Uworld Qbank Flashcards
mid-systolic click followed by a short late-systolic murmur
disappears with squatting
Mitral Valve Prolapse
(MVP)
Squatting increases venous return (preload) and raises peripheral vascular resistance (augmented afterload)
Ehlers-Danlos syndrome
abnormal collagen formation
over-flexible joints
over-elastic skin
fragile tissues
Start and Stop codons
start -
AUG
stop -
UAA, UAG, UGA
5’ –> 3’ translation
Langerhans cells
dendritic cells in the skin
APCs
derived from myeloid cell line
racquet shaped intracytoplasmic granules - Birbeck granules
Delayed Type Hypersensitivity (IV)
contact dermatitis, granulomatous inflammation, TB skin test, Candida extract skin test
mediated by Th1 lymphocytes, release interferon-g to recruit and stimulate macrophages
Filtration fraction
FF = GFR / RPF
fraction of RPF filtered across the glomerular capillaries into Bowman’s space, usually 20%
GFR ~ inulin or creatinine clearance
RPF ~ PAH clearance
Reaction formation
replacement of an unpleasant or unacceptable thought or desire with an emphasis on its opposite
irregularly irregular tachyarrhythmia
in a conscious pt
Most likely atrial fibrillation
EKG shows absent P waves and irregularly spaced ventricular contractions (variable R-R)
Cisplatin
Platinum based chemotherapeutic regimen
Pts should receive aggressive hydration and amifostine (scavenges free radicals) to prevent nephrotoxicity
Flattening of the deltoid muscle after a shoulder injury
anterior shoulder dislocation
most commonly results from forceful external rotation and abduction at the shoulder joint
often associated with ancillary nerve injury –> deltoid paralysis, loss of sensation over the lateral arm
Anterior cruciate ligament
can be damaged by forceful anterior motion of the tibia with respect to the femur
(anterior drawer test)
athletes are at risk for:
tibial (medial) collateral ligament, meninsci and ACL damage
FSH secretion inhibition (male)
Inhibin B produced by sertoli cells (mass significantly reduced in pts with 1 testicle)
LH concentration is controlled primarily by testosterone feedback
varicose veins
dilated, tortuous veins resulting from impairment of the venous valves and reflux of venous blood
–> stasis/congestion, edema and increased incidence of superficial venous thrombosis
Venous stasis ulcers are common, often occur over medial malleolus
(thromboembolism is rare)
Seborrheic keratosis
benign epidermal tumor
tan/brown, round, flat, greasy, coin-like lesion with stuck on appearance
Cryptococcus neoformans
pathogenic fungus with a polysaccharide capsule
appears red on mucicarmine stain and as clear unstained zone in india ink
Activating mutation of
phosphoribosyl pyrophosphate synthetase
increased production and degradation of purines –> hyperuricemia
Gout!
Acute gouty arthritis tx
NSAIDs are first line
inhibit COX and exert broad anti-inflammatory effect: inhibit neutrophils
when NSAIDs are contraindicated, use Colchicine
inhibits neutrophil chemotaxis and phagocytosis by preventing microtubule formation
Delerium
reversible, acute-onset confusional state characterized by a fluctuating level of consciousness with deficits in attention, memory, and executive function
vs.
dementia: gradual onset, irreversible, no fluctuations in consciousness
Splenic artery
branch of the celiac trunk, the primary blood supply of the foregut
however, the spleen is not a gut derivative
it forms from the mesodermal dorsal mesentery
COPD
associated with smoking
may consist of both emphysema (progressive exertion dyspnea) and chronic bronchitis (frequent respiratory infections)
decreased FEV1/FVC ratio
emphysema increases TLC and RV
contrast with:
restrictive lung diseases that can increase FEV1/FVC and reduce lung volumes
Acyclovir
tx for herpesviridae family
provide hydration to avoid crystalline nephropathy
Neurophysins function
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
continuous murmur
best heard in the left infraclavicular region with maximal intensity at S2
Patent ductus arteriosus (PDA)
often asymptomatic, usually detected incidentally
occurs most commonly in pts born prematurely and those with cyanotic congenital heart disease
Reassortment
exchange of entire genome segments
(more dramatic than point mutations responsible for genetic drift)
Viruses with segmented genomes = orthomyxovieus, rotavirus
ANOVA
analysis of variance
compares the difference between the means of 2+ groups
t-test compares the diff btwn means of 2 groups
febrile maculopapular rash that begins on the face and spreads to the trunk and extremities
Rubeola (measles) or Rubella (German measles)
Postauricular lymphadenopathy –> rubella (togavirus)
Warfarin - drug interactions
Fifampin, phenobarbital and phenytoin are universal enhancers of the cytochrome P450 pathway –> decreased efficacy of warfarin
Cimetidine, amiodarone, TMP-SMX inhibit warfarin metabolism
unilateral vesicular rash localized on a single dermatome in an elderly pt
Herpes zoster
post-herpetic neuralgia is the most common neurological complication of varicella zoster virus infection
Primidone
narrow spectrum anticonvulsant + first line agent for benign essential tremor
active metabolites include phenobarbital (which can be monitored in blood) and phenylethylmalonamide
Sedation = potential side effect during drug initiation/toxicity
Glucocorticoids
catabolic, causing muscle weakness, skin thinning, impaired wound-healing, osteoporosis, and immunosuppression
Increase liver protein synthesis, specifically the enzymes involved in gluconeogenesis and glycogenesis
+ Peripheral antagonism of the effects of insulin
–> hyperglycemia
Benzodiazepines
increase the frequency of opening of the CNS GABAa receptor-chloride channels and have anxiolytic, anticonvulsant, and muscle relaxant effects as well as sedative-hypnotic effects
compare to:
Barbituates - increase the duration of opening of the GABAa receptor-chloride channel, longer half-lifes, hangover effect decreases their use for insomnia
B12 deficiency tx
parenteral B21 administration
Poor absorption secondary to gastric atrophy, intrinsic factor deficiency, or terminal ileal disease is the most common cause of deficiency, with dietary vitamin B12 deficiency far less common
Statins
metabolized by cytochrome P450 (except pravastatin)
coadministration with drugs that inhibit its metabolism (ex. erythromycin) –> increased incidence of statin induced myopathy and rhabdomyolysis
acute renal failure is a possible sequelea of rhabdo
Hereditary angioedema
low C1 esterase inhibitor activity leads to increases in bradykinin activity
ACE inhibitors should not be used in these patients (ACE converts bradykinin to inactive metabolites).
Viral invasion - binding
Essential to viral invasion of cells and the viral tropism for specific tissues is the initial attachment of the virion envelope or capsid surface proteins to the complementary host cell surface receptors. Many viruses bind to normal host cell plasma membrane receptors in order to enter host cells.
Known host cell receptor – virion/virion protein binding specificities include: CD4 and HIV gp120; CD21 and EBV gp350; and erythrocyte P antigen and parvovirus B19
Left sided heart disease
Pulmonary effect?
Left-sided heart disease can cause pulmonary hypertension by increasing pulmonary venous pressure and congestion. This leads to a passive increase in pulmonary arterial pressure, which is made worse by reactive vasoconstriction and structural remodeling of the pulmonary vasculature secondary to impaired nitric oxide availability and increased endothelin expression.
Minimal Alveolar Concentration
MAC
measure of the potency of an inhaled anesthetic (inversely proportional)
concentration of the anesthetic in the alveoli that renders 50% of the pts unresponsive to painful stimuli (ED50)
Transverse spinal cord section
more proximal levels have increasing amount of white matter (around the butterfly) and more ovoid sections; lower cervical and lumbosacral regions have large ventral horns; thoracic and early lumbar sections (T1-L2) contain lateral grey matter horns (sympathetic preganglionic neurons)
Iron deficiency
decreased serum ferritin, increased serum transferrin, and increased total iron binding capacity
Anemia in a woman of childbearing age is most commonly caused by iron deficiency secondary to menstrual blood loss
PTH action on bone
increased bone resorption
PTH acts on osteoclasts by an indirect method, it is the osteoblasts that have PTH receptors.
PTH causes osteoblasts to increase the production of RANK-ligant and monocyte colony stimulating factor (M-CSF)
these two factors stimulate osteoclastic presursors to differentiate into bone-resorbing, mature osteoclasts.
PTH increases serum calcium level and decreases serum phosphate level (lost in urine)
MAP-kinase signal transduction pathway
includes Ras protein, a G-protein that exists in inactive (GDP containing) and active (GTP containing) forms
Mutated Ras –> tumors
MEN2B
multiple endocrine neoplasia type 2B
medullary thyroid cancer
pheochromocytomas
mucosal neuromas
marphanoid habitus
Decreased outward K+ current during the repolarization phase of the cardiac action potential
–>
results in QT prolongation
The major cardiac pathophysiological consequences of QT prolongation is an increased risk of episodic polymorphic ventricular tachycardia, including torsades de pointes.
Bilateral acoustic neuromas
associated with neurofibromatosis type 2, an autosomal dominant condition caused by mutation of the NF-2 gene on chromosome 22
Duchenne muscular dystrophy
X-linked recessive myopathy
results from deletion of dystrophin gene
Dystrophin is a protein that allows interaction between extracellular connective tissue and the intracellular contraction apparatus
manifests in boys 2-5 years old with proximal muscle weakness and enlargement of the distal muscles
Poststreptococcal glomerulonephritis - prognostic factors
Age
95% of affected children, but only 60% of affected adults, recover completely
Gastrinoma
upper GI ulcerations (jejunal ulcers are specific), abdominal pain and diarrhea
Chi-square test
The chi-square test for independence is used to test the association between 2 categorical variables.
In the case of an exposure status and a binomial outcome, patients are divided into 2 groups based on exposure, and the number of pts that experience each outcome is recorded in a 2x2 table
a-adrenergic blockers
side effect
a1-mediated vasoconstriction prevents cerebral hypoperfusion upon standing. a-adrenergic blockers disrupt this mechanism and cause orthostatic hypotension
Tumor lysis syndrome
occurs when tumors with a high cell turnover are treated with chemo
The lysis of tumor cells causes intracellular ions, such as potassium and phosphorus, 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
prevention: urine alkalinization and hydration
Graft-versus-host disease
mediated by T-lymphocytes of the donor tissue that are sensitized against MHC antigens of recipient. Skin, liver and intestine are commonly involved
develops within 1 week of transplant
in severe cases - skin desquamation
Displacement
one of the less mature defense mechanisms
redirect emotions from the person/object causing them to a more acceptable, but still inappropriate, person/object
ex. angry at wife, punch wall
Filtration Fraction
fraction of plasma flowing through the glomeruli that is filtered across the glomerular capillaries into Bowman’s space
FF=GFR/RPF
renal plasma flow can be determined from renal blood flow by multiplying the renal blood flow by (1-hematocrit)
Left atrium - anatomy
The left atrium forms the majority of the posterior surface of the heart and resides adjacent to the esophagus
Enlargement of the left atrium can compress the esophagus and cause dysphagia
Descending thoracic aorta - anatomy
lies posterior to the esophagus and left atrium
clearly visualized by transesophageal echocardiography
allowing for the detection of abnormalities such as dissection or aneurysm
Superficial inguinal lymph nodes
All the skin from the umbilicus down, including the anus (up to the dentate/pectinate line) but excluding the posterior calf, drains to the superficial inguinal lymph nodes
(testes drain to abdominal aortic lymph nodes)
Gestational Diabetes
tx
Insulin is the medication of choice for the tx of gestational diabetes in pts for whom diet and light exercise have failed to control blood glucose levels
Oral hypoglycemic medications are avoided b/c risk of fetal hyperinsulinemia and hypoglycemia
Pulmonary capillary wedge pressure
PCWP
measures the left atrial end diastolic pressure (LAEDP)
Normal: LAEDP ~ LV end-diastolic pressure (LVEDP)
Mitral stenosis elevates the LAEDP and PCWP relative to the LVEDP
Hashimoto’s thyroiditis
mononuclear, parenchymal infiltration with well-developed germinal centers on histology
Most common cause of hypothyroidism (in iodine sufficient areas)
Acetyl-CoA
allosteric activator of gluconeogenesis that acts by increasing the activity of pyruvate carboxylase
Ruptured cerebral aneurysm w/ extensive intracranial hemorrhage, young adult
Patients with adult-type coarctation of the aorta commonly die of hypertension-associated complications, including left ventricular failure, ruptured dissecting aortic aneurysm, and intracranial hemorrhage.
