Some Notes

SPECIAL NOTES


1. In an acute respiratory alkalosis, the bicarbonate typically decreases by 2 mM for each 10 mmHg decrease in PCO2; in a chronic respiratory alkalosis, the bicarbonate typically decreases 4 mM for each 10 mmHg decrease in PCO2. In this case the PCO2 has decreased by 30 mmHg. Because bicarbonate has decreased by 12 mM, the diagnosis is consistent with a chronic respiratory alkalosis.



pH = 6.1 + log [HCO3–] / (PaCO2 × 0.03 mmol/L/mmHg)
pH = 6.1 + log 12 mmol/L / (10 mmHg × 0.03 mmol/L/mmHg)
pH = 6.1 + log 40 = 6.1 + 1.6 = 7.7




2. The anion gap is equal to the difference between the plasma concentration of sodium, the major cation in the plasma, and the sum of the concentrations of plasma chloride and bicarbonate, the major measured anions in the plasma.

Anion gap = [Na+]–([Cl–] + [HCO3–])



3. The normal plasma concentrations of Na+, Cl–, and HCO3–are 142, 105,and 24 mEq/L, respectively. The normal anion gap is about 12 mEq/L, and is comprised of minor ions, such as lactate, phosphate, and sulfate. The anion gap is useful in differentiating the causes the metabolic acidosis. In normal anion gap metabolic acidosis, the decline in plasma bicarbonate ion is replaced by an increase in plasma chloride concentration with the concentration of unmeasured minor anions remaining normal, such as occurs with renal or gastrointestinal (GI) losses (e.g., diarrhea). High anion gap metabolic acidosis results from an increase in unmeasured organic anions, such as occurs in the lactic acidosis accompanying tissue hypoxia, the accumulation of ketoacids in diabetes and its resultant coma, or by an increase in organic anions or their metabolic byproducts produced from
such ingested toxins as ethylene glycol, methanol, and salicylates. COPD and myasthenia gravis are causes of respiratory acidosis. Nasogastric suctioning causes metabolic alkalosis.




4. The alkaline pH resulting from the hyperventilation is keeping most of the aspirin in an ionized form in which it cannot easily cross the blood-brain barrier. If the patient is placed on a ventilator to prevent muscle fatigue, it is important to maintain hypocapnic alkalosis or the aspirin will cross the
blood-brain barrier and the situation may become far worse. Gastric lavage with isotonic saline followed by administration of activated charcoal is indicated. Excessive insensible water loss from vaporization of sweat may cause severe volume depletion, requiring fluid replacement. Glucose
should be administered to prevent hypoglycemia.


5. Absorption of cobalamin occurs exclusively from the ileum, where specific receptors on ileal enterocytes bind a complex of cobalamin and intrinsic factor. Although intrinsic factor is secreted by gastric parietal cells, binding of the vitamin to intrinsic factor occurs primarily in the proximal small intestine. The acidic environment of the gastric lumen favors the binding of cobalamin to R protein-type binding proteins that originate from salivary and gastric secretions. Pancreatic proteases in the small intestine degrade the R proteins, and the rise in pH favors rapid and complete transfer of the vitamin to intrinsic factor.




6. The patient’s condition is caused by a decrease in the serum concentration of ionized calcium
(Ca2+), which increases nerve and muscle excitability, leading to spontaneous axonal discharges and muscle contractions, calledhypocalcemic tetany. Decreased serum ionized calcium and thus the symptoms of tetany can appear at higher total calcium levels when respiratory alkalosis is present because the H+ that dissociates from plasma proteins in the presence of a high pH is replaced by Ca2+.





7. Hypothermia reduces hemoglobin’s affinity for oxygen, causing the oxyhemoglobin dissociation curve to shift to the left. With a leftward shift, the saturation of hemoglobin with oxygen is greater than normal at any PO2, as denoted by a lower P50 value than normal. Acidosis, hypercapnia (increased PCO2), and an increase in erythrocyte [2,3–BPG] all cause rightward shifts of the oxyhemoglobin dissociation curve.

8. Factors that shift the curve to the left, such as a decrease in PCO2, an increase in pH, or a decrease in temperature, would increase the percentage of hemoglobin saturated with oxygen as would an
increase in PO2, provided that the percentage of saturation was not already at 100%. At a given PO2, increasing the concentration of hemoglobin would not affect the percentage of saturation but would increase the oxygen content of the blood.



