11Physiology
C Activation of S2-S4 α-motor neurons causing contraction of the external urethral sphincter striated muscle fibers.
The external urethral sphincter is under voluntary (somatic) control, and muscle fiber contraction causes closure of the sphincter. A full bladder sends afferent signals causing inhibition of sympathetic tone and an increase in parasympathetic activity to the bladder through the pelvic splanchnic nerves. The parasympathetic activity relaxes the internal urethral sphincter and induces bladder contraction.
D Acetylcholine
Acetylcholine acts through nicotinic receptors at the ganglionic synapse. (A) Norepinephrine is the neurotransmitter used in most postganglionic sympathetic fibers.
A Botulism toxin
C Diphtheria toxin
(B) Tetanus toxin inhibits the release of GABA and glycine in the spinal cord. (D) Alpha bungarotoxin inhibits acetylcholine from binding to its receptors at the neuromuscular junction. (E) Tetrodotoxin blocks action potentials by binding to and inhibiting fast, voltage-gated sodium channels.
C Increasing axonal membrane resistance The length constant (λ) describes the distance over which a passively conducted electrical signal decays to 37% of its initial voltage. A larger length constant means a slower rate of degradation. The equation is:
where rm is the membrane resistance, ri is the internal axonal resistance, and r0 is the extracellular resistance. Increasing myelination increases membrane resistance, and internal axonal resistance is decreased with increasing axonal cross-sectional area (i.e., diameter).
E Thrombin
Factor VIII is bound to von Willebrand factor (vWF) and inactive in circulation. Under the action of thrombin, factor VIII is released form vWF and thus activated. When not bound to vWF, factor VIII quickly degrades.
C The lack of cerebral autoregulation causes an increase in ICP.
With brain death, there is a loss of cerebral autoregulation, so the brain’s normal response of maintaining a vascular tone sufficient to counteract increases in mean arterial pressure (MAP) is lost. The brain experiences the increases in MAP, which translate to increases in intracranial pressure.
A Unipolar
Sensory neurons are classified as unipolar with an axon and dendrites on each end and a cell body branching from some point along the axon. (B) Bipolar neurons have an axon with dendrites on each end with a cell body along the axon. They are found as interneurons, like in the retina. (C) Multipolar neurons have dendrites surrounding a cell body from which a single axon originates. They are found as motor neurons. (D) Pyramidal neurons appear as bipolar neurons with numerous arboretic dendritic processes extending from the cell body and axons. Prime examples are found in the cerebellum as Purkinje cells. (E) Multiaxonic neurons do not exist.
C Stopping at a stop sign in a motor vehicle
Both the utricle and saccule respond to changes in linear acceleration with the utricle being oriented horizontally and the saccule vertically. Deceleration in a motor vehicle traveling straight or a head tilt downward each causes anterior displacement of the otoliths in the macula of the utricle and excites hair cells that respond to movement in that direction. In contrast, the act of jump roping mainly would be sensed by action in the saccule. (A, D) Both of these activities cause a shift of endolymph in the semicircular canals that is detected in the ampulla of each canal. The ampullae respond to angular acceleration. (B, E) The vestibular system only responds to changes in acceleration and will adapt with no or constant motion in the same direction.
B Growth hormone
Excess growth hormone in adults results in arthropathy, paresthesias, polyneuropathy, cardiomyopathy, arrhythmias, upper airway obstruction due to palatal/pharyngeal tissue overgrowth, increased risk for malignancies and colon polyps, and diabetes. (A) Excess adrenocorticotropic hormone (ACTH) secretion results in Cushing disease, characterized by weight gain, hypertension, mood changes, hypertelorism, fatigue, and “moon face.” (C) High prolactin levels are associated with infertility, spontaneous lactation, loss of libido, erectile dysfunction, and abnormal menstrual cycles. (D) Excess thyroid-stimulating hormone results in hyperthyroidism with symptoms of tremors, anxiety, weight loss, heat intolerance, brittle hair, and insomnia. (E) Excess follicle-stimulating hormone results in infertility.
B IL-1 and TNF-α
The major proinflammatory cytokines are the interleukins (IL) IL-1, IL-6, IL-8, TNF-α (tumor necrosis factor-alpha), and IFN-γ (interferongamma). These produce fever, tissue destruction, and inflammation. The major anti-inflammatory cytokines include IL-4, IL-6, IL-10, IL-11, and IL-13. Of note, IL-6 can be anti- or proinflammatory depending on how it is used in a signaling cascade. (A) TGF-α and VEGF are examples of growth factors.
