Tuesday, May 15, 2012

Histology and cytology SBC 204



Cytology = study of cells
Histology = study of tissues

Tissues are:
Collections of specialized cells and cell products organized to perform a limited number of functions

The four tissue types are:
Nerve = control
Muscle = movement
Connective = support
Epithelial = covering


Learning Objective: To identify the components of neural tissue and describe their structure,                        composition & function.

Nervous tissue integrates & coordinates the functions of other tissues in the body
Nervous tissue is primarily cellular in nature. 
Only 20% of the CNS is extracellular space.
Between “Epithelial” &“Connective” Tissues in cellularity
Nervous tissue is made up of basically 2 types of cells:
A.Neurons (nerve cells) - Receive stimuli and transmit action potentials
B.Neuroglia (Gial cells) -Support and protect neurons
                            -Produce myelin,
                    -Nourishment,                                                     -Repair, waste disposal,
                            -Perform phagocytosis
      -Neuroglia outnumbers neurons 10 to 1.
      -smaller than neurons
      -do NOT generate electrical impulses
      -divide by mitosis

Neurons are the principal functional cells of the nervous system
They have a great longevity.
They are amitotic.
They maintain a high metabolic rate.

Structure of a neuron

The cell body or soma contains:
the nucleus
the protein synthesizing components
extensive rough ER known as Nissl bodies for protein synthesis
also contains extensive Golgi.
large number of mitochondria
This part of the cell is the integration part of the neuron.
It can also function as a receptive or input region.
Nucleus (pl. nuclei) is a collection of cell bodies in the CNS. (Grey Matter ; non-myelinated  neurons)
Ganglion (pl. ganglia) is a collection of cell bodies in the PNS.
There are 2 types of processes that extend from neurons:
Dendrites – the main receptive region of the neuron.
Axon– the main signal transmission part of the neuron.
The axon hillock is the initial part of the axon, where the outgoing signal is triggered.
Although only one axon leaves the cell body, this can branch into collaterals ending in the axon terminals.
The terminals release neurotransmitters.
A tract is a collection of axons in the CNS. (White Matter; Myelinated  neurons)
A nerve is collection of axons in the PNS.

            -Cytoplasm = axoplasm
          -Plasma membrane = axolemma
Perikaryon-cytoplasm around the cell body
Axolemma- axon plasma membrane.
Neurilemma – outer layer of myelin sheath
                           – essential for regeneration
Myelin Sheath – a white, multi layered, fatty covering for some nerve processes.                               – arranged in segments, separated by Nodes of Ranvier (enables salutatory                 conduction)
Insulation of nerve process
Increased speed of conduction

Nervous tissue connective sheaths
Endoneurium a delicate connective tissue sheath surrounding each axon
Clusters of axons, Schwann cells, and endoneurial fibroblasts are gathered into bundles called fascicles
Fascicles are encapsulated by a connective tissue sheath of collagen fibers and fibroblasts called the perineurium.
Bundles of fascicles are surrounded by a connective tissue capsule of collagen fibers, adipocytes, and blood vessels called the epineurium

Classification of Neurons
Classified based on:
A.Structural classification – Based on the number of extensions (processes) that extend from                     the neuron's cell body (soma)

B.Functional classification – Based on the direction that they send information

A.Structural classification
1 process that divides into two branches
Part that extends to the periphery has dendrite-like sensory receptors
Found in ganglia of PNS. Example: dorsal root ganglion cells
2.Bipolar neuron
2 processes
Examples: retinal cells, olfactory epithelium cells
3.Multipolar neuron
3 or more processes
most (99%) neurons in CNS
all motor neurons
Examples: spinal motor neurons, pyramidal neurons, Purkinje cells).