These pts are at increased risk for ruptured intracranial aneurysms because of the increased incidence of congenital berry aneurysms of the circle of willis as well as aortic arch hypertension
Phenylethanolamine-N-methyltransferase
PNMT
conversion of norepinephrine to epinephrine
occurs in adrenal medulla
PNMT transcription is unregulated by cortisol (drainage of adrenal cortex goes through medulla, so there’s a high concentration –> catecholamine content 80% epic
Bioavailability
Oral administration subjects a drug to a large amount of first-pass metabolism (metabolized by liver and doesn’t reach systemic circulation), whereas IV, sublingual, and rectal administration bypasses some or all of this process and allows more drug to reach the systemic circulation
Enterobius vermicularis tx
Enterobiasis occurs most frequently in school-age children and presents with perianal pruritus. Diagnosis is made by the scotch tape test.
Albendazole is the first-line treatment, with pyrantel permeate as an alternative agent preferred in pregnant patients
Ethics - informal treatment to friends
Informal treatment to friends is ethically problematic, should be limited to emergency situations or when no other physical is available
Acute hemolytic transfusion reaction
Antibody-mediated (type II) hypersensitivity
caused by pre-existing into-ABO antibodies that bind antigens on transfused donor erythrocytes
–> complement activation: erythrocyte lysis, vasodilation, symptoms of shock
common findings: fever, hypotension, chest and back pain and hemoglobinuria
Hypovolemia: effects on kidney
Dehydration –> decrease in RPF and GFR
compensatory activation of the renin-angiotensin mechanism in response to hypotension –> constriction of the efferent arteriole to maintain GFR as best as possible.
Therefore, FF increases
Human papilloma virus (HPV)
HPV types 16, 18 and 31 are strongly associated with anal and cervical squamous cell carcinoma. HIV infection increases the prevalence of HPV infection and the risk of anal carcinoma; this risk is further augmented in men who have sex with men
VIPoma
non-beta cell pancreatic islet cell tumors that hypersecrete VIP
–> ‘pancreatic cholera’, ‘WDHA syndrome’ (watery diarrhea, hypokalemia, achlorhydria)
VIP increases intestinal chloride loss in the stool, which causes excess losses of the accompanying water, sodium and potassium as well
VIP also inhibits gastric acid secretion
Tx: Somatostatin inhibits the secretion of VIP
central venous catheter - infection prevention measures
proper hand washing, full barrier precautions during insertion of a central line, chlorhexidine for skin disinfection, avoidance of the femoral insertion site, removal of catheter when no longer needed
MRSA - colonization site
Nasal
In the general population at any given time, 25-30% of individuals have nasal colonization with Staphylococcus aureus. The anterior nares are the most common site of colonization for both methicillin-sensitive and methicillin-resistant staph aureus
Shiga-like toxins
aka Vero cytotoxins
produced by EHEC (enterohemorrhagic E. coli), nearly identical to the Shiga toxin produced by Shigella dysenteriae
Inhibit the 60s ribosomal subunit in human cells, thereby blocking protein synthesis by preventing binding of tRNA
[this differs from diphtheria toxin and exotoxin A of pseudomonas, which act on EF-2 not the 60S ribosomal subunit
HSV-1
Children aged 1-3 years who develop gingivostomatitis characterized by ulcerative lesions with intranuclear inclusions are likely experiencing primary infection with herpes simplex virus type 1 (HSV-1).
HSV-1 and other herpesviruses are enveloped and possess double-stranded DNA genomes
Isoniazid
antimyobacterial agent that specifically inhibits the synthesis of mycolic acids
Mycelia acids 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
Atropine poisoning
“Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, the bowel and bladder lose their tone, and the heart runs alone”
Atropine is a reversible cholinergic antagonist that acts selectively on muscarinic receptors. Its effects can be reversed by cholinesterase inhibitors (physostigmine)
Note: Jimson Weed (Datura stramonium) poisoning, also called ‘Gardener’s mydriasis’ is similar to atropine poisoning
Benztropine
centrally acting anti-cholinergic used to treat idiopathic and drug-induced Parkinson’s
ACE inhibitors
ex. ramipril
block the effect of ACE, decreasing angiotensin II and aldosterone levels
By decreasing angiotensin II levels, ACE inhibitors directly interrupt negative feedback loops, thus increasing renin and angiotensin I levels.
Without effective ACE, bradykinin metabolism decreases and bradykinin levels will increase
Nyastatin
Polyene antifungal and the drug of choice for oropharyngeal candidiasis in pts without advanced immunodeficiency
Acts by binding ergosterol in the fungal cell membrane, causing the formation of pores and leakage of fungal cell contents
Not absorbed from the GI tract and administered as an oral ‘swish and swallow’ agent
Barr body
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
Somatostatinoma
Rare pancreatic islet tumor
Somatostatin is secreted from pancreatic ‘delta cells’ and decreases the secretion of secretion, cholecystokinin, glucagon, insulin and gastrin
Gallbladder stones form because of poor gallbladder contractility, which is secondary to inhibition of cholecystokinin release
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)
Carbamazapine is the drug of choice
Inhibits neuronal high-frequency firing by reducing the ability of Na channels to recover from inactivation
Can cause aplastic anemia
P450 inducer
Charcot-Bouchard aneurysm
Associated with HTN
Located in basal ganglia, cerebellum, thalamus, pons
Size
Saccular (berry) aneurysm
Associated with ADPKD, Ehlers-Dalos syndrome, HTN
Located in circle of willis
size 2-25mm
Rupture results in subarachnoid hemorrhage
sx include sudden severe headache, focal neuro defecits uncommon
Atherosclerosis pathogenesis
Initiated by repetitive endothelial injury, which leads to a chronic inflammatory state in the underlying intima of large elastic arteries as well as large and medium-size muscular arteries
Peroxisomal disease
rare inborn errors of metabolism where peroxisomes are either absent or nonfunctional
very long chain fatty acids with branched points at odd-numbered C can not undergo mitochondrial beta-oxidation; these fatty acids are metabolized by a special form of beta oxidation or by alpha oxidation within peroxisomes
These diseases commonly lead to neurologic defects from improper CNS myelination
Pheochromocytoma
catecholamine-secreting tumor that presents with episodic hypertension, tachycardia, headaches, diaphoresis and tremors. Detection of elevated levels of catecholamines and metanephrines (catecholamine breakdown products) in the urine or plasma confirms diagnosis
Malignant mesothelioma
rare neoplasm that arises from the pleura or peritoneum
associated with ASBESTOS exposure (shipbuilding)
Hemorrhagic pleural effusions and pleural thickening are characteristic
EM = gold standard for diagnosis: tumor cells with numerous, long, slender microvilli and abundant tonofilaments
Rickets
Unmineralized osteoid matrix and widened osteoid seams
bowed legs, rachitic rosary, Harrison’s sulci, craniotabes, and growth retardation
Atrial fibrillation
occurs due to irregular, chaotic electrical activity within the atria
presents with absent P waves, irregularly irregular R-R intervals and narrow QRS complexes
AV node refractory pd regulates the number of atrial impulses that reach the ventricle and determines the ventricular contraction rate in conditions where the atria undergo rapid depolarization
Lacunar infarcts
small ischemic infarcts (
Rate of glycogen degradation in skeletal muscle increases after contraction compared to resting state - enzyme activation by ___
Ca++
Glycogen degradation is coupled with skeletal muscle contraction due to calcium-mediated myophosphorylase activation. Increased Ca++ in the cytosol allosterically activates phosphorylase kinase, which then phosphorylates (activates) muscle phosphorylase
Colonic diverticula
Pulsion - mechanism
False - structure
usually develop due to increased intraluminal pressure, composed of mucosa and submucosa
sigmoid colon most commonly
asymptomatic or manifest with painless rectal bleeding or acute diverticulitis
risk factor: chronic constipation
Acute lymphoblastic leukemia
Precursor B-ALL: TdT+, CD10+, CD19+
Precursor T-ALL: TdT, CD1a, CD2/3/4…
Chloramphenicol
suppresses bacterial protein synthesis by binding the ribosomal 50S subunit and inhibiting the peptide transferase enzyme
can lead to dose-dependent (reversible) and dose independent (irreversible) aplastic anemia (bone marrow failure due to hematopoietic stem cell deficiency CD34+)
Vitamin E deficiency
can occur in individuals suffering from fat malabsorption or abetalipoproteinemia
increases susceptibility of the neuronal and erythrocyte membranes to oxidative stress
manifests as neuromuscular disease and hemolytic anemia
Eosinophils:
role in host defense during parasitic infection
destroy the parasite via antibody-dependent cell-mediated cytotoxicity with enzymes from their cytoplasmic granules
Eosiniphils also regulate type 1 hypersensitivity reactions
COPD
COPD encompasses a spectrum of disease between chronic bronchitis and emphysema
Emphysema: destruction of interalveolar walls and decreased lung elastic recoil –> increased residual volume, functional residual capacity and total lung capacity
Arginase
enzyme of the urea cycle that produces urea and ornithine from arginine
Urethral injury
Pelvic fracture - Posterior urethra damage
Straddle injury - Anterior urethra damage
symptoms: Inability to void with full bladder sensation, high-riding boggy prostate, and blood at the urethral meatus
Foley catheter is contraindicated
Highly active antiretroviral therapy for HIV
HAART
side effect
Body fat redistribution
subcutaneous lipoatrophy involving the face/extremities is associated with nucleoside reverse transcriptase inhibitors (stavudine, zidovudine)
central fat accumulation in the trunk and viscera can occur with any HAART regimen
Endometriosis
presence of endometrial glands and stroma outside the uterus
asymptomatic or severe dysmenorrhea, dyspareunia and infertility
Embolic phenomena
Simultaneous development of stroke, intestinal or foot ischemia and renal infarction
These emboli may arise from left atrial clots, left ventricular clots, valvular vegetations, or aortic atherosclerotic plaques
Boltulism
3 main types:
food borne, wound, infant
In food-borne botulism, botulinum neurotoxin in food (produced by the organism Clostridium botulinum) prevents release of acetylcholine from nerve terminals at the neuromuscular junction, thereby preventing muscular contraction
Granulosa cell tumors
sex-cord stromal tumors that secrete estrogen
Histology: Call-Exner bodies
Polyethylene glycol
osmotic laxative
Diarrhea associated with lactase deficiency is also osmotic
