Uworld11 Flashcards
vasopressin-2 receptor mutations are a cause of?
congenital nephrogenic diabetes insipidus, a condition in which renal resistance to antidiuretic hormone results in excessive urinary water losses.
findings: high baseline serum osmolality (typically with hypernatremia), persistently dilute urine after water deprivation (low urine osmolality) and lack of response to desmopressin.
Autism spectrum disorder is characterized by?
impaired social communication/interactions and restricted, repetitive interests or behaviors.
It can occur with or without language and intellectual impairment.
Defective anterior (rostral) neuropore closure (eg, anencephaly) results in?
failure of the skull and meninges to form, allowing exposure of the developing brain to the destructive effects of amniotic fluid.
Open neural tube defects are a result of defects in primary neuralation (development and closure of the neural tube).
Aside from cigarette smoke, what is the most important environmental risk factor for lung cancer?
Radon is a radioactive gas found throughout the earth that enters homes through contaminated soil and groundwater. It emits highly ionzing alpha radiation, causing DNA damage in the respiratory tract epithelium when inhaled.
Folate deficiency inhibits?
the synthesis of nucleic acids, particularly the formation of thymidine.
This leads to defective DNA synthesis and increased apoptosis affecting hemopoietic cells (megaloblastic anemia).
Thymidine supplementation bypasses the enzyme thmidylate synthase and can reduce erythroid cell apoptosis.
How can glycerol be be used to synthesize glucose during gluconeogenesis?
Glycerol produced by the degradation of triglycerides in adipose tissue can be used by glycerol kinase in the liver and kidney to synthesize glucose during gluconeogensis.
What is cholesteatomas?
collections of squamous cell debris that form a mass behind the tympanic membrane.
Can be congenital or may occur as an acquired primary lesion or following infecton, trauma, or surgery of the middle ear.
Can cause hearing loss due to erosion into auditory ossicles.
The histopathologic features of esophageal squamous cell carcinoma include?
solid nests of neoplastic squamous cells with abundant eosinophilic cytoplasm and distinct borders.
Areas of keratinization and the presence of intercellular bridges are also present.
Patients present with progressive solid and eventually liquid dysphasia and weight loss.
What is sick sinus syndrome>
Sick sinus syndrome results from degeneration (usually age related) of the sinoatrial node, leading to impaired conduction and reduced cardiac output with symptoms of dyspnea, fatigue, lightheadedness, presyncope, and syncope.
ECG: bradycardia with sinus pauses (delated P waves), sinus arrest (dropped P waves) and junctional escape beats
Calcium efflux from cardiac cells prior to relaxation is primarily mediated via?
Na/Ca exchange pump and sarcoplasmic reticulum Ca-ATPase pump
What is the most common cause of renal infarction?
Systemic thromboembolism, often due to thrombus formation during atrial fibrillation.
Renal infarction presents with flank pain, hematuria, elevated lactate dehydrogenase, and a wedge shaped kidney lesion on CT.
The brain and kidneys are more likely to suffer embolic infarctions because they are perfused at a higher rate.
The initial management of septic shock requires rapid fluid resuscitation to replace intravascular volume and restore adequate end-organ perfusion. This is best accomplished with?
intravenous boluses of isotonic crystalloid in the form of 0.9% (normal) saline or lactated Ringer solution because these solutions remain in the extracellular space.
What is Kartagener syndrome?
a form of primary ciliary dyskinesia characterized by the triad of situs inversus, chronic sinusitis, and bronchiectasis.
Occurs due to mutations that impair the structure or function of cilia
Scaphoid fracture increase the risk of?
Scaphoid fracture can disrupt retrograde blood supply to the proximal scaphoid, increasing risk of avascular necrosis.
Fracture of the scaphoid bone may result from a fall on an outstretched hand and should be suspected if exam shows tenderness in the anatomic snuff box.
Patients with Bell Palsy may experience?
Because of the diverse functions of the facial nerve CNVII, patients with Bell palsy may experience decreased tear production, hyperacusis, and/or loss of taste over the anterior 2/3 tongue, in addition to unilateral facial weakness.
