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Chapter 4: Histology 45

Types of Tissues
Four primary tissue types
a.  Epithelial tissues (epithelia)
– tightly packed sheets of cells with no visible ECM
SEM of adipocytes & protein fibers
-
- glands that manufacture secretions (______________)
Histology – study of normal structures of _________ or chemical messengers (____________)
Tissue: b.  Connective tissues (CT)
a. Discrete population of ______ related in structure & - connect tissues to one another;
function - ECM is a prominent feature for most CT
b. Have surrounding material: _____________ with cells scattered throughout
(ECM) -

Types of Tissues The Extracellular Matrix

Extracellular matrix
c. Muscle tissues a.  Composed of substances in a liquid, gel, or
solid that surround cells
- ___________
b.  Functions:
– Provides tissue with strength to resist tensile
(stretching) and compressive forces
d.  Nervous tissues – Directs cells to proper positions within tissue
consist of cells: and holds those cells in place
- neurons – Regulates development, mitotic activity, and
survival of cells
- neuroglia

The Extracellular Matrix The Extracellular Matrix

c. 2 main components Macromolecules:
a. Glycosaminoglycans (GAGs)
[ground substance & protein fibers] – ex. chondroitin sulfate (cartilage) and hyaluronic acid

1) Ground substance b. Proteoglycans

- GAGs bound to a protein core (bottle brush)
- makes up most of ECM extracellular fluid
(ECF or interstitial fluid)
c. Cell-adhesion molecules (CAMs)
- components: – made up of different types of glycoproteins
- bind surface proteins
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Chapter 4: Histology 46

The Extracellular Matrix The Extracellular Matrix

2. Protein fibers
a. Collagen fibers (white, fibrous)
- 20–25% of all proteins in body
-
b. Elastic fibers (yellow)
– protein elastin surrounded by glycoproteins
-
c. Reticular fibers (weblike)
– meshwork or scaffold that supports cells and
ground substance of many tissues
Figure 4.1 Extracellular matrix.

Diseases of Collagen
The Extracellular Matrix and Elastic Fibers (p.126)
•  Protein fibers vital to structural integrity of
many tissues and organs
Ehlers-Danlos syndrome

Marfan syndrome

Figure 4.1 Extracellular matrix.

Epithelial Tissues Epithelial Tissues

Epithelial tissues 3.  Secretion –
–
Functions: 4. Transport into other tissues – form
1. Protection – selectively permeable membranes

2. Immune defenses – form physical barriers; 5.  Sensation – detects changes in internal and
contain cells of immune system external environments (ex.
)
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Chapter 4: Histology 47

Components and Classification of Components and Classification of

Epithelia Epithelia
•  Consist of tightly packed cells Classified based on:
that form continuous sheets • 
•  Fairly impermeable and - Simple epithelia consist of a ________ cell layer
resistant to physical - Stratified epithelia consist of __________ layers
stresses and mechanical - Pseudostratified looks layered but is not
injury
• 
•  BM (basement membrane)
Pseudostratified
Figure 4.3 Structure of epithelial tissue.
Figure 4.4a Classification of epithelial cells.

Components and Classification of Covering and Lining Epithelia

•  Four types of simple epithelia:
Epithelia
1. Simple squamous epithelium
•  – very thin single layer of cells with a “fried egg”
–  Squamous cells appearance;
–  Cuboidal cells - adapted for _____________________
–  Columnar cells -  found in air sacs of lung, parts of kidney, and
lining blood vessel walls (endothelium)

Figure 4.4b Classification of epithelial cells.

Figure 4.5a Structure of simple epithelia.

Covering and Lining Epithelia Covering and Lining Epithelia

2. Simple cuboidal epithelium 3. Simple columnar epithelium
– single layer of _________________ – single layer of rectangular-shaped cells
- found in renal tubules, respiratory passages, - often has ____________ (increases surface area
ducts of glands, and thyroid gland for absorption of substances) or ______
(propel substances through hollow organs)

