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Janet Smith, Ph.D.
Microscopic Anatomy
SLIDE REVIEW
ABNORMAL AMNIOCENTESIS
I. EPITHELIUM
EPITHELIAL CLASSIFICATION IS BASED ON:
Number of cell layers
Simple epithelium is 1 cell thick
Stratified epithelium is more than 1 cell thick
Pseudostratified: All cells sit on the basement membrane; some (but not all)
reach the free surface of the epithelium
Shape of cells in the surface layer of the epithelium
Squamous: Height much less than width; flat, "fried egg" cells
Cuboidal:
Height and width about equal; nucleus usually round
Columnar:
Height greater than width; nucleus often oval & at basal end of cell
Transitional: A stratified epithelium where the shape of surface cells changes
from dome-shaped to rectangular as the organ becomes distended
TYPES OF SIMPLE EPITHELIA:
Simple squamous
e.g., endothelium, mesothelium, parietal layer of Bowman’s capsule
Simple cuboidal
e.g., proximal & distal tubules of kidney
Simple columnar
e.g., stomach, intestine, gall bladder
PSEUDOSTRATIFIED EPITHELIA:
e.g., “the respiratory epithelium” of trachea & bronchi (pseudostratified columnar
with ciliated cells & goblet cells); epididymis of male reproductive tract
(pseudostratified columnar with stereocilia)
TYPES OF STRATIFIED EPITHELIA:
Stratified columnar
e.g., parts of penile urethra, parts of large ducts in some glands, e.g., salivary
Stratified cuboidal
e.g., ducts of eccrine sweat glands
Maximally keratinized stratified squamous (no nuclei in surface cells)
e.g., epidermis (the epithelial layer of the skin)
Minimally keratinized stratified squamous (= nonkeratinized; nuclei are present
in surface cells)
e.g., esophagus, vagina, anal canal, inner surface of eyelid
Transitional
e.g., urinary bladder, ureter
MICROSCOPIC ANATOMY
BASIC CHARACTERISTICS OF EPITHELIA:
Cells are in close contact with one another; there is little intercellular matrix
Cells form:
Sheets that line body surfaces (internal and external)
Glands derived from the surface sheets
Cells are often linked by many types of membrane junctions
Functions include:
Protect against mechanical abrasion, infection, desiccation, etc.
Regulate movement of materials across the epithelial layer
Secretion
Absorption
Almost all are avascular: Supplied by vessels in the underlying connective tissue
Not specialized for contraction (as muscle is) or impulse conduction (as nerve is)
Rapid turnover: Many have a stem cell population with high mitotic rate
High mitotic rate makes them targets for malignant transformation (most
malignancies in adults are epithelial in origin)
MANY EPITHELIAL CELLS ARE MORPHOLOGICALLY POLARIZED & HAVE:
Apical surface – in contact with or oriented toward the free surface of the
epithelium
Basal surface – in contact with or oriented toward the basement membrane
Lateral surfaces – in contact with neighboring cells
FEATURES THAT ARE SOMETIMES PRESENT ON THE APICAL SURFACE:
Motile cilia:
Core is an axoneme made of microtubules (9 doublets + 2 central)
Grow from basal bodies (9 triplets; no central pair)
Beat in a coordinated wave to move material in lumen
Longer and more fringe-like than most microvilli
Primary cilia:
Non-motile; one per cell; 9+0 arrangement of microtubules
Microvilli:
Increase membrane surface area to allow for more molecular transport
Have a core of actin filaments that are anchored in the terminal web
When visible by LM they form a brush border
Glycocalyx:
Fuzzy exterior coating on the apical plasma membrane; visible by EM
Well developed in some cells (e.g., intestine); inconspicuous in others
Composed of carbohydrate side chains of glycolipids & glycoproteins of
apical membrane (is PAS positive)
MICROSCOPIC ANATOMY
FEATURES THAT ARE SOMETIMES PRESENT ON THE LATERAL SURFACES:
Terminal bar: LM term for a junctional complex
Junctional complex = zonula occludens, zonula adherens, & desmosome
Other desmosomes that are not part of a junctional complex
Gap junctions (nexus): A communicating junction; made of many paired
connexons composed of the protein, connexin
FEATURES THAT ARE SOMETIMES PRESENT ON THE BASAL SURFACE:
Basal striations:
Visible by LM
Faint eosinophilic stripes running perpendicular to the basement membrane
Caused by infoldings of basal plasma membrane with mitochondria lined up in
the cytoplasmic pockets created by the folds
Usually associated with active transport (“ion pumping”)
Hemidesmosomes
Present on the basal surface of cells that contact the basement membrane
Help to anchor epithelium to basement membrane
Resemble half of a desmosome, but the proteins involved are different
Basement membrane:
An epithelium rests on a basement membrane that separates it from
connective tissue
Only visible by LM if very thick or is stained by PAS technique
Includes a basal lamina (= lamina rara + lamina densa) made by epithelial cells,
plus a reticular lamina (lamina reticularis) made by fibroblasts
II. GLANDS
GLANDS CAN BE CLASSIFIED BY:
1. EXOCRINE VS. ENDOCRINE GLANDS:
Exocrine:
Secrete into a duct system or directly onto an internal or external free surface
of the body
Examples with no ducts: goblet cells, surface mucous cells (stomach)
Examples with ducts: eccrine sweat glands, salivary glands, exocrine pancreas
Endocrine:
Secrete products across a basement membrane into the surrounding
connective tissue, not into ducts or onto free surfaces
Secretion is picked up by blood vessels in the connective tissue & travels to a
distant target organ in the blood
Examples of endocrine glands: adrenals, thyroid, parathyroids
MICROSCOPIC ANATOMY
2. UNICELLULAR VS. MULTICELLULAR
Unicellular glands:
A goblet cell is a unicellular exocrine gland
Unicellular endocrine glands also exist (DNES cells, to be covered in later
modules)
Multicellular glands:
Most glands are multicellular (sweat, salivary, sebaceous, etc.)
