Terms in this set (483)

14. Ans. (A). Classic (or neurological) migraine is generally a familial disorder that begins in childhood or early adult life. Typically the onset of an episode is marked by the progression of a neurological disturbance over 5 to 15 mm, followed by a unilateral (or occasion ally bilateral) throbbing headache for several hours up to a day. The most common neurological disturbance involves formed or unformed flashes of light that impair vision in one of the visual fields (scintillating scotoma). Other possible neurological symptoms include numbness and tingling of the unilateral face, lips, and hand; weakness of an arm or leg; mild aphasia; and mental confusion. The transience of the neurological symptoms distinguishes migraine from other, more serious conditions that cause headache. Persistence of a visual field defect, speech disturbance, or mild hemiparesis suggests a focal lesion (e.g., arteriovenous malformation with hemorrhage or infarct). In the case of persistent ataxia, limb incoordination and nausea, one should consider a posterior fossa (possibly cerebellar) mass lesion.
Monocular visual loss in an elderly patient with throbbing headache should initiate a search for cranial (temporal) arteritis. This should include a sedimentation rate (usually elevated) and a temporal artery biopsy (which would show a giant cell arteritis). Fifty percent of these patients have the generalized muscle aches seen with polymyalgia rheumatica. Unilateral orbital or retro orbital headaches that occur nightly for a period of 2 to 8 weeks are characteristic of cluster headaches. These headaches are often associated with ipsilateral injection of the Conjunctivum, nasal stuffiness, rhinorrhea, and, less commonly miosis, ptosis and cheek edema. Although both migraine and cluster headaches may respond to treatment with ergotamine, they are generally considered to be distinct entities.
26. Ans. (B).
Cholera toxin inhibits the conversion of Gs-GTP to Gs-GDP. In contrast, pertussis toxin inhibits the activation of Gi-GDP to Gi-GTP.
Some substances that react with cell surface receptors bind to guanine nucleotide regulatory proteins. These proteins, called G proteins, may be classified into four categories, namely Gs, Gi, Gt, and Gq. Two of these receptors, Gs and Gi, regulate the intracellular concentration of cyclic adenosine 5'-monophosphate (cAMP). In contrast, Gt regulates the intracytoplasmic levels of cyclic guanosine 5'-monophosphate (cGMP), and Gq regulates the intracytoplasmic levels of calcium ions. Gs and Gi regulate intracellular cAMP levels by their actions on adenyl cyclase, an enzyme located on the inner surface of the plasma membrane that catalyzes the formation of cAMP from ATP. The adenylate cyclase G protein complex is composed of the following components: the receptor, the catalytic enzyme (i.e., adenyl cyclase), and a coupling unit. The coupling unit consists of GTP-dependent regulatory proteins (G proteins), which may either be stimulatory (Gs) or inhibitory (Gi). When hound to GTP and active, Gs stimulates adenyl cyclase and increases cAMP levels. (Gs can he thought of as the "on switch.") In contrast, when bound to GTP and active, Gi inhibits adenyl cyclase and decreases cAMP levels. (Gi can be thought of as the "off switch.")
Therefore, both cholera toxin and pertussis toxin prolong the functioning of adenyl cyclase and therefore increase intracellular cAMP, but their mechanisms are different. Cholera toxin keeps the "on switch" in the "on" position, while pertussis toxin keeps the "off switch" in the "off' position.
27. Ans. (B).
Two important control points of the coagulation cascade are the fibrinolytic system and certain plasma protease inhibitors. The main component of the fibrinolytic system is plasmin, which is converted from plasminogen by either factor XII or a plasminogen activator (PA). Examples of PAs include tissue plasminogen activator (tPA), urokinase plasminogen activator, and streptokinase. Once formed, plasmin splits fibrin and also degrades both fibrinogen and coagulation factors VIII and V. Plasma protease inhibitors include antithrombin III and protein C. Antithrombin III in the presence of heparin inhibits thrombin, XIIa, XIa, Xa, and IXa, while protein C inhibits Va and VIIIa.
Deficiencies of antithrombin III, protein C, or protein S are associated with hypercoagulable states and increased risk of thrombosis, as the main factors leading to thrombosis include injury to endothelium, alterations in blood flow, and hypercoagulability of the blood. Hypercoagulability may be a primary (genetic) or secondary abnormality. Primary hypercoagulable states include the previously mentioned deficiencies of antithrombin III, protein C, or protein S. These deficiencies are associated with recurrent thromboembolism in early adult life and recurrent spontaneous abortions in women. The causes of secondary hypercoagulable states are numerous and include severe trauma, burns, disseminated cancer, and pregnancy. Lower risk factors for the development of secondary hypercoagulable states include age, smoking, and obesity Some patients with high titers of autoantibodies against anionic phospholipids such as cardiolipin (the antibody being called a lupus anticoagulant) have a high frequency of arterial and venous thrombosis. To summarize, it is important to remember that the differential diagnosis of recurrent spontaneous abortions in women includes deficiencies of protein C and protein S and the presence of the lupus anticoagulant, which is part of the antiphospholipid syndrome.
