UWorld Incorrects

DNA synthesis can only occur in the

5'-->3' direction

Heparin-induced thrombocytopenia and thrombosis occurs

5-10 days following exposure to heparin products and is characterized by a large drop in platelet count

A result is considered statistically significant if the 95% confidence interval does not cross the null value, which corresponds to a p-value

<0.05

What is the presentation of VZV?

A characteristic finding in varicella is the development of successive crops of lesions on the face, trunk, and extremities, as seen in this patient with lesions in different stages of development (eg, crusted lesions, new vesicles). Vesicles crust over and resolve within 1-2 weeks

Propofol:

A highly lipophilic GABA agonist that has the advantage of reducing airway resistance. Disadvantages include vasodilation, which can result in hypotension and an increase in serum triglycerides and lipase

When a fetal neural tube defect is suspected, amniotic fluid is sampled to measure the level of:

AFP

What reduces the rate of spontaneous depolarization in cardiac pacemaker cells by prolonging phase 4?

Acetylcholine and adenosine

contraction of the ocular pupillary dilator muscle, resulting in mydriasis (pupillary dilation) results from (stimulation of which receptor)?

Alpha -1 receptor stimulation

Serotonin/norepinephrine reuptake inhibitors (duloxetine, venlafaxine) work by

Altering central transmission of pain by increasing NE in the central synapses

HLA-B27-associated spondyloarthropathy that affects primarily young Caucasian males and causes debilitating pain and deformity of the spine and hips

Ankylosing spondylitis

Cluster B Dramatic/erratic personality disorders

Antisocial: disregard & violation of the rights of others Borderline: chaotic relationships, abandonment fears, labile mood, impulsivity, inner emptiness, self-harm Histrionic: superficial, theatrical, attention-seeking Narcissistic: grandiosity, lack of empathy

Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is an autosomal recessive disorder characterized by elevated cholesterol and triglyceride levels. It is caused by defects in

ApoE3 and ApoE4, leading to decreased clearance of chylomicrons and VLDL remnants. Patients can develop eruptive and palmar xanthomas and premature atherosclerosis.

Patients with profound and prolonged neutropenia are at especially high risk for viral and fungal infections. The most common fungal causes are

Aspergillus and Candida species. Invasive pulmonary aspergillosis presents with some combination of fever, chest pain, cough, dyspnea, and hemoptysis.

Type 1 hypersensitivity ex:

Asthma, allergic rhinitis

Primary central nervous system lymphoma is typically composed of

B-lymphocytes

Squamous metaplasia is a reversible, adaptive response to chronic irritation, such as smoking. The normal columnar epithelium is replaced by squamous epithelium, which is more resistant to irritation but has reduced mucociliary clearance. Metaplasia also occurs with

Barrett esophagus, in which esophageal squamous epithelium is replaced by columnar epithelium in response to chronic acid exposure.

Clostridium botulinum releases botulinum toxin which

Blocks presynaptic release of acetylcholine at the neuromuscular junction, resulting in flaccid paralysis It also releases toxin A which recruits & activates neutrophils, leading to release of cytokines that cause mucosal inflammation, fluid loss & diarrhea

Rituximab is a monoclonal antibody used in lymphoma immunotherapy that specifically targets the

CD20 surface immunoglobulin

A patient presents with dyspnea, productive cough, hypoxemia, expiratory wheezing, accessory muscle use, and smoking history is consistent with:

COPD exacerbation

Pt who presents with a 30-pack-year smoking history, low-grade fever, productive cough, normal pulse oximetry, and pulmonary rhonchi suggests what?

COPD exacerbation

CREST syndrome (limited scleroderma) manifests with calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasias. Anti-centromere antibodies are found in about 40% of patients with

CREST syndrome. Anti-DNA topoisomerase I (Scl-70) antibodies are highly specific for systemic sclerosis.

the most common type of renal cell carcinoma and originates from the epithelial cells of the proximal renal tubules

Clear cell carcinoma Gross pathology typically demonstrates a sphere-like mass composed of golden-yellow cells (due to high lipid content) with areas of necrosis and hemorrhage.

poor intestinal absorption of levothyroxine can happen with

Co-administration with various foods (eg, soy products) or drugs (eg, iron, calcium, antacids)

common cause of self-limited diarrhea in immunocompetent hosts, but may cause life-threatening diarrhea in immunocompromised patients (eg, advanced AIDS). Diagnosis may be made by visualizing oocysts with modified acid-fast stain in stool or basophilic organisms lining the brush-border in a biopsy.

Cryptosporidium

Drug-induced parkinsonism is an extrapyramidal side effect caused by medications that block

D2 receptors (ex. antipsychotics) Management strategies include decreasing or discontinuing the offending medication and treatment with an anticholinergic medication, such as benztropine

During bacterial DNA replication, DNA polymerase I functions to remove RNA primers (via 5' to 3' exonuclease activity) and replace them with

DNA (via 5' to 3' polymerase activity). DNA polymerase I is the only bacterial DNA polymerase that possesses 5' to 3' exonuclease activity.

Southern blotting is a technique that can be used to detect

DNA mutations It involves restriction endonuclease digestion of sample DNA, gel electrophoresis, and gene identification with a labeled DNA probe

mRNA synthesis occurs in 2 stages:

During the first, the DNA template is transcribed into a complementary strand of pre-mRNA. In the second, pre-mRNA is processed into mature mRNA through the following steps: 1. RNA capping: Addition of a methylated guanine nucleotide to the 5' end. 2. RNA polyadenylation: Addition of several adenine nucleotides to the 3' end (poly-A tail). 3. RNA splicing: Removal of introns (noncoding regions) by spliceosomes, which consist of snRNPs and other proteins. Mature mRNA then transfers the genetic code to the cytoplasm and serves as a template for protein synthesis (translation).

___is an important cause of urinary tract infections. These organisms are gram-positive cocci in pairs and chains and, when grown on blood agar, they do not cause hemolysis (gamma-hemolytic).

Enterococcus

Urinary tract infections are most common in women and are typically caused by enteric pathogens

Escherichia coli is the leading pathogen.

Protein A is a virulence factor found in the peptidoglycan cell wall of Staphylococcus aureus that binds to the

Fc portion of IgG, leading to impaired complement activation, opsonization, and phagocytosis.

Patients who have overdosed on beta blockers should be treated with glucagon, which increases heart rate and contractility independent of adrenergic receptors. Glucagon activates

G-protein-coupled receptors on cardiac myocytes, causing activation of adenylate cyclase and raising intracellular cAMP. The result is calcium release from intracellular stores and increased sinoatrial node firing.

Nonbenzodiazepine medications (eg, zolpidem, zaleplon, eszopiclone) stimulate specific subtypes of

GABAA receptors. As a result, nonbenzodiazepines are primarily hypnotics and do not produce the anxiolytic, muscle relaxant, or anticonvulsant effects associated with benzodiazepines.

Systemic sclerosis may result in esophageal dysmotility and incompetence of the lower esophageal sphincter due to atrophy and fibrous replacement of the esophageal muscularis. This can cause

GERD with an increased risk of Barrett's esophagus and stricture formation

GTP is synthesized by succinyl-CoA synthetase during the conversion of succinyl-CoA to succinate in the citric acid cycle. During gluconeogenesis, phosphoenolpyruvate carboxykinase uses

GTP to synthesize phosphoenolpyruvate from oxaloacetate.

What organism can cause pericarditis (purulent pericarditis) but rarely?

Gram-positive cocci (staphylococcus aureus, streptococcus pneumoniae) affected patients are quite ill and present with high fever and sepsis

Foreign bodies (retained sutures) can cause what kind of response?

Granulomatous response, seen as a tender, erythematous, brown or purple papule, nodule, or plaque Characterized by aggregates of activated macrophages and surrounded by a rim of lymphocytes

The presence of ____ (a soluble protein that is a marker of viral replication and increased infectivity) in the mother significantly increases the risk of vertical transmission of the virus

HBeAg

Patients with chronic hepatitis B have elevated

HBsAg >6 months after initial infection

Tumors located in the lung apex (superior sulcus) are called Pancoast tumors. Invasion of surrounding structures can lead to ipsilateral

Horner syndrome, rib destruction, atrophy of hand muscles, and pain in the distribution of C8, T1, and T2 nerve roots.

Acute adrenal insufficiency (adrenal crisis) treatment:

Hydrocortisone or dexamethasone Rapid intravenous volume repletion

Second aortic arch forms which adult derivative?

Hyoid artery, stapedial artery

Patients undergoing treatment with amphotericin B may have electrolyte disturbances like:

Hypokalemia and hypomagnesemia and reflect an increase in distal tubular membrane permeability

Acute adrenal insufficiency (adrenal crisis) clinical features:

Hypotension & shock Nausea, vomiting, abdominal pain Fever, generalized weakness

the only cytokine with anti-inflammatory properties

IL-10 IL-10 reduces production of proinflammatory TH1 cytokines (IL-2 and interferon gamma) and major histocompatibility complex class II expression (important for antigen presentation and T-helper cell response)

What stimulates the differentiation of naïve Th0 cells into Th1 cells?

IL-12 Patients with IL-12 receptor deficiency are susceptible to severe mycobacterial infections due to the inability to mount a strong cell-mediated granulomatous immune response; therefore, they require treatment with IFN-γ.

Sarcoidosis is characterized by noncaseating granulomas due to dysregulated cell-mediated immunity. Activated antigen-presenting cells produce IL-12, which stimulates the differentiation of Th1-type CD4+ cells. Th1 cells produce

IL-2 and interferon-γ, which stimulate Th1 cell proliferation and macrophage activation, respectively.

Penicillins and cephalosporins are common triggers for drug-induced hemolytic anemia because they can bind to the erythrocyte surface and act as haptens for IgG attachment. Subsequent clearance of

IgG-coated erythrocytes by splenic macrophages leads to hemolytic anemia. Withdrawal of the offending drug usually leads to complete resolution of symptoms.

With maternal blood types A or B, hemolytic disease of the fetus and newborn very rarely occurs because maternal antibodies (anti-A or anti-B) are of the

IgM type and cannot cross the placenta. In contrast, mothers with blood type O also produce IgG antibodies (anti-A and anti-B), which can cross the placenta and cause fetal hemolysis.

How does the immune system defend against Giardia?

Immune defense against Giardia involves CD4+ T helper cell induction of secretory IgA production. Secretory IgA helps prevent and clear infection by binding to trophozoites and impairing their adherence to the upper small-bowel mucosa.

Meningoencephalitis is the most common presentation of Cryptococcus neoformans infection. It occurs in immunosuppressed patients and can be diagnosed by

India ink staining of the cerebrospinal fluid. Cryptococcal pneumonia is diagnosed by mucicarmine staining of lung tissue and bronchoalveolar washings.

TCA (nortriptyline, amitriptyline) modulate pain transmission by

Inhibiting voltage-gated sodium channels in sensory nerves and increasing NE signaling in the CNS

Recurrent respiratory infections and dextrocardia are suggestive of what syndrome?

Kartagener syndrome, a form of primary ciliary dyskinesia

Polycystic ovary syndrome is characterized by elevated

LH levels, excess androgen production, and insulin resistance. Clinical features include obesity, menstrual irregularities, hirsutism, enlarged ovaries, and an increased risk of diabetes mellitus and endometrial hyperplasia.

Diastolic heart failure (DHF) is caused by decreased ventricular compliance and is characterized by normal left ventricular (LV) ejection fraction, normal LV end-diastolic volume, and elevated

LV filling pressures. Hypertension, obesity, and infiltrative disorders (eg, transthyretin-related amyloidosis, sarcoidosis) are important causes of DHF.

obligate intracellular protozoa that mature in macrophages and can be identified on biopsy by the presence of rod-shaped kinetoplasts

Leishmania They are transmitted to humans by infected sand flies and cause the clinical syndrome of cutaneous leishmaniasis, characterized by a chronic, pinkish papule that evolves into a nodule or plaque.

Li-Fraumeni syndrome is caused by an autosomal dominant mutation in the tumor suppressor gene TP53.

Leukemia, sarcomas, and tumors of the breast, brain, and adrenal cortex are most common.

Creatinine clearance has limitations on patients with

Low muscle mass (malnutrition, lower extremity amputation), or high/low protein diets

PDA allows left ventricular output to flow from the aorta into the

Low-resistance pulmonary circulation

The finding of a high peak in the gamma-globulin region on serum protein electrophoresis (SPEP) usually represents an M protein consisting of an overproduced monoclonal immunoglobulin. Multiple myeloma causes an

M protein peak on SPEP as well as anemia (weakness), lytic bone lesions (back pain, pathologic fractures), and renal insufficiency (related to amyloid deposition and hypercalcemia).

The major virulence factor of Streptococcus pyogenes is

M protein, an alpha-helical coiled-coil protein that shares structural homology with tropomyosin and myosin. It extends from the cell wall and prevents phagocytosis, inhibits complement binding, and mediates bacterial adherence. Antibodies against M protein form shortly after acute infection and may cross-react with epitopes on myosin, leading to rheumatic carditis.

Vomiting is a reflex regulated mainly by 5 receptors, including

M1 muscarinic, D2 dopaminergic, H1 histaminic, 5-HT3 serotonergic, and neurokinin 1 (NK1) receptors. 5-HT3 and NK1 receptor antagonists are particularly useful for chemotherapy-induced vomiting.

Graft-versus-host disease can occur following transplantation of organs rich in lymphocytes (eg, liver). T lymphocytes found in the donor organ become sensitized against the

MHC antigens of the recipient and subsequently attack the host's tissues. The skin, liver, and gastrointestinal tract are most frequently affected.

toxic shock syndrome is typically associated with the prolonged use of tampons or wound packing, which allows Staphylococcus aureus to replicate locally and release pyrogenic toxic superantigens (eg, toxic shock syndrome toxin-1) into the blood. Superantigens bind to the

MHC-II complex of antigen-presenting cells without processing and nonspecifically activate T cells. This leads to a dramatic release of inflammatory cytokines, which causes the manifestations of the disease (eg, hypotension; high fever; organ failure; diffuse, erythematous rash).

T helper subtype 1 cells release interferon-gamma, leading to the activation of macrophages, a process critical for control of

Mycobacterium tuberculosis infection. Activated macrophages form mature phagolysosomes that destroy phagocytosed mycobacteria and can differentiate into epithelioid and Langhans giant cells to wall off extracellular mycobacteria within caseating granulomas.

drug-induced lupus erythematosus (DILE) is characterized by abrupt onset of lupus symptoms (eg, fever, arthralgias, pleuritis) with positive anti-histone antibodies. It has been linked to drugs metabolized by

N-acetylation in the liver (eg, procainamide, hydralazine, isoniazid). Genetically predisposed individuals who are slow acetylators are at greater risk for developing DILE.

Ketamine

N-methyl-d-aspartate antagonist that is similar to PCP, it preserves the respiratory drive during induction of anesthesia. Ketamine also provides an analgesic effect. It stimulates the release of catecholamines, which can cause bronchodilation but also increase heart rate, myocardial contractility, and cerebral blood flow.

Chronic granulomatous disease occurs most commonly due to an X-lined mutation affecting

NADPH oxidase deficiency of this enzyme leads to an inability of neutrophils to form the oxidative burst necessary to kill organisms in their phagolysosomes

Chronic granulomatous disease is an X-linked disorder resulting from deficiency of

NADPH oxidase, the enzyme responsible for formation of reactive oxygen species in phagosomes. Neutrophils affected by this disorder are unable to kill catalase-producing organisms, resulting in recurrent bacterial and fungal infections that frequently involve the lungs, skin, and lymph nodes.

Chronic granulomatous disease (CGD) results from a genetic defect in

NADPH oxidase. Normally, NADPH oxidase participates in the killing of microbes within neutrophil and macrophage phagolysosomes.

What facilitates opening of L-type Ca2+ channels and Na+ channels in phase 4 of the nodal action potential? This leads to more rapid depolarization.

NE

Neurofibromatosis type I is an autosomal dominant disorder caused by mutations in the:

NF1 tumor suppressor gene

calcium efflux from cardiac cells prior to relaxation is primarily mediated via an

Na/Ca exchange pump and sarcoplasmic reticulum Ca/ATPase pump

Tricuspid regurgitation is best heard where?

Near the left sternal border at the second and third intercostal spaces

common cause of rapid-onset sepsis and circulatory collapse in otherwise healthy young individuals Infections usually start suddenly with myalgias, high fever, headache, and altered level of consciousness and quickly progress to hypotension, organ failure, and death Many patients also develop a petechial/ecchymotic rash due to underlying disseminated intravascular coagulation

Neisseria meningitidis

Deficiencies of C5-C9, the components of the complement membrane attack complex, can lead to recurrent infections with

Neisseria meningitidis or gonorrhoeae

As the partial pressure of O2 increases, O2 binds to 1 of the 4 binding sites on hemoglobin and increases the

O2-binding affinity of the other available binding sites (steepening of the curve), a phenomenon known as cooperative binding.

The most important steps for prevention of central venous catheter infections are as follows:

Proper hand hygiene Full barrier precautions during insertion Chlorhexidine skin disinfection Avoidance of the femoral insertion site Removal of the catheter when it is no longer needed

Warfarin is an oral anticoagulant that inhibits the carboxylation of vitamin K-dependent coagulation factors II, VII, IX, and X. It is used in atrial fibrillation, deep venous thrombosis, and pulmonary thromboembolism. What should be monitored with treatment?

Prothrombin time (PT)/International Normalized Ratio (INR) should be monitored regularly during treatment with warfarin. Activated partial thromboplastin time (aPTT) is used for monitoring unfractionated heparin.

Ecthyma gangrenosum is a cutaneous necrotic disease with a strong association 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 patients who are neutropenic, are hospitalized, have burns, or have indwelling catheters.

In patients with cystic fibrosis, pathogenic bacteria colonize the respiratory tract early in the disease course. The leading pathogen in adults is

Pseudomonas aeruginosa, which forms a thick biofilm to prevent its full elimination from the body

List the cardiac tissue conduction velocity from fastest to slowest

Purkinje system, atrial muscle, ventricular muscle, AV node

Amiodarone (and other class III and class IA antiarrhythmic agents) causes lengthening of the cardiac action potential, which manifests as

QT interval prolongation on ECG. QT prolongation caused by amiodarone, in contrast to other drugs, is associated with a very low risk of torsades de pointes.

Methadone slows the delayed rectifier potassium current responsible for ventricular repolarization, and high doses are associated with

QT interval prolongation. QT interval prolongation predisposes to the development of torsade de pointes, a serious ventricular arrhythmia that can cause syncope and sudden cardiac death.

Inferior MIs are often due to blockage of which artery?

RCA, the artery usually responsible for SA and AV node perfusion Thus, inferior MIs are often associated with bradycardia

What synthesizes both mRNA and snRNA, the latter of which combines with specific proteins to form snRNPs?

RNA polymerase II

The hepatitis C virus is genetically unstable because it lacks proofreading 3' → 5' exonuclease activity in its

RNA polymerase. Its envelope glycoprotein sequences also contain a hypervariable region prone to frequent genetic mutation.

Relative risk is the probability of an outcome occurring in the exposed group compared with the probability of the outcome occurring in the unexposed group. It is calculated by the formula:

RR=a/a+b/c/c+d

Craniopharyngiomas are suprasellar tumors found in children and composed of calcified cysts containing cholesterol crystals. They arise from remnants of

Rathke's pouch, an embryonic precursor of the anterior pituitary.

Segmented, nonenveloped, double-stranded RNA virus that is transmitted via fecal-oral route

Rotavirus It is a major cause of infectious diarrhea in children and presents in those <5 years old with acute, self-limited fever and watery diarrhea

PDA results in increased left ventricular preload due to increased pulmonary venous return to the left atrium and decreased

SVR due to continuous left to right shunt

Neural crests are embryological structures composed of parallel strips of cells arising from the ectoderm at the margin of the neural tube. Structures derived from neural crest cells include

Schwann cells, odontoblasts, melanocytes, enterochromaffin cells, spinal membranes, adrenal medulla/ganglia, laryngeal cartilage, and tracheal cartilage.

In neurofibromatosis type 1, patients develop numerous cutaneous neurofibromas made mostly of:

Schwann cells, which are embryologically derived from the neural crest

Shiga-like toxins (Vero cytotoxins), produced by enterohemorrhagic Escherichia coli, are nearly identical to the

Shiga toxin produced by Shigella dysenteriae. They inhibit the 60S ribosomal subunit in human cells, thereby blocking protein synthesis by preventing binding of tRNA

Histamine causes

Smooth muscle contraction leading to bronchoconstriction, increased vascular permeability leading to edema, and increased mucus secretion from glandular tissue

Trimethoprim-sulfamethoxazole inhibits bacterial replication by blocking 2 successive steps in bacterial folate metabolism:

Sulfamethoxazole competes with para-aminobenzoic acid in the synthesis of dihydrofolic acid, and trimethoprim inhibits dihydrofolate reductase.

Calcineurin is an essential protein in the activation of interleukin-2, which promotes the growth and differentiation of

T cells Immunosuppressants such as cyclosporine and tacrolimus work by inhibiting calcineurin activation

Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. B-cell ALL is responsible for approximately 70-80% of all cases of ALL, whereas

T-cell ALL accounts for 15-17% of all cases of ALL. T-cell ALL often presents as a mediastinal mass that can cause respiratory symptoms, dysphagia, or superior vena cava syndrome.

First-line treatment options for localized psoriasis include high-potency topical corticosteroids and vitamin D analogs. Vitamin D analogs inhibit

T-cell and keratinocyte proliferation and stimulate keratinocyte differentiation. Corticosteroids also have anti-inflammatory and antiproliferative properties; their mechanism of action is complementary to the vitamin D analogs.

Streptococcus pneumoniae vaccination reduces the risk of invasive disease and is recommended for young patients and the elderly. The pneumococcal polysaccharide vaccine is an unconjugated vaccine that induces a

T-cell-independent humoral immune response. In contrast, the pneumococcal conjugate vaccine contains polysaccharide material attached to a protein antigen, which creates a robust T-cell-mediated humoral immune response.

IL-2 is a cytokine that regulates the activation and differentiation of

T-cells to aid in tumor cell destruction used for treatment of renal cell carcinoma and melanoma

Intracellular bacterial organisms such as Legionella pneumophila are primarily countered by the cell-mediated immune response. Intracellular pathogens that replicate within phagosomes (eg, Legionella, Mycobacterium tuberculosis) trigger activation and differentiation of

T-helper subtype 1 cells with subsequent macrophage activation via interferon-gamma.

Specificity =

TN/(TN + FP)

The binding of O2 molecules to hemoglobin in the lungs has two consequences, known as the Haldane effect:

The affinity of hemoglobin for CO2 is decreased, resulting in unloading of CO2 from hemoglobin (this accounts for a small percentage of overall CO2 in the blood and is not pictured above). The acidity of the hemoglobin molecule is increased; in response, protons (H+ ions) are released from the hemoglobin binding sites.

Case-control study

The frequency of factors (ie, exposure to insertion of a central line or urinary catheter, surgical site infection) is subsequently compared between cases and controls. The most appropriate measure of association between an exposure and a disease in case-control studies is the odds ratio (OR), which represents the odds of disease among exposed patients relative to non-exposed patients. The odds ratio is 1 for the null hypothesis

The eustachian tube connects

The middle ear to the nasopharynx

How do thiazide diuretics affect bone mineral density?

Thiazide diuretics increase calcium absorption in the distal convoluted tubules within the nephron. Thiazides are associated with increased bone mineral density and are recommended for treatment of hypertension in patients at risk for osteoporosis. Loop diuretics increase urinary calcium loss.

Type 1 hypersensitivity involves

Triggering the allergic response via the binding of previously recognized antigen to IgE antibodies on mast cells

The specificity of a test is its ability to correctly identify individuals without the disease. Specificity can be calculated as follows: Specificity =

True negatives / (True negatives + False positives)

Streak ovaries, amenorrhea, and infertility are the gynecologic complications of

Turner syndrome (TS). In addition, patients with TS usually have short stature, webbed neck, shield chest, and low posterior hairline. Bicuspid aortic valve is the most common cardiac comorbidity.

Postural skeletal muscles such as the soleus and paraspinal muscles contain predominantly

Type I, slow twitch muscle fibers that derive ATP primarily via oxidative (aerobic) metabolism.

HPV types ? that can result in warts?

Types 6 and 11

Sporadic and hereditary (associated with von Hippel-Lindau disease) renal cell carcinomas are associated with mutations involving the

VHL gene on chromosome 3p. The VHL gene is a tumor suppressor that inhibits hypoxia-inducible factors; mutations lead to constitutive activation of these proteins, resulting in the activation of multiple angiogenic and tumorigenic growth factors (eg, VEG-F, PDG-F).

What can be used to reverse warfarin effects?

Vitamin K and FFP

Atrophy of the lentiform nucleus (eg, globus pallidus and putamen) occurs in

Wilson disease, which is characterized by liver (eg, hepatitis, cirrhosis), psychiatric (eg, depression, personality changes), and neurologic (eg, dysarthria, movement disorder) abnormalities

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).

Atrial septal defects cause right-sided volume overload resulting in right atrial and ventricular enlargement. Excessive right-sided blood flow causes

a characteristic systolic ejection murmur (ie, pulmonic flow murmur) and wide and fixed splitting of S2.

The endothelial nitric oxide synthase makes nitric oxide from:

arginine, NADPH, and O2

The internal laryngeal nerve mediates the afferent limb of the cough reflex above the vocal cords. Foreign bodies (eg, fish bones) can

become lodged in the piriform recess and may cause damage to the nerve, impairing the cough reflex.

Heparin-induced thrombocytopenia type 2 results from the formation of IgG antibodies to

complexes of heparin and endogenous platelet factor 4 The major manifestation is thrombocytopenia, which typically occurs 5-10 days after heparin initiation due to the destruction of antibody-coated platelets by splenic macrophages. Widespread intravascular platelet activation also results in a high risk of arterial and venous thrombosis.

Potter sequence results from a renal anomaly that causes decreased fetal urine output leading to oligohydramnios. The lack of amniotic fluid causes

compression of the fetus (characteristic facies and limb abnormalities) and pulmonary hypoplasia, which is the most common cause of death in affected infants.

Beta error

conclusion that there is no difference between the groups studied when a difference exists-random error not systemic

X-inactivation occurs in genetically normal females and results in conversion of the inactivated X chromosome into compact heterochromatin (Barr body). Heterochromatin is

condensed chromatin composed of heavily methylated DNA in tight association with deacetylated histones. It has a low level of transcriptional activity. In contrast, euchromatin is loosely arranged and exhibits a high level of transcriptional activity.

Salicylate toxicity typically presents with mixed primary respiratory alkalosis and anion gap metabolic acidosis. Sodium bicarbonate facilitates

conversion to the lipophobic, ionized form of salicylate (Sal−), which traps much of the compound in the bloodstream and increases its urinary excretion.

Under anaerobic conditions, NADH transfers electrons to pyruvate to form lactate and regenerate NAD+. NAD+ is required to

convert glyceraldehyde-3-phosphate to 1-3-bisphosphoglycerate in glycolysis.

The reduced cardiac output in heart failure leads to decreased renal perfusion and consequent stimulation of the renin-angiotensin-aldosterone system in a maladaptive effort to maintain effective blood volume. Inactive angiotensin I is

converted into active angiotensin II by endothelial-bound angiotensin-converting enzyme in the lungs.

5-alpha-reductase inhibitors (eg, finasteride) reduce conversion of testosterone to

dihydrotestosterone. In men with benign prostatic hyperplasia, these agents reduce prostate volume and alleviate obstruction of urinary flow. However, they are associated with androgen-deficiency effects, including decreased libido, erectile dysfunction, and decreased ejaculate volume.

Aminoglycoside (eg, gentamicin) resistance is most commonly due to antibiotic-modifying enzymes. These enzymes add chemical groups to the antibiotic, which

diminishes its ability to bind to the 16S ribosomal RNA within the 30s ribosomal subunit.

The psoas muscle originates from the anterior surface of the transverse processes and lateral surface of the vertebral bodies and functions primarily as a hip flexor. Psoas abscess may form due to

direct spread of infection from an adjacent structure (eg, vertebral bodies, appendix, hip joint) or from hematogenous seeding from a distant site.

Informed consent is comprised of 4 major elements:

disclosure, understanding, voluntariness, and authorization

Osteoarthritis of the hands is characterized by osteophyte formation leading to hard bony enlargement of the

distal interphalangeal joints (Heberden nodes) and proximal interphalangeal joints (Bouchard nodes). Brief morning stiffness may be present.

Tumor lysis syndrome occurs when tumors with a high cell turnover are treated with chemotherapy. The lysis of tumor cells causes intracellular ions, such as potassium and phosphorous, and uric acid (metabolite of tumor nucleic acid) to be released into serum. Uric acid is soluble at physiologic pH, but it can precipitate in the normally acidic environment of

distal tubules and collecting ducts. The prevention of tumor lysis syndrome includes urine alkalinization and hydration, as high urine flow and high pH along the nephron prevents crystallization and precipitation of uric acid.

Diphtheria toxin is an AB exotoxin that ribosylates and inactivates

elongation factor-2. This action inhibits protein synthesis and ultimately leads to cell death.

The most common metastatic tumors to the brain are lung cancer, renal cancer, and melanoma. Melanoma is a malignancy of melanocytes, which are

embryologically derived from neural crest cells.

Subgaleal hemorrhage is a rare neonatal extracranial head injury caused by damage to:

emissary veins, typically from traction on scalp during vacuum-assisted delivery These veins connect the veins of the scalp to the meningeal veins and dural sinuses, leading to hemorrhage in the space between the periosteum and galea aponeurosis

A complete mole usually results when an

empty ovum is fertilized by a haploid sperm. Subsequent duplication of the paternal genetic complement (23X) results in the characteristic 46,XX genotype

Deficiency of the C1 complement component causes increased susceptibility to:

encapsulated bacteria (streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis)

Measles virus, or rubeola, is an

enveloped, nonsegmented, negative-sense RNA virus of the Paramyxoviridae family.

Graves ophthalmopathy is caused by stimulation of orbital fibroblasts by thyrotropin receptor antibodies and cytokines released by activated T-cells. Excess deposition of extracellular glycosaminoglycans and inflammatory infiltration lead to

expansion of extraocular muscles and retro-orbital tissues. Glucocorticoids improve Graves ophthalmopathy by decreasing the severity of inflammation and reducing the excess extraocular volume.

A discharge checklist detailing medication changes and follow-up appointments can significantly facilitate a patient's transition from the hospital and improve adherence to outpatient treatment. Individuals who

experience a smooth transition from the inpatient to the outpatient setting are at lower risk for early rehospitalization.

High-potency first-generation antipsychotics are more likely to cause

extrapyramidal symptoms, like dystonia, akathisia, and parkinsonism

Intravenous benzodiazepines (eg, lorazepam) are the initial drug of choice for status epilepticus. They work by enhancing the effect of

gamma-aminobutyric acid (GABA) at the GABA-A receptor, leading to increased chloride influx and suppression of action potential firing.

Enterococcus is a component of the normal colonic and urogenital flora and is capable of growing in hypertonic saline and bile. It is

gamma-hemolytic, catalase-negative, and pyrrolidonyl arylamidase-positive. Genitourinary instrumentation or catheterization has been associated with enterococcal endocarditis.

sensation from the upper limbs is carried in the cuneate fasciculus, which is located

in the lateral aspect.

beta1 adrenergic agonists:

increase heart rate and contractility and increase cardiac output

Treatment with statins causes hepatocytes to increase their LDL receptor density, leading to

increased uptake of circulating LDL.

The hepatitis B surface antigen of hepatitis B virus must coat the hepatitis D antigen of hepatitis D virus before it can

infect hepatocytes and multiply.

In patients with airway obstruction at the level of the larynx, they would be expected to have

inspiratory stridor

Subfalcine herniation occurs when the cingulate gyrus is displaced under the falx cerebri. Subfalcine herniation may compress the

ipsilateral anterior cerebral artery, resulting in ischemia and contralateral leg weakness.

A cohort study is used to compare incidence of disease between exposed and nonexposed individuals. A common measure of association in cohort studies

is the relative risk.

The splenic flexure and rectosigmoid junction lie between regions of perfusion of major arteries. These "watershed" areas are susceptible to

ischemic damage during hypotensive states, especially in patients with underlying arterial insufficiency.

Decreased activity of bacterial catalase-peroxidase is a mechanism of mycobacterial resistance to

isoniazid.

Alpha-fetoprotein is a serum tumor marker that is often moderately elevated in patients with chronic viral hepatitis. However,

it can be strikingly elevated in those with hepatocellular carcinoma, and a sudden rise can be a sign that a patient with chronic liver disease is harboring hepatocellular carcinoma.

Opioids (eg, morphine) can generate a pseudoallergic response by directly activating mast cells to stimulate degranulation, releasing histamine and other vasoactive mediators. This nonimmunologic reaction can cause

itching, urticarial rash, wheezing, hypotension, and tachycardia that closely mimic true IgE-mediated type 1 hypersensitivity. However, true IgE-mediated allergic reaction is rare with opioids.

Ehlers-Danlos syndrome is a group of rare hereditary disorders characterized by defective collagen synthesis. It can be caused by procollagen peptidase deficiency, which results in impaired cleavage of terminal propeptides in the extracellular space. Patients often have

joint laxity, hyperextensible skin, and tissue fragility due to the formation of soluble collagen that does not properly crosslink.

Insulin is cleared from the body via?

kidney and liver

The etiology of transposition of the great arteries is due to

linear (rather than spiral) development of the aorticopulmonary septum in utero, resulting in an anteriorly positioned aorta connected to the right ventricle and a posteriorly positioned pulmonary artery connected to the left ventricle Therefore, pulmonary and systemic circulations are abnormally separated and exist as 2 parallel circulations.

Xanthelasma is a cutaneous lesion commonly found on the eyelid that contains

lipid-laden macrophages (foam cells)

DiGeorge syndrome causes an extreme deficiency in the number of

mature T lymphocytes, leading to poor development of the lymph node paracortex. In contrast, agammaglobulinemia causes an absence of B cells, preventing primary lymphoid follicles and germinal centers from forming in the lymph node cortex.

A precise/reliable test is reproducible in that it gives similar results on repeat measurements. Reliability is

maximal when random error is minimal.

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy resulting in

microangiopathic hemolytic anemia and thrombocytopenia, findings that are essential for making the diagnosis. It is triggered by severe deficiency in ADAMTS13 levels.

Hemolytic uremic syndrome is a common cause of acute renal failure in children. It is characterized by the triad of

microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Most cases develop following a diarrheal illness caused by Shiga toxin-producing organisms (eg, Escherichia coli O157:H7, Shigella dysenteriae).

Aortic stenosis is characterized by a:

mid-systolic ejection murmur that starts after S1 and ends before S2 crescendo-decrescendo

Gout results from the deposition of

monosodium urate crystals in the joints and soft tissues. Under polarized light, urate crystals appear needle-shaped and negatively birefringent. Conditions that increase uric acid production or decrease uric acid clearance can increase the risk of gout.

chronic renal allograft rejection manifests

months to years after a transplant and presents with worsening HTN and a gradual decline in renal function It involves a chronic cell-mediated and antibody-mediated response against donor antigens and leads to obliterative vascular wall thickening, tubular atrophy, and interstitial fibrosis. Usually leads to graft failure

Meconium ileus is a distal small bowel obstruction due to abnormally dehydrated meconium in a patient with cystic fibrosis (CF). Persistent, treatment-resistant infectious pneumonias, bronchiectasis, and cor pulmonale account for

most deaths due to CF.

Exposure-based cognitive-behavioral therapy, in which patients are systematically confronted with their feared objects or situations, is the

most effective long-term treatment for specific phobia.

Piperacillin-tazobactam is a combination of extended-spectrum penicillin with β-lactamase inhibitor. It is effective against

most gram-negative enteric rods (including Pseudomonas aeruginosa) and against Bacteroides fragilis.

Supracondylar humeral fractures commonly occur after hyperextension of the elbow as a result of a fall onto an outstretched arm. The radial nerve runs along the anterolateral aspect of the elbow and is the structure

most likely to be injured with anterolateral displacement of the proximal fracture fragment. The brachial artery runs with the median nerve on the anteromedial aspect of the elbow and will usually be spared in these patients (eg, intact radial pulse).

In general, in a positively skewed distribution, the mean is the

most shifted in the positive direction (to the right), followed by the median and then the mode. In such a situation, the median often reflects a central tendency better than the mean does.

Absence of the submucosal (Meissner) and myenteric (Auerbach) plexuses in Hirschsprung disease causes the affected rectosigmoid region to become narrowed. The submucosa of the narrowed area is the

most superficial layer where the absence of ganglion cells can be confirmed during biopsy procedures.

Oral thrush, interstitial pneumonia, and severe lymphopenia during the first year of life are consistent with

mother-to-child vertical transmission of HIV-1.

Neurocysticercosis is a relatively common cause of seizures in patients from Central and South America and should be considered in

patients with suggestive symptoms and imaging (eg, cystic brain lesion) and characteristic epidemiological risk factors.

The unit of analysis in ecological studies is

populations rather than individuals.

Viridans streptococci are normal inhabitants of the oral cavity and are a cause of transient bacteremia after dental procedures in healthy and diseased individuals. In patients with

pre-existing valvular lesions, viridans streptococci can adhere to fibrin-platelet aggregates and establish infection that leads to endocarditis.

Common manifestations of Turner syndrome include

primary amenorrhea, short stature, a high arched palate, and widely spaced nipples. Primary amenorrhea occurs in these patients due to in utero degeneration of the ovarian follicles (gonadal dysgenesis).

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).

Cryptococcus neoformans is the only pathogenic fungus that has a polysaccharide capsule. The capsule appears

red on mucicarmine stain and as a clear unstained zone with India ink.

The relative risk (RR) represents the

risk of an outcome in the exposed divided by the risk of that outcome in the unexposed. Applying the correct formula for RR calculations depends on the proper formatting of a 2×2 (contingency) table.

In response to tissue hypoxia, specialized interstitial cells in the renal medulla and cortex release erythropoietin to stimulate the bone marrow to increase red blood cell production and improve the oxygen-carrying capacity of the blood. This response, known as

secondary polycythemia, is an expected finding in diseases or conditions that cause significant chronic hypoxemia (eg, chronic obstructive pulmonary disease).

Congenital pyloric stenosis arises

secondary to hypertrophy of the pyloric muscularis mucosae.

Familial retinoblastoma occurs as a result of mutations of each of the two Rb genes ("two hits"). These patients have an increased risk of

secondary tumors, especially osteosarcomas, later in life.

Aspergillus has:

septate hyphae that branch at 45 degree angles

Renal retention of bicarb occurs with

severe vomiting and diuretic overuse, commonly contributes to metabolic alkalosis

A moderately elevated alkaline phosphatase of unclear etiology should be followed up with

γ-glutamyl transpeptidase.

Delusional disorder is characterized by

≥1 delusions for ≥1 months in the absence of other psychotic symptoms. Behavior is not obviously bizarre, and functioning is not significantly impaired apart from the direct impact of the delusions.

Schizophreniform disorder is characterized by psychotic symptoms (delusions, hallucinations, disorganized speech and behavior, negative symptoms) lasting

≥1 month and <6 months.

antifungal agent that blocks synthesis of the glucan component of the fungal cell wall

caspofungin

Wheezing (high-pitched whistling noise) occurs with

constriction of the smaller airways of the lungs, asthma

The frontal lobes are involved in personality, language, motor functions, and executive functions (eg, abstraction). Frontal lobe function may be diagnosed by testing abstraction ability

(eg, asking about the similarities between two related objects) on the mental status examination.

Down syndrome is most commonly caused by maternal meiotic nondisjunction, a process by which the fetus receives 3 full copies of chromosome 21. Dysmorphic features

(eg, flat facial profile, protruding tongue, small ears, upslanting palpebral fissures) and cardiac defects (eg, endocardial cushion defects) are characteristic.

Type IV hypersensitivity ex:

contact dermatitis

Abacavir hypersensitivity reaction occurs in 2%-8% of patients and is strongly associated with

the HLA-B*57:01 allele.

Vitamin A can be beneficial in the treatment of measles infection by reducing comorbidities

(eg, ocular complications, diarrhea, pneumonia), recovery time, and length of hospital stay.

Treatments for hepatic encephalopathy include lactulose

(increases conversion of ammonia to ammonium) and rifaximin (decreases intraluminal ammonia production).

The odds ratio (OR) is a measure of association calculated as: OR =

(odds of exposure in cases) / (odds of exposure in controls). For a contingency table in the standard format: OR = (ad) / (bc).

Relative risk reduction =

(absolute riskcontrol − absolute risktreatment) / absolute riskcontrol

Acute angle-closure glaucoma occurs when the space between the cornea and iris is narrowed, limiting the flow of aqueous humor out of the anterior chamber and raising pressure in the eye. Medications that cause pupillary dilation

(eg, alpha-adrenergic agonists, anticholinergics) can trigger acute angle-closure glaucoma.

Nephrotic syndrome presents as:

-lipid droplets in renal tubules -heavy proteinuria -edema not seen: hypertension and hematuria

Pregnancy results in significant plasma expansion and widespread vasodilation, leading to increased renal plasma flow and glomerular filtration rates. Serum creatinine is reduced by approximately

0.4 mg/dL in this population; therefore, a rise in serum creatinine, even to levels that are normal in nonpregnant patients, represents significant renal dysfunction.

The probability of at least 1 event turning out differently is given as

1 - P(all events being the same)

The power of a study indicates the probability of seeing a difference when there is one. The formula is Power =

1 - β, where β is the type II error rate

A regression analysis is a statistical technique used to describe the effect that 1 or more independent variables (eg, exposures, risk factors), which may be quantitative or qualitative, can have on

1 quantitative dependent variable (ie, outcome).

Sunlight exposure catalyzes conversion of 7-dehydrocholesterol to cholecalciferol (vitamin D3) in the skin. Subsequent 25-hydroxylation in the liver and 1-hydroxylation in the kidneys produce

1,25-dihydroxyvitamin D, the active form. Inadequate exposure to sunlight can lead to vitamin D deficiency.

2,3-BPG decreases hemoglobin's affinity for oxygen. Therefore, in the presence of lower blood oxygen concentrations, higher 2,3-BPG levels within erythrocytes enable increased oxygen delivery in the peripheral tissues. 2,3-BPG is produced from

1,3-BPG by the enzyme bisphosphoglycerate mutase. This reaction bypasses an ATP-generating step of glycolysis, causing no net gain in ATP.

The probabilities that a given sibling will share some or all of the same HLA genes are as follows:

1/4 chance of inheriting all the same HLA genes (identical HLA match) 1/2 chance of inheriting half of the same HLA genes (haploidentical HLA match) 1/4 chance of inheriting none of the same HLA genes (HLA mismatch)

Number needed to treat represents the number of patients that need to be treated with a medication in order to prevent an additional negative outcome It is calculated by:

1/ARR (absolute risk reduction) NNT=1/control event rate-experimental event rate

Patients with advanced or castration-resistant prostate cancer are often treated with a

17-alpha-hydroxylase inhibitors (eg, abiraterone), which block the generation of androgens in the adrenal glands, testes, and tumor cells. This reduces systemic androgen levels, which limit prostate cancer growth.

Hemoglobin F (Hb F) is the predominant hemoglobin type in the second and third trimesters of pregnancy and during the first few months after birth. Hb F consists of

2 alpha and 2 gamma protein subunits (α2γ2) and has a high affinity for oxygen, which facilitates oxygen transport across the placenta to the fetus. Hb A (α2β2) is the major hemoglobin in adults.

Chi-square tests can be used to evaluate the association between:

2 categorical variables

two sample t-test can be used when:

2 group means are compared

Randomized control trial is an experiment in which participants are randomly allocated to

2 or more groups to assess the effect of specific interventions, like treatments

The DSM-5 diagnosis of persistent depressive disorder (dysthymia) is characterized by chronic depressed mood and at least

2 other depressive symptoms lasting for at least 2 years.

Acute stress disorder is characterized by intrusive experiences (flashbacks, nightmares), arousal (poor concentration, restless sleep), dissociative symptoms, and avoidance of traumatic reminders, as well as mood disturbances in response to a life-threatening trauma. Symptoms last between

3 days and 1 month.

Cyanide toxicity can occur in patients treated with nitroprusside. Cyanide toxicity presents with altered mental status, seizures, cardiovascular collapse, lactic acidosis, and bright red venous blood. Antidotal treatment of cyanide toxicity can be achieved by

3 different strategies: direct binding of cyanide ions (hydroxocobalamin), induction of methemoglobinemia (sodium nitrite), and use of detoxifying sulfur donors (sodium thiosulfate).

When mRNA is first transcribed from DNA, it is in an unprocessed form called pre-mRNA or heterogeneous nuclear mRNA (hnRNA). Several processing steps are required before finalized mRNA molecules can leave the nucleus, including

5'-capping, poly A tail addition, and intron splicing. Cytoplasmic P bodies play an important role in mRNA translation regulation and mRNA degradation.

Papillary muscle rupture is a life-threatening complication that typically occurs

3-5 days after MI and presents with acute mitral regurgitation and pulmonary edema

Absence seizures are a type of generalized epilepsy characterized by brief staring spells with momentary loss of awareness followed by an abrupt return to full consciousness. A classic

3-Hz spike-wave is seen on electroencephalogram; the treatment is ethosuximide.

Cystic fibrosis (CF) is most commonly due to a

3-base pair deletion in the CF transmembrane conductance regulator (CFTR) gene at amino acid position 508 (ΔF508). 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.

Myasthenia gravis is associated with abnormalities of the thymus (e.g. thymoma, thymic hyperplasia). The thymus and inferior parathyroid glands arise from the

3rd pharyngeal pouch.

Loss of cardiomyocyte contractility occurs within

60 seconds after the onset of total ischemia When ischemia lasts less than 30 minutes, restoration of blood flow leads to reversible contractile dysfunction (myocardial stunning), with contractility gradually returning to normal over the next several hours to days. After 30 minutes, ischemic injury becomes irreversible.

Quick clinical tests to assess attention and concentration include

counting down from 100 by intervals of 3 or 7, reciting the months of the year in reverse order, and spelling "world" backwards.

Unbalanced Robertsonian translocations account for a minority of Down syndrome cases. Karyotyping shows

46 chromosomes with a translocation between 2 acrocentric nonhomologous chromosomes [eg, 46, XX, t(14;21)].

Patients with Müllerian aplasia (ie, Mayer-Rokitansky-Küster-Hauser syndrome) have no upper vagina (eg, short vagina) and variable uterine development. These patients are

46,XX females with normal ovaries and secondary sexual characteristics.

Thoracentesis should be performed below the 6th rib in the midclavicular line, the 8th rib along the midaxillary line, or the 10th rib along the paravertebral line in order to minimize the risk of lung injury. Insertion of a needle lower than

9th rib increases the risk of penetrating abdominal structures. The needle should also be inserted along the upper border of the rib to prevent injury to the intercostal vessels.

Etomidate:

A GABA agonist that has the advantage of being the most hemodynamically neutral. It does not cause changes in heart rate, blood pressure, or cardiac output. However, it inhibits cortisol synthesis, which can lead to adrenocortical suppression that is typically reversible. Because of this, etomidate is often avoided in patients with septic shock, and it should not be used as maintenance of sedation after induction

A complete atrioventricular (AV) canal defect is comprised of an atrial septal defect, a ventricular septal defect, and a common AV valve. It is the most common congenital cardiac anomaly associated with

Down syndrome.

Gastric acid is neutralized by bicarbonate from the submucosal glands of the

duodenum (Brunner glands) and from pancreatic duct secretions. Chronic overproduction of gastric acid can lead to hyperplasia of the submucosal glands

Iron absorption occurs predominantly in the

duodenum and proximal jejunum

Following myocardial infarction, collagen deposition and fibrosis within the infarct region and eccentric hypertophy of surviving myocytes can lead to progressive left ventricular (LV) dilation and worsening contractile dysfunction. Because much of this remodeling is driven by neurohormonal signaling via angiotensin II,

ACE inhibitors (eg, lisinopril) reduce deleterious cardiac remodeling following myocardial infarction, minimizing LV dilation and helping preserve contractile function.

What drug reduces mortality in patients with HFrEF via a reduction in angiotensin II-mediated (and downstream aldosterone-mediated) cardiac remodeling?

ACE inhibitors (eg, lisinopril), angiotensin-receptor blockers (eg, losartan), and mineralocorticoid receptor antagonists (eg, spironolactone, epleronone)

Transient behavioral disturbances are common in children after the death of a loved one. Hallucinations of recently deceased relatives are

part of a normal grief reaction and may not be indicative of major psychiatric illness.

The urachus is a remnant of the allantois that connects the bladder with the yolk sac during fetal development. Failure of the urachus to obliterate at birth results in

a patent urachus, which can facilitate discharge of urine from the umbilicus.

First aortic arch forms which adult derivative?

part of maxillary artery

Heme oxygenase converts heme to biliverdin,

a pigment that causes the greenish color to develop in bruises several days after an injury.

False vocal cords (AKA ventricular folds) are folds of mucous membrane lined in respiratory epithelium, which is: (the paranasal sinuses and trachea are lined by resp epithelium as well)

ciliated, pseudostratified, columnar, and mucus-secreting

Rotavirus invades the villous epithelium of the

duodenum and proximal jejunum infection causes diarrhea via villous blunting (loss of absorptive capacity), proliferation of secretory crypt cells (secretory diarrhea), and reduced brush border enzymes

Narcolepsy is a chronic sleep disorder characterized by

excessive daytime sleepiness, cataplexy, and REM sleep-related phenomena (ie, hypnagogic/hypnopompic hallucinations, sleep paralysis).

Guillain-Barré syndrome represents a group of immune-mediated polyneuropathies that are thought to be caused by molecular mimicry, leading to demyelination of the peripheral nerves. Up to one-third of GBS cases are preceded by a

Campylobacter jejuni infection, which is a common cause of acute diarrheal illness.

Antibiotics suppress the normal vaginal flora and facilitate Candida overgrowth. Antibiotic use is the most common cause of

Candida vaginitis. Other potential causes include pregnancy, systemic corticosteroid use, diabetes mellitus, and immunosuppression.

The omphalomesenteric (vitelline) duct normally obliterates during the 7th week of embryonic development. Both enterocysts and Meckel diverticula result from a

failure of obliteration involving the omphalomesenteric duct.

Oxidative metabolism of glucose in pancreatic beta cells generates ATP. ATP-induced closure of the

ATP-sensitive potassium channels leads to membrane depolarization and subsequent insulin release.

Primary ciliary dyskinesia can result from:

failure of the dynein arms to develop normally, which contain an ATPase that generates energy to slide the microtubules past each other, producing ciliary movement

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

The zona reticularis is the inner zone of the cortex and contains cells in anastomosing cords (rete is Latin for net) that secrete

androgens

Glucose-6-phosphate dehydrogenase deficiency presents with signs of

anemia (eg, fatigue, pallor) and hemolysis (eg, jaundice, dark urine) after oxidative stress (eg, sulfa drug)

Decreased levels of factor VIII or IX lead to

failure to convert prothrombin into thrombin and deficient thrombus formation the addition of thrombin to the blood of a patient with hemophilia results in clotting

A preventable adverse event is defined as injury to a patient due to

failure to follow evidence-based best practice guidelines.

Infliximab is a chimeric (human/murine) IgG1 monoclonal antibody to

TNF-alpha This med is used for rheumatoid arthritis, ankylosing spondylitis, and fistulizing Crohn's disease

Autosomal dominant mutations in the TTN gene, which encodes for the sarcomere protein titin, are the most common cause of

familial dilated cardiomyopathy.

In a case-control study, potential participants are initially identified as cases or controls according to their disease status. The frequency of past exposure to ≥1 risk factors of interest is then compared

between cases and controls to estimate the association between the risk factors and the outcomes.

The infusion of excessive normal saline (sodium chloride) is a common cause of nonanion gap metabolic acidosis. The excess intravascular chloride (Cl−) causes intracellular shifting of

bicarbonate (HCO3−) to reduce serum HCO3− and decrease blood pH.

The C5-C6 spinal nerves mediate the

biceps and brachioradialis reflexes.

The tibial nerve may be injured at the level of the popliteal fossa due to deep penetrating trauma or knee surgery. Patients typically have weakness on

foot plantarflexion, foot inversion, and toe flexion, with sensory loss over the sole.

Young children who reside in homes built before 1978 are at significant risk for lead toxicity. Lead directly inhibits ferrochelatase and δ-aminolevulinic acid (ALA) dehydratase, resulting in

anemia, ALA accumulation, and elevated zinc protoporphyrin levels. Neurotoxicity is also a significant long-term complication.

Absolute risk reduction (ARR) describes the difference in risk between control and treatment groups. It is calculated as follows:

ARR = (Riskcontrol − Risktreatment)

Sulfonylureas inhibit the

ATP-sensitive potassium channel on the pancreatic beta cell membrane, inducing depolarization and L-type calcium channel opening. The increased Ca2+ influx stimulates beta cell insulin release independent of blood glucose concentrations. Sulfonylureas stimulate insulin secretion, even when blood glucose levels are normal, which can lead to hypoglycemia.

Enthesitis (inflammation at the bony insertions of tendons, ligaments, and joint capsules) is a prominent manifestation of spondyloarthritis (eg, ankylosing spondylitis). Common clinical syndromes include

Achilles tendinitis, plantar fasciitis, and dactylitis. Achilles tendinitis affects the site of insertion of the Achilles tendon on the calcaneus and presents with severe pain at the posterior aspect of the foot.

Acute adrenal insufficiency (adrenal crisis) etiology:

Adrenal hemorrhage or infarction Illness/injury/surgery in patient with chronic AI Pituitary apoplexy

Lateral epicondylitis (ie, tennis elbow) is characterized by overuse of wrist extensor muscles (eg, extensor carpi radialis, extensor digitorum), leading to

angiofibroblastic tendinosis at their attachment on the lateral epicondyle.

Reduced compliance means:

for any given volume the pressure will be significantly increased Reduced pulmonary parenchymal compliance is the hallmark of pulmonary fibrosis.

In the eye, atropine causes mydriasis (dilation), resulting in narrowing of the anterior chamber angle and diminished outflow of aqueous humor. This can precipitate:

angle-closure glaucoma in patients with shallow anterior chambers or higher than normal intraocular pressures

Cluster C Anxious/fearful personality disorders

Avoidant: avoidance due to fears of criticism & rejection Dependent: submissive, clingy, needs to be taken care of Obsessive-compulsive: rigid, controlling, perfectionistic

Severe tricuspid valve regurgitation (TR) can lead to right-sided heart failure, evidenced by jugular venous distension, hepatomegaly, lower extremity edema, and the absence of pulmonary edema. Permanent pacemaker placement can cause

TR because the right ventricular lead passes through the tricuspid valve orifice and can disrupt valve closure.

Primary CNS lymphomas occur in immunosuppressed patients, such as those suffering from AIDS. These tumors arise from

B cells and are universally associated with EBV. They are high-grade tumors with a poor prognosis.

Rituximab is a monoclonal antibody directed against CD20, a cell surface receptor on developing and mature B cells. Binding of rituximab to CD20 results in

B-cell cytotoxicity and phagocytosis, which reduces the B-cell population. This reduces inflammatory symptoms in a wide range of rheumatologic diseases.

Tay Sachs is caused by what kind of deficiency?

B-hexosaminidase A, which results in accumulation of the cell membrane glycolipid GM2 ganglioside

Epinephrine increases heart rate, myocardial contractility, and cardiac output by stimulating B1 receptors. At low doses, stimulation of:

B2 receptors in the skeletal muscle vasculature produces vasodilation that can cause decreased blood pressure.

In most cases of CLL, B-cell survival is promoted by the overexpression of:

BCL-2 on the mitochondrial membrane BCL-2 is an antiapoptotic protein that prevents stress signals from triggering the intrinsic apoptotic cascade, which is mediated by the release of cytochrome c from the mitochondria and subsequent activation of caspases

Bulimia nervosa (BN) is characterized by recurrent episodes of binge eating followed by compensatory behaviors to prevent weight gain (eg, fasting, exercising, vomiting, using laxatives). In contrast to patients with anorexia nervosa,

BN patients are normal weight to overweight.

Protein kinase A is responsible for the intracellular effects of the G protein-mediated adenylate cyclase second messenger system. Hormone receptors that use this system include the

TSH, glucagon, and PTH receptors.

A lesion in Wernicke's area can cause receptive aphasia, which is characterized by well-articulated, nonsensical speech paired with a lack of language comprehension (Wernicke-Word salad). Wernicke's area is located in the auditory association cortex within the posterior portion of the superior temporal gyrus in the dominant temporal lobe. The middle cerebral artery supplies

Broca's area (superior division) and Wernicke's area (inferior division).

Epstein-Barr virus causes infectious mononucleosis in teenagers and young adults. It is also associated with a number of malignant conditions, including

Burkitt lymphoma and nasopharyngeal carcinoma.

The most common cause of secondary hyperthyroidism is a

TSH-secreting pituitary adenoma. In addition to hyperthyroid symptoms, TSH causes generalized hypertrophy of the thyroid gland (diffuse goiter). Laboratory evaluation shows elevated levels of thyroid hormone (triiodothyronine and thyroxine) and TSH.

Seizures are the major cause of morbidity and mortality from theophylline intoxication.

Tachyarrhythmias are the other major concern.

The patients grandiose ideas about his special mission, impulsive risk taking behavior, and decreased need for sleep lasting more than 1 week are suggestive of a

Manic episode consistent with bipolar 1 disorder Other features of mania include elevated/euphoric/ irritable mood, increased energy, and hyperactivity Pressured speech and racing thoughts are also common

Mycobacterium tuberculosis triggers

CD4 T lymphocytes to release interferon-gamma, which leads to macrophage activation (improves intracellular killing ability) and differentiation into epithelioid histiocytes. These cells, along with horseshoe-shaped, multinucleated Langhans giant cells (fused, activated macrophages) are a key component of granuloma formation.

Mycobacteria tuberculosis primarily replicates within the phagosome, leading to display of mycobacterial antigens on major histocompatibility complex class II molecules. This results in the activation of

CD4 cells and subsequent control of the infection with macrophages.

Interleukin-2 (IL-2) is produced by helper T cells and stimulates the growth of

CD4+ and CD8+ T cells and B cells. IL-2 also activates natural killer cells and monocytes. The increased activity of T cells and natural killer cells is thought to be responsible for IL-2's anti-cancer effect on metastatic melanoma and renal cell carcinoma.

Hepatitis A triggers a robust

CD8+ lymphocytic and natural killer cell response to clear infected hepatocytes; the resulting hepatocellular damage is self-limited, with complete resolution within 2-3 months

Fragile X syndrome is caused by an increased number of

CGG trinucleotide repeats on the fragile X mental retardation 1 (FMR1) gene on the long arm of the X chromosome. This leads to hypermethylation and inactivation of FMR1.

Trigeminal neuralgia presents with brief episodes of sudden and severe "electric shock-like" or "stabbing" pain in the distribution of

CN V (particularly V2 and V3). Carbamazepine is the drug of choice.

Matching is used in case-control studies in order to control confounding. Matching variables should always be the potential confounders of the study (eg, age, race).

Cases and controls are then selected based on the matching variables so that both groups have a similar distribution in accordance with the variables.

Classically presents between age 6-24 months with abdominal pain, diarrhea, vomiting, and weight loss. Duodenal biopsy reveals crypt hyperplasia, villous atrophy, and intraepithelial lymphocyte infiltration. Treatment with a gluten-free diet resolves symptoms and normalizes serology and histology

Celiac disease (gluten-sensitive enteropathy)

an immunosuppressant used in transplant recipients to prevent rejection

Cyclosporine

monosaccharide that is absorbed directly without the action of pancreatic enzymes, and can be used to test for brush border absorptive function independent of pancreatic function.

D-xylose

The acid-fast stain identifies organisms that have mycolic acid present in their cell walls, including Mycobacterium and some Nocardia species. Acid-fast staining is carried out by applying an

aniline dye (eg, carbolfuchsin) to a smear and then decolorizing with acid alcohol to reveal whether the organisms present are "acid fast."

Cerebellar ataxia, telangiectasias, and increased risk of sinopulmonary infections constitute a characteristic triad of ataxia telangiectasia. This illness exhibits autosomal recessive inheritance, and the defect is in a gene that codes for the "ATM" gene which plays a role in

DNA break repair. The immune deficiency primarily manifests as an IgA deficiency and predisposes to infections of the upper and lower airways.

primary mechanism of action of antipsychotics is

antagonism at postsynaptic dopamine D2 receptors

Acute arsenic poisoning (insecticide) impairs cellular respiration and presents with abdominal pain, vomiting, diarrhea, hypotension, and a garlic odor on the breath. Insecticides and contaminated water are common sources of arsenic. What is the chelating agent?

