{"id":3496,"date":"2023-08-16T20:47:00","date_gmt":"2023-08-16T20:47:00","guid":{"rendered":"https:\/\/www.osmosis.org\/blog\/?p=3496"},"modified":"2025-10-01T11:39:34","modified_gmt":"2025-10-01T19:39:34","slug":"usmle-step-1-question-of-the-day-lower-extremity-pain","status":"publish","type":"post","link":"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain","title":{"rendered":"USMLE\u00ae Step 1 Question of the Day: Lower extremity pain"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_80 ez-toc-wrap-center counter-hierarchy ez-toc-counter ez-toc-custom ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">In This Article<\/p>\n<span class=\"ez-toc-title-toggle\"><a href=\"#\" class=\"ez-toc-pull-right ez-toc-btn ez-toc-btn-xs ez-toc-btn-default ez-toc-toggle\" aria-label=\"Toggle Table of Content\"><span class=\"ez-toc-js-icon-con\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #999;color:#999\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #999;color:#999\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/span><\/a><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\/#The_correct_answer_to_todays_USMLE%C2%AE_Step_1_Question_is%E2%80%A6\" >The correct answer to today&#8217;s USMLE\u00ae Step 1 Question is&#8230;<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\/#C_Rupture_of_the_lysosomal_membranes\" >C. Rupture of the lysosomal membranes<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\/#Incorrect_answer_explanations\" >Incorrect answer explanations<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\/#A_Detachment_of_ribosomes_from_the_endoplasmic_reticulum\" >A. Detachment of ribosomes from the endoplasmic reticulum<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\/#B_Loss_of_microvilli_on_the_cellular_surface\" >B. Loss of microvilli on the cellular surface<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-6\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\/#D_Clumping_of_chromatin_within_the_nucleus\" >D. &nbsp;Clumping of chromatin within the nucleus<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-7\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\/#E_Swelling_of_the_mitochondria\" >E. Swelling of the mitochondria<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-8\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\/#Main_Explanation\" >Main Explanation<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-9\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\/#Major_Takeaway\" >Major Takeaway<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-10\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\/#i\" >&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;________________________<\/a><\/li><\/ul><\/li><\/ul><\/nav><\/div>\n\n<p class=\"wp-block-paragraph\"><strong><em>Discover the case of a 57-year-old man with acute-onset right lower extremity pain in the emergency department. Explore the medical history and symptoms that led to a concerning diagnosis. Learn about the histological findings that indicate irreversible cellular injury in the affected extremity.&nbsp;<\/em><em>Find out more here.<\/em><\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A 57-year-old man presents to the emergency department due to acute-onset right lower extremity pain. The symptoms began two hours ago. Past medical history is notable for atrial fibrillation and hypercholesterolemia. Temperature is 37.0\u00b0C (98.6\u00b0F), blood pressure is 158\/83 mmHg, and pulse is 117\/min. The right lower extremity is cold to touch below the knee on physical examination. The suitable posterior tibial and dorsalis pedis pulses are absent. Which of the following histological findings, if present, is most suggestive of irreversible cellular injury in the affected extremity?<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>A. Detachment of ribosomes from the endoplasmic reticulum<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>B. Loss of microvilli on the cellular surface<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>C.&nbsp;<\/strong><strong>Rupture of the lysosomal membranes<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>D. Clumping of chromatin within the nucleus<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>E. Swelling of the mitochondri<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Scroll down for the correct answer!<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"The_correct_answer_to_todays_USMLE%C2%AE_Step_1_Question_is%E2%80%A6\"><\/span>The correct answer to today&#8217;s USMLE\u00ae Step 1 Question is&#8230;<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"C_Rupture_of_the_lysosomal_membranes\"><\/span>C. Rupture of the lysosomal membranes<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Before we get to the Main Explanation, let&#8217;s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Incorrect_answer_explanations\"><\/span>Incorrect answer explanations<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"A_Detachment_of_ribosomes_from_the_endoplasmic_reticulum\"><\/span>A. Detachment of ribosomes from the endoplasmic reticulum<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Incorrect:<\/strong>&nbsp;During cellular hypoxia, the Na+\/K+&nbsp;ATPase pumps stop working. Sodium and water accumulate intracellularly, and the cell begins to swell. These changes can damage the endoplasmic reticulum and cause the ribosomes to detach.