The autonomic nervous system (ANS) is activated by centres within the spinal cord, brain stem and hypothalamus, and also by portions of the cerebral cortex, especially the limbic system, via the hypothalamus. Efferent autonomic signals are transmitted to the body by either the sympathetic or parasympathetic division. In the ANS, both the sympathetic and parasympathetic ganglia are supplied by preganglionic fibers that exit the CNS. A ganglion (pl. gangia) is a collection of neuronal cell bodies outside the CNS. Within the sympathetic nervous system, ganglia are of two types: paravertebral ganglia and prevertebral ganglia. Paravertebral ganglia lie next to the vertebrae, concentrated in two long chains that extend on either side of the spinal column, from the neck to the coccyx, and are all interconnected. Prevertebral ganglia are located in front of the vertebrae, supplying the viscera with sympathetic nerves. Preganglionic nerves in the sympathetic nervous system are short, synapsing with a postganglionic nerve that is much longer. Parasympathetic ganglia, on the other hand, are located close to the effector they innervate. Thus, the preganglionic fibers in the parasympathetic division are long and the postganglionic fibers are short, opposite of the sympathetic nervous system. The functional difference between this arrangement is that parasympathetic responses are rapid and precise, and more likely to affect a single effector, such as a specific organ. Sympathetic responses, on the other hand, tend to be slower and more diffuse, affecting the entire body (e.g. the “fight or flight” response). Not all sympathetic responses are diffuse however: pupil dilation and sexual orgasm are both sympathetic responses that need not occur simultaneously, otherwise going from a brightly lit room into a darkened one could be a potentially embarrassing situation. The primary difference, therefore, between the parasympathetic and sympathetic nervous systems is anatomical placement, and secondarily, their function.
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
There are two principle types of synapses found in the ANS, called cholinergic and adrenergic. Cholinergic synapses are nerve synapses that release acetylcholine (ACh), whereas adrenergic synapses release epinepherine (E) and norepinepherine (NE). All preganglionic nerves are cholinergic in both the sympathetic and parasympathetic divisions. Postganglionic nerves of the parasympathetic system are also cholinergic. After binding with the receptor site and initiating a nervous impulse in the postsynaptic neuron, ACh quickly degrades into acetic acid and choline under the influence of an enzyme called acetylcholinesterase (AChE). Choline is then pumped back into presynaptic neuron to be recycled into ACh. Cholinergics are exogenous substances (e.g. drugs, botanical agents and bacterial toxins) that promote the release, prevent the degradation or otherwise enhance the actions of ACh. Anticholinergics are exogenous substances (e.g. drugs, botanical agents and bacterial toxins) that inhibit the synthesis, release or receptor binding of ACh. Cholinergic receptors are of two basic types: nicotinic receptors, located in the brain, smooth muscle, heart and glands such as the adrenal medullae; and muscarinic receptors, located in the brain, sweat glands and blood vessels. The binding and stimulation nicotinic receptors leads to the upregulation of autonomic functions such as increased muscle tone, blood pressure and heart rate. Nicotinic receptors are called such because the alkaloid nicotine (derived from tobacco) was found to stimulate both sympathetic and parasympathetic postganglionic nerves. Examples of exogenous agonists to nicotinic receptors include nicotine from tobacco and the piperidine alkaloids of Lobelia inflata. An example of a nicotinic antagonist is curare, a plant poison coated on arrows used by some of the First Nations people in South America to bring down prey. The binding and stimulation of muscarinic receptors promotes parasympathetic responses such as sweating, salivation, pupil constriction, peristalsis, hypotension and a decrease of heart rate. Muscarinic receptors are also associated with learning, memory, posture and temperature regulation. Muscarinic receptors are called such because
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
the alkaloid muscarine, derived from the mushroom Amanita muscaria, was found to stimulate parasympathetic responses. An example of a muscarinic agonist is pilocarpine, an alkaloid of Pilocarpus jaborandi used in the treatment of glaucoma. An example of a muscarinic antagonist are the tropane alkaloids (atropine, hyoscine and hyoscyamine) found in Atropa belladonna, Datura stramonium and Hyocyamus niger, sympathomimetics used in the treatment of cerebral palsy and Crohn’s disease. Adrenergic synapses are nerve synapses that release epinepherine and nor-epinepherine. Most postganglionic sympathetic neurons are adrenergic. Adrenergics are agents that accumulate in the synaptic cleft and lead to an increase in norepinepherine release, such as amphetamines, the amino acid tyramine, and the alkaloid ephedrine from Ephedra sinica. Adrenergic receptors are of two major types, alpha (α) and beta (β), and have somewhat opposing effects. Alpha receptors are stimulated primarily by norepinepherine and to a lesser extent by epinepherine, and promote vasoconstriction, iris dilation, intestinal relaxation, intestinal sphincter contraction, pilomotor contraction and bladder sphincter contraction. An example of an α-receptor antagonist is the alkaloid yohimbine from Pausinystalia yohimbe, which induces a downregulation of α-adrenergic function. There are two primary types of b-receptors, stimulated mostly by epinepherine, and to a lesser extent by norepinepherine. Stimulation of β1-receptors cause cardioacceleration, increased myocardial strength and lipolysis. Stimulation of β2-receptors cause vasodilation, intestinal relaxation, uterine relaxation, bronchodilation, glycogenolysis and bladder wall relaxation. Many botanicals such as Cimicifuga racemosa and Viburnum opulus are β2-agonists, and are thus uterine antispasmodics. Pharmaceuticals used to inhibit β-adrenergic activity are called “beta-blockers,” and are often used in the treatment of hypertension and angina pectoris. Some of these drugs, such as propranolol hydrochloride, are non-specific beta-blockers, inhibiting both β1 and β2-receptors. While these drugs may be effective for reducing blood pressure, they can have unwanted side-effects such as bronchoconstriction, mediated by β2-receptors. If these side effects pose any risk, a β2-receptor blocker, such as metoprolol hydrochloride may be used instead.
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
The relative effects of norepinepherine and epinepherine on different effector organs is determined by the types of receptors in the organs. If they are all β-receptors, for example, then epinepherine will be a stimulant. If the effector contains both α and β-receptors then the activity of epinepherine will be considerably less.