9. CO2 is transported in arterial blood in three forms: as physically dissolved CO2 (about 5%), in combination with the amino groups of hemoglobin as carbaminohemoglobin (about 10%), and as bicarbonate ion HCO3– (about 85%). The amount of CO2 actually carried as carbonic acid, H2CO3, is negligible. Carboxyhemoglobin refers to the combination of carbon monoxide (CO) and hemoglobin.




10. Vitamin K is a fat-soluble vitamin produced by intestinal bacteria that is essential for maintaining normal clotting of blood. The vitamin is essential for hepatic synthesis of prothrombin and factors VII, IX, and X. Common causes of vitamin K deficiency include cholestasis, and factors that limit fat absorption.





11. Warfarin is often prescribed for patients at risk for thromboembolic episodes. Vitamin K is necessary for the conversion of prothrombin to thrombin. Thrombin is an important intermediate in the coagulation cascade. It converts fibrinogen to fibrin and is a powerful activator of platelets. Warfarin interferes with the activity of vitamin K and therefore reduces the likelihood of clot formation. Administering vitamin K can restore coagulation if warfarin therapy leads to excessive bleeding.





12. Normal Hb is 50% saturated at a PO2 of approximately 27 mmHg (the P50), 75% saturated at a PO2 of 40 mmHg (the normal PO2 of mixed venous blood), and 97% saturated at a PO2 of 100 mmHg (the normal arterial PO2). Fetal blood has a higher-than-normal oxygen affinity and therefore is represented by the curve labeled a. Increasing the affinity of Hb for O2 shifts the HbO2 saturation curve to the left and decreases the P50.



13. Aphasias are caused by lesions to the language centers, which are located in the categorical hemisphere of the neocortex. There are a number of different classifications of aphasias, but one divides them into fluent, nonfluent, and anomic aphasias. In this case, the boy developed an anomic aphasia, in which there was no difficulty with his speech and he was able to understand and follow commands, but he had difficulty understanding written language and pictures. Anomic aphasia is the single most common language disturbance seen in head trauma, metabolic encephalopathy, and Alzheimer’s disease. Anomic aphasia can be caused by lesions anywhere within the language
network, but often is caused by damage to the angular gyrus without damage to Broca’s or Wernicke’s areas. A lesion in Broca’s area leads to nonfluent aphasia, such as seen in Pick’s disease. Fluent aphasias are due to lesions to Wernicke’s area or to lesions in and around the auditory cortex. Language disorders caused by memory loss, which could be the result of a hippocampal lesion, are not classified as aphasias, nor are language disorders caused by vision or hearing abnormalities or motor paralysis.





14. The precentral gyrus is the motor area of the cortex that contains the cell bodies of the neurons that form the corticospinal tract (also referred to as the pyramidal tract). The corticospinal tract contains axons that cross to the contralateral side of the brain within the pyramids and end within the motor areas of the spinal cord. These structures are essential for the generation of fine voluntary movements. Kinesthesia, the sense of movement and position of the limbs, is handled primarily by the Ia and Ib afferents that innervate the muscle spindles and Golgi tendon organs, respectively, and by the parietal lobe.



15. In a normal sleep cycle, a person passes through the four stages of slow-wave sleep before entering REM sleep. In narcolepsy, a person may pass directly from the waking state to REM sleep. REM sleep is characterized by irregular heart beats and respiration and by periods of atonia (loss of
muscle tone). Hypoventilation is characteristic of both REM and non-REM sleep because sleep depresses the central chemoreceptors. Brain activity during REM sleep is higher than during wakefulness so there is an increase in brain metabolism. It is also the state of sleep in which
dreaming occurs.


16. In a totally relaxed adult with eyes closed, the major component of the electroencephalogram (EEG) will be a regular pattern of 8 to 12 waves per second, called the α rhythm. The α rhythm disappears when the eyes are opened. It is most prominent in the parieto-occipital region. In deep sleep, the α rhythm is replaced by larger, slower waves called delta waves. In REM sleep, the EEG will show fast, irregular activity.



17. Those within the anterior cerebellum produce ataxia; those within the substantia nigra produce Parkinson’s disease; and those within the limbic system yield emotional disorders. Ataxia, dysmetria, and an intention tremor all are classic findings in a patient with a lesion involving the cerebellum. Affected persons also exhibit adiadochokinesia, which is a loss of ability to accomplish a swift succession of oscillatory movements, such as moving a finger rapidly up and down. High-amplitude EEG waves occur in the late stages of slow-wave sleep.

