24 USMLE Road Map: Physiology CLINICAL PROBLEMS A 27-year-old woman with muscle weakness, including eyelid ptosis, slurred speech, and difficulty sw The history shows that she is being treated for a gram in. The following tests have been ordered: thyroid fund tion studies, serum creatine kinase, an electromyogram, and a muscle biopsy administered intravenously all of the other tests returned with normal values 1. The resident's working diagnosis is A. Duchenne muscular dystrophy B. Monoadenylate deaminase deficiency C. Myasthenia gravis 2. This patient's condition most likely results from A Inadequate acetylcholinesterase in the synaptic cle B. Production of defective acetylcholine receptors C Impaired synthesis or storage of acetylcholine in presynaptic vesicles D. Impaired release of acetylcholine from presynaptic terminals E. Blockade and increased turnover of acetylcholine receptors Cholera toxin can affect cells by blocking the guanosine triphosphatase(GTPase)activity of their Proteins 3. On a cellular level, which one of the following would be helpful in reducing the harm- ful effect of cholera toxin? A. Increasing the amount of intracellular cyclic adenosine monophosphate(cAMP) B. Inhibiting the activity of the adenylate cyclase in the cell C. Inhibiting the Giprotein within the cell D. Adding ligand for the Gs-Protein-linked receptor E. Increasing the amount of protein kinase A in the cell A 45-year-old woman experiences blurred vision and difficulty swallowing after some home-canned vegetables. These symptoms are followed by respiratory distres flaccid paralysis. 4. The symptoms of her illness are most associated with which of the following? A. Black widow spider toxin B. Botulinum toxin
24 USMLE Road Map: Physiology N CLINICAL PROBLEMS A 27-year-old woman presents with muscle weakness, including eyelid ptosis, slurred speech, and difficulty swallowing. The history shows that she is being treated for a gramnegative infection with gentamicin. The following tests have been ordered: thyroid function studies, serum creatine kinase, an electromyogram, and a muscle biopsy. The attending physician chides the resident on the case for not ordering an edrophonium test, which produces a dramatic improvement in the woman’s muscle strength when administered intravenously. All of the other tests returned with normal values. 1. The resident’s working diagnosis is A. Duchenne muscular dystrophy B. Monoadenylate deaminase deficiency C. Myasthenia gravis D. Hyperthyroidism E. Toxic drug myopathy 2. This patient’s condition most likely results from A. Inadequate acetylcholinesterase in the synaptic cleft B. Production of defective acetylcholine receptors C. Impaired synthesis or storage of acetylcholine in presynaptic vesicles D. Impaired release of acetylcholine from presynaptic terminals E. Blockade and increased turnover of acetylcholine receptors Cholera toxin can affect cells by blocking the guanosine triphosphatase (GTPase) activity of their GS-proteins. 3. On a cellular level, which one of the following would be helpful in reducing the harmful effect of cholera toxin? A. Increasing the amount of intracellular cyclic adenosine monophosphate (cAMP) B. Inhibiting the activity of the adenylate cyclase in the cell C. Inhibiting the Gi -protein within the cell D. Adding ligand for the GS-protein-linked receptor E. Increasing the amount of protein kinase A in the cell A 45-year-old woman experiences blurred vision and difficulty swallowing after eating some home-canned vegetables. These symptoms are followed by respiratory distress and flaccid paralysis. 4. The symptoms of her illness are most associated with which of the following? A. Black widow spider toxin B. Botulinum toxin 5506ch01.qxd_ccII 2/17/03 2:09 PM Page 24
Chapter 1: Cell 5. This toxin exerts its action by A. Binding irreversibly to the acetylcholine receptor to cause paraly B. Causing a clumping of acetylcholine-containing vesicles, resulting in excessive release of acetylcholine into the synaptic cleft C. Inhibiting the release of acetylcholine from the nerve terminal D. Inhibiting anticholinesterase to increase the concentration of acetylcholine in the Inhibiting the release of calcium from the sarcoplasmic reticulum A 5-year-old boy has a history of growth retardation; pulmonary infections; and bulky, ly, malodorous stools 6. Which of the following test results would be expected in this patient? A. Abnormal sweat chloride test B. Low C3 complement level C. Abnormal nitroblue tetrazolium(nBT)dye test D. Positive wheel and flare reaction with antigen scratch testing E. Sputum with gram-positive diplococci 7. This disease is due A. a direct blockade of sodium channels in the plasma membrane B. A d number of chloride channels on the cell membra C. The direct blockade of the potassium channel gated by a G-protein