Dimercaprol, which increases urinary excretion of heavy metals by forming stable, nontoxic soluble chelates

What clotting factor is deficient in hemophilia B?

Factor IX, vitamin K-dependent clotting factor made in the liver

Renal excretion of a drug is dependent on:

Glomerular filtration (reduced with low renal blood flow, kidney disease, and high drug protein binding) Renal tubular secretion (reduced by coadministration of drugs with overlapping substrate specificity) Tubular reabsorption (may be altered by changes in urine pH)

Androgen abuse suppresses

GnRH, LH, and FSH secretion, leading to reduced endogenous testosterone secretion, impaired spermatogenesis, and testicular atrophy. In addition, excess testosterone is converted by aromatase to estradiol, which can lead to gynecomastia.

The H+ ions released from the hemoglobin binding sites combine with bicarbonate ions (the primary form of CO2 in the blood) in the lungs to facilitate the production of:

H2O and CO2

Chronic hepatitis B with high infectivity is represented by persistent elevation of

HBsAg, HBeAg, and HBV DNA with no anti-HBe

Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor that is overexpressed in 20% of breast cancer patients. In such patients,

HER2 blockade with the monoclonal antibody trastuzumab downregulates cellular proliferation and promotes apoptosis.

HIV-associated dementia has become rare since the advent of antiretroviral treatment but may still develop in patients with inadequately treated, late-stage HIV infection. In the CNS,

HIV preferentially infects and replicates in macrophages.

The seronegative spondyloarthropathies include ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and arthritis associated with inflammatory bowel disease. Individuals expressing

HLA B27 are at increased risk for the seronegative spondyloarthropathies.

Condylomata acuminatum is caused by

HPV, a small double-stranded DNA virus

Chancroid is due to

Haemophilus ducreyi and presents as a deep, painful ulcers with ragged borders that are associated with grey exudate and inguinal lymphadenopathy. Dx is established by gram stain and culture of organism from a scraping of the ulcer base

Pharmacologic closure of a PDA can be achieved by

PGE2 synthesis inhibitors (eg, indomethacin) in premature infants. However, older patients usually require surgical ligation or percutaneous PDA occlusion.

Maple syrup urine disease classically presents with irritability, dystonia, poor feeding, and a "maple syrup" scent to the patient's urine within the first few days of life. Dietary restriction of

branched-chain amino acids (eg, leucine, isoleucine, valine) is the hallmark of treatment.

Sirolimus binds to the 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.

Initial management of septic shock requires rapid fluid resuscitation to replace intravascular volume and restore adequate end-organ perfusion. This is best accomplished with

IV boluses of isotonic crystalloid in the form of 0.9% (normal) saline or lactated Ringer solution because these solutions remain in the EC space

The most highly oxygenated blood in the fetus is carried by the umbilical vein, which empties directly into the

IVC via the ductus venosus

IgA nephropathy is characterized as recurrent hematuria that occurs spontaneously or within 5-7 days of an upper respiratory or pharyngeal infection (synpharyngitic hematuria). Unlike other causes of immune complex-mediated nephritic syndromes (eg, poststreptococcal glomerulonephritis),

IgA nephropathy is associated with normal serum complement levels.

prominent N meningitidis virulence factors include

IgA protease (destroys mucosal antibodies that would otherwise inhibit epithelial colonization), capsular polysaccharides (prevent phagocytosis and phagolysosome destruction), lipo-oligosaccharide (an endotoxin that is the major source of toxicity), and Opa-proteins (aid in endothelial attachment and invasion)

Common adverse effects of nondihydropyridine calcium channel blockers (eg, diltiazem, verapamil) include

constipation, bradycardia, atrioventricular block (negative chronotropic effect), and worsening of heart failure in patients with left ventricular systolic dysfunction (negative inotropic effect).

Bohr effect

In the peripheral tissues, high levels of CO2 create an increase in ambient acidity that shifts the hemoglobin dissociation curve to the right and facilitates the unloading of O2

Stretch reflex is responsible for deep tendon reflexes (patellar, achilles) and the maintenance of muscle tone by constant muscular activity occurring even at rest, so a hyperactive stretch reflex leads to

Increased muscle tone

Small cell carcinoma of the lung is the most aggressive type of lung cancer and is commonly associated with paraneoplastic syndromes (eg, SIADH, Cushing syndrome).

It is thought to have a neuroendocrine origin; tumor cells express neuroendocrine markers (eg, neural cell adhesion molecule, chromogranin, synaptophysin) and contain neurosecretory granules in the cytoplasm. This malignancy frequently synthesizes hormones or hormone-like substances, resulting in paraneoplastic syndromes (eg, vasopressin resulting in SIADH, adrenocorticotropic hormone resulting in Cushing syndrome).

The chronic myeloproliferative disorders (polycythemia vera, essential thrombocytosis, and primary myelofibrosis) often have a mutation in

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).

Patients with spirochetal illness (eg, syphilis, Lyme disease) can develop the

Jarisch-Herxheimer reaction after the initiation of antimicrobial therapy It is caused by massive release of bacterial products into the circulation due to widespread bacterial lysis. However, most cases arise several hours (not minutes) after antimicrobial therapy and are marked by high fever and worsened constitutional symptoms, like headache and myalgia

___ is a nonselective vasodilatory beta blocker that blocks beta-1, beta-2, and alpha-1 adrenergic receptors. Alpha-1 receptor blockade outweighs beta-2 receptor blockade to cause peripheral vasodilation with decreased venous return and lower systemic vascular resistance. The relatively balanced vasodilation reduces blood pressure without changing stroke volume. Beta-1 receptor blockade overrides the expected baroreflex-mediated increase in heart rate, resulting in overall decreased heart rate.

Labetalol

This condition is caused by deficiency of myophosphorylase, an isoenzyme of glycogen phosphorylase present in muscle tissue. Deficiency of this enzyme leads to decreased breakdown of glycogen during exercise, resulting in poor exercise tolerance, muscle cramps, and rhabdomyolysis.

McArdle disease (glycogen storage disease type V)

Congenital hypothyroidism is usually asymptomatic at birth. After maternal T4 wanes, infants develop

constipation, lethargy, hypotonia, macroglossia, an umbilical hernia, and a large anterior fontanelle.

In CKD, reduced excretion of phosphate can cause hyperphosphatemia. This induces hypocalcemia directly by binding free calcium and depositing in tissues, and indirectly by triggering fibroblast growth factor 23 secretion (decreases calcitriol production and intestinal calcium absorption). The resulting hypocalcemia can manifest as

Neuromuscular excitability (carpal spasm)

Fourth aortic arch forms which adult derivative?

On left, aortic arch On right, proximal right subclavian artery

The quadriceps muscle group is connected to the patella, which is attached to the tibial tubercle by the patellar ligament. Repetitive quadriceps contraction (eg, jumping) in adolescents can result in

Osgood-Schlatter disease, which is characterized by focal anterior knee pain and swelling due to chronic avulsion of the tibial tubercle.

St John's wort induces cytochrome

P450 hepatic microsomal enzymes. As a result, a wide variety of drugs that are metabolized by these enzymes, such as warfarin, will have lower plasma concentrations and decreased efficacy.

Acute benzodiazepine (eg, alprazolam, lorazepam) overdose causes central respiratory depression with hypoventilation. The hypoventilation leads to CO2 retention and acute respiratory acidosis. It also decreases the

PAO2, leading directly to hypoxemia (PaO2 <75 mm Hg). The efficiency of gas transfer between the lungs and the circulation is intact; therefore, a normal alveolar-arterial O2 gradient (eg, <15 mm Hg) is expected.

Cancer cells avoid immune recognition by overexpressing programmed death-ligand 1 (PD-L1), which binds to the programmed cell death-1 (PD-1) receptor on cytotoxic T cells and inhibits their response (T-cell exhaustion). Monoclonal antibodies that block

PD-L1 and PD-1 are effective against cancers that express high levels of neoantigens on their surface because these tumors are particularly susceptible to immune recognition by cytotoxic T cells.

The positive predictive value (PPV) of the test (the probability that a person has the disease given a positive test result) is given by:

PPV = TP / (TP + FP), where FP is false positives.

Cluster A Odd/eccentric personality disorders

Paranoid: suspicious, distrustful, hypervigilant Schizoid: prefers to be a loner, detached, unemotional Schizotypal: unusual thoughts, perceptions & behavior

results from an inability to convert phenylalanine to tyrosine by the phenylalanine hydroxylase system, making tyrosine an essential amino acid in these patients. Classic clinical features of untreated PKU include intellectual disability, seizures, light pigmentation, and a "musty" odor.

Phenylketonuria (PKU)

act by binding ergosterol in the fungal cell membrane

Polyene antifungals (eg, amphotericin B, nystatin)

Precursor B-ALL and precursor T-ALL can only be distinguished by immunophenotyping. The lymphoblasts in precursor B-ALL are

TdT+, CD10+ and CD19+, whereas the lymphoblasts in precursor T-ALL express T-cell markers (e.g. CD2, CD3, CD4, CD5, CD7 and CD8), TdT and CD1a.

Multiple logistic regression is a method used to:

predict the probability of a binary outcome (presence or absence of gastric cancer) based on 1 or more independent variables that can be either continuous or categorical

The proximal humerus and glenohumeral joint receive their blood supply via the

anterior and posterior circumflex humeral arteries, which are branches of the axillary artery that form an anastomosis at the neck of the humerus. Humeral neck fractures can disrupt this blood flow, leading to avascular necrosis of the humeral head.

This patient's clinical presentation with severe back pain, hypertension, ECG abnormalities, and transesophageal echocardiogram finding of a dissection flap in the descending aorta is consistent with

Stanford type B aortic dissection (Stanford type A refers to aortic dissections that involve any part of the ascending aorta)

Septic abortion typically presents with fever, abdominal pain, uterine tenderness, and/or foul-smelling discharge after pregnancy termination. Common offending pathogens include

Staphylococcus aureus and Escherichia coli due to seeding of the uterine cavity during instrumentation.

Nosocomial bloodstream infections are usually associated with intravascular catheters, which allow skin commensals such as

Staphylococcus aureus and coagulase-negative staphylococci to enter the bloodstream.

Haemophilus influenzae is a "blood-loving" organism that requires X (hematin) and V (NAD+) factors for growth. This can be accomplished by growing H influenzae in the presence of

Staphylococcus aureus and demonstrating the "satellite phenomenon," whereby H influenzae grow only near the β-hemolytic S aureus colonies that produce the needed X and V factors.

Patients with CGD develop recurrent bacterial and fungal infections that are predominantly caused by 5 catalase-positive organisms:

Staphylococcus aureus, Burkholderia cepacia, Serratia marcescens, Nocardia, and Aspergillus.

Patients with cystic fibrosis are at risk for pulmonary exacerbations due to

Staphylococcus aureus, Pseudomonas aeruginosa, nontypeable Haemophilus influenzae, and Burkholderia cepacia complex.

Translation of the mRNA template proceeds in the 5' to 3' direction. Because complementary sequences align in antiparallel fashion, during translation tRNA anticodons will be oriented in the opposite 3' to 5' direction.

Stop codons (UAA, UAG, and UGA) halt protein synthesis by binding a release factor; they do not add amino acids to the polypeptide chain.

The most common cause of community-acquired pneumonia in both HIV-infected and HIV-uninfected individuals is

Streptococcus pneumoniae. Risk of invasive pneumococcal disease is significantly increased in patients with HIV regardless of CD4 count.

The Haemophilus influenzae serotype b vaccine consists of a capsular polysaccharide conjugated to a carrier protein (tetanus toxoid [TT] protein or outer membrane protein [OMP] of Neisseria meningitidis). Protein conjugation causes a

T cell-mediated immune response leading to long-term immunity through production of memory B-lymphocytes.

Type IV (delayed) hypersensitivity reactions (eg, Candida extract skin test, contact dermatitis) are characterized by erythema and induration that develops 24-48 hours after repeat exposure to an antigen. What mediate the inflammation in these reactions through cytokine release, CD8+ cytotoxicity, and macrophage recruitment?

T lymphocytes

Interferon-gamma (IFN-γ) release assays test for latent tuberculosis infection by measuring the amount of IFN-γ released by

T lymphocytes when exposed to antigens unique to Mycobacterium tuberculosis.

Common complications of psoriasis include

psoriatic arthritis, nail changes, and uveitis.

Lithium is commonly used to treat bipolar disorder. Its use during pregnancy is associated with Ebstein's anomaly, which is characterized by

apical displacement of the tricuspid valve leaflets, decreased right ventricular volume, and atrialization of the right ventricle.

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.

Aplastic anemia is most commonly due to a toxic effect or autoimmune response causing

apoptosis of pluripotent stem cells (pancytopenia). Bone marrow biopsy reveals hypocellularity with an abundance of fat cells.

In silicosis, internalized silica particles impair macrophage function by disrupting phagocytosis and promoting

apoptosis. This increases the risk of mycobacteria infection (particularly M tuberculosis).

The resting membrane potential is the difference in the electrical charges across the cell membrane under steady-state conditions. The ions that are most permeable to the cell membrane make the largest contribution to the resting membrane potential. In general,

a high potassium efflux and some sodium influx are responsible for the value of the resting potential, which is typically about -70 mV.

Glioblastoma is the most common primary cerebral neoplasm of adults that is typically located within the cerebral hemispheres and may cross the midline ("butterfly glioma"). These tumors are

highly malignant and grossly contain areas of necrosis and hemorrhage.

Volume contraction and expansion can be divided into isosmotic, hyposmotic, and hyperosmotic states. Hyperosmotic volume contraction is caused by

a loss of free water (with retention of electrolytes). It can occur in patients with diabetes insipidus or as a result of decreased fluid intake/excessive sweating.

Use of concentrated oxygen therapy for neonatal respiratory distress syndrome may be complicated by retinopathy of prematurity. This abnormal retinal neovascularization is

a major cause of blindness in developed nations.

Aging is associated with steady decreases in chest wall compliance but increases in lung compliance due to a loss of elastic recoil. This results in

a marked increase in residual volume, a decrease in forced vital capacity, and relatively unchanged total lung capacity.

Annular pancreas, or pancreatic tissue encircling the descending duodenum, is caused by failure of the ventral pancreatic bud to properly migrate and fuse with the dorsal bud during the seventh and eighth week of fetal development. Annular pancreas is usually

asymptomatic but may present with duodenal obstruction or pancreatitis.

Contraction initiation in cardiac and smooth muscle cells is dependent on extracellular calcium influx through L-type calcium channels, which can be prevented by calcium channel blockers (eg, verapamil). Skeletal muscle is resistant to calcium channel blockers, as calcium release by the sarcoplasmic reticulum is triggered by

a mechanical interaction between L-type and RyR calcium channels.

Thiazolidinediones (TZDs) lower blood glucose by decreasing insulin resistance. TZDs activate peroxisome proliferator-activated receptor gamma,

a nuclear receptor that alters the transcription of genes involved in glucose and lipid metabolism.

Acne is characterized by the obstruction of pilosebaceous follicles (ie, comedones) due to hyperkeratinization and excessive sebum accumulation. Androgens stimulate production of sebum, which serves as

a nutrient source for Cutibacterium acnes. Within the follicles, C acnes proliferation triggers an inflammatory response, resulting in formation of red papules and pustules.

Thiazide diuretics decrease intravascular fluid volume, which stimulates aldosterone secretion and leads to

increased excretion of potassium and hydrogen ions in the urine. This results in hypokalemia and metabolic alkalosis.

The underlying biochemical feature of megaloblastosis is a defect in DNA synthesis. In chronic alcoholics, megaloblastic macrocytic anemia can result from

a nutritional deficiency of vitamin B12 or of folate, which impairs synthesis of purine and pyrimidine bases.

Central retinal artery occlusion presents with sudden, painless, and permanent monocular blindness. Funduscopic examination reveals

a pale retina and a "cherry-red" macula.

A communicating hydrocele results when serous fluid accumulates within the tunica vaginalis in the setting of

a patent processus vaginalis. It presents as a painless swelling that transilluminates on examination.

If a protein is targeted for lysosomes:

a golgi body phosphotransferase enzyme must catalyze the phosphorylation of mannose residues on the proteins to allow them to traverse the golgi network and ultimately be transported to the lysosome

CD8+ cells recognize foreign antigens presented with MHC class I proteins. Each MHC class I molecule consists of

a heavy chain and a β2-microglobulin.

External hemorrhoids drain via the

inferior rectal vein into the internal pudendal vein, which communicates with the internal iliac veins

Most kidney stones are made of calcium salts and are idiopathic, but conditions that increase renal calcium excretion can increase the risk of stones. Hyperparathyroidism is

a common cause of recurrent kidney stones and is typically associated with mild hypercalcemia and hypophosphatemia.

Gallstone ileus is a mechanical bowel obstruction caused when a large gallstone erodes into the intestinal lumen. Pneumobilia (air in the biliary tract) is

a common finding.

Organophosphates are acetylcholinesterase inhibitors that are commonly used as agricultural pesticides. Toxicity is characterized by signs of cholinergic excess (eg, miosis, bronchospasm, muscle fasciculations/weakness, diarrhea, vomiting, lacrimation). First-line therapy is atropine,

a competitive inhibitor of acetylcholine at the muscarinic receptor.

Prion diseases are rapidly progressive neurodegenerative disorders caused by the accumulation of an abnormally folded protein within the brain. Prion proteins are normally found in an alpha helix form;

a conformation change into a beta-sheet form confers resistance to proteases and can trigger similar conformational changes in other normally folded proteins. Characteristic microscopic findings include spongiform degeneration of the gray matter with vacuolization of neurons, gliosis, and cyst formation.

In chronic obstructive pulmonary disease, air-trapping leads to an increase in residual volume (RV) and total lung capacity (TLC), as well as an increase in the RV/TLC ratio. Airway obstruction causes

a decrease in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and the FEV1/FVC ratio.

Pulmonary function testing in cystic fibrosis reveals an obstructive pattern, characterized by

a decreased FEV1/FVC ratio and an increased total lung capacity and residual volume.

Deficiency of vitamin B12 is associated with both megaloblastic anemia and neurologic dysfunction, while folate deficiency is associated with megaloblastic anemia alone. Moderate improvement in the hemoglobin level often occurs when

a deficiency in vitamin B12 is treated with folate, or vice versa. Treatment of vitamin B12 deficiency with folate alone can actually worsen neurologic dysfunction.

The medial femoral circumflex artery and its branches provide the majority of the blood supply to the femoral head and neck. Injury to these vessels due to

a displaced femoral neck fracture can cause osteonecrosis of the femoral head.

Nondisjunction is the failure of chromosome pairs to separate properly during cell division. This could be due to

a failure of homologous chromosomes to separate in meiosis I or a failure of sister chromatids to separate during meiosis II or mitosis.

Type 1 diabetes mellitus typically presents subacutely with polyuria and polydipsia accompanied by fatigue and weight loss. The diagnosis can be confirmed with

a fasting blood glucose or hemoglobin A1c measurement.

The changes in the log dose-response curve expected for the effect of a reversible competitive antagonist added to

a full agonist are: 1) a parallel shift to the right in the log-dose response curve, illustrating an increase in the ED50, and 2) no change in the maximum effect (Emax).

CNS injury is associated with astrocyte hypertrophy and proliferation (gliosis). This process leads to the formation of

a glial scar, which compensates for the volume loss that occurs after neuronal death.

Unilateral renal artery stenosis causes hypoperfusion and activation of the renin-angiotensin-aldosterone system. Angiotensin II causes arteriolar vasoconstriction and increases aldosterone and antidiuretic hormone synthesis. The resultant hypertension helps reduce the decline in glomerular filtration rate in the affected kidney, but causes

a pressure natriuresis with increased sodium excretion in the unaffected kidney.

Carotid sinus hypersensitivity is most commonly seen in elderly men and involves an exaggerated vasovagal response to tactile stimulation of carotid sinus baroreceptors (eg, adjusting a shirt collar or necktie). The resulting increase in parasympathetic output leads to

a prolonged sinus pause that contributes to the excessive drop in blood pressure, leading to transient loss of cerebral perfusion that manifests as presyncope (eg, lightheadedness) or syncope.

Common side-effects of ACE-inhibitors include decreased glomerular filtration rate (GFR), hyperkalemia, and cough. Angioedema is

a rare, but life-threatening, side-effect.

Chronic aortic regurgitation (AR) causes

a reduction in diastolic blood pressure and a compensatory increase in left ventricular stroke volume. These changes create a high-amplitude, rapid rise-rapid fall pulsation (ie, widened pulse pressure) and the other characteristic findings of AR (eg, head bobbing, "pistol-shot" femoral pulses).

akathisia is an extrapyramidal side effect of antipsychotic medication characterized by inner restlessness and an inability to sit or stand in one position. Treatment involves

a reduction in the antipsychotic dose, if possible, or the addition of a beta blocker or benzodiazepine.

In chronic aortic regurgitation, persistent left ventricular volume overload triggers eccentric hypertrophy, which causes a compensatory increase in stroke volume to maintain cardiac output. This compensatory mechanism allows for

a relatively long asymptomatic period in most patients; however, left ventricular dysfunction eventually occurs, leading to heart failure.

Hyperprolactinemia suppresses secretion of GnRH, which leads to reduced estrogen in women. Low estrogen levels are

a risk factor for accelerated bone loss.

Delayed cerebral ischemia due to cerebral vasospasm usually presents 3-12 days after the initial subarachnoid hemorrhage (SAH) with an acute change in mental status and/or new focal neurological deficits. Nimodipine

a selective calcium channel blocker, improves outcomes in patients with cerebral vasospasm by inducing cerebral vasodilation and decreasing calcium-dependent excitotoxicity.

Kawasaki disease is a vasculitis of medium-sized arteries that presents with persistent fever for >5 days, bilateral conjunctivitis, cervical lymphadenopathy, and mucocutaneous involvement. Coronary artery aneurysms are

a serious complication of Kawasaki disease.

Dizygotic twins occur due to fertilization of 2 oocytes by 2 different sperm, can be different sexes, and almost always have 2 chorions and 2 amnions (eg, dichorionic/diamniotic). In contrast, monozygotic twins arise from the fertilization of

a single oocyte, are the same sex, and can be dichorionic/diamniotic (days 0-4), monochorionic/diamniotic (days 4-8), monochorionic/monoamniotic (days 8-12), or monochorionic/monoamniotic conjoined twins (> 13 days).

Stress-induced (takotsubo) cardiomyopathy is characterized by hypokinesis of the mid and apical segments and hyperkinesis of the basal segments of the left ventricle, resulting in systolic dysfunction. The condition is likely caused by

a surge of catecholamines in the setting of physical or emotional stress. It usually affects postmenopausal women and resolves on its own within several weeks.

Simvastatin decreases hepatic cholesterol production, while cholestyramine increases hepatic cholesterol and bile acid synthesis. Combination therapy results in

a synergistic reduction in plasma LDL level.

cerebral arteriovenous malformations are vascular malformations histologically characterized by

a tangle of abnormal vessels, including large veins with thickened walls and irregular arteries AVMs may present with intracranial hemorrhage, headache, and/or seizures radiologic findings include abnormal vasculature with a "bag of worms" appearance and multiple dark flow voids

Mitochondrial DNA (mtDNA) is the most common non-nuclear DNA found in eukaryotic cells. It resembles prokaryotic DNA and is maternally derived. Mutations involving mtDNA (or nuclear DNA that codes for mitochondrial proteins) can cause

a variety of mitochondrial disorders, including Leigh syndrome and MELAS.

Botulinum neurotoxin produced by Clostridium botulinum prevents the release of

acetylcholine from presynaptic nerve terminals. The toxin impairs peripheral muscarinic and nicotinic neurotransmission, causing both autonomic symptoms (eg, fixed pupillary dilation, dry mouth) and skeletal muscle weakness (eg, diplopia, dysphagia, respiratory depression). Its effects at the neuromuscular junction can be seen on electromyography as a decrease in muscle response following stimulation of a motor nerve.

Echinococcus granulosus is the most common cause of hydatid cysts. Spilling of cyst contents can cause

anaphylactic shock. Surgical manipulation should be performed with caution.

Metronidazole is used to treat trichomonal vaginitis and bacterial vaginosis. It can cause disulfiram-like effects, which are

abdominal cramps, nausea, headache when combined with alcohol due to acetaldehyde accumulation

Acute intermittent porphyria is an autosomal dominant condition caused by porphobilinogen deaminase deficiency. Most patients remain asymptomatic, but a minority present with acute attacks characterized by

abdominal pain and vomiting, peripheral neuropathy, neuropsychological symptoms, and reddish-brown urine. Treatment consists of intravenous glucose or heme preparations, which downregulate ALA synthase activity.

Which nerve is most likely to be damaged by an expanding aneurysm?

abducens nerve compression or stretching of the nerve results in ipsilateral lateral rectus weakness, which can cause esotropia or inward eye deviation and horizontal diplopia (double vision) that is worse when looking toward the side of the lesion

Both unfractionated heparin and LMWH can bind to antithrombin to increase its activity against Factor Xa. Only unfractionated heparin is

able to bind to both antithrombin and thrombin to allow antithrombin to inactivate thrombin.

Migraines are episodic, unilateral, throbbing headaches associated with nausea, vomiting, and sensitivity to light. The pathogenesis of migraines involves a genetic predisposition to increased cerebral excitability (eg, cortical spreading depression), which leads to

abnormal neuronal activation of trigeminal afferents and the release of calcitonin gene-related peptide, a vasoactive neuropeptide involved in the transmission of pain signals.

Lynch syndrome is an autosomal dominant disease caused by

abnormal nucleotide mismatch repair. The mismatch repair system involves several genes, including MSH2 and MLH1, which code for components of the human MutS and MutL homologs. Mutations in these 2 genes account for around 90% of cases of Lynch syndrome.

Debranching enzyme deficiency (Cori disease) leads to accumulation of glycogen with

abnormally short outer chains (limit dextrins) due to the inability to degrade α-1,6-glycosidic branch points. Patients present with hypoglycemia, ketoacidosis, hepatomegaly, and muscle weakness and hypotonia.

Migraine is an episodic disorder characterized by severe, often unilateral headache, commonly associated with nausea and sensitivity to light and sound. Treatment is divided into

abortive therapy (eg, mild analgesics, triptans, antiemetics, ergotamines) for acute symptoms and preventive therapy (eg, beta blockers, tricyclic antidepressants, anticonvulsants [topiramate, valproate]) to reduce the frequency of headaches.

CGD can be diagnosed by

absence of fluorescent green pigment on dihydrorhodamine flow cytometry testing or an abnormal nitroblue tetrazolium test

Isosorbide dinitrate has a low bioavailability due to extensive first-pass hepatic metabolism prior to release in systemic circulation. Sublingual nitroglycerin is

absorbed directly from oral mucosa into the venous circulation and has a higher bioavailability.

Auer rods are deformed azurophilic granules found in the cytoplasm of myeloblasts that stain positively for myeloperoxidase. Auer rods are found in

abundance in AML M3 (acute promyelocytic leukemia).

The amyloid precursor protein gene is located on chromosome 21. The extra copy of APP present in trisomy 21 is thought to:

accelerate amyloid accumulation and lead to early-onset AD

The recurrent laryngeal nerve travels in close proximity to the

inferior thyroid artery and can be injured during thyroid surgery, resulting in vocal cord paralysis (eg, hoarseness).

Loperamide is an opioid agonist that exerts its antidiarrheal effects by binding to mu opiate receptors in the colonic myenteric plexus, which inhibits

acetylcholine release, decreases intestinal smooth muscle activity, and slows peristalsis. It undergoes high first-pass metabolism and does not cross the blood-brain barrier, thus avoiding systemic opiate-related adverse events (eg, sedation, respiratory depression).

Competitive inhibitors compete with substrate for active binding sites on enzymes. Additional substrate is required to

achieve the same rate of reaction, increasing the measured value of the Michaelis constant (Km). Competitive inhibitors do not affect enzyme function; therefore, maximal velocity (Vmax) is unchanged in their presence.

MHC class II is expressed on the surface of antigen presenting cells (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.

Adverse effects associated with the use of excessive doses of anabolic steroids include

acne, gynecomastia, azoospermia, decreased testicular size, and increased aggression. When measured, serum testosterone is typically normal or elevated. However, endogenous testosterone production and spermatogenesis are decreased.

Malignancy is a common cause of pericardial effusion, which is often subacute due to slower accumulation of pericardial fluid with compensatory pericardial stretching. Pericardiocentesis can

acquire fluid for cytologic analysis (eg, atypical cells) to help confirm the etiology.

Riboflavin is a precursor of the coenzymes FMN and FAD. FAD participates in the tricarboxylic acid cycle and electron transport chain by

acting as an electron acceptor for succinate dehydrogenase (complex II), which converts succinate into fumarate.

Hereditary pulmonary arterial hypertension develops in 2 steps. An abnormal BMPR2 gene predisposes affected individuals to excessive endothelial and smooth muscle cell proliferation. An insult (eg, infection, drugs) is thought to then

activate the disease process, resulting in vascular remodeling, increased pulmonary vascular resistance, and progressive pulmonary hypertension.

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.

Beta blockers inhibit release of renin from renal juxtaglomerular cells through antagonism of beta-1 receptors on these cells. Inhibition of renin release prevents

activation of the renin-angiotensin-aldosterone pathway, which results in decreased vasoconstriction and decreased renal sodium and water retention.

Cardiorenal syndrome is due to hemodynamic alterations related to a low cardiac output state and maladaptive neurohormonal changes. Low cardiac output results in renal hypoperfusion, leading to

activation of the renin-angiotensin-aldosterone system, antidiuretic hormone release, and increased sympathetic nervous system activity. The resultant increase in sodium and water reabsorption and systemic vasoconstriction have detrimental effects on left ventricular systolic function, further worsening cardiac output and renal perfusion.

Asthma and chronic obstructive pulmonary disease (COPD) exacerbation are the most frequent causes of pulsus paradoxus in the absence of significant pericardial disease. Beta-adrenergic agonists control

acute asthma and COPD exacerbations by causing bronchial smooth muscle relaxation via increased intracellular cAMP.

Acute bacterial prostatitis is usually caused by reflux of urine and organisms from the bladder and urethra. The risk is greater in patients with anatomic abnormalities (eg, strictures) or bladder catheterization. Escherichia coli is the most common cause of

acute bacterial prostatitis and other urinary tract infections because of adhesins on its fimbriae that promote adherence to urothelial or mucosal cells.

Patients with Down syndrome are at increased risk of developing

acute lymphoblastic leukemia and acute megakaryoblastic leukemia

The presence of rod-shaped intracytoplasmic inclusions known as Auer rods is characteristic of many forms of

acute myeloblastic leukemia (AML). The M3 variant of AML, acute promyelocytic leukemia, is associated with the cytogenetic abnormality t(15;17).

Hypovolemia (eg, excessive diuresis) can cause acute kidney injury due to reduced renal blood flow (prerenal azotemia). Urine sodium and fractional excretion of sodium levels are low, and the BUN/creatinine ratio is elevated. In severe cases,

acute tubular necrosis can occur and cause an intrinsic renal injury pattern (ie, high urine sodium, normal BUN/creatinine ratio) with muddy brown casts on urinalysis.

retinal artery occlusion is a cause of

acute, painless, monocular vision loss usually caused by thromboembolic complications of atherosclerosis traveling from the internal carotid artery and through the ophthalmic artery

The second most common cause of severe combined immunodeficiency is autosomal recessive deficiency of adenosine deaminase, an enzyme necessary for the elimination of excess adenosine within cells. Toxic levels of

adenosine accumulate within lymphocytes in this condition, leading to lymphocyte cell death and resultant cellular and humoral immunodeficiency. Patients with this condition can be treated with hematopoietic cell transplantation or gene therapy.

Bacillus anthracis edema factor is an adenylate cyclase that increases intracellular cyclic AMP, leading to neutrophil and macrophage dysfunction and tissue edema. This mechanism of action is similar to that of

adenylate cyclase toxin, produced by Bordetella pertussis

Degradation of circulating insulin in the kidneys is dependent on:

adequate GFR, which allows for delivery of insulin to the proximal tubule cells where it is broken down

The alternative hypothesis:

is a statement of difference or association

The null hypothesis:

is a statement of no difference or no association

Asthma is characterized by reversible airway obstruction, and lung function tests may be normal between exacerbations. Bronchoprovocation can be used to aid diagnosis in patients with normal spirometry; methacholine is

administered and followed by serial spirometry. Patients with asthma demonstrate hyperresponsivity to the stimulus, leading to FEV1 reductions at lower doses than in those without asthma.

Malignant hyperthermia presents with widespread muscle rigidity after

administration of inhalation anesthetics and/or succinylcholine to genetically susceptible individuals. It is treated with dantrolene, which blocks ryanodine receptors to prevent the release of calcium from the sarcoplasmic reticulum into the cytoplasm of skeletal muscle fibers.

This patient's markedly elevated blood urea nitrogen (BUN) and serum creatinine in the setting of uncontrolled hypertension suggest

advanced chronic kidney disease (CKD), a condition commonly presenting with fatigue, generalized weakness, and evidence of volume overload (eg, jugular venous distension, peripheral edema). Once CKD becomes advanced (eg, serum creatinine >3 mg/dL), anion gap metabolic acidosis with respiratory compensation is expected.

Nonbacterial thrombotic endocarditis is a form of noninfectious endocarditis characterized by valvular deposition of sterile platelet-rich thrombi. It likely results from valvular damage due to inflammatory cytokines in the setting of an underlying hypercoagulable state, and it is most commonly seen with

advanced malignancy (especially mucinous adenocarcinoma) or systemic lupus erythematosus.

Empyema is 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.

Osteoarthritis is characterized by progressive fissuring and erosion of articular cartilage. Risk factors include

advancing age, obesity, joint trauma, and repetitive stress. Patients may have mild effusion and crepitus on physical examination, but signs of synovitis (eg, redness, warmth) are less prominent than in the classic inflammatory arthritic disorders.

The treatment of myasthenia gravis involves the use of a cholinesterase inhibitor, immunosuppressants, and possible thymectomy. Cholinesterase inhibitors may cause

adverse effects related to muscarinic overstimulation, which can be ameliorated by the use of an antimuscarinic agent such as glycopyrrolate, hyoscyamine, or propantheline.

Pappenheimer bodies

aggregated iron deposits in erythrocytes that are often seen in patients with sideroblastic anemia appear as dark blue inclusions

Hemorrhagic cystitis during therapy with cyclophosphamide or ifosfamide is caused by the urinary excretion of the toxic metabolite acrolein. It can be prevented by

aggressive hydration, bladder irrigation, and administration of mesna, a sulfhydryl compound that binds acrolein in the urine.

Lipofuscin is the product of lipid peroxidation, accumulating in

aging cells (especially in patients with malnutrition and cachexia).

Selective estrogen receptor modulators (eg, tamoxifen, raloxifene) are competitive inhibitors of estrogen binding to estrogen receptors. They can have

agonist or antagonist effects depending on the specific tissue. Tamoxifen has an estrogenic effect on the uterus and can cause endometrial hyperplasia and cancer.

How is measles transmitted?

airborne or person-to-person contact

Ethylene glycol and methanol are toxic alcohols that cause anion gap metabolic acidosis and an elevated osmolar gap. Toxicity occurs after metabolization by

alcohol dehydrogenase; fomepizole is a competitive inhibitor of alcohol dehydrogenase and is used for the treatment of acute poisoning

Meckel's diverticulum is a remnant of the omphalomesenteric (vitelline) duct. It is connected to the ileum and is located 2 feet proximal to the ileocecal valve. It often contains acid-secreting ectopic gastric tissue, which may cause ulceration of the adjacent mucosa and lower GI bleeding (melena/hematochezia). Meckel's diverticulum is a true diverticulum and consists of

all parts of the intestinal wall.

A bursa is a fluid-filled synovial sac that serves to

alleviate pressure from bony prominences and reduce friction between muscles and tendons. Acute trauma or chronic repetitive pressure can cause injury, leading to localized pain and tenderness. Prepatellar bursitis causes anterior knee pain and is usually due to repetitive or prolonged kneeling

A permissive hormone has no effect on a physiologic process by itself but

allows another hormone to exert its maximal effect on that process. Cortisol exerts a permissive effect on catecholamines to potentiate vasoconstriction and bronchodilation; it also has a permissive effect on glucagon to increase glucose release from the liver.

Listeria monocytogenes is a facultative intracellular, gram-positive rod that most often causes febrile gastroenteritis. Pathogenesis is mediated largely by listeriolysin O, an enzyme that creates pores in phagosomes, which

allows the bacteria to escape lysosomal destruction. Pregnant women in the third trimester are at greatest risk; infection increases the risk of fetal demise, early labor, and neonatal infection.

Dupuytren contracture is caused by progressive fibrosis of the superficial palmar fascia due to excessive fibroblast proliferation. Pathognomonic fibrotic nodules and cords form

along the flexor tendons, limiting extension of the affected digits.

Where do the immune complexes in post-streptococcal glomerulonephritis deposit?

along the glomerular basement membrane They are visible on electron microscopy as large, dome-shaped, subepithelial, electron-dense deposits ("humps"). They can be further visualized on immunofluorescence as granular deposits of IgG, IgM, and C3 along the GBM and glomerular mesangium ("lumpy-bumpy" appearance)

The rubber-like properties of elastin are due to high content of nonpolar (hydrophobic) amino acids and extensive cross-linking between elastin monomers facilitated by lysyl oxidase. Patients with

alpha-1 antitrypsin deficiency can develop early-onset, lower lobe-predominant emphysema due to excessive alveolar elastin degradation.

Norepinephrine potently stimulates

alpha-1 receptors to cause peripheral vasoconstriction, increasing systemic vascular resistance and blood pressure. This triggers a baroreceptor-mediated reflexive decrease in heart rate that completely offsets or overrides the direct beta-1-mediated increase in heart rate caused by norepinephrine, resulting in overall unchanged or slightly decreased heart rate.

Epinephrine increases heart rate, myocardial contractility, and cardiac output by stimulating B1 receptors. At high doses, stimulation of:

alpha1 induced vasoconstriction in the skin and viscera become more pronounced.

Autologous hematologic stem cell transplantations reinfuse host cells from the peripheral blood or banked cord blood to reconstitute the bone marrow. Because the cells are genetically identical to the host, there is no risk of graft rejection or graft versus host disease. Although there is

also no risk of transferring a new bloodborne pathogen, chronic or latent infections (eg, Epstein-Barr virus, cytomegalovirus, varicella zoster virus) may worsen due to immunosuppression following myeloablative chemotherapy.

Growth hormone binds to cell surface receptors, leading to intracellular activation of the JAK-STAT pathway. Cytokines (eg, interferon) and hematopoietic growth factors (eg, erythropoietin, G-CSF)

also use this pathway.

Ethylene glycol ingestion causes acute tubular necrosis with vacuolar degeneration and ballooning of the proximal tubular cells. Typical clinical findings include

altered mentation, renal failure, high anion gap metabolic acidosis, increased osmolar gap, and calcium oxalate crystals in the urine.

Alpha-1 antitrypsin (AAT) is a serine protease inhibitor that regulates the activity of elastase in the lung. Inherited deficiency of AAT leads to

alveolar destruction and panacinar emphysema; in addition, accumulation of improperly folded AAT proteins in hepatocytes can lead to liver dysfunction and cirrhosis in some patients.

The secretion of prolactin is controlled by the inhibitory effect of hypothalamic dopamine. Risperidone and other antipsychotics cause hyperprolactinemia by blocking D2 receptors on lactotrophs. Elevated prolactin leads to

amenorrhea (inhibition of gonadotropin-releasing hormone release), galactorrhea, and breast soreness.

Transfer RNA (tRNA) is a small, noncoding form of RNA that contains chemically modified bases (eg, dihydrouridine, ribothymidine, pseudouridine). tRNA has a CCA sequence at its 3'-end that is used as a recognition sequence by proteins. The 3' terminal hydroxyl group of the CCA tail serves as the

amino acid binding site

The 3' CCA tail of tRNA serves as the

amino acid binding site. Aminoacyl tRNA synthetase is the enzyme responsible for "loading" the appropriate amino acid to the 3' terminal hydroxyl group of the CCA tail.

Transamination reactions typically occur between an amino acid and an α-keto acid. The amino group from the amino acid is transferred to the α-keto acid, and the α-keto acid in turn becomes an

amino acid. Pyridoxal phosphate (active vitamin B6) serves as a cofactor in amino acid transamination and decarboxylation reactions.

Pseudomonas aeruginosa is a major pathogen in burn patients. Only a few specific penicillins (eg, ticarcillin, piperacillin) and cephalosporins (eg, ceftazidime, cefepime) have activity against it. Certain

aminoglycosides, fluoroquinolones (eg, ciprofloxacin, levofloxacin), and carbapenems (eg, imipenem, meropenem) are also effective.

A radioimmunoassay uses specific antibodies and a fixed quantity of radiolabeled antigen to determine the

amount of antigen present in an unknown sample. This is done by measuring the amount of radiolabeled antigen displaced from the antibodies in the system.

Alzheimer dementia typically presents insidiously with memory loss (especially of recent events), executive dysfunction, and visuospatial impairment. Classic histopathologic findings include

amyloid plaques (central amyloid beta core surrounded by dystrophic neurites) and neurofibrillary tangles (aggregates of hyperphosphorylated tau protein).

common adverse effects of PPIs include malabsorption of calcium, iron, magnesium, and vitamin B12 because absorption depends on:

an acidic environment

McCune-Albright syndrome is characterized by the triad of fibrous dysplasia of the bone, endocrine abnormalities, and café-au-lait spots. The condition results from

an activating mutation in the G protein/CAMP/adenylate cyclase signaling pathway.

Patella fractures are most commonly due to a direct impact to the anterior aspect of the knee. Signs include

an acutely swollen knee, focal patella tenderness, inability to extend the knee against gravity, and a palpable gap in the extensor mechanism.

Approximately 25% of patients with active TB have false-negative tuberculin skin testing (TST) (anergy) due to

an impaired cell-mediated immune response. These individuals are at greater risk for severe, disseminated disease and death. False-negative TST can also be seen with immunocompromise, improper injection technique, and recent infection.

Bupropion is a first-line antidepressant that is not associated with sexual side effects or weight gain. However, it is associated with

an increased seizure risk at high doses and is contraindicated in patients with seizure disorders, anorexia nervosa, and bulimia.

West Nile virus is harbored in birds and transmitted to humans by mosquitos. Most patients are asymptomatic, but the virus can cause

an influenza-like illness or neuroinvasive disease with meningitis, encephalitis, and flaccid paralysis.

Ocular manifestations in giant cell arteritis (temporal arteritis) can lead to rapid, severe, and irreversible vision loss. Involvement of the ciliary arteries in GCA leads to

anterior ischemic optic neuropathy, which presents with a painless, rapidly progressive decrease in visual acuity. Treatment includes systemic glucocorticoids (eg, prednisone, methylprednisolone).

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.

Major adaptive immune mechanisms that prevent reinfection with the influenza virus include

anti-hemagglutinin antibodies.

Elevated blood glucose induces the release of reactive oxygen species and proinflammatory cytokines from neutrophils while inhibiting the production of

anti-inflammatory cytokines (eg, IL-10) and growth factors needed for fibroblast proliferation and re-epithelialization in a healing wound. As a result, patients with uncontrolled diabetes frequently have nonhealing wounds with evidence of ongoing inflammation.

Most tumors possess multiple cytogenetic abnormalities. Activation of proto-oncogenes results in stimulation of cellular proliferation. Inactivation of

anti-oncogenes eliminates oversight of the cell cycle.

BRM, biologic response modifiers, include

antibodies, cytokines, and other substances intended to restore or induce the immune system's ability to overcome disease

IL-4 is produced by the TH2 subset of T helper cells. It facilitates proliferation of B cells and TH2 lymphocytes and stimulates

antibody isotype switching to IgE which mediates type I hypersensitivity (allergic) reactions.

Immunosenescense is the normal age-related decline that impairs most aspects of immune function, including the production of naive B and T cells. This results in a diminished

antibody-based immune response to novel antigens (eg, infections, vaccinations). The immune response to previously experienced pathogens is typically intact due to normal or increased levels of memory B and T cells and preserved antibody quality.

Eosinophils play a role in host defense during multicellular parasitic infection. When stimulated by antibodies bound to a parasitic organism, they destroy the parasite via

antibody-dependent cell-mediated cytotoxicity with enzymes from their cytoplasmic granules. Another function of eosinophils is regulation of type I hypersensitivity reactions.

First-generation antihistamines are nonspecific and interact with multiple receptors, including the muscarinic receptor. This leads to

anticholinergic effects (eg, fever, flushing, mydriasis, urinary retention, tachycardia, altered mental status).

The Beers criteria identify drugs that should be used with caution in geriatric patients. Common drugs to avoid include

anticholinergics (eg, first-generation antihistamines), centrally acting alpha-2 agonists, tricyclic antidepressants, benzodiazepines (and other sedating medications), antipsychotics, many antiarrhythmics (eg, digoxin), and skeletal muscle relaxants.

Vulvovaginal candidiasis typically presents with thick, white, clumpy vaginal discharge, vulvovaginal erythema and pruritus, and pseudohyphae on wet mount microscopy. Treatment is with an

antifungal medication (eg, fluconazole).

Bacillus anthracis is a large, sporulating, gram-positive rod that is encased in an

antiphagocytic polypeptide capsule composed of D-glutamic acid. Inhalation of B anthracis spores can cause pulmonary anthrax, which is usually characterized by nonspecific symptoms followed by hemorrhagic mediastinitis, shock, and death.

Transient ischemic attacks (TIAs) are transient episodes of focal neurologic impairment that occur due to local brain ischemia; tissue infarction does not occur, and brain imaging is normal. Patients with TIA are at increased risk of future stroke; secondary prevention includes

antiplatelet agents (eg, aspirin, clopidogrel), statins, and lifestyle modifications (eg, tobacco cessation, exercise) to reduce future risk.

drug of choice for treatment-resistant schizophrenia

antipsychotic clozapine Treatment requires monitoring of the absolute neutrophil count due to the risks of neutropenia and agranulocytosis

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are

antiretroviral drugs that do not require activation via intracellular phosphorylation. The more common NNRTIs include nevirapine and efavirenz.

Enoxaparin is a low-molecular-weight heparin (LMWH) that functions like heparin in that it binds and activates

antithrombin III (AT III). Activated AT III binds to factor Xa and stops factor Xa from converting prothrombin to thrombin. Due to its fewer number of molecules, LMWH acts primarily on factor Xa, not thrombin.

Panic disorder consists of recurrent and unexpected panic attacks characterized by an abrupt surge of anxiety and distressing cardiopulmonary/neurologic symptoms. Agoraphobia, a common comorbid disorder, results in

anxiety about and avoidance of situations where patients may feel trapped and helpless in the event of a panic attack (eg, crowds, enclosed spaces, public transportation).

Benzodiazepine withdrawal is characterized by

anxiety, tremor, insomnia, and sympathetic hyperactivity (eg, diaphoresis, palpitations). Severe benzodiazepine withdrawal may also be accompanied by psychosis, seizures, or death.

Highly-active antiretroviral therapy (HAART) for HIV is commonly associated with body fat redistribution. Subcutaneous lipoatrophy involving the face and extremities is associated with nucleoside reverse transcriptase inhibitors (especially stavudine and zidovudine) and protease inhibitors. Central fat accumulation in the trunk and viscera can occur with

any HAART regimen.

Analysis of the variance is used to determine whether there are:

any significant differences between the means of several independent groups ANOVA compares the means between the groups relative to the variability within the groups (F-test) and determines whether any of those means are significantly different from one another

Ruptured abdominal aortic aneurysm is a surgical emergency that usually presents with the acute onset of severe abdominal and back pain in patients with

appropriate risk factors (eg, advanced age, smoking, atherosclerosis). Accompanying syncope, hypotension, and shock may occur quickly (intraperitoneal rupture) or may be delayed (retroperitoneal rupture).

The femoral triangle (lateral to medial) consists of the femoral nerve, femoral artery, femoral vein, and deep inguinal nodes/lymphatic vessels. Cannulation of the femoral vein should occur

approximately 1 cm below the inguinal ligament and just medial to the femoral artery pulsation.

Dipalmitoyl phosphatidylcholine (lecithin, L) and phosphatidylglycerol are major constituents of surfactant. Fetal lung lecithin production increases sharply after 30 weeks gestation, and phosphatidylglycerol production increases at 36 weeks gestation. The amniotic fluid sphingomyelin (S) level should remain

approximately constant during the third trimester. An L/S ratio > 2.0 indicates adequate surfactant production to avoid neonatal hyaline membrane disease.

Fusion inhibitors (eg, enfuvirtide) bind the HIV transmembrane glycoprotein gp41 and prevent it from

approximating the viral and host cellular membranes, which prevents HIV penetration into new host cells.

Hereditary angioedema is characterized by recurrent episodes of cutaneous and/or mucosal swelling due to C1 inhibitor deficiency. C4 levels

are low due to uninhibited cleavage of C4 by excess activated C1.

Bacterial vaginosis is caused by a disruption of the vaginal bacterial flora and is characterized by a thin, gray-white, malodorous vaginal discharge. Clue cells (squamous epithelial cells with adherent bacteria)

are seen on wet mount microscopy.

Cleavage of proinsulin in pancreatic beta-cell secretory granules yields insulin and C-peptide, which

are stored in the granules until they are secreted in equimolar amounts.

Severe systemic hypotension (eg, shock) is most likely to cause ischemia first in areas of high metabolic demand (eg, hippocampus) or watershed zones, which are areas that

are supplied by the distal branches of two different major arteries. Commonly affected areas in the colon include the splenic flexure and rectosigmoid junction.

Infants born to HBeAg-positive mothers have a high risk of acquiring perinatal hepatitis B virus (HBV) infection. Infected neonates have high levels of HBV replication and are at high risk for chronic infection, but

are usually asymptomatic or have only mildly elevated liver function tests.

Oppositional defiant disorder is a behavioral disorder of childhood characterized by

argumentative and defiant behavior toward authority figures. It does not involve the more severe violations of the basic rights of others seen in conduct disorder.

Subclavian steal syndrome occurs due to severe stenosis of the proximal subclavian artery, which leads to reversal in blood flow from the contralateral vertebral artery to the ipsilateral vertebral artery. Patients may have symptoms related to

arm ischemia in the affected extremity (eg, exercise-induced fatigue, pain, paresthesias) or vertebrobasilar insufficiency (eg, dizziness, vertigo).

Ventricular fibrillation is the most common mechanism of sudden cardiac death due to acute myocardial infarction. It results from

arrhythmogenic foci triggered by electrical instability in the ischemic myocardium.

Aortic stenosis most commonly results from age-related calcific aortic valve disease (CAVD). The early pathogenesis of CAVD closely mimics that of

arterial atherosclerosis. In the later stages, fibroblasts differentiate into osteoblast-like cells and deposit bone matrix, leading to progressive valvular calcification and stenosis.

Perfusion pressure decreases distal to a significant coronary artery stenosis, resulting in an initial decrease in blood flow. Coronary autoregulation stimulates

arteriolar vasodilation, which reduces vascular resistance and helps return blood flow to near-normal levels to prevent myocardial ischemia

Thiazide diuretics work by blocking Na+-Cl- symporters in the distal convoluted tubules, causing enhanced Na, Cl, and water excretion. Since only a small amount of filtered Na+ reaches the distal tubules, thiazides are not

as efficacious as loop diuretics. Unlike loop diuretics, thiazides can cause hypercalcemia.

fungus with dichotomous, branching hyphae, can colonize preexisting lung cavities, creating a fungus ball (aspergilloma):

aspergillus fumigatus

Patients with alcohol use disorder are at increased risk for lung abscess due to

aspiration of oral flora during periods of unconsciousness. Although many cases are polymicrobial, the main pathogens are strict and facultative anaerobic oral flora (eg, Bacteroides, Prevotella, Fusobacterium, Peptostreptococcus). Manifestations include subacute fever, cough, and foul-smelling sputum.

Second-generation antipsychotics block 5-HT2A receptors and have lower binding affinity at dopamine D2 receptor sites, which is

associated with a lower risk of extrapyramidal side effects.

Meningococcal meningitis is a rapidly progressive infection that can spread systemically (ie, meningococcemia) and lead to septic shock, multiorgan failure, and disseminated intravascular coagulation. Meningococcemia is also

associated with bilateral hemorrhagic infarction of the adrenal glands, which can result in acute adrenal insufficiency (Waterhouse-Friderichsen syndrome) with worsening shock and rapid clinical deterioration.

IgE-binding monoclonal antibodies (eg, omalizumab) are effective in treating

asthma that remains uncontrolled despite optimal therapy with bronchodilators and inhaled corticosteroids. IgE-binding monoclonal antibodies reduce airway inflammation by blocking the binding of IgE to the IgE receptors on mast cells and preventing the release of proinflammatory substances, including histamine and leukotrienes.

Accessory nipples are the most common congenital breast anomaly resulting from failed regression of the mammary ridge in utero. They are usually

asymptomatic but can become tender along with breast tissue during times of hormonal fluctuation.

Cryptococcus neoformans is a 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.

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.

Unlike hereditary fructose intolerance (aldolase B deficiency) and classic galactosemia (galactose-1-phosphate uridyl transferase deficiency), essential fructosuria (fructokinase deficiency) is a benign disorder. Although affected patients are

asymptomatic, their urine will test positive for a reducing sugar due to the presence of unmetabolized fructose.

chronic mesenteric ischemia is characterized by

atherosclerosis of the mesenteric arteries, resulting in diminished blood flow to the intestines after meals this causes postprandial epigastric pain (intestinal angina) with associated food aversion/weight loss. Pathogenesis is similar to angina pectoris

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.

Atrial fibrillation is associated with increased risk of systemic thromboembolism. The left

atrial appendage is the most common site of thrombus formation.

Thyrotoxicosis, whether due to endogenous hyperthyroidism or over-replacement with thyroid hormone in patients with hypothyroidism, causes a hyperadrenergic state that can lead to

atrial fibrillation, high-output heart failure, and worsening of angina pectoris

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.

Temporal lobe epilepsy is most commonly due to hippocampal sclerosis. Histopathology of hippocampal sclerosis demonstrates

atrophy of the hippocampal neurons with marked reactive gliosis (astrocyte proliferation in response to injury).

Organophosphates inhibit acetylcholinesterase, leading to symptoms of muscarinic (mnemonic: DUMBELS) and nicotinic (neuromuscular dysfunction) cholinergic hyperstimulation. Management includes

atropine, a competitive inhibitor of acetylcholine at the muscarinic receptor (reverses muscarinic symptoms), followed by pralidoxime, a cholinesterase-reactivating agent that treats both nicotinic and muscarinic symptoms.

Vitiligo is a common condition characterized by the loss of epidermal melanocytes. It occurs more commonly in patients with

autoimmune disorders (eg, autoimmune thyroiditis, type I diabetes) and results in well-defined, variably sized patches of hypopigmentation.

Antinuclear antibodies are found in almost all patients with systemic lupus erythematosus but are also found in many other

autoimmune disorders and have low specificity. Anti-double-stranded DNA antibodies and anti-Smith antibodies have lower sensitivity but higher specificity.

Bullous pemphigoid is characterized by an

autoimmune process that causes the epidermis to separate from the dermis, forming sub-epidermal blisters. It presents with tense, fluid-filled bullae on the inner thighs, forearms, axillae, groin, and abdomen.

Strongyloides stercoralis infection begins following skin penetration by filariform (infectious) larva and can be diagnosed by finding rhabditiform (noninfectious) larvae in the stool. Rhabditiform larvae can mature into filariform larva in the human gastrointestinal tract, precipitating an

autoinfection cycle that occurs entirely within the affected individual. This can result in a hyperinfection syndrome characterized by massive dissemination of the organism, leading to multiorgan dysfunction and septic shock.

Radial head subluxation (ie, nursemaid's elbow) is the displacement of the annular ligament into the radiohumeral joint, classically resulting from sudden axial traction (eg, pulling) on the arm of a child age <5. Although most patients do not have any obvious swelling or deformity, they

avoid moving the arm due to pain and hold it with the elbow flexed and forearm pronated.

Patients experiencing a major depressive episode should be carefully screened for past manic episodes to rule out bipolar disorder. Antidepressant monotherapy should be

avoided in patients with bipolar disorder due to the risk of precipitating mania.

Beta blockers provide rapid relief of the adrenergic-mediated symptoms of thyrotoxicosis and can be given while

awaiting diagnostic evaluation and definitive management.

The caseating granulomas of tuberculosis are almost always surrounded by large epithelioid macrophages with pale pink granular cytoplasm. CD14

is a surface marker specific to the monocyte-macrophage cell lineage.

Achalasia

is an esophageal motility disorder characterized by the absence of esophageal peristalsis in the distal esophagus and incomplete relaxation of a hypertonic lower esophageal sphincter (LES)

As the dosage increases, dopamine begins to stimulate:

b1 adrenergic receptors in the heart, increasing cardiac contractility, heart rate, and systolic blood pressure. At the high end of the dose range, stimulation of alpha1 receptors in the systemic vasculature leads to generalized vasoconstriction which can result in decreased cardiac output due to the increased afterload

Viridans streptococci produce dextrans that aid them in colonizing host surfaces, such as dental enamel and heart valves. These organisms cause subacute

bacterial endocarditis, classically in patients with preexisting cardiac valvular defects after dental manipulation.

Croup is a viral infection in which edema and narrowing of the proximal trachea (ie, subglottis) result in a

barky cough and inspiratory stridor

Gastroesophageal reflux disease is caused primarily by gastroesophageal junction incompetence and can be associated with extraesophageal symptoms (eg, nocturnal cough) in the absence of heartburn ("silent GERD"). Acidic gastric contents irritate the esophageal mucosa, leading to characteristic histologic findings that include

basal zone hyperplasia, elongation of the lamina propria papillae, and scattered eosinophils.

Head and neck squamous cell carcinoma is likely in a patient with cervical adenopathy and a

base of tongue mass, especially with a history of tobacco use. Classic histologic findings include intercellular bridges and keratin pearls.

Short non-coding RNA sequences (eg, microRNA and small interfering RNA) induce posttranscriptional gene silencing by

base-pairing with complementary sequences within target mRNA molecules.

Cystic medial degeneration (necrosis) is the classic histologic finding in aortic dissection, as it weakens the aortic wall and allows a small intimal tear to readily propagate. Collagen, elastin, and smooth muscle are replaced by a

basophilic mucoid extracellular matrix with elastic tissue fragmentation and cystic collections of mucopolysaccharide.

Empyema involves bacterial invasion of the intrapleural space with progressive inflammation, pus accumulation, and organized fibrosis. Drainage 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 fibrinolytic agent (eg, tissue plasminogen activator) in combination with a nucleic acid cleaving enzyme (ie, deoxyribonuclease).

Common side effects of HMG-CoA reductase inhibitors (statins) include muscle and liver toxicity. Hepatic transaminases should

be checked prior to initiating therapy and repeated if symptoms of hepatic injury occur.

Pressure in the left renal vein may become elevated due to compression where the vein crosses the aorta beneath the superior mesenteric artery. This "nutcracker effect" can cause hematuria and flank pain. Pressure can also

be elevated in the left gonadal vein, leading to formation of a varicocele.

Phosphorylation of serine and threonine residues of insulin receptor and insulin receptor substrate by serine kinase leads to insulin resistance. This type of phosphorylation can

be induced by TNF-α, catecholamines, glucocorticoids, and glucagon.

Poststreptococcal glomerulonephritis presents most commonly in children with hematuria, hypertension, and periorbital edema. Red blood cell casts and mild proteinuria may

be present on urinalysis, and serum creatinine may be elevated.

Chronic lymphocytic (Hashimoto) thyroiditis is the most common cause of hypothyroidism. Histopathology characteristically shows an intense lymphocytic infiltrate, often with germinal centers. Residual follicles may

be surrounded by Hürthle cells (large oxyphilic cells filled with granular cytoplasm).

Cryptococcus neoformans is a round/oval yeast with a thick polysaccharide capsule. It is a common cause of meningoencephalitis (eg, headache, vomiting, confusion, seizure) in patients with untreated AIDS. The yeast can frequently

be visualized in the cerebrospinal fluid by India ink or silver stain.

Myxomas are the most common primary cardiac neoplasm, and approximately 80% originate in the left atrium. Patients may have systemic embolization (eg, stroke) or symptomatic mitral valve obstruction that may

be worse with certain body positions. Histopathologic examination reveals amorphous extracellular matrix with scattered stellate or globular myxoma cells within abundant mucopolysaccharide ground substance.

