The structure of neurons

A neuron has three components: a cell body (soma) and the thin processes of the cell; the dendrites; and the axon (see Figure 6-3). The cell body contains the nucleus, cytoplasm and other normal organelles of a cell. There are also neurofibrils, which are collections of neurofilaments within the cell that extend away from the cell body to assist with carrying substances produced in the cell body along the axon. The dendrites are branching extensions that receive signals and carry them towards the cell body. Axons are long projections from the cell body that carry nerve impulses away from the cell. When the signal reaches the dendrite, it travels to the cell body and is then transmitted through the axon so that it can reach another neuron or another cell. In this way nerve impulses can be sent to various parts of the body.

FIGURE 6-3 The general structure of a neuron.

A A neuron consists of dendrites (receive signals), a cell body (or soma) and an axon (send signals). B A photomicrograph of a neuron.

Source: B Thibodeau GA. The human body in health & disease. 5th edn. St Louis: Mosby; 2010.

Neurons can be classified according to the number of dendrites that branch from the cell body. Some neurons have only one dendrite, typical of sensory neurons in the cranial and spinal nerves. Others have two dendrites, but by far the most common are the multipolar neurons, which have multiple dendrites and one axon, typical of motor neurons (nerves that innervate a muscle).

A typical neuron has only one axon, which may be covered with a segmented layer of lipid material called myelin, an insulating substance. This entire membrane is referred to as the myelin sheath (see Figure 6-3). The myelin sheaths are interrupted at regular intervals by the nodes of Ranvier. Axons branch extensively at the nodes of Ranvier. Myelin is an extremely important component of the nervous system; without it, nerve impulses would not be as fast, and the ability of neurons to send signals to one discrete area might be impeded. We examine the function of myelin later in the chapter when discussing the nerve impulse.

The function of neurons

Functionally, there are three types of neurons: (1) sensory neurons, which send afferent information towards the central nervous system; (2) interneurons, which are between sensory and motor; and (3) motor neurons, which transmit efferent signals outwards from the central nervous system.

Sensory neurons carry impulses from peripheral sensory receptors to the central nervous system. There are a range of different sensory neurons, each being capable of sensing a different type of stimulus (see Table 6-1). For example, thermoreceptors located throughout the skin detect temperature, while a chemoreceptor in the mouth (taste bud) can detect a particular chemical such as acid or sour, and other chemoreceptors located in the walls of blood vessels can sense the amount of oxygen in the blood. Some body regions have more sensory neurons than others; for example, the fingertips and lips have more sensory neurons than the legs and feet. Nerve impulses are continually being sent to the central nervous system with information about the external environment and, equally importantly, the condition of the internal environment. The central nervous system controls bodily functions in response to this constant supply of sensory information.

Interneurons transmit impulses from neuron to neuron — that is, they assist in the transmission between sensory and motor neurons. They are located solely within the central nervous system and provide the billions of connections between neurons in the brain.

Motor neurons transmit impulses away from the central nervous system to an effector (i.e. skeletal muscle or organ). In skeletal muscle, the innervation of the neuron to the muscle forms the neuromuscular junction. The function of the neuromuscular junction is discussed in Chapter 20.

Table 6-1 TYPES OF SENSORY NEURONS

Resting membrane potential

In a neuron at rest, sodium ions are more concentrated in the extracellular fluid, and potassium ions are in greater concentration in the intracellular fluid (see Figure 6-6). When the neuron is resting, a few of the potassium channels in the cell membrane are actually open, which allows small amounts of potassium to diffuse down its concentration gradient and ‘leak out’ or exit the cell. As a result of the positively charged potassium exiting the cell, the inside of the cell becomes negative. Consequently, the recording of the electrical potential is actually a negative number, due to there being a loss of positive charge from inside the cell. There is a range of electrical potentials in neurons, but the average value at rest is approximately −70 millivolts (see Figure 6-7A, stage 1).

FIGURE 6-6 Normal concentration gradient of sodium, potassium and calcium ions between the intracellular fluid of a neuron at rest and the surrounding extracellular fluid.

These differences in ion concentrations between inside and outside of the cell produce changes in membrane voltage, which can be measured using a voltmeter.

FIGURE 6-7 The action potential.

A Opening and closing of sodium and potassium ion channels occurs throughout the action potential. B Changes in membrane potential with the action potential. Stages: 1 Rest — resting membrane potential; a few potassium channels open. 2 Depolarisation — sodium channels open; sodium enters the cell. 3 Repolarisation —potassium channels open; potassium exits the cell (sodium channels are shut). 4 Return to resting membrane position.

Action potential

Neurons are excitable and their resting membrane potential changes in response to stimuli. For example, a thermoreceptor in your hand that detects cold will be stimulated when you grasp a cold drink from the fridge. This stimulus changes into an electrical signal that is interpreted by the nervous system through the generation of an action potential. The stimulus causes sodium channels in the neuron cell membrane to open. As there is a higher concentration of sodium in the extracellular fluid compared with the intracellular fluid, sodium diffuses down its concentration gradient and enters the cell. These positively charged sodium ions make the inside of the cell become more positive, so that the membrane potential moves from −70 millivolts towards zero. This is referred to as depolarisation. The membrane potential actually continues upwards to about +30 millivolts (see Figure 6-7A, stage 2).

When the membrane potential reaches +30 millivolts, this causes closing of the sodium channels, so that further sodium entry is prohibited. At the same time, the voltage change causes the potassium channels to open and thus potassium moves down its concentration gradient and exits the cell. The positively charged potassium ions exiting the cell cause the inside of the cell to become less positive, so that the membrane potential returns down to where it started (–70 millivolts). This is known as repolarisation (see Figure 6-7A, stage 3).

When the action potential is completed, the sodium–potassium pump located in the cell membrane returns the membrane to the resting potential by pumping potassium back into the cell and sodium out of the cell, in order to restore the normal concentration gradients (see Figure 6-7A, stage 4). Three molecules of sodium are pumped out for every two potassium ions returned to the cell in one cycle of the pump. The sodium–potassium pump requires energy in the form of ATP as molecules are being transported against their concentration gradients (see Chapter 3 for details). Note that there is a brief undershoot of the graph in Figure 6-7B, which occurs because the potassium channels close slowly, so that slightly more potassium is allowed to exit than is necessary. This is termed hyperpolarisation and it is corrected by the action of the sodium–potassium pump.