II. Neurotransmitters
A c e t y l c h o l i n e It’s difficult to say with any surety what the effect of acetylcholine (ACh) is on the brain, because depending upon the nature of the postsynaptic neurons, ACh may be excitatory or inhibitory. Within the brain cholinergic pathways can be organized into those which function locally, and those that connect two or more different regions. Of the cholinergic pathways that are of the latter type, two major constellations have been found, in the basal forebrain and in the pontomesencephalotegmental cholinergic complex, and together these pathways extend to almost all areas of the brain. Within cholinergic neurons acetylcholine is synthesized in a reaction catalyzed by choline acetyltransferase (CAT), combing acetyl coenzyme A with choline to form ACh and coenzyme A (CoA). Choline appears to be the rate-limiting factor in the synthesis of ACh. The release of ACh is stimulated by the invasion of an action potential into the synaptic bulb, causing the intracellular flow of Ca2+, which in turn promotes exocytosis of the synaptic vesicles and the release of ACh into the synaptic cleft. ACh is rapidly degraded by acetylcholinesterase to choline and acetic acid. Choline is then taken up by the presynaptic neuron to resynthesize ACh. There is some evidence to suggest that ACh may participate in pain reception. That the tiny hairs of the botanical Urtica dioica contains ACh, as well as histamine, indicates a relationship between ACh and pain. ACh may also act as a sensory transmitter in thermal receptors, taste fiber endings and chemoreceptors.
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
Acetylcholine plays a role in a few nervous disorders, such as myasthenia gravis, an autoimmune disorder that directs antibodies against ACh. Alzheimer’s disease and Huntington’s chorea involve the destruction of cholinergic pathways in the brain.
A m i n o a c i d n e u r o t r a n s m i t t e r s
Glutamic acid Glutamate is found in uniquely high concentrations in the CNS and it has been known for some time that it can exert a powerful stimulatory effect on neuronal activity. Within the brain L-glutamate is synthesized in presynaptic neurons by two sources: from glucose, via the Krebs cycle and the transamination of a-oxoglutatrate, and from glutamine that is synthesized in glial cells, transported into nerve cells and converted into glutamate by glutaminase. Synaptic vesicles containing L-glutamate are induced to exocytosis by the depolarization of the terminal end of the presynaptic axon and the movement of Ca2+ into the intracellular fluid. Glutamate binds with receptors on the postsynaptic cell and promotes the opening of chemically gated ion channels permeable to Na+ and Ca2+. After causing the depolarization of the postsynaptic cell, glutamic acid is reabsorbed by the presynaptic neuron, or taken up by the glial cells and converted into glutamine by glutamine synthetase. Although glutamate is ubiquitous in the CNS, it seems to be predominant in the spinal cord, released by primary afferent nerve endings. Other high-density regions for glutamate include the hippocampus and cerebral cortex. Glutamate, as well as aspartate, are called excitatory amino acids (EAAs) and bind to at least five different receptor subtypes that have slightly different activities, some to initiate fast EPSPs and some initiate slow EPSPs. EAA receptors appear to play an important role in memory and learning. A relative deficiency of EAAs has been implicated in long term depression. Excessive levels of EAAs, however, have been implicated in neurotoxicity and brain cell damage, and play a role in the neurodegenerative aspects of such diseases as Huntington’s disease, cerebral ischemia, epilepsy, hypoglycemia and AIDS. Neurolathyrism is a spastic disorder common to East Africa and Southern Asia that is associated with the consumption of chick peas (Lathyrus sativus), which contains the amino acid b-N-oxalylamino-L-alanine (BOAA) and is an agonist to a specific EAA receptor subtype. The consumption of
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
domoic acid, synthesized by seaweeds and consumed by mussels that feed on the seaweed, is a potent excitatory neurotoxin that can damage the hippocampus and produce dementia. An outbreak of domoic poisoning occurred in 1987 in British Columbia.
Gamma aminobutyric acid (GABA) GABA is also an important neurotransmitter in the human body, found in no other location except the CNS and the retina. GABA is synthesized from glutamic acid by glutamic acid decarboxylase (GAD) and has a discrete distribution in the brain, primarily in the superior and inferior colliculi, thalamus, hypothalamus and occipital lobes of the cerebrum. The enzyme GAD requires pyridoxal phosphate (vitamin B6) as a coenzyme, and the use of this vitamin is an important adjunct in the treatment of seizure disorders. GAD is also known to coexist in the b-cells of the pancreas, perhaps playing a role in the endocrine pancreas. In almost all type I diabetes patients antibodies to GAD can be observed, and it is thought that it is these antibodies that are responsible for the destruction of the pancreatic b-cells. GABA is metabolized by GABA-transaminase, which also requires vitamin B6 as a cofactor, into succinic semialdehyde. There are two major types of GABA receptors in the human brain that have been determined largely through pharmacological evidence, GABAA and GABAB. The binding of GABA to GABAA receptors causes a shift in the membrane permeability to inorganic ions, in particular to chloride, inhibiting the firing of the neurons by inducing a state of hyperpolarization. Thus GABAA receptors have an inhibitory action in the CNS. Benzodiazepines and barbiturates are commonly used drugs that function as GABAA agonists by enhancing the electrophysiological effects of GABA. Other drugs, including muscimole, a metabolite of Amanita muscaria that appears upon drying, and the volatile oil isovaleric acid and valepotriates of Valeriana officinalis, appear to be GABA mimetics. Other botanicals which either improve receptor sensitivity to GABA or are GABA mimetics include Passiflora incarnata, Withania somniferum and Tilia cordata. Certain hormones are also known to bind with GABAA receptors, such as deoxycorticosterone and progesterone, and thus hormonal changes experienced during puberty, pregnancy and during the luteal phase of the menstrual cycle could account for certain behavioral adaptations to stress.
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
GABAB receptors are present in lesser volume than GABAA receptors, and the binding of GABA to GABAB receptors initiate inhibitory postsynaptic potentials by increasing the transmembrane permeability of K+. GABAB receptors are unaffected by GABAA agonists, and GABA antagonists appear to have none of the activity on GABAB receptors as they do on GABAA receptors (i.e. seizure). This has lead to the hypothesis that GABAB receptors may only be activated under certain psychological states. GABA appears to have an inhibitory (hyperpolarizing) activity in the brain, but an excitatory (depolarizing) role in the spinal cord. Within the brain GABA is released in amounts up to three times higher in delta wave EEG patterns than in alpha wave patterns. It is interesting to note that there is a 30-40% increase in GABA levels postmortem, in part resulting from a transient activation of GAD.
Glycine Glycine is a simple amino acid that is ubiquitous in the human body, essential in the metabolism of protein, peptides, nucleic acids, porphyrins and bile salts, as well as neurotransmitters in the CNS. Little is known about glycine synthesis and metabolism, but much evidence has been accumulated to suggest that it is an inhibitory neurotransmitter, primarily in the gray matter of spinal tissue. Glycine also seems to play an important role in increasing the responsive of EAA receptors.