B.Functional classification
1.Sensory (afferent): carry impulses/AP from sensory receptors toward CNS
2.Motor (efferent):  carry impulses/AP from CNS to muscles or glands.
3.Interneurons (association neurons): Within CNS, connect sensory & motor neurons

The Reflex Arc
Reflex – rapid, predictable, and involuntary responses to stimuli
Reflex arc – direct route from a sensory neuron, to an interneuron, to an effector
B. Neuroglia
Outnumber neurons by about    10 to 1
6 types of supporting cells
4 are found in the CNS:
a.b)Ependymal Cells
2 are found in PNS
a)Schwann cells or neurolemmocytes
b)Satellite cells


Largest of glial cells
Most numerous
Star shaped with many processes projecting from the cell body
Provide structural support for neurons
Maintain the appropriate chemical environment for generation of nerve impulses/action potentials
Regulate nutrient concentrations for neuron survival
Regulate ion concentrations - generation of action potentials by neurons
Take up excess neurotransmitters
Assist in neuronal migration during brain development
Perform repairs to stabilize tissue
Help form and maintain blood-brain barrier
The expanded endings of the astrocyte processes are known as end-feet. While the blood-brain-barrier is formed by tight junctions between endothelial cells, the end-feet function to induce and maintain the blood-brain barrier by:
removal of potassium ion from vicinity of firing neurons;
removal of glutamate, the principal excitatory transmitter, from vicinity of firing neurons;
metabolism of glutamate to lactate which is then liberated from the astrocyte and may serve as partial energy source for neurons;
production of diverse cytokines

b)Ependymal Cells
Help form choroid plexuses that secrete CSF
Low columnar epithelial-esque cells that line the ventricles of the brain and the central canal of the spinal cord
Some are ciliated which facilitates the movement of cerebrospinal fluid

c)Microglia (Microcytes)

few processes
Small cells found near blood vessels
derived from mesodermal cells that also give     rise to monocytes and macrophages “brain macrophages”
phagocytize cellular wastes & pathogens
migrate to areas of injury where they clear away debris of injured cells - may also kill healthy cells
Take up extracellular K+


fewer processes than astrocytes
 round or oval cell body
Most common glial cell type
Each forms myelin sheath around the axons of neurons in CNS
Analogous to Schwann cells of PNS
Form a supportive network around CNS neurons

Neuroglia of PNS
a)Schwann cells or neurolemmocytes
Form myelin sheaths around the larger nerve fibers in the PNS.
Hold neurons in place
Keep messages from getting scrambled
Increase Speed of Transmission
Vital to neuronal regeneration/Can reconnect a cut axon

b)Satellite cells
Protects neuronal cell bodies in the PNS
Provide support and nutrition

Myelin Sheath is formed by 2 types of Glia
The myelin sheath is the wrapping seen around the axons of some neurons. 
Oligodendrocytes – form myelin sheaths on axons in the CNS
Schwann cells – form myelin sheaths on axons in the PNS
Schwann cells are vital to PNS nerve repair and regrowth of axons of damaged but living neurons
Myelinated fibers can conduct electrical signals much faster than unmyelinated fibers (about 150 times faster).
Gaps between myelin sheath cells are the Nodes of Ranvier.
Voltage gated ion channels only occur at these nodes.
Multiple Sclerosis (MS) leads to demyelination of CNS neurons resulting in numbness and paralysis.

In higher animals, the most rapid and complex intercellular communications are mediated by nerve impulse. A neuron electrically transmits such a signal along its axon as a travelling wave of ionic currents. Signal transmission between neurons, as well as between neurons and muscles or glands, is usually chemically mediated by neurotransmitters.

Neuron Signaling
Neuron cell has sodium-potassium (Na+-K+) pump along its axon
The effect of the Na+-K+ pump is to create a difference between the inside and the outside of a cell.
By actively pumping positively charged sodium ions (Na+) out of the cell (move three Na+ out and 2 K+ in), while leaving behind negatively charged proteins, the cell ends up with more positive charges on the outside and more negative charges on the inside.
Voltage is the measurement used to quantify such a difference in charge.
The basic unit of measure is the volt. For cells, the mV.
The difference in charge (voltage) between the inside and the outside of the cell membrane is also known as the membrane potential difference or just membrane potential.
The resting membrane potential results from the concentrations of ions that are inside & outside the cell and the permeability of the membrane to those ions.
If we measure the membrane potential (difference in charge) between the inside of a neuron and the outside we find that the neuron is more negative inside than outside.
The difference in charge is typically 70 mV.
Because the inside of the cell is more negative, by convention, we say that a cell’s resting membrane potential is –70 mV.
Neurons can use changes in membrane potentials to receive, integrate and send signals.
When a cell has a membrane potential, we say the membrane is polarized (has 2 poles, positive and negative).
Because membrane potentials are differences in electrical charges these signals can be described as electrical signals.
All changes in electrical potential refer to changes from the resting membrane potential of -70mV.
The changes in membrane potential that occur in the dendrites and cell body are of varying strength.
Because the strength varies from weak to strong, these signals are known as “graded” potentials.
If the graded potential is large enough, it can cause the voltage gated channels of the axon to open. Resulting in a cascade of opening voltage gated channels along the axon, known as a nerve impulse or action potential.
Threshold for initiation of an action potential is usually -55 MV
Action Potentials
Action potentials are simply large depolarization’s of the axon made possible by voltage-gated (copy cat) ion channels.
An action potential will only occur if the preceding graded potential (caused by chemically-gated ion channels) was strong enough to cause the voltage-gated ion channels of the axon hillock to open.
Once the voltage-gated ion channels of the axon begin to open at the axon hillock, the wave of depolarization continues along the membrane until it reaches the axon terminal.
As the depolarization of the membrane continues down the axon, the strength of the depolarization remains the same. 
The action potential is an all-or-none phenomenon.
The neuron either fires an action potential or not.