During the action potential, there are two different refractory periods during which the neuron cannot respond to a stimulus in the same way that it could when it was resting:

The absolute refractory period occurs during sodium entry (depolarisation), and when a neuron is in this stage it is completely unable to respond to another stimulus. Remember that the neuron responded to the initial stimulus by opening the sodium channels, which led to changes in the membrane potential; the neuron is incapable of responding again during the absolute refractory period as the sodium channels are already open.

The relative refractory period occurs after the sodium channels are shut (commencement of repolarisation) and during the later parts of the action potential. During this time, it is possible, although more difficult, to restimulate the neuron.

The refractory periods are important because they allow the neuron to be ready for the next action potential. Remember that there are changes in electrical charge and the refractory period allows the neuron to be electrically neutral again; in this way, the nervous system has the ability to recognise differences in the strength of different stimuli.

The cerebral hemispheres

The cerebral hemispheres — or cerebrum — comprise the largest portion of the brain. This is the structure that most people would recognise as the brain, and it is divided broadly into the cerebral cortex, cerebral white matter and the basal nuclei.

The surface of the cerebral hemispheres, the cerebral cortex, is covered with convolutions called gyri (singular = gyrus), which greatly increase the surface area and the number of neurons. It should be stressed that this is important for fitting billions of neurons into a tight space. Grooves between adjacent gyri are termed sulci, and deeper grooves are known as fissures. The two cerebral hemispheres, left and right, are separated by the longitudinal fissure. The surface of each hemisphere is divided into lobes named after the region of the skull under which it lies — frontal, parietal, occipital and temporal — with each having a left and right (see Figure 6-11).

FIGURE 6-11 The cerebral hemispheres, lateral surface.

A Structural divisions. B Functional areas.

Source: A Based on Patton KT, Thibodeau GA. Anatomy & physiology. 7th edn. St Louis: Mosby; 2010. B Based on Guyton AC, Hall JE. Textbook of medical physiology. 11th edn. Philadelphia: Saunders; 2006.

The principle of contralateral control occurs with the brain, meaning that the left side of the brain receives sensory input and controls the motor activities of the right side of the body, and vice versa. This is because the neurons that communicate with the cerebral cortex actually cross over to the other side of the body (the cross-over usually occurs in the spinal cord or brainstem). The crossover is referred to as where the neurons decussate.

Interestingly, it is common for one side of the brain to be more dominant than the other; a concept known as cerebral lateralisation. If the left side of the brain is dominant, then logical and analytical skills are enhanced, such as mathematics and language. The left side of the brain is dominant in controlling the writing skills of most of our population, as the majority of people are right-handed. If the right side is dominant, then creative and emotional activities are more pronounced, such as art, music and spatial relationships. Although one side of the brain tends to dominate, it also communicates extensively with the other side. If the dominant side is damaged, then the non-dominant side may be able to increase its control over that function.

Cerebral tracts

Inside the cerebral hemispheres are numerous tracts or axons (white matter; see Figure 6-12). This white matter lies beneath the cerebral cortex and is composed of myelinated nerve fibres. Lying directly beneath the longitudinal fissure is a mass of white matter pathways called the corpus callosum. This structure connects the two cerebral hemispheres and is essential in coordinating activities between the hemispheres (see also Figure 6-10).

FIGURE 6-12 Cerebral tracts.

A Lateral perspective, showing various association fibres. B Frontal (coronal) perspective, showing commissural fibres that make up the corpus callosum and the projection fibres that communicate with lower regions of the nervous system.

Source: Patton KT, Thibodeau GA. Anatomy & physiology. 7th edn. St Louis: Mosby; 2010.

The association fibres are a range of fibres that connect regions of the brain between gyri and between lobes. There are extensive amounts of association fibres that allow effective communication and coordination between brain regions. For example, the communication between the motor and sensory areas allows appropriate motor response to sensory inputs.

The limbic system

The limbic system is a group of structures, many of which are in the cerebral hemispheres and surrounding the corpus callosum, which influence emotions through connections in the prefrontal cortex. The system is composed of many regions including parts of the prefrontal cortex, hippocampus, amygdala and thalamus. Its principal effects are believed to be involved in basic behavioural responses, visceral reaction to emotions, feeding behaviours, biological rhythms and sense of smell (see Figure 6-13). This system is powerful and has a great influence on how we interpret our environment and experiences, such as whether something makes us happy or not.

FIGURE 6-13 The limbic system.

The limbic system is composed of a group of structures deep in the brain that are important in memory and emotion. These structures include the limbic lobe, amygdala, fornix, hippocampus, olfactory cortex and portions of the thalamus.

Source: Based on Copstead L-EC, Banasik JL. Pathophysiology. 4th edn. Philadelphia: Saunders; 2010.

The diencephalon

The diencephalon, surrounded by the cerebrum, consists mainly of the thalamus and hypothalamus (see Figure 6-9). The thalamus borders and surrounds the third ventricle. It is a major integrating centre for afferent impulses to the cerebral cortex. Various sensations are perceived at this level, but processing by the cerebral cortex is required for interpretation. The thalamus serves also as a relay centre for information from the basal nuclei and cerebellum to the appropriate motor area.

The hypothalamus forms the base of the diencephalon. The hypothalamus functions to: (1) maintain a constant internal environment; and (2) implement behavioural patterns. Integrative centres control autonomic nervous system function, regulate body temperature and endocrine function, and regulate emotional expression. The hypothalamus exerts its influence through the endocrine system, as well as through neural pathways (see Box 6-1).

The brainstem

The brainstem is the vital centre of the brain. Damage to this area affects basic life functions such as breathing and blood pressure control. It is divided into the midbrain (the superior portion of the brainstem), the pons and the medulla oblongata (at the most inferior part). The medulla is continuous with the spinal cord (see Figure 6-9).

The midbrain is composed of several structures, including the superior and inferior colliculi, the red nucleus and substantia nigra, and the cerebral peduncles. The superior colliculi are involved with voluntary and involuntary visual motor movements (e.g. the ability of the eyes to track moving objects in the visual field); while the inferior colliculi accomplish similar motor activities but involve movements affecting the auditory system (e.g. positioning the head to improve hearing). The red nucleus receives ascending sensory information from the cerebellum and projects a minor motor pathway to the cervical part of the spinal cord. The substantia nigra, which produces the neurotransmitter dopamine, may also be considered part of the basal nuclei. Other notable structures of this region are the nuclei of cranial nerves III (called oculomotor) and IV (called trochlear), and the cerebral aqueduct, which carries cerebrospinal fluid.