B i o g e n i c a m i n e n e u r o t r a n s m i t t e r s The biogenic amines are monoamine neurotransmitters synthesized from dietary sources of amino acids. The monoamines include the catecholamines and the indolamines. The monoamines (dopamine, epinepherine, norepinepherine) are derived from tyrosine, and are called the catecholamines due to a common catechol nucleus (a six carbon benzene ring and two adjacent hydroxyl groups) and an amine group. Inactivation of these catecholamines occurs after they are pumped back into the presynaptic neuron and destroyed by either catechol-O-methyltransferase (COMT), monoamine oxidase (MAO), or recycled back into synaptic vesicles. The indolamines (serotonin and melatonin) are derived from tryptophan, and are degraded only by MAO. MAO inhibitors such as phenelzine are drugs that prolong the activity of monoamine neurotransmitters and act as
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
stimulants and antidepressants. Drugs such as cocaine disable the active transport mechanisms of these neurons and also prolong the life of the monoamines. Dopamine Neurons that contain dopamine (DA) are clustered primarily in the midbrain within the substansia nigra. Some of the dopaminergic axons project from the substansia nigra into the cerebral cortex, where DA is thought to be involved in emotional responses. Other axons project into areas of the basal ganglia, where DA is known to have an inhibitory activity upon the autonomic movements of the skeletal muscles, lending stability to motor control. It is the destruction of these dopaminergic neurons in the basal ganglia that plays a role in the dopamine deficiency of Parkinson’s disease. Dopamine synthesis, like all of the catecholamines, is derived from the non-essential amino acid tyrosine, synthesized from phenylalanine in the liver by phenylalanine hydroxylase, and is transported across the BBB into dopaminergic neurons. The absorption of tyrosine, as well as tryptophan (which is used in serotonin production) is regulated by the presence of other amino acids that compete for absorption. In conditions such as phenylketonuria1 in which serum levels of phenylalanine are abnormally high, both tyrosine and tryptophan uptake by the brain may be diminished. Once tyrosine enters the neuron it is converted into L-dihydroxyphenylalanine (L-DOPA) by tyrosine hydroxylase (TH). The activity of TH is dependent upon molecular O2, Fe2+ and a tetrahydropteridine cofactor. L-DOPA is then rapidly converted into DA by L-aromatic amino acid decarboxylase, which is dependent upon pyridoxal phosphate (vitamin B6) as a cofactor. A deficiency of vitamin B6 can interfere with the rate of repletion of adrenal catecholamines. Calcium dependent release of dopamine is thought to occur as the result of an action impulse reaching the terminal end of the axon. The release of dopamine appears to be
1 Phenylketonuria is a defect of metabolism that is characterized by an elevation of phenylalanine in the blood, due to a genetic deficiency of the enzyme phenylalanine hydroxylase which converts phenylalanine into tyrosine. Excessive levels of phenylalanine in early development leads to brain damage and mental retardation. It is prevented by performing a PKU test on newborns, and in positive infants, special steps are to limit dietary phenylalanine.
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
dependent upon the rate and pattern of neuronal firing. Dopamine release is also inhibited by the presence of presynaptic release-modulating autoreceptors. Upon release and stimulation of the postsynaptic cell, DA is rapidly metabolized into dihydroxyphenylacetic acid (DOPAC) by intracellular MAO after reuptake by the presynaptic neuron. The majority of the released DA in the human brain however is converted into homovanillic acid (HVA) by MAO, and concentrations of HVA in the brain and CSF can be used as an index of dopaminergic activity. Reduction of HVA from normal can be detected in the CSF of patients with Parkinson’s disease. At present there are five postsynaptic receptors of DA, and D2 in particular is thought to be associated with behaviour and emotion. In post mortem studies of dopamine receptors in schizophrenia, the number of D2 receptors appear to be abnormally elevated. Some herbs, specifically Vitex agnus castus, appear to have a dopaminergic activity. This is why Vitex is useful in hyperprolactinemia, since dopamine is a prolactin antagonist. Norepinepherine and epinepherine Like dopamine, norepinepherine (NE) and epinepherine (E) belong to a class of compounds called catecholamines. Epinepherine, and to a lesser extent, norepinepherine, are concentrated in the tissues of the adrenal medullae and are secreted in response sympathetic stimulation. The adrenal medullae are actually modified sympathetic ganglionic fibers, as opposed to an effector organ, and secrete E and NE directly into the blood stream. The highest concentration of these compounds in the brain is usually found in the hypothalamus and other areas of central sympathetic representation, more often in gray rather than white matter. As previously mentioned, all of the catecholamines require tyrosine as the base nutrient for their creation. Tyrosine is converted into L-DOPA by TH, and L-DOPA is converted into NE by the enzymatic activity of dopamine-b-hydroxylase. This enzyme is dependent upon molecular O2 and ascorbic acid (vitamin C) as cofactors. NE can be further synthesized into E by phenylethanolamine-N-methyl transferase. The enzymes that facilitate the metabolic degradation of the
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
catecholamines are MAO and catechol-O-methyltransferase. The presynaptic release of catecholamines is generally dependent upon Ca2+, and a deficiency of serum Ca2+ can inhibit their release. Drugs such as cocaine, amitryptaline and other related tricyclic antidepressants inhibit the reuptake of norepinepherine, allowing it to linger longer in the synaptic cleft. These drugs, along with MOA inhibitors, potentiate adrenergic transmission. “Adrenal stress” is a term often used by herbalists in a rather unspecific way, to describe, in part, a depletion of the cofactors needed to secrete NE and E. The theory is that there is some disruption to homeostasis, typically sympathetic in origin, but diffuse and mediated by external factors such as social customs and life experiences. These stressors of ‘everyday life’ causes physical reactions that: 1) cause an increase in the utilization of O2 and vitamin C, and; 2) cause physical reactions such as visceral vasoconstriction that inhibit nutrient supply to key organs, creating an even greater need for these and other nutrients. It is a subtle group of mechanisms at best, addressed by herbalists with comparatively subtle remedies and nutritional supplementation. The adrenal stress dynamic also refers to the exhaustion of the adrenal cortex in its role as a mediator of sympathetic stress as well, and a relative deficiency of adrenal cortical secretion. There are two major clusterings of norepinepherine cell bodies in the brain, one localized in an area called the locus ceruleus, contained within the caudal pontine central gray anterior to the cerebellum, and the other, scattered loosely through the ventral tegmental fields. Noradrenergic pathways that have been studied physiologically are efferent fibers from the locus ceruleus to the cerebellum, the hippocampus, and the cerebral cortex. Noradrenergic neurons of the lateral tegmental fields send fibers downward into the mesencephalon and the spinal cord, and anteriorly to the forebrain and diencephalon, including the amygdala. Norepinepherine has been implicated in maintaining arousal, dreaming and the regulation of mood. There are considerably fewer epinepherine-containing neurons than noradrenergic neurons, but their discrete anatomical distribution in the brain is believed to play a
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
