UWorld Flashcards
Leukotriene B4
stimulates neutrophil migration to sites of inflammation. Other important chemotactic agents include 5-HETE (leukotriene precursor), complement component C5a, and IL-8
The morphology of Candida includes branching pseudohyphae with blastoconidia (budding cells). Most species are susceptible to ….
echinocandins, and C albicans is nearly always susceptible to fluconazole.
Urinalysis in patients with Chlamydia trachomatis infection classically shows ….
sterile pyuria (positive urine white blood cells, no bacteria on Gram stain, no growth on culture) because the C trachomatis bacterium is an obligate intracellular bacterium with minimal peptidoglycan in its cell wall. The diagnostic test of choice is nucleic acid amplification testing.
Thrombotic thrombocytopenic purpura classically presents with the pentad of ….
severe thrombocytopenia, microangiopathic hemolytic anemia (eg, schistocytes on peripheral smear), renal insufficiency, neurologic symptoms, and fever. However, all these signs and symptoms are rarely present. Diagnosis is often made by identifying severe deficiency of ADAMTS-13, a protease that cleaves large von Willebrand factor multimers off the endothelium
TTP labs
Hemolytic anemia (↑ LDH, ↓ haptoglobin) with schistocytes on peripheral smear
Thrombocytopenia (↑ bleeding time, normal PT/PTT)
Sometimes with:
Renal failure
Neurologic manifestations
Fever
Glutamate causes hyperactivation of what….
Glutamate is released from injured neurons, causing pathologic hyperactivation of NMDA receptors and leading to depolarization, calcium overload, and death of neighboring cells. This cascade of excitotoxicity contributes to neurodegeneration and propagation of neuron death after focal injury.
What do you give burn patients to prevent protein catabolism?
Patients with severe burn injury commonly develop a hypermetabolic response that results in an increased basal metabolic rate and, often, lean muscle wasting. Administration of oxandrolone, a synthetic testosterone analogue, enhances muscle protein synthesis and decreases protein catabolism, reducing lean muscle loss.
How does doxycycline work?
Rocky mountain spotted fever is a tick-borne illness due to Rickettsia rickettsii, a weakly gram-negative, obligate intracellular organism that has an affinity for vascular endothelial cells. Patients usually have nonspecific symptoms (eg, fever, malaise, myalgia) followed by a macular-petechial rash that begins on the ankles and wrists and spreads to the center of the body as well as to the palms and soles. Urgent treatment with doxycycline, an inhibitor of bacterial protein synthesis, is required.
Labs/Xrays for RA
Positive rheumatoid factor & anti–CCP antibodies
C-reactive protein & ESR correlate with disease activity
X-ray: soft tissue swelling, joint space narrowing, bony erosions
whats defective in Xeroderma pigmentosum
Xeroderma pigmentosum is an autosomal recessive disorder characterized by defective nucleotide excision repair often caused by a deficiency in UV-specific endonuclease. Affected children usually have severe photosensitivity, hyperpigmentation in sun-exposed areas, and a greatly increased risk for skin cancer.
Giant Cell arteritis
Giant cell arteritis (GCA) is characterized by granulomatous inflammation of the mediawith fragmentation of the internal elastic lamina most often affectingthe medium and small branches of the carotid artery. Ischemic optic neuropathy with irreversible blindness is a potential complication of GCA; therefore, patients with suspected GCA require immediate glucocorticoid therapy.
How does colchicine work?
Colchicine is a second-line agent for treating acute gouty arthritis. It inhibits tubulin polymerization and microtubule formation in leukocytes, reducing neutrophil chemotaxis and emigration to sites inflamed by tissue deposition of monosodium urate crystals. Gastrointestinal mucosal function is also impaired by microtubule disruption, leading to diarrhea and, less commonly, nausea, vomiting, and abdominal pain.
What is GFAP?
Glial fibrillary acidic protein (GFAP) is normally found in glia, and tumors of glial lineage are often positive for GFAP. Synaptophysin is normally found in neurons and neuroendocrine cells; tumors with neuronal or neuroendocrine differentiation are typically positive for synaptophysin.
metabolic acidosis, NAG
loss bicarb: diarrhea, RTA, excessive saline infusion
metabolic acidosis elevated anion gap
acc of. acidic compounds: LA, diabetic ketoacidosis, renal failure, methanol, ethylene glycol, salicylate toxicity
what initially offsets PE in heart failure
lymph drainage, increased
what does FAS do
The Fas receptor acts to initiate the extrinsic pathway of apoptosis. Mutations involving the Fas receptor or Fas ligand can prevent apoptosis of autoreactive lymphocytes, thereby increasing the risk of autoimmune disorders such as systemic lupus erythematosus.
What receptor important to isotype switch
Isotype switching is the process through which activated B lymphocytes switch production from IgM immunoglobulins to IgG and IgA isotypes. This process requires the interaction of CD40 on activated B cells with CD40 ligand expressed by activated T cells and is modulated by cytokines secreted by T cells.
What can cause ineffective hematopoesis
Folate is essential for nucleic acid metabolism, and deficiency 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.
The chronic myeloproliferative disorders (polycythemia vera, essential thrombocytosis, and primary myelofibrosis) often have a mutation in what?
Janus kinase 2 (JAK2), a cytoplasmic tyrosine kinase. This results in constitutive tyrosine kinase activity, and consequently, in the cytokine-independent activation of signal transducers and activators of transcription (STAT) proteins (JAK-STAT signaling pathway).