Parkinson’s disease ischaracterized by resting tremor rigidity and akinesia. It is caused by destruction of the dopamine secreting neurons within the substantia nigra of the basal ganglia. Levo (L)-dopa is a precursor for dopamine. L-dopa, rather than dopamine, is administered because it can cross the blood-brain barrier, but dopamine cannot. In contrast to the resting tremor of Parkinson’s disease, cerebellar disease is characterized by an intention tremor. In contrast to damage to the nigrostriatal dopaminergic system in Parkinson’s disease, Huntington’s disease results in a loss of the intrastriatal GABAergic and cholinergic neurons in the caudate nucleus and putamen of the basal ganglion.





18. Pathologic vertigo is generally classified as peripheral (labyrinthine) or central (brainstem or cerebellum). The clinical presentation in this case is most consistent with central vertigo. Positional (especially horizontal) nystagmus (to-and-fro oscillation of the eyes) is common in vertigo of central origin, but absent or uncommon in peripheral vertigo. The chronicity of the vertigo is characteristic of central vertigo, whereas the symptoms of peripheral vertigo generally have a finite duration and may be recurring. Tinnitus and/or deafness is often present in peripheral vertigo, but absent in central vertigo. The flocculonodular lobe, or vestibulocerebellum, is connected to the vestibular nuclei and participates in the control of balance and eye movements, particularly changes in the vestibuloocular reflex (VOR), which serves to maintain visual stability during head movement; a lesion of this area of the cerebellum may result in vertigo and nystagmus, whereas the spinocerebellum is involved in the coordination of limb movement. Labyrinthitis and Ménière’s syndrome are examples of vertigo of peripheral origin. In psychogenic versus organic vertigo, nystagmus is absent during a vertiginous episode.



19. The catecholamines, norepinephrine and epinephrine, will activate both α- and β-adrenergic receptors. When the α1-adrenergic receptors are stimulated, they activate a G protein, which in turn activates phospholipase C, which hydrolyzes PIP2 and produces IP3 and DAG. The IP3 causes the release of Ca2+ from the sarcoplasmic reticulum, which in turn increases muscle contraction. α1-Adrenergic receptors predominate on arteriolar smooth muscle, so these muscles contract when stimulated with norepinephrine. The bronchiolar, pupillary, and ciliary smooth muscles all contain β- receptors, which cause smooth muscle relaxation. The intestinal smooth muscle relaxation is initiated by an α2-adrenergic receptor.




20. These variations in activity are called circadian rhythms and are controlled by the suprachiasmatic nucleus of the hypothalamus. The paraventricular nucleus secretes oxytocin and vasopressin, the ventromedial and lateral nuclei control food intake, and the arcuate nucleus secretes gonadotropin-releasing hormone.



21. Activating nociceptors on the free nerve endings of C fibers produces ischemic pain. The C fibers synapse on interneurons located within the substantia gelatinosa (laminas II and III) of the dorsal horn of the spinal cord. The pathway conveying ischemic pain to the brain is called the paleospinothalamic system. In contrast, well-localized pain sensations are carried within the neospinothalamic tract. Ischemic pain does not adapt to prolonged stimulation. Pain is produced by specific nociceptors and not by intense stimulation of other mechanical, thermal, or chemical receptors.



22. The hypothalamus regulates body temperature. Core body temperature, the temperature of the
deep tissues of the body, is detected by thermoreceptors located within the anterior hypothalamus. The anterior hypothalamus also contains neurons responsible for initiating reflexes, such as vasodilation and sweating, which are designed to reduce body temperature. Heat-producing reflexes, such as shivering, and heat-maintenance reflexes, such as vasoconstriction, are initiated by neurons located within the posterior hypothalamus.


23. The visual receptor cells, the rods and cones, are depolarized when the eyes are in the dark. When exposed to light, they hyperpolarize. Light causes the rods and cones to hyperpolarize by activating a G protein called transducin, which leads to the closing of Na+ channels. Auditory receptors are depolarized by the flow of K+ into the hair cells. Touch receptors are activated by opening channels through which both Na+ and K+ can flow. Depolarization is caused by the inward flow of Na+. Smell and taste receptors are activated by G protein-mediated mechanisms, some of which cause the receptor cell to depolarize; other G proteins cause the release of synaptic transmitter without any change in membrane potential.

