Uworld 7 Flashcards
Poststreptococcal glomerulonephritis occurs after exposure to?
Strains of group A streptococcus that produce nephritogenic antigens; antigen-antibody complexes deposit on the glomerular basement membrane and activate the alternate complement pathway.
What is seen on IF for poststreptococcal glomerulonephritis?
Granular deposits of IgG, IgM, and C3 in the basement membranes and mesangium.
When does intestinal malrotation occur?
When the midgut undergoes incomplete counterclockwise rotation during embryologic development
How does intestinal malrotation present?
In the neonatal period with biliois emesis due to extrinsic duodenal compression by Ladd bands or due to midgut volvulus with intestinal ischemia.
How does antibiotics alter the normal vaginal flora?
Antibiotics use alters the balance of normal vaginal flora (eg, decrease the number of gram+ lactobacilli and facilitates Candida overgrowth.
Patients can develop vulvovaginal candidiasis, which presents with vulvar/vaginal/perianal pruiritis; erythema; and a thick, white vaginal discharge.
Pudendal nerve injury can occur due to?
Excessive stress on the pelvic floor during labor and delivery (eg, prolonged second stage).
Nerve injury leads to denervation and weakness of the perineal musculature (eg, external anal sphincter), which can present as new-onset fecal incontinence.
Homecystinuria is most commonly caused by?
Cystathionine synthase deficiency.
Affected individuals have marfanoid habitus, ectopia lentis, and developmental delay.
What is the significant morbidity and mortality for homocystinuria?
Due primarily to thromboembolism.
Many patients with homocystinuria respond dramatically to pyridoxine (vitamin B6) supplementation.
How is GFR estimated in common practice?
GFR is estimated using creatinine clearance.
However, creatinine is actively secreted by the proximal tubules, so uncorrected creatinine clearance overestimates the GFR by approximately 10%-20%.
What is atrophy?
A cellular adaptation characterized by a decrease in cell size and number, leading to decreased organ size.
Pathologic atrophy physical workload, loss of innervation, decreased blood supply, inadequate nutrition, absent endocrine stimulation, aging, and mechanical pressure.
Testosterone replacement therapy is indicated for men with?
Symptomatic hypogonadism.
It is associated with an increase in serum prostate-specific antigen and may raise the risk of prostate cancer.
In addition, testosterone therapy can cause erythrocytosis (leading to thromboembolism), and hematocrit should be regularly monitored.
What causes the green discoloration of pus/sputum?
Green discoloration of pus/sputum seem during common bacterial infections is due to the presence of myeloperoxidaase, a blue-green heme-based enzymes that is released from neutrophil azurophilic granules and forms hypochlorous acid (bleach).
What is the MOA of glucocorticoids?
Inhibit transcription of proinflammatory mediators and promote apoptosis of eosinophils, T cells, and monocytes
What is stimulant withdrawal is characterized by?
Dysphoric mood, fatigue, hypersomnia, hyperplasia, and vivid dreams.
Stimulant withdrawal is not associated with significant findings on PE.
What steps are required before finalized mRNA molecules?
When mRNA is first transcribed from DNA, it is an unprocessed form called pre-mRNA or heterogeneous nuclear mRNA (hnRNA).
Several processing steps are required before finalized mRNA molecules can leave the nucleus, including 5’-capping, poly A tail addition, and intron splicing.
Cytoplasmic P bodies an important role in mRNA translation regulation and mRNA degradation.
Name the seronegative spondyloarthropathies associated with inflammatory bowel disease
Ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and arthritis.
Individuals expressing HLA B27 (a specific HLA class I molecule) are at increased risk for seronegative spondylarthropathies.
The chemotherapeutic effet of methotrexate is overcome by?
Overcome by N5-formyl-tetrahydrofolate (folinic acid, leucovorin) supplementation
Methotrexate and 5-FU both inhibit what?
Inhibit thymidylate formation
What are the primary mediators of disease in chronic obstructive pulmonary disease?
Neutrophils, macrophages, and CD8+T lymphocytes.
They secrete enzymes and proteases that cause and perpetuate both the alveolar destruction of emphysema and the mucus hypersecretion found in chronic bronchitis.
Midshaft fractures of the humerus risk injury to what?
The deep brachial (profunda brachii) artery and radial nerve run together along the posterior aspect of the humerus
V3 Mandibular branch of trigeminal nerve innervates what muscles?
The muscles of mastication: masseter, the medial and lateral pterygoids, and the temporalis muscle.
V3 mandibular branch of trigemal nerve exits the skull through?