The pons is easily recognised by its bulging appearance below the midbrain and above the medulla. Primarily it transmits information from the cerebellum to the brainstem and between the two cerebellar hemispheres. The nuclei of the cranial nerves V (trigeminal) to VIII (vestibulocochlear) are located in this structure.

The medulla oblongata forms the lowest portion of the brainstem. Reflex activities, such as heart rate, breathing, blood pressure, coughing, sneezing, swallowing and vomiting, are controlled in this area. The nuclei of cranial nerves IX (glossopharyngeal) to XII (hypoglossal) also are located in this region. The medulla is the most important region of the brain to keep you alive. Damage to other areas of the brain may cause alterations in function, yet not be fatal; however, injury to the medulla is likely to damage the neurons that control the vital functions of the cardiovascular and respiratory systems, which usually results in death.

A collection of nerve cell bodies (nuclei) within the brainstem makes up the reticular formation (see Figure 6-14). The reticular formation is a large network of connected tissue that contains portions of vital reflexes, such as those controlling cardiovascular function and ventilation. The reticular formation is essential for maintaining wakefulness and therefore is referred to as the reticular activating system. We now discuss the sleep process and the role of the reticular activating system.

FIGURE 6-14 The reticular activating system.

System consists of nuclei in the brainstem reticular formation plus fibres that conduct to the nuclei from below and fibres that conduct from the nuclei to widespread areas of the cerebral cortex. Functioning of the reticular activating system is essential for consciousness.

The sleep process

Sleep is a temporary state of unconsciousness from which the individual can be aroused either spontaneously or by an external stimulus such as an alarm clock, a baby crying or light in the room. It is distinguished from the unconsciousness of coma, whereby arousal cannot be prompted (consciousness is discussed in Chapter 8). The brain remains constantly active during sleep. Interestingly, the brain consumes the same amount of glucose and oxygen whether awake or asleep, indicating that sleep does not reduce the nutrient or energy requirements of the brain.

Normal sleep has two phases that alternate through the night, as distinguished by electroencephalogram (EEG) (recording of the electrical activity of the cerebral cortex from the skull surface):

rapid eye movement (REM) sleep

non-rapid eye movement (NREM) sleep.

Rapid eye movement (REM) sleep occurs about every 90 minutes beginning 1–2 hours after NREM sleep begins. The EEG pattern is similar to the normal awake pattern and the brain is very active. The changes associated with REM sleep include increased parasympathetic activity and variable sympathetic activity associated with rapid eye movement; muscle relaxation; loss of temperature regulation; altered heart rate, blood pressure and breathing rate; penile erection in men and clitoral engorgement in women; release of steroids; and many memorable dreams. Respiratory control appears largely independent of metabolic requirements and oxygen variation. Loss of normal voluntary muscle control in the tongue and upper pharynx may produce some respiratory obstruction. Cerebral blood flow increases. The exact reason for all these changes is not fully understood and researchers are exploring the physiological and pathophysiological implications.

Non-rapid eye movement (NREM) sleep is divided into four stages (I–IV) from light to deep sleep.⁴ NREM sleep accounts for 75–80% of sleep time in adults. Sympathetic tone is decreased and parasympathetic activity is increased during NREM sleep, which creates a state of reduced activity. The basal metabolic rate falls by 10–15%; the core temperature decreases 0.5° to 1.0°C; the heart rate decreases by 10–30 beats per minute; and there are also decreases in the breathing rate, blood pressure and muscle tone. During the various stages, cerebral blood flow to the brain decreases and growth hormone is released, with secretion of corticosteroids (such as cortisol and aldosterone) and catecholamines (adrenaline and noradrenaline) depressed.

The importance of sleep

Sleep is restful and allows restoration. The essential and unavoidable nature of sleep suggests that there must be distinct advantages to the body. After insufficient sleep, there is an increased amount of sleep at the next opportunity, usually at a higher intensity (seen on the EEG).⁵ Sleep is an important part of the consolidation of memories,⁶ which makes it critical for students to undertake an appropriate pattern of sleep throughout their studies. In addition, sleep deprivation can result in impaired function of some regions of the brain that are involved in learning.⁷ During the deepest stage of NREM sleep, serotonin is released, which actually maintains the wellbeing of the brain.⁸ The role of sleep in setting daily rhythms of hormone secretion is discussed in Chapter 34.

Control of the sleep–wake cycle

The sleep control centre is coordinated in the hypothalamus (in a region known as the suprachiasmatic nucleus), which sets and regulates the circadian rhythms of body function around a 24-hour cycle. The hypothalamus receives information from the environment regarding the amount of light (via the eyes), and other sources assist, including alarm clocks and social cues (such as the pattern of sleep following dinner). In addition, the pineal gland (within the brain) also receives light information from the eyes and secretes melatonin, which interacts with the hypothalamus to induce drowsiness, thus marking the onset of sleep. The details of these processes and their interactions are still under investigation.

Arousal from sleep involves increased activity in the brainstem (the reticular activating system). Prior to waking, sensory information that ascends from the body periphery provides the reticular activating system with inputs such as an increasing amount of light or noise in the morning (refer to Figure 6-14); it also receives the sudden loud noise of someone calling you or an alarm clock. The reticular activating system then communicates with other brain regions, the most important being the cerebral cortex, to restore consciousness (awakening). During sleep, the flow of communication between the cerebral cortex and the reticular activating system is inhibited. The hypothalamus also has an important role in initiating sleep and coordinates this essential function by receiving information on the amount of light from the eyes, as well as the amount of melatonin secreted from the pineal gland.

The cerebellum

The cerebellum (literally meaning ‘little brain’) is located inferior to the occipital lobe of the cerebral hemispheres (see Figure 6-9) and is composed of grey and white matter; its outside surface is convoluted like the surface of the cerebrum. It is divided into two lobes (left and right) connected by the vermis.

The cerebellum is responsible for reflexive, involuntary fine-tuning of motor control for precise activities such as throwing a ball directly to a target, and the delicate functions of the hands of a neurosurgeon or an expert musician. It is also involved in maintaining balance and posture through extensive neural connections with the medulla through the inferior cerebellar peduncle and with the midbrain through the superior cerebellar peduncle. These roles allow precise control of regular activities, such that conscious control is not needed. In this way, you can avoid having to consciously think about not falling over when you walk, as the cerebellum controls that function.

A major portion of the descending motor pathways (corticospinal tracts) cross to the other side, or decussate, at the medulla. These pathways, together with other areas of decussation in the central nervous system, are the basis for the phenomenon of contralateral control.

