Fatigue & Weakness

8/7/2019 Fatigue & Weakness

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normocellular, moderate to severe iron deficiency usually is associated withmany hypochromic microcytes. None of the other disorders cause a cravingfor ice.

Question 3 of 8

Examination of a peripheral blood smear would most likely reveal which of thefollowing?/ A. Microcytes/ B. Schistocytes/ C. Sickled cells/ D. Spherocytes/ E. Spur cells

Explanation - Q: 1.3 CloseThe correct answer is A. While mild iron deficiency anemia is sometimesnormocellular, moderate to severe iron deficiency anemia usually showsmany hypochromic microcytes.

Schistocytes (choice B) are seen in traumatic hemolytic anemia andimmunohemolytic anemia.

Sickled cells (choice C) are seen in the various sickle cell syndromes.

Spherocytes (choice D) are seen in hereditary spherocytosis.

Spur cells (choice E) are seen in spur cell anemia and paroxysmal nocturnalhemoglobinuria.

Question 4 of 8

Which of the following conditions would be most likely to predispose for thispatient's disorde/ A. Dermoid cyst of the ovary/ B. E.Coli bladder infection/ C. Intraductal carcinoma of the breast/ D. Menorrhagia/ E. Squamous cell carcinoma of the skin

Explanation - Q: 1.4 CloseThe correct answer is D. Iron deficiency anemia in this country is most oftenseen in the setting of chronic blood loss. Menorrhagia, or prolonged, heavymenstrual flow, and occult gastrointestinal bleeding are the most commonlyencountered predisposing conditions. The other conditions listed in the
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choices are distracters that do not have a particular tendency to causechronic bleeding

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The deficient substance in this patient is typically absorbed at which of thefollowing sites?/ A. Colon/ B. Distal small bowel/ C. Esophagus/ D. Proximal small bowel/ E. Stomach

Explanation - Q: 1.5 CloseThe correct answer is D. The proximal small bowel is the site of absorptionof many vitamins and minerals, including iron. The absorptive epithelial cellsof the proximal small bowel alter iron absorption to match the body losses,and contain considerable intracellular iron in patients with adequate iron. Iniron deficient subjects (and also in hemachromatosis, possibly contributing tothe pathology), the stainable iron stores in these cells are nearly absent. Theiron that is absorbed can be in the forms of heme, ferric iron, and ferrous iron(using different pathways). Unlike with many substances, the entire control ofbody levels is at the stage of absorption, since there is no physiologicmechanism other than bleeding for removal of large amounts of iron from thebody.

The colon (choice A) primarily absorbs water and electrolytes.

The distal small bowel (choice B) notably absorbs vitamin B12.

The esophagus (choice C) and stomach (choice E) are not absorptive sites.

Question 6 of 8

The substance deficient in this patient is typically delivered to non-intestinal cellsby which of the following?/ A. Ceruloplasmin/ B. Erythropoietin/ C. Hematoxylin/ D. Hemosiderin/ E. Transferrin

Explanation - Q: 1.6 CloseThe correct answer is E. The iron which is delivered to other tissues isprimarily delivered bound to transferrin. The transferrin-iron complex enters


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the cell within an endosome which forms after the complex binds to areceptor on the cell surface. Subsequent acidification of the endosomecontents releases the iron so that it can be transported across the endosomemembrane and into the cytoplasm of the cell.

Ceruloplasmin (choice A) is a copper-transporting molecule.

Erythropoietin (choice B) is a hormone that stimulates erythrocyteproduction.

Hematoxylin (choice C) is a commonly used stain in histology.

Hemosiderin (choice D) is a common storage form of iron in tissues.

*** Cross | Popup menu | Order Online Now! ***Question 7 of 8

The patient is prescribed supplementation for her deficiency. Her 3-year-old childfinds the bottle of pills, and ingests some of them. If the childingested enough to become clinically poisoned, which of the following symptomswould most likely be seen earliest in the course?/ A. Hepatic cirrhosis/ B. Intestinal obstruction/ C. Seizures/ D. Shock/ E. Vomiting and explosive diarrhea

Explanation - Q: 1.7 CloseThe correct answer is E. Poisoning with iron supplements is always apotential problem in households with young children and a mother with iron-deficiency anemia, and the problem is exacerbated by the fact that some ofthe commonly available iron supplements are small round pills with bright redcoating that very much resemble small candies such as M&M's and Skittles.Fortunately, most commonly the poisoning is mild, although fatal cases ofpoisoning have been encountered with doses as small as 130 mg ofelemental iron. The advice to parents about keeping the medication well outof reach of little hands is obvious, but should be emphasized by the clinicianat the time of prescribing the supplementation.