How does phenytoin cause vitamin D def?
Phenytoin and other antiepileptic meds are inducers of cytochrome P450 enzymes, including CYP24, which converts 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D (inactive from).
As a result, there is less 25-hydroxyvitamin D available for conversion to 1,25-dihydroxyvitamin D (Active form), leading to def
Parathyroid hormone is released in a combination continuous/tonic and pulsatile pattern. Continous high levels of PTH lead to?
excessive release of calcium from bones and increase risk of osteoporosis.
Parathyroid hormone is released in a combination continuous/tonic and pulsatile pattern. Pulsatile secretion leads to?
an anabolic effect on bone metabolism, stimulating osteoblast proliferation and inducing increased formation of new bone.
Atrial natriuretic peptide, brain natriuretic peptide, and nitric oxide activates?
guanylyl cyclase and increase conversion of guanosine 5’-triphosphate to cyclic guanosine 3’,5’-monophosphate (cGMP).
MOA of phosphodiesterase inhibitors (eg, sildenafil)
decrease the degradation of cGMP.
Elevated intracellular cGMP levels lead to relaxation of vascular smooth muscle and vasodilation.
What is pleiotropy?
pleiotropy describes instances where multiple phenotypic manifestations result from a single genetic mutation
Rheumatoid arthritis has what antibodies?
Rheumatoid arthritis: symmetric polyarthritis (involving the metacarpophalangeal and proximal interphalangeal joints) with prolonged morning stiffness and fatigue.
Antibodies to citrullinated peptides/proteins have a high specificity for the condition.
What is polycythemia vera?
a myeloproliferative disorder characterized by uncontrolled erythrocyte production.
Almost all patients have a mutation in the JAK2 gene, which encodes a non-receptor (cytoplasmic) tyrosine kinase a/w the erythropoietin receptor.
What makes the pulmonary vascular bed unique?
The pulmonary vascular bed is unique in that tissue hypoxia results in a vasoconstrictive response.
Such hypoxic vasoconstriction occurs in the small muscular pulmonary arteries to divert blood flow away from underventilated lung regions and toward well-ventilated lung areas to minimize ventilation-perfusion mismatch, leading to more efficient overall gas exchange.
Pathogenesis of chronic granulomatous disease
Defective intracellular killing of phagocytized organisms within neutrophils due to an impaired respiratory burst.
CGD should be suspected in a child with recurrent infections by catalase+ organisms (staph aureus, aspergillus) who has normal immunoglobins and no leukopenia.
Why can repeat infection of dengue be more severe?
There are 4 different serotypes of dengue virus. Repeat infection occurs when a person is exposed to a serotype not previously encountered. Secondary infections are often far more severe than primary infections and may be a/w a life threatening shock syndrome.
MOA of class IA antiarrythmics (quinidine, procainamide, disopyramide)
sodium channel blocking agents that depress phase 0 depolarization. They also prolong repolarization due to moderate potassium channel blocking activity, increasing action potential duration in cardiac myocytes
What is hereditary hemochromatosis?
AR disease characterized by excessive gastrointestinal absorption of iron, which is then stored as hemosiderin in various tissues.
Secondary arthritis is common and typically involves the second and third metacarpophalangeal joints.
Liver disease, skin hyperpigmentation, diabetes, pituitary hormone def (eg central hypogonadism) and cardiomyopathy can also manifest.
What is croup
croup is a viral infection in which edema and narrowing of the proximal trachea (subglottis) result in a barky cough and inspiratory stridor.
MOA of penicillins
penicillins, structurally similar to D-alanine-D-alanine, inhibit transpeptidase by binding covalently to its active site.
The result is failed synthesis of the bacterial peptidoglycan cell wall
What does the murmur of aortic stenosis sound like?
systolic ejection type, crescendo-decrescendo murmur that starts after the first heart sound and typically ends before the A2 component of the second heart sound.
The intensity of the murmur is proportional to the magnitude of the left ventricle to aorta pressure gradient during systole.
what is the formula of maintenance dose?
clearance (CL) determines the dose rate required to maintain a given steady-state plasma concentration (Css)
maintenance dose= Css x CL x dosing interval
What does helicobacter pylori produce?