3. METHOD OF SECRETION:
Merocrine:
Product is released by exocytosis
Only the secretory product is lost from the cell
Can occur in exocrine or endocrine glands
e.g., eccrine sweat gland, salivary glands, parathyroids, protein secretion by
the mammary gland
Apocrine:
In addition to secretory product, some other part of the cell is lost in the
process of secretion
e.g., lipid secretion by the mammary gland
Holocrine:
Entire cell is secreted
e.g., sebaceous gland
4. TYPE OF SECRETORY PRODUCT:
Serous:
Produce a watery secretion containing glycoproteins & ions
Cells tend to have round nuclei
Secretory product less likely to be extracted, therefore apical cytoplasm
(where secretory granules usually accumulate) tends to be eosinophilic
e.g., parotid gland, exocrine pancreas
Mucous:
Produce a viscous secretion rich in sulfated & sialylated glycoproteins called
mucinogens
Nuclei tend to be flattened against basal plasmalemma by numerous
secretory granules
Secretory product likely to be extracted, therefore cytoplasm is usually pale
e.g., goblet cells, sublingual gland
NOTES:
Some glands are mixed mucoserous
In a mixed gland with relatively few serous cells, the serous cells often form
serous demilunes
MICROSCOPIC ANATOMY
5. SHAPE OF SECRETORY UNIT (MULTICELLULAR GLANDS ONLY)
Gland is acinar (alveolar) if secretory cells are organized into spherical units
Gland is tubular if secretory cells are organized into tubular units
Gland is tubuloacinar (tubuloalveolar) if it has some tubular & some spherical
secretory units
NOTE: Serous secretory units tend to be acinar, while mucous secretory units
are more likely to be tubular
6. SIMPLE VS. COMPOUND (EXOCRINE GLANDS ONLY)
Gland is a simple gland if its duct is unbranched
Gland is a compound gland if its duct is branched
DUCTS OF COMPOUND GLANDS: INTRALOBULAR VS. INTERLOBULAR
Interlobular ducts
Are found in the connective tissue that lies between lobules (inter = between)
Unite & eventually form the main excretory duct
Usually start as simple cuboidal; larger ones may become stratified cuboidal
or columnar
Intralobular ducts
Are located within a lobule (intra = within)
Are therefore directly surrounded by the secretory units of the gland
Gradually enlarge, unite, & leave the lobule to become interlobular ducts
There are at least three different varieties of intralobular ducts
Intercalated ducts
Are the first part of the duct system, i.e., receive secretion directly from
the secretory unit
Lined by a simple epithelium that is usually low cuboidal
Unite to form striated or ordinary intralobular ducts (depends on which
gland)
Striated ducts
Have basal striations due to folding of basal plasma membrane
Associated with ion pumping, so not all glands have striated ducts
Usually simple cuboidal epithelium
"Ordinary" intralobular ducts
Usually simple cuboidal epithelium
No basal striations
NOTE: Simple exocrine glands have neither intralobular nor interlobular ducts
because simple glands don’t have lobules
MICROSCOPIC ANATOMY
III. CONNECTIVE TISSUE (CT)
Functions:
Provides the structural framework (stroma) for most organs
Forms the capsule that surrounds some organs (e.g., liver, spleen)
Ensheaths muscles and nerves
Fills spaces between organs
Makes up layers in the wall of many hollow organs (lamina propria &
submucosa of gut)
Site of many inflammatory and immune responses
Important in exchange between blood and surrounding tissues
Characterized by extensive extracellular matrix (ECM), so that cells that are
widely separated from one another
Most CTs (except dense regular) contain a wide variety of different cell types
TWO MAJOR GROUPS OF CONNECTIVE TISSUE CELLS
Fixed cells (resident cells):
Can be consistently found in CT
e.g., fibroblasts, adipocytes, mast cells, some macrophages
Transient cells (elicited or wandering cells):
Migrate into CT (usually from blood), often in response to a specific signal
Numbers fluctuate significantly over time
Involved in defensive functions (inflammation & immune responses)
e.g., plasma cells, leukocytes (lymphocytes, monocytes, neutrophils,
eosinophils, basophils), & some macrophages
FIBROBLASTS
Are the predominant cell type in most connective tissues
Elongated spindle-shaped cells by LM
Elongated flattened nucleus; cytoplasm often poorly visible
By EM, has long, thin cytoplasmic processes
Produce fibers & ground substance of most connective tissues
Have extensive RER when actively producing ECM proteins
MACROPHAGES (HISTIOCYTES)
Are one of the two highly phagocytic cell types in humans
Irregular cell shape & nuclear shape; plasma membrane often indistinct
Relatively large, pale staining cells
Best identified by presence of phagocytized debris in their cytoplasm
Derived from monocytes
Prominent in chronic inflammation
MICROSCOPIC ANATOMY
Have several roles in the immune response including antigen presentation
Specialized macrophages in specific organs have other names (e.g. Hofbauer
cells in placental villi, Kupffer cells in liver)
MAST CELLS
Round to oval cells often located near capillaries & venules
Nucleus round to oval (not lobulated) & usually centrally located in cell
Many large basophilic cytoplasmic granules; contents include histamine
Granules can stain metachromatically with some basic dyes (e.g., toluidine
blue)
Function: To increase permeability of small venules & capillaries in response to
inflammation
LYMPHOCYTES
The major cell type of the immune system
Found in blood, lymph, CT, lymphoid tissue & organs, & in epithelia
Inactive lymphocytes are small, round cells with a heterochromatic nucleus
& a small amount of moderately basophilic (sky blue) cytoplasm
Activated lymphocytes (participating in an immune response) enlarge & have
relatively more cytoplasm; nucleus becomes more euchromatic
PLASMA CELLS
Eccentric nucleus with “clock-face” distribution of heterochromatin (or a
“cartwheel” distribution of euchromatin)
Basophilic cytoplasm, due to extensive RER
Cytoplasm often has pale-staining centrosome (contains centrioles & Golgi)
Derived from B lymphocytes activated during an immune response
Produce antibodies and secrete them constitutively
EXTRACELLULAR MATRIX (ECM) INCLUDES:
3 types of fibers: Collagen fibers, reticular fibers & elastic fibers
Ground substance: GAGs, proteoglycans, proteoglycan aggregates,
adhesive glycoproteins, etc.