unique role in assisting in neuroendocrine control and blood pressure regulation. Serotonin Serotonin (5-hydroxytryptamine, or 5-HT) is found in many cells that are not neurons, including platelets, mast cells and the enterochromaffin cells of the intestinal mucosa. Only 1 – 2% of the serotonin that is produced in the body is actually made in the brain, but since this neurotransmitter cannot pass the BBB, the brain must manufacture its requirements. Serotonin synthesis in the brain begins with the amino acid tryptophan derived from the diet. The botanical Avena sativa is exceptionally high in this amino acid, but there are many other sources of dietary tryptophan, including turkey, eggs and aged cheeses. The rate-limiting enzyme tryptophan hydroxylase (TH) then acts upon tryptophan to complete its hydroxylation into 5-hydroxytryptophan (5-HTP), which undergoes almost immediate decarboxylation by amino acid decarboxylase (AADC) to form 5-hydroxytryptamine (5-HT). Drugs such as Lithium increase tryptophan uptake by the brain, increasing the amount of 5-HT produced. Over a 14 – 21 day period however, tryptophan uptake is still increased, but the activity of TH is gradually decreased so that normal levels of 5-HT are eventually produced. In manic depressive-psychosis there is a minimum of 7 – 10 days before Lithium can foster this state of equilibrium. The activity of TH also appears to be dependent upon the level of molecular oxygen in the brain, and in rats permitted to breathe 100% O2 the level of 5-HT is greatly increased. The administration of the precursor 5-HTP avoids the rate-limiting activities of TH and results in the non-specific formation of serotonin in any sites containing AADC. Serotonin production is particularly concentrated in an area of the brain stem called the raphe nuclei, which enervates areas of the hypothalamus involved with pituitary releasing hormones such as prolactin, growth hormone and adrenocorticotropin. All the enzymes needed to produce 5-HT are also found in the pineal gland however, and 5-HT concentrations within the pineal are 50 times greater (per gram) than in the rest of the brain. Within the pineal, 5-HT undergoes two additional enzymatic steps to form melatonin. Melatonin production is increased by darkness and decreased by light, and its secretion has a suppressive
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
effect upon sexuality. Perhaps the increasing conversion of 5-HT to melatonin during the winter season is a possible cause of seasonal affective disorder (SAD). At present, there are at least eight subtypes of serotonin receptors known to exist in the brain, and fifteen total in the whole body. Upon release free serotonin in the synaptic cleft is metabolized by MAO into 5-hydroxyindolacetaldhehyde, which is further oxidized into 5-hydroxyindoleacetic acid (5-HIAA). Drugs such as isocarboxazid (Marplan®) and phenelzine (Nardil®) inhibit the activity of MAO, and although it is still being argued, some feel that the botanicals Hypericum and Passiflora are MAO inhibitors. Another mode of serotonin metabolism is its uptake by the presynaptic neuron into synaptic vesicles. Some antidepressant drugs such as fluoxetine (Prozac®) and sertraline (Zoloft®) selectively inhibit the reuptake of 5-HT by the presynaptic neuron, as dose cocaine. Serotinergic activity cannot be characterized simply: it seems to be responsible in coordinating a wide range of complex sensory and motor patterns during varied behavioral states. Serotinergic activity has been found to be highest during periods of arousal, reduced in quiet waking, reduced even more in slow-wave sleep and absent during REM sleep. An increase in the activity of serotinergic neurons during waking states serves to enhance motor neuron excitability. A suppression of sensory input during REM sleep impedes motor activity, even though there is increased internal arousal. Altered serotinergic function has been reported in several psychopathological conditions, including schizophrenia, hyper-aggressive states, major depression, anxiety, eating disorders, migraine, obsessive compulsive disorder and suicidal behaviour. The diversity of receptors and receptor subtypes in different areas of the brain, as well as other factors in serotonin metabolism, help to explain why it’s possible for a single neurotransmitter to be associated with such a large array of behaviours, clinical conditions and drug activities. There is a wide range of psychotropic agents that are known to affect 5-HT neurotransmission including antidepressants (e.g. fluoxetine), antipsychotics (e.g. clozapine), antiemetics (e.g. ondansetron), appetite suppressants (e.g. fenfluramine) and antimigrane drugs (e.g. sumatriptan), all working in a unique fashion.
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
Hallucinogens such as lysergic acid diethylamide (LSD) and psilocin are said to affect 5-HT neurotransmission as well, and can be either serotinergic agonists or antagonists dependent upon their location within the brain (i.e. the mode by which LSD functions in the brain is still poorly understood).
N e u r o a c t i v e p e p t i d e s The neuropeptides represent the brave new world of neuropharmacology. New peptides are constantly being discovered and the race is on to understand their biological properties so pharmacologists can tweak them and pharmaceutical manufacturers can amass even greater fortunes. So far they are the largest family of neurotransmitters, and can have both inhibitory and excitatory activities. Neuropeptides consist of chains of 3 to about 40 amino acids. In 1974 scientists discovered that certain neurons in the brain have receptors for opiate drugs such as heroin and morphine. The quest to find the endogenous complement to these drugs provoked the discovery of the first neuropeptides. These two molecules, comprised of a chain of 5 amino acids, were enkephalin and endorphin. Candice Pert’s book, Molecules of Emotion, provides an interesting human insight into how she and her colleagues discovered these compounds. Some of the more important neuropeptides, beyond the two already mentioned, include substance P, dynorphin, hypothalamic regulating hormones, angiotensin II, cholecystokinin, oxytocin and vasopressin. Neurons that secrete peptides are different from other neurons in the manner of how each synthesizes its respective neurotransmitters. Unlike amino acid or monoamine-releasing neurons that utilize dietary sources of amino acids for synthesis, synthesis of neuroactive peptides is directed by mRNA on ribosomes, located only in the dendrites or cell bodies of peptide-secreting neurons. This synthesis creates large protohormones, which are then cleaved by proteolytic enzymes, packaged into vesicles in the smooth endoplasmic reticulum and transported to the axon terminals for eventual release. The release of neuroactive peptides seems to be mediated, however, by the same factors that are responsible for neurotransmitter release in the monoamine and amino acid secreting neurons. An action potential travels down the axon and invades the synaptic bulb, initiating the influx of
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
extracellular Ca2+, thereby promoting exocytosis of the neuroactive peptides. The postsynaptic effects of neuropeptides, as well, appear to be similar to its cousins, regulating ion channels through secondary messengers. Neuropeptides also seem to exhibit many properties of hormones however, such as the capacity to target sites that are distant from the site of release. Additionally, the immune system seems to be much more closely linked to the nervous system that was previously realized. Lymphocytes have been found to manufacture and secrete neuropeptides, such as endorphins. Candice Pert describes in Molecules of Emotion how she and her associate found that every known neuroactive peptide receptor present in the brain could be found on the plasma membrane of a monocyte. Neuropeptides challenge orthodox ideas about how the nervous system works, and the belief that the nervous system is in any way independent from other bodily systems. At one time all pharmacologists believed that there were only two kinds of autonomic neurons, cholinergic and adrenergic. But soon neuroactive peptides began to show up in autonomic neurons where they shouldn’t be found. So far, neuropeptides have been found in every neuron that has been looked at, and in many non-nervous tissues. This has lead to the theory that neuropeptides may be used to modulate the activity of neurotransmitters to refine the postsynaptic effect. It also shows, as Candace Pert postulates, that neuropeptides may be a link between the diverse functions of different body systems, possibly regulated by emotional control. Interest in neuropeptides has sparked a whole new discipline called psychoneuroimmunology (PNI) that will no doubt change many orthodox ideas of how the body works.