The clinical course following iron poisoning has been divided into four stages.Stage I occurs within 6 hours, and can be characterized by vomiting,hematemesis, explosive diarrhea, irritability, and abdominal pain (choice E).The presence of shock (choice D) or coma within the first 6 hours isconsidered a grave prognostic sign. Other clinical features that can bepresent in stage I if iron levels are particularly high include tachypnea,tachycardia, hypotension, and metabolic acidosis. Stage II occurs 6-24 hours
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after ingestion and is characterized by a latent period of apparent (butdeceptive) clinical improvement. Stage III, which typically begins 12 to 48hours after ingestion is a life-threatening stage characterized by liver damage,shock (choice D), hypoperfusion, seizures (choice C), hypoglycemia, fever,

ECG changes, bleeding disorders, lethargy, coma, acidosis, and sometimesdeath. Stage IV which occurs 2 to 5 weeks later in those patients that developlate complications may manifest with gastrointestinal obstruction (choice B),hepatic cirrhosis (choice A), or permanent CNS damage.

Question 8 of 8

Which of the following is the most appropriate pharmacotherapy for her child?/ A. Deferoxamine/ B. Dimercaprol/ C. Edetate (EDTA)/ D. Penicillamine/

E. Protamine/ F. Succimer

Explanation - Q: 1.8 CloseThe correct answer is A. Deferoxamine is an iron chelator that binds theabsorbed iron, but not the iron in iron-carrying proteins such as hemoglobin,myoglobin, hemosiderin, or ferritin. It is given parenterally; IV is generally thepreferred route.

Dimercaprol (choice B) is a chelator used for arsenic and mercury poisoning.

Edetate (EDTA) (choice C) is a chelator used for lead poisoning.

Penicillamine (choice D) is a chelator used for copper poisoning (and Wilsondisease). It is sometimes used for adjunctive therapy for gold, arsenic, andlead poisoning.

Protamine (choice E) is used for heparin overdose.

Succimer(choice F) is used in the treatment of lead poisoning; it can begiven orally. It can also be used for arsenic and mercury poisoning if used

soon after exposure.

A 52-year-old woman presents with complaints of fatigue, mood changes, diffusejoint aches, and dry skin. She also states that she has


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gained about 10 pounds in the last few months, without any change in appetite.Her last menstrual period was 2 months ago and she has beenhaving very irregular menses in the last 8 months. Review of systems issignificant for constipation, but she denies hot flashes or insomnia.Physical examination is significant for an obese woman who appears tired. An

asymmetric goiter is noted, but no bruit is appreciated. Herjoint examination is unremarkable; there is no swelling/redness and no triggerpoints are painful to palpation. Labs were sent.Question 1 of 6

Which of the following is the most likely diagnosis?/ A. Depression/ B. Diabetes mellitus/ C. Fibromyalgia/ D. Hypothyroidism/ E. Perimenopause

Explanation - Q: 2.1 CloseThe correct answer is D. Any patient with symptoms of fatigue/dryskin/weight loss/ constipation coupled with the presence of a goiter should beinvestigated for hypothyroidism. About 8% of the population over the age of65 has hypothyroidism. It can be diagnosed by a high serum TSH.

Depression (choice A) can account for most the above symptoms butmedical conditions such as hypothyroidism, anemia, and diabetes should beexcluded first.

Diabetes (choice B) can produce multiple symptoms and should be includedin any workup of fatigue/weight gain, etc.

Fibromyalgia (choice C) is a chronic pain syndrome characterized bydifficulty sleeping and having at least 11 out of 16 specific tender pointsdesignated by the American College of Rheumatology. Hypothyroidism andfibromyalgia can coexist and the former is always included in the initialworkup of the latter.

Perimenopausal women (choice E) can have similar complaints as thosewith hypothyroidism but they will all have hot flashes. Hypothyroid patientsare actually cold intolerant.