Produces the enzyme urease, which spilts urea into CO2 and ammonia and neutralizes the local acidic gastric pH.
Active infection can be confirmed through rapid urease testing, in which a biopsy specimen of gastric mucosa is evaluated in the presence of urea and a pH indicator.
Evidence of alkalization (due to ammonia formation) confirms the diagnosis
What are some complications of hand foot and mouth disease?
hand foot and mouth disease (oral ulcerations and rash on palms/soles) is a common manifestation of enterovirus infection.
Although enterovirus are typically self-limited, rare but serious complications include myocarditis and aseptic meningitis.
Closure of a patent ductus arteriosus results in?
decreased pulmonary venous return to the left atrium (decreased left ventricular preload) and increased diastolic blood pressure in the aorta (increased left ventricular afterload).
Together, these changes acutely lower left ventricular stroke volume and cardiac output
What is the virulence factor for group B strep
GBS is a major cause of neonatal sepsis.
Virulence factor: polysaccharide capsule, which contains sialic acid residues that prevent phagocytosis via molecular mimicry
What is a complication of giant cell arteritis?
GCA: granulomatous inflammation of the media with fragmentation of the internal elastic lamina most often affecting the medium and small branches of the carotid artery
Ischemic optic neuropathy with irreversible blindness is a potential complication; therefore patients require immediate glucocorticoid therapy
function of osteocytes
Osteocytes detect increased mechanical load in the bones (eg, weight-bearing exercise) and communicate with one another through gap junctions to orchestrate bone remodeling.
What is adenovirus
self-limiting, year round infection that causes the acute onset of fever, cough, congestion, pharyngitis, and conjunctivitis.
This pharyngoconjunctival disease can occur in outbreaks among those living in close quarters (eg, camp dormitories, military barracks).
Side effects of ketamine
Ketamine can be used for anesthesia induction.
The side effects of increased catcecholamine release (eg, bronchodilation) are often exploited in patients with bronchospasm
What is the difference between live attenuated oral (Sabin) poliovirus vaccine and inactivated poliovirus (Salk) vaccine?
The live attenuated oral (Sabin) poliovirus vaccine produces a stronger mucosal secretory IgA immune response than does the inactivated poliovirus (Salk) vaccine.
This increase in mucosal IgA offers immune protection at the site of viral entry by inhibiting attachment to intestinal epithelial cells.
Function of incretin?
Incretin functions by stimulating insulin release following oral consumption of glucose.
Incretin-stimulated insulin release is independent of the increase in insulin secretion brought on by elevations in the blood glucose level
Function of erythropoietin (EPO)?
EPO is produced by peritubular fibroblast cells in the renal cortex in response to decreased renal oxygen delivery.
EOP acts on erythrocyte precursors in the bone marrow to increase red blood cell production.
Patients with chronic kidney disease often have damage to renal EPO-producing cells, which results in normocytic anemia.
Patients with preeclampsia are at risk for?
fetal growth restriction and oligohydramnios due to abnormal placental spiral artery development, which leads to increased placental vascular resistance, decreased uteroplacental perfusion, and decreased umbilical vein oxygen delivery
What is low grade atrioventricular block (ie, first degree, Mobitz type 1 second degree)?
low grade atrioventricular block (ie, first degree, Mobitz type 1 second degree) involves conduction disruption within the AV node.
The occurence of low grade AV block in the setting of myocardial infarction suggests obstruction of the right coronary artery because it supplies blood to the AV node in approximately 90% of patients.
What is glioblastoma?
Most common primary cerebral tumor of adults
Typically located within the cerebral hemispheres, occasionally crossing the midline (butterfly glioma).
Gross exam of glioblastoma
highly malignant tumor often shows a poorly circumscribed, variegated mass containing areas of necrosis and hemorrhage
What is relaxin?
during pregnancy, increased relaxin levels promote sacroiliac joint laxity and widening of the pubic symphysis to help facilitate vaginal delivery
What is a brain abscess?
