1.

Neuron(perikaryon,Nissl bodies,cytoskeleton)
Most neurons have three main parts: cell body (also called the perikaryon or soma),
which contains the nucleus and most of the cell’s organelles and serves as the
synthetic or trophic center for the entire neuron. A typical neuron has an unusually
large, euchromatic nucleus with a prominent nucleolus, indicating intense synthetic
activity. Cytoplasm of perikarya often contains numerous free polyribosomes and
highly developed RER, indicating active production of both cytoskeletal proteins and
proteins for transport and secretion. Histologically these regions with concentrated
RER and other polysomes are basophilic and are distinguished as chromatophilic
substance (or Nissl substance, Nissl bodies). The amount of this material varies with
the type and functional state of the neuron and is particularly abundant in large
nerve cells such as motor neurons.The Golgi apparatus is located only in the cell
body, but mitochondria can be found throughout the cell and are usually abundant
in the axon terminals. In both perikarya and processes microtubules, actin filaments
and intermediate filaments are abundant, with the latter formed by unique protein
subunits and called neurofilaments in this cell type.Some nerve cell bodies also
contain inclusions of pigmented material, such as lipofuscin, consisting of residual
bodies left from lysosomal digestion.
Nissl bodies are Subcellular structures found in nerve cell bodies and DENDRITES.
They consist of granular endoplasmic reticulum (RER) and RIBOSOMES. functions of
Nissl bodies are thought to be the same as those of the rough endoplasmic reticulum
in general, primarily the synthesis and segregation of proteins.

2. Dendrities and axons

The dendrites, which are the numerous elongated processes extending from the
perikaryon and specialized to receive stimuli from other neurons at synapses.Unlike
axons, which maintain a nearly constant diameter, dendrites become much thinner
as they branch, with cytoskeletal elements predominating in these distal regions. In
the CNS most synapses on dendrites occur on dendritic spines,which are dynamic
membrane protrusions along the small dendritic branches, visualized with silver
staining and studied by confocal or electron microscopy. Dendritic spines serve as
the initial processing sites for synaptic signals.Changes in dendritic spines are of key
importance in the constant changes of the neural plasticity that occurs during
embryonic brain development and underlies adaptation, learning, and memory
postnatally.
The axon (Gr. axon, axis), which is a single long processending at synapses
specialized to generate and conduct nerve impulses to other cells (eg, nerve, muscle,
and gland cells). Axons may also receive information from other neurons,
information that mainly modifies the transmission of action potentials to those
neurons.The plasma membrane of the axon is often called the axolemma and its
contents are known as axoplasm. Axons originate from a pyramid-shaped region of
the perikaryon called the axon hillock, just beyond which the axolemma has
concentrated ion channels that generate the action potential. Axons of interneurons
and some motor neurons also have major branches called collaterals that end at
smaller branches with synapses influencing the activity of many other neurons. Each
small axonal branch ends with a dilation called a terminal bouton (Fr. bouton, button)
that contacts another neuron or non-nerve cell at a synapse to initiate an impulse in
that cell. Axoplasm contains mitochondria, microtubules, neurofilaments, and
transport vesicles, but very few polyribosomes or cisternae of RER, features that
emphasize the dependence of axoplasm on the perikaryon. If an axon is severed
from its cell body, its distal part quickly degenerates and undergoes phagocytosis.
Organelles and macromolecules synthesized in the cell body move by anterograde
transport along axonal microtubules via kinesin from the perikaryon to the synaptic
terminals. Retrograde transport in the opposite direction along microtubules via
dynein carries certain other macromolecules, such as material taken up by
endocytosis (including viruses and toxins), from the periphery to the cell body.
T(თაუ)-პროტეინი - მონაწილეობს რეტრო და ანტეროგრადულ ტრანსპორტში.

3. Types of nerve cells

Neurons can be classified according to the number of processes extending from the
cell body: Multipolar neurons, each with one axon and two or more dendrites, are
the most common. Bipolar neurons, with one dendrite and one axon, comprise the
sensory neurons of the retina, the olfactory epithelium, and the inner ear. Unipolar
or pseudounipolar neurons, which include all other sensory neurons, each have a
single process that bifurcates close to the perikaryon, with the longer branch
extending to a peripheral ending and the other toward the CNS. Anaxonic neurons,
with many dendrites but no true axon, do not produce action potentials, but
regulate electrical changes of adjacent CNS neurons.

4. Multipolar and bipolar neurons

5. Neuromediator types
Most synapses act by releasing neurotransmitters, which are usually small molecules
that bind specific receptor proteins to either open or close ion channels or initiate
second messenger cascades.
ACETYLCHOLINE (ACh) - Chemical structure significantly different from that of other
neurotransmitters; active in CNS and in both somatic and autonomic parts of PNS;
binds to ACh receptors (cholinergic receptors) in PNS to open ion channels in
postsynaptic membrane and stimulate muscle contraction.
AMINO ACIDS: Glutamate - Excites activity in neurons to promote cognitive function
in the brain (learning and memory); most common neurotransmitter in the brain;
opens Na+ channels. Gamma-aminobutyric acid (GABA) - Synthesized from
glutamate; primary inhibitory neurotransmitter in the brain; also influences muscle
tone; opens or closes various ion channels. Glycine - Inhibits activity between
neurons in the CNS, including retina; opens Cl– channels.
MONOAMINES: Serotonin or 5-hydroxytryptamine (5-HT) - Has various functions in
the brain related to sleep, appetite, cognition (learning, memory), and mood;
modulates actions of other neurotransmitters. Catecholamines - A distinct group of
monoamines. Dopamine - Produces inhibitory activity in the brain; important roles in
cognition (learning, memory), motivation, behavior, and mood; opens K+ channels,
closes Ca2+ channels. Norepinephrine (noradrenaline) - Neurotransmitter of PNS
(sympathetic division of autonomic nervous system) and specific CNS regions
Epinephrine (adrenaline) - Has various effects in the CNS, especially the spinal cord,
thalamus, and hypothalamus.
NEUROPEPTIDES: Enkephalin - Helps regulate response to noxious and potentially
harmful stimuli. Neuropeptide Y -Involved in memory regulation and energy balance
(increased food intake and decreased physical activity). Somatostatin - Inhibits
activities of neurons in specific brain areas. Substance P -Assists with pain
information transmission into the brain. Cholecystokinin (CCK) - Stimulates neurons
in the brain to help mediate satiation (fullness) and repress hunger. Beta-endorphin -
Prevents release of pain signals from neurons and fosters a feeling of well-being.
Neurotensin - Helps control and moderate the effects of dopamine.
Adenosine - Also part of a nucleotide, inhibits activities in certain CNS neurons.
Nitric oxide - Involved in learning and memory; relaxes muscle in the digestive tract;
important for relaxation of smooth muscle in blood vessels (vasodilation).

6. Synapses
Synapses are sites where nerve impulses are transmitted from one neuron to
another, or from neurons and other effector cells.Synapses convert an electrical
signal (nerve impulse) from the presynaptic cell into a chemical signal that affects
the postsynaptic cell. synapse has the following components: The presynaptic axon
terminal (terminal bouton) contains mitochondria and numerous synaptic vesicles
from which neurotransmitter is released by exocytosis. The postsynaptic cell
membrane contains receptors for the neurotransmitter, and ion channels or other
mechanisms to initiate a new impulse. A 20- to 30-nm-wide intercellular space called
the synaptic cleft separates these presynaptic and postsynaptic membranes.
At the presynaptic region the nerve impulse briefly opens calcium channels,
promoting a Ca2+ influx that triggers neurotransmitter release by exocytosis or
similar mechanisms. Immediately the released neurotransmitter molecules diffuse
across the synaptic cleft and bind receptors at the postsynaptic region. This produces
either an excitatory or an inhibitory effect at the postsynaptic membrane, as follows:
Neurotransmitters from excitatory synapses cause postsynaptic Na+ channels to
open, and the resulting Na+ influx initiates a depolarization wave in the postsynaptic
neuron or effector cell as just described. At inhibitory synapses neurotransmitters
open Cl– or other anion channels, causing influx of anions and hyperpolarization of
the postsynaptic cell, making its membrane potential more negative and more
resistant to depolarization.
Branched axon terminals usually associate with and transmit a nerve impulse to
another neuron’s cell body (or soma) or a dendritic spine. These types of
connections are termed an axosomatic synapse and an axodendritic synapse,
respectively. Less frequently, an axon terminal forms a synapse with an axon
terminal of another neuron; such an axoaxonic synapse functions to modulate
synaptic activity in the other two types.
Levels of neurotransmitters in the synaptic cleft and available for binding
postsynaptic receptors are normally regulated by several local mechanisms. Selective
serotonin reuptake inhibitors (SSRIs), a widely used class of drugs for treatment of
depression and anxiety disorders, were designed to augment levels of this
neurotransmitter at the postsynaptic membrane of serotonergic CNS synapses by
specifically inhibiting its reuptake at the presynaptic membrane.

7. Neuroglia - general considerations

Glial cells support neuronal survival and activities, and are 10 times more abundant
than neurons in the mammalian brain. Like neurons most glial cells develop from
progenitor cells of the embryonic neural plate. In the CNS glial cells surround both
the neuronal cell bodies, which are often larger than the glial cells, and the processes
of axons and dendrites occupying the spaces between neurons. Except around the
larger blood vessels, the CNS has only a very small amount of connective tissue and
collagen. Glial cells substitute for cells of connective tissue in some respects,
supporting neurons and creating immediately around those cells micro
environments that are optimal for neuronal activity. fibrous intercellular
network of CNS tissue superficially resembles collagen by light microscopy, but is
actually the network of fine cellular processes emerging from neurons and glial cells.
Such processes are collectively called the neuropil.