Reflexes

Neural circuits in the spinal cord, when activated, display specific sets of motor responses. Reflex arcs form basic units that respond to stimuli and provide protective circuitry for motor output. They are referred to using many different terms. First, there are four aspects of all reflexes: they are involuntary, rapid and require a stimulus to trigger them, and the reflex response is similar every time it is activated. The structures needed for a reflex arc are a receptor, a sensory (afferent) neuron and an integration centre (within the central nervous system), followed by a motor (efferent) neuron and an effector muscle or gland. The receptor senses the stimuli and the sensory neuron transmits that signal as an action potential to the site of integration within the central nervous system. In response, the motor neuron relays the signal to the effector, which is often to a muscle. When the reflex arc occurs through the spinal cord, it is classified as a spinal reflex.

The two main reflex arcs are the stretch and withdrawal reflexes:

The stretch reflex is the simplest of the spinal reflex arcs and contains only two neurons, meaning that there is only one synapse between the two neurons (monosynaptic). An example of this is a common reflex test performed in clinical practice: the patellar reflex or knee jerk. When the patellar ligament is tapped, the extensor muscle stretches, sending an afferent signal to the spinal cord. This triggers motor neurons that cause the quadriceps to contract, which completes the reflex arc (see Figure 6-17).

The withdrawal reflex involves multiple synapses (polysynaptic). These reflexes are associated with involuntary removal from a painful or injury-provoking stimuli — for instance, removing your hand when you touch a hot stove or pulling your leg up when you step on a sharp object (see Figure 6-18). The polysynaptic reflex arcs are usually associated with the sensation of pain, as nociceptive fibres (neurons that carry pain signals; see Chapter 7) transmit the signal to the cerebral cortex, where the individual becomes aware of the pain. It is important to realise that this occurs after the reflex, as the distance to the brain is longer than the reflex and the sensation of pain needs to be interpreted in the cerebral cortex. These processes take time, and the withdrawal reflex working through a reflex arc means that the body is already removed from pain prior to awareness. This means the reflexes are protective and prevent further injury to the body (see Chapter 7).

FIGURE 6-17 The stretch or knee-jerk reflex.

A stretch to the muscle stimulates the stretch receptor. 1 The stretch receptor within the quadriceps muscle detects the stretch caused by tapping the patellar tendon. 2 The stretch receptor sends an afferent signal to the spinal cord. 3 In the spinal cord, there is an excitatory synapse with the motor neuron that innervates the quadriceps muscle, as well as an inhibitory synapse with the motor neuron for the hamstrings. 4 As a result, the quadriceps muscle contracts (extensor muscle) 5 Also, the hamstring muscle relaxes, which prevents it from limiting the action of the quadriceps.

Source: Boron WF, Boulpaep EL. Medical physiology: a cellular and molecular approach. 2nd edn. Philadelphia: Saunders; 2009.

FIGURE 6-18 The withdrawal reflex.

A painful stimulus to the right foot elicits a withdrawal reflex. 1 The cutaneous nociceptor is triggered by the sharp object and sends an afferent signal to the spinal cord. 2 The interneurons in the spinal cord relay motor efferent signals to the flexor muscles and inhibit the extensor muscles in the right leg. 3 Collectively, this causes the right leg to withdraw from the painful source. 4 At the same time, interneuron connections in the spinal cord relay efferent signals to the opposite leg that cause the extensor muscles to contract and flexor muscles to relax. 5 This causes the opposite leg to stabilise your position so that you do not fall over.

Source: Boron WF, Boulpaep EL. Medical physiology: a cellular and molecular approach. 2nd edn. Philadelphia: Saunders; 2009.

In addition to the spinal reflexes, which are associated with the somatic nervous system, there are many reflexes associated with the autonomic nervous system. These occur without conscious control and involve organ responses, such as increasing the heart rate when frightened. The autonomic reflexes are controlled by the sympathetic and parasympathetic nervous systems and are discussed with individual body systems in later chapters.

Sensory pathways

Afferent pathways transmit information from peripheral receptors, through the spinal cord and eventually terminate in the cerebral cortex or cerebellum, or both. The three clinically important spinal afferent pathways are the posterior (dorsal) column, the anterior spinothalamic tract and the lateral spinothalamic tract (see Figure 6-19). The posterior part of the spinal cord carries information about where the body is positioned in space, called proprioception. An example of this is knowing where your arms and legs are positioned relative to your body without having to see them. The anterior spinothalamic tract carries vague touch information, while the lateral spinothalamic tract is responsible for pain and temperature.

FIGURE 6-19 Somatic motor and sensory pathways (or tracts).

A Lateral corticospinal tract sending signals to skeletal muscles. B Reticulospinal pathway sending signals to muscles involved in posture. C Dorsal column, transmits touch and propioception. D Lateral spinothalamic tract, transmits pain and temperature signals.

Source: Based on Thibodeau GA, Patton KT. Anatomy & physiology. 6th edn. St Louis: Mosby; 2007.

Motor pathways

Efferent pathways primarily relay information from the cerebral hemispheres to the brainstem or spinal cord. The initiation of movement occurs in neurons within the central nervous system, which synapse with interneurons, which then synapse with motor neurons before projecting into the periphery. Motor neurons directly influence muscles. Their cell bodies lie in the grey matter of the brainstem and spinal cord, but their processes extend out of the central nervous system and into the peripheral nervous system. Muscle activity (i.e. stimulation and contraction) is regulated by nerve impulses. Motor neurons innervate one or more muscle cells, forming the neuromuscular junction (this is discussed in greater detail in Chapter 14).

The four clinically relevant motor pathways are the lateral corticospinal, corticobulbar, reticulospinal and vestibulospinal tracts.⁹ The corticospinal and corticobulbar pathways are essentially the same tract and their cell bodies originate in and around the precentral gyrus — this is the region where most motor information is initiated. These motor neurons are involved in precise motor movements. The reticulospinal tract (see Figure 6-19) controls motor movement by inhibiting and exciting spinal activity. The vestibulospinal tract arises from a vestibular nucleus in the pons (responsible for balance) and causes the muscles of the body to rapidly contract. For example, this becomes activated when an individual starts to fall backwards.

The cranium and vertebral column

The cranium (skull) is composed of eight bones. The cranial vault encloses and protects the brain and its associated structures. The floor of the cranial vault is irregular and contains many foramina (openings) for cranial nerves, blood vessels and the spinal cord to exit. The vertebral column (see Figure 6-15) provides physical protection for the spinal cord by the bones of the spine.