A brain abscess appears as a ring enhancing lesion on imaging and typically causes headache with or without fever and neurologic symptoms (eg, seizure).
Pathogenesis often involves direct spread from head and neck space infections, such as acute otitis media.
Chronic kidney disease causes what to phosphate and vitamin D levels?
Chronic kidney disease usually causes hyperphosphatemia (binds serum Ca2+) and low 1,25-dihydroxy vitamin D (decreases intestinal Ca2+ absorption and Ca2+ release from bone).
The resulting hypocalcemia stimulates release of parathyroid hormone, causing secondary hyperparathyroidism
What is stasis dermatitis?
Chronic erythema, fibrosis, and reddish brown discoloration due to deposition of hemosiderin (from breakdown of extravasated red cells).
Symptoms are typically bilateral, and usually worse at or above the ankles.
Complications: poor wound healing, weeping, ulceration
What is the function of glucose-6-phosphate dehydrogenase?
Catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconolactone.
It is the rate limiting enzyme of the pentose phosphate pathway.
What is glucose-6-phosphate deficiency?
a common X-linked recessive disorder resulting in episodes of hemolytic anemia during times of increased oxidative stress (eg, use of antimalarials/sulfonamide, infections)
Eccrine sweat glands and the adrenal medullae are innervated by?
cholinergic neurons
the sympathetic nervous system typically regulates visceral fuction via?
2-neuron signal transmission involving cholinergic preganglionic neurons and adrenergic postganglionic neurons
MOA of fibrates (gemfibrozil, fenofibrate)
Fibrates lower triglyceride levels by activating peroxisome proliferator-activated receptor alpha, which leads to decreased hepatic VLDL production and increased lipoprotein lipase activity.
Fish oil supplements containing high concentrations of omega-3-fatty acids lower triglycerides by decreasing production of VLDL and apolipoprotein B.
Location of the third part of the duodenum
The third part of the duodenum courses horizontally across the abdominal aorta and inferior vena cava at the level of the third lumbar vertebra.
The superior mesenteric vessels lie anterior to the duodenum at this location.
At high altitude, the low partial pressure of inspired oxygen (PiO2) leads to?
At high altitude, the low partial pressure of inspired oxygen (PiO2) leads to hypoxemia that triggers hyperventilation with increased exhalation of CO2 and resulting respiratory alkalosis.
The kidneys compensate by increasing bicarbonate (HCO3-) excretion to decrease serum HCO3- and help normalize pH.
Hypoxemia persists, but physiologic adjustments take place to improve O2 use.
What is helpful for delirium prevention and management?
Because disruption of the sleep-wake cycle is both a risk factor and manifestation of delirium, facilitation of nocturnal sleep (eg, minimizing noise and patient interventions, appropriate day/night lighting) is helpful for delirium prevention and management.
What is ecthyma gangrenosum?
A cutaneous necrotic disease with a strong associated with Pseudomonas aeruginosa bacteremia.
It occurs from perivascular invasion and release of tissue-destructive exotoxins, causing vascular destruction and insufficient blood flow to patches of skin that become edematous and subsequently necrose.
Pseudomonas infections are common in which patients?
neutropenic, are hospitalized, have burns, or have indwelling catheters.
Integral membrane proteins contain?
transmembrane domains composed of alpha helices with hydrophobic amino acid residues (eg, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline, glycine.)
These transmembrane domains help anchor the protein to the phospholipid bilayer of the cell membrane.
Abortive therapy for migraines
Migraine is an episodic disorder characterized by severe, often unilateral headache commonly associated with nausea and sensitivity to light and sound.
Abortive therapy: mild analgesics, triptans, antiemetics, ergotamine) for acute symptoms
What is preventative therapy for migraines?
beta blockers, tricyclic antidepressants, anticonvulsants, CGRP monoclonal antibodies) to reduce the frequency of headaches
Where is the somatosensory cortex located?
just posterior to the central sulcus
A lesion in the somatosensory cortex leads to?
