NBME26 Flashcards
Lesch-Nyhan syndrome has impaired salvage of which purines?
Lesch-Nyhan syndrome presents with intellectual disability, aggressive behavior, self mutilation, gout, and dystonia.
Mutations in HGPRT cause this disorder by impaired salvage of the purines guanine and hypoxanthine, which leads to increased levels of xanthine and uric acid.
Hyperuricemia in Lesch-Nyhan syndrome is treated with xanthine oxidase inhibitors, such as allopurinol or febuxostat, in order to reduce synthesis of uric acid.
MOA of mannitol
Mannitol, an osmotically active carbohydrate monomer, raises serum osmolality when given as an infusion.
Osmoreceptors detect the change in osmolality and trigger the production of antidiuretic hormone by the hypothalamus
Respiratory depression results in hypoventilation, which is characterized by?
hypoxemia, respiratory acidosis (Due to CO2 retention) and a normal alveolar-arterial gradient on arterial blood gas analysis.
An increase A-a gradient is seen in conditions that cause V/Q mismatch, shunt, and/or diffusion limitation
Function of adenosine diphosphate
ADP rapidly and irreversibly causes platelet aggregation through its action on the P2Y1 and P2Y12 receptors
What is placenta accreta?
the abnormal attachement of the placenta directly to the myometrium, which most commonly presents with retained products of conception and postpartum hemorrhage.
Risk factors: prior uterine instrumentations (including cesarean delivery), increased maternal age, placenta previa, and multiparity.
Given the high risk of morbidity and mortality, elective surgical delivery at 34 to 36 weeks is recommended.
Giant cell pneumonia is a severe complication of?
measles that is rare in patients who ar not immunosuppressed.
Histo: inclusion bodies and multinucleated giant cells in the respiratory epithelium
What is the function of the pelvic parasympathetic nerves in the pelvic nerve plexus?
function to excite and contract the bladder via muscarininc acetylcholine receptors while sympathetic nerves control the function of the internal urethral sphincter via alpha-1 adrenergic receptors, leading to normal urination.
Damage to the pelvic nerve plexus can affect both bladder contraction and internal sphincter relaxation, leading to overflow incontinence
MOA of doxycycline
prevents the attachment of aminoacyl-tRNA to ribosomes
Adverse effects of doxyclicine
gastrointestinal distress, photosensitivity, and in children- discoloration of teeth and inhibition of bone growth, which makes it contraindicated in pregnancy
The testes drain which veins?
The testes are drained by the gonadal veins, which drain into the left renal vein on the left side and directly into the inferior vena cava on the right side.
Obstruction of or increased pressure within the left gonadal vein or left renal vein leads to a left-sided varicocele
When does oxidation of fatty acids occur?
Oxidation of fatty acids in the mitochondrial matrix occurs during a state of starvation, or a state with increased glucagon levels, in order to maintain nutrition when glycogen stores have been depleted.
What is seen in folate deficiency?
Folate deficiency is often seen in patients with malnutrition, alcoholism, or high cell turnover conditions such as acute leukemia and sickle cell disease.
It is associated with megaloblastic anemia, hypersegmented neutrophils, erythrocyte macrocytosis, and increased serum homocysteine levels with normal methylmalonic acid levels.
What is anemia of chronic disease
anemia of chronic disease is a common finding in autoimmune and inflammatory diseases, chronic infections, and malignancy.
Increased hepcidin levels decrease intestinal iron absorption and increase iron storage in the bone marrow and reticuloendothelial system, preventing use of iron by erythrocyte precursors, thereby resulting in anemia.
What is responsible for granuloma formation in tuberculosis?
MTB infects macrophages and results in granuloma formation within the lungs via the actions of IL-12 and interferon-gamma on macrophages, Th1 helper T cells, and NK cells.
What is zollinger-ellison syndrome?
Zollinger-Ellison syndrome stems from a gastrin-secreting tumor located typically within the pancreas or duodenum that results in excessive production of acid by the gastric parietal cells.
Patients develop recurrent, chronic duodenal or jejunal ulcers, which can present with abdominal pain, diarrhea secondary to malabsorption, and possible hematemesis, melena, or hematochezia.
