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CHAPTER 13 Nervous and Locomotor Systems
271
• at the Z lines the membrane of the muscle cell (sarcolemma) forms narrow tubes that traverse the sarcomere; these are called the T-tubules.
• e myosin laments consist of a long tail and a head
section; the head has a binding site for ATP.
• e actin laments contain three dierent proteins:
• actin: a thin contractile protein, arranged in a dou-
ble-stranded helix
• tropomyosin: lies in the groove between the actin
laments
• troponin: lies at regular intervals along the lament,
attached to both actin and tropomyosin; it also has
binding sites for Ca2+ and is involved in the regulation of contraction. Troponin and tropomyosin
block the myosin-binding site on actin.
Skeletal Muscle Classification
• Skeletal muscle is classied according to the speed of
contraction:
• type I or slow twitch: act as postural muscles, e.g.
in the back; they are designed to perform slow, sustained contractions and resist fatigue well. ey rely
on aerobic metabolism and contain myoglobin
• type II or fast twitch:
• type IIa or fast oxidative bres, e.g. calf muscles:
they rely on aerobic metabolism and contain myoglobin; they have moderate resistance to fatigue
• type IIb or fast glycolytic bres, e.g. extraocular muscle: do not contain myoglobin and thus
appear white; they contain a large amount of glycogen and rely on anaerobic metabolism.
Sliding Filament Hypothesis (Fig. 13.9)
• Muscle contraction is known to occur by the actin and
myosin laments sliding past each other: the sliding
lament theory.
• e process of muscle contraction occurs, as the head
section of myosin is able to form cross-links with actin.
• When ATP binds to the head section of myosin it dissociates from its binding site on the actin lament.
• e ATP is hydrolysed and changes the angle of the
myosin head (relative to its tail); as the ATP has been
hydrolysed, the myosin is again able to bind to the actin
lament.
• e release of phosphate from the myosin head restores
the angle and moves the actin lament along the myosin
lament; this is called the power stroke.
• ATP will bind to myosin and start the process again.
• Creatine phosphate is present in very high concentrations within muscle and provides sucient
energy reserves for the above processes to take place.
e enzyme creatine kinase catalyses the transfer of the
phosphate group from creatine phosphate to ADP, thus
replenishing ATP stores.
Excitation Contraction Coupling
• Skeletal muscle only contracts if it receives an excitatory
impulse from a motor nerve (see below).
• An action potential is conducted down the motor nerve
and activates an electrical signal to be conducted across
the sarcolemma; this impulse is conducted deep within the
cell by the invaginations in the sarcolemma (T-tubules).
• Depolarization of the cell leads to the release of Ca2+
from the sarcoplasmic reticulum within the cell. e
rise in Ca2+ activates contraction by binding to troponin on the thin laments; this leads to a conformational
change and removes troponin and tropomyosin from
the myosin binding site on actin.
• As the cell repolarizes, the Ca2+ is actively pumped back
into the sarcoplasmic reticulum.
• e Ca2+ is removed from the troponin and thus the troponin and tropomyosin block the myosin binding site.
Neuromuscular Transmission
• Muscles are supplied by nerves from the spinal cord,
known as α motor neurons; they innervate the muscle
directly and lie in the anterior horn of the spinal cord
grey matter.
• α motor neurons are myelinated and conduct action
potentials to the muscle bre surface; here they form a
modied synapse called the neuromuscular junction.
• e motor neurons lose their myelin sheath and terminate in grooves in the muscle known as synaptic gutters; this is known as the motor end-plate. It is separated
from the axon terminal of the motor neuron by a gap;
this is called the neuromuscular cle.
• Transfer of the action potential from the motor neuron to the muscle is very similar to nerve conduction
described above:
• action potential depolarizes the terminal axon of the
motor neuron
• axon membrane becomes more permeable to Ca
2+
• the rise in Ca2+ stimulates secretory vesicles to fuse
with the cell membrane and release acetylcholine
(ACh) into the neuromuscular cle
• the ACh binds to receptors on the muscle bres; this
leads to the opening of ion channels, in turn leading
to the inux of Na+ and K+ and depolarization of the
cell; this is called the end-plate potential
• an action potential is initiated when the threshold is
reached; this leads to the impulse being propagated
across the plasma membrane
272
actin filament forwards;
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SECTION II Physiology
Actin
Myosin
ADP
ATP
ATP
ADP
ADP
ATP binds to myosin
head-group
Dissociation from actin
Hydrolysis of ATP leads
Pi
to change in head angle
and binding to actin
Pi
Release of Pi changes
angle of myosin head
group and 'pushes' the
this is called the
'power stroke'
Fig. 13.9 Molecular events involved in contraction of skeletal muscle.