*** Time goes. Kleptomania is expiring. Order now athttp://www.structurise.com/kleptomania/order.htm ***Question 2 of 6

The most common cause for this patient's condition is associated with which ofthe following?/ A. High antimitochondrial antibodies/ B. High antithyroid peroxidase (anti-TPO) antibodies


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/ C. High RAIU/ D. Low anti-smooth muscle antibodies/ E. Low antithyroglobulin antibodies

Explanation - Q: 2.2 CloseThe correct answer is B. Hashimoto thyroiditis is the most common cause ofhypothyroidism. It is believed to be a result of an autoimmune response (Tcell-mediated hypersensitivity) against the thyroid. Clinically, it is associatedwith an asymmetric nodular goiter with a high TSH and low T4. Like Graves'disease, it has a strong autoimmune association and has high titers ofantithyroid peroxidase antibodies and high antithyroglobulin antibodies(compare to choice E).

Antimitochondrial antibodies (choice A) are associated with primary biliarycirrhosis.

A high RAIU (radioactive iodine uptake scan, choice C) is only seen inpatients who are hyperthyroid and is not used to diagnosis hypothyroidism.

Anti-smooth muscle antibodies (choice D) are associated with autoimmunehepatitis.

Question 3 of 6

Which of the following would a thyroid biopsy most likely show?/ A. Thyroid follicle destruction and fibrosis by macrophages and giant cells/ B. Thyroid follicle destruction by lymphocytes; presence of Hurthle cells/ C. Thyroid follicles with finger-Iike growths and "Orphan Annie eyes"/ D. Thyroid follicles with large colloid and flattened epithelial cells/ E. Thyroid follicles with scant colloid and hyperplastic epithelial cells

Explanation - Q: 2.3 CloseThe correct answer is B. Thyroid follicular infiltration by lymphocytes alongwith the presence of Hurthle cells is characteristic of Hashimoto disease.Hurthle cells are the surviving follicular epithelial cells that are transformedinto large cells with abundant pink cytoplasm.

Thyroid follicle destruction by macrophages and giant cells (choice A) isfound in subacute thyroiditis.

Finger-like growths or papillary formation of the thyroid follicles (choice C) ischaracteristic of papillary carcinoma of the thyroid; Orphan Annie eyes (clear


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nuclei in the follicular epithelial cells) are pathognomonic.

Thyroid follicles with large colloid centers (choice D) are typical for toxicmultinodular goiter.

Initially, the euthyroid multinodular goiter can also have findings similar toGraves' disease, with hyperplastic epithelial cells with scant central colloids(choice E).

Question 4 of 6

Which of the following is the most appropriate pharmacotherapy?/ A. Amitriptyline/ B. Aspirin or NSAIDS/ C. Conjugated estrogen and progesterone/ D. Levothyroxine/ E. Selective serotonin reuptake inhibitors (SSRI)

Explanation - Q: 2.4 CloseThe correct answer is D. Levothyroxine (T4) is the most commonly usedform of the thyroid hormone for supplement. It is converted to T3 (active form)in the peripheral tissues and has a half-life of 7 days.

Amitriptyline (choice A), a tricyclic antidepressant, is used to correct thedisturbed stage 4 sleep in patients with fibromyalgia.

Aspirin/NSAIDS (choice B) is used to treat the discomfort of subacutethyroiditis.

Hormone replacement (choice C) is very helpful to alleviate the hot flashsymptoms associated with perimenopause.

SSRI's (choice E), such as fluoxetine (Prozac), are used to treat depression.

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The patient had unknown cardiac risk factors and developed a myocardialinfarction after therapy was initiated. Which of the following is themost likely mechanism by which the therapy lead to this complication?/ A. Enhances adrenergic effects/ B. Enhances lipid turnover/ C. Increases calcium mobilization in bone/ D. Increases metabolic rate/ E. Regulates body temperature


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Explanation - Q: 2.5 CloseThe correct answer is A. Thyroxine has multiple effects on the body such asimproving the lipid profile (choice B); increasing calcium mobilization from

the bone (choice C), which can cause chronic hyperthyroid patients to beosteoporotic; increasing the metabolic rate (choice D); and regulating bodytemperature (choice E). It also enhances adrenergic actions therebyincreasing heart rate and cardiac contractility. For older patients or those withcoronary artery disease, thyroid supplements must be given in smaller andslower titrations to prevent this complication.