8. Astorcytes
unique to the CNS astrocytes have a large number of long radiating, branching
processes. Proximal regions of the astrocytic processes are reinforced with bundles
of intermediate filaments made of glial fibrillary acid protein (GFAP), which serves as
a unique marker for this glial cell. Astrocytes originate from progenitor cells in the
embryonic neural tube and are by far the most numerous glial cells of the brain, as
well as the most diverse structurally and functionally. ქმნიან ნეირონის ზრდის
ფაქტორს(მეხსიერების ცილა). There are 2 types: Fibrous(in white matter) has
long axons(spider), ამოავსებს Wirschow-robbins სივრცეს; Protoplasmic(in grey
matter) mossy fibers, longer processes.
Functions attributed to astrocytes of various CNS regions include the following:
 Extending processes that associate with or cover synapses, affecting the
formation, function, and plasticity of these structures.
 Regulating the extracellular ionic concentrations around neurons, with
particular importance in buffering extracellular K+ levels.
 Guiding and physically supporting movements and locations of differentiating
neurons during CNS development.
 Extending fibrous processes with expanded perivascular feet that cover capillary
endothelial cells and modulate blood flow and help move nutrients, wastes,
and other metabolites between neurons and capillaries.
 Forming a barrier layer of expanded protoplasmic processes, called the glial
limiting membrane, which lines the meninges at the external CNS surface.
 Filling tissue defects after CNS injury by proliferation to form an astrocytic scar.

Markers of Astrocytes: Laminin, Fibronectin, S100(protein), Filopidin.

Alzheimer disease, a common type of dementia in the elderly, affects both neuronal
perikarya and synapses within the cerebrum. Functional defects are due to
neurofibrillary tangles, which are accumulations of tau protein associated
with microtubules of the neuronal perikaryon and axon hillock regions, and neuritic
plaques, which are dense aggregates of β-amyloid protein that form around the
outside of these neuronal regions.

9. Olygodendrocytes
Oligodendrocytes extend many processes, each of which becomes sheetlike and
wraps repeatedly around a portion of a nearby CNS axon. During this wrapping most
cytoplasm gradually moves out of the growing extension, leaving multiple
compacted layers of cell membrane collectively termed myelin. An axon’s full length
is covered by the action of many oligodendrocytes. The resulting myelin sheath
electrically insulates the axon and facilitates rapid transmission of nerve impulses.
Originates from neural tube. Only in CNS. Can be injured in Multiple sclerosis,
progressive multifocal leukoencepalopathy(PML), Leukodystrophies.
Prolipidin is a marker for olygodendrocytes. There are 2 types of olygodendrocytes:
Gray(satelite) main function neurophagia; Interfascicular in white matter.

10. Schwann cells

Schwann cells sometimes called neurolemmocytes, are found only in the PNS and
differentiate from precursors in the neural crest. Schwann cells are the counterparts
to oligodendrocytes of the CNS, having trophic interactions with axons and most
importantly forming their myelin sheathes. However unlike an oligodendrocyte, a
Schwann cell forms myelin around a portion of only one axon.
Markers for schwann cells: P0+P2(MAP-major acidic protein); S100B; Connexin32

11. Myelin sheath formation

მეცხრეში წერია

12. Microglia
Less numerous than oligodendrocytes or astrocytes but nearly as common as
neurons in some CNS regions, microglia are small cells with actively mobile processes
evenly distributed throughout gray and white matter. Unlike other glial cells
microglia migrate, with their processes scanning the neuropil and removing
damaged or effete synapses or other fibrous components. Microglial cells also
constitute the major mechanism of immune defense in the CNS,removing any
microbial invaders and secreting a number of immunoregulatory cytokines. MIcroglia
can be originate from: Red bone marrow; Neuroectoderm; Mixture of previous two.
მიკროგლია შეიძლება იყოს პერივენტრიკულარული ან პერიკაპილარული.
Activation in response to tissue damage releases inflammatory mediators(nitric
oxide and glutamate). NOT discernible by Nissl stain. მრავლდება ასტროციტების
მიერ გამოყოფილი ზრდის ფაქტორის ხარჯზე.
Markers are: IL-3 and MHC2
In multiple sclerosis (MS) the myelin sheaths surrounding axons are damaged by an
autoimmune mechanism that interferes with the activity of the affected neurons and
produces various neurologic problems. T lymphocytes and microglia, which
phagocytose and degrade myelin debris,play major roles in progression of this
disease. In MS, destructive actions of these cells exceed the capacity of
oligodendrocytes to produce myelin and repair the myelin sheaths.

13. Node of Ranvier, Schmidt-Lanterman’s cleft

Membranes of Schwann cells have a higher proportion of lipids than do other cell
membranes, and the myelin sheath serves to insulate axons and maintain a constant
ionic microenvironment most suitable for action potentials. Between adjacent
Schwann cells on an axon the myelin sheath shows small nodes of Ranvier (or nodal
gaps),where the axon is only partially covered by interdigitating Schwann cell
processes. At these nodes the axolemma is exposed to ions in the interstitial fluid
and has a much higher concentration of voltage-gated Na+ channels,which renew
the action potential and produce saltatory conduction (L. saltare, to jump) of nerve
impulses, their rapid movement from node to node. The length of axon ensheathed
by one Schwann cell, the internodal segment, varies directly with axonal diameter
and ranges from 300 to 1500 μm.
a thick electron-dense axonal covering in which the concentric membrane layers may
be visible. The prominent electron-dense layers visible ultrastructurally
in the sheath, the major dense lines, represent the fused, protein-rich cytoplasmic
surfaces of the Schwann cell membrane. Along the myelin sheath, these surfaces
periodically separate slightly to allow transient movement of cytoplasm for
membrane maintenance; at these myelin clefts (or Schmidt Lanterman clefts) the
major dense lines temporarily disappear. Faintly seen ultrastructurally in the light
staining layers are the intraperiod lines that represent the apposed outer bilayers of
the Schwann cell membrane.

14. BBB
The blood-brain barrier (BBB) is a functional barrier that allows much tighter control
than that in most tissues over the passage of substances moving from blood into the
CNS tissue. The main structural component of the BBB is the capillary endothelium,
in which the cells are tightly sealed together with well-developed occluding junctions,
with little or no transcytosis activity, and surrounded by the basement membrane.
The limiting layer of perivascular astrocytic feet that envelops the basement
membrane of capillaries in most CNS regions contributes to the BBB and further
regulates passage of molecules and ions from blood to brain. The BBB protects
neurons and glia from bacterial toxins, infectious agents, and other exogenous
substances, and helps maintain the stable composition and constant balance of ions
in the interstitial fluid required for normal neuronal function. The BBB is not present
in regions of the hypothalamus where plasma components are monitored, in the
posterior pituitary which releases hormones, or in the choroid plexus where CSF
is produced.

15. CNS - white matter, gray matter, spinal cord

The major structures comprising the CNS are the cerebrum, cerebellum, and spinal
cord. The CNS is completely covered by connective tissue layers, the meninges, but
CNS tissue contains very little collagen or similar material, making it relatively soft
and easily damaged by injuries affecting the protective skull or vertebral bones..
Many regions show organized areas of white matter and gray matter, differences
caused by the differential distribution of lipid-rich myelin. The main components of
white matter are myelinated axons, often grouped together as tracts, and the
myelin-producing oligodendrocytes. Astrocytes and microglia are also present, but
very few neuronal cell bodies. Gray matter contains abundant neuronal cell bodies,
dendrites, astrocytes, and microglial cells, and is where most synapses occur. Gray
matter makes up the thick cortex or surface layer of both the cerebrum and the
cerebellum; most white matter is found in deeper regions. Deep within the brain are
localized, variously shaped darker areas called the cerebral nuclei, each containing
large numbers of aggregated neuronal cell bodies. Neurons of the cerebral cortex
function in the integration of sensory information and the initiation of voluntary
motor responses. The sharply folded cerebellar cortex coordinates muscular activity
throughout the body and is organized with 6 layers:
 Molecular(plexiform) - dense network of tangentially oriented nerve fibers. has
much neuropil and scattered neuronal cell bodies.
 External granular layer - small pyramidal and stellate cells
 External pyramidal layer - cell body size grows from superficial to deeper
borders
 Internal granular - closely packed stellate cells, horizontally arranged fibers
called external band of Baillarger
 Ganglionic(internal pyramidal) - horizontally arranged fibers form inner band of
Baillarger, მარტენსის უჯრედები მხოლოდ occipital cerebral cortexში.
 Multiform - layer of polymorphic cells, pyramidal and Martinotti cells.

Great pyramidal cells are called Bretz cells(in motor precentral gyrus of frontal lobe).
Horizontal cells of Cajal - small, fusiform cells in most superficial layer.
Purkinje cells - large golgy type1 neurons, flisk shaped, 1 layerd, covered by dendritic
spines, only in cerebellum Bergman’s glia. These are conspicuous even in H&E-
stained sections, and their dendrites extend throughout the molecular layer as a
branching basket of nerve fibers.
In cross sections of the spinal cord, the white matter is peripheral and the gray
matter forms a deeper, H-shaped mass. The two anterior projections of this gray
matter, the anterior horns, contain cell bodies of very large motor neurons whose
axons make up the ventral roots of spinal nerves. The two posterior horns contain
interneurons which receive sensory fibers from neurons in the spinal (dorsal root)
ganglia. Near the middle of the cord the gray matter surrounds a small central canal,
which develops from the lumen of the neural tube, is continuous with the ventricles
of the brain, is lined by ependymal cells, and contains CSF.

16. Cerebellum
The cerebellum is situated in the posterior cranial fossa and is covered superiorly by
the tentorium cerebelli. It ls the largest part of the hindbrain and Iles posterior to
the fourth ventricle, the pons, and the medulla oblongata. The cerebellum is
somewhat ovoid in shape and constricted in its median part. It consists of two
cerebellar hemisphere joined by a narrow median vermls. The cerebellum is
connected to the posterior aspect of the brainstem by three symmetrical bundles of
nerve fibers called the superior, middle, and Inferior cerebellar peduncles. The
cerebellar cortex can be regarded as a large sheet with folds lying In the coronal or
transverse plane. Each fold or follum contains a core of white matter covered
superficially by gray matter. The gray matter of the cortex throughout Its extent
has a uniform structure. It may be devided into three layers: (1) an external layer,
the molecular layer contains two types of neurons: the outer stellate cells and the
inner basket cells.Neurogllal cells are found between these structures. (2) a middle
layer, the purkinje cell layer; and (3) an internal layer, the granular layer.