• acetylcholine is released from the receptor and
the muscle cell repolarizes and is broken down by
acetylcholinesterase.
Muscle Stretch Reflex (Fig. 13.10)
• Simplest reex: it is monosynaptic and consists of the
aerent input from stretch receptors in skeletal muscle
and the eerent output to the stretched muscle.
LOCOMOTION
• e sensory organ for the stretch reex is the muscle
spindle: this consists of intrafusal muscle bres which
Spinal Cord Reflexes
• Reex: involuntary, stereotyped response as a result of a
sensory stimulus.
• e reex pathways consist of an aerent neuron that
conveys impulses from a sensory receptor, and an eerent neuron that runs from the brain to the eector
organ, i.e. muscle.
lie in parallel to the skeletal muscle bres. ere are two
types of intrafusal muscle bre:
• nuclear bag bres
• nuclear chain bres.
• e muscle spindle is divided into three regions: a contractile region at either end and a receptor region in the
centre.
CHAPTER 13 Nervous and Locomotor Systems
muscle fibre
Inhibitory interneuron
Intrafusal muscle fibre
Ia afferent
Quadriceps muscle
273
Alpha motor
neuron
Knee flexor
muscles
A
Extrafusal
Ia afferent neuron
muscle fibres
Intrafusal
Patellar tendon
Alpha motor neuron
B
Gamma motor neuron
Fig. 13.10 (A) Quadriceps stretch reflex: striking the patellar tendon produces knee extension. Reciprocal
innervation leads to inhibition of the knee flexors. (B) The gamma reflex loop. (From Crossman AR & Neary D.
Neuroanatomy: An Illustrated Colour Text, 2nd edn. Churchill Livingstone, Edinburgh, 2000, with permission.)
• e contractile regions are supplied by γ motor neurons
from the anterior horn of the spinal cord.
• e chain of events in the stretch reex is as follows:
• muscle spindle is stretched: this causes the receptor
region to depolarize; this generates an action potential in the aerent nerve (Ia aerent)
• the aerent impulse enters the spinal cord via the
dorsal horn and synapses with an α motor neuron
that supplies the stretched muscle
• the action potential in the α motor neuron signals
the muscle to contract to oppose the stretch
274
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SECTION II Physiology
• the aerent impulse also synapses with inhibitory neurons that synapse with α motor neurons that supply
antagonist muscles (reciprocal inhibition). is reduces
resistance to contraction of the stretched muscle.
• e anterior horn also contains γ motor neurons
(innervate the contractile ends of the muscle spindle).
Activation of γ motor neurons leads to contraction of
the ends of the muscle spindle; this lowers the threshold
for action potential generation, and thus increases the
sensitivity to stretch stimuli applied to the muscle. is
reex is called the gamma reex loop.
• e stretch reex and gamma reex are important for a
number of reasons:
• the control of voluntary activity: the muscle spindle
is able to contract with muscle bres and thus maintain sensory output
• control of muscle tone: the stretch reex resists pas-
sive changes in muscle length; this is particularly
important in the maintenance of body posture, i.e.
antigravity muscles of the neck, trunk and legs.
• e stretch reex is the physiological basis underlying
tendon reexes in clinical examination:
• biceps reex: C5–6
• brachioradialis reex: C5–6
• triceps reex: C6–7
• quadriceps reex: L3–4
• Achilles tendon reex: S1–2.
Golgi Tendon Organ Reflex
• e Golgi tendons are another stretch receptor. ey
are located in the tendon of muscles and are sensitive to
tension.
• e reex they are involved in is an inhibitory response.
It involves:
• aerent impulse acting on α motor neurons that sup-
ply the contracting muscle
• reduction in the level of active contraction (via
inhibitory interneurons)
• the reex is protective and limits muscle/tendon
stretch.
Withdrawal Reflex (Fig. 13.11)
• is is a more complex reex; it is polysynaptic.
• e withdrawal or exor reex is a response to painful
or noxious stimuli.
• e aerent input is from pain receptors; these synapse
with several eerent neurons:
• α motor neurons: this results in stimulation of ex-
ors in the limb in which the painful stimulus was
experienced, thus withdrawing the aected limb
• inhibitory signals are passed to α motor neurons in
the opposing extensor muscles
• this pattern is reversed in the opposing limb: exor
muscles are inhibited and extensor muscles are stimulated; this is called the crossed extensor reex. It
enables us to balance or push away from a noxious
stimuli, e.g. if you stand on a sharp object and pull
away your foot, the reex will lead to extension of the
contralateral limb to maintain balance.