Transducin is the G protein activated by rhodopsin when light strikes the eye. Transducin activates a phosphodiesterase that hydrolyzes cGMP. When cGMP concentrations within the rods or cones decrease, sodium channels close, sodium conductance decreases, and the cell membrane potential becomes more negative (hyperpolarizes). Hyperpolarization of the cell causes a decrease in the
release of neurotransmitter. Eventually the all-trans retinal dissociates from opsin and reduces the concentration of rhodopsin in the cell



24. g-Aminobutyric acid (GABA) is the major inhibitory mediator in the brain. GABA-A receptors are pentameric Cl–ion channels that are widely distributed in the CNS. The increase in Cl–
conductance produced by GABA-A receptors is potentiated by the anxiolytic drug, diazepam, and other benzodiazepines. Glutamate is the major excitatory transmitter in the brain. Neuropeptide Y is an excitatory neurotransmitter that has a stimulatory effect on food intake. Central nervous system actions of histamine have been implicated in arousal, sexual behavior, drinking, pain thresholds, and the sensation of itch. Antagonism of central NK-1 receptors has antidepressant activity in humans.




25. Among the causes of acute vision loss, detachment of the retina is painless, and accompanied by floaters, flashing lights, and a scotoma in the peripheral visual field corresponding to the detachment. Another cause of sudden painless vision loss is a transient ischemic attack of the retina, also called amourosis fugax. Amourosis fugax usually results from an embolus that lodges in a retinal arteriole. Complete occlusion of the central retinal artery produces arrest of blood flow and a milky retina with a cherry red spot on the fovea. Optic neuritis is a common inflammatory disease of the optic nerve that is accompanied by eye pain, especially with eye movements. It is caused by demyelination, and often progresses to multiple sclerosis. Glaucoma and macular degeneration cause chronic vision loss. Glaucoma is the leading cause of blindness in African-Americans; it is a slowly progressive, insidious optic neuropathy. Macular degeneration is the major cause of gradual, painless, bilateral central blindness in the elderly.



26. Mammalian nerve fibers are classified into A, B, and C groups, and A fibers are further subdivided into α, β, γ, and δ fibers, each of which has different histologic characteristics and functions. Aβ fibers have touch, pressure, and motor functions. The dorsal root C fibers conduct some impulses generated by touch and other cutaneous receptors, as well as impulses generated by pain and temperature receptors. Aβ fibers are most susceptible to pressure and C fibers are least susceptible to pressure, which explains why a limb with a transiently compressed nerve loses motor function, but not pain sensation. B fibers are preganglionic autonomic nerves (autonomic postganglionic fibers, vagal fibers); they are most susceptible to hypoxia, whereas C fibers are least susceptible to hypoxia. Local anesthetics depress transmission in the group C fibers before they affect the touch fibers in the A group. C fibers are unmyelinated, whereas A and B fibers are myelinated. In addition, C fibers generally have smaller diameters than A or B fibers. For both reasons, C fibers have lower conduction velocities than A fibers.

The upstroke of the action potential is caused by an inward flow of sodium ions, and therefore its magnitude depends on the extracellular sodium concentration. Decreasing the external Na+
concentration decreases the size of the action potential, but has little effect on the resting membrane potential because the permeability of the membrane to Na+ at rest is low. Conversely, increasing the external K+ concentration decreases the resting membrane potential. Changes in external Ca2+ concentration affect the excitability of nerve and muscle cells, but not the magnitude of the resting potential or the action potential

When the permeability of a particular ion is increased, the membrane potential moves toward the equilibrium potential for that ion. The equilibrium potentials for chloride (–80 mV) and potassium (–92 mV) are close to the resting membrane potential, so increases in their permeability have little effect on the resting membrane potential. The equilibrium potential for sodium (+60 mV) is very far from the resting membrane potential. Thus, increasing the permeability for sodium causes a large depolarization.