Figure 4.5b Structure of simple epithelia. Figure 4.5c Structure of simple epithelia.
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Chapter 4: Histology
Covering and Lining Epithelia
4. Pseudostratified columnar epithelium
- appears to be layered because nuclei are found at
various heights, but only one cell-layer thick
- found in segments of respiratory tract and nasal
cavity; ciliated
Figure 4.5d Structure of simple epithelia.
Covering and Lining Epithelia
b. Nonkeratinized stratified squamous epithelium
§ apical cellular layers retain nuclei; still alive
§ ___________________ (ex. mouth, throat,
esophagus, anus, and vagina)
Figure 4.7a Structure of stratified epithelia.
Covering and Lining Epithelia
3. Stratified columnar epithelium
§  relatively rare in humans
§  found in male urethra, cornea of eye, ducts of
salivary glands
Figure 4.7c Structure of stratified epithelia.
48
Covering and Lining Epithelia
Stratified epithelium
– more than one layer of cells;
- protective barriers due to wear and tear
1. Stratified squamous epithelium
a.  Keratinized stratified squamous epithelium
b.  outer cellular layers are dead
•  lack nuclei
•  filled with protein ________
•  outer layers of skin (epidermis)
Figure 5.3 Structure of the epidermis.
Covering and Lining Epithelia
2. Stratified cuboidal epithelium
§  rare in humans
§  lines ________________
Figure 4.7b Structure of stratified epithelia.
Covering and Lining Epithelia
4. Transitional epithelium
§  only found in urinary system ___________________________
§  basal cell layers are cuboidal while apical cell layers are dome-
shaped when tissue is relaxed
§  ability of apical cells to flatten contributes to ability of urinary
tissues to ___________
Figure 4.7d Structure of stratified epithelia.
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Chapter 4: Histology 49

Covering and Lining Epithelia Glandular Epithelia

•  Gland – specialized cells that produce secretions
Products are released by two mechanisms:
•  Endocrine
•  Exocrine

Figure 4.8 Summary of epithelial tissues.

Glandular Epithelia Glandular Epithelia

Exocrine glands
Endocrine glands secrete ____________, directly into
•  ______________
bloodstream (no ducts)
•  Secretions have only local effects on cells in
•  Allows products to have widespread systemic
general vicinity
effects on distant cells in different areas of body
•  Unicellular (__________à mucus)
- digestive & respiratory tracts
•  Glands vary in complexity from single cells to large
multicellular glands with branching - protects underlying epithelia

•  Ex. •  Multicellular (sweat glands, salivary glands)

Glandular Epithelia Glandular Epithelia

Types of Exocrine glands secretions:
•  Merocrine secretion
- fluid product in vesicles
- salivary and sweat glands;

•  Holocrine secretion
– entire cells released
- sebaceous gland

Figure 4.10 Multicellular exocrine glands.

Figure 4.11a,b Modes of secretion in exocrine glands.
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Chapter 4: Histology 50

Carcinogens and
Connective Tissue
Epithelial Tissues (p. 130)
•  Epithelia cover all body surfaces; therefore Connective tissues
•  Connective tissue proper
more subject to injury than most other tissues –  Loose Widely distributed
•  Carcinogens –  Dense (regular & irregular) Connects tissues & organs
–  Reticular Internal structure of some organs
–  Adipose
•  Carcinoma –
•  Specialized connective tissue
–  Cartilage
•  Basal Cell Carcinoma – –  Bone
–  Blood

Connective Tissue Connective Tissue

Connective tissue functions:
•  Characteristics of CT:
•  __________________
–  Cells are surrounded by protein fibers and
– anchor tissue layers in organs and link organs together
embedded in ground substance
•  Support
– bone and cartilage support weight of the body
–  ECM plays an extensive role in the function of CT
•  ______________
– bone tissue protects certain internal organs
-  cartilage and fat provide shock absorption –  Usually vascular
-  components of immune system found throughout CT
•  Transport – blood main transport medium in body

Connective Tissue Cells Connective Tissue Proper

Fibroblasts – ____________ Mast cells – produce histamine
that causes inflammation •  Four basic types of connective tissue proper:
–  Loose connective tissue
–  Dense connective tissue
–  Reticular tissue
Phagocytes -includes macrophages –  Adipose tissue
Adipocytes – _________ that ingest foreign invaders

Figure 4.12a Cells of connective tissue proper.