Teratomas are the most common subtype of ovarian germ cell neoplasms and occur most frequently in women age 10-30. Mature teratomas are

benign and show mature tissues derived from multiple germ layers, frequently including skin, hair, and teeth.

Drugs that have been shown to improve long-term survival in patients with heart failure due to left ventricular systolic dysfunction include

beta blockers, ACE inhibitors, angiotensin II receptor blockers, and aldosterone antagonists.

Severe physiologic stress (MI, head injury) results in significant endogenous catecholamine (NE, EP) release. EP activates which receptor?

beta-2 receptor, leading to an increased activity of the Na/K ATPase pump and the Na/K/Cl cotransporter, both of which transport potassium intracellularly

Edrophonium:

short-acting acetylcholinesterase inhibitor used in the diagnosis of myasthenia gravis Through its cholinergic effects, edrophonium reduces heart rate, cardiac conduction, and cardiac contractility.

Brown pigment gallstones are composed of calcium salts of unconjugated bilirubin and arise secondary to bacterial or helminthic infection of the biliary tract. Beta-glucuronidase released by injured hepatocytes and bacteria hydrolyzes

bilirubin glucuronides to unconjugated bilirubin. The liver fluke Clonorchis sinensis has a high prevalence in East Asian countries and is a common cause of pigment stones.

IgA protease is produced by Neisseria meningitidis, N gonorrhoeae, Streptococcus pneumoniae, and Haemophilus influenzae. This enzyme cleaves secretory IgA at its hinge region, rendering it ineffective. Secretory IgA exists on mucosal surfaces and in secretions and acts to

bind and inhibit the action of pili as well as other cell surface antigens that normally mediate mucosal adherence and subsequent penetration.

The cysteinyl-containing leukotrienes (ie, leukotriene C4, D4, and E4) are inflammatory mediators that stimulate bronchoconstriction, bronchial mucus secretion, and bronchial edema to contribute to the pathogenesis of asthma. Leukotriene receptor antagonists (eg, montelukast, zafirlukast) treat asthma by

binding to leukotriene receptors on bronchial smooth muscle cells and blocking these effects.

2,3-bisphosphoglycerate (2,3-BPG) normally forms ionic bonds with the beta subunits of deoxygenated hemoglobin A, facilitating oxygen release in the peripheral tissues. Mutations that result in loss of the 2,3-BPG binding pocket's positive charge cause hemoglobin A to resemble fetal hemoglobin, which

binds oxygen with a higher affinity due to its inability to interact with 2,3-BPG.

Patients with cystic fibrosis have thick, viscous mucus that accumulates in the airways and promotes colonization of bacteria, particularly Pseudomonas. This gram-negative rod can produce

biofilms, which act as a protective matrix that allows bacterial macrocolonies to develop, causing persistent infection.

The anticonvulsant valproate has mood-stabilizing properties and is an effective maintenance treatment for bipolar disorder. Other maintenance options for

bipolar disorder include lithium, lamotrigine, and quetiapine.

Medication-induced esophagitis is a common adverse effect of

bisphosphonates. Bisphosphonates are also associated with increased risk of osteonecrosis of the jaw and atypical femoral fractures.

Severe hypertension in retinal precapillary arterioles causes endothelial disruption, leakage of plasma into the arteriolar wall, and fibrinous necrosis. The necrotic vessels can then

bleed into the nerve fiber layer, which can be seen on examination as dot- or flame-shaped hemorrhages.

Adalimumab is a recombinant human IgG that binds tumor necrosis factor-alpha (TNF-alpha). Antidrug antibodies can develop against adalimumab (or other immunoglobulin-based anti-TNF agents) that can

block its interaction with TNF-alpha, preventing the drug from functioning and leading to more rapid drug clearance.

Ependymomas originate from the ependymal cells that line the ventricular system and the central canal of the spinal cord. Ventricular ependymomas can

block the flow of cerebrospinal fluid through the interventricular foramina, causing signs of increased intracranial pressure (eg, headache, papilledema) due to obstructive (noncommunicating) hydrocephalus.

Diabetic ketoacidosis is initially treated with an intravenous infusion of regular insulin, which allows for rapid adjustments in dose based on

blood glucose levels. When given subcutaneously, regular insulin starts working within 30 minutes, peaks in 2-4 hours, and lasts 5-8 hours.

The inferior epigastric artery branches off the external iliac artery immediately proximal to the inguinal ligament. It provides

blood supply to the lower anterior abdominal wall as it runs superiorly and medially up the abdomen.

Communicating hydrocephalus is a common complication of subarachnoid hemorrhage that presents with deteriorating mental status. It typically results from

blood-induced impairment of absorption of cerebrospinal fluid by the arachnoid granulations.

Blood solubility of an anesthetic is indicated by its

blood/gas partition coefficient-anesthetics with higher blood solubility have larger blood/gas partition coefficients

Hyperthyroidism causes upregulation of beta-adrenergic receptor expression, leading to increased catecholamine effect. Beta blockers are used to

blunt the adrenergic manifestations of hyperthyroidism. In addition, lipid-soluble beta blockers reduce conversion of T4 to T3 by inhibiting 5'-monodeiodinase in peripheral tissues.

The chest x-ray in acute decompensated heart failure typically shows prominent pulmonary vessels; patchy, bilateral airspace opacification; and

blunting of the costophrenic angles due to pleural effusions.

The first-line treatment for trigeminal neuralgia is carbamazepine, a neuroleptic medication that inhibits neuronal high-frequency firing by reducing the ability of sodium channels to recover from inactivation. Carbamazepine can cause

bone marrow suppression; therefore, complete blood cell counts should be monitored periodically.

Type I collagen is the primary collagen in mature scars (eg, remote myocardial infarction). It is the most prevalent type of collagen and provides strength and support throughout the human body, particularly in

bones, tendons, ligaments, and skin

The duodenal brush border enzyme enteropeptidase activates trypsin from its inactive precursor, trypsinogen. Trypsin degrades complex polypeptides to dipeptides, tripeptides, and amino acids while activating other pancreatic enzymes. Enteropeptidase deficiency impairs

both protein and fat absorption, leading to diarrhea, failure to thrive, and hypoproteinemia.

Physostigmine is a cholinesterase inhibitor with a tertiary ammonium structure that can reverse

both the central and peripheral nervous system symptoms of anticholinergic toxicity. Neostigmine, edrophonium, and pyridostigmine have a quaternary ammonium structure that limits central nervous system penetration.

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 typically demonstrates

bradycardia with sinus pauses (delayed P waves), sinus arrest (dropped P waves), and junctional escape beats.

Giant cell arteritis is characterized by granulomatous inflammation of the media with intimal thickening and predominantly involves

branches of the carotid artery, especially the temporal artery. It is strongly associated with polymyalgia rheumatica; both conditions respond promptly to glucocorticoid therapy.

The presence of a central vascular catheter and receipt of parenteral nutrition are risk factors for candidemia. Candida display a morphology of

branching pseudohyphae with blastoconidia.

the most common cancers (excluding basal and squamous cell skin cancer) in 2019 among women living in the United States are (by order of incidence)

breast, lung, and colorectal cancer

Patients with a long history of asbestos exposure are at risk for developing asbestosis, pleural disease, and malignancies such as

bronchogenic carcinoma and mesothelioma. Bronchogenic carcinoma is the most common malignancy in this population, although mesothelioma is more specific for asbestos exposure.

Beta blockers are used in acute myocardial infarction to reduce morbidity and mortality by decreasing cardiac output and myocardial oxygen demand. Non-cardioselective beta blockers (eg, propranolol, nadolol) can trigger

bronchospasm in patients with underlying asthma or chronic obstructive pulmonary disease. Cardioselective beta blockers (eg, metoprolol) predominantly affect beta-1 receptors and are preferred in such patients.

Amyotrophic lateral sclerosis causes degeneration of both upper and lower motor neurons and can result in

bulbar and skeletal muscle weakness. Denervation atrophy can affect the diaphragm and contribute to respiratory failure.

Succinylcholine can cause significant potassium release and life-threatening arrhythmias in patients at high risk for hyperkalemia, including those with

burns, myopathies, crush injuries, and denervating injuries or disease.

Benign prostatic hyperplasia (BPH) is associated with stromal and glandular growth in the periurethral and transitional zone of the prostate. The hyperplastic cells are supported

by the formation of new blood vessels, which may be friable. Therefore, BPH is often associated with microscopic or gross hematuria.

The carpal tunnel is formed by the carpal bones and the transverse carpal ligament (flexor retinaculum). Carpal tunnel syndrome results from compression of the median nerve as it passes through the

carpal tunnel with 9 flexor tendons. Longitudinal incision of the transverse carpal ligament can decrease pressure within the carpal tunnel, improving patients' symptoms.

VWF serves as a ____ for factor VIII

carrier protein

Cyclosporine and tacrolimus, 2 of the more commonly used immunosuppressants in transplant patients, inhibit

calcineurin activation

Giardia lamblia is the most common enteric parasite in the United States and Canada and is a common cause of diarrhea in

campers/hikers. Iodine-stained stool smear classically shows pear-shaped, flagellated trophozoites or ellipsoidal cysts with smooth, well-defined walls and 2+ nuclei. Metronidazole is the treatment of choice.

R5 strains (macrophage-tropic) of HIV attach to the host CD4 receptor and CCR5 chemokine coreceptor; CCR5 inhibitors such as maraviroc

can be used in the treatment of R5 virus.

the iliohypogastric nerve provides sensation to the suprapubic and gluteal regions and motor function to the anterolateral abdominal wall muscles. Abdominal surgery (eg, appendectomy)

can damage the nerve and cause decreased sensation and/or burning pain at the suprapubic region.

Oval, budding yeast that forms true hyphae (germ tubes) when incubated at body temp (37 C):

candida albicans

Abetalipoproteinemia is an inherited inability to synthesize apolipoprotein B, an important component of chylomicrons and very low-density lipoprotein. Lipids absorbed by the small intestine

cannot be transported into the blood and accumulate in the intestinal epithelium, resulting in enterocytes with clear or foamy cytoplasm.

X4 strains (T lymphotropic) of HIV bind to the CD4 receptor and CXCR4 chemokine receptor; X4 virus

cannot be treated with CCR5 inhibitors.

Bioavailability is the fraction of an administered drug that reaches the systemic circulation unchanged. Drugs administered orally enter the portal circulation and are subject to first-pass metabolism. Rectal administration is

capable of partially bypassing first-pass metabolism as a proportion of rectal blood flow enters the systemic circulation directly. Drugs that undergo extensive first-pass metabolism have increased bioavailability when administered rectally.

Vitamin C is necessary for the hydroxylation of proline and lysine residues in pro-collagen. Vitamin C deficiency (scurvy) is most often seen in severely malnourished individuals and leads to

capillary bleeding, poor wound healing, and periodontal disease. In children, bony deformities and subperiosteal hemorrhages are also characteristic.

Carbon monoxide binds heme iron in hemoglobin with an affinity much greater than oxygen, generating carboxyhemoglobin. Remaining binding sites on

carboxyhemoglobin have an increased affinity for oxygen that causes the oxygen dissociation curve to shift to the left, impeding oxygen delivery to tissues.

mitral regurgitation causes a high-pitched holosystolic murmur over the:

cardiac apex

Digoxin toxicity typically presents with

cardiac arrhythmias and nonspecific gastrointestinal (nausea, vomiting), neurological (confusion, weakness), and visual symptoms. Elevated potassium is another sign of digoxin toxicity and is caused by inhibition of Na-K-ATPase pumps

Pulsus paradoxus refers to an exaggerated drop (>10 mm Hg) in systolic blood pressure during inspiration. It is most commonly seen in patients with

cardiac tamponade but can also occur in severe asthma, chronic obstructive pulmonary disease, hypovolemic shock, and constrictive pericarditis.

The combination of jugular venous distension, hypotension, and muffled heart sounds is highly suggestive of

cardiac tamponade. Tachycardia and pulsus paradoxus are also frequently seen with tamponade. Lung examination is normal, which can help distinguish cardiac tamponade from tension pneumothorax.

Where are B1 adrenergic receptors found?

cardiac tissue and on renal juxtaglomerular cells but not in vascular smooth muscle selective blockade of the B1 receptor like with atenolol will lead to decreased cAMP levels in cardiac and renal tissue without significantly affecting cAMP levels in vascular smooth muscle

Acid maltase (α-glucosidase) deficiency presents in early infancy with

cardiomegaly, macroglossia, and profound muscular hypotonia. Abnormal glycogen accumulation within lysosomal vesicles is seen on muscle biopsy.

The clinical presentation of tertiary syphilis includes

cardiovascular involvement and gummas. Gummas are necrotizing granulomas occurring on the skin, mucosa, subcutaneous tissue, and bones and within other organs. Neurosyphilis can occur at any stage of infection.

Glomerulonephritis is associated with prior streptococcal pharyngeal or skin infection; acute rheumatic fever is associated with prior streptococcal pharyngitis but not skin infection. Streptococci are

catalase-negative, staphylococci are catalase-positive. Streptococcus pyogenes (Group A Streptococcus) is β-hemolytic, bacitracin-susceptible, and pyrrolidonyl arylamidase-positive. Streptococcus pneumoniae is bile-soluble and optochin-susceptible.

Carbonic anhydrase is found in high concentrations in the proximal tubule and is responsible for

catalyzing reactions necessary for NaHCO3 reabsorption

Diphtheria exotoxin inhibits host cell protein synthesis by

catalyzing the ADP-ribosylation of host cell elongation factor-2

Hirschsprung disease is caused by abnormal migration of neural crest cells (ganglion cell precursors) during embryogenesis. Because neural crest cells migrate

caudally down the bowel from the foregut, the rectum is always affected.

Adenomatous polyps are either tubular, villous, or tubulovillous, depending on their histologic appearance. Villous adenomas tend to be larger, sessile, and more severely dysplastic than tubular adenomas. Villous adenomas can

cause a secretory diarrhea from increased mucin production; patients may develop hypoproteinemia and hypokalemia.

The receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANK-L) interaction is essential for the formation and differentiation of osteoclasts. Osteoprotegerin blocks binding of RANK-L to RANK and reduces formation of mature osteoclasts. Low estrogen states

cause osteoporosis by decreasing osteoprotegerin production, increasing RANK-L production, and increasing RANK expression in osteoclast precursors.

beta2 adrenergic agonists:

cause peripheral vasodilation and decrease SVR

D1 adrenergic agonists:

cause renal arteriolar vasodilation

Traumatic pneumothorax can involve puncture of either the chest wall (eg, penetrating chest trauma) or the lung (eg, by fractured ribs), allowing air to enter the pleural space. Patients usually experience chest pain and difficulty breathing. Crepitus,

caused by air in the subcutaneous tissues of the chest wall, is often present on physical examination.

Cardiac auscultation in patients with mitral stenosis reveals a loud first heart sound, an early diastolic opening snap after the second heart sound, and a low-pitched diastolic rumble best heard at the cardiac apex. The opening snap is

caused by the sudden opening of the mitral valve leaflets when the left ventricular pressure falls below the left atrial pressure at the beginning of diastole.

long-term hyperglycemia most likely contributed to cataract formation by

causing oversaturation of the polyol pathway (an alternative route of glucose metabolism) First, there is conversion of glucose into sorbitol by aldose reductase. Sorbitol cannot readily cross cell membranes and is therefore trapped inside the cells where it forms. The second enzyme in the pathway, sorbitol dehydrogenase, is able to convert sorbitol into fructose at a sufficient rate to prevent accumulation when glucose levels are normal. However, the process is slow; in long-standing hyperglycemia, sorbitol accumulates in tissues with lower sorbitol dehydrogenase activity, such as the retina, lens, kidney, and peripheral nerves.

Urethritis in a young man is most likely to be due to Neisseria gonorrhoeae or Chlamydia trachomatis, both of which cause dysuria and mucopurulent urethral discharge. The standard treatment for suspected gonococcal urethritis presumes infection by both organisms. Therefore,

ceftriaxone is given for N gonorrhoeae, and doxycycline or azithromycin is given for C trachomatis

Dermatitis herpetiformis most commonly occurs in patients with

celiac disease and is characterized by micro-abscesses containing fibrin and neutrophils at the dermal papillae tips. Clinical manifestations include pruritic papules, vesicles, and bullae that appear symmetrically on the extensor surfaces (eg, elbows, knees), upper back, and buttocks.

Cytochrome c is a mitochondrial enzyme that activates caspases and indirectly brings about

cell death through intrinsic pathway apoptosis.

Hyperkalemia typically occurs with:

cell lysis (rhabdomyolysis, tumor lysis syndrome), metabolic acidosis (due to intracellular to extracellular K+ shift), or abnormalities with renal excretion

Epithelial ovarian cancer is the most common ovarian malignancy. Histologic findings include anaplasia of epithelial cells with invasion into the stroma, along with multiple papillary formations with

cellular atypia. Epithelial ovarian tumors produce CA-125, which can be used as a serum marker for this condition.

Refeeding syndrome occurs after the reintroduction of carbohydrates in patients with chronic malnourishment, which stimulates insulin secretion and drives phosphorus intracellularly in an effort to maintain

cellular energy metabolism (eg, ATP production); this redistribution of phosphorus can result in severe hypophosphatemia.

A scotoma is a visual field defect that occurs due to a pathologic process that involves parts of the retina or the optic nerve resulting in a discrete area of altered vision surrounded by zones of normal vision. Lesions of the macula cause

central scotomas.

Anaphylaxis can cause distributive shock due to widespread release of inflammatory mediators (eg, histamine) that leads to massive peripheral vasodilation. Arteriolar vasodilation decreases systemic vascular resistance to cause hypotension, and venular vasodilation decreases

central venous pressure and pulmonary capillary wedge pressure. Cardiac output is often increased in early distributive shock due to reduced SVR and a baroreceptor reflex-mediated increase in heart rate.

Friedreich ataxia is characterized by

cerebellar ataxia (spinocerebellar tract degeneration) and loss of position/vibration sensation (dorsal column/dorsal root ganglia degeneration), kyphoscoliosis, and hypertrophic cardiomyopathy. Foot abnormalities and diabetes mellitus are also common

This patient with respiratory failure, hypoxemia, and thickened bronchial walls with inflammatory infiltrates and mucous gland enlargement likely had

chronic bronchitis chronic, productive cough with airflow limitation and is part of the spectrum of chronic obstructive pulmonary disease It is most commonly caused by tobacco smoking

Cyclin-dependent kinases (CDKs) 4/6 regulate the movement of cells from G1→S phase. Cancers often have mutations that enhance the activity or downstream effects of CDK 4/6, which contribute to unregulated cellular growth. Inhibitors to CDK 4/6 can be used to treat

certain forms of cancer. However, they can inhibit cellular replication in other rapidly dividing cells such as the hematologic cells in the bone marrow (eg, neutropenia, anemia, or thrombocytopenia).

Motor and sensory deficits across multiple peripheral upper extremity nerves (eg, radial and median) indicate a lesion in the brachial plexus proximal to the formation of the terminal branches. In the absence of history of trauma or malignancy, the most likely cause is nerve root compression due to

cervical spondylosis (cervical radiculopathy).

Actinomyces species are gram-positive, branching, filamentous bacteria that may cause

cervicofacial infections when introduced to the submucosa during mechanical trauma (eg, tooth extraction). Manifestations include a slowly enlarging, nonpainful, chronic mandibular mass that evolves into multiple abscesses and sinus tracts draining yellow-orange sulfur granules.

Zinc-finger motifs are composed of

chains of amino acids bound together around a zinc atom via linkages with cysteine and histidine residues. They recognize specific DNA sequences and are used by many transcription factors to bind DNA and alter activity of target genes. Intracellular receptors that bind steroids, thyroid hormone, and fat-soluble vitamins act directly as transcription factors and contain zinc-finger binding domains.

Primary syphilis commonly presents as a characteristically painless single genital ulcer called a

chancre Dx is established by ID of organisms on darkfield microscopy, serologic testing, or syphilis antibody testing

Reduced ability to compensate for hypoxemia in older adults results due to:

changes to the respiratory system, including decreased chest wall compliance and decreased alveolar elastic recoil with resulting alveolar enlargement and air trapping These changes limit the potential increase in tidal volume and also increase the alveolar-arterial O2 gradient (decrease the efficiency of alveolar-capillary gas exchange)

Kaposi's sarcoma usually involves the skin and GI tract and is common in HIV patients not on antiretroviral therapy. Endoscopy reveals

characteristic lesions, which range from reddish/violet flat maculopapular lesions to raised hemorrhagic nodules or polypoid masses. Biopsy can show spindle cells, neovascularization, and extravasated red blood cells.

Uterine sarcoma is a rare but aggressive malignant tumor of the uterine myometrium and/or endometrial stromal tissue. Patients typically have clinical features similar to those with uterine leiomyomas (eg, abnormal uterine bleeding, immobile pelvic mass), but uterine sarcoma can be distinguished by microscopy, which typically shows

characteristic malignant features such as nuclear atypia, abundant mitoses, and tumor necrosis.

The anterior pituitary is formed from an out-pouching of the pharyngeal roof and is called Rathke's pouch. The posterior pituitary gland arises from an extension of the hypothalamic neurons. Craniopharyngiomas are tumors arising from Rathke's pouch remnants in the anterior pituitary. They

characteristically have three components: solid, cystic, and calcified. They present during childhood, usually, with mass effect and visual deficits.

Enterohemorrhagic Escherichia coli (EHEC) is primarily contracted after eating undercooked ground beef. EHEC produces Shiga toxin, which causes hemorrhagic colitis and can lead to hemolytic-uremic syndrome (HUS). HUS is

characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia; children age <10 are at greatest risk.

Mutation of the APC tumor suppressor gene is the first step in the classic adenoma-to-carcinoma sequence; it is found in most cases of sporadic colon cancer and in all patients with familial adenomatous polyposis. The microsatellite instability pathway is

characterized by mutations in DNA mismatch repair genes and is implicated in the development of hereditary nonpolyposis colorectal cancer (Lynch syndrome).

Thoracic aortic aneurysms are usually asymptomatic until they grow large enough to compress surrounding structures or cause rupture. The most common symptomatic presentation is

chest or back pain, but compression of nearby structures can cause dysphagia, hoarseness, cough, or dyspnea.

Primary sclerosing cholangitis is characterized by inflammation, fibrosis, and stricture of intrahepatic and extrahepatic bile ducts. Histologic findings include fibrous obliteration of bile ducts and periductal concentric connective tissue deposition (eg, onion-skin pattern). Manifestations reflect

cholestasis and include jaundice, pruritus, fatigue, and a cholestatic pattern of liver injury (ie, elevated alkaline phosphatase, direct hyperbilirubinemia).

Unlike the process of intramembranous ossification that forms flat bones, endochondral ossification proceeds along a cartilage template and is responsible for the formation of long bones. Achondroplasia is characterized by an exaggerated inhibition of

chondrocyte proliferation in the growth plates of long bones and manifests with proximal limb shortening, midface hypoplasia, and macrocephaly.

Etoposide is a chemotherapeutic agent that inhibits the sealing activity of topoisomerase II. Treatment with etoposide causes

chromosomal breaks to accumulate in dividing cells, ultimately causing cell death.

Neurofibromatosis type 1 is a single-gene autosomal-dominant disorder. It occurs due to mutation of the NF1 gene located on

chromosome 17. Café-au-lait spots, multiple neurofibromas, and Lisch nodules are the most common symptoms.

Granulomas are characterized by a large number of epithelioid macrophages that may fuse together to form multinucleated cells (Langhans giant cells) surrounded by a band of lymphocytes. Granuloma formation involves

chronic Th1 and macrophage activation in response to a difficult-to-eradicate antigen.

Thickened bronchial walls, lymphocytic infiltration, mucous gland enlargement, and patchy squamous metaplasia of the bronchial mucosa are features of

chronic bronchitis

The vagus nerve provides cutaneous sensation to the posterior external auditory canal via its

small auricular branch. Sensation to the rest of the canal is from the mandibular division of the trigeminal nerve.

The flow-volume loop for chronic obstructive pulmonary disease is characterized by increased residual volume and total lung capacity, as well as a "scooped-out" expiratory pattern due to reduced expiratory flow rates. Both airway narrowing due to

chronic bronchitis and decreased elasticity due to emphysematous destruction of interalveolar walls are responsible for the hyperinflation and airflow limitation.

Metaplasia is the substitution of one differentiated cell type for another due to the presence of an adverse environmental stimulus. It is often seen in the bronchi of

chronic cigarette smokers (substitution of ciliated columnar epithelium with stratified squamous cells) and the distal esophagus of patients with chronic gastroesophageal reflux (substitution of stratified squamous epithelium with intestinal columnar cells). Metaplasia can lead to subsequent dysplasia and malignant transformation.

Formation of uric acid kidney stones is promoted by low urine pH, which favors formation of insoluble uric acid over soluble urate ion. Gastrointestinal bicarbonate loss due to

chronic diarrhea leads to chronic metabolic acidosis and production of acidic urine, promoting formation of uric acid stones.

Anemia of chronic disease (ACD) occurs in patients with rheumatologic diseases, chronic infection, malignancy, congestive heart failure, and morbid obesity due to

chronic elevation of inflammatory cytokines. The primary 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.

Alveolar hemosiderin-laden macrophages indicate alveolar hemorrhage. They most commonly result from

chronic elevation of pulmonary capillary hydrostatic pressure in the setting of left-sided heart failure.

Stasis dermatitis is characterized by

chronic erythema, fibrosis, and reddish-brown discoloration due to deposition of hemosiderin (from breakdown of extravasated red cells-happens due to chronic venous insufficiency). Symptoms are typically bilateral, and usually worse at or above the ankles. Complications include poor wound healing, weeping, and ulceration.

Children with IgA deficiency, X-linked agammaglobulinemia, and common variable immune deficiency have a predisposition to developing

chronic giardia

Hemoglobin A1c is produced by nonenzymatic glycosylation of the hemoglobin molecule. A hemoglobin A1c assay provides an estimate of

chronic glycemic control over the life span of circulating erythrocytes (~3 months). However, rapid erythrocyte turnover (eg, hemolytic anemia) can give a misleadingly low hemoglobin A1c in relation to glycemic status.

Black pigment stones arise from conditions that increase the amount of unconjugated bilirubin in bile, which promotes calcium bilirubinate precipitation. This may occur in the setting of

chronic hemolysis (eg, sickle cell anemia, β-thalassemia, hereditary spherocytosis) and increased enterohepatic cycling of bilirubin (eg, ileal disease).

If HBeAg persists for several months and host anti-HBeAg remain at low or undetectable levels, suspect

chronic hepatitis B infection with high infectivity.

Histologic findings of idiopathic pulmonary fibrosis are most prominent in the lung periphery and include a heterogeneous mixture of

chronic inflammation and patchy interstitial fibrosis, focal fibroblast proliferation, and formation of fibrotic cystic spaces in a honeycomb pattern.

A patient who has lymphadenopathy, splenomegaly, and increased number of mature lymphocytes in the blood that express B-cell markers (CD20+, kappa light chains) indicate:

chronic lymphocytic leukemia This disease is characterized by the progressive accumulation of mature B cells in hematopoietic tissues (leading to anemia, thrombocytopenia, lymphadenopathy, and splenomegaly) and peripheral blood (leading to leukocytosis) due to genetic mutations that lengthen B-cell survival

Renal artery stenosis is most often due to atherosclerosis. It can cause severe, refractory hypertension due to activation of the renin-angiotensin-aldosterone system. Over time, renal atrophy may occur due to

chronic oxygen and nutrient deprivation. Histologic examination may show crowded glomeruli, tubulointerstitial atrophy and fibrosis, and focal inflammatory infiltrates.

Diarrhea, weight loss, and epigastric calcifications in a patient with chronic alcoholism suggest

chronic pancreatitis with resulting pancreatic exocrine insufficiency and malabsorption.

Abdominal aortic aneurysm is associated with risk factors (eg, age >60, smoking, hypertension, male sex, family history) that lead to

chronic transmural inflammation and extracellular matrix degradation within the wall of the aorta. This leads to weakening and progressive expansion of the aortic wall, resulting in aneurysm formation, typically below the renal arteries.

Endometrial hyperplasia and cancer often present with postmenopausal bleeding. A common risk factor for endometrial cancer is obesity due to the peripheral aromatization of androgens to estrogens in adipose tissue, which leads to

chronic unopposed estrogen exposure and uncontrolled endometrial tissue proliferation.

Mycobacterium tuberculosis spondylitis (Pott disease) is usually the result of hematogenous seeding of vertebrae from primary pulmonary infection. Manifestations typically arise months or years later (due to reactivation) and include

chronic, progressive back pain, fever, and radiographic evidence of vertebral bone destruction and fluid collection.

Anemia of chronic disease is a consequence of

chronically elevated inflammatory cytokines, most importantly hepcidin. This peptide inactivates iron channels on enterocytes and reticuloendothelial macrophages, leading to reduced iron absorption and reduced iron release from the reticuloendothelial system. The net result is normocytic or slightly microcytic anemia with low reticulocyte response, low serum iron level, and normal or low total iron-binding capacity.

Varicose veins are dilated, tortuous veins most commonly found in the superficial veins of the leg. They are caused by

chronically increased intraluminal pressure and/or loss of tensile strength in the vessel wall, leading to incompetence of the venous valves. Common complications include edema, stasis dermatitis, skin ulcerations, poor wound healing, and infections.

Rifampin, phenobarbital, and phenytoin are potent enhancers of the cytochrome P-450 pathway; concurrent use of warfarin with these medications results in decreased efficacy of warfarin. In contrast,

cimetidine, amiodarone, and trimethoprim-sulfamethoxazole inhibit warfarin metabolism, increasing the risk of bleeding.

Rheumatoid arthritis is characterized by symmetric polyarthritis (involving the metacarpophalangeal and proximal interphalangeal joints) with prolonged morning stiffness and associated fatigue. Antibodies to

citrullinated peptides/proteins have a high specificity for the condition.

Patients with polycystic ovary syndrome who desire fertility can be treated with

clomiphene. Clomiphene is an estrogen receptor modulator that decreases negative feedback inhibition on the hypothalamus by circulating estrogen, thereby increasing gonadotropin production.

S saprophyticus is responsible for almost half of all UTIs in sexually active young women. Staphylococcus saprophyticus belongs to

coagulase negative staphylococci and is unique among these because it is resistant to novobiocin.

Psoriasis is characterized by hyperkeratosis and confluent parakeratosis of the stratum corneum, and epidermal hyperplasia (acanthosis) with elongated rete ridges. Neutrophilic foci in the stratum corneum and epidermis may

coalesce to form microabscesses (Munro microabscesses).

Nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line therapy for treating acute gouty arthritis. They inhibit cyclooxygenase and exert a broad anti-inflammatory effect that includes inhibition of neutrophils. When NSAIDs are contraindicated (eg, peptic ulcer disease, renal impairment),

colchicine is useful in the acute management of gout as it inhibits neutrophil chemotaxis and phagocytosis by preventing microtubule formation.

Presbyopia and skin wrinkles are age-related changes. Presbyopia occurs due to denaturation of structural proteins within the lens, leading to loss of lens elasticity which can result in improved vision in patients with mild myopia. Decreased synthesis and increased breakdown of

collagen and elastin contribute to the development of skin wrinkles.

Anti-glomerular basement membrane (GBM) antibodies react with

collagen type IV, causing rapidly progressive glomerulonephritis with glomerular crescent formation on light microscopy. Immunofluorescence demonstrating linear deposits of IgG and C3 along the GBM is characteristic.

Glycine is the most abundant amino acid in

collagen. The triple helical conformation of collagen molecules occurs due to the repetitive amino acid sequence within each alpha chain, in which glycine (Gly) occupies every third amino acid position (Gly-X-Y).

The metanephros (metanephric blastema) gives rise to the glomeruli, Bowman's space, proximal tubules, the loop of Henle, and distal convoluted tubules. The ureteric bud becomes the

collecting system of the kidney, including the collecting tubules and ducts, major and minor calyces, renal pelvis, and the ureters.

Aspergillus fumigatus causes a wide spectrum of disease. It can be an opportunistic infection in immunosuppressed and neutropenic patients (invasive pulmonary aspergillosis). Aspergillosis can be

colonizing (aspergilloma) when it forms a fungus ball within a preexisting lung cavity. It can also cause a lung hypersensitivity reaction in allergic bronchopulmonary aspergillosis in individuals with asthma.

Severe combined immune deficiency is characterized by

combined T and B cell dysfunction. It is a life-threatening condition that presents in infancy with severe bacterial and viral infections; mucocutaneous candidiasis; persistent diarrhea; and failure to thrive. Laboratory findings include absent T cells and hypogammaglobulinemia. The thymic shadow is not usually present due to severe T cell deficiency.

Leptospirosis is a zoonotic infection caused by the motile spirochete Leptospira. Transmission primarily occurs when humans

come into contact with water contaminated with animal urine during outdoor recreational or occupational activities Patients classically have a mild, self-limited, flulike illness but may develop more serious complications such as renal or hepatic failure

Third aortic arch forms which adult derivative?

common carotid artery, proximal internal carotid artery

Dilated cardiomyopathy results from direct damage to cardiomyocytes leading to myocardial contractile dysfunction (systolic dysfunction), volume overload, and ventricular dilation. Viral myocarditis is a

common cause of dilated cardiomyopathy and should be suspected in young patients who develop heart failure following a symptomatic viral prodrome.

Neonatal intraventricular hemorrhage usually originates from the fragile germinal matrix in infants born before 32 weeks gestation and/or with birth weight <1,500 g (3 lb 5 oz). It is a

common complication of prematurity that can lead to long-term neurodevelopmental impairment.

The celiac trunk is the first main branch of the abdominal aorta; it provides oxygenated blood to the spleen, stomach, liver, abdominal esophagus, and parts of the duodenum and pancreas. The proper hepatic artery branches off the

common hepatic artery from the celiac trunk and provides arterial blood supply to the liver. Additional Information

Acromegaly is caused by excessive production of growth hormone, usually due to a pituitary somatotroph adenoma. Musculoskeletal manifestations include bony hypertrophy (eg, frontal bossing; enlarged jaw, hands, and feet) and osteoarthritis. Left ventricular hypertrophy is often

common in acromegaly and may progress to heart failure.

Local defense against Candida is performed by T cells, whereas systemic infection is prevented by neutrophils. For this reason, localized candidiasis is

common in patients who have HIV, but neutropenic individuals are more likely to have the systemic form of the disease.

Spore-forming bacteria can survive boiling temperatures. Bacillus and Clostridium species are

common pathogenic spore-forming bacteria.

Takayasu arteritis is a chronic, large-artery vasculitis that primarily involves the aorta and its branches. It presents with

constitutional (eg, fever, weight loss) and arterio-occlusive (eg, claudication, blood pressure discrepancies, pulse deficits) findings in patients age <40. Histopathology shows granulomatous inflammation of the vascular media.

Anemia with an elevated reticulocyte count (ie, reticulocytosis) indicates that the bone marrow is responding appropriately to the anemia by generating new erythrocytes. Reticulocytosis is

commonly seen in patients with hemolysis or acute bleeding. Many other causes of anemia are associated with low reticulocyte count, including bone marrow suppression (eg, parvovirus), iron deficiency anemia, vitamin B12/folate deficiency, and anemia of chronic disease.

Lithium and the anticonvulsants valproate, carbamazepine, and lamotrigine are mood-stabilizing agents used in bipolar disorder. Valproate is

commonly used in the treatment of generalized as well as myoclonic seizures.

Bacterial meningitis causes an increase in cerebrospinal fluid (CSF) neutrophil count and protein concentration as well as a decrease in CSF glucose. Streptococcus pneumoniae is a leading cause of

community-acquired pneumonia, otitis media, and meningitis in adults. S pneumoniae appears on Gram stain as lancet-shaped, Gram-positive cocci in pairs.

Diabetic ketoacidosis (DKA) is characterized by polydipsia, polyuria, and a fruity odor to the breath and/or urine. DKA is associated with elevated anion gap metabolic acidosis that is usually accompanied by

compensatory respiratory alkalosis. This combination yields a low pH, low serum bicarbonate, and low PaCO2.

acyclovir:

competitive inhibitor of viral DNA polymerase

Patients with diabetes insipidus (DI) are unable to concentrate their urine in response to dehydration. Following desmopressin administration during the water deprivation test, urine osmolality increases to normal levels in central DI but does not change in

complete nephrogenic DI

Vibrio cholerae must survive the acidic environment of the stomach to reach the small intestine and cause disease. Because the organism is easily destroyed by acid, a high burden of organisms must be ingested to cause infection. However,

conditions that decrease gastric acidity (eg, antacid use) lower the minimum infectious dose of V cholerae by multiple orders of magnitude.

Lung abscess is most often due to aspiration of anaerobic oral bacteria such as Peptostreptococcus, Prevotella, Bacteroides, and Fusobacterium species. Risk factors for lung abscess include

conditions that increase aspiration risk, such as alcoholism, drug abuse, seizure disorders, previous stroke, and dementia.

Observer bias occurs when the investigator's evaluation is affected by preconceived expectations or prior knowledge, typically leading to overestimation of the disease association or treatment effects. This type of bias can be reduced by

conducting a blinded study in which observers are unaware of study details and patient characteristics that could unduly influence them.

common with acute inferior wall myocardial infarction

conduction impairment Sinus bradycardia often occurs due to nodal ischemia and an increase in vagal tone triggered by infarction of myocardial tissue; the enhanced vagal tone can be counteracted by the anticholinergic effects of atropine.

Tricyclic antidepressants have strong anticholinergic properties. Potential side effects include

confusion, constipation, and urinary retention. These medications should be used with caution in elderly patients.

A decrease-in-function mutation affecting the KCNH2 gene is one of the most common causes of

congenital long QT syndrome (LQTS); it can be inherited in autosomal dominant (Romano-Ward syndrome) or autosomal recessive (Jervell and Lange-Nielsen syndrome) fashion

Pregnant women should avoid consumption of undercooked meat to prevent infection with Toxoplasma gondii, an intracellular, crescent-shaped parasite that can cross the placenta to the fetus. Typical features of

congenital toxoplasmosis include chorioretinitis, hydrocephalus, and diffuse intracranial calcifications.

Delirium is a reversible, acute-onset confusional state characterized by a fluctuating level of

consciousness with deficits in attention, memory, and executive function. In contrast, dementia has a gradual onset, is irreversible, and does not involve fluctuations in consciousness.

Chronic lymphedema is most commonly caused by an acquired disruption of lymphatic drainage (eg, due to malignancy or lymphadenectomy), and typically presents with swelling and thickened skin in one or more extremities. Treatment is usually

conservative and involves compression bandages and physiotherapy; diuretics are ineffective and contraindicated.

Countertransference

consists of a provider's response (eg, attitudes, thoughts, feelings, behaviors) toward a patient based on past personal relationships. Countertransference can be positive or negative, conscious or unconscious; if unrecognized, it may have detrimental effects on patient care.

During physical exercise, there is increased skeletal muscle CO2 production that increases the CO2 content of venous blood. Arterial O2 and CO2 content remains constant via increases in alveolar ventilation and gas exchange efficiency. Venous O2 content remains

constant or is decreased due to increased O2 extraction by the tissues that matches or exceeds the rate of oxygen delivery (ie, O2 consumption during exercise is limited by cardiac output).

Subserosal uterine leiomyomas (fibroids) can cause irregular uterine enlargement and bulk-related symptoms (eg, pelvic pressure). Posterior leiomyomas can cause

constipation due to pressure on the colon.

Histoplasma capsulatum replicates within macrophages and often spreads from the lungs through the pulmonary lymphatics to the reticuloendothelial system (eg, spleen, liver). Most healthy individuals quickly

contain the infection within granulomas and do not become ill; a minority develop self-limited pneumonia. Over time, the granulomas at the initial sites of infection calcify and may be seen incidentally on radiographic imaging.

Hiatal hernia

contents of the abdominal cavity herniate through the diaphragm into the thoracic cavity at the esophageal hiatus can by caused by laxity of the phrenoesophageal membrane

Physical examination of a patient with patent ductus arteriosus (PDA) will show a

continuous "machinery-like" murmur and palpable thrill over the left infraclavicular region due to turbulent blood flow through the PDA.

The circulatory system is a continuous circuit, and therefore the volume output of the left ventricle must closely match the output of the right ventricle. This balance is necessary to maintain

continuous blood flow through the body and exists both at rest and during exercise.

Empiric antibiotic therapy for patients with uncomplicated upper respiratory infections is

contraindicated. Responding to requests for inappropriate antibiotics involves a patient-centered approach that validates the patient's concerns, educates the patient about the adverse effects of antibiotics and their lack of efficacy in treating viral infections, and provides options to treat the patient symptomatically.

Posterior cerebral artery territory infarction typically results in

contralateral hemianopia due to infarction of the visual cortex. The macula is often spared due to collateral circulation from the MCA.

Patients with MCA occlusion usually present with

contralateral hemiparesis and hemisensory loss involving the face and upper limb due to infarction of the corresponding motor and sensory cortices

Trendelenburg sign:

contralateral hip drop that is observed with weakened gluteus medius and gluteus minimus Can occur with superior gluteal nerve injury

Uncal herniation is a possible complication of an expanding ipsilateral mass lesion (eg, hemorrhage, tumor). The first sign of uncal herniation is a fixed, dilated pupil on the side of the lesion. Contralateral or ipsilateral hemiparesis and

contralateral homonymous hemianopsia with macular sparing may also occur.

Homonymous hemianopia is a defect in half of the visual field due to a:

contralateral lesion in the visual pathways posterior to the optic chiasm (optic tract, optic radiations)

The anterior cerebral artery (ACA) supplies the medial aspects of the frontal and parietal lobes, which contain the upper motor neurons responsible for contralateral lower extremity motor control. Thromboembolic occlusion of the ACA characteristically results in

contralateral lower extremity weakness with hyperreflexia.

Meningiomas are common adult intracranial tumors that typically arise in regions of dural reflection (eg, falx cerebri, tentorium cerebelli). Parasagittal lesions compressing the medial portion of the primary somatosensory cortex in the parietal lobe can result in

contralateral lower limb sensory loss along with contralateral hemineglect if there is also damage to the parietal association cortex (nondominant hemisphere).

Tension pneumothorax involves progressively increasing intrapleural pressure that leads to

contralateral mediastinal shifting (eg, tracheal deviation) and vena cava collapse. Hypotension, tachycardia, and obstructive shock develop due to decreased venous return to the heart.

The anterior cerebral arteries supply the medial portions of the 2 hemispheres (frontal and parietal lobes). Occlusion can cause

contralateral motor and sensory deficits of the lower extremities, behavioral changes, and urinary incontinence.

The primary somatosensory cortex (postcentral gyrus) is responsible for processing all somatic sensory input from the contralateral side of the body. A focal onset seizure originating in this region of the cerebral cortex often results in

contralateral sensory disturbance (eg, numbness, paresthesia).

Injury to Meyer's loop in the temporal lobe results in

contralateral superior quadrantanopia.

Inhibin B is produced by the Sertoli cells and is the physiological inhibitor of FSH secretion. LH concentration is

controlled primarily by testosterone feedback.

LH stimulates the theca interna cells of the ovarian follicle to produce androgens. Aromatase within the follicle's granulosa cells subsequently

converts these androgens to estradiol under FSH stimulation. The theca externa cells serve as a connective tissue support structure for the follicle.

Penicillamine, a first-line treatment for Wilson disease, is a

copper chelating agent that increases the urinary excretion of copper.

Vasospastic angina involves hyperreactivity of

coronary artery smooth muscle. Patients are usually young (age <50) and without significant risk factors for coronary artery disease; they experience recurrent episodes of chest discomfort that typically occur during rest or sleep and resolve within 15 minutes.

Most of the venous drainage from the myocardium traverses the:

coronary sinus, which delivers deoxygenated blood to the right atrium through the CS orifice (between the IVC and tricuspid valve)

In a fasting state, glucagon and epinephrine bind to transmembrane receptors and prevent hypoglycemia by increasing hepatic glycogenolysis and gluconeogenesis. Prolonged fasting increases the secretion of

cortisol, a steroid hormone that binds to an intracellular receptor and acts to increase transcription of enzymes involved in gluconeogenesis, lipolysis, and proteolysis.

Hypersensitivity pneumonitis results from an exaggerated immunologic response to an inhaled antigen (eg, mold, animal protein), and presents with

cough and dyspnea of variable acuity. Bronchoalveolar lavage typically shows high relative lymphocyte count (eg, >20%), which helps support the diagnosis.

Hemolytic disease of the newborn most commonly occurs from maternal sensitization to Rh antigens during a prior pregnancy with an Rh(D)+ fetus. In subsequent Rh(D)+ pregnancies, maternal anti-Rh(D) IgG antibodies

cross the placenta and cause a severe autoimmune hemolytic anemia in the fetus and life-threatening hydrops fetalis.

Wheal-and-flare lesions usually result from allergic (type I hypersensitivity) reactions. On initial exposure, an allergen (eg, insect venom) promotes antibody class switching to IgE. Subsequent exposure promotes

cross-linking of IgE on basophils and mast cells, resulting in degranulation and release of multiple vasoactive mediators, including histamine.

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.

Niacin is used in the treatment of hyperlipidemia. It increases HDL levels and decreases LDL levels and triglycerides. Niacin causes

cutaneous flushing, which is mediated by prostaglandins and can be diminished by pretreatment with aspirin.

Nonsteroidal anti-inflammatory drugs are the first-line treatment for acute gouty arthritis. They inhibit

cyclooxygenase and therefore decrease prostaglandin synthesis and exert a broad anti-inflammatory effect that includes inhibition of neutrophils.

Gastrointestinal (GI) mucosal injury and bleeding are the most common side effects of aspirin. These are due primarily to

cyclooxygenase-1 inhibition, which results in impaired prostaglandin-dependent GI mucosal defense and decreased platelet aggregation.

In a young Caucasian patient, the combination of recurrent respiratory infections with Pseudomonas aeruginosa, diarrhea, and failure to thrive suggests a diagnosis of:

cystic fibrosis Cystic fibrosis causes steatorrhea and failure to thrive due to malabsorption secondary to pancreatic insufficiency, which can be corrected by pancreatic enzyme supplementation.

leptin is produced by fat cells in response to short-term food intake and long-term adequacy of fat stores. It acts on the hypothalamus to:

decrease appetite (obesity blunts this action) during fasting, leptin levels fall

Regurgitant flow into the left atrium in acute mitral regurgitation leads to increased left atrial pressure and increased left ventricular end-diastolic volume (preload). The low-resistance regurgitant pathway also decreases left ventricular afterload with a resulting increase in ejection fraction but overall

decrease in forward stroke volume. Increased left atrial pressure and decreased cardiac output result in pulmonary edema and severe hypotension, respectively.

Estrogen is the main hormone responsible for the growth and development of estrogen receptor (ER)-positive breast tumors. Aromatase inhibitors (eg, anastrozole, letrozole, exemestane)

decrease the synthesis of estrogen from androgens, suppressing estrogen levels and slowing progression of ER-positive tumors.

A new-onset genital vesicular rash with a positive Tzanck smear in a previously asymptomatic patient is suggestive of primary genital herpes simplex virus (HSV) infection due to HSV-2. Recurrences of genital herpes can be reduced through

daily treatment with oral valacyclovir, acyclovir, or famciclovir. Condom use can help prevent a primary genital HSV infection but does not prevent reactivation of latent infection.

Prolonged exposure to loud noises causes hearing loss due to

damage to the stereociliated hair cells of the organ of Corti.

Dystrophic calcification occurs in

damaged or necrotic tissue in the setting of normal calcium levels; metastatic calcification occurs in normal tissue in the setting of hypercalcemia.

Patients with early syphilis (eg, chancre) often have false-negative initial serologic testing. Direct visualization of the organism (Treponema pallidum) by

dark-field microscopy or fluorescent antibody testing is the gold standard for diagnosis but is not widely available.

Autosomal recessive disorders affect 25% of offspring of asymptomatic heterozygous carrier parents. Classical galactosemia is the most common and severe galactosemic disorder and presents within

days of birth with jaundice, vomiting, and hepatomegaly.

Acute myocarditis is most commonly caused by a viral infection (eg, coxsackievirus, adenovirus, influenza). It often resolves without noticeable symptoms, but patients can develop serious complications, including

decompensated heart failure due to dilated cardiomyopathy or sudden cardiac death due to ventricular arrhythmia. Histopathology typically demonstrates myofibrillary necrosis with inflammatory mononuclear infiltrate.

Chronic alcohol use downregulates inhibitory GABA receptors and upregulates excitatory NMDA glutamate receptors. Therefore, sudden cessation of alcohol leads to

decreased GABA activity and increased glutamate activity, resulting in CNS overexcitation (eg, agitation, disorientation, tremulousness, autonomic hyperactivity).

Chronic thiamine (vitamin B1) deficiency impairs glucose utilization in the central nervous system. This occurs due to

decreased activity of the enzymes that use thiamine as a cofactor (eg, pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, transketolase). Thiamine deficiency can be diagnosed if baseline erythrocyte transketolase activity is low but increases after addition of thiamine pyrophosphate.

Myxomas are the most common primary cardiac neoplasm and usually arise within the left atrium. 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. Histologically, the tumors demonstrate scattered cells within a mucopolysaccharide stroma and abnormal blood vessels with hemorrhaging.

Fibrate medications (eg, fenofibrate, gemfibrozil) inhibit cholesterol 7α-hydroxylase, which catalyzes the rate-limiting step in the synthesis of bile acids. The reduced bile acid production results in

decreased cholesterol solubility in bile and favors the formation of cholesterol gallstones.

Classic 21-hydroxylase deficiency causes

decreased cortisol and aldosterone production with increased adrenal androgen production. In boys, this deficiency presents 1-2 weeks after birth with vomiting, hypotension, hyponatremia, and hyperkalemia due to salt wasting; genitalia are normal. In girls, it presents at birth with ambiguous genitalia.

Septic shock causes widespread arteriolar vasodilation, which leads to a decrease in systemic vascular resistance and a compensatory increase in cardiac output. Central venous pressure and pulmonary capillary wedge pressure are also

decreased due to pooling of blood in the dilated veins. Increased flow rates through the peripheral capillaries lead to incomplete oxygen extraction by the tissues and high mixed venous oxygen saturation.

Heparin is an indirect anticoagulant that alters the shape of antithrombin (AT) III, thereby converting it from a slow to rapid inactivator of clotting factors. Because AT primarily neutralizes factor Xa and thrombin, patients on heparin have

decreased factor Xa activity and prolonged thrombin time/partial thromboplastin time. In contrast, direct oral anticoagulants specifically target a single enzyme in the coagulation cascade, such as thrombin (eg, dabigatran) or factor Xa (eg, rivaroxaban).

Patients with type 1 diabetes mellitus are at increased risk of hypoglycemia because exogenous insulin will continue to be absorbed from the injection site despite falling glucose levels. Those with long-standing diabetes may also have

decreased glucagon secretion and therefore have an even greater risk of rapid hypoglycemia.

Hereditary hemochromatosis can cause secondary hypogonadism due to deposition of iron in the pituitary gland, resulting in

decreased gonadotropin secretion. Patients who develop secondary hypogonadism are also at risk for deficiencies in other pituitary hormones (eg, central hypothyroidism).

Hemolytic uremic syndrome (HUS) manifests with acute kidney injury, microangiopathic hemolytic anemia, and thrombocytopenia. Characteristic laboratory abnormalities include

decreased hemoglobin and platelet count and increased bleeding time, lactate dehydrogenase, bilirubin, blood urea nitrogen, and creatinine.

Chronic myelogenous leukemia (CML) and leukemoid reaction can have presentations similar to leukocytosis; however, leukocyte (neutrophil) alkaline phosphatase level is normal or elevated in a leukemoid reaction but

decreased in CML. The definitive diagnosis of CML requires demonstration of the Philadelphia chromosome t(9;22) or BCR-ABL fusion gene or mRNA.

Constipation is common during pregnancy and results from the inhibitory effect of progesterone on colonic smooth muscle contractions and the fasting migrating myoelectric complex. Other common pregnancy-related changes of the gastrointestinal system include

decreased lower esophageal sphincter pressure (leading to gastroesophageal reflux) and gallbladder stasis (leading to gallstone formation).

The median nerve is most commonly injured within the carpal tunnel, leading to pain and numbness in the first 3 digits and lateral half of the fourth, as well as weakness of thumb flexion and opposition. More proximal injury (in the forearm) additionally causes

decreased sensation over the thenar eminence and weakness of flexion in the wrist and second and third digits.

Fluid in the pleural space acts to insulate sound vibrations that originate in the airways; therefore, pleural effusion causes

decreased tactile fremitus and decreased intensity of breath sounds. The high density of pleural fluid compared to normal lung tissue also causes dullness to percussion.

In addition to unilateral facial paralysis, patients with Bell's palsy may experience

decreased tearing, hyperacusis, and/or loss of taste sensation over the anterior two-thirds of the tongue.

Open-angle glaucoma is characterized by progressive loss of peripheral vision from elevated intraocular pressure. Timolol and other nonselective beta blockers work by diminishing the secretion of aqueous humor by the ciliary epithelium. Acetazolamide, a carbonic anhydrase inhibitor, also

decreases aqueous humor secretion by the ciliary epithelium. Prostaglandin F2α (eg, latanoprost, travoprost) and cholinomimetics (eg, pilocarpine, carbachol) decrease intraocular pressure by increasing the outflow of aqueous humor.

Bronchi have a ciliated pseudostratified columnar epithelium with mucin-secreting goblet cells and submucosal mucoserous glands. The airway epithelium gradually changes to ciliated simple cuboidal by the level of the terminal bronchioles. Bronchioles lack glands and cartilage, and the number of goblet cells

decreases distally, ending before the terminal bronchioles. Ciliated epithelium persists up to the respiratory bronchioles.

Duodenal S-cells secrete secretin in response to increasing H+ concentrations. Secretin increases pancreatic bicarbonate secretion. The chloride content of pancreatic secretions

decreases in proportion to bicarbonate concentration increases.

Carbon dioxide is a potent vasodilator of cerebral vasculature. Tachypnea causes hypocapnia and cerebral vasoconstriction, thereby

decreasing cerebral blood volume and intracranial pressure.

Thiazide diuretics effectively increase renal calcium reabsorption. In patients with recurrent calcium nephrolithiasis, thiazide diuretics can help prevent stone formation by

decreasing urine Ca2+ excretion

Cystinuria results from

defective dibasic amino acid transport in intestinal and proximal renal tubular epithelial cells. It most often presents with recurrent stone formation at a young age due to decreased reabsorption of cysteine from the urine. Urinalysis shows pathognomonic hexagonal cystine crystals, and the sodium cyanide-nitroprusside test can be used to detect excess cystine in the urine.

Hyperimmunoglobulin M (hyper-IgM) syndrome results from

defective immunoglobulin class switching due to a defect in CD40 ligand-CD40 interaction. Absence of the CD40 ligand is the most common cause and is inherited in an X-linked recessive pattern. Clinical features include recurrent sinopulmonary, gastrointestinal, and opportunistic infections.

Patau syndrome (trisomy 13) usually occurs secondary to meiotic nondisjunction in mothers of advanced maternal age. Key physical findings reflect

defective prechordal mesoderm fusion resulting in midline defects (eg, holoprosencephaly, microphthalmia, cleft lip/palate, omphalocele) as well as polydactyly and cutis aplasia.

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.

Gastric bypass surgery can cause small intestinal bacterial overgrowth (SIBO) due to excessive bacterial proliferation in the blind-ended gastroduodenal segment. SIBO results in

deficiency of most vitamins (B12, A, D, and E) and iron, but increased production of folic acid and vitamin K.

Beta-thalassemia is caused by mutations that result in defective transcription, processing, and translation of beta-globin mRNA. This leads to

deficiency of the beta-globin chains required for normal hemoglobin synthesis.

Patients with milder forms of autism spectrum disorder frequently have normal language and cognitive development. Characteristic features include

deficits in social communication and reciprocal social interactions, restricted interests, and behavioral rigidity that become more apparent as social and academic demands increase.

Spinal stenosis occurs most commonly in the lumbar region and presents with posture-dependent lower extremity pain, numbness/paresthesia, and weakness. The most common cause is

degenerative arthritis of the spine, which results in narrowing of the spinal canal due to intervertebral disc herniation, ligamentum flavum hypertrophy, and osteophyte formation affecting the facet joints.

Type I hypersensitivity reactions are mediated by the interaction of allergen with preexisting IgE bound to basophils and mast cells. This facilitates cross-linking of the surface IgE molecules that signals the cell to

degranulate releasing chemical mediators (eg, histamine, heparin). These agents are responsible for the immediate signs and symptoms of allergy, from a local wheal and flare to life-threatening anaphylaxis.

Branches of the vagus nerve (ie, anterior and posterior vagal trunks) pass through the esophageal hiatus. Damage to these branches, which can occur during esophageal hiatal hernia repair (eg, fundoplication), may result in

delayed gastric emptying and gastric hypochlorhydria.

Diabetic gastroparesis results from the destruction of enteric neurons due to chronic hyperglycemia, leading to impaired relaxation and disordered and ineffective peristalsis. This causes

delayed gastric emptying, which presents as postprandial fullness, regurgitation of undigested food, nausea, and vomiting.

Most medications that prolong the QT interval do so by

delaying the repolarizing potassium current via blockade of the same voltage-gated potassium channels affected by the KCNH2 gene mutation

Gap junctions facilitate communication and coordination between cells and play an important role in labor contractions. Connexins are proteins that assemble into gap junctions and their density increases in the uterus before

delivery in response to rising estrogen levels.

What mutation is common in patients with CF?

deltaF508 mutation in the CF transmembrane conductance regulator (CTFR) protein

The diagnosis of schizophrenia requires ≥2 of the following 5 symptoms:

delusions, hallucinations, disorganized speech, grossly disorganized behavior, and negative symptoms. The total impairment duration must be ≥6 months.

Primary biliary cholangitis is an autoimmune disorder that most commonly affects middle-aged women and is characterized by fatigue, pruritus, jaundice, cholestasis (eg, elevated alkaline phosphatase, elevated gamma-glutamyl transferase, direct hyperbilirubinemia), and antimitochondrial antibodies. Histologic findings include

dense lymphocytic portal tract inflammation with granulomatous destruction of interlobular bile ducts (ie, florid duct lesions).

Anthracycline chemotherapeutic agents (eg, doxorubicin, daunorubicin) cause cardiotoxicity mainly through the formation of anthracycline-topoisomerase II DNA cleavage complexes that affect healthy cardiomyocytes. The cardiotoxicity is

dependent on the cumulative dose of anthracycline received, and it manifests as dilated cardiomyopathy.

Acute salicylate toxicity causes a primary respiratory alkalosis and a primary metabolic acidosis with an anion gap due to increased lactate production. Symptoms include

tinnitus, tachypnea, hyperthermia, vomiting, and altered mental status.

In renal artery stenosis, increased production of angiotensin II causes increased systemic blood pressure (to increase renal perfusion) and preferential constriction of the glomerular efferent arteriole (to increase glomerular filtration). Patients with bilateral renal artery stenosis are

dependent on this response to maintain renal function; initiation of ACE inhibitors or angiotensin II receptor blockers can precipitate acute renal failure. However, urinalysis is typically unremarkable (ie, no hematuria, proteinuria, or casts).

Type III hypersensitivity ex

deposited immune complexes activate complement and cause neutrophil-mediated tissue damage

Hereditary hemochromatosis is characterized by increased intestinal iron absorption with

deposition of excess iron in parenchymal tissues. Men typically develop manifestations in their 30s and 40s. However, premenopausal women have ongoing blood and iron losses due to menstruation, which partially offsets the excess iron absorption and delays the onset of symptoms.

The lateral pterygoid muscles are the only muscles of mastication that aid in

depressing the mandible (ie, opening the jaw). Spasm of the lateral pterygoids prevents spontaneous reduction of an anterior dislocation of the temporomandibular joint.

A case series is a

descriptive observational study design in which a group of patients with a similar diagnosis or treatment is described at a point in time or followed over a certain period. This study design has no comparison group; therefore, it cannot establish associations between risk factors (eg, treatments) and outcomes (eg, diseases).

Alpha-1 blockers such as doxazosin, prazosin, and terazosin are useful for the treatment of both benign prostatic hyperplasia and hypertension. To minimize adverse effects and drug interactions, it is

desirable to prescribe a medication that can address multiple issues at once.

Alveolar fluid contains neutral 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.

Sickle cell anemia is an autosomal recessive hemoglobinopathy. In order for a child to have sickle cell disease, both parents must be carriers. Hemoglobin electrophoresis can be used to

determine the carrier status of a prospective parent who has no history of sickle cell anemia.

Total body chloride depletion is often important in the pathophysiology of metabolic alkalosis. Measurement of urine chloride can be helpful in

determining the underlying etiology.

