Block 10 Metabolic And Hemodynam Disord MCQ's

1. Clinical symptoms associated with metabolic dysfunctions in mitochondria are associated with?

Insufficient renal clearance

Heart murmurs and clammy skin

Fatigue and metabolic acidosis

Loss of hair and nausea

Dry skin and dehydration

Clinical symptoms associated with metabolic dysfunctions in mitochondria are fatigue and metabolic acidosis. Mitochondria are responsible for producing energy in the form of ATP through oxidative phosphorylation. When there is a dysfunction in mitochondria, it leads to a decrease in ATP production, resulting in fatigue. Additionally, the dysfunction can also disrupt the normal metabolic processes, leading to an accumulation of acidic byproducts in the body, causing metabolic acidosis. Therefore, fatigue and metabolic acidosis are common symptoms associated with mitochondrial metabolic dysfunctions.

Explanation

Clinical symptoms associated with metabolic dysfunctions in mitochondria are fatigue and metabolic acidosis. Mitochondria are responsible for producing energy in the form of ATP through oxidative phosphorylation. When there is a dysfunction in mitochondria, it leads to a decrease in ATP production, resulting in fatigue. Additionally, the dysfunction can also disrupt the normal metabolic processes, leading to an accumulation of acidic byproducts in the body, causing metabolic acidosis. Therefore, fatigue and metabolic acidosis are common symptoms associated with mitochondrial metabolic dysfunctions.

2. An anemic adult patient has the following red cell indices: Mean Corpuscular Volume: 70mm (MCV normal: 76-96) Mean Corpuscular Hemoglobin: 22g (MCH normal: 27-32) Mean Corpuscular Hemoglobin Concentration: 34% (MCHC normal: 30-35) A blood film shows hypochromic and microcytic RBCs. Quantitative Hb studies show a significant increase in HbA2 levels and a moderate elevation in HbF levels. These values are most consistent with which of the following diagnoses?

Folic acid deficiency

Iron-deficiency anemia

Thalassemia minor

Pernicious anemia

Sideroblastic anemia

The given red cell indices indicate a decrease in the size of red blood cells (microcytic) and a decrease in the amount of hemoglobin in each cell (hypochromic). This pattern is commonly seen in thalassemia, a genetic disorder that affects the production of hemoglobin. The increased levels of HbA2 and moderately elevated levels of HbF further support the diagnosis of thalassemia minor, as these are characteristic findings in this condition. Folic acid deficiency, iron-deficiency anemia, pernicious anemia, and sideroblastic anemia would not typically present with this specific pattern of red cell indices and hemoglobin levels.

Explanation

The given red cell indices indicate a decrease in the size of red blood cells (microcytic) and a decrease in the amount of hemoglobin in each cell (hypochromic). This pattern is commonly seen in thalassemia, a genetic disorder that affects the production of hemoglobin. The increased levels of HbA2 and moderately elevated levels of HbF further support the diagnosis of thalassemia minor, as these are characteristic findings in this condition. Folic acid deficiency, iron-deficiency anemia, pernicious anemia, and sideroblastic anemia would not typically present with this specific pattern of red cell indices and hemoglobin levels.

3. A 1-year-old child with mental retardation is found to have a deficiency of dihydrobiopterin reductase. This enzyme deficiency is most closely related to which of the following disorders?

Galactosemia

Phenylketonuria

Wilson’s disease

Maple syrup urine disease

Niemann-Pick disease

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Explanation

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4. A 42-year-old woman has a history of repeated urinary tract infections. One of these episodes was recently complicated by acute pyelonephritis. She became septic, and a blood culture grew Escherichia coli. She developed severe hypotension and presented purpuric areas on her skin. A stool for occult blood was positive. Patient was hospitalized with B.P. 80/50 mm Hg, septic, and died next day in spite of treatment. Microscopic study (Image # 2), most likely confirms one of the following diagnoses:

Hemophilia A

Disseminated intravascular coagulation

Von Willebrand disease

Antiphospholipid syndrome

Thrombocytopenia

The microscopic study most likely confirms the diagnosis of disseminated intravascular coagulation (DIC) because the patient presented with purpuric areas on her skin, which are indicative of bleeding under the skin. DIC is a condition characterized by widespread activation of blood clotting throughout the body, leading to the formation of small blood clots in the blood vessels. This can result in organ damage and bleeding, as seen in this patient. The positive stool occult blood test suggests gastrointestinal bleeding, which can occur in DIC. Additionally, the patient's severe hypotension and sepsis are also consistent with DIC.

