WBR252

Author	[[PageAuthor::Gerald Chi (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Gastrointestinal, SubCategory::Neurology
Prompt	[[Prompt::A 24-year-old woman gradually develops throbbing headache, pulsatile tinnitus, and blurred vision that are worse in the morning and often accompanied by nausea and vomiting. She is awake, alert, afebrile and has no other focal neruologic deficit on exmaination. She has a past medical history significant for acne vulgaris, for which she takes daily oral isotretinoin. Neuroimaging is negative for space-occupying lesions. Cerebrospinal fluid pressure is elevated with a normal composition. Accumulation of the culprit substance is most likely to be found in which of the following cell types in the liver?]]
Answer A	AnswerA::Kupffer cell
Answer A Explanation	AnswerAExp::Kupffer cells are specialized macrophages (reticuloendothelial cells) in the liver. They play a role in the hepatic response to toxic compounds but are not the main storage site of vitamin A metabolites.
Answer B	AnswerB::Sinusoidal endothelial cell
Answer B Explanation	AnswerBExp::A liver sinusoid is a type of sinusoidal blood vessel (with fenestrated, discontinuous endothelium) that serves as a location for the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein.
Answer C	AnswerC::Perisinusoidal cell
Answer C Explanation	[[AnswerCExp::Hepatic stellate cells, also known as either perisinusoidal cells or Ito cells (earlier lipocytes or fat-storing cells), are pericytes found in the perisinusoidal space of the liver also known as the space of Disse. Following ingestion, vitamin A, a lipid soluble vitamin, undergoes hepatic metabolism, whereby hepatic parenchymal cells absorb vitamin A in the form of retinyl esters. Parenchymal cells metabolize the retinyl esters, which is subsequently transferred to the stellate cells for either storage with other long-chain fatty acids or mobilization into the plasma (bound to RBP).]]
Answer D	AnswerD::Cholangiocyte
Answer D Explanation	AnswerDExp::Cholangiocytes are the epithelial cells of the bile duct. They are cuboidal epithelium in the small interlobular bile ducts, but become columnar and mucus secreting in larger bile ducts approaching the porta hepatis and the extrahepatic ducts.
Answer E	AnswerE::Hepatocyte
Answer E Explanation	AnswerEExp::Hepatocytes are involved in protein synthesis, protein storage, transformation of carbohydrates, synthesis of cholesterol, bile salts and phospholipids, and detoxification, modification, and excretion of exogenous and endogenous substances.
Right Answer	RightAnswer::C
Explanation	[[Explanation::Pseudotumor cerebri is a neurological disorder that is characterized by increased intracranial pressure in the absence of a tumor or other diseases. The main symptoms are headache, nausea, and vomiting, as well as pulsatile tinnitus, double vision and other visual symptoms. Intracranial pressure may be increased due to medications such as high-dose vitamin A derivatives (e.g. isotretinoin), long-term tetracycline antibiotics, lithium, or hormonal contraceptives. Following ingestion, vitamin A, a lipid soluble vitamin, undergoes hepatic metabolism, whereby hepatic parenchymal cells absorb vitamin A in the form of retinyl esters. Parenchymal cells metabolize the retinyl esters, which is subsequently transferred to the stellate cells for either storage with other long-chain fatty acids or mobilization into the plasma (bound to RBP). The advantage of vitamin A storage in the stellate cells is the capacity of the liver to maintain adequate supply of vitamin A by metabolizing stored vitamin A during periods of low dietary intake. In cases of hypervitaminosis, vitamin A saturates in the hepatic stellate cells and leaks from the liver into the bloodstream beyond the blood brain barrier. The mechanism by which vitamin A excess results in pseudotumor cerebri is poorly understood. Educational Objective: Hepatic stellate cells, also known as either perisinusoidal cells or Ito cells (earlier lipocytes or fat-storing cells), are pericytes found in the perisinusoidal space of the liver also known as the space of Disse. Following ingestion, vitamin A, a lipid soluble vitamin, undergoes hepatic metabolism, whereby hepatic parenchymal cells absorb vitamin A in the form of retinyl esters. Parenchymal cells metabolize the retinyl esters, which is subsequently transferred to the stellate cells for either storage with other long-chain fatty acids or mobilization into the plasma (bound to RBP). References: Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr. 2006;88(2):191-201. Morrice Jr, G, Havener WH, Kapetansky F. Vitamin A intoxication as a cause of pseudotumor cerebri. JAMA. 1960;173(16):1802-5. Toren G, Nilsson A, Norum KR, et al. Characterization of liver stellate cell retinyl ester storage. Biochem J. 1994;300:793-8. First Aid 2015 page 89, 468.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Stellate cells, WBRKeyword::Hepatocytes, WBRKeyword::Retinyl esters, WBRKeyword::Perisinusoidal cells, WBRKeyword::Ito cells, WBRKeyword::Vitamin A, WBRKeyword::Isotretinoin, WBRKeyword::Acne, WBRKeyword::Pseudotumor cerebri, WBRKeyword::Headache
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