High-altitude pulmonary edema presents with dyspnea and cough within several days of arrival at high altitude. It is driven by reduced ambient oxygen, which leads to hypoxic pulmonary vasoconstriction and pulmonary arterial hypertension. Individuals with unevenly distributed pulmonary vasoconstriction can

develop areas of high capillary perfusion pressure that disrupts the alveolar-capillary membrane, leading to patchy, bilateral pulmonary edema.

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by germline mutation to the tumor suppressor gene adenomatous polyposis coli. Patients with FAP

develop hundreds or thousands of colonic polyps; lifetime risk of colon cancer is close to 100%.

Adults with coarctation of the aorta often have chronic hypertension and are at increased risk of

developing life-threatening aneurysms of the aorta (eg, dissection, rupture) and cerebral vessels (ie, intracranial hemorrhage).

The embryonic testis secretes testosterone and müllerian inhibiting factor (MIF). MIF is responsible for regression of the paramesonephric (müllerian) ducts that normally give rise to the internal genitalia in the female fetus. Testosterone mediates

development of male internal genitalia and DHT mediates development of the external genitalia.

Fragile X syndrome is an X-linked disorder that presents with a long, narrow face, a prominent chin and forehead, and large testes. Patients often have

developmental delay and neuropsychiatric findings that overlap with anxiety disorders, autism, and attention deficit-hyperactivity disorder.

Pt has anion-gap metabolic acidosis in the setting of abdominal pain and hyperglycemia. These findings are suggestive of

diabetic ketoacidosis

Nodular glomerulosclerosis is characterized by glomerular basement membrane thickening, increased mesangial matrix deposition, and formation of Kimmelstiel-Wilson nodules. It is most commonly caused by

diabetic nephropathy and indicates irreversible glomerular damage with a rapid decline in kidney function.

Kimmelstiel-Wilson nodules are part of what disease?

diabetic nephropathy-hyaline acellular deposits made of plasma proteins

After a ligand binds to a G protein-coupled receptor that activates phospholipase C, membrane phospholipids are broken down into

diacylglycerol (DAG) and inositol triphosphate (IP3) Protein kinase C is subsequently activated by DAG and calcium; the latter is released from the endoplasmic reticulum under the influence of IP3

Reverse transcription polymerase chain reaction (RT-PCR) is used to detect and quantify levels of mRNA in a sample. It uses reverse transcription to create a complementary DNA template that is then amplified using the standard PCR procedure. RT-PCR can be used to

diagnose chronic myelogenous leukemia by identifying an mRNA transcript containing both BCR and ABL exons in affected cells.

Carcinoembryonic antigen (CEA) levels are increased in colon cancer but are also elevated in a number of other conditions (eg, pancreatic cancer, COPD, cirrhosis). CEA cannot be used to

diagnose colon cancer, but it is helpful for detecting residual disease and recurrence.

Hereditary hemochromatosis is characterized by excessive intestinal iron absorption with deposition of iron in parenchymal tissues. Cardiac manifestations include

diastolic dysfunction (initial), dilated cardiomyopathy (later), and conduction system disease (eg, sinus node dysfunction).

The tissue tropism of viruses is primarily mediated by viral surface glycoproteins that bind to specific host cell receptors. Mutations to viral surface glycoproteins can alter

tissue tropism and cause noninfective viruses to become infectious.

Rheumatic mitral stenosis is characterized by diffuse fibrous thickening and distortion of the mitral valve leaflets along with commissural fusion at the leaflet edges. Patients often present with a

diastolic murmur, dyspnea, and fatigue and are at increased risk of atrial fibrillation and thromboembolism (eg, stroke).

Alternative splicing is a process where the exons of a gene are reconnected in multiple ways during post-transcriptional processing. This creates different mRNA sequences and subsequently,

different protein isoforms. It is a normal phenomenon in eukaryotes that greatly increases the biodiversity of proteins encoded by the genome.

D-xylose is a monosaccharide whose absorption is not affected by exocrine pancreatic insufficiency, and can be used to

differentiate between pancreatic versus mucosal causes of malabsorption

Cocaine intoxication can produce psychotic symptoms (eg, paranoid delusions), euphoria, and agitation. Physical signs indicating sympathetic stimulation (eg, tachycardia, diaphoresis, mydriasis) can assist in

differentiating cocaine intoxication from primary psychiatric disorders.

A learning disorder is characterized by

difficulties with key academic skills (reading, writing, or mathematics) Many children display symptoms of anxiety, inattention, defiance, or hyperactivity when under stress to perform in an area of weakness, as exemplified by this child's struggle to pay attention and his emotional outburst in class.

There are 2 morphological variants of gastric adenocarcinoma. The intestinal type forms a solid mass that projects into the stomach lumen and is composed of glandular-forming cuboidal or columnar cells. In contrast,

diffuse carcinoma (linitis plastica) infiltrates the stomach wall and displays signet-ring cells on light microscopy.

Asbestosis is a pneumoconiosis that occurs with inhalation of asbestos fibers, most commonly in patients with occupational exposure (eg, insulation installation, shipbuilding, pipe work). Histopathology demonstrates

diffuse interstitial fibrosis and ferruginous asbestos bodies (translucent fibers coated with a golden iron-containing material). Pleural disease (eg, plaques, benign effusions) is common.

Neuroleptic malignant syndrome is a life-threatening reaction to antipsychotic medications characterized by

diffuse muscle rigidity, hyperthermia, autonomic instability, and altered sensorium. The antipsychotic should be stopped and supportive care provided; dantrolene, a ryanodine receptor blocker that inhibits calcium release from the sarcoplasmic reticulum, is an effective antidote.

Contrast-induced nephropathy is characterized by an acute rise in creatinine and blood urea nitrogen after radiologic contrast administration, followed by a gradual return to baseline. It is characterized histologically by

diffuse necrosis of the proximal tubular cells (ie, acute tubular necrosis). Urinalysis usually demonstrates muddy brown casts.

Viral bronchiolitis is most commonly caused by respiratory syncytial virus and presents with low-grade fever, cough, and respiratory distress (eg, tachypnea, retractions) in children age <2 years. Examination typically shows

diffuse wheezes and/or crackles.

The accumulation of blood 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

Diffusion of oxygen across the alveolar-capillary membrane is normally very rapid. Decreased diffusion rate (eg, interstitial lung disease) can lead to

diffusion-limited oxygen transfer, especially when the perfusion rate increases (eg, exertion).

Tetrahydrobiopterin (BH4) is a cofactor used by hydroxylase enzymes in the synthesis of tyrosine, dopamine, and serotonin. Phenylketonuria can result from BH4 deficiency due to

dihydropteridine reductase deficiency. Intellectual disability is the hallmark of this condition and results in neurotransmitter (eg, serotonin) deficiency and hyperphenylalanemia. Treatment involves a low phenylalanine diet and BH4 supplementation.

Somatic mosaicism affects the cells forming the body, causing:

disease manifestations to develop in affected individuals

adenomyosis

disorder caused by an abnormal collection of endometrial glands and stroma within the uterine myometrium common in multiparous women and prior uterine surgery is a risk factor symptoms include painful and heavy periods and a uniformly enlarged uterus

Prostate cancer is common in older men and metastasizes primarily to bone due to bone-specific tumor adhesion molecules and receptor ligands on the cellular surface. Prostate cancer causes osteoblastic lesions that result in new bone growth. Biopsy would show

disordered trabeculae and signs of prostate cancer such as irregular glands with enlarged nuclei and prominent nucleoli.

Hamartomas are the most common benign lung tumors. They present as asymptomatic peripherally located "coin lesion" in patients 50-60 years old. These tumors are composed of

disorganized cartilage, fibrous and adipose tissue.

The development of derivatives of the first (eg, trigeminal nerve, mandible, maxilla, zygoma, incus, malleus) and second (eg, facial nerve, stapes, styloid process, lesser horn of hyoid) pharyngeal arches can be

disrupted in genetic disorders (eg, Treacher-Collins syndrome), resulting in hypoplasia of the mandibular and zygomatic bones.

The absence of normal enteral stimulation in patients receiving total parenteral nutrition leads to decreased cholecystokinin release, biliary stasis, and increased risk of gallstones. Resection of the ileum can also increase the risk of gallstones due to

disruption of normal enterohepatic circulation of bile acids.

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. Raltegravir is an integrase inhibitor that

disrupts HIV genome integration, preventing synthesis of viral mRNA.

Helicobacter pylori antral gastritis is associated with the formation of

duodenal ulcers due to increased gastric acid production. This increase in acidity is caused by unchecked gastrin production due to the destruction of somatostatin-secreting cells in the gastric antrum.

The lungs exert collapsing force, and the resting chest wall exerts expanding force. These opposing forces are in equilibrium at the functional residual capacity and generate sustained intrapleural negative pressure that allows the lung and chest wall to move together as a combined respiratory unit. Loss of intrapleural negative pressure (eg, pneumothorax)

disrupts the combined system, causing the chest wall to spring outward to its equilibrium position, enlarging the hemithorax. Similarly, the lung collapses to its equilibrium position where inspiratory compliance is decreased.

Paroxysmal nocturnal hemoglobinuria may be treated with a monoclonal antibody to the complement component C5 (ie, terminal complement inhibitor), increasing the risk of

disseminated Neisseria meningitidis infection. Therefore, these patients should receive immunization and antibiotic prophylaxis against N meningitidis.

Coccidioides immitis infection can be asymptomatic or it can cause pulmonary disease ranging from a flulike illness to chronic pneumonia. It causes

disseminated disease in immunocompromised patients. Spherules containing endospores are found in tissue samples.

Neisseria gonorrhoeae is spread sexually by genitourinary secretions and can be prevented by the consistent use of condoms. Genitourinary infections are often asymptomatic, which increases the risk of spread through the bloodstream, leading to

disseminated gonococcal infection. Patients with disseminated disease typically present with the triad of polyarthralgia, tenosynovitis, and dermatitis or purulent arthritis.

Phencyclidine (PCP) is primarily an N-methyl-D-aspartate receptor antagonist, with lesser effects on the reuptake inhibition of biogenic amines and other receptors. It can have

dissociative and anesthetic effects but may also cause psychosis and severe agitation, leading to violent trauma. Ataxia, horizontal and vertical nystagmus, and memory loss can also be present.

Sacral spinal cord injury can lead to lower motor neuron injury of the S2-S4 nerve rootlets; these contribute parasympathetic innervation to the distal colon to stimulate peristalsis and voluntary motor innervation to the external anal sphincter. Lesions in this area can lead to

distal colon stool retention, fecal incontinence, and a weak external anal sphincter.

Increases in the capillary hydrostatic pressure or the Bowman's space oncotic pressure will increase GFR, while increases in capillary oncotic pressure or Bowman's space hydrostatic pressure will decrease GFR. The filtration fraction (FF) can be calculated by

dividing the GFR by the renal plasma flow (RPF). Increases in GFR or decreases in RPF will increase the FF.

Most prostate cancer arises in the peripheral zone of the gland, which abuts the rectum. Therefore, prostate biopsies are primarily obtained via the transrectal approach; multiple random core samples of the prostate are typically taken. Because only a small part of the peripheral zone encases the distal urethra, patients with prostate cancer

do not typically present with urinary symptoms.

Projection is an immature defense mechanism involving the misattribution of one's unacceptable feelings or thoughts to another person who

does not actually have them.

Dopamine receptor blockers (eg, metoclopramide, prochlorperazine) act as antiemetics and pain relievers for severe migraine headache associated with nausea and vomiting. However,

dopamine blockade can also result in excess cholinergic activity (eg, acute dystonic reactions); diphenhydramine can be co-administered with dopamine receptor blockers to prevent these reactions due to its anticholinergic activity.

Positive symptoms of schizophrenia (eg, delusions, hallucinations) are associated with increased activity of

dopamine in the mesolimbic pathway. Antipsychotics work by antagonizing dopamine receptors in this pathway.

Prolactin release is negatively regulated by

dopamine, which acts on the dopamine D2 receptors of lactotrophs, the prolactin-producing cells of the pituitary

Neurologic damage associated with vitamin B12 deficiency classically includes subacute combined degeneration of the

dorsal columns (loss of position and vibration sensation, positive Romberg sign) and lateral corticospinal tracts (spastic paresis).

Dihydrobiopterin reductase deficiency results in impaired tetrahydrobiopterin (BH4) levels. BH4 is an important cofactor for both phenylalanine hydroxylase and tyrosine hydroxylase. Although phenylalanine levels can be corrected with dietary restriction,

downstream deficiencies of dopamine, norepinephrine, epinephrine, and serotonin lead to progressive neurologic deterioration.

Lymphatic drainage of the rectum proximal to the anal dentate line occurs via the inferior mesenteric and internal iliac lymph nodes. Areas distal to the dentate line

drain primarily into the inguinal nodes.

Leuprolide is a GnRH agonist used to treat prostate cancer. It initially stimulates pituitary LH secretion, which leads to a rise in androgen levels. However, the GnRH receptor is subsequently down-regulated, which

dramatically drops LH release and leads to a long-term decrease in androgen production.

REM sleep is characterized by

dreaming and voluntary muscle paralysis, and occurs more often during the final third of the night. Nightmares occur during REM sleep and can be differentiated from sleep terrors, a non-REM parasomnia characterized by incomplete arousals and lack of recall of dream content.

Pulsus paradoxus is a

drop in systolic blood pressure >10 mm Hg during inspiration It can be seen in cardiac tamponade, constrictive pericarditis, and severe asthma or chronic obstructive pulmonary disease.

Procainamide and hydralazine have the highest risk of causing

drug-induced lupus erythematosus (DILE), which is characterized by the development of lupus-like symptoms in addition to positive ANA and anti-histone antibodies. Unlike with SLE, anti-dsDNA antibodies are rarely seen.

Celiac disease is an autoimmune disorder triggered by dietary gluten that develops almost exclusively in patients with HLA-DQ2 or -DQ8 serotypes. It often causes diarrhea and malabsorption (eg, iron deficiency anemia). The earliest histologic finding is

duodenal intraepithelial lymphocytosis; crypt hyperplasia and villous blunting develop later.

Infarcts involving the anterior portion of the medial pons can produce

dysarthria and contralateral hemiparesis/lower facial palsy due to disruption of the ipsilateral corticospinal and corticobulbar tracts. The trigeminal nerve arises at the level of the middle cerebellar peduncle at the lateral aspect of the mid-pons.

Endometriosis causes chronic pelvic pain due to ectopic implantation of endometrial glands and stroma in the abdominopelvic cavity. Bladder implants may also result in dysuria while rectovaginal implants may cause

dyschezia, rectovaginal nodularity, and pelvic fibrosis (eg, immobile uterus).

Entamoeba histolytica is an ameba that causes

dysentery (bloody diarrhea)

Choriocarcinoma is a malignant form of gestational trophoblastic disease composed of anaplastic cytotrophoblasts and syncytiotrophoblasts without villi. It often presents as

dyspnea/hemoptysis due to pulmonary metastasis from hematogenous spread

Pulmonic regurgitation yields what kind of murmur?

early diastolic murmur that starts with S2 and ends before S1 decrescendo may increase in intensity during inspiration high-pitched blowing sound that is heard best over the left second and third intercostal spaces

Patients with cystic fibrosis are at risk for fat-soluble vitamin (ie, A, D, E, K) deficiency due to fat malabsorption from pancreatic insufficiency. Vitamin K is an important cofactor in the activation of coagulation factors II, VII, IX, and X. Vitamin K deficiency leads to

easy bruising, mucosal bleeding, and prolonged PT.

paraneoplastic hypercortisolism, most commonly caused by small cell lung cancer, is due to

ectopic ACTH secretion clinical features include HTN, hyperglycemia, edema, and hyperpigmentation

Atrial fibrillation is recognized by an irregularly irregular rhythm with variable R-R intervals and absence of P waves on ECG. The development of AF most commonly involves

ectopic electrical foci in the pulmonary veins that trigger fibrillatory conduction in abnormal (remodeled) atrial tissue.

Staphylococcal food poisoning is mediated by the ingestion of a preformed, heat-stable enterotoxin that induces rapid-onset (<6 hours) nausea and vomiting. Most cases arise due to improper food handling and storage. Common culprit foods include

eggs, dairy products, and mayonnaise-based salads.

Vascular calcifications occur more commonly in patients with chronic kidney disease due to

electrolyte abnormalities (eg, hyperphosphatemia, hypercalcemia) and chronic inflammation (secondary to atherosclerosis and/or uremia). These changes promote calcification and suppress calcification inhibitors, which can result in extensive vascular calcifications.

Zollinger-Ellison syndrome is caused by gastrinomas located in the small intestine/pancreas and presents with peptic ulcers (especially distal duodenal ulcers), heartburn, and diarrhea. Patients typically have

elevated gastrin levels that rise in response to exogenous secretin administration. In contrast, secretin inhibits release of gastrin from normal gastric G cells.

Dermatomyositis is characterized by proximal muscle weakness (similar to polymyositis) and dermal manifestations (eg, heliotrope rash, Gottron papules). Laboratory testing shows

elevated muscle enzymes (eg, creatine kinase) and autoantibodies (eg, antinuclear, anti-Jo-1). Initial treatment includes systemic glucocorticoids and evaluation for potential underlying malignancy.

The most common cause of coronary sinus dilation evident on ECG is:

elevated right-sided heart pressure secondary to pulmonary HTN

Celiac disease is caused by an immune-mediated reaction to gluten and classically leads to chronic gastrointestinal symptoms. Diagnosis is confirmed by

elevated tissue transglutaminase IgA antibody levels and duodenal biopsy showing villus flattening, intraepithelial lymphocyte infiltration, and crypt hyperplasia.

Mefloquine chemoprophylaxis for malaria must be continued for 4 weeks after return from an endemic region to ensure the

elimination of hepatic schizonts (which develop in the liver over 8-30 days).

Diphtheria toxin and pseudomonal exotoxin A act by ribosylating and inactivating

elongation factor-2, inhibiting host cell protein synthesis and causing cell death.

Patients with sickle cell disease become functionally asplenic within the first few years of life due to repeated microinfarction of splenic vascular beds. This dramatically increases the risk for fulminant infections with

encapsulated bacterial organisms, particularly Streptococcus pneumoniae. Patients with sickle cell disease are also at increased risk for other bacterial infections, most notably salmonella osteomyelitis.

Arboviruses, small RNA viruses transmitted by biting arthropods, are the most common cause of

encephalitis outbreaks in the United States. Because no vaccines are currently available, prevention primarily involves eliminating the vector arthropods (eg, infected mosquitos).

Progesterone is the primary hormone responsible for stimulating the endometrium so that it is suitable for implantation. Progesterone withdrawal causes

endometrial cells to undergo apoptosis, resulting in menstrual bleeding.

Polycystic ovary syndrome (PCOS) is associated with oligomenorrhea, hirsutism, and polycystic ovaries. Disruption in intraovarian steroidogenesis causes anovulatory cycles and results in chronic estrogen stimulation with decreased progesterone secretion, placing PCOS patients at risk for

endometrial hyperplasia/carcinoma

Cardiac tamponade involves restriction of diastolic filling of the right-sided heart chambers, with

engorgement and decreased inspiratory collapse of the inferior vena cava seen on echocardiography. Pulsus paradoxus (>10 mm Hg drop in systolic blood pressure during inspiration) is commonly present with tamponade.

Bullous pemphigoid is characterized by autoantibodies against hemidesmosomes along the basement membrane of the dermal-epidermal junction. This causes the

entire epidermis to separate from the dermis, forming tense, subepidermal blisters.

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.

Febrile, ill-appearing patient with respiratory distress who is in the tripod position likely has

epiglottitis-rare and potentially fatal infection most commonly caused by Hib. Edema of the epiglottis can cause laryngeal obstruction that leads to inspiratory stridor

Pheochromocytoma is a tumor arising from the chromaffin cells of the adrenal medulla characterized by excess production of catecholamines. Clinical features include

episodic hypertension, diaphoresis, and palpitations. Microscopic examination of the tumor cells shows electron-dense, membrane-bound secretory granules, and immunohistochemistry is positive for synaptophysin, chromogranin, and neuron-specific enolase.

Intraductal papilloma is 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.

methotrexate and other folic acid antagonists adversely affect rapidly dividing cells, like

epithelial cells, stem cells, neural tube cells by limiting the production of precursors essential to DNA synthesis and repair

Sarcoidosis commonly presents with hilar adenopathy, pulmonary infiltrates, and skin (eg, erythema nodosum) and ocular findings. Biopsy shows noncaseating granulomas composed of

epithelioid cells (activated macrophages) and giant multinucleated cells. Oral glucocorticoids are the treatment of choice for significant disease.

Azoles inhibit synthesis of

ergosterol by the fungal cytochrome P450 enzymes. They also suppress the human P450 system, resulting in many drug-drug interactions.

Amphotericin B binds the

ergosterol of fungal cell membranes to exert its antifungal effects. However, it also binds cholesterol to some degree, causing toxicity to human tissues. The most important adverse effects of amphotericin B are nephrotoxicity, hypokalemia, and hypomagnesemia.

Erythema multiforme is a cell-mediated inflammatory disorder of the skin characterized by

erythematous papules that evolve into target lesions. It is most commonly associated with herpes simplex virus.

Pityriasis versicolor (tinea versicolor) is a superficial skin infection caused by Malassezia species. It causes

erythematous, hyper- or hypopigmented macules and patches. Malassezia forms spores and hyphae, producing the characteristic "spaghetti and meatballs" appearance on KOH preparation light microscopy.

Acute hemolytic transfusion reaction is a antibody-mediated (type II) hypersensitivity reaction caused by pre-existing anti-ABO antibodies that bind antigens on transfused donor erythrocytes. Subsequent complement activation results in

erythrocyte lysis, vasodilation, and symptoms of shock. Common findings include fever, hypotension, chest and back pain, and hemoglobinuria.

voltage-gated sodium channels are important for the generation and propagation of action potentials. When the action potential reaches the axon terminal, voltage-gated calcium channels open and allow the influx of calcium, which is

essential for the fusion and release of neurotransmitter vesicles into the synaptic cleft.

Thyroxine-binding globulin deficiency is a benign disorder characterized by low total thyroxine (T4) and normal free T4 and TSH levels. Patients are

euthyroid and do not require treatment.

Absolute risk reduction =

event rate in the control group − event rate in the treatment group.

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).

carotid sinus hypersensitivity is a common cause of syncope associated with tactile stimulation of the carotid sinus (eg, shaving). The syncope results from an

exaggerated vagal response stimulated by the carotid baroreceptors, which leads to slowed heart rate and marked peripheral vasodilation with a resulting transient loss of cerebral perfusion.

The sympathetic nervous system typically regulates visceral function via 2-neuron signal transmission involving cholinergic preganglionic neurons and adrenergic postganglionic neurons. Eccrine sweat glands and the adrenal medullae are

exceptions to this rule as they are both innervated by cholinergic neurons. The parasympathetic system uses both preganglionic and postganglionic cholinergic neurons.

Fibroblast and vascular proliferation (ie, granulation tissue) induced by vascular endothelial growth factor (VEGF) is essential to normal wound healing. However, if this tissue proliferation becomes

excessive (eg, in wounds left to heal by secondary intention), the resulting hypergranulation tissue can impair wound reepithelization and remodeling.

Neonates born to mothers with poorly controlled diabetes during pregnancy are exposed to high maternal glucose levels in utero, resulting in

excessive fetal insulin production and islet hyperplasia. Fetal hyperinsulinemia persists for several days following birth and predisposes the infant to transient hypoglycemia.

Tracheoesophageal fistula with esophageal atresia results from failure of the primitive foregut to appropriately divide into separate trachea and esophageal structures. Infants present shortly after birth with

excessive secretions and choking/cyanosis during feeds.

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.

Pseudomonas aeruginosa produces

exotoxin A, similar in function to diphtheria toxin in that it halts human cellular protein synthesis by inhibiting elongation factor-2

Selection of control subjects in case-control studies is intended to provide an accurate estimation of exposure frequency among the nondiseased general population. Cases and controls should be selected based on disease status, not

exposure status

A case-control study is used to compare the exposure status of people with the disease (ie, cases) to the

exposure status of people without the disease (ie, controls). The main measure of association is the odds ratio.

Primary amebic encephalitis occurs when the free-living, motile protozoan Naegleria fowleri penetrates the olfactory mucosa and migrates in a retrograde fashion through the olfactory nerve to the brain. This rare, deadly infection primarily occurs after

exposure to warm, fresh water during recreational activities.

Misclassification bias is an incorrect categorization of subjects regarding their

exposure, outcome status, or both. In case-control studies, recall bias usually leads to misclassification of the exposure status.

The multiplication law of probability states that the probability of 2 or more independent events occurring together can be calculated by multiplying the individual probabilities of each event. The multiplication law of probability can be

extended to complementary events (1 − probability of event) in the same manner.

The piriformis passes through the greater sciatic foramen and is involved with

external hip rotation. Muscle injury or hypertrophy can compress the sciatic nerve in the foramen, causing piriformis syndrome.

Hereditary nonpolyposis colon cancer (HNPCC), or Lynch syndrome, leads to occurrence of colonic adenocarcinomas at a young age (age <50) along with a predisposition for

extraintestinal malignancies. Mutations of DNA mismatch repair genes are responsible for HNPCC.

Myasthenia gravis is characterized by autoantibodies against postsynaptic nicotinic acetylcholine receptors at the neuromuscular junction, which result in receptor degradation. Patients typically have

extraocular, bulbar, and facial weakness that worsens with activity. In severe cases, the respiratory muscles may be affected, leading to hypoventilation and respiratory failure.

Second-generation antipsychotics are associated with a lower risk of

extrapyramidal side effects compared with first-generation antipsychotics but may cause adverse metabolic effects.

Pleural effusions that develop due to inflammation and consequent increased vascular membrane permeability (eg, infection, malignancy, rheumatologic disease), are typically

exudative

hemophilia B is due to decreased levels of

factor IX

hemophilia A is due to decreased levels of

factor VIII

Andexanet alfa is a factor Xa decoy that has no proteolytic effect. It is administered to patients on

factor Xa inhibitors (eg, rivaroxaban, apixaban) who have life-threatening bleeding in order to reverse the anticoagulation effect.

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.

Neurotoxicity is the dose-limiting side effect of vincristine therapy. This toxicity results from

failure of microtubule polymerization in neuronal axons. Other notable adverse effects classically associated with chemotherapeutic agents include pulmonary fibrosis and flagellate skin discoloration with bleomycin use; congestive heart failure with doxorubicin; and hemorrhagic cystitis with cyclophosphamide.

Malabsorption is a syndrome of impaired intestinal digestion and absorption. Fats are typically the most severely affected macronutrient in generalized malabsorption, and testing the stool for

fat (eg, with Sudan III stain) is the most sensitive strategy for screening for malabsorptive disorders.

Vitamin K deficiency is typically seen in patients with:

fat malabsorption (pancreatic insufficiency) or those on warfarin, a vitamin K antagonist

Cocaine withdrawal is characterized by the development of acute depression accompanied by

fatigue, hypersomnia, hyperphagia, and vivid dreams.

Autoimmune hepatitis results from an immune response against hepatic antigens, leading to a lymphoplasmacytic infiltrate in the portal and periportal regions of the liver. Manifestations include

fatigue, weight loss, nausea, and/or signs of acute hepatitis (eg, jaundice, abdominal discomfort). Characteristic laboratory abnormalities include a hepatocellular pattern of liver injury, anti-smooth muscle autoantibodies, and hypergammaglobulinemia.

Carnitine deficiency impairs

fatty acid transport from the cytoplasm into mitochondria, preventing β-oxidation of fatty acids into acetyl CoA. This leads to cardiac and skeletal myocyte injury (lack of ATP from citric acid cycle) and impaired ketone body production by the liver during fasting periods.

The optimal site for obtaining vascular access in the lower extremity during cardiac catheterization is the common

femoral artery below the inguinal ligament. Cannulation above the inguinal ligament can significantly increase the risk of retroperitoneal hemorrhage.

Femoral hernias can present with groin discomfort and a tender bulge on the upper thigh inferior to the inguinal ligament, lateral to the pubic tubercle and lacunar ligament. The structure that lies immediately lateral to the hernia within the femoral sheath is the

femoral vein. Incarceration and strangulation are common complications of femoral hernias.

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

Trisomy 18, or Edwards syndrome, is most commonly the result of meiotic nondisjunction due to advanced maternal age. Key findings include

fetal growth retardation, hypertonia (clenched hands with overlapping fingers), rocker bottom feet, and cardiac/gastrointestinal/renal defects.

Measles presents with

fever, cough, rhinorrhea, and conjunctivitis followed by a maculopapular rash that starts on the face and spreads downwards Koplik spots are pathognomonic for measles and characterized by tiny white or blue-gray lesions on the buccal mucosa

Classically, measles presents with a prodrome of

fever, cough, rhinorrhea, and conjunctivitis. Koplik spots on the buccal mucosa are a pathognomonic finding and consist of small white, blue, or gray specks on an erythematous base. These symptoms precede a maculopapular exanthem that starts on the face and spreads down the trunk and extremities

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome typically occurs 2-8 weeks after exposure to high-risk drugs such as anticonvulsants (eg, phenytoin, carbamazepine), allopurinol, sulfonamides (eg, sulfasalazine), and antibiotics (eg, minocycline, vancomycin). Patients typically develop

fever, generalized lymphadenopathy, facial edema, diffuse skin rash, eosinophilia, and internal organ dysfunction.

Serum sickness is a type III hypersensitivity reaction to nonhuman proteins characterized by vasculitis resulting from tissue deposition of circulating immune complexes. Clinical findings include

fever, pruritic skin rash, arthralgias, and low serum C3 and C4 complement levels.

Lobar pneumonia is marked by the cytokine-mediated accumulation of neutrophils and proteinaceous material in the alveoli. Over several days, the proteinaceous material becomes

fibrinous, neutrophils are replaced by macrophages, and macrophages digest the fibrinous exudate, thereby restoring normal lung histology.

Crescent formation on light microscopy is diagnostic for rapidly progressive glomerulonephritis. Crescents consist of glomerular parietal cells, lymphocytes, and macrophages along with abundant fibrin deposition. Crescents eventually become

fibrotic, disrupting glomerular function and causing irreversible renal injury.

Pulmonary actinomycosis develops most commonly following aspiration and can be confused with lung abscess, malignancy, or tuberculosis. Microscopic findings include

filamentous, branching, gram-positive bacteria and sulfur granules

Sexual dysfunction is seen in up to 50% of patients treated with selective serotonin reuptake inhibitors. Bupropion, a norepinephrine-dopamine reuptake inhibitor, is a

first-line treatment for major depressive disorder and does not cause sexual dysfunction.

Delirium is characterized by the acute onset of

fluctuating disturbance in attention and general cognition (eg, altered level of consciousness, disorientation, hallucinations). Common medications that may precipitate delirium in high-risk populations (eg, elderly patients) include sedative-hypnotics, benzodiazepines, opioids, and anticholinergic medications.

Delirium is frequently associated with psychotic symptoms. It is differentiated from primary psychotic disorders by

fluctuating levels of consciousness, impaired attention, and disorientation. Delirium can occur postoperatively and/or in association with underlying medical illnesses or the introduction of certain medications.

Aminoglycosides are filtered across the glomerulus and concentrate in the renal tubules, leading to proximal tubular injury and acute tubular necrosis. This is visualized histologically as

focal tubular epithelial necrosis, often with extensive granular casts that obstruct the tubular lumen and lead to rupture of the basement membrane.

Multiple sclerosis is an immune-mediated disorder of the central nervous system characterized by focal demyelination (plaques). Histologically, plaques contain foci of perivenular inflammatory infiltrates made up primarily of autoreactive T lymphocytes and macrophages. Patchy demyelination occurs

followed by astrocyte hyperplasia (glial scarring).

CSF flows from the third ventricle to the fourth ventricle via the cerebral aqueduct of Sylvius. Obstruction at this level can cause dilated lateral and third ventricles with a normal-sized fourth ventricle. Obstruction at the

foramen of Monro would cause enlargement of only the affected lateral ventricle, while obstruction at the foramen of Magendie and Luschka causes enlargement of all 4 ventricles.

The spleen is of mesodermal origin (the dorsal mesentery). Although it is supplied by the splenic artery (a branch of the major foregut vessel, the celiac trunk), it is not a

foregut derivative.

Because expression of the MHC class II-peptide complex is necessary for activation of B and T cells, its absence (eg, bare lymphocyte syndrome type II) causes a

form of severe combined immunodeficiency.

Digoxin directly inhibits the Na-K-ATPase pump in myocardial cells, leading to a decrease in sodium efflux and an increase in intracellular sodium levels. This reduces the

forward activity of the sodium-calcium exchanger, causing increased intracellular calcium concentration and improved myocyte contractility.

Giardia lamblia is a protozoal organism that classically causes

foul-smelling, greasy diarrhea and excessive flatulence after consumption of contaminated water

Type 2 diabetes mellitus is due to insulin resistance and relative insulin deficiency. Chronically elevated

free fatty acid levels contribute to insulin resistance by impairing insulin-dependent glucose uptake and increasing hepatic gluconeogenesis

The pathogenesis of alcohol-induced hepatic steatosis appears related primarily to a decrease in

free fatty acid oxidation secondary to excess NADH production by the 2 major alcohol metabolism enzymes, alcohol dehydrogenase and aldehyde dehydrogenase.

Mitral valve prolapse with regurgitation is the most common predisposing condition for native valve infective endocarditis (IE) in developed nations. Rheumatic heart disease remains a

frequent cause of IE in developing nations.

Retroperitoneal hematoma is a common complication of abdominal and pelvic trauma. The pancreas is a retroperitoneal organ, and pancreatic injury is

frequently a source of retroperitoneal bleeding.

Typical clinical and laboratory features of Epstein-Barr virus (EBV) mononucleosis include fever, pharyngitis, lymphadenopathy, splenomegaly, and atypical lymphocytosis. EBV is generally transmitted

from an asymptomatic virus shedder to a susceptible individual through saliva transfer (eg, kissing).

Rickets is characterized by an excess of unmineralized osteoid matrix and epiphyseal cartilage due to vitamin D deficiency. Clinical manifestations include

frontal bossing, craniotabes, costochondral junction deformity ("rachitic rosary"), and bowed legs.

Aldolase B deficiency causes hereditary fructose intolerance. This disease manifests after introduction of fructose into the diet with vomiting and hypoglycemia about 20-30 minutes after

fructose ingestion. These infants can present with failure to thrive, jaundice, and hepatomegaly.

Acquired methemoglobinemia can be precipitated by benzocaine and result in the conversion of Fe2+ to Fe3+, which results in

functional anemia and a left shift of the oxygen dissociation curve. Patients have cyanosis that does not improve with supplemental oxygen.

Antipsychotic medications work by blocking dopamine-2 receptors in the mesolimbic dopamine pathway. Dopamine-2 receptor blockade in the tuberoinfundibular pathway can result in

galactorrhea and amenorrhea

Pituitary tumors can present with headaches, bitemporal hemianopsia, and hypopituitarism; the most common hormonally active (functional) adenomas are prolactin-secreting adenomas (prolactinomas). Prolactinomas can cause

galactorrhea and amenorrhea in women. In men, they often present with hypogonadism.

Classic galactosemia results from deficiency of

galactose-1-phosphate uridyl transferase. Clinical features include vomiting, lethargy, jaundice, and Escherichia coli sepsis. Cessation of breastfeeding and switching to soy milk-based formula is recommended.

CCK stimulates:

gallbladder contraction and pancreatic enzyme and bicarbonate secretion it is secreted in the duodenum and jejunum in response to fat and protein in the intestinal lumen and levels rise following meals

Eighty percent of acute pancreatitis cases are caused by

gallstones and chronic alcoholism. Less common causes account for the other 20%. Inherited or acquired hypertriglyceridemia can cause acute pancreatitis if the serum level of triglycerides exceeds 1000 mg/dL.

Osteocytes have long intracanalicular processes that extend through the ossified bone matrix. These cytoplasmic processes send signals to and exchange nutrients and waste products with the osteocytes within neighboring lamellae via

gap junctions. Osteocytes can sense mechanical stresses and send signals to modulate the activity of surface osteoblasts, thereby helping to regulate bony remodeling.

This patient's weight loss, early satiety, positive smoking history, and left supraclavicular adenopathy are concerning for

gastric adenocarcinoma (GA). Patients with GA can also have epigastric pain, hematemesis, and occult blood loss in the stool. Physical examination findings in advanced (metastatic) disease include left supraclavicular (Virchow node) or left axillary lymphadenopathy, or a periumbilical mass (Sister Mary Joseph nodule).

5-HT3 receptor antagonists are useful for the treatment of visceral nausea due to

gastrointestinal insults, such as gastroenteritis, chemotherapy, and general anesthesia. Antihistamines and anticholinergics are recommended for vestibular nausea. Dopamine antagonists are useful for nausea associated with migraine.

Acute extrapyramidal symptoms (eg, dystonia, akathisia, parkinsonism) are due to D2 blockade in the nigrostriatal pathway. First-generation,

high-potency antipsychotics (eg, haloperidol, fluphenazine) strongly block D2 receptors and are most likely to cause extrapyramidal symptoms.

Polyhydramnios (excessive accumulation of amniotic fluid) presents with increased abdominal circumference out of proportion to gestational age. The etiology is decreased fetal swallowing or increased fetal urination. Fetal anomalies associated with impaired swallowing include

gastrointestinal obstruction (eg, duodenal, esophageal, or intestinal atresia) and anencephaly.

Broad-spectrum anticonvulsants (eg, levetiracetam, valproic acid) treat both focal and generalized onset seizures, whereas narrow-spectrum anticonvulsants (eg, carbamazepine, phenytoin) are primarily used only for focal onset seizures. Because the seizures in juvenile myoclonic epilepsy are usually

generalized onset (ie, affect both cerebral hemispheres at onset), treatment is with a broad-spectrum agent such as valproic acid.

Melanoma is a highly aggressive malignancy that often metastasizes early in the disease course. Patients may be asymptomatic for years prior to onset of metastatic manifestations. Diagnosis is

generally made when a histopathologic sample shows cellular atypia with cells containing brown pigment (melanin granules); immunostaining for melanocytic markers (eg, S-100, HMB-45) is generally positive.

This patient with headaches, visual and muscular symptoms, an enlarged temporal artery, and elevated erythrocyte sedimentation rate has typical features of

giant cell arteritis

Herpetic gingivostomatitis is a severe vesicular or ulcerative disease following primary infection with herpes simplex virus type 1. The diagnosis is supported by the presence of multinucleated giant cells in a Tzanck smear. Involvement of the

gingiva, tongue, palate, and pharynx along with systemic symptoms (eg, fever, malaise) is common. In contrast, herpes reactivation in the trigeminal ganglia generally results in mild perioral vesicles.

The common cardinal veins of the developing embryo drain directly into the sinus venosus. These cardinal veins ultimately

give rise to the superior vena cava and other constituents of the systemic venous circulation.

Two allele loci are said to be in linkage disequilibrium when a pair of alleles are inherited together in the same gamete (haplotype) more often or less often than would be expected

given random pairing. This most often occurs when the genes are in close physical proximity on the same chromosome.

Pauci-immune rapidly progressive glomerulonephritis frequently occurs as a manifestation of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (eg, granulomatosis with polyangiitis, microscopic polyangiitis). It is characterized by

glomerular crescent formation without immunoglobulin or complement deposits.

The zona fasciculata is the middle zone and contains foamy-appearing cells in columns (fascis is Latin for bundle or stack) that secrete

glucocorticoid hormones (primarily cortisol)

Giant cell arteritis (GCA) is characterized by 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 of GCA; therefore, patients with suspected GCA require immediate

glucocorticoid therapy.

Long-term acid suppression with proton pump inhibitors may be associated with an increased risk of osteoporotic fractures, possibly due to decreased calcium absorption. Other medications associated with an increased risk of osteoporosis include

glucocorticoids, aromatase inhibitors, and anticonvulsants that induce cytochrome P450.

After 12-18 hours of fasting, gluconeogenesis becomes the principal source of blood glucose. Gluconeogenesis uses many glycolytic enzymes, but hexokinase, phosphofructokinase, and pyruvate kinase need to be bypassed as they are unidirectional. The initial steps of

gluconeogenesis involve the conversion of pyruvate to oxaloacetate and oxaloacetate to phosphoenolpyruvate by pyruvate carboxylase and phosphoenolpyruvate carboxykinase, respectively.

Acute intermittent porphyria attacks are due to the accumulation of aminolevulinate (ALA) and porphobilinogen (PBG), resulting from inherited PBG deaminase deficiency combined with ALA synthase induction (typically due to certain medications, alcohol use, or a low-calorie diet). Management with

glucose or hemin inhibits ALA synthase activity.

In hyperglycemic states, aldose reductase converts

glucose to sorbitol at a rate faster than sorbitol can be metabolized. Sorbitol accumulates in certain cells such as lens cells, causing an influx of water and resulting in osmotic cellular injury. Depletion of NADPH by aldose reductase also increases oxidative stress, which accelerates development of cataracts and diabetic microvascular complications (eg, neuropathy, retinopathy).

Glucagon-like peptide-1 (GLP-1) regulates glucose by slowing gastric emptying, suppressing glucagon secretion, and increasing glucose-dependent insulin release. Dipeptidyl peptidase-4 inhibitors (eg, sitagliptin, saxagliptin) decrease the breakdown of GLP-1 and improve glycemic control in patients with type 2 diabetes. Because the effect on insulin is

glucose-dependent, these medications have a low risk of hypoglycemia.

Hyperammonemia in advanced liver failure occurs as a direct result of the cirrhotic liver's inability to metabolize nitrogenous waste products. Ammonia crosses the blood-brain barrier and causes excess

glutamine to accumulate within astrocytes. This decreases the amount of glutamine available for conversion to glutamate in the neurons, resulting in disruption of excitatory neurotransmission.

The patient has acute ischemic colitis, which is most likely due to embolic disease related to his atrial fibrillation. The ischemic bowel undergoes anaerobic metabolism, causing lactate accumulation in the blood that leads to an anion gap metabolic acidosis. Acidosis stimulates renal ammoniagenesis, a process by which renal epithelial cells metabolize?

glutamine, generating ammonium and bicarbonate. Ammonium ions are transported into the tubular fluid and excreted in the urine while peritubular capillaries absorb bicarbonate, which functions to buffer acids in the blood.

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 gluconeogenesis.

Tetanospasmin is a neuro-exotoxin released by Clostridium tetani. The toxin blocks the release of

glycine and gamma-aminobutyric acid (GABA) from the spinal inhibitory interneurons that regulate the lower motor neurons. These disinhibited motor neurons cause increased activation of muscles, leading to spasms and hyperreflexia.

Androgen receptor dysfunction in patients with partial androgen insensitivity syndrome leads to decreased facial, axillary, and pubic hair; oligospermia; gynecomastia; and undervirilization of external genitalia (eg, microphallus). Loss of feedback inhibition of

gonadotropin-releasing hormone results in elevated LH and testosterone levels.

Epiglottitis causes rapidly progressive respiratory distress and a swollen epiglottis ("thumbprint sign") on lateral neck x-ray. The most common pathogen is Haemophilus influenzae (ie, type b, nontypeable strains), a

gram-negative coccobacillus that often causes concomitant bacteremia.

Septic arthritis in a young, sexually active adult should raise suspicion for disseminated Neisseria gonorrhoeae infection. Patients may also have the triad of polyarthritis, a vesiculopustular skin rash, and tenosynovitis. N gonorrhoeae is a

gram-negative diplococci that is usually identified by microscopy, culture, or nucleic acid amplification.

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.

Poststreptococcal glomerulonephritis is most common in children and presents with nephritic syndrome (eg, renal failure, hypertension, hematuria with red blood cell casts) 2-4 weeks after an infection with group A beta-hemolytic Streptococcus. Immunofluorescence microscopy shows

granular deposits of IgG, IgM, and C3 in the mesangium and basement membranes.

Reducing the significance level alpha (α) in a study allows researchers to report any significant findings with

greater confidence.

Acute rheumatic fever is an autoimmune reaction following an untreated

group A streptococcal pharyngitis Anti-group A Streptococcus antibodies (eg, anti-M protein, anti-N-acetyl-beta-D-glucosamine) cross-react and attack cardiac and central nervous system antigens

Neisseria can be isolated by culture on selective media such as the Thayer-Martin VCN (vancomycin/colistin/nystatin) medium, which inhibits

growth of contaminants such as gram-positive organisms, gram-negative organisms other than Neisseria, and fungi.

Nitric oxide diffuses into the adjacent smooth muscle cells where it activates:

guanylyl cyclase and increases formation of cyclic GMP high levels of cyclic GMP activate protein kinase G, which causes a reduction in cytosolic calcium levels and relaxation of vascular smooth muscle cells

Human papillomavirus (HPV) infection causes cutaneous and genital warts as well as benign and malignant intraepithelial neoplasia. Koilocytosis is a

hallmark sign of HPV infection. Koilocytes are pyknotic, superficial or immature squamous cells with a dense, irregularly staining cytoplasm and perinuclear halo-like clearing.

A bicuspid aortic valve is a common cause of aortic stenosis in the United States. The classic auscultatory finding in patients with aortic stenosis is a

harsh, crescendo-decrescendo systolic ejection murmur heard best in the right second intercostal space with radiation to the carotids.

Carcinoid tumors are composed of islands or sheets of uniform cells with eosinophilic cytoplasm and oval-to-round stippled nuclei. These tumors are often derived from neuroendocrine cells in the gastrointestinal tract. Appendiceal carcinoids typically

have a benign course but may cause appendicitis or, rarely, carcinoid syndrome (eg, with liver metastasis).

Cytomegalovirus (CMV) is a common cause of colitis in patients with advanced AIDS. It is the second most common CMV reactivation disease in this population (CMV retinitis is the most common). Patients with CMV colitis often

have abdominal pain, fever, diarrhea, and weight loss. Colonoscopy usually shows erythema, erosions, and ulcerations; colonic biopsy typically reveals large cells with prominent basophilic intranuclear inclusions.

Hypocretin-1 (orexin-A) and hypocretin-2 (orexin-B) are neuropeptides produced in the lateral hypothalamus that promote wakefulness and inhibit REM sleep-related phenomena. Most patients who

have narcolepsy with cataplexy have undetectable levels of hypocretin-1 in their cerebrospinal fluid.

Inactivation of retinoblastoma protein activity by human papillomavirus can lead to the formation of

head and neck squamous cell carcinoma.

Infection of the medial face, sinuses (ethmoidal or sphenoidal), or teeth may spread through the valveless facial venous system into the cavernous sinus, resulting in cavernous sinus thrombosis. Patients typically present with

headache, fever, proptosis, and ipsilateral deficits in cranial nerves III, IV, VI, and V (ophthalmic and maxillary branches).

Amlodipine is a dihydropyridine calcium channel blocker commonly used as monotherapy or in combination with other agents for treatment of hypertension. Major side effects include

headache, flushing, dizziness, and peripheral edema.

In patients with patent ductus arteriosus, left-to-right shunting of oxygenated blood from the aorta into the pulmonary artery results in a

higher-than-expected oxygen concentration in the pulmonary artery. Oxygen saturation in the left and right heart chambers is unchanged.

Many patients with hypertrophic cardiomyopathy have poor cardiac reserve (eg, exercise intolerance) due to left ventricular (LV) outflow tract obstruction. This outflow obstruction is worsened by decreased LV blood volume. Beta blockers decrease

heart rate and LV contractility to increase LV blood volume, reduce LV outflow tract obstruction, and improve symptoms.

Nonexertional heat stroke (NHS) is a life-threatening disorder characterized by hyperthermia (typically >40 C [104 F]) associated with CNS dysfunction (eg, encephalopathy, syncope). Anticholinergic medications promote

heat stroke by impairing diaphoresis. Other medications associated with NHS include sympathomimetics, dopamine antagonists, diuretics, and beta blockers.

Ulnar neuropathy is characterized by numbness of the fourth and fifth digits, pain, and weakness. It is most commonly caused by compressive injury, leading to tissue ischemia and demyelination (Schwann cell injury). A nerve conduction study can

help differentiate demyelinating versus axonal neuropathies; demyelination causes slowed or blocked nerve conduction velocity whereas axonal injury leads to a reduction in signal strength.

The 3 variables that affect the total oxygen content of blood are

hemoglobin concentration, oxygen saturation of hemoglobin (SaO2), and the partial pressure of oxygen dissolved in blood (PaO2). Anemia is characterized by decreased hemoglobin concentration in the setting of normal SaO2 and PaO2.

Staphylococcus aureus can cause hepatic abscesses via hematogenous seeding of the liver. Enteric bacteria (eg, Escherichia coli, Klebsiella, and enterococci) can cause

hepatic abscesses by ascending the biliary tract (ie, ascending cholangitis), portal vein pyemia, or direct invasion from an adjacent area (eg, cholecystitis).

Theophylline is an adenosine receptor antagonist and indirect adrenergic agent with a narrow therapeutic index. It is predominantly metabolized by the

hepatic cytochrome oxidases. Inhibition of these enzymes by concurrent illness (eg, infection with fever) or ingestion of certain drugs or substances (eg, ciprofloxacin) can raise serum theophylline concentrations and cause toxicity (eg, seizures, cardiac arrhythmias).

Stellate (Ito) cells are the primary cells involved in

hepatic fibrosis. In response to hepatic injury, the stellate cells are activated and transform into myofibroblasts capable of proliferating, promoting chemotaxis, and producing large quantities of collagen. Collagen stains blue with Masson trichrome stain.

Metformin inhibits

hepatic gluconeogenesis and increases peripheral glucose utilization. Lactic acidosis is a rare complication of metformin therapy, but its risk is increased in patients with underlying renal insufficiency.

Primary biliary cholangitis is a chronic autoimmune liver disease characterized by lymphocytic infiltrates and destruction of small and midsized intrahepatic bile ducts. Similar findings are seen in

hepatic graft versus host disease, highlighting the immunologic etiology of both disorders.

Patients with cirrhosis complicated by abdominal ascites may develop a:

hepatic hydrothorax, which is a transudative, usually right-sided pleural effusion that results from passage of intraabdominal fluid into the chest cavity through small fenestrations in the diaphragm

Isoniazid can be directly hepatotoxic, causing acute, mild hepatic dysfunction in 10%-20% of patients and frank

hepatitis (fever, anorexia, and nausea, sometimes progressing to hepatic failure) in a small percentage of patients.

Thionamide antithyroid drugs (eg, propylthiouracil [PTU], methimazole) are used to decrease thyroid hormone production. Methimazole is preferred for most patients due to the

hepatotoxicity of PTU. However, methimazole has potential teratogenic effects, so PTU is preferred in the first trimester of pregnancy.

Essential tremor most often presents as a tremor of the hands that is suppressed at rest, exacerbated by outstretched arms, and more pronounced during goal-directed movements. It is often

hereditary (autosomal dominant) and can be associated with a head tremor, but it is not associated with other neurologic symptoms.

Multiple inhibitory mechanisms exist to prevent premature activation of trypsinogen before it reaches the duodenal lumen, including cleavage inactivation of trypsin by trypsin itself and production of trypsin inhibitors (eg, SPINK1). Gene mutations that render trypsin insensitive to cleavage inactivation cause

hereditary pancreatitis.

Erythema multiforme is a target-shaped, inflammatory skin lesion that typically arises in the setting of infection, particularly with

herpes simplex virus or Mycoplasma pneumoniae. It is caused by the deposition of infectious antigens in keratinocytes, leading to a strong cell-mediated (eg, cytotoxic T-cell) immune response.

The Monospot test is positive in most cases of Epstein-Barr virus-associated mononucleosis. In immunocompetent patients with a

heterophile antibody-negative mononucleosis-like syndrome, the most likely diagnosis is cytomegalovirus infection.

Achondroplasia is an autosomal dominant (AD) disorder that results in a gain-of-function mutation in the FGFR3 gene. Most individuals affected by AD disorders are

heterozygous and have a 50% chance of transmitting the mutation to their offspring.

Essential fructosuria is a benign disorder of fructose metabolism caused by fructokinase deficiency. In patients with essential fructosuria, some of the dietary fructose load is converted by

hexokinase to fructose-6-phosphate, which can then enter glycolysis; this pathway is not significant in normal individuals.

Heterozygous familial hypercholesterolemia (autosomal dominant LDL receptor defect that causes--)

high LDL levels and increases the risk of premature atherosclerosis

Nigrostriatal degeneration in Parkinson disease reduces activity of the thalamus and its projections to the cortex, resulting in bradykinesia and rigidity. Patients with medically intractable symptoms of Parkinson disease may benefit from

high-frequency deep brain stimulation of the globus pallidus internus or subthalamic nucleus as it promotes thalamo-cortical disinhibition with improved mobility.

Bacillary angiomatosis is primarily seen in patients with advanced AIDS. It is caused by the gram-negative bacterium Bartonella henselae, which is typically transmitted by a cat scratch. Patients usually develop

highly vascular, violaceous, cutaneous lesions over weeks or months. Histology of the lesions reveals large endothelial cells forming small vascular channels with a surrounding inflammatory infiltrate.

The greater trochanter of the femur serves as the site of insertion for the gluteus medius muscle, which is responsible for

hip abduction and stabilization of the pelvis during ambulation. Fractures of the greater trochanter (eg, fragility fracture from a fall) can disrupt the integrity of the gluteus medius tendon and result in lateral hip pain with gait instability and weakness of hip abduction.

Portal vein thrombosis causes portal hypertension, splenomegaly, and varicosities at portocaval anastomoses. It does not cause

histologic changes to the hepatic parenchyma. Ascites is uncommon as the obstruction is presinusoidal; ascites typically only develops in conditions that cause sinusoidal hypertension.

dimorphic fungus that is inhaled as microconidia and converts to a small, ovoid yeast in the lungs:

histoplasma capsulatum it replicates by forming narrow-based buds but not germ tubes. Associated with pneumonia, not bronchitis

Pt presenting with skeletal abnormalities, lens dislocation, intellectual deficits, vascular thromboses, and a genetic defect in the cystathionine beta-synthase enzyme likely has

homocystinuria

First-line therapy for CMV colitis and retinitis is ganciclovir. This medication inhibits viral synthesis by blocking CMV DNA polymerase. However, ganciclovir also blocks

host DNA polymerase to a lesser degree, which can lead to hematologic side effects such as neutropenia, anemia, and thrombocytopenia.

Genetic variations created during hepatitis C virus (HCV) replication result in marked variety in the antigenic structure of HCV envelope proteins. The production of

host antibodies lags behind that of new mutant HCV strains, preventing infected individuals from mounting an effective immune response.

Influenza epidemics and pandemics are typically caused by reassortment of the RNA segments coding for hemagglutinin or neuraminidase proteins (major antigenic shifts). This process can occur between

human and animal strains of influenza A virus in avian or swine hosts.

Cutaneous warts (ie, verruca vulgaris) are caused by

human papillomavirus and typically present as rough, skin-colored papules. If necessary, biopsy can confirm the diagnosis and shows epidermal hyperplasia, thickened stratum corneum, papilloma formation, and cytoplasmic vacuolization.

Condylomata acuminata (anogenital warts) present as pink- or skin-colored plaques, papules, and verrucous lesions on the genitalia, perineum, or perianal skin; they are caused by

human papillomavirus, primarily types 6 and 11. These lesions are associated with increased risk for HIV infection, and HIV testing is recommended.

In the forearm, the median nerve courses between the

humeral and ulnar heads of the pronator teres muscle and between the flexor digitorum superficialis and flexor digitorum profundus muscles. Compression prior to the takeoff of the palmar branch (eg, between the heads of the pronator teres) results in sensory loss over the lateral palm and palmar aspects of the first 3½ digits.

Hydrocephalus is an enlargement of the ventricles (with or without elevated pressure) caused by either neuronal volume loss (eg, hydrocephalus ex-vacuo) or excessive cerebrospinal fluid accumulation (due to flow obstruction or impaired absorption). Neurodegenerative diseases (eg, AIDS dementia) can be associated with

hydrocephalus ex-vacuo due to significant cortical atrophy, which allows the ventricles to expand while maintaining normal pressure.

Congenital toxoplasmosis is an infection acquired in utero that can present with

hydrocephalus, intracranial calcifications, and chorioretinitis due to prolonged CNS inflammation

Irreversible ischemic injury to brain tissue causes tissue digestion by

hydrolytic enzymes (liquefactive necrosis). The infarcted CNS tissue is eventually replaced with a cystic astroglial scar. In other organs, lethal ischemic injury results in coagulative necrosis.

Benign prostatic hyperplasia 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.

Hemoglobin S (HbS) contains valine in place of glutamic acid at the sixth amino acid position of the beta globin chain. This promotes

hydrophobic interaction among Hb molecules and results in HbS polymerization and erythrocyte sickling

Infection with parvovirus B19 (a nonenveloped single-stranded DNA virus) can cause arthralgia with or without rash in adults. An infected fetus may develop

hydrops fetalis (severe anemia, heart failure, pleural effusions, pericardial effusions, and ascites).

Methylmalonic acidemia is an organic acidemia due to complete or partial deficiency of methylmalonyl-CoA mutase. Complete deficiency classically presents with lethargy, vomiting, and tachypnea in a newborn. Laboratory testing shows

hyperammonemia, ketotic hypoglycemia, and metabolic acidosis. The diagnosis is confirmed by elevated urine methylmalonic acid and propionic acid.

The individual subunits of the hemoglobin molecule are structurally analogous to myoglobin. If separated, the monomeric subunits will demonstrate a

hyperbolic oxygen-dissociation curve similar to that of myoglobin.

Multiple myeloma should be suspected in elderly patients with any combination of

hypercalcemia, normocytic anemia, bone pain, elevated gamma gap, or renal failure. Renal failure is commonly caused by light chain cast nephropathy; large, waxy, eosinophilic casts composed of Bence Jones proteins are seen in the tubular lumen.

What is the most common risk factor for calcium (calcium oxalate and calcium phosphate) kidney stones in adults?

hypercalciuria contributing factors may include increased GI absorption, increased mobilization of calcium from bone, or decreased renal tubular calcium reabsorption most patients remain normocalcemic due to regulation of plasma calcium levels by vitamin D and parathyroid hormone

Obesity hypoventilation syndrome commonly presents with chronic fatigue, dyspnea, and difficulty concentrating. Patients will have BMI >30 kg/m2 and arterial blood gas while awake showing evidence of hypoventilation, including

hypercapnia (PaCO2 >45 mm Hg) and usually hypoxemia (PaO2 <75 mm Hg). The expected alveolar to arterial oxygen gradient is normal (4-15 mm Hg) with hypoventilation.

Mothers with diabetes often have hyperglycemia, causing fetal hyperglycemia. In utero, this results in compensatory

hyperfunctioning of pancreatic beta cells, which then produce increased amounts of insulin to handle the excessive glucose load once the maternal glucose supply is interrupted at delivery, persistent hyperinsulinemia causes increased glucose consumption and transient neonatal hypoglycemia

Elevated gastric pH stimulates secretion of gastrin, a polypeptide hormone that increases gastric acid production. Proton pump inhibitors block gastric acid production by parietal cells; the resultant increase in pH leads to

hypergastrinemia, which can cause rebound hypersecretion of gastric acid when the drug is withdrawn.

Multiple endocrine neoplasia type 1 consists of

hyperparathyroidism (eg, hypercalcemia, constipation, kidney stones), pituitary tumors, and pancreatic endocrine tumors (eg, gastrinoma). The genetic defect involves mutations of the MEN1 gene.

The hypothalamus is a key region responsible for homeostasis. The ventromedial nucleus mediates satiety; lesions of this area of the hypothalamus can result in

hyperphagia and obesity.

Patients with hematologic malignancies that have high tumor cell burdens or rapid turnover rates are at high risk for electrolyte abnormalities following the initiation of cytotoxic chemotherapy due to the massive lysis of tumor cells. Patients generally develop

hyperphosphatemia, hyperkalemia, hyperuricemia, and elevated lactate dehydrogenase.

Adenosine causes

hyperpolarization of the nodal pacemaker to briefly block conduction through the atrioventricular node, and it is effective in the initial treatment of paroxysmal supraventricular tachycardia. Common adverse effects include flushing, chest burning (due to bronchospasm), hypotension, and high-grade atrioventricular block.

A drug that binds to and activates GABA-A receptors (or enhances their activity) will increase the conductance of chloride ions, leading to increased passive transport of chloride into the cell interior. This causes the membrane potential to become

hyperpolarized (more negative than the resting membrane potential) by approaching or reaching the equilibrium potential for chloride.

Systemic mastocytosis is characterized by the abnormal proliferation of mast cells and increased histamine release. Histamine causes

hypersecretion of gastric acid by parietal cells in the stomach as well as a variety of other symptoms (eg, hypotension, flushing, pruritus).

