Anatomical Physiological Components, Orientations, Effects on the Neurones, and Efferents Fibres.

The effects of the central nervous system (CNS) are proportional to the ethanol BAL concentration. The extent and severity rise with the BAL correspondingly to individual variations, and the factors involved, in its effects, will be discussed firstly from the aspect of the Brainstem. The Brainstem consists of the Medulla oblongata, the Pons, the Mesencephalon and contains the corticospinal and reticulospinal tracts. It has effects on motor sensory and reflex functions.

Medulla Oblongata.

The Medulla oblongata is situated at the inferior aspect of the brainstem and measures approximately three centimetres. ^_9. It is the gateway for the ascending and descending communicating fibre tracts that links the brain with the spinal cord, and the area where the phenomenon of ‘decussation’ take place, viz., the fibre tracts, originating from the Cerebral cortex on each side of the pyramid, cross to the opposite side, and pass inferiorly to the Medulla, descending laterally into the spinal cord.

Synapsis, i.e., the neural impulse moves from the synaptic bulbs into the synaptic clefts through the release of neurotransmitters (vide 1, 2, 3, and 4 in diagram above.). Synthesized molecules in neural axon terminals synapse in response to neural impulses initiating membrane potential of postsynaptic neurones, within the grey horns, and terminate in skeletal muscular effectors that give rise to locomotion, posture variation, and equilibrium.

The nuclei (nerve cells) in the Medulla, include the vestibulocochlear nuclei which control the auditory function, the glossopharyngeal nuclei which control salivation, taste and swallowing, the hypoglossal nuclei that initialize tongue movement, and the vagus nuclei that are concerned with the abdominal and thoracic viscera.

Neural impulses release the adrenal hormone and synthetic adrenergic vasoconstrictor epinephrine, from the cardio acceleratory centre (CAC), that increases the rate and force of the heartbeat. The neurotransmitter substance acetylcholine (ACh) released from the cardioinhibitory centre (CIC) decreases the rate and force of the heartbeat. Ethanol at high dosage can depress these systems as well as the respiratory system. It can initiate peripheral vasoconstriction, inhibit functions of the GI tract, and effect controls of the walking, sleeping states; and equilibrium. ^_10.

The Pons.

The Pons is at the superior aspect of the Medulla oblongata and measures 2½ centimetres. Like the Medulla, it associates the spinal cord with the brain. ^_11. The nuclei contained in the Pons include: the nervus abducens that control outward movement (external rectus) of the eyeball. Also, the facial mediating the sense of taste, salivation, facial movements; and the vestibulocochlear that maintain equilibrium, the pneumonia ataxia that coordinates inspiration and expiration. The apneustic area that prolongs inspiration and reduces expiration; and the Medulla (medullary rhythmicity area) that control respiratory activity.

High or low dosage of ethanol combined with CNS depressant substances – sedative, hypnotics and other minor tranquillizers – can cause severe depression of the respiration centre, in the brainstem, and has been reported to have had lethal consequences at a BAL concentration of between 0.4% and 0.6% by volume. ^_12.13.Julien has indicated that, “To date, specific pharmacological actions on the Pons have not been clearly delineated”. ^_14.

The Mesencephalon.

The Mesencephalon, also called the ‘Midbrain’, spreads to the inferior aspect of the Diencephalon; from the Pons. It measures approximately 2½ centimetres. It provides a pathway called: the cerebral peduncle fibre bundles; for motor impulse activity from the Cerebral cortex to the Pons, Medulla oblongata, and the spinal cord. ^_15.

The superior Colliculi in the reflex nuclei responds to auditory, tactile and visual stimuli for the impulses that give movement to: the neck, head and eyes. The inferior Colliculi is the reflex centre for: head and trunk and responds from auditory stimuli. The oculomotor nuclei conduct some impulses that move the eyes, vary the lens and pupil.

The medial Lemniscus has the communicating axons that transmit impulses, from the Medulla to the Thalamus ; viz, tactile, position, location and movement of the body and its parts. Also it is thought to be a centre of auditory and/or hallucinatory sensations; ^_16. 17. ethanol may effect muscle and eye movement from this centre.

The Thalamus.

The Thalamus, is at the superior aspect of the Midbrain, and measures approximately 3 centimetres in length. ^_18. 19 It has several subdivisions that organically relate to specific sites, viz., the sensory organs but excluding the olfactory organ. These subdivisions disseminate information signals to specific localities of the Cerebral cortex. ^_20. Ethanol can cause the receptors of the Thalamus to effect the analgesic mechanism by suppressing endorphins, from blocking the polypeptide neurotransmitter substance P, depress respiratory activity; and induce physical dependence.

The Subthalamus.

