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Dr. Janet Smith
Microscopic Anatomy
SLIDE REVIEW
MUSCLE WEAKNESS & WEIGHT LOSS MODULES
I. MUSCLE
One of the 4 major tissue types
Specialized for contraction
Contraction is based on interaction of 2 types of myofilaments
Thin filaments (actin-containing)
Thick filaments (myosin-containing)
Three types of muscle:
Skeletal
Cardiac
Smooth
Striated muscle – skeletal & cardiac are classified as striated muscle
A. SKELETAL MUSCLE
ORGANIZATION:
Thick & thin (myo)filaments form a sarcomere
Sarcomeres are arranged end-to-end form a myofibril
Many myofibrils are arranged side by side in the cytoplasm of
each skeletal muscle cell
A skeletal muscle cell is also called a muscle fiber
Many muscle cells are bundled together by connective tissue
(perimysium) to form a muscle fascicle
Many muscle fascicles are bundled together by connective
tissue (epimysium) to form a single muscle
Summary: Myofilaments à Sarcomeres à Myofibrils à
Cells (Fibers) à Fascicles à Muscles
CONNECTIVE TISSUE IN SKELETAL MUSCLE:
Endomysium
Loose connective tissue that surrounds individual muscle cells
Consists mainly of reticular fibers; contains capillaries
Perimysium
Dense irregular connective tissue that surrounds a
muscle fascicle; contains larger blood vessels
Epimysium
MICROSCOPIC ANATOMY
Dense irregular connective tissue that surrounds an
entire muscle (= the investing fascia of the muscle)
MICROSCOPIC ANATOMY
THE SARCOMERE:
Found in skeletal & cardiac muscle, i.e., in all striated muscle
Runs from one Z-line to the next
Contains:
An A band in the center of the sarcomere
Half of an I band at each end of the sarcomere
I-BAND
Light-staining band
Contains the parts of thin filaments that are not
overlapped by thick filaments
Bisected by Z-line, which anchors the actin filaments
Its length decreases during contraction
A-BAND
Dark staining band of constant length
Length corresponds to the length of the thick filaments
Also contains the part of the thin filaments that overlaps the
thick
At EM level the A-band also contains:
H-zone:
Lighter staining region at center of A band
Contains only thick filaments (i.e., is the region of the
thick filaments that doesn’t overlap with thin)
Length decreases during contraction
Bare zone:
An even lighter staining region within the H zone
Contains shafts of thick filaments but no myosin heads
Constant in length
M-line:
A darker line at the center of bare zone
Site of cross-connections between thick filaments
Contains myomesin and C protein
SKELETAL MUSCLE CELLS:
Mature fibers are long, unbranched, cylindrical cells
Multinucleated, with peripheral nuclei
Each cell is a syncytium formed by fusion of uninucleate cells
(myoblasts)
Average diameter of mature skeletal muscle cells is wider than
cardiac or smooth muscle
MICROSCOPIC ANATOMY
T-tubules (transverse tubules):
Invaginations of the sarcolemma (muscle cell plasmalemma)
Located at A-I junction in mammalian skeletal muscle
Located near Z-line in most other vertebrates (e.g., frogs)
Carry depolarization of sarcolemma deep into muscle cell
Depolarization of T tubule membrane causes release of
calcium from terminal cisternae of sarcoplasmic reticulum
Sarcoplasmic reticulum (SR):
Is the equivalent of smooth ER in other cell types
Sequesters calcium within its lumen to prevent contraction
Encircles each myofibril within the skeletal muscle cell
Forms a discontinuous network, with each segment
extending from one T tubule to the next
Each segment has two parts:
Terminal cisternae (the expanded terminal portions
located near each T tubule)
Longitudinal elements that connect terminal cisternae
- transports calcium back into the SR after each
contraction
Triad: Is a T tubule plus the 2 terminal cisternae that flank it
NEUROMUSCULAR JUNCTIONS (NMJ)
Are the terminations of motor neurons on skeletal muscle cells
Neurons that innervate skeletal muscle cells are
called somatic motor neurons
The axon branches near its end (terminal arborization)
Each muscle cell is innervated by only one motor endplate
NOTE: One neuron plus all the muscle cells innervated by it is
known as a motor unit
Each axonal branch
Ends in a motor endplate
Loses its myelin sheath at the motor endplate, but
remains partially covered by a Schwann cell
Has many mitochondria in the axon terminal
Releases acetylcholine (ACh) from round, clear synaptic
vesicles into the synaptic cleft
The motor endplate sits in a depression in the muscle cell
sarcolemma called the primary synaptic cleft
Secondary synaptic clefts are formed by junctional folds of the
sarcolemma
ACh receptors are located at the crests of the junctional folds
MICROSCOPIC ANATOMY
Subneural clefts (secondary synaptic clefts) are the spaces
created between junctional folds
External lamina of muscle cell (equivalent to a basal lamina)
extends into synaptic cleft & subneural clefts
Acetylcholinesterase is localized in external lamina
B. CARDIAC MUSCLE
CHARACTERISTICS BY LM:
Each cell contains 1 or 2 centrally located nuclei
Cells are joined together end-to-end by intercalated disks,
which are unique to cardiac muscle
Cells may branch
Average cell diameter is intermediate between
skeletal & smooth muscle
INTERCALATED DISKS
Have transverse and longitudinal portions
Transverse portions run at right angles to the myofibrils
Contain fasciae adherentes (singular = fascia adherens)
- sites of actin filament attachment to the
membrane
- sites of end-to-end attachment of cardiac myocytes
Desmosomes most common on transverse portions;
also found on longitudinal
Longitudinal (lateral) portions run parallel to myofibrils
Gap junctions are common on longitudinal portions
CHARACTERISTICS BY EM:
More mitochondria than skeletal muscle
They form almost continuous rows between myofibrils
T tubules:
Are at Z-line, not at A-I junction as in human skeletal
muscle
Are wider than in skeletal muscle
Sarcoplasmic reticulum:
Not as well developed as in skeletal muscle
Terminal cisternae are not continuous along each T tubule
Results in formation of diads (dyads) more often than triads
Diad: Consists of one T tubule & one terminal cisterna of SR
MICROSCOPIC ANATOMY
INNERVATION
Ordinary cardiac muscle cells are usually not directly
innervated
Autonomic (sympathetic & parasympathetic) fibers
innervate the modified cardiac muscle fibers that form
the conduction system of the heart (SA node, AV node)
Autonomic nerve endings are less elaborate than the
neuromuscular junctions on skeletal muscle
Resemble nerve endings associated with smooth muscle
C. SMOOTH MUSCLE
CHARACTERISTICS BY LM:
Spindle shaped (fusiform) cells
Single central nucleus
Has a distorted or “corkscrew” appearance in contracted
cells
Cells have smallest average diameter of any type of
muscle
Cells are usually packed tightly together
Can be organized in orderly layers (in tubular organs,
e.g., gut) or in interlacing bundles (in spherical
organs, e.g. uterus)
CHARACTERISTICS BY EM:
Has no sarcomeres
Has dense bodies
Some are attached to the plasma membrane
Form a branching network extending into the cytoplasm
Are analogous to Z-lines:
Contain attachment plaque proteins (e.g., alpha-actinin)
Thin filaments & intermediate filaments insert on
dense bodies
Actin-myosin interaction pulls on the network of intermediate
filaments, which twist & cause contraction of cell
Has caveolae (pits)
Invaginations of the sarcolemma
Analogous to T tubules
Lack a well-organized sarcoplasmic reticulum
Sparse SER membranes are located near caveolae
MICROSCOPIC ANATOMY
Smooth muscle filaments include:
Thin filaments that contain actin but lack troponin
Thick filaments that contain myosin & are hard to preserve
Networks of intermediate filaments that contain
desmin (in GI, respiratory & urogenital tracts) or
predominantly vimentin (vascular smooth muscle)
Gap junctions are common between smooth muscle cells,
especially where muscle cells are not individually innervated
INNERVATION
Is by autonomic nerves (sympathetic, parasympathetic & enteric)
Innervation involves varicosities (boutons) located:
At the end of each axon (terminal boutons)
At intervals along the length of the axon before it
terminates (boutons “en passant”, i.e., “in passage”)
Both types of boutons form synapses with smooth
muscle cells
Synaptic morphology differs from that of skeletal muscle
In smooth muscle:
Sarcolemma has no junctional folds
Synaptic cleft is much wider than in skeletal muscle
A single bouton can innervate several nearby smooth
muscle cells
Not all smooth muscle cells receive direct individual innervation
Cells that are individually innervated form “multiunit” smooth muscle
(e.g., in the iris of the eye)
Cells that lack individual innervation are coupled to innervated
cells by gap junctions, and form “unitary” or “single unit”
smooth muscle where co-ordinated contraction can occur
(e.g., uterus, GI tract, urinary bladder)
Contraction of smooth muscle can also be initiated by non-neural
stimuli such as certain hormones (e.g., oxytocin) or by stretching
the muscle cell
II. NERVE
CELL TYPES OF THE NERVOUS SYSTEM INCLUDE:
Neurons: Transmit action potentials
Neuroglia or glia: Non-neuronal cells specific to the nervous system
CNS glia = oligodendrocytes, astroglia, microglia &
ependymal cells
PNS glia = Schwann cells & satellite cells
MICROSCOPIC ANATOMY
FUNCTIONAL TYPES OF NEURONS INCLUDE:
Somatic motor neurons
Innervate skeletal muscle
Cell bodies are located in ventral horn of spinal cord
Autonomic neurons
Preganglionics in brain stem or spinal cord
Postganglionics in autonomic ganglia (sympathetic,
parasympathetic & enteric)
Innervate smooth muscle, cardiac conduction system, & glands
Sensory neurons
Receive sensory input from receptors & free nerve endings
Found in dorsal root ganglia (spinal ganglia) & in sensory
ganglia associated with some cranial nerves
CLASSIFICATION OF NEURONS BY SHAPE:
Bipolar: One axon & one dendrite extend from the soma
e.g., Bipolar neurons of retina
Olfactory neurons in olfactory epithelium
Multipolar: One axon and multiple dendrites extend from the soma
e.g., Somatic motor neurons
Autonomic neurons
Pseudounipolar: One process extends from the soma & then
branches into a central process & a peripheral process
e.g., Most sensory neurons (e.g., DRG neurons)
Note: The terms “peripheral process” & “central process” are preferred here
instead of “dendrite” & “axon” because some peripheral processes of
sensory nerves are myelinated. Thus although we could logically call them
dendrites because they carry nerve impulses toward the soma, that would
violate the rule that dendrites are never myelinated. We avoid the problem
by making up the alternate name of “peripheral process” to refer to them.
A TYPICAL NEURON HAS:
Cell body (soma) that includes:
Nucleus: Large & euchromatic
Prominent nucleolus
Perikaryon: The cytoplasm surrounding (“peri”) the nucleus
(“karyon”)
Nissl bodies: Basophilic aggregates of free & fixed
polysomes; most evident in large somatic motor neurons
MICROSCOPIC ANATOMY
Dendrites: Are usually multiple, branched, rapidly tapering,
unmyelinated processes
Purpose is to increase the surface available for synapses
carrying incoming signals to the neuron
Axon: A single process leaves the perikaryon
Originates from the axon hillock, an area of the perikaryon
that is pale staining because it contains no Nissl bodies
Axons carry action potentials away from the cell body
toward one or more synapses on other neurons or
effector cells (muscle, gland cell)
Axons have relatively few branches until they reach
their terminal arborization
May be myelinated:
Oligodendrocytes produce myelin in the CNS
Schwann cells produce myelin in the PNS
CENTRAL NERVOUS SYSTEM (CNS) INCLUDES:
Brain & spinal cord
PERIPHERAL NERVOUS SYSTEM (PNS) INCLUDES:
Ganglia
Is a cluster of neuronal cell bodies located outside the CNS
There are two types of ganglia:
Sensory ganglia, e.g.:
Dorsal root ganglia (DRGs)
Sensory ganglia of cranial nerves
Autonomic ganglia, e.g.:
Sympathetic
Parasympathetic
Enteric (found in the wall of the GI tract)
Nerves (= Peripheral nerves)
Includes spinal nerves and cranial nerves
Composed of nerve fibers (axons plus Schwann cells)
Do not contain neuronal cell bodies
Sensory receptors
Free nerve endings
Expanded tip endings – Merkel discs
Encapsulated receptors
MICROSCOPIC ANATOMY
SPINAL CORD
White matter (axons and glia) surrounds gray matter (neuronal
cell bodies, glia, dendrites & axons)
Gray matter is divided into ventral horns (contents include somatic
motor neurons) and dorsal horns (receive sensory input)
Dorsal roots carry afferent (sensory) impulses to spinal cord
Ventral roots carry motor impulses (somatic & autonomic) to
the periphery
SENSORY VS. AUTONOMIC GANGLIA:
Sensory ganglia (DRGs & cranial nerve sensory ganglia)
Often have a layered appearance (alternating layers
of nerve processes & neurons)
Contain pseudounipolar neurons
Neurons are larger on average than in autonomic ganglia
Nucleus tends to be centrally placed within the neuron
Satellite cells form an almost complete single layer
around neuronal soma
Autonomic ganglia (sympathetic, parasympathetic & enteric)
Contain multipolar postganglionic motor neurons
Contain synapses between preganglionic axons and
postganglionic neurons
Most autonomic neurons are smaller than those in sensory ganglia
Neuronal nuclei are more likely to be eccentric
Fewer satellite cell nuclei are seen surrounding the neuron
PERIPHERAL NERVES:
ARE COMPOSED OF NERVE FIBERS
Fiber = an axon (myelinated or unmyelinated) & Schwann cells
Nerve fibers are bundled together to form a peripheral nerve
UNMYELINATED VS. MYELINATED AXONS IN THE PNS
In the PNS, myelinated & unmyelinated axons are both associated
with Schwann cells
Unmyelinated PNS axons are embedded in invaginations
(grooves) in the Schwann cell plasma membrane
Invagination forms the mesaxon (the point where the extracellular
surfaces of the Schwann cell plasma membrane contact one
another as they encircle the axon)
MICROSCOPIC ANATOMY
Several unmyelinated axons are usually embedded in one
Schwann cell
Myelinated PNS axons:
Each Schwann cell contributes to the myelination of only one axon