17. Dura matter

The thick external dura mater consists of dense irregular connective tissue organized
as an outer periosteal layer continuous with the periosteum of the skull and an inner
meningeal layer. These two layers are usually fused, but along the superior sagittal
surface and other specific areas around the brain they separate to form the blood-
filled dural venous sinuses. Around the spinal cord the dura mater is separated from
the periosteum of the vertebrae by the epidural space, which contains a plexus of
thinwalled veins and loose connective tissue. The dura mater may be separated from
the arachnoid by formation of a thin subdural space.

18. Arachnoid anf CSF circulation

The arachnoid has two components: (1) a sheet of connective tissue in contact with
the dura mater and (2) a system of loosely arranged trabeculae composed of
collagen and fibroblasts, continuous with the underlying pia mater layer.
Surrounding these trabeculae is a large, sponge-like cavity, the subarachnoid space,
filled with CSF. This fluid-filled space helps cushion and protect the CNS from minor
trauma. The subarachnoid space communicates with the ventricles of the brain
where the CSF is produced. The connective tissue of the arachnoid is said to be
avascular because it lacks nutritive capillaries, but larger blood vessels run through it.
Because the arachnoid has fewer trabeculae in the spinal cord, it can be more
clearly distinguished from the pia mater in that area. The arachnoid and the pia
mater are intimately associated and are often considered a single membrane called
the pia-arachnoid. In some areas, the arachnoid penetrates the dura mater and
protrudes into blood-filled dural venous sinuses located there . These CSF-filled
protrusions, which are covered by the vascular endothelial cells lining the sinuses,
are called arachnoid villi and function as sites for absorption of CSF into the blood of
the venous sinuses.

19. Pia Matter

The innermost pia mater consists of flattened, mesenchymally derived cells closely
applied to the entire surface of the CNS tissue. The pia does not directly contact
nerve cells or fibers, being separated from the neural elements by the very thin
superficial layer of astrocytic processes (the glial limiting membrane, or glia limitans),
which adheres firmly to the pia mater. Together, the pia mater and the layer of
astrocytic end feet form a physical barrier separating CNS tissue from CSF in the
subarachnoid space. Blood vessels penetrate CNS tissue through long perivascular
spaces covered by pia mater, although the pia disappears when the blood vessels
branch to form the small capillaries. However, these capillaries remain completely
covered by the perivascular layer of astrocytic processes.

20. Choroid plexus

The choroid plexus consists of highly vascular tissue, elaborately folded and
projecting into the large ventricles of the brain. It is found in the roofs of the third
and fourth ventricles and in parts of the two lateral ventricular walls, all regions in
which the ependymal lining directly contacts the pia mater. Each villus of the choroid
plexus contains a thin layer of well-vascularized pia mater covered by cuboidal
ependymal cells. The function of the choroid plexus is to remove water from blood
and release it as the CSF. CSF is clear, contains Na+, K+, and Cl– ions but very little
protein, and its only cells are normally very sparse lymphocytes. It is produced
continuously and it completely fills the ventricles, the central canal of the spinal cord,
the subarachnoid and perivascular spaces. It provides the ions required for CNS
neuronal activity and in the arachnoid serves to help absorb mechanical shocks.
Arachnoid villi provide the main pathway for absorption of CSF back into the venous
circulation. There are very few lymphatic vessels in CNS tissue.
A decrease in the absorption of CSF or a blockage of outflow from the ventricles
during fetal or postnatal development results in the condition known as
hydrocephalus, which promotes a progressive enlargement of the head followed by
mental impairment.

21. CSF

22. Nerve fibers

The main components of the peripheral nervous system (PNS) are the nerves,
ganglia, and nerve endings. Peripheral nerves are bundles of nerve fibers (axons)
individually surrounded by Schwann cells and connective tissue. Nerves are
analogous to tracts in the CNS, containing axons enclosed within sheaths of glial cells
specialized to facilitate axonal function. In peripheral nerves, axons are sheathed by
Schwann cells or neurolemmocytes. The sheath may or may not form myelin around
the axons, depending on their diameter.

23. Myelinated and unmyelinated fibers

As axons of large diameter grow in the PNS, they are engulfed along their length by a
series of differentiating neurolemmocytes and become myelinated nerve fibers. The
plasma membrane of each covering Schwann cell fuses with itself at an area termed
the mesaxon and a wide, flattened process of the cell continues to extend itself,
moving circumferentially around the axon many times. The multiple layers of
Schwann cell membrane unite as a thick myelin sheath. Composed mainly of lipid
bilayers and membrane proteins, myelin is a large lipoprotein complex that, like cell
membranes, is partly removed by standard histologic procedures. Unlike
oligodendrocytes of the CNS, a Schwann cell forms myelin around only a portion of
one axon. Along the myelin sheath, these surfaces periodically separate slightly to
allow transient movement of cytoplasm for membrane maintenance; at these myelin
clefts (or SchmidtLanterman clefts) the major dense lines temporarily disappear.
Faintly seen ultrastructurally in the light staining layers are the intraperiod lines that
represent the apposed outer bilayers of the Schwann cell membrane.
Membranes of Schwann cells have a higher proportion of lipids than do other cell
membranes, and the myelin sheath serves to insulate axons and maintain a constant
ionic microenvironment most suitable for action potentials. Between adjacent
Schwann cells on an axon the myelin sheath shows small nodes of Ranvier (or nodal
gap), where the axon is only partially covered by interdigitating Schwann cell
processes. At these nodes the axolemma is exposed to ions in the interstitial fluid
and has a much higher concentration of voltage-gated Na+ channels, which renew
the action potential and produce saltatory conduction of nerve impulses, their rapid
movement from node to node. The length of axon ensheathed by one Schwann cell,
the internodal segment, varies directly with axonal diameter and ranges from 300 to
1500 μm.
Unlike the CNS where many short axons are not myelinated at all but course among
other neuronal and astrocytic processes, the smallest diameter axons of peripheral
nerves are still enveloped within simple folds of Schwann cells. These very small
unmyelinated fibers do not however undergo multiple wrapping to form a myelin
sheath. In unmyelinated nerves each Schwann cell can enclose portions of many
axons with small diameters. Without the thick myelin sheath, nodes of Ranvier are
not seen along unmyelinated nerve fibers. Moreover, these small-diameter axons
have evenly distributed voltage-gated ion channels; their impulse conduction is not
saltatory and is much slower than that of myelinated axons.

24. Connective tissue sheets

Axons and Schwann cells are enclosed within layers of connective tissue.
Immediately around the external lamina of the Schwann cells is a thin layer called
the endoneurium, consisting of reticular fibers, scattered fibroblasts, and capillaries.
Groups of axons with Schwann cells and endoneurium are bundled together as
fascicles by a sleeve of perineurium, containing flat fibrocytes with their edges
sealed together by tight junctions. From two to six layers of these unique connective
tissue cells regulate diffusion into the fascicle and make up the blood-nerve
barrier which helps maintain the fibers’ microenvironment. Externally, peripheral
nerves have a dense, irregular fibrous coat called the epineurium, which extends
deeply to fill the space between fascicles. Very small nerves consist of one fascicle.
Small nerves can be found in sections of many organs and often show a winding
disposition in connective tissue.

25. Ganglia(sensory, autonomic ganglia)

Ganglia are typically ovoid structures containing neuronal cell bodies and their
surrounding glial satellite cells supported by delicate connective tissue and
surrounded by a denser capsule. Because they serve as relay stations to transmit
nerve impulses, at least one nerve enters and another exits from each ganglion. The
direction of the nerve impulse determines whether the ganglion will be a sensory or
an autonomic ganglion.
Sensory ganglia receive afferent impulses that go to the CNS. Sensory ganglia are
associated with both cranial nerves (cranial ganglia) and the dorsal roots of the
spinal nerves (spinal ganglia). The large neuronal cell bodies of ganglia are associated
with thin, sheetlike extensions of small glial satellite cells. Sensory ganglia are
supported by a distinct connective tissue capsule and an internal framework
continuous with the connective tissue layers of the nerves. The neurons of these
ganglia are pseudounipolar and relay information from the ganglion’s nerve endings
to the gray matter of the spinal cord via synapses with local neurons.
Autonomic nerves effect the activity of smooth muscle, the secretion of some glands,
heart rate, and many other involuntary activities by which the body maintains a
constant internal environment (homeostasis). Autonomic ganglia are small bulbous
dilations in autonomic nerves, usually with multipolar neurons. Some are located
within certain organs, especially in the walls of the digestive tract, where they
constitute the intramural ganglia. The capsules of these ganglia may be poorly
defined among the local connective tissue. Autonomic nerves use two neuron
circuits. The first neuron of the chain, with the preganglionic fiber, is located in the
CNS. Its axon forms a synapse with postganglionic fibers of the second multipolar
neuron in the chain located in a peripheral ganglion system. The chemical mediator
present in the synaptic vesicles of all preganglionic axons is acetylcholine.

26. Autonomic nervous system

autonomic nerves make up the autonomic nervous system. This has two parts: the
sympathetic and the parasympathetic divisions. Neuronal cell bodies of
preganglionic sympathetic nerves are located in the thoracic and lumbar segments of
the spinal cord and those of the parasympathetic division are in the medulla and
midbrain and in the sacral portion of the spinal cord. Sympathetic second neurons
are located in small ganglia along the vertebral column, while second neurons of the
parasympathetic series are found in very small ganglia always located near or within
the effector organs, for example in the walls of the stomach and intestines.
Parasympathetic ganglia may lack distinct capsules altogether, perikarya and
associated satellite cells simply forming a loosely organized plexus within the
surrounding connective tissue.

27. Merkel’s cell

Merkel cells, or epithelial tactile cells,(დიფუზური ნეირო ენდოკრინული
სისტემის ნაწილია) are low-threshold mechanoreceptors essential for sensing
gentle touch. They are abundant in highly sensitive skin like that of fingertips and at
the bases of some hair follicles. Joined by desmosomes to keratinocytes of the basal
epidermal layer, present in both thick and thin skin Merkel cells resemble the
surrounding keratinocytes, with which they share a stem cell origin, but contain few,
if any, melanosomes. Instead, they are characterized by small, Golgi-derived dense-
core granules concentrated in areas near the basolateral surface where the cells
have synaptic contacts with the expanded terminal discs of unmyelinated afferent
fibers penetrating the basal lamina. Light touch to the skin initiates release of
neurotransmitters and sensation from that location.The nucleus is lobed, and the
cytoplasm is somewhat denser than that of melanocytes and Langerhans’ cells. They
may contain some melanosomes in their cytoplasm, but they are best characterized
by the presence of 80-nm dense-cored neuro secretory granules that resemble those
found in the adrenal medulla and carotid body Merkel’s cells are closely associated
with the expanded terminal bulb of aferent myelinated nerve fibers.
Merkel cell carcinoma (MCC) is a rare but highly aggressive type of skin cancer that
develops when Merkel cells undergo uncontrolled proliferation. It starts most often in
areas of skin exposed to the sun, such as the head, neck, and upper and lower limbs.
MCC tends to grow quickly and to metastasize via lymph vessels at an early stage.