Autosomal dominant (adult) polycystic kidney disease is caused by mutations in the polycystin genes (PKD1, PKD2), which result in cystic enlargement of the kidneys and progressive renal dysfunction. Clinical features include

hypertension, abdominal/flank pain, and gross hematuria; extrarenal manifestations include liver cysts and intracranial aneurysms.

Febrile seizure is usually a benign neurologic disorder that occurs most commonly in children age 6 months to 5 years who have high fever due to a viral illness. The pathophysiology involves

hyperthermia-induced neuronal dysfunction triggering a short (<5 min) generalized seizure; treatment is generally supportive with antipyretics for fever reduction.

Amiodarone is 40% iodine by weight. It can cause hypothyroidism due to decreased production of thyroid hormone. Amiodarone can also cause

hyperthyroidism due to increased thyroid hormone synthesis or destructive thyroiditis with release of preformed thyroid hormone

Friedreich ataxia is an autosomal recessive condition that presents during childhood/adolescence with progressive gait ataxia (due to degeneration of the spinocerebellar tracts) and impaired joint and vibration sense (due to degeneration of the posterior columns and dorsal root ganglia). Other features include

hypertrophic cardiomyopathy (most common cause of death), skeletal abnormalities (eg, kyphoscoliosis, pes cavus), and diabetes mellitus.

Transforming growth factor-β (TGF-β) is critical for fibroblast migration, proliferation, and connective tissue synthesis. Increased TGF-β activity is responsible for the

hypertrophic/keloid scarring and fibrosis of the lung, liver, and kidney that occur with chronic inflammation.

Foscarnet is an analog of pyrophosphate that can chelate calcium and promote nephrotoxic renal magnesium wasting. These toxicities can result in

hypocalcemia and hypomagnesemia, which can cause seizures.

Severe vomiting characteristically causes hypokalemic, hypochloremic metabolic alkalosis. The metabolic alkalosis is initiated by loss of gastric H+ from the body, worsened by hypovolemia-induced activation of the renin-angiotensin-aldosterone system, and perpetuated by profound gastric and renal losses of Cl− that lead to

hypochloremia and impaired renal HCO3− excretion. Hypokalemia primarily results from aldosterone-mediated renal K+ losses.

Primary hyperaldosteronism causes increased Na+ reabsorption in the renal collecting tubules, leading to increased urinary excretion of K+ and H+. Patients typically have secondary hypertension as well as

hypokalemia and metabolic alkalosis. The serum Na+ concentration remains normal due to aldosterone escape.

Bulimia nervosa is characterized by episodes of binge eating and compensatory weight-reduction behaviors. Signs of self-induced vomiting include

hypokalemia, metabolic alkalosis, parotid gland enlargement, dorsal hand calluses, and dental erosion.

Patients who experience major depressive and hypomanic episodes are diagnosed with bipolar II disorder. In contrast to manic episodes,

hypomanic episodes are less severe, do not involve psychosis, and cause a lesser degree of functional impairment.

Electrolyte abnormalities in primary adrenal insufficiency include

hyponatremia, hyperkalemia, hyperchloremia, and non-anion gap metabolic acidosis

Cardiac tamponade typically presents with

hypotension with pulsus paradoxus, elevated jugular venous pressure, and muffled heart sounds (Beck's triad). Pulsus paradoxus refers to an abnormal exaggerated decrease in systolic blood pressure >10 mm Hg on inspiration, and is a common finding in patients with pericardial effusion with cardiac tamponade.

The syndrome of inappropriate antidiuretic hormone (SIADH) presents with

hypotonic hyponatremia (ie, low serum osmolality and serum sodium), concentrated urine (ie, high urine osmolality), and euvolemia. Carbamazepine can cause SIADH by increasing antidiuretic hormone (ADH) secretion and renal sensitivity to ADH.

Obturator nerve injury presents with weakness of thigh adduction and medial thigh sensory loss. It is most commonly seen as an:

iatrogenic complication of pelvic surgery

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.

The histologic findings of patchy lymphoplasmacytic infiltrates, focal fibroblastic proliferation, areas of dense fibrosis and honeycombing, and hyperplasia of type 2 pneumocytes are highly suggestive of

idiopathic pulmonary fibrosis (IPF)

Endothelin-1 inhibitors (eg, ambrisentan, bosentan) are used to treat

idiopathic pulmonary hypertension. Histologic findings of pulmonary hypertension include pulmonary vascular media and intima hypertrophy and intimal fibrosis.

Most available rodenticides contain brodifacoum, a long-acting 4-hydroxycoumarin derivative. A patient who has ingested a quantity of rodenticide sufficient to cause coagulopathy and abnormal bleeding (similar to warfarin toxicity) requires

immediate treatment with fresh frozen plasma in addition to vitamin K.

Systemic lupus erythematosus is characterized by loss of immune self-tolerance with production of autoantibodies against nuclear antigens. Binding of autoantibodies to self antigens leads to deposition of

immune complexes in tissues and consumption of complement.

Chédiak-Higashi syndrome is an autosomal recessive disorder affecting vesicle fusion and lysosome transport that results in neurologic abnormalities, partial albinism, and

immunodeficiency caused by defective neutrophil and natural killer cell function.

Osteonecrosis (avascular necrosis) occurs due to

impaired blood supply to a segment of bone. The femoral head is the most common location. Common causes include sickle cell disease, glucocorticoid therapy, vasculitis, and alcoholism.

Concentric left ventricular (LV) hypertrophy involves uniform thickening of the LV walls with reduction in LV cavity size and most commonly results from prolonged systemic hypertension. It can progress to hypertensive heart disease with

impaired diastolic filling and heart failure with preserved ejection fraction. Histopathology demonstrates transverse thickening of cardiomyocytes with prominent hyperchromatic nuclei and interstitial fibrosis.

Amyloid cardiomyopathy, caused by the accumulation of misfolded amyloid fibrils, appears as pink, amorphous extracellular material on light microscopy. The ventricular walls become stiff and uniformly thickened, leading to

impaired diastolic relaxation, a dilated left atrial cavity, and progressive left- and right-sided heart failure. Left ventricular cavity size is typically normal or decreased.

Right ventricular infarction (right-sided heart failure) can lead to shock via

impaired forward blood flow to the left heart, which lowers left-sided preload (decreased pulmonary capillary wedge pressure) and decreases cardiac output. The reduced right ventricular output also raises right atrial and central venous pressure.

Diffuse esophageal spasm is characterized by periodic, simultaneous, and non-peristaltic contractions of the esophagus due to

impaired inhibitory innervation within the esophageal myenteric plexus. Patients typically present with liquid/solid dysphagia and chest pain due to inefficient propulsion of food into the stomach.

Orotic aciduria is a rare autosomal recessive disorder of de novo pyrimidine synthesis that occurs due to a defect in uridine 5'-monophosphate (UMP) synthase. Children typically present with physical and mental retardation, megaloblastic anemia, and large amounts of urinary orotic acid. Uridine supplementation can

improve symptoms as uridine is converted to UMP via nucleoside kinases.

Branched-chain α-ketoacid dehydrogenase requires several coenzymes: Thiamine, Lipoate, Coenzyme A, FAD, NAD (mnemonic: Tender Loving Care For Nancy). Some patients with maple syrup urine disease

improve with high-dose thiamine treatment, but most require lifelong restriction of leucine, isoleucine, and valine.

Anemia of chronic disease is caused by elevated inflammatory cytokine levels (eg, hepcidin), which increase sequestration of iron within the reticuloendothelial system and reduce circulating iron levels. Many patients have

improvement in anemia with treatment of the underlying condition that caused the inflammation.

Tetanus is caused by infection with toxigenic strains of the anaerobic bacterium Clostridium tetani. Transmission typically occurs when spores are inoculated into the skin via a puncture wound. The bacteria germinate, replicate locally, and elaborate tetanospasmin (tetanus toxoid). The toxin spreads

in a retrograde fashion through the lower motor neurons to the spinal cord, where it blocks inhibitory interneurons and causes spasmodic muscle contraction (eg, trismus, risus sardonicus).

In constrictive pericarditis, normal pericardium is replaced by dense, rigid pericardial tissue that restricts ventricular filling, leading to low cardiac output and progressive right-sided heart failure. Physical examination findings

in such patients include elevated jugular venous pressure (JVP), pericardial knock, pulsus paradoxus, and a paradoxical rise in JVP with inspiration (Kussmaul sign).

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.

Beta-lactamase inhibitors (eg, clavulanic acid, sulbactam, tazobactam) prevent beta-lactamase from

inactivating penicillin class drugs, which extends the spectrum of their activity.

The aminoglycoside streptomycin inhibits protein synthesis by

inactivating the 30S (small) ribosomal subunit.

Neonatal respiratory distress syndrome is characterized by

inadequate surfactant production, resulting in increased alveolar surface tension and decreased alveolar compliance. Diffuse alveolar collapse (atelectasis) is seen on chest x-ray as ground-glass opacities with air bronchograms.

Hyponatremia following cerebral injury (eg, subarachnoid hemorrhage) is commonly due to the syndrome of

inappropriate antidiuretic hormone secretion. Injury to the hypothalamus leads to increased secretion of antidiuretic hormone, which in turn leads to water retention, low serum osmolality, and increased urinary sodium excretion.

Salicylate poisoning causes mixed primary respiratory alkalosis and primary anion gap metabolic acidosis. Mixed acid-base disturbances can be recognized by

inappropriate secondary compensation for one of the primary disturbances, indicating that an additional primary disturbance must be present.

Clear cell carcinoma is the most common subtype of renal cell carcinoma and is composed of large, rounded, or polygonal cells with clear cytoplasm. These tumors are often detected

incidentally at an advanced stage; the lung is the most common site for metastasis, followed by osteolytic bone and liver.

Patent ductus arteriosus (PDA) is characterized by a continuous murmur heard best in the left infraclavicular region with maximal intensity at S2. A small PDA is often asymptomatic and is usually detected

incidentally during routine cardiac auscultation. It occurs most commonly in patients born prematurely and those with cyanotic congenital heart disease.

Campylobacter infection is a common cause of gastroenteritis and is typically acquired from contaminated food (eg, undercooked poultry) or domesticated animals (eg, household dogs). Manifestations usually

include fever, cramping abdominal pain, and watery diarrhea that may be bloody. Stool studies typically show blood and leukocytes. Campylobacter infection is associated with Guillain-Barré syndrome.

Epiglottitis causes rapidly progressive airway obstruction and classically presents with fever, dysphagia, drooling, stridor, and tripod positioning. Individuals with

incomplete immunization against Haemophilus influenzae type b are at greatest risk.

A ventricular septal defect (VSD) is associated with a low-pitched, holosystolic murmur at the mid to lower left sternal border. It accentuates during maneuvers that

increase afterload (eg, handgrip maneuver). A small VSD is usually asymptomatic and produces a louder murmur due to higher interventricular pressure gradient.

alpha1 adrenergic agonists:

increase peripheral vasoconstriction and increase SVR

Methadone is a mu-opioid receptor agonist used for maintenance treatment for opioid use disorder; it is metabolized by the cytochrome P-450 system, particularly by CYP3A4. Certain inhibitors of CYP3A4 (eg, azoles, fluvoxamine, ciprofloxacin, clarithromycin, cimetidine) can

increase plasma methadone concentration and lead to opioid toxicity (eg, sedation, respiratory depression, miosis).

The LV systolic failure (from MI) increases LV end-diastolic pressure, which is transmitted backward to

increase pulmonary capillary wedge pressure and pulmonary arterial pressure

Supplemental oxygen administration in patients with COPD can lead to:

increased CO2 retention (oxygen-induced hypercapnia), resulting in confusion and depressed consciousness Major cause is reversal of hypoxic pulmonary vasoconstriction, which increases physiologic dead space as blood is shunted away from well-ventilated alveoli

Carbonic anhydrase inhibitors (eg, acetazolamide) are weak diuretics that block reabsorption of sodium bicarbonate (NaHCO3) in the proximal tubule. The main effect is

increased HCO3- excretion, leading to increased urine pH, mild metabolic acidosis (with compensatory respiratory alkalosis), and mild hypokalemia.

Hypertrophic cardiomyopathy (HCM) typically involves interventricular septal hypertrophy that obstructs left ventricular (LV) outflow and creates a systolic murmur that decreases in intensity with maneuvers that increase LV blood volume (eg, hand grip, passive leg elevation). HCM is characterized by

increased LV muscle mass with a small LV cavity, preserved ejection fraction, and impaired LV relaxation leading to diastolic dysfunction.

Reduced aldosterone production in primary adrenal insufficiency leads to renal sodium wasting with consequent hypovolemia, orthostasis, and potassium retention (hyperkalemia). Low cortisol stimulates

increased antidiuretic hormone secretion, which leads to water retention and hyponatremia.

The von Willebrand factor (vWF) enhances clotting through both augmentation of platelet binding and stabilization of factor VIII. Patients with von Willebrand disease are deficient in functional vWF and present with

increased bruisability and prolonged mucosal bleeding. Desmopressin can alleviate bleeding through endothelial release of vWF.

Ketamine can be used for anesthesia induction. The side effects of

increased catecholamine release (eg, bronchodilation) are often exploited in patients with bronchospasm.

In emphysema, the lung parenchyma has

increased compliance

Disseminated intravascular coagulation is marked by widespread activation of the coagulation cascade, leading to excessive thrombin production and formation of microthrombi. Subsequent conversion of plasminogen to plasmin results in

increased fibrinolysis to clear the thrombi. Laboratory studies show a consumption of clotting factors (prolonged PT/PTT) and platelets (thrombocytopenia) and signs of excessive fibrinolysis (eg, elevated D-dimer).

The net filtration pressure is a result of pressure gradients formed by Starling forces and is calculated by subtracting the oncotic pressure gradient from the hydrostatic pressure gradient. Angiotensin II preferentially constricts the efferent arteriole, resulting in an

increased hydrostatic pressure gradient and an increased net filtration pressure.

Hypercalcemia in sarcoidosis is caused by parathyroid hormone-independent formation of 1,25-dihydroxyvitamin D by activated macrophages. This leads to

increased intestinal absorption of calcium.

Mallory-Weiss tears account for about 10% of cases of upper GI hemorrhage. They occur due to

increased intraluminal gastric pressure due to retching, vomiting, or other abdominal straining.

Vitamin B12 is an essential cofactor in the recycling of 5-methyl-tetrahydrofolate to tetrahydrofolate, which is required for amino acid, purine, and thymidine synthesis. Deficiency primarily affects hematopoietic cell maturation and is marked by

increased nuclear-cytoplasmic ratio, leading to macrocytic red blood cells and hypersegmented neutrophils; increased apoptosis often also leads to anemia and mild thrombocytopenia/leukopenia.

A left shift of the hemoglobin oxygen dissociation curve indicates increased hemoglobin O2 affinity and can be caused by

increased pH, decreased 2,3-bisphosphoglycerate, and decreased temperature. Leftward shifts of the curve inhibit the release of O2 within peripheral tissues.

With moderate to heavy exercise, the changes to the left ventricular pressure-volume loop include

increased preload and increased contractility that both contribute to increased stroke volume. Although reduced systemic vascular resistance decreases afterload, the increase in systolic pressure caused by increased preload and contractility override the decrease, resulting in overall increased afterload.

Gout occurs with increased frequency in patients with activating mutations involving phosphoribosyl pyrophosphate synthetase due to

increased production and degradation of purines.

Dobutamine is a β-adrenergic agonist with predominant activity on β1 receptors and weak activity on β2 and α1 receptors. Stimulation of β1 receptors leads to an

increased production of cAMP and increased cytosolic Ca2+ concentration. This facilitates the interaction between actin and myosin, resulting in increased myocardial contractility.

Interstitial lung disease is associated with decreased lung volumes and increased lung elastic recoil caused by fibrotic interstitial tissue. The increased elastic recoil results in

increased radial traction (outward pulling) on the airways, leading to increased expiratory flow rates when corrected for the low lung volume.

Compensatory mechanisms for hypovolemia include activation of the renin-angiotensin-aldosterone system and increased antidiuretic hormone release. This results in

increased renal sodium, chloride, water, and urea reabsorption with increased potassium excretion.

Uterine leiomyoma (ie, fibroids) can present with bulk symptoms (eg, pelvic pressure, urinary frequency) and an irregularly enlarged uterus. African American women are at

increased risk of developing fibroids.

Xeroderma pigmentosum develops due to a defect in nucleotide excision repair. This disease is characterized by

increased sensitivity to ultraviolet radiation and a high incidence of cutaneous malignancy.

Statins, primarily simvastatin, lovastatin, and atorvastatin, are metabolized by CYP3A4. Drugs that inhibit this enzyme (eg, macrolide antibiotics, ketoconazole, non-dihydropyridine calcium channel blockers, amiodarone) can cause

increased statin drug levels and lead to statin myopathy.

Cocaine is a stimulant that inhibits the presynaptic reuptake of norepinephrine, dopamine, and serotonin. Intoxicated patients develop agitation, tachycardia, hypertension, and light-responsive mydriasis due to

increased sympathetic activity. Cocaine is also a potent vasoconstrictor that can cause myocardial ischemia and atrophy of the nasal mucosa and septum.

Following unilateral orchiectomy, the drop in testosterone stimulates pituitary LH secretion, which stimulates

increased testosterone production in the remaining testis and maintains libido, erectile function, and secondary sex characteristics. However, the loss of sperm-producing tissue usually causes a drop in sperm counts.

Achalasia is caused by reduced numbers of inhibitory ganglion cells in the esophageal wall. Esophageal manometry in achalasia shows decreased amplitude of peristalsis in the mid esophagus, with

increased tone and incomplete relaxation at the lower esophageal sphincter.

Renal calculi occur due to an imbalance of the factors that facilitate or inhibit stone formation. Increased urinary concentrations of calcium, oxalate, and uric acid promote salt crystallization, whereas

increased urinary citrate concentration and high fluid intake prevent calculi formation.

Glioblastoma multiforme is the most common primary brain tumor in adults. Histopathology showing

increased vascularity and pseudopalisading tumor cells around areas of necrosis is diagnostic.

Postoperative urinary retention, with incomplete bladder emptying, is a common complication thought to involve decreased micturition reflex activity, decreased contractility of the bladder detrusor, and/or

increased vesical sphincter tone. This condition may be treated with a muscarinic agonist (bethanechol) or an α1 blocking drug.

The muscle spindle system is a feedback system that monitors and maintains muscle length, while the Golgi tendon system is a feedback system that monitors and maintains muscle force. GTOs are exquisitely sensitive to

increases in muscle tension but are relatively insensitive to passive stretch.

Myocardial oxygen extraction exceeds that of any other tissue or organ; therefore, the cardiac venous blood in the coronary sinus is the most deoxygenated blood in the body. Due to the high degree of oxygen extraction,

increases in myocardial oxygen demand can only be met by an increase in coronary blood flow.

Beta-2 agonists and insulin increase the activity of the Na+-K+-ATPase in skeletal muscles, which transiently

increases intracellular translocation of potassium. These medications are used in the treatment of acute, severe hyperkalemia

Unlike amylase and protease, which are activated by the low pH of the stomach, lipase, which plays a vital role in fat digestion, is inactivated by the acidic environment of the stomach. Therefore, by decreasing gastric hydrochloric acid production, PPI use:

increases lipase activity (ie, it prevents exogenous lipase from being denatured as it passes through the stomach), enhancing fat absorption in patients dependent on pancreatic enzyme replacement therapy.

Chronic obstructive pulmonary disease causes air trapping and hyperinflation; consequently, these patients breathe at higher baseline lung volumes (higher functional residual capacity). The absolute volume of air in the lungs that is not respired (residual volume)

increases substantially, as does the fraction of air in the lungs that is not involved in respiration (residual volume/total lung capacity ratio).

Chronic obstructive pulmonary disease causes air trapping and hyperinflation; consequently, these patients breathe at higher baseline lung volumes (higher functional residual capacity). The volume of air in the lungs that is not respired (residual volume)

increases substantially, as does the fraction of air in the lungs that is not involved in respiration (residual volume/total lung capacity ratio).

Chronic inflammation is associated with increased circulating pro-inflammatory cytokines (eg, IL-1, IL-6, tumor necrosis factor-alpha), which stimulates the liver to release acute-phase reactants (eg, C-reactive protein, fibrinogen). The presence of acute-phase reactants

increases the erythrocyte sedimentation rate, a nonspecific marker for inflammation.

Predictive values change depending on the prevalence of disease in a study population. As disease prevalence increases, the positive predictive value

increases, and the negative predictive value decreases.

Primary hyperparathyroidism is characterized by oversecretion of parathyroid hormone despite normal (or elevated) serum calcium levels. Parathyroid hormone raises serum calcium and lowers serum phosphorus by

increasing bone resorption (freeing calcium and phosphate), increasing renal reabsorption of calcium, and decreasing proximal tubular reabsorption of phosphate.

Digoxin is used for ventricular rate control in atrial fibrillation as it decreases atrioventricular nodal conduction by

increasing parasympathetic vagal tone. Digoxin is also used in heart failure due to its positive inotropic effect. These effects are accomplished via inhibition of the sodium-potassium ATPase pump.

Bisacodyl is a commonly used stimulant laxative that stimulates the enteric neurons within the colonic myenteric plexus, thereby

increasing peristaltic activity and enhancing colonic motility.

Sulfonylureas inhibit the ATP-sensitive potassium channel on the pancreatic beta cell membrane, inducing depolarization and L-type calcium channel opening. The increased Ca2+ influx stimulates beta cell insulin release independent of blood glucose concentrations. Sulfonylureas can

induce hypoglycemia because they stimulate insulin secretion even when blood glucose levels are normal.

Sodium-glucose cotransporter 2 inhibitors (eg, canagliflozin, dapagliflozin) decrease renal reabsorption of glucose and sodium, leading to lower blood glucose levels. The decreased reabsorption of sodium and glucose also

induces osmotic diuresis, which causes a decrease in blood pressure. Excess urinary glucose also leads to an increased risk for genitourinary tract infections.

Immunization against hepatitis B virus uses recombinant HBsAg to generate anti-HBs antibodies. These antibodies prevent

infection by binding to the envelope of circulating virus and inhibiting viral entry.

The spleen acts as both a blood filter capable of removing circulating pathogens and as a major site of opsonizing antibody synthesis. Asplenic patients are prone to

infections caused by encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.

Infection with Mycoplasma pneumoniae 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. Other illnesses resulting in cold agglutinin formation include

infectious mononucleosis and certain hematologic malignancies.

The ureter can be injured during hysterectomy due to its close proximity to the uterine structures. The distal ureter may be severed during ligation of the uterine vessels because the ureter passes

inferior and lateral to the uterine artery at the level of the internal cervical os prior to entering the bladder (eg, "water under the bridge").

Direct inguinal hernias occur most commonly in older men due to weakness of the transversalis fascia. They protrude medial to the

inferior epigastric vessels into the Hesselbach triangle and pass only through the superficial inguinal ring with no direct route to the scrotum.

The distal one-third of the transverse colon, descending colon, sigmoid colon, and rectum are all hindgut derivatives. Hindgut structures receive blood from the

inferior mesenteric artery (IMA), a branch of the aorta

In horseshoe kidney, the kidneys are fused at the poles. The isthmus of the horseshoe kidney usually lies anterior to the aorta and posterior to the

inferior mesenteric artery (IMA). During fetal development, the IMA limits the ascent of the horseshoe kidney.

External hemorrhoids, which originate below the dentate line, are covered by modified squamous epithelium and have cutaneous (somatic) nervous innervation from the

inferior rectal nerve, a branch of the pudendal nerve.

Pulsatile administration of gonadotropin-releasing hormone (GnRH) stimulates FSH and LH release and is useful for the treatment of

infertility. Nonpulsatile (constant) infusion of GnRH, or a long-acting analog, suppresses FSH and LH release and subsequently suppresses gonadal function.

Malignant pleural effusions are usually exudative by Light criteria and can occur via several mechanisms, including an

inflammation-induced increase in vascular permeability (leading to increased inflow) and blockage of pleural fluid reabsorption by parietal pleura lymphatics (leading to decreased outflow).

Thromboangiitis obliterans (Buerger disease) is a segmental, inflammatory vasculitis that affects the small- and medium-sized arteries and veins of the distal extremities with

inflammatory, intraluminal thrombi and sparing of the vessel wall. It is usually seen in young, heavy smokers, and can present with digital ischemia and ulceration, extremity claudication, Raynaud phenomenon, and superficial thrombophlebitis.

Lactose intolerance presents with flatulence, crampy abdominal pain, and watery diarrhea after dairy product consumption. It can be acquired by

inflammatory/infectious conditions that injure the mucosal brush border of the small intestine where lactase is expressed. Studies can show increased breath hydrogen content, reduced stool pH, and elevated stool osmolality.

The maxillary division of the trigeminal nerve (CN V2) provides sensory innervation to the cheek. It passes through the foramen rotundum, then the pterygopalatine fossa, and then exits the maxilla through the

infraorbital foramen. Nerve blocks to provide anesthesia to the cheek are frequently performed at the infraorbital foramen.

In the lower extremities, the superficial lymphatic system is divided into medial and lateral tracks. The medial track runs up to the superficial inguinal lymph nodes, bypassing the popliteal nodes. Consequently, lesions on the medial foot cause

inguinal lymphadenopathy, whereas lateral lesions are more likely to cause lymphadenopathy in both the popliteal and inguinal areas.

This patient's initial symptoms (eg, lethargy, ataxia, disorientation, slurred speech) followed by rapid improvement and a perioral and perinasal rash on examination are most likely due to

inhalant use disorder Inhalants, in the form of glue, toluene, nitrous oxide, amyl nitrite, and spray paints, are often the first drugs that adolescents misuse as they are inexpensive and readily available. They may be inhaled from a saturated cloth held near the face, from a bag placed over the nose and mouth, or by sniffing directly

Essential tremor is the most common movement disorder. Patients experience a slowly progressive, symmetric postural and/or kinetic tremor that most commonly affects the upper extremities. Essential tremor is often

inherited in an autosomal dominant fashion (referred to as familial tremor). First-line treatment is the nonspecific β-adrenergic antagonist propranolol.

Bisphosphonates have a chemical structure similar to that of pyrophosphate and attach to hydroxyapatite binding sites on bony surfaces to

inhibit bone resorption by osteoclasts.

Potassium-sparing diuretics are often added to loop or thiazide diuretics to prevent hypokalemia. Amiloride and triamterene directly

inhibit the epithelial sodium channel, preventing sodium from entering the principal cell, which reduces the electrochemical gradient (ie, negative luminal charge) that helps drive potassium secretion.

Cyclooxygenase-2 (COX-2) is an inducible enzyme upregulated during inflammation by interleukin-1 and TNF-α. Selective COX-2 inhibitors (eg, celecoxib) decrease inflammation by

inhibiting COX-2 production of pro-inflammatory arachidonic acid metabolites. Because they do not affect COX-1, they have minimal gastroduodenal toxicity.

Loop diuretics (eg, furosemide, torsemide, bumetanide), the most commonly used first line agents, work by

inhibiting Na/K/2Cl symporters in the ascending limb of the loop of Henle. Inhibition of similar symporters in the inner ear is believed to cause ototoxicity (tinnitus, vertigo, hearing impairment, or deafness). It usually occurs with higher dosages, preexisting CKD, rapid intravenous administration, or when used in combination with other ototoxic agents (aminoglycosides, salicylates, cisplatin). Symptoms are usually reversible but hearing impairment may be permanent in some cases. Additional side effects of loop diuretics include hypokalemia, hypomagnesemia, and hypocalcemia.

Cytosolic acetyl-CoA carboxylase converts acetyl-CoA to malonyl-CoA during the rate-limiting step of de novo fatty acid synthesis. Malonyl-CoA also inhibits the action of mitochondrial carnitine acyltransferase, thereby

inhibiting beta-oxidation of newly formed fatty acids.

The binding of programmed cell death protein 1 to one of its ligands (programmed death-ligand 1) downregulates the immune response by

inhibiting cytotoxic T cells Many types of cancers evade immunodetection by increasing expression of PD-L1 on their surface. Monoclonal antibodies against PD-1 upregulate the T-cell response and promote tumor cell apoptosis

The main mechanism of contraceptives with systemically active progestins (eg, combined hormonal oral contraceptives) is

inhibiting ovulation by decreasing FSH and LH synthesis in the anterior pituitary

Therapies are directed at slowing the progression of fibrosis by

inhibiting transforming growth factor-beta and other fibrogenic growth factors (eg, PDGF, fibroblastic growth factor, and VEGF)

Beta blockers are used in the treatment of essential tremor. 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 pulmonary beta-2 receptors in patients with underlying reactive airway disease can cause bronchoconstriction, leading to cough, wheeze, and dyspnea.

Haemophilus influenzae type b is the most invasive strain due to its PRP capsule, which:

inhibits complement-mediated phagocytosis and allows it to invade tissues and survive in the bloodstream

Acromegaly is usually treated with resection of the somatotroph pituitary adenoma, but additional medical therapy is needed for patients with residual tumor. Octreotide is a long-acting somatostatin analogue that

inhibits growth hormone secretion and, subsequently, insulin-like growth factor-1 release. It also reduces residual adenoma size in many patients.

Status epilepticus is a single seizure lasting >5 minutes or the occurrence of multiple discrete seizures with incomplete recovery of consciousness between episodes. The initial treatment includes intravenous lorazepam and phenytoin given concurrently. Phenytoin is a long-acting anticonvulsant that

inhibits neuronal high-frequency firing by reducing the ability of sodium channels to recover from inactivation.

Chronic hepatitis C virus infection is treated with direct-acting antiviral (DAAs) medications such as ledipasvir and sofosbuvir. These medications target specific HCV enzymes (eg, protease, NS5A, RNA polymerase), which

inhibits viral replication and assembly. Treatment with DAAs results in cure in >97% of patients.

The supraspinatus muscle assists in abduction of the arm and stabilization of the glenohumeral joint. The supraspinatus tendon is vulnerable to

injury due to impingement between the acromion and the head of the humerus. Supraspinatus tendinopathy is the most common cause of rotator cuff syndrome.

Familial adenomatous polyposis is an autosomal-dominant hereditary disorder that results in the formation of

innumerable colonic polyps and a nearly 100% risk of colorectal cancer. It arises due to germline mutation in the adenomatous polyposis coli tumor suppressor gene.

Patients with amyotrophic lateral sclerosis often develop respiratory failure due to

inspiratory muscle weakness (causing decreased vital capacity), expiratory muscle weakness (causing a weak cough), and bulbar dysfunction (causing dysphagia and chronic aspiration).

Bordetella pertussis, a small, gram-negative coccobacillus, can cause outbreaks of whooping cough in unvaccinated individuals. Infected infants and children generally develop mucoid rhinorrhea followed by severe, paroxysmal cough that may be associated with an

inspiratory whoop and vomiting. The bacterium is largely noninvasive and secretes several exotoxins that severely damage ciliated respiratory epithelium.

Effective discharge planning requires collaboration of multiple disciplines (physician, nurse, social worker). A social worker can be

instrumental in assessing whether the patient has adequate family or caregiver support at home.

Adhesion of cells to the extracellular matrix involves integrin-mediated binding to fibronectin, collagen, and laminin. Differential expression of

integrin subtypes affects adhesion properties of individual cells, and has been found to correlate with malignant behavior in a number of tumors.

Hookworm infections are transmitted via direct contact between human skin and contaminated soil/sand (eg, walking barefoot). Dermal penetration is often characterized by an

intensely pruritic papule that may form serpiginous tracks due to the subcutaneous migration of hookworm larvae.

Sensation to the parietal pleura, chest wall, and skin of the chest is supplied by the

intercostal nerves that derive from the ventral nerve rami. A nerve block can be used to control pain from these areas when opioids are ineffective, contraindicated, or have intolerable adverse effects.

A patient who underwent axillary lymph node dissection has persistent sensory dysfunction (burning, aching, diminished sensation) in her medial upper arm, consistent with injury to which nerve?

intercostobrachial nerve

Primary tuberculosis infection is marked by initial unchecked Mycobacterium tuberculosis replication within the alveolar space and alveolar macrophages. After a few weeks, CD4 lymphocytes are stimulated to release

interferon-gamma, which activates macrophages and leads to control of the infection.

Intussusception most often occurs in children younger than 2 years of age and in the region of the ileocecal valve. It manifests with

intermittent, severe, colicky abdominal pain, "currant jelly" stools, and sometimes a palpable mass in the right lower abdominal quadrant.

Postpartum hemorrhage is an obstetrical emergency. Bilateral ligation of the

internal iliac artery can decrease uterine blood flow and control postpartum hemorrhage that is unresponsive to medical management (eg, uterine massage, uterotonic medications).

Although expiration is largely achieved through passive recoil, active expiration is aided by the

internal intercostals (innervated by thoracic nerve rootlets) and abdominal muscles (innervated by thoracic and lumbar nerve roots).

Intestinal malrotation results when the midgut undergoes incomplete embryological counterclockwise rotation. It can present as

intestinal obstruction (due to compression by the adhesive bands) and midgut volvulus (intestinal ischemia due to twisting around the blood vessels).

patient with diffuse abdominal pain, rebound tenderness with guarding, and hemodynamic instability (eg, hypotension, tachycardia, syncope) likely has

intraabdominal bleeding (ie, hemoperitoneum)

Olecranon bursitis presents with localized swelling at the olecranon process. Pain and erythema are typically minimal or absent unless significant inflammation is present. A bursa is not an

intraarticular structure; therefore, range of motion of the associated joint is typically preserved and pain-free.

Ion pump failure due to ATP deficiency during cardiac ischemia causes

intracellular accumulation of Na+ and Ca2+. The increased intracellular solute concentration draws free water into the cell, causing the cellular and mitochondrial swelling that is observed histologically

Using nitrates together with phosphodiesterase (PDE) inhibitors used for erectile dysfunction and pulmonary hypertension causes a profound systemic hypotension because they both increase

intracellular cGMP which causes vascular smooth muscle relaxation. Their use together is absolutely contraindicated.

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. Statin-induced myopathy (eg, myalgia, elevated creatine kinase) is the most common complication of statin use.

Antiviral drugs currently recommended for the treatment of primary genital herpes include the nucleoside analogs (eg, acyclovir). These are incorporated into newly replicating viral DNA and

ultimately terminate viral DNA chain synthesis.

Molluscum contagiosum is caused by a poxvirus and presents with small, firm, rounded, papules that often have a central umbilication. Adults who are immunocompromised (eg, HIV) or sexually active are at increased risk. Biopsy shows

intracytoplasmic eosinophilic inclusion bodies of poxvirus in keratinocytes.

Celiac disease is an immune-mediated disorder triggered by dietary gluten that causes small-bowel malabsorption. Because the proximal small bowel is primarily affected, iron deficiency leading to microcytic anemia is common. Histopathology is characterized by

intraepithelial lymphocytosis, loss of intestinal villi, and mucosal atrophy.

Atrial natriuretic peptide and brain natriuretic peptide are released from the atria and ventricles, respectively, in response to myocardial wall stretch due to

intravascular volume expansion. These endogenous hormones promote increased glomerular filtration rate, natriuresis, and diuresis.

The most effective treatment for herpes simplex virus encephalitis is

intravenous acyclovir; whose mechanism of action is complete inhibition of the viral DNA polymerase (synthesizes viral DNA).

Tumor lysis syndrome primarily develops during chemotherapy for cancers with rapid cell turnover, substantial tumor burden, or high sensitivity to chemotherapy. It is characterized by hyperphosphatemia, hypocalcemia, hyperkalemia, and hyperuricemia. Prevention involves

intravenous fluids to flush the kidneys and the use of hypouricemic agents (eg, rasburicase, allopurinol, febuxostat).

Apoptosis can occur through either the

intrinsic (mitochondria-mediated) pathway or the extrinsic (receptor-initiated) pathway. Both pathways converge in the activation of caspases. Caspases are proteolytic enzymes that cleave cellular proteins.

Listeria monocytogenes has

intrinsic resistance to 3rd-generation cephalosporins, like cefotaxime, ceftriaxone due to the presence of penicillin-binding proteins that have a low-affinity for this drug class

Small nuclear ribonucleoproteins (snRNPs) are important components of the spliceosome, a molecule which removes

introns from pre-mRNA during processing within the nucleus. Spinal muscular atrophy is a disorder caused by mutations in the SMN1 gene, resulting in impaired assembly of snRNPs in lower motor neurons. Infants often have flaccid paralysis due to degeneration of anterior horn cells in the spinal cord.

Staphylococcus 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.

Ductal carcinoma in situ is characterized by ducts distended by pleomorphic cells with prominent central necrosis that do not penetrate the basement membrane. It is the precursor to

invasive ductal carcinoma, the most common type of breast cancer.

Listeria is a relatively common foodborne illness associated with outbreaks after the consumption of contaminated food, particularly processed meats and dairy products. Healthy patients may develop gastroenteritis; patients with impaired cell-mediated immunity are at risk for

invasive infection (eg, sepsis, meningoencephalitis) and listeriosis in pregnancy is associated with adverse fetal outcomes (eg, fetal death, premature birth).

Blood flow is directly proportional to the vessel radius raised to the fourth power. Resistance to blood flow is

inversely proportional to the vessel radius raised to the fourth power.

Vasopressin and oxytocin are synthesized within neurons found in the paraventricular and supraoptic nuclei and are released into the circulation from axon terminals in the posterior pituitary. Neurophysins are

involved in the posttranslational processing and stabilization of oxytocin and vasopressin within neurosecretory vesicles during transport to the posterior pituitary.

Mitochondrial vacuolization is typically a sign of irreversible cell injury, signifying that the

involved mitochondria are permanently unable to generate ATP.

Pancoast tumors are non-small cell lung cancers (eg, squamous cell carcinoma, adenocarcinoma) that arise near the superior sulcus. Patients may develop ipsilateral shoulder pain, upper limb paresthesias, and areflexic arm weakness due to

involvement of the brachial plexus. Horner's syndrome (eg, ipsilateral partial ptosis, miosis, anhydrosis) can also occur due to involvement of the cervical sympathetic ganglia.

Damage to the left temporal hemiretina will disrupt the transmission of visual information along the

ipsilateral optic nerve, lateral optic chiasm, optic tract, lateral geniculate body, optic radiations, and primary visual cortex.

The optic nerve carries the afferent limb of the pupillary light reflex pathway, which activates the efferent limb bilaterally and causes both direct and consensual pupillary constriction. Unilateral optic nerve lesions (eg, demyelination due to optic neuritis) can result in impaired pupillary constriction bilaterally when light enters the eye

ipsilateral to the lesion. When light enters the contralateral eye, pupillary constriction occurs normally in both eyes.

Anemia of chronic disease is caused by chronic elevations in inflammatory cytokines, which lead to reduced iron absorption and increased iron retention in the reticuloendothelial system. This impairs

iron availability and causes a normocytic or slightly microcytic anemia with low serum iron and low total iron-binding capacity.

Phenoxybenzamine is an

irreversible α1 and α2 adrenergic antagonist that effectively reduces the arterial vasoconstriction induced by norepinephrine. Because phenoxybenzamine is an irreversible antagonist, even very high concentrations of norepinephrine, such as those seen in pheochromocytoma, cannot overcome its effects.

Huntington Disease is an autosomal dominant, progressive neurodegenerative disorder characterized by chorea, psychiatric symptoms, and dementia. Psychiatric symptoms may occur early in the disease course and include

irritability, anxiety, apathy, depression, and psychosis.

Trazodone is a highly sedating antidepressant commonly used to treat insomnia. Priapism

is a rare but serious adverse effect.

Schistosomiasis, a parasitic blood fluke infection, is common in rural portions of sub-Saharan Africa. Initial infection is often asymptomatic, but some patients develop chronic hepatosplenic (eg, portal hypertension, hepatosplenomegaly, esophageal varices) or urinary (eg, bladder cancer) complications years or decades later. The presence of eosinophilia

is an important diagnostic clue.

Pseudomonas aeruginosa:

is an oxidase-positive, non-lactose-fermenting, Gram-negative organism. It is a common cause of urinary tract infections in patients with indwelling bladder catheters.

Crohn disease is associated with oxalate kidney stones. Impaired bile acid absorption in the terminal ileum leads to loss of bile acids in feces with subsequent fat malabsorption. Intestinal lipids then bind calcium ions, and the resulting soap complex

is excreted. Free oxalate (normally bound by calcium to form an unabsorbable complex) is absorbed and forms urinary calculi (enteric oxaluria).

Prostacyclin (prostaglandin I2) is synthesized from prostaglandin H2 by prostacyclin synthase in vascular endothelial cells. Once secreted,

it inhibits platelet aggregation and causes vasodilation to oppose the functions of thromboxane A2 and help maintain vascular homeostasis.

Dermatophyte infections (eg, tinea corporis, tinea pedis, tinea cruris) infect

keratinized matter in the stratum corneum of the superficial epidermis but do not invade the dermis and subcutaneous tissues

Patients with noncoronary atherosclerotic disease, diabetes mellitus, or chronic kidney disease are at the same risk of cardiovascular events (eg, myocardial infarction, stroke) as patients with

known coronary heart disease. Coronary heart disease is the most common cause of death in patients with diabetes mellitus.

When glycogen stores are depleted during fasting, ketone bodies are produced in the liver and can be used as an energy source in the mitochondria of peripheral tissues. The brain preferentially uses glucose, but will utilize ketones for most of its energy needs during prolonged starvation. Erythrocytes

lack mitochondria and are unable to use ketones.

All organisms in the Mycoplasma genus, including Ureaplasma urealyticum,

lack peptidoglycan cell walls and are therefore resistant to agents that target the cell wall such as penicillins, cephalosporins, carbapenems, and vancomycin. Mycoplasma infections can be treated with antiribosomal agents (eg, tetracyclines, macrolides).

Bacterial mRNA can be polycistronic, meaning that one mRNA codes for several proteins. An example of polycistronic mRNA is the bacterial lac operon, which codes for the proteins necessary for

lactose metabolism by E. coli; the transcription and translation of these bacterial proteins is regulated by a single promoter, operator, and set of regulatory elements.

The most common renal malignancy is clear cell carcinoma, which arises from renal proximal tubular cells. Rounded or polygonal cells with abundant clear cytoplasm are seen on light microscopy. The cells contain

large amounts of glycogen and lipids that dissolve during routine tissue preparation, leaving clear spaces within the cytoplasm.

A Krukenberg tumor is a gastric tumor that has metastasized to the ovary and can present with unintentional weight loss, epigastric pain, and adnexal masses. Histologically, the metastatic tumor cells have

large amounts of mucin with displaced nuclei, resulting in a signet ring appearance.

The arteriovenous concentration gradient reflects the overall tissue solubility of an anesthetic. Anesthetics with high tissue solubility are characterized by

large arteriovenous concentration gradients and slower onsets of action.

Duchenne muscle dystrophy manifests with proximal muscle weakness and atrophy. True hypertrophy of the distal muscle is noted early in the disease as distal muscles compensate for weak proximal ones. Muscle fibers of the distal extremities are

later replaced by fat and connective tissue (pseudohypertrophy).

Meralgia paresthetica is caused by compression of the

lateral femoral cutaneous nerve, typically due to tight clothing. It presents with pain, paresthesia, and numbness in the lateral thigh without motor weakness. Risk factors include obesity, pregnancy, and diabetes mellitus.

Cervical spine trauma can cause dissection of the vertebral artery, resulting in ischemic manifestations due to occlusion of the vertebral artery and/or its branches. Posterior inferior cerebellar artery occlusion causes

lateral medullary (Wallenberg) syndrome, characterized by vertigo/nystagmus, ipsilateral cerebellar signs, loss of pain/temperature sensation in the ipsilateral face and contralateral body, bulbar weakness, and ipsilateral Horner syndrome.

Occlusion of the anterior inferior cerebellar artery causes

lateral pontine syndrome. Patients with this condition typically have ipsilateral loss of pain or temperature in the face (trigeminal nucleus), ipsilateral facial weakness (facial nucleus), ipsilateral hearing impairment (cochlear nucleus), contralateral loss of pain and temperature in the trunk and extremities (lateral spinothalamic tract), and cerebellar dysfunction (eg, ataxia, dysmetria).

In conductive hearing loss, bone conduction will be greater than air conduction (abnormal Rinne test), and the Weber test will

lateralize to the affected ear. In sensorineural hearing loss, air conduction will be greater than bone conduction (normal Rinne test), and the Weber test will lateralize to the unaffected ear.

thoracodorsal nerve innervates the:

latissimus dorsi and damage results in loss of powerful adduction of the arm and weakness while extending and medially rotating the arm

Fracture of the posterior vertebral arch often occurs at the pars interarticularis (ie, spondylolysis). Bilateral disruption of the pars interarticularis can

lead to anterior displacement of the vertebral body (ie, spondylolisthesis).

Endothelin is a potent

vasoconstrictor that also promotes smooth muscle cell proliferation Typically found in high concentrations in patients with PAH and is an important target of therapy for the disease

Atrial septal defects cause wide, fixed splitting of the second heart sound due to right-sided volume overload from left-to-right shunting. Uncorrected defects can

lead to irreversible medial hypertrophy of the pulmonary arteries with pulmonary hypertension and reversal to right-to-left shunting (ie, Eisenmenger syndrome).

The lung apices extend above the level of the clavicle and first rib through the superior thoracic aperture. Penetrating injury in this area may

lead to pneumothorax, tension pneumothorax, or hemothorax.

Neural tube defects most often occur when the neural folds fail to fuse in the region of the anterior or posterior neuropores. Persistent communication between the spinal canal and the amniotic cavity allows

leakage of alpha-fetoprotein (AFP) and acetylcholinesterase (AChE) into the amnionic fluid, leading to elevated levels of AFP and AChE that can be detected on amniocentesis.

Isolated mitral stenosis causes elevated upstream pressures in the

left atrium and pulmonary veins and arteries. Left ventricular end diastolic pressure (LVEDP) is normal or decreased due to obstruction of blood flow through the stenotic valve. An elevated LVEDP suggests additional downstream pathology (eg, aortic valve disease, left ventricular failure).

Cardiovascular dysphagia can result from external compression of the esophagus by a dilated and posteriorly displaced

left atrium in patients with rheumatic heart disease and mitral stenosis/regurgitation.

Type B dissections involving the descending aorta typically originate close to the origin of the

left subclavian artery

An S4 sound is best heard near the cardiac apex at the point of maximal impulse with the patient in the left lateral decubitus position. It results from the atrial contraction, which forces blood into an LV that has reached its limit of compliance. Chronic hypertension causes

left ventricular hypertrophy, which itself may promote the generation of an S4 sound.

During the normal cardiac cycle, central aortic pressure is higher than right ventricular pressure during systole and diastole. Consequently, an intracardiac fistula between the aortic root and right ventricle will most likely demonstrate a

left-to-right cardiac shunt as blood continuously flows from the aortic root (high pressure) to the right ventricle (low pressure).

Patency of the ductus arteriosus after birth results in a

left-to-right shunt that can cause left ventricular volume overload and symptoms of heart failure (eg, failure to thrive, respiratory distress).

Sodium-glucose cotransporter 2 inhibitors (eg, canagliflozin, dapagliflozin) decrease renal reabsorption of glucose, leading to urinary glucose loss and decreased blood glucose levels. In patients with chronic kidney disease, these medications are

less effective. Therefore, serum creatinine should be measured prior to therapy.

Direct oral anticoagulants (DOACs) such as rivaroxaban are often preferred over vitamin K antagonists (VKAs) such as warfarin in the treatment of conditions that require anticoagulation due to

less variability in therapeutic drug effect; in contrast to VKAs, the efficacy of DOACs is unaffected by dietary changes and most medications. Therefore, patients given DOACs do not require laboratory monitoring.

Recurring skin and mucosal infections as well as absence of purulence are suggestive of:

leukocyte adhesion deficiency, which is characterized by absence of CD18 antigens, which are needed to form integrins Integrins are needed for leukocytes to adhere to endothelial surfaces and migration to peripheral tissues in response to infection or inflammation Persistent leukocytosis is a common finding due to leukocytes not being able to migrate out of the blood vessels.

Pelvic organ prolapse, the herniation of pelvic organs (eg, rectum) into the vagina, occurs due to damage to the

levator ani muscle complex. Patients with prolapse of the posterior vaginal wall (ie, rectocele) classically have chronic constipation and a vaginal bulge

The main adverse effects seen with nitrate therapy include headaches and cutaneous flushing along with

lightheadedness and hypotension due to systemic vasodilation.

Anal fissures are longitudinal tears in the mucosa. They are usually due to passage of hard stool in patients with chronic constipation. Most fissures occur at the posterior midline,

likely due to decreased blood flow in this area. Fissures in other areas may be due to less common causes.

Inflammatory bowel disease, especially ulcerative pancolitis, is associated with a significant risk for colorectal carcinoma. Compared with sporadic colorectal cancer, colitis-associated colorectal cancer is more

likely to occur at a younger age, is typically more aggressive with a higher histopathologic grade, often evolves from flat (nonpolypoid) lesions, and is frequently multifocal. Patients should be monitored regularly via colonoscopy with random biopsies.

Umbilical hernias are caused by a defect in the

linea alba and present as protrusions at the umbilicus that are soft, reducible, and benign. They can occur in isolation or in association with other conditions, such as Down syndrome.

N meningitidis has an outer cell membrane virulence factor called

lipo-oligosaccharide (LOS)

Lethal tissue ischemia causes coagulative necrosis in most tissues (eg, kidney, myocardium); cellular architecture is maintained but nuclei are absent. The exception is ischemic cell death in the CNS, which causes

liquefactive necrosis.

Lithium-induced diabetes insipidus is the result of

lithium's antagonizing effect on the action of vasopressin on principal cells within the collecting duct system.

Pregnant women with severe preeclampsia can develop HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome. Nausea/vomiting and right upper quadrant pain occur due to

liver ischemia and/or hemorrhage (eg, subcapsular hematoma). These patients are also at risk for seizure, renal insufficiency, and disseminated intravascular coagulation due to widespread endothelial dysfunction.

DiGeorge syndrome results from

maldevelopment of the third (inferior parathyroid and thymus) and fourth (superior parathyroid) pharyngeal/branchial pouches. Subsequent parathyroid and thymic hypoplasia results in hypocalcemia and T cell deficiency.

Neoplastic spinal cord compression most commonly results from

local extension of vertebral metastases into the epidural space. Presenting symptoms typically include severe back pain (often worse at night), motor weakness, and/or sensory deficits. Urinary and fecal retention or incontinence are common late-stage findings.

Osteosarcoma is the most common primary bone malignancy in children and young adults. It occurs most frequently at the metaphyses of

long bones and presents with local pain and swelling. Most cases are associated with sporadic or inherited mutations in RB1 (hereditary retinoblastoma) and TP53 (Li-Fraumeni syndrome).

Dissection of the axillary lymph nodes can injure the

long thoracic nerve. This results in weakness of the serratus anterior with winging of the scapula and impaired abduction of the shoulder past the horizontal.

Barrett esophagus is a metaplastic condition in which the normal squamous epithelium of the distal esophagus is replaced by intestinal-type columnar epithelium. It occurs most often in

longstanding acid reflux and is associated with an increased risk of adenocarcinoma.

Severe vomiting leads to metabolic alkalosis through multiple mechanisms, including

loss of H+ from the gastrointestinal tract, volume and Cl− depletion that induces renal retention of HCO3−, and hypokalemia-induced intracellular shifting of H+. The anion gap is caused by unmeasured anions that acidify the blood; it is not significantly elevated in metabolic alkalosis.

Normal anion gap metabolic acidosis is usually caused by

loss of bicarbonate which can occur with prolonged diarrhea recurrent vomiting causes metabolic alkalosis, not acidosis

Local cutaneous adverse effects of chronic topical corticosteroid administration include atrophy/thinning of the dermis that is associated with

loss of dermal collagen, drying, cracking, and/or tightening of the skin, telangiectasias, and ecchymoses.

upper motor neuron damage leads to spastic paralysis, hyperreflexia, and an upgoing plantar reflex (Babinski sign) due to

loss of descending inhibition over lower motor neurons in the anterior horn. Conversely, lower motor neuron lesions cause flaccid paralysis, hypotonia, hyporeflexia, muscle atrophy, and fasciculations.

peroneal nerve injury often presents with:

loss of dorsal foot sensation and foot drop due to weakness of foot eversion, dorsiflexion, and toe extension typically caused by compression of the nerve at the proximal fibula (from leg casting)

Somatic symptoms of depression (weight loss, low energy, sleep disturbance) are less reliable indicators of major depressive disorder in patients with advanced medical illness. Focusing on nonsomatic symptoms, such as

loss of interest, anhedonia, worthlessness, excessive guilt, and suicidality, can assist in diagnosing comorbid depression in these patients.

Tabes dorsalis, a late form of neurosyphilis, causes progressive degeneration of the dorsal columns and dorsal roots of the spinal cord. Manifestations include

loss of proprioception and vibratory sensation, severe lancinating pains, and sensory ataxia (eg, wide-based gait, positive Romberg sign). Many patients also have Argyll Robertson pupils.

Rett syndrome is characterized by

loss of speech and motor skills, deceleration of head growth, and stereotypic purposeless hand movements after a period of normal development. It affects mainly girls and is associated with mutations in the MECP2 gene.

Aortic regurgitation causes a decrescendo diastolic murmur with maximal intensity occurring just after closure of the aortic valve, when the pressure gradient between the aorta and left ventricle is the highest. The pressure tracing for aortic regurgitation is characterized by

loss of the aortic dicrotic notch, steep diastolic decline in aortic pressure, and high-peaking systolic pressures.

Lesions of the glossopharyngeal nerve result in

loss of the gag reflex (afferent limb); loss of sensation in the upper pharynx, posterior tongue, tonsils, and middle ear cavity; and loss of taste sensation on the posterior third of the tongue.

Pulmonary hypertension can be recognized on physical examination by a

loud pulmonic component of S2 and an accentuated, palpable impulse at the left sternal border (left parasternal lift due to right ventricular heave).

Negative predictive value (NPV) is the probability of not having a disease when the test result is negative. The NPV will vary with the pretest probability of a disease. A patient with a high probability of having a disease will have a

low NPV with a negative test, but a patient with a low probability of having a disease will have a high NPV with a negative test.

Characteristics of a drug such as high molecular weight, high plasma protein binding, high charge, and hydrophilicity tend to trap the drug in the plasma compartment resulting in a

low Vd (3-5 L)

Cerebellar tremors are classically

low frequency (<5 Hz) and high amplitude and increase as an action approaches a target. They are often accompanied by other cerebellar signs, including ataxia, dysmetria, and impaired rapidly alternating movements.

Hemoglobin S (HbS) aggregates in the deoxygenated state. HbS polymers form fibrous strands that reduce red blood cell membrane flexibility and promote sickling. Sickling occurs under conditions associated with anoxia including

low pH and high levels of 2,3-bisphosphoglycerate. These inflexible erythrocytes predispose to microvascular occlusion and microinfarcts.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by

low plasma sodium and osmolality, inappropriately concentrated urine, and clinically normal volume status (euvolemic hyponatremia)

Patients with severe iron deficiency anemia (IDA) typically have evidence of hypochromic, microcytic erythrocytes on peripheral blood smear with poikilocytosis. Laboratory studies will reveal

low red blood cell count, low hepcidin, and high transferrin. Although erythropoietin is markedly elevated in IDA, there is not enough iron to efficiently generate erythrocytes; therefore, reticulocyte count is low.

Most common inherited bleeding disorder:

von Willebrand disease causes prolonged mucosal bleeding, easy bruising, and is responsive to desmopressin

Central hypothyroidism is characterized by

low serum TSH and thyroxine (T4) levels and is due to hypothalamic-pituitary dysfunction. Sheehan syndrome is ischemic necrosis of the pituitary gland and is typically caused by systemic hypotension during delivery. In addition to central hypothyroidism, patients may also develop deficiencies of other pituitary hormones (eg, ACTH, prolactin, gonadotropins).

Rhonchi are:

low-pitched rattling sounds produced with air flows through bronchi that have excessive secretions can be heard on both inspiration and expiration

mitral stenosis is associated with an opening snap of the mitral valve and what kind of murmur?

low-pitched rumbling murmur heard throughout diastole

Aortic coarctation classically leads to

lower extremity claudication and increased blood pressure in the arms, as compared to the legs. Over time, unrepaired defects may lead to a compensatory collateral circulation that supplies blood to the descending aorta and creates a continuous murmur heard over the back.

Aortic coarctation in a child/young adult presents with

lower-extremity claudication (eg, pain and cramping with exercise), blood pressure discrepancy between the upper and lower extremities, and delayed or diminished femoral pulses. Turner syndrome (45,XO) is associated with coarctation of the aorta in up to 10% of cases

Adenosine deaminase (ADA) inhibition/absence is highly lymphocytotoxic. Medications that block ADA are used to treat

lymphocyte-derived cancers. Inherited gene mutations in ADA lead to the autosomal recessive disease of severe combined immunodeficiency.

Sjögren syndrome (SS) is an autoimmune disorder characterized by

lymphocytic inflammation in exocrine glands (eg, lacrimal, salivary glands). It presents with dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia). Chronic B-cell proliferation in patients with SS increases the risk of developing non-Hodgkin lymphoma.

Chronic rejection is a major problem in lung transplant recipients; it affects small airways, causing bronchiolitis obliterans. It is characterized by

lymphocytic inflammation, fibrosis, and, ultimately, destruction of the bronchioles.

What is responsible for converting nonpathogenic Corynebacterium into toxigenic Corynebacterium?

lysogenic bacteriophages Toxigenic strains elaborate the diphtheria exotoxin, which causes pseudomembranous pharyngitis and potentially life-threatening systemic effects like myocarditis and neuritis

inclusion cell (I-cell) disease:

lysosomal storage disorder that occurs due to defects in protein targeting, a process by which proteins are transported to their appropriate intra- or extracellular location pts present with failure to thrive and cognitive deficits in the first year of life with characteristic physical features like coarse facial features, corneal clouding

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.

Clostridium difficile infection can be treated with oral vancomycin or fidaxomicin. Fidaxomicin is a

macrocyclic antibiotic that inhibits RNA polymerase. It is bactericidal against C difficile.

Folic acid deficiency anemia commonly occurs in alcoholism. It is a megaloblastic anemia that can develop within weeks. Peripheral blood smear shows

macrocytosis, ovalocytosis, and neutrophils with hypersegmented nuclei.

Mycobacterium tuberculosis grows in long, serpentine cords due to the presence of cord factor, a surface glycolipid, on the cell wall. Cord factor is a primary virulence factor of M tuberculosis; it prevents

macrophages from being bactericidal due to the inhibition of phagolysosome acidification and also leads to the formation of caseating granulomas.

Host defense against mycobacterial infections depends on the ability of

macrophages to sequester mycobacteria in granulomas and directly kill the bacteria in phagosomes Infected macrophages produce IL-12, which stimulates T cells and natural killer cells to produce interferon-γ (IFN-γ)

Sodium nitroprusside is a short-acting agent that causes balanced vasodilation of the veins and arteries to decrease both left ventricular (LV) preload and afterload. The balanced vasodilation allows for

maintenance of stroke volume and cardiac output at a lower LV pressure (lower cardiac work).

The late phase of dermatologic type I hypersensitivity reactions manifests as an indurated skin lesion hours after exposure to the allergen due to local tissue damage caused by

major basic protein released from eosinophils. In contrast, type IV hypersensitivity reactions develop over days because of the time needed to produce a cell-mediated immune response.

Eosinophils have bilobed nuclei and numerous eosinophilic granules in the cytoplasm and are important in allergic disease and defense against parasitic infection. The eosinophilic granules predominantly contain

major basic protein, which acts as a potent antihelminthic toxin. Major basic protein also damages epithelial and endothelial cells and is a major cause of chronic lung damage in asthma.

Polymyositis causes symmetric proximal muscle weakness. Muscle biopsy reveals inflammation, necrosis, and regeneration of muscle fibers. Over-expression of

major histocompatibility complex class I proteins on the sarcolemma leads to infiltration with CD8+ T lymphocytes and myocyte damage.

Amyloid light-chain amyloidosis is associated with multiple myeloma and other monoclonal plasma cell dyscrasias due to the deposition of insoluble immunoglobulin light-chain fibrils in

major organs (eg, kidneys, heart, neurologic system). A bone marrow sample with >10% plasma cells is strongly suggestive of multiple myeloma.

Lacunar infarctions are the result of small vessel occlusion (eg, due to lipohyalinosis and microatheroma formation) in the penetrating vessels supplying the deep brain structures. Uncontrolled hypertension and diabetes mellitus are

major risk factors for this condition

Some patients with non-small cell lung carcinoma (NSCLC) harbor a chromosomal rearrangement that creates a fusion gene between EML4 (echinoderm microtubule-associated protein-like 4) and ALK (anaplastic lymphoma kinase). This results in a constitutive active tyrosine kinase that causes

malignancy.