Myelinated axons tend to be wider in diameter than unmyelinated
MYELIN SHEATH
Viewed in cross section at high mag, it is a spiral that consists
of alternating major dense lines & intraperiod lines
Major dense line: formed by fusion of the cytoplasmic
faces of Schwann cell plasma membrane
Intraperiod line: formed by fusion of the extracellular
surfaces of Schwann cell plasma membrane in
successive layers of the myelin sheath
NOTE: Schwann cell cytoplasm persists in several locations:
Inner collar (between axon and myelin sheath
Outer collar (exterior to the myelin sheath; the
Schwann cell nucleus is located there)
Perinodal cytoplasm (near the nodes of Ranvier)
Clefts of Schmidt-Lanterman (see below)
Outer mesaxon: Where the outer surfaces of the Schwann cell
membrane contact one another exterior to the myelin sheath
Inner mesaxon: Where the outer surfaces of Schwann cell
membrane contact one another interior to the myelin sheath
The process of myelination in the PNS
The mesaxon forms by invagination of the axon into the Schwann
cell
Mesaxon elongates as new Schwann cell membrane is added to it
The elongated mesaxon begins to spiral around the axon
We can now identify an inner mesaxon at the end of the mesaxon
closest to the axon, and an outer mesaxon at the opposite end
Cytoplasm is “squeezed out” from between successive turns of the
mesaxon, forming the major dense lines of the myelin sheath
Node of Ranvier
Is the gap between two Schwann cells (PNS) or oligodendrocytes
(CNS) that myelinate adjacent segments along the axon
The myelinated portion of the axon between sequential
nodes is called an internodal segment or internode
MICROSCOPIC ANATOMY
Clefts of Schmidt-Lanterman
By LM they resemble pale-staining arrowheads in myelin sheaths
sectioned longitudinally
Are cytoplasmic tunnels that spiral through the myelin sheath of
one Schwann cell (not gaps between 2 adjacent Schwann
cells)
Form where cytoplasmic faces of Schwann cell plasma membrane
have not fused, i.e. they contain Schwann cell cytoplasm
They connect the Schwann cell cytoplasm that lies exterior to the
myelin sheath (which also contains the nucleus) with the
Schwann cell cytoplasm that lies interior to the myelin sheath,
adjacent to the axon
Are a mechanism for keeping the inner collar of Schwann cell
cytoplasm alive
MIXED NERVES:
A single peripheral nerve is often mixed, i.e., contains
myelinated & unmyelinated axons
MYELINATION IN THE CNS:
Oligodendrocytes (not Schwann cells) make myelin
Each oligodendrocyte can contribute to the myelination of
several different axons
Unmyelinated axons are not associated with oligodendrocytes at all
CONNECTIVE TISSUE COVERINGS OF NERVES
Epineurium:
Binds the nerve fascicles together to form a peripheral
nerve, and covers the outer surface of the nerve
Dense connective tissue; many collagen fibers
Also has areas of adipose tissue
Blood vessels travel in the epineurium
Perineurium:
One or more layers of contractile, squamous cells that
surround a fascicle of nerve fibers
Cells are joined together by tight junctions
- forms a barrier that regulates ionic environment for
optimal transmission of action potential
Endoneurium:
Delicate reticular fibers between individual nerve fibers
MICROSCOPIC ANATOMY
SYNAPSES:
Site of impulse transmission from one neuron to another neuron,
or to an effector cell (muscle or gland cell)
Several types of synapses:
Chemical (uses neurotransmitters)
Electrical (gap junctions): less common than chemical
FEATURES OF A CHEMICAL SYNAPSE BETWEEN NEURONS:
Presynaptic terminal has:
Synaptic vesicles containing neurotransmitter
May be spherical or elliptical, clear or dense-cored
- ACh-containing vesicles tend to be clear and round
- Adrenergic vesicles tend to be dense-cored and round
Numerous mitochondria
Presynaptic density is often present on cytoplasmic
side of membrane
Synaptic cleft (synaptic gap) is narrow, with no elaborate folds
of presynaptic or postsynaptic membranes
Postsynaptic membrane has:
Postsynaptic density on cytoplasmic side of membrane
Includes receptors for neurotransmitters
SENSORY RECEPTORS
Free nerve endings
Found in skin, in connective tissue & around hair follicles
Respond to touch, temperature or pain
Expanded tip endings (e.g., the Merkel disk in a Merkel corpuscle)
Encapsulated endings include:
Meissner’s corpuscles
Pacinian corpuscles
Muscle spindles
Golgi tendon organs
Ruffini corpuscles – slowly-adapting receptors (not rapidly adapting as
Ross says on p. 503); capsule encloses collagen fibers; respond to
sustained pressure; found in deep dermis, joint ligaments, & joint
capsules; respond to skin stretch or change in joint position
Krause end bulbs
MICROSCOPIC ANATOMY
MERKEL CORPUSCLES (= Merkel Cell + Merkel Disk)
Found in stratum basale of skin
Slowly adapting mechanoreceptors (i.e., nerve impulses fire throughout
duration of stimulus; good for detecting steady pressure)
Consist of modified epidermal cells that are closely associated with the
expanded tip of a nerve ending
Cells have dense secretory granules localized near the nerve ending
MEISSNER’S CORPUSCLES:
Found in dermal papillae immediately beneath epidermis
Found in hairless (glabrous) skin, especially fingertips, toes, lips
Elliptical; oriented perpendicular to skin’s surface
Capsule composed of flattened Schwann cells
Arranged in layers that are stacked parallel to skin surface
Axons enter the deep pole of the corpuscle & lose myelin sheath
Axons follow a spiral path toward apical pole of corpuscle
Rapidly adapting mechanoreceptors (i.e., nerve impulses fire only at
beginning & end of a stimulus; good for detecting changes in stimulation)
PACINIAN CORPUSCLES:
Found for example in deep dermis, hypodermis, joints & internal organs
Much larger than Meissner’s corpuscles
Have an onion-like appearance
Myelinated axon enters capsule and then loses myelin sheath
Axon remains within the tubular inner core formed by Schwann cells
Multiple layers of flattened fibroblastic cells form the outer core
Layers of the outer core are separated from one another by fluid-filled spaces
Rapidly-adapting mechanoreceptors that respond to mechanical deformation
& especially to vibration
MUSCLE SPINDLES:
Found within skeletal muscle
Arranged in parallel with the extrafusal muscle cells
Contain 2 types of intrafusal fibers (also called spindle cells)
Nuclear bag fibers – have a cluster of nuclei in central part of cell
Nuclear chain fibers – have a row of nuclei in central part of cell
Surrounded by an internal capsule, then a fluid-filled space, &
then an external capsule
MICROSCOPIC ANATOMY
Intrafusal fibers are modified skeletal muscle fibers
Are much smaller in diameter than extrafusal
Respond to passive stretch of the muscle
Are innervated by sensory neurons
Stretching the intrafusal fibers causes extrafusal fibers of the
same muscle to contract via a spinal reflex (the stretch reflex)
Prevents damage to the muscle from stretching
Is an important postural mechanism for maintaining constant
muscle length
NOTE: Ross says on p. 326 that stretching the intrafusal fibers
INHIBITS contraction of the muscle. That is wrong.