28. Vater-Pachinian corpuscle

Lamellated (pacinian) corpuscles are large oval structures, approximately 0.5 mm by
1 mm, found deep in the reticular dermis and hypodermis, with an outer capsule
and 15-50 thin, concentric lamellae of flattened Schwann cells and collagen
surrounding a highly branched, unmyelinated axon. Lamellated corpuscles are
specialized for sensing coarse touch, pressure (sustained touch), and vibrations, with
distortion of the capsule amplifying a mechanical stimulus to the axonal core where
an impulse is initiated. Pacinian corpuscles are also found in the connective tissue of
organs located deep in the body, including the wall of the rectum and urinary
bladder, where they also produce the sensation of pressure when the surrounding
tissue is distorted.

29. Meissnerian corpuscle

Meissner corpuscles are elliptical structures, 30-75 μm by 50-150 μm, consisting of
sensory axons winding among flattened Schwann cells arranged perpendicular
to the epidermis in the dermal papillae. They initiate impulses when light-touch or
lowfrequency stimuli against skin temporarily deform their shape. They are
numerous in the fingertips, palms, and soles but decline slowly in number during
aging after puberty.

30. Epidermis organization

The epidermis consists mainly of a stratified squamous keratinized epithelium
composed of cells called keratinocytes. There are also three much less abundant
epidermal cell types: pigment-producing melanocytes, antigen-presenting
Langerhans cells, and tactile epithelial cells called Merkel cells. Epidermis forms
major distinction between thick skin, found on the palms and soles, and thin skin
found elsewhere on the body. The designations “thick” and “thin” refer to the
thickness of the epidermal layer, which alone varies from 75 to 150 μm for thin
skin and from 400 to 1400 μm (1.4 mm) for thick skin. Total skin thickness (epidermis
plus dermis) also varies according to the site. For example, full skin on the back is
about 4-mm thick, whereas that of the scalp is about 1.5-mm thick. Like all epithelia,
the stratified squamous epidermis lacks microvasculature, its cells receiving
nutrients and O2 by diffusion from the dermis.
Terminal diferentiation of the epidermal cells, which begins with the cell divisions in
the stratum basale, is considered a specialized form of apoptosis. Cells in the stratum
granulosum exhibit typical apoptotic nuclear morphology, including fragmentation of
their DNA. However, the cellular fragmentation associated with normal apoptosis
does not occur; instead, the cells become filled with filaments of the intracellular
protein keratin and are later sloughed from the skin surface.
CK5 and CK7 marker for basal differentation. CK13 and CK14 markers for terminal
differentiation.

31. Keratinocytes types

the epidermis consists of four layers of keratinocytes:
(1) The basal layer (stratum basale) is a single layer of basophilic cuboidal or
columnar cells on the basement membrane at the dermal-epidermal junction.
Hemidesmosomes in the basal cell membranes join these cells to the basal lamina,
and desmosomes bind the cells of this layer together in their lateral and upper
surfaces. The stratum basale is characterized by intense mitotic activity and contains,
along with the deepest part of the next layer, progenitor cells for all the epidermal
layers. An important feature of all keratinocytes in the stratum basale is the
cytoskeletal keratins, intermediate filaments about 10 nm in diameter. During
differentiation, the cells move upward and the amount and types of keratin
filaments increase until they represent half the total protein in the superficial
keratinocytes.
(2) The spinous layer (stratum spinosum) is normally the thickest layer, especially in
the epidermal ridges, and consists of generally polyhedral cells having central nuclei
with nucleoli and cytoplasm actively synthesizing keratins. Just above the basal layer,
some cells may still divide and this combined zone is sometimes called the stratum
germinativum. The keratin filaments assemble here into microscopically visible
bundles called tonofibrils, which converge and terminate at the numerous
desmosomes holding the cell layers together. The epidermis of thick skin subject to
continuous friction and pressure (such as the foot soles) has a thicker stratum
spinosum with more abundant tonofibrils and desmosomes.
(3) The granular layer (stratum granulosum) consists of three to five layers of
flattened cells, now undergoing the terminal differentiation process of keratinization.
Their cytoplasm is filled with intensely basophilic masses called keratohyaline
granules. These are dense, non-membrane-bound masses of filaggrin and other
proteins associated with the keratins of tonofibrils, linking them further into large
cytoplasmic structures. Characteristic features in cells of the granular layer also
include Golgi-derived lamellar granules, small ovoid structures with many lamellae
containing various lipids and glycolipids. Among the last activities of the
keratinocytes, the lamellar granules undergo exocytosis, producing a lipid-rich,
impermeable layer around the cells. This material forms a major part of the skin’s
barrier against water loss.
(4) The stratum lucidum, found only in thick skin, consists of a thin, translucent layer
of flattened eosinophilic keratinocytes held together by desmosomes. Nuclei and
organelles have been lost, and the cytoplasm consists almost exclusively of packed
keratin filaments embedded in an electron-dense matrix.
(5) The stratum corneum consists of 15-20 layers of squamous, keratinized cells
filled with birefringent filamentous keratins. Keratin filaments contain at least six
different polypeptides with molecular masses synthesized during cell differentiation
in the immature layers These fully keratinized or cornified cells called squames are
continuously shed at the epidermal surface as the desmosomes and lipid-rich cell
envelopes break down. CK-10 and CK-9 are markers.
In the chronic skin condition called psoriasis, keratocytes are typically produced and
differentiate at accelerated rates, causing at least slight thickening of the epidermal
layers and increased keratinization and desquamation. Psoriasis is caused by
overactive T lymphocytes triggering an autoimmune reaction in the skin, which can
also lead to inflammation with redness, irritation, itching, and scaling, with defective
skin barrier.

32. Melanocytes and development of Melanin granule

The color of the skin is the result of several factors, the most important of which are
the keratinocytes’ content of melanin and carotene and the number of blood vessels
in the dermis. Eumelanins are brown or black pigments produced by the melanocyte,
a specialized cell of the epidermis found among the cells of the basal layer and in
hair follicles. The similar pigment found in red hair is called pheomelanin.
Melanocytes are neural crest derivatives that migrate into the embryonic epidermis’
stratum basale, where eventually one melanocyte accumulates for every five or six
basal keratinocytes. They have pale-staining, rounded cell bodies attached by
hemidesmosomes to the basal lamina, but lacking attachments to the neighboring
keratinocytes. Several long irregular cytoplasmic extensions from each melanocyte
cell body penetrate the epidermis, running between the cells of the basal and
spinous layers and terminating in invaginations of 5-10 keratinocytes.
Ultrastructurally a melanocyte has numerous small mitochondria, short cisternae
of RER, and a well-developed Golgi apparatus.
The first step in melanin synthesis is catalyzed by tyrosinase, a transmembrane
enzyme in Golgi-derived vesicles. Tyrosinase activity converts tyrosine into
3,4-dihydroxyphenylalanine (DOPA), which is then further transformed and
polymerized into the different forms of melanin. Melanin pigment is linked to a
matrix of structural proteins and accumulates in the vesicles until they form
mature elliptical granules about 1-μm long called melanosomes. Melanosomes are
then transported via kinesin to the tips of the cytoplasmic extensions. The
neighboring keratinocytes phagocytose the tips of these dendrites, take in the
melanosomes, and transport them by dynein toward their nuclei. The melanosomes
accumulate within keratinocytes as a supranuclear cap that prior to keratinization
absorbs and scatters sunlight, protecting DNA of the living cells from the ionizing,
mutagenic effects of UV radiation. Although melanocytes produce melanosomes, the
keratinocytes are the melanin depot and contain more of this pigment than the cells
that make it. One melanocyte plus the keratinocytes into which it transfers
melanosomes make up an epidermal-melanin unit. The density of such units in skin
is similar in all individuals. Melanocytes of people with ancestral origins near the
equator, where the need for protection against the sun is greatest, produce melanin
granules more rapidly and accumulate them more abundantly in keratinocytes.

33. Skin macrophages - Langerhan’s cells

Antigen-presenting cells called Langerhans cells, derived from monocytes, represent
2%-8% of the cells in epidermis and are usually most clearly seen in the spinous layer.
Cytoplasmic processes extend from these dendritic cells between keratinocytes
of all the layers, forming a fairly dense network in the epidermis. Langerhans cells
bind, process, and present antigens to T lymphocytes in the same manner as
immune dendritic cells in other organs. Microorganisms cannot penetrate the
epidermis without alerting these dendritic cells and triggering an immune response.
Langerhans cells, along with more scattered epidermal lymphocytes and other APCs
in the dermis, comprise a major component of the skin’s adaptive immunity.
Because of its location, the skin is continuously in close contact with many antigenic
molecules. Various epidermal features participate in both innate and adaptive
immunity, providing an important immunologic component to the skin’s overall
protective function.
CD68 and CD117 are markers for Langerhan’s cells.