Foramen ovale
Classic triad for acute bacterial meningitis? evaluation?
fever, stiff neck, and altered mentation
Evaluation requires prompt blood cultures, empiric antibiotics, and lumbar puncture with cerebrospinal fluid analysis
What is the mechanism of reperfusion injury?
Reperfusion injury is thought to occur secondary to oxygen free radical generation, mitochondrial damage, and inflammation.
IV drug users are at increased risk for what?
Increased risk of tricupsid valve endocarditis, which can cause multiple septic pulmonary infarcts due to embolization of tricuspid valve vegetation fragments.
Pulmonary infarcts are typically hemorrhagic (red) and wedge-shaped in the periphery of the lung
Amyotrophic lateral sclerosis can cause?
Causes degeneration of both upper and lower motor neurons and can result in bulbar and skeletal muscle weakness.
Denervation atrophy can affect the diaphragm and contribute to respiratory failure.
What is fluorescence in situ hybridization (FISH) used for?
FISH can identify specific chromosomal translocations, duplications, or deletions using a single-stranded, complementary DNA segment that is tagged with a radiotracer.
FISH is rapid, highly sensitive and specific, and can be used on tissues with low mitotic rates.
However, the targeted chromosomal abnormality must be somewhat large in order to be identified.
What happens to the O2 and Co2 levels in the body during exercise?
During physical exercise, there is increased skeletal muscle CO2 production that increases the CO2 content of venous blood.
Arterial O2 and CO2 content remains constant via increases in alveolar ventilation and gas exchange efficiency.
Venous O2 content remains constant or is decreased due to increased O2 extraction by the tissues that matches or exceeds the rate of oxygen delivery (ie, O2 consumption during exercise is limited by cardiac output)
Overuse/abuse of loop diuretics (eg, furosemide) will show what on electrolyte panel?
Hypokalemic, hypochloremic metabolic alkalosis.
Urine electrolytes findings depend on how recently the diuretic was last ingested, increased urine Na, Cl and K are expected with recent ingestion
What is MOA behind cough secondary to ACE inhibitor therapy?
Cough secondary to ACE inhibitor therapy is characterized as dry, nonproductive, and persistent.
The mechanism behind ACE inhibitor induced cough is accumulation of bradykinin, substance P, or prostaglandins.
How does allogeneic hematopoietic stem cell grafts initiate graft versus host disease?
Allogeneic hematopoietic stem cell grafts normally induce donor CD3+T cells that can initiate graft versus host disease, a widespread inflammatory response that can damage multiple organs.
Depletion of donor CD3+T cells prior to transplant decreased the risk of GVHD but also decreased the beneficial graft versus tumor effect, increasing the likelihood of cancer relapse.
What are quick clinical tests to assess attention and concentration?
Counting down from 100 by intervals of 3 or 7, reciting the months of the year in reverse order, and spelling “world” backwards.
Drugs that should be used with caution in geriatric patients
Anticholinergics (eg first-gen antihistamines), centrally acting alpha-2 agonists, tricyclic antidepressants, benzodiazepines (and other sedating meds), antipsychotics, many antiarrhythmics (eg, digoxin), and skeletal muscle relaxants.
Injury to the C5 and C6 nerve roots causes what?
Erb-Duchenne palsy: waiter’s tip posture. The affected arm may have decreased/absent Moro and biceps reflexes; grasp reflex remains intact.
What is acute respiratory distress syndrome?
A severe inflammatory reaction that occurs in the lungs and results in hypoxemia and noncardiogenic pulmonary edema.
Pulmonary injury leads to an inflammatory response resulting in breakdown of the capillary-alveolar barrier (created by type 1 pneumocytes and endothelial cells), increased capillary permeability, intraalveolar fluid accumulation, and hyaline membrane formation.
In patients with cirrhosis, hyperestrinism can cause?
gynecomastia, spider angiomata, loss of sexual hair, testicular atrophy and palmar erythema.
What is the greatest complication of a hookworm infection?
Hookworms are transmitted when human skin comes into contact with soil contaminated with human feces.
The larvae penetrate the skin, travel to the lungs, are coughed up, and then swallowed.
Adult hookworms live in the small intestine and feed on human blood. Therefore, chronic iron deficiency anemia (microcytic anemia) is the greatest complication.
What is the function of Inhibin B?
Inhibin B, produced by heat-sensitive Sertoli cells, is a physiologic inhibitor of FSH secretion.
In patients with cryptorchidism what happens to the levels of reproductive hormones?
atrophy of Sertoli cells results in decreased inhibin B, and in turn will elevate FSH.