Peripheral nerves consist of primary sensory afferent axons, motor neurons, and sympathetic
postganglionic neurons. Primary sensory afferent nerves include those with large-diameter A-beta (Aβ), which normally are not involved in pain, as well as two populations of primary afferent nociceptors, the small-diameter myelinated A-delta (Aδ) and unmyelinated (C fiber) axons, which are both present in nerves to the skin and to deep somatic and visceral structures. Many Aδ and C fibers innervating viscera are completely insensitive in normal, uninjured, noninflamed tissue, but become sensitive to mechanical stimuli in the presence of inflammatory mediators. An important concept to emerge in recent years is that afferent nociceptors also have a neuroeffector function, in that they contain polypeptide mediators that are released from their nerve terminals when activated. Most notably, Substance P, an 11-amino acid polypeptide found in neurons within the hypothalamus and spinal cord, is released from small Aδ and C fibers that relay information from nociceptors to neurons within the substantia gelatinosa of the spinal cord. The biologic actions of substance P include vasodilation, neurogenic edema and the accumulation of bradykinin, the release of histamine from mast cells and the release of seratonin from platelets. Endorphins and other opioid peptides such as the enkephalins may partially inhibit the perception of pain by presynaptically inhibiting the release of substance P from nociceptor afferent fibers.





27. Guillain-Barré Syndrome (GBS) is an acute, rapidly evolving demyelinating polyradiculopathy, that generally manifests as an areflexic ascending motor paralysis and is autoimmune in nature. The basis for the flaccid paralysis and sensory disturbance is conduction block in the Aβ fibers; axonal conduction remains intact unless there is secondary axonal degeneration. Most cases are preceded by a viral upper respiratory infection or a GI infection.The
postulated immunopathogenesis of GBS associated with C. jejuni infection involves production of autoantibodies against gangliosides present on the surface of Schwann cells, causing widespread myelin damage. The wide spread administration of the swine influenza vaccine in the United States in 1976 was associated with an increased occurrence of GBS, but influenza vaccines in use from 1992 to 1994 resulted in only one additional case of GBS per million persons vaccinated. Older type rabbies vaccines prepared in nervous system tissue are still used in developing countries and are thought to be a trigger for GBS, presumably via immunization of neural antigens. Nerve growth factor is necessary for the growth and maintenance of sympathetic neurons and some sensory neurons, not motoneurons. Experimental injection of antiserum against nerve growth factor in new born animals produces an immunosympathectomy. Oligodendrogliocytes are involved in myelin formation in the CNS, whereas Schwann cells are involved in myelin fomation in peripheral nerves.




28. Muscarine binds to acetyl- choline muscarinic receptors on cardiac and smooth muscle. These are the same receptors activated by the release of acetylcholine by the vagus nerve. Cardiac muscarinic receptors decrease the rate of phase 4 depolarization and therefore, decrease the heart rate. A heart rate less than 60 beats per minute is called bradycardia. Acetylcholine receptors on the skeletal muscle end plate are nicotinic receptors and do not respond to muscarine. Dilation of the pupils and hypertension are signs of sympathetic, not parasympathetic activity.



29. Epinephrine (adrenalin) acts on both α- and β-adrenergic receptors, but has a greater affinity for β-adrenergic receptors. Activation of β2-adrenergic receptors leads to relaxation of smooth muscle in the bronchi, vasculature, intestine, uterus, and bladder, to increased pancreatic insulin and glucagon secretion, and an increase in liver glycogenolysis. The bronchodilator effects of epinephrine are key in the treatment of the life-threatening effects of anaphylactic shock. Activation of β1- and β2-adrenergic receptors in the heart leads to an increase in the rate of SA nodal phase 4 depolarization and thus heart rate (positive chronotropic response), an increase in contractility (positive inotropic response), an increase in conduction velocity (positive dromotropic response), and an increase in cardiac excitability/irritability. The transport of Ca2+ into skeletal muscle fibers is not affected by β-receptors. The effects of epinephrine-induced β-adrenergic receptor activation are due to G-protein mediated activation of adenylate cyclase, which catalyzes the formation of cyclic adenosine monophosphate (cAMP) and activation of protein kinase A.




30. The Ruffini ending is a tonic receptor that produces a train of action potentials proportional to the intensity of pressure applied to the skin. The Pacinian corpuscle is a very rapidly adapting receptor that fires once or twice in response to skin deformation, but can produce a continuous train of action potentials if the stimulus is repetitively applied and withdrawn. Therefore, the Pacinian corpuscle is used to encode vibration.



31. Narcolepsy is associated with low CSF levels of the orexins and a defect in one of the receptors for orexins (hypocretins) in the hypothalamus. Adenosine induces sleep and serotonin agonists suppress sleep. Fatal familial insomnia is a progressive prion disease, characterized by worsening insomnia, impaired autonomic and motor functions, dementia, and death.