C Response of the postsynaptic terminal caused by the release of a single vesicle into the synaptic cleft
MEPs summate in the postsynaptic terminal to induce a response of either hyperpolarization or depolarization. (A, B) Miniature end-plate potentials (MEPs) can be excitatory or inhibitory.
B Between the resting and threshold potentials
Found initially in cardiac smooth muscle cells, T-type calcium channels are unique voltage-gated calcium channels that open at around −55 mV, which is slightly higher than the resting potential in cardiac cells of −60 mV. T-type calcium channels open to allow a large calcium flux into the cell to aid in the depolarization required to reach the triggering threshold for an action potential.
D Prolong action potential duration and maintain normal conduction velocity
By blocking only potassium channels (notably the inward rectifier channels), hyperpolarization (returning to a negative resting potential) is inhibited, and cardiac cells remain depolarized longer. This prolongs the action potential and the refractory period. Conduction velocity is unaffected, as there is no prevention of the opening of subsequent sodium channels and depolarizing adjacent membrane segments.
E All neurotransmitters can be used to upregulate downstream neural network activation
Although neurotransmitters are labeled as excitatory or inhibitory, this refers only to the effect of a neurotransmitter on a specific type of receptor at a specific synapse. It is how the various receptors and neurons containing the receptors are organized that causes a downstream effect. For example, the basal ganglia circuitry is full of circuits that inhibit inhibitory circuits so that an inhibitory synapse/receptor on an inhibitory neuron could result in the activation of a downstream neuron.
B Phosphodiesterase inhibition
By inhibiting phosphodiesterase, cAMP degradation is reduced. All of the actions of caffeine serve to upregulate the nervous system in a stimulatory manner. (A) Caffeine competitively inhibits glycine receptors. (C) Caffeine competitively inhibits adenosine receptors. Activation of adenosine receptors leads to the sensation of drowsiness. (D) Caffeine competitively inhibits acetylcholinesterase. (E) Caffeine is an agonist for the ryanodine receptor.
A Inhibition of the presynaptic uptake of monoamines
Cocaine blocks the monoamine transporter proteins on the presynaptic cleft, thus preventing monoamine reuptake and vesicular storage in the presynaptic terminal. (B) Amphetamines both block the reuptake of monoamines into the presynaptic terminal and induce the release of monoamines into the synaptic cleft.
D Choline and acetate
Following the breakdown of acetylcholine by acetylcholinesterase in the extracellular space, acetate is transported into the intracellular space, where it is converted to acetyl CoA, which then can combine with choline to reform acetylcholine.
C Caspases typically are not part of necrosis
Caspases are proteases necessary for apoptosis. They signal and regulate the controlled process by which DNA and cellular components are fragmented and degraded. In contrast, necrosis is uncontrolled cell death and results in inflammation. Caspases typically play little to no role in necrosis.
A Glutamate and glycine
Two molecules of either glutamate or aspartate and two molecules of either glycine or serine need to bind to an NMDA receptor in order to activate it. The receptor also has a voltage-gated component requiring depolarization of the neuron on which it is located. The voltage-gated component of the receptor is controlled by the calcium channel being blocked by either a zinc or magnesium ion when the receptor is inactive.
D Inhibition of osteoclasts
Bisphosphonates bind to calcium and are taken up by osteoclasts. Bisphosphonates then induce apoptosis of these bone-reabsorbing cells. These are useful agents in osteopenia and osteoporosis. (A) Bisphosphonates have no effect on the body total stores of calcium. (B) Osteocytes are osteoblasts that have entrapped themselves in their secretory bony matrix. They do not divide, but they do play a role in the turnover and maintenance of the bony matrix. They express TGF-β to suppress bone resorption. (C) Inhibition of osteocytes would lead to increased bone resorption. (E) Osteoblasts form new, nonmineralized bony matrix on the surface of mature, mineralized bone. They are regulated and recruited in part by osteocytes.
C Between the α and β subunits
(E) The benzodiazepine binding site on the GABAA receptor is between the α and γ subunits.