Leydig cell function is not significantly affected, so testosterone and LH are typically normal.
What is primary adrenal insufficiency?
Characterized by weight loss, abdominal pain, fatigue, and hyperpigmentation.
Physiologic stress in patients with PAI can trigger acute adrenal crisis (eg fever, shock, mental status changes)
What is the most common cause of primary adrenal insufficiency?
Autoimmune adrenalitis is the most common cause of PAI and leads to bilateral adrenal atrophy.
What is diabetic gastroparesis?
Diabetic gastroparesis results from the destruction of enteric neurons due to chronic hyperglycemia, leading to impaired relaxation and disordered and ineffective peristalsis.
This causes delated gastric emptying, which presents as postprandial fullness, regurgitation of undigested food, nausea, and vomitting.
MOA of etomidate
Etomidate, a GABA agonist, is often used for anesthesia induction to provide sedation and amnesia.
It is hemodynamically neutral, but it can result in transient adrenocortical suppression because it inhibits cortisol synthesis.
What is vitiligo?
Vitiligo is a common condition characterized by the loss of the epidermal melanocytes. It occurs more commonly in patients with autoimmune disorders (eg, autoimmune thyroiditis, type I diabetes) and results in well-defined, variably sized patches of hypopigmentation.
X-linked agammaglobinemia is characterized by?
low or absent circulating mature B cells (ie, CD 19,20,21 cells) and pan-hypogammaglobinenmia.
Affected patients have increased susceptibility to pyogenic bacteria, enteroviruses, and Giardia lamblia due to the absence of opsonizing and neutralizing antibodies.
Inheritance pattern for sickle cell disease
Autosomal recessive
disorder characterized by a predominance of hemoglobin S, causing red blood cells to sickle, hemolyze, and cause vascular obstruction.
Early embryonic development is described in weeks postfertilization (ie, approximate time of ovulation), and major events during this time include implantation (week 1), grastrulation (week 3), and neurulation (week 4).
As neurulation occurs, neuroectodermal cells differentiate into?
Into neural crest cells, which then migrate to distant sites during week 5 postfertilization.
HPV has a tropism for what type of cells?
Human papilloma virus is s small DNA virus with a tropism for stratified squamous epithelium, which protectively lines anatomical areas that undergo frequent friction and abrasion, including true vocal cords, cervix, and anus.
Infants can acquire respiratory papillomatosis via passage through an HPV-infected birth canal.
What is Lynch Syndrome due to?
AD disorder caused by abnormal nucleotide mismatch repair.
The mismatch repair system involves several genes, including MSH2 and MLH1, which code for components of the human MutS and MutL homologs. Mutations in these 2 genes account for around 90% of cases of Lynch syndrome.
Edema formation in nephrotic syndrome occurs due to?
A combination of intravascular underfilling and overfilling.
Underfilling results from hypoalbuminemia, which decreases plasma oncotic pressure and results in sodium retention (ie, secondary sodium retention).
Overfilling results from sodium retention due to primary defects in renal sodium handling (ie, primary sodium retention).
How does glucagonoma present?
With hyperglycemia (often as newly diagnosed diabetes mellitus) and necrolytic migratory erythema (blistering erythematous plaques with central clearing) affecting the groin, face, and extremities.
Dx is made by detecting elevated glucagon levels.
What is the function of ghrelin?
Stimulates appetite and promotes weight gain.
What does leptin and insulin function in terms of appetite?
Leptin and insulin act in the CNS to decrease appetite.
Caloric restriction will cause what to happen to ghrelin, insulin, and leptin?
Caloric restriction leads to increased ghrelin levels along with decreased insulin and leptin levels, causing an increase in appetite that can make it difficult to maintain weight loss
Sarcoidosis is characterized by?
Noncaseating granulomas due to dysregulated cell-mediated immunity.
Activated antigen-presenting cells produce IL-12, which stimulates the differentiation of Th1-type CD4 cells.
Th1 cells produce IL-2 and interferon-gamma, which stimulate Th1 cell proliferation and macrophage activation, respectively.
Individuals who are successfully immunized against Hep B will show what serological marker?
will have protective anti-HBs antibody.
Individuals who recover from hep B infection will have which serological markers?
anti-HBs and anti-HBc antibodies
The presence of circulating HBsAg means what?
active infection
The common cardinal veins of the developing embryo drain directly into?
Into the sinus venosus
The cardinal veins give rise to?
the superior vena cava
Helicobacter pylori antral gastritis is associated with the formation of what?
Duodenal ulcers due to increased gastric acid production.