The meninges

Surrounding the brain and extending down the spinal column beyond the end of the spinal cord are three protective membranes: the dura mater, the arachnoid mater and the pia mater. Collectively they are called the meninges (see Figure 6-20A).

FIGURE 6-20 Meninges of the brain and spinal cord.

A Layers of meninges. Note that the meninges seen here are also continuous with the spinal cord. B The filum terminale is the extension of the pia mater, which assists in anchoring the spinal cord inside the vertebral column.

Source: Based on Patton KT, Thibodeau GA. Anatomy & physiology. 7th edn. St Louis: Mosby; 2010.

Cerebrospinal fluid and the ventricular system

Cerebrospinal fluid (CSF) is a clear, colourless fluid similar to blood plasma and interstitial fluid, but it has a different composition to these other fluids. The intracranial and spinal cord structures float in cerebrospinal fluid and are thereby provided some protection from trauma. The buoyant properties of the cerebrospinal fluid also prevent the brain from tugging on meninges, nerve roots and blood vessels. The constituents of cerebrospinal fluid are listed in Table 6-6. Between 125 mL and 150 mL of cerebrospinal fluid is circulating within the ventricles (small cavities) of the brain and subarachnoid space at any given time.

Table 6-6 THE COMPOSITION OF CEREBROSPINAL FLUID

Four ventricles within the brain serve to provide buoyancy and allow circulation of the cerebrospinal fluid: two lateral ventricles (one within each of the right and left cerebral hemispheres); the third ventricle between the left and right sides of the thalamus; and the fourth ventricle between the cerebellum and the brainstem (see Figure 6-21). A choroid plexus in each ventricle produces the cerebrospinal fluid. These plexuses are characterised by a rich network of blood vessels (supplied by the pia mater) that lie close to the ependymal cells (a type of neuroglial cell) of the ventricles.

FIGURE 6-21 The ventricles within the brain and the circulation of cerebrospinal fluid.

A Frontal view of the ventricles. B Lateral view of the ventricles. C Each ventricle contains a choroid plexus, which secretes cerebrospinal fluid. The CSF escapes from the fourth ventricle and into the subarachnoid space.

Source: A & B Copstead L-EC, Banasik JL. Pathophysiology. 4th edn. Philadelphia: Saunders; 2010. C Boron WF, Boulpaep EL. Medical physiology: a cellular and molecular approach. 2nd edn. Philadelphia: Saunders; 2009.

The cerebrospinal fluid exerts pressure within the brain and spinal cord. When a person is lying down, cerebrospinal fluid pressure is about 5–14 mmHg, or 6.8–19 cmH₂O, but this can double when the person sits up. Beginning in the lateral ventricles, the cerebrospinal fluid flows through the interventricular foramen into the third ventricle and passes through the cerebral aqueduct into the fourth ventricle. From the fourth ventricle the cerebrospinal fluid then continues to the subarachnoid spaces of the brain and spinal cord. The cerebrospinal fluid does not accumulate; instead, it is reabsorbed into the venous circulation through the arachnoid villi. Approximately 600 mL of cerebrospinal fluid is produced and reabsorbed daily. The arachnoid villi protrude from the arachnoid space, through the dura mater, and lie within the blood flow of the venous sinuses. The villi function as one-way valves directing cerebrospinal fluid outflow into the blood but preventing blood flow into the subarachnoid space. Thus, cerebrospinal fluid is formed from the blood, and after circulating throughout the central nervous system, it returns to the blood.

It should be noted that increases in cerebrospinal fluid pressure can cause severe damage to the brain: this pathophysiological condition, known as hydrocephalus, is examined in Chapter 8.

The blood–brain barrier

The blood–brain barrier describes cellular structures that inhibit some potentially harmful substances in the blood from entering the interstitial spaces of the brain or cerebrospinal fluid. In this way, the neurons that are particularly sensitive to change are protected from the changing environment of the blood, as only some substances from the blood can reach the neurons. The tight junctions between endothelial cells of capillaries in the brain are important in limiting the flow of substances out of the blood and into the cerebrospinal fluid. The astrocytes also assist with this barrier (see Figure 6-22). Metabolites, electrolytes and chemicals can cross into the brain to varying degrees. This has substantial implications for drug therapy because certain types of antibiotics and chemotherapeutic drugs show a greater propensity than others for crossing this barrier — which can limit the choices of drugs that can reach the brain. Importantly, not all potentially harmful substances are blocked by this barrier; for example, alcohol can easily pass through the blood–brain barrier, where it can affect the brain.

FIGURE 6-22 Tight junctions between brain capillary endothelial cells prevent substances from passing between the endothelial cell lining and thereby entering the neural tissue.

Astrocytes have foot processes on the capillary that help to maintain the integrity of the blood–brain barrier.

Source: Copstead L-EC, Banasik JL. Pathophysiology. 4th edn. Philadelphia: Saunders; 2010.

Blood supply to the brain

The brain receives approximately 15–20% of cardiac output, or 800–1000 mL of blood flow per minute. This constant delivery is vital to brain function — without it, the brain rapidly starves of oxygen and nutrients and the person will be rendered unconscious within a matter of minutes. Carbon dioxide is the primary regulator for blood flow within the central nervous system. It is a potent vasodilator and its effects ensure an adequate blood supply. This is most graphically illustrated when an individual hyperventilates (breathes rapidly and deeply). If the individual continues to hyperventilate, the carbon dioxide levels will decrease as it is expelled from the body, cerebral blood flow will decrease and the individual may become light-headed and feel faint.

The brain derives its arterial supply from two systems: the internal carotid arteries and the vertebral arteries (see Figure 6-23). The internal carotid arteries supply a proportionately greater amount of blood to the brain. They take their origin from the common carotid arteries, enter the cranium through the base of the skull and pass through the cavernous sinus. After giving rise to some small branches, these arteries divide into the anterior and middle cerebral arteries. The vertebral arteries originate at the subclavian arteries and pass through the transverse foramina of the cervical vertebrae, entering the cranium through the foramen magnum. They join at the junction of the pons and medulla to form the basilar artery. The basilar artery divides at the level of the midbrain to form paired posterior cerebral arteries.

FIGURE 6-23 Major arteries of the head and neck.

Source: Thibodeau GA, Patton KT. Anatomy & physiology. 6th edn. St Louis: Mosby; 2007.