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Chapter 4: Histology 51

Connective Tissue Proper Connective Tissue Proper

1. Loose connective tissue (_______________)
– mostly ground substance, also fibers, fibroblasts, and
occasionally adipocytes
-  located beneath epithelium of skin, in membranes
lining body cavities, and within walls of hollow organs
2. Dense connective tissue (fibrous connective tissue)
a. Dense irregular connective tissue
– mostly disorganized collagen bundles
- located in _________, surround organs and joints

Connective Tissue Proper Connective Tissue Proper

b. Dense regular connective tissue (Figure 4.14b)
– Organized into parallel collagen bundles
– Located in ______________________
c. Dense regular elastic CT(elastic tissue)
– Mostly parallel-oriented elastic fibers with some
collagen fibers
– Found in walls of organs that need to _________
(large blood vessels and some ligaments)

Connective Tissue Proper

Connective Tissue Proper
3. Reticular tissue
Note: arrangement of fibers in
dense regular and irregular
– composed mostly of reticular fibers produced by
connective tissues is another fibroblasts (reticular cells);
example of the Structure-Function
Core Principle
- form fine networks that support vessels (Figure 4.15)
•  Also found in ____________________
•  Forms part of B.M. that supports epithelia, internal
structure of liver and bone marrow

Figure 4.14 Structure of dense connective tissue.

Figure 4.15 Structure of reticular tissue.
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Chapter 4: Histology 52

Connective Tissue Proper Adipose Tissue

4. Adipose tissue (fat tissue)
and Obesity (p. 142)
– consists of fat-storing ______________ •  Obesity – condition of having excess adipose tissue in
proportion to lean body mass:
(& surrounding fibroblasts and ECM) –  Hypertrophic
•  Fat storage (major energy reserve)
• 
–  Hypercellular
•  Shock absorption and protection

Both types increase risk for certain health problems;

depends on distribution of adipose tissue and genetic
factors

Specialized Connective Tissues Specialized Connective Tissues

Specialized connective tissues Cartilage
•  Cartilage – –  Rigid matrix
–  Chondroblasts – immature cells that divide by mitosis
àECM
•  Bone tissue (osseous tissue) – _______________; –  _______________ in lacunae
muscle attachments; stores calcium, and bone –  Mostly avascular (blood supply limited to outer sheath -
marrow (produces blood cells and stores fat) perichondrium)

•  Blood – liquid ECM called __________; consists of

mostly water, dissolved solutes, and proteins

Specialized Connective Tissues

3 types of cartilage:
Specialized Connective Tissues
•  Hyaline cartilage •  Bone
– –  Hard matrix
- ends of long bone, trachea, nose, most of fetal skeleton –  Supports and protects
•  Fibrocartilage –  Hemopoiesis
- great tensile strength –  Skeleton
- ___________________,
–  Osteoblasts, osteocytes in lacunae, osteoclasts
menisci of knee, symphysis pubis
•  Elastic
-  _______________
-  external ear, auditory tube,
epiglottis
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Chapter 4: Histology 53

Specialized Connective Tissues Osteoarthritis and Glucosamine

•  Blood Supplements (p. 144)
– ECM is fluid = plasma •  Osteoarthritis
–  Plasma proteins – not like fibers in other CT;
smaller and involved in transport & blood
clotting
–  Erythrocytes (______________) transport oxygen •  Glucosamine
–  Leukocytes (_____________) function in immunity
–  Thrombocytes (___________) – cell fragments; major
role in blood clotting

Connective Tissues Connective Tissues

Figure 4.20 Summary of connective tissues. Figure 4.20 Summary of connective tissues.

Types of Muscle Tissue

Muscle Tissues •  Skeletal muscle
– Attached to bone
•  Muscle tissues are specialized for ____________ – Striated
(use ATP as energy source) – ___________
•  Cardiac
•  Movement of skeleton, heart beating, and propulsion of
substances through hollow - Heart
- Striated
•  Muscle cell or myocyte; ___________ (ability to respond
- ____________
to electrical or chemical stimulation)
- Intercalated discs
•  3 types of muscle tissue:
•  Smooth
- Skeletal muscle - Walls of hollow organs, blood vessels

- Cardiac muscle - Non-striated

- ____________
- Smooth muscle
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Chapter 4: Histology 54

Nervous Tissues The Big Picture of

Tissues in Organs
•  Nervous tissue Two or more tissues that combine structurally
- brain, spinal cord, nerves and functionally form an organ:
•  Simple organ example – skeletal muscle:
- two main cell types: –  Composed of two main tissues—skeletal muscle
and dense irregular collagenous connective
Neurons – –  Each has distinct functional role; skeletal muscle
tissue allows it to contract; surrounding connective
tissue binds muscle cells together and supports
Neuroglial cells – them so that their activity produces a contraction
of whole organ

The Big Picture of The Big Picture of

Tissues in Organs Tissues in Organs
•  More complex organ; consists of many
different tissue types – trachea
–  Hollow organ; provides passageway through
which air passes on its way into/out of lungs
–  Figure 4.23 (next slide) – illustration of tissues of
trachea from superficial to deep with list of their
main functions
–  Each tissue layer serves an important role in
overall function of trachea: conducting air
Figure 4.23 The Big Picture of Tissues in Organs.