D. A net increase in ion flex through the calcium channel, stimulating neurotrans- Imitter secretIo E. A blockade of ligand-gated ion channels in neuronal cell membranes ANSWERS 1. The answer is C. Edrophonium is an anticholinesterase agent that improves muscle strength in myasthenic patients by increasing the acetylcholine concentration in the haptic cleft. The test is diagnostic for myasthenia gravis. Duchenne muscular dystro- hy(choice A)is a defect in the gene encoding dystrophin, a cytoskeletal protein. Pa tients with this disorder experience progressive muscle weakness. Adenosine deaminase and B cell function. Hyperthyroidism (choice D) is characterized by palpitate/ deficiency(choice B) ombined immunodeficiency with impaired T sweating, heat intolerance, functional muscle tremor, and exophthalmos, not by the
Chapter 1: Cell Physiology 25 N C. Organophosphate poisoning D. Benzodiazepine ingestion E. α-Bungarotoxin 5. This toxin exerts its action by A. Binding irreversibly to the acetylcholine receptor to cause paralysis B. Causing a clumping of acetylcholine-containing vesicles, resulting in excessive release of acetylcholine into the synaptic cleft C. Inhibiting the release of acetylcholine from the nerve terminal D. Inhibiting anticholinesterase to increase the concentration of acetylcholine in the synaptic cleft E. Inhibiting the release of calcium from the sarcoplasmic reticulum A 5-year-old boy has a history of growth retardation; pulmonary infections; and bulky, oily, malodorous stools. 6. Which of the following test results would be expected in this patient? A. Abnormal sweat chloride test B. Low C3 complement level C. Abnormal nitroblue tetrazolium (NBT) dye test D. Positive wheel and flare reaction with antigen scratch testing E. Sputum with gram-positive diplococci 7. This disease is due to A. A direct blockade of sodium channels in the plasma membrane B. A reduced number of chloride channels on the cell membrane C. The direct blockade of the potassium channel gated by a G-protein D. A net increase in ion flex through the calcium channel, stimulating neurotransmitter secretion E. A blockade of ligand-gated ion channels in neuronal cell membranes ANSWERS 1. The answer is C. Edrophonium is an anticholinesterase agent that improves muscle strength in myasthenic patients by increasing the acetylcholine concentration in the synaptic cleft. The test is diagnostic for myasthenia gravis. Duchenne muscular dystrophy (choice A) is a defect in the gene encoding dystrophin, a cytoskeletal protein. Patients with this disorder experience progressive muscle weakness. Adenosine deaminase deficiency (choice B) causes severe combined immunodeficiency with impaired T cell and B cell function. Hyperthyroidism (choice D) is characterized by palpitations, sweating, heat intolerance, functional muscle tremor, and exophthalmos, not by the 5506ch01.qxd_ccII 2/17/03 2:09 PM Page 25
26 USMLE Road Map: Physiology e, a mptoms described in this case. The edrophonium test differentiates myasthen ivis from toxic drug myopathy(choice E) The answer is E. Myasthenia gravis is a neuromuscular disorder resulting in muscle weakness. It is caused by an autoimmune response to acetylcholine receptors, leading to increased turnover and a reduced number of these receptors 3. The answer is B. Cholera toxin causes a functional derangement of sodium and wate transport in the gut. The toxin binds to the GMrganglioside receptors of the luminal membrane of enterocytes and activates epithelial adenylate cyclase. Thus, inhibiting denylate cyclase activity would reduce the harmful effects of cholera toxin. 4. The answer is B. Botulinum toxin inhibits the release of acetylcholine from the nerve terminal, resulting in blurred vision, ptosis, unreactive pupils, paralysis, and respiratory ider toxin (choice A)causes clumping of acetylcholin release into a massive cholinergic response. Benzodiazepines(choice D) induce muscle relaxatior a-Bungarotoxin(choice E) blocks the binding of acetylcholine to its receptor by irre- 5. The answer is C. Toxins produced by Clostridium botulinum cleave specific presynaptic proteins, preventing neurotransmitter release at both neuromuscular and parasympa- thetic cholinergic synapses 6. The answer is A. An abnormal sweat chloride test is an expected diagnostic feature of cystic fibrosis. The chloride channel is thought to be regulated by the cystic fibrosis transmembrane regulator(CFTR) protein, which is defective in cystic fibrosis. A low C3 complement level (choice B)may cause severe infections. The nitroblue tetrazolium (NBT) dye test(choice C)is an in vitro test for a respiratory burst in neutrophils. Aller- gic type I hypersensitivity(choice D)conditions are characterized by an increase im- munoglobulin E antibodies associated with bronchial asthma. The finding of gram-positive diplococci in the sputum(choice E)is associated with Streptococcus pneu moniae infection 7. The ar B. Cystic fibrosis is a congenital autosomal recessive disease caused by mutations that result in failure of the fibrosis transmembi which regulates the chloride channel, to be inserted in the plasma membrane