ANP and BNP
secreted by atrial and ventricular cardiomyocytes in response to myocardial stretching induced by hypervolemia. These natriuretic peptides inhibit the renin-angiotensin-aldosterone system and stimulate peripheral vasodilation and increased urinary excretion of sodium and water. Neprilysin inhibitors (eg, sacubitril) prevent the degradation of ANP and BNP, enhancing their beneficial effects in heart failure.
ANP and BNP
increase GFR, increase diuresis, renin inhibition, decrease aldo, vasodilator, increase cap permeability
sarcomere is defined as the distance between two Z lines. Thin (actin) filaments in the I band are bound to structural proteins at the Z line, whereas thick (myosin) filaments in the A band are bound to structural proteins at the M line.
Mycobacterial resistance to isoniazid (INH) is primarily mediated by
reductions in the catalase-peroxidase enzyme or through genetic modification of the INH binding site on the mycolic acid synthesis enzyme.
what happens in postpartum thyroiditis
within 12 months of pregnancy and is characterized by autoimmune destruction of thyroid follicles. It typically has a hyperthyroid phase due to release of preformed thyroid hormone, followed by a hypothyroid phase due to depletion of thyroid hormone stores and eventual return to a euthyroid state. Thyroid metabolic activity during the hyperthyroid phase is suppressed, and glandular blood flow and radioiodine uptake are low.
whats hawthorn effect
is the tendency of study subjects to change their behavior as a result of their awareness that they are being studied.
antisocial not diagnosed in individuals under 18!!!
XL recessive pattern
In X-linked recessive inheritance 1) affected males will always produce unaffected sons and carrier daughters, and 2) carrier females have a 50% chance of producing affected sons and carrier daughters. G6PD deficiency follows this inheritance pattern and causes acute hemolytic anemia in response to oxidant drugs.
what encourages more blood to RA
Paradoxical embolization, or passage of a thromboembolism from the venous to the arterial circulation, most commonly occurs through a patent foramen ovale (PFO). A PFO is a one-way tissue valve in the atrial septum that opens only when right exceeds left atrial pressure; venous return to the right atrium increases during the release (ie, relaxation) phase of the Valsalva maneuver and encourages the PFO to open.
Xlinked dom
In X-linked dominant inheritance, affected individuals have at least 1 parent (of either sex) that is also affected. An affected male will always produce affected daughters, but none of his sons will be affected.
what is pierre robin
Pierre Robin is characterized as a sequence because the primary defect (hypoplasia of the mandibular prominence) leads to a cascade of further malformations (ie, micrognathia, posteriorly displaced tongue, U-shaped cleft palate).
what is retinoblastoma associated with
Retinoblastoma is associated with inactivating mutations of the RB1 tumor suppressor gene, which normally restricts cells from passing the G1/S checkpoint until the cell is ready to divide. Impaired function of the Rb protein allows unrestricted progression through the G1/S checkpoint, leading to uncontrolled cell division.
porphyrin synthesis
Enzyme deficiencies of the early steps in porphyrin synthesis cause neuropsychiatric manifestations without photosensitivity, whereas late step derangements lead to photosensitivity. Photosensitivity manifests as vesicle and blister formation on sun-exposed areas as well as edema, pruritus, pain, and erythema.
IVC anatomy
inferior vena cava (IVC) courses through the abdomen and inferior thorax in a location anterior to the right half of the vertebral bodies. The renal veins join the IVC at the level of L1/L2, and the common iliac veins merge to become the IVC at the level of L5. IVC filters are placed in patients with deep venous thrombosis who have contraindications to anticoagulation therapy.
intraductal papilloma
characterized by epithelial and myoepithelial cells lining fibrovascular cores in a cyst wall or duct. It is the most common cause of bloody nipple discharge and typically presents without breast masses or skin changes.
pagets of breasts
characterized by epithelial and myoepithelial cells lining fibrovascular cores in a cyst wall or duct. It is the most common cause of bloody nipple discharge and typically presents without breast masses or skin changes.
Derivatives of the third pharyngeal pouch
include the thymus and inferior parathyroid glands. Disrupted development of the third pharyngeal pouch (eg, DiGeorge syndrome) leads to thymic hypoplasia/aplasia with impaired T-cell development and immunodeficiency.
1st pouch/cleft
1st Eustachian tubeTympanic cavityMastoid air cells External auditory meatusTympanic membrane 1st cleft: preauricular cyst/fistula
2nd pouch /cleft
2nd Palatine tonsilSupratonsillar fossa Cervical sinus (obliterated by development of 2nd arch) 2nd cleft: persistent cervical sinus/fistula2nd pouch: cleft palate
3rd pouch / cleft
Cervical sinus (obliterated by development of 2nd arch) 2nd cleft: persistent cervical sinus/fistula2nd pouch: cleft palate
3rd & 4th pouches**: 22q11 microdeletion syndrome (eg, DiGeorge, velocardiofacial)
4th pouch/cleft
4th Dorsal wings: superior parathyroid glandsVentral wings: parafollicular C cells of thyroid
cervical sinus/fistula2nd pouch: cleft palate
3rd & 4th pouches**: 22q11 microdeletion syndrome (eg, DiGeorge, velocardiofacial)
V3 exits skull through what
The third (mandibular) branch of the trigeminal nerve exits the skull through the foramen ovale and innervates the muscles of mastication, including the masseter, the medial and lateral pterygoids, and the temporalis muscles.
optic canal
CNII opthalmic artery, central retinal vein
superior orbital fissure
CN 3, 4, V1, V5 opthalmic vein, sympathetic fibers
foramen rotundumm
CNV2
spinosum
middle meningeal a and vein
internal acoustic meatus
CN VII, VIII
jugular
CN 9, 10, 11, jugular vein
hypoglossal
CN 12
foramen magnum
spinal roots of XI, brain stem, vertebral a.
ankylosing spondylitis
The pathogenesis of ankylosing spondylitis likely originates with defects in the intestinal mucosal barrier and exposure to the gut microbiome that lead to an enhanced IL-17–mediated inflammatory response. IL-17 stimulates production of additional inflammatory factors, primarily tumor necrosis factor-alpha and prostaglandins, which have synergistic proinflammatory effects and induce bony erosions and abnormal bone regrowth in the skeleton. elevated esr and crp
IL-2 and interferon gamma
have broad immune functions, including activation of the response against viruses and mycobacteria. Both cytokines inhibit Th17 cell differentiation and do not have a significant role in the pathogenesis of AS.