Membranes Membranes
Membranes – thin sheets of tissues that
_____________________: •  Mucous
–  line tubes/organs that connect
•  Serous membranes to outside of body
– line pericardial, peritoneal, and pleural cavities –  _______________
_____________ –  secrete mucus

•  Cutaneous
•  Synovial membranes
- _______
- composed of CT
- _____________
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Chapter 5: The Integumentary System 57

Tiny sweat pores open and leave thin

Skin Structure
film called a fingerprint on most
surfaces.

Skin (__________________) = largest organ (10-15% of TBW)

Note correction of
bracket compared
2 main regions: to textbook.

Epidermis – keratinized stratified squamous epithelium

Dermis – _____________________
Figure 5.1 Basic anatomy of the skin.

Skin Structure
Skin Structure
•  Accessory structures: •  Hypodermis – aka superficial fascia or
- sweat glands, sebaceous glands, hair, nails subcutaneous fat, is _________________
– not part of skin, anchors skin to deeper
•  Sensory receptors
structures
- detect ______, ______, ______, _______
– _______________
•  Arrector pili muscles
– ______________
- small bands of SMC associated with hair
•  Epidermis is _____________
–  Transport of O2 and nutrients via diffusion
•  Dermis is vascular Figure 5.1 Basic anatomy of the skin.

Cellulite (p. 162) Functions of Integumentary System

•  Dimpled or “orange peel” appearance 1. Protection- mechanical trauma, pathogens, and ___________
2. Sensation –perceive changes in the body’s _______________
environment
•  Thighs, hips, and gluteal area
3. Thermoregulation (Figure 5.2):
due to:
–  relies on _______________ loops to maintain stable internal
temperature (due to muscle activity and metabolism)
•  Normal condition
4. Excretion – process where waste products and toxins are
• 
eliminated (sweat)
5. Synthesis – Vitamin D, calcitriol
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Chapter 5: The Integumentary System 58

Thermoregulation Functions of the Integumentary System

[Body Temperature above normal] •  Stimulus: body is too HOT (due to weather extremes or
fever)
•  Receptors: thermoreceptors detect an increase in
_______________
•  Control center: thermoregulatory center in brain
(_______________) acts as a thermostat
•  Effector/Response: Control center stimulates sweating
and vasodilation (VD) of vessels in dermis
•  Homeostasis and negative feedback:
- body temp. returns to normal
- thermoregulatory center decreases output to
glands and vessels

Thermoregulation Functions of the Integumentary System

[Body Temperature below normal] •  Stimulus: body temperature drops below normal range;
too COLD
•  Thermoreceptors: detect drop in temperature and
relay information to hypothalamus
•  Control center reacts
•  Effector/response: blood vessels in dermis
vasoconstrict (VC) ; decreased sweating; _________
•  Homeostasis and negative feedback:
- body temp. returns to normal
- thermoregulatory center decreases output to
vessels and muscles (reduce shivering)
Figure 5.2b Homeostatic regulation of body temperature by integumentary system.

Functions of the Integumentary System Functions of the Integumentary System

– Lose heat: ______________ •  Vitamin D synthesis:

precursor to Vit.D UV light__ à Vit. D3 (cholecalciferol)

(active form)
– Conserve heat: ________________ (dehydrocholesterol)
(in skin)

à intermediate product à calcitriol (hormone)

– Produce heat: ______________ (in liver) (in kidneys)

•  Calcitriol - nec. for absorption of Ca++ by S.I.

