hair follicle
subaceous gland
sweat gland                   
thin skin                         
thick skin



stratified squamous keratinized epithelium
stratum basale = stratum germinativum                     
intermediate filaments
stratum spinosum      
malpighian layer         
stratum granulosum
keratohyaline granules           
membrane-coating granules
stratum lucidum                        
stratum corneum
keratinized cells                         
horny cells                     
neural crest                   
Golgi vesicles (stages I, II, III, IV)                                     
Langerhans cells                         
Merkel cells                   
epidermal ridges


dermal papillae                          
papillary layer             
collagen fibrils
reticular layer                             
elastic fibers


I. General considerations:

A. Skin is an organ that fulfills and/or mediates many different functions. (i.e. excretion, temperature control, communication with external environment, protection (insulation and protection from abrasion and some dissolved substances), retards dehydration.)

B. It is the heaviest single organ in body (16% body wt.)

C. Consists of two major tissue layers

1. epidermis (ectodermally derived) - stratified squamous epithelium

2. dermis (mesodermally derived) - connective tissue

D. Thickness and structure of these layers varies according to whether we are dealing with thick or thin skin.

1. Most of the body is covered with thin skin.

2. Parts of the body that are subject to frequent abrasion such as the palms of the hands and soles of the feet are covered with thick skin.

E. Where epidermis and dermis meet, both are thrown into a series of folds that interdigitate.

1. The dermal folds are called dermal papillae.

2. Epidermal folds are called epidermal ridges.

F. We can also consider a third layer that is NOT actually part of the skin, but that binds dermis to underlying tissues. This is the subcutaneous layer or hypodermis.


I. Epidermis - keratinized stratified squamous epithelium:

A. There are 4 cell types

1. Keratinocytes (skin cells that form the keratinized stratified squamous epithelium)

2. Melanocytes - pigment producing cells

3. Langerhans cells - found in the stratum spinosum, may have immune function

4. Merkel cells - present in epidermis of thick skin of palms and soles and may have sensory and/or hormonal function.

B. First and most abundant cell type - cells of the keratinized stratified squamous epithelium.

1. These cells are called keratinocytes.

2. They form a protective outer layer that is continuously shed and replaced from below.

3. The keratinized stratified squamous epithelium can be divided into a series of sub-layers.

Sub-layers of the epidermis. Starting at layer next to dermis.

a. Stratum basale = stratum germinativum

b.Stratum spinosum

c. Stratum granulosum

d. Stratum lucidum

e. Stratum corneum

f. In thick skin such as palms of hands and soles of feet, all layers can be easily identified. In thin skin that covers rest of body the stratum lucidum may not be evident.

4. Stratum basale = stratum germinativum

a. A basophilic cuboidal to columnar epithelium which lies on basement membrane that attaches it to the underlying dermis.

b. Desmosomes bind the lateral surfaces of these cells so they adhere strongly to each other.

c. Hemi-desmosomes are found in the basal cell membranes and are involved in binding cells to the basal lamina.

e. There is lots of mitosis occurring in this layer since it is responsible for providing cells to replace those shed as the upper layer of keratinocytes is worn away.

f. These cells synthesize small amounts of keratin that is stored as intermediate filaments in their cytoplasm.

5. Stratum spinosum

a. Consists of cuboidal, polygonal, or slightly flattened cells which have a plasmalemma that is thrown into a series of many short processes.

b. These processes are filled with intermediate filaments and terminate with desmosomes formed between processes of adjacent cells or with the apical survacees of cells in the stratum basale.

c. The processes of these cells give them a spiny appearance when viewed with the light microscope. Thus the name "spinosum". Also sometimes called the "prickly" layer.

d. These interdigitating, tightly bound processes are thought to give the skin some flexibility and thus impart resistance to abrasion to the epidermis. This is supported by the fact that the stratum spinosum is thicker in portions of skin subject to frequent abrasion such as palms and soles.

e. The basal portion of the spinosum, directly next to the stratum basale, also contains mitosing cells. This germinative area is called the malpighian layer.