Prolonged alcohol consumption, recent viral infection, and repeated blood transfusions (ie, iron overload) are all potential causes of dilated cardiomyopathy. Dilated cardiomyopathy can lead to cardiac arrest and death via generation of a

malignant arrhythmia (ie, ventricular tachycardia or fibrillation); however, autopsy is expected to reveal an enlarged heart with eccentric hypertrophy of the LV and no tears in the myocardium

Pseudomonas aeruginosa is a nonlactose-fermenting, oxidase-positive, motile, Gram-negative rod. It is the most common cause of

malignant otitis externa (MOE), a serious infection of the ear seen in elderly diabetic patients. MOE presents with exquisite ear pain and drainage, and granulation tissue is often seen within the ear canal.

Congenital torticollis is typically noted by 2 to 4 weeks of age, after which the child prefers to hold the head tilted to one side. It is most commonly the result of

malposition of the head in utero or birth trauma. Most cases resolve with conservative therapy and stretching exercises.

Botulinum toxin blocks the presynaptic exocytosis of ACh vesicles, causing impaired muscarinic and nicotinic neurotransmission; it characteristically presents as a symmetric, descending paralysis that first

manifests with cranial nerve abnormalities, often following consumption of home-canned foods.

Germinal centers are the sites where activated B cells proliferate and undergo affinity maturation during generation of a humoral immune response. The formation of multiple germinal centers is typically

marked by lymphadenopathy, pain, and inflammation in the affected lymph node due to cellular recruitment and the release of inflammatory cytokines.

Proinsulin is cleaved into mature insulin and C-peptide, which are co-secreted from pancreatic beta cells in equimolar amounts. Circulating levels of C-peptide can be used as a

marker of endogenous insulin secretion. Sulfonylureas and meglitinides lower blood glucose by stimulating pancreatic insulin secretion; hypoglycemia due to these agents is associated with elevated C-peptide levels.

A single brain abscess is usually caused by direct spread of a contiguous infection. Temporal lobe abscess is usually a result of otitis media that has spread to the

mastoid air cells, while frontal lobe abscess is usually due to ethmoid or frontal sinusitis. Multiple brain abscesses typically indicate hematogenous dissemination of a distant infection (eg, endocarditis, empyema).

X-linked agammaglobulinemia is characterized by low or absent circulating

mature B cells (ie, CD19+, CD20+, CD21+ cells) and pan-hypogammaglobulinemia. Affected patients have increased susceptibility to pyogenic bacteria, enteroviruses, and Giardia lamblia due to the absence of opsonizing and neutralizing antibodies.

Sensation from the lower limbs is carried in the gracile fasciculus, which is located in the

medial aspect

Acute pituitary hemorrhage (pituitary apoplexy) is characterized by severe headaches, bitemporal hemianopsia (compression of the optic chiasm), and ophthalmoplegia (compression of the oculomotor nerve). It usually occurs in a preexisting pituitary adenoma. Pituitary apoplexy is a

medical emergency that requires urgent treatment with glucocorticoids to prevent acute adrenal crisis and circulatory collapse.

Management of gastroesophageal reflux disease includes lifestyle and dietary modifications (eg, weight loss, tobacco avoidance) and

medications such as proton pump inhibitors (PPIs) (eg, pantoprazole, omeprazole) or histamine 2 receptor antagonists (eg, ranitidine). PPIs irreversibly inhibit the H+/K+ ATPase on parietal cells, which decreases gastric acid secretion.

Multiple endocrine neoplasia type 2 is caused by germline activating mutations in the RET proto-oncogene and frequently results in both

medullary thyroid cancer and pheochromocytoma. In patients with undiagnosed pheochromocytoma, induction of anesthesia (eg, preparation for thyroidectomy) can precipitate a catecholamine surge, leading to hypertensive crisis, flash pulmonary edema, and atrial fibrillation.

Multiple endocrine neoplasia type 2B is characterized by

medullary thyroid cancer, pheochromocytomas, mucosal neuromas, and marfanoid habitus. Hyperparathyroidism is not a feature of this syndrome.

Patients with Turner syndrome may have karyotype 45,X (complete monosomy), 45,X/46,XX (mosaicism), or 46,XX (with partial deletion of one X chromosome). Complete monosomy X usually results from

meiotic nondisjunction during gametogenesis.

The HER2 oncogene encodes for a transmembrane glycoprotein with intrinsic tyrosine kinase activity and is a

member of the family of epidermal growth factor receptors. Overexpression of this protein is associated with a worse prognosis and increased risk of disease recurrence.

Lecithinase (alpha toxin) is the main toxin produced by Clostridium perfringens. It degrades lecithin, a component of cellular phospholipid membranes, which leads to

membrane destruction, cell death, and widespread necrosis and hemolysis.

In contrast to the prostatic and bulbous segments, the ____ segment is relatively unsupported by the adjacent tissues and is the weakest point of the posterior urethra

membranous

Without protection from the Hib vaccine, the child is at risk for:

meningitis, bacteremia, pneumonia, and epiglottitis

West Nile virus is a single-strand flavivirus transmitted by mosquitoes, most commonly in the summer. Most infections are asymptomatic or may present with a flu-like illness (West Nile fever), often with a maculopapular or morbilliform rash. Neuroinvasive disease manifests as

meningitis, encephalitis, or asymmetric flaccid paralysis; patients may have parkinsonian features.

Cryptococcus neoformans primarily causes

meningoencephalitis (headache, confusion, altered mental state) in patients who are immunocompromised (particularly in those with advanced AIDS)

Recurrent focal impaired awareness seizures that are preceded by a distinctive aura (eg, uneasy epigastric sensation, olfactory hallucinations) are characteristic of

mesial temporal lobe epilepsy. The most common etiology is hippocampal sclerosis (mesial temporal sclerosis), which is associated with childhood febrile seizures.

Second-generation antipsychotics are associated with

metabolic adverse effects like weight gain, dyslipidemia, hyperglycemia, increased risk of diabetes Within the class, olanzapine and clozapine carry the greatest risk

Patients with severe emphysema typically have chronic CO2 retention leading to chronic respiratory acidosis with

metabolic compensation (high PaCO2, compensatory high bicarbonate, slightly acidic pH), often accompanied by hypoxemia (PaO2 <75 mm Hg on room air).

Barrett esophagus

metaplastic replacement of normal squamous cells in the distal esophagus with squamocolumnar cells and occurs as a result of chronic acid reflux

Lead poisoning in adults typically occurs through occupational exposure. Symptoms include colicky abdominal pain, constipation, lead lines on the gum, peripheral neuropathy, and anemia. Laboratory testing shows

microcytic anemia with normal iron studies, and peripheral blood smear may reveal basophilic stippling.

HIV-associated dementia should be suspected in patients with AIDS who have progressive cognitive decline. The characteristic histopathologic finding is

microglial nodules (groups of activated microglia/macrophages around small areas of necrosis) and multinucleated giant cells.

Reye syndrome occurs in children with febrile illness treated with salicylates (aspirin). It consists of hepatic failure and encephalopathy. The characteristic histological finding is

microvesicular steatosis of hepatocytes without inflammation and cerebral edema.

Thyroglossal duct cysts form from epithelial remnants of the thyroglossal duct along the path of thyroid descent. They present as

midline masses that rise with swallowing or tongue protrusion.

In spherocytosis, mean corpuscular hemoglobin concentration (MCHC) is increased due to

mild dehydration of the red blood cell. Markers of hemolysis are often evident and include elevated lactate dehydrogenase, reticulocytosis, and decreased haptoglobin.

Vibrio vulnificus is a curved, gram-negative, free-living bacterium that grows in marine environments. Transmission primarily occurs due to the consumption of raw seafood (eg, oysters) or wound contamination. Manifestations are often

mild, but individuals with liver disease or iron overload are at very high risk of severe, fulminant infection (eg, sepsis, necrotizing fascitis).

Parvovirus B19 causes erythema infectiosum (fifth disease) in children and arthritis in adults. Parvovirus arthritis can

mimic rheumatoid arthritis but is usually self-resolving.

The zona glomerulosa is the outermost zone of the cortex and is composed of cells arranged in rounded or arched clusters (glomus is Latin for ball) that secrete

mineralocorticoid hormones (primarily aldosterone)

Potency of a gas anesthetic is determined by the

minimal alveolar concentration it is defined as the concentration of gas in the lungs that produces the desired effect in 50% of patients

"Red ragged" muscle fibers are seen in

mitochondrial diseases. Muscle fibers have this appearance because abnormal mitochondria accumulate under the sarcolemma. Mitochondrial diseases show maternal inheritance.

Opioid antagonist naltrexone is a first-line pharmacotherapy for

moderate-to-severe alcohol use disorder and works by preventing the reinforcing effects of alcohol use

Benzodiazepines act by binding to the benzodiazepine binding site, which allosterically

modulates the binding of GABA, resulting in an increased frequency of chloride ion channel opening. The influx of chloride ions into the neurons causes neuronal hyperpolarization and inhibition of the action potential

Mucor, rhizopus, and absidia fungi exist in:

mold form only they form broad, nonseptate hyphae that branch at wide, often 90 degree angles

Uterine leiomyomas (ie, fibroids) are common, benign tumors arising from the uterine myometrium that occur due to

monoclonal proliferation of myocytes and fibroblasts.

Acute cardiac transplant rejection occurs weeks following transplantation and is primarily a cell-mediated process. On histopathologic analysis of an endomyocardial biopsy, a dense

mononuclear lymphocytic infiltrate with cardiac myocyte damage will be visualized. Treatment with immunosuppressive drugs is aimed primarily at preventing this form of rejection.

Alveolar consolidation occurs when the alveoli become filled with fluid (eg, inflammatory exudate in bacterial pneumonia). The increased compactness of the alveolar fluid (compared to air) causes sound to travel faster and

more efficiently, resulting in bronchophony, increased tactile fremitus (vibration), and increased intensity of breath sounds over the affected area. Dullness to percussion is also present.

Renal infarction presents with flank pain, hematuria, elevated lactate dehydrogenase, and a wedge-shaped kidney lesion on CT scan. The most common cause of renal infarction is systemic thromboembolism, often due to thrombus formation during atrial fibrillation. The brain and kidneys are

more likely than other organs to suffer embolic infarctions because they are perfused at a higher rate.

Colon adenocarcinoma is the most common gastrointestinal malignancy. Right-sided lesions are more likely to bleed and cause iron deficiency anemia; left-sided lesions tend to present with

obstructing symptoms (eg, altered bowel habits, constipation, abdominal distension, nausea and vomiting).

Gradually developing myocardial ischemia encourages the formation and maturation of collateral vessels and is most likely to occur in the setting of a slow-growing, stable atherosclerotic plaque. An unstable atherosclerotic plaque (eg, that with active inflammation, a lipid-rich core, and/or a thin fibrous cap) is

more likely to rupture, resulting in the abrupt onset of ischemia/infarction that precludes the development of viable collateral vessels.

In displacement, emotions are transferred from the person causing the negative emotions to a

more neutral, less threatening person or object.

Treatment of CLL with BCL-2 inhibitors makes tumor cells

more sensitive to stress signals by increasing the activation of caspases, which leads to cell death

The best and most reliable auscultatory indicator of the degree of mitral stenosis is the A2-OS interval. A shorter interval indicates

more severe stenosis. Other auscultatory findings can include a diastolic rumbling murmur with presystolic accentuation due to left-atrial contraction.

The genetic code is considered "degenerate" because

more than 1 codon can code for a particular amino acid. Some of this degeneracy is explained by the wobble hypothesis, which states that the first 2 nucleotide positions on the mRNA codon require traditional (Watson-Crick) base pairing, whereas the third "wobble" nucleotide position may undergo less stringent (nontraditional) base pairing.

The superficial and deep inguinal rings are physiologic openings in the external abdominal oblique aponeurosis and the transversalis fascia, respectively. Surgical repair of an undescended testicle lodged in the inguinal canal involves

moving the testis through the superficial inguinal ring and fixing it in the scrotum (ie, orchiopexy).

Naltrexone blocks

mu-opioid receptor

Hereditary hemorrhagic telangiectasia presents with

mucocutaneous telangiectasias, epistaxis, and visceral arteriovenous malformations. Lung involvement includes pulmonary AVMs (digital clubbing, platypnea) and pulmonary htn (loud P2) due to high-output heart failure from underlying systemic AVMs.

Mucor, rhizopus, and absidia species are saprophytic fungi that are transmitted by spore inhalation. They cause:

mucormycosis, which is strongly associated with diabetic ketoacidosis patients with underlying immunosuppression are also at high risk.

Acute calculous cholecystitis is an acute inflammation of the gallbladder initiated by gallstone obstruction of the cystic duct. Subsequent steps in pathogenesis include

mucosal disruption by lysolecithins, bile salt irritation of the luminal epithelium, prostaglandin release with transmural inflammation, gallbladder hypomotility, increased intraluminal pressure causing ischemia, and bacterial invasion.

Medullary thyroid cancer is a neuroendocrine tumor that arises from calcitonin-secreting C (parafollicular) cells. It is often seen in the context of

multiple endocrine neoplasia type 2 (A and B), although the majority of cases are sporadic. Both sporadic and familial medullary thyroid cancers are associated with mutations in the RET proto-oncogene.

Pleiotropy describes instances where

multiple phenotypic manifestations result from a single genetic mutation Most syndromic genetic illnesses exhibit pleiotropy

Amyloid A protein is an acute-phase reactant that is associated with the development of:

multisystemic amyloidosis in reaction to chronic disease states (rheumatoid arthritis, inflammatory bowel disease)

The murmur of aortic stenosis (AS) is a 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.

Stimulant intoxication can present with paranoid ideation and must be differentiated from primary psychiatric disorders. Physical signs of stimulant intoxication include

mydriasis, tachycardia, hypertension, and diaphoresis.

The green discoloration of pus or sputum seen during common bacterial infections is due to the presence of

myeloperoxidase, a blue-green heme-based enzyme that is released from neutrophil azurophilic granules and forms hypochlorous acid (bleach).

Nitrates (via conversion to nitric oxide) activate guanylate cyclase and increase intracellular levels of cyclic guanosine monophosphate (cGMP). Increased levels of cGMP lead to

myosin light-chain dephosphorylation, resulting in vascular smooth muscle relaxation.

Cholinomimetics are indicated in non-obstructive urinary retention, paralytic ileus, and glaucoma. Their side effects include

nausea, vomiting, abdominal cramps, diarrhea, dyspnea and increased secretions (sweating, lacrimation and salivation).

Suppression of endogenous flora, colonization of the distal urethra by pathogenic gram-negative rods, and attachment of these pathogens to the bladder mucosa are the stages of pathogenesis in lower urinary tract infections. Anatomic or functional vesicoureteral reflux is almost always

necessary for the development of acute pyelonephritis.

mucormycosis tends to affect the paranasal sinuses sx include facial and periorbital pain, headache, and purulent nasal discharge Fungi proliferate in the walls of blood vessels and cause

necrosis of the corresponding tissue black eschar may be seen on the palate or nasal turbinates

Gout occurs in the setting of hyperuricemia and causes an inflammatory arthritis characterized by

negative birefringent, needle-shaped crystals visible on joint fluid microscopy. Most diuretics (eg, hydrochlorothiazide, furosemide) can cause hyperuricemia and trigger gout flares by causing relative volume depletion, which decreases the fractional excretion of uric acid.

Topical preparations of α-adrenergic agonists cause vasoconstriction of the nasal mucosa vessels and are used as decongestants. Overuse of these drugs causes

negative feedback, resulting in decreased norepinephrine synthesis and release from nerve endings, which diminishes their effect (ie, tachyphylaxis).

The lungs generate a collapsing force and the chest wall generates an expanding force; the point at which these opposing forces are equivalent is the resting equilibrium of the respiratory system, where alveolar pressure is equal to atmospheric pressure (ie, 0 cm H2O) and lung volume is the functional residual capacity. The opposing forces create

negative intrapleural pressure throughout the respiratory cycle; intrapleural pressure at resting equilibrium (ie, end-tidal expiration) is approximately -5 cm H2O.

Escherichia coli is a frequent cause of neonatal meningitis, second only to group B streptococci. E coli strains that cause

neonatal meningitis possess the K1 capsular antigen. The K1 capsule is a virulence factor that allows the bacteria to survive in the bloodstream and establish meningeal infection.

A patient with hypertension, hematuria, proteinuria, RBC casts, and edema suggests what disease?

nephritic syndrome

Poststreptococcal glomerulonephritis is the most common cause of

nephritic syndrome in children. Light microscopy demonstrates enlarged, hypercellular glomeruli. Laboratory findings in poststreptococcal glomerulonephritis include elevated antistreptococcal antibodies (eg, antistreptolysin O, anti-DNase B) and decreased C3 and total complement levels. C4 levels are usually normal.

Penicillamine is a copper-chelating agent used as first-line treatment in Wilson disease. Adverse effects include

nephrotic syndrome (ie, proteinuria) due to membranous nephropathy.

The most dangerous adverse effect of amphotericin B is its

nephrotoxicity, due to both a decrease in glomerular filtration rate and direct toxic effects on the tubular epithelium Nephrotoxicity can lead to anemia (decreased erythropoietin production) and electrolyte abnormalities

Medullary thyroid cancer is a neuroendocrine tumor that arises from parafollicular calcitonin-secreting C cells. It is characterized by

nests or sheets of polygonal or spindle-shaped cells with extracellular amyloid deposits derived from calcitonin.

Oseltamivir is a

neuraminidase inhibitor useful in the treatment of both influenza A and B virus infections Neuraminidase is required for the release of virus from infected cells and for the spread of virus within the respiratory tract

Bilateral acoustic neuromas are associated with

neurofibromatosis type 2, an autosomal dominant condition caused by mutation of the NF-2 gene on chromosome 22

Neural tube gives rise to neurons of the CNS system as well as the:

neurohypophysis, retina, pineal gland, preganglionic autonomic fibers, astrocytes, and ependymal cells

Conversion disorder is characterized by

neurologic symptoms and examination findings that are incompatible with a known neurological disease. Patients do not consciously produce the symptoms like in factitious disorder or malingering, and the condition may cause significant distress/impairment.

Reactivation of latent herpes simplex virus requires anterograde transport of viral particles from

neuronal cell bodies in the sensory ganglia to the skin and oral mucosa

Creutzfeldt-Jakob disease is a prion disease characterized by rapidly progressive dementia, myoclonus, and death within a year of symptom onset. Histopathology shows widespread

neuronal loss with small, uniform vacuoles in the gray matter of the brain (eg, spongiform encephalopathy).

Neurophysins are carrier proteins for oxytocin and vasopressin (ADH). Oxytocin and vasopressin are carried by unique neurophysins from their site of production in the cell bodies of the paraventricular and supraoptic nuclei to their site of release in the axon terminals of the posterior pituitary. Point mutations in

neurophysin II underlie most cases of hereditary hypothalamic diabetes insipidus, a disorder resulting from insufficient ADH release into the systemic circulation.

Vertebral osteomyelitis should be suspected in patients with

new or worsening back pain, fever, and recent endocarditis or bacteremia (especially Staphylococcus aureus). It should also be suspected if there are new neurologic findings and fever with or without back pain. MRI of the spine is preferred for diagnosis.

Rabies virus has a bullet-shaped envelope with knob-like glycoproteins that bind to

nicotinic acetylcholine receptors. Once transmission occurs (usually due to a bite wound from an infected animal), the virus replicates locally in muscle tissue for several days or weeks before spreading in a retrograde fashion through the peripheral nerve axons to the central nervous system.

Monoclonal antibodies (mAbs) are not eliminated by hepatic or renal clearance. Therefore,

no dose adjustment is necessary with impaired hepatic/renal function or use of cytochrome P450 inducers or inhibitors.

Melanoma often has an early horizontal growth phase with low metastatic potential followed by a

nodular, vertical growth phase with a significantly increased risk of metastasis. Depth of invasion (Breslow thickness) is the most important prognostic indicator in malignant melanoma.

Chronic kidney disease can cause hyperphosphatemia due to decreased renal excretion of phosphorus. Dietary phosphorus restriction is recommended, but oral phosphate binders are often needed. Sevelamer is a

nonabsorbable anion-exchange resin that binds intestinal phosphate to reduce absorption.

red man syndrome

nonallergic reaction that occurs when vancomycin is infused too rapidly; rapid vancomycin infusion can directly activate mast cells, leading to the release of potent vasoactive mediators (eg, histamine) Manifestations of RMS include flushing, pruritus, and an erythematous rash, which is usually seen on the upper torso, neck, and face. Myalgias and hypotension can occasionally occur.

Sarcoidosis classically causes

noncaseating granulomas involving the lungs, lymph nodes, and skin but granulomas can form in any tissue

Kawasaki disease is a vasculitis characterized by fever for ≥5 days and ≥4 of the following findings:

nonexudative conjunctivitis, extremity changes, cervical lymphadenopathy, mucositis, and polymorphous rash.

The pentose phosphate pathway consists of an oxidative (irreversible) branch and a nonoxidative (reversible) branch, and each can function independently based on cellular requirements. Transketolase, an enzyme of the

nonoxidative branch, is responsible in part for the interconversion of ribose-5-phosphate (nucleotide precursor) and fructose-6-phosphate (glycolytic intermediate).

Ehrlichia chaffeensis is harbored in white-tailed deer and transmitted to humans by tick bite. It replicates in vacuoles within monocytes and forms mulberry-shaped, intraleukocytic inclusions (morulae). Manifestations usually include

nonspecific symptoms (eg, fever, chills, myalgia), maculopapular rash, and significant laboratory abnormalities, particularly lymphopenia.

Mycobacterium avium complex (MAC) infections are common in patients with advanced AIDS. The bacterium often spreads through the bloodstream and reticuloendothelial system and causes

nonspecific symptoms (eg, fever, fatigue, weight loss, diarrhea), lymphadenopathy, and hepatosplenomegaly. Diagnosis is often made on blood culture or bone marrow aspirate (intracellular acid-fast bacteria that are not Mycobacterium tuberculosis).

Streptococcus pneumoniae is virulent primarily due to a polysaccharide capsule. A conjugant vaccine provides long-lasting immunity against serotypes in the vaccine but provides no significant immunity against

nonvaccinated serotypes. Therefore, infection can still occur due to serotypes not covered by the vaccine.

Nonselective beta blockers exacerbate hypoglycemia and mask hypoglycemic symptoms mediated by

norepinephrine/epinephrine.

Abnormal bleeding in patients with uremia is due to a qualitative platelet disorder that causes prolonged bleeding time with

normal platelet count, prothrombin time, and activated partial thromboplastin time.

Von Willebrand disease is the most common inherited bleeding disorder and is usually transmitted in an autosomal dominant fashion. Symptomatic patients typically present with easy bruising and mucosal bleeding. Laboratory evaluation will show

normal platelets, normal PT, and either normal or prolonged PTT due to low levels of factor VIII.

There are 5 major causes of hypoxemia (low arterial partial pressure of oxygen [PaO2]): alveolar hypoventilation, low partial pressure of inspired oxygen, ventilation-perfusion mismatch, diffusion impairment, and right-to-left shunting. The A-a gradient is

normal with alveolar hypoventilation and low partial pressure of inspired oxygen, which helps distinguish these causes from other causes of hypoxemia.

Positive and negative predictive values depend on disease prevalence in the tested population. The sensitivity and specificity of a diagnostic test are

not affected by disease prevalence.

Tension headaches are the most common form of headache. They are characterized by an achy or pressure-like pain that is often bilateral and associated with pericranial muscle tenderness. Tension headaches are

not associated with other neurologic symptoms and do not typically limit a patient's ability to perform daily functions.

Somatic symptom disorder is best managed with regularly scheduled medical visits that are

not contingent on having active symptoms. Unnecessary diagnostic testing and specialist referrals should be avoided.

Legionella pneumophila has a propensity to affect older adults with chronic lung disease who smoke. It causes Legionnaires' disease which is characterized by high fever, diarrhea, headache, and confusion. L. pneumophila is a gram-negative rod that is typically

not detected on Gram stain but can be diagnosed by PCR of a lower respiratory tract sample or detection of Legionella antigen in the urine.

Congenital hypothyroidism, most commonly caused by abnormal thyroid gland development or location (ie, ectopy), is identified by elevated TSH and decreased thyroxine (T4) levels. Clinical manifestations of hypothyroidism are

not present at birth due to the transplacental transfer of small amounts of maternal T4.

potassium iodide competitively inhibits thyroid uptake of radioactive iodine isotopes and is often administered following

nuclear accidents to protect the thyroid and prevent development of radiation-induced thyroid carcinoma

Budesonide, like other glucocorticoids, reduces inflammation by binding to a cytosolic receptor, translocating into the nucleus, and inhibiting proinflammatory transcription factors such as

nuclear factor-kappa-B (NF-κB) It is especially useful in reducing transmural bowel inflammation in patients with Crohn disease because it has high topical potency and limited systemic adverse effects due to high first-pass metabolism.

As such, the function of RNA polymerase I is restricted to the

nucleolus

It is the primary site of ribosomal RNA (rRNA) transcription

nucleolus

Zidovudine (ZDT) is a

nucleoside reverse transcriptase inhibitor used to prevent maternal to fetal transmission of HIV during labor (when the mother is not virally suppressed). It is a thymidine analogue that does not have the normal 3′-hydroxyl group found on thymidine. Because new nucleotides are added to growing DNA chains only at the 3′-hydroxyl group, the addition of ZDT into DNA results in chain termination.

The notochord almost completely regresses in humans, and its only major derivative is the:

nucleus pulposus of the intervertebral disc

Tibial nerve injury causes:

numbness at the sole and is typically associated with decreased inversion and plantarflexion of the foot and flexion of the toes common causes include knee trauma and tarsal tunnel syndrome

Treatment options for bulimia nervosa include

nutritional rehabilitation, cognitive-behavioral therapy, and pharmacotherapy with selective serotonin reuptake inhibitors. Fluoxetine is the drug of choice.

An obstructive lesion in a mainstem bronchus can prevent ventilation of an entire lung, leading to

obstructive atelectasis and complete lung collapse. Characteristic findings on chest x-ray include unilateral pulmonary opacification and deviation of the mediastinum toward the opacified lung.

Germinomas are the most common pineal gland tumor and present with

obstructive hydrocephalus and dorsal midbrain (Parinaud) syndrome. Germinomas in the suprasellar region cause endocrinopathies due to pituitary/hypothalamic dysfunction.

Cardiac tamponade involves increased pericardial pressure that restricts diastolic filling of the right-sided heart chambers, leading to

obstructive shock with increased central venous pressure and decreased stroke volume and cardiac output. As tamponade progresses, diastolic pressures in all 4 cardiac chambers increase and equalize with pericardial pressure (and with one another), stagnating blood flow within the heart.

Factitious disorder involves the conscious and deceptive feigning or self-production of physical or psychological symptoms to

obtain attention and medical care from health care personnel.

Entamoeba histolytica is an amoeba that causes colitis characterized by ulcers with undermining edges (ie, flask-shaped) that may contain cysts and trophozoites. Trophozoites can

occasionally (~1%) invade the colonic wall and disseminate through the blood to the liver, brain, or lungs. Amebic hepatic abscess is the most common extraintestinal manifestation.

A third heart sound (S3) occurs due to sudden limitation of ventricular movement during passive ventricular filling in diastole. An S3 in patients age >40 suggests abnormal ventricular cavity enlargement such as

occurs in chronic severe mitral regurgitation, chronic aortic regurgitation, or dilated cardiomyopathy.

In addition to blocking histamine receptors, first-generation antihistamines (eg, chlorpheniramine, diphenhydramine) have antimuscarinic, anti-alpha adrenergic, and anti-serotonergic properties. Anticholinergic effects on the

ocular ciliary muscles impair accommodation and cause blurring of vision for close objects.

Wernicke encephalopathy is a complication of thiamine deficiency and is characterized by

oculomotor dysfunction, encephalopathy, and ataxia. Chronic deficiency results in Korsakoff syndrome (eg, anterograde and retrograde amnesia, confabulation, apathy). Thiamine is involved in glucose metabolism, and areas of the brain with high metabolic demands are particularly susceptible; the mammillary bodies are most commonly affected.

The classical complement cascade begins with binding of the C1 complement component to either two molecules of IgG or to two molecules of IgM. Because IgM circulates in pentameric form, it is a much better activator

of the complement system. The C1 molecule binds to the Fc region of the heavy immunoglobulin chain in the region near the hinge point.

Multiple sclerosis (MS) is an autoimmune demyelinating disease that results from

oligodendrocyte depletion Within the lesions, inflammatory infiltrates of lymphocytes and macrophages are seen surrounding oligodendrocytes and myelin sheaths. Oligoclonal bands are highly sensitive but nonspecific in patients with MS.

In its most severe phenotype, autosomal recessive polycystic kidney disease can be detected on prenatal sonogram along with oligohydramnios. Potter sequence (flattened facies, limb deformities, pulmonary hypoplasia) is caused by

oligohydramnios and is associated with high mortality.

Preeclampsia is new-onset hypertension after 20 weeks gestation with signs of end-organ damage (eg, headache). Renal effects of preeclampsia include

oliguria with increased specific gravity, proteinuria, and serum creatinine levels.

Surgeries complicated by significant blood loss or those requiring the use of cardiopulmonary bypass or clamping of the aorta can cause sustained renal hypoperfusion and result in acute tubular necrosis (ATN). ATN presents with

oliguria, increased serum creatinine, and blood urea nitrogen/creatinine ratio <20:1. Urinalysis is characterized by muddy brown granular casts composed of sloughed renal tubular epithelial cells.

Glioblastoma is an aggressive primary brain neoplasm that generally presents with slowly worsening headache, seizure, and/or focal neurologic issues. Most cases are associated with

oncogenic mutations that increase epidermal growth factor receptor expression on the tumor cells, leading to increased transduction of growth signals that promote cellular survival and proliferation.

Positive end-expiratory pressure helps treat acute respiratory distress syndrome by

opening collapsed alveoli to reduce intrapulmonary shunting and increase functional residual capacity (FRC). The increased FRC decreases ventilation-perfusion mismatching and increases the oxygen reserves in the lungs.

Constipation is a common adverse effect of non-dihydropyridine calcium channel blockers (eg, diltiazem, verapamil). Other medications that cause constipation include

opiates, 5-HT3 antagonists, iron tablets, aluminum-containing antacids, and medications with anticholinergic properties.

Diphenoxylate is an

opioid antidiarrheal drug that binds mu opiate receptors in the gut to slow motility. Overuse can lead to euphoria and physical dependence. To discourage abuse, diphenoxylate is combined with atropine, which induces adverse effects if taken in high doses.

Candida albicans is the most common cause of

opportunistic mycosis. It can affect any organ and cause generalized candidemia. Yeasts and pseudohyphae on light microscopy and a positive germ tube test are diagnostic of Candida albicans infection.

Cryptococcus neoformans is an

opportunistic yeast that can be visualized with India ink staining

Multiple sclerosis is characterized by episodic, progressive neurologic deficits involving multiple anatomic regions within the central nervous system. Demyelinating plaques are commonly seen as hyperintense lesions on T2-weighted MRI of the brain and spinal cord. Common manifestations include

optic neuritis, internuclear ophthalmoplegia, sensory deficits, and fatigue, which may worsen with heat exposure.

Several months to years after ischemic brain infarction, the necrotic area appears as a cystic cavity surrounded by a

wall composed of dense fibers formed by astrocytic processes (glial scar).

Nystatin is a polyene antifungal and the drug of choice for

oropharyngeal candidiasis in patients without advanced immunodeficiency. It acts by binding to ergosterol in the fungal cell membrane, causing the formation of pores and leakage of fungal cell contents. Nystatin is not absorbed from the gastrointestinal tract and is administered as an oral "swish and swallow" agent.

Initial HIV infection is often associated with mononucleosis-like symptoms (eg, fever, lymphadenopathy, sore throat) 2-4 weeks after transmission. Important diagnostic clues are

oropharyngeal ulcers and a diffuse maculopapular rash. As the humoral antibody response is not fully activated early in infection, laboratory results typically show HIV in the serum (positive viral load and p24 antigen) but negative HIV serology.

Polyethylene glycol is an osmotic laxative. Diarrhea associated with lactase deficiency is also osmotic and occurs due to accumulation of nonabsorbable lactose in the intestinal lumen. Magnesium hydroxide (and other magnesium-containing compounds, such as magnesium citrate) is another

osmotic laxative that is often used, although its efficacy is questionable and there is not enough evidence to support its widespread use.

Calcitonin is released by the parafollicular cells of the thyroid. It inhibits

osteoclast activity, leading to decreased (not increased) bone resorption. Calcitonin is regulated primarily by circulating calcium levels, not thyroid hormone

Multiple myeloma is a plasma cell malignancy associated with purely radiolucent (osteolytic) bone lesions due to the stimulation of osteoclasts and the inhibition of osteoblasts. Myeloma cells stimulate

osteoclast development by secreting RANK-ligand and destroying osteoprotegerin, which increases RANK activity and results in osteoclast differentiation.

Multiple myeloma is a plasma cell malignancy that replicates in the bone marrow and causes

osteolytic bone lesions, bone destruction, hypercalcemia, and pathologic fractures. Histopathology will show replacement of the normal bone marrow with plasma cells and blasts.

Multiple myeloma should be suspected in elderly patients who have any combination of:

osteolytic lesions, hypercalcemia, anemia, or acute kidney injury Renal disease is most commonly caused by light chain cast nephropathy, in which free light chains form obstructive casts in the renal tubules

Imaging of bone metastases assists in cancer diagnosis. Bone metastases are characterized as

osteolytic or osteoblastic. Bony pain in an older man with osteoblastic lesions on imaging is highly suspicious for prostate cancer.

Osteoporosis is a common cause of fragility fractures, which occur in the absence of significant trauma. Chronic or recurrent use of glucocorticoids (eg, prednisone) promotes

osteoporosis and increases the risk of fractures.

Excessive vitamin D intake can lead to hypercalcemia and cause mental status changes, muscle weakness, constipation, and polyuria/polydipsia. Activated macrophages in sarcoidosis and

other granulomatous diseases express 1-α-hydroxylase, leading to excess production of 1,25-dihydroxyvitamin D and hypercalcemia.

Colonic diverticula often involve the sigmoid colon and develop due to exaggerated contractions of colonic smooth muscle segments. This results in increased intraluminal pressure, causing

outpouching of the mucosa and submucosa through the muscularis (false diverticula). Individuals (typically age >60) may be asymptomatic or have hematochezia or diverticulitis.

The suspensory ligament of the ovary contains the

ovarian artery, vein, lymphatics, and nerves. The ovarian artery is the major blood supply to the ovary and must be ligated during an oophorectomy to prevent heavy bleeding.

VSD produces a holosystolic murmur that is typically loudest where?

over the left sternal border in the 3rd or 4th intercostal spaces

Methotrexate and 5-FU both effectively inhibit thymidylate formation, but the chemotherapeutic effect of methotrexate is

overcome by N5-formyl-tetrahydrofolate (folinic acid, leucovorin) supplementation.

The process of negative selection in T cell maturation is essential for eliminating T cells that bind to self MHC or self antigens with

overly high affinity. This process occurs in the thymic medulla. If these cells were permitted to survive, they would likely induce immune and inflammatory reactions against self antigens leading to autoimmune disease.

As an antioxidant, superoxide dismutase neutralizes reactive oxygen species, preventing cell injury. In a pathologic state such as post-ischemic reperfusion,

oxidative stress is high and reactive oxygen species production exceeds the neutralizing capability of antioxidants, leading to increased cell damage and death.

Carbon monoxide (CO) binds to hemoglobin with much higher affinity than oxygen, thereby preventing oxygen binding to hemoglobin. It also reduces

oxygen unloading from hemoglobin in the tissues. CO poisoning increases carboxyhemoglobin concentrations but does not affect the partial pressure of oxygen and does not precipitate methemoglobinemia.

Increased ventilation-perfusion mismatch can lead to:

oxygen-induced hypercapnia

The most commonly injured structure in rotator cuff syndrome is the tendon of the supraspinatus muscle. Because the supraspinatus is an abductor of the humerus, injury to its tendon causes

pain on abduction of the arm.

Clinical features of rheumatoid arthritis

pain, swelling, and morning stiffness in multiple joints Small joints (PIP, MCP, MTP); spares DIP joints Systemic sx like fever, weight loss, anemia cervical spine involvement: subluxation, cord compression

The triad of hemolytic anemia, hypercoagulability, and pancytopenia suggests

paroxysmal nocturnal hemoglobinuria (PNH). PNH results from an acquired mutation in the PIGA gene that causes absence of the glycosylphosphatidylinositol anchor and associated deficiency of CD55 and CD59 complement inhibitor proteins

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 ankle jerk reflex.

Abruptio placentae is caused by rupture of maternal vessels at the uteroplacental interface that leads to premature separation of the placenta from the myometrium. Patients typically have

painful vaginal bleeding and a tender, firm uterus preeclampsia increases the risk of abruptio placentae

Herpes zoster (shingles) develops due to reactivation of varicella zoster virus in the dorsal root ganglia (sensory neurons). It presents with a

painful vesicular rash in a dermatomal distribution. Intranuclear inclusions in keratinocytes and multinucleated giant cells are seen on light microscopy.

Meckel diverticulum results from failed obliteration of the vitelline (omphalomesenteric) duct and usually presents with spontaneous but

painless lower gastrointestinal bleeding. 99mTc-pertechnetate localizes ectopic gastric mucosa, and its increased uptake is diagnostic for Meckel diverticulum.

Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in adults. It is of B-cell origin and presents with

painless waxing and waning (ie, fluctuating) lymphadenopathy. The cytogenetic change t(14;18) is characteristic and results in overexpression of the BCL2 oncogene.

Ganglion cysts are benign, fluid-filled masses that occur due to mucoid degeneration of periarticular tissue. They present as

painless, smooth, rubbery, round structures that overlie joints (eg, wrist) or tendons and transilluminate with a penlight. Most resolve spontaneously without intervention.

Cleft lip results when the maxillary prominence fails to fuse with the intermaxillary segment during the fifth-sixth week of embryonic development. Cleft palate occurs when the

palatine shelves fail to fuse with one another or with the primary palate. Cleft lip and palate can occur together or in isolation.

The teniae coli are 3 separate smooth muscle ribbons that travel longitudinally on the outside of the colon and converge at the root of the vermiform appendix. If the appendix cannot be identified by

palpation during an appendectomy, it can be located by following the teniae coli to their origin at the cecal base.

The dorsal pancreatic bud forms the majority of pancreatic tissue (body, tail, and most of the head). The ventral pancreatic bud is a precursor of the uncinate process, inferior/posterior portion of the head, and major pancreatic duct (of Wirsung). Failure of the dorsal and ventral pancreatic buds to fuse leads to

pancreas divisum. In this condition, the pancreatic ductal systems remain separate, with the accessory duct draining the majority of the pancreas.

The most common gastrointestinal disorder in patients with cystic fibrosis is

pancreatic insufficiency. Mutations in the cystic fibrosis transmembrane conductance regulator gene lead to thick, viscous secretions in the lumens of the pancreas, resulting in obstruction, inflammation, and subsequent fibrosis. Clinical manifestations include steatorrhea, failure to thrive, and deficiency of fat-soluble vitamins.

In patients with severe hypertriglyceridemia, pancreatic lipases can cause toxic levels of free fatty acids to be released within the

pancreatic tissue, leading to acute pancreatitis. Fibrates (eg, fenofibrate) are the most effective agents for the treatment of hypertriglyceridemia.

Kussmaul sign:

paradoxical increase in jugular venous pressure on inspiration It occurs because of impaired right-sided diastolic filling in conditions such as constrictive pericarditis, restrictive cardiomyopathy, and tricuspid stenosis

An important cause of SIADH is a

paraneoplastic effect secondary to small cell carcinoma of the lung

squamous cell carcinoma can lead to

paraneoplastic hypercalcemia (due to tumor secretion of parathyroid hormone-related protein)

Lung adenocarcinoma may cause

paraneoplastic hypertrophic osteoarthropathy

Prolonged hyperglycemia in diabetes mellitus can injure the

parasympathetic and sympathetic nervous system, resulting in diabetic autonomic neuropathy This can lead to disordered small-bowel and colonic motility and increased intestinal secretions, resulting in secretory-like diarrhea (eg, fasting bowel movements).

Hypocalcemia can cause muscle cramps, perioral paresthesias, hypotension, and neuromuscular hyperexcitability. Injury to the

parathyroid glands during thyroid surgery is a common cause of hypoparathyroidism and acute hypocalcemia.

As calcium is released from the bones into the circulation, it suppresses

parathyroid hormone (PTH) secretion, which leads to decreased reabsorption of calcium in the renal tubules and gut. This maintains normal blood calcium levels as bone mineralization is progressively depleted.

Fractures to the orbital floor commonly result from direct frontal trauma to the orbit. The infraorbital nerve runs along the orbital floor in a groove in the maxilla before exiting the skull just inferior to the orbit. Damage can result in

paresthesia of the upper cheek, upper lip, and upper gingiva. In addition, the inferior rectus muscle can also become entrapped, limiting vertical gaze.

Gastrin stimulates:

parietal cell acid production and rises in response to meals

Appendicitis causes dull visceral pain at the umbilicus due to afferent pain fibers entering at the T10 level in the spinal cord. Progressive inflammation in the appendix irritates the

parietal peritoneum and abdominal wall to cause more severe somatic pain shifting from the umbilicus to McBurney's point (two-thirds of the distance from the umbilicus to the anterior superior iliac spine).

Pertussis should be considered in any adult who has not had updated vaccination boosters. The clinical presentation is a

paroxysmal cough lasting >2 weeks that is associated with post-tussive emesis or inspiratory whoop after a severe coughing episode.

Invasive vascular procedures can be complicated by atheroembolic disease, which may involve the kidneys, gastrointestinal tract, CNS, and the skin. Light microscopy shows a

partially or completely obstructed arterial lumen with needle-shaped cholesterol clefts within the atheromatous embolus.

Most oropharyngeal carcinomas (eg, tonsil, base of tongue) are caused by human papilloma virus (HPV) infection. HPV-16 and HPV-18 are

particularly likely to cause malignant transformation.

Erythema infectiosum (fifth disease) is caused by

parvovirus B19 and presents with a nonspecific prodrome (eg, malaise, fever, congestion) followed by a classic "slapped-cheek" facial rash and a lacy, reticular body rash. Parvovirus is highly tropic for erythroid precursor cells and replicates predominantly in the bone marrow.

In patients with sickle cell anemia and other chronic hemolytic disorders, the most common viral cause of an aplastic crisis is infection of erythroid progenitor cells with

parvovirus B19, a nonenveloped single-stranded DNA virus.

Neonatal tetanus can be prevented by hygienic delivery and umbilical cord care and universal immunization of women who are pregnant or may become pregnant. Immunized mothers provide

passive immunity via transplacental IgG, protecting infants until they receive active immunization (vaccination) around age 2 months.

Temporomandibular joint disorder is associated with dysfunction of the temporomandibular joint and hypersensitivity of the mandibular nerve (CN V3). This can result in

pathologic contraction of the muscles of mastication, including the masseter and pterygoids.

Chronic opioid use leads to the development of tolerance to analgesic effects and most side effects, with the exception of constipation and miosis. To prevent bowel complications, it is recommended that

patients be treated prophylactically with adequate fluid intake and daily laxatives.

A femoral nerve block below the inguinal ligament (ie, in the inguinal crease) will anesthetize the skin and muscles of the anterior thigh, femur, and knee. This type of block can be used in

patients requiring tendon repair after a knee injury (eg, quadriceps rupture).

Monoamine oxidase (MAO) is a mitochondrial enzyme that breaks down monoamine neurotransmitters (eg, dopamine, norepinephrine, serotonin). Tyramine-induced hypertensive crisis can occur in

patients taking MAO inhibitors who consume foods containing high amounts of tyramine (eg, aged cheeses, cured meats, draft beer).

Active tuberculosis is never treated with drug monotherapy due to the fast emergence of mycobacterial antibiotic resistance from rapid, selective gene mutations. Isoniazid monotherapy may be used for

patients who have a positive PPD and a negative chest x-ray (ie, no evidence of clinical disease).

Vitamin A deficiency causes night blindness and hyperkeratosis. Deficiency of this fat-soluble vitamin can develop in

patients with biliary disorders, exocrine pancreatic insufficiency, or intestinal malabsorption.

Pulsus paradoxus is defined by a decrease in systolic blood pressure of >10 mm Hg with inspiration. It is most commonly seen in

patients with cardiac tamponade but can also occur in severe asthma, chronic obstructive pulmonary disease, and constrictive pericarditis.

The work of breathing is minimized in patients with increased elastic resistance (eg, pulmonary fibrosis) when their respiratory rate is high and tidal volume is low (fast, shallow breaths). In contrast,

patients with diseases that increase airflow resistance (eg, asthma, chronic obstructive pulmonary disease) breathe at a lower respiratory rate and higher tidal volume (slow, deep breaths) to minimize the work of breathing.

Creatinine, a waste product generated by the breakdown of creatine in the muscles, is used to estimate the glomerular filtration rate (GFR). Creatinine formation is dependent on muscle mass and meat intake; therefore,

patients with low muscle mass (eg, elderly patient, those with amputations) or low intake (eg, low-protein vegetarian diet) can have significantly lower GFRs for any given creatinine level.

A low-frequency, late diastolic sound on cardiac auscultation that immediately precedes the first heart sound (S1) is most often a fourth heart sound (S4). An abnormal S4 can be heard in

patients with reduced ventricular compliance (eg, hypertensive heart disease, aortic stenosis, hypertrophic cardiomyopathy) due to a sudden rise in end-diastolic pressure with atrial contraction.

Allergic rhinitis often causes nasal congestion, sneezing, rhinorrhea, and conjunctivitis due to an IgE-mediated hypersensitivity response. Patients can often distinguish

patterns that suggest reactions to specific allergens.

Capitation is an arrangement in which a payor pays a fixed, predetermined fee to provide all the services required by a patient. Payors may negotiate a capitated contract with an insurance company that then

pays the providers, or a large medical group may negotiate directly with the payor. Additional Information

medial pectoral nerve innervates the:

pectoralis minor and major the lateral pectoral nerve also innervates pectoralis major

A deficiency of niacin results in

pellagra, which is characterized by dermatitis, diarrhea, and dementia

Hartnup disease is caused by impaired transport of neutral amino acids in the small intestine and proximal tubule of the kidney. Symptoms include

pellagra-like skin eruptions and cerebellar ataxia, which occur as a result of niacin deficiency. The diagnosis can be confirmed through detection of excessive amounts of neutral amino acids in the urine.

Syphilis is caused by the corkscrew-shaped organism Treponema pallidum. Secondary syphilis develops in untreated patients weeks or months after the initial infection, and presents with a diffuse, macular rash and generalized lymphadenopathy. First-line treatment is

penicillin, which blocks the last step in bacterial cell wall synthesis (transpeptidation).

Fibrinous pericarditis is the most common type of pericarditis and is characterized by

pericardial inflammation with a serous, fibrin-containing exudate in the pericardial space. Pleuritic chest pain and a triphasic friction rub are frequently seen. Common causes include viral infection, myocardial infarction, uremia, and rheumatologic disease (eg, systemic lupus erythematosus, rheumatoid arthritis)

Septic shock can present with either hyper- or hypothermia. The initial disturbance is

peripheral vasodilation leading to decreased systemic vascular resistance, decreased central venous pressure, and decreased pulmonary capillary wedge pressure. A compensatory increase in sympathetic drive causes an increase in cardiac output; the resulting high flow rates lead to incomplete oxygen extraction in the tissues, resulting in high mixed venous oxygen saturation.

Acute interstitial nephritis manifests as:

peritubular T-lymphocyte, monocyte, and eosinophilic infiltration AIN resolves when the offending agent is discontinued, usually drugs like penicillin and cephalosporin

Erythropoietin (EPO) is produced primarily by

peritubular fibroblast cells in the renal cortex in response to decreased renal oxygen delivery (eg, decreased blood hemoglobin content). EPO acts on erythrocyte precursor cells in the bone marrow to stimulate red blood cell production. Patients with chronic kidney disease have inflammatory damage to renal EPO-producing cells and often develop normocytic anemia due to insufficient EPO.

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.

Human papillomavirus (HPV) infection, especially with strain 16 or 18, is the strongest risk factor for development of cervical dysplasia and invasive cervical carcinoma. HIV coinfection allows HPV infection to

persist and enhances expression of HPV oncogenes, increasing the risk for cervical dysplasia/cancer.

Wilson disease is associated with copper accumulation in the liver, brain, and cornea. It can present in childhood or adolescence with abnormal liver function tests and/or neuropsychiatric symptoms. Psychiatric symptoms may predate other manifestations and include

personality changes, depression, mania, and/or psychosis.

Patients with orbitofrontal cortex injury often experience

personality changes, disinhibition, and irritability secondary to impairment of the behavioral and emotional modulatory systems.

Deficiency of 17 alpha-hydroxylase is a rare form of congenital adrenal hyperplasia characterized by impaired synthesis of androgens, estrogens, and cortisol with excess production of mineralocorticoids. Genetic males with this deficiency may have

phenotypically female external genitalia and present with hypertension and hypokalemia around the expected time of puberty.

Cortisol increases the conversion of norepinephrine to epinephrine in the adrenal medulla by increasing the expression of

phenylethanolamine-N-methyltransferase.

Phenytoin metabolism depends on the function of hepatic P450 oxidases and is dose-dependent. Drugs that induce hepatic microsomal enzymes (phenobarbital, carbamazepine, and rifampin) enhance

phenytoin metabolism and decrease its serum concentration. You should know all of the commonly-prescribed medications that are metabolized by the P450 system, and you should know which drugs induce or inhibit the function of these enzymes.

The kidneys compensate for metabolic acidosis by completely reabsorbing filtered bicarbonate (HCO3-) and excreting excess H+ in the urine. Most of the excreted H+ is buffered by

phosphate (H2PO4-) and ammonium (NH4+), which allows for large amounts of acid to be excreted without precipitously dropping the pH.

The phosphoinositol second messenger system begins with ligand-receptor binding and Gq-protein activation leading to activation of phospholipase C (PLC). PLC then hydrolyzes

phosphatidyl inositol bisphosphate and forms diacylglycerol and inositol triphosphate (IP3). Finally, IP3 activates protein kinase C via an increase in intracellular Ca2+.

Fructose 2,6-bisphosphate (F2,6BP) activates phosphofructokinase-1 (increasing glycolysis) and inhibits fructose 1,6-bisphosphatase (decreasing gluconeogenesis). F2,6BP concentration is regulated by a bifunctional enzyme complex:

phosphofructokinase-2 increases F2,6BP levels in response to insulin, and fructose 2,6-bisphosphatase decreases F2,6BP levels in response to glucagon.

Pathologic atrophy can be caused by decreased

physical workload, loss of innervation, decreased blood supply, inadequate nutrition, absent endocrine stimulation, aging, or mechanical pressure.

Seborrheic keratoses are

pigmented macules or plaques with a greasy surface and well-demarcated borders. Rapid onset of numerous lesions is an indicator of internal malignancy (Leser-Trélat sign), especially gastric adenocarcinoma.

Multiple endocrine neoplasia type 1 syndrome is characterized by tumors of the

pituitary, parathyroid gland, and pancreas (the "3 Ps").

Placenta accreta spectrum occurs due to

placental invasion into the myometrium through defects in the decidua basalis. This creates a morbidly adherent placenta that does not detach after fetal delivery, leading to postpartum hemorrhage. Manual placental extraction typically yields small placental fragments and increases bleeding.

Neonates have a higher proportion of body water compared to adults. This can result in lower

plasma concentrations of water-soluble drugs if they are administered at the same weight-based dosage as given to adult patients.

Minimal change disease is the most common childhood nephrotic syndrome. Increased glomerular capillary permeability causes massive protein (eg, albumin) loss in the urine. Hypoalbuminemia reduces

plasma oncotic pressure, which causes a fluid shift into the interstitial space, resulting in edema. Low oncotic pressure also triggers increased lipoprotein production in the liver (ie, hyperlipidemia).

The majority of CO2 produced in the tissues is transported to the lungs as bicarbonate ion (HCO3−). Within red blood cells (RBCs), the enzyme carbonic anhydrase forms HCO3− from CO2 and water. The excess HCO3− is then transferred out of RBCs into the

plasma via exchange with chloride ions (Cl−). This exchange is known as "chloride shift" and is the principal cause of high RBC chloride content in venous blood.

Extended-spectrum beta-lactamases can be produced by gram-negative bacteria, rendering cephalosporins and other beta-lactam antibiotics inactive. These genes can be transmitted between organisms through

plasmid conjugation.

Undifferentiated (anaplastic) tumors bear no resemblance to the tissue of origin. They are composed of

pleomorphic cells with large, hyperchromatic nuclei that grow in a disorganized fashion. Anaplastic tumors may also contain numerous, abnormal mitoses and giant tumor cells.

Pleural effusion results from an increased rate of fluid inflow from the nearby vasculature or a decreased rate of fluid outflow through the parietal pleural lymphatics. Decompensated heart failure causes

pleural effusion primarily due to increased fluid inflow from increased pulmonary capillary hydrostatic pressure; lymphatic outflow increases but is unable to keep up with the increased inflow.

Exudative effusions are characterized by a high ratio of

pleural fluid to serum total protein (>0.5) or lactate dehydrogenase (>0.6), or high absolute levels of lactate dehydrogenase

Interstitial myocardial granulomas (Aschoff bodies) are found in carditis due to acute rheumatic fever, which develops after an untreated group A streptococcal pharyngeal infection. Aschoff bodies contain

plump macrophages with abundant cytoplasm and central, slender ribbons of chromatin (Anitschkow, or caterpillar, cells).

Nocardia is a filamentous, branching, gram-positive bacteria that is partially acid-fast. It most commonly causes

pneumonia and brain abscesses in immunocompromised patients.

Nephrogenic diabetes insipidus is characterized by

polyuria, dilute urine (low urine specific gravity), hypernatremia, and high antidiuretic hormone. Treatment includes thiazide diuretics and replacement of water losses.

Fluoroquinolones can form insoluble chelate complexes with

polyvalent cations (eg, calcium, iron, aluminum, magnesium) 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.

Rheumatoid arthritis presents with what on lab/imaging studies?

positive rheumatoid factor and anti-CCP antibodies C-reactive protein and ESR X-ray: soft tissue swelling, joint space narrowing, bony erosions

Synovial fluid analysis showing rhomboid-shaped calcium pyrophosphate crystals is diagnostic of pseudogout. These crystals are

positively birefringent under polarized light. The knee joint is involved in >50% of cases.

In a susceptible child, a febrile maculopapular rash that begins on the face and spreads to the trunk and extremities is suggestive of rubeola (measles) or rubella (German measles). The additional finding of

postauricular lymphadenopathy indicates that rubella is the most likely etiology.

The posteromedial papillary muscle is supplied solely by the

posterior descending artery, making it susceptible to ischemic rupture

The posterior cruciate ligament prevents posterior displacement of the tibia relative to the femur. It originates from the anterolateral surface of the medial femoral condyle and inserts into the posterior intercondylar area of the tibia. Its integrity can be tested in the clinical setting by using the

posterior drawer test.

Injury to the hypothalamus or posterior pituitary (eg, head trauma, transsphenoidal neurosurgery, suprasellar masses) can result in central diabetes insipidus (DI). Damage to the

posterior pituitary gland typically causes transient DI, whereas damage to the hypothalamic nuclei often causes permanent DI.

Short bowel syndrome typically occurs in patients with massive small bowel resection and/or Crohn disease due to loss of intestinal absorptive surface area and a decrease in intestinal transit time. Patients usually present with

postprandial voluminous diarrhea and weight loss due to malabsorption. Loss of functional distal ileum may result in vitamin B12 deficiency.

Onset of nephritic syndrome symptoms 3 weeks after a bacterial skin infection suggests:

poststreptococcal glomerulonephritis, an immune complex-mediated disease that occurs 2-4 weeks after exposure to group A beta-hemolytic streptococcus

Myasthenia gravis is an autoimmune disease that causes a decrease in the number of functional acetylcholine receptors within the neuromuscular junction. This reduces the number of

postsynaptic cation channels that can open in response to acetylcholine, which reduces the amplitude of motor end plate potential and prevents muscle fiber depolarization.

Class III antiarrhythmic drugs (eg, amiodarone, sotalol, dofetilide) predominantly block

potassium channels and inhibit the outward potassium currents during phase 3 of the cardiac action potential, thereby prolonging repolarization and total action potential duration

Amatoxins are found in a variety of poisonous mushrooms (eg, Amanita phalloides, known as death cap) and are

potent inhibitors of RNA polymerase II (halting mRNA synthesis).

Schistocytes suggest microangiopathic hemolytic anemia (eg, hemolytic-uremic syndrome [HUS], thrombotic thrombocytopenic purpura [TTP], disseminated intravascular coagulation [DIC]) or mechanical damage [eg, prosthetic valve]). In childhood, HUS is often

preceded by bloody diarrhea. Coagulation studies (prothrombin time and partial thromboplastin time) are normal in HUS-TTP but abnormal in DIC.

Telomeres help maintain chromosomal integrity and are preserved in rapidly dividing cell lines (eg, epithelial cells, lymphocytes, hematopoietic stem cells) by telomerase. Disorders involving telomerase function (eg, dyskeratosis congenita) result in

premature death of cells with high turnover, characteristically causing mucocutaneous changes (eg, oral leukoplakia, dystrophic nails), bone marrow failure, and pulmonary fibrosis.

Mosaicism:

presence of multiple, genetically different cell lines within the body it can result from chromosomal nondisjunction and mutations during the first stages of embryonic development

Endometriosis refers to the presence of endometrial glands and stroma outside the uterus. It may be asymptomatic or

present with dysmenorrhea, dyspareunia, and/or infertility.

Cavernous hemangiomas are vascular malformations composed of abnormally dilated capillaries separated by thin connective tissue septa. The lack of structural support gives them a tendency to bleed, and those that occur in the brain can

present with neurologic deficits and seizures.

Gallstone ileus results from passage of a large gallstone through a cholecystenteric fistula into the small bowel, where it ultimately causes obstruction at the ileum. Patients typically

present with symptoms/signs of small bowel obstruction, and an abdominal x-ray may reveal gas within the gallbladder and biliary tree.

Fluoroquinolones

prevent DNA gyrase and topoisomerase from unwinding bacterial double-stranded circular DNA Fluoroquinolones can be used to treat typhoid fever, a Salmonella infection that typically occurs in individuals who travel to developing nations.

Hypo-acetylated histones bind tightly to DNA and

prevent transcription of genes in their associated regions. Alteration of gene expression in Huntington disease occurs in part due to deacetylation of histones. This prevents the transcription of certain genes that code for neurotrophic factors, contributing to neuronal cell death.

Blanching of a vein into which norepinephrine is being infused together with induration and pallor of the tissues surrounding the IV site are signs of norepinephrine extravasation and resulting vasoconstriction. Tissue necrosis is best

prevented by local injection of an α receptor blocking drug, such as phentolamine.

Dihydrofolate reductase and DNA polymerase are enzymes involved in DNA synthesis, which occurs during the S phase of the cell cycle. The Rb protein, in its active (dephosphorylated) form, regulates cell cycle progression by

preventing the transition from the G1 phase to the S phase. Phosphorylation of the Rb protein inactivates it, allowing cells to progress through the G1/S checkpoint and proliferate

Naegleria fowleri is a free-living, motile protozoan that lives in warm water. Exposure can result in

primary amebic encephalitis, which is characterized by acute fever, headache, confusion, and neck stiffness. The diagnosis is confirmed when motile trophozoites are seen on cerebrospinal fluid wet mount. Nearly all patients die.

Imperforate hymen is caused by incomplete degeneration of the central portion of the fibrous tissue band connecting the walls of the vagina. Adolescent patients typically present with

primary amenorrhea, normal secondary sexual characteristics, and cyclic abdominal or pelvic pain due to accumulation of menstrual blood in the vagina and uterus (eg, hematocolpos).

Xanthelasma and other forms of xanthoma (tuberous, eruptive, tendinous) are classically associated with

primary or secondary hyperlipidemia Chronic cholestatic processes including obstructive biliary lesions and primary biliary cholangitis result in hypercholesterolemia due to leakage of bile back into the circulation, leading to the formation of xanthelasmas.

K+ is freely filtered by the glomeruli and is mostly reabsorbed in the proximal tubule and loop of Henle. As such, the late distal and cortical collecting tubules are the

primary sites for regulation of K+ excretion in the urine. K+ depletion stimulates α-intercalated cells to reabsorb extra potassium; principal cells secrete K+ under conditions of increased K+ load.