Intrafusal fibers are also innervated by efferent motor fibers that
cause intrafusal fibers to contract
Is a mechanism for adjusting the sensitivity of the spindle
The more contracted the intrafusal fibers are when stretch is
applied, the less stretch it will take for them to trigger an
afferent nerve impulse
GOLGI TENDON ORGAN
Found at musculotendinous junctions
Contains thick collagen fibers rather than intrafusal muscle fibers
Surrounded by a thin connective tissue capsule
Collagen fibers are continuous at one end with the tendon & at
the other with the skeletal muscle cells (i.e., are in series
with skeletal muscle fibers rather than in parallel)
Innervated by a sensory axon that loses it myelin sheath,
branches, & wraps around the collagen fibers
No motor innervation since collagen fibers can’t contract
Responds to excessive muscle tension by inhibiting the
contraction of the muscle with which it is associated
III. ENDOCRINE ORGANS:
A. HYPOPHYSIS (PITUITARY)
Located in the hypophyseal fossa (part of the sella turcica) of
the sphenoid bone
Consists of:
Adenohypophysis:
Pars distalis
Pars tuberalis
Pars intermedia
MICROSCOPIC ANATOMY
Neurohypophysis:
Infundibulum
Pars nervosa
ADENOHYPOPHYSIS:
Epithelial in appearance (i.e., has closely packed cells) as opposed to
the more fibrillar appearance of the neurohypophysis
The parts of the adenohypophysis can be identified based on location:
Pars tuberalis
Surrounds the infundibulum to form the stalk
May see some large veins that are part of a portal system
Pars intermedia
Lies between pars nervosa and pars distalis
Contains many basophils (see below)
Often contains cysts (Rathke’s cysts) filled with colloid
Colloid is the term used for any PAS+ material that
accumulates extracellularly in endocrine glands
Pars distalis
Forms part of the body of the pituitary (along with pars
intermedia & pars nervosa)
Contains more acidophils (see below) than pars intermedia
Adenohypophysis is a derivative of an outpocketing of the oral
ectoderm (Rathke’s pouch)
Contains 3 classes of cells by routine LM:
Acidophils, basophils & chromophobes
Acidophils & basophils are collectively called chromophils
Acidophils & basophils often difficult to distinguish in H&E
Special trichromes make identification easier
Acidophils & basophils produce hormones
Secretory activity of acidophils and basophils is regulated by:
Releasing or inhibiting hormones produced in the hypothalamus
Negative feedback by hormones of the target organs
ACIDOPHILS
Two types:
Somatotropes: produce growth hormone (GH, somatotropin)
Mammotropes: produce prolactin
Mnemonic for cell types:
SAM – Somatotropes are Acidophils & so are Mammotrophs
Mnemonic for hormones:
GPA – Growth hormone & Prolactin are produced by Acidophils
MICROSCOPIC ANATOMY
(NOTE: Somatotropes & mammotropes can be distinguished
from one another using EM. It is not necessary for you to be
able to do this.)
BASOPHILS
At least three types:
Gonadotropes: produce follicle stimulating hormone
(FSH) or luteinizing hormone (LH)
Corticotropes: produce adrenocorticotropin (ACTH) &
other derivatives of pro-opiomelanocortin (POMC)
Thyrotropes: produce thyroid-stimulating hormone (TSH)
Mnemonic for hormones:
B-FLAT: Basophils produce FSH, LH, ACTH, TSH
Melanotropes usually considered to be a fourth type of basophil
Related to corticotropes
Produce melanocyte-stimulating hormone (MSH)
- MSH is also a POMC derivative
- involved in pigmentation in lower vertebrates
- function and importance in humans is uncertain
(NOTE: The various types of basophils can be distinguished
from one another using EM. It is not necessary for you to be
able to do this.)
CHROMOPHOBES
Cytoplasm stains poorly
May be undifferentiated cells or degranulated chromophils
HOW THE ADENOHYPOPHYSIS WORKS
Hypothalamic neurons (in the paraventricular nucleus) produce
releasing or inhibiting hormones (RH & IH) that stimulate or
inhibit hormone secretion by specific acidophils or basophils in
the adenohypophysis
The hypothalamic neurons secrete the RH & IH into a venous portal
system (the hypothalamic-hypophyseal portal system) that
carries them to the adenohypophysis
The portal system consists of:
A primary capillary plexus
Located in the floor of the hypothalamus & the infundibular stalk
RH & IH are secreted into this plexus
Hypophyseal portal veins
Located in infundibular stalk (especially pars tuberalis)
Connect primary and secondary capillary plexuses
MICROSCOPIC ANATOMY
Secondary capillary plexus
Located mainly in pars distalis; also pars intermedia
Hypophyseal portal veins deliver RH & IH to this plexus
RH & IH stimulate or inhibit secretion from acidophils and
basophils
Secondary plexus picks up the hormonal products of the
acidophils & basophils and feeds into veins that carry the
hormones out of the pituitary
Both plexuses have fenestrated capillaries (those in the
secondary plexus are sometimes called fenestrated
sinusoids since the vessels are wider and more irregular
than ordinary capillaries)
NEUROHYPOPHYSIS
Is the site of release (NOT synthesis) of oxytocin & ADH
(vasopressin), which are synthesized in the hypothalamus
Is of neuroectodermal origin (downgrowth of floor of 3rd ventricle)
Contains:
Pituicytes:
- are glial cells
- most nuclei in pars nervosa belong to pituicytes
Nonmyelinated axons of neurons whose cell bodies
are in the hypothalamus (magnocellular system)
Herring bodies
- poorly visible by LM
- are dilations along an axon where neurosecretory
granules temporarily accumulate
- the granules contain oxytocin or vasopressin, (ADH) plus
neurophysins (hormone-binding proteins)
HOW THE NEUROHYPOPHYSIS WORKS:
Hypothalamic neurons in the magnocellular system
synthesize oxytocin or ADH
The hormones are transported down the axons of the
hypothalamic neurons into the pars nervosa
- they are not transported to pars nervosa via blood
vessels
The axon terminals release oxytocin & ADH into the
fenestrated capillaries of the pars nervosa
Oxytocin & ADH leave the pituitary in veins and travel
to their specific target organs throughout the body
MICROSCOPIC ANATOMY
B. THYROID GLAND
Derived from the thyroglossal duct that originated in the tongue
Contains two endocrine systems:
Follicular cells that produce T3 & T4
Parafollicular cells that produce calcitonin
THYROID FOLLICLE
Is the structural & functional unit of the thyroid
Is a spherical structure with a single layer of follicular cells
surrounding a lumen filled with colloid
Main component of colloid in the thyroid is thyroglobulin (TG)