A lesion in the somatosensory cortex, located just posterior to the central sulcus, leads to contralateral sensory deficits and cortical sensory signs.
What is an empyema?
An accumulation of pus within the pleural space that can result from multiple sources of bacterial contamination.
It usually represents advanced progression of a complicated parapneumonic effusion resulting from bacterial translocation from the alveoli
What is holoprosencephaly?
Due to failure of the primitive forebrain (prosencephalon) to divide into the right and left hemispheres, resulting in a spectrum of brain and midface abnormalities (eg, facial clefts, cyclopia)
Trisomy 13 (Patau) is the most commonly associated etiology
Cystic fibrosis is most commonly due to?
Due to a 3-base pair deletion in the CF transmembrane conductance regulator gene at amino acid position 508.
This mutation impairs post translational processing of CFTR, resulting in shunting of CFTR toward the proteasome, with complete absence of the protein on the cell surface.
Elevated sweat chloride concentrations are found in most patients with CF.
Primary tuberculosis causes?
the formation of Ghon foci in the lower lungs.
Secondary (reactivation) tuberculosis occurs in?
patients with prior tuberculosis infection that never cleared completely.
reactivation TB occurs most often in immunosuppressed patients and is characterized by apical cavitary lesions and hemoptysis.
MOA of proton pump inhibitors (omeprazole, lansoprazole)
block the final common pathway of gastric acid secretion from parietal cells, in which is stimulated by acetylcholine, histamine, and gastrin
Whitish/gray areas in melanoma
whitish/gray areas occur when cytotoxic T cells recognize tumor antigens and destroy malignant cells, leading to melanocyte regression.
Red areas of melanoma
Red areas arise due to vessel actasia and local inflammation
brown or black areas in melanoma
due to advancing malignant melanocytes
What is seen in salicylate intoxication?
Salicylate intoxication should be suspected in patients with the triad of fever, tinnitus, and tachypnea.
Salicylates both stimulate central respiratory drive to cause primary respiratory alkalosis and disrupt cellular metabolism to cause primary anion gap metabolic acidosis.
Therefore, toxicity classically presents with a mixed acid-base disturbance and a blood pH sometimes within the normal range.
What is used for the txt of essential tremor?
Beta blockers.
Propranolol, a nonselective beta blocker, is the most commonly used therapy and prevents the interaction of epinephrine and norepinephrine with beta 1 and beta 2 receptors to relieve tremor symptoms.
However, inhibition of pulomnary beta 2 receptors in patients with underlying reactive airway disease can cause bronchoconstriction, leading to cough, wheeze, and dyspnea.
The most common form of congenital adrenal hyperplasia?
21-hydroxylase deficiency.
genetically female infants typically have ambiguous genitalia (virilzation) at birth, whereas males have phenotypically normal genitalia, with salt-wasting or precocious puberty appearing later.
Elevated 17-hydroxyprogesterone is diagnostic.
What are compensatory mechanisms for hypovolemia?
Activation of renin-angiotensin-aldosterone system and increased antidiuretic hormone release
This results in increased renal sodium, chloride, water, and urea reaborption with increased potassium excretion.
Role of nucleolus?
The nucleolus is the site of ribosomal RNA (rRNA) transcription and ribosomal subunit assembly.
RNA polymerase I functions exclusively within the nucleolus to transcribe the 45S pre-rRNA gene, which codes for most of the rRNA components (18S, 5.8S, and 28S rRNAs)
What is Toxoplasma gondii?
an intracellular parasite that typically transmitted to humans after accidental ingestation of contaminated cat feces (eg, cat handling, litter box).
Most initial cases are asymptomatic. However, the organism establishes a latent infection that can reactivate in the setting of severe immunocompromise, particularly advanced AIDS.
Patients usually develop encephalitis with multiple ring-enhancing lesions.
Deficiency in folate causes?
Folate is essential for nucleic acid metabolism, and def causes ineffective hematopoiesis with a low reticulocyte count.
Characteristic megaloblastic changes include hypersegmented neutrophils and macrocytic red blood cells.
Macrocytic erythrocytes are prone to hemolysis, which can increase serum bilirubin and lactate dehydrogenase.