26 USMLE Road Map: Physiology N symptoms described in this case. The edrophonium test differentiates myasthenia gravis from toxic drug myopathy (choice E). 2. The answer is E. Myasthenia gravis is a neuromuscular disorder resulting in muscle weakness. It is caused by an autoimmune response to acetylcholine receptors, leading to increased turnover and a reduced number of these receptors. 3. The answer is B. Cholera toxin causes a functional derangement of sodium and water transport in the gut. The toxin binds to the GM1-ganglioside receptors of the luminal membrane of enterocytes and activates epithelial adenylate cyclase. Thus, inhibiting adenylate cyclase activity would reduce the harmful effects of cholera toxin. 4. The answer is B. Botulinum toxin inhibits the release of acetylcholine from the nerve terminal, resulting in blurred vision, ptosis, unreactive pupils, paralysis, and respiratory failure. Black widow spider toxin (choice A) causes clumping of acetylcholinecontaining vesicles, resulting in excessive acetylcholine release into the synaptic cleft. Organophosphate poisoning (choice C) blocks acetylcholinesterase action, resulting in a massive cholinergic response. Benzodiazepines (choice D) induce muscle relaxation through the depression of the reticular formation in the central nervous system. α-Bungarotoxin (choice E) blocks the binding of acetylcholine to its receptor by irreversibly binding to the acetylcholine receptor. 5. The answer is C. Toxins produced by Clostridium botulinum cleave specific presynaptic proteins, preventing neurotransmitter release at both neuromuscular and parasympathetic cholinergic synapses. 6. The answer is A. An abnormal sweat chloride test is an expected diagnostic feature of cystic fibrosis. The chloride channel is thought to be regulated by the cystic fibrosis transmembrane regulator (CFTR) protein, which is defective in cystic fibrosis. A low C3 complement level (choice B) may cause severe infections. The nitroblue tetrazolium (NBT) dye test (choice C) is an in vitro test for a respiratory burst in neutrophils. Allergic type I hypersensitivity (choice D) conditions are characterized by an increase immunoglobulin E antibodies associated with bronchial asthma. The finding of gram-positive diplococci in the sputum (choice E) is associated with Streptococcus pneumoniae infection. 7. The answer is B. Cystic fibrosis is a congenital autosomal recessive disease caused by multiple mutations that result in failure of the cystic fibrosis transmembrane regulator, which regulates the chloride channel, to be inserted in the plasma membrane. 5506ch01.qxd_ccII 2/17/03 2:09 PM Page 26
P三这2 CARDIOVASCULAR PHYSIOLOGY . General Principles A. The cardiovascular system consists of two pumps (left and cles)and two circuits(pulmonary and systemic)( Figure 2-1) 1. Cardiac output from the left side of the heart is the systemic blood flow 2. Cardiac output from the right side of the heart is the pulmonary blood 3. Because the two circuits are connected in series, flow(mL/min)must be B. The systemic circuit begins as a large vessel, the aorta, and branches into smaller vessels until capillaries are reached within organs C. Vascular components include arteries, arterioles, and capillarie 1. Arteries are thick-walled vessels under high pressure that deliver oxygenated blood to the tissues 2. Arterioles are the smallest branches of arteries a. They have the highest resistance in the cardiovascular system and are reg- ulated by the autonomic nervous b. Arteriolar smooth muscle tone depends on sympatheti local metabolites, hormones, and other mediators 3. Capillaries have the largest total cross-sectional and surface areas and are the site of exchanges of nutrients, water, and gases D. In the venous circuit, small veins(venules)merge to form larger veins until the argest vein, the vena cava, returns blood to the heart. 1. veins are thin-walled vessels under low pressure that contain most of the blood in the cardiovascular system. 2. Venules are the most permeable components of the microcirculation. Il Hemodynamics A. Velocity and Blood Flow 1. Velocity refers to the rate of displacement of blood within vessels with re pect to time, and it has the dimensions of distance per unit time(eg, cm/s) It is expressed by the following equation Q 27 Copyright o 2003 by The McGraw-Hill Companies, Inc. Click here for Terms of Us