IL 4
IL-4 is important in the differentiation of naïve Th cells into the Th2 subset, alternative macrophage activation (M2 type), and IgE production. It may also have a protective role in AS by limiting IL-17 production by Th1 and Th17 cells. Interferon alpha is involved primarily in antiviral activity and is not a significant factor in the pathogenesis of AS.
IL 5
IL-5 induces B-cell growth, IgA production, and eosinophil activity. IL-5 and IL-4 are important in the etiology of certain allergic disorders (eg, allergic rhinitis, asthma), but do not contribute significantly to AS.
IL 10
IL-10 is an antiinflammatory cytokine. Transforming growth factor-beta has antiinflammatory and profibrotic effects. These cytokines have only a minor effect in AS.
GLUT 4
Glucose uptake in skeletal muscle occurs primarily via glucose transporter (GLUT) 4. Muscle contraction and insulin induce translocation of GLUT4 to the cell surface, increasing glucose uptake during exercise and the fed state, respectively. Over time, regular exercise causes increased expression of GLUT4, leading to increased skeletal muscle glucose uptake at any given insulin level and therefore lower blood glucose levels.
GLUT 2
GLUT2 is found primarily in the liver and pancreatic beta cells, where it facilitates insulin-independent glucose uptake. It is not expressed significantly in muscle or translocated in response to muscle contraction.
Ehlers-Danlos syndrome (EDS) is
a heritable connective tissue disease associated with abnormal collagen formation. EDS usually manifests clinically as overflexible (hypermobile) joints, overelastic (hyperelastic) skin, and fragile tissue susceptible to bruising, wounding, and hemarthrosis
Elastin, a fibrous protein in the connective tissue,
Elastin, a fibrous protein in the connective tissue, is named for the elastic properties it imparts to skin, blood vessels, and lung alveoli. Elastin fibers can be stretched to several times their original length but will recoil when the stretching forces are withdrawn. Elastin is synthesized from the polypeptide precursor tropoelastin.
receptors of urinary bladder
Urgency incontinence, or overactive bladder, is caused by uninhibited bladder contractions (detrusor instability) that results in a sudden urge to void followed by an involuntary loss of urine. Treatment with beta-3 adrenergic receptor activation (eg, mirabegron) relaxes the detrusor muscle, promotes urine storage, and decreases incontinent episodes.
Beta-3 receptor agonists (eg, mirabegron),
which causes detrusor smooth muscle relaxation, allowincreased urine storageand decreaseincontinent episodes. Because they are selective receptor agonists, they are often better tolerated with fewer systemic adverse effects.
Antimuscarinics (eg, oxybutynin), which block
M3 receptors at the bladder, prevent detrusor contractions. However, antimuscarinics often act on several types of muscarinic receptors and should be used with caution, especially in elderly patients and those with cognitive impairment due to medication adverse effects (eg, decreased cognition, blurred vision, drowsiness).
internal sphincter receptors
a1
external sphincter receptors
Nm receptors
tach sachs
Tay-Sachs disease is an autosomal recessive disorder caused by β-hexosaminidase A deficiency, which results in GM2 ganglioside accumulation in neuronal lysosomes. Key clinical features include progressive neurodegeneration (eg, developmental regression), an exaggerated startle reflex, and a cherry-red macular spot.
Krabbe disease
(galactocerebroside accumulation) is a lysosomal storage disease that causes progressive neurodegeneration. However, affected infants have optic atrophy, which is visualized as optic nerve pallor rather than a bright red fovea.
Gaucher
is a lysosomal storage disorder in which glucocerebroside accumulation results in bone pain, hepatosplenomegaly, and bone marrow suppression (eg, anemia, thrombocytopenia).
Mucopolysaccharidoses (eg, Hurler syndrome, Hunter syndrome)
are lysosomal storage disorders characterized by the build-up of glycosaminoglycans such as heparan and dermatan sulfate. Patients have neurocognitive decline, but coarse facial features and hepatosplenomegaly are also expected. Although Hurler syndrome is associated with corneal clouding, neither mucopolysaccharidosis causes a cherry-red macula.
Niemann Pick
Neurodegeneration and a cherry-red macular spot occur in Niemann-Pick disease, which is characterized by sphingomyelin accumulation. However, hepatosplenomegaly would be present
hyperplasia in cells for renal artery stenosis
Neurodegeneration and a cherry-red macular spot occur in Niemann-Pick disease, which is characterized by sphingomyelin accumulation. However, hepatosplenomegaly would be present
Macula densa
cells are tall, narrow cells located in the distal tubule that monitor salt content and tubular flow rate. This information is transmitted to nearby JG cells that are located mainly in the wall of the afferent arteriole. JG cells are modified smooth muscle cells with renin-containing zymogen granules.
ADH, urine sodium, total body volume in ascites?