6. Stratum granulosum

a. This layer is sometimes difficult to discern in thin skin

b. It consists of 3-5 layers of flattened polygonal cells that are characterized by two types of non-membrane bound granules.

* keratohyaline granules - contain a histidine rich protein.

*membrane-coating granules

** These granules are membrane bound and formed by the golgi bodies.

**They move to the plasmalemma closest to the external environment and are exocytosed into the intercellular space.

**The contents of these granules are glycosaminoglycans and phospholipids.

**These two substances help to cement cells together and also act as a barrier to penetration of the skin by foreign materials. (i.e. they seal the skin and decrease its permeability).

7. Stratum lucidum

a. This layer is most apparent in thick skin.

b. It consists of a thin layer of extremely flattened cells.

c. Organelles and nuclei are no longer evident in the cytoplasm.

d. The cytoplasm is rich in densely packed keratin filaments in an electron-dense matrix called eleidin.

8. Stratum corneum

a. This is the outermost layer of the skin.

b. Consists of flattened, non-nucleated, dead, keratinized cells.

c. The cytoplasm of these cells is filled with keratin filaments embedded in matrix.

d. These keratinized cells are called horny cells.

e. The stratum corneum is very thick in areas subject to frequent abrasion such as the palms and soles (e.g. 3mm on soles). In thin skin, this layer is relatively thin and delicate.

9. Since the upper layer of skin is heavily keratinized and the lower layer (stratum germinativum) is not, it is clear that as cells of the epidermis progress toward the external surface, one of the things that is happening is that higher and higher concentrations of keratin are being synthesized and deposited in the cytoplasm.

10. Also, since cells of the stratum corneum lack organelles, something is occurring to rid the cells of these structures.

a. So, what we find is that as keratinization proceeds, more and more autophagosomes and lysosomes are present in the cytoplasm of epidermal cells.

b. The autophagosomes are responsible for engulfing and degrading cytoplasmic organelles.

C. Second skin cell type - melanocytes - pigment producing cells

1. Melanocytes are derived from neural crest cells (which you'll recall are also involved in the formation of the adrenal medulla).

2. Cell bodies of melanocytes are found between or beneath those of the stratum basale and stratum spinosum.

3. They extend cytoplasmic processes between cells of these two layers. These processes end in invaginations in the plasmalemma of the cells of the stratum spinosum and stratum basale.

4. Melanin is synthesized by melanocytes via the action of an enzyme called tyrosinase on the amino acid tyrosine.

5. Melanin synthesis occurs in vesicles formed by the Golgi body and consists of 4 stages.

a. Tyrosinase precursors are synthesized on ribosomes of endoplasmic reticulum and accumulate in vesicles formed by the Golgi body.

* Stage I vesicle - slight tyrosinase activity, so either the golgi packaged precursor is undergoing further processing, or tyrosinase in being added to Golgi vesicles as these vesicles fuse with each other.

* Stage II vesicle - vesicle contains intermediate filaments which melanin is deposited on.

* Stage III vesicle - concentration of melanin increases obscuring the filaments.

* Stage IV vesicle - mature melanin granule, no filaments visible.

6. These vesicles are transported into the processes of the melanocytes and are transferred to epidermal cells in the stratum basale and stratum spinosum.

7. Pigmentation of the skin is due to accumulations of melanin in epidermal cells rather than in the melanocytes. Darker skin is due to greater accumulation of melanin in these cells and not to a change in the number of melanocytes.

8. Thus, differences in skin color in people of the same race and of different races are due to differences in the concentration of melanin granules in epidermal cells and not to differences in the number of melanocytes present.

9. As skin cells mature and become keratinized, melanin is enzymatically broken down such that dead cells of the stratum corneum have lost their pigmentation by time they are shed.

D. Third skin cell type - Langerhans cells

1. These cells are found in the stratum spinosum

2. They may have an immune function and are a specialized type of macrophage that "entraps" foreign antigens that enter the skin.

E. Fourth type of skin cell - Merkel cells

1. Present in hair follicles, thick skin of palms and soles, and oral mucous membrane

2. Large, oval, poorly stained

3. Unmyelinated axons penetrate the stratum basale and terminate as expanded disks on the base of Merkel cells - suggests sensory function.