34. Cells of dermis

35. Derlma Fibrous tissue types
The dermis is the layer of connective tissue that supports the epidermis and binds it
to the subcutaneous tissue (hypodermis). The thickness of the dermis varies with the
region of the body and reaches its maximum of 4 mm on the back. The surface of the
dermis is very irregular and has many projections (dermal papillae) that interdigitate
with projections (epidermal pegs or ridges) of the epidermis, especially in skin
subject to frequent pressure, where they reinforce the dermal-epidermal
junction. A basement membrane always occurs between the stratum basale and the
dermis, and follows the contour of the interdigitations between these layers.
Nutrients for keratinocytes diffuse into the avascular epidermis from the dermal
vasculature through the basement membrane.
The dermis contains two sublayers with indistinct boundaries:
(1) The thin papillary layer, which includes the dermal papillae, consists of loose
connective tissue, with types I and III collagen fibers, fibroblasts and scattered
mast cells, dendritic cells, and leukocytes. From this layer, anchoring fibrils of type
VII collagen insert into the basal lamina, helping to bind the dermis to the
epidermis.
(2) The underlying reticular layer is much thicker, consists of dense irregular
connective tissue (mainly bundles of type I collagen), with more fibers and fewer
cells than the papillary layer. A network of elastic fibers is also present, providing
elasticity to the skin. Between the collagen and elastic fibers are abundant
proteoglycans rich in dermatan sulfate.
Both dermal regions contain a rich network of blood and lymphatic vessels. Nutritive
vessels form two major plexuses: Between the papillary and reticular dermal layers
lies the microvascular subpapillary plexus, from which capillary branches extend into
the dermal papillae and form a rich, nutritive capillary network just below the
epidermis. A deep plexus with larger blood and lymphatic vessels lies near the
interface of the dermis and the subcutaneous layer.
In addition to the nutritive function, dermal vasculature has a thermoregulatory
function, which involves numerous arteriovenous anastomoses or shunts located
between the two major plexuses. The shunts decrease blood flow in the papillary
layer to minimize heat loss in cold conditions and increase this flow to facilitate heat
loss when it is hot, thus helping maintain a constant body temperature. Lymphatic
vessels begin in the dermal papillae and converge to form two plexuses located
with the blood vessels. The dermis is also richly innervated. Sensory afferent nerve
fibers form a network in the papillary dermis and around hair follicles, ending at
epithelial and dermal receptors. Autonomic effector nerves to dermal sweat glands
and smooth muscle fibers in the skin of some areas are postganglionic fibers of
sympathetic ganglia; no parasympathetic innervation is present.
With age changes in the dermal ECM are normal: thickening of collagen fibers, less
collagen synthesis, and loss of hyaluronan and other GAGs. In old age, extensive
cross-linking of collagen fibers and the loss of elastic fibers, especially after
excessive exposure to the sun (solar elastosis), cause the skin to become more fragile,
lose its suppleness, and develop wrinkles. The epidermis also normally thins and
becomes more transparent during aging. In several disorders, such as cutis laxa and
Ehlers-Danlos syndromes, there is a considerable increase in skin and ligament
extensibility caused by defective collagen fibril processing.

36. Subcutaneous Tissue - Hair

Hairs are elongated keratinized structures that form within epidermal invaginations,
the hair follicles. All skin has at least minimal hair except the glabrous skin of the
palms, soles, lips, glans penis, clitoris, and labia minora. Hairs grow discontinuously,
with periods of growth followed by periods of rest, and this growth does not occur
synchronously in all regions of the body or even in the same area. The growing hair
follicle has a terminal dilation called a hair bulb. A dermal papilla inserts into the
base of the hair bulb and contains a capillary network required to sustain the hair
follicle. Keratinocytes continuous with those of the basal epidermis cover the dermal
papilla. These cells form the matrix of the elongating hair root; the part of a hair
extending beyond the skin surface is the hair shaft. The keratinocytes of the hair
bulb are generally similar to those in the basal and spinous layers of epidermis. They
divide rapidly in a matrix region immediately around the dermal papilla and then
undergo keratinization, melanin accumulation, and terminal differentiation. In most
thick hairs large, vacuolated, and moderately keratinized cells form the central
medulla of the hair root. Heavily keratinized, densely packed cells make up the
cortex around the medulla. The most peripheral cells of the hair root comprise the
cuticle, a thin layer of heavily keratinized, squamous cells covering the cortex.
The outermost cells of the hair bulb are continuous with the epithelial root sheath, in
which two layers can be recognized. The internal root sheath completely surrounds
the initial part of the hair root but degenerates above the level of the attached
sebaceous glands. The external root sheath covers the internal sheath and extends
all the way to the epidermis, where it is continuous with the basal and spinous
layers. Separating the hair follicle from the dermis is an acellular hyaline layer, the
thickened basement membrane called the glassy membrane. The surrounding
dermis forms a connective tissue sheath. The arrector pili muscle, a small bundle of
smooth muscle cells, extends from the midpoint of the fibrous sheath to the
dermal papillary layer.
37. Sebaceous gland
Sebaceous glands are embedded in the dermis over most of the body, except in the
thick, glabrous skin of the palms and soles. Sebaceous glands are branched acinar
glands with several acini converging at a short duct that usually empties into the
upper portion of a hair follicle. A hair follicle and its associated sebaceous glands
make up a pilosebaceous unit. In certain hairless regions, such as the penis, clitoris,
eyelids, and nipples, sebaceous ducts open directly onto the epidermal surface.The
acini of sebaceous glands are the classic example of holocrine secretion. They have a
basal layer of flattened epithelial cells on the basal lamina, which proliferate and are
displaced centrally, undergoing terminal differentiation as large, lipid-producing
sebocytes filled with small fat droplets. Their nuclei shrink and undergo autophagy
along with other organelles, and near the duct the cells disintegrate, releasing the
lipids as the main secretory product. This product, called sebum, gradually covers the
surfaces of both the epidermis and hair shafts. Sebum is a complex mixture of lipids
that includes wax esters, squalene, cholesterol, and triglycerides that are hydrolyzed
by bacterial enzymes after secretion. Sebum helps maintain the stratum corneum
and hair shafts and exerts weak antibacterial and antifungal properties.

38. Sweat gland types

Sweat glands develop as long epidermal invaginations embedded in the
dermis.Sweating is a physiologic response to increased body temperature during
physical exercise or thermal stress and is the most effective means of temperature
regulation of humans.
There are two types of sweat glands:
(1)Eccrine sweat glands are widely distributed in the skin and are most numerous on
the foot soles. Both the secretory components and ducts of eccrine sweat glands are
coiled and have small lumens. The secretory part is generally more pale-staining than
the ducts and consists of an unusual stratified cuboidal epithelium with three cell
types:Pale-staining clear cells located on the basal lamina produce the sweat, having
abundant mitochondria and microvilli to provide large surface areas. Interstitial fluid
from the capillary-rich dermis around the gland is transported through the clear cells,
either directly into the gland’s lumen or into intercellular canaliculi that open to
the lumen. Dark cells filled with strongly eosinophilic granules line most of the
lumen and do not contact the basal lamina. The granules undergo merocrine
secretion to release a poorly understood mixture of glycoproteins with bactericidal
activity. Myoepithelial cells on the basal lamina contract to move the watery
secretion into the duct.
(2)Apocrine sweat glands are largely confined to skin of the axillary and perineal
regions. Their development depends on sex hormones and is not complete and
functional until after puberty. The secretory components of apocrine glands
have much larger lumens than those of the eccrine glands and consist of simple
cuboidal, eosinophilic cells with numerous secretory granules that also undergo
exocytosis. Thus the glands are misnamed: their cells show merocrine, not apocrine,
secretion. The ducts of apocrine glands are similar to those of the eccrine glands, but
they usually open into hair follicles at the epidermis and may contain the protein
rich product. The slightly viscous secretion is initially odorless but may acquire a
distinctive odor as a result of bacterial activity. The production of pheromones by
apocrine glands is well established in many mammals and is likely in humans,
although in a reduced or vestigial capacity. Apocrine sweat glands are innervated by
adrenergic nerve endings, whereas eccrine sweat glands receive cholinergic fibers.

39. Nail Matrix, Nail plate, Nail bed

Nails are hard plates of keratin on the dorsal surface of each distal phalanx. The
proximal part of the nail is the nail root and is covered by a fold of skin, from which
the epidermal stratum corneum extends as the cuticle, or eponychium. The nail plate
is bound to a bed of epidermis, the nail bed, which contains only the basal and
spinous epidermal layers. The nail root forms from the nail matrix in which cells
divide, move distally, and become keratinized in a process somewhat similar to hair
formation but without keratohyaline granules. The nail root matures and hardens as
the nail plate. Continuous growth in the matrix pushes the nail plate forward over
the nail bed (which makes no contribution to the plate). The distal end of the plate
becomes free of the nail bed at the epidermal fold called the hyponychium.
The nearly transparent nail plate and the thin epithelium of the nail bed provide a
useful window on the amount of oxygen in the blood by showing the color of blood
in the dermal vessels.

40. Photoreceptor system - Fibrous layer

Eyes are highly developed photosensitive organs for analyzing the form, intensity,
and color of light reflected from objects and providing the sense of sight. Protected
within the orbits of the skull which also contain adipose cushions, each eyeball
consists externally of a tough, fibrous globe, which maintains an eye’s overall shape.
Internally the eye contains transparent tissues that refract light to focus the image, a
layer of photosensitive cells, and a system of neurons that collect, process, and
transmit visual information to the brain.
Fibrous layer(corneoscleral coat) - This layer includes two major regions, the
posterior sclera and the anterior cornea, joined at the limbus.
In the 4-week embryo epithelial optic vesicles bulge bilaterally from the forebrain,
then elongate as the optic stalks bearing optic cups. Inductive interactions between
the optic cups and the overlying surface ectoderm cause the latter to invaginate and
eventually detach as the initially hollow lens vesicles. The optic stalk develops as the
optic nerve and in an inferior groove called the choroid fissure encloses the hyaloid
vessels, which supply blood for the developing lens and optic cup. In the ensuing
weeks, head mesenchyme differentiates to form most of the tissue in the eye’s two
outer layers and the vitreous. Ectoderm of the optic cup differentiates as the retina
and surface ectoderm forms the corneal epithelium (Figure 23–2d). When the lens is
fully formed, the distal hyaloid artery and vein disappear, leaving only the blood
supply to the retina.
41. Sclera and corneal epithelium
The sclera averages 0.5 mm in thickness and consists mainly of dense connective
tissue, with flat bundles of type I collagen parallel to the organ surface but
intersecting in various directions; microvasculature is present near the outer surface.
Tendons of the extraocular muscles which move the eyes insert into the anterior
region of the sclera. Posteriorly the sclera thickens to approximately 1 mm and joins
with the epineurium covering the optic nerve. Where it surrounds the choroid, the
sclera includes an inner suprachoroid lamina, with less collagen, more fibroblasts,
elastic fibers, and melanocytes.It is devided into 3 layer: (1) Episcleral layer - loose
connective tissue adjacent to periorbital fat. (2) Substantia propria(Tenon’capsule) -
investing fascia. (3) Suprachoroid lamina(lamina fusca). Episcleral space allow eye to
rotate freely within the orbit.
cornea—is transparent and completely avascular. A section of the cornea shows five
distinct layers:
(1) An external corneal epithelium, which is a stratified squamous
epithelium.nonkeratinized, five or six cell layers thick, and comprises about 10% of
the corneal thickness.Has regenerating capacity. Epithelial cell nuclei contain Ferritin.
(2) An anterior limiting membrane (Bowman membrane), which is the basement
membrane beneath the corneal epithelium. Contains Collagen type IV. Does not
regenerate. Protect against infections.
(3) The thick stroma(substantia propria) - 60 layers of parallel collagen bundles.
Cytoplasmic extensions of flattened fibroblast-like cells called keratocytes, ground
substancearound them containns proteoglycans(lumican,keratan,chondroitin sulfate)
that maintain precise orgainzation of collagen fibrils.
(4) A posterior limiting membrane (Descemet’s membrane), which is the basement
membrane of the endothelium; has thick basal lamina. Positive to PAS. Can
regenerate. Forms pectinate ligament that penetrates ciliary muscle and sclera.
Contains type VIII collagen.
(5) An inner simple squamous endothelium - Cells are joined by zonula adherens,
zonula occludens, desmosomes. Has Na/k ATPase pumps in basolateral membranes.
Regulates proper hydration for maximal transparency and optimal light reflection.