Enkephalins Enkephalins are concentrated in the thalamus, the hypothalamus, parts of the limbic system and in spinal pathways that relay impulses for pain. They are believed to be the body’s way of mediating the negative effects of pain by suppressing substance P release, and are on average, over 200 times stronger than morphine. The effects, however, are short lived. Dynorphins Dynorphins are found in the posterior pituitary gland, hypothalamus and small intestine. Like enkephalins,
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
dynorphins are important in mediating the effects of pain by inhibiting substance P release, and seem to have some activity in controlling emotion. Endorphins Endorphin is a generalized term for any endogenous agent that resembles morphine. They are concentrated in the pituitary gland and function similarly to enkephalins in inhibiting substance P release. Endorphins have also been linked to improved memory and learning, feelings of pleasure and euphoria, control of body temperature, the initiation of puberty and sexual activity. Substance P Substance P is found in sensory nerves, spinal cord pathways and parts of the brain associated with pain transmission, such as the substansia nigra, basal ganglia, amygdala, hypothalamus and cerebral cortex. When it is released from neurons, substance P transmits pain-related input from the peripheral pain receptors into the CNS. Substance P has also been found to counter the activities of neurotoxins, prompting speculation that it might be useful nerve degeneration. Capsicum spp. is a counter-irritant to sensory nerve endings and is known to promote the release of substance P. N i t r i c o x i d e Nitric oxide (NO) is a gas that is found throughout the body, as a neurotransmitter and a regulatory molecule, but also as a toxin, used by components of the immune system to kill microbes and tumor cells, and has been implicated in the production of a free radical called peroxynitrite, when it reacts with super oxide. Nitric oxide is formed by the combination of a single atom of oxygen and a single atom of nitrogen, catalyzed by the enzyme nitric oxide synthetase from the amino acid arginine. Unlike other neurotransmitters NO is not synthesized in advance, but is formed on demand and acts immediately. The activities of NO were first elucidated when it was discovered that endothelial cells release NO to promote vasodilation (and was previously called endothelium-derived relaxing factor, EDRF), which is the activity that is harnessed by the drug sildenafil (Viagra) that promote erections in men. NO is thought to play a role in memory and learning
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
E i c o s a n o i d s Arachidonic acid is synthesized from dietary linoleic acid and is responsible for a large number of metabolites called eicosanoids. There are three major groups of eicosanoids, the prostaglandins, leukotrienes and thromboxanes. The activity of these compounds has been well studied and although they seem to play an important modulatory role in nervous tissue, how and where they act is still a question. Unlike neurotransmitters they are not stored in tissues but are synthesized on demand, acting for short periods of time in very low concentrations. The eicosanoids perhaps act as secondary messengers: a neuroactive substance binds with its receptor and either inhibits or stimulates the release of an enzyme called phospholipase A2. This enzyme then promotes the release of arachidonic acid from phospholipids, which undergoes further enzymatic change by either lipoxygenase, cyclooxygenase or epoxygenase to form leukotrienes (LTs), hydroxyeicosatetraenoic acids (HETEs), prostaglandins (PGs), thromboxanes (TXs) and epoxides. Researchers have had difficulties in developing assay techniques for these chemicals but it has become clear that they have a profound activity in neurophysiology. In the late 1980’s, researchers found a specific protein receptor for tetra-hydrocannabinol (THC), the active ingredient of marijuana, in mouse nerve cells. THC is well known for its activity to promote changes in mood, memory, appetite, movement and perception, and pain. The wide-ranging activities of THC are probably due to an abundance of THC receptors found in many parts of the brain including the hippocampus, basal ganglia and cerebral cortex. It is unlikely however, that THC receptors evolved for the singular purpose of ‘getting high,’ so researchers put themselves to the task of finding an endogenous compound that binds with these receptors. In the early 1990’s a fat soluble hair-pinned shaped chemical was teased out from bovine brain tissue which bound to these receptors to cause a parallel activity to THC, and was termed anandamide (arachidonoylethanolamine), from the Sanskrit word ‘ananda,’ meaning ‘bliss.’ It appears that the brain is able to enzymatically synthesize anandamide and the existence of cannabinoid receptors for this eicosanoid suggests the presence of anandamide-containing (anandaergic) neurons. Researchers so far have been unable to create a compound that has all of the benefits of anandamide, such as its antispasmodic properties, without also creating the characteristic mood altering effects. The
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
medical use of marijuana has become a prominent issue in our society, and even though the jury is still out as to the negative, cumulative effects of using this drug, it’s usage, both medically and recreationally, is unlikely to go away any time soon.
III. The senses
Sensation is the conscious or sub-conscious awareness of external and internal stimuli. The nature of the sensation and the reaction elicited varies according to the destination of the afferent nerve in the CNS. Perception is our conscious awareness, that which interprets the sensory experience. In order for us to be aware of particular sensations, they must be received by the cerebral cortex, which accesses a huge assortment of memories that compare the particular sensation to a representation of our past experiences. Some sensory receptors, such as those that monitor our blood pressure, do not input into the cerebral cortex, and thus these sensations are not apart of our perception. Sensation is divided into two basic sensory modalities, referred to as the general senses and the special senses. The general senses include somatic and visceral senses, the former relating to components such as tactile sensations, thermal sensations and proprioception, whereas visceral senses provide information about the status of the internal organs. The special senses are comprised of specialized sensory organs that receive sensations such as smell, taste, vision, hearing and balance. Sensation begins with a sensory receptor, such as a specialized cell or the dendrites of a sensory neuron. Each type of sensory receptor is adapted to receive only one kind of sensory modality, responding to specific changes that elicit a stimulus. When the sensory receptor receives the stimulus it transduces it into an action potential of varying amplitude depending upon the strength of the stimulus. The impulse is then propagated along the afferent nerves until a particular region of the CNS receives and integrates the impulse. Sensory neurons that conduct impulses from the PNS into the CNS are called first order neurons.