Magnesium hydroxide is another osmotic laxative often used (less evidence though)
TCA-associated cardiac abnormalities
Tx = Sodium bicarbonate
TCAs (tricyclic anti-depressants) can have quinidine-like effect on the cardiac conduction system, potentially causing QRS and QT prolongation and cardiac dysrhythmias (inhibit fast Na channels)
Anti-centromere antibodies
Found in 40% of pts with: CREST syndrome (limited scleroderma) manifests with Calcinoshs, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasias
Anti-DNA topoisomerase 1 (Scl-70) ab are specific for systemic sclerosis
C. diphtheriae - culture
cultured on cysteine-tellurite agar, resultant colonies are black in color
The bacterium produces intracellular polyphosphate granules, called metachromatic granules, that can be detected on microscopy after methylene blue staining
Polymyositis
symmetrical proximal muscle weakness
muscle biopsy: inflammation, necrosis, regeneration of muscle fibers
preceding damage to myocytes with subsequent over-expression of MHC class I proteins on the sarcolemma leads to infiltration with CD8+ T lymphocytes and myocyte damage
Vascular reaction to endothelial and intimal injury
intimal hyperplasia and fibrosis, predominantly mediated by reactive smooth muscle cells that migrate from the media to the intima
Airway pressure of 0
The central airway pressure-volume curve is the functional residual capacity of the lungs, it identifies the resting state where the airway pressure equals 0
At the FRC, the intrapleural pressure is negative with a value of -5 cm H2O (chest wall tendency to expand opposes lungs tendency to collapse)
Streptococcus pyogenes (group A Strep)
B hemolytic, bacitracin-susceptible, pyrrolidonyl arylamidase-positive
Glomerulonephritis is associated with prior strep pharyngeal or skin infection
Acute rheumatic fever is associated with prior streptococcal pharyngitis (but not skin infection)
Mitral Regurg
Apical holosystolic murmur radiating to the axilla
Left ventricular afterload is the major determinant of the forward-to-regurgitant flow ratio in patients with mitral regurgitation
Decreasing afterload will increase forward flow while reducing regurgitant flow
Congenital rubella syndrome
The congenital rubella syndrome is predominantly characterized by neonatal defects of the head (microcephaly, mental retardation), eyes (cataracts), ears (deafness) and heart/CV system (PDA)
Vaccine for children, non-pregnant females of childbearing age with live, attenuated rubella virus vaccine
Amyotrophic lateral sclerosis (ALS)
causes both upper and lower motor neuron lesions
Loss of neurons of the anterior horns of the spinal cord (LMN lesion) causes muscle weakness and atrophy. Demyelination of the lateral corticospinal tract (UMN lesion) leads to spasticity and hyperreflexia
Effect of increase in circulating volume on pressure-volume loop
increase preload and cause a rightward widening of the PV loop
(the PV loop represents the relationship btwn pressure and volume in the left ventricle during systole and diastole)
Septic arthritis
High synovial fluid white blood cell count and absent crystals on microscopic examination suggest bacterial joint infection
Septic arthritis requires immediate antibiotic treatment to prevent joint destruction, osteomyelitis and sepsis
Give ceftriaxone
QRS complex
corresponds to ventricular depolarization (phase 0 on AP graph)
Ventricular myocyte depolarization is mediated by inward sodium movement and can be modulated by class 1 antiarrhythmics
Ureteral constriction
GFR and FF __
acutely decreases GFR and glomerular FF
Gastric acid secretion (phases)
The cephalic and gastric phases stimulate gastric acid secretion, while intestinal influences tend to reduce gastric acid secretion
Drug-induced lupus erythematosus (DILE)
Procainamide and hydrazine have the highest risk
lupus-like symptoms and positive ANA and anti-histone antibodies (anti-dsDNA ab rarely seen)
Graves’ ophthalmopathy tx
High-dose glucocorticosteroids such as prednisone
decrease the severity of inflammation and decrease extra ocular volume
conventional antithyroid drugs do not improve ophthalmopathy
Celecoxib
Selective COX2 inhibitor (preferentially expressed at sites of inflammation)
potent anti-inflammatory effects without the side effect of bleeding and GI ulceration associated with non-selective COX inhibitors
Selective COX 2 inhibitors do not impair platelet function because platelets predominantly express COX 1 (physiological role in tissues)
Janeway lesions
small, erythematous, possibly hemorrhagic merciless that may appear on the soles of the feet and palms of the hands in a pt with bacterial endocarditis
(blowing holosystolic murmur over apex + dyspnea + fatigue –> mitral regurgitation
fever + acuity –> bacterial endocarditis)
Sarcoidosis
hilar adenopathy, pulmonary disease, constitutional symptoms
Histology: non-caveating granulomas (distinguish it from TB)
Trigeminal nerve - origin
arises at the level of the middle cerebellar peduncle at the lateral aspect of the mid-pons
Infarcts involving the anterior portion of the medial pons can produce dysarthria and contralateral ataxic hemiparesis
Monospot test
positive in most cases of EBV associated mono (serum heterophile antibodies that agglutinate with erythrocytes from unrelated species)
In immunocompetent pts with a heterophile antibody-negative mononucleosis-like syndrome, the most likely diagnosis is cytomegalovirus infection
Vertical diplopia
most noticeable when the affected eye looks down toward the nose
usually caused by Trochlear nerve (CN IV) palsy
Meningioma
slow growing, well-circumscribed benign tumor
Psammoma bodies (core of dense calcification with surrounding collagen-fiber bundles) are characteristic
Aplastic anemia - diagnosis
pancytopenia, bone marrow replaced by fat cells and fibrous stroma, absence to splenomegaly
to distinguish between aplastic anemia and myeloproliferative diseases that also cause pancytopenia, a bone marrow biopsy is required
Galactosemia
Galacticol accumulates in the lens of pts, causing osmotic damage –> cataract formation
Galacticol is formed from excess circulating galactose in galactosemia by aldose reductase
Body dysmorphic disorder
preoccupation with a perceived defect in appearance and repetitive behaviors in response to the preoccupation. Can present with absent insight/delusional beliefs and result in significant psychosocial dysfunction
Delusional disorder
one or more delusions 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
Respiratory component that clears particles lodged in the bronchial tree
proximal transport of mucus by ciliated epithelial cells (mucoclliary clearance)
distal to the terminal bronchioles - macrophages
Mucus-secreting cells are present to the level of the larger bronchioles, after which club cells become the prominent secretory cell type
Chronic granulomatous disease
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
Tamoxifen and raloxifene
“selective estrogen receptor modulators” (SERMs)
tissue-selective estrogen agonist/antagonist properties
Used in the tx of osteoporosis and breast cancer
associated with an increased incidence of endometrial cancer and thromboembolitic disease
Brown pigment stones
typically arise secondary to infection of the biliary tract, which results in the release of B-glucuronidase by injured hepatocytes and bacteria.
The presence of this enzyme contributes to the hydrolysis of bilirubin glucuronides and increases the amount of unconjugated bilirubin in bile
Informed consent
should be obtained by the physician performing the procedure
Actinic keratoses (AKs)
small (
Right upper quadrant bleeding
hepatic artery, portal vein and common bile duct run through the hepatoduodenal ligament (portal triad)
Occlusion of the portal triad (pringle maneuver) is a surgical technique used to distinguish the source of right upper quadrant bleeding. If bleeding persists, the inferior vena cava or hepatic veins are likely to be injured
Kidney - position
The left kidney lies immediately deep to the tip of the 12th rib on the left
Glucose filtration
glucose is normally filtered at the glomerulus and completely reabsorbed by the proximal tubule
Inhibition of Na-coupled, carrier-mediated transport of glucose by the proximal tubule would cause the glucose clearance to approach the value of the GFR (typically estimated with inulin)
Anterior surface of the heart
Right ventricle
A penetrating injury at the left sternal border in the 4th intercostal space would puncture the anterior surface of the heart
Low Vd (3-5L)
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)
Pulmonary circulation
part of a continuous circuit with the systemic circulation
rate of blood flow through the pulmonary circulation must equal the rate of blood flow in the systemic circulation at all times
arterial pressures and oxygen contents of the pulmonary and systemic arterial systems are considerably different both at rest and during exercise
Atypical / malignant phenylketonuria (PKU)
Deficient dihydrobiopterin reductase (BH2 –> BH4)
Tetrahydrobiopterin (BH4) is a cofactor used in the synthesis of tyrosine, DOPA, serotonin and nitric oxide. Initially, tyrosine is converted to DOPA by the enzyme tyrosine hydroxyls, with BH4 used as a cofactor. Next, DOPA is decarboxylated to dopamine by the enzyme DOPA decarboxylase
Acute v Chronic Mitral Regurgitation
Pts with acute mitral regurg have near-normal left atrial compliance. Therefore, they tend to develop marked pulmonary hypertension and pulmonary edema
Pts with chronic mitral regurg acquire an adaptive increase in LA volume and compliance. Thus, they are less prone to pulmonary hypertension/edema but are more prone to atrial fibrillation and mural thromboembolism
Elastin - plasticity and ability to recoil upon release of tension
attributable to a unique form of desmosine crosslinking between four different lysine residues on four different elastin chains. This crosslinking is accomplished by the action of extracellular lysyl hydroxylase
Crohn’s disease
causes transmural inflammation of any area of the GI tract. The involvement of all layers of the intestinal wall explain the most common complications of chorine’s disease: strictures and fistula formation
Red blood cell fragments, burr cells and helmet cells
associated with either microangiopathic hemolytic anemia or mechanical red cell destruction
In pts with prosthetic valves, RBCs are exposed to excessive shear and turbulence in the circulation, causing damage from mechanical trauma
Urge incontinence
detrusor overactivity –> sudden, overwhelming or frequent need to empty bladder
Patients with MS most commonly develop urge incontinence due to loss of central nervous system inhibition of detrusor contraction of the bladder
As the disease progresses, the bladder can become atonic and dilated, leading to overflow incontinence
Spleen
The spleen acts both a blood filter capable of removing circulating pathogens and as a major site of opsonizing antibody synthesis.
