S-UW Flashcards
Cardiac tissue conduction velocity
Purkinje system -> atrial muscle -> ventricular muscle -> AV node
Globus hysterecticus
Sensation of “lump in the throat”
DNA Laddering
Appearance of DNA fragments in mutiples of 180 bp’s on electrophoresis d/t endonucleases; indicates apoptosis
Anticholinergic SE’s
Antihistamines, antipsychotics, tricyclic antidepressants
Popliteal injury
Penetrating trauma: tibial nerve injury
Dislocation of knee joint: popliteal artery (fixed deep in the fossa)
Light’s Criteria
Pleural fluid protein/Serum protein > 0.5
Pleural flud LDH/Serum LDH > 0.6, PF LDH > 2/3 normal serum LDH
Myasthenia Gravis
Associated with thymoma
Intraventricular hemorrhage
Prominent cause of brain injury in premature infants (
Palmitoylation
Process by which FA’s are covalently anchored to plasma membranes –> increased hydrophobicity
Bacterial drug resistance
Antibiotic efflux pumps are commonly driven by a H+ gradient
Pulmonary Embolism
Causes hypoxemia 2ndry to V/Q mismatch –> hyperventillation
ABG: increased pH, decreased PaCO2, Decreased PaO2
Platelet Activating Factor (PAF)
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Activates platelets via Gq -> PLC -> calcium release
Whipple Disease
Infection with Tropheryma whipplei (G+)
PAS + foamy macrophages in intestinal lamina propria
Cardiac, Arthralgias, Neuro sx’s (Foamy whipped cream in a CAN)
Unmyelinated nerve fibers
Heat, slow pain, olfaction, autonomic postganglionic nerves
Aseptic meningitis
Enteroviruses (part of the picornavirus family): poliovirus, coxsackie A/B, echovirus, enterovirus, hepatitis A
Symptoms of anemia
Weakness, fatigue, headache, irritability, glossal pain, dry mouth, atrophy of tongue papillae, alopecia
Lichen Sclerosus et atrophicus
Autoimune; atrophic white macules/patches that begin with “cigarette paper” quality; cause pain, pruritis, dyspareunia, dysuria
Imperforate hymen
One of the most common obstructive lesions of thte female GU
Presents as absent menses in an eugonadotropic female
Hematocolpos –> vaginal distension, back pain, difficulty urinating
Increased risk or osteoporosis
Anticonvulsants that induce CYP450 (incr. vitamin D catabolism)
Aromatase inhibitors, Medroxyprogesterone (decr. Estrogen)
GnRH agonists (decr. T/estrogen), PPI’s (decr. Calcium absorption)
Glucocorticoid, heparin, thiazolidinedione (Decr. Bone formation)
VIPoma
Causes watery diarrhea, hypokalemia, achlorhydria
Influenza vaccine
Injectable variant is killed - induces neutralizing Ab’s against the HA antigen preventing binding to sialylated receptors + endocytosis
Fat embolism
Classic triad: respiratory distress, neurlogical sx’s, petechial rash
Functional regurgitation
Volume overload -> LV dilation -> functional mitral regurgitation; Reduction of LV preload w/diuretics –> disappearance of murmur
Secondary bacterial pneumonia
Patients > 65 are prone to 2 bacterial pneumonia after the flu
Pathogens: S. pneumo, S. aureus, H. influenzae
Liver clearance
Drugs w/high intrinsic hepatic clearance have high VOD, high lipophilicity (reabsorbed at kidney, easily enter hepatocytes)
Tumor grading
Bromodeoxyuridine is a thymidine analog that is taken up in high amounts during the S phase by high-grade tumors
Serotonin syndrome
Neuromuscular excitation, autonomic stimulation, AMS
Antidote: cyproheptadine (5-HT2 receptor antagonist)
Methemoglobinemia
Nitrates can oxidize ferrous iron (Fe2+) to ferric iron (Fe3+)
Methemoglobin cannot bind O2; causes a left shift on the O2 curve
Cachexia
TNF-_ from M_ is main mediatior of paraneoplastic cachexia (also causes fever, septic shock, acute-phase protein release)
Inheritance patterns
Structural abnormalities are generally autosomal dominant (hered. spherocytosis), enzyme deficiencies are autosomal recessive
Nucleosome
Histone H1 binds segments of DNA between nucleosomes, forms more compact structures (not part of the nucleosome)
Conn’s syndrome
Aldosterone-secreting adrenal adenoma –> HTN, hypokalemia (muscle weakness), metabolic alkalosis (paresthesias)
Ethylene glycol poisoning
Metabolized to glycolic acid (toxic to renal tubules) and oxalic acid (precipitates as calcium oxalate crystals) –> anion gap metabolic acidosis, osmolar gap
Henoch-Schonlein purpura
Childhood post-infectious vasculitis; often follows URI
Palpable purpura on butt/legs, arthralgias, abdominal pain
Associtaed with IgA nephropathy (Berger disease)
Develops in 2-3 days vs. 2-3 weeks for post-infectious nephritis
Chemoreceptors
Central: respond to decr. pH in CSF (H+ generated by incr. PaCO2)
–> decreased sens. in COPD (O2 sup. affects periph -> decr. resp.)