COLLAGEN FIBERS
Provide resistance to stretch or tension (tensile strength)
Composed of type I collagen in most connective tissues
Organization of collagen type I
3 alpha chains assemble and are further processed to form a collagen
molecule (= tropocollagen)
Tropocollagens line up head-to-tail with a gap between them
MICROSCOPIC ANATOMY
Collagen molecules form a fibril
Fibrils are banded in several types of collagen including type I
Fibrils form fibers (not banded because fibrils don't line up in perfect register)
Fibers may aggregate to form fiber bundles
Fibers & fiber bundles are visible by LM
RETICULAR FIBERS:
Composed of type III collagen, but no one knew that when they were named
Form fine supportive network in soft organs: e.g., liver, lymph nodes, spleen
Are mixed with collagen & elastic fibers in loose CT and in dense irregular CT
such as dermis
ELASTIC FIBERS:
Provide resiliency (ability to stretch & then return to original shape)
Composed of two major proteins:
Elastin forms the large irregular core of the fiber
Fibrillin forms microfibrils that surround the elastin & are embedded in it
Fibrillin is defective in Marfan syndrome
Common in dermis, lungs, & blood vessel walls (especially arteries)
In arteries and arterioles elastic tissue can be so abundant that it forms
fenestrated elastic sheets rather than individual fibers
Stain poorly with H&E; well stained by aldehyde fuchsin, orcein, resorcinol, etc.
GROUND SUBSTANCE INCLUDES:
Glycosaminoglycans (GAGs), proteoglycans (PGs) & proteoglycan aggregates:
GAGs (long, unbranched polysaccharide chains with a repeating
disaccharide unit)
PGs have a protein core with GAG side chains covalently attached
PGs & GAGs are highly hydrated due to their high net negative charge; this
gives the tissue a viscous, gel-like consistency
Proteoglycan aggregates are abundant in cartilage matrix
Consist of proteoglycans that are associated noncovalently with a long
molecule of hyaluranon (hyaluronic acid) via link proteins
Structural (adhesion) glycoproteins:
e.g., laminin, fibronectin, chondronectin
Important in adhesion of cells to ECM, & in cell migration
Each molecule has several different binding sites (domains)
Some domains bind to cell membranes; some to ECM components
Allows the adhesive glycoprotein to bind cells to ECM
Differ from PGs in that the adhesive glycoproteins:
Contain short, branched polysaccharide chains
MICROSCOPIC ANATOMY
Have no repeating disaccharide unit
Have lower molecular weights than PGs
Contain relatively more protein, less carbohydrate chain than PGs
CLASSIFICATION OF CONNECTIVE TISSUES
Connective tissue proper (“ordinary” CT)
Found in most organs and in the regions between organs
Specialized connective tissues
Adipose tissue
Embryonic CT: e.g., mucous CT (umbilical cord) & mesenchyme
Blood & hematopoietic tissue
Cartilage
Bone
3 TYPES OF CONNECTIVE TISSUE PROPER:
Loose connective tissue (areolar CT)
Compared to dense CT, loose CT has:
Fewer fibers, thinner fibers, more abundant ground substance, more cells
per unit volume, greater variety of cell types
Found around blood vessels, beneath epithelia (e.g., in papillary layer of
dermis), within the lobules of most compound glands
Lamina propria of the gut is a loose cellular CT
Lamina propria is the CT layer beneath the epithelial lining of a hollow
organ
Abundant cells (mostly lymphocytes) obscure the fibers of the ECM
Dense irregular connective tissue:
Fibers are oriented irregularly, in response to stresses on the tissue from
many different directions, e.g., reticular layer of dermis
Fibroblast is main cell type
Dense regular connective tissue:
Fibers are regularly oriented, in response to stresses that come from
predictable directions e.g., tendons, ligaments, cornea
Fibroblast is main cell type
WHITE VS. BROWN FAT
White fat:
Unilocular when mature; multilocular during differentiation of the cell
Signet ring appearance: single large lipid droplet nearly fills cytoplasm &
flattens the nucleus at the edge of the cell
Closely spaced adipocytes give the tissue a “chicken-wire“ appearance
MICROSCOPIC ANATOMY
Specialized for energy storage, shock absorption, thermal insulation, body
contouring
Most of the body’s fat is white fat
Found in hypodermis, breast, & loose connective tissue throughout the body
Brown fat:
Specialized for heat production
Multilocular even when mature (many small lipid droplets in each cell)
Nucleus likely to be round and more centrally located
Highly vascular (many capillaries) to carry heat to rest of body