Asplenic pts are prone to infections caused by encapsulated organisms such as Strep pneumo, H influenzae, and N meningitidis
Anemia with neurologic abnormalities
vit B12 deficiency
Neurological damage associated with B12 deficiency includes subacute, combined degeneration of the posterior and lateral spinal columns
Increased serum level of methylmalonic acid is diagnostic of vit B12 deficiency
hyperlipidemia tx options and toxicities
Statins: used for high LDL, toxicity includes hepatitis and myopathy
Niacin: used for low HDL, toxicity includes cutaneous vasodilation, hyperglycemia, hyperuricemia / gout, hepatitis
Fibric acid derivatives (gemfibrozil, fenofibrate): used for high TG, toxicity includes gallstones, myopathy
osteomyelitis in a sickle cell pt
Pts with sickle cell disease (SCD) have functional asplenia as a result of multiple infarctions of the spleen, so they are more prone to infection by encapsulated organisms such as Salmonella
Salmonella has a capsule called the ‘Vi antigen’ that protects it from opsonization and phagocytosis
Staph aureus and Salmonella are common causes of osteomyelitis in pts with SCD
Raw shellfish
Hep A
Airway resistance
Regional airway resistance within the first 10 generations of bronchi contributes to most of the total airway resistance of the lower respiratory tract. Resistance is maximal in the 2-5th generation airways, including the segmental bronchi. In contrast, airways
Guillain-Barre syndrome
immune mediated acute demyelinatation of the peripheral neuropathy
affects young adults and is usually preceded by a febrile illness (Campylobacter jejuni)
sx: ascending muscle weakness and areflexia
segmental demyelination of peripheral nerves and an endoneural inflammatory infiltrate are seen on microscopy
Kartagener syndrome
primary ciliary dyskinesia
situs inversus, chronic sinusitis and bronchiectasis
mutations that impair the structure or function of cilia (dyenein arms)
Foscarnet
analog of pyrophosphate that can chelate calcium and promote nephrotoxic renal magnesium wasting. These toxicities can result in symptomatic hypocalcemia and hypomagnesemia (seizures)
Foscarnet is used to treat CMV induced retinitis in an HIV-infected pt
Class III antiarrhythmics:
amiodarone, sotalol, ibutilide, dofetilide
slow K+ efflux from the ventricular myocyte, prolong repolarization and prolong the refractory period
a-adrenergic agonists
increase both systolic and diastolic blood pressure via stimulation of a1-adrenoreceptors in the vascular walls
elevated systemic blood pressure is associated with a reflex increase in vagal tone, resulting in decreased heart rate and slower atrioventricular node conduction velocity
Necrotizing fasciitis
severe infection of the subcutaneous tissue and deep fascia, surgical emergency
Can be due to Strep pyogenes (PYR-positive, beta-hemolytic, gram pos cocci that grows in chains)
Serotonin syndrome
confusion, agitation, tremor, tachycardia, hypertension, clonus, hyperreflexia, hyperthermia, diaphoresis
Any drug that increases serotonin levels (SSRI and MAO inhibitor combinations, high doses of SSRIs) can precipitate this syndrome
Tryptophan is a precursor for serotonin
Cyproheptadine
antihistamine with anti-serotonergic properties that can be used in the treatment of the serotonin syndrome
epidural hematoma
due to tear of the middle meningeal artery
associated with temporal bone fracture
located between the bone and dura mater
‘lucid interval’ followed by loss of consciousness
McArdle’s syndrome (type 5 glycogen storage disease)
glycogenolysis provides immediate energy for strenuous muscle contraction
Myophosphorylase deficiency leads to a failure of glycogenolysis with clinical manifestations of decreased exercise tolerance, myoglobinuria, and muscle pain with physical activity
Viridans streptococci
produce dextrans from glucose that aid these organisms in colonizing host surfaces such as dental enamel and heart valves
—> subacute bacterial endocarditis (in pts with preexisting valvular defects after a dentist visit - use antibiotic prophylaxis!)
RANK receptor / RANK-ligand interaction
essential for the formation and differentiation of osteoclasts
over-expression of RANK receptors in hypoestrogenic states causes increased bone resorption due to increased osteoclastic activity
(low estrogen –> lower bone mass)
Cerebellar tumor in a child
most likely a pilocytic astrocytoma (cystic and solid components on imaging) or a medulloblastoma (always solid)
Psoriasis
sharply demarcated salmon-colored plaques covered with loosely adherent silvery scale
frequently associated with psoriatic arthritis - deforming joint disease
localized amyloidosis precursor proteins/peptides
Cardiac atria: atrial natriuretic peptide
thyroid gland: calcitonin
pancreatic islets: islet amyloid protein (amylin)
cerebrum: B-amyloid protein
pituitary: prolactin
Immune globulin light chains cause multi-organ amyloid deposition in primary systemic amyloidosis
Effect of the hypothalamus on prolactin secretion
inhibitory via dopamine production
Drug induced lupus
linked to drugs that are metabolized by N-acetylation in the liver
ex. hydralazine, procainamide
genetic predisposition determines acetylator phenotype - slow –> greater risk
discontinue only in pts with clinical symptoms of lupus
Deep brachial artery
courses along the posterior aspect of the humerus with the radial nerve
Midshaft fractures of the humerus risk injury to these structures
supracondylar fractures are associated with injury to the brachial artery
Selective IgA deficiency
predisposes to recurrent sinopulmonary and GI tract infections due to the absence of secretory IgA. It is also associated with anaphylactic response to transfused blood products due to an immune response against transfused blood products due to an immune response against transfused IgA which the pts body recognizes as foreign
Leukocyte adhesion deficiency
delayed seperation of the umbilical cord, recurrent cutaneous infections without pus formation and poor wound healing
insulin resistance - factors
FFA and serum triglycerides increase insulin resistance in overweight people
Age 3 developmental milestones
play in parallel (social), speak in simple sentences (language), copy a circle and use utensils (fine motor) and ride a tricycle (gross motor)
Overflow incontinence
often caused by diabetic autonomic neuropathy in type 1 diabetics, causes 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
Clostridium difficile
In absence of normal intestinal microbial flora (ex. after antibiotics), C diff can overgrow and produce enterotoxin (toxin A) and cytotoxin (toxin B). Clinical disease resulting from C. difficile overgrowth can range from transient diarrhea to severe pseudomembranous colitis
Superior mesenteric artery syndrome
transverse portion of the duodenum is entrapped between the SMA and aorta, causing symptoms of partial intestinal obstruction
occurs when the aortomesenteric angle critically decreases, secondary to diminished mesenteric fat, pronounced lordosis, or surgical correction of scoliosis
Hepatitis B virus (HBV) replication
double stranded DNA –> +RNA template –> double-stranded DNA progeny
Although it is a DNA virus it replicates via reverse transcription
Insulin
anabolic hormone that acts via a tyrosine kinase second messenger system to stimulate the synthesis of glycogen, proteins, fatty acids and nucleic acids
Tyrosine kinase leads to the activation of protein phosphatase within cells, and protein phosphatase directly modulates the activity of enzymes in the metabolic pathways regulated by insulin
Helicase
unwinds DNA at the replication fork and separates dsDNA into ssDNA during the replication process
Initial separation of dsDNA at the origin of replication is facilitated by DnaA protein and strand binding proteins (SSB) proteins.
Osteoarthritis v Rheumatoid
usually involves the distal interphalangeal joints whereas rheumatoid arthritis typically affects the metacarpophalangeal and proximal interphalangeal joints
Acute Pancreatitis
Acute Interstitial pancreatitis: pancreas is grossly edematous, focal areas of fat necrosis, calcium deposition and interstitial edema are seen on light microscopy
Necrotizing (hemorrhagic) pancreatitis: chalky-white areas of fat necrosis interspersed with hemorrhage are seen on macroscopic exam
Akathisia
extrapyramidal side effect of antipsychotic medication characterized by inner restlessness and an inability to sit or stand in one position. Akathisis is frequently misdiagnosed because the restlessness is misinterpreted as worsening psychotic agitation. The pts antipsychotic dose is often increased rather than decreased, exacerbating the akathisia
Paroxysmal supraventricular tachycardia
common dysrhythmia that frequently occurs in pts with no other heart disease
cause: re-enterant circuit in the AV node
tx: adenosine, vagal maneuvers (carotid sinus massage and valsalva - increase baroreceptor firing –> increased parasympathetic influence –> prolonged AV node refractory pd)
Mu receptors
G protein-linked receptors whose actions are mediated through various secondary messenger pathways, including
increased potassium efflux
Binding of morphine to mu receptors results in G protein-coupled activation of potassium conductance. Potassium efflux increases and causes hyperpolarization of postsynaptic neurons effectively blocking pain transmission
Dimorphic fungi
grow as molds at 25-30C and as yeast at body temperatures (35-37C)
ex. Sporothrix, Coccidioides, Histoplasma, Blastomyces, Paracoccidioides
Kleinfelter syndrome - gonadal failure
reflected by increased FSH
Monoamine oxidase inhibitors (MAOIs)
useful in pts with atypical depression (mood reactivity, rejection sensitivity, increased sleep and appetite) and treatment-resistant depression
phenelzine, tranylcypromine
radial nerve
extension of the hand
damage –> wrist drop
Peptidoglycan cell wall of Gram + and Gram - organisms
gives them the ability to survive osmotic stress
disrupted by: penicillins, cephalosporins (ex. Cefuroxime), vanco
Pituitary adenoma
most common type is a prolactinoma, sometimes called a lactotroph adenoma
(somatotrophs, which secrete GH, are the most common cell type in the normal pituitary though)
Effect of age on renal clearance
Elderly pts typically have age-related renal insufficiency, even in the presence of normal creatinine levels
the dose of drugs that are renally cleared (like digoxin - a cardiac glycoside) should be reduced to prevent toxicity
Erythrocytosis
hematocrit >52% in men and >48% in women
RBC mass - distinguish absolute from relative
normal RBC mass indicates plasma volume contraction as the cause
Daptomycin
lipopeptide antibiotic with activity limited to Gram+ organisms, including MRSA
causes depolarization of bacterial cellular membrane and inhibition of DNA, RNA and protein synthesis
associated with increased CPK levels and an increased incidence of myopathy
phosphoinositol second messenger system
begins with the 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 Ca++
First generation antipsychotics -
Side effects of high v low potency
Low: Chlorpromazine, Thioridazine
High: Haloperidol, Fluphenazine
Low potency: non-neuro side effects (sedation, anticholinergic effects, orthostatic hypotension)
High potency: extrapypamidal symptoms (Potent =extraPyramidal)
ex. acute dystonia, akathisia
Angioedema
rare but serious adverse effect of ACE inhibitor therapy
most commonly involves swelling of the tongue, lips, or eyelids and pts can also experience laryngeal edema and difficulty breathing
most likely due to increased bradykinin levels as a result of ACE inhibition
Lyme disease stages
Early - flu-like symptoms, erythema chronicum migrans
Second stage - AV block, Bell’s palsy
Chronic - chronic asymmetric large joint arthritis and encephalopathy
Treat with doxycycline or penicillin-type antibiotic
Foscarnet
one of the few antiviral agents that bind and inhibit DNA polymerase in herpesvirus and reverse transcriptase in HIV that does not require intracellular activation by viral or cellular kinases
pyrophosphate analog
Sarcoidosis diagnosis
dry cough, pulmonary infiltrates, hilar adenopathy, non-caseating granulomas on lung biopsy, African American
Scleroderma - effect on lung
Pulmonary hypertension develops as a result of damage to the pulmonary arterioles
manifests with an accentuated pulmonary component of the second heart sound and signs of R heart failure
Xeroderma pigmentosum
defect in DNA excisional repair
increased sensitivity to UV radiation
high incidence of all forms of cutaneous malignancy
Enterococcus
component of the normal colonic flora, capable of growing in hypertonic saline and bile
gamma-hemolytic, catalase-negative, pyrrolidonyl arylamidase-positive
genitourinary instrumentation or catheterization has been associated with enterococcal endocarditis
Vasectomy - what to expect post-surgery
After vasectomy, viable sperm remain in the portion of the vas deferens proximal to the ligation
Twenty percent of pts still have viable sperm in their ejaculate after 3 months and at least 20 ejaculations
acute rheumatic fever (ARF) - main cause of death
heart failure due to severe myocarditis
(rare)
mitral stenosis after ARF requires years or decades to develop
Squamous cell carcinoma of the esophagus
presents with progressive dysphagia
risk factors: chronic alcohol, cigarette smoke
light microscopy: squamous cells with various degrees of atypia, foci of keratinization (if well-differentiated)
