Uworld 6 Flashcards
Benign prostatic hyperplasia leads to?
Leads to progressive bladder outlet obstruction. Over time, increased urinary pressures can cause hydronephrosis and renal parenchymal atrophy with scarring. This can progress to chronic kidney disease.
What are transverse tubules (T-tubules)?
Invaginations of the sarcolemma that transmit depolarization signals to the sarcoplasmic reticulum to trigger the release of calcium and induce muscle contraction.
The uniform distribution of T-tubules in striated muscle fibers ensures that each myofibril contracts at the same time, which is necessary for efficient contraction.
Hypertrophic cardiomyopathy is caused by?
Genetic mutations affecting structural proteins of cardiac sarcomeres (eg, beta myosin heavy chain, myosin-binding protein C) and is one of the most common causes of sudden cardiac death in young adults.
Congenital diaphragmatic hernia (herniation of abdominal contents into the thorax) causes?
Hypoplasia from compression of the lungs.
Neonates present with respiratory distress shortly after birth.
What is seen on histo for hypertrophic cardiomyopathy?
cardiomyocyte hypertrophy with haphazard cellular arrangement and interstitial fibrosis
What is seen on x-ray for congenital diaphragmatic hernia?
thoracic bowel loops; the distal end of a feeding tube may also be seen within the thorax
Long-standing rheumatoid arthritis can affect what?
Can affect the cervical spine, causing vertebral malalignment (subluxation) that can affect the atlantoaxial joint.
Extension of the neck during endotrachael intubation can worsen the subluxation, leading to acute compression of the spinal cord and/or vertebral arteries.
Which HIV drug is associated with HLA-B*57:01?
Abacavir
What is Rett syndrome?
a genetic disorder characterized by normal development until age 6-18 months, when regression of speech, loss of purposeful hand movements, development of sterotypical movements, and gait abnormalities occur.
Neutropathology shows arrested brain development rather than neurodegeneration.
Cholecystokinin (CCK) stimulates what?
The release of cholecystokinin from the duodenum and jejunum after exposure to fat and protein rich meals stimulates gallbladder contraction.
In patients with gallstones or biliary sludge, contraction can force the stones/sludge against the gallbladder outlet, causing temporary occlusion of outflow and increased intragallbladder pressure. This manifests as postprandial upper abdominal pain that waxes and wanes with CCK levels (biliary colic).
The gag reflex is mediated by?
afferents from glossopharyngeal nerve (CN IX) and efferents from the vagus nerve (CN X)
An absent gag reflex may indicate dysfunction of what?
Medulla oblongata.
Fat embolism syndrome should be suspected in what kind of patients?
Patient with severe long bone and/or pelvic fractures who develops acute-onset neurologic abnormalities, hypoxemia, and a petechial rash.
Occlusion of the pulmonary microvessels by fat globules is an early histo finding
What are symptoms of lead poisoning?
Lead poisoning in adults typically occurs through occupational exposure.
Symptoms: colicky abdominal pain, constipation, lead lines on the gum, peripheral neuropathy and amenia
What are labs for lead poisoning?
Microcytic anemia with normal iron studies and peripheral blood smear may reveal basophilic stippling
Ethanol inhibits what?
Inhibits gluconeogenesis and can cause hypoglycemia once hepatic glycogen stores are depleted.
Classic 21-hydroxylase deficiency causes?
decreased cortisol and aldosterone production with increased adrenal androgen production
Classic 21-hydroxylase deficiency causes what in boys?
presents 1-2 weeks after birth with vomiting, hypotension, hyponatremia, and hyperkalemia due to salt wasting; genitalia are normal
Classic 21-hydroxylase deficiency presents how in girls?
presents at birth with ambiguous genitalia
Traits of blastomyces dermatitdis
dimorphic fungus seen in tissue as round or oval yeasts with thick walls and broad based budding
Endemic in southeastern US (states east of Mississippi River)
Lungs are primary site of involvement, and the skin and bone are the major sites of dissemination
MOA of raltegravir
an integrase inhibitor that disrupts HIV genome integration, preventing synthesis of viral mRNA
What is necessary to induce viral HIV gene expression?