Explanation

The microscopic study most likely confirms the diagnosis of disseminated intravascular coagulation (DIC) because the patient presented with purpuric areas on her skin, which are indicative of bleeding under the skin. DIC is a condition characterized by widespread activation of blood clotting throughout the body, leading to the formation of small blood clots in the blood vessels. This can result in organ damage and bleeding, as seen in this patient. The positive stool occult blood test suggests gastrointestinal bleeding, which can occur in DIC. Additionally, the patient's severe hypotension and sepsis are also consistent with DIC.

5. A 63-year-old male has not seen a physician for years. He reports reduced exercise tolerance over the past 5 years. On occasion in the past year he has noted chest pain after ascending a flight of stairs. He smokes 2 packs of cigarettes per day. He is found to have a blood pressure of 155/95 mm Hg. His body mass index is 30. Laboratory findings include: total serum cholesterol of 245 mg/dL with an HDL cholesterol that is 22 mg/dL. This patient will most likely have one of the following serious life threatening hemodynamic risk alterations:

Lymphedema

Chronic congestive lung disease

Deep venous thrombosis (DVT)

Acute coronary artery thrombosis

Emphysema

The patient's history of reduced exercise tolerance, chest pain after exertion, and risk factors such as smoking, elevated blood pressure, and high cholesterol levels suggest that he is at high risk for cardiovascular disease. Acute coronary artery thrombosis refers to the sudden formation of a blood clot in the coronary arteries, which can lead to a heart attack. Given the patient's symptoms and risk factors, this is the most likely serious life-threatening hemodynamic risk alteration he may have.

Explanation

The patient's history of reduced exercise tolerance, chest pain after exertion, and risk factors such as smoking, elevated blood pressure, and high cholesterol levels suggest that he is at high risk for cardiovascular disease. Acute coronary artery thrombosis refers to the sudden formation of a blood clot in the coronary arteries, which can lead to a heart attack. Given the patient's symptoms and risk factors, this is the most likely serious life-threatening hemodynamic risk alteration he may have.

6. An 18-year-old Caucasian female with a lifelong history of easily bruising, presents to her gynecologist complaining of heavy period. She also admits to occasional nosebleeds as well as bleeding from her gums. She has no family history of bleeding disorders and takes aspirin for migraine headaches. Physical exam is normal. Lab values: Hemoglobin - 9.0 g/dl (12-18 g/dl) Hematocrit - 27% (37-47%) Platelets - 280,000/mm³ (150,000-400,000/mm³) PT - Normal PTT - Prolonged Bleeding time - 8 minutes (2-4 minutes) Which of the following is the most likely diagnosis?

Hemophilia A

Hemophilia B

Von Willebrand disease

Thrombocytopenia

Sickle cell disease

The most likely diagnosis in this case is Von Willebrand disease. This is supported by the patient's lifelong history of easy bruising, heavy periods, and bleeding from the gums and nose. The normal PT and prolonged PTT suggest a defect in the intrinsic pathway of coagulation, which is consistent with Von Willebrand disease. Additionally, the low hemoglobin and hematocrit levels indicate chronic bleeding. The normal platelet count rules out thrombocytopenia as the cause. Hemophilia A and B are unlikely since they typically present with more severe bleeding and are associated with a family history of bleeding disorders. Sickle cell disease is not associated with easy bruising or bleeding from the gums and nose.