Sodium-potassium (Na+-K+) pump
The effect of the sodium-potassium (Na+-K+) pump is to create a difference between the inside and the outside of a cell.
By actively pumping positively charged sodium ions (Na+) out of the cell (move three Na+ out and 2 K+ in), while leaving behind negatively charged proteins, the cell ends up with more positive charges on the outside and more negative charges on the inside.

action potential/nerve impulse takes place in two stages: depolarizing phase (more positive) and repolarizing phase (more negative - back toward resting potential), followed by a hyperpolarizing phase or refractory period in which no new AP can be generated
Depolarization is movement of resting membrane potential towards zero (0 mV) difference (less polarized). Change from -70mV to +30 mV. Achieved by allowing Na+ in.
Repolarization is the reversal from +30 mV back to  -70 mV)
Hyperpolarization is movement of resting membrane potential away from zero towards an even more negative resting potential (more polarized). Achieved by allowing Cl- in.           -K+ equilibrium potential (hyperpolarization)

Action potential conduction
If an AP is generated at the axon hillock, it will travel all the way down to the synaptic knob.
The manner in which it travels depends on whether the neuron is myelinated or unmyelinated.
Unmyelinated neurons undergo the continuous conduction of an AP whereas myelinated neurons undergo saltatory conduction of an AP.
1.Continuous conduction
Occurs in unmyelinated axons.
In this situation, the wave of de- and repolarization simply travels from one patch of membrane to the next adjacent patch.
E.g along the sarcolemma of a muscle fiber

2.Saltatory conduction
Occurs in myelinated axons
Saltare is a Latin word meaning “to leap.”
Recall that the myelin sheath is not completed.  There exist myelin free regions along the axon, the nodes of Ranvier

Nerve impulse velocity is increased by Myelination
Impulses in myelinated nerves propagate with velocities of up to 100m.s-1, whereas those in unmyelinated nerves are no faster than 10 m.s-1

How does myelination increase the velocity of nerve impulses? Myelin sheaths are interrupted every millimeter or so along the axon by narrow unmyelinatated gaps known as nodes of Ranvier, where the axon contracts the extracellular medium. Binding studies using radioactive tetrodotoxin indicate that the voltage-gated Na+ channels of unmyelinated axons have rather sparse although uniform distributions in the axonal membrane of ~20 channels. µm-2. In contrast, the Na+ channels of myelinated axons occur only at the nodes of Ranvier, where they are concentrated with a density of ~104 channels. µm-2.  The action potential of a myelinated axon evidently hops between these nodes, a process named saltatory conduction (latin: saltare, to jump). Nerve impulse transmission between the nodes must therefore occur by the passive conduction of an ionic current a mechanism that is inherently much faster than the continuous proportion of an action potential but that is also dissipative. The nodes act as amplification stations to maintain the intensity of the electrical impulses as it travels down the axon. Without the myelin insulation, the electrical impulse would become too attenuated through transmembrane ion leakage and capacitive effects to trigger on action potential at the next node. Infact, multiple sclerosis, an autoimmune disease that demyelinates nerve fibers in the brain and spinal cord, results in serious and often fatal neurological deficiencies. 