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
Sensory receptors can be classified according to their microscopic features, the location of the receptor, and the type of stimulus detected. On a histological basis, sensory receptors can be classified into free nerve endings, encapsulated nerve endings, and separate cells. Free nerve endings are the bare dendrites of neurons, and are associated with pain, thermal, tickle, touch and itching sensations. Free encapsulated nerve endings are dendrites enclosed within a connective tissue capsule, such as a corpuscle of touch. Separate cells synapse with first order neurons, and are located in places like the retina, hair cells of the ear, and taste buds of the tongue. Another method of classifying sensory receptors is based upon their location in the body. Exteroreceptors are located near the surface of the body and convey information to the CNS in regard to the external environment, such as sights, sounds, tastes, temperature, touch, pressure, vibration and pain. Interoreceptors are located inside the body to provide information relating to the status of the internal environment, such as blood pressure and the activities of the viscera. Proprioreceptors are located in tissues such as muscles, joints, tendons and the inner ear, providing information about body posture, muscle tension and balance. The third method of classifying sensory receptors is based upon the kind of stimulus detected. Thus mechanoreceptors receive mechanical stimuli such as pressure, vibration and touch; thermoreceptors detect changes in temperature; nociceptors detect physical or chemical damage; photoreceptors detect light by the eye; chemoreceptors detect the smell and taste of chemicals; and osmoreceptors detect the osmotic pressure of body fluids. All sensory receptors have the capacity to adapt to stimuli, such that the original stimulus, if it becomes constant, results in a decrease in the amplitude of the action potential. Rapidly adapting receptors have the capacity to adapt very quickly to changing sensory stimuli, whereas slowly acting receptors adapt slowly and continue to generate nerve impulses as long as the stimulus exists. S o m a t i c s e n s a t i o n s Somatic sensations arise from the stimulation of sensory receptors embedded in tissues and organs such as the skin
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
and subcutaneous layers, in mucous membranes, in muscles, tendons and joints, and in the inner ear. The sensory receptors for somatic sensations have an uneven distribution, and some tissues such as the lips can be seen to have a high density of these receptors. Somatic sensations are comprised of four modalities: tactile, thermal, pain and proprioceptive. Tactile sensations Tactile sensations include touch, vibration, pressure, itching and tickling. Touch sensory receptors can be divided into those that can perceive specific and subtle stimuli, called fine touch, and those that while detecting the sensation of touch, cannot give the same discrete characteristics, and is thus called crude touch. Touch receptors can also be either rapidly or slowing adapting. The corpuscles of touch, or Meissner corpuscles, are an example of rapidly adapting touch receptors, predominating in certain areas such as the hands, eyelids, lips, nipples, soles, clitoris and penis. Hair root plexuses are another form of rapidly adapting touch receptors that detects movement that disturbs hairs. Slowly adapting touch receptors include type I and II cutaneous mechanoreceptors. Type I cutaneous mechanoreceptors, or Merkel cells, are found in the stratum basale of the epidermis, innervating the skin, and especially the hands, lips, and genitalia. Type II cutaneous mechanoreceptors, or Ruffini corpuscles, are located deep in the dermis, ligaments and tendons, as well as the hands and soles, sensitive to stretching that occurs as limbs move. Pressure is another tactile sensation that is felt over a larger area than touch, occurring with the deformation or displacement of deeper tissues. A variety of sensory receptors contribute to the sensation of pressure, including lamellated corspuscles. Vibration results from rapidly repetitive sensory signals from tactile receptors. Itching results from sensory nerve endings excited by locally released chemicals such as bradykinnin or histamine. Thermal sensations Thermoreceptors are free nerve endings that can receive sensations of cold or warmth. Cold receptors are located in the stratum basale of the epidermis, and detect temperatures between 10-40°C. Warm receptors are located in the dermis and are activated by temperatures of
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
32-48°C. Temperatures above and below these stimulate nociceptors. Pain sensations Without a doubt pain is a key component of homeostasis, providing valuable information about the health and status of various tissues and organs. Sensory receptors for pain are called nociceptors, comprised of free nerve endings found in every tissue of the body except the brain. Irritation or damage to these receptors, from exogenous factors such as temperature changes, chemical and mechanical agents, as well as endogenous factors such as pro-inflammatory compounds such as bradykinnin and prostaglandins, can stimulate these nociceptors. In many cases pain will persist even once the factors that stimulated the sensory impulse are removed, because nociceptors display little ability to adapt. Some forms of pain, such as fast pain, felt as an immediately acute, sharp and pricking pain, occurs very quickly because the impulse is propagated along medium-diameter myelinated nerve fibers. Slow pain, described as a burning, aching or throbbing pain, is felt much more slowly, gradually increasing in intensity, because the impulse is propagated along small diameter unmyelinated nerve fibers. Pain receptors can also be understood to be somatic, providing indication of health and status of the skin (superficial somatic pain) or the muscles, joint and tendons (deep somatic pain), or visceral, relating to the stimulation of nociceptors in the visceral organs. In some cases pain is experienced at a location some distance from the site of stimulus. This is called referred pain, and happens because the areas of referred pain are innervated by the same nerves that supply the area that originally registered the pain stimulus. A good example is the neck and shoulder pain experienced on the right side of the body that refers pain for the liver and gall bladder. Proprioceptive sensations Proprioception is the ability for us to be conscious of where are head and limbs are in relation to our environment without having to look at them. The senses that convey this ability are called proprioceptors, and are imbedded in tissues such as tendons and muscles, and in the hair cells that line the vestibular apparatus in the inner ear that helps to maintain balance and equilibrium.