Lobules make it appear gland-like
Brown color due to many mitochondria & blood vessels
Prominent in newborns; much reduced in adults
EMBRYONIC CONNECTIVE TISSUE
Mesenchyme:
Is the undifferentiated precursor of all connective tissues
Found in the embryo & fetus
Cells are undifferentiated mesenchymal cells
Their elongated cytoplasmic processes can be mistaken for extracellular fibers
Differentiate into cells such as fibroblasts, adipocytes, smooth muscle
Ground substance contains very few fibers
Mucous CT:
Found in the umbilical cord (= Wharton’s jelly)
Cells are fibroblasts (i.e., differentiated cells)
Matrix contains fine collagen fibers and large amounts of proteoglycans
Matrix therefore more gelatinous than in mesenchyme
IV. MAMMARY GLANDS
Compound tubuloalveolar glands
15-20 lactiferous ducts opens onto the nipple
Lactiferous ducts branch to form lobules
A lactiferous duct has a dilated portion (lactiferous sinus) near its opening
The type of epithelium varies along the length of the duct system:
Begins in the lobules as simple cuboidal to columnar
Lactiferous sinus usually lined by stratified cuboidal (2 layers)
Near the opening of the lactiferous duct on the nipple, the epithelium
becomes stratified squamous
MICROSCOPIC ANATOMY
The type of connective tissue (CT) present helps define a lobule:
The CT within a lobule is loose, but contains little adipose tissue
The CT between lobules is denser, but contains more adipose tissue
Myoepithelial cells are present around ducts and secretory acini (alveoli)
Are more difficult to see by LM than in sweat glands
Difficult to distinguish secretory acini from intralobular ducts unless the ducts
are cut longitudinally, revealing their elongated cylindrical shape
Nipple & areola
Have a more highly pigmented epidermis than surrounding skin
Have tall dermal papillae interdigitating with long epidermal ridges
INACTIVE VS. PROLIFERATING (PREGNANT) VS. LACTATING
INACTIVE (RESTING) MAMMARY GLAND OF REPRODUCTIVE AGE FEMALE
Each lobule contains abundant loose CT & a few intralobular ducts
Few if any secretory alveoli are present
Intralobular ducts have little or no lumen early in menstrual cycle
In secretory phase of the cycle, a small lumen appears in some intralobular ducts
PROLIFERATING MAMMARY GLAND (OF PREGNANCY)
Ducts elongate & branch
Alveoli develop along the ducts
The major morphological criteria:
Each lobule becomes more crowded with ducts and alveoli (i.e., the relative
amount of loose intralobular CT decreases)
Lobules begin to enlarge, and amount of CT between lobules decreases
The alveoli have simple cuboidal epithelium surrounded by myoepithelial cells
that are very difficult to see
Some alveoli contain a small amount of secretory material (colostrum)
Plasma cells, lymphocytes increase in number in the intralobular CT
LACTATING MAMMARY GLAND:
In each lobule, alveoli are tightly packed together (very little intralobular CT)
Lobules enlarge so much that the septa of CT between lobules become highly
compressed & often difficult to find
Secretory cells hypertrophy
Intracellular lipid droplets may be visible by LM
Alveolar lumens may be greatly dilated by secretory product (milk), but there can
be great variation from lobule to lobule
EM shows that the protein portion of milk (mainly casein) is released by merocrine
secretion, but the lipid portion is released by apocrine secretion
Number of plasma cells & lymphocytes decreases after parturition
MICROSCOPIC ANATOMY
V. PLACENTA
HAS MATERNAL & FETAL COMPONENTS:
Decidua basalis is the maternal component of the placenta
Chorion frondosum is the fetal component of the placenta
Decidua basalis is part of the lining of the uterus (i.e., part of endometrium)
In the pregnant uterus the endometrium can be divided into 3 parts:
Decidua basalis (the maternal part of the placenta)
Decidua capsularis (covers the surface of the fetal membranes that bulges
into the uterine lumen)
Decidua parietalis (lines the wall of the uterus at points where the placenta
is not attached)
Only the decidual basalis is part of the placenta
As the fetus grows, decidua capsularis fuses with decidua parietalis
The chorion is fetal tissue, and consists of:
Chorion frondosum (frondosum = “leafy”, due to the presence of villi)
Is part of placenta
Includes the chorionic plate and villi
Chorion laeve (laeve = smooth, because it has lost its villi)
Is not part of placenta
Lies deep to the decidua capsularis and fuses with it
AMNION
Is a simple cuboidal epithelium plus a small amount of CT)