28. Ans. (D).
Purine synthesis involves adding carbons and nitrogens to ribose 5-phosphate (R5P), which is a product of the hexose monophosphate (HMP) shunt. R5P is then converted to ribose phosphate pyrophosphate (RPPP), which is subsequently converted to 5'-phosphonbosylamine, the latter step being the committed step in purine nucleotide biosynthesis. Through a series of steps RPPP is converted to inosine 5'-monophosphate (IMP). Several of these biochemical steps involve transferring methyl groups from folate. This is important because folate analogues, such as methotrexate, inhibit DNA synthesis, especially in rapidly growing tumor cells, by inhibiting purine synthesis. Finally IMP is converted into either AMP or GMP. These last biochemical steps are also connected to biochemical reactions that involve adenosine deaminase, an enzyme that is deficient in individuals with the autosomal recessive form of SCID, and hypoxanthine-guanine phosphoribosyl transferase (HGPRT), an enzyme of the purine salvage pathway for recycling guanine and hypoxanthine that is deficient in individuals with the X-linked recessive disorder Lesch-Nyhan syndrome. This disorder is characterized by excess uric acid production, which may produce symptoms of gout, mental retardation, spasticity, self-mutilation, and aggressive behavior, in contrast, a deficiency of homogentisticoxidase, which is involved in the conversion of homogentisic acid to methylacetoacetate, is associated with alkaptonuria. Abnormal degradation of galactocerebroside is seen in Krabbe's disease, while abnormal breakdown of branched-chain amino acids is seen in maple syrup urine disease.
32. Ans. D.
The complement system is a cascade of plasma proteins whose basic function is the direct lysis of cells, attraction of leukocytes to sites of inflammation (ichemotaxis), and activation of leukocytes. The complement system can be activated by one of two basic pathways. The classic pathway is initiated by antigen-antibody (immune) complexes binding to Cl - The antibodies that are involved in forming these complement-activating immune complexes are IgM and IgG (subtypes 1, 2, and 3). There are also some non-immunologic activators of the classic complement pathway, such as urate crystals, which may be part of the patho physiologic process of gout. In contrast, with the alternate complement pathway the early complement components (Cl, C4, and C2) are bypassed and C3 is activated directly by such things as bacterial endotoxins, cobra venom factor, lipopolysaccharide, and aggregated immunoglobulin (mainly IgA, but also IgG). C3 nephritic factor is an unusual substance capable of activating the alternate complement system within the glomerulus, producing glomerular injury.
Finally, the mechanism through which organisms with increased amounts of sialic acid can inhibit the activation of the alternate complement system is as follows: first note that normally low levels of C3 in the blood are converted into C3a and C3b by a slow process called "C3 tick- over." The C3b may combine with factor B to form C3bB, which subsequently will react with factor D and properdin, both of which are part of the alternate complement pathway Some of the C3h formed by "C3 tick- over" may instead attach to factor H. This will cause C3b to be inactivated by being converted to C3bi by factor I. This attachment to factor H is increased by sialic acid
37. Ans. (C.) An X-linked recessive disorder that results from a deficiency of coagulation factor VIII is hemophilia A. Clinically, patients with hemophilia exhibit a wide range of severity of symptoms that depends upon the degree to which factor VII activity is decreased. Petechiae and small ecchymoses are characteristically absent, but large ecchymoses and subcutaneous and intramuscular hematomas are common. Other types of bleeding that are characteristic include massive hemorrhage following trauma or surgery and "spontaneous" hemorrhages in parts of the body that are normally subject to trauma, such as the joints (hemarthroses). Intra-abdominal hemorrhage and intracranial hemorrhage also occur. The latter is a major cause of death for these individuals. Because of the decreased factor VIII activity, patients with hemophilia A have a prolonged PTT, which measures the intrinsic coagulation cascade. Other clinical tests, including bleeding time, tourniquet test, platelet count, and PT are normal. Treatment is with factor VIII concentrates, but this carries a risk for the transmission of viral hepatitis and AIDS.
In contrast, hemorrhagic urticaria is seen with Henoch-Schönlein purpura, a disorder of children characterized by the deposition of IgA immune complexes in the small vessels of the skin. Perifollicular hemorrhages are seen with scurvy; which is caused by a deficiency of vitamin C. In this disorder, the defective synthesis of collagen will increase the fragility of the basement membrane of capillaries causing periosteal and perifollicular hemorrhages.