Explanation

The most likely diagnosis in this case is Von Willebrand disease. This is supported by the patient's lifelong history of easy bruising, heavy periods, and bleeding from the gums and nose. The normal PT and prolonged PTT suggest a defect in the intrinsic pathway of coagulation, which is consistent with Von Willebrand disease. Additionally, the low hemoglobin and hematocrit levels indicate chronic bleeding. The normal platelet count rules out thrombocytopenia as the cause. Hemophilia A and B are unlikely since they typically present with more severe bleeding and are associated with a family history of bleeding disorders. Sickle cell disease is not associated with easy bruising or bleeding from the gums and nose.

7. A 3 year-old patient has 2 % of the normal amounts of iduronate sulfatase. What clinical symptoms are associated with this deficiency, typically?

High ketone levels in urine

Hepatosplenomegaly and mental retardation

Pain and jaundice

Induction of liver cytochrome P450 enzymes

Ceramide accumulation

Hepatosplenomegaly refers to the enlargement of the liver and spleen, which is a common symptom in patients with a deficiency in iduronate sulfatase. This enzyme is responsible for breaking down certain substances in the body, and a deficiency can lead to the accumulation of these substances, causing the liver and spleen to enlarge. Mental retardation is also associated with this deficiency, as the accumulation of these substances can affect brain development and function.

Explanation

Hepatosplenomegaly refers to the enlargement of the liver and spleen, which is a common symptom in patients with a deficiency in iduronate sulfatase. This enzyme is responsible for breaking down certain substances in the body, and a deficiency can lead to the accumulation of these substances, causing the liver and spleen to enlarge. Mental retardation is also associated with this deficiency, as the accumulation of these substances can affect brain development and function.

8. About 75 % of patients with Von Gierke's Disorder Type 1a have elevated cholesterol and triglycerides. What precursor substrate is overproduced in the liver of these patients to stimulate biosynthesis?

Ribose

Glycogen

Uric acid

Acetyl-CoA

Phosphoribosyl-pyrophosphate

In Von Gierke's Disorder Type 1a, there is a deficiency in the enzyme glucose-6-phosphatase, which leads to impaired gluconeogenesis and glycogenolysis in the liver. As a result, the liver produces excess glucose, which is then converted to fatty acids and triglycerides. Acetyl-CoA is a key intermediate in fatty acid synthesis, and its overproduction in the liver of these patients stimulates the biosynthesis of cholesterol and triglycerides, leading to elevated levels of these substances in the blood.

Explanation

In Von Gierke's Disorder Type 1a, there is a deficiency in the enzyme glucose-6-phosphatase, which leads to impaired gluconeogenesis and glycogenolysis in the liver. As a result, the liver produces excess glucose, which is then converted to fatty acids and triglycerides. Acetyl-CoA is a key intermediate in fatty acid synthesis, and its overproduction in the liver of these patients stimulates the biosynthesis of cholesterol and triglycerides, leading to elevated levels of these substances in the blood.

9. A newborn presents with severe acidosis, vomiting, hypotonia and neurologic deficits. Serum analysis reveals elevated levels of lactate and alanine. These observations suggest a deficiency in which of the following enzymes ?

Alanine aminotransferase

Glutamate dehydrogenase

Lactate dehydrogenase

Pyruvate dehydrogenase

Pyruvate carboxylase

The newborn's symptoms of severe acidosis, vomiting, hypotonia, and neurologic deficits, along with elevated levels of lactate and alanine in the serum, suggest a deficiency in pyruvate dehydrogenase. Pyruvate dehydrogenase is responsible for converting pyruvate into acetyl-CoA, which is an important step in the production of energy in the form of ATP. A deficiency in this enzyme leads to an accumulation of pyruvate and a shift towards anaerobic metabolism, resulting in the symptoms observed in the newborn.

Explanation

The newborn's symptoms of severe acidosis, vomiting, hypotonia, and neurologic deficits, along with elevated levels of lactate and alanine in the serum, suggest a deficiency in pyruvate dehydrogenase. Pyruvate dehydrogenase is responsible for converting pyruvate into acetyl-CoA, which is an important step in the production of energy in the form of ATP. A deficiency in this enzyme leads to an accumulation of pyruvate and a shift towards anaerobic metabolism, resulting in the symptoms observed in the newborn.

