Flashcards in Bio chem Enz contd 8-3 Deck (29):
This patient presents with hematuria and hemoptysis, as indicated by his dark urine with 2+ protein and blood with casts and red-tinged sputum, respectively. These findings together are often indicative of pulmonary-renal syndrome. The most common cause is ?
Goodpasture syndrome, which results from autoantibodies to type IV collagen. It leads to destruction of basement membrane proteins, primarily in the kidneys and lungs
Defects in type I collagen would lead to bone disorders, not lung and kidney disease. Issues with type III collagen would cause elasticity disorders along with cardiovascular dysfunction. Loss of type I or II pneumocytes would have little effect on kidney function, since these cells make up the alveoli. Deficiency of surfactant is associated with?
neonatal respiratory distress syndrome, and because this patient is an adult, surfactant deficiency is not likely.
Goodpasture syndrome is a type II hypersensitivity reaction to type IV collagen, characterized by dypsnea, hemoptysis, and hematuria in adult men. Because type IV collagen is incorporated into the cells of the glomerulus and lung alveoli, anti–glomerular basement memberane antibodies that cross-react with this fiber cause?
rapid damage that can lead to bleeding from these organs.
This patient’s seizures, tachycardia (heart rate of 180), and tachypnea (respiratory rate of 75) are secondary to her confirmed hypoglycemia (glucose level of 55 mg/dL). Considering her hepatomegaly and age at presentation, her hypoglycemia is most consistent with a defect in ?
storing glycogen, an important source of energy during fasting. Her low blood sugar is also responsible for her seizures. Typically, infants begin to have spaced out feedings around 6 months of age and thus are more prone to having symptoms during these periods of fasting between meals, when glycogen would be utilized. Of the glycogen storage diseases, the finding of hepatomegaly on examination is most consistent with von Gierke disease (type 1 glycogen storage disease), a genetic condition characterized by deficiency of glucose-6-phosphatase (G-6-P).
A deficiency in fructokinase is a benign, asymptomatic condition.
Galactokinase deficiency is benign and would not manifest with clinical signs beyond galactosuria or infantile cataracts.
Although galactose-1-phosphate uridyltransferase deficiency can manifest with?
hepatomegaly, signs and symptoms manifest as soon as the infant begins consuming breast milk and would not be likely to be first observed at 6 months of age.
Although a-1,6-glucosidase and a-1,4-glucosidase deficiency are glycogen storage diseases, neither disorder presents with hypoglycemia or hepatomegaly.
Glucose-6-phosphatase is required for the final step of?
gluconeogenesis and glycogenolysis. Deficiency causes von Gierke disease, in which infants may exhibit hypoglycemia, seizures, hepatomegaly, lactic acidosis, hypertriglyceridemia, and hyperuricemia.
This patient presents with weakness, increased respiratory effort, an enlarged liver on exam, and a chest X-ray suggesting an enlarged cardiac contour. Based on his presentation and X-ray, he most likely has?
Pompe disease. This disease is also called glycogen storage disease type II
In Pompe disease, or glycogen storage disease type II, lysosomal α1,4-glucosidase deficiency leads to an inability to break down stored glycogen. This results in an accumulation of glycogen in the heart, skeletal muscle, brain, and liver. Infants with Pompe disease suffer from?
hypotonia, weakness, and congestive heart failure and rarely survive beyond infancy unless they receive enzyme replacement therapy.
Patients with hyperglycemia will likely present with polyuria and symptoms of dehydration. Glucose may be stored as glycogen in cells and is also freely present in blood. However, this patient does not show the signs or symptoms of hyperglycemia.
Oxaloacetate is the first intermediate in the Krebs cycle (shown in this diagram). It is regenerated with each turn of the cycle, but is not present in excessive amounts in the cell.
Pyruvate is a component of the cellular respiration pathway (portion shown in this diagram) and an intermediate in ?
gluconeogenesis. It is not stored in cells in any significant quantity.
Disorders of the urea cycle (shown below) lead to accumulation of ammonium in the blood and result in progressive lethargy and coma. Hyperammonemia due to a urea cycle defect is not associated with myopathy and cardiomegaly, and it rarely causes hepatomegaly.
This patient initially presented with abdominal pain, nausea, and vomiting with elevated lipase levels, suggestive of acute pancreatitis. Hypertriglyceridemia (HTG) and the absence of common risk factors for acute pancreatitis make the most likely diagnosis HTG-associated pancreatitis. In isolated hypertriglyceridemia, fibrates would be the best intervention, particularly in a patient with a history of diabetes.
Studies show fibrates reduce high triglycerides, modestly increase HDL, and may reduce the progression of coronary artery disease in patients with type 2 diabetes. Fibrates decrease the levels of?