•  Ca++ nec. for _____________, _____________, _______

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Chapter 5: The Integumentary System 59

The Epidermis The Epidermis

Organized into 5 layers (strata) :
•  Epidermis
•  Stratum basale (stratum germinativum)
– most superficial region
-
- composed of mostly keratinocytes
- most metabolically and mitotically active
- produce _________ (protein)
•  Stratum spinosum
– still close to blood supply
- metabolically and mitotically active

The Epidermis The Epidermis

•  Stratum granulosum
- three to five layers of cells
- keratin filled cells (provides water resistance)

•  Stratum lucidum
– narrow layer of clear, dead keratinocytes
- found ______________

•  Stratum corneum (outermost)

– outermost layer of epidermis
- several layers of dead flattened
- sloughed off or exfoliated mechanically
Figure 5.3 Structure of the epidermis.

The Epidermis Concept Boost: Understanding Epidermal Growth

•  Keratinocyte life cycle:

- Dead keratinocytes are replaced by _________ of
cells in stratum basale and spinosum close
to blood supply
- As keratinocytes in deeper strata divide they
push cells above them into more superficial
layers (40-50 days)
- Mitosis takes place at night?!
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Chapter 5: The Integumentary System 60

Other Cells of the Epidermis

Thick and Thin Skin
•  Dendritic (Langerhans) cells
– located in ______________ • Thick skin
- ______________ of immune system - all five epidermal layers
- protect skin and deeper tissues from pathogens - thick stratum corneum
- ______________, many sweat glands
•  Merkel cells
- located in _______________ •  Thin skin
- sensory receptors detect ______________ - has only four layers (no ______________)
- fingertips, lips, and at base of hairs - Many hairs, sweat glands, and sebaceous glands
•  Melanocytes
– located in _____________ ____________ – additional layers of st.corneum; form
in either thick or thin skin due to repetitive pressure
- produce _______________ (protein skin pigment)

Thick and Think Skin The Dermis

The image cannot be displayed. Your computer may not have enough memory to open the image,
or the image may have been corrupted. Restart your computer, and then open the file again. If the
red x still appears, you may have to delete the image and then insert it again. Dermis – highly vascular layer deep to
________
•  Functions:
–  Provides
–  Contains
–  Anchors epidermis in place
•  Composed of two distinct layers:
–  Papillary
–  Reticular
Figure 5.4 Thick and thin skin.

The Reticular Layer

The Papillary Layer Reticular layer
– deepest thicker layer of dermis
Papillary layer - mostly ________________ (collagen and elastic
fibers)
– composed of ______________ - rich in proteoglycans ( keeps skin firm and hydrated)
- Lamellated (Pacinian) corpuscles (___________
_____________________)
Dermal papillae - Blood vessels, sweat glands, hairs, sebaceous glands,
- tiny projections and adipose tissue are found in reticular layer
- capillary loops
- Tactile (Meissner) corpuscles (_______________)
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Skin Markings Skin Wrinkles, p. 170

Epidermal ridges
•  Due to age-related decrease in collagen and
- enhance _____________________ elastic fibers, proteoglycans, and adipose
–  characteristic patterns; loops, arches, and whorls; tissue in the _____________

–  Sweat pores open along these ridges and leave a thin

film or _______________ on most surfaces
•  Reduces

Melanin
Skin Wrinkles
Skin color
•  Appearance can be minimized by: •  Melanin (melanocytes)
–  Botox -protect keratinocyte DNA from mutations induced by UV rays
- number of melanocytes is ___________________
–  Fillers - spectrum of skin tones due to ____________________
•  Carotene (ingest yellow orange vegetables)
–  Topical creams –  Imparts yellowish color to ________________
•  Hemoglobin (RBCs)
Delay wrinkles: –  coloration depends on blood flow to dermis

Melanin Melanin
•  Increased melanin synthesis with exposure to
natural or artificial UV radiation (tan)
•  Erythema – ____________ blood flow
•  Pallor – _____________ blood flow
•  Cyanosis - low ____________ blood

Figure 5.8 Melanocytes and melanin function.

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Chapter 5: The Integumentary System 62

Tanning and a
Melanin
“Healthy Tan” (p. 172)
•  Common variations of pigmentation: •  Tanning – salons promote notion of “healthy tan”
–  Freckle – small area of __________ pigmentation •  THERE IS NO SUCH THING AS A HEALTHY
(melanin production) TAN!
–  Mole or nevus – area of increased pigmentation •  UVA and UVB rays are associated
due to __________________ (not increase in
melanin production)
–  Albinism – melanocytes fail to manufacture •  ANY amount of tanning damages
tyrosinase _____________ results in lack of
pigmentation

Hair Hair
Cuticle - outer
Accessory structures (appendages): Cortex -middle
- ____________________ Medulla -inner
- derived from epithelium only
•  Hair (pili)
– protrude from surface of skin
over entire body except
thick skin, lips, and parts
of external genitalia

(Figure 5.9)
Figure 5.9 Hair structure.