The circle of Willis, named after the British physician Thomas Willis (see Figure 6-24), provides an alternative route for blood flow when one of the contributing arteries is obstructed (collateral blood flow). The circle of Willis is formed by the posterior cerebral arteries, posterior communicating arteries, internal carotid arteries, anterior cerebral arteries and anterior communicating artery. The anterior cerebral, middle cerebral and posterior cerebral arteries leave the circle of Willis and extend to various brain structures.

FIGURE 6-24 Arteries at the base of the brain.

The arteries that compose the circle of Willis are the two anterior cerebral arteries, joined to each other by the anterior communicating artery and two short segments of the internal carotids, off of which the posterior communicating arteries connect to the posterior cerebral arteries.

Source: Thibodeau GA, Patton KT. Anatomy & physiology. 6th edn. St Louis: Mosby; 2007.

Cerebral venous drainage does not parallel its arterial supply, whereas the venous drainage of the brainstem and cerebellum does parallel the arterial supply of these structures. The cerebral veins are classified as superficial and deep veins. The veins drain into venous plexuses and dural sinuses (formed between the dural layers) and eventually join the internal jugular veins at the base of the skull (see Figure 6-25). Adequacy of venous outflow can significantly affect intracranial pressure. For example, individuals with head injuries who turn or let their heads fall to the side partially occlude venous return, and the intracranial pressure can increase because of decreased flow through the jugular veins.

FIGURE 6-25 Large veins of the head.

Deep veins and dural sinuses are projected on the skull. Note connections (emissary veins) between the superficial and deep veins.

Source: Thibodeau GA, Patton KT. Anatomy & physiology. 6th edn. St Louis: Mosby; 2007.

Blood supply to the spinal cord

The spinal cord derives its blood supply from branches off the vertebral arteries and from branches from various regions of the aorta (see Figure 6-26). The anterior spinal artery and the paired posterior spinal arteries branch off from the vertebral artery at the base of the cranium and descend alongside the spinal cord. Arterial branches from vessels exterior to the spinal cord follow the spinal nerve through the intervertebral foramina, pass through the dura and divide into the anterior and posterior radicular arteries.

FIGURE 6-26 Arteries of the spinal cord.

A Arteries of the cervical cord exposed from the rear. B Arteries of the spinal cord diagrammatically shown in horizontal section.

Source: Redrawn from Ruby EB (ed.). Advanced neurological and neurosurgical nursing. St Louis: Mosby; 1984.

The radicular arteries eventually connect to the spinal arteries. Branches from the radicular and spinal arteries form plexuses whose branches penetrate the spinal cord, supplying the deeper tissues. Venous drainage parallels the arterial supply closely and drains into venous sinuses located between the dura and periosteum of the vertebrae.

Neurotransmitters and receptors of the sympathetic nervous system

The sympathetic nervous system has three main neurotransmitters: acetylcholine, adrenaline and noradrenaline. Acetylcholine is released from the sympathetic preganglionic fibres. In contrast, most postganglionic sympathetic fibres release noradrenaline (with some adrenaline as well) and thus are described as being adrenergic. The adrenaline (and noradrenaline) released as hormones by the adrenal medulla have the same effects on target cells, as they bind to the same receptor types. There is one exception: sweat glands that are innervated by the sympathetic nervous system. The postganglionic fibres release acetylcholine to stimulate the release of sweat. The reason for this remains unknown.

Adrenaline and noradrenaline are known together as catecholamines. These catecholamines stimulate two major classes of adrenergic receptors: α-(alpha)adrenergic receptors (α₁ and α₂); and β-(beta)adrenergic receptors (β₁, β₂ and β₃). The adrenergic receptors are structurally similar to each other, with slight differences that still allow the catecholamines to bind (see Figure 6-32). Cells of the effector organs have particular types of receptors located on their surface; a cell may actually have more than one type of adrenergic receptor (see Table 6-8). α₁-adrenergic receptors are found on the smooth muscle of blood vessels, so that when adrenaline or noradrenaline binds to the receptors, it causes contraction of the smooth muscle, resulting in vasoconstriction (a narrowing of the blood vessels). Most of the α-adrenergic receptors on effector organs belong to the α₁ class. α₂-adrenergic receptors are located in the pancreas to inhibit secretion of insulin.

FIGURE 6-32 Schematic representation of adrenergic neurotransmitters and receptors.

Noradrenaline and adrenaline are structurally very similar and both are capable of binding to all adrenergic receptor subtypes (although only some particular receptor types are found on target cells). Pharmacological agents can be targeted to specific receptor subtypes, limiting their interactions and adverse effects at other receptor types on other target cells. (α = alpha; β = beta.)

Table 6-8 THE EFFECTS OF THE SYMPATHETIC AND PARASYMPATHETIC NERVOUS SYSTEMS ON DIFFERENT ORGANS

β₁-adrenergic receptors are located mainly on the heart, both in the conduction system and in the muscle of the atria and ventricles. The effects of catecholamines on the heart are increased heart rate and contractility. β₁-receptors are also located on the kidney and cause it to release renin (which leads to an increase in blood pressure). β₂-adrenergic receptors are located in smooth muscle of the respiratory system and cause bronchodilation; they are also located in other organs, including arterioles and cause vasoconstriction. β₃ receptors are located on adipose cells.

Neurotransmitters and receptors of the parasympathetic nervous system

In the parasympathetic nervous system, both the preganglionic and the postganglionic fibres release acetylcholine. Because the neurotransmitter is acetylcholine, these neurons are known as cholinergic.

Acetylcholine works through cholinergic receptors, which are broadly categorised into nicotinic and muscarinic receptors (see Figure 6-33). The nicotinic receptors are located at the first synapse (at the ganglia) of both the sympathetic and the parasympathetic nervous systems. Although it is not a part of the autonomic nervous system, the synapse between neuron and voluntary skeletal muscle (of the somatic nervous system) also has nicotinic receptors (see Figure 6-30). When considering drugs that interact with nicotinic receptors, it is important to remember that these nicotinic receptors are found in both the autonomic and the somatic nervous systems and can affect both systems.

FIGURE 6-33 Schematic representation of cholinergic receptors.

Acetylcholine interacts with nicotinic and muscarinic receptors.

Acetylcholine is the neurotransmitter released at the effector organs of the parasympathetic nervous system, but these effector organs have the muscarinic receptors (see Table 6-8). Muscarinic receptors are located in the heart, and the effects of acetylcholine cause a slowing of the heart rate. Muscarinic receptors are also distributed throughout the body in smooth muscle and glands, and are found within the central nervous system as well as the parasympathetic nervous system.