Contains amniotic fluid in which the fetus floats
As the fetus grows, the amnion fuses with the:
Inner surface of chorion laeve and chorionic plate
Outer surface of umbilical cord
UMBILICAL CORD
Covered by amnion
Has a core of mucoid connective tissue (Wharton’s jelly)
Contains 2 umbilical arteries that carry deoxygenated fetal blood to placenta
Contains 1 umbilical vein that carries oxygenated fetal blood back to fetus
Arteries and vein branch radially in chorionic plate and then enter stem villi
MICROSCOPIC ANATOMY
PLACENTAL CIRCULATION
The fetal side:
The 2 umbilical arteries branch in chorionic plate; branches enter stem villi
Capillaries in villi pick up oxygen from maternal blood in the intervillous space
One umbilical vein forms from branches in the chorionic plate
The maternal side:
Spiral arteries of the uterus deliver oxygenated maternal blood to the
intervillous space (maternal blood space) of each cotyledon
Intervillous space is completely lined by syncytiotrophoblast
Endometrial veins carry maternal blood from intervillous space back into uterus
CLASSIFYING VILLI ACCORDING TO THEIR LOCATION (I.E,. THEIR RELATION TO
THE FETAL OR MATERNAL SIDE OF THE PLACENTA)
Villi are like trees, with their:
Stem villi attached to the chorionic plate like the trunk of a tree
Anchoring villi attached to the decidua basalis like the crown of a tree
Terminal villi ending free in the intervillous space like the side branches of a
tree
CLASSIFICATION OF VILLI BASED ON THEIR HISTOLOGY:
Primary villus:
Syncytiotrophoblast surrounds a solid core of cytotrophoblast cells
Secondary villus:
Mesenchyme (CT) grows into the villus from chorionic plate & forms its core
Mesenchyme is surrounded by cytotrophoblast & syncytiotrophoblast
Tertiary villus
Fetal blood vessels grow into the CT core from the chorionic plate
COTYLEDONS
Decidua basalis sends septa into the intervillous space to divide the placenta
into cotyledons
Each cotyledon contains one or more stem villi and its branches, and
receives blood from many spiral arteries
TROPHOBLASTIC SHELL
Located where anchoring villi contact decidua basalis
Formed when cytotrophoblast cells within the villus break through the
syncytiotrophoblast and migrate into the decidua basalis
Such cells are called peripheral cytotrophoblast cells
MICROSCOPIC ANATOMY
Peripheral cytotrophoblast cells are difficult to distinguish from decidual cells
Decidual cells are derived from stromal cells of the uterine endometrium
(i.e., are maternal in origin)
CELL TYPES IN PLACENTA
CYTOTROPHOBLAST
Are always separated from maternal blood by syncytiotrophoblast
Are pale-staining, mononucleated cells
Are stem cells that fuse to form the syncytiotrophoblast
At first they form a continuous layer just deep to syncytiotrophoblast
Later, cytotrophoblast layer becomes discontinuous as rate of fusion with
syncytiotrophoblast exceeds rate of cytotrophoblast cell division
SYNCYTIOTROPHOBLAST
Multinucleated syncytium formed by fusion of cytotrophoblast cells
Has invasive properties (invades endometrium, maternal blood vessels &
glands)
By EM, cells have numerous microvilli
Later in pregnancy, the nuclei cluster in groups called syncytial knots
Formation of knots leaves large areas where cytoplasm is very thin,
favoring efficient exchange between fetal & maternal circulations)
HOFBAUER CELL
Macrophage
Pale foamy cytoplasm and a central nucleus
Found mainly in the CT core of the villi
In HIV-infected placentas, HIV virus is found in Hofbauer cells &
syncytiotrophoblast
DECIDUAL CELLS
Found in decidua basalis
Large, polygonal cells with pale cytoplasm & central nuclei
Form clusters of cells, giving them an epithelioid appearance
Derived from fibroblast-like stromal cells of uterine endometrium
DISTINGUISHING MATERNAL VS. FETAL SIDE OF THE PLACENTA:
BLOOD VESSELS:
Large artery and vein branches are found in the chorionic plate (fetal side)
but not in the decidua basalis (maternal side)
Maternal side has small spiral arteries (most of which are actually arterioles)
& endometrial veins (most of which are venules or small veins)
MICROSCOPIC ANATOMY
NUCLEATED RED BLOOD CELLS:
Early in development (until ~6-8 weeks) all fetal RBCs are nucleated. All lack
nuclei by 12 weeks. If a vessel contains nucleated RBCs, then the tissue
in which the vessel lies must be fetal tissue that is younger than 12 weeks.
If a vessel contains non-nucleated RBCs it is either in maternal tissue or in
fetal tissue older than 12 weeks. That distinction must then be made on
the basis of vessel location.