Multiple Sclerosis
(most commonly)
relapsing-remitting central nervous system disorder characterized by recurrent episodes of demyelination and subsequent partial remyelination
relative preservation of axons in acute MS plaques, with axonal degeneration seen mostly in chronic plaques
Internuclear ophthalmoplegia and optic neuritis are common symptoms
Adenomyosis
uniformly enlarged uterus with normal appearing endometrial tissue within the myometrium
menorrhagia and dysmenorrhea are common presenting sx
Organophosphates
stimulate muscarinic and nicotinic cholinergic receptors (clinical presentation = DUMBELS.. liquid from everywhere)
Atropine reverses the muscarinic effects but does not prevent the development of nicotinic effects such as muscle paralysis
pralidoxime is the only medication that reverses both, by ‘restoring’ cholinesterase from its bond with these substances
Odds Ratio
measure of association between an exposure and an outcome
OR = ad/bc
Aortic coarctation
in a child/young adult:
presents with lower-extremity claudication (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
Ethambutol
antimyobacterial agent that inhibits carbohydrate polymerization, thereby preventing peptidoglycan cell wall synthesis
unique adverse effect: optic neuritis, typically presents in conjunction with decreased visual acuity, central scotoma and color blindness
Schizophrenia
2 of the following:
delusions, hallucinations, disorganized speech, grossly disorganized behavior, and negative symptoms
one must be delusions, hallucinations or disorganized speech
total illness duration must be at least 6 months (including prodromal and residual pds) with at least 1 month of active symptoms
Diffuse esophageal spasm (DES)
occurs due to uncoordinated contractions of the esophagus
inefficient in propelling food into the stomach
may cause symptoms of dysphagia and chest pain
Chest pain may mimic unstable angina (do a cardiac workup)
Para-aminohippuric acid (PAH)
primarily secreted into the nephron by the proximal tubule
some is freely filtered by the glomerulus
not reabsorbed by any portion
tubular fluid concentration of PAH is lowest in Bowman’s space
Testes - lymph drainage
para-aortic lymph nodes
however,
the scrotum drains to the superficial inguinal lymph nodes
Obstructive sleep apnea
nocturnal upper airway obstruction (manifested by snoring) and episodic nocturnal apnea
associated with systemic hypertension
prolonged, untreated obstructive sleep apnea can also cause pulmonary hypertension and right heart failure
Celiac disease
hypersensitivity to gluten, manifests with symptoms of malabsorption (diarrhea, steatorrhea, flatulence, and symptoms of nutrient deficiencies)
serologic testing for IgA anti-endomysial and anti-tissue transglutaminase antibodies for diagnosis
small bowel biopsy: atrophy of villi, flattening of the mucosa and chronic inflammation of the lamina propria
tx: gluten free diet
Cause of the rapid plasma decay of thiopental (and other barbituates)
redistribution of the drug to other tissues throughout the body
not metabolism
Medications that cause seizures
bupropion (antidepressant) clozapine (antipsychotic at high doses) isoniazid (anti-TB drug, if given without pyridoxine) ciprofloxacin (antibiotic) imipenem (antibiotic)
Motion sickness prevention
antimuscarinic agents and antihistamines with antimuscarinic action
ex. meclizine, dimendyrinate, scopolamine
side effects: blurry vision, dry mouth, palpitations, urinary retention, constipation
2,3-BPG
increased concentrations in erythrocytes enable increased oxygen delivery in the peripheral tissues in the presence of lower blood oxygen concentration b/c 2,3-BPG decreases the affinity of hemoglobin for oxygen
Produced from 1,3-BPG by the enzyme bisphosphoglycerate mutase
consumes energy that would otherwise have been used by the erythrocyte to produce ATP
Huntington disease
inherited, autosomal dominant (CAG)n
progressive dementia and choreiform movements
loss of neurons in the caudate nucleus and putamen
hepatitis D
The HBsAg of hepatitis B virus must coat the HDAg of hepatitis D virus before it can infect hepatocytes and multiply
Pulsus paradoxus
decrease in systolic blood pressure of greater than 10 mmHg with inspiration
occurs in the setting of acute cardiac tamponade, constrictive pericarditis, severe obstructive lung disease, and restrictive cardiomyopathy
Acute asthma tx
Beta-adrenergic agonists (Gs coupled, activate adenylyl cyclase) control acute asthma exacerbations by causing bronchial smooth muscle relaxation via increased intracellular cAMP
Pulsus paradoxus can occur in the setting of severe obstructive pulmonary disease such as asthma
Niacin (vit B3)
Can be endogenously synthesized from tryptophan
essential component of NAD
(coenzyme in the metabolism of fats, carbohydrates and amino acids) and NADPH (HMP shunt)
deficiency –> pellagra: dermatitis, diarrhea, and dementia
Arteriovenous (AV) shunt
acquired forms can result from medical interventions or penetrating injuries
increase preload and decrease afterload by routing blood directly from the arterial system to the venous system, bypassing the arterioles
High output AV shunts can lead to high-output cardiac failure
Candida: risk factors
Broad-spectrum antibiotics suppresses the normal bacterial flora of the vagina and facilitate Candida overgrowth
contraceptive use, systemic corticosteroid use, diabetes mellitus, immunosuppression
Pseudomonas aerginosa tx
major pathogen in burn patients
Only a few specific penicillins (ticarcillin, piperacillin) and cephalosporins (ceftazidime, cefepime) have activity against it. Certain aminoglycosides, fluoroquinolones (ciprofloxacin, levofloxacin) and carbapenems (imipenem, meropenem) are also effective
Superior gluteal nerve injury
weakness/paralysis of gluteus medius, gluteus minimus and tensor fascieae latae muscles
Trendelenburg sign: pelvis tilts downward toward the contralateral side
Gluteus medius gate: pts lean toward ipsilateral side when walking to help stabilize the pelvis
Thiazide diuretics
block Na+/Cl- symporters in the distal convoluted tubules, causing enhanced Na, Cl and water excretion
not as efficacious as loop diuretics
can cause hypercalcemia
Protein A
virulence factor found in the peptidoglycan wall of Staphylococcus aureus that binds to the Fc portion of IgG, leading to impaired complement activation, opsonization and phagocytosis
Maternal antibodies
With maternal blood types A and B, erythroblastosis fetalis and hemolytic disease of the newborn do not occur, as the naturally occuring antibodies (anti-A and -B) are of the IgM type and cannot cross the placenta
In type O mothers, the antibodies are predominantly IgG and can cross the placenta to cause fetal hemolysis
Wilson disease- brain anatomy
cystic degeneration of the putamen as well as damage to other basal ganglia structures
The putamen is located medial to the insula and lateral to the globus pallidus on coronal sections
Signal pathways in the autonomic nervous system:
cAMP, IP3, ion channels
Nicotinic receptors are ligand-gated ion channels that open after binding acetylcholine. This results in immediate influx of Na+ and Ca++ into the cell and an outflux of K+ from the cell
Clopidogrel
antiplatelet agent that works by inhibiting the platelet surface ADP receptor
as efficacious as aspirin in the prevention of thromboembolic disease
PID
mucopurulent cervicitis with cervical motion tenderness is a frequent indicator of PID caused by N. gonorrhoeae or Chlamydia trachomatis
can potentially lead to ectopic pregnancy and infertility due to salpingitis leading to scarring of the fallopian tubes if not treated appropriately
protein structure
Primary: amino acids linked by covalent peptide bonds
Secondary: hydrogen bonds (ex. a-helix v B-sheet)
Wet age-related macular degeneration
characterized by retinal neovascularization due to increased vascular endothermal growth factor (VEGF) levels
Acute vision loss and metamorphosia (distorted lines)
fundoscopy showing a grayish-green subretinal membrane and/or subretinal hemorrhage
tx: smoking cessation and VGEF inhibitor (ranibizumab, bevacizumab)
Pyruvate dehydrogenase deficiency
presentations range from neonatal death to mild episodic symptoms in adulthood
by preventing the conversion of pyruvate to acetyl CoA, pyruvate is shunted to lactic acid resulting in lactic acidosis
Lysine and leucine are exclusively ketogenic and would not increase the blood lactate level in pts suffering from pyruvate dehydrogenase deficiency
Subarachnoid hemorrhage
occurs due to rupture of saccular (berry) aneurysm or arteriovenous malformation.
Severe vasospasm 4-12 days after the initial insult is the major cause of morbidity and mortality in pts recovering from SAH
Nimodipine (selective calcium channel blocker) is often prescribed to prevent this vasospasm
Sarcomere: H band
region of the sarcomere containing only myosin thick filaments
part of the A band on either side of the M line where myosin thick filaments do not have any overlapping actin thin filaments
Organ susceptibility to infarct after occlusion of a feeding artery:
Greatest to least -
Central nervous system, myocardium, kidney, spleen, and liver
The presence of 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
Shock + hyponatremia + hyperkalemia + hypoglycemia
adrenal crisis!
Meningococcal septicemia can cause adrenal hemorrhage leading to acute adrenal crisis
(Neisseria meningitidis septicemia + adrenal hemorrhage = Waterhouse-Friderichsen syndrome)
Differential cyanosis restricted to the lower body in a child
most suggestive of patent ductus arteriosus (PDA) with late onset reversal of shunt flow (from L-to-R to R-to-L)
Whole body cyanosis results when there is shunt reversal in pts with septal defects or tetralogy of Fallot.
Coarctation of the aorta can limit lower-extremity exercise tolerance but does not cause cyanosis in children or adults
Phrenic nerve
arises from the C3-5 segments of the spinal cord and innervates the ipsilateral hemidiaphragm
Intrathoracic spread of a lung cancer may irritate the phrenic nerve, causing hiccups and diaphragmatic paralysis with dyspnea
brachial plexus involvement can cause pain in the distribution of the C8, T1 and T2 nerve roots
Early visceral manifestation of systemic sclerosis
esophageal hypomotility and incompetence of the lower esophageal sphincter due to atrophy and fibrous replacement of the esophageal muscles
esophageal dilation causes reflux, which increases the risk of Barrett esophagus and esophageal adenocarcinoma
CREST
Calcinosis Raynaud Esophageal dysmotility Sclerodactyly Telangiectasia
Major determinant of whether a coronary artery plaque will cause ischemic myocardial injury
rate at which it occludes the involved artery
A slowly developing occlusion would allow for formation of collaterals that could prevent myocardial necrosis
A thin fibrous cap, rich lipid core, and active inflammation in the atheroma would all decrease plaque stability and thus potentially promote rapid coronary occlusion via superimposed thrombosis if the plaque were to rupture
Atopic dermatitis (eczema)
common chronic inflammatory skin disorder of childhood
presents with pruritis and erythematous, weeping/crusted papules and plaques that occur in response to certain environmental antigens
associated with other atopic diseases: allergic rhinitis, asthma
Glomangioma (benign glomus tumor)
can produce a very tender, small (mm diameter) red-blue lesion under the nail bed
originates from the modified smooth muscle cells that control thermoregulatory functions of dermal glomus bodies
Migraine headaches
unilateral, pulsatile or throbbing quality, associated with photophobia, phonophobia and nausea
Triptans are serotonin 5-HT agonists used as abortive therapy during an acute migraine
Beta blockers, antidepressants (amitriptyline, venlafaxine) and anticonvulsants (valproate, topiramate) are commonly used for migraine prophylaxis
Psoriasis tx
Topical vitamin D analogs (calcipotriene, calcitriol, and tacalcitol) bind to the vitamin D receptor (a nuclear transcription factor) and inhibit keratinocyte proliferation and stimulate keratinocyte differentiation
Desmopressin analog DDAVP
used in patients with von Willebrand disease because it induces endothelial procoagulatory protein release (including vWF). (It has a minimal effect on the V1 vasopressin receptor). Desmopressin can also be used for the treatment of enuresis
Atypical lymphocytes observed in peripheral blood smears of patients with infectious mononucleosis
(large, eccentric nucleus, cell membrane conforming to borders of neighboring cells)
activated CD8+ cytotoxic T-lymphocytes. These activated T-lymphocytes function to destroy virally infected B-lymphocytes
Isoniazid monotherapy
patients who have a positive PPD and a negative chest x-ray (no clinical disease)
Active tuberculosis is never treated with drug monotherapy due to the fast emergence of mycobacterial antibiotic resistance from rapid, selective gene mutations
Gallstone ileus
rare type of mechanical bowel obstruction caused when a large gallstone erodes into the intestinal lumen. Pneumobilia (air in the biliary tract) is suggestive of the diagnosis
medial femoral artery
provides the majority of the blood supply to the femoral head and neck; injury to this vessel can cause avascular necrosis of the femoral head
A femoral neck fracture can damage the blood supply to the femoral head and neck. This is most common with displaced fractures.