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
S p e c i a l s e n s e s The special senses are those housed in specialized organs such as the nose, tongue, eyes and ears that allow us to smell, taste, see, hear and maintain balance. Olfaction Olfaction is a termed used to describe the sense of smell through the activity of up 100 million tiny receptors embedded in and comprising a small part of the epithelium of the superior portion of nasal cavity. This tissue is comprised of three cell types that play a role in olfaction. Olfactory receptors are first order bipolar neurons of the olfactory pathway whose dendrites are connected to specialized cilia called olfactory hairs that transduce inhaled odorants into a graded action potential. Supporting cells are found in adjacent areas of the nasal epithelium that protect and support the olfactory receptors. Basal stem cells reside between the supporting cells, and undergo mitosis to produce new olfactory receptors, a feature that is unique, as mature neurons cannot generally be replaced. The process of olfaction is related to the olfactory hair being able to transduce a chemical odorant into a graded potential. Researchers estimate that we can recognize over 10,000 different and distinct odors. In some cases it is thought that odorants chemically bind to G proteins in the plasma membrane, which results in a chain of events that result in the generation of a nerve impulse in the dendrite of the olfactory neuron. Adaptation however occurs relatively quickly, such that we are only 50% as sensitive to the original stimulus after the first second of exposure, which then gradually decreases so that after a minute we may no longer be conscious of the odor. There are about 40 bundles of unmyelinated axons of olfactory neurons that extend through the foramina of the ethmoid bone to form the left and right olfactory nerve (cranial nerve I). These nerves terminate in the olfactory bulbs located below the frontal lobes of the cerebrum. In turn, axons of the olfactory bulbs extend posteriorly as the olfactory tract into the lateral olfactory area located in the temporal lobe, interfacing with the limbic system and amygdala, where the sense is given discrete characteristics that evoke emotions based on memory. Pathways are also found extending from this area into the frontal lobe, where the odors are identified.
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
Gustation Gustation is the term used to described chemical stimuli detected by gustatory receptors on the tongue, soft palate, pharynx and epiglottis. This sense is also referred to as taste, and at least five tastes have been identified, including sweet, sour, salty and bitter, as well as a fifth described by Japanese scientists as a meaty or savoury taste called umami. In ancient India six tastes are described, including pungent and astringent, in addition to sweet, sour, salty and bitter. When a substance is placed in the mouth gustatory receptors are stimulated, but also are olfactory receptors, the latter of which appear to be thousands of times more sensitive than gustation. Thus when the olfactory receptors are congested with mucus from a cold or allergy, the sense of taste is minimized. Gustatory receptors are comprised of taste buds, an oval shaped tissue that in turn is formed from supporting cells, gustatory receptors and basal cells. Within each taste bud supporting cells surround a clump of about 50 gustatory cells, which each extend a microvillus connected to the dendrite of the gustatory cell, through a pore in the taste bud to the external surface. Basal cells are found around the edges of the taste bud, producing supporting cells that develop into gustatory cells that live for about 10 days. On the tongue, tastes buds are borne on elevations called papillae, most of which are fungiform papillae, scattered over the surface of the tongue. On the posterior surface of the tongue are the circumvallate papillae that form an inverted V-shape. Foliate papillae are found in childhood on the lateral margins of the tongue, but degenerate well before maturity. The process of certain elements of gustation are similar to that of olfaction, with a tastant binding to a G-protein on the surface of the plasma membrane, which in turn sets to activity a number of secondary messengers that initiate an action potential. In the case of salt however, it is Na+ dissolved in the saliva that enters into the gustatory cells via Na+ channels, which then act to depolarize the membrane and stimulate an action potential. Similarly, the H+ of sour tastants dissolved in the saliva flow into the receptor via H+ channels, promoting the depolarization of the membrane. Differences in taste are thought to arise
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
from the activation of different neurons that synapse with the gustatory receptors, each that responding more powerfully to different kinds of tastants. The impulse transduced by the gustatory receptors is propagated along cranial nerves VII, IX and X to the medulla oblongata, then to the limbic system, hypothalamus and thalamus that integrate the impulses into a conscious awareness of the taste sensation. Vision Vision is the term used to describe the process of photoreception by the eye. Structurally the eye is comprised of the eyeball, eye muscles, the eye lid, eyelashes and eyebrows, and the lacrimal apparatus. The eye muscles position the eyeball within the eye socket, and the eyelids, eyelashes and eyebrows serve as a mechanical barrier to foreign objects and light. The lacrimal apparatus functions to produce a watery fluid containing salts, mucus and antimicrobial lysozymes that hydrates, lubricates, and protects the exterior surface of the eye. The eyeball itself is comprised of a superficial coating called the fibrous tunic that forms the transparent coating called the cornea, and the sclera, or the “white” of the eye. Internal to the fibrous tunic is the vascular tunic, which is comprised of the choroid, ciliary body and iris. The choroid is highly vascularized and lines the posterior, internal surface of the sclera. The ciliary body is continuous with the choroid but anteriorly located, and is comprised of the ciliary muscle from which extends ciliary processes that contain capillaries that secrete the aqueous humor of the eye, and attach to ligaments that controls the shape of the lens. The iris is the colored portion of the eyeball suspended between the cornea and lens, regulating the amount of the light that enters the eyeball through the opening called the pupil. The third and final coat of the eyeball is the retina, located in the posterior three quarters of the eyeball, internal to the choroid. Looking through the iris with a special implement called an ophthalmoscope onto the back of the surface of the retina one can see the optic disc, which is where the optic nerve enters the eyeball, bundled with the central retinal artery and vein.
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
The retina contains three basic neural layers: a photoreceptive layer, a bipolar layer and the ganglion cell layer. Lying behind the photoreceptive layer is a pigmented layer containing melanin that reduces the glare of bright light as it comes into the eye, and just above this is a series of rod and cones imbedded into the photoreceptive layer that act to transduce light rays into visual receptor potentials. Rods have a low light threshold, allowing one to see low light levels in shades of grey, whereas cones have a higher light threshold and allow us to discern color. These synapse with number of neurons such as bipolar cells, horizontal cells and amacrine cells in the bipolar layer that modify the visual data before it is transduced into an action potential, which in turn synapses with ganglion cells that propagate the nervous impulse along the optic nerve to the optic disc. The transduction of light into a receptor potential within the rods in cones begins with the absorption of light by photopigments, such as rhodopsin in rods and photopsin in cones, that undergo structural changes when exposed to light. These pigments are comprised of two parts: an amino acid sequence that can vary according to the particular photopigment, and a derivative from vitamin A called retinal. Upon visual inspection with an ophthalmoscope the macula lutea is a small flat spot can be seen in the exact center of the posterior retina, and within this lies a small depression called the central fovea that contains only cones, with the bipolar and ganglion cells located at the periphery of the central fovea, thus ensuring that there is no scattering of light, making the central fovea the highest area of visual acuity. For low light images however, such as faint star, the peripheral areas of the retina that contain more rods are actually more efficient receptors, which is why it is easier to see the star when not directly viewing it. In addition to the varying arrangement of rods and cones in the retina that work to together to receive visual data, the portion of the retina that receives the optic nerve contains no rods or cones at all, and thus represents a blind spot. Just posterior to the iris in the cavity of the eye ball lies the lens, comprised of crystalline proteins arranged in layers much like an onion, and is normally transparent. It is enclosed by a connective tissue capsule and held in place