VLDL cholesterol and slightly reduce the levels of LDL. Fibrates activate peroxisome proliferator-activated receptor-α (PPARα), a nuclear transcription factor. Activated PPARα increases lipoprotein TG lysis via lipoprotein lipase and increases HDL levels.
Along with lifestyle modification, fibrates are recommended for persistently elevated triglyceride levels in patients with symptoms, including pancreatitis. Fibrates increase the activity of ?
lipoprotein lipase through activation of peroxisome proliferator-activated receptor-α (PPARα).
Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase and reduce LDL cholesterol. Ezetimibe inhibits intestinal cholesterol absorption. Niacin, or vitamin B3, inhibits ?
lipolysis by hormone-sensitive lipase and reduces triglyceride synthesis. Bile acid sequestrants lower serum lipid levels through sequestration of charged bile acids.
This child’s combination of xanthomas on the eyelid, arcus lipoides (the opaque rings found on the corneal margin), and highly elevated LDL is pathognomonic for familial hypercholesterolemia, or type IIa familial dyslipidemia. An autosomal dominant disease, familial hypercholesterolemia is due to defects in the ?
LDL receptor, which is responsible for removing LDL from the circulation in the liver and other tissues. Without the ability to take up LDL from circulation, tissues continue to synthesize cholesterol at high levels. Patients with this condition may also present with xanthomas on the Achilles tendon. Heterozygous patients have elevated levels of LDL, which may manifest in middle age; homozygous patients may suffer a myocardial infarction in the first decade of life.
A defect in apolipoprotein C-II does not present with these symptoms and signs. A defect with apolipoprotein E would present with elevated levels of LDL, VLDL, and total cholesterol levels. Lipoprotein lipase deficiency would present with?
increased chylomicrons, and a VLDL production defect would show increase VLDL and LDL levels.
Familial hypercholesterolemia is an autosomal dominant disorder that causes defects in ?
the LDL receptor, which results in increased LDL. Common presentations include xanthomas and arcus lipoides.
This patient presents with recurrent fractures from minimal trauma and discolored teeth despite adequate brushing. Given this patient’s age and symptoms, the physician should suspect osteogenesis imperfecta (OI). OI is an inherited disorder of type I collagen synthesis. Type I collagen is found in bone, skin, tendons, dentin, and the corneas. Because type I collagen is found in bone and connective tissue, a deficiency of it can cause recurrent fractures, and children can have ossicular dislocation, stapes fixation, or fracture of the ossicles, leading to ?
progressive, conductive hearing loss. Patients can also have blue sclerae, secondary to translucent connective tissue covering the choroidal veins, and opalescent (discolored) teeth due to lack of dentin (dentinogenesis imperfecta). OI may be difficult to differentiate from child abuse, so physicians should be sure to look for attributes that are unique to OI, including blue sclerae or discolored/opalescent and damaged teeth.
Arachnodactyly is found in patients with Marfan syndrome, a connective tissue disorder that results from a genetic defect in fibrillin. Patients with Marfan syndrome do not have an increased risk for fractures.
Hypotonia is a manifestation of Menkes disease, an X-linked connective tissue disease caused by impaired copper absorption and transport. Patients with Menkes disease do not have an increased risk for fractures.
Aortic aneurysm is a manifestation of Ehlers-Danlos syndrome, a disorder of collagen synthesis that leads to?
hyperextensible skin, hypermobile joints, and easy bruising. Patients with Ehlers-Danos syndrome do not have an increased risk for fractures.
Bowing of legs is a manifestation of rickets in children, which is caused most commonly by vitamin D deficiency. Patients with rickets are more prone to fractures, but the discoloration of this patient's teeth suggests a different diagnosis.
Recurrent fractures associated with minor injuries in a child suggest a diagnosis of OI, an autosomal dominant structural defect in type I collagen synthesis. A deficiency in type I collagen, found in bone and connective tissue, can lead to progressive hearing loss resulting from ossicular dislocation, stapes fixation, or fracture of the ossicles. Patients with OI can also have two distinctive attributes: ?
blue sclerae caused by coverage of the choroidal veins with translucent connective tissue and discolored teeth caused by a lack of dentin. These unique attributes can be used to differentiate OI from child abuse, another cause of recurrent fractures.
The key to this question is recognizing that in the setting of ischemia, the patient's acidosis is likely due to lactic acid production under anaerobic conditions. Glycolysis is the biochemical pathway in which glucose is oxidized to pyruvate within the cytosol, as shown in the illustration. In anaerobic conditions, pyruvate is converted to lactic acid by lactate dehydrogenase, an enzyme located in ?
the cytoplasm. In aerobic conditions, pyruvate is then transported into the mitochondria, where the citric acid cycle occurs as the final common pathway of oxidative metabolism.