Silicosis
disruption of macrophage phagolysosomes by internalized silica particles. Macrophage killing of intracellular mycobacteria may be impaired as a result, causing increased susceptibility of patients with silicosis to pulmonary TB
Naloxone
pure opioid receptor antagonist used for treating opioid intoxication or overdose. Although it binds to mu, kappa and delta opioid receptors, it has the greatest affinity for mu receptors, making it an ideal agent for treating opioid intoxication. Mu receptors: physical dependence, euphoria, respiratory and cardiac depression, reduced GI motility, sedation
ascending limb of the loop of Henle
impermeable to water regardless of serum vasopressin levels. Reabsorption of electrolytes by the Na+/K+/2Cl- cotransporter occurs in the thick ascending limb and contributes to formation of the corticomedullary concentration gradient
Folic acid deficiency anemia
commonly occurs in the setting of chronic alcoholism. It is a megaloblastic anemia that develops due to decreased synthesis of purines and thymidine. The peripheral blood smear reveals macrocytosis, ovalocytosis and neutrophils with hypersegmented nuclei.
V/Q ratio - apex v base of lung
Perfusion greatly increases from the apex of the lung to the base; ventilation increases slightly from the apex to the base. Therefore, the ventilation/perfusion ratio (V/Q) decreases in the lung from apex to base
Cryptococcus neoformans
causes meningeocephalitis in HIV (+) pts. The latex agglutination test detects the polysaccharide capsule antigen of Cryptococcus and is used for diagnosis. India ink staining of the CSF shows round or oval budding yeast. Present in soil and pigeon droppings.
Splenic artery
originates from the celiac artery and gives off several branches to the stomach and pancreas (pancreatic, short gastric, and left gastroepiploic arteries) before finally reaching the spleen. Due to poor anastomoses, the gastric tissue supplied by the short gastric arteries is vulnerable to ischemic injury following splenic artery blockage.
Androgenic alopecia
most common cause of hair loss in both males and females, and demonstrates polygenic inheritance with variable penetrance. The pattern and severity of the baldness varies between males and females, and circulating androgen levels along with the degree of genetic predisposition are thought to play a prominent role in determining clinical manifestations
Fabry disease
inherited deficiency of alpha-galactosidase A that causes accumulation of the globoside ceramide trihexoside in tissues.
The earliest manifestations of Fabry disease are angiokeratomas (punctuate, dark red, non-blanching macules and papules that classically occur between the umbilicus and the knees), hypohidrosis and acroparesthesia (episodic, often debilitating, burning neuropathic pain in the extremities).
Without enzyme replacement, patients typically develop progressive renal failure.
RVH
Under normal circumstances, the right ventricular thickness is between 3-4mm during diastole, significantly thinner than the left ventricular wall thickness (1 cm).
RVH is a feature of cor pulmonale, a condition caused by pulmonary hypertension resulting from disease of the lung parenchyma or the pulmonary vasculature.
In young females between 20-40, primary pulmonary hypertension may be responsible for cor pulmonale.
Listeria tx
Ampicillin is the treatment of choice for Listeria (facultative intracellular organism). It is not sensitive to cephalosporins. Listeria causes disease in neonates and immunocompromised adults (deficiencies of cell-mediated immunity).
Cancer risk associated with ulcers
Duodenal ulcers are not associated with an increased risk of carcinoma in the same location. In contrast, esophageal, gastric, and colorectal cancers are frequently identified as ulcerative lesions on endoscopy. Ulcerative colitis is associated with increased risk of colorectal cancer
Aortic stenosis
A bicuspid valve is a common cause of aortic stenosis in the US.
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.
Mitral valve prolapse
mid-systolic click and late systolic murmur
A febrile upper respiratory illness in a child followed by sudden appearance of red, flushed cheeks approximately 2-5 days later
characteristic of erythema infectiosum (‘fifth disease’, parvovirus B19 infection – small, nonenveloped DNA virus). This virus is highly tropic for erythroid precursor cells and replicates predominantly in the bone marrow.
most common malignant hepatic lesion
metastasis from another primary site (breast, lung, colon), not hepatocellular carcinoma. The liver is the second most common site of metastatic spread after lymph nodes
Pulmonary actinomycosis
develops most commonly following aspiration and can be confused with lung abscess, malignancy, or TB.
Microscopic findings include filamentous, branching, gram-positive bacteria and sulfur granules.
Myocardial infarction: cardiac function curve
causes a sharp decrease in cardiac output due to loss of function of a zone of myocardium. On a cardiac function curve, myocardial infarction would decrease both the slope and the maximal height of the line
Sedation - drug side effect
First generation Hi-histamine receptor antagonists, including diphenhydramine (Benadryl) and chlorpheniramine, can cause significant sedation, especially when used with other medications that cause CNS depression (such as benzodiasepines)
Clostridium tetani
responsible for tetanus, a toxim-mediated disease that causes uncontrolled muscle spasms and respiratory failure. Toxin travels within the motor neuron by retrograde transport into the spinal cord where it causes inhibition of inhibitory interneurons and unregulated firing of primary motor neurons
secretion of prolactin
controlled by the inhibitory effect of hypothalamic dopamine. Hyperprolactinemia causes hypogonadism by inhibiting the release of gonadotrophin-releasing hormone from the hypothalamus. Rispiridone and other antipsychotics cause hyperprolactinemia by their antidopaminergic action
Vit D deficiency
The diarrhea caused by celiac disease can lead to vitamin D deficiency through malabsorption. Patients with vitamin D deficiency have decreased serum phosphorus, increased serum parathyroid hormone (secondary hyperparathyroidism), and low serum calcium. They may also have symptoms such as bone pain and muscle weakness.
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
Methadone
drug of choice for treating heroine addiction and abuse. It is a very potent, long acting opiate with good oral bioavailability. Its long half-life allows for prolonged effects to suppress withdrawal symptoms in heroin dependent patients
Isoniazid
chemically related to pyridoxine, also known as Vitamin B6. It inhibits mycolic acid synthesis in mycobacterial cells and is specific to the mycobacteria. Myocolic acid is a long branched chain saturated fatty acid used in the mycobacterial cell wall and in the formation of virulence factors
Calcification
Dystrophic calcification occurs in damaged or necrotic tissue in the setting of normal calcium levels; metastatic calcification occurs in normal tissues in the setting of hypercalcemia
Anorexia nervosa
eating disorder characterized by low body weight, intense fear of becoming fat, and distorted body image. Medical complications, including bradycardia, hypotension, osteoporosis, amenorrhea, and cardiac atrophy are a result of malnutrition and starvation
Nephritic / Nephrotic syndrome
Nephritic syndrome is manifested by hypertension, mild proteinuria (3.5g/day), lipiduria, absence of RBC casts in the urine, and usually normal renal function.
Opsoclonus-myoclonus
paraneoplastic syndrome associated with neuroblastoma. This tumor, associated with an increased number of copies of the N-myc gene, is the most common extracranial neoplasm in children.
Clinical presentation: retroperitoneal mass, hypertension, anorexia, weight loss, increased excretion of catecholamines in urine
Atrial myxoma
Constitutional symptoms, a mid-diastolic rumbling murmur heard best at the apex, positional cardiovascular symptoms (dyspnea, syncope), embolic symptoms, and a large pedunctulated mass in the left atrium
Histologically, these tumors are composed of scattered cells within a mucopolysaccharide stroma, abnormal blood vessels and hemorrhaging
Pure red blood cell aplasia
rare form of bone marrow failure characterized by severe hypoplasia of marrow erythroid elements in the setting of normal granulopoiesis and thrombopoiesis. Pure red blood cell aplasia (often involves the inhibition of erythropoietic precursors and progenitors by IgG autoantibodies or cytotoxic T lymphocytes) is associated with thymoma, lymphocytic leukemias, and parvovirus B19 infection
Fibrinolytics
may cause reperfusion arrhythmia on arterial re-opening. These arrhythmias are usually benign. Thrombolytic or bibrinolytic drugs increase clot lysis by increasing the formation of plasmin from plasminogen. Fibrinolytic drugs can be nonfibrin specific (like streptokinase) or fibrin-specific, such as tissue plasminogen activator (tPA), and reteplase, tenecteplase (these act only on fibrin attached to recently focmed clot, no systemic activation)
Viridans streptococci
normal inhabitants of the oral cavity and are a cause of transient bacteremia after dental procedures in healthy and diseased individuals. In order to cause subacute bacterial endocarditis they require preexisting valve damage leading to the local deposition of fibrin required for them to adhere
Acanthosis nigricans
thickening and hyperpigmentation of skin in the flexural areas. The lesions have a classic ‘velvety’ texture. Acanthosis nigricans is commonly associated with insulin-resistant states (diabetes mellitus, acromegaly, obesity) and gastrointestinal malignancies.
Acid maltase (alpha glucosidase) deficiency
leads to glycogen accumulation within lysosomal vesicles.
Clinical manifestations of this disease include hepatomegaly, cardiomegaly, macroglossia, hypotonia, and mental retardation in its most severe form
Secondary lactase deficiency
can occur after viral gastroenteritis or other diseases that damage the intestinal epithelium. This disease causes abdominal distention, flatulence, and diarrhea after lactose ingestion (lactose = galactosyl beta-1,4-glucose)
Propionyl CoA
derived from amino acids (Val, Ile, Met, Thr), odd numbered fatty acids and cholesterol side chains. 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
Autoimmune platelet destruction (immune thrombocytopenic purpura)
common cause of thrombocytopenia and should be suspected in patients with ecchymoses, petechiae, and mucosal bleeding without signs or symptoms of TTP/HUS, pancytopenia, marrow failure, or splenomegaly
Serotonin syndrome
Commonly used drugs such as the analgesic tramadol, the antiemetic ondansetron, and the antibiotic linezolid can induce serotonin syndrome (neuromuscular excitation, autonomic stimulation, altered mental status) when used concomitantly with other serotonergic drugs (many antidepressants)
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.
Pituitary tumor
Anytime a pt has bitemporal hemianopsia, a pituitary tumor should be suspected. The most common functional pituitary tumor is a prolactinoma. Secreting prolactinomas inhibit the entire axis of GnRH-LH/FSH-sex hormones, causeing impotence in men and amenorrhea in women of reproductive age (hypogonadotropic amenorrhea)
Folate deficiency
inhibits the formation of deoxythymidine monophosphate (dTMP), which limits DNA synthesis and promotes megaloblastosis and erythroid precursor cell apoptosis.
Because thymidine supplementation can moderately increase dTMP levels, it can reduce erythroid precursor cell apoptosis
Bartonella henselae
causes cat-scratch disease, bacillary angiomatosis and culture-negative endocarditis. Cat-scratch disease is characterized by low fever, lymphadenopathy and self-limited course
Course of the ureters
The ureters cross over the common / external iliac vessels and under the gonadal vessels (and uterine vessels in females). They lie anterolateral to the internal iliac vessels and medial to the ovarian vessels within the true pelvis
Bone pain and an elevated level of alkaline phosphatase in an elderly patient
suggestive of Paget disease of bone (PDB); biopsy showing a mosaic pattern of lamellar bone is diagnostic. The initial abnormality in PDB is an increase in the number and activity of osteoclasts (excessive RANK signaling and NF-kB activation), followed by increased osteoblastic activity and bony overgrowth
Small cell carcinoma (oat cell)
strongly associated with smoking and usually is centrally located. This tumor arises from the primitive cells of the basal layer of the bronchial epithelium. Immunohistochemical stains are frequently positive for neuroendocrine markers, such as neuron specific enolase, chromogranin and synaptophysin
treatment of choice for diabetic ketoacidosis
intravenous hydration with normal saline and insulin. These therapies will result in decreases in the serum glucose, osmolality, and potassium, as well as increases in serum bicarbonate and sodium.