Control of Locomotion
• A number of areas in the brain are involved in the control of movement; these include:
• cerebral cortex
• brainstem
• cerebellum
• basal ganglia.
• Control of movement by these centres can be via
descending pathways that synapse with the spinal motor
neurons, or via inputs into the motor area of the cerebral cortex from the cerebellum and basal ganglia.
Cerebral Cortex
• e motor area of the cerebral cortex lies in the frontal
lobe immediately anterior to the central sulcus; this area
is called the precentral gyrus.
• Descending pathways leave this area to supply spinal
motor neurons:
• corticobulbar tracts: supply the motor portions of
the cranial nerves
• corticospinal tracts: supply the spinal motor neu-
rons; they are concerned with voluntary movements.
• e descending bres from the cerebral cortex cross the
midline and innervate the opposite side of the body, i.e.
the le hemisphere supplies the right (contralateral side).
Brainstem
• ere are four descending inputs from the brainstem;
these are:
1. e rubrospinal tract: originates in the red nucleus
and primarily innervates distal limb muscles.
2. e tectospinal tract: bres arise in the superior col-
liculus of the midbrain; it receives inputs from the
visual cortex and is believed to control reex activity
in response to visual stimuli.
3. e vestibulospinal tract: originates in the vestibular
nuclei; it supplies muscles of the ipsilateral side of the
body. It innervates muscles concerned with balance
and posture in response to inputs from the vestibular
apparatus.
4. e reticulospinal tract: bres are derived from the
pons and medulla; they supply muscles on the ipsilateral side of the body and are important in maintaining posture and muscle tone.
Lumbar cord
Interneuron
ferent
Quadriceps
CHAPTER 13 Nervous and Locomotor Systems
Cutaneous af
neuron
275
muscle
Fig. 13.11 The flexor (withdrawal) reflex and crossed extensor reflex. (From Crossman AR & Neary D.
Neuroanatomy: An Illustrated Colour Text, 2nd edn. Churchill Livingstone, Edinburgh, 2000, with permission.)
Cerebellum
• ere are no descending pathways from the cerebellum; they inuence movement via inputs directly to the
motor cortex.
• e cerebellum receives information from the vestibular apparatus, visual system, corticospinal tracts and
peripheral proprioceptors.
• e cerebellum collates information from these sources,
and is important in maintaining balance and producing
smooth, co-ordinated movements.
Alpha motor neurons
Knee flexor
BONE PHYSIOLOGY
• Bone is a type of connective tissue. It has an organic and
• e organic component is referred to as osteoid; this
• e inorganic component contains complexes of cal-
muscles
inorganic component.
consists of collagen I, keratan sulfate, hyaluronic acid
and glycoproteins.
cium and phosphate (hydroxyapatite); it also contains
calcium carbonate, uoride, magnesium and sodium
ions.
• Bone has four main functions; these are:
Basal Ganglia
• e basal ganglia have no descending tracts; they receive
information from the substantia nigra, the thalamus
and the motor cortex.
• e basal ganglia appear to be involved in the initiation
of movement, ensuring that body posture is appropriate
for a particular movement and eliminating unwanted
movements.
• mechanical support
• locomotion (by means of joints)
• calcium and phosphate homeostasis
• haemopoiesis.
• Bones contain four main cell types; these are:
• osteoprogenitor cells: undierentiated cells
• osteoblasts: these cells secrete the organic matrix of
bone; they are also involved in mineralization
276
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SECTION II Physiology
• osteocytes: mature cells; they are trapped in gaps
(lacunae) aer they deposit matrix. ey are
involved in calcium homeostasis as they are able to
transport Ca2+ from the bone interior to the extracellular environment
• osteoclasts: these cells are responsible for the absorption of bone; this is via the release of lytic enzymes,
i.e. collagenase, acid phosphatase. ese cells are
considered part of the mononuclear macrophage
system.
Bone Formation and Reabsorption
• Bone is not an inert tissue; it is constantly remodelling
in order to cope with changes in the demands placed
upon it.
OSCE SCENARIOS
OSCE Scenario 13.1
An 18-year-old male is admitted to A&E following an
assault. He has severe head injuries. His Glasgow coma
score (GCS) is 6.
1. How is brain injury classied?
2. Describe the mechanism of compensation for an acute
rise in intracranial pressure.
3. Describe the possible management options.
• 5–10% of the bone mass is recycled each week; this can
be much greater in those undertaking strenuous activity. During immobility then bone mass can be rapidly
lost – disuse osteoporosis.