Question 6 of 6

If the patient had a very tender and nodular goiter with pain radiating to the ear,which of the following would be the most likely diagnosis?/ A. Graves' disease/ B. Hashimoto's thyroiditis/ C. Lymphocytic thyroiditis/ D. Subacute thyroiditis/ E. Toxic multinodular goiter

Explanation - Q: 2.6 CloseThe correct answer is D. Patients with subacute thyroiditis have very tenderasymmetrical goiters with pain radiating to the ear. It usually starts after aviral infection. The patient may range from being hyperthyroid to hypothyroid,but eventually will become euthyroid.

Graves' disease (choice A) occurs in patients who are hyperthyroid with agoiter.

Hashimoto thyroiditis (choice B) is not associated with a painful goiter anddoes not occur after a viral infection.

Lymphocytic thyroiditis (choice C) is a painless thyroiditis, which is self-limited; it can progress from hyperthyroid to hypothyroid and then to theeuthyroid state. Some consider lymphocytic thyroiditis and subacutethyroiditis variants of the same thyroid inflammation.

Patients with toxic multinodular goiter(choice E) will be hyperthyroid insteadof hypothyroid.


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A 23-year old female student notices double vision while studying for herexaminations. She goes to see an ophthalmologist, who said shehad a "Iazy eye." These symptoms come and go for the next 2 years withoutbecoming significant. Then, she starts to have difficulties withchewing food, and has troubles with getting in and out of the car. SIowly,

problems with using her arms and legs develop. She thinks she is outof shape and needs more exercise. She begins spilling drinks and missing hermouth when using utensils. Her vision is double by afternooneach day, and by the evening, one eye is closed. The next morning, her situationis improved, but again worsens by the evening. Finally, shegoes to see a neurologist. On examination, ptosis is noted. The ptosis worsenswhen she is asked to sustain an upward gaze, and closing hereyes for a short period improves it. Her voice has a nasal quality. Sensoryexamination and deep tendon reflexes are normaI.

Question 1 of 5

Which of the following is the most likely diagnosis?/ A. Botulism/ B. Guillain-Barr syndrome/ C. Lambert-Eaton syndrome/ D. Myasthenia gravis/ E. Wernicke syndrome

Explanation - Q: 3.1 CloseThe correct answer is D. Myasthenia gravis (MG) is a chronic autoimmunedisease of neuromuscular transmission. It is characterized by fluctuating

weakness of commonly used voluntary muscles, causing symptoms such asptosis, diplopia, dysphagia, drooping head, poor posture, difficulty climbingstairs, and difficulty chewing and talking. Weakness is improved by rest andworsens with activity. Short-acting anti-cholinesterases transiently improvethe weakness. The disorder can occur at all ages, sometimes in associationwith a thymic tumor, or thyrotoxicosis, rheumatoid arthritis, and systemiclupus erythematosus. Extraocular muscles and other cranial muscles(masticatory, facial, and pharyngeal) are especially likely to be affected, andthe respiratory and limb muscles may also be involved. Pupillary responses,sensation, and deep tendon reflexes are normal. Symptoms often fluctuate inintensity during the day, and these diurnal variations are superimposed on a

tendency to have spontaneous relapses and remissions. The disorder followsa slowly progressive course and may have a terminal outcome due torespiratory complications.

Botulism (choice A) is a potentially fatal paralytic illness caused by thebacterium Clostridium botulinum. Botulism would not slowly worsen over twoyears.


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Guillain-Barr syndrome (choice B) is an acute autoimmune demyelinatingneuropathy characterized by progressive symmetric ascending weakness,bilateral hyporeflexia, paresthesias, pain, cranial nerve involvement,dysautonomia, and eventually, respiratory insufficiency.

Lambert-Eaton syndrome (choice C) is an autoimmune disease ofneuromuscular transmission, often associated with malignancy, which ischaracterized by weakness of proximal muscles and facilitation (strengthimprovement) after exercise.

Chronic progressive external ophthalmoplegia (choice E) is a disordercharacterized by slow progressive paralysis of extraocular muscles.