Hep B virus
associated with a serum-sickness like syndrome (malaise, fever, skin rash, pruritis, lymphadenopathy, joint pain) in the prodromal period. ALT > AST, both elevated
Beta-thalassemia
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 who are heterozygous for these mutations are typically asymptomatic and have what is termed beta-thalassemia minor. Laboratory tests will show a mild hypochromic microcytic anemia with increased hemoglobin F, hemoglobin A2 and target cells
Essential fructosuria
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
GLUT-4
expressed primarily in muscle cells and adipocytes and is the major glucose transporter that is responsive to insulin
Benzodiazepines
substitute for the action of alcohol on GABA receptors and are indicated for the treatment of alcohol withdrawal. Long acting benzodiazepines (chlordiasepoxide, diazepam) are first line medications. Short acting Benzodiazepines (lorazepam, oxazepam) are preferred in patients with advanced liver dysfunction
Nontypable strains of Haemophilus influenzae
strains of H. influenza that do not form an antiphagocytic capsule. They are part of the normal flora of the upper respiratory tract, but can cause otitis media, sinusitis and bronchitis. Immunity to nontypable strains, as well as capsular strains other than type b, is not conferred by vaccination with the Hib vaccine (just memory B-lymphocytes, humoral immunity to Hib)
amiodarone: side effects
Thyroid function tests should be monitored in patients receiving amiodarone therapy (class III anti-arrhythmic agent used to suppress life threatening cardiac conduction abnormalities). Amiodarone is associated with many side effects: thyroid dysfunction, corneal micro-deposits, blue-gray skin discoloration, drug-related hepatitis and pulmonary fibrosis
staphylococcal scalded skin syndrome
occurs in infants and children due to the production of the exotoxin exfoliatin (EXfoliatin is an EXotoxin, not endotoxin) by Staphylococcus species. It causes widespread epidermal sloughing, especially with gentle pressure (Nikolsky’s sign)
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. Dephosphorylated Rb is active and does not allow the cell to proceed from G1 to the S stage of the cell cycle
Heart - anatomy
The left ventricle forms the apex of the heart and reaches as far as the fifth intercostal space at the left midclavicular line. All other chambers of the heart lie medial to the left midclavicular line. The lungs overlap much of the anterior surface of the heart
elevated CK
Hypothyroidism is a common cause of elevated creatinine kinase (CK) due to hypothyroid myopathy (myocyte damage and leakage of muscle enzymes). It can be the first manifestation of hypothyroidism. Other causes of elevated CK include autoimmune diseases (polymyositis, dermatomyositis), muscular hystrophies, and medications such as HMG-CoA reductase inhibitors
Antidepressant side effects
Antidepressants (such as Venlafaxine, a serotonin-norepi reuptake inhibitor) can induce mania in susceptible patients, especially those with unrecognized bipolar disorder. Patients treated with antidepressants should be monitored for mood elevation and symptoms suggestive of mania that require emergency treatment.
Zolpidem
short-acting hypnotic medication chemically unrelated to benzodiazepines (such as temazepam, estazolam, triazolam, flurazepam). It has the same mechanism of action as benzodiazepines, but a much lower risk of tolerance and dependence
Haemophilus influenzae type b (Hib) vaccine
contains bacterial capsular polysaccharide conjugated with diphtheria toxoid
Kallmann syndrome
an absence of GnRH secretory neurons in the hypothalamus due to defective migration from the olfactory placode. These patients have central hypogonadism and anosmia, and present with delayed puberty
Cocaine
acts as an indirect sympathomimetic by inhibiting the presynaptic reuptake of norepinephrine, dopamine, and serotonin. Intoxicated pts 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
Clozapine
Unlike other traditional antipsychotics, which act on D2 receptors, clozapine acts on D4 receptors.
Effective in tx of treatment-resistant schizophrenia.
Due to the risk of life-threatening agranulocytosis with clozapine, the FDA requires periodic monitoring of the WBC count for the duration of treatment. The other important side effect of clozapine is seizures
An old infarct (months or years since onset of ischemia)
consists of a cystic cavity surrounded by a dense wall. The wall of this cyst is formed by astrocyte processes
Winging of the scapula
serratus anterior muscle serves to fix the scapula against the posterior chest wall and rotate the scapula to allow abduction of the arm over the head.
Paralysis of this muscle occurs with injury to the long thoracic nerve and results in winging of the scapula
Adrenal insufficiency
Depression of the entire hypothalamus-pituitary-adrenal axis by glucocorticoid therapy is the most common cause of adrenal insufficiency. Adrenal crisis can be precipitated in these patients under stressful situations (infections, surgery) if their glucocorticoid dose is not appropriately increased
Nitrate drugs (like nitroglycerin infusion)
mimic the action of endothelial derived relaxing factor (nitric oxide, NO). They are transformed to NO at the vascular smooth muscle cell membrane which leads to increased cGMP, decreased intracellular calcium and myosin dephosphorylation (→ pain relief and decreased BP)
Actinic keratosis
develops on chronically sun-exposed areas of the skin in predisposed individuals. The lesions consist of erythematous papules with a central scale and a rough ‘sandpaper-like’ texture. AKs are considered premalignant lesions and have the potential to progress to squamous cell carcinoma
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. Later, muscle fibers of the distal extremities are replaced by fat and connective tissue (pseudohypertrophy)
Enterococci
produce aminoglycoside-modifying enzymes that transfer different chemical groups (acetyl, adenyl or phosphate) to the aminoglycoside molecule and therefore impair antibiotic binding to ribosomal subunits
Pericarditis
In contrast to angina, the chest pain of pericarditis is sharp and pleuritic, and may be exacerbated by swallowing or relieved by leaning forward.
Early-onset pericarditis develops in about 10-20% of patients between days 2 and 4 following a transmural myocardial infarction. It represents an inflammatory reaction to cardiac muscle necrosis that occurs in the adjacent visceral and parietal pericardium.
Late-onset post-MI pericarditis (Dressler’s syndrome) begins one week to a few months following the MI, and affects less than 4% of cases. Dressler’s syndrome is thought to be an autoimmune polyserositis
Theca and granulosa cell functions
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
Scarlet fever
characterized by fever, pharyngitis, sandpaper-like rash, circumoral pallor, and a strawberry tongue. It is caused by strains of Group A streptococcus that produce pyrogenic exotoxins. Scarlet fever can predispose to acute rheumatic fever and glomerulonephritis
alpha-1-antitrypsin deficiency
should be suspected in all patients with premature onset (
Acute bacterial arthritis
Acute bacterial arthritis in sexually active young adults is commonly caused by Neisseria gonorrhoeae, which are facultative intracellular organisms often seen within neutrophils
Holoprosencephaly
results from failure of forebrain cleavage into cerebral hemispheres.
It is an example of a congenital malformation, a primary abnormality in a development process.
Disruption v deformation v sequence
Amniotic band syndrome is an example of a disruption (secondary destruction of a previously well-formed tissue or organ)
Congenital hip dislocation, clubbed feet and flat facies (Potter syndrome) are examples of deformations (secondary to extrinsic compression)
Potter syndrome is also an example of a sequence (number of abnormalities from a single defect – oligohydramnios, low volume of amniotic fluid)
Screening test for primary hypothyroidism
Serum TSH level is the most sensitive
Although TSH is not elevated in patients with central hypothyroidism, this form of hypothyroidism is uncommon and usually occurs in pts with hypothalamic or pituitary dysfunction
Holosystolic murmur that increases with intensity on inspiration
most likely represents tricuspid regurgitation
tricuspid regurg is loudest near the left lower sternal border
(Mitral regurg and VSD do not typically increase with inspiration)
Negative predictive value
probability of not having a disease given a negative test result
varies based on prevalence (inversely proportional)
NPV = d/(c+d)
systems-based approach to addressing problems in the hospital
Root cause analysis is a quality improvement measure that identifies what, how and why a preventable adverse outcome occurred. It involves collecting data mainly through interviewing multiple individuals involved in the steps leading to the outcome
Hernias
Indirect inguinal hernias are located lateral to the inferior epigastric vessels. They can continue into the scrotum and are felt by deep palpation of the external inguinal ring with the tip of the finger
Direct inguinal hernias are located medially to the inferior epigastric vessels. They do not protrude into the scrotum and are best felt with the pulp of the finger
Phrenic nerve
Irritation of the mediastinal or diaphragmatic parietal pleura will cause sharp pain, worse on inspiration, in the C3-C5 distribution. Pain sensation from these areas is carried by the phrenic nerve
Glioblastoma multiforme
most common primary brain tumor in adults
areas of necrosis and hemorrhage seen on gross exam
light micrsoscopy shows pseudopalisading tumor cells around areas of necrosis
Effect of stimulation of the vagus nerve branches that supply the lung
bronchoconstriction and increased bronchial mucus secretion (ACh acts on M3)
These effects increase airway resistance and the work of breathing
Anticholinergic agents such as tiotropium and ipatropium work to counteract these effects
Nondisjunction
failure of chromosome pairs to separate properly during cell division. This could be due to failure of homologous chromosomes to separate in meiosis I or failure of sister chromatids to separate during meiosis II or mitosis
Hypo- or hyperpigmented skin patches that become more visible after tanning
characteristic of pityriasis versicolor, a condition caused by Malassezia furfur. KOH preparation of skin scrapings reveals a ‘spaghetti and meatballs’ appearance on light microscopy
Maple syrup urine disease (MSUD)
caused by a defect in a-keto acid dehydrogenase, leading to an inability to degrade branched chain amino acids beyond their deaminated a-keto acid state
classically results in dystonia and poor feeding as well as the ‘maple syrup scent’ of the pts urine within the first few days of life
tx: dietary restriction of branched-chain amino acids
Optic nerve, light reflex
The afferent limb of the light reflex pathway is the optic nerve
The efferent limb is the parasympathetic fibers of the oculomotor nerve
When an optic nerve is damaged, light in that eye will cause neither pupil to constrict (the nerve can’t sense the light). However, light in the contralateral eye will cause both pupils to constrict (because the motor pathways are intact)
Digitalis: mechanism of action
inhibition of the Na-K-ATPase in cardiac pacemaker cells leading to AV nodal blockade (increased diastolic filling time for greater contraction by the Frank-Starling mechanism) and increased contractility from increased intracellular calcium
most common cause of calcium kidney stone disease
idiopathic hypercalciuria
normal serum calcium levels with high levels of Ca++ excreted in the urine
other causes of calcium nephrolithiasis include hyperoxaluria, hyperuricosuria, low urinary volume, and hypocitraturia
Hemoglobin S (HbS) - sickling
aggregated in the deoxygenated state
HbS polymers form fibrous strands that reduce RBC membrane flexibility and promote sickling.
Sickling occurs under all conditions associated with anoxia including low pH and high 2,3-DPG.