42. Limbus
Encircling the cornea is the limbus, a transitional area where the transparent cornea
merges with the opaque sclera. Here Bowman’s membrane ends and the surface
epithelium becomes more stratified as the conjunctiva that covers the anterior part
of the sclera (and lines the eyelids).epithelial stem cells located at the limbus surface
give rise to rapidly dividing progenitor cells, which then move centripetally into the
corneal epithelium. The stroma becomes vascular and less well-organized at the
limbus, as the collagen bundles merge with those of the sclera. Also at the limbus
Descemet’s membrane and its simple endothelium are replaced with a system of
irregular endothelium-lined channels called the trabecular meshwork(Spaces of
Fontana). These penetrate the stroma at the corneoscleral junction and allow slow,
continuous drainage of aqueous humor from the anterior chamber. This fluid moves
from these channels into the adjacent larger space of the scleral venous sinus, or
canal of Schlemm, which encircles the eye. From this sinus aqueous humor drains
into small blood vessels (veins) of the sclera.

43. Vascular or middle layer - Choroid, Bruch’s membrane

The eye’s more vascular middle layer, known as the uvea, consists of three parts,
from posterior to anterior: the choroid, the ciliary body, and the iris.
Choroid - loose, well-vascularized connective tissue and contains numerous
melanocytes.These form a characteristic black layer in the choroid and prevent light
from entering the eye except through the pupil. 0.25mm thick. Two layers can be
identified: (1) Choriocapillary layer - inner vascular layer, provide nutrients to retina.
(2) Bruch’s membrane - extends from optic nerve to ora serrate, composed of
collagen and elastic fibers surrounding the adjacent microvasculature and basal
lamina of the retina’s pigmented layer. Amorphous refrectile layer. Also called
Lamina Vitrea. ჰიალინური ქსოვილია.

44. Ciliary body, ciliary processes, Iris

ciliary body - the anterior expansion of the uvea that encircles the lens, lies posterior
to the limbus. Like the choroid, most of the ciliary body rests on the sclera.
Ciliary muscle makes up most of ciliary body’s stroma. Consists of 3 groups of
smooth muscle fibers: (1) Meridional(longtitudinal) portion - outer muscle fibers,
stretching choroid, facilitate drainage of aqueous humor. (2) Radial(oblique) portion
- deeper muscle fibers, flatten of lens, focus for distant vision. (3) Circular(sphincteric)
portion - reduces tension on lens, accommodate for near vision.
Ciliary processes - are a radially arranged series of about 75 ridges extending from
the inner highly vascular region of the ciliary body. These provide a large surface
area covered by a double layer of low columnar epithelial cells, the ciliary
epithelium(secrets aqueos humor and participates in Blood-aqueous barrier, secrets
and anchors zonular fibers that form the sunspensory ligament of lens). The
epithelial cells directly covering the stroma contain much melanin and correspond to
the anterior projection of the pigmented retina epithelium. The surface layer of cells
lacks melanin and is contiguous with the sensory layer of the retina.
Aqueous humor is derived from plasma and maintains intraocular pressure, similar
to plasma but contains less then 0.1% protein, flows through pupil into anterior
chamber, drains into trabecular meshwork and scleral venous sinus(canal of schlimm)
finally enters venule of sclera.
ciliary zonule is a system of many radially oriented fibers composed largely of
fibrillin-1 and -2 produced by the nonpigmented epithelial cells on the ciliary
processes. The fibers extend from grooves between the ciliary processes and attach
to the surface of the lens, holding that structure in place.
Aqueous humor is produced continuously. If its drainage from the anterior chamber is
impeded, typically by obstruction of the trabecular meshwork or scleral venous
sinus, intraocular pressure can increase, causing the condition called glaucoma.
Untreated glaucoma can cause pressing of the vitreous body against the retina,
affecting visual function and possibly leading to neuropathy in that
tissue. When the iridocorneal angle is more narrow than usual, the thickening of the
peripheral iris that occurs with dilation of the pupil can occlude the angle and
obstruct drainage of aqueous humor at the trabecular meshwork. This can result in
the rapid development of intraocular hypertension known as angle closure glaucoma,
acute glaucoma, or closed (narrow) angle glaucoma. This condition usually affects
both eyes and causes blurred vision, eye pain, and headache. Treatment of this type
of glaucoma usually includes some form of surgical intervention or carbonic
anhudrase inhibitors(Dorzolamide, Brizolamide).

Iris - most anterior extension of the middle uveal layer which covers part of the lens,
leaving a round central pupil. Form a contractile diaphragm in front of lens. The
anterior surface of the iris, exposed to aqueous humor in the anterior chamber,
consists of a dense layer of fibroblasts and melanocytes with interdigitating
processes and is unusual for its lack of an epithelial covering. Deeper in the iris, the
stroma consists of loose connective tissue with melanocytes and sparse
microvasculature. The posterior surface of the iris has a two-layered epithelium
continuous with that covering the ciliary processes, but very heavily filled with
melanin. The highly pigmented posterior epithelium of the iris blocks all light from
entering the eye except that passing through the pupil. Myoepithelial cells form a
partially pigmented epithelial layer and extend contractile processes radially as the
very thin dilator pupillae muscle. Smooth muscle fibers form a circular bundle near
the pupil as the sphincter pupillae muscle. The dilator and sphincter muscles of the
iris have sympathetic and parasympathetic innervation, respectively, for enlarging
and constricting the pupil.

45. Lens, Vitrous body, Caveum Vitreum(?)

The lens is a transparent biconvex structure suspended immediately behind the iris,
which focuses light on the retina. Derived from an invagination of the embryonic
surface ectoderm, the lens is a unique avascular tissue and is highly elastic, a
property that normally decreases with age. Has 3 principal components:
(1) Lens Capsule - thick (10-20 μm), homogeneous,composed of proteoglycans and
type IV collagen surrounds the lens and provides the place of attachment for the
fibers of the ciliary zonule.
(2) lens epithelium - consists of a single layer of cuboidal cells present only on the
anterior surface of the lens. The epithelial cells attach basally to the surrounding lens
capsule and their apical surfaces bind to the internal lens fibers. At the posterior
edge of this epithelium, near the equator of the lens, the epithilial cells divide to
provide new cells, which differentiate as lens fibers. This process allows for growth
of the lens and continues at a slow, decreasing rate near the equator of the lens
throughout adult life.
(3) Lens fibers - are highly elongated, terminally differentiated cells that appear as
thin, flattened structures. Developing from cells in the lens epithelium.The
cytoplasm becomes filled with a group of proteins called crystallins, and the
organelles and nuclei undergo autophagy. Lens fibers are packed tightly together
and form a perfectly transparent tissue highly specialized for light refraction.
Presbyopia - when lens loses elasticity and ability of accomodation.

The vitreous body - occupies the large vitreous chamber behind the lens. It consists
of transparent, gellike connective tissue that is 99% water (vitreous humor), with
collagen fibrils and hyaluronate, contained within an external lamina called the
vitreous membrane. The only cells in the vitreous body are a small mesenchymal
population near the membrane called hyalocytes, which synthesize the hyaluronate
and collagen, and a few macrophages.

46. Retina - Neuronal types and functions

The retina - the innermost tunic of the eye. Has two layers:
• The nonphotosensitive region (nonvisual part), located anterior to the ora serrata,
lines the inner aspect of the ciliary body and the posterior surface of the iris.
• The photosensitive region (optic part) lines the inner surface of the eye posterior
to the ora serrata except where it is pierced by the optic nerve.
Neurons and supporting cells in retina can be classifified into four groups of cells:
• Photoreceptor cells—the retinal rods and cones
• Conducting neurons—bipolar neurons and ganglion cells
• Association neurons and others—horizontal, centrifugal, interplexiform, and
amacrine neurons
• Supporting (neuroglial) cells—Müller’s cells, microglial cells, and astrocytes
The ten layers of the retina, from outside inward, are:
1. Retinal pigment epithelium (RPE)—the outer layer of the retina, actually not part
of the neural retina but intimately associated with it
2. Layer of rods and cones—contains the outer and inner segments of photoreceptor
cells
3. Outer limiting membrane—the apical boundary of Müller’s cells
4. Outer nuclear layer—contains the cell bodies (nuclei) of retinal rods and
cones,receives O2 and nutrients by diffusion from choroidcapillary
5. Outer plexiform layer—contains the processes of retinal rods and cones and
processes of the horizontal,amacrine, and bipolar cells
6. Inner nuclear layer—contains the cell bodies (nuclei) of horizontal, amacrine,
bipolar, and Müller’s cells
7. Inner plexiform layer—contains the processes of horizontal, amacrine, bipolar,
and ganglion cells that connect to each other
8. Ganglion cell layer—contains the cell bodies (nuclei) of ganglion cells
9. Layer of optic nerve fibers—contains processes of ganglion cells that lead from the
retina to the brain
10. Inner limiting membrane—composed of the basal lamina of Müller’s cells