Beta-endorphin is one endogenous opioid peptide that is derived from proopiomelanocortin (POMC). POMC is a polypeptide precursor that goes through enzymatic cleavage and modification to

produce not only beta-endorphins, but also ACTH and MSH. The fact that beta-endorphin and ACTH are derived from the same precursor suggests that there may be a close physiological relationship between the stress axis and the opioid system.

IL-1

produced by macrophages and epithelial cells, has proinflammatory properties such as endothelium activation, increased chemokine expression (promoting leukocyte recruitment), and induction of fever. IL-1β is important for differentiation of TH17 cells.

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.

Phosphofructokinase-1 (PFK1) catalyzes the rate-limiting step in glycolysis, and the most potent stimulator of PFK1 is fructose 2,6-bisphosphate. Insulin increases

production of fructose 2,6-bisphosphate by phosphofructokinase-2 (PFK2), thereby stimulating glycolysis.

Phenotypic mixing refers to coinfection of a host cell by 2 viral strains, resulting in

progeny virions that contain nucleocapsid proteins from one strain and the unchanged parental genome of the other strain. Because there is no change in the underlying viral genomes (no genetic exchange), the next generation of virions revert to their original, unmixed phenotypes.

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 characteristic. Patients typically present with

progressive solid and eventually liquid dysphagia and weight loss.

During glycogenolysis, glycogen phosphorylase shortens glycogen chains by cleaving

α-1,4-glycosidic linkages between glucose residues, liberating glucose 1-phosphate in the process

The airway resistance at each level of the lower respiratory tract is inversely related to the total cross-sectional area of all the airways at that level. Airway resistance is high in the trachea and reaches a peak in the medium-sized bronchi, where total cross-sectional area is at a minimum. Airway resistance then

progressively decreases as total cross-sectional area increases through the smaller bronchioles, terminal bronchioles, and alveoli.

Disseminated intravascular coagulation commonly occurs in the setting of sepsis and is characterized by widespread activation of the coagulation cascade with formation of microthrombi. Laboratory results reveal

prolonged PT/PTT, thrombocytopenia, and low fibrinogen (ie, a consumptive coagulopathy), and patients usually have signs of bleeding (eg, oozing from venipuncture sites).

Analgesic nephropathy is a form of chronic kidney disease caused by

prolonged, heavy intake of nonsteroidal anti-inflammatory drugs and/or acetaminophen. Pathologic characteristics include chronic interstitial nephritis and papillary necrosis.

Class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide) predominantly block potassium channels and inhibit the outward potassium currents during phase 3 of the cardiac action potential, thereby

prolonging repolarization and total action potential duration.

The TATA and CAAT boxes are

promoters of transcription in eukaryotic cells and are located approximately 25 and 75 bases upstream from the transcription start site, respectively. They promote initiation of transcription by serving as binding sites for transcription factors and RNA polymerase II.

The classic triad of fever, stiff neck, and altered mentation should raise suspicion for acute bacterial meningitis. Evaluation requires

prompt blood cultures, empiric antibiotics, and lumbar puncture with cerebrospinal fluid analysis.

Acute rheumatic fever is a complication of untreated group A streptococcal pharyngitis. Rheumatic heart disease is the most common cause of acquired valvular heart disease and cardiovascular death in developing countries. The incidence of acute rheumatic fever and rheumatic heart disease has been reduced in industrialized nations with

prompt treatment of streptococcal pharyngitis with penicillin.

Acute promyelocytic leukemia (APL, M3 acute myeloid leukemia) can present with persistent infection and coagulopathy causing hemorrhagic signs and symptoms. Bone marrow biopsy classically reveals

promyelocytes with intracytoplasmic Auer rods. APL is associated with a t(15;17) chromosomal translocation that causes fusion of the retinoic acid receptor-α gene and promyelocyte leukemia gene.

Congenital deficiency of propionyl-CoA carboxylase, the enzyme responsible for the conversion of propionyl-CoA to methylmalonyl-CoA leads to the development of

propionic acidemia The condition presents with lethargy, poor feeding, vomiting, and hypotonia 1-2 weeks after birth

Cyclooxygenase initiates the synthesis

prostanoids like prostaglandins, thromboxane from arachidonic acid

The prostatic plexus (inferior hypogastric nerves plus pelvic and sacral splanchnic nerves) lies within the fascia of the prostate and innervates the corpus cavernosa of the penis, which facilitates penile erection. As a result,

prostatectomy or injury to the prostatic plexus can cause erectile dysfunction.

Bleeding due to heparin toxicity is treated with

protamine sulfate, a specific antagonist

Multiple myeloma, a plasma cell malignancy associated with significant production of secretory proteins (eg, monoclonal immunoglobulins), is frequently treated with

proteasome inhibitors (eg, bortezomib). These drugs block the degradation of ubiquitinated proteins by the proteosome, which leads to accumulation of abnormally folded proteins that trigger cellular apoptosis.

Individuals who are successfully immunized against hepatitis B virus develop

protective anti-HBs antibody. Individuals who recover from hepatitis B infection, however, have anti-HBs as well as anti-HBc antibodies. The presence of circulating HBsAg indicates active infection.

ΔF508 is the most common mutation in the cystic fibrosis transmembrane regulator (CFTR) protein in patients with cystic fibrosis. This mutation leads to

protein misfolding and failure of glycosylation, followed by proteasome-mediated degradation and significantly decreased number of transmembrane CFTR proteins

Insulin is an anabolic hormone that acts via receptor tyrosine kinase signaling to increase the synthesis of glycogen, proteins, fatty acids, and nucleic acids. Tyrosine kinase/phosphatidylinositol-3-kinase stimulation promotes glycogen synthesis by activating

protein phosphatase, an enzyme that dephosphorylates (activates) glycogen synthase.

General sensation from the anterior 2/3 of the tongue is carried by the mandibular division of the trigeminal nerve. Gustatory innervation of the anterior 2/3 of the tongue is

provided by the chorda tympani branch of the facial nerve.

The ductus arteriosus is an embryonic derivative of the sixth aortic arch that allows fetal blood to pass directly from the pulmonary artery to the

proximal descending aorta (bypassing the pulmonary circulation) This vessel usually closes shortly after birth, secondary to decreased prostaglandin E2 (PGE2) levels and increased oxygen concentration.

Sixth aortic arch forms which adult derivative?

proximal pulmonary arteries on left, ductus arteriosus

Regardless of the patient's hydration status, the majority of water reabsorption in the nephron occurs in the

proximal tubule passively with the reabsorption of solutes.

Atopic dermatitis (eczema) is a common, chronic inflammatory disorder caused by impairment of the skin's barrier function. Eczema presents with

pruritus and erythematous papules and plaques and is associated with other atopic diseases, such as allergic rhinitis and asthma.

Muscles used when sitting up from the supine position include the external abdominal obliques, the rectus abdominis, and the hip flexors. The iliopsoas muscle is the most important of the hip flexors and includes the

psoas major, psoas minor, and iliacus. The rectus femoris, sartorius, tensor fascia lata, and the medial compartment of the thigh also contribute to hip flexion.

The middle meningeal artery is a branch of the maxillary artery, which enters the skull at the foramen spinosum and courses intracranially deep to the

pterion (where the frontal, parietal, temporal, and sphenoid bones meet). Skull fractures at this site may cause laceration of this vessel, leading to an epidural hematoma.

Acute respiratory distress syndrome is characterized by hypoxia and bilateral pulmonary infiltrates and is associated with pneumonia, sepsis, trauma, and pancreatitis. The associated

pulmonary edema is noncardiogenic in nature, so the pulmonary capillary wedge pressure will be within the normal range (6-12 mm Hg).

Congenital diaphragmatic hernia (herniation of abdominal contents into the thorax) causes

pulmonary hypoplasia from compression of the lungs X-ray findings include thoracic bowel loops; the distal end of a feeding tube may also be seen within the thorax.

Tetralogy of Fallot (TOF) is a cyanotic, congenital heart defect characterized by

pulmonary stenosis, an overriding aorta, right ventricular hypertrophy, and a ventricular septal defect

Isoniazid is structurally similar to

pyridoxine (vitamin B6) this antibiotic increases the urinary excretion of pyridoxine - often causing a frank deficiency of vitamin B6 — and competes for vitamin B6-binding sites, leading to the defective synthesis of neurotransmitters like GABA. Isoniazid-induced neuropathy can usually be prevented with pyridoxine supplementation

Sickle cell disease is the result of a missense mutation that causes valine to replace glutamic acid at position 6 in the hemoglobin beta-globin chain. RNA contains the

pyrimidine base uracil, whereas DNA contains the base thymidine.

In the presence of oxygen, pyruvate produced during glycolysis is converted by pyruvate dehydrogenase to acetyl coenzyme A, which is subsequently metabolized by oxidative phosphorylation. However, if inadequate oxygen is present in the tissues,

pyruvate is converted to lactate by lactate dehydrogenase, leading to lactic acidosis.

Biotin acts as a CO2 carrier on the surface of carboxylase enzymes and is an essential cofactor for numerous reactions, including the conversion of

pyruvate to oxaloacetate and fatty acid metabolism. Excess ingestion of avidin, found in egg whites, has been associated with biotin deficiency. This condition presents with mental status changes, myalgias, anorexia, macular dermatitis, and lactic acidosis.

Findings of a femoral nerve mononeuropathy include:

quadriceps weakness, decreased patellar reflex, and sensory loss over the anterior and medial thigh and medial leg

Osmotic demyelination syndrome results from overly rapid correction of chronic hyponatremia. Clinical features include

quadriplegia, pseudobulbar palsy, and reduced level of consciousness. MRI demonstrates focal demyelination of the pons.

Long-acting insulin analogs (eg, degludec, detemir, glargine) have an extended duration of action without a noticeable peak in activity and are typically given once daily to mimic basal insulin secretion. Rapid-acting insulins (eg, aspart, lispro, glulisine) are

quickly absorbed from the injection site and are given at mealtimes to replicate postprandial insulin secretion.

Langerhans cells are dendritic cells found in the skin that act as professional antigen presenting cells. These cells are derived from the myeloid cell line and they possess characteristic

racquet-shaped intracytoplasmic granules known as Birbeck granules.

The pelvic splanchnic nerves (S2-S4) provide parasympathetic innervation to the bowel and bladder, and their impairment in cauda equina syndrome can cause constipation and difficulty urinating. Other signs of cauda equina syndrome include

radicular low back pain and leg weakness (sciatic nerve) as well as saddle anesthesia (pudendal, ilioinguinal nerves).

Group A streptococcus (GAS) should be suspected in those with acute-onset sore throat, exudative tonsillopharyngitis, and no evidence of viral symptoms (eg, coryza, cough, conjunctivitis). In-office throat swab with

rapid antigen detection testing (immunoassay for GAS antigens) can provide on-site microbiologic confirmation, allowing for early initiation of treatment.

An S3 typically results from

rapid cessation of diastolic filling into an enlarged ventricle It is usually associated with heart failure such as occurs with dilated cardiomyopathy, severe mitral regurgitation, or severe aortic regurgitation. A right-sided S3 can occur with right-sided heart failure.

Propofol and other highly lipophilic drugs readily diffuse across membranes, quickly accumulating in tissues receiving high blood flow; this accounts for their

rapid onset of action. These compounds are subsequently redistributed to organs receiving less blood flow, which explains their short duration of action.

Cluster headaches often present with

rapid-onset, severe, unilateral pain accompanied by ipsilateral autonomic symptoms (eg, ptosis, miosis, nasal congestion, conjunctival injection).

Ionizing radiation induces DNA damage (eg, double-strand breakage, free radical generation) that predominantly affects highly proliferative cells (eg, skin stem cells, hematogenous progenitors, intestinal crypt cells). These

rapidly dividing cells are the first to be lost following significant radiation exposure, resulting in hair loss, pancytopenia, diarrhea, and nausea/vomiting.

Struma ovarii is an ovarian germ cell tumor composed of >50% mature thyroid tissue that can secrete thyroid hormone. Therefore, struma ovarii can be a

rare cause of thyrotoxicosis (eg, weight loss, irregular menses, low TSH level).

Lamotrigine can be used to treat partial and generalized seizures and works by blocking voltage-gated sodium channels. Stevens-Johnson syndrome and toxic epidermal necrolysis are

rare, life-threatening adverse effects characterized by flu-like symptoms followed by widespread mucocutaneous epidermal necrosis.

Glucose-6-phosphate dehydrogenase is the

rate-limiting enzyme in the pentose phosphate pathway, the major source of cellular NADPH. This molecule is necessary for reducing glutathione (protects red blood cells from oxidative damage) and for the biosynthesis of cholesterol, fatty acids, and steroids.

Isoniazid inhibits pyridoxine phosphokinase, leading to impaired activation of pyridoxine (vitamin B6). Pyridoxine is a cofactor for δ-aminolevulinic acid synthase, the enzyme that catalyzes the

rate-limiting step of heme synthesis. Inhibition of this step can result in sideroblastic anemia.

The concentrations of creatinine and urea increase as fluid runs along the proximal tubule, whereas the concentrations of bicarbonate, glucose, and amino acids decrease. Sodium and potassium are

reabsorbed with water in the proximal tubule, resulting in no concentration change.

Reactive (atypical) lymphocytes are activated, pathogen-specific cytotoxic T cells or natural killer cells that form in response to certain intracellular infections. In contrast to normal lymphocytes,

reactive lymphocytes are large, scalloped, and have abundant cytoplasm. Reactive lymphocytosis is a diagnostic feature of infectious mononucleosis.

Symptomatic management of peripheral artery disease (PAD) includes a graded exercise program and cilostazol. Cilostazol is a phosphodiesterase inhibitor that inhibits platelet aggregation and acts as a direct arterial vasodilator. Patients with PAD should also

receive an antiplatelet agent (aspirin or clopidogrel) for secondary prevention of coronary heart disease and stroke.

Tolerance to alpha-adrenergic decongestants develops quickly due to

receptor internalization can also be seen with beta-adrenergic (bronchodilators) agonists

The HLA genes encode MHC molecules that are expressed on the cell surface and are key to:

recognition of cells as self or non-self by the immune system

An essential step in the activation of the cellular immune response to a virus is the breakdown of intracellular viral proteins by the ubiquitin proteasome pathway. This pathway is initiated by ubiquitin ligases, which

recognize specific protein substrates and attach a ubiquitin tag. The target proteins are then degraded by a proteasome into peptide fragments, which are coupled with major histocompatibility complex class I proteins and presented on the cell surface for surveillance by cytotoxic CD8+ lymphocytes.

In the United States, bats are the main source of rabies (only transmitted by mammals). Agitation and spasms progressing to coma within weeks of exposure is strongly suggestive of rabies encephalitis. Prophylactic vaccination is

recommended for individuals at high risk for exposure to rabid animals or their tissues. The approved rabies vaccines consist of various rhabdovirus strains grown in tissue cell culture and then inactivated.

Individuals on a vegan diet are at increased risk for deficiencies in calcium and vitamin D. Supplementation is

recommended to avoid long term consequences, including osteoporosis and bone fractures. Cobalamin (vitamin B12) deficiency can also occur.

The rectus femoris, iliopsoas, and sartorius are the major hip flexors. Of these, only the

rectus femoris and sartorius also affect knee movement. The sartorius flexes the knee while the rectus femoris extends the knee.

Obstructive sleep apnea, the most common sleep-related breathing disorder, is characterized by

recurrent obstruction of the upper airways. Relaxation of the oropharyngeal and/or soft palate musculature during sleep results in a functional collapse of the airway, producing periods of reduced (hypopnea) or absent (apnea) airflow despite continued breathing efforts.

The primary goal of medical therapy for acute aortic dissection is to

reduce aortic wall shear stress by minimizing the change in aortic blood pressure per time (dP/dt). Esmolol, a selective beta-1 receptor blocker, decreases left ventricular contraction velocity and heart rate to reduce dP/dt.

Mannitol is an osmotic diuretic that works by increasing plasma or tubular fluid osmolality. Increased plasma and fluid osmolality causes extraction of water from the interstitial space into the vascular space or tubular lumen, with subsequent diuresis. In the brain, water redistribution from the tissues into the plasma helps

reduce edema and intracranial pressure in the setting of cerebral edema. One of the more severe toxicities of aggressive osmotic diuretics is pulmonary edema.

The lamellar bodies of type II pneumocytes store and release pulmonary surfactant into the fluid layer lining the inner surfaces of alveoli. The major function of surfactant is to

reduce surface tension in this fluid layer, and so a surfactant deficiency can cause alveolar atelectasis, as seen in neonatal respiratory distress syndrome.

Systemic corticosteroids (eg, oral prednisone) are used in short courses to treat acute asthma exacerbations, whereas inhaled corticosteroids (eg, fluticasone)

reduce the frequency and severity of exacerbations and are used for long-term asthma control in patients with persistent symptoms. Suppression of airway inflammation is evident within hours of administration but reaches maximal effect after several months of inhaled therapy. Nonadherence to long-term therapy can increase the risk of life-threatening asthma exacerbation.

Phosphodiesterase-4 inhibitors (ie, roflumilast) block the degradation of cyclic AMP, leading to

reduced airway inflammation and smooth muscle relaxation in patients with chronic obstructive pulmonary disease

Direct factor Xa inhibitors (eg, apixaban) are anticoagulants that block the active site of factor Xa, which leads to

reduced conversion of prothrombin to thrombin. This class of medications is administered orally and requires no drug level monitoring.

Survivors of acute respiratory distress syndrome commonly have reduced lung function that persists for months or years and is sometimes permanent. The majority of patients have

reduced diffusion capacity that eventually normalizes after several years, whereas a small percentage develop extensive fibrosis with a marked and permanent reduction in diffusion capacity.

Folinic acid (leucovorin) can reverse the toxicity of methotrexate in non-cancerous cells in the gastrointestinal mucosa and bone marrow if administered at the appropriate time. Leucovorin serves as a

reduced form of folic acid that does not require the action of dihydrofolate reductase.

Digoxin is a cardiac glycoside that is predominantly cleared by the kidneys. Elderly patients typically exhibit age-related renal insufficiency, even in the presence of normal creatinine levels. The dose of digoxin must be

reduced in these patients to prevent toxicity.

Hypovolemic shock results from markedly decreased blood volume, which reduces central venous pressure and cardiac output and leads to increased systemic vascular resistance (peripheral vasoconstriction). Shock causes

reduced organ and tissue perfusion, which leads to lactic acidosis (metabolic acidosis) and a compensatory increase in ventilation (ie, compensatory respiratory alkalosis)

Chronic kidney disease is commonly associated with normocytic anemia due to

reduced production of EPO by the kidneys EPO signal transduction is primarily mediated by the Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT) pathway, which promotes erythrocyte precursor survival

Dilation of the left ventricular cavity commonly occurs in response to systolic dysfunction (eg, ischemic heart disease, dilated cardiomyopathy) or certain types of valvular disease (ie, aortic regurgitation, mitral regurgitation). Chronic volume overload causes progressive eccentric hypertrophy that eventually leads to

reduced ventricular contractility and decompensated heart failure.

After myocardial infarction, transforming growth factor-beta (TGF-β)

reduces inflammation and promotes tissue remodeling due to fibroblast proliferation and collagen deposition, resulting in fibrosis in the area damaged by ischemia. Abnormal myocardium at the scar border can predispose patients to sudden death as a result of arrhythmia.

Mannitol increases plasma osmolality, leading to the flow of water down its concentration gradient from the intracellular space to the plasma, helping to reduce intracranial pressure. The resulting plasma expansion also

reduces serum sodium levels and increases glomerular filtration/tubular flow. Mannitol is freely filtered and not reabsorbed by the renal tubules, resulting in a hyperosmolar glomerular filtrate.

Antiretroviral therapy during pregnancy

reduces the risk of perinatal transmission of HIV to 1%-2% and is recommended for all pregnant women with HIV.

Nitrates are primarily venodilators and increase peripheral venous capacitance, thereby

reducing cardiac preload and left ventricular end-diastolic volume and pressure. Nitrates also have a modest effect on arteriolar dilation and cause a decrease in systemic vascular resistance and cardiac afterload.

Varenicline is a partial agonist of nicotinic acetylcholine receptors. It can assist patients with cessation of tobacco use by

reducing withdrawal cravings and attenuating the rewarding effects of nicotine.

Any abdominal process (eg, ruptured spleen, peritonitis, hemoperitoneum) irritating the phrenic nerve sensory fibers around the diaphragm can cause

referred pain to the C3-C5 shoulder region (Kehr sign).

Phenylephrine increases blood pressure via an alpha-1 receptor-mediated increase in inositol triphosphate in vascular smooth muscle cells. The abrupt increase in blood pressure triggers a

reflexive increase in parasympathetic activity while decreasing sympathetic outflow. This leads to decreased cyclic AMP activity in the heart (mediated by beta-1 adrenergic and muscarinic-2 receptors), which decreases heart rate and myocardial contractility. The reduction in heart rate is driven in part by decreased inward calcium current in sinoatrial cells.

Classical conditioning involves a neutral stimulus being repeatedly paired with a non-neutral stimulus that elicits a

reflexive, unconditioned response. Over time, the formerly neutral stimulus is able to evoke a conditioned response by itself in absence of the non-neutral stimulus.

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.

Atrial fibrillation occurs due to irregular, chaotic electrical activity within the atria and presents with absent P waves, irregularly irregular R-R intervals, and narrow QRS complexes. The atrioventricular node refractory period

regulates the number of atrial impulses that reach the ventricle and determines the ventricular contraction rate in conditions where the atria undergo rapid depolarization.

Atrial natriuretic peptide, brain natriuretic peptide, and nitric oxide activate guanylyl cyclase and increase conversion of guanosine 5′-triphosphate to cyclic guanosine 3′,5′-monophosphate (cGMP). Phosphodiesterase inhibitors (eg, sildenafil) decrease the degradation of cGMP. Elevated intracellular cGMP levels lead to

relaxation of vascular smooth muscle and vasodilation.

Large prolactin-secreting pituitary tumors can compress the optic chiasm, causing bitemporal hemianopsia. In addition, elevated prolactin levels suppress

release of GnRH, leading to decreased LH secretion and subsequently impaired testosterone production in men.

Acetazolamide is a diuretic that works by inhibiting carbonic anhydrase, which effectively blocks NaHCO3 and water reabsorption in the proximal tubules resulting in urinary bicarbonate wasting. Carbonic anhydrase inhibitors are also used to

relieve intraocular pressure in open-angle and angle-closure glaucoma

Mitral stenosis usually occurs due to underlying rheumatic heart disease and initially presents with exertional dyspnea. Orthopnea, paroxysmal nocturnal dyspnea, productive cough, and hemoptysis can develop as the disease becomes more advanced. At rest, left ventricular diastolic pressure, afterload, and contractility

remain normal until the mitral stenosis is severe.

snRNPs are an essential component of spliceosomes, which

remove introns from pre-mRNA to form mature mRNA. Patients with systemic lupus erythematosus can have autoantibodies directed against snRNPs (eg, anti-Smith antibody)

All 3 prokaryotic DNA polymerases can

remove mismatched nucleotides via their 3' to 5' exonuclease ("proofreading") activity. Only DNA polymerase I has 5' to 3' exonuclease activity, which is used to remove the RNA primer synthesized by RNA primase.

In prokaryotes, DNA polymerase I has 5' to 3' exonuclease activity in addition to 5' to 3' polymerase and 3' to 5' exonuclease activities. This 5' to 3' exonuclease activity functions to

remove the RNA primer created by RNA primase and repair damaged DNA sequences.

Multiple myeloma is associated with increased bone resorption due to the production of tumor-related cytokines. This results in elevated serum calcium levels, which reduce parathyroid hormone (PTH) production. Low PTH decreases

renal calcium reabsorption (hypercalciuria), and, in combination with renal insufficiency, reduces 1,25-dihydroxyvitamin D synthesis.

Patients undergoing solid organ transplantation are at increased risk of gout due to medications that impair

renal clearance of uric acid. Cyclosporine is particularly associated with gout in the post-transplantation period due to decreased uric acid excretion.

Normal aging results in multiple physiologic and structural alterations that lead to a slow decline in renal function. These include reductions in

renal mass and functional glomeruli (ie, reduced glomerular filtration rate and creatinine clearance), decreased renal blood flow, and limited hormonal responsiveness (eg, renin, parathyroid hormone). Additional Information Pathophysiology Subject Renal, Urinary Systems & Electrolytes System Aging

Acute tubular necrosis is caused by renal ischemia and is characterized by oliguria, increased serum creatinine, and muddy brown casts. Ischemic injury predominantly affects the

renal medulla, which has a relatively low blood supply. The terminal (straight) portion of the proximal tubules and the thick ascending limb of the loop of Henle are the most commonly involved portions of the nephron due to their high metabolic rate and location within the medulla.

In the absence of other findings, what should be considered as a cause of bleeding from the upper urinary tract?

renal papillary necrosis It is characterized by infarction of the renal medullary vessels, leading to sloughing of the renal papillae and gross hematuria.

Nonanion gap metabolic acidosis (NAGMA) results from the loss of bicarbonate (HCO3−) (usually from the kidneys or gastrointestinal tract), leading to a relative increase in H+. Common causes include

renal tubular acidosis and severe diarrhea. NAGMA is also referred to as hyperchloremic acidosis because the decrease in serum HCO3− is compensated for by an increase in serum chloride to maintain electronegative balance.

Beta-adrenergic blocking drugs inhibit

renin release by blocking beta-1 receptor-mediated regulation of the renin-angiotensin-aldosterone system. This reduces plasma renin activity, with a resulting reduction in angiotensin I, angiotensin II, and aldosterone levels.

Renal artery stenosis causing significant renal hypoperfusion will result in a decreased glomerular filtration rate and activation of the renin-angiotensin-aldosterone system. This leads to increased

renin release by modified smooth muscle (juxtaglomerular) cells in the walls of afferent glomerular arterioles. Chronic renal hypoperfusion can cause hyperplasia of the juxtaglomerular apparatus.

Wiskott-Aldrich syndrome is characterized by the triad of eczema, thrombocytopenia, and combined B and T cell deficiency. Patients can have thrombocytopenia at birth, with eczema and

repeated infections due to encapsulated and/or opportunistic organisms usually developing later around 6 to 12 months of age.

A Mallory-Weiss tear is a tear in the gastric mucosa near the gastroesophageal junction. It typically results from

repetitive forceful vomiting, which can also cause metabolic alkalosis

Idiopathic pulmonary fibrosis is an interstitial lung disease characterized by chronic progressive dyspnea, nonproductive cough, inspiratory crackles, and subpleural (peripheral) lung honeycombing. In IPF,

repetitive microinjury to the alveolar epithelium (eg, smoking, acid reflux) is focally repaired by fibroblast proliferation/collagen deposition instead of normal restoration via type 2 pneumocyte differentiation.

Injury to the radial nerve at the supinator muscle may occur due to

repetitive pronation/supination of the forearm, direct trauma, or subluxation of the radius. Patients typically have weakness during finger and thumb extension (ie, finger-drop) without wrist drop or sensory deficits.

Obsessive-compulsive disorder (OCD) is characterized by persistent, intrusive thoughts leading to

repetitive, ritualistic behaviors. Selective serotonin reuptake inhibitors are considered first-line treatment for OCD and exert their effects by inhibiting serotonin reuptake.

Chronic or recurrent glucocorticoid (eg, prednisone) use can lead to loss of bone density. Glucocorticoids inhibit

replication and differentiation of osteoblast precursor cells, increase osteoclast activity, and promote intestinal and renal calcium wasting.

Costosternal syndrome (costochondritis) usually occurs after repetitive activity and is characterized by pain that is

reproducible with palpation and worsened with movement or changes in position.

Naloxone is a short-acting opioid antagonist used for the treatment of opioid overdose (eg, respiratory depression, decreased level of consciousness, miosis, decreased bowel sounds). Naloxone frequently

requires redosing to prevent recurrent overdose symptoms due to its short half-life (<1 hr).

Lead poisoning can cause neurologic, gastrointestinal, renal, and hematologic complications. Although symptoms can be vague, lead poisoning should be suspected if these symptoms arise while

residing in a home built before 1978. Diagnosis is made by measuring the patient's blood lead level.

Low pH (<7.35) with elevated PaCO2 (>40 mm Hg) indicates:

respiratory acidosis Urine bicarb is low as the kidneys increase bicarb reabsorption for metabolic compensation

Haemophilus influenzae is a gram-negative coccobacillus that requires both X factor (hematin) and V factor (NAD+) to grow. Hib has an antiphagocytic polysaccharide capsule, which allows it to

spread hematogenously and cause invasive disease such as septic arthritis and meningitis

An acute ventilation/perfusion mismatch (eg, due to pulmonary embolism or pneumonia) causes hypoxemia and triggers hyperventilation. Because the removal of CO2 is directly dependent on ventilation but the absorption of O2 is capped by the high baseline saturation of hemoglobin, the hyperventilation response typically leads to

respiratory alkalosis (low arterial partial pressure of carbon dioxide) with persistent hypoxemia.

Hyperventilation of pregnancy creates an expected:

respiratory alkalosis (pH >7.45 and pp of CO2 in arterial blood <40 mm Hg) with metabolic compensation (increased renal bicarb excretion)

Acute otitis media usually occurs after a viral upper respiratory infection causes obstruction of the eustachian tube. This obstruction leads to the accumulation of secretions, which encourages bacterial growth. The most common bacterial causes are

respiratory colonizers, including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

Congenital diaphragmatic hernia is caused by failure of the pleuroperitoneal folds to close. Immediately after birth, newborns have

respiratory distress, unilateral decreased breath sounds, and a scaphoid abdomen, with imaging revealing thoracic bowel loops and mediastinal shift.

Emphysema consists of alveolar destruction and enlargement that results from a combination of inflammation and leukocyte infiltration, increased protease activity, and oxidative stress, usually in

response to exposure to cigarette smoke. In severe disease, large air spaces known as subpleural blebs can form in the lung apices.

Programmed-death receptor 1 (PD-1) is a checkpoint inhibitor that downregulates the cytotoxic T-cell response. Neoplastic cells often exploit this receptor via the overexpression of PD-1 ligand. PD-1 receptor inhibitors (eg, Pembrolizumab)

restore the T-cell response, allowing cytotoxic T cells to invade the tumor and induce apoptosis of neoplastic cells.

The fourth heart sound (S4) is a low frequency sound heard at the end of diastole just before S1. It is due to decreased left ventricular compliance and is often associated with

restrictive cardiomyopathy and left ventricular hypertrophy.

Left atrial enlargement can sometimes cause left recurrent laryngeal nerve impingement. Neurapraxia

resulting in left vocal cord paresis and hoarseness may result.

Hemolysis is associated with

reticulocytosis, increased lactate dehydrogenase, decreased haptoglobin, and elevated indirect bilirubin.

In patients with hemolytic anemia, peripheral blood smear usually reveals evidence of

reticulocytosis, spherocytes, and nucleated red blood cells.

A case-control study is an observational study design; it begins with selecting individuals who have the outcome ("cases") and individuals who do not have the outcome ("controls") and then

retrospectively comparing their history of exposure to risk factors.

The inferior vena cava is formed by the union of the right and left common iliac veins at the level of L4-L5. The renal arteries and veins lie at the level of L1. The inferior vena cava

returns venous blood to the heart from the lower extremities, portal system, and abdominal and pelvic viscera.

What can be seen on a Tzanck smear for HSV?

reveal the characteristic cytopathic effects of the virus, including multinucleated giant cells, ground-glass opacities, acantholytic cells, keratinocyte ballooning, and nuclear molding.

The hepatitis B virus (HBV) replicates via the following sequence: double-stranded DNA → +RNA template → partially double-stranded DNA progeny. Although it is a DNA virus, HBV uses

reverse transcription to generate new viral DNA from a positive-sense RNA template.

Hydroxyurea increases fetal hemoglobin production, which reduces erythrocyte sickling in patients with sickle cell disease. It also inhibits

ribonucleoside reductase, which decreases deoxynucleoside triphosphates available for DNA synthesis; this leads to macrocytosis and, with high doses, pancytopenia.

Releasing factors recognize stop codons (UAA, UAG, UGA) and terminate protein synthesis. They facilitate release of the polypeptide chain from the

ribosome and dissolution of the ribosome-mRNA complex

The nucleolus is a dense intranuclear body visible by light and electron microscopy that functions as the primary site of

ribosome synthesis and assembly. All ribosomal RNA except 5S rRNA is transcribed in the nucleolus.

Structural alteration of enzymes involved in RNA synthesis (DNA-dependent RNA polymerase) is the mechanism through which organisms become resistant to

rifampin.

Acute hepatitis B infection can cause a serum sickness-like syndrome with joint pain, lymphadenopathy, and a pruritic urticarial rash. Other features may include​​​​​​​

right upper quadrant pain, hepatomegaly, and elevated hepatic transaminase levels.

A ventricular septal defect, classically characterized by a harsh, holosystolic murmur at the left lower sternal border, causes left-to-right shunting of oxygenated blood from the left ventricle to the right ventricle. Therefore,

right ventricular oxygen saturation is increased compared to normal.

Staphylococcus aureus causes acute bacterial endocarditis with rapid onset of symptoms, including shaking chills (rigors), high fever, dyspnea on exertion, and malaise. In intravenous drug users, it can cause

right-sided endocarditis with septic embolization into the lungs.

Candida albicans can cause a variety of sx in immunosuppressed patients, like

right-sided endocarditis, renal abscesses, and esophagitis budding yeast and pseudo hyphae are seen on light microscopy

Patients who inject drugs are at high risk for infective endocarditis (IE) due to the concurrent injection of abrasive particulate material and microorganisms. Most cases arise on the tricuspid valve. Patients with tricuspid valve IE often present with

right-sided heart failure or septic pulmonary emboli. Echocardiography generally reveals valvular vegetations and incomplete valve closure (regurgitation).

Bubonic plague is a zoonotic infection that causes febrile illness with regional inflammatory lymphadenopathy (buboes). The underlying pathogen is Yersinia pestis, a gram-negative coccobacillus that exhibits bipolar staining (resembling a closed safety pin). The major environmental reservoir is

rodents, and transmission usually occurs via rodent flea bite.

Blastomyces dermatitidis is a dimorphic fungus seen in tissue as

round or oval yeasts with thick walls and broad-based budding. It is endemic in the southeastern United States (states east of the Mississippi River). The lungs are the primary site of involvement, and the skin and bone are the major sites of dissemination.

Selective serotonin reuptake inhibitors (SSRIs) have improved tolerability and a better side-effect profile compared with tricyclic antidepressants and monoamine oxidase inhibitors but are associated with sexual dysfunction. Physicians should

routinely inquire about sexual dysfunction because it is a relatively common side effect of SSRIs that may lead to nonadherence.

Female sexual interest/arousal disorder is characterized by lack of, or significantly reduced, sexual interest and/or arousal. Diagnosis requires

ruling out psychological, medical, and substance/medication-related causes and relationship problems.

Deep intraparenchymal hemorrhage is most commonly caused by hypertensive vasculopathy of the small penetrating branches of the cerebral arteries (Charcot-Bouchard aneurysm rupture). This is in contrast to

rupture of saccular aneurysms, which typically cause subarachnoid hemorrhage.

Organophosphates are cholinesterase inhibitors that are widely used as pesticides in agriculture. They inhibit the breakdown of acetylcholine, leading to a state of cholinergic excess. Symptoms of organophosphate poisoning include

salivation, lacrimation, diaphoresis, bradycardia, and bronchospasm

Alkaptonuria is an autosomal-recessive disorder caused by a deficiency of homogentisic acid dioxygenase, an enzyme involved in tyrosine metabolism. Excess homogentisic acid causes diffuse blue-black deposits in connective tissues. Adults have

sclerae and ear cartilage hyperpigmentation along with osteoarthropathy of the spine and large joints.

Testicular torsion presents with acute, severe, progressive unilateral scrotal pain. Classic examination findings include

scrotal edema and discoloration, a high-riding testicle, and an absent cremasteric reflex (ie, absence of testicular elevation when stroking the ipsilateral thigh).

Cromolyn and nedocromil are mast cell-stabilizing agents that inhibit mast cell degranulation independent of the triggering stimulus. They are less effective than inhaled glucocorticoids and are considered

second-line treatments for allergic rhinitis and bronchial asthma.

IL-5

secreted by TH2 cells and promotes the humoral response by stimulating differentiation of B cells and increasing IgA production. It also promotes the growth and differentiation of eosinophils and is implicated in the pathogenesis of many allergic diseases (eg, asthma).

Pernicious anemia is an autoimmune disorder caused by the cell-mediated destruction of parietal cells in the superficial upper glandular layer of the gastric body and fundus. Parietal cells are responsible for the

secretion of hydrochloric acid and intrinsic factor, a glycoprotein involved in the absorption of B12. Deficiency leads to megaloblastic anemia and neurologic dysfunction.

First-generation antipsychotics can be classified according to high or low potency and have characteristic side effect profiles. Low-potency antipsychotics are more likely to cause

sedation, anticholinergic side effects, and orthostatic hypotension

Polyarteritis nodosa (PAN) is a systemic vasculitis characterized by constitutional manifestations and ischemic symptoms in the kidneys, skin, gastrointestinal tract, and neurologic system. Biopsy will show

segmental, transmural arterial inflammation with fibrinoid necrosis and damage to the internal and external elastic lamina. PAN is often associated with underlying viral hepatitis B and C.

Polyarteritis nodosa is a systemic vasculitis of medium-sized muscular arteries marked by

segmental, transmural, arterial wall inflammation with fibrinoid necrosis. This narrows the arterial lumen and increases risk of thrombosis and tissue ischemia/infarction. Damage to the internal and external elastic laminae also increases the risk of microaneurysm. Tissue damage primarily occurs in the kidneys, gastrointestinal tract, neurologic system, and skin; the lungs are usually spared.

Symptoms of tricyclic antidepressant overdose include

seizures, anticholinergic toxicity, hypotension, and cardiac toxicity (eg, QRS widening, ventricular arrhythmias).

Spironolactone is an aldosterone antagonist commonly used to treat heart failure. It has significant antiandrogenic effects and can cause gynecomastia, decreased libido, and impotence. Eplerenone is a more

selective aldosterone antagonist with fewer adverse effects.

Phenylephrine is a:

selective alpha1 adrenergic receptor agonist that causes a generalized increase in peripheral vascular resistance and blood pressure Use results in significant renal, splanchnic, and mesenteric vasoconstriction

Minimal change disease is caused by immune dysregulation and overproduction of a glomerular permeability factor, which damages podocytes and decreases the anionic properties of the glomerular basement membrane. This results in

selective loss of albumin in the urine, in contrast to the nonselective proteinuria seen in other forms of nephrotic syndrome.

Antibody-drug conjugates improve 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).

Chikungunya is an alphavirus spread by mosquitos to humans in tropical and subtropical areas. Initial manifestations include

self-limited fever, severe polyarthralgia, and rash. Relapsed or chronic arthralgias, polyarthritis (eg, wrist, fingers, ankles), or tenosynovitis occur in >50% of infected individuals.

Topical capsaicin causes defunctionalization of afferent pain fibers and depletion of

substance P. Initial application results in a burning and stinging sensation, but chronic exposure leads to reduced pain transmission.

The ventral posterior lateral nucleus (receives input from the spinothalamic tract and dorsal columns) and ventral posterior medial nucleus (receives input from the trigeminal pathway) of the thalamus

send somatosensory projections to the cortex via thalamocortical fibers. Damage to these nuclei results in complete contralateral sensory loss.

Diabetic autonomic neuropathy 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.

Epstein-Barr virus (EBV) commonly infects B cells, stimulating them to proliferate continuously ("transformation" or "immortalization"). EBV is an oncogenic virus that promotes polyclonal B cell proliferation and heterophile antibody production. The heterophile antibody test is

sensitive and highly specific for EBV infection.

The Romberg test is a test of proprioception in which patients are observed for unsteadiness as they stand with their feet close together, arms to the sides, and eyes closed. Failure to maintain this posture indicates

sensory ataxia, which may be caused by defects in the posterior column or peripheral nerves (eg, tabes dorsalis, vitamin B12 deficiency).

Spinal nerves in the lumbosacral spine exit through the neural foramina that is below the corresponding vertebral body level (eg, L5 nerve root exits between L5 and S1 vertebral bodies) and can be compressed at the neural foramina due to osteophyte formation. In addition to back pain, L5 radiculopathy often presents with

sensory loss over the lateral thigh, calf, and dorsal foot and weakness of great toe extension and foot dorsiflexion, inversion, and eversion.

Von Hippel-Lindau (VHL) disease is an autosomal dominant condition caused by a mutation in a tumor suppressor gene, which is associated with the development of pheochromocytomas, retinal and cerebellar hemangioblastomas, and renal cell carcinomas. Because of the potential for

serious complications from these tumors, patients with VHL should receive annual surveillance, including plasma metanephrines, abdominal imaging, ophthalmologic examination, and MRI of the brain and spine.

Synovitis is characterized by pain, erythema, swelling, and reduced range of motion in a joint. Acute synovitis may represent

serious pathology (eg, septic arthritis), especially if accompanied by fever or leukocytosis; it should be evaluated urgently with synovial fluid analysis.

The classic triad of reactive arthritis is nongonococcal urethritis, conjunctivitis, and arthritis. It is an HLA-B27-associated arthropathy that occurs within several weeks following a genitourinary or enteric infection. It belongs to the group of

seronegative spondyloarthropathies (including ankylosing spondylitis) and can cause sacroiliitis in about 20% of cases.

Chemotherapy-induced nausea and vomiting is mediated by peripheral and central mechanisms. It can be treated with

serotonin receptor antagonists (eg, ondansetron) to prevent serotonin stimulation of afferent vagal fibers in the bowel wall (peripheral cause) and neurokinin-1 receptor antagonists (eg, aprepitant) to prevent the effects of substance P in the brainstem (central cause).

The long thoracic nerve innervates the:

serratus anterior and damage results in scapular winging and weakness in arm abduction above the horizontal level

The treatment of choice for diabetic ketoacidosis is intravenous normal saline and insulin. These therapies increase

serum bicarbonate and sodium and decrease serum glucose, osmolality, and potassium.

Patients with osteoporosis have low bone mass, resulting in increased susceptibility to fragility fractures (ie, those occurring with minimal or no trauma). In primary osteoporosis (not caused by a medical disorder),

serum calcium, phosphorus, and parathyroid hormone levels are typically normal.

Defects in T-cell IL-2 receptors can cause:

severe combined immunodeficiency disease (SCID)

Zika virus is a single-stranded RNA virus that infects fetal neural progenitor cells, causing

severe congenital malformations (eg, microcephaly, arthrogryposis), cerebral cortical thinning, and possible fetal demise.

monoclonal antibodies directed at interleukin-5 (eg, reslizumab) inhibit eosinophil recruitment and proliferation, and are used in patients with

severe eosinophilic asthma Histologic findings in asthma include goblet cell hyperplasia, bronchial smooth muscle hypertrophy, edema, eosinophilia, and Charcot-Leyden crystals

Stress hyperglycemia is transiently elevated blood glucose levels in the context of

severe illness (eg, sepsis, burns, major hemorrhage) in patients without preexisting diabetes mellitus. Cortisol and catecholamines released in response to severe metabolic stress act on the liver to increase glycogenolysis and gluconeogenesis.

Neuroleptic malignant syndrome (NMS) is an adverse reaction to antipsychotic medication characterized by severe "lead-pipe" rigidity, hyperthermia, sympathetic hyperactivity, and mental status changes. NMS is characterized by

severe rigidity rather than the neuromuscular irritability (eg, hyperreflexia, myoclonus) seen in serotonin syndrome.

X-linked agammaglobulinemia, an immunodeficiency characterized by low circulating B lymphocytes and immunoglobulins, should be suspected in an infant with

severe, life-threatening enteroviral infection.

Epididymitis presents with acute testicular pain, tenderness, and pyuria. It is caused by retrograde passage of organisms from the urethra into the ejaculatory duct and vas deferens. The microbiology is largely influenced by patient age: epididymitis in young men is usually due to

sexually acquired infections (eg, Chlamydia trachomatis, Neisseria gonorrhoeae), whereas in older men (age >35) it is usually due to gram-negative colonic flora.

Renal infarctions are most commonly caused by cardioembolic disease; atrial fibrillation is the greatest risk factor. Clinical features include flank pain, nausea, vomiting, low-grade fever, and hypertension (due to renin release from hypoxic tissue). Gross pathology demonstrates

sharply demarcated, yellow-white, wedge-shaped areas with surrounding hyperemia.

Primase is a DNA-dependent RNA polymerase that incorporates

short RNA primers into replicating DNA.

Supraventricular tachycardia is characterized by an elevated heart rate with a regular rhythm and narrow QRS complexes due to an abnormal electrical impulse originating above the ventricles. Sustained tachycardia

shortens ventricular diastole, leading to decreased stroke volume and cardiac output and subsequent hypotension.

The rotator cuff muscles (supraspinatus, infraspinatus, teres minor, and subscapularis) all insert onto the humeral head, allowing them to stabilize the shoulder joint and move the arm at the shoulder. An infraspinatus injury would result in

shoulder pain and weak, painful external rotation of the arm against resistance

Hypoxia causes vasoconstriction of the pulmonary arterioles, which act to:

shunt blood toward alveoli with the highest ventilation to minimize physiologic dead space providing high-concentration supplemental oxygen allows lung regions with relatively poor ventilation to have higher oxygen levels, reversing pulmonary vasoconstriction The redistribution of blood flow away from the well-ventilated alveoli leads to an increase in physiologic dead space (well-ventilated alveoli are less perfused) with a corresponding reduction in CO2 excretion

Pyruvate dehydrogenase complex deficiency is an inherited inborn error of metabolism causing lactic acidosis and neurologic defects. Patients are unable to convert pyruvate to acetyl-CoA, resulting in a

shunting of pyruvate to lactic acid. In these patients, metabolism of exclusively ketogenic amino acids (eg, lysine, leucine) can provide energy in the form of acetyl-CoA without increasing lactate production.

Renal papillary necrosis classically presents with gross hematuria, acute flank pain, and passage of tissue fragments in urine. It is most commonly seen in patients with

sickle cell disease or trait, diabetes mellitus, analgesic nephropathy, or severe obstructive pyelonephritis.

Renal papillary necrosis is common with

sickle cell nephropathy, analgesic use, obstructive uropathy, diabetes mellitus

Failure of neural tube closure at 4 weeks gestation results in neural tube defects (NTDs). First trimester use of valproate is a

significant risk factor for NTDs, but periconceptional folate (vitamin B9) supplementation reduces this risk.

First generation H1-histamine receptor antagonists, including diphenhydramine and chlorpheniramine, can cause

significant sedation, especially when used with other medications that cause CNS depression (such as benzodiazepines).

Tetracyclines interact with polyvalent cations (eg, iron, calcium, aluminum, magnesium) to form nonabsorbable chelate complexes in the gastrointestinal tract. This can lead to

significantly decreased drug absorption and therapeutic effect. Fluoroquinolones and thyroxine are also susceptible to chelation.

X-linked agammaglobulinemia (XLA) is an immunodeficiency disorder characterized by

significantly reduced mature B cell production

Alveoli are made of what kind of cells?

simple squamous epithelium-facilitates transmembrane exchange of O2 and CO2

Primary ciliary dyskinesia results from an 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.

Warfarin inhibits proteins C and S (natural anticoagulants present in blood), which can lead to

skin necrosis, particularly in patients with protein C or S deficiency. This complication is usually seen in the first few days of warfarin therapy.

Crohn disease is an inflammatory bowel disease characterized by patchy inflammation that can occur throughout the entire gastrointestinal tract. Gross pathology demonstrates

skip lesions, cobblestoning of the mucosa, bowel wall thickening, and creeping fat.

Diastolic blood pressure (DBP) is largely determined by systemic vascular resistance (SVR), and pulse pressure is largely determined by stroke volume. During aerobic exercise, reduced SVR leads to

slightly decreased or unchanged DBP, and increased stroke volume leads to increased pulse pressure and systolic blood pressure.

Buspirone is a nonbenzodiazepine anxiolytic used to treat generalized anxiety disorder. It has a

slow onset of action, lacks muscle relaxant or anticonvulsant properties, and carries no risk of dependence.

Dofetilide and ibutilide are class III antiarrhythmics that treat atrial fibrillation by blocking the rapid component of the delayed-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)

Sleepwalking, a common non-REM parasomnia of childhood, occurs during

slow-wave sleep (stage N3), which is characterized by delta waves on EEG. Sleepwalking typically occurs during the first half of the night, when slow-wave sleep is most prominent.

Sustained-release drug preparations have reduced and delayed peak levels compared to immediate-release preparations due to

slower absorption in the gastrointestinal tract. Dampening of peak levels and prolonged absorption of the drug help maintain effective drug levels while minimizing toxicity.

Glucagon-like peptide-1 (GLP-1) is secreted by intestinal L cells in response to food intake and regulates glucose levels by

slowing gastric emptying, suppressing glucagon secretion, and increasing glucose-dependent insulin release. GLP-1 agonists are parenteral antidiabetic agents that can improve glycemic control with low risk of hypoglycemia. They are also associated with significant weight loss unlike many other antidiabetic agents.

Patients with advanced AIDS can have reactivation of JC virus, which causes progressive multifocal leukoencephalopathy. This condition usually presents with

slowly progressive confusion, ataxia, and motor deficits. Brain MRI reveals multifocal areas of white matter demyelination with no mass effect or enhancement.

Patients with cryptococcal meningitis usually develop

slowly worsening headache, fever, and lethargy Immunocompromised individuals are at greatest risk, particularly those who have AIDS or hematologic cancers or patients on chronic glucocorticoids

Caused by the gram-positive actinomycete Tropheryma whippelii, Whipple disease is a rare systemic illness that involves the small intestine, joints, and central nervous system. Classic histologic findings include

small intestine mucosa containing enlarged, foamy macrophages packed with both rod-shaped bacilli and PAS-positive, diastase-resistant granules.

Scabies is a highly contagious disease that presents with an intensely pruritic rash (usually worse at night) involving the flexor surfaces of the wrist, lateral surfaces and webs of the fingers, elbow extensor surfaces, and axillary folds. Patients usually have excoriations with

small, crusted, red papules scattered around the affected areas. Diagnosis is confirmed by skin scrapings from excoriated lesions that show mites, ova, and feces under light microscopy.

Urothelial (transitional cell) bladder cancer typically affects the elderly and presents with gross hematuria. A history of

smoking or occupational exposure to rubber, plastics, aromatic amine-containing dyes, textiles, or leather increases the risk.

motilin stimulates:

smooth muscle contraction in the upper GI tract and generally increases gastric motility secretion appears to increase during fasting and decreases following meals it is produced primarily in the duodenal mucosa rather than the stomach

Avoidant personality disorder is a maladaptive pattern of behavior characterized by

social inhibition, feelings of inadequacy, and fear of embarrassment and rejection.

The class IA antiarrhythmics (quinidine, procainamide, and disopyramide) are

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.

In patients without CF, CFTR protein serves as a chloride channel that regulates the flow of:

sodium, chloride, and water across the epithelial membranes of the airways, biliary tree, intestines, sweat ducts, and pancreatic ducts

Hyperkalemia is a common adverse effect of trimethoprim-sulfamethoxazole due to the trimethoprim-induced blockade of the sodium channels in the collecting duct, which prevents

sodium-potassium exchange and reduces renal excretion of potassium (similar to the action of amiloride). This effect is often magnified in the elderly population, those with renal failure, or those given other potassium-sparing diuretics, ACE inhibitors, or angiotensin receptor blockers.

A painless, solid scrotal mass should be considered testicular cancer until proven otherwise. Examination generally reveals a

solid, firm, or fixed nodule in the tunica albuginea that is ovoid in shape and painless to palpation. Testicular tumors do not transilluminate.

Arginase is a urea cycle enzyme that produces urea and ornithine from arginine. Arginase deficiency results in progressive

spastic diplegia, growth delay, and abnormal movements. Treatment includes an arginine-free, low-protein diet.

Western blotting is used to identify proteins, Northern blotting identifies specific RNA sequences, and Southern blotting identifies

specific DNA sequences in an unknown sample.

A developmental field defect describes multiple malformations that occur secondary to an embryonic disturbance in an adjoining group of cells. Holoprosencephaly is a developmental field defect characterized by a

spectrum of fetal anomalies due to incomplete division of the forebrain (prosencephalon).

Rett syndrome is a genetic disorder characterized by normal development until age 6-18 months, when regression of

speech, loss of purposeful hand movements, development of stereotypical movements, and gait abnormalities occur. Neuropathology shows arrested brain development rather than neurodegeneration.

In Fabry disease, α-galactosidase A deficiency causes accumulation of the

sphingolipid globotriaosylceramide. The earliest manifestations of Fabry disease are neuropathic pain and angiokeratomas. Glomerular (eg, proteinuria, renal failure), cardiac (eg, left ventricular hypertrophy), and cerebrovascular (eg, transient ischemic attack, stroke) complications develop in adulthood.

Niemann-Pick disease is an autosomal recessive disorder that is common in the Ashkenazi Jewish population. This disorder is characterized by

sphingomyelinase deficiency and sphingomyelin accumulation, which cause hepatosplenomegaly and neurologic regression in infancy

Acute management of variceal hemorrhage requires rapid lowering of portal pressure. Somatostatin and octreotide (a long-acting somatostatin analog) inhibit the release of hormones that induce

splanchnic vasodilation, indirectly causing splanchnic vasoconstriction and reduced portal blood flow.

Howell-Jolly bodies on peripheral smear reflect

splenic dysfunction, which occurs in sickle cell disease due to recurrent infarction of the splenic vasculature. Functional asplenia increases the risk of invasive infection with encapsulated organisms.

Aplastic anemia causes pancytopenia as the bone marrow is replaced by fat cells and marrow stroma. The absence of

splenomegaly on physical examination is characteristic. A bone marrow biopsy can be extremely useful in making the diagnosis.

In vitro fertilization using a donated ovum is the most promising means of achieving pregnancy in a woman with Turner syndrome. Pregnancy can occasionally occur spontaneously in some patients with Turner syndrome, but the risk of

spontaneous abortion, Down syndrome and Turner syndrome are all increased in such cases.

Dysplasia is characterized by disruption of organized epithelial cell differentiation with marked cellular pleomorphism. Although high-grade dysplasia (involving most or the entire epithelial layer) often progresses to invasive cancer, low-grade dysplasia (involving a small portion of epithelium) typically

spontaneously regresses. Invasive cancer occurs when the abnormal cells penetrate the basement membrane.

Clostridium septicum is a

spore-forming, exotoxin-producing, gram-positive organism that is the most common cause of spontaneous gas gangrene (eg, rapid-onset pain, hemorrhagic bullae, tissue crepitus). Underlying colonic malignancy is the greatest risk factor for infection.

Sublingual nitroglycerin is used for rapid symptom relief in patients with

stable angina. The primary anti-ischemic effect of nitrates is mediated by venodilation with a decrease in left ventricular end-diastolic volume and wall stress, resulting in decreased myocardial oxygen demand and relief of angina symptoms.

Reactive arthritis is a spondyloarthropathy associated with HLA-B27 that can occur following infection with Chlamydia, Campylobacter, Salmonella, Shigella, or Yersinia. It presents with

sterile arthritis due to deposition of immune complexes.

Ghrelin is produced in the stomach in response to fasting. Levels surge leading up to meals and fall after eating. Ghrelin acts to:

stimulate appetite and promote weight gain pts who have undergone gastrectomy have reduced ghrelin levels, which leads to weight loss

The pathogenesis of migraines is complex and multifactorial but includes neurogenic inflammation, vasodilation, and sensitization of trigeminal afferents in the meninges. Triptans are serotonin 5-hydroxytryptamine 1B/1D agonists that

stimulate the trigeminovascular serotonin receptors, resulting in inhibition of vasoactive peptide release, intracranial vasoconstriction, and decreased pain. They are used as abortive therapy for acute migraine.

At low doses, dopamine:

stimulates D1 receptors in the renal vasculature and tubules, inducing an increase in renal blood flow, glomerular filtration rate, and sodium excretion Vasodilation of the mesenteric, cerebral, and coronary vascular beds is also prominent at low doses.

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.

Hormone-sensitive lipase is found in adipose tissue, where it functions to drive the breakdown of

stored triglycerides into free fatty acids and glycerol. During times of starvation, this enzyme provides substrates for hepatic gluconeogenesis and ketone body formation.

HPV has a predilection for what kind of cells?

strat. squamous epithelium, found in the anal canal, vagina, and cervix In the resp tract, the true vocal cords are the only area covered with stratified squamous epithelium

Pearson correlation coefficient is a measure of the:

strength and direction of a linear relationship between 2 quantitative (continuous) variables

Correlation analysis is a statistical technique used to assess the

strength and direction of a linear relationship between 2 quantitative variables (often, but not always, a dependent and an independent variable)

The odds ratio is a measure of the

strength of an association between an exposure and an outcome Specifically, it represents the odds that an outcome occurred in the presence of a particular exposure compared with the odds that the outcome occurred in the absence of that exposure OR=ad/bc

A patient with a cocaine-induced MI most likely developed acute hypokalemia due to:

stress-related beta-adrenergic hyperactivity which causes potassium to shift intracellularly

Intravenous fluids increase the intravascular and left ventricular end-diastolic volumes. The increase in preload

stretches the myocardium and increases the end-diastolic sarcomere length, leading to an increase in stroke volume and cardiac output by the Frank-Starling mechanism.

Crohn disease is characterized by patchy, transmural inflammation of the gastrointestinal tract. It can affect any part of the tract from the mouth to the anus. Complications include

strictures (due to bowel wall edema, fibrosis, and thickening of the muscularis mucosae), fistulas (due to penetration of ulcers through the intestinal wall), and abscesses.

The lepromin skin test will be positive in patients with tuberculoid leprosy as they exhibit a

strong CD4+ TH1 cell-mediated immune response to Mycobacterium leprae. Patients with lepromatous leprosy will test negative due to their weak TH1 cell-mediated immune response.

Vascular smooth muscle cells (VSMCs) are the only cells within the atherosclerotic plaque capable of synthesizing

structurally important collagen isoforms and other matrix components. Progressive enlargement of the plaque results in remodeling of the extracellular matrix and VSMC death, promoting development of vulnerable plaques with an increased propensity for rupture.

Myelopathy associated with vitamin B12 deficiency is called

subacute combined degeneration. "Combined" refers to myelin degeneration of both the ascending (dorsal columns) and descending (corticospinal tract) pathways. Loss of position and vibration sensation, sensory ataxia, and spastic paresis are common manifestations.

Tuberculous (TB) meningitis is characterized by formation of a thick, gelatinous exudate in the base of the brain; cerebral vasculitis; and hydrocephalus. It frequently presents with

subacute, slowly progressive nausea, vomiting, fever, cranial nerve deficits, and strokes.

Intracranial berry aneurysms of the circle of Willis are often seen in patients with ADPKD; when ruptured, they cause

subarachnoid hemorrhage that presents with sudden onset of "thunderclap headache".

In the HIV replication cycle, polyprotein precursors are encoded by the structural genes gag, pol, and env. Only the env gene polyprotein product (gp160) is glycosylated. This polyprotein is

subsequently cleaved in the Golgi apparatus to form the envelope glycoproteins gp120 and gp41.

Ascaris lumbricoides is transmitted via contaminated food or water. Eggs hatch into larvae in the small intestine, penetrate the intestinal wall, and migrate across the lung into the alveoli. Larvae are

subsequently coughed up and swallowed into the gastrointestinal tract, where they mature to adult worms. Most patients are asymptomatic, but some develop early pulmonary manifestations (Loeffler syndrome) or later gastrointestinal symptoms.

How does pericarditis typically present?

substernal pleuritic chest pain that may radiate to the bilateral scapulae posteriorly Worse when lying flat and improves with sitting and leaning forward Cardiac auscultation classically reveals a pericardial friction rub-but may be absent in presence of pericardial effusion

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

Most of the cutaneous lymph from the umbilicus down, including the anus below the dentate line, drains to the

superficial inguinal lymph nodes Exceptions are the glans penis and posterior calf, which drain to the deep inguinal nodes.

Normally, metabolic acidosis is partially compensated for by respiratory alkalosis. When the steady-state PaCO2 persists above the range given by the Winter formula (PaCO2 = [1.5 * HCO3−] + 8 ± 2), the patient has a

superimposed respiratory acidosis (respiratory failure).

The venous components of internal hemorrhoids drain into the

superior rectal vein, which communicates with the inferior mesenteric vein

Extrinsic compression of the superior vena cava by a mediastinal mass (eg, malignancy) can cause

superior vena cava syndrome, with impaired venous return from the upper body. Signs and symptoms include facial swelling, distended collateral veins, headache, and dyspnea.