Immunohistochemical labeling of neoplastic cells will reveal positive staining for gastrin.
The precentral gyrus of the frontal lobe contains?
the primary motor cortex controlling the voluntary movement of the contralateral body.
Laterally, the precentral gyrus controls the contralateral face.
pathology affecting the upper motor neuron innervation to the contralateral face typically presents with only lower face weakness as the facial nerve nucleus that controls forehead musculature is dually innervated by upper motor neurons from bilateral precentral gyri.
What is chromosome instability?
There are two primary mechanisms of genomic instability in the pathogenesis of colon cancer: microsatellite instability (15% of cases) and chromosome instability (85%).
Chromosome instability results initially in activating mutations of oncogenes and/or loss of function mutations of tumor suppressor genes, resulting in the consequent aberrant entry into the cell cycle.
Once cells enter mitosis, genomic instability occurs during chromosome replication (S phase), fidelity checks of the chromosomes (G2 phase), and during separation of the chromosomes (M phase), which results in the accumulation of mutations, potentially causing increased proliferation and resistance to chemotherapy.
Hardy-Weinberg equilibrium models what?
the frequency of alleles within a population from generation to generation, which considered alleles to be in stable equilibrium over time.
Violation of its assumptions will cause deviation from this ideal behavior and variation in the prevalence of alleles over time.
Movement of fluid between capillaries and the interstitial space is dependent on the hydrostatic and oncotic pressures of both compartments.
High capillary hydrostatic pressure and low plasma oncotic pressure will increase the movement of fluid out of the capillaries and into the interstitial space.
High interstitial fluid hydrostatic pressure and low interstitial fluid oncotic pressure will drive fluid back into the capillaries and away from the interstitial space
What is central retinal artery occlusion?
presents with sudden, painless, monocular vision loss, relative afferent pupillary defect, retinal whitening with a cherry red spot, and retinal arteriolar narrowing with boxcarring.
The most common cause of CRAO is a retinal artery embolism from a carotid artery atheroma or a cardiac valvular vegetation. CRAO is considered a form of embolic stroke affecting the eye, and suspicion of CRAO should therefore prompt an immediate stroke risk factor.
Induction time of anesthesia with volatile anesthetics depends on?
the blood solubility of the anesthetic, cardiac output, and minute ventilation.
Low blood solubility decreased cardiac output, and high minute ventilation will increase the speed of induction.
Conversely, high blood solubility, increased cardiac output, and low minute ventilation will decrease the speed of induction
Damage to the mesial temporal lobe leads to?
Memory and emotional regulation are mediated by the limbic system, which includes the hippocampus, parahippocampal gyrus, and amygdala, located in the mesial temporal lobe.
Cancer-related radiation and chemotherapy commonly damage these mesial temporal lobe structures, leading to emotional dysregulation and the development of short term memory loss.
Function of prostaglandin E2
potent bronchodilator that acts by stimulating adenylyl cyclase in smooth muscle cells to increase the intracellular concentration of cAMP.
cAMP leads to smooth muscle relaxation by inhibiting myosin light chain kinase
Proliferative endometrium is present during the follicular phase of menstruation prior to ovulation. What is seen histo?
straight uterine glands, extension of the spiral arteries, and abundant stromal cells/
What is long chain acyl-coA dehydrogenase deficiency?
AR disorder of fatty acid metabolism. Signs and symptoms include irritability, lethargy, hepatomegaly (due to excess fat accumulation) and hypoglycemia.
Episodes can be triggered by illness, fasting, stress or exercise.
Immediate treatment involves correction of hypoglycemia and long term management involves preventing acute episodes of hypoglycemia and dietary supplementation with medium chain fatty acids.
function of histone acetyltransferase?
serves to add acetyl groups to histone lysine residues, causing a decreased affinity of histone for DNA.
This results in relaxation of the DNA histone complex (euchromatin), which allows for gene transcription
What is a parasternal heave?
most commonly associated with right ventricular hypertrophy, which is the most anterior chamber of the heart.