Portal hypertension in cirrhosis leads to vasodilation and decreased systemic perfusion pressure, which causes antidiuretic hormone release and activation of the renin-angiotensin-aldosterone system, promoting sodium and water retention. However, due to resistance to splanchnic flow, low oncotic pressure, and hyperdynamic circulation, the fluid is third-spaced into the extravascular compartments (eg, ascites). Therefore, despite increased total body volume, patients with cirrhosis remain intravascularly volume depleted.
JAK2/STAT
Chronic kidney disease is commonly associated with normocytic anemia due to reduced production of erythropoietin by the kidneys. Erythropoietin signal transduction is primarily mediated by the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which promotes erythrocyte precursor survival and differentiation.
camp
Cyclic AMP mediates the effects of a variety of hormones, including glucagon, antidiuretic hormone (V2 receptor), and corticotropin.
membrane phospholipids by phospholipase A2
Cleavage of membrane phospholipids by phospholipase A2 leads to the formation of arachidonic acid, which is then converted to prostaglandins and leukotrienes that help regulate the inflammatory response. Various medications directly or indirectly affect this system, including glucocorticoids, nonsteroidal anti-inflammatory drugs, and leukotriene inhibitors.
nuclear receptor hormones
Commonly used therapeutic hormones that activate a nuclear receptor include thyroid hormone, vitamins A and D, and the steroid hormones (eg, glucocorticoids, mineralocorticoids, sex hormones).
pip/itp pathway
Therapeutic hormones that activate the phosphatidylinositol/inositol trisphosphate second messenger system include antidiuretic hormone (V1 receptor), GnRH, and oxytocin.
The Ras/mitogen-activated protein kinase signal transduction system
The Ras/mitogen-activated protein kinase signal transduction system is used by a variety of growth factors (eg, epidermal growth factor, platelet-derived growth factor) that primarily act to stimulate cell proliferation. Uncontrolled activation of this system can lead to malignancy.
atopic dermatitis
Atopic dermatitis presents with dry, erythematous patches or papules that are caused in part by a Th2-skewed immune response. Th2 cytokines (eg, IL-4, IL-13) stimulate IgE production, suppress epidermal barrier component expression, and impair host immune responses against secondary microbial infections.
IL-8 and C3b
are involved in neutrophil migration and activation in bacterial infections. IL-8 attracts neutrophils to infected areas, whereas C3b opsonizes pathogens for phagocytosis. This patient has no sign of infection (eg, cellulitis), such as tenderness, fever, or drainage.
IL-12 and interferon-gamma
are involved in granuloma formation and host defense against mycobacterial infections (eg, enhanced intracellular killing of tuberculosis in phagolysosomes).
IL-17 and IL-23
are involved in the pathogenesis of psoriasis. Plaque psoriasis typically presents as pruritic, erythematous plaques with thick, silvery scales, which are not seen in this patient.
TNF-alphaand IL-1
are involved in the pathogenesis of septic shock. Endotoxins in the outer membrane of gram-negative bacteria induce the release of endogenous pyrogen (eg, IL-1, prostaglandins) and inflammatory mediators (eg, TNF-alpha), leading to fever, hypotension, increased vascular permeability, and organ failure.
Transcatheter aortic valve implantation (TAVI)
allows for minimally invasive management of severe aortic stenosis in elderly patients who are unable to tolerate open surgical valve replacement. Paravalvular aortic regurgitation is a common complication of TAVI, resulting from improper sealing of the prosthetic valve to the native aortic valve annulus.
Antibody-drug conjugates improve what?
drug efficacy and minimize toxicity by allowing conventional chemotherapeutic agents (eg, cisplatin) to selectively target and kill cancer cells while sparing healthy cells (ie, targeted delivery).
gonadal veing /artery anatomy
Testicular torsion is due to twisting of the testis around the spermatic cord (containing the gonadal artery), which can eventually lead to ischemia. The gonadal arteries arise from the abdominal aorta. The right gonadal vein drains directly into the inferior vena cava while the left gonadal vein drains into the left renal vein.
plasmodium treatment
Blood microscopy findings that show red blood cells filled with multiple small rings suggest Plasmodium infection (malaria). Erythrocytic forms of this parasite are treated with antimalarials such as chloroquine (in nonresistant areas), atovaquone-proguanil, or artemisinins. Primaquine is required to kill Plasmodium vivax and Plasmodium ovale liver hypnozoites.
wilson disease
Wilson disease is caused by defective copper transport within hepatocytes, which leads to impaired biliary excretion of copper. Hepatic copper accumulation eventually results in the release of free copper into the bloodstream and copper deposition into extrahepatic tissues (eg, basal ganglia, cornea). increased hepatocellular copper, oxidative stress, necrosis, apoptosis -> release free copper into bloodstream, extrahepatic copper deposition
Alveolar fluid contains proteases (eg, elastases) that are derived from alveolar macrophages and infiltrating neutrophils. These proteases can cause destruction of terminal lung parenchyma (eg, emphysema) when secreted in excess (or if left unchecked by deficient antiprotease activity).
ANOVA
analysis of variance test compares the means of ≥3 groups. The test requires a categorical independent variable (ie, exposure) that is used to divide the study pool into ≥3 groups and a quantitative dependent variable (ie, outcome) for which an average (eg, mean) can be calculated.
acute stress disorder
3 days - 1 month
ptsd
> 1 month of intrusive thoughts, nightmares, flashback, avoidance of trauma reminders, hypervigilance, sleep disturbance
SDs from median
In a normal (bell-shaped) distribution, 68% of all values are within 1 standard deviation (SD) of the mean; 95% are within 2 SDs of the mean; and 99.7% are within 3 SDs of the mean.