The Subthalamus, is at a small site in inferior aspect of the Thalamus and includes a variety of other parts (viz., somatic motor nuclei: the ‘ventral lateral’ for voluntary motor impulses and the ‘ventral anterior’ for stimulus for somatic and mental activity); that contain the source of the extrapyramidal motor system. The control and co-ordination of these motor activities may be effected by ethanol. ^_21.

The Hypothalamus.

The Hypothalamus is located at the inferior aspect of the Thalamus and is in juncture with the Midbrain. ^_22. Many of its functions include the integrating and control of the peripheral autonomic nervous system and many somatic functions such as appetite, body temperature; and sleep. It produces releasing factor substances for the production of menstrual cycling, the release of the secondary oocyte, and spermatozoal production hormones. It has a prolific blood supply, and ethanol is found in high concentration at this site. This site produces the so-called ‘stimulation’ effect that, ipso facto, result in the depression of inhibitory synapses (gamma-aminobutyric acid (GABA)) earlier than the excitatory (serotonin (5-HT)); emotional (dopamine (DA)); and motor (norepinephrine (NE)) control functions.

Ethanol may effect the control levels of body fluids, body temperature (5-HT), memory, learning and sexual functions (endorphins). Julien quotes W.R. Hess’ view that ‘the Hypothalamus is the mechanism involved in the mediation of the fight, flight, fright response’. ^_23.

The Cerebellum.

The Cerebellum is at the posterior aspect of the Medulla oblongata and Pons, and occupies approximately 1/8th of the cranial cavity at the inferior aspect of the Cerebrum lobes. ^_24. The anterior and posterior lobes, and the Flocculonodular lobe direct the unconscious skeletal muscle movements, and equilibration respectively. The effects of ethanol at this site produces loss of equilibrium and co-ordination. The scientific community has the Cerebellum under ongoing studies.

The Limbic System.

The Limbic system consists of the hippocampus, hippocampal gyrus, isthmus, cingulate gyrus, and the uncus. These structures are in the rhinencephalon of the brain. They are identified with feelings and emotions (depression, pleasure, anger, fear, and sexual arousal).

This system is maintained by homeostasis (control functions) by other areas of the cortex to offset uncontrollable feelings and emotions. The Limbic system and the Hypothalamus has recently drawn attention from the research community, with respect to the effects drugs have on emotional manifestations. Ethanol at this system may effect the homoeostasis of the emotional, eating (drinking), behaviour, learning, memory and sexual modes.

The Cerebral Cortex.

The Cerebral cortex consists of two grey coloured hemispheres, the right and the left, and are situated at a superior aspect to the Thalamus; and transverse into the Brainstem. The Cerebral cortex is extremely convoluted and solidly clefted, in appearance resembling a walnut. Its functions include mental activity, behavioural responses, movement, visceral functions, sensory perceptions; visual and auditory.

Ethanol impairs the inhibitory controls, dopamine (DA), in the substantia nigra of the cortex; producing the so called “drunken” behaviour effect. ^_25.  Disinhibition could be due to inhibitory synapses taking down earlier than excitatory ones. The inhibitory mechanism may be due to the releasing of calcium dependent neurotransmitters at the neuronal pre-synaptic site.

The Behavioural Effects.

The swings of the emotional state can be affected by ‘setting’ (drinking context) as well as by the volume of consumed ethano. ^_26. Behavioural effects range from gaiety, extroversion and self assurance to: hostility, depression and withdrawal. ^_27.Perceptual and motor activities may be adversely affected, e.g., distance assessment, time awareness, sensation of pain and reflex reaction. A low BAL may produce a mild sedative effect, slightly higher levels may produce behavioural changes, e.g., aggressiveness, loquaciousness and hyperactivity. This, ut sup., is the result of inhibitory depression in the upper cortical centres of the brain, and is not direct stimulation. This produces an aplomb effect over motor skills and rationalization of complex thought processes. As the BAL increases, the depressant effects appear in the areas of muscular co-ordination, breathing, speech and vision.^_28. Impaired functional depression, or incapacitation, has been demonstrated, in laboratory testing, to have occurred from BALs of 0.03% to 0.15%. ^_29. These tests exhibited decreased awareness, visual selectivity, reflex responses; and a multiple processing of incoming information; to stimulate basic spontaneous reflexes. ^_30.

The Organ Systems.

The organ systems are the anatomical parts of the body consisting of specialized tissue and cells that perform specific functions; e.g., the digestive organs and the liver.

The liver is the most complex gland of the body with more than 500 functions including: haemoglobin processing, bile production, secretion of vitamins, glucose, fats, proteins and other compounds, the reproductive organs, the spleen (for blood storage, destruction of platelets and red blood cells, hemopoiesis, and defence), sensory organs (visual, olfactory, tactile, gustatory, and auditory).