TG is the inactive storage form of the thyroid hormones
Thyroid is unique among endocrine glands because it stores
most of its secretory product extracellularly instead of in
vacuoles in the cytoplasm
Extensive network of fenestrated capillaries surrounds each follicle
Follicular cell height increases from squamous to columnar as
TSH stimulation increases
Follicular epithelium also includes occasional parafollicular cells
(see below)
THYROID FOLLICULAR CELLS
Are morphologically polarized cells with obvious basal & apical ends
Have abundant RER in basal cytoplasm
Is the site of TG synthesis
RER cisternae of follicular cells are characteristically
dilated & irregular in shape
Cells are joined together by tight junctions
Apical plasma membrane has short sparse microvilli
Small, clear secretory vesicles in apical cytoplasm
Contain newly synthesized TG about to be released
into follicular lumen
Larger PAS-positive phagocytic vacuoles called colloid droplets
Contain colloid recently taken up from the lumen
TSH stimulation causes:
- increase in surface projections of apical membrane
- formation of increased number of colloid droplets
- extensive phagocytosis can cause “scalloping” of colloid
MICROSCOPIC ANATOMY
Have many lysosomes
Concentrated at basal end of less active follicular cells
Under TSH stimulation they migrate toward apical end of cell
They fuse with colloid droplets to form secondary lysosomes
where TG is degraded to release T3 & T4
Have a well-developed Golgi is involved in:
Glycosylation & packaging of TG
Production of lysosomes
PARAFOLLICULAR CELLS (C CELLS)
Rare in human thyroid
Cytoplasm typically appears pale or clear (hence C cells)
Derived from neural crest cells that form the ultimobranchial
body associated with the 5th pharyngeal pouch of the fetus
Most are part of the follicular epithelium
Rest on basement membrane but do not reach follicular lumen
By EM, have small secretory granules in basal cytoplasm
Secrete calcitonin in response to high blood calcium
Calcitonin lowers blood calcium levels by:
Stimulating calcium uptake into cells
Inhibiting osteoclasts, thus decreases calcium release from bone
Calcitonin is not essential for life, but it protects lactating
mothers from excessive bone loss by inhibiting osteoclasts
Calcium for milk must then come from other sources such
as diet or reabsorption from the glomerular filtrate
C. PARATHYROID GLAND
Embedded in capsule of thyroid gland; also has its own thin
capsule
In young parathyroid, cells are arranged like beads on a string
Contains:
Principal cells (chief cells)
Oxyphils (less common in young parathyroid)
Adipocytes (increase in number with age)
CHIEF CELLS
Most numerous cell type
Small polygonal cells with round centrally placed nucleus
Cells sometimes contain large amounts of glycogen
Extraction of glycogen makes cytoplasm pale-staining
MICROSCOPIC ANATOMY
In young parathyroids the cells are arranged in linear swirls
(“beads on a string”)
EM: Has small secretory granules that contain parathyroid
hormone (PTH)
PTH increases blood calcium levels by increasing:
Bone resorption (stimulates osteoclast activity indirectly)
Calcium reabsorption (and phosphate excretion) by kidney
Calcium absorption by intestine
OXYPHILS
Larger than chief cells
Very eosinophilic due to many mitochondria
Nuclei often smaller & darker staining by LM than those of chief cells
Oxyphils often occur in clusters
Number increases with age, but they never outnumber chief cells
Function unknown
HOW TO DISTINGUISH PARATHYROID FROM PARS DISTALIS
OF HYPOPHYSIS
The eosinophilic cell is the major cell type in the pars distalis
(acidophils), & the minor cell type in the parathyroid (oxyphils)
Adipocytes are rare in pars distalis at any age, but common in
older parathyroids
Oxyphils often occur in clusters, while acidophils are more
evenly distributed among the basophils & chromophobes
Less difference in average cell size among chromophils &
chromophobes of the adenohypophysis than in parathyroid where
oxyphils are usually significantly larger than chief cells
D. ADRENAL GLANDS (SUPRARENAL GLANDS)
Divided into cortex & medulla
Both contain fenestrated sinusoidal capillaries (sinusoids)
Medulla also characteristically contains some very large veins
3 ZONES OF ADRENAL CORTEX:
ZONA GLOMERULOSA
Lies just deep to capsule
Small closely packed cells arranged mainly in clusters (glomeruli)
Produce mineralocorticoids: (e.g., aldosterone) that are
important in maintenance of electrolyte balance
MICROSCOPIC ANATOMY
Secretion is stimulated by angiotensin II (produced via the
renin-angiotensin system in response to a fall in blood
pressure, low blood sodium or increased plasma K+)
ZONA FASCICULATA
Largest & palest-staining cortical region
Cells arranged in straight cords (fascicles) that are 1 or 2 cells thick
Sinusoidal capillaries lie between the cords
Cords run perpendicular to surface of gland
Extraction of lipid during tissue processing makes cytoplasm pale-staining
Cells sometimes called spongiocytes because extracted lipid droplets
give cytoplasm a spongy or lacy appearance
Produce glucocorticoids: (e.g., cortisol and corticosterone) & small
amount of adrenal androgens
Secretion is regulated by ACTH
ZONA RETICULARIS
Cells arranged in irregular anastomosing network (hence reticularis)
rather than straight cords
Fewer lipid droplets than fasciculata, therefore cytoplasm stains darker
Cells are smaller than in fasciculata
Cytoplasm often contains lipofuscin pigment
Secrete mainly weak androgens (mostly dehydroepiandrosterone)
Secretion controlled by ACTH
CORTEX BY EM:
Zona glomerulosa has unusual steroid-secreting cells because
they have mitochondria with shelf-like cristae (not tubular)
Zona fasciculata & zona reticularis cells have the 3 features
typical of steroid-secretors:
Extensive SER
Many lipid droplets in cytoplasm
Mitochondria with tubular cristae
Zona reticularis cells have more residual bodies (which contain
the lipofuscin)
ADRENAL MEDULLA
Composed mainly of chromaffin cells
Contains large veins that unite to form the adrenal vein
True postganglionic neurons are present but rare
Probably innervate vascular smooth muscle
MICROSCOPIC ANATOMY
MEDULLA RECEIVES A DUAL BLOOD SUPPLY:
Blood from cortical sinusoids (rich in glucocorticoids)
Blood from medullary arterioles that pass through cortex without
breaking up into sinusoids (low glucocorticoid concentration)
Glucocorticoids induce the synthesis of the enzyme PNMT
in chromaffin cells