32. In both smooth and striated muscle, contraction is produced by the cross-bridge cycle in which the cross-bridge on the thick filament binds to the actin molecule on the thin filament. In excitation-contraction coupling in striated muscle, calcium initiates contraction by binding to troponin. The calcium-activated troponin then acts to remove the tropomyosin-mediated inhibition of the actin-myosin interaction. In excitation-contraction coupling in smooth muscle, calcium initiates contraction by binding to calmodulin. The calcium-activated calmodulin then activates the myosin light chain protein kinase enzyme, which phosphorylates the myosin light chains. Actin-myosin interaction follows light-chain phosphorylation.



33. Strenuous exercise and a high protein diet can cause overproduction of uric acid. Allopurinol, which inhibits xanthine oxidase, decreases the primary cause of gout by decreasing uric acid production. Colchicine is given in acute gout to inhibit phagocytosis of uric acid crystals by leukocytes, a process that in some way produces the joint symptoms. Nonsteroidal anti-inflammatory agents, particularly indomethacin, are also used to relieve the acute arthritic symptoms of gout. Aspirin is contraindicated in acute gout because it decreases urate excretion. Uricosurics are effective in increasing the excretion of uric acid in patients whose gout is caused by decreased urate excretion, such as chronic renal disease, diabetes ketoacidosis, use of thiazide diuretics, and ethanol ingestion.



34. Decreasing extracellular Ca2+ will increase the excitability of skeletal muscle fibers but does not have a direct effect on contractile force. Increasing the Mg2+ concentration will decrease skeletal muscle excitability. Increasing the preload beyond 2.2 mm decreases the overlap between thick and thin filaments and therefore decreases the force of contraction. Increasing the activity of
acetylcholine esterase enhances the hydrolysis of ACh and therefore decreases the likelihood that muscle contraction will be initiated.


36. The end-plate potential in skeletal muscle is produced by an influx of sodium into the cell, which results from the increase in sodium permeability that occurs with acetylcholine binding to the nicotinic receptors on the membrane of the motor end plate. Acetylcholine binding at the motor end plate also increases the potassium conductance of the membrane. The plateau phase of ventricular muscle action potentials and the upstroke of smooth muscle action potentials are produced by an increase in calcium conductance. An increase in potassium conductance is responsible for the down stroke of the action potential. The refractory period is caused by an increase in potassium conductance and a decrease in the number of sodium channels available to produce an action potential (i.e., sodium channel inactivation).



38. The alveolar oxygen tension is calculated using the modified alveolar gas equation:
PAO2 = PIO2 – PaCO2/R.
PAO2 = [0.5 × (747 – 47 mmHg)] – 40 mmHg/0.8
PAO2 = 350 mmHg – 50 mmHg = 300 mmHg.



37. Both the central chemoreceptors, located on or near the ventral surface of the medulla, and the peripheral chemoreceptors, in the carotid and aortic bodies, cause an increase in ventilation in
response to an increase in PaCO2. The peripheral chemoreceptors also cause an increase in ventilation in response to a decrease in arterial pH and a decrease in PaO2, but the central chemoreceptors are unresponsive to hypoxemia and do not cause an increase in ventilation in response to a decrease in arterial pH because the blood-brain barrier is relatively impermeable to
hydrogen ions. Neither the central chemoreceptors nor the carotid bodies are stimulated by a decrease in arterial blood pressure or O2 content.




38. The oxygen consumption can be calculated if the cardiac output (CO) and the difference between the arterial and venous oxygen content are known using the Fick equation:
V ˙O2 = CO × (CaO2 – CVO2)
V ˙O2 = 6 L/min × (18 mL/dL – 14 mL/dL)
V ˙O2 = 240 mL/min


The fraction of the pulmonary blood flowing bypassing the lung (the shunt, Q ˙S) compared to the total pulmonary blood flow (Q ˙T) is calculated using the equation
Q ˙S/Q ˙T = C´ cO2 – CaO2 / C´ cO2 – CVO2
= 19 mL/dL – 18 mL/dL
19 mL/dL – 14 mL/dL
= 0.2
where C´ c is the end pulmonary capillary blood oxygen content, CaO2 is thearterial oxygen content, and CVO2 is the mixed venous oxygen content. At a resting cardiac output, the normal amount of shunting is 3–5% of the cardiac output. In this case, there is a 20% shunt.