47. Photoreceptors, Pigment Epithelium

The pigmented epithelial layer consists of cuboidal or low columnar cells with basal
nuclei and surrounds the neural layer of the retina. The cells have well-developed
junctional complexes, gap junctions, and numerous invaginations of the basal
membranes associated with mitochondria. The apical ends of the cells extend
processes and sheath-like projections surrounding the tips of the photoreceptors.
Melanin granules are numerous in these extensions and in the apical cytoplasm .
This cellular region also contains numerous phagocytic vacuoles and secondary
lysosomes, peroxisomes, and abundant smooth ER (SER) specialized for retinal
(vitamin A) isomerization. The diverse functions of the retinal pigmented epithelium
include the following:
 The pigmented layer absorbs scattered light that passes through the neural layer,
supplementing the choroid in this regard.
 With many tight junctions, cells of the pigmented epithelium form an important
part of the protective blood-retina barrier isolating retina photoreceptors from
the highly vascular choroid and regulating ion transport between these
compartments.
 The cells play key roles in the visual cycle of retinal regeneration, having enzyme
systems that isomerize all-trans-retinal released from photoreceptors and
produce 11-cis-retinal that is then transferred back to the photoreceptors.
 Phagocytosis of shed components from the adjacent photoreceptors and
degradation of this material occurs in these epithelial cells.
 Cells of pigmented epithelium remove free radicals by various protective
antioxidant activities and support the neural retina by secretion of ATP, various
polypeptide growth factors, and immunomodulatory factors.

ROD CELLS - They are extremely sensitive to light, responding to a single photon, and
allow some vision even with light low levels, such as at dusk or nighttime. Rod cells
are thin, elongated cells (50 μm × 3 μm), composed of two functionally distinct
segments: The outer segment is a modified primary cilium, photosensitive, and
shaped like a short rod; the inner segment contains glycogen, mitochondria, and
polyribosomes for the cell’s biosynthetic activity. Inner segment has Outer
ellipsoid(Mitochondrias) and inner myoid(RER and free ribosomes) portion.
The rod-shaped segment consists mainly of 600-1000 flattened membranous discs
stacked like coins and surrounded by the plasma membrane. Proteins on the
cytoplasmic surface of each disc include abundant rhodopsin (or visual purple) which
is bleached by light and initiates the visual stimulus. Between this outer segment and
the cell’s inner segment is a constriction, the connecting stalk, which is part of the
modified primary cilium arising from a basal body. In rod cells the newly assembled
discs detach from the plasma membrane and are displaced distally as new discs form.
Eventually the discs arrive at the end of the rod, where they are shed, phagocytosed,
and digested by the cells of the pigmented epithelium. The chromophore of rods is a
vitamin A–derived carotenoid called retinal.
CONE CELLS - Less numerous and less light-sensitive than rods. in the typical human
retina produce color vision in adequately bright light. There are three
morphologically similar classes of cones(L,M,S wavelengthsensitive), each containing
one type of the visual pigment iodopsin (or photopsins). Each of the three iodopsins
has maximal sensitivity to light of a different wavelength, in the red, blue, or green
regions of the visible spectrum, respectively. By mixing neural input produced by
these visual pigments, cones produce a color image.The outer segments of cones
differ from those of rods in their shorter, more conical form and in the structure of
their stacked membranous discs, which in cones remain as continuous invaginations
of the plasma membrane along one side,discs in cones are shed much less frequently
than in rods.

48. Retinal Histophysiology

The optic disc, or blind spot, occurs at the posterior of the retina where the axons in
the retina’s NFL) converge at the optic nerve head and leave the eye as the optic
nerve. The optic disk is approximately 1.7 mm in diameter and lacks photoreceptors
and other retinal layers except the NFL from ganglion cells.
The fovea centralis is a shallow depression located about 2.5 mm lateral to the optic
disc. It is the area of greatest visual acuity. The visual axis of the eye passes through
the fovea. A yellow-pigmented zone called the macula lutea(axons of the cone cells
contain various carotenoids, giving this area its yellowish color)surrounds the fovea.
Cone cells in the fovea are long, narrow, and closely packed. Devoid of most
conducting neurons as well as capillaries, the fovea allows light to fall directly on its
cones with very little light scatter.
Within the GL of the entire retina a subset of ganglion cells serve as nonvisual
photoreceptors. These neurons contain 11-cis-retinal bound to the protein
melanopsin and serve to detect changes in light quantity and quality during
each 24-hour dawn/dusk cycle.
The conversion of the incident light into electrical nerve impulses is called visual
processing and involves several steps:
• A photochemical reaction occurs in the outer segment of the rods and cones. In
the dark, rhodopsin molecules contain a chromophore called retinal in its isometric
form of 11-cis-retinal. When rods are exposed to light, the11-cis-retinal undergoes
conformational change from a bent to a more linear molecule called all-trans-retinal.
The conversion of 11-cis-retinal to all-trans-retinal activates opsin, which results in
the release of all-trans-retinal into the rod’s cytoplasm (a reaction called bleaching).
• The activated opsin interacts with a G-protein called transducin, which
subsequently activates phosphodiesterase that breaks down cyclic GMP (cGMP). In
the dark, high levels of cGMP molecules produced in the photoreceptor cells by
guanylyl cyclase are bound to the cytoplasmic surface of cGMP-gated Na+ channels,
causing them to stay open.Steady influx of Na+ into the cells results in depolarization
of the plasma membrane and continuous release of the neurotransmitter (gluta
mate) at the synaptic junction with the bipolar neurons.
• A decrease in the concentration of cGMP within the cytoplasm of the inner
segment of the photoreceptor cells is due to the action of phosphodiesterase.
Dissociation of cGMP from Na+ channels efectively closes the channels and reduces
influx of Na+ into the cell, resulting in hyperpolarization of the plasma membrane.
The hyperpolarization causes a decrease of glutamate secretion at the synapses with
bipolar cells, which is detected and conveyed as electrical impulses.

49. Accessory structures of the eye

The conjunctiva is a thin, transparent mucosa that covers the exposed, anterior
portion of the sclera and continues as the lining on the inner surface of the eyelids. It
consists of a stratified columnar epithelium, with numerous small goblet cells,
supported by a thin lamina propria of loose vascular connective tissue. Mucous
secretions from conjunctiva cells are added to the tear film that coats this epithelium
and the cornea.
Eyelids are pliable, protective structures consisting of skin, muscle, and conjunctiva.
The skin is loose and elastic, lacks fat, and has only very small hair follicles and fine
hair, except at the distal edge, where large follicles with eyelashes are present.
Associated with the follicles of eyelashes are sebaceous glands and modified
apocrine sweat glands. Beneath the skin are striated fascicles of the orbicularis oculi
and levator palpebrae muscles, which fold the eyelids. Adjacent to the conjunctiva is
a dense fibroelastic plate called the tarsus supporting the other tissues. The tarsus
surrounds a series of 20-25 large sebaceous glands, each with many acini secreting
into a long central duct that opens among the eyelashes. Oils in the sebum produced
by these tarsal glands, also called Meibomian glands, form a surface layer on the tear
film, reducing its rate of evaporation, and help lubricate the ocular surface.
The lacrimal glands produce fluid continuously for the tear film that moistens and
lubricates the cornea and conjunctiva and supplies O2 to the corneal epithelial cells.
Tear fluid also contains various metabolites, electrolytes, and proteins of innate
immunity such as lysozyme. The main lacrimal glands are located in the upper
temporal portion of the orbit and have several lobes, which drain through individual
excretory ducts into the superior fornix, the conjunctiva-lined recess between
the eyelids and the eye. The lacrimal glands have acini composed of large serous
cells filled with lightly stained secretory granules and surrounded by well-developed
myoepithelial cells and a sparse, vascular stroma.Tear film moves across the ocular
surface and collects in other parts of the bilateral lacrimal apparatus: flowing
through two small round openings (0.5 mm in diameter) to canaliculi at the medial
margins of the upper and lower eyelids, then passing into the lacrimal sac, and finally
draining into the nasal cavity via the nasolacrimal duct. The canaliculi are lined
by stratified squamous epithelium, but the more distal sac and duct are lined by
pseudostratified ciliated epithelium like that of the nasal cavity.

50. External ear

The auricle, or pinna (L. pinna, wing) is an irregular, funnel shaped plate of elastic
cartilage, covered by tightly adherent skin, which directs sound waves into the ear.
Sound waves enter the external acoustic meatus, a canal lined with stratified
squamous epithelium that extends from the auricle to the middle ear. Near its
opening hair follicles, sebaceous glands, and modified apocrine sweat glands called
ceruminous glands are found in the submucosa. Cerumen, the waxy material formed
from secretions of the sebaceous and ceruminous glands, contains various proteins,
saturated fatty acids, and sloughed keratinocytes and has protective, antimicrobial
properties. The wall of the external acoustic meatus is supported by elastic cartilage
in its outer third, while the temporal bone encloses the inner part. Across the deep
end of the external acoustic meatus lies a thin, somewhat transparent sheet called
the tympanic membrane or eardrum. This membrane consists of fibroelastic
connective tissue covered externally with epidermis and internally by the simple
cuboidal epithelium of the mucosa lining the middle ear cavity. Sound waves cause
vibrations of the tympanic membrane, which transmit energy to the middle ear.

51. Middle ear - Tympanic cavity

The middle ear contains the air-filled tympanic cavity, an irregular space lying within
the temporal bone between the tympanic membrane and the bony surface of the
internal ear. Anteriorly, this cavity communicates with the pharynx via the auditory
tube (also called the eustachian or pharyngotympanic tube) and posteriorly
with the smaller, air-filled mastoid cavities of the temporal bone. The simple
cuboidal epithelium lining the cavity rests on a thin lamina propria continuous with
periosteum. Entering the auditory tube, this simple epithelium is gradually replaced
by the ciliated pseudostratified columnar epithelium that lines the tube. Below the
temporal bone this tube is usually collapsed; swallowing opens it briefly, which
serves to balance the air pressure in the middle ear with atmospheric pressure. In
the medial bony wall of the middle ear are two small, membrane-covered regions
devoid of bone: the oval and round windows with the internal ear behind them.The
tympanic membrane is connected to the oval window by a series of three small
bones, the auditory ossicles, which transmit the mechanical vibrations of the
tympanic membrane to the internal ear. The three ossicles are named for their
shapes the malleus, incus, and stapes. The malleus is attached to the tympanic
membrane and the stapes to the membrane across the oval window. The ossicles
articulate at synovial joints, which along with periosteum are completely covered
with simple squamous epithelium. Two small skeletal muscles, the tensor tympani
and stapedius, insert into the malleus and stapes, respectively, restricting ossicle
movements and protecting the oval window and inner ear from potential damage
caused by extremely loud sound.