Sympathetic nervous system: functions

In general, sympathetic stimulation promotes responses for the protection of the individual — hence the ‘fight or flight’ response. For example, sympathetic activity increases blood glucose levels and temperature and raises blood pressure.

In emergency situations, a generalised and widespread discharge of the sympathetic system occurs, known as sympathetic mass discharge. This is accomplished by an increased firing frequency of sympathetic fibres and by activation of sympathetic fibres normally at rest (fibres to the sweat glands, pilomotor muscles and the adrenal medulla, as well as vasodilator fibres to muscle).

Regulation of blood vessel tone is considered the single most important function of the sympathetic nervous system, as maintaining adequate blood pressure is essential to ensure appropriate blood flow to organs (Figure 6-34 illustrates some of the most important functions of the sympathetic nervous system). The sympathetic nervous system can actually cause both vasodilation (widening of blood vessels) and vasoconstriction (narrowing of blood vessels) at the same time in vessels of different parts of the body. This marvellous feat allows blood flow to be directed to tissues that need it most — for instance, vasoconstriction limits the amount of blood being supplied to the skin and digestive system, and simultaneous vasodilation in the heart, skeletal muscles and respiratory system maximises blood flow to those areas, thereby increasing their potential performance.

FIGURE 6-34 Some important functions of the sympathetic nervous system.

A Control of cardiac contractility and blood pressure. B Systemic activation during strenuous muscular exercise (‘fight or flight’ response). (β = beta.)

Parasympathetic nervous system: functions

Increased parasympathetic activity promotes rest and tranquillity and is characterised by a reduced heart rate and enhanced and increased digestion. Stimulation of the vagus nerve (cranial nerve X) in the gastrointestinal tract increases peristalsis and secretion, as well as relaxation of the sphincters. The vagus nerve has widespread functions in innervating the organs of the abdomen. Activation of parasympathetic fibres in the head (provided by cranial nerves III, VII and IX) causes constriction of the pupils, tear secretion and increased salivary secretion. Stimulation of the sacral division of the parasympathetic system contracts the urinary bladder and facilitates the process of genital erection.

The parasympathetic system lacks the generalised and widespread response of the sympathetic system. In Table 6-8 you will notice that some areas do not have parasympathetic receptors. For instance, most blood vessels involved in the control of blood pressure are innervated by sympathetic nerves. To decrease blood pressure, therefore, it is more important to block or paralyse the continuous (tonic) discharge of the sympathetic system than to promote parasympathetic activity.

Touch

Receptors sensitive to touch are present in the skin and are particularly abundant in the fingers and lips. The sensation of touch involves several neuron types, so that a variety of physical stimuli can be sensed and distinguished. In broad terms, these mechanoreceptors sense mechanical stimuli such as light touch, deep pressure, stretching and vibration. Because a sensitive area of the skin, such as the hands, has a large number of mechanoreceptors, it is easily possible to distinguish between these different types of touch stimulus. In addition, most of these sensations evoke affective or emotional responses that determine whether the sensation is unpleasant, pleasant or neutral.

Temperature

Neurons that sense temperature are known as thermoreceptors, with some being specialised to sense cold and others to sense warm. The more extreme the temperature, the more action potentials the neuron will send. Putting your hand into an esky filled with icy water will cause cold thermoreceptors in your skin to send many action potentials to the central nervous system, giving you thermal awareness of the cold water.

Chemical

The chemoreceptors are a diverse group of neurons that detect the proportion of particular chemicals. Obvious examples of chemoreceptors are the ‘taste buds’ on the tongue that detect sour, salty, sweet and bitter, and those located within the nasal cavity that allow you to distinguish scents as diverse as peppermint and putrid in the air.

We also have other chemoreceptors that have a vital role in maintaining normal body function. Chemoreceptors located in blood vessels sense particular substances in the blood such as the proportions of oxygen, carbon dioxide and acid; while chemoreceptors located in the brain detect substances within the cerebrospinal fluid. Detecting these substances is essential, so that any alterations can be corrected to restore homeostasis. We look at the specialised functions of these chemoreceptors in Chapters 22 and 24.

Proprioception

Awareness of the position of the body and its parts depends on impulses from the inner ear and from proprioceptors in joints and ligaments. These stimuli are necessary for the coordination of movements, the grading of muscular contraction and the maintenance of equilibrium.

Visual dysfunction

Alterations in ocular movements

Abnormal ocular movements result from dysfunction of cranial nerves III (oculomotor), IV (trochlear) or VI (abducens), and include nystagmus and strabismus:

Nystagmus is an involuntary rhythmic movement of the eyes. It may be caused by an imbalanced reflex activity of the inner ear, vestibular nuclei, cerebellum or nuclei of relevant cranial nerves. Drugs and retinal disease may produce nystagmus.

In strabismus, one eye deviates from the other when the person is looking at an object. This is caused by a hypertonic (weak) muscle in one eye. The primary symptom is diplopia (double vision), often caused by thyroid disease.

Alterations in visual acuity

Visual acuity is the ability to see objects in sharp detail. With advancing age, the lens of the eye becomes less flexible and adjusts slowly, and the sclera changes shape, so that visual acuity declines with age.

Cataracts are caused by a cloudy area within the lens and result from degeneration during ageing.

Retinal detachment occurs as fluid accumulates and separates the retina from underlying tissues, and may result from diabetes.

Glaucoma is characterised by high intraocular pressures (greater than 12–20 mmHg), usually due to excessive fluid. Fluid may be unable to be circulated or drained adequately. This may occur acutely, with a sudden rise in intraocular pressure causing pain and visual disturbances. Increased pressure on the optic nerve blocks its blood supply, leading to nerve destruction. More than 300,000 Australians have glaucoma, and those with diabetes are at increased risk of developing the condition.¹²

Age-related macular degeneration (AMD) is a severe and irreversible loss of vision and a major cause of blindness in older individuals. Hypertension, cigarette smoking, diabetes mellitus and age over 60 are risk factors. AMD includes abnormal blood vessel growth, leakage of blood or serum, retinal detachment and loss of photoreceptors, resulting in loss of central vision. This may be treated by laser photocoagulation.

Alterations in refraction

Alterations in refraction are the most common visual problem, and may be due to the focusing power of the lens or structural abnormalities. The major symptoms are blurred vision and headache.