39. The decrease in arterial oxygen saturation caused by carbon monoxide poisoning reduces the oxyhemoglobin and thus total arterial oxygen contents but does not reduce the amount of oxygen dissolved in the plasma, which determines the arterial oxygen tension. Carbon monoxide is odorless and tasteless and dyspnea and resiratory distress are late signs, which is the reason that it is so important to install carbon monoxide detectors in homes and businesses. Respiratory distress becomes manifest with severe tissue hypoxia and anaerobic glycolysis, which leads to lactic acidosis. The decrease in arterial pH stimulates ventilation via the peripheral chemoreceptors. The resultant hyperventilation decreases arterial (and CSF) PCO2, causing CSF pH to rise. Carboxyhemoglobin has a cherry-red color.




40. Lung compliance is an index of lung distensibility or the ease with which the lungs are expanded; thus, compliance is the inverse of elastic recoil. Compliance is defined as the ratio of change of lung volume to the change in pressure required to inflate the lung (∆V/∆P). Compliance decreases in patients with pulmonary edema or surfactant deficiency and increases when there is a loss of elastic fibers in the lungs, such as occurs in patients with emphysema and with aging.




41. Early systolic murmurs begin with the first heart sound and end in mid-systole. The higher-than-normal height of the jugular blood column reflects an increased right atrial pressure. The combination of an early systolic murmur and high right atrial pressure is indicative of tricuspid regurgitation. This lesion is common in narcotic abusers with infective endocarditis. Mitral stenosis and aortic regurgitation produce diastolic murmurs.



42. Phase-4 depolarization is caused by the activation of a Na+ channel. The channel is activated
when the membrane hyperpolarizes in contrast to the Na channel responsible for the action potential, which is activated when the cell depolarizes. Potassium conductance decreases during phase-4 depolarization and thus the flow of potassium out of the cell is diminished. However, this change in potassium current is not responsible for phase-4 depolarization. Chloride conductance does not change during phase 4. The Na/Ca exchanger maintains low intracellular calcium at rest and may reverse its direction and pump calcium into the cell during phase 2 of the cardiac action potential. However, neither the Na/Ca exchanger nor the Na-K pump is involved in phase-4 depolarization.


43. The increase in radius of the dilated ventricle increases wall tension (stress) according to the Laplace relation-ship,
T = Pr/w,
(where T = tension, P = systolic pressure, r = ventricularradius, and w = ventricular wall thickness.) The increase in wall tension requires an increase in energy consumption. The increase in preload
increases the left ventricular end-diastolic pressure. Because the pulmonarycapillaries are supplying the blood to the left ventricle, an increase in left ventricular end-diastolic pressure must be accompanied by an increase in pulmonary capillary hydrostatic pressure. The decrease in left ventricular contractility associated with heart failure causes the ejection fraction to decrease. Heart rate will be increased by the increased sympathetic nerve activity that accompanies heart failure.



At which point on the ventricular action potential is membrane potential most dependent on calcium
permeability?
The plateau phase (phase 2) is the result of the influx of calcium. Although calcium channels
begin to open during the upstroke (phase 0), the greatest number of calcium channels is open during the plateau. The upstroke is primarily dependent on the opening of Na+ channels. The initial repolarization (phase 1) is dependent on the inactivation of Na+ channels and the opening of a tran-
sient K+ channel. Repolarization (phase 3) is produced by the inactivation of Ca2+ channels and the activation of the delayed rectifier K+ channels.


44. he left ventricular pressure-volume loop represents the changes in pressure and volume that
occur during a cardiac cycle. Point E represents the end of the filling phase and the beginning of the isovolumic contraction phase. At this point, the pressure in the left ventricle increases above the pressure in the left atrium, causing the mitral valve to close. The retrograde flow of blood against the closed mitral valve produces the first heart sound. Systole is defined as the period between the first and second heart sounds and includes the isovo lumic contraction and ejection phases. Aortic pressure continues to fall during the isovolumic contraction phase so that the rise in aortic blood
pressure (which begins at point D) lags behind the beginning of systole. Point B represents the end of the ejection phase. At this point, the pressure in the left ventricle falls below the pressure in the aorta, and the aortic valve closes. The retrograde flow of blood against the closed aortic valve pro-
duces the second heart sound. Point A represents the end of the isovolumic relaxation phase and the beginning of the filling phase. At the point the pressure in the left ventricle falls below that in the left atrium, the mitral valve opens and blood begins to flow into the left ventricle.