10. Zellweger syndrome is caused by a defect in peroxisomal oxidation of very long chain fatty acids (VLCFA) which subsequently results in accumulation of these fatty acids in plasma. It is also associated with low levels of which of the following substances?

Phosphatidylinositol

Ketone bodies

Methylmalonyl CoA

Plasmalogens

Acetyl CoA

Zellweger syndrome is a genetic disorder that affects the peroxisomes, leading to a defect in the oxidation of very long chain fatty acids (VLCFA). This defect causes an accumulation of these fatty acids in the plasma. Plasmalogens, which are a type of phospholipid found in cell membranes, are also known to be reduced in individuals with Zellweger syndrome. Therefore, low levels of plasmalogens are associated with this condition.

Explanation

Zellweger syndrome is a genetic disorder that affects the peroxisomes, leading to a defect in the oxidation of very long chain fatty acids (VLCFA). This defect causes an accumulation of these fatty acids in the plasma. Plasmalogens, which are a type of phospholipid found in cell membranes, are also known to be reduced in individuals with Zellweger syndrome. Therefore, low levels of plasmalogens are associated with this condition.

11. Use the following figure to assist you in answering the question: Names of syndromes which result from enzyme deficiencies are provided in order of the steps in the metabolic pathway, above : [1] MPS II, Hunter syndrome [2] MPS I, Hurler, Hurler-Scheie, and Scheie syndromes [3] MPS VI, Maroteaux-Lamy syndrome [4] Sandhoff disease for beta-hexosaminidase A and B [5] MPS VII, Sly syndrome. In Maroteaux-Lamy syndrome, what is the expectation for urinary "limit dextrans"?

There will be no dextrans in the urine

AB -glucuronide at the non-reducing-end

A B-hexosamine at the non-reducing-end

AB -hexosamine sulfate at the non-reducing-end

A high concentration of urinary glucose

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Explanation

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12. A 68-year-old man had a myocardial infarction which involved 40% of the left ventricular free wall 3 months ago. He has had increasing dyspnea and orthopnea. On examination he has poor capillary filling in hands and feet. He has also clammy cold skin. A chest x-ray shows pulmonary edema and on echocardiography his ejection fraction is 32%. Which one of the following serious health risk hemodynamic complications is most likely to be present in this man at this point in time?

Chronic congestion of liver (‘Nut meg’)

Deep arterial mesenteric thrombosis

Pitting edema ++ (bilateral)

Disseminated intravascular coagulation (DIC)

Cardiac tamponade (pericardial bleeding)

The patient in the scenario is experiencing symptoms of heart failure, including dyspnea, orthopnea, poor capillary filling, and pulmonary edema. These symptoms, along with a low ejection fraction on echocardiography, suggest that the patient's heart is not pumping effectively. Cardiac tamponade occurs when there is bleeding into the pericardial sac, which can compress the heart and impair its ability to fill and pump blood. Given the patient's history of myocardial infarction and the presence of symptoms consistent with heart failure, cardiac tamponade is the most likely serious health risk complication in this case.

Explanation

The patient in the scenario is experiencing symptoms of heart failure, including dyspnea, orthopnea, poor capillary filling, and pulmonary edema. These symptoms, along with a low ejection fraction on echocardiography, suggest that the patient's heart is not pumping effectively. Cardiac tamponade occurs when there is bleeding into the pericardial sac, which can compress the heart and impair its ability to fill and pump blood. Given the patient's history of myocardial infarction and the presence of symptoms consistent with heart failure, cardiac tamponade is the most likely serious health risk complication in this case.