Isoniazid
is an antimycobacterial agent that specifically inhibits the synthesis of mycolic acids, which are essential components of the mycobacterial peptidoglycan cell wall. Without mycolic acids, the mycobacteria lose their acid-fastness and become unable to synthesize new cell walls or multiply.
rifampin
Inhibition of bacterial DNA-dependent RNA polymerase Gastrointestinal effects, rash, red-orange body fluids, cytopenia
pyrazinamide
MOA: Unclear Hepatotoxicity, hyperuricemia
ethambutol
Inhibition of arabinosyl transferase (?) Optic neuropathy
Follicular lymphoma
is a common, indolent non-Hodgkin lymphoma. It is characterized by a translocation involving BCL2 on chromosome 18, which becomes positioned near the immunoglobulin heavy-chain gene on chromosome 14, resulting in overexpression of BCL2 (an antiapoptotic protein).
APML
t(15;17) involving PML & RARA → PML-RARα oncoprotein → myeloid differentiation inhibited
RARα: nuclear receptor involved in myeloid differentiation
PML: fusion forms receptor with dominant negative activity
burkitt lymphoma
t(8;14) involving MYC & IGH → MYC overexpression → cell growthMYC: transcription factor regulating cell growthIGH: immunoglobulin heavy chain (high expression in B cells)
CML
t(9;22) involving ABL1 & BCR → BCR-ABL1 oncoprotein → cell proliferation
ABL1: nonreceptor tyrosine kinase
BCR: fusion leads to activation
follicular lymphoma
t(14;18) involving IGH & BCL2 → BCL2 overexpression → apoptosis evasionBCL2: antiapoptotic protein
mantle cell lymphoma
t(11;14) involving CCND1 & IGH → cyclin D1 overexpression → cell cycle progressionCyclin D1: regulates cell cycle
The Thayer-Martin medium
is used to isolate pathogenic Neisseria species such as N meningitidis and N gonorrhoeae. It is a chocolate sheep blood agar that contains vancomycin to inhibit the growth of gram-positive organisms; colistin and trimethoprim to inhibit gram-negative bacteria (other than pathogenic Neisseria); and nystatin to inhibit yeasts.
pulm edema and compliance
Left-sided heart failure is common following myocardial infarction affecting the left ventricle. The resulting accumulation of edema in the pulmonary interstitium makes the lungs heavy and stiff, restricting inspiratory expansion and decreasing lung compliance.
Ventilation-perfusion (V/Q) mismatch
exists on a spectrum with intrapulmonary shunting (perfusion without ventilation) and dead space ventilation (ventilation without perfusion) on either end. Pulmonary edema causes V/Q mismatch via increased intrapulmonary shunting with a corresponding decrease in dead space ventilation. V/Q mismatch via increased dead space ventilation is seen with pulmonary embolism.
Functional residual capacity
is the volume of air in the lungs at the end of normal expiration. It is increased in conditions with increased lung compliance (eg, chronic obstructive pulmonary disease) and decreased in conditions such as pulmonary edema that reduce lung compliance.
Diabetic autonomic neuropathy and bladder function
is common in type 1 diabetics and can cause overflow incontinence due to inability to sense a full bladder and incomplete emptying. Postvoid residual (PVR) testing with ultrasound or catheterization can confirm inadequate bladder emptying.
SSRI and MAOI
Coadministration of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase (MAO) inhibitors can produce excessive synaptic serotonin levels secondary to decreased reuptake and decreased degradation of serotonin, potentially causing serotonin syndrome. To avoid this risk, a 2-week washout period after discontinuing an MAO inhibitor and before initiating SSRI therapy is required to allow sufficient time for MAO regeneration.
Hereditary hemochromatosis and joints
is an autosomal recessive 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. Other manifestations include liver disease, skin hyperpigmentation, diabetes mellitus, pituitary hormone deficiencies (eg, central hypogonadism), and cardiomyopathy.
tests for herpes
tzanck smear and PCR, chancroid from h ducreyi is gram stain and PCR
how is enzyme replacement therapy given?
Certain lysosomal storage diseases, including Gaucher disease, can be treated with enzyme-replacement therapy (eg, recombinant glucocerebrosidase). Because enzymes are large proteins that cannot be orally absorbed, the replacement enzyme must be administered intravenously. Entry into the cell occurs by endocytosis after the replacement enzyme binds to mannose 6-phosphate receptors on the cell surface.
migratory thrombophlebitis (trousseau syndrome)
A paraneoplastic syndrome of hypercoagulability may be seen in some patients with cancer, especially adenocarcinomas of the pancreas, colon, or lung. Superficial venous thromboses may therefore appear in one site and then resolve, only to recur in another site. This is known as Trousseau syndrome (migratory superficial thrombophlebitis), an indication of visceral cancer.
cyclophosphamide
Chemotherapeutic drugs that induce DNA damage increase the risk for secondary malignancy (eg, treatment-related myeloid neoplasms). Cyclophosphamide is an alkylating agent that induces apoptosis in malignant cells via formation of DNA cross-links.cyclophos = hemorrhagic cystitis and bladder cancer
Anthracyclines
Anthracyclines*(eg, doxorubicin) Binds with topoisomerase II to cleave DNABinds with iron to generate free radicals Dilated cardiomyopathy
Bleomycin
Bleomycin Induces free radical formation Pulmonary fibrosis
Cisplatin
Cisplatin* Cross-links DNA to inhibit DNA synthesis NephrotoxicityOtotoxicityPeripheral neuropathy
Paclitaxel
Paclitaxel Inhibits microtubule disassembly Neuropathy
Vincristine/vinblastine
Vincristine/vinblastine Binds β-tubulin to inhibit microtubule formation Neuropathy
——-increases the conversion of norepinephrine to epinephrine in the adrenal medulla by increasing the expression of phenylethanolamine-N-methyltransferase.
