WBR0279: Difference between revisions

Jump to navigation Jump to search
mNo edit summary
m (refreshing WBR questions)
 
(4 intermediate revisions by 2 users not shown)
Line 1: Line 1:
{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Ochuko}} (Edited by Alison Leibowitz)
|QuestionAuthor= {{Ochuko}} (Reviewed by {{YD}} and  {{AJL}})
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Biochemistry
|MainCategory=Biochemistry
Line 8: Line 8:
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|SubCategory=General Principles
|SubCategory=General Principles
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|MainCategory=Biochemistry
Line 20: Line 21:
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|SubCategory=General Principles
|SubCategory=General Principles
|Prompt=A 55-year old male with a history of diabetes and hypertension presents to the physician’s office regarding a progressive loss of vision. Upon physical examination, the blood pressure is 160/90 mm Hg and the pulse is 90 beats per minute. Laboratory findings include a blood glucose level of 160 mg/dl. An eye examination confirms the presence of bilateral cataracts. The accumulation of which of the following substances is the most likely cause of the patient’s progessive vision loss?
|Prompt=A 72-year-old man with a history of type 2 diabetes presents to the physician’s office for progressive loss of vision. He explains that recently, he has been sensing that all lights are too bright and has been seeing halos around lights. His night vision has become much worse in the past few months, and he has been avoiding driving at night. His temperature is 36.6 °C (97.88 °F), his blood pressure is 136/80 mmHg, and his heart rate is 76/min. Laboratory findings are remarkable for a blood glucose level of 320 mg/dL and HbA1c of 9.9 mmol/mol. The accumulation of which substance is associated with the development of this patient’s progressive vision loss?
|Explanation=In glucose metabolism, an alternative method of trapping glucose in the cell is its conversion to [[sorbitol]] by the enzyme [[aldose reductase]]. In diabetics, augmented glucose levels result in the intracellular accumulation of sorbitol leading to osmotic damage in the form of cataracts.
|Explanation=Cataract is the progressive and cumulative loss of lens transparency (opacification) that results in vision loss in the affected eye. Cataract is the leading cause of blindness worldwide. It is considered an early complication of diabetes mellitus. The incidence of cataract increases by 2 to 5 times among diabetic patients, and the incidence further increases significantly among diabetics who are diagnosed with diabetes before the age of 40. Patients often complain of light scatter, subjective glare with halos around lights, and vision loss that may affect daily activities such as reading or driving. The pathophysiology of cataracts involves 3 molecular mechanisms: First, non-enzymatic glycation of lens proteins; second, oxidative stress; and third, activation of polyol pathway, which is mediated by the intracellular aldose reductase enzyme, and consequent accumulation of intracellular sorbitol. Excess sorbitol within the fibrils of the lens results in movement of water into the lens fibrils and leads to swelling of the lens fibrils and cataract formation.
|AnswerA=Fructose
|AnswerA=Fructose
|AnswerAExp= Fructose accumulation causes essential fructosuria which would result due to the deficiency of fructokinase. It is a benign condition that is most often asymptomatic
|AnswerAExp=Fructose accumulation causes essential fructosuria, which would result in the deficiency of fructokinase. It is a benign condition, and patients are usually asymptomatic.
|AnswerB=Sorbitol
|AnswerB=Sorbitol
|AnswerBExp= See explanation
|AnswerBExp=The activation of polyol pathway, which is mediated by the intracellular aldose reductase enzyme, and the consequent accumulation of intracellular sorbitol are responsible for the swelling of lens fibrils. This osmotic-induced damage is associated with the development of cataracts among diabetic patients.
|AnswerC=Galactose
|AnswerC=Galactose
|AnswerCExp= Galactose accumulation would result as a result of galactokinase deficiency and galactose appears in blood and urine and may cause infantile cataracts. It is a relatively mild condition
|AnswerCExp=Galactose accumulation results from galactokinase deficiency. Galactose appears in blood and urine and may cause infantile cataracts. It is a relatively mild condition.
|AnswerD=Galactitol
|AnswerD=Galactitol
|AnswerDExp= Galactitol accumulation is due to the deficiency or the absence of the enzyme galactose-1-phosphate uridyltransferase, which causes galactosemia, an autosomal recessive disorder with symptoms such as failure to thrive, jaundice, hepatomegaly, infantile cataracts and mental retardation.
|AnswerDExp=Galactitol accumulation is due to the deficiency or the absence of the enzyme galactose-1-phosphate uridyltransferase, which causes galactosemia. Galactosemia is an autosomal recessive disorder associated with failure to thrive, jaundice, hepatomegaly, infantile cataracts, and mental retardation.
|AnswerE=Glycogen
|AnswerE=Glycogen
|AnswerEExp= Intracellular accumulations of glycogen would lead to abnormal glycogen metabolism and could lead to a group of disorders called glycogen storage diseases
|AnswerEExp=Intracellular accumulation of glycogen results in abnormal glycogen metabolism and glycogen storage diseases.
|EducationalObjectives=
|EducationalObjectives=The activation of polyol pathway, which is mediated by the intracellular aldose reductase enzyme, and the consequent accumulation of intracellular sorbitol are responsible for the swelling of lens fibrils. This osmotic-induced damage is associated with the development of cataracts among diabetic patients.
|References=First AID for the USMLE Step 1 2011 Pgs 104, 110
|References=Javadi M, Zarei-Ghanavati S. Cataracts in diabetic patients: a review article. J Ophthalmic Vis Res. 2008;3(1):52-65.<br>
Malone JI, Lowitt S, Cook WR. Nonosmotic diabetic cataracts. Pediatr Res. 1990;27(3):293-6.<br>
Lightman S. Does aldose reductase have a role in the development of the ocular complications of diabetes? Eye. 1993;7:238-241.<br>
First Aid 2014 page 107, 327
|RightAnswer=B
|RightAnswer=B
|WBRKeyword=Diabetes mellitus, Diabetes, Cataract, Cataracts, Sorbitol, Accumulation, Aldose reductase, Osmotic damage
|Approved=Yes
|Approved=Yes
}}
}}