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
and its shape modified by ligaments called the zonular fibers. The function of the lens is to focus and refract light onto the retina. Located in the interior of the eyeball are two cavities, the anterior cavity and the vitreous chamber. The anterior cavity is composed of two chambers: the anterior chamber, located between the cornea and iris, and the posterior chamber, comprised of the areas immediately posterior to the iris and anterior to the lens. Both chambers are filled with the aqueous humor, a watery fluid secreted by the capillaries of the ciliary processes that nourishes the lens and cornea, and drains into the scleral venous sinus (canal of Schlem) in the anterior chamber. The posterior chamber is comprised of the area immediately posterior to the lens and extending to the retinal surface, and is filled with a clear jelly-like substance called the vitreous humor that gives structure to the eye while allowing light to pass through it. The vitreous humor is formed in utero and while it does not undergo constant replacement like the aqueous humor, it does receive an indirect supply of nutrition via osmosis from the nutrients that are fed into the back of the eye. “Floaters” are caused by poor nutrition and oxidative damage to the vitreous humor as light passes through it, causing it to dry out and solidify in certain areas, causing distortions that are seen as floaters. If this condition progresses the distortions may become worse, and eventually the vitreous humor may detach from the retina, causing the retina in turn to detach from the choroid. As the visual signals are processed by neurons in the retina the action potentials generated exit the eyeball along the optic nerve (cranial nerve II). The axons that pass through the optic chasm, in which some axons cross to the opposite side and some remain uncrossed. After passing through the optic chasm the axons now form what is called the optic tract, which enter the brain and terminate in the thalamus, where they synapse with axons from neurons that project to the visual areas in the occipital regions of the cerebral cortex. Hearing and equilibrium The ear is the organ responsible for transducing sound vibrations into an action potential. The ear is comprised of three parts, the external, middle and inner ear. The outer ear consists of the auricle, the external auditory canal and
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
the ear drum. The auricle is a folded flap of elastic cartilage covered by skin, and attached to the head by ligaments. The external auditory canal is a curved tube that lies within the auricle that is lined with ceruminous glands that produce cerumen. At the end of the external auditory canal sits the eardrum or tympanic membrane, a thin, semitransparent membrane covered by epidermis and lined with simple cuboidal epithelium. Interior to the ear drum is an air-filled cavity called the middle ear, which contains three of the smallest bones in the body called the auditory ossicles, bound together in synovial joints. The malleus (or “hammer”) is attached to the internal surface of the ear drum, which articulates with the incus (“anvil”), which in turn articulates with the stapes (“stirrup”). The base of the stapes fits into the oval window, an opening within a bony partition that separates the middle ear from the inner ear. Just below this is another opening in this partition called the round window, which is enclosed by a membrane called the secondary tympanic membrane. The ossicles are manipulated by a series of ligaments and muscles, controlled by the cranial nerve V and VII. A further opening found in the middle ear is the auditory or Eustachian tube, connecting the middle ear with the nasopharynx. The inner ear is also called the labyrinth because it is a highly complex series of canals, and consists of two main divisions: an outer bony labyrinth and an inner membranous labyrinth. The bony labyrinth is divided into three components: the semicircular canals, the vestibule and the cochlea. The bony labyrinth is lined with periosteum and contains a fluid that is chemically similar to cerebrospinal fluid called perlymph. This fluid surrounds the series of sacs and tubes within the bony labyrinth called the membranous labyrinth, which is lined with epithelium and contains a fluid called endolymph. The vestibule is the oval portion of the inner ear and contains two sacs of the membranous labyrinth called the urticle and saccule. Projecting superiorly and posteriorly from the vestibule are three semicircular canals that contain portions of the membranous labyrinth called the semicircular ducts. Anterior to the vestibule is the cochlea, a bony spiral canal that resembles a snail shell that makes about two and a half turns around a bony core called the modiolus. Internally, the cochlea is divided into three channels. Two of these are
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
filled with perilymph: the superior channel, called the scala vestibuli, and the inferior channel called the scala tympani. The third, medial channel is called the scala media or cochlear duct, and contains endolymph. It is separated from the scala vestibuli and scala tympani by the vestibular and basilar membranes, respectively. Lining the basilar membrane is the spiral organ or organ of Corti, which is a coiled sheet of thickened epithelium that contains hair cells that are the receptors for hearing, so-named because the long microvilli on their apical surfaces. These hair cells synapse with first order sensory neurons and motor neurons from the cochlear branch of the vestibulocochlear nerve (cranial nerve VIII). Lying over top of the hair cells is a gelatinous membrane called the tectorial membrane. The process of hearing involves the direction of sound waves into the auditory canal by the auricle, causing the sound waves to strike the ear drum, causing it to vibrate back and forth, faster with higher pitched frequencies, and more slowly with lower pitched frequencies. This vibration causes the malleus to vibrate, and then the incus and then the stapes. As the stapes begins to vibrate it pushes the membrane of the oval window, which alters the pressure of the perilymph in the scala vestibuli and scala tympani, transmitting the pressure to the oval window, causing the membrane to bulge outwards into the middle ear. At the same time, the pressure which deforms the walls of the scala vestibuli and scala tympani presses upon the vestibular membrane, creating pressure waves within the endolymph of the cochlear duct. This causes the basilar membrane to vibrate, which moves the microcilli against the overlying tectorial membrane, producing receptor potentials that result in action potentials. Beyond its function as an organ of hearing the ear also serves to sense equilibrium, called the vestibular apparatus. Physiologists divide equilibrium into two processes, one called static equilibrium and the other called dynamic equilibrium. Within the saccule and urticle of the vestibule of the inner ear are two small regions called the maculae that lie perpendicular to one another, and are the receptors for static equilibrium. Each macula contains bundles of hair cells and supporting cells. The supporting cells are thought to secrete a thick gelatinous glycoprotein layer called the osolithic
Anatomy and Physiology: A Phytotherapeutic Perspective Lesson Seven By Todd Caldecott
membrane, which features a layer of dense calcium carbonate crystals called otoliths that are held in the osolithic membrane. It is the movement of the osolithic membrane sliding across the hair cells according to the influence of gravity that causes the hair cells to bend, depolarizing and repolarizing, causing the formation of a receptor potential which is then transduced into an action potential. Dynamic equilbrium occurs in the semicircular ducts of the semicircular canals, which lie at right angles to other in three planes. Within the distal portion of each semicircular duct is a small elevation called the crista that contains a group of hair cells and supporting cells covered in a gelatinous material called the cupula. As the head is moved the endolymph slightly lags behind due its to inertia, causing the bending of the hair cells, which produces receptors potentials. Both the hair cells in the semicircular canals and vestibule synapse with the vestibular branch of the vestibulocochlear nerve (cranial nerve VIII), which enters the brain stem, most synapsing in the medulla and pons, some axons of the vestibulocochlear nerve continuing further to synapse with the cerebellum.