Question 2 of 5

The underlying pathophysiology in this disease involves which of the followingmechanisms?/ A. Antibodies to nicotinic acetylcholine receptors/ B. Antibodies to voltage-gated calcium channels/ C. Bacterial toxin/ D. Infection-induced autoimmune response/ E. Thiamine deficiency

Explanation - Q: 3.2 CloseThe correct answer is A. Myasthenia gravis (MG) is an acquired

autoimmune disorder characterized by autoantibodies directed toacetylcholine receptors (AChR) at the neuromuscular junction. Specificacetylcholine receptor autoantibodies lead to reduced impulse transmission inthe neuromuscular junction. Cholinergic receptors of smooth and cardiacmuscle (muscarinic) have a different antigenicity and therefore are notaffected by the disease. T-helper cells, which have been activated in thethymus, probably stimulate the production of these antibodies. They reactmainly with the alpha subunit of the receptor, reducing the functional activityat the postsynaptic membrane. There are several postulated mechanisms ofautoimmune damage: modulation (increased endocytosis and degradation ofAChR), blocking the binding site for ACh on AChR, and initiating

complement-binding to ACh-AChR complex and damage to postjunctionalmembranes.

In Lambert-Eaton myasthenic syndrome antibodies induce downregulation ofvoltage-gated calcium channels (VGCC) at the presynaptic terminal ofneuromuscular junction (choice B). This reduces calcium-dependentacetylcholine release, which leads to fatigable muscle weakness and loss of


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tendon reflexes.

Clostridium botulinum neurotoxin causes botulism by binding to peripheralcholinergic synapses and preventing neurotransmitter release, which leads to

muscle paralysis (choice C).

Guillain-Barr syndrome is considered to be a postinfectious, autoimmunedisease (choice D). The mechanism most likely involves cross-reactivitybetween antibodies against infectious agents and axonal and/or myelincomponents e.g., GM1, GM2, GD1b.

Thiamine deficiency is associated with Wernicke encephalopathy, (choice E)characterized by ataxia, ophthalmoplegia, and confusion. This disorderusually occurs in alcoholics, or those with severe nutritional deficiencies.

Question 3 of 5

The structures primarily affected in this disease belong to which of the followingsuperfamilies?/ A. Cytokine receptors/ B. Intracellular receptors/ C. Ligand-gated ion channels/ D. Receptors linked to effectors via G proteins/ E. Receptors located on a membrane-spanning enzyme

Explanation - Q: 3.3 CloseThe correct answer is C. The structures involved in this disease are thenicotinic cholinergic receptors, which are ligand-gated ion channels. Thereceptor located at the neuromuscular junction is a pentamer composed of 5polypeptide units (2, 1, 1, and 1). Each polypeptide has fourtransmembrane-spanning regions, which form a cylindrical structure when allfive are joined together. ACh binds to the subunits, producing aconformational change that results in the opening of the channel, allowingsodium to enter the cell.

Cytokine receptors (choice A) respond to a variety of peptide ligands,

including erythropoietin, several types of interferon, growth hormone, andother regulators of growth and differentiation. Their mechanism is similar tothe receptor tyrosine kinases (e.g., insulin receptor), however, in this case,the tyrosine kinase is not actually part of the receptor. Instead, a separatetyrosine kinase (Janus kinases; JAKs) binds noncovalently to the receptor.Once the receptor is activated, the cytokine receptors dimerize (like the EGF-receptor), activating the JAKs to phosphorylate tyrosine residues on thereceptor. This leads to activation of another set of proteins (STATs, signal


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transducers and activators of transcription), which dimerize, detach from thereceptor, and travel to the nucleus where it regulates specific genetranscription.

Intracellular receptors (choice B) can bind lipid-soluble agents that diffuseacross the lipid bilayer (e.g., steroid hormones), which then stimulate genetranscription by binding to specific DNA sequences. A specializedtransmembrane signalling device is not needed with this type of receptor.

Receptors linked to effectors via G proteins (choice D) are comprised of onepolypeptide chain that crosses the membrane seven times. The receptoractivates a G protein, which mediates a variety of effects. There are severaldifferent types of G proteins, e.g., Gs (stimulates adenylyl cyclase), Gi(inhibits adenylyl cyclase, opens cardiac K+ channels), and Gq (activatesphospholipase C).