Right ventricular hypertrophy results from pulmonary hypertension, which is frequently a complication of chronic lung disease due to hypoxia induced pulmonary vasoconstriction and vascular remodeling
What is neonatal respiratory distress syndrome?
characterized by the reduced production of pulmonary surfactant. Surfactant is critical for reducing alveolar surface tension and collapsing pressure; without it, alveolar collapse results in impaired gas exchange, decreased lung compliance, and increased lung elastic recoil
What is the most common cause of primary hyperparathyroidism?
Parathyroid chief cell adenoma, and presents with symptoms of hypercalcemia, including reccurent nephrolithiasis, bone pain from osseous resorption, polyuria, dehydration, constipation and psychiatric disturbances
What is meckel diverticulum?
results from persistence of the vitelline duct and presents as an approximately two inch diverticulum located two feet proximal to the ileocecal valve.
It can cause abdominal pain, hematochezia, or melena.
Meckel diverticulum frequently harbors ectopic tissue, which is most commonly gastric or pancreatic tissue. Rarely, Meckel diverticulum may contain ectopic endometrial tissue
Large arteriovenous fistulas can result in?
high-output cardiac failure. The abnormal connection between an artery and vein results in decreased systemic vascular resistance and an increased venous return to the right heart, with a consequent increase in stroke volume and cardiac output
What is the incidence rate of disease in a population?
equals the number of new cases of the disease divided by the number of persons at risk for contracting the disease.
Incidence is a measure of risk and is the porbability of a given condition occuring within a specified period of time. Importantly, when individuals are added to or are removed from a population, the denominator must also change to reflect the new number of persons at risk for contracting the condition
Atypical lymphocytes in infectious mononucleosis are?
Infectious mononucleosis is a viral illness caused often by infection with EBV.
While EBV infects B lymphocytes through CD21, the atypical lymphocytes seen on peripheral blood smear are cytotoxic CD8+ T lymphocytes reacting to the viral infection
What pathway produces ketone bodies?
During a prolonged fasting state (greater than 3 days), the brain is dependent upon ketone bodies as its primary source of energy.
Beta-oxidation, which requires the carnitine-acylcarnitine cycle to transfer acyl groups from the cytoplasm to the matrix, allows for the production of ketone bodies. This manifests on labs with hypoglycemia, metabolic acidosis, and ketonuria
What is hereditary hemorrhagic telangiectasia?
an inherited disorder of vascular formation that results in arteriovenous malformations and telangiectasias throughout the body. It is characterized by recurrent bleeding. Pulmonary arteriovenous shunting can result in chronic hypoxemia
How is non-anion gap metabolic acidosis identified?
pH less than 7.35 (acidemia), with decreased PCO2 and HCO3.
The respiratory system compensates for the acidosis by increasing minute ventilation, which eliminates carbon dioxide, an acid.
Decreased levels of carbon dioxide with persistent acidic pH suggests partial compensation.
How does proteasome inhibitors work in patients with multiple myeloma?
Multiple myeloma is a malignant plasma cell neoplasm that presents with fatigue, weight loss, bone pain, hepatosplenomegaly, immune deficiency, anemia, hypercalcemia, renal dysfunction, hypergammaglobinuemia, and lytic bone lesions.
Proteasome inhibitors function by inducing apoptosis of neoplastic plasma cells as misfolded proteins accumulate. Patients undergoing induction of chemotherapy should be monitored for tumor lysis syndrome.
what is mammary duct ectasia?
often occurs in perimenopausal women when a lactiferious duct becomes blocked and accumulating lipid and debris cause dilation to occur
The 6th aortic arch gives rise to?
ductus arteriosus, a structure that allows shunting of placental oxygenated blood from the pulmonary artery to the systemic circulation during development in utero but closes shortly after birth.
Persistence of this structure is called a patent ductus arteriosus. Symptoms are dependent upon the size of the PDA and the degree of left to right shunting, with severe shunts causing right-sided heart failure and pulmonary hypertension
Oocytes remain arrested in which phases?
arrested in prophase of meiosis I until the follicle matures in preparation for ovulation.
As oocytes mature, they arrest again in metaphase II until fertilization.
Nondosjunction in either meiosis I or II can result in the inheritance of an abnormal number of chromosomes leading to disorders such as Down syndrome (trisomy 21)
What is aortic stenosis?