Cortisol
steps in production of catecholamines
Norepinephrine and dopamine are produced in the central as well as the peripheral nervous system, whereas epinephrine is predominantly produced in the adrenal medulla. The first step conversion of tyrosine to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase. This is the rate-limiting step in the synthesis of catecholamines. DOPA is converted to dopamine by dopa decarboxylase (Choice B), which is then converted to norepinephrine by dopamine beta-hydroxylase (Choice C). In the adrenal medulla, norepinephrine is rapidly converted to epinephrine by phenylethanolamine-N-methyltransferase (PNMT).
Expression of PNMT in the adrenal medulla is upregulated by cortisol. Because the venous drainage of the adrenal cortex passes through the adrenal medulla, cortisol concentrations in the medulla can be very high, and PNMT is expressed at a high level. However, following pituitary resection, the loss of ACTH leads to decreased synthesis of cortisol in the adrenal cortex. The result is decreased PNMT activity and reduced conversion of norepinephrine to epinephrine.
hematogenous osteomyelitis bacteria
Hematogenous osteomyelitis is predominantly a disease of children that most frequently affects the long bones. Staphylococcus aureus is implicated in most cases secondary to a bacteremic event. Streptococcus pyogenes (group A streptococcus) is the second most common cause of hematogenous osteomyelitis.
sickle cell
seeding to bone, salmonella, long bones
pott disease
seeding from lungs, m. TB in vertebrae
If events are independent, the probability that all events will turn out the same is ….
the product of the separate probabilities for each event. The probability of at least 1 event turning out differently is given as 1 - P(all events being the same).
The —– of a test refers to its ability to correctly identify those with the disease.
A highly sensitive test should always be considered over a highly specific test when screening for life-threatening diseases, where identification of every person with the disease is important.
pleural fluid characteristics uncomplicated parapneumonic effusion
ph>7.2, glucose > 60, WBC < 50k (*opposite for complicated)
——- can form insoluble chelate complexes with polyvalent cations (eg, calcium, iron, aluminum, magnesium)
fluoroquinolones -in the gastrointestinal tract, leading to impaired absorption. This effect can be seen with over-the-counter antacids containing calcium, magnesium, and/or aluminum salts and in patients taking calcium salts (eg, calcium carbonate, calcium citrate) for treatment of osteoporosis.
chelation drug interactions - what drugs
tetracyclines, fluoroquinolones, levothyroxine
Myophosphorylase deficiency (McArdle disease, or glycogen storage disease type V) causes failure of muscle glycogenolysis, resulting in decreased exercise tolerance, muscle pain, cramping, and myoglobinuria shortly after initiating physical activity.
what enzyme???
During glycogenolysis, glycogen phosphorylase shortens glycogen by cleaving 1,4-alpha-glycosidic linkages liberating glucose-1-phosphate This occurs until 4 residues remain before a branch point (the limitdextrin). At this point, the debranching enzyme 1.
Glucosyltransferase cleaves the 3 outer glucose residues of the 4 that are left by glycogen phosphorylase and transfers them to a nearby branch 2. alpha-1,6-glucosidase removes the single remaining branch residue, producing free glucose and a linear glycogen chain that can be further shortened by glycogen phosphorylase
how do you catch chagas?
Chagas disease is a protozoal illness that is endemic to Latin America. Patients in rural areas are at greatest risk when their houses harbor the vector (Triatome bug) in adobe walls or thatched roofs. Acute infections are often asymptomatic, but patients can develop Chagas cardiomyopathy (eg, heart failure, ventricular arrhythmias, ventricular aneurysms) several decades later.
Gestational thrombocytopenia is common in the third trimester and is typically mild, asymptomatic, and not associated with other laboratory abnormalities. It occurs due to
hemodilution (ie, maternal plasma volume expansion) and increased sequestration/consumption of platelets in the placenta.
Drainage of empyema with a chest tube is often difficult due to loculations and high fluid viscosity, but it can be aided by the intrapleural administration of a——- in combination with a nucleic acid cleaving enzyme (ie, deoxyribonuclease).
fibrinolytic agent (eg, tissue plasminogen activator)
SVR, CO, and venous return in high output HF
High-output heart failure results from markedly decreased systemic vascular resistance (eg, large arteriovenous fistula) that leads to increased venous return and increased cardiac output. Despite a sustained increase in cardiac output, the left ventricle is unable to keep up with the increased venous return, and decompensated heart failure develops.
Kartagener syndrome
is a form of primary ciliary dyskinesia characterized by the triad of situs inversus, chronic sinusitis, and bronchiectasis. It occurs due to mutations that impair the structure or function of cilia. Cystic fibrosis also causes chronic respiratory infections, but it is not associated with situs inversus.
half lifes of different benzos
Duration of action of common benzodiazepines
Short(half-life <6 hr) Triazolam, midazolam
Intermediate(half-life 6-50 hr) Oxazepam, alprazolam, lorazepam, clonazepam
Long(half-life >50 hr) Diazepam, chlordiazepoxide, flurazepam
ACD pathogenesis
with rheumatologic diseases, chronic infection, malignancy, congestive heart failure, and morbid obesity due to elevation of cytokines. The mediator is hepcidin, a peptide released from the liver that inhibits iron channels on enterocytes and reticuloendothelial macrophages. This reduces iron availability for erythropoiesis, which leads to normocytic (or slightly microcytic) anemia with a poor reticulocyte response. — decrease fe absorption and inc. fe sequestration
labs ACD
Normocytic/slightly microcytic anemia
↓ serum iron, iron-binding capacity, reticulocyte count
↑ bone marrow iron
Lower than expected erythropoietin for degree of anemia
labs of different anemias
MS and bladder findings
Patients with multiple sclerosis often develop a spastic bladder a few weeks after developing an acute lesion of the spinal cord. These patients present clinically with increased urinary frequency and urge incontinence. Urodynamic studies show the presence of bladder hypertonia.