Integration of double-stranded HIV DNA into the host cell’s chromosomes is necessary to induce viral gene expression and prevent degradation of the viral genome.
Hypovolemia triggers a variety of compensatory mechanisms to improve tissue perfusion. These include:
-activation of the renin-angiotensin-aldosterone system (resulting in increased aldosterone and endothelin release)
-increased vasopressin release
-increased sympathetic tone
What are most common side effects of aspirin?
GI mucosal injury and bleeding.
These are due primarily to cyclooxygenase-1 inhibition, which results in impaired prostaglandin-dependent GI mucosal defense and decreased platelet aggregation.
What is bullous pemphigoid?
Autoimmune blistering disease that typically occurs in patients >60
It presents with tense bullae with rare mucosal involvement. Autoantibodies against hemidesmosomes create subepidermal cleavage.
What is seen on immunofluorescence for bullous pemphigoid?
liner deposition of IgG and/or C3 along the basement membrane
Intracranial pressure can be temporarily reduced with what?
intravenous mannitol, an osmotically active agent that increases plasma oncotic pressure, causing water from the interstitial space to be drawn into the vascular compartment.
In some patients (eg, history of heart failure, low left ventricular reserve function), rapidly increased intravascular volume can cause pulmonary edema by abruptly increasing pulmonary capillary hydrostatic pressure.
What are chromaffin cells?
Modified neuroendocrine cells derived from the neural crest
Chromaffin cells in the adrenal medulla are stimulated by?
Acetylcholine released by sympathetic preganglionic neurons and secrete catecholamines directly into the bloodstream to amplify sympathetic nervous system activity
Communicating hydroceles and indirect inguinal hernias are caused by?
An incomplete obliteration of the processus vaginalis.
The resultant connection between the scrotum and abdominal cavity can allow for fluid leakage (hydrocele) or the passage of abdominal contents (indirect inguinal hernia)
What is heard on ausculation for aortic regurgitation?
High pitched, diastolic murmur with a decrescendo intensity pattern
Where is the murmur of aortic regurgitation due to aortic root dilation best heard at?
At the right upper sternal border
Where is the murmur of aortic regurgitation due to valvular pathology best heard at?
At the 3rd intercostal space
How is a premature ventricular contraction seen on ECG?
wide QRS complex, opposite-facing T wave, and brief ensuing sinus pause
Left ventricular filling is less than normal at the time of the PVC
The ensuring sinus pause allows for greater than normal filling during the post-PVC beat
What is the most common primary immune deficiency?
Selective IgA deficiency
How does selective IgA def present?
Recurrent sinopulmonary and gastrointestinal infections as well as autoimmune disease
Patients with severe IgA def can have anaphylaxis during transfusion of blood products that contain small amounts of IgA
What is seen in Kawasaki disease?
Vasculitis characterized by fever for >5 days and >4 of the following: nonexudative conjunctivitis, extremity changes, cervical lymphadenopathy, mucositis, and polymorphous rash
Alpha-1 antitrypsin def can cause?
Can induce early onset emphysema, which is further accelerated by smoking
What is emphysema?
Characterized by expiratory airflow obstruction (decreased FEV1/FVC ratio), airspace enlargement and hyperinflation (increased total lung capacity), and a decreased diffusing capacity due to loss of alveolar surface area
MOA of statins
Statins inhibit the intracellular rate-limiting step of cholesterol biosynthesis via competitive inhibition of HMG-CoA reductase.
This leads to enhanced hepatic LDL receptor recycling and increased LDL clearance from the circulation.
What is the most common complication of statin use?
Statin-induced myopathy (eg, myalgia, elevated creatine kinase)
What are the levels in exogenous thryrotoxicosis?
Radioactive iodine uptake and serum thyroglobulin level are low, indicating suppression of endogenous thyroid metabolic activity
Serum T3 are often elevated.
What happens to the liver in right-sided heart failure?
Congestive hepatopathy is a common complication of right-sided heart failure.
Patchy hemorrhage and necrosis predominantly affect the centrilobular regions (zone 3) where hepatic congestion is most prominent.