These inflexible erythrocytes predispose to microvascular occlusion and microinfarction
Diphenoxylate
opiate anti-diarrheal structurally related to meperidine. It binds to mu opiate receptors in the GI tract and slows motility. Low therapeutic doses allow for potent anti-diarrheal effects without euphoric effects. Since higher doses can lead to euphoria and physical dependence, the drug is combined with atropine at therapeutic doses to discourage abuse
Octreotide
helpful for secretory diarrhea
Polycythemia vera (PV)
clonal myeloproliferative disease of pluripotent hematopoietic stem cells
increased RBC mass, increased plasma volume, low erythropoietin levels
majority of pts have a JAK2 V617F mutation, rendering te hematopoietic stem cells more sensitive to growth factors
secondary polycythemia is a misnomer (only red cells increase, not all). Should be called secondary erythrocytosis
Normal (adult) pressures in the cardiac chambers and pulmonary artery (mmHg)
RA: 0-8 RV: 4-25 PA: 9-25 LA: 2-12 LV: 9-130 Aorta: 70-130
impaired CFTR transmembrane protein
Respiratory and gastric glands: reduces luminal Cl- secretion and increases Na+ and net water absorption, resulting in dehydrated mucus and a more negative transepithelial potential difference
Sweat glandsL reduced luminal salt absorption, leading to the production of hypertonic sweat with high Cl- content
Hepatitis E
unenveloped, single-stranded RNA virus spread through the fecal-oral route
high mortality rate observed in infected pregnant women
Aspergillus fumigatus infection
this fungus produces thin, septate hyphae with acute V-shaped branching. It causes invasive aspergillosis, aspergillomas, and allergic pulmonary aspergillosis
Immunosuppressed pts are at risk
Hemosiderin-laden macrophages in pulmonary alveoli
indicates chronic elevation of pulmonary capillary hydrostatic pressures, which is usually the result of left-sided heart failure
Golden cytoplasmic granules that turn dark blue with Pussian blue staining (Prussian blue stain detects intracellular iron)
Vibrio cholera and enterotoxigenic Escherichia coli
cause a purely toxin-mediated watery diarrhea
toxins secreted by these organisms modify electrolyte handling by enterocytes but do not cause cell death, therefore no erythrocytes or leukocytes are typically noted on stool microscopy
Class 3 antiarrythmic agents (ex. dofetilide)
block potassium efflux from cardiac myocytes and prolong phase 3 of the myocyte action potential
Loss of conciousness from severe hypoglycemia tx
intramuscular glucagon in the nonmedical setting and intravenous dextrose in the medical setting
Second generation antihistamines
fexofenadine - minimal sedative and antimuscarinic effects
v 1st gen: hydroxyzine, promethazine, chlorpheniramine, diphenhydramine
lymphokines -
Sensitized Th2 cells secrete IL-4 and IL-13, which together promote B-lymphocyte class switching for IgE synthesis. They also secrete IL-5, which activates eosinophils and promotes IgA synthesis
An excess of these Th2-produced lymphokines may contribute to the pathogenesis of extrinsic allergic asthma
IL-1 is secreted by macrophages to stimulate helper T-cells
IL-3 from helper T-cells recruits bone marrow stem cells
y-interferon from helper T-cells functions mainly to activate macrophages
TGF-B is a growth factor involved in tissue regeneration and repair
Kidney stone formation
Renal calculi occur when there is an imbalance of factors that facilitate and prevent stone formation
increased concentration of calcium, phosphate, oxalate, and uric acid promotes salt crystallization, wheras increased citrate and high fluid intake help prevent calculi formation
Dobutamine
relatively selective B1-adrenergic agonist that increases heart rate, contractility, conduction velocity and myocardial oxygen consumption
used in the tx of acute heart failure associated with decreased myocardial contractility (cardiogenic shock)
Type II diabetes: defects of the KATP channel gene
ATP is the regulatory substance that stimulates KATP channel closure in insulin-producing pancreatic beta cells
(closure –> depolarization –> opening of voltage gated Ca++ channels –> insulin release)
D-Ala-D-Ala
amino acid sequence on peptidoglycan precursor molecules that is recognized by the enzyme transpeptidase
Penicillins are structural analogs of D-Ala-D-Ala that inhibit this enzyme by binding convalently to its active site. The result is failed synthesis of the bacterial peptidoglycan wall
Mifepristone
anti-progestin agent that can be used to terminate early pregnancy
The prosteglandin-E1 analogue (–> uterine contraction and cervical dilation), misoprostol, is available for clinical use in combination with the abortifactant, mifepristone
Jervell and Lange-Nielsen syndrome
one of the most common congenital long-QT syndromes. This is an autosomal recessive condition which is accompanied by congenital neurosensory deafness. QT-interval prolongation predisposes to syncopal episodes and possible sudden cardiac death due to torsades de pointes
Verrucous endocarditis (Libman-Sacks endocarditis)
occurs in up to 25% of pts with systemic lupus erythematosus (SLE)
can cause small cardiac valvular vegetations on either side of a valve, resulting in fibrotic valve thickening and deformity
may cause an acute coronary syndrome at a young age even with angiographically normal coronary arteries
Secretin
Pancreatic exocrine secretions are the major source of bicarbonate entering the duodenum
Secretin is the hormone that stimulates the release of bicarbonate-rich secretions from the exocrine pancreas. Secretin is produced by S enteroendocrine cells in the duodenal mucosa in response to stimulation by intraluminal acidity. Hydrochloric acid is the most potent stimulus for secretin release
Pancreatic islet amyloid deposition
characteristic of type 2 diabetes mellitus
A strong linkage with HLA class II gene makeup (DR3, DR4), pancreatic islet infiltratio with leukocytes (insulitis) and antibodies against islet antigens are frequently seen in type 1 diabetes
Males with classic, non-salt wasting 21-hydroxylase deficiency
present at age 2-4 years with early virilization, increased linear growth, elevated levels of 17-hydroxyprogesterone and androgens
Females with classic 21-hydroxylase deficiency (with or without salt-wasting) present with ambiguous genitalia at birth
Congenital adrenal hyperplasia tx
low doses of exogenous corticosteroids to suppress excessive ACTH secretion and reduce stimulation of the adrenal cortex
Erythropoietin
Renal cortical cells sense hypoxia and respond by synthesizing and releasing erythropoietin. Erythropoietin stimulates the production of erythrocytes in the bone marrow
middle-aged Caucasian female with a long history of pruritis and fatigue who now develops pale stool and xanthelasma (suggestive of cholestasis)
Classic picture of primary biliary cirrhosis (PBC)
chronic liver disease characterized by autoimmune destruction of the intrahepatic bile ducts and cholestasis
Herpes zoster (shingles)
develops due to reactivation of varicella-zoster virus in the dorsal root ganglia (sensory neurons)
presents with painful vesicular rash in a dermatomal distribution
Light microscopy: intranuclear inclusions in keratinocytes and multinucleated giant cells are seen
blood/gas partition coefficient
The onset of action of a gas anesthetic depends on its solubility in the blood (blood/gas partition coefficient).
Drugs with high blood/gas partition coefficients are more soluble in the blood, demonstrate slower equilibration with the brain and have longer onset times
mitochondrial DNA (mtDNA)
most common non-nuclear DNA found in eukaryotic cells
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
oxidative reactions of the HMP
necessary for anabolic reactions that use NADPH as an electron donor (including cholesterol and fatty acid synthesis). In addition, NADPH produced via the HMP shunt is the only method of reducing glutathione (and thus repairing oxidative damage) available to red blood cells
carboxy terminal of the Fc portion of the heavy immunoglobulin chains
site that binds to the Fc receptors on neutrophils and macrophages. Antibody bound to antigen is able to signal for the phagocytosis of that antigen by a conformational change of the Fc region allowing binding to the Fc receptor on phagocytes. This leads to subsequent phagocytosis of the organism / antibody complex and subsequent destruction of the organism
Hep A
most commonly silent or subclinical (‘anicteric’) in young children but can also present as an acute, self-limited illness characterized by jaundice, malaise, fatigue, anorexia, nausea, vomiting, right upper quadrant pain, or an aversion to smoking (would have anti-hep A IgG positive, current infection would be anti-HAV IgM)
Silicosis
Of the pneumoconiosis that can cause exertional dyspnea and interstitial densities on chest x-ray, silicosis is the only one that produces eggshell calcifications of hilar nodes and birefringent particles surrounded by fibrous tissue on histologic exam.
pneumoconiosis
o Asbestosis is associated with calcified pleural plaques and ferruginous bodies.
o Berryliosis and hypersensitivity pneumonitis may produce noncaseating granulomas.
o Coal miner’s lung is associated with perilymphatic accumulations of coal dust-laden macrophages
Wide, fixed splitting of the second heart sound
characteristic auscultatory finding in patients with ASD. A hemodynamically significant ASD can produce chronic pulmonary hypertension as a result of left-to-right intracardiac shunting.
Eisenmenger syndrome is the late-onset reversal of a left-to-right shunt due to pulmonary vascular sclerosis resulting from chronic pulmonary hypertension. Closure of the ASD may be required to prevent irreversible pulmonary vascular sclerosis and a permanent Eisenmenger syndrome
thalamic syndrome
total sensory loss on the contralateral side of the body. Although there are no motor deficits, proprioception is often profoundly affected and may lead to difficulty ambulating and falls.
brain lesions
o Frontal cortex lesions – deficits of higher brain functioning, creativity, sexual interest, social behavior
o Internal capsule – motor deficit
o Pons – coma, bilateral paralysis, decerebrate rigidity, pinpoint pupils, death
o Caudate nucleus – transient hemiparesis, frontal lobe symptoms (inattentiveness, forgetfulness), agitation, psychosis, choreoathetosis, dyskinesias
Lacunar infarctions
result of small vessel lipohyalinosis and atherosclerosis involving the penetrating vessels supplying the deep brain structures. Uncontrolled hypertension and diabetes mellitus are risk factors for this condition
Type 1 slow twitch muscles
Postural skeletal muscles such as the soleus and paraspinal muscles contain predominantly Type 1 slow twitch, red muscle fibers that derive ATP primarily from oxidative (aerobic) metabolism (so high myoglobin (oxygen storage) and mitochondrial (aerobic respiration) concentrations). Low level sustained force.
Type II are specialized for rapid, forceful pulses of movement
Myasthenia gravis
autoimmune disease that results in a decrease in functional acetylcholine receptors on the postsynaptic terminal of the neuromuscular junction.
This results in decreased ability of acetylcholine to bind and open postsynaptic cation channels, thereby decreasing the end-plate potential and preventing the formation of muscular action potentials.
o Fluctuating weakness of certain voluntary muscles (particularly innervated by motor nuclei of brainstem)
o Progressive weakening of muscle groups over course of day / with exercise
o Decreased compound muscle action potential amplitude on EM with repeated excitation
o Rapid restoration of strength of affected muscle with rest
o Improvement in strength following administration of cholinesterase inhibitors
o Caused by autoantibodies against postcynaptic nicotinic acetylcholine receptors
myasthenia gravis tx
cholinesterase inhibitors, immunosuppressants, and possible thymectomy. Cholinesterase inhibitors may cause adverse effects related to muscarinic overstimulation, which can be ameliorated by use of an antimuscarinic agent such as scopolamine (doesn’t affect nicotinic receptors in skeletal muscle)
Vitamin supplements for breastfed newborns
The breast milk content of vitamins D and K is typically insufficient for the nutritional needs of the newborn. Vit K is given parenterally at birth to prevent hemorrhagic disease in the newborn. Exclusively breastfed infants may develop vit D deficiency due to lack of sun exposure
Cause of anaplastic crisis
In pts 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 non-enveloped, single-stranded DNA virus