• Remodelling of bone is a two-stage process:
• osteoclastic reabsorption of bone
• osteoblastic phase in which new bone is laid down.
• e control of bone remodelling is not completely
understood (particularly at a cellular level); however,
a number of hormones are known to be involved,
including:
• parathyroid hormone
• calcitonin
• thyroxine
• oestrogen
• vitamin D.
1. What are the pre-conditions required before diagnosing
brainstem death?
2. What are the exclusion criteria?
3. Which cranial nerves are involved in the following tests:
a. Corneal reex
b. Gag reex
c. Cough reex
d. Vestibulocochlear reex
OSCE Scenario 13.2
A 55-year-old male presents to a pain clinic with a long
history of lumbar back pain that has become more severe
recently. ere is no history of sciatica and there is no neurological decit on examination. Paracetamol has been of
no benet.
1. Why is paracetamol unlikely to have been of benet?
2. Why is ibuprofen more likely to be of benet than
paracetamol?
3. What is the mechanism of action of TENS?
4. What is the purpose of the local anaesthetic injec-
tion and what is the mechanism of action of local
anaesthetics?
5. What is the mechanism of action of oramorph and what
side eects might be expected?
OSCE Scenario 13.3
A 24-year-old male is in a critical condition on ITU following a road trac accident. He has severe head injuries.
e ITU consultant has discussed his poor prognosis with
the family and they ask about organ donation. Answer the
following questions regarding testing for brainstem death.
OSCE Scenario 13.4
A 75-year-old male patient is found confused during a
night shi, ve days following le hemicolectomy. He has
past medical history of TIA, IHD and BPH. On examination, his GCS is 13/15, he appears combative and hallucinating, his temperature is 38.9°C, RR is 25/min, PR is 120/
min and irregular and blood pressure is 115/65. His chest
examination shows possible reduced air entry on the le
side, he is diusely tender in the abdomen, and he has a
urinary catheter with urine output averaging 20/h over the
last 3 h. Bedside ECG shows new fast AF. You are the night
surgical SPR and asked to review the patient.
1. How would you manage this patient?
2. What is the dierential diagnosis?
3. What is the most likely cause?
4. Who would you inform at this stage?
OSCE Scenario 13.5
A 65-year-old male patient has been stepped down from
the high-dependency unit to the ward on day two following
open repair of abdominal aortic aneurysm. As you review
him on the ward round, you notice that he is comfortable
CHAPTER 13 Nervous and Locomotor Systems
277
in bed; however, his blood pressure is low at 95/60 and
pulse rate is 58/min. He is apyrexial, his RR is 16/min and
his oxygen saturation is 98% on room air. His abdominal
examination is unremarkable, and his pain is well controlled, having epidural catheter in situ. e night FY1 gave
him intravenous uid challenge 2 h earlier which improved
his BP reading slightly and arranged for blood tests. His Hb
is 12.5 g/dL, WBC 11.2 × 106/dL, while the rest of his blood
tests are unremarkable.
1. What are the possible causes of his low blood pressure?
2. What drugs are usually infused in epidural catheters?
Please check your eBook at https://studentconsult.inkling.com/ for more self-assessment questions. See inside cover for
registration details.
3. How does epidural infusion cause hypotension?
4. Why is postoperative analgesia important for surgical
patients?
5. What are the side eects and complications of epidural
catheters?
6. How would you treat hypotension related to epidural
catheters?
Answers in Appendix pages 458–461
SECTION III
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Pathology
14. Cellular Injury, 279
15. Disorders of Growth, Morphogenesis and Dierentiation, 297
16. Inammation, 305
17. rombosis, Embolism and Infarction, 311
18. Neoplasia, 317
19. Immunology, 330
20. Haemopoietic and Lymphoreticular System, 342
21. Basic Microbiology, 360
22. System-Specic Pathology, 386
278
14
Cellular Injury
Causes of cellular injury include:
• trauma
• thermal injury – heat and cold
• chemical agents – drugs, poisons, hypoxia
• infectious organisms
• immunological mechanisms
• nutritional deciencies
• ionizing radiation.
MECHANISMS OF CELLULAR INJURY
Cells may be damaged either reversibly or irreversibly in a
variety of ways:
• Mechanical disruption:
• trauma by direct mechanical force
• extremes of heat and cold
• osmotic pressure changes.
• Failure of cell membrane integrity:
• damage to ion pumps.
• Membrane damage:
• free radicals.
• Interference with metabolic pathways:
• respiratory poisons and mitochondria
• disruption of protein synthesis.
• Deciency of metabolites:
• hypoxia/anoxia
• glucose (hypo- or hyperglycaemia)
• hormones.