Latest revision as of 00:02, 28 October 2020

 
Author [[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1] (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [2])]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Biochemistry
Sub Category SubCategory::General Principles
Prompt [[Prompt::A 72-year-old man with a history of type 2 diabetes presents to the physician’s office for progressive loss of vision. He explains that recently, he has been sensing that all lights are too bright and has been seeing halos around lights. His night vision has become much worse in the past few months, and he has been avoiding driving at night. His temperature is 36.6 °C (97.88 °F), his blood pressure is 136/80 mmHg, and his heart rate is 76/min. Laboratory findings are remarkable for a blood glucose level of 320 mg/dL and HbA1c of 9.9 mmol/mol. The accumulation of which substance is associated with the development of this patient’s progressive vision loss?]]
Answer A AnswerA::Fructose
Answer A Explanation AnswerAExp::Fructose accumulation causes essential fructosuria, which would result in the deficiency of fructokinase. It is a benign condition, and patients are usually asymptomatic.
Answer B AnswerB::Sorbitol
Answer B Explanation [[AnswerBExp::The activation of polyol pathway, which is mediated by the intracellular aldose reductase enzyme, and the consequent accumulation of intracellular sorbitol are responsible for the swelling of lens fibrils. This osmotic-induced damage is associated with the development of cataracts among diabetic patients.]]
Answer C AnswerC::Galactose
Answer C Explanation AnswerCExp::Galactose accumulation results from galactokinase deficiency. Galactose appears in blood and urine and may cause infantile cataracts. It is a relatively mild condition.
Answer D AnswerD::Galactitol
Answer D Explanation [[AnswerDExp::Galactitol accumulation is due to the deficiency or the absence of the enzyme galactose-1-phosphate uridyltransferase, which causes galactosemia. Galactosemia is an autosomal recessive disorder associated with failure to thrive, jaundice, hepatomegaly, infantile cataracts, and mental retardation.]]
Answer E AnswerE::Glycogen
Answer E Explanation AnswerEExp::Intracellular accumulation of glycogen results in abnormal glycogen metabolism and glycogen storage diseases.
Right Answer RightAnswer::B
Explanation [[Explanation::Cataract is the progressive and cumulative loss of lens transparency (opacification) that results in vision loss in the affected eye. Cataract is the leading cause of blindness worldwide. It is considered an early complication of diabetes mellitus. The incidence of cataract increases by 2 to 5 times among diabetic patients, and the incidence further increases significantly among diabetics who are diagnosed with diabetes before the age of 40. Patients often complain of light scatter, subjective glare with halos around lights, and vision loss that may affect daily activities such as reading or driving. The pathophysiology of cataracts involves 3 molecular mechanisms: First, non-enzymatic glycation of lens proteins; second, oxidative stress; and third, activation of polyol pathway, which is mediated by the intracellular aldose reductase enzyme, and consequent accumulation of intracellular sorbitol. Excess sorbitol within the fibrils of the lens results in movement of water into the lens fibrils and leads to swelling of the lens fibrils and cataract formation.

Educational Objective: The activation of polyol pathway, which is mediated by the intracellular aldose reductase enzyme, and the consequent accumulation of intracellular sorbitol are responsible for the swelling of lens fibrils. This osmotic-induced damage is associated with the development of cataracts among diabetic patients.
References: Javadi M, Zarei-Ghanavati S. Cataracts in diabetic patients: a review article. J Ophthalmic Vis Res. 2008;3(1):52-65.
Malone JI, Lowitt S, Cook WR. Nonosmotic diabetic cataracts. Pediatr Res. 1990;27(3):293-6.
Lightman S. Does aldose reductase have a role in the development of the ocular complications of diabetes? Eye. 1993;7:238-241.
First Aid 2014 page 107, 327]]

Approved Approved::Yes
Keyword WBRKeyword::Diabetes mellitus, WBRKeyword::Diabetes, WBRKeyword::Cataract, WBRKeyword::Cataracts, WBRKeyword::Sorbitol, WBRKeyword::Accumulation, WBRKeyword::Aldose reductase, WBRKeyword::Osmotic damage
Linked Question Linked::
Order in Linked Questions LinkedOrder::