Peripheral: stimulated by decr. PaO2, incr. PaCO2/blood pH
Estrogen effect on TBG
High estrogen states increase TBG by decreasing catabolism –> increased total T4 but normal free thyroid hormone
Nursemaid’s elbow
Traction on outstretched arm -> Radial head subluxation -> annular ligament tear; most common elbow injury in children
Medial pontine lacunar stroke
Anterior pontine infarcts can affect corticospinal, corticobulbar and cerebellar tracts tracts; trigeminal nerve exits at this level
Overflow incontinence
D/t impaired detrusor contractility or bladder outlet obstruction; diabetic autonomic neuropathy or tumor/prostate obstruciton
Complications: nocturla enuresis, incr. postvoid residual volume
AV shunts/fistulas
Abnormal communication between artery/vein bypasses capillary resistance –> incr. cardiac preload, decr. Afterload
Nephrotic syndrome
Pathogenesis: increased permiability of glom to protein -> decreased plasma oncotic pressure -> fluid shift into interstitum -> increased aldosterone/ADH/liver protein synth. -> hyperlipidemia
Antimuscarinic side effects
Atropine, tricyclic antidepressants, H1 antagonists, neuroleptics, antiparkinsonian drugs
Lyonization
X-inactivation: 1 copy is condensed into heterchromatin, consisting of heavily methylated DNA and deacetylated histones –> low level of transcriptional activity
Diabetic neuropathy
Non-enzymatic glycosylation –> endoneural areriole hyalinization
Intracellular hyperglycema –> osmotic damage
Primary Myelofibrosis
JAK2 mutataion -> atypical megakaryocyte hyperplasia -> fibroblast activation -> replacemnet of marrow space by collagen deposition
Pancytopenia -> extramedullary hematopoesis -> dacrocytes
Causes of aplastic anemia
Carbamazepine, chloramphenicol, sulfonamides, PTU, methimazole
Bosentan
Endothelin-receptor antagonist that acts to vasodilate lung vasculature and block endothelial proliferation; treat PAH
Kallman syndrome
Congenital deficiency of GnRH: presents with anosmia
Demyelination
Leads to decrease in length constant: how far an impulse can prop.; results from increased charge dissipation along the axon
Increase in time constant: time for a change in potential to occur; results from decreased membrane capacitance
Cheyne-Stokes respiration
Cyclic breathing with apnea followed by incr./decr. tidal volumes
d/t slow respiratory feedback loop, enhanced response to PaCO2
Cause: cardiac disease (CHF), neurologic disease
Pancytopenia + splenomegaly
Ddx: B12/folic acid deficiency, aleukemic leukemia, myelodysplatic syndrome (aplastic anemia)
Thionamide toxicity
Methimazole/PTU carry the risk of developing agranulocytosis; patients taking these meds when presenting with fever/sore throat should be evaluated with a CBC w/diff and drugs should be stopped
Thyrotoxicosis
Propranolol contributes to decreased sympathetic outflow/_ blockade, as well as decreased peripheral conversion T4 -> T3 through inhibition of iodothyronine deiodinase
Ataxia-telangietasia
Triad: Cerebellar ataxia (poor smooth pursuit), telangiectasias, increased risk of sinopulmonary infections (IgA deficiency)
Autosomal recessive mutataion in ATM: DNA break repar
Tetrahydrobiopterin (BH4)
Cofactor in the synthesis of tyrosin/dopa and serotonin
Deficiency results in a form of PKU
S3 Heart sound
Ventricular gallop, d/t LV systolic failure; blood rushing into partially filled or very stiff ventricle; best heard in the LL decubitus position, and at the end of expiration
Hepatitis E
Enteric, expectant mothers epidemic; High mortaility in pregnant women; unenveloped RNA virus (not destroyed by gut)
Scabies
D/t infestation by Sarcoptes scabiei mite; type IV hypersensitivity
Causes rapidly spreading pruritic rash w/erythematous papules/ excoriations, linear burrows, crusting on the extremities/hands
Hereditary angioedema
Caused by C1 esterase inhibitor deficiency
C1EI suppresses actiation of complement, inactivates kallikrein
Ace inhibitors are a contraindication (cause angioedema)
Psoriasis histology
Hyperparakeratosis, acanthosis, rete ridge elongation, mitotic activity above basal cell layer, reduced/absent stratum granulosum, dilated BV’s above the dermal papillae, clustered neutrophils
DRESS
Drug reaction with eosinophilia and systemic symptoms: occurs 2-8 weeks post exposure - anticonvulstants, allopurinol, sulfonamides, antibiotics
_-blocker overdose
Antidote: Glucagon - Activates Gs receptors on cardiac myocytes -> incr. intracellular cAMP, calcium release to inrc. SA node firing
Sound transduction
TM vibration -> oval window vibration via ossicles -> movement of perilymph in scala vestibuli -> transmit to scala tympani -> basilar membrane vibration -> bending of hair cell cilia -> high frequency transmission at base, low at apex (helicotrema) of cochlea