The centrilobular necrosis, combined with relatively normal appearing periportal regions (zone 1), creates an overall heterogenous appearance sometimes referred to as “nutmeg liver”
Illnesses that result in cold agglutinin formation
Mycoplasma pneumoniae
Infectious mononucleosis
Infection with mycoplasma pneumonia can result in the formation of cold agglutinins, which are IgM antibodies (primarily) that bind red blood cells and cause clumping/agglutinations at low body temperatures
Maple syrup urine disease is caused by a deficiency of?
Branched-chain alpha-keto acid dehydrogenase, an enzyme that requires several coenzymes (thiamine, lipoate, coenzymes A, FAD, NAD) to metabolize branched chain amino acids
Some patients with milder forms of MSUD improve with high dose thiamine treatment.
Pelvic splanchnic nerves S2-S4 innervate what?
Provide parasympathetic innervation to the bowel and bladder
What is cauda equina syndrome?
Impairment of S2-S4 = constipation and difficulty urinating
Radicular low back pain and leg weakness (sciatic nerve) and saddle anesthesia (pudendal, ilioinguinal nerves)
Untreated cervicitis can progress to what?
Pelvic inflammatory disease and long term complications such as tubal factor infertility and ectopic pregnancy
Neisseria gonorrhoeae and Chlamydia trachomatis can cause acute cervicitis (eg purulent cervical discharge, friable cervix)
Occlusion of the portal triad can be used to distinguish the source of RUQ bleeding. If the bleeding subsides following occlusion, the source is likely to be?
The hepatic artery or portal vein
Occlusion of the portal triad can be used to distinguish the source of RUQ bleeding. If the bleeding persists after occlusion, what is injured?
Inferior vena cava or hepatic veins.
MOA of mycophenolate
An immunosuppression drug that inhibits inosine 5’-monophosphate dehydrogenase in the de novo purine synthesis pathway.
It provides relatively specific suppression of lymphocyte proliferation, largely because activated lymphocytes lack an established purine salvage pathway that is present in other hematopoietic cell lines
What is the most common primary cardiac neoplasm?
Myxomas usually in the left atrium
How does myxomas present?
The tumors typically cause position-dependent obstruction of the mitral valve, leading to a mid-diastolic murmur and symptoms of decreased cardiac output (eg, dyspnea, syncope)
Constitutional symptoms (eg fever, weight loss) may also be present.
How does myxomas look on histo?
Scattered cells within a mucopolysaccharide stroma and blood vessels with hemorrhage
What are the key findings in Edwards Syndrome (trisomy 18)?
fetal growth retardation, hypertonia (clenched hands with overlapping fingers), rocker bottom feet, and cardiac/GI/renal issues
Edwards Syndrome (trisomy 18) is most commonly the result of?
Meiotic nondisjunction due to advanced maternal age
Why is the right ventricle relatively protected from myocardial infarction and contractile function of the RV usually returns to normal following MI?
Relatively small muscle mass with high capacity to increased oxygen extraction, perfusion throughout the cardiac cycle, and heightened ischemic preconditioning.
What is a melanoma derived from?
Melanoma is a malignancy of melanocytes, which are embryologically derived from neural crest cells.
Where do neural crest cells originate from?
From the ectoderm and give rise to a diverse cell lineage, including neural ganglia (eg dorsal root ganglia, sympathetic/parasympathetic ganglia) and the adrenal medulla.
Down Syndrome (trisomy 21) patients are increased risk for which hematologic malignancies?
Acute lymphoblastic leukemia and acute megakaryoblastic leukemia
How does trochlear nerve palsy present?
Trochlear nerve palsy is typically traumatic or idiopathic.
Presents: vertical diplopia that worsens when the affected eye looks down and toward the nose (eg walking downstairs, up-close reading)
Patients compensate by tucking the chin and tilting the head away from the affected eye
The trochlear nerve innervates what?
Superior oblique muscle, which causes the eye to intort (internally rotate) and depress while adducted
Elevated levels of plasma homocysteine are an independent risk factor for?
Thrombotic events
Homocysteine can be metabolized to?
Methionine, via remethylation or to cystathionine, via transsulfuration
Hyperhomocysteinemia is most commonly due to what?
Genetic mutations in critical enzymes or def of vitamin B12, b6, and folate
How does dofetilide and ibutilide (class III antiarrhythmics) used to treat atrial fibrillation?