Hair Hair Structure

•  Hair - stratified squamous keratinized epithelial
– Shaft
•  Hair • 
–  Protect by preventing __________________ •  dead keratinized cells
______________ – Root
• 
–  Protect underlying skin of scalp from __________
•  surrounded by sensory neuron
____________ •  hair papilla -projection of blood
- Sensory neuron detect changes in environment vessels in indented base
•  hair bulb = root and hair papilla
•  many epithelial cells are still alive
(have not completed keratinization process)

Figure 5.9 Hair structure.

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Chapter 5: The Integumentary System 63

Hair Structure Hair Structure

– Strand of hair has three visible regions:
•  Inner medulla – soft keratin
–  Matrix – small number of
actively dividing keratinocytes •  Middle cortex – hard keratin provides strength
found at base of root •  Outermost cuticle – single layer of overlapping
keratinocytes containing hard keratin; provides
–  Root is embedded in hair
mechanical strength
follicle

Figure 5.9b Hair structure. Figure 5.9a Hair structure.

Hair Structure Hair Pigment and Texture

•  arrector pili muscles = _______________
•  Hair color is determined by ______________
•  Blond hair has _________ melanin
•  “goosebumps” = hair stands up (piloerection)
•  Black hair which contains ________ of melanin
•  Red hair has a special reddish pigment
•  hair growth varies, averages ~ 1-1.5 cm per month
containing iron
•  Gray or white hair melanocytes produce

Figure 5.9 Hair structure.

Nails Glands
•  Sweat (sudoriferous) glands à sweat
Nails – composed of stratified squamous epithelium filled –  Eccrine : widespread, mostly water , wastes, electrolytes
Merocrine

with hard keratin

o  Nail plate – sits on top of __________ –  Apocrine: axillary, & anal regions, _________________,
odoriferous, associated with hair follicle
o  Lunula - half-moon shaped region of proximal nail plate
Modified sweat glands:
o  Eponychium - ___________ –  Ceruminous: __________ (ear canal)
o  Hyponychium – St. corneum under free edge of nail –  Mammary: _________

•  Sebaceous glands à ___________

Holocrine

–  Thin skin only

–  Hydrophobic barrier

Figure 5.10a Nail structure. Figure 5.11 Sweat glands and sebaceous glands.
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Chapter 5: The Integumentary System 64

Glands Acne (p. 177)

•  Acne vulgaris

•  Cause
– accumulation of _______________________
- may be infected by bacteria à _______________
- _________________ (testosterone)

Figure 5.11b Sweat glands and sebaceous glands.

Skin Cancer
Skin Cancer •  Three cancers affect skin
- linked to UV radiation exposure
•  Cancer – one of most common diseases in world; - carcinogens (Cancer-inducing chemicals, toxins)
caused by mutations in DNA that induce a cell to 1. Basal cell carcinoma
lose control of cell cycle (Figure 5.14): –  Most common of all cancer types, including skin cancer
–  Unchecked cell division eventually leads to formation –  Arises from keratinocytes in stratum basale
of a large population of undifferentiated cells known as 2. Squamous cell carcinoma
a _____________ –  Second most common skin cancer
–  Cancerous tumors are able to metastasize; tumor cells –  Cancer of keratinocytes of stratum spinosum
spread through ______________________________
3.  Malignant melanoma
________________________
– cancer of _____________
–  Damage caused by metastatic tumor cells alters
- Arms” of cancerous melanocytes extend down into dermis
function of invaded organs
and access dermal blood vessels(metastasis)

Skin Cancer
•  Malignant melanoma can be distinguished from other
skin cancers and normal moles using ABCDE rule:
–  (A): _________________ (two sides do not match)
–  (B): _______________ irregularity
–  (C): ____________, usually blue-black or a variety of colors
–  (D): __________ generally larger than 6 mm (pencil eraser size)
–  (E): _____________ (changing)
shape and size

Figure 5.14c The three main forms of skin cancer.