AMNION:
Amnion is a simple cuboidal epithelium plus a small amount of connective
tissue
It eventually fuses with the connective tissue of the chorionic plate, thus
obliterating the chorionic cavity
Amnion therefore may be present on the fetal side of the placenta (chorionic
plate) if the two have already fused
Amnion is never present on the maternal side of the placenta (decidua basalis)
since this surface is continuous with the uterine endometrium
TYPE OF CT:
Chorionic plate tends to be more mucoid
Decidua basalis tends to be more fibrous
FIBRINOID:
Is an extracellular eosinophilic material that accumulates during pregnancy
Tends to be more abundant on the maternal side
DECIDUAL CELLS/PERIPHERAL CYTOTROPHOBLAST:
Present only in the decidua basalis; not in the chorionic plate
MINIMUM PLACENTAL BARRIER (BETWEEN FETAL & MATERNAL BLOOD):
Consists of:
Syncytiotrophoblast cytoplasm
Fused basal laminae of syncytiotrophoblast and fetal capillary endothelium
Fetal capillary endothelial cell
Human placenta is classified as “hemochorial” because maternal blood is in
direct contact with chorionic plate & villi, not separated from them by any
other tissue such as the wall of a maternal blood vessel
EARLY VS. LATE PLACENTA
Early placenta has:
Relatively few villi (lots of open space in maternal blood space)
Fetal capillaries (in chorionic plate & villi) that contain nucleated fetal red
cells
Continuous layer of cytotrophoblast cells in villi
MICROSCOPIC ANATOMY
Late placenta has:
More villi & villi that are more highly branched (look more crowded together)
Discontinuous cytotrophoblast layer in villi
Syncytial knots increasing in number
More fibrinoid
Fetal capillaries closer to the surface of the villi to minimize thickness of
diffusion barrier between fetal and maternal blood
VI. INTEGUMENT (SKIN)
TWO LAYERS OF SKIN:
Epidermis:
Is a maximally keratinized stratified squamous epithelium
Is avascular; receives nourishment from underlying dermis
Major cell type: keratinocyte
Other cell types:
melanocyte
Langerhans cell
Merkel cell
stem cells – give rise only to keratinocytes and Merkel cells
Dermis: A connective tissue layer; located deep to epidermis
Has a papillary layer and a reticular layer
NOTE: Hypodermis is usually not considered a true part of skin
Hypodermis is characterized by large deposits of white fat
LAYERS OF EPIDERMIS ARE BASED ON MORPHOLOGY OF KERATINOCYTES
Epidermis has a maximum of 5 layers:
1. Stratum basale (stratum germinativum)
Stem cell layer; most division occurs at night
Single layer of cuboidal to columnar cells
Is the deepest layer of the epidermis (sits on basal lamina)
Site where synthesis of keratin begins, forming tonofilaments
Contains stem cells, melanocytes & Merkel cells in addition to keratinocytes
2. Stratum spinosum
Consists of several layers of large polygonal keratinocytes
Characterized in LM by many spinous processes extending from cell to cell
EM shows that spines are formed by cytoplasmic processes of neighboring
cells that are connected by desmosomes
MICROSCOPIC ANATOMY
Keratinocytes of stratum spinosum begin to produce:
Lamellar bodies (membrane-coating granules) help waterproof the skin
Keratohyalin (KH) granules involved in keratinization
Layer also includes Langerhans cells (a type of antigen-presenting cell)
3. Stratum granulosum
Keratinocyte cytoplasm contains many keratohyalin granules that are strongly
basophilic because they contain highly sulfated proteins
Contents of lamellar bodies are released by merocrine secretion
Cell envelope (see keratinization below) forms on inner surface of plasma
membrane; provides increased mechanical strength
4. Stratum lucidum
By LM it is only visible in thick skin
Thin, refractile or eosinophilic layer
Keratohyalin granules are dispersing (no longer visible by LM)
Cytoplasm is packed with immature keratin that may stain differently from
the mature keratin in the stratum corneum
Cells are dying; nucleus & other organelles break down
5. Stratum corneum
Many layers of dead, flat, anucleate cells
Packed with mature keratin
Cells are desquamated individually or in small sheets called squames
Desquamation involves degradation of desmosomal proteins by a serine
protease at the lower pH that exists in the superficial layers of the
epidermis
THICK VS. THIN SKIN
Both are maximally keratinized stratified squamous epithelia
The distinction is based on the thickness of the epidermis (not dermis)
Thickness of stratum corneum varies most
Thick skin:
Lacks hairs
Has abundant eccrine sweat glands
Stratum corneum is the thickest layer
Found on palms of hands and soles of the feet
Thin skin
Has hairs and sweat glands in most locations
Hairless on lips, labia minora, penis
Stratum spinosum is usually the thickest layer
Covers the rest of the body
MICROSCOPIC ANATOMY
KERATINIZATION
Tonofilament production begins in stratum basale
Tonofilaments are aggregated into tonofibrils in stratum spinosum
KH granule production begins in upper part of stratum spinosum
KH granules have no limiting membrane
Consist of free polysomes & the proteins they make, e.g., profilaggrin (which
promote further aggregation of tonofilaments)
Granules are numerous enough to become visible by LM in stratum granulosum
KH granules disperse in stratum lucidum/corneum & their proteins coat the
tonofibrils & tonofilaments
Tonofilaments become cross-linked, & are anchored in the cell envelope
Cell envelope is a layer of insoluble proteins (loricin, involucrin, elafin, etc.)