Calcification and fibrosis of the aortic valve occurs in most people as they age as a result of chronic mechanical stress and can sometimes result in aortic stenosis, which presents with a systolic crescrendo-decrescendo murmur best heard at the right upper sternal border, with radiation to the carotid.
Symptoms depend on the severity of aortic valve stenosis.
what is leukocyte adhesion deficiency?
characterized by impaired leukocyte adhesion to the vascular endothelium in response to infection.
Leukocytes retain the ability to phagocytose and eliminate foreign pathogens but are unable to migrate to sites of infection or inflammation in the extravascular space.
Thyroid hormone is produced via?
the iodination of the tyrosine residues within thyroglobulin.
Thyroxine has 4 iodine atoms attached, while triiodothyronine exhibits 3 attached iodine atoms.
alkaline phosphatase and gamma-glutamyltransferase are enzymes present where?
in bile ductules; located on the canalicular membrane of hepatocytes.
Increased serum levels of these enzymes are commonly associated with disorders of the biliary tract
What is hypersplenism?
defined as the presence of one or more cytopenias in the setting of splenomegaly, which is a common complication of cirrhosis and portal hypertension.
Labs: indicate normal or hyperproliferation of bone marrow precursor cells (a normal or increased reticulocyte index) and normal markers of coagulation cascade activations (normal PT, aPTT, fibrinogen, fibrin split products)
Formula of relative risk
RR= (a/ a+b) / (c/c+d )
MOA of statins
statin medications inhibit HMG-CoA reductase, the enzyme that catalyzes the rate limiting step in cholesterol synthesis.
This results in decreased intrahepatic cholesterol levels and consequently leads to increased expression of LDL receptors on hepatocytes, which further reduces circulating levels of LDL
Transmembrane proteins such as peptide hormone receptors (eg, growth hormone receptor) have what kind of domains?
hydrophilic extracellular and intracellular domains, and hydrophobic transmembrane domains.
In turn, the structure of transmembrane domains in human is composed of multiple nonpolar amino acids that have affinity with the hydrophobic, nonpolar phospholipid bilayer
What is one mechanusm by which leukemic cells develop resistance to specific drugs?
The active efflux of chemotherapy agents out of the cell is one mechanism by which leukemic cells develop resistance to specific drugs.
This manifests as low or absent intracellular levels of these chemotherapy agents despite adequate dosing
What is a granulosa cell tumor?
malignant sex-cord stromal tumor in women that produce female sex hormones.
In children and young women, they often result in precocious puberty or premenstrual vaginal bleeding.
Primary inhibitor neutrotransmitter and primary excitatory?
inhibitor= glycine
excitatory= glutamate
what is rickets?
childhood vitamin D deficiency, referred to as rickets, leads to decreased mineralization of the bones often presenting with resultant bowing of the long bones.
what is the association between ethanol and acetaminophen toxicity?
Chronic ethanol ingestion leads to the induction of cytochrome P450.
Cytochrome P450 is responsible for the generation of the toxic acetaminophen metabolite NAPQI. Patients with a history of chronic ethanol ingestion are at an increased risk of hepatotoxicity when consuming high doses of acetaminophen
what occurs in the third week of embryogenesis?
In the 3rd week of embryogenesis, gastrulation has occured, and the neural plate is present.
The neural tube will form during week 4. The embryo is highly sensitive to teratogens at this time.
What is pseudotumor cerebri?
an idiopathic disorder of increased ICP that is most common in obese women of childbearing age that presents with headaches and PE findings of increased ICP.
Acetazolamide can decrease CSF production by the choroid plexus, thereby decreasing ICP
how does asthma exacerbations present?
acutely with symptoms developing over minutes to hours.
Diffuse wheezing is typically appreciated on exam. Viral upper respiratory tract infections are the most common trigger in children.
what is slipped strand mispairing?
occurs at regions of repetitive nucleotides within the DNA due to the slipping of DNA polymerase. When nucleotides are not added or deleted in multiples of 3, a frameshift mutations occurs, altering the sequence of amino acids in the final protein.
what is neomycin?
an antibiotic that kills gram-negative gut flora, thereby reducing ammonia production.
