COMATOSE

Consciousness is a person’s awareness of themselves and their surroundings. Normal consciousness is

maintained by an intact reticular activating system in the brain stem and its central connections to the
thalamus and cerebral hemispheres. The reticular activating system keeps us awake and alert during the
waking hours. Disorders that physically affect these areas can lead to disordered arousal, awareness and to
altered states of consciousness. A focal brain lesion occurring below the tentorium (Figs.9.1 & 2) interfering
with the reticular activating system can result in coma whereas a focal lesion occurring above the tentorium
in one cerebral hemisphere results in coma only if the contralateral side of the brain is simultaneously
involved or compressed (Fig.9.3) Diffuse lesions which affect the function of the brain as a whole including
the reticular activating system can result in coma (Howlett, 2012)

Coma Due to Cerebral Mass Lesions and Herniations

Coma due to Metabolic Disorders
Many systemic metabolic abnormalities
cause coma by interrupting the delivery of energy substrates
(e.g., oxygen, glucose) or by altering neuronal excitability (drugs and
alcohol, anesthesia, and epilepsy). The metabolic abnormalities that
produce coma may, in milder forms, induce an acute confusional state.
Thus, in metabolic encephalopathies, clouded consciousness and coma
are in a continuum.
Cerebral neurons are fully dependent on cerebral blood flow (CBF)
and the delivery of oxygen and glucose. CBF is ~75 mL per 100 g/
min in gray matter and 30 mL per 100 g/min in white matter (mean
~55 mL per 100 g/min); oxygen consumption is 3.5 mL per 100 g/
min, and glucose utilization is 5 mg per 100 g/min. Brain stores of
glucose are able to provide energy for ~2 min after blood flow is interrupted,
and oxygen stores last 8–10 s after the cessation of blood flow.
Simultaneous hypoxia and ischemia exhaust glucose more rapidly. The
electroencephalogram (EEG) rhythm in these circumstances becomes
diffusely slowed, typical of metabolic encephalopathies, and as substrate
delivery worsens, eventually brain electrical activity ceases.
Unlike hypoxia-ischemia, which causes neuronal destruction, 1773
most metabolic disorders such as hypoglycemia, hyponatremia,
hyperosmolarity, hypercapnia, hypercalcemia, and hepatic and renal
failure cause only minor neuropathologic changes. The reversible
effects of these conditions on the brain are not understood but may
result from impaired energy supplies, changes in ion fluxes across
neuronal membranes, and neurotransmitter abnormalities. For
example, the high ammonia concentration of hepatic coma interferes
with cerebral energy metabolism and with the Na+, K+-ATPase
pump, increases the number and size of astrocytes, and causes
increased concentrations of potentially toxic products of ammonia
metabolism; it may also affect neurotransmitters, including the
production of putative “false” neurotransmitters that are active at
receptor sites. Apart from hyperammonemia, which of these mechanisms
is of critical importance is not clear. The mechanism of the
encephalopathy of renal failure is also not known. Unlike ammonia,
urea does not produce central nervous system (CNS) toxicity, and a
multifactorial causation has been proposed for the encephalopathy,
including increased permeability of the blood-brain barrier to toxic
substances such as organic acids and an increase in brain calcium and
cerebrospinal fluid (CSF) phosphate content.
Coma and seizures are common accompaniments of large shifts in
sodium and water balance in the brain. These changes in osmolarity
arise from systemic medical disorders, including diabetic ketoacidosis,
the nonketotic hyperosmolar state, and hyponatremia from any
cause (e.g., water intoxication, excessive secretion of antidiuretic
hormone, or atrial natriuretic peptides). Sodium levels <125 mmol/L
induce confusion, and levels <115 mmol/L are typically associated
with coma and convulsions. In hyperosmolar coma, the serum osmolarity
is generally >350 mosmol/L. Hypercapnia depresses the level
of consciousness in proportion to the rise in carbon dioxide (CO2)
tension in the blood. In all of these metabolic encephalopathies, the
degree of neurologic change depends to a large extent on the rapidity
with which the serum changes occur. The pathophysiology of other
metabolic encephalopathies such as those due to hypercalcemia,
hypothyroidism, vitamin B12 deficiency, and hypothermia are incompletely
understood but must reflect derangements of CNS biochemistry,
membrane function, or neurotransmitters.
Epileptic Coma
Toxic (Including Drug-Induced) Coma
Coma due to Widespread Damage to the Cerebral Hemispheres

THE ANATOMY AND PHYSIOLOGY OF COMA

Almost all instances of diminished alertness can be traced to widespread
abnormalities of the cerebral hemispheres or to reduced activity
of a special thalamocortical alerting system termed the reticular
activating system (RAS). The proper functioning of this system, its
ascending projections to the cortex, and the cortex itself are required to
maintain alertness and coherence of thought. It follows that the principal
causes of coma are (1) lesions that damage the RAS in the upper
midbrain or its projections; (2) destruction of large portions of both
cerebral hemispheres; or (3) suppression of reticulocerebral function
by drugs, toxins, or metabolic derangements such as hypoglycemia,
anoxia, uremia, and hepatic failure.
The proximity of the RAS to midbrain structures that control pupillary
function and eye movements permits clinical localization of the
cause of coma in many cases. Pupillary enlargement with loss of light reaction and loss of vertical
and adduction movements of the eyes suggests
that the lesion is in the upper brainstem where the nuclei subserving
these functions reside. Conversely, preservation of pupillary light
reactivity and of eye movements absolves the upper brainstem and
indicates that widespread structural lesions or metabolic suppression
of the cerebral hemispheres is responsible for coma (Harrison, 2015).

Referensi
Howlett, W. (2015). PREFACE. In Neurology in Africa: Clinical Skills and Neurological Disorders (p. Ix).
Cambridge: Cambridge University Press. doi:10.1017/CBO9781316287064.001
KASPER, D., FAUCI, A., HAUSER, S., LONGO, D., & JAMESON, J. (2015). Harrison's Principles of Internal Medicine. New York,
McGraw-Hill Education.