PNMT catalyzes conversion of norepinephrine (NE) to
epinephrine (E)
Therefore chromaffin cells that receive blood from:
Cortical sinusoids (high glucocorticoid concentration) make E
Medullary arterioles (low glucocorticoids) make NE
CHROMAFFIN CELLS
Called chromaffin because they stain with chromium salts
Derived from neuroectoderm (neural crest)
Innervated by preganglionic sympathetic neurons
Are essentially modified postganglionic sympathetic neurons
that lack axons & dendrites
By EM contain many small, dark-staining secretory granules
containing either NE or E
NE-producing & E-producing chromaffin cells are distinguishable
by EM based on morphology of their secretory granules:
NE-producing cells have larger, darker secretory granules
that often contain an eccentrically located dense core
E-producing cells have less intensely staining granules
whose contents are more centered in the granule
FETAL ADRENAL
Has no well-defined medulla
Precursors of chromaffin cells are scattered in clusters
throughout the fetal gland
At first, the fetal cortex resembles zona fasciculata
Permanent cortex appears outside fetal cortex
At first resembles zona glomerulosa in cell arrangement
Fetal cortex regresses a few weeks after birth
Chromaffin cells coalesce to form the medulla
MICROSCOPIC ANATOMY
IV. CARTILAGE
Is classified as a specialized connective tissue
Is usually avascular
Provides support & allows rapid growth
Forms the fetal skeleton
Persists wherever great resiliency is needed, e.g., articular (joint)
surfaces, ear, Eustachian tube, nasal cartilages, larynx
CARTILAGE IS COMPOSED OF
Chondrocytes in lacunae
In growing cartilage the chondrocytes divide to form isogenous groups
Matrix
Perichondrium (absent in fibrocartilage & articular hyaline cartilage)
PERICHONDRIUM
Nutrients diffuse from blood, through perichondrium, into the matrix
Divided into 2 layers:
Fibrous layer is outermost
- contains fibroblasts, collagen fibers (mainly type I)
Chondrogenic layer is in contact with cartilage matrix
- contains stem cells that can differentiate into chondroblasts
- cells are called chondrocytes when completely
surrounded by matrix
Chondrogenic layer is only clearly identifiable by LM when
appositional growth is actively occurring (otherwise the
chondrogenic cells are flat like fibroblasts)
MATRIX
Territorial matrix (= capsular or pericellular matrix)
Immediately surrounds each lacuna
Interterritorial matrix = the remainder of the matrix
Staining affinity of the matrix:
Territorial matrix contains relatively more GAGs & proteoglycans
Interterritorial contains relatively more collagen
If GAGs have been preserved, territorial matrix is
more basophilic & more strongly PAS positive
If GAGs have been lost during tissue preparation, all
parts of matrix are eosinophilic due to collagen
MICROSCOPIC ANATOMY
Matrix contains:
Collagen
- type II in hyaline & elastic cartilage
- mainly type I in fibrocartilage
GAGs, proteoglycans, & proteoglycan aggregates
Smaller “adhesive” glycoproteins, e.g. chondronectin
(promotes adherence of chondrocytes to matrix
collagen)
Elastic fibers (in elastic cartilage only)
CHONDROCYTES
Defining characteristic: Are completely surrounded by matrix
Round to oval cells that often shrink during fixation
Produce most components of the matrix
Receive poor oxygen supply
Limits the thickness of a cartilage
Makes cartilage slow to heal if damaged
Often accumulate lipid droplets in cytoplasm as they age
CARTILAGE GROWS IN TWO WAYS:
INTERSTITIAL GROWTH
Defined as addition of new molecules to the matrix by
chondrocytes in the interior of the cartilage
Often involves mitosis of chondrocytes to form isogenous groups
New matrix is then laid down between cells, which gradually
pushes cells of isogenous group further apart
APPOSITIONAL GROWTH
Stem cells in chondrogenic layer of perichondrium
differentiate into chondroblasts and add new matrix
to the outer surface of the cartilage
3 TYPES OF CARTILAGE (HYALINE, ELASTIC & FIBROCARTILAGE)
CAN BE DISTINGUISHED BY:
Appearance of matrix (homogeneous & glassy vs. visible fibers)
Presence or absence of perichondrium
Location in body
MICROSCOPIC ANATOMY
HYALINE CARTILAGE
Most common type
Matrix looks homogeneous or glassy (= hyaline) because
collagen type II fibrils are so thin they are not visible by LM
Has a perichondrium (except for articular cartilage)
May calcify with age
Adult locations:
Articular cartilage
Costal cartilages (of ribs)
Most laryngeal cartilages
Tracheal rings & bronchi (as irregular cartilage plates)
Other locations:
Fetal skeleton
Epiphyseal plates
ELASTIC CARTILAGE:
More cellular than mature hyaline cartilage
Less likely to calcify
Matrix contains elastic fibers visible by LM as well as collagen
type II
Has a perichondrium
Found in locations such as (think of the letter E):
Auricle (pinna) of the ear
Cartilaginous part of external auditory canal
Wall of auditory (Eustachian) tubes
Epiglottis
Corniculate & cuneiform cartilages of larynx
FIBROCARTILAGE:
Interterritorial matrix is highly fibrous
Contains many thick collagen I fibers visible by LM
Territorial matrix is more homogeneous
Contains some type II collagen
Chondrocytes often form linear isogenous groups between fibers
Can be confused with fibroblasts in dense regular CT, but
chondrocytes are rounder, less flattened cells
No perichondrium
Found in:
Annulus fibrosus of the intervertebral disks
Symphysis pubis
Some bone-ligament or bone-tendon junctions
MICROSCOPIC ANATOMY
THE MATRIX DISTINGUISHES THE 3 TYPES OF CARTILAGE BY EM
Fibrocartilage contains bundles of banded collagen type I fibrils
Elastic cartilage contains elastic fibers
Hyaline cartilage contains only a fine feltwork of thin collagen
type II fibrils
V. BONE
FUNCTIONS OF BONES:
Support & protect fragile tissues & organs (e.g. brain, spinal cord)
Contain hematopoietic tissue in marrow cavities
Form system of levers and pulleys with muscles that makes
movement possible
Store calcium
BONE TISSUE VS. THE ORGANS CALLED BONES:
Bone tissue is a specialized connective tissue composed of:
Bone cells: Osteoprogenitor cells, osteoblasts, bone-lining cells,
osteocytes, osteoclasts
Bone matrix, which consists of:
Organic components: Collagen type I, GAGs, proteoglycans, &
glycoproteins such as osteonectin, osteocalcin & osteopontin
Inorganic components: Minerals, mainly calcium salts such as
hydroxyapatite
NOTE: Even "decalcified" bone tissue will usually still contain
some calcium salts that are visible in EMs as black crystals.