It is not commonly used in current clinical practice given its numerous side effects and has largely been supplanted by rifaximin, another antibiotic that targets colonic ammoniagenic bacteria
what is ammoniagenesis?
takes place in the proximal convoluted tubule using glutamine as the primary substrate.
Ammoniagenesis is critical to the process of acid excretion in the urine and is impaired in renal tubular acidosis
side effect of cisplatin
cisplatin chemotherapy can damage dorsal root ganglia.
Patients can present with a symmetric peripheral sensory neuropathy and consequent hyporeflexia due to disruption of the reflex pathway
what is a distal radius fracture?
are a common injury in patients with osteoporosis.
Smith fracture (volar displacement) and Colles fractures (dorsal displacement) are common fracture patterns.
Complications include acute carpal tunnel syndrome and delayed tendon rupture
Where is the placement of a transjugular intrahepatic portosystemic shunt (TIPS)?
portal hypertension is a frequent complication of cirrhosis.
Placement of a transjugular intrahepatic portosystemic shunt (TIPS) between the portal vein and the hepatic vein reliably relieves increased portal pressures but predisposes to more frequent bouts of hepatic encephalopathy
pathogenesis of CML
CML is defined by the presence of the Philadelphia chromosome, which occurs secondary to a translocation of chromosomes 9 and 22, placing the tyrosine kinase ABL1 next to BCR, leading to constitutive activation of ABL1.
This results in activation of multiple downstream pathways and causes unregulated cellular proliferation of white blood cells.
Why does deoxygenated blood carry more carbon dioxide for a given PCO2 than oxygenated blood?
More carbon dioxide is carried in the blood at any given PCO2 in the presence of deoxyhemoglobin because the taut form (unloaded) of hemoglobin is an excellent buffer of hydrogen ions, resulting in a higher concentration of bicarbonate, the soluble transport for of carbon dioxide
what is a common cause of secondary polycythemia?
COPD is a common cause of secondary polycythemia resulting from chronic hypoxemia.
Polycythemia presents with increased hemoglobin concentration and an increased density of normochromic, normocytic erythrocytes on peripheral blood smear
formula for attributable risk?
(a/a+b) - (c/c+d)
attributable risk describes the risk of developing disease that can be attributed to the exposure as compared to the risk that exists without exposure. AR is calculated as the difference between disease incidence among those with the exposure and those without the exposure
Parathyroid hormone causes an increase in serum calcium via what mechanism?
Parathyroid hormone stimulates 1alpha-hydroxylase in the kidney, which leads to the conversion of 25-hydroxycholecalciferol to active 1,25-duhydroxycholecalciferol (vitamin D).
The active form of vitamin D then stimulates the increase absorption of calcium and phosphate from the intestines.
PTH regulares calcium and phosphate concentrations by stimulating osteoclastic bone reabsorption and distal convoluted tubular calcium reabsorption and phosphate excretion in the nephron
Increased doses of neostigmine can lead to?
Neostigmine is a potent acetylcholinesterase inhibitor used in the treatment of myasthenia gravis.
Increased doses can lead to a cholinergic crisis with muscular weakness, including weakness of the respiratory muscles, due to desensitization of the nicotinic receptors secondary to prolonged expsoure to high levels of acetylcholine
Protease inhibitors block which step in HIV?
HIV attaches to CD4 cells, enters via fusion, reverse transcribes its genome which is then integrated into the lymphocyte genome, and hijacks cellular machinery to produce new viral particles that require protease activity to become fully mature.
Protease inhibitors block this last step. They therefore allow for the preceding steps of viral replication but block the formation of mature viral core from immature precursors
Strokes affecting the lateral aspect of the post central gyrus results in?
The lateral aspect of the post central gyrus mediates sensation of the contralateral upper extremity.
Strokes affecting this region can result in sensory deficits of the contralateral hand and/or arm
what is carnitine-acylcarnitine translocase deficiency?
Long chain and very long chain fatty acids require carnitine-acyclcarnitine translocase to enter the mitochondrial matrix for beta-oxidation.
Patients with deficiency may present with encephalopathy, vomiting, hypoketotic hypoglycemia, hyperammonemia, muscle weakness, skeletal myopathy, cardiomyopathy, and ventricular dysrhythmias.