By blocking the rapid component of the delated-rectifier potassium current to slow repolarization and increase the effective refractory period.
As a result, the QT interval is prolonged, creating an increased risk of polymorphic ventricular tachycardia (torsade de pointes)
What is the action of carbon dioxide on cerebral vasculature?
Carbon dioxide is a potent vasodilator of cerebral vasculature
Tachypnea causes hypocapnia and cerebral vasoconstriction, thereby decreasing cerebral blood volume and intracranial pressure
Anesthetics with high tissue solubility are characterized by?
Large arteriovenous concentration gradients and slower onsets of action.
The arteriovenous concentration gradient reflects the overall tissue solubility of an anesthetic.
What is kinesin?
A microtubule-associated, ATP powered motor protein that facilitates the anterograde transport of neurotransmitter-containing secretory vesicles down axons to synaptic terminals
Right border of the heart on chest X-ray is formed by?
The right atrium.
the right middle lobe is adjacent to the right border of the heart.
Consolidation in the right middle lobe can obscure the xray silhoutette of the right heart border.
Whar are the most common cause of subungual splinter hemorrhages?
Microemboli from the valvular vegetations of bacterial endocarditis are the most common cause of subungual splinter hemorrhages.
The presence of these lesions necessitates careful cardiac auscultation to detect a possible new-onset regurgitant murmur.
Selective vasoconstriction of the efferent arteriole (up to certain extent) increases what?
Hydrostatic pressure in the glomerular capillaries, and therefore increases the glomerular filtration rate.
As efferent arteriolar constriction continues to increase, the glomerular filtration rate begins to decrease due to a flow-mediated rise in oncotic pressure in the glomerular capillaries.
The filtration fraction always increases with increasing efferent arteriole constriction.
Renal amyloidosis typically presents how?
With proteinuria and nephrotic syndrome.
Diagnosis confirmed by kidney biopsy: apple-green birefringence with Congo red stain under polarized light
Serum protein electrophoresis demonstrating a monoclonal protein helps establish the diagnosis of immunoglobulin light chain (AL) amyloidosis.
Sirolimus MOA
binds to immunophilin FK binding protein (FKBP) in the cytoplasm, forming a complex that binds and inhibits mTOR (mammalian target of rapamycin).
Inhibition of mTOR signaling blocks IL-2 signal transduction and prevents cell cycle progression and lymphocyte proliferation.
Histo for small bowel mucosa in patients with primary lactase def
appears normal
Traits of cryptococcus neoformans
Yeast with a thick polysaccharide capsule that is found primarily in soil contaminated by bird droppings.
Inhalation of the pathogen into the lungs leads to asymptomatic primary infection usually followed by life-long latent infection.
However, immunocompromised (eg, advanced AIDS) patients are at high risk for reactivation with spread to the CNS
What is highly suggestive of mucormycosis?
Facial pain, headache, and a black necrotic eschar in the nasal cavity of a patient with diabetic ketoacidosis.
The fungi show broad nonseptate hyphae with right angle branching.
Txt: surgical debridement and antifungal therapy
What are the physiologic changes for the cardiovascular in pregnancy?
During pregnancy, increased metabolic demands leads to multiple physiologic cardiovascular changes, including decreased systemic vascular resistance and increased blood volume,
These changes increased preload and decreased afterload, resulting in increased stroke volume and cardiac output.
Heart rate also gradually increases during pregnancy and is the major contributor to increased cardiac output in late pregnancy.
Oligohydramnios (low amniotic fluid) is often associated with what?
kidney dysfunction in the fetus (eg, diffuse cysts seen in autosomal recessive polycystic in the fetus).
Extrinsic fetal compression from a low amniotic fluid levels leads to Potter sequence with characteristic findings of flattened facies, limb deformities, and pulmonary hypoplasia.
Paroxysmal nocturnal hemoglobinuria leads to the formation of what?
Formation of membrane attack complexes on erythrocytes.
Treatment with monoclonal antibody against C5, the first component of the membrane attack complex, can improve symptoms.