All-or-Nothing Principle.
Once an action potential has been elicited at any point on the membrane of a normal fiber, the depolarization process travels over the entire membrane if conditions are right, or it does not travel at all if conditions are not right. This is called the all-or-nothing principle, and it applies to all normal excitable tissues. Occasionally, the action potential reaches a point on the membrane at which it does not generate sufficient voltage to stimulate the next area of the membrane. When this occurs, the spread of depolarization stops. Therefore, for continued propagation of an impulse to occur, the ratio of action potential to threshold for excitation must at all times be greater than 1. This “greater than 1” requirement is called the safety factor for propagation.

Plateau in Some Action Potentials
In some instances, the excited membrane does not repolarize immediately after depolarization; instead, the potential remains on a plateau near the peak of the spike potential for many milliseconds, and only then does repolarization begin. Such a plateau greatly prolongs the period of depolarization. This type of action potential occurs in heart muscle fibers, where the plateau lasts for as long as 0.2 to 0.3 second and causes contraction of heart muscle to last for this same long period. The cause of the plateau is a combination of several factors. First, in heart muscle, two types of channels enter into the depolarization process: (1) the usual voltage-activated sodium channels, called fast channels, and (2) voltage-activated calcium-sodium channels, which are slow to open and therefore are called slow channels. Opening of fast channels causes the spike portion of the action potential, whereas the slow, prolonged opening of the slow calcium-sodium channels mainly allows calcium ions to enter the fiber, which is largely responsible for the plateau portion of the action potential as well. A second factor that may be partly responsible for the plateau is that the voltage-gated potassium channels are slower than usual to open, often not opening very much until the end of the plateau. This delays the return of the membrane potential toward its normal negative value of –80 to –90 millivolts.

Inhibitors of voltage-Gated Na+ channel
a.Local Anesthetics.
Among the most important stabilizers are the many substances used clinically as local anesthetics, including procaine and tetracaine. Novocaine and lidocaine – blocks nerve impulses along nerves that detect pain. Most of these act directly on the activation gates of the sodium channels, making it much more difficult for these gates to open, thereby reducing membrane excitability. When excitability has been reduced so low that the ratio of action potential strength to excitability threshold (called the “safety factor”) is reduced below 1.0, nerve impulses fail to pass along the anesthetized nerves.
b.Neurotoxins including: Tetrodotoxin, Saxitoxin, Batrachotoxin.

Nerve impulses are chemically transmitted across most synapses by the release of neurotransmitters. Acetylcholine (ACh), the best characterized neurotransmitter, is packaged in synaptic vesicles that are exocytotically released into the synaptic cleft. This process is triggered by an increase in cytosolic [Ca+] resulting from the arriving action potential’s opening of voltage-gated Ca2+ channels. The ACh diffuses across the synaptic cleft, where it binds to the ACh receptor, a transmembrane cation channel that opens in response to ACh binding. The resultant flow of Na+ into and K+ out of the postsynaptic cell depolarizes the postsynaptic membrane, which, if sufficient neurotransmitter has been released, triggers postsynaptic action potential. The ACh receptor is the target of numerous deadly neurotoxins, including histrionicatoxin, d-tubocurarine, α-bungarotoxin, erabutoxin and cobra toxin, which all bind to the ACh receptor so as to prevent its opening. The ACh is rapidly degraded, before the possible arrival of the next nerve impulse, through the action of acetylcholinesterase, a fast-acting serine esterase that has an unusual aromatic side chain-lined active site gorge. Nerve gases (tabun & sarin) and Succinylcholine inhibit acetylcholinesterase and therefore block nerve impulse transmission at cholinergic synapses.
Many specific regions of the nervous system employ neurotransmitters other than ACh. Most of these neurotransmitters are amino acids, such as glycine and glutamate, or their decarboxylation products and their derivatives, including, GABA, histamine, and serotonin. Many of these compounds are also hormonally active, but are excluded from the brain by the blood-brain barrier. Although many neurotransmitters, such as ACh, are excitatory, others are inhibitory. The latter stimulate the opening of anion (Cl-) channels, thereby causing the postsynaptic membrane to become hyperpolarized, so that it must be more depolarized than otherwise to trigger an outgoing action potential. There is also a growing list of polypeptide neurotransmitters, many of which are also polypeptide hormones that elicit complex behavior patterns.   

    Neurotransmitter Removal
NTs are removed from the synaptic cleft via: Enzymatic degradation, Diffusion or reuptake

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