Dihydrofolate reductase and DNA polymerase are enzymes involved in DNA synthesis, which occurs during the S phase of the cell cycle. The ——protein, in its active (dephosphorylated) form, regulates cell cycle progression by preventing the transition from the G1 phase to the S phase.
RB!!! Phosphorylation of the Rb protein inactivates it, allowing cells to progress through the G1/S checkpoint and proliferate.
p27
p27 protein is a cell cycle inhibitor. It acts during the G1 phase by inhibiting cyclin-dependent kinases. Normal tissues (composed primarily of differentiated cells) contain high levels of p27, and malignant tissues contain very low levels of p27. Upregulation of p27 would stop the cell cycle.
Ras
Ras protein is a component of the MAP-kinase signal transduction system. It transmits growth signals from cell surface receptors into the nucleus, leading to the transcription of cyclin D complexes. Although involved in cell cycle progression, Ras protein signaling would occur before phosphorylation of RB protein and would not immediately precede the S phase.
turner is caused by what chromosome issue
meitotic nondisjunction during gametogenesis
skewed X-chromosome inactivation
occurs when one X chromosome is inactivated more often than would occur by chance alone. However, because many of the genes that contribute to TS (eg, SHOX) normally escape X inactivation, findings of TS are not typical with this mechanism.
uniparental disomy occurs when …
both copies of a chromosome are inherited from 1 parent. Disease occurs when the inherited chromosomes contain genes that are physiologically imprinted (silenced), and gene expression normally relies on the other parent’s genes (which are absent), as in Prader-Willi/Angelmansyndrome.
most adverse drug effect of amphotericin
hypokalemia and hypomagnesemia , increases distal tubular membrane permeability; hypokalemia on ECG t wave flattening, st depression, prominant U and premature atrial and vent contractions
how does OD on b blockers present
Beta blockers act as competitive antagonists for endogenous catecholamines; therefore, toxicity presents with hypotension, bradycardia, bronchospasm, and hypoglycemia. The hypotension and hypoglycemia contribute to altered mental status.
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primary ciliary dyskinesia
autosomal recessive mutation in the proteins responsible for normal flagellar and ciliary structure and function (eg, dynein, assembly proteins). Clinical manifestations include situs inversus, chronic sinusitis, bronchiectasis, and infertility.
cardiac contractility, baroreceptor firing, and ANP release in low BP
Low blood pressure results in decreased arterial distension and reduced firing of aortic and carotid baroreceptors. This leads to an increase in sympathetic outflow and decrease in parasympathetic outflow, stimulating vasoconstriction and increased heart rate and contractility in order to help maintain blood pressure. Hypovolemia reduces atrial stretch, causing decreased atrial natriuretic peptide secretion.
whats on surface of APC ?
MHC class II is expressed on the (APC) and presents extracellular antigens to T cells after extracellular protein is degraded within acidified lysosomes. Failure to acidify lysosomes would lead to deficient expression of MHC class II-antigen complexes with subsequent impaired interaction between APCs and T cells.
MCH is on what cells
MHC Class I molecules present intracellular antigens produced in tumor or virus-infected cells. Cytoplasmic proteins are degraded by a proteasome and transported into the rough endoplasmic reticulum (via TAP proteins) where they are loaded onto MHC Class I molecules and routed to the cell surface.
TCR
membrane-bound protein on T cells that is responsible for recognizing specific antigens bound to an MHC molecule. Although the TCR is essential for T cell activation in response to antigens presented on MHC Class II molecules, prevention of lysosome acidification would have no effect on the expression of TCR on the surface of T cells.
deep intracerebral hemorrhage
Spontaneous deep intracerebral hemorrhage is typically caused by hypertensive vasculopathy involving the small, penetrating branches of the major cerebral arteries. The most frequently affected locations include the basal ganglia (putamen), cerebellar nuclei, thalamus, and pons. The putamen is supplied by the lenticulostriate arteries, which are deep, small vessel branches off the middle cerebral arteries.
acute putaminal hemorrhage (affects basal ganglia)
most always affect the adjacent internal capsule, leading to dysarthria, contralateral hemiparesis, and contralateral hemisensory loss due to disruption of the corticobulbar, corticospinal, and somatosensory fibers. As the hemorrhage expands, it leads to increase intracranial pressure (headache, nausea/vomiting, and altered mental status), midline shift from mass effect, and possible cerebral herniation.
Hypertensive vasculopathy
involving the small, penetrating branches of the major cerebral arteries is the most common cause of spontaneous deep intracerebral hemorrhage. Chronic hypertension leads to the formation of Charcot-Bouchard aneurysms, which may ultimately rupture and bleed within the deep brain structures. The most frequently affected locations include the basal ganglia (putamen), cerebellar nuclei, and pons. The basal ganglia are supplied by the lenticulostriate arteries, which are deep, small vessel branches off the middle cerebral arteries.
cytokines of asthma
Paroxysmal breathlessness and wheezing in a young patient that are unrelated to ingestion of aspirin, pulmonary infection, inhalation of irritants, and/or exercise should raise a strong suspicion for atopic (extrinsic) asthma. Classic sputum findings include eosinophils and Charcot-Leyden crystals. Eosinophils are recruited and activated by IL-5 secreted by TH2 type T cells.