This increase in acidity is caused by unchecked gastrin production due to the destruction of somatostatin-secreting cells in the gastric antrum.
Norovirus is the most common cause of?
Viral gastroenteritis. Outbreaks in crowded settings (eg, schools, cruise ships, nursing homes) are common, and symptoms: vomitting and watery diarrhea
What is the Warburg effect?
Rapidly dividing cells such as stem cells and cancer cells generate energy through anaerobic glycolysis (Warburg effect).
This pathway converts the majority of glucose to lactate despite the presence of adequate oxygen to run oxidative phosphorylation. Therefore, cancer cells generally produce far more lactate than a normal terminally differentiated cell.
How do human acquire schistosomiasis?
Via contact with freshwater sources that contain snails infected with Schistosoma larvae.
S japonicum and S mansoni cause intestinal and hepatic schistosomiasis, and S haematobium causes urinary schistosomiasis.
Congenital hypothyroidism is usually asymptomatic at birth. After maternal T4 wanes, infants develop?
constipation, lethargy, hypotonia, macroglossia, an umbilical hernia, and a large anterior fontanelle.
What is FOXP3?
FOXP3 is a transcriptional regulator protein that is required for the development of regulatory T cells; it triggers production of cytokines (eg, IL-10, transforming growth factor-beta) and ligands (eg, cytotoxic T-lymphocyte antigen-4) that suppress immune activation.
FOXP3 mutations result in?
Immune dysregulation marked by excessive immunoglobin production and the development of autoimmunity.
How does a permanent pacemaker placement cause tricuspid regurgitation?
Severe tricuspid valve regurgitation can lead to right-sided heart failure, evidenced by jugular venous distention, hepatomegaly, lower extremity edema, and the absence of pulmonary edema.
Permanent pacemaker placement can cause TR because the right ventricular lead passes through the tricuspid valve orifice and can disrupt valve closure.
Genetic variations created during Hep C replication result in?
Result in marked variety in the antigenic structure of GCV envelope proteins. The production of host antibodies lag behind that of new mutant HCV strains, preventing infected individuals from mounting an effective immune response.
What can be useful for chemotherapy-induced vomitting?
5-HT3 serotonin and neurokinin 1 receptor antagonists
What does an abdominal aortic aneurysm lead to?
Abdominal aortic aneurysm is associated with risk factors (eg, age>60, smoking, hypertension, males, family hx) that lead to chronic transmural inflammation and extracellular matrix degradation within the wall of the aorta.
This leads to weakening and progressive expansion of the aortic wall, resulting in aneurysm formation, typically below the renal arteries.
What is cardiac output according to the Fick principle?
cardiac output = rate of O2 consumption / arteriovenous O2 content difference
What is chronic lymphocytic leukemia?
A lymphoproliferative disorder marked by the progressive accumulation of mature B cells.
Most patients are asymptomatic for years but eventually develop anemia, thrombocytopenia, and/or neutropenia.
How is the diagnosis of chronic lymphocytic leukemia made?
Generally made when complete blood count reveals dramatic leukocytosis with B-cell markers such as CD19,20,23
Niacin (vitamin b3) can be synthesized endogenously from?
Tryptophan and is an essential component of NAD and NADP.
Deficiency results in pellagra: dermatitis, diarrhea, and dementia
MOA of labetalol?
A nonselective vasodilatory beta blocker that blocks beta 1, beta 2, and alpha 1 adrenergic receptors.
Alpha 1 receptor blockade outweighs beta 2 receptor blockade to cause peripheral vasodilation with decreased venous return and lower systemic vascular resistance.
The relatively balanced vasodilation reduces blood pressure without changing stroke volume.
Beta-1 receptor blockade overrides the expected baroreflex-mediated increase in heart rate, resulting in overall decreased heart rate.
Malabsorption caused by celiac disease can lead to vitamin D deficiency. Patients will have what on labs?
Patients have decreased serum phosphorus, increased serum parathyroid hormone (secondary hyperparathyroidism), and low (or normal) serum calcium.
What is essential to normal wound healing?
Fibroblast and vascular proliferation (ie, granulation tissue) induced by vascular endothelial growth factor (VEGF) is essential to normal wound healing.
However, if this tissue proliferation becomes excessive (eg, in wounds left to heal by secondary intention), the resulting hypergranulation tissue can impair wound reepithelization and remodeling
What is urticaria?
A transient hypersensitivity disorder characterized by pruritic erythematous plaques that arise suddenly and resolve over hours.