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"B_Loss_of_microvilli_on_the_cellular_surface\"><\/span>B. Loss of microvilli on the cellular surface<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Incorrect:<\/strong>&nbsp;During cellular hypoxia, the Na+\/K+&nbsp;ATPase pumps stop working, which causes water and sodium to accumulate within the cell. These changes lead to cellular swelling and loss of microvilli on the plasma membrane. However, this is a reversible process.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"D_Clumping_of_chromatin_within_the_nucleus\"><\/span>D. &nbsp;Clumping of chromatin within the nucleus<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Incorrect:<\/strong>&nbsp;Clumping chromatin within the nucleus signifies reversible cell damage. In contrast, symptoms of membrane damage (e.g. mitochondrial or lysosomal membrane rupture) are more suggestive of irreversible damage.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"E_Swelling_of_the_mitochondria\"><\/span>E. Swelling of the mitochondria<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Incorrect:<\/strong>&nbsp;Mitochondrial swelling is a sign of reversible cell damage. In contrast, signs of membrane damage (e.g. mitochondrial or lysosomal membrane rupture) suggest irreversible damage.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Main_Explanation\"><\/span><strong>Main Explanation<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">This patient has findings suggestive of&nbsp;<strong>acute limb ischemia<\/strong>. The condition can lead to tissue hypoxia, and the presence of ruptured lysosomal membranes is consistent with the irreversible cellular injury.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Hypoxia<\/strong>&nbsp;develops when cells receive insufficient oxygen. As a result, the cells fail to generate adequate ATP. Reversible and irreversible findings of cellular damage can subsequently create.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A common reversible finding is&nbsp;<strong>cellular swelling<\/strong>, which develops since the Na+\/K+&nbsp;ATPase pumps stop working. Sodium and water accumulate intracellularly, which expands the cytosol and causes mitochondrial swelling. These changes lead to&nbsp;<strong>ribosomal detachment<\/strong>&nbsp;from the endoplasmic reticulum and&nbsp;<strong>plasma membrane changes<\/strong>&nbsp;(e.g., loss of microvilli, blebbing). Similarly, calcium pumps stop working, and&nbsp;<strong>intracellular calcium levels&nbsp;<\/strong>become elevated. Furthermore, cells will increase anaerobic respiration to produce more ATP. This process leads to lactic acid accumulation and decreased intracellular pH, resulting in&nbsp;<strong>chromatin clumping<\/strong>&nbsp;and protein denaturation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Over time, the damage becomes irreversible. This transition is partly caused by elevated intracellular calcium levels, which activate enzymes (e.g., endonuclease, phospholipase) and precipitate further cellular injury. The hallmark of irreversible injury is\u00a0<strong>membrane damage<\/strong>, manifesting as\u00a0<strong>plasma membrane breakdown<\/strong>, increased\u00a0<strong>mitochondrial permeability<\/strong>, and\u00a0<strong>lysosomal rupture<\/strong>.<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"840\" height=\"384\" src=\"https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/09\/image_b547da.png\" alt=\"table of findings suggestive of cellular injury\" class=\"wp-image-3498\" srcset=\"https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/09\/image_b547da.png 840w, https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/09\/image_b547da.png?resize=300,137 300w, https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/09\/image_b547da.png?resize=768,351 768w\" sizes=\"auto, (max-width: 840px) 100vw, 840px\" \/><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Major_Takeaway\"><\/span>Major Takeaway<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Hypoxia<\/strong>&nbsp;can lead to reversible and irreversible cellular damage.&nbsp;<strong>Reversible damage<\/strong>&nbsp;is characterized by&nbsp;<strong>cellular swelling, increased intracellular calcium levels<\/strong>, and&nbsp;<strong>chromatin clumping<\/strong>. In contrast,&nbsp;<strong>irreversible injury<\/strong>&nbsp;is characterized by&nbsp;<strong>membrane damage<\/strong>.