Myopia, or nearsightedness, occurs when light rays are focused in front of the retina when the person is looking at a distant object (the person can see near objects clearly but distant objects are blurry; see Figure 6-41).

Hyperopia, or farsightedness, occurs when light rays are focused behind the retina when a person is looking at a near object (the person can see distant objects clearly but close objects are blurry; see Figure 6-41).

FIGURE 6-41 Alterations in refraction.

A Myopic eye. Parallel rays of light are brought to a focus in front of the retina. B Hyperopic eye. Parallel rays of light come to a focus behind the retina in the unaccommodative eye.

Source: Stein HA, Slatt BJ, Stewin RM. The ophthalmic assistant: fundamentals and clinical practice. 5th edn. St Louis: Mosby; 1998.

External eye structure disorders

Infection and inflammatory responses are the most common conditions affecting the supporting structures of the eyes. Conjunctivitis is an inflammation of the conjunctiva caused by bacteria, viruses, allergies or chemical irritants.¹⁴

Acute bacterial conjunctivitis (pinkeye) is highly contagious and often caused by Staphylococcus, Haemophilus, Streptococcus pneumoniae and Moraxella catarrhalis, although other bacteria may be involved.

Viral conjunctivitis is caused by an adenovirus. Common symptoms are watering, redness and photophobia.

Allergic conjunctivitis is associated with a variety of antigens, including pollens.

Chronic conjunctivitis results from any persistent conjunctivitis.

Preventing spread of the microorganism with hand-washing and use of separate towels is important. Bacterial conjunctivitis is treated with antibiotics.

Auditory dysfunction

Impaired hearing is the most common sensory defect. The major categories of auditory dysfunction are conductive hearing loss, sensorineural hearing loss, mixed hearing loss and functional hearing loss.¹⁵ Hearing loss may range from mild to profound. Auditory changes caused by ageing are common and incremental.

Ear infections

Otitis externa is the most common infection of the outer ear and may be acute or chronic.¹⁸ The most common cause of acute infections are bacterial microorganisms including Pseudomonas, Escherichia coli and Staphylococcus aureus. Infection usually follows prolonged exposure to moisture (swimmer’s ear). The earliest symptoms are inflammation with pruritus, swelling and clear drainage, progressing to purulent drainage with obstruction of the canal. Acidifying solutions and topical antibiotics are used for treatment.

Otitis media is the most common infection of infants and children.¹⁹ Most children have one episode by 3 years of age. The most common pathogens include Streptococcus pneumoniae and Haemophilus influenzae. Predisposing factors include sinusitis, adenoidal hypertrophy and immune deficiency. Breast-feeding is a protective factor. Recurrent acute otitis media may be genetically determined.²⁰ Acute otitis media is associated with ear pain, fever, irritability, inflamed tympanic membrane and fluid in the middle ear. The tympanic membrane progresses from erythema to opaqueness with bulging as fluid accumulates. Otitis media with effusion is the presence of fluid in the middle ear. Treatment includes symptom management, particularly of pain, with watchful waiting, antimicrobial therapy for severe illness and placement of tympanotomy tubes when there is persistent bilateral effusion and significant hearing loss.²¹ Complications include mastoiditis, brain abscess, meningitis and chronic otitis media with hearing loss. Persistent middle ear effusions may affect speech, language and cognitive abilities.

Olfactory and taste dysfunction

Olfactory dysfunctions can be mild or detrimental. In the person with anosmia — a complete loss of smell — less variety may be incorporated into food choices, which may impact negatively on nutritional status. Malnutrition is a concern in some groups within our community (refer to Chapter 27), and anosmia may contribute to the condition. Of more immediate concern is the inability to smell harmful substances such as fire, chemicals and spoiled foods, which may have a substantial impact on the individual. A less severe condition is hyposmia, an impaired sense of smell.

The sense of taste can be impaired by injury. Altered taste may be attributed to impaired smell associated with injury near the hippocampus. Hypogeusia is a decrease in taste sensation, whereas ageusia is an absence of the sense of taste. These disorders result from cranial nerve injuries and can be specific to the area of the tongue innervated. These conditions can also contribute to the likelihood of developing malnutrition.

PAEDIATRICS

GROWTH AND DEVELOPMENT OF THE NERVOUS SYSTEM

Environmental influences have a significant role in nervous system development. Nutrition, hormones, oxygen levels and external stimulation all affect normal growth. The proper proportions of essential nutrients are necessary for proliferation of the nervous system tissue. Maternal lifestyle, nutrition and state of health also have a crucial impact on nervous system development at certain critical periods of maturation.

The growth and development of the brain occurs rapidly during weeks 15–20 of gestation and again at week 30 through the first year of life, reflecting the development and multiplication of neurons. The head is the fastest growing body part during infancy. One half of postnatal brain growth is achieved by the first year and is 90% complete by age 6 years. The cortex thickens with maturation and the sulci deepen as cortical functions develop. Cerebral blood flow and oxygen consumption is about twice that of the adult brain during these years.

The bones of the infant’s skull are separated at the suture lines forming two fontanels or ‘soft spots’: one diamond-shaped anterior fontanel and one triangular-shaped posterior fontanel. The fontanels allow for expansion of the rapidly growing brain. The posterior fontanel may be open until 2–3 months of age; the anterior fontanel normally does not fully close until 18 months of age (see Figure 6-42). Abnormal intracranial conditions, such as those characterised by increased intracranial pressure, may also result in distention or bulging of the fontanels and an increased head circumference in excess of that expected with normal growth. Healthcare providers carefully monitor the fontanels for 2 years and head growth during the first 5 years by measuring head circumference and comparing the results with a standardised growth chart.

FIGURE 6-42 Cranial sutures and fontanels in infancy.

Fibrous union of suture lines and interlocking of serrated edges (occurs by 6 months; solid union requires approximately 12 years).

Human neurological functioning is primarily at a sub-cortical level at birth (impulses are handled by the brainstem and spinal cord). Many reflex patterns mediated by brainstem and spinal cord mechanisms are present at birth and then disappear at predictable times during infancy. Absence of expected reflex responses at the appropriate age indicates general depression of central or peripheral motor functions. Asymmetric responses may indicate lesions in the motor cortex or may occur with fractures of bones after traumatic delivery or postnatal injury. As the infant matures, the neonatal reflexes disappear in a predictable order as voluntary motor functions supersede them. Abnormal persistence of these reflexes is seen in infants with developmental delays or with central motor lesions.