They help distinguish bone tissue from cartilage by EM
Bones, the organs contain:
Bone tissue
Connective tissue proper (in the periosteum)
Usually some cartilage (epiphyseal plates &/or articular cartilage)
Hematopoietic tissue (marrow cavity)
Adipose tissue (marrow cavity, especially in yellow marrow)
Nerve tissue
Smooth muscle (in blood vessel walls)
HOW TO DISTINGUISH BONE TISSUE VS. CARTILAGE
Bone tissue always has:
Canaliculi (best seen in ground bone preps rather than in
decalcified sections); cartilage never has canaliculi
MICROSCOPIC ANATOMY
Some bone tissue has:
Blood vessels in the matrix (compact bone only); rapidly
growing cartilage sometimes surrounds blood vessels
Lamellae (in lamellar bone)
Cartilage commonly has:
Isogenous groups, which bone never has
DECALCIFIED VS. GROUND BONE
Decalcified bone:
Most of the inorganic components are removed
Organic components (including cells) remain
Can be embedded, sectioned, & stained with
conventional histologic stains such as H&E
Ground bone:
Is mechanically ground down to make specimens so
thin that they are translucent
Organic components are los
Inorganic components remain
Usually stained with India ink, which fills empty spaces
(canaliculi, lacunae, Haversian canals)
4 TYPES OF BONE CELLS:
BONE CELL INTER-RELATIONSHIPS
MICROSCOPIC ANATOMY
Osteoprogenitor cells give rise to osteoblasts
Osteoblasts can become bone-lining cells if they become inactive
before being completely surrounded by bone matrix
Bone-lining cells can become osteoblasts again if they start laying
down bone matrix again
Osteoblasts become osteocytes once they are completely
surrounded by bone matrix
The origin of osteoprogenitor cells depends on the type of
ossification involved
In intramembranous ossification, osteoprogenitor cells
differentiate directly from mesenchymal cells
In endochondral ossification, mesenchymal cells first give rise
to chondrogenic cells (in the perichondrium), which
differentiate into osteoprogenitor cells once endochondral
ossification began
Osteoclasts come from a completely different cell lineage; they
differentiate from the stem cell (hematopoietic stem cell)
that also gives rise to all blood cell types
OSTEOPROGENITOR CELLS
Found in two locations:
Inner (osteogenic) layer of periosteum
Endosteum
Difficult to identify because they resemble the fibroblasts of the
periosteum and the bone-lining cells of the endosteum
OSTEOBLASTS
Are uninucleate cells
Cuboidal to columnar depending on their level of activity
Basophilic cytoplasm due to extensive RER
Found on any surface of bone (periosteum or endosteum) where
matrix is being actively deposited
May line up side by side so they resemble a simple epithelium
Communicate with each other & with osteocytes via gap junctions
Produce the organic components of bone matrix (osteoid)
Release matrix vesicles into the matrix
The alkaline phosphatase contained in matrix vesicles
is important for mineralization
When quiescent, osteoblasts become squamous cells called bonelining cells
MICROSCOPIC ANATOMY
OSTEOCYTES
Each occupies a space within bone matrix called a lacuna
Canaliculi (“little canals”) = tunnels that run through the matrix
& connect neighboring lacunae
Contain cytoplasmic processes from neighboring osteocytes
Gap junctions connect the processes
Osteocytes function to maintain bone matrix
Probably help maintain blood Ca++ levels by resorbing
matrix from a narrow zone surrounding the lacuna,
thus releasing Ca++ into the blood (= osteocytic
osteolysis)
OSTEOCLASTS
Large multinucleated cells (2-50 nuclei)
Derived from uninucleate cells that fuse, i.e., a true syncytium
Differentiate from the hematopoietic stem cell; share a common
precursor with monocytes (i.e., do not differentiate from
osteoprogenitor cells)
Acidophilic cytoplasm due to numerous lysosomes & mitochondria
Found on any surface of bone (periosteal or endosteal) where
bone resorption is occurring
They resorb bone matrix for modeling or remodeling purposes by
secreting:
- Lysosomal enzymes (e.g., collagenase) to digest organic matrix
- Acid (HCl) to solubilize inorganic components of bone matrix
Ruffled border = an area of plasma membrane with many long,
elaborate folds; is a region where bone resorption is occurring
Increases surface area for active transport of ions (e.g. H+)
and for endocytosis of matrix degradation fragments
The “clear zone” (sealing zone) forms a ring around the area
where the ruffled membrane is located
It seals the plasma membrane tightly to bone
It contains abundant actin filaments
Resorption produces a depression in the bone surface within the
sealing zone (= a resorption bay or Howship's lacuna)
PERIOSTEUM VS. ENDOSTEUM:
Periosteum covers outer surface of a bone except at the
articular surfaces
Has an outer fibrous layer and an inner osteogenic layer
MICROSCOPIC ANATOMY
Fibrous layer contains collagen fibers & fibroblasts
Osteogenic layer contains osteoprogenitor cells
- can also contain osteoblasts, bone-lining cells &
osteoclasts
Sharpey’s fibers = bundles of collagen fibers that anchor:
Periosteum to bone
Tendons, ligaments, or teeth to bone by penetrating
through the periosteum & into bone matrix
Endosteum lines most inner surfaces of bone
It lines Haversian canals, Volkmann’s canals, & the
marrow cavity (including inner surface of compact
bone & the outer surface of all trabeculae)
It DOES NOT line lacunae or canaliculi
Can include osteoprogenitor cells, osteoblasts, bonelining cells & osteoclasts
BONE TISSUE CAN BE CLASSIFIED IN TWO WAYS:
1. CANCELLOUS (SPONGY) VS. CORTICAL (COMPACT) BONE:
Describes the amount of bone tissue per unit volume
The distinction is visible macroscopically with the unaided eye
Cancellous (spongy) bone:
Has thin anastomosing trabeculae of bone surrounded by
interconnected spaces that are part of the marrow cavity
Has a “honey-comb” appearance
Trabeculae contain no blood vessels (are thin enough that
osteocytes within them can be nourished by diffusion
from vessels in the marrow cavity)
Cancellous bone is found in interior of bones, especially:
At epiphyses & metaphyses of long bones
In the diploë of flat bones
Cortical (compact) bone:
Has a more solid appearance with the naked eye; no trabeculae
Found on outer surface of all bones
Contains blood vessels that often run within canals (e.g.,
Haversian canals, Volkmann’s canals)
NOTE: No individual bone is entirely cortical or entirely cancellous.
All mature bones have cortical bone on their exterior & at least
some cancellous bone somewhere within their interior.
MICROSCOPIC ANATOMY
2. WOVEN VS. LAMELLAR BONE:
Describes whether the collagen fibers and lacunae are arranged
in an orderly fashion (lamellar) or a disorderly fashion (woven)
in the matrix
Woven bone
Characterized by random orientation of collagen fibers, creating an
irregular or “woven” appearance
Is more cellular than lamellar bone
Lacunae are distributed & oriented more randomly than in lamellar
bone
Formed before lamellar bone in embryonic development & in repair
of fractures
Laid down more rapidly than lamellar bone
Normally replaced by lamellar bone during remodeling
Less mineralized than lamellar bone
Can be cortical or cancellous
Lamellar bone
Characterized by layers (lamellae) of bone matrix
Collagen fibers within an individual lamella are oriented in the same
direction
Fibers in one lamella are oriented at an angle to those in the
neighboring lamellae (“plywood” arrangement for added strength)
Osteocytes lie in the plane between successive lamellae & hence
have an orderly distribution & orientation
Can be cortical or cancellous
LAMELLAR BONE IS FOUND IN AT LEAST 5 LOCATIONS:
1. Outer circumferential lamellae
These encircle the outer surface of the entire bone just deep to
the periosteum
2. Inner circumferential lamellae
Encircle the inner surface of compact bone just superficial to the
endosteum & the marrow cavity
May not be present in areas where cancellous bone lines the
marrow cavity (e.g., near metaphyses or epiphyses)
3. Concentric lamellae
Make up the osteons surrounding Haversian canals
4. Interstitial lamellae:
Remnants of old lamellae that were partially removed
by osteoclasts during remodeling
5. Trabeculae of mature cancellous bone
MICROSCOPIC ANATOMY
HAVERSIAN SYSTEMS (OSTEONS) INCLUDE:
Haversian canal (= central canal) is a channel lined by endosteum
Contains blood vessels & loose connective tissue
Runs roughly parallel to the long axis of a long bone
Osteocytes lie in lacunae that are layered between the lamellae
Canaliculi that connect lacunae
Cement lines that separate neighboring osteons
Represent the point of reversal during remodeling (i.e., the
point where osteoclasts stopped resorbing bone and
osteoblasts began depositing new bone)
VOLKMANN'S CANALS:
Endosteum-lined channels that interconnect Haversian canals
Carry blood vessels from periosteum and marrow cavity to
Haversian canals
Oriented transverse or oblique to the Haversian canals
Cut across the concentric lamellae of osteons
NOTE: Blood also enters bones through much larger arteries
than those in Volkmann’s canals. These are called nutrient
arteries. They pass through a nutrient foramen in the bone,
and then branch in the marrow cavity.