deposited on the inner surface of the plasma membrane
WATERPROOFING THE SKIN (LAMELLAR BODIES)
Lamellar bodies (membrane coating granules or MCGs) provide waterproofing
Are produced by keratinocytes in upper part of stratum spinosum
Are membrane-bounded bodies that bud off the Golgi
Contain a mixture of lipids
Most important component is acylglucoslyceramide
Contents are released by merocrine secretion into the extracellular spaces at
boundary between stratum granulosum and stratum lucidum or corneum
Secreted lipids form a water barrier that prevents excess fluid loss from skin
NOTE: Lamellar bodies also contain the serine proteases that destroy
desmosomes during the process of desquamation
MELANIN SYNTHESIS
Produced by melanocytes
Are neural crest derivatives
Pale cells amid keratinocytes of stratum basale
Do not form desmosomes with neighboring cells
Long cytoplasmic processes called dendrites (visible by EM) extend up into
stratum spinosum
Melanin is synthesized within melanosomes
Membrane-bounded organelles derived from the Golgi
Contain tyrosinase (enzyme necessary to produce melanin from tyrosine)
Is a marker enzyme for melanocytes
Mature melanosomes (melanin granules) are transferred to keratinocytes
soon after they are produced
Are eventually destroyed by lysosomal enzymes in keratinocytes
Melanocytes contain few melanosomes & are thus less pigmented than
keratinocytes
MICROSCOPIC ANATOMY
LANGERHANS CELLS
Located mainly in stratum spinosum
Bone marrow-derived & part of mononuclear phagocyte system
Pale cytoplasm contains no melanin, no KH granules, or tonofilaments
No desmosomes
Contain a unique organelle, the Birbeck granule, shaped like a tennis racket
Have long cytoplasmic processes that extend between keratinocytes
Are members of a group of cells called dendritic cells
Dendritic cells are antigen-presenting cells that help initiate immune responses
Langerhans cells can carry antigens from the skin to the regional lymph
nodes
Carry CD1 marker surface antigens
Serve as a reservoir for HIV virus in individuals with AIDS
MERKEL CELLS
Rare cells located in stratum basale
Most numerous in thick skin, especially fingertips
Are connected to keratinocytes by desmosomes
Most are in contact with the enlarged, flattened end of a sensory nerve (called a
Merkel disk)
By EM, Merkel cell contains small dense-cored granules near the Merkel disk
Merkel cell + Merkel disk = Merkel corpuscle
Functions as a mechanoreceptor (touch)
DERMIS:
LAYERS OF THE DERMIS
Papillary layer
Thin superficial layer that includes the dermal papillae
Composed of loose CT
Reticular layer
Thicker, deeper layer of the dermis
Composed of dense irregular CT
DERMAL-EPIDERMAL JUNCTION
Basement membrane lies between stratum basale & papillary layer of dermis
Dermal papillae:
Fingerlike upward projections of dermis
More numerous in areas of greater mechanical stress
Contain capillary loops and Meissner’s corpuscles
Interdigitate with epidermal ridges
MICROSCOPIC ANATOMY
Dermal ridges:
Form in areas of greatest mechanical stress
Are true ridges, with many dermal papillae sitting on each ridge
Form fingerprints
HYPODERMIS
Also called superficial fascia (or the subcutis in Wheater)
Lies deep to the dermis
Contains loose connective tissue, adipose tissue, large blood vessels, some
Pacinian corpuscles, some hair bulbs
Eccrine sweat glands may extend into hypodermis
Flexibly binds skin to deeper structures
Where very thick and rich in fat, called panniculus adiposus
INTEGUMENTARY APPENDAGES
Sebaceous glands
Eccrine sweat glands
Apocrine sweat glands
Hairs
Nails
SEBACEOUS GLANDS
Usually secrete into hair follicles; in a few areas they open directly onto the
surface of the skin
Small sebaceous glands have an unbranched duct; larger ones can have
branched ducts
Stem cells lie on basement membrane at periphery of gland
Differentiating cells enlarge, accumulate many lipid droplets in cytoplasm, and
move toward duct
Mature cells have pale, foamy cytoplasm due to extraction of lipid
Nuclei become small, heterochromatic and irregular in shape (pyknotic)
Holocrine method of secretion
Secrete: triglycerides, waxes, esters, etc.
Bacteria on skin produce fatty acids from triglycerides
Secrete in response to androgen hormones, not neural stimulation or heat
Activity increases greatly at puberty (fatty acids can contribute to acne)
MICROSCOPIC ANATOMY
ECCRINE SWEAT GLANDS
Are simple coiled tubular glands
Open directly onto skin surface, not into hair follicles
Extend deep into reticular layer of dermis or upper part of the hypodermis
Secrete in merocrine (eccrine) fashion
Secrete a watery fluid containing glycoproteins, sodium, etc.
Myoepithelial cells surround secretory portion (not duct)
Secretory portion stains paler & is wider in diameter than duct
Secretory portion has a small lumen compared to apocrine gland
By EM clear cells & dark cells are visible in secretory portion
Dark cells secrete glycoproteins
Light cells pump ions & thus produce the watery component of sweat
Duct is stratified cuboidal epithelium (2 layers)
Duct resorbs some of the sodium to produce a hypotonic sweat
Duct lacks myoepithelial cells
Secretion is controlled by sympathetic innervation
The postganglionic sympathetic neurons that control thermoregulatory sweating
are unusual because they are cholinergic (ACh) rather than adrenergic
APOCRINE SWEAT GLANDS
Open into hair follicles above the opening of sebaceous glands
Secretory portion has simple cuboidal to columnar epithelium
Duct is stratified cuboidal epithelium
Diagnostic feature is the wide lumen of the secretory portion
Secretory portion is surrounded by myoepithelial cells; duct lacks them
Secrete a viscous, odorless fluid that is metabolized by bacteria to produce
malodorous compounds
Secretory granules are released in a merocrine fashion
Some cytoplasm may be pinched off in apocrine fashion. This remains
controversial
Limited to a few areas, e.g., axilla, perianal region, areola of the nipple
Become active at puberty
Secrete in response to emotional stimuli, but not in response to heat
In many mammals similar glands produce pheromones
HAIR
Skin that has hair is called vellus skin; skin without hair is called glabrous