The Golgi apparatus is an organelle involved in the trafficking of newly synthesized proteins to the plasma membrane and many other functions; however, it is not involved in glycolysis.
The mitochondrial intermembranous space is where protons are pumped by the electron transport chain during aerobic respiration, not anaerobic respiration (glycolysis).
The mitochondrial matrix harbors the citric acid cycles, which are active during aerobic conditions, but it is not responsible for?
the production of lactic acid.
The smooth endoplasmic reticulum is the site of steroid synthesis and drug detoxification and is not involved in glycolysis.
This infant presents with unusual odor, poor feeding, and pale, dry, flaky skin. Given the presumed lack of newborn screening, these symptoms raise concern for phenylketonuria (PKU). PKU is an inherited metabolic disease that results from a deficiency of phenylalanine hydroxylase (PAH) activity. This enzyme normally converts phenylalanine into?
tyrosine. Tyrosine is an important precursor to L-DOPA and the neurotransmitter dopamine. To compensate for this deficiency, infants require a special diet that is rich in tyrosine and contains a small quantity of phenylalanine.
Arginine and tryptophan are not related to the function of phenylalanine hydroxylase. They are not implicated in any of the more common disorders of amino acid metabolism.
A point mutation that leads to a change from glutamate to valine is involved in the pathophysiology of sickle cell anemia, but these amino acids have no relevance to PKU.
Isoleucine is implicated in?
the pathophysiology of maple syrup urine disease, but similarly has no relevance to PKU.
Phenylalanine avoidance, rather than supplementation, is recommended.
This patient presents with symptoms that are consistent with those of seasonal allergies. The patient has a history of asthma, eczema, and allergies, which are most likely the result of atopy. Seasonal allergies are a result of?
peripheral histamine1 (H1)–receptor activation by environmental allergens, which results in pruritus, bronchoconstriction, and increased nasal and bronchial mucus production.
Centrally located H1-receptors, although rarely involved in seasonal allergies, play an important role in wakefulness or alertness and nausea/vomiting. Seasonal allergy symptoms can be treated with antihistamines, which are H1 antagonists.
Activation of a1-receptors results in vasoconstriction and increased blood pressure. ß1-receptor activation leads to inotropy (contractility) and chronotropy (tachycardia). ß2-receptor activation causes?
vasodilation and bronchodilation, and activation of H2-receptors leads to increased gastric acid secretion.
Histamine release in response to allergens predominantly activates peripheral H1-receptors, leading to itching, bronchoconstriction, and increased nasal and bronchial mucus production. H1-receptors are also located centrally, where they play a role in?
alertness and emesis.
His wife states that his hand performs a jerky, rhythmic motion, but the patient will pretend to have done this on purpose by smoothing his hair or scratching his head after it happens. In addition, she says that he has grown increasingly irritable. His father experienced similar symptoms in his mid-fifties. Neurologic exam is notable for seemingly unpurposeful, fluid motions of his right upper extremity. Reflexes, sensation, and strength are normal.
The patient in the vignette is displaying choreiform movements as well as personality changes that are concerning for a diagnosis of Huntington disease.
Huntington disease is an autosomal dominant inherited neurodegenerative disease. The genetic cause for the disease is a CAG trinucleotide repeat on the allele of the huntingtin gene on chromosome 4. This trinucleotide repeat is an example of variable number tandem repeats (VNTRs), a type of DNA polymorphism created by a tandem arrangement of multiple copies of short DNA sequences. The expansion of the CAG repeat in the huntingtin gene produces a?
mutated protein, which is neurotoxic and leads to the degeneration of the caudate and putamen. The disease is characterized by increased levels of dopamine and decreased levels of GABA and acetylcholine.
VNTRs are best detected by DNA-DNA hybridization, or, more specifically, a Southern blot.
In Southern blotting, DNA is cleaved by restriction enzymes on either side of a VNTR region. This produces DNA fragments in varying sizes, depending on the number of repeats the individual has. The DNA fragments are then separated by size, using gel electrophoresis, and hybridized to specifically labeled DNA probes for detection. In a patient with Huntington disease, the DNA fragments will be longer, indicating more CAG repeats.
Trinucleotide repeat disorders, such as Huntington disease, tend to show a pattern of anticipation, which means?
the disease manifests earlier and sometimes more severely in subsequent generations. This is due to the further expansion of the VNTRs and may explain why this patient developed symptoms earlier than his father.
When reviewing the uses of different lab techniques, remember the mnemonic SNoW DRoP:
Southern - DNA
Northern - RNA
Western - Protein