C Cell bodies in the lumbar prominence of the spinal cord
The patellar reflex occurs independently of input from the brain; however, the brain does work to suppress the reflex when all spinal circuitry is intact. This is why hyperreflexia and clonus can be seen with significant spinal cord compression. The actual reflex only requires the sensory nerves from the patellar tendon to be intact and synapse on cell bodies within the lumbar spinal cord. The reflex arc then stimulates motor neurons at that same level to provide the motor component of the reflex.
D DNA alkylation
Temozolomide and procarbazine are DNA alkylating (methylating) agents that interfere with protein synthesis. (A) Microtubule function inhibitors include vincristine and vinblastine. (B) DNA cross-links by carbamylation of amino groups are formed by the nitrosoureas such as BCNU and CCNU. (C) Bevacizumab (Avastin) is an anti-VEGF antibody. (E) Tamoxifen is a topoisomerase inhibitor.
D ACTH, β-lipotrophin, and γ-MSH
Following the initial cleavage of pro-opiomelanocortin into ACTH, β-lipotrophin, and γ-MSH, ACTH can be processed further to α-MSH and CLIP. β-lipotrophin can be processed into β-endorphin and γ-lipotrophin with the latter eventually becoming β-MSH.
A The H-wave disappears
The H-wave is the electrophysiological equivalent of the stretch reflex and represents the muscle’s electrical response to a square wave stimulus to the skin that first propagates in the antidromic direction (away from the muscle) to the cell bodies. The reflex arc continues with an electrical signal sent in the orthodromic direction (toward the muscle) to elicit a response. This response is the H-wave. As stimulation amplitude increases, the H-wave diminishes and disappears with supramaximal stimulation. It is most useful for evaluating the Ia sensory afferents. (B, D) The M-wave is the orthodromic response recorded in the muscle to electrical stimulation of the skin overlying the muscle. It bypasses the reflex arc and increases with increasing stimulation amplitude. (E) The F-wave increases with increases in amplitude but not to the extent seen in the M-wave. The F-wave is the result of alpha-fiber stimulation and is useful to evaluate proximal (near the spinal cord) nerve conduction velocities.
D Arginine
Arginine along with cofactors NADPH and oxygen react in the presence of nitric oxide synthetase to produce nitric oxide, NADP, and citrulline. (A, E) Tyrosine and asparagine are not involved in nitric oxide synthesis. (B, C) NADP and citrulline are products in the reaction creating nitric oxide.
B The curve is wider with smooth muscle, as shown in this image.
(A) Tension equals the force of the muscle. (C) Tension increases to its maximum as the muscle is stretched beyond its ideal working length (at the point of maximal myosin and actin overlap). Tension will increase indefinitely at the far right of the tension-length curve until muscle tissues begin to tear. (D) When the single peak of active muscle tension versus length is added to the exponential relationship of tension to length in resting muscle, there is a tension peak, followed by a trough, followed by a continued rise in tension with both smooth and skeletal muscle.
B Glutamate
Glutamate triggers the activation of NMDA receptors. When the magnesium ion is displaced from its channel-blocking site, there is calcium influx into the cytosol. Elevated calcium levels trigger apoptotic changes in the affected cells.
C Pericytes
Pericytes are the cells surrounding the endothelial cells of capillaries and venules throughout the body. In the brain, pericytes create and maintain the tight junctions between endothelial cells and regulate vesicle trafficking between endothelial cells. It is this role that creates the selectivity of the blood-brain barrier. Pericytes also inhibit the expression of endothelial markers that increase vascular permeability. (A) Astrocytic foot processes historically were thought to be the key component creating the blood-brain barrier; however, their role is to provide biochemical support to the endothelial cells creating the barrier. (B) Arachnoid “cap” cells are cells of the arachnoid villi from which meningiomas originate. (D) The endothelial cells themselves are not the key component to the blood-brain barrier. Instead, the highly selective tight junctions between endothelial cells allow for the specialized function of the blood-brain barrier.
A Irreversible binding to and inhibition of acetylcholinesterase
Organophosphates irreversibly bind to acetylcholinesterase and inactivate this acetylcholine-degrading enzyme. Pralidoxime can be used as an antidote in organophosphate poisoning, as it is able to reactivate the enzyme prior to degradation.
B The affinity of hemoglobin for oxygen decreases, and the oxygen-hemoglobin dissociation curve shifts to the right, as shown in this image.
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