• DNA loss or damage:
• ionizing radiation
• chemotherapy
• free radicals.
e eect of cell injury on a tissue will depend on:
• the nature of the injurious agent
• the duration of the injury
• the proportion of the type of cell aected
• the ability of the tissues to regenerate.
CELL DEATH
Cell death is the irreversible loss of the cell’s ability to
maintain independence from the environment. Two major
forms of cell death are recognized:
• necrosis
• apoptosis.
Necrosis
Necrosis is cellular or tissue death in a living organism, irrespective of the cause. Several types of necrosis are described:
• coagulative
• colliquative
• caseous
• gangrenous
• brinoid
• fat.
Coagulative Necrosis
• Denaturation of intracytoplasmic proteins.
• Dead tissue will initially become rm and swollen, but
later becomes so (ventricle may rupture aer myocardial infarction).
• Typically occurs in ischaemic injury (except brain).
Colliquative Necrosis
• Seen in brain, probably due to lack of supporting stroma.
• Necrotic brain tissue liquees.
• Glial reaction at periphery with cyst formation occurs
eventually.
Caseous Necrosis
• Characteristic of TB.
• Macroscopically cheese-like (caseous).
• Microscopically structureless.
Gangrenous Necrosis
• Necrosis with putrefaction of tissues due to certain bacteria, e.g. clostridia, streptococci.
279
280
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SECTION III Pathology
• Tissue black due to iron sulde from degraded
haemoglobin.
• Ischaemic gangrene may be either ‘dr y’ or ‘wet’ gangrene.
• Gas gangrene is the result of infection with Clostridium
perfringens.
• Synergistic gangrene follows infection by a specic
combination of organisms (see Chapter 21).
Fibrinoid Necrosis
• Associated with malignant hypertension.
• Necrosis of arteriole smooth muscle wall with seepage
of plasma into tunica media and deposition of brin.
• Smudgy eosinophilic appearance in H and E sections.
Fat Necrosis
• Direct trauma to adipose tissue and extracellular liberation of fat (e.g. fat necrosis causing breast lump).
• Enzymatic lysis of fat by lipases, e.g. pancreatic lipase in
acute pancreatitis. Fats split into fatty acids, which combine with calcium to precipitate as soaps (seen as white
spots on the peritoneum and omentum).
Apoptosis
Apoptosis is an energy-dependent process for the deletion
of unwanted individual cells. It is to be distinguished from
necrosis (Table 14.1). It is a biochemically specic mode of
cell death characterized by activation of endogenous endonuclease, which digests nuclear DNA into smaller DNA
fragments.
Function of Apoptosis
• Morphogenesis (elimination of cells in embryonal
development).
• Removal of cells which have undergone DNA damage.
• Removal of virally infected cells.
• Induction of tolerance to self-antigens by removal of
autoreactive T-lymphocytes.
Mediators of Apoptosis
p53
• A tumour suppressor gene which checks the integrity of
the genome prior to mitosis.
• Switches cells with damaged DNA into apoptosis.
• Loss of p53 expression is associated with poor prognosis
in tumours.
bcl-2
• Inhibits apoptosis.
• Excess bcl-2 expression results in failure of initiation of
apoptosis with cell accumulation.
• Overexpression in neoplasia.
fas (CD 95)
• Plasma membrane receptor which, when activated, is
directly coupled to the activation of intracellular proteases, which lead to apoptosis.
Caspases
• Present in all cells and unless inhibited lead to morphological changes of apoptosis.
Morphological Features of Apoptosis
• Cell shrinkage with intact plasma membrane.
• Nuclear shrinking (pyknosis).
• Nuclear fragmentation (karyorrhexis).
• Margination of chromatin.
• Surface blebbing of cell.
• Formation of apoptotic bodies (cells break up into
membrane-bound fragments).
• Fragments are either shed (if epithelial cells are involved)
or phagocytosed (by neighbouring cells).
TABLE 14.1 Comparison of Apoptosis and Necrosis
Feature Apoptosis Necrosis
Induction Physiological or pathological stimuli Invariably pathological injury
Extent Single cells Groups of cells
Biochemical Energy-dependent fragmentation of DNA
by endogenous endonucleases
Lysosomes intact
Cell membrane integrity Preserved Lost
Morphology Cell shrinkage and fragmentation to form
apoptotic bodies with dense chromatin
Inflammatory response None Usual
Fate of dead cells Phagocytosed by neighbouring cells Phagocytosed by neutrophils and
Impairment or cessation of ion homeostasis
Lysosomes leak lytic enzymes
Cell swelling and lysis
macrophages
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