TGFB
(TGF-β) is a growth factor involved in tissue regeneration and repair; high levels are associated with subepithelial fibrosis and airway remodeling seen in chronic asthma. However, it is not chemotactic for eosinophils.
IL1
Although IL-1 release from macrophages is involved in asthma pathogenesis, it is not a specific cytokine. IL-1 release is a component of almost all inflammatory processes and does not necessarily cause eosinophil infiltration.
pulm infarcts
usually hemorrhagic wedge shaped and on periphery. IVDU increases risks of tricuspid endocarditis causes septic pulm infarcts due to embolization of vegetation fragments
Sciatica
is a nonspecific term for low back pain that radiates down the leg due to compression of the lumbosacral nerve roots (eg, from vertebral disc herniation). The S1 nerve root is commonly involved, resulting in pain/sensory loss down the posterior thigh and calf to the lateral aspect of the foot. Patients may also have weakness on thigh extension, knee flexion, and foot plantarflexion with an absent Achilles reflex.
l2-l4
Patellar Anteromedial thighMedial shin Hip flexion (iliopsoas)Hip adductionKnee extension (quadriceps)
L5
None reflex affected Lateral shinDorsum of the foot Foot dorsiflexion & inversion (tibialis anterior)Foot eversion (peroneus)Toe extension (extensor hallucis & digitorum)
s2
Anocutaneous Perineum Urinary or fecal incontinenceSexual dysfunction
s1
Achilles Posterior calfSole & lateral foot Hip extension (gluteus maximus)Knee flexion (hamstrings)Foot plantarflexion (gastrocnemius)
Coccidioides immitis
is a dimorphic fungus endemic to the southwestern United States. It exists in the environment as a mold (with hyphae) that forms spores. These spores are inhaled and turn into spherules in the lungs.
Cryptococcus neoformans
present in pigeon droppings. This fungus causes pulmonary disease and meningoencephalitis in immunocompromised patients.
Histoplasma capsulatum
endemic to the Mississippi and Ohio River basins and found in bird and bat droppings. Patients with histoplasmosis often have a history of cleaning bird coops or caving.
Aspergillus fumigatus
colonize old lung cavities (e.g., those formed by tuberculosis) to form a “fungal ball” (i.e., aspergilloma). Symptoms include cough, dyspnea, and hemoptysis.
potassium and DKA
Most patients with diabetic ketoacidosis have normal to increased serum potassium levels despite a total body potassium deficit. Replacement of potassium is a crucial step in the management of patients with diabetic ketoacidosis.
Allergic contact dermatitis (eg, nickel allergy)
is a type IV hypersensitivity reaction characterized by epidermal intercellular edema (ie, spongiosis) and an inflammatory infiltrate (eg, lymphocytes, eosinophils). Clinical findings can include vesicles, erythema, and pruritus for acute lesions and lichenification for chronic lesions.
neurofibromas
benign nerve sheath tumors composed of cells normally found in peripheral nerves, including neoplastic Schwann cells, as well as non-neoplastic fibroblasts, perineural cells, and mast cells. Cutaneous neurofibromas often arise from small nerves in the dermis.
The area just anterior to the central sulcus (precentral gyrus) is the primary motor cortex. A lesion in this area would lead to
weakness according to the somatotopic organization of the cortex.
Frontal eye fields (anterior to central sulcus), an area that …
directs gaze to produce conjugate horizontal gaze. An ischemic lesion in this area would lead to gaze deviation toward the side of the lesion (ie, rightward deviation if the right hemisphere is impacted).
somatosensory cortex
A lesion of the somatosensory cortex, located just posterior to the central sulcus, leads to contralateral sensory deficits and cortical sensory signs.
NAS
Neonatal abstinence syndrome due to maternal opioid use causes neurologic, gastrointestinal, and autonomic symptoms; irritability, tremors, diarrhea, and sneezing are classic findings. Patients with symptoms refractory to nonpharmacologic therapy warrant opioid replacement (eg, morphine).
UMN
Upper motor neuron lesions (ie, internal capsule stroke) cause contralateral weakness with clasp-knife spastic rigidity, hyperreflexia, and a positive Babinski sign. These lesions damage the pyramidal motor system (eg, corticospinal tracts), which runs from the precentral gyrus (primary motor cortex) through the internal capsule to the brainstem and spinal cord.
insular cortex
The insular cortex (insula) plays a role in emotional experience (in conjunction with the limbic system), autonomic function, and introspection/awareness of visceral sensations.
The caudate nucleus, putamen, and globus pallidus (ie, basal ganglia) are part of the extrapyramidal motor system, which regulates both voluntary and involuntary motor function (eg, posture, muscle tone, prevention of erratic movements). Lesions to these structures can result in:
motor dysfunction, including chorea (ie, random, jerky, uncontrollable movements), tremor, bradykinesia, or rigidity, as well as changes in cognition and behavior.
Imiquimod
is a widely used topical immunomodulatory agent that stimulates a potent cellular and cytokine-based immune response to aberrant cells (eg, human papillomavirus-infected cells in anogenital warts) by activating toll-like receptors and upregulating NF-κB. Other antiproliferative effects of imiquimod include inhibition of angiogenesis and induction of apoptosis.
NF-κB
NF-κB increases transcription of proinflammatory genes, activating antigen-presenting cells (eg, Langerhans cells in the skin) and initiating an immune response involving natural killer cells, cytotoxic T cells, and type 1 helper T cells. This results in increased cytokine production (eg, IL-1, IL-12, interferon-alfa/gamma, tumor necrosis factor-alpha) and enhanced immune-mediated killing of aberrant cells (eg, cancer cells, virus-infected cells).