52. Internal ear

The three semicircular ducts extend from and return to the wall of the utricle. They
lie in three different spatial planes, at approximately right angles to one another.
Each semicircular duct has one enlarged ampulla end containing hair cells and
supporting cells on a crest of the wall called the crista ampullaris. Each crista
ampullaris is perpendicular to the long axis of the duct.The cupula extends
completely across the ampulla, contacting the opposite nonsensory wall.The hair
cells of the cristae ampullares act as mechanoelectrical transducers like those of the
maculae in the utricle and saccule, signaling afferent axons by pulsed transmitter
release determined by depolarization and hyperpolarization states. Here the
mechanoreceptors detect rotational movements of the head as they are deflected
by endolymph movement in the semicircular ducts. The cells are oriented with
opposite polarity on each side of the side, so that turning the head causes hair cell
depolarization on one side and hyperpolarization on the other. Neurons of the
vestibular nuclei in the CNS receive input from the sets of semicircular ducts on each
side simultaneously and interpret head rotation on the basis of the relative
transmitter discharge rates of the two sides.Inputs from the semicircular ducts travel
together with those from the utricle and saccule along the eighth cranial nerve to
vestibular nuclei in the CNS.
The organ of Corti, or spiral organ, where sound vibrations of different frequencies
are detected, consists of hair cells and other epithelial structures supported by the
basilar membrane. Here the sensory hair cells have precisely arranged V-shaped
bundles of rigid stereocilia each loses its single larger kinocilium during development.
Two major types of hair cells are present: (1) Outer hair cells occur in three rows
near the saccule, increasing to five rows near the apex of the cochlea. Each columnar
outer hair cell bears a V-shaped bundle of stereocilia. (2) Inner hair cells form a
single row of about 3500 cells, each with a single more linear array of shorter
stereocilia. Both outer and inner hair cells have synaptic connections with afferent
and efferent nerve endings, with the inner row of cells more heavily innervated. The
cell bodies of the afferent bipolar neurons constitute the spiral ganglion located in
the bony core of the modiolus.
Two major types of columnar supporting cells are attached to the basilar membrane
in the organ of Corti: (1) Inner and outer phalangeal cells extend apical processes,
which intimately surround and support the basolateral parts of both inner and outer
hair cells and the synaptic nerve endings. The apical ends of phalangeal cells are
joined to those of the hair cells by tight zonulae occludens, forming an apical plate
across the spiral organ through which the stereocilia bundles project into endolymph.
(2) Pillar cells are stiffened by heavy bundles of keratin and outline a triangular space,
the inner tunnel, between the outer and inner complexes of hair cells and
phalangeal cells. The stiff inner tunnel also plays a role in sound transmission.
On the outer hair cells the tips of the tallest stereocilia are embedded in the gel-like
tectorial membrane, an acellular layer extending over the organ of Corti from the
connective tissue around the modiolus. The tectorial membrane consists of fine
bundles of collagen (types II, V, IX, and XI) associated with proteoglycans and forms
during the embryonic period from secretions of cells lining this region.

53. Sensory cells in cochlear duct and Labyrinth - hair cell types, Differentation
patterns
Hair cells have an apical hair bundle consisting of one rigid cilium, the kinocilium,
unbranched stereocilia. The base of each stereocilium is tapered and connected to
an actin-rich region of apical cytoplasm, the cuticular plate, which returns these rigid
projecting structures to a normal upright position after bending. They are arranged
in rows of decreasing length, with the longest adjacent to the kinocilium. The tips of
the stereocilia and kinocilium are embedded in a thick, gelatinous layer of
proteoglycans called the otolithic membrane. The outer region of this layer contains
barrel-shaped crystals of CaCO3 and protein called otoliths (or otoconia).
All hair cells have basal synapses with afferent (to the brain) nerve endings but are of
two types: (1)Type I hair cells have rounded basal ends completely surrounded by an
afferent terminal calyx. (2) The more numerous type II hair cells are cylindrical,
with bouton endings from afferent nerves.
Hair cells are in:
 Two maculae of the utricle and saccule,
 Three cristae ampullares in the enlarged ampullary regions of each semicircular
duct
 The long spiral organ of Corti in the cochlear duct.

54. Saccule and Utricle

The interconnected, membranous utricle and the saccule are composed of a very
thin connective tissue sheath lined with simple squamous epithelium and are bound
to the periosteum of the bony labyrinth by strands of connective tissue containing
microvasculature. Each consists of a thickening of the wall containing several thou
sand columnar hair cells, each with surrounding supporting cells and synaptic
connections to nerve endings. Hair cells act as mechanoelectrical transducers,
converting mechanical energy into the electrical energy of nerve action potentials.
Sensory information from the utricle and saccule allows the brain to monitor the
static position and linear acceleration of the head. This information, along with that
provided visually and by musculoskeletal proprioceptors, is important for
maintaining equilibrium and allowing the eyes to remain fixed on the same point
while moving the head. The head’s position determines the position of the otolithic
membrane in contact with hair cells of the two maculae. Because the otoliths are
heavier than endolymph, the hair bundles are deflected by gravity when the head is
not moving, when the head is tilted, and when the individual is moving in a straight
line and inertia causes drag on the otolithic membrane. Deflection or bending of the
stereocilia changes the hair cells’ resting potential and their rate of neurotransmitter
release to the afferent nerves, which is the basis for mechanoelectrical transduction.
When the hair bundle is deflected toward the kinocilium, protein fibrils called tip
links connecting the stereocilia are pulled and mechanically gated channels open to
allow an influx of K+ ions (the major cation in endolymph). The resulting
depolarization of the hair cell opens voltage-gated Ca2+ channels in the basolateral
membrane, and Ca2+ entry stimulates release of neurotransmitter and generates an
impulse in the afferent nerve.Head movements that bend the stereocilia away
from the kinocilium cause the tip links to be slack, allowing closure of the apical
cation channels and hyperpolarization of the cell. This in turn closes Ca2+ channels
and reduces neurotransmitter release.
Ménière disease involves episodes of vertigo accompanied by hearing loss and
ringing in the ears (tinnitus) and is caused when increased pressure within the
membranous labyrinth (endolymphatic hydrops) leads to rupture and leakage of
endolymph into the perilymph.

55. Spiral lamina - Endolymph, Perilymph, contacts with CNS meninges

Perilymph fills all regions of the bony labyrinth and has an ionic composition similar
to that of cerebrospinal fluid and the extracellular fluid of other tissues, but it
contains little protein. Perilymph emerges from the microvasculature of the
periosteum and drains via a perilymphatic duct into the adjoining subarachnoid
space. Perilymph suspends and supports the closed membranous labyrinth,
protecting it from the hard wall of the bony labyrinth.
Endolymph fills the membranous labyrinth and is characterized by a high-K+ (150
mM) and low-Na+(16 mM) content, similar to that of intracellular fluid. Endolymph is
produced in a specialized area in the wall of the cochlear duct and drains via a small
endolymphatic duct into venous sinuses of the dura mater.
56. Cochlear duct - Hair cells, supporting cell types
The cochlear duct, a part of the membranous labyrinth shaped as a spiral tube,
contains the hair cells and other structures that allow auditory function. Held in
place within the bony cochlea, this duct is one of three parallel compartments,
or scalae which coil 2¾ turns within the cochlea. The cochlear duct itself forms the
middle compartment, or scala media, filled with endolymph. It is continuous with the
saccule and ends at the apex of the cochlea. The larger scala vestibuli contains
perilymph and is separated from the scala media by the very thin vestibular
membrane (Reissner membrane) lined on each side by simple squamous epithelium.
Extensive tight junctions between cells of this membrane block ion diffusion
between perilymph and endolymph. The scala tympani also contains perilymph and
is separated from the scala media by the fibroelastic basilar membrane. The scalae
tympani and vestibuli communicate with each other at the apex of the cochlea via a
small opening called the helicotrema. Thus these two spaces with perilymph are
actually one long tube; the scala vestibuli begins near the vestibular oval window
and the scala tympani ends at the round window. The stria vascularis, located in the
lateral wall of the cochlear duct (scala media), produces the endolymph with high
levels of K+ that fills the entire membranous labyrinth. Stratified epithelial cells of
the stria vascularis extend cytoplasmic processes and folds around the capillaries of
an unusual intraepithelial plexus. K+ released from the capillaries is transported
across tightly joined cells at the strial surface into the endolymph, which bathes the
stereocilia of hair cells and produces conditions optimal for these cells’depolarization.
Pressure waves within the perilymph begin at the oval window and move along the
scala vestibuli. Each pressure wave causes momentary displacement of the
vestibular and/or basilar membranes and the endolymph surrounding the organ of
Corti. High-frequency sounds displace the basilar membrane maximally near the oval
window. Sounds of progressively lower frequency produce pressure waves that
move farther along the scala vestibuli and displace the spiral organ at points farther
from the oval window. The main mechanoreceptors for the sense of hearing are the
more heavily innervated inner hair cells in the organ of Corti. The outer hair cells,
with their stereocilia tips embedded in the tectorial membrane, are depolarized
when stereocilia are deformed. Depolarization of the outer hair cells causes these
columnar cells to shorten very rapidly, an effect mediated by an unusual 80-kD
transmembrane protein called prestin abundant in the lateral cell membranes.
Prestin undergoes a voltage-dependent conformational change that affects the
cytoskeleton, rapidly shortening the cells when the membrane is depolarized and
elongating them again with membrane hyperpolarization. Piston-like movements of
the outer hair cells pull down the tectorial membrane against the stereocilia of the
inner hair cells, causing depolarization of these cells which then send the signals to
the brain for processing as sounds. This sequential role for outer and inner hair cells
produces further cochlear amplification of the sound waves.