Receptors located on a membrane-spanning enzyme (choice E) arepolypeptides with an extracellular hormone-binding domain and anintracellular enzyme domain, which may be a tyrosine kinase, a serinekinase, or a guanylyl cyclase. The two domains are connected via ahydrophobic spanning region. Insulin and many growth factors stimulatereceptors that dimerize and initiate a tyrosine kinase signalling pathway.

*** Stop manually reprinting mechanically printed! Automate! ***Question 4 of 5

Which of the following would be likely to exacerbate this patient's symptoms?/ A. Aminoglycosides/ B. Edrophonium/ C. Neostigmine/ D. Pyridostigmine/ E. Thymectomy

Explanation - Q: 3.4 CloseThe correct answer is A. Patients with MG are extremely sensitive to theaction of curariform drugs or other drugs that interfere with neuromusculartransmission. Aminoglycosides (e.g., streptomycin, neomycin, gentamycin,tobramycin, amikacin) are antibacterial agents that inhibit protein synthesis byacting directly on the ribosome. Ototoxicity and neurotoxicity are the mostserious side effects. Neuromuscular blockade may result when anaminoglycoside is used in high doses, or with curariform drugs. Themechanism is probably decreased presynaptic release of ACh and decreasedsensitivity of the postsynaptic membrane. Many other agents can exacerbateMG symptoms, e.g., chloroquine, ciprofloxacin, muscle relaxants, botulinum


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toxin, quinidine, procainamide, phenytoin, and d-penicillamine.

Edrophonium (choice B) is a rapidly-acting, short-duration, parenteralcholinesterase inhibitor. It is used as a diagnostic test for MG.

Anticholinesterase agents are used for symptomatic therapy of myastheniagravis. Neostigmine (choice C) is a synthetic reversible acetylcholinesteraseinhibitor that is used for long-term therapy of MG. Neostigmine does notpenetrate blood-brain barrier, and provides an additional direct nicotinicagonist effect. Pyridostigmine (choice D) is another anticholinesterase drugused in the treatment of MG.

The role of the thymus in the pathogenesis of MG is not clear, but it wasfound that 75% of MG patients has some type of thymic abnormality. That isthe rationale for thymectomy (choice E) as a therapeutic tool. Thymectomyusually improves symptoms, and should be considered in patients younger

than 60, unless the disease has affected only extraocular muscles. Plasmaexchange may also be used in patients unresponsive to other treatments, butproduces only short-term clinical improvement.

Question 5 of 5

Administration of which of the following agents would confirm the diagnosis ofthis disease?/ A. Edrophonium/ B. Nicotine/ C. Pilocarpine/ D. Pralidoxime/ E. Succinylcholine

Explanation - Q: 3.5 CloseThe correct answer is A. An edrophonium (Tensilon) IV challenge (doubleblind) test is used to confirm the diagnosis of MG. Edrophonium is a drug ofchoice for diagnosing MG because of its rapid onset of action andreversibility. If the patient has MG, an improvement in muscle strength thatlasts 5 minutes or so will usually be seen. Other uses include assessing thetreatment of MG with longer-acting cholinesterase inhibitors (too much or toolittle), differentiating cholinergic and myasthenic crises (in myasthenic crisis,

edrophonium improves muscle strength, but in cholinergic crisis, it furtherreduces muscle strength) and reversing the effects of nondepolarizingblocking agents after surgery.

Nicotine (choice B) is a natural alkaloid found in tobacco that mimics theeffects of ACh at nicotinic receptors. It has no therapeutic actions but isimportant for its toxicity.


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Pilocarpine (choice C) is a direct-acting muscarinic receptor agonist. It isused in glaucoma to produce pupillary miosis and ciliary muscle contraction,thereby increasing aqueous humor outflow.

Pralidoxime (2-PAM, pyridine-2-aldoxime methyl chloride, choice D) reversesthe effects of organophosphates, which are irreversible anticholinesteraseagents. Treatment must be within hours because of the "aging" phenomenon,i.e., establishing a form that cannot be reversed.

Succinylcholine (choice E) is a depolarizing neuromuscular blocking agent. Ithas the briefest duration of action of all neuromuscular blocking drugs.Therefore, it is a drug of choice for endotracheal intubation, electroconvulsiveshock therapy, and termination of laryngospasm.

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