Acetylation
Polymorphism in drug metabolizing capacity leads to 2 distinct groups w/I in the population: fast and slow acetylators; this leads to a bimodal distribution of drug metab. for drugs such as isoniazid
JG Cells
Modified smooth muscle cells with renin-containing zymogen granules located in the wall of the afferent arteriole; hypertrophy/ hyperplasia with renal hypoperfusion
Crohn’s Disease
Terminal iluem commonly involved: decr. bile acid reabsorption -> loss in feces -> impaired fat absorption -> incr. calcium excretion -> decreased oxalate excretion -> oxalate kidney stones
Payment Plans
Capitation: physicians are paid a fixed amount per enrollee, not per service; carries incentive to contain costs/provide preventative care
MELAS
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; presents with seizure disorder, stroke-like episodes, lactic acidosis. Can demonstrate heteroplasmy
Sorbitol metabolism
Polyol pathway: aldose reductase followed by sorbitol dehydrog. convert glucose -> sorbitol ->fructose, predominantly in seminal vessicles, lense; with prolonged hyperglycemia sorbitol accumuliates increasing osmotic pressure -> cataract formation
Heart failure cells
Golden/yellow/brownish cytoplasmic granules in the alveoli that turn dark blue with Prussian blue staining = hemosiderin-laiden macrophages (“heart failure cells”) that result from L heart failure
Respiratory Epithelium
Anterior epiglottis/upper 1/2 of posterior epiglottis/vocal folds are stratified squamous epithelium; majority of the respiratory tract is pseudostratified, columnar, mucus-secreting epithelium
Fragile X Syndrome
Full mutations of > 200 CGG repeats on the FMR1 gene result in hypermethylation of the FMR gene, leading to gene inactivation; X-chromosome appears thin or “fragile” when karyotype
SIADH
Incr. ADH -> incr. H20 absorption -> suppression of renin-aldosterone -> natriuresis -> clinically normal body fluid volume + low plasma osmolality
Pacemaker potential
Adenosine/acetylcholine act on phase 4: reduce rate of spontaneous depolarization in pacermaker cells via activation of K+ channels (which opposed iNa+), prolonging time taken to reach threshold
Readioactive iodine exposure
Tx: Potassium iodide; High serum levels of non-radioactive iodide can competitively inhibit entry into thyroid follicular cells; also,
Wolff-Chaikoff effect: high iodide level inhibits iodine organification
Hematogenous osteomyelitis
Predominantly affects children, affets the metaphysis d/t slow-flowing sinusoidal vasculature; microbial seeding -> bone ischemia -> necrosis -> osteomyelitis
Suspect in a child who refuses to use a limb, signs of infection
Thiopental
Short-acting barbiturate/general anesthetic; highly lipid soluble: equilibrates in brain tissue w/I 1 min, causes LOC; Redistribution into fat/skeletal muscle (not metabolism) -> recovery
Adrenal crisis
Response to stress in patients with adrenal insufficiency -> shock- like state; present with hypotension, tachycardia, hypoglycemia
Tx: Corticosteroid
Hx: vomiting, abdominal pain, weight loss, hyperpigmentation
Mu opioid analgesics
Can cause contraction of smooth muscles in the sphincyer of Oddi leading to increased pressure, biliary colic
Acute acalculous cholecystits
Acute inflammation in the absence of gallstones; seenin hospitalized patients with severe injuries/conditions; arises secondary to stasis and ischemia; Tx: antibiotics, cholecystectomy
Vitamin D Deficiency
Classic presentation: bony prominence at costochondral junctions, “rosary chest”, bowed legs;Histology: increased unmineralized osteoid around trabeculae, widening between osteoid seams
PCWP
RA: 0-8, RV: 4-25, PA: 9-25, LA: 2-12, LV: 9-130, Aorta: 70-130
Amphotericin B
Nephrotoxicity is the most dangerous adverse effect; increase in permeability of DT -> hypokalemia/hypomagnesemia -> weakness, arrhythmias (flat T wave, ST depression, U waves, PVCs)
Polymyalgia Rheumatica
Bilateral stiffness of shoulders/pelvic girdle, fever, weight loss, ESR
Associated with temporal arteritis
TCA’s
Inhibit fast sodium channel conduction resulting in arrhythmias; Vfib most common cause of death in TCA toxicity
Tx: fluid resuscitation, hypertonic sodium bicarb
Familal Chylomicronemia
LPL deficiency; normally bound to heparin sulfate moieties on vascular endothelium - heparin admin causes release allowing for acitvity level to be measured; presents with milky plasma/creamy supernatant, hypertrigs, acute pancreatitis, lipemia retinalis
Huntington Disease
Transcriptional repression is a proposed mechanism of mutated huntington protein: inhibition of histone acetyltransