinocytes are larger than those in the stratum basale • Make cytokeratins/keratin filaments • Exhibit numerous cytoplasmic processes or spines - Prickle cell layer - Processes of neighboring cells are connected to each other via desmosomes > Appears as a slight thickening and is known as node of Bizzozero • Gradually change their appearance as they move closer to the surface - Increase in size and become flattened in a plane parallel to the surface

Distinguishing between thick and thin skin The distinction of thick vs think skin is made on the thickness of the _____ Thick Skin • Found only in the _____ and ____ • Usually ___ and much _____ epidermis • Carries a stratum ____ Thin Skin • Found everywhere else • ____ epidermis than thick skin • ______ follicles are widespread except for a few locations

The distinction of thick vs think skin is made on the thickness of the epidermis Thick Skin • Found only in the palms and soles • Usually hairless and much thicker epidermis • Carries a stratum lucidum Thin Skin • Found everywhere else • Thinner epidermis than thick skin • Hair follicles are widespread except for a few locations

Arteries ______ walls • Tunica intima - inner endothelial lining • Tunica media - numerous layers of smooth muscle and elastic fibers. • Tunica externa (adventitia) - outer connective tissue layer - Further subdivided into three classes • Large • Medium • Small

Thick

Veins ____ walls • Tunica intima - inner endothelial lining, folded to form valves • Tunica media -limited layers of smooth muscle and elastic fibers • Tunica externa (adventitia) - Thick outer connective tissue layer - Further subdivided into three classes • Large • Medium • Small

Thin

Two forms of melanin • Pigment produced by melanocytes consist of 2 different types: - ______ - brownish - ______ - reddish • The ratio between these 2 determines skin and hair color • Melanin is dispersed differently in dark vs light skinned individuals - Light skinned individuals have their melanin concentrated in the stratum ____ - Dark skinned individuals have the pigment dispersed throughout the _____ and ______ layers

Two forms of melanin • Pigment produced by melanocytes consist of 2 different types: - Eumelanin - brownish - Pheomelanin - reddish • The ratio between these 2 determines skin and hair color • Melanin is dispersed differently in dark vs light skinned individuals - Light skinned individuals have their melanin concentrated in the stratum basale - Dark skinned individuals have the pigment dispersed throughout the basale and spinosum layers

Conditions affecting pigmentation Vitiligo • _____ disorder • _____ immune • Destruction of ______ • Types: Focal, Segmental, Generalized Treatment: -Medical: • Topical ____ therapy • Psolaren Photochemotherapy • Depigmentation -Surgical: • Autologous skin graft • Micropigmentation • _____ transplants

Vitiligo • Depigmentation disorder • Auto immune • Destruction of melanocytes • Types: Focal, Segmental, Generalized Treatment: -Medical: • Topical steroid therapy • Psolaren Photochemotherapy • Depigmentation -Surgical: • Autologous skin graft • Micropigmentation • Melanocyte transplants

Cells of bone tissue identification 1) Osteoblasts: cuboidal cells located on the periphery of bone. Displays euchromatic nuclei with a basophilic cytoplasm. 3) Osteocytes: mature osteoblasts entrapped in boney matrix 2) Osteoclasts: large, multinucleated macrophages located along the endosteum

switch 2 & 3

Wound Healing -Skin damage sets in motion a sequence of events that repairs the skin to its normal (or near normal) structure and function. • 2 types: 1. ____ wound healing: Occurs following wounds that affect only the epidermis 2. _____ wound healing: Occurs following wounds that penetrate the dermis.

• 2 types: 1. Epidermal wound healing: Occurs following wounds that affect only the epidermis 2. Deep wound healing: Occurs following wounds that penetrate the dermis.

Epidermis Stratified squamous keratinized epithelium • 5 Layers (deep to superficial) • Stratum basale - Can _____ • Stratum spinosum - Maturing and slowly ___ cells • Stratum granulosum - Cells that are about to die • Stratum lucidum - _____ skin only • Stratum corneum - _____ keratinized cells

• 5 Layers (deep to superficial) • Stratum basale - Can differentiate • Stratum spinosum - Maturing and slowly dying cells • Stratum granulosum - Cells that are about to die • Stratum lucidum - Thick skin only • Stratum corneum - Dead keratinized cells

Psoriasis • A chronic inflammatory and hyperproliferative disorder of the skin • Clinically manifested as well-circumscribed, erythematous and itchy plaques covered with silvery scales - knees, elbows, lower back, scalp • Epidermal turnover is on average 8-10 days • Characterized by hyperkeratosis and parakeratosis Predisposing factors: • Genetic background • Inciting factors Pathogenesis: -Exogenous/Endogenous antigens -Antigen presentation by APCs -T-lymphocyte- mediated immune response -Cytokine secretion -Clinical lesions of psoriasis

• A chronic inflammatory and hyperproliferative disorder of the skin • Clinically manifested as well-circumscribed, erythematous and itchy plaques covered with silvery scales - knees, elbows, lower back, scalp • Epidermal turnover is on average 8-10 days • Characterized by hyperkeratosis and parakeratosis Predisposing factors: • Genetic background • Inciting factors Pathogenesis: -Exogenous/Endogenous antigens -Antigen presentation by APCs -T-lymphocyte- mediated immune response -Cytokine secretion -Clinical lesions of psoriasis

Deep wound healing • As the injury involves _____ layers, healing process is more complex. Healing involves ____ formation and can include loss of _____ • This type of healing occurs in 4 phases:

• As the injury involves multiple tissue layers, healing process is more complex. Healing involves scar formation and can include loss of function - Inflammatory Phase - Migratory Phase - Proliferative Phase - Maturation Phase

Formation of Epithelial Water Barrier present in all layers superficial to the stratum granulosum • Cell envelope - ______ on inside of cell membrane - Mechanical part of barrier • Lipid envelope - ______ layer on outer surface of the cell membrane - ______ bodies • Formed by the golgi apparatus of the ____ cells • Content rich in lipids (ceramides, cholesterol) and lipid processing enzymes • Secreted by _____ in the granulosum layer into the intercellular spaces • Travels with the corneum cells until they are exfoliated

• Cell envelope - Insoluble proteins on inside of cell membrane - Mechanical part of barrier • Lipid envelope - Lipid layer on outer surface of the cell membrane - Lamellar bodies • Formed by the golgi apparatus of the spinosum cells • Content rich in lipids (ceramides, cholesterol) and lipid processing enzymes • Secreted by exocytosis in the granulosum layer into the intercellular spaces

Dermis • Gives the ___ & ____ to skin • Contains many of the epidermal appendages, nerve corpuscles, and glands • Contains the smooth muscle cells that move the hairs • Around areolae, penis, scrotum and perineum, smooth muscle cells form a loose plexus in the reticular layer • This accounts for the puckering of the skin at these sites, particularly in erectile organs Papillary Layer: ____ CT Reticular Layer: ____ CT

• Gives the strength and elasticity to skin Papillary Layer: Loose CT Reticular Layer: Dense Irregular CT

• _____ - thickening of the stratum corneum • _____ - retention of nuclei in the keratinocytes of the stratum corneum • _____ - increase in thickness of the stratum spinosum

• Hyperkeratosis - thickening of the stratum corneum • Parakeratosis - retention of nuclei in the keratinocytes of the stratum corneum • Acanthosis - increase in thickness of the stratum spinosum

Epidermal wound healing • In response to an injury, the ____ cells of the epidermis surrounding the wound, break contact with the basement membrane, ____ and ____ across the wound. • The cells migrate from ____ sides until they meet (in a _____ formation). • ______ stimulates stem cells to _____ and ______ the lost cells, that have moved into the wound. • These new cells divide to _____ the new epithelium.

• In response to an injury, the basal cells of the epidermis surrounding the wound, break contact with the basement membrane, enlarge and migrate across the wound. • The cells migrate from opposite sides until they meet (in a sheetlike formation). • Epidermal growth factor stimulates stem cells to divide and replace the lost cells, that have moved into the wound. • These new cells divide to thicken the new epithelium.

Merkel's Cell: Structure • _____ numerous • Most abundant in skin where sensory perception is ____ (____) • Closely associated with the expanded _____ bulb of afferent _____ nerve fibers - Merkel's ______ • Function: Detect _____ sensations • Have _____ and contain ____ filaments • Nucleus is _____ • Cytoplasm contains _____ granules • Possess _____ markers of both epidermal and neural type

• Least numerous • Most abundant in skin where sensory perception is acute (fingertips) • Closely associated with the expanded terminal bulb of afferent myelinated nerve fibers - Merkel's corpuscle • Function: Detect touch sensations • Have desmosomes and contain keratin filaments • Nucleus is lobed • Cytoplasm contains neurosecretory granules • Possess antigenic markers of both epidermal and neural type

Factors Associated With Skin Pigmentation • Melanin production is influenced by the surrounding keratinocytes in response to _____ radiation • Each type of melanin has a different function and is driven by different genetic factors • Eumelanin - brownish - ____ against UVR damage - scatter and absorb UV rays and eliminate UV-generated free radicals - _____ faster in light skinned individuals • Pheomelanin -reddish - allows more ____ to pass through thereby increasing _____ production at altitudes where light intensity is low - found more commonly in atypical _____ and _____ - increased _____ damage

• Melanin production is influenced by the surrounding keratinocytes in response to UV radiation • Each type of melanin has a different function and is driven by different genetic factors • Eumelanin - brownish - protection against UVR damage - scatter and absorb UV rays and eliminate UV-generated free radicals - degrades faster in light skinned individuals • Pheomelanin -reddish - allows more light to pass through thereby increasing vitamin D production at altitudes where light intensity is low - found more commonly in atypical nevi and melanomas - increased oxidative damage

• _____ - a small, circumscribed elevation of the skin containing fluid, other liquid or gas • _____ - a large blister appearing as a circumscribed area of separation of the epidermis from underlying structures, or of the epidermal cells • _____ - a small, circumscribed elevation of the skin, containing purulent material

• Vesicle - a small, circumscribed elevation of the skin containing fluid, other liquid or gas • Bulla - a large blister appearing as a circumscribed area of separation of the epidermis from underlying structures, or of the epidermal cells • Pustule - a small, circumscribed elevation of the skin, containing purulent material