They are most often caused by IgE-mediated degranulation of mast cells, leading to increased permeability of the microvasculature with edema of the superficial dermis
Indirect inguinal hernias protrude through?
The deep inguinal ring into the inguinal canal lateral to the inferior epigastric vessels.
Direct inguinal hernias protrude through?
Hesselbach’s triangle medial to the inferior epigastric vessels.
With moderate to heavy exercise, the changes to the left ventricular pressure-volume loop include increased preload and increased contractility that both contribute to increased stroke volume. Although reduced systemic vascular resistance decreases afterload, the increase in systolic pressure caused by increased preload and contractility override the decrease, resulting in overall increased afterload.
MOA of cocaine
A stimulant that inhibits the presynaptic reuptake of norepinephrine, dopamine, and serotonin. Also a potent vasoconstrictor that can cause myocardial ischemia and atrophy of the nasal mucosa and septum.
Intoxication: agitation, tachycardia, HTN, and light responsive mydriasis due to increased sympathetic activity.
What is important in the pathophysiology of metabolic alkalosis?
Total body chloride depletion.
Measurement of urine chloride can be helpful in determining the underlying cause.
What can C diffucule infection be treated with?
Oral fidaxomicin or oral vancomycin.
What the the MOA of fidaximicin?
Macrolide antibiotic that inhibits RNA polymerase. It is bactericidal against C diff.
Characteristics of a cerebellar tremor
Classically low frequency (<5 Hz) and high amplitude and increase as an action approaches a target.
They are often accompanied by other cerebellar signs, including ataxia, dysmetria, and impaired rapidly alternating movements.
What is alpha-1 antitrypsin?
A serum protein that inhibits neutrophil elastase, thereby reducing tissue damage caused by inflammation.
Patients with alpha-1 antitrypsin def will develop?
Early-onset emphysema; those with specific mutations (including the Z allele) are also at risk for liver disease due to accumulation of unsecreted, polymerized AAT (reddish-pink globules on periodic acid-Schiff stain) in the periportal hepatocytes.
Closed spinal dysraphism (spina bifida occulta or closed neural tube defect) presents how? Pathogenesis?
Often presents with cutaneous lumbosacral findings (eg, deep pit, hemangioma, tuft of hair) in the newborn period.
Pathogenesis involves failure of vertebral arch fusion, and imaging may suggest an underlying tethered cord (eg, low lying conus medullaris, thickened filum terminale)
Lobar pneumonia is marked by?
The cytokine-mediated accumulation of neutrophils and proteinaceous material in the alveoli.
Over several days, the proteinaceous material becomes fibrinous, neutrophils are replaced by macrophages and macrophages digest the fibrinous exudate, thereby restoring normal lung histology.
What is locus heterogeneity?
Describes when a similar phenotype is produced by mutations in different genetic loci (eg, oculocutaneous albinism)
Function of the supraspinatus muscle?
Assists in abduction of the arm and stabilization of the glenohumeral joint
What is the most common cause of rotator cuff syndrome?
Supraspinatus tendinopathy.
The supraspinatus tendon is vulnerable to injury due to impingement between the acromion and the head of the humerus
Riboflavin is a precursor for which coenzymes?
FMN and FAD.
FAD participates in the tricarboxylic acid cycle and electron transport chain by acting as an electron acceptor for succinate dehydrogenase (complex II), which converts succinate into fumarate.
Acute promyelocytic leukemia is the M3 variant of acute myelogenous leukemia. It is associated with?
It affects adults and associated with disseminated intravascular coagulation.
What is the cytogenetic abnormality for acute promyelocytic leukemia?
t(15;17); leads to formation of the promyelocytic leukemia-retinoic acid receptor alpha (PML/RARa) fusion gene, which is unable to signal for proper cellular differentiation, unlike the normal retinoic acid receptor.
Where does perfusion pressure decrease?
Perfusion pressure decreases distal to a significant coronary artery stenosis, resulting in an initial decrease in blood flow.
Coronary autoregulation stimulates arteriolar vasodilation, which reduces downstream vascular resistance and helps return blood flow to near-normal levels to prevent myocardial ischemia.
What is a frequent source of retroperitoneal bleeding?
Retroperitoneal hematoma is a common complication of blunt abdominal trauma.
The pancreas is a retroperitoneal organ, and pancreatic injury is frequently a source of retroperitoneal bleeding
What is the treatment choice for Listeria?
Ampicillin is the treatment choice for Listeria, which is not sensitive to cephalosporins.
Listeria most commonly causes disease in those with deficient cell-mediated immunity, such as young infants or immunocompromised patients.