However, it also increases risk for encapsulated bacterial infection. Therefore, patients require vaccination and antibiotic prophylaxis against Neisseria meningitidis and Streptococcus pneumonia.
What is a major limitation of single gene sequencing?
Single gene sequencing is the initial genetic test for suspected disorders most commonly caused by a mutation in a single gene, such as beta thalassemia trait.
A major limitation is the detection of whole gene deletions because the primers used in gene sequencing require complementary sequences within the gene to bind.
What are common asthma triggers?
Exercise, cold air, respiratiory infection, and exposure to inhaled allergens (eg, dust mites, cockroaches, pet dander, mold, pollen)
What suggests asthma?
Intermittent respiratory symptoms in a patient with a normal chest x-ray, sputum eosinophils, and reduced FEV1 suggest asthma.
What is the MOA of sulfonylureas (eg, glyburide, glimepiride)? AE?
Increase insulin secretion by pancreatic beta cells independent of blood glucose concentration.
These meds have a high incidence of hypoglycemia, especially in the elderly population.
Where does blood accumulate in a subgaleal hemorrhage?
Between the periosteum and galea aponeurosis presents with a diffuse, progressive, fluctuant scalp and neck swelling; massive blood loss can lead to shock and death if not promptly recognized.
What is a subgaleal hemorrhage?
A potentially fatal neonatal bleed that occurs during delivery when emissary veins between the dural sinuses and scalp are sheared.
Why does bone erosions occur in ankylosing spondylitis?
Bone erosions occur primarily in vertebral bodies; however, new bone formation typically occurs at the junction of the periosteal margin and adjacent cartilage, leading to bridging syndesmophytes and ankylosis.
This causes spinal rigidity, postural alteration, and increased risk of fracture.
What is ankylosing spondylitis?
An inflammatory spondyolarthropathy characterized by simultaneous erosion of bone and new bone formation.
A number of changes occur in the liver with aging that can affect drug metabolism. Typical changes include?
-decreased liver mass and blood flow
-decreased cytochrome P-450 expression and concentration
-reduced hepatic regeneration after injury
However, hepatic aminotransferase levels are unchanged.
The most common indicator of obesity-related disease is?
A reduction in expiratory reserve volume and functional residual capacity, but forced expiratory volume in 1 second, forced vital capacity, and total lung capacity are also typically decreased.
What can cause a pattern of extrinsic restrictive pulmonary function tests?
Obesity, particularly morbid, central obesity
Case-fatality rate formula
dividing the number of fatal cases of a disease or condition by the total number of people with that disease or condition
Mycobacterial resistance to isoniazid (INH) mediated by?
Primarily mediated by reductions in the catalase-peroxidase enzyme or through genetic modification of INH binding site on the mycolic acid synthesis enzyme
What is minute ventilation?
Equal to the product of tidal volume and respiratory rate and includes dead space ventilation
What alveolar ventilation?
Equal to the product of respiratory rate and the difference between tidal volume and dead space volume.
MOA of digoxin
Directly inhibits the Na-K-ATPase pump in myocardial cells, leading to a decrease in sodium efflux and an increase in intracellular sodium.
This reduces the forward activity of the sodium-calcium exchanger, causing increased intraceullar calcium concentration and improved myocyte contractility.
What is Reye syndrome?
Should be suspected in a young child with acute liver failure and encephalopathy after receiving aspirin for a virus-induced fever.
Can lead to hepatic steatosis, hyperammonemia, and diffuse astrocyte swelling (ie, cerebral edema)
What is seen on IF for rapidly progressive glomerulonephritis?
Linear (ribbon-like) deposits of IgG and C3 along the GBM
What antibodies is seen in rapidly progressive glomerulonephritis?
Anti-glomerular basement membrane (GBM) antibodies react with collagen type IV, causing rapidly progressive glomerulonephritis with glomerular crescent formation on light microscopy.
What is the pathophysiology of neonatal hypoglycemia?
Neonatal hypoglycemia is common in infants of diabetic mothers.
The pathophysiology involves maternal hyperglycemia, which in turn causes fetal hyperglycemia and compensatory hyperfunctioning of the pancreas (ie, hyperinsulinemia).
After birth, persistently elevated insulin levels lead to transient hypoglycemia.