Symptoms can be triggered by illness or fasting, and treatment involves the adminstration of a low-fat (medium chain fatty acids), high carbohydrate formula and carnitine supplementation
Damaged muscle replaced by fibrotic scar will lead to?
After injury to muscles, there is limited regeneration capacity. Damaged muscle is often replaced by fibrotic scar, which leads to stiffness, reduced passive stretching, and joint contractures
what is horner syndrome?
lesions of the intermediolateral cell column, or intermediate horn, between spinal cord levels C8 and T2 can interrupt the sympathetic nerve supply to the ipsilateral face and ete, and cause horner syndrome.
Horner syndrome: ipsilateral ptosis, miosis, and anhidrosis
What are the layers of the scrotum?
Each layer of the testes is derived from a later of the abdominal wall (listed in parentheses).
From superficial to deep, the laters of the scrotum include:
-skin (skin)
-dartos muscle and fascia (scarpa fascia)
-external spermatic fascia (external abdominal oblique muscle and fascia)
-cremaster muscle and fascia (internal abdominal oblique muscle)
-internal spermatic fascia (trasversalis fascia)
-tunica vaginalis (peritoneum)
what is a pulmonary hamartoma?
disorganized collections of histolically normal lung tissue, which are commonly discovered as solitary pulmonary nodules. They have a low risk of transforming into a malignant neoplasm
MOA of fomepizole
Methanol can be metabolized to formic acid, a toxic metabolite that can cause visual distrubances, retinal edema, optic disc hyperemia, gastrointestinal distress, putaminal hemorrhage and neurological depression.
Fomepizaole inhibits alcohol dehydrogenase and thus blocks the conversion of methanol to its toxic metabolites
what is a lacunar infarct?
lacunar infarcts are ischemic strokes that occur in small penetrating arteries, most commonly involving the basal ganglia or internal capsule.
Lacunar strokes of the internal capsule typically result in contralateral hemiparesis
What is seen in perforation of a duodenal ulcer?
an emergent complication characterized by acute abdominal pain, peritonitis, fever, and free air on radiographs and CT.
Given the retroperitoneal location of the duodenal second thorugh fourth segments, perforation would result in retroperitoneal air, not pneumoperitoneum as in the case of intraperitoneal bowel structures
What is I cell disease?
AR inherited lysosomal storage disease that results from a defect in N-acetylglucosaminyl-1-phosphotransferase enzymes.
This results in the failure of mannose residue phosphorylation of lysosomal hydrolases, which subsequently leads to their abnormal expulsion from the cell instead of to their normal site of action within the lysosome
what causes the development of erythema (rubor) and edema (tumor) of inflammation?
The innate immune system conducts the initial response of the body to tissue injury and infection.
Histamine-stimulated vasodilation, primarily released by mast cells and basophils, leads to the development of erythema and edema
What is diverticulosis?
The layeres of the GI wall: mucosa, submucosa, muscularis propria, and serosa.
Diverticulosis is characterized by sac like protrusions of the colonic wall, which are hypothesized to develop secondary to increased intraluminal pressure that predisposes the herniation of mucosa and submucosa through the muscularis propria
what is graft versus host disease?
GVHD typically following bone marrow or liver transplantation and manifests with fevers, rash, hepatitis.
The risk for GVHD is higher in patients who receive transplants with a greater degree of HLA mismatch
what is hungtinton disease?
a heritable progressive neurodegenerative disorder that presents with psychiatric, cognitive, and motor symptoms including chorea.
Huntington disease demonstrates an AD pattern of heritability
What is the splanchnic circulation?
The splanchnic circulation at rest utilizes a significant percentage of cardiac output.
Intensive exercise requires increased cardiac output to meet the metabolic demands of contracting skeletal muscle.
Action of the sympathetic nervous system during exercise leads to increased cardiac output via augmentation of the heart rate, increased splanchnic vascular resistance, and increased pulmonary, skeletal muscle, coronary and cutaneous blood flow
What is seen on spirometry for COPD?
Obstructive lung disease is assessed with spirometry, with the presence of obstruction defined as a reduced FEV1/FVC ratio.
Obstructive disease is characterized by decreased breaths sounds and a prolonged expiratory phase on exam. Wheezing may be absent in the setting of reduced air flow