40. Ans. (C). Focal seg mental glomerulosclerosis (FSGS) is a glomerular disorder that accounts for about 10% of the cases of nephrotic syndrome. FSGS, which affects children and adults, begins as a focal process, affecting only some glomeruli. In the earliest stage, only some of the juxtamedullary glomeruli show changes. Eventually, some glomeruli in other parts of the cortex are affected. In the late stages of the disease, the process may become diffuse, affecting most or all glomeruli. Initially, the process is also segmental, involving some but not all of the lobules within an individual glomerular tuft. The involved area shows sclerosis and may show hyalinosis lesions. Eventually some glomeruli show sclerosis of the entire tuft (global sclerosis). Electron microscopy shows increased mesangial matrix and dense granular mesangial deposits. Immunofluorescence typically shows granular mesangial fluorescence for IgM and C3 Because of the focal nature of FSGS, early cases can he difficult to distinguish from minimal change disease (MCD). Clinically, the nephrotic syndrome of FSGS is more severe than that of MCD and is nonselective. The process is much less responsive to steroids and is much more prone to progress to chronic renal failure. It tends to recur in trans planted kidneys. FSGS can be seen in the setting of AIDS nephropathy and heroin nephropathy. Note: FSGS, with no cellular proliferation, is different from focal segmental glomerulonephritis (FSGN), which involves cellular proliferation. The main cause of FSGN is IgA (Berger's) nephropathy while FSGS is most notably seen in patients with AIDS.
43. Ans. (B)
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a degenerative disorder of motor neurons, principally the anterior horn cells of the spinal cord, the motor nuclei of the brainstem, and the upper motor neurons of the cerebral cortex. Clinically, this disease is a combination of lower motor neuron (LMN) disease with weakness and fasciculations and upper motor neuron (UMN) disease with spasticity and hyperreflexia. Early symptoms include weakness and cramping and then muscle atrophy and fasciculations. Reflexes are hyperactive in upper and lower extremities, and a positive extensor plantar (Babinski) reflex develops because of the loss of upper motor neurons. The triad of atrophic weakness of hands and forearms, slight spasticity of the legs, and generalized hyperreflexia—in the absence of sensory changes—suggests the diagnosis. The clinical course is rapid, and death may result from respiratory complications. There is no effective treatment for ALS. Theories about the etiology of ALS include viral infections, immunologic causes, or oxidative stress. The latter is related to a defect in zinc-copper binding superoxide dismutase (SOD) on chromosome 21. Decreased SOD activity leads to apoptosis of spinal motor neurons.
In contrast, metachromatic leukodystrophy is an autosomal recessive disorder of sphingomyelin metabolism that results from deficiency of cerebroside sulfatase (aryl-sulfatase A). Sulfatides accumulate in lysosomes and stain metachromatically with cresyl violet. Diagnostic measures include amniocentesis, enzyme analysis, and measuring decreased urinary aryl sulfatase A. Demyelination is widespread in the cerebrum and peripheral nervous system. Acute inflammatory demyelinating polyradiculoneuropathy thy (Guillain-Barre syndrome) is a life-threatening disease of the peripheral nervous system. The disease usually follows recovery from an influenza- like upper respiratory tract infection and is characterized by a motor neuropathy that leads to an ascending paralysis that begins with weakness in the distal extremities and rapidly involve proximal muscles. Sensory changes are usually minimal. The disease is due to immune- mediated segmental demyelination. Huntington's disease is characterized by choreiform movements and progressive dementia that appear after the age of 30. Wilson's disease (hepatolenticular degeneration) is an autosomal recessive disorder of copper metabolism in which the total circulating copper is decreased, but the free copper is increased. This leads to athetoid movements, cirrhosis of the liver, and copper deposits in the limbus of the cornea that produce the Kayser-Fleischer ring.
84. Ans. B.
Parkinson's disease (PD) is marked by depletion of dopamine-rich cells in the substantia nigra. The resulting decrease in striatal dopamine is the basis for the classic symptoms of rigidity, bradykinesia, and tremor. The most widely used treatment for PD has been levodopa. Levodopa is converted to dopamine in the substantia nigra and then transported to the striatum, where it stimulates dopamine receptors. This is the basis for the drug's clinical effect on PD. Levodopa is usually administered with carbidopa (a decarboxylase inhibitor) which prevents levodopa's destruction in the blood and allows it to be given at a dose that is lower and less likely to cause nausea and vomiting. The major problems with levodopa have been (1) significant limb and facial dyskinesias in most patients on chronic therapy and (2) the fact that levodopa treats PD only symptomatically, and the disease process of neuronal loss in the substantia nigra continues despite drug treatment. Other drugs can be used in the treatment of PD. Anticholinergic agents, such as trihexyphenidyl and benztropine mesylate work by restoring the balance between striatal dopamine and acetylcholine. They can have significant anticholinergic effects on the CNS, including confusional states and hallucinations. Bromocriptine and pergolide are dopamine agonists that work directly by stimulating dopamine receptors in the striatum; side effects of these drugs are similar to those of levodopa. Selegiline is a selective monoamine oxidase-B inhibitor that blocks the breakdown of intracerebral dopamine.