CHAPTER 2 CHAPTER 2 N CARDIOVASCULAR PHYSIOLOGY 27 I. General Principles A. The cardiovascular system consists of two pumps (left and right heart ventricles) and two circuits (pulmonary and systemic) (Figure 2–1). 1. Cardiac output from the left side of the heart is the systemic blood flow. 2. Cardiac output from the right side of the heart is the pulmonary blood flow. 3. Because the two circuits are connected in series, flow (mL/min) must be equal in both; however, transient differences do occur. B. The systemic circuit begins as a large vessel, the aorta, and branches into smaller vessels until capillaries are reached within organs. C. Vascular components include arteries, arterioles, and capillaries. 1. Arteries are thick-walled vessels under high pressure that deliver oxygenated blood to the tissues. 2. Arterioles are the smallest branches of arteries. a. They have the highest resistance in the cardiovascular system and are regulated by the autonomic nervous system. b. Arteriolar smooth muscle tone depends on sympathetic input, local metabolites, hormones, and other mediators. 3. Capillaries have the largest total cross-sectional and surface areas and are the site of exchanges of nutrients, water, and gases. D. In the venous circuit, small veins (venules) merge to form larger veins until the largest vein, the vena cava, returns blood to the heart. 1. Veins are thin-walled vessels under low pressure that contain most of the blood in the cardiovascular system. 2. Venules are the most permeable components of the microcirculation. II. Hemodynamics A. Velocity and Blood Flow 1. Velocity refers to the rate of displacement of blood within vessels with respect to time, and it has the dimensions of distance per unit time (eg, cm/s). It is expressed by the following equation: V = Q A , 5506ch02.qxd_ccII 2/17/03 2:15 PM Page 27 Copyright © 2003 by The McGraw-Hill Companies, Inc. Click here for Terms of Use
28 USMLE Road Map: Physiology Pulmonary circuit Figure 2-1. Cardiovascular system. where V= velocity (cm/s) Q= blood flow(cm/s) A= cross-sectional area(cm) 2. Velocity is inversely related to the total cross-sectional area of all vessels of a particular segment of the cardiovascular system a. The cross-sectional area of the aorta is approximately 2.8 cm, whereas the area of the combined capillaries is approximately 1357 cm b. The aorta, therefore, has the highest velocity, and the capillaries the low 3. Blood flow is frequently designated as volume flow, and it has the dimen sions of volume per unit time, for example, cubic centimeters per second 4. Linear velocity and blood flow are then related by an area, for example, uare centimeters(cm/s= cm/s x+) 5. For a given flow, the ratio of the velocity through one vessel segment relative to that in another segment depends on the inverse ratio of the respective 6. This rule applies regardless of whether a given cross-sectional area pertains to a system comprising a single large tube or to a system made up of several smaller tubes in parallel 7. Because the flow through the aorta per minute(ie, cardiac lent to the flow to the right atrium per t to the mbined capilla B. Hemodynamic Equivalent of Ohms Law 1. The relationship between current flow and its potential difference across a ing resistance is known as Ohm's Law E=R
28 USMLE Road Map: Physiology N Right heart Left heart Pulmonary circuit Systemic circuit Figure 2–1. Cardiovascular system. where V = velocity (cm/s) Q = blood flow (cm3 /s) A = cross-sectional area (cm2 ) 2. Velocity is inversely related to the total cross-sectional area of all vessels of a particular segment of the cardiovascular system. a. The cross-sectional area of the aorta is approximately 2.8 cm2 , whereas the area of the combined capillaries is approximately 1357 cm2 . b. The aorta, therefore, has the highest velocity, and the capillaries the lowest. 3. Blood flow is frequently designated as volume flow, and it has the dimensions of volume per unit time, for example, cubic centimeters per second. 4. Linear velocity and blood flow are then related by an area, for example, square centimeters (cm3 /s = cm/s × cm2 ). 5. For a given flow, the ratio of the velocity through one vessel segment relative to that in another segment depends on the inverse ratio of the respective areas: 6. This rule applies regardless of whether a given cross-sectional area pertains to a system comprising a single large tube or to a system made up of several smaller tubes in parallel. 7. Because the flow through the aorta per minute (ie, cardiac output) is equivalent to the flow to the right atrium per minute (ie, venous return), this must also be equivalent to the flow through the combined capillaries per minute. B. Hemodynamic Equivalent of Ohm’s Law 1. The relationship between current flow and its potential difference across a conducting resistance is known as Ohm’s Law: E = IR V V A A 1 2 = 2 1 5506ch02.qxd_ccII 2/17/03 2:15 PM Page 28