13. I.J., a white, 3a old ~, is brought to you by her mother because of spasticity and increasing difficulty walking. The previous medical history of the patient is unremarkable. Physical exam: wide-based gait, ataxia, hyperreﬂexia. Lab: elevated sulphatide levels in urine, increased protein in CSF. Decreased peripheral nerve conduction velocity. MRI: brain demyelinization. The most likely diagnosis is

Metachromatic leucodystrophy

Tay-Sachs disease

Gaucher´s disease

Krabbe disease

Sandhoff´s disease

The patient's presentation of spasticity, difficulty walking, wide-based gait, ataxia, hyperreflexia, and elevated sulphatide levels in urine suggests a diagnosis of metachromatic leucodystrophy. This is further supported by the findings of increased protein in CSF, decreased peripheral nerve conduction velocity, and brain demyelination on MRI. Metachromatic leucodystrophy is a rare genetic disorder characterized by the accumulation of sulfatides, leading to progressive demyelination of the central and peripheral nervous systems.

Explanation

The patient's presentation of spasticity, difficulty walking, wide-based gait, ataxia, hyperreflexia, and elevated sulphatide levels in urine suggests a diagnosis of metachromatic leucodystrophy. This is further supported by the findings of increased protein in CSF, decreased peripheral nerve conduction velocity, and brain demyelination on MRI. Metachromatic leucodystrophy is a rare genetic disorder characterized by the accumulation of sulfatides, leading to progressive demyelination of the central and peripheral nervous systems.

14. A 72-year-old man was hospitalized with a three-month history of a dry hacking cough, dyspnea, and chest pain with the diagnosis of congestive heart failure due to viral myocarditis. Three days after admission the patient had cardio/respiratory arrest and died. At autopsy the liver weighed 1,630 grams and displayed the pattern seen in Image #1. These features in the liver are most likely related to one of the following causal mechanisms?

Sustained hypoxia within the sinusoids of centrilobular structures

Markedly dilated sinusoids throughout the organ

Increased peripheral venous pressure with reduced outflow

Red blood cell accumulation in the sinusoidal spaces around the central vein

Lowered oxygen tension with resulting liver cell atrophy and necrosis

The features seen in the liver, as shown in Image #1, are most likely related to increased peripheral venous pressure with reduced outflow. This can occur in congestive heart failure, where the heart is unable to pump blood effectively, leading to a backup of blood in the veins. This increased pressure can affect the liver, causing congestion and dilation of sinusoids throughout the organ.

Explanation

The features seen in the liver, as shown in Image #1, are most likely related to increased peripheral venous pressure with reduced outflow. This can occur in congestive heart failure, where the heart is unable to pump blood effectively, leading to a backup of blood in the veins. This increased pressure can affect the liver, causing congestion and dilation of sinusoids throughout the organ.

15. A 2 y.o. female patient presents with malaise. A blood test indicates elevated lactic acid (hyperlactatemia). Lymphocyte culture indicates poor utilization of oxygen, but oxygen uptake increases after addition of succinate to the cell culture medium. The child's mother reports that her 4 y.o. son also suffers from the same symptoms. A pedigree of the family's "malaise" incidence is shown below. This patient is likely to suffer from which enzyme deficiency?

Pyruvate Dehydrogenase

Pyruvate Carboxylase

Cytochrome P450

Cytochrome Oxidase

NADH Oxidoreductase

The patient is likely to suffer from NADH Oxidoreductase deficiency based on the symptoms and the information provided. The elevated lactic acid and poor utilization of oxygen suggest a defect in the oxidative phosphorylation pathway, which is associated with NADH Oxidoreductase (also known as Complex I) deficiency. The increase in oxygen uptake after addition of succinate indicates that the defect is located upstream of Complex II in the electron transport chain. This is consistent with NADH Oxidoreductase deficiency, as it is the first complex in the chain. The family pedigree also suggests a genetic inheritance pattern for this enzyme deficiency.

Explanation

The patient is likely to suffer from NADH Oxidoreductase deficiency based on the symptoms and the information provided. The elevated lactic acid and poor utilization of oxygen suggest a defect in the oxidative phosphorylation pathway, which is associated with NADH Oxidoreductase (also known as Complex I) deficiency. The increase in oxygen uptake after addition of succinate indicates that the defect is located upstream of Complex II in the electron transport chain. This is consistent with NADH Oxidoreductase deficiency, as it is the first complex in the chain. The family pedigree also suggests a genetic inheritance pattern for this enzyme deficiency.