Subacute (granulomatous, de Quervain) thyroiditis presents with fever; a painful, tender goiter; and an elevated erythrocyte sedimentation rate. Patients initially develop hyperthyroidism due to the destruction of thyroid follicles and release of preformed thyroid hormone. TSH is

suppressed due to feedback inhibition on the pituitary; as a result, thyroid metabolic activity and organification of iodine are decreased, and radioactive iodine uptake is low.

Sertoli cells produce inhibin in response to FSH from the anterior pituitary. Inhibin

suppresses FSH production in the pituitary. Sertoli cells also facilitate spermatogenesis within the seminiferous tubules. Impaired Sertoli cell function would lead to decreased production of inhibin, increased FSH levels, and impaired fertility.

Tumor necrosis factor-α is thought to mediate paraneoplastic cachexia in humans by

suppressing appetite and increasing basal metabolic rate

Male-pattern hair growth in a woman is called hirsutism; the most common cause is polycystic ovary syndrome. Combination oral contraceptive pills can treat hirsutism by

suppressing pituitary LH secretion and subsequently decreasing ovarian androgen production.

Lidocaine is a class IB antiarrhythmic drug that tends to bind to inactivated sodium channels and rapidly dissociates. As a result, it is effective in

suppressing ventricular tachyarrhythmias induced by rapidly depolarizing and ischemic myocardium.

In exogenous thyrotoxicosis, radioactive iodine uptake and serum thyroglobulin level are low, indicating

suppression of endogenous thyroid metabolic activity. Serum T3 levels are often elevated.

suprascapular nerve provides sensation to the shoulder joint (glenohumeral and acromioclavicular joints) and motor innervation to the:

supraspinatus and infraspinatus muscles

Intestinal flora produce vitamin K as a byproduct of metabolism. Therefore, antibiotics that target gram-negative bacteria such as metronidazole, macrolides, and fluoroquinolones can cause

supratherapeutic INR due to destruction of vitamin K-producing bacteria in the gut

The rough endoplasmic reticulum (RER) is covered with ribosomes and is involved in the transfer of proteins to the cell membrane and extracellular space. The RER is well developed in protein-secreting cells. The smooth ER lacks

surface ribosomes and functions in lipid synthesis, carbohydrate metabolism, and detoxification of harmful substances.

Horizontal transection of the rectus abdominis muscle must be performed with great caution as the inferior epigastric arteries enter this muscle at the level of the arcuate line. The inferior epigastric arteries below the arcuate line are

susceptible to injury (eg, hematoma) due to lack of a supporting posterior rectus sheath.

Cavernous hemangioma is the most common benign liver tumor. Microscopically, these tumors consist of cavernous, blood-filled vascular spaces of variable size lined by a single epithelial layer. The biopsy of a

suspected hemangioma is not advisable, as the procedure has been known to cause fatal hemorrhage and is of low diagnostic yield.

Type I muscle fibers (slow-twitch or red fibers) primarily use oxidative phosphorylation and contain high quantities of lipids, myoglobin, and mitochondria. They specialize in

sustained, low force contraction, and their function is amplified by endurance training. Type II muscle fibers (fast-twitch or white fibers) primarily use glycolysis and specialize in rapid bursts of high force contraction. Their function is amplified by resistance training.

Thiamine deficiency causes beriberi and Wernicke-Korsakoff syndrome. Dry beriberi is characterized by

symmetrical peripheral neuropathy; wet beriberi includes the addition of high-output congestive heart failure.

The hypothalamus controls thermoregulation by promoting alterations in the autonomic nervous system and the adrenal and thyroid axes. Physiologic adaptations in response to hypothermia include increased

sympathetic activity and thyroid hormone release, shivering, and peripheral vasoconstriction. These actions normalize body temperature by reducing heat loss and increasing metabolic rate (promoting thermogenesis).

A number of ectopic tissues are found in Meckel diverticulum−most commonly, gastric epithelium. Gastric mucosa is present in 80% of cases of

symptomatic Meckel diverticulum. Gastric acid production leads to ulceration and subsequent bleeding.

Critical shortening in telomere length can signal for programmed cell death. Telomerase is a reverse transcriptase (RNA-dependent DNA polymerase) that lengthens telomeres by adding TTAGGG repeats to

the 3' end of chromosomes. Stem cells have long telomeres due to high telomerase activity, allowing them to proliferate indefinitely in a controlled manner.

Wolff-Parkinson-White syndrome is characterized by

symptomatic paroxysmal supraventricular tachycardia (eg, atrioventricular reentrant tachycardia) due to the presence of an accessory conduction pathway. During normal sinus rhythm, the presence of this accessory pathway causes ventricular preexcitation, which can be identified on ECG by the triad of a shortened PR interval, early upslope of the QRS complex (delta wave), and a widened QRS interval.

At high altitude, the low partial pressure of inspired oxygen (PiO2) leads to hypoxemia with consequent hyperventilation and respiratory alkalosis. The hypoxemia and alkalemia can cause

symptoms of altitude sickness (eg, headache, fatigue, lightheadedness). The kidneys respond by creating a compensatory metabolic acidosis and by increasing erythropoietin secretion.

Syncope results from a transient loss of cerebral perfusion, and numerous medications can cause or contribute to syncope. Acetylcholinesterase inhibitors (eg, donepezil, rivastigmine) may cause

syncope due to enhanced parasympathetic tone that leads to bradycardia and atrioventricular block with reduced cardiac output.

Desmopressin is a:

synthetic analogue of ADH that does not induce vasoconstriction This drug induces a rapid and transient increase in vWF and factor VIII by indirectly releasing these compounds from endothelial storage sites

Obstructive sleep apnea is due to relaxation of oropharyngeal muscle tone with occlusion of the upper airway. Symptoms include daytime sleepiness, headaches, and depression. Complications include

systemic and pulmonary hypertension, right heart failure, and an increased risk for cardiac events.

This patient's constellation of symptoms (eg, malar rash, photosensitivity, Raynaud phenomenon ["blue fingers"], fatigue) is consistent with

systemic lupus erythematosus, an autoimmune disease associated with anti-Smith antibodies (highly specific)

Secondary syphilis is often characterized by

systemic sx, lymphadenopathy, grey mucous patches, raised grey genital papules (Condylomata lata), and a diffuse rash involving the palms and soles

An arteriovenous fistula allows blood to shunt from the arterial circulation to the venous circulation, bypassing the high resistance of the systemic arterioles. This leads to reduced

systemic vascular resistance (ie, reduced afterload), increased venous return (ie, increased preload), and increased stroke volume. Left ventricular contractility is unchanged.

In patients with Tetralogy of Fallot, squatting during a Tet spell increases

systemic vascular resistance and decreases right-to-left shunting, thereby increasing pulmonary blood flow and improving oxygenation status

Henoch-Schönlein purpura is an IgA-mediated type III hypersensitivity reaction in children that generally follows infection. Deposition of circulating IgA-containing immune complexes in small vessels results in

systemic vasculitis. Common manifestations include palpable lower-extremity purpura, abdominal pain, arthralgias, and hematuria.

Follicular lymphoma is characterized by aggregates of packed follicles that obscure the normal lymph node architecture. Ninety percent of patients with follicular lymphoma have the

t(14;18) translocation, which causes overexpression of the antiapoptotic BCL-2 protein.

Direct arteriolar vasodilators lower blood pressure but trigger reflex sympathetic activation and stimulate the renin-angiotensin-aldosterone axis. This results in

tachycardia and edema. To counteract such compensatory effects, these agents are often given in combination with sympatholytics and diuretics.

Streptococcus pneumoniae is able to undergo transformation, which allows the bacterium to

take up exogenous DNA fragments and express the encoded proteins. Through this method, strains of S pneumoniae that do not form a capsule can acquire the genes that code for the capsule and therefore gain virulence

Left-sided heart failure leads to chronically elevated pulmonary venous and capillary pressures, with resulting pulmonary edema and extravasation of red blood cells into the alveolar parenchyma. The iron from red blood cells is

taken up by alveolar macrophages and stored as hemosiderin, appearing as brown pigment on histopathology.

Olfactory signals are relayed via the olfactory nerve (CN I) through the cribriform plate to the olfactory bulb, which then projects to the primary olfactory cortex in the medial temporal lobe. Head trauma can

tear olfactory nerve (CNI) rootlets as they cross the cribriform plate, causing anosmia. Anosmia is often interpreted by patients as loss of taste.

Telomerase is an RNA-dependent DNA polymerase that synthesizes

telomeric DNA sequences that can replace the lost chromosomal ends of the telomeres. Cancer cells typically contain increased telomerase activity to allow for continued proliferation.

Restless legs syndrome is characterized by an uncomfortable sensation in the legs accompanied by an urge to move them; symptoms worsen with inactivity and at night and are

temporarily relieved with movement. Dopamine agonists (eg, pramipexole, ropinirole) are the preferred therapy for persistent symptoms.

Temporomandibular joint disorder is associated with derangement of the

temporomandibular joint and hypersensitivity of the mandibular nerve (CN V3)

The SRY gene on the Y chromosome codes for the testes-determining factor, which differentiates the primitive gonads into testes. Sertoli cells produce anti-Müllerian hormone, which causes regression of the Müllerian ducts and suppresses female internal reproductive organ development. Leydig cells produce

testosterone, differentiating Wolffian ducts into internal male reproductive organs. Dihydrotestosterone is required for differentiation of the external male genitalia.

Pufferfish poisoning is caused by

tetrodotoxin, a neurotoxin produced by microorganisms associated with the fish. Tetrodotoxin binds to voltage-gated sodium channels in nerve and cardiac tissue, preventing sodium influx and depolarization

The posterior cerebral artery branches off the basilar artery and supplies cranial nerves III and IV and other structures in the midbrain. It also supplies the

thalamus, medial temporal lobe, splenium of the corpus callosum, and occipital lobe. The most common finding with posterior cerebral artery stroke is contralateral homonymous hemianopia, often with macular sparing.

The number needed to harm (NNH) represents the number of people who must be treated before 1 additional adverse event occurs. In order to calculate NNH,

the absolute risk increase between the treatment and control groups must be known: NNH = 1 / Absolute risk increase

Germline mosaicism affects the cells that give rise to gametes, allowing:

the affected genes to pass to the offspring the chance of a child being affected depends on the proportion of gametes that carry the mutation affected parent does not develop clinical manifestations if mosaicism is limited to the germline

Kinesin is a microtubule-associated motor protein that functions in

the anterograde transport of materials and organelles within cells

Traumatic aortic rupture is most often caused by the rapid deceleration that occurs in motor vehicle collisions. The most common site of injury is

the aortic isthmus, which is tethered by the ligamentum arteriosum and is relatively fixed and immobile compared to the adjacent descending aorta.

Left ventricular leads in biventricular pacemakers course through the coronary sinus, which resides in

the atrioventricular groove on the posterior aspect of the heart.

Wallerian degeneration refers to the process of axonal degeneration and breakdown of the myelin sheath that occurs distal to a site of injury. Axonal regeneration does not occur in

the central nervous system due to the persistence of myelin debris, secretion of neuronal inhibitory factors, and development of dense glial scarring.

Subacute sclerosing panencephalitis is a rare complication of measles infection that occurs several years after apparent recovery from initial infection. Oligoclonal bands of measles virus antibodies are found in

the cerebrospinal fluid of these patients.

The phase 4 slow depolarization in cardiac pacemaker cells occurs due to

the closure of repolarizing K+ channels, the slow influx of Na+ through funny channels, and the opening of T-type Ca2+ channels

Human placental lactogen increases maternal insulin resistance during the second and third trimesters, leading to a rise in serum glucose that helps provide adequate nutrition to the growing fetus. Gestational diabetes occurs when

the compensatory rise in maternal insulin secretion is inadequate to prevent serum glucose levels from reaching excessively high levels.

In unilateral renal artery stenosis, the narrowed renal artery causes hypoperfusion of the affected kidney with subsequent ischemic damage (eg, tubular atrophy, interstitial ischemia, glomerular crowding). In contrast,

the contralateral kidney is exposed to high blood pressure and typically shows changes of hypertensive nephrosclerosis (eg, arteriolar wall thickening due to hyaline or hyperplastic arteriolosclerosis).

A single 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.

Cholecystokinin (CCK) is the hormone responsible for gallbladder contraction. It is made in

the duodenum and jejunum in response to fatty acids and amino acids.

An increased number of trinucleotide repeats on the HTT gene is associated with Huntington disease. The larger the number of repeats,

the earlier the onset of the disease. Trinucleotide expansion occurs more frequently during paternal transmission, causing a genetic phenomenon called anticipation.

Heparin is commonly used for the prevention of deep venous thrombosis in nonambulatory patients or those undergoing elective surgery, especially hip and knee surgery. Heparin increases

the effect of the naturally occurring anticoagulant antithrombin III.

The pupillary light reflex is assessed by shining light in an eye and observing the response in that eye (direct) and the opposite eye (consensual). The optic nerve (CN II) is responsible for the afferent limb of the pupillary reflex, and the oculomotor nerve (CN III) is responsible for

the efferent limb.

Hyperacusis (increased sensitivity to sound) is an indication of damage to

the facial nerve (CN VII) close to its origin from the brainstem.

The great saphenous vein is a superficial vein of the leg that originates on the medial side of the foot, courses anterior to the medial malleolus, and then travels up the medial aspect of the leg and thigh. It drains into

the femoral vein within the region of the femoral triangle, a few centimeters inferolateral to the pubic tubercle.

Ulnar nerve injury most commonly occurs at the elbow (eg, compression due to resting arm on a hard surface while using a computer) and usually presents with discomfort and sensory loss/paresthesia in

the fifth digit, medial half of the fourth digit, and the hypothenar eminence. In severe cases, patients can also have weakness on wrist flexion and adduction (ie, ulnar deviation) along with finger weakness/clumsiness.

Hepatitis E virus is an unenveloped, single-stranded RNA virus spread through the fecal-oral route. The most concerning feature of hepatitis E infection is

the high mortality rate observed in infected pregnant women.

The optimal location for needle insertion during a lumbar puncture is the L3/L4 or L4/L5 space as this is well below the spinal cord termination site (L1 in adults). The L4 vertebral body lies on a line drawn between

the highest points of the iliac crests.

Hepatitis B virus does not have a cytotoxic effect itself; however, the presence of viral HBsAg and HBcAg on the cell surface stimulate

the host's cytotoxic CD8+ T lymphocytes to destroy infected hepatocytes.

Babesiosis should be considered in patients with febrile illness who reside in geographic areas where they are exposed to Ixodes ticks. Diagnosis can be established with

the identification of intraerythrocytic organisms on peripheral blood smear.

Prolactin production is regulated primarily by inhibitory effects of hypothalamic dopaminergic pathways. However, prolactin secretion is stimulated by thyrotropin-releasing hormone (TRH). In patients with primary hypothyroidism,

the increased production of TRH by the hypothalamus can lead to hyperprolactinemia.

In cystic fibrosis, impairment of the cystic fibrosis transmembrane conductance regulator (CFTR) protein reduces chloride secretion and increases sodium absorption by the respiratory epithelia, resulting in dehydrated mucus. When saline is applied to the nasal mucosa,

the increased sodium absorption in patients with CF causes a more negative nasal transepithelial potential difference, which can be used to diagnose cystic fibrosis.

Methotrexate is a folic acid antagonist used to treat ectopic pregnancy. It competitively inhibits the enzyme dihydrofolate (DHF) reductase, which catalyzes the synthesis of tetrahydrofolate. DHF reductase inhibition causes

the intermediate DHF to accumulate intracellularly.

In patients with malignant hyperthermia, exposure to certain anesthetic agents (eg, succinylcholine, inhalational gasses) causes unregulated passage of calcium from the sarcoplasmic reticulum into

the intracellular space. This results in sustained muscle contraction that leads to hypercarbia, hyperthermia, and acidosis.

Rheumatoid arthritis is characterized by synovial hyperplasia with inflammatory infiltrates. The accelerated metabolic rate of the inflamed synovium causes local hypoxia, which leads to synovial angiogenesis. As the disease progresses,

the joint space is replaced by a rheumatoid pannus (an invasive mass of fibroblast-like synovial cells, granulation tissue, and inflammatory cells) which can destroy the articular cartilage and underlying subchondral bone.

The valgus stress test is performed with

the knee extended by placing one hand along the lateral thigh and pressing inward while the other hand is placed on the medial aspect of the ankle and pushed outward Laxity of the knee and/or medial joint line widening indicates MCL injury.

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.

Posterior hip dislocation (ie, femoral head displaced posteriorly from the acetabulum) can occur in motor vehicle collisions in which the knee strikes the dashboard or from falls in elderly patients. On examination,

the leg appears shortened and internally rotated, with the hip held in flexion and adduction. The sciatic nerve is vulnerable to injury in posterior hip dislocation.

Ezetimibe reduces intestinal absorption of cholesterol. As a result, the amount of dietary cholesterol reaching the liver decreases. To compensate,

the liver increases LDL receptor expression, which draws cholesterol out of the circulation.

Staphylococcus aureus is the most common cause of skin and soft-tissue abscess (eg, furuncle). Treatment of the abscess with incision and drainage and antibiotics can eliminate

the local infection but does not eliminate colonization of the anterior nares and skin. Therefore, recurrent infections are common.

Typhoid strains of Salmonella contain a capsular antigen (Vi) that inhibits neutrophil phagocytosis, neutrophil recruitment, and macrophage-mediated destruction. Therefore, typhoid strains are able to undergo extensive replication within the intracellular space of macrophages with subsequent spread through

the lymphatic and reticuloendothelial system, leading to a widespread systemic disease (typhoid fever).

In patients with diabetes, excess glucose in the proximal tubule causes increased reabsorption of sodium by sodium-glucose cotransporter 2 (SGLT2). This leads to decreased delivery of sodium to

the macula densa and increased secretion of renin, ultimately increasing glomerular filtration pressure and causing hyperfiltration. SGLT2 inhibitors increase the delivery of sodium to the macula densa, decreasing renin production and reducing hyperfiltration.

The high systolic intraventricular pressure and wall stress of the left ventricle prevent myocardial perfusion during systole; therefore, the majority of left ventricular myocardial perfusion occurs during diastole. Shorter duration of diastole is

the major limiting factor for coronary blood supply to the left ventricular myocardium during periods of tachycardia (eg, exercise).

Neuroleptic malignant syndrome (NMS) is characterized by severe muscular rigidity, mental status changes, autonomic dysregulation, and hyperthermia. Dopamine antagonism,

the mechanism of action of most antipsychotics, has been implicated as a primary cause of NMS.

Cellular compartmentalization allows multiple biochemical processes to occur simultaneously at maximum efficiency. Beta-oxidation of fatty acids, the TCA cycle, and the carboxylation of pyruvate (gluconeogenesis) all occur within

the mitochondria. The enzymes responsible for glycolysis, fatty acid synthesis, and the pentose phosphate pathway reside in the cytosol.

Recombination refers to gene exchange that occurs through the crossing over of 2 double-stranded DNA molecules. Reassortment describes

the mixing of genome segments in segmented viruses that infect the same host cell.

Deletion or addition of a number of bases that is not divisible by 3 in the coding region of a gene will cause a frameshift mutation. Frameshift mutations alter

the reading frame of the genetic code, resulting in the formation of nonfunctional proteins.

Many frequently encountered diseases (eg, hypertension, spinal bifida) display multifactorial inheritance, which involves the complex interaction of numerous genetic and environmental factors to determine phenotypic expression. Although the exact inheritance risk cannot be determined, the closer a relative is to the affected person,

the more likely the relative is to develop the trait.

minimal change disease

the most common cause of nephrotic syndrome in children

Cirrhosis is characterized by diffuse hepatic fibrosis with replacement of the normal lobular architecture by fibrous-lined parenchymal nodules. Chronic viral hepatitis (eg, hepatitis B and C), alcohol, hemochromatosis, and nonalcoholic fatty liver disease are

the most common causes of cirrhosis in the United States.

Patients with urea cycle disorders typically have discrete episodes of vomiting, tachypnea, and confusion/coma secondary to hyperammonemia (a metabolic emergency). Ornithine transcarbamylase deficiency is

the most common disorder of the urea cycle and is characterized by hyperammonemia and elevated urinary orotic acid.

The Valsalva maneuver increases vagal tone and can be used to abolish paroxysmal supraventricular tachycardia. The rectus abdominis is

the most important muscle in achieving the increased intraabdominal and intrathoracic pressure of the Valsalva maneuver.

Digoxin toxicity presents with nonspecific gastrointestinal (eg, anorexia, nausea, vomiting) and neurologic (eg, fatigue, confusion, weakness) symptoms. Changes in color vision are a more specific, but rarer, finding. Life-threatening ventricular arrhythmias are

the most serious complication.

Diminished relaxation of cricopharyngeal muscles during swallowing results in increased intraluminal pressure in the oropharynx. This may eventually cause

the mucosa to herniate through a zone of muscle weakness in the posterior hypopharynx, forming a Zenker (false) diverticulum, which presents in elderly patients with oropharyngeal dysphagia, halitosis, regurgitation, and recurrent aspiration.

Isoniazid is an antimycobacterial agent that specifically inhibits the synthesis of mycolic acids, which are essential components of the unique mycobacterial peptidoglycan cell wall. Without mycolic acids,

the mycobacteria lose their acid-fastness and become unable to synthesize new cell walls or multiply.

Cystinuria is an autosomal recessive disorder caused by defective transportation of cystine, ornithine, arginine, and lysine across the intestinal and renal tubular epithelium. Recurrent nephrolithiasis is

the only clinical manifestation. Urinalysis shows pathognomonic hexagonal cystine crystals.

In females, the paramesonephric ducts fuse to form the fallopian tubes, uterus, cervix, and upper vagina. Disruptions of this process can lead to a variety of müllerian tract anomalies, and renal anomalies are a common comorbidity. Incomplete lateral fusion of

the paramesonephric ducts results in a bicornuate uterus characterized by an indentation in the center of the fundus.

When pulmonary stenosis is severe, TOF is a ductal-dependent lesion that relies on

the patency of the ductus arteriosus (DA) for adequate oxygenation

Tetralogy of Fallot results from anterior and cephalad deviation of the infundibular septum during embryologic development, resulting in a malaligned ventricular septal defect (VSD) with an overriding aorta. As a result,

the patient has right ventricular outflow obstruction (resulting in a systolic murmur) and squats to increase the peripheral systemic vascular resistance (afterload) and decrease right-to-left shunting across the VSD.

Echinocandins (eg, caspofungin, micafungin) are antifungal medications that inhibit synthesis of

the polysaccharide glucan, an essential component of the fungal cell wall.

Meta-analysis involves:

the pooling of data from several studies to perform an analysis with greater statistical power than the individual studies alone

Most hepatic neoplasms are due to metastatic disease from a distant site. Colorectal cancer is the most common cause of hepatic metastases due to direct blood flow from the colon (and superior rectum) to the liver via

the portal venous circulation.

The posterior cruciate ligament prevents posterior displacement of the tibia relative to the femur when the knee is flexed. It attaches to

the posterior part of the intercondylar area of the tibia and the anterior part of the lateral surface of the medial epicondyle of the femur.

Toxic megacolon is a well-recognized complication of ulcerative colitis. Patients typically present with abdominal pain/distension, bloody diarrhea, fever, and signs of shock. Plain abdominal x-ray is

the preferred diagnostic imaging study. Barium contrast studies and colonoscopy are contraindicated due to the risk of perforation.

The primary immune response to Epstein-Barr virus is mediated by CD8+ T lymphocytes, which are activated through

the presentation of viral antigens on infected CD21+ B lymphocytes. These reactive (atypical) CD8+ T lymphocytes can be observed in the peripheral blood smears of patients with infectious mononucleosis.

The superior mesenteric artery and inferior mesenteric artery are the 2 main vessels supplying the small and large intestines. They are connected by a pair of anastomoses: the marginal artery of Drummond, which is

the principal anastomosis, and the inconsistently present arc of Riolan (mesenteric meandering artery).

Relative risk is the ratio of

the probability of an event (eg, disease outcome) occurring in the exposed group (eg, treatment group) versus the probability of the event occurring in the unexposed group (eg, control group).

Azathioprine is an immunosuppressant that functions via inhibition of purine synthesis by its pharmacologically active 6-thioguanine metabolites. In addition to the desired effect of reduced lymphocyte proliferation,

the proliferation of other hematologic cell lines (eg, neutrophils, erythrocytes, platelets) is reduced, leading to a common adverse effect of pancytopenia.

Superantigens (eg, toxic shock syndrome toxin) interact with major histocompatibility complex molecules on antigen-presenting cells and the variable region of the T lymphocyte receptor to cause nonspecific, widespread activation of T cells. This results in

the release of interleukin (IL)-2 from the T cells and IL-1 and tumor necrosis factor from macrophages. This immune cascade is responsible for the manifestations of toxic shock syndrome.

Traumatic injury to the eye, a site that displays immune privilege, can lead to

the release of previously sequestered antigens that T cells recognize as foreign. This can lead to sight-threatening inflammation in both the injured and uninjured eye.

When a specific ion channel opens, the respective ions will flow across the membrane in a direction that brings

the resting membrane potential closer to that ion's equilibrium potential.

Primary infection with herpes simplex virus type 2 (HSV-2) typically presents with fever and a painful vesicular genital rash. HSV-2 primarily infects

the sacral dorsal root ganglia and can be reactivated to cause recurrent genital lesions.

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.

Black gallstones form due to supersaturation of the bile with bilirubin, which precipitates with calcium to form calcium bilirubinate stones. This typically occurs in

the setting of chronic hemolysis (eg, sickle cell disease) or altered enterohepatic circulation of bilirubin (eg, Crohn disease, ileal resection).

Hookworms are transmitted when human skin comes into contact with soil contaminated with human feces. The larvae penetrate the skin, travel to the lungs, are coughed up, and then subsequently swallowed. Adult hookworms live in

the small intestine and feed on human blood. Therefore, chronic iron deficiency anemia (microcytic anemia) is the greatest complication.

Calcineurin inhibitor nephrotoxicity with resultant impairment of renal function is the most significant adverse effect of cyclosporine. Cytochrome P450 3A (CYP3A) is responsible for cyclosporine metabolism in

the small intestine and liver. Grapefruit juice inhibits this enzyme and increases the nephrotoxicity of cyclosporine by raising circulating drug levels (pharmacokinetic interaction).

Portal hypertension, as seen in alcoholic liver disease, produces splenomegaly by causing congestion of blood within

the spleen, which produces expansion of the red pulp.

Prognosis of colorectal adenocarcinoma is directly related to

the stage of the tumor (not to the grade!).

The clavicle is commonly fractured in children after a fall on an outstretched arm. In a distal clavicle fracture, the deltoid muscle and the weight of the arm cause inferolateral displacement of the distal fragment, whereas

the sternocleidomastoid and trapezius muscles cause superomedial displacement of the proximal fragment.

The lac operon is regulated by two distinct mechanisms: negatively by binding of the repressor protein to the operator locus and positively by cAMP-CAP binding upstream from the promoter region. Constitutive expression of

the structural genes of the lac operon occurs with mutations that impair the binding of the repressor protein (Lac I) to its regulatory sequence in the operator region.

All adult cells and tissues can be traced back to the 3 primary germ layers: ectoderm, mesoderm, and endoderm. The ectoderm gives rise to

the surface ectoderm, neural tube, and neural crest.

Direct factor Xa inhibitors (eg, apixaban, rivaroxaban) increase the prothrombin and activated partial thromboplastin times but do not affect

the thrombin time. Unfractionated heparin and direct thrombin inhibitors (eg, dabigatran) prolong the thrombin time.

Nephrotic syndrome is a hypercoagulable state. Sudden-onset abdominal or flank pain, hematuria, and left-sided varicoceles suggest renal vein thrombosis, a well-known complication of nephrotic syndrome. Loss of anticoagulant factors, especially antithrombin III, is responsible for

the thrombotic and thromboembolic complications of nephrotic syndrome.

The thyroid gland is formed from evagination of the pharyngeal epithelium and descends to the lower neck. Due to failure of migration,

the thyroid can reside anywhere along the thyroglossal duct's usual path, including the tongue (lingual thyroid).

Cumulative incidence (CI) is calculated as

the total number of new cases of a disease (eg, neurodegenerative condition) over a specific period (eg, during 2016) divided by the number of people at risk at the beginning of the period

Granulosa cell tumors are sex-cord stromal tumors of the ovary that secrete estrogen and can cause endometrial hyperplasia. Call-Exner bodies (cells arranged in a microfollicular or rosette pattern) are seen on microscopy. On gross pathology,

the tumor appears yellow due to the lipid content in theca cells.

The suffix of a biological agent indicates whether a medication is a monoclonal antibody (mab), a receptor molecule (cept), or a kinase inhibitor (nib). Monoclonal antibodies also include in their names

the type of target (eg, bacterial or immune system) and their origin (eg, human or mouse).

The musculocutaneous nerve innervates the major forearm flexors (eg, biceps brachii, brachialis) and coracobrachialis (flexes and adducts the arm) and provides sensory innervation to the lateral forearm. It is derived from

the upper trunk of the brachial plexus (C5-C7) and can be injured by trauma or strenuous upper extremity exercise.

Colonic diverticula form at weak points in the colon wall, typically in areas where the vasa recta penetrate through the smooth muscle. As diverticula enlarge,

the vasa recta are exposed and become vulnerable to chronic injury, which can lead to intraluminal hemorrhage and painless hematochezia.

Minute ventilation is equal to the product of

tidal volume and respiratory rate and includes dead space ventilation. Alveolar ventilation is equal to the product of respiratory rate and the difference between tidal volume and dead space volume.

Increases in resting blood flow to ischemic myocardium are primarily mediated by locally-acting substances (eg, adenosine, nitric oxide) that trigger coronary arteriolar vasodilation. Pharmacologic arteriolar vasodilators (eg, adenosine, dipyridamole) mimic

the vasodilation that occurs with exercise and may cause redistribution of blood flow from ischemic to nonischemic areas of myocardium (ie, coronary steal).

Pneumococcal conjugate vaccines are strongly immunogenic in infancy due to both B and T cell recruitment. They provide higher, longer-lasting antibody titers relative to pneumococcal polysaccharide vaccines. The pneumococcal polysaccharide vaccine is poorly immunogenic in infants due to

their relatively immature humoral antibody response.

Alanine is the major amino acid responsible for transferring nitrogen to the liver for disposal. During the catabolism of proteins, amino groups are transferred to α-ketoglutarate to form glutamate. Glutamate is

then processed in the liver to form urea, the primary disposal form of nitrogen in humans. Free ammonia is also excreted into the urine by the kidney for regulation of acid-base status.

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.

Alpha-1 antitrypsin (AAT) is a serum protein that, through the inhibition of neutrophil elastase, reduces tissue damage caused by inflammation. Histologically, AAT deficiency can demonstrate reddish-pink globules on periodic acid-Schiff stain;

these globules represent unsecreted, polymerized AAT in the periportal hepatocytes.

Anaphylactic shock is characterized by vasodilatation, increased vascular permeability, and bronchoconstriction. Epinephrine counteracts

these physiological mechanisms and is the drug of choice for the treatment of anaphylaxis.

The Ghon complex describes the two initial sites (lower lobe of lung, ipsilateral hilar lymph node) of primary tuberculosis infection. Over time,

these sites become calcified and fibrosed and can be visualized on gross pathology and radiographic imaging (Ranke complex).

Malabsorption of what is common following gastric bypass procedures?

thiamine, folate, vitamin B12, fat-soluble vitamins, and calcium

Pyruvate dehydrogenase and α-ketoglutarate dehydrogenase require thiamine as a cofactor. Administration of glucose to

thiamine-deficient patients (eg, alcoholics) can result in Wernicke encephalopathy (eg, acute confusion, ophthalmoplegia, and ataxia) due to increased thiamine demand.

Chronic lithium toxicity (eg, confusion, ataxia, neuromuscular excitability) can be precipitated by volume depletion and drug interactions with

thiazide diuretics, ACE inhibitors, and nonsteroidal anti-inflammatory drugs.

The common carotid artery and the proximal portion of the internal carotid artery are derived from the

third aortic arch. The third aortic arch is associated with the third pharyngeal arch, which gives rise to the glossopharyngeal nerve (CN IX), parts of the hyoid bone, and the stylopharyngeus muscle.

Thyroid hormone stimulates (not inhibits) osteoblast differentiation and activity, leading to increased formation of new bone. However, in the hyperthyroid state

this effect is outweighed by a greater increase in bone loss.

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.

Early disseminated Lyme disease can have cardiac involvement (Lyme carditis) that most commonly manifests with varying degrees of atrioventricular (AV) conduction block. Patients may be asymptomatic, but

those with complete AV conduction block are likely to have dyspnea, lightheadedness, or syncope.

Smoking cessation is by far the most effective preventive intervention in almost all patients, and this is especially true in

those with diabetes.

Disseminated intravascular coagulation (DIC) can occur with abruptio placentae due to release of tissue factor, a procoagulant that activates the coagulation cascade, from the damaged decidua into the maternal circulation. DIC classically presents with

thrombocytopenia and bleeding from mucosal surfaces (eg, gums) and intravenous line sites.

Wiskott-Aldrich syndrome is characterized by:

thrombocytopenia, immunodeficiency, and eczema it is caused by a defect in cytoskeleton rearrangement, not by CD18 deficiency

Pure red cell aplasia is a rare form of marrow failure characterized by severe hypoplasia of marrow erythroid elements in the setting of normal granulopoiesis and thrombopoiesis. Pure red cell aplasia is associated with

thymoma, lymphocytic leukemias, and parvovirus B19 infection.

Thioamides (eg, methimazole, propylthiouracil) decrease the formation of thyroid hormones via inhibition of

thyroid peroxidase, the enzyme responsible for both iodine organification and coupling of iodotyrosines. Propylthiouracil also decreases the peripheral conversion of T4 to T3.

Lymph node enlargement is most commonly due to infection-triggered cellular proliferation but can be caused by clonal expansion of malignant cells. Enlargement of the supraclavicular lymph nodes, which drain the chest and abdomen, is unlikely

to be caused by common childhood infections and is concerning for malignancy

Heart failure leads to reduced liver and kidney perfusion, resulting in reduced drug clearance. Metformin is excreted unchanged by the kidney; therefore, patients with significant renal insufficiency due

to heart failure or other causes (eg, chronic kidney disease) are at increased risk of toxicity (eg, lactic acidosis).

After birth, the lungs fill with oxygen and pulmonary vascular resistance decreases, causing the direction of flow through the DA

to reverse (ie, from aorta to pulmonary artery

Patients taking daily maintenance nitrates need to have a nitrate-free period every day to avoid

tolerance to the drug.

Organ susceptibility to infarction after occlusion of a feeding artery is ranked from greatest to least as follows: central nervous system, myocardium, kidney, spleen, and liver. The presence of a dual and/or collateral blood supply (as seen in the liver, which is supplied by the hepatic artery and portal vein) enables an organ to

tolerate arterial occlusion better than those with end-arterial circulations.

Angioedema is a rare and serious adverse effect of ACE inhibitor therapy. ACE inhibition increases bradykinin levels, which increase vascular permeability and lead to angioedema. Symptoms include

tongue, lips, or eyelid swelling and, less frequently, laryngeal edema and difficulty breathing. ACE inhibitors should be discontinued in affected patients.

Elderly patients are at increased risk of developing heat-related illness due to several features of normal aging that impair normal thermoregulatory mechanisms, including

tonic contraction of the peripheral vasculature, reduced sweat gland density, and reduced effective epidermal area available for heat transfer.

Older children with absence seizures may also develop generalized onset tonic-clonic or myoclonic seizures. Although ethosuximide is effective against isolated absence seizures, it is not effective for

tonic-clonic seizures. Valproic acid is a broad-spectrum antiepileptic that treats both types of seizures.

Rhabdomyolysis is characterized by the release of intracellular muscle contents (eg, myoglobin, electrolytes) due to myocyte injury; it is common with crush injuries, seizures, or drug use (eg, statins). Heme pigment (released from myoglobin after degradation in the kidney) is

toxic to tubular cells and can cause acute tubular necrosis. Positive blood on urine dipstick in the absence of red blood cells on microscopic urinalysis suggests myoglobinuria.

Clostridium difficile produces

toxin A (enterotoxin) and toxin B (cytotoxin) and causes pseudomembranous colitis, most commonly in patients recently treated with antibiotics. Toxin B depolymerizes actin filaments, causing gastrointestinal mucosal cell death

In patients with HIV, the presence of multiple ring-enhancing lesions with mass effect is most often indicative of

toxoplasmosis, followed by primary central nervous system lymphoma.

The finding of multiple ring-enhancing lesions in an HIV patient is most likely due to

toxoplasmosis.

Physiologic renal adaptations during pregnancy include increased glomerular filtration rate, greater basement membrane permeability, and decreased tubular resorption of filtered protein. As a result,

trace urinary protein excretion (ie, <300 mg/24 hr) is a normal finding in pregnancy.

Neisseria meningitidis is transmitted primarily by aerosolized droplets and subsequently colonizes the nasopharyngeal epithelium. Penetration of the epithelium can lead to bloodstream infection. Spread to the meninges occurs via

transcellular penetration of the cerebral capillary endothelium or entry at the choroid plexus.

The TATA box is a promoter region that binds

transcription factors and RNA polymerase II during the initiation of transcription. It is located approximately 25 bases upstream from the beginning of the coding region.

Southwestern blotting is used to detect DNA-binding proteins such as

transcription factors, nucleases, and histones.

Transient global amnesia is a self-limited syndrome characterized by the sudden onset of prominent anterograde amnesia accompanied by repetitive questioning. Symptoms correlate with

transient dysfunction of the hippocampus, the brain area responsible for the formation of new memories

LV free-wall rupture, an uncommon but devastating mechanical complication of

transmural myocardial infarction (MI) that occurs within 5 days or up to 2 weeks following the event

Acute pulmonary edema is a common consequence of acute myocardial infarction affecting the left ventricle. Elevated hydrostatic pressure in the pulmonary venous system leads to engorged alveolar capillaries with

transudation of fluid into the alveoli, appearing as acellular pink material on histology. Hemosiderin-laden macrophages are indicative of chronic lung congestion and are not present acutely.

Pleural effusions that develop due to pressure changes (eg, heart failure, cirrhosis, nephrotic syndrome) are typically

transudative

The spinal accessory nerve is vulnerable to injury in the posterior triangle of the neck. Injury results in weakness of the

trapezius muscle, which presents with drooping of the shoulder, impaired abduction of the arm above 100 degrees, and lateral displacement of the scapula.

Femoral nerve mononeuropathy can occur due to:

trauma, compression from a retroperitoneal hematoma or abscess, or injury during surgery or childbirth

Tricyclic antidepressant overdose can cause fatal cardiac arrhythmias and refractory hypotension due to inhibition of fast sodium channels in cardiac myocytes. Sodium bicarbonate is used to

treat associated cardiac toxicity and works by increasing serum pH and extracellular sodium (alleviating fast sodium channel blockade).

Alcohol withdrawal should be considered in hospitalized patients who develop

tremulousness, agitation, and elevated pulse and blood pressure within 48 hours following admission. Benzodiazepines act as a substitute for the effects of alcohol on GABA receptors, preventing alcohol withdrawal from occurring

Carvallo sign:

tricuspid regurgitation murmur that increases in intensity during inspiration

Holosystolic murmurs are associated with which 3 conditions?

tricuspid regurgitation, mitral regurgitation, VSD

Pulmonary infarcts are typically hemorrhagic (red) and wedge-shaped in the periphery of the lung. Intravenous drug users are at increased risk of:

tricuspid valve endocarditis, which can cause multiple septic pulmonary infarcts due to embolization of tricuspid valve vegetation fragments.

Hypovolemia due to loss of sodium and/or water causes increased concentration of red blood cells (ie, hematocrit) and albumin as both of these blood components are trapped within the intravascular space. Hypovolemia also

triggers increased absorption of uric acid in the proximal renal tubule, resulting in an increased serum uric acid level.

The bone loss in hyperthyroidism is driven by

triiodothyronine (T3), the more active form of thyroid hormone that is generated primarily by deiodination of thyroxine (T4) in peripheral tissues. T3 stimulates osteoclast differentiation, increased bone resorption, and release of calcium.

Patients with advanced HIV and low CD4 counts are at risk for opportunistic infections and require antimicrobial prophylaxis. Pneumocystis jiroveci pneumonia prophylaxis with

trimethoprim-sulfamethoxazole (TMP-SMX) is indicated when CD4 count is <200/mm3

What are the 2 forms of Giardia?

trophozoite (pathogenic stage) or a cyst (infective stage)

During skeletal muscle contraction, calcium is released from the sarcoplasmic reticulum and binds

troponin C, thereby allowing the binding of actin to myosin.

Sensitivity =

true positives / (true positives + false negatives). Screening tests should have high sensitivity.

Positive predictive value is the probability that an individual has a disease given a positive test. It is calculated as follows:

true positives / (true positives + false positives).

Pancreatic zymogens are normally converted into their active form by

trypsin in the duodenal lumen. Premature cleavage of trypsinogen to trypsin within the pancreas leads to uncontrolled activation of these zymogens, causing pancreatic autodigestion and acute pancreatitis.

Niacin (vitamin B3) can be synthesized endogenously from

tryptophan and is an essential component of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)

The severity of leprosy, a systemic illness caused by Mycobacterium leprae, depends on the strength of the cell-mediated immune (CMI) response, with

tuberculoid leprosy representing the milder form (intact Th1 CMI response) and lepromatous leprosy, the more severe form (weak CMI response).

Renal angiomyolipoma is a benign tumor composed of blood vessels, smooth muscle, and fat. Bilateral renal angiomyolipomas are associated with

tuberous sclerosis, an autosomal dominant condition.

The pathogenesis of rheumatoid arthritis involves early activation of CD4+ T cells (especially Th1 and Th17 subsets) with release of cytokines such as

tumor necrosis factor-alpha and IL-1 that cause destruction of cartilage and bone. Monoclonal antibodies that inhibit tumor necrosis factor-alpha or IL-1 receptors can slow progression of the disease.

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.

Osteogenesis imperfecta results from defective synthesis of

type 1 collagen by osteoblasts. Clinical findings include a hx of fractures after only minimal trauma, blue sclerae, and small malformed teeth

Pancreatic islet amyloid deposition is characteristic of

type 2 diabetes mellitus. A strong linkage with HLA class II gene makeup, pancreatic islet infiltration with leukocytes (insulitis), and antibodies against islet antigens are frequently seen in type 1 diabetes.

Acute respiratory distress syndrome is a severe inflammatory reaction that occurs in the lungs and results in hypoxemia and noncardiogenic pulmonary edema. Pulmonary injury leads to an inflammatory response resulting in breakdown of the capillary-alveolar barrier (created by

type I pneumocytes and endothelial cells), increased capillary permeability, intraalveolar fluid accumulation, and hyaline membrane formation.

Poststreptococcal glomerulonephritis is the most common cause of nephritic syndrome (eg, hematuria, edema, hypertension) in children, typically occuring 2-4 weeks after a streptococcal infection (eg, impetigo, cellulitis, pharyngitis). It is caused by a

type III (immune-complex-mediated) hypersensitivity reaction resulting from nephritogenic strains of group A beta-hemolytic Streptococcus.

Aldosterone excess will cause hypertension, hypokalemia, metabolic alkalosis and depressed renin. Alternatively, hypoaldosteronism is the cause of

type IV renal tubular acidosis. Aldosterone antagonists such as spironolactone or eplerenone can be used as medical therapy for Conn's syndrome.

Organ rejection can be hyperacute, acute, or chronic. Acute rejection most often occurs within weeks or up to 6 months after transplant and is predominantly cell-mediated, involving sensitization of host T lymphocytes against donor MHC antigens. There is

typically graft dysfunction with histology showing a dense, mononuclear (ie, lymphocytic) infiltrate.

The cerebellar hemispheres 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.

Pyrimidine dimers are formed in DNA as a result of

ultraviolet light exposure. They are recognized by a specific endonuclease complex that initiates the process of repair by nicking the damaged strand on both sides of the pyrimidine dimer. The damaged segment is then excised, and replacement DNA is synthesized by DNA polymerase.

Right-sided heart failure promotes the formation of ascites due to increased central venous pressure, which is transmitted to the hepatic sinusoids, leading to increased capillary hydrostatic pressure. Capillary permeability is

unaffected. Although chronic passive congestion may eventually result in hepatic synthetic dysfunction (hypoalbuminemia) with low oncotic pressures, the oncotic pressure will remain normal for several weeks at least.

Paroxysmal nocturnal hemoglobinuria is due to a gene defect that leads to

uncontrolled complement-mediated hemolysis. The classic triad includes hemolytic anemia (hemoglobinuria), pancytopenia, and thrombosis at atypical sites. Chronic hemolysis can cause iron deposition in the kidney (hemosiderosis).

TSH from the anterior pituitary stimulates the thyroid to produce thyroxine (T4) and a small amount of triiodothyronine (T3). T4 is converted in peripheral tissues to T3 (active form) and reverse T3 (inactive form). TSH secretion is

under negative feedback by thyroid hormone on the hypothalamus and pituitary.

Ewing sarcoma is the second most common malignant bone tumor of childhood (after osteosarcoma). It most commonly involves the lower extremity and pelvis and often metastasizes to the lungs. Histopathology is characterized by

uniform, small, round, cells; fibrous septae; and patches of necrosis and hemorrhage.

Asymmetric breath sounds can occur with:

unilateral obstruction below the level of the carina (foreign body aspiration) or with pleural disorders (effusion, pneumothorax)

Thoracic outlet syndrome (TOS) is most often caused by compression of the brachial plexus as it passes through the scalene triangle, the space bordered by the anterior and middle scalene muscles and the first rib. Symptoms typically include

upper extremity numbness, tingling, and weakness that worsen with repetitive overhead arm movements. The presence of an anomalous cervical rib is a risk factor for TOS.

Helicobacter pylori produces the enzyme

urease, which splits urea into CO2 and ammonia and neutralizes the local acidic gastric pH. Active infection can be confirmed through rapid urease testing, in which gastric mucosa is evaluated in the presence of urea and a pH indicator. Evidence of alkalization (due to ammonia formation) is confirmatory.

Escherichia coli are lactose-fermenting, indole-positive gram-negative rods that are an important cause of

urinary tract infection in women.

Loop diuretics act by inhibiting the Na-K-2Cl cotransporter in the thick ascending limb of the loop of Henle, increasing Na+, Cl−, and H2O excretion. They are the most potent diuretics and are

used as first-line therapy for rapid relief of symptoms in patients with acute decompensated heart failure.

Carbonic anhydrase inhibitors (eg, acetazolamide) block the reabsorption of sodium bicarbonate in the proximal tubule to cause metabolic acidosis. These drugs can be

used to help offset the metabolic alkalosis caused by loop diuretics.

Fenoldopam is a selective peripheral dopamine-1 receptor agonist. It causes vasodilation of systemic and renal arterioles to lower blood pressure while also increasing renal perfusion, urine output, and natriuresis, making it

useful in the treatment of hypertensive emergency in patients with renal insufficiency.

Heart failure can cause transudative pleural effusion due to an increase in pulmonary capillary hydrostatic pressure. Light criteria are

useful to differentiate transudative and exudative pleural effusions; transudative effusions are characterized by low protein and lactate dehydrogenase content compared to serum values.

Familial chylomicronemia syndrome frequently presents in childhood with recurrent episodes of acute pancreatitis. Patients with this disorder are not

usually at increased risk for premature coronary artery disease. Eruptive skin xanthomas may be present in hypertriglyceridemia, but tendon xanthomas and xanthelasmas are primarily seen with hypercholesterolemia.

Primary myelofibrosis is a myeloproliferative disorder associated with the clonal expansion of megakaryocytes. Bone marrow fibrosis accounts for most of the major manifestations, including hepatosplenomegaly, cytopenias, and blood smear evidence of dacrocytes. Bone marrow aspiration is

usually dry, but bone marrow biopsy will show marked fibrosis with occasional clusters of atypical megakaryocytes.

Propionyl-CoA is derived from the metabolism of

valine, isoleucine, methionine, threonine, and odd-chain fatty acids

Intestinal atresia distal to the duodenum occurs due to

vascular accidents in utero "Apple-peel" atresia occurs when the superior mesenteric artery is obstructed. The result is a blind-ending proximal jejunum; a length of absent bowel and mesentery; and, finally, a terminal ileum spiraled around an ileocolic vessel.

Wet age-related macular degeneration is characterized by retinal neovascularization due to increased

vascular endothelial growth factor (VEGF) levels. Patients typically have acute vision loss and metamorphopsia with funduscopy showing a grayish-green subretinal membrane and/or subretinal hemorrhage. Treatment includes smoking cessation and VEGF inhibitor therapy (eg, ranibizumab, bevacizumab).

The reduced cardiac output in heart failure triggers compensatory activation of the sympathetic nervous system and renin-angiotensin-aldosterone pathway, resulting in

vasoconstriction (increased afterload), fluid retention (increased preload), and deleterious cardiac remodeling. These mechanisms perpetuate a downward spiral of cardiac deterioration, leading to symptomatic decompensated heart failure.

Dactylitis (painful swelling of the hands and feet) is a common presentation of sickle cell disease (SCD) in young children. It is one of many

vasoocclusive manifestations of SCD. Sickling episodes result in hemolysis, which leads to increased indirect bilirubin and lactate dehydrogenase and decreased levels of haptoglobin.

Chromosome 22q11.2 microdeletion results in DiGeorge syndrome (cardiac anomalies, hypoplastic or absent thymus, and hypocalcemia) and

velocardiofacial syndrome (cleft palate, cardiac anomalies, dysmorphic facies). Fluorescence in situ hybridization is the "gold standard" for detecting a microdeletion.

Raloxifene is a selective estrogen receptor modulator (SERM) that has estrogen agonist activity on bone and decreases bone resorption. Medicines with estrogen agonist activity, including SERMs, oral contraceptives, and hormone replacement therapy, can increase the risk for

venous thromboembolism.

Hypertrophic cardiomyopathy is a common cause of sudden cardiac death (SCD) in young adults. Histologic features include cardiomyocyte hypertrophy and myofiber disarray with increased interstitial fibrosis. The structural disarray creates a substrate for

ventricular arrhythmia (eg, ventricular tachycardia, ventricular fibrillation) that can lead to SCD.

Normal pressure hydrocephalus presents with progressive gait difficulties, cognitive disturbances, and urinary incontinence. It is a form of communicating hydrocephalus characterized by

ventriculomegaly without persistent elevations in intercranial pressure. Brain imaging reveals ventricular enlargement out of proportion to sulci enlargement.

Long-standing rheumatoid arthritis can affect the cervical spine, causing

vertebral malalignment (subluxation) that can affect the atlantoaxial joint. Extension of the neck during endotracheal intubation can worsen the subluxation, leading to acute compression of the spinal cord and/or vertebral arteries.

Posterior inferior cerebellar artery occlusion causes lateral medullary (Wallenberg) syndrome. This disorder is characterized by

vertigo/nystagmus, ipsilateral cerebellar signs, loss of pain/temperature sensation in the ipsilateral face and contralateral body, bulbar weakness, and ipsilateral Horner syndrome.

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.

After vasectomy, viable sperm remain in the portion of the vas deferens distal to the ligation. Patients can still have

viable sperm in the ejaculate for 3 months and at least 20 ejaculations.

This patient's lesion is affecting the dorsal columns, which convey

vibration and proprioception sensation as well as fine touch (ie, 2-point discrimination)

Antisocial personality disorder involves a pattern of

violating the rights of others, engaging in unlawful behaviors (eg, physical aggression, illegal occupations), and lacking remorse for transgressions. Individuals must be age ≥18 for diagnosis and have a history of conduct disorder prior to age 15.

The chemokine receptor CCR5 is a coreceptor that enables the HIV virus to enter cells. Blockade of CCR5 by chemokine receptor antagonists prevents

viral entry into host cells.

Norovirus is the most common cause of

viral gastroenteritis. Outbreaks (eg, schools, cruise ships, nursing homes) are common, and symptoms include vomiting and watery diarrhea.

What is the most common cause of pericarditis?

viral infection (adenovirus, coxsackievirus, echovirus, influenza virus)

Hepatitis B virus has a partially double-stranded DNA genome and contains a viral DNA polymerase with reverse transcriptase activity. Reverse transcriptase serves a crucial step in

viral replication; it converts transcribed positive sense single-stranded RNA into the partially double-stranded DNA genome of viral progeny.

The locus ceruleus is a paired brainstem nucleus located in the posterior rostral pons near the lateral floor of the fourth ventricle and functions as the principal site for norepinephrine synthesis in the brain. It projects to

virtually all parts of the central nervous system and helps control mood, arousal (reticular activating system), sleep-wake states, cognition, and autonomic function.

E coli is one of the dominant components of the normal flora in the intestinal tract of humans and animals. It causes approximately 80% of all urinary tract infections. P fimbriae are the most important

virulence factor that uropathogenic E coli express. Without P fimbriae, E coli would not be able to bind to uroepithelial cells and infect the bladder, ureters, and kidneys. Instead, the bacteria would simply be washed away during urination.

Atrophic gastritis can result in profound hypochlorhydria, inadequate intrinsic factor production, vitamin B12 deficiency, and elevated methylmalonic acid levels. The reticulocyte count increases dramatically once

vitamin B12 replacement therapy is initiated in an individual with pernicious anemia. Hemoglobin and erythrocyte count levels rise more gradually and take up to 8 weeks to normalize.

The hydroxylation of proline and lysine residues in collagen helps it attain its maximum tensile strength. This process occurs in the rough endoplasmic reticulum and requires vitamin C as a cofactor. Impaired collagen synthesis resulting from

vitamin C deficiency (scurvy) can lead to fragile vessels, predisposing to gingival bleeding, ecchymosis, and petechia.

Breast milk contains all vitamins and trace minerals in adequate amounts except for:

vitamin D and K

Vitamin K deficiency results in impaired clotting factor carboxylation. Newborns are at risk for vitamin K deficiency due to poor transplacental transfer of vitamin K and low content in breast milk. All newborns should receive

vitamin K prophylaxis to prevent bleeding complications.

A neuroma forms when regenerating axons are unable to find their distal target and create a haphazard mass of axons and supporting cells. Upregulation of

voltage-gated sodium channels, which generate and propagate action potentials, is likely responsible for the increased pain of these lesions.

Vasopressin and desmopressin cause a V2 receptor-mediated increase in

water and urea permeability at the inner medullary collecting duct. The resulting rise in urea reabsorption (decreased urea clearance) enhances the medullary osmotic gradient, allowing the production of maximally concentrated urine.

Myotonic dystrophy is an autosomal-dominant disorder. It is caused by an increased number of trinucleotide repeats on myotonia-protein kinase gene. Sustained muscle contraction (myotonia), along with

weakness and atrophy, is common. Cataracts are seen in almost all patients. Frontal balding and gonadal atrophy are other common features.

Volar dislocation of the lunate from its normal position within the floor of the carpal tunnel can cause median nerve compression and/or injury. Median nerve injury at the level of the carpal tunnel may result in

weakness of thumb abduction, flexion, and opposition.

The obturator nerve is the only major nerve that exits the pelvis through the obturator foramen. Nerve injury typically results from compression (eg, due to pelvic trauma, surgery, or tumor) and presents with

weakness on thigh adduction and sensory loss over the distal medial thigh.

Functional hypothalamic amenorrhea results from loss of pulsatile gonadotropin-releasing hormone release from the hypothalamus and is caused by

weight loss, strenuous exercise, systemic illness, or abnormal eating habits. Loss of cyclic gonadotropin release leads to a decrease in LH and FSH secretion from the pituitary, which in turn causes low circulating estrogen levels.

Acute compartment syndrome (ACS) is caused by increased pressure within fascial compartments of the limbs, leading to impaired perfusion. ACS can cause severe pain, myonecrosis, and nerve injury. The anterior compartment of the leg,

which contains the deep peroneal (fibular) nerve, is the most common site of ACS.

Clostridium difficile infection is associated with

white, patchy pseudomembranes on the bowel mucosa. These pseudomembranes consist of a neutrophil-predominant inflammatory infiltrate, fibrin, bacteria, and necrotic epithelium. Patients may develop a nonobstructive colonic dilation known as toxic megacolon, which can lead to colonic perforation.

Meningiomas are slow-growing, well-circumscribed, benign intracranial tumors typically found at the cerebral convexities in adults. Characteristic histopathologic features include a

whorled pattern of cellular growth that forms nests, which may calcify into round, eosinophilic laminar structures called psammoma bodies

Aortic regurgitation causes an increase in total stroke volume with abrupt distension and rapid falloff of peripheral arterial pulses, resulting in a

wide pulse pressure. This leads to bounding peripheral pulses and head bobbing with each heartbeat.

Respiratory distress syndrome classically presents in premature infants with increased work of breathing and hypoxia at birth due to surfactant deficiency. Poor alveolar compliance leads to

widespread atelectasis and decreased functional residual capacity. Airway resistance is often increased due to lung inflammation and edema.

Preeclampsia is new-onset hypertension (systolic ≥140 mm Hg or diastolic ≥90 mm Hg) with proteinuria and/or signs of end-organ damage (eg, renal insufficiency). Preeclampsia is associated with

widespread maternal endothelial dysfunction, which occurs due to increased antiangiogenic factor release and decreased proangiogenic factor activity (eg, vascular endothelial growth factor)

Methemoglobinemia causes dusky discoloration of the skin (similar to cyanosis), and because methemoglobin is unable to carry oxygen, a state of functional anemia is induced. However, the blood partial pressure of oxygen

will be unchanged as it is a measure of oxygen dissolved in plasma and is unrelated to hemoglobin function.

New-onset odynophagia in the setting of chronic gastroesophageal reflux disease should raise suspicion for erosive esophagitis

with esophageal ulcers. Diagnosis is made by upper endoscopy.

Hyperplasia of the submucosal bronchial glands is the major contributor to bronchial wall thickening in chronic bronchitis. The Reid index is the ratio of the thickness of the submucosal bronchial glands to the thickness of the bronchial wall between the epithelial basement membrane and the bronchial cartilage. Higher values correlate

with increased duration and severity of chronic bronchitis.

Tertiary syphilis can result in thoracic aortic aneurysm. If the aneurysm compresses adjacent structures and dilates the aortic valve ring, a murmur and mediastinal widening might be present. The pathogenesis begins

with vasa vasorum endarteritis and obliteration, resulting in inflammation, ischemia, and weakening of the aortic adventitia. Fluorescent treponemal antibody absorption testing is specific for syphilis.

Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric ventricular septal hypertrophy and dynamic left ventricular outflow tract (LVOT) obstruction. Decreases in LV blood volume, via maneuvers or conditions that decrease preload (eg, abrupt standing, Valsalva strain phase) or afterload,

worsen LVOT obstruction and increase the intensity of the HCM murmur.

6-mercaptopurine is an immunosuppression drug that is inactivated by 2 enzymes,

xanthine oxidase and thiopurine methyltransferase Reduced function of either enzyme causes increased levels of the active metabolites of 6-MP, leading to increased immunosuppression and risk of toxicity

The primary cause of morbidity in acute rheumatic fever is heart failure from severe pancarditis. Mitral stenosis develops

years or decades after the original illness. Joint involvement is usually transient.

Trichomonas vaginalis is a sexually transmitted motile protozoan which can be seen on wet mount microscopy of vaginal discharge. It presents with

yellow-green, frothy vaginal discharge and vulvovaginal erythema.

Campylobacter jejuni is an oxidase-positive, curved, gram-negative rod that is a leading cause of gastroenteritis. The pathogen is a

zoonotic organism most commonly contracted by consuming contaminated, undercooked poultry. Cases are marked by fever, abdominal pain, and diarrhea that may be bloody.

Fabry disease

α-galactosidase A deficiency causes globotriaosylceramide (ceramide trihexoside) accumulation. Disease manifestations include neuropathic pain and angiokeratomas in adolescence and multi-organ involvement (renal, cerebrovascular, cardiac) in adulthood.

Streptococcus pneumoniae are gram-positive, α-hemolytic, optochin-sensitive, bile-soluble diplococci. Viridans group streptococci are also

α-hemolytic, but they are optochin-resistant and bile insoluble. Streptococcus pyogenes (Group A Streptococcus) appear as gram-positive cocci in chains with bacitracin susceptibility.

α-adrenergic agonists increase systolic and diastolic blood pressure by stimulating

α1-adrenoreceptors in the vascular walls, causing vasoconstriction. The elevated systemic blood pressure then causes a reflexive increase in vagal tone, resulting in decreased heart rate and slowed atrioventricular node conduction.

Isoproterenol is a