Thick skin is glabrous; most thin skin is vellus
MICROSCOPIC ANATOMY
A hair follicle consists of:
Dermal papilla:
Contains vessels that supply the hair
The epithelial sheath:
Surrounds & gives rise to the hair shaft
Lower end of sheath widens to form the hair bulb
Hair bulb surrounds the dermal papilla
The cells that form the hair bulb are called matrix cells
The matrix cells closest to the dermal papilla include stem cells that give
rise to the hair shaft & inner root sheath
Hair bulb also contains melanocytes that give the hair shaft its color
Layers of a hair follicle
Above the level of the hair bulb, the epithelial cells of the hair follicle can be
divided into an internal and an external root sheath
Internal root sheath:
Is the layer of the follicle closest to hair shaft
Cells become keratinized (soft keratin), & then degenerate
Layer extends from hair bulb up to the level of the sebaceous duct
External (outer) root sheath:
Surrounds internal root sheath
Continuous with the epidermis
Morphologically resembles a stratum basale & stratum spinosum
Does not become keratinized
Glassy (vitreous) membrane surrounds the hair follicle:
Is a thick basement membrane that lies between external root sheath & dermis
Is continuous with the basement membrane of the epidermis
A connective tissue sheath lies exterior to the glassy membrane
Parts of a hair shaft:
Medulla:
The thin central core of the hair shaft
Contains large, pale, vacuolated cells
Found only in thick (terminal) hairs
Cortex:
Between medulla and cuticle
Cuticle:
Outermost layer of hair shaft; faces internal root sheath
Consists of highly keratinized cells that overlap like shingles on a roof
Pigmentation:
Cortex is highly pigmented
Medulla & cuticle are pale
Pigment is produced by melanocytes in hair bulb
MICROSCOPIC ANATOMY
Keratinization:
Cortex & cuticle are highly keratinized
Medulla is lightly keratinized
Hair contains hard keratin
NAILS:
Nail plate:
The hard fingernail or toenail
Nail bed:
Stratified epithelial layer on which nail plate rests
Continuous with stratum basale & stratum spinosum of epidermis
Eponychium:
Also called the cuticle
Hyponychium:
Thickened skin under the free end of nail plate
Nail matrix:
The proximal end of the nail bed
Contains stem cells that divide to produce nail plate
Nail root:
Proximal part of nail plate; covered by eponychium
Is the most recently produced part of nail plate
Lunula:
The lighter colored half-moon shaped area at the proximal end of the
visible nail plate
Caused by immature keratin in that part of nail plate
Is more opaque than mature keratin & masks the underlying blood
vessels that make the rest of the nail look darker
NAIL GROWTH
Nail plate grows from its proximal end
Is produced by division of stem cells in the nail matrix
Nail plate slides over nail bed toward fingertip as it increases in length
MICROSCOPIC ANATOMY
IMPORTANT INFORMATION FOR ANSWERING PRACTICAL EXAM QUESTIONS
I. Since some questions may ask you to identify the organ shown, you need to understand the
definition of an organ.
An organ is a structure composed of more than one tissue type and serving a specific
function.
Example: A salivary gland, even though it is small, is still an organ. It is composed of
epithelium, nerve, smooth muscle (in its arteries & veins), intralobular connective
tissue, & interlobular connective tissue. Many times in the past we have had students
say, “I got that question wrong because I didn’t know that something as small as a
salivary gland could be an organ”.
II. “Identify” vs. “classify”
In dealing with epithelium and connective tissue, there is a difference between "identifying" a
structure & "classifying" it:
Ø To identify means to give the unique name of that structure.
Ø To classify means to place the structure into a grouping that includes other similar
structures.
For example, if asked to identify your course director for Microscopic Anatomy, you would say
“Janet Smith”. That is the unique (or in the case of someone named Smith, not so very
unique) identifier by which I am known.
If asked to classify your course director you might say “adult female”. You have then put me
into a group with other similar individuals.
In concrete histological terms:
Ø To classify an epithelium means to say whether it is:
Simple squamous
Simple cuboidal
Simple columnar
Minimally keratinized stratified squamous
Maximally keratinized stratified squamous
Stratified cuboidal
Stratified columnar
Pseudostratified columnar
Transitional
Ø To classify a connective tissue means to tell us whether it is:
Loose CT (the loose cellular CT of the lamina propria is a subtype)
Dense irregular CT
Dense regular CT
White adipose tissue
Brown adipose tissue
MICROSCOPIC ANATOMY
Examples of classify vs. identify:
Ø If we point to the epithelium covering the outer surface of the lung and say:
Classify this tissue
Answer: simple squamous epithelium
Identify this tissue
Answer: mesothelium
Ø If we point to the superficial layer of the dermis and say:
Classify this tissue
Identify this tissue
Answer: loose connective tissue
Answer: papillary layer of the dermis
III. Always be as specific as possible in your answers.
Examples:
Ø “Sweat gland” is not a specific answer. Even “eccrine sweat gland” (vs. apocrine
sweat gland) is not as specific as possible because you studied how to
distinguish the secretory portion from the duct. So to be as specific as possible
you would have to say “secretory portion of eccrine sweat gland” or “duct of
eccrine sweat gland”.
Ø “Stratified squamous epithelium” is not a specific answer. You must say whether
it is minimally or maximally keratinized stratified squamous epithelium.
Ø Nonspecific answers generally receive no credit at all.
IV. Answer the question that is asked.
Ø Be sure to read the question and answer the question that is actually asked. The arrow
may be pointing to a structure that you can identify, but the question may be asking you
something about that structure rather than asking you what that structure is. For
example we may be asking what its major function is, or to name a major secretory
product. If you give us the name of the structure instead of answering the question that
we asked about it, your answer will be marked wrong.