Cerebellar hemisphere lesions result in?
Cerebellar hemisphere are responsible for motor planning and coordination of the ipsilateral extremities via their connections with the lateral descending motor systems.
Consequently, cerebellar hemisphere lesions typically result in ipsilateral dysdiadochokinesia, limb dysmetria, and/or intention tremor.
Immunoflorescence and EM of poststrep glomerulonephritis?
lumpy bumpy granular deposits of IgG and C3 on the glomerular basement membrane, and subepithelial, electron dense deposits are seen on EM.
What is poststrep glomerulonephritis?
an immune complex deposition disease that occurs 2-4 weeks after exposure to group A beta hemolytic Strep species (pharyngitis, skin infection)
Light microscopy shows enlarged, hypercellular glomeruli
What is transformation?
allows bacterium to take up exogenous DNA fragments and express the encoded proteins.
Strep pneumo can undergo transformation. Through this method, strains of S pneumo that do not form a capsule can acquire the genes that code for the capsule and therefore gain virulence.
Interferon-gamma release assays test for latent tuberculosis infection by?
measuring the amount of IFN-gamma released by T lymphocytes when exposed to antigens unique to Mycobacterium tuberculosis.
Meckel diverticulum results from?
incomplete obliteration of the vitelline duct and usually presents with painless lower GI bleeding.
99m-Tc-pertechnetate localizes to heterotopic gastric mucosa that is often contained within a Meckel diverticulum, and uptake in the periumbilical area or right lower quadrant is diagnostic.
Function of poly-A tail
The poly-A tail is not transcribed from DNA; instead, it is added as a post-transcriptional modification downstream of the consensus sequence (AAUAAA) located near the 3’ end of the mRNA molecule.
This tail protects mRNA from degradation within the cytoplasm after it exits the nucleus
What is De Quervain tendinopathy?
Characterized by tendinous myxoid degeneration and thickening of tendon sheaths involving the abductor pollicis longus and extensor pollicis brevis in the first extensor compartment.
It presents with sharp pain in the lateral hand and wrist, with reproduction of symptoms by passive thumb flexion with the hand in ulnar deviation
Impaired beta-oxidation of fatty acids causes?
hypoglycemia after prolonged fasting and insufficient levels of ketone bodies.
What enzymes is most commonly deficient in impaired beta-oxidation?
Acyl-CoA dehydrogenase catalyzes the first step in the beta-oxidation pathway and is the most commonly deficient enzyme
What recognizes stop codons?
Releasing factors recognize stop codons (UAA, UAG, UGA) and terminate protein synthesis.
They facilitate the release of the polypeptide chain from the ribosome and dissolution of the ribosome-messenger RNA complex
The glomerular filtration rate (GFR) can be estimated by?
the inulin or creatinine clearance
Renal plasma flow (RPF) is calculated using?
the para-aminohippuric acid clearance.
What is filtration fraction?
FF= GFR/RPF
The fraction of the RPF that is filtered across the glomerular capillaries into Bowman’s space.
It is usually equal to 20% in healthy individuals.
How can staph aureus cause necrotizing pneumonia?
staph aureus strains that express Panton-Valentine leukocidin (PVL), a protease that kills leukocytes and causes necrosis, are most likely to cause skin or soft-tissue abscess and invasive disease (eg necrotizing pneumonia)
PVL expression is most common in community-acquired, methicillin-resistant strains.
The most common cancers in women in order of incidence?
2019 estimates, the most common cancers (exclusing basal and squamous cell skin cancer) in women by order of incidence are breast, lung, and colorectal.
In terms of mortality, lung cancer claims the most lives, followed by breast and colorectal cancer.
What is retinitis pigmentosa?
a genetic condition resulting in progressive dystophy of retinal pigmented epithelium and photoreceptors.
Patients typically present with progressive night blindness and loss of peripheral vision due to early loss of rods, which are highly metabolically active.
Funduscopic exam: show dark pigments deposited in a bone-spicule pattern in addition to retinal vessel attenuation and optic disc pallor.