INTRAMEMBRANOUS VS. ENDOCHONDRAL OSSIFICATION:
Intramembranous ossification:
Bone forms directly in mesenchyme (no cartilaginous precursor)
Mesenchymal cells differentiate into osteoprogenitor cells &
then into osteoblasts
Osteoblasts lay down bone matrix to form many isolated spicules
Spicules gradually connect with one another to form trabeculae
Connective tissue surrounding this region condenses to form
periosteum
Trabeculae near the periosteum grow & fuse together
to form compact bone
Endochondral ossification of a long bone:
A hyaline cartilage model of the bone forms from
mesenchyme in the fetus
MICROSCOPIC ANATOMY
Primary center of ossification forms at midshaft
- chondrocytes at midshaft hypertrophy
- perichondrium at midshaft becomes a periosteum;
osteoblasts differentiate from it & lay down a
periosteal collar of bone
- chondrocyte lacunae coalesce, leaving thin irregular
spicules
- matrix of cartilage becomes calcified
- an osteogenic bud grows into the coalesced lacunae
- bud consists of blood vessels & osteoprogenitor
cells that adhere to the exterior of the vessels
- osteoblasts differentiate from osteoprogenitor cells
in the osteogenic bud
- osteoblasts lay down bone matrix on the spicules of
calcified cartilage, forming mixed spicules
NOTE: Areas of calcified cartilage in a spicule contain no
cells since the chondrocytes have already died, & few,
if any, lacunae since most have already coalesced to
form the space (marrow cavity) between spicules
Secondary centers of ossification form in each epiphysis
- not associated with a periosteal bone collar
An epiphyseal plate (growth plate) of hyaline cartilage
remains between the primary ossification center & each
secondary ossification center
Interstitial growth continues in the cartilage of the
epiphyseal plate, resulting in increase in length of the
bone
Bone forms mainly on diaphyseal side of growth plate,
replacing cartilage
When rate of ossification exceeds the rate of interstitial
growth of the epiphyseal cartilage, the epiphyseal plate
becomes completely replaced by bone (closure of the
epiphyses)
After epiphyseal closure, the bone can no longer grow in
length
Remodeling eventually removes the calcified cartilage in the
spicules & replaces woven bone with lamellar
MICROSCOPIC ANATOMY
EPIPHYSEAL PLATE:
You are responsible for identifying the following zones:
Zone of reserved cartilage (Resting zone):
- characterized by individual cells in randomly scattered
lacunae or by small isogenous groups (clusters)
Zone of proliferation:
- dividing chondrocytes line up in isogenous columns
Zone of hypertrophy:
- chondrocytes enlarge, accumulate glycogen, & die
Zone of calcification
- matrix becomes calcified as the chondrocytes die
- lacunae in each isogenous column coalesce, leaving only
thin strips of calcified cartilage matrix (i.e., the spicules)
Zone of ossification:
- osteoblasts lay down the organic matrix of bone
(eosinophilic) on the surface of calcified cartilage
spicules (more basophilic)
BONE GROWTH
Bone tissue grows only by appositional growth, i.e., by osteoblasts
adding new matrix to the periosteal or endosteal surface of
existing bone tissue
A bone (the organ) grows in width by appositional growth, i.e.
osteoblasts add new matrix to the periosteal surface
An immature long bone (the organ) grows in length by interstitial
growth of the cartilage in the epiphyseal plate
Osteoclasts resorb bone matrix in bone modeling & remodeling
Surface modeling = adding (via osteoblasts) or removing (via
osteoclasts) matrix in order to affect the overall shape of the bone
Examples:
Metaphyseal “waisting” (metaphyseal cut back)
- narrowing the former metaphysis down to match the diameter
of the diaphysis as the bone grows in length
- requires periosteal bone resorption and endosteal deposition
Diaphyseal drift
- maintaining the same diaphyseal diameter while
adjusting the position of the diaphysis in space
- usually done to accommodate changes in mechanical
load on the bone
MICROSCOPIC ANATOMY
- requires periosteal resorption coupled with endosteal
deposition on one side of the diaphysis, and
periosteal deposition coupled with endosteal
resorption on the other
Remodeling = a turnover process where an area of bone matrix
is removed and then new bone is laid down in the same
place without overall change in bone shape
An example is the conversion of woven compact bone
to lamellar compact bone
SYNOVIAL JOINTS
Hyaline cartilage covers the articular surfaces of the bones
Articular cartilage has no perichondrium & is not covered by the
synovial membrane
The rest of the synovial cavity is covered by the synovial
membrane, forming the synovial fold
Synovial fold is one of the few body surfaces not covered
by an epithelium
Synovial membrane is composed of 2 types of non-epithelial cells:
Type A synoviocytes (phagocytic)
Type B synoviocytes (fibroblastic), which appear to
make some components of synovial fluid
IMPORTANT INFORMATION FOR ANSWERING
PRACTICAL EXAM QUESTIONS
I. “Identify” vs. “classify”
You will undoubtedly be asked to classify some tissue types in this exam. Recall that:
To identify means to give the unique name of that structure
To classify means to place the structure into a grouping that
includes other similar structures.
To classify muscle tissue means to say whether it is:
Skeletal muscle
Smooth muscle
Cardiac muscle
To classify cartilage means to say whether it is:
Hyaline cartilage
Elastic cartilage
Fibrocartilage
MICROSCOPIC ANATOMY
Bone tissue can be classified in at least two ways:
Woven vs. lamellar
Compact vs. cancellous
NOTE: We may use a multiple-choice format and ask you to decide if a
particular tissue is:
Woven compact bone
Woven cancellous bone
Lamellar compact bone
Lamellar cancellous bone
Examples of classify vs. identify:
If we point to the cartilage on the surface of a bone in a synovial joint and say:
Classify this tissue:
Answer = hyaline cartilage
Identify this tissue:
Answer = articular cartilage
If we point to cartilage between the epiphysis & diaphysis of a growing long bone & say:
Classify this tissue:
Answer = hyaline cartilage
Identify this tissue:
Answer = epiphyseal plate
II. Always be as specific as possible
If we point to the region of the adrenal just beneath the capsule and ask you to identify the
layer, “adrenal cortex” is not sufficiently specific. “Zona glomerulosa” would be correct.
III. As always, answer the question that is asked
IV. Use the correct terminology. We do not take off for spelling, but we also do not accept
answers that are way out in left field. For example, if we asked you to identify canaliculi,
we would not accept “cannelloni”, “cannoli” or “canola” (all answers that we have
received in the past) as valid answers. Take the time to learn the correct terms.