The paired organs, viz., the kidneys, lungs and testes/ovaries; are able to function autonomously of the other. The brain, pancreas, liver and spleen can tolerate 30% damage and maintain near normal activity.

Ethanol may adversely affect the organ systems, particularly the GI tract and the cardiovascular system. The direct and indirect physiological consequences are, e.g.,cirrhosis (a disorder of the liver in which parenchymal cells are broken down and supplanted by fibrous tissue) and nutritional deficiencies respectively. Daily dosage of 50-75ml of ethanol or 4.2-6.3 oz of spirits can increase the chances of developing cirrhosis, and malignant carcinoma at the site of the oesophagus. ^_31.

Anterograde Amnesia.

The declination of the brains function increases at a moderate rate over a several year duration. The signs and symptoms form a constellation that are a form of anterograde amnesia (customarily referred to as “blackouts”); this occurs at individual attainment of BAL.

The other signs and symptoms are: confusion, dysarthria (impaired articulatory ability), diminished emotional restraint, impairment to co-ordination of perceptual/motor functions, and inability to reason and rationalize. ^_32. There appears to be no correlation, of the symptoms of memory loss (anterograde amnesia); to the conscious or sober faculties.

Three Consecutive Phases in The Physical Dependence Syndrome.

There is a considerable intermixing of signs and symptoms among the three phases. The First phase can occur two hours following sudden cessation of ethanol intake.^_33. Ordinarily it is not severe in cases of mild dependency. The signs and symptoms include: tremors, profuse perspiration, debility, agitation, anorexia (loss of appetite), headache, nausea, vomiting, abdominal cramps, rapid and irregular heartbeat and hyperflexia (exaggerated and rapid reflexes) and ethanol hallucinations. ^_34.

The Second phase begins within twenty four hours after cessation of ethanol intake and is distinguished by one or several grand mal seizures resulting in loss of consciousness and control of autonomic functions, exempli gratia, bladder and bowel controls; deaths have occurred during this phase as a result of traumatic injury. ^_35.

The Third phase is elongated and is called ‘delirium tremens’ – the colloquial abbreviation is “D.T’s”. When it occurs, it usually has a duration of three or four days. The typical symptoms are: agitation, confusion, disorientation, hyperactivity, sweating, high body temperature. Rapid heart beats and high blood pressure, hallucinations (auditory, tactile or visual) often accompanied by fantastic and bizarre delusions. The withdrawal illness lapses within five to seven days resulting in symptoms of severe exhaustion and dehydration. Deaths are not unusual and are due to high fever; traumatic injury or cardiovascular collapse. ^_36. 37.

Wernicke-Korsakoff’s Syndrome.

Wernicke-Korsakoff’s syndrome was, at first, described as two separate brain diseases: ‘Wernicke’s encephalopathy’ and ‘Korsakoff’s psychosis’. Symptoms, from a psychological perspective, of the former are: disorientation in time and space, ataxia, confusion, and eye movement dysfunction, the latter, memory loss of recent prior events.

Wernicke’s encephalopathy is a degenerative condition characterized by excessive bleeding and lesions in the brain, chiefly in the mammillary bodies, the hypothalamus, the cavities and canals that result from deficiency in thiamine (C 12 H ¹⁷ CIN ⁴ OS.-HCI) or vitamin B¹.

The role of thiamine is to provide the body with energy by converting carbohydrates into glucose. They play an important role in the metabolism of fats and protein; and necessary for normal functioning of the nervous system. Thiamine is essential in the diet to prevent beriberi, i.e., deficiency symptoms and disorders involving, in part, paralysis of the GI tract’s smooth muscle, causing disturbances to the digestive processes, atrophy of the limbs and paralysis of the skeletal muscular system.

The body requires a daily intake of 0.5 mg of thiamine per 1000 calories daily for all ages (Krause and Hunscher 1972), and during pregnancy and lactation 1.4 mg, as it is not retained in the body in any great quantity and it is rapidly destroyed by heat. Thiamine depletion results in difficulty of digestion of carbohydrates and excessive levels of pyruvic acid in the blood that lead to oxygen deficiency causing loss of mental alertness, confusion, difficulty in breathing; nystagmus (involuntary rhythmic movement of the eyes), and ataxia (impaired ability to coordinate movement).

Studies by Victor, Adams and Collins (1971) have revealed areas of the brain susceptible to impairment and paralleled these to clinical observation.

Lesions to areas of the thalamus, cerebellum, lateral aspects of the third ventricle, periaqueductal area, inferior aspect of the fourth ventricle; and mammillary bodies (two small bodies at the posterior aspect of the tuber cinereum); that involve olfactory reflexes.

Thiamine deficiency is the prime cause of Wernicke’s encephalopathy and is associated with ethanol abuse. Thiamine (or vitamin B1) therapy may reverse these effects minimally; but for most patients the prognosis are dismal.

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