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"i\"><\/span><strong><em>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;________________________<\/em><\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><em><strong>Want more USMLE\u00ae Step 1 practice questions? Try Osmosis today! Access your\u00a0<em><strong><a href=\"https:\/\/www.osmosis.org\/login?type=create\" target=\"_blank\" rel=\"noreferrer noopener\">free trial<\/a><\/strong><\/em>\u00a0and find out why millions of current and future clinicians and caregivers love learning with us.<\/strong><\/em><\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><a href=\"https:\/\/www.osmosis.org\/ultimate-guide\/usmle-step-1\"><img loading=\"lazy\" decoding=\"async\" width=\"700\" height=\"250\" src=\"https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/09\/image_594136.png\" alt=\"Osmosis sign up ad\" class=\"wp-image-3499\" srcset=\"https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/09\/image_594136.png 700w, https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/09\/image_594136.png?resize=300,107 300w\" sizes=\"auto, (max-width: 700px) 100vw, 700px\" \/><\/a><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\"><a href=\"https:\/\/www.osmosis.org\/ultimate-guide\/usmle-step-1\" target=\"_blank\" rel=\"noreferrer noopener\"><\/a><em><sub>The United States Medical Licensing Examination (USMLE\u00ae) is a joint program of the Federation of State Medical Boards (FSMB\u00ae) and National Board of Medical Examiners (NBME\u00ae). Osmosis is not affiliated with NBME nor FSMB.\u00a0<\/sub><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Discover the case of a 57-year-old man with acute-onset right lower extremity pain in the emergency department. Explore the medical history and symptoms that led to a concerning diagnosis. Learn about the histological findings that indicate irreversible cellular injury in the affected extremity.&nbsp;Find out more here. A 57-year-old man presents to the emergency department due [&hellip;]<\/p>\n","protected":false},"author":202,"featured_media":3497,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_feature_clip_id":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_post_was_ever_published":false},"categories":[27,20,1369,44],"tags":[],"class_list":["post-3496","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicine","category-exam-prep","category-step-1-questions","category-step-1"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.6 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>USMLE\u00ae Step 1 Question of the Day: Lower extremity pain - Osmosis Blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.osmosis.org\/blog\/usmle-step-1-question-of-the-day-lower-extremity-pain\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"USMLE\u00ae Step 1 Question of the Day: Lower extremity pain - Osmosis Blog\" \/>\n<meta property=\"og:description\" content=\"Discover the case of a 57-year-old man with acute-onset right lower extremity pain in the emergency department. Explore the medical history and symptoms that led to a concerning diagnosis. Learn about the histological findings that indicate irreversible cellular injury in the affected extremity.&nbsp;Find out more here. 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Dive into the details and sharpen your clinical skills for effective patient care!","rel":"","context":"In &quot;Allopathic Medicine (MD)&quot;","block_context":{"text":"Allopathic Medicine (MD)","link":"https:\/\/www.osmosis.org\/blog\/category\/medicine"},"img":{"alt_text":"Step 2 CK Question of the Day Leg pain","src":"https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/12\/Step_2_CK_Question-of-the-day-leg-pain.jpg","width":350,"height":200,"srcset":"https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/12\/Step_2_CK_Question-of-the-day-leg-pain.jpg 1x, https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/12\/Step_2_CK_Question-of-the-day-leg-pain.jpg 1.5x, https:\/\/www.osmosis.org\/blog\/wp-content\/uploads\/sites\/2\/2024\/12\/Step_2_CK_Question-of-the-day-leg-pain.jpg 2x"},"classes":[]}],"jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/posts\/3496","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/users\/202"}],"replies":[{"embeddable":true,"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/comments?post=3496"}],"version-history":[{"count":1,"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/posts\/3496\/revisions"}],"predecessor-version":[{"id":3500,"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/posts\/3496\/revisions\/3500"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/media\/3497"}],"wp:attachment":[{"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/media?parent=3496"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/categories?post=3496"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.osmosis.org\/blog\/wp-json\/wp\/v2\/tags?post=3496"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}