4. Granules resembling neurosecretory vesicles sugget a possible hormonal function for these cells.

II. Dermis

A. This is the connective tissue that supports epidermis and binds it to subjacent tissue

B. The dermis is composed of two layers:

1. Papillary layer

2. Reticular layer

C. Papillary layer

1. Composed of loose connective tissue, mostly fibroblasts, but also mast cells, macrophages, and extravasated leukocytes.

2. This portion of the dermis interdigitates with the epidermis forming folds of the dermis that are called dermal papillae.

a. Most papillae contain a capillary bed that provides nutrients to overlying and surrounding cells.

b. Some palillae are "tactile papillae" and house sensory structures for touch called Meissner's corpuscles.

3. From this layer, collagen fibrils penetrate the dermal papillae and insert into the basal lamina of the epidermis, just beneath the stratum germinativum.

a. This binds the two layers together.

b. The collagen fibrils are called anchoring fibrils.

D. Reticular layer

1. This layer is thicker than the papillary layer and is composed of dense irregular connective tissue that contains collagen and elastic fibers.

a. Fibers are the major component.

b. There are fewer cells in the reticular layer than in the papillary layer.

2. Thick elastic fibers emerge from this layer and penetrate the papillary layer.

a. These thick fibers end in the fine fibrotubular component of the elastic fibers.

b. As is the case with the anchoring fibers mentioned above, the ends of these thick fibers penetrate the papillary layer and insert on the basal lamina below the stratum basale.

c. This elastic network is responsible for the elasticity of the skin.

3. The functional cells of hair follicles, sweat glands, and oil glands are found in the reticular layer of the dermis. Hair follicles may be considered specializations of the epidermis that penetrate into the reticular layer of the dermis.

E. While the epidermis contains no blood or lymph vessels, the dermis contains many.

IV. Underlying the dermis is a fatty, loose connective tissue layer called the hypodermis.

V. Appendages of the skin

A. There are a number of structures that can be defined as appendages of the skin:

1. Hair

2. Finger and toe nails

3. Sebaceous glands

4. Sweat glands

B. Hair follicles

1. The hair follicle is a deep invagination of the epidermis that involves the stratum basale and stratum spinosum.

2. The hair itself is essentially a specialized form of the keratinized layers of the epidermis.

3. The hair follicle extends deep into the reticular layer of the dermis and terminates at a vascularized "dermal papilla".

* Note that the dermal papilla is close to the base of the reticular layer and is different from the "dermal papilla" that forms as an interdigitation with the epidermis in the papillary layer of the dermis.

* The basal region of the follicle, including the dermal papilla, is called the bulb.

* The epidermal cells covering the dermal papilla in the lower half of the bulb are called matrix cells and are responsible for producing the shaft of the hair.

2. The hair shaft itself, consists of 3 regions,

a.The Medulla

* 2-3 layers of vacuolated cuboidal cells

* present near base of hair, doe not extend through entire shaft

b. The Cortex

* several layers of elongated, heavily keratinized cells.

* Melanin is sequestered between or within these cells

* These cells become more flattened as you move toward the tip of the hair.

c. The Hair Cuticle

* a layer of clear, flat, enucleate, cells

* these cells overlap one and other in a scale like fashion

3. In the root of the follicle the cuticle is surrounded by an inner sheath consisting of 3 layers. These are,

a. The innermost cuticle - innermost layer

* Flat overlapping cells that abut the cuticle of the hair shaft

* The edges of the cells of the innermost zone interdigitate with those of the hair cuticle forming a robust bond between the hair and the follicle wall.

b. Huxley's layer - the middle layer

* Several layers of elongated cells

* Contain trichohyalin granules (a type of kerotohyalin granule)

c. Henle's layer - the outermost layer

* Single layer of flat, clear cells that contain keratin fibrils

4. Henle's layer is surrounded by the outer (or external) root sheath.

* This is continuous with the stratum spinosum and stratum basale

* A thin, hyalin, modified basement membrane called the glassy membrane, surrounds the outer root sheath

* Outside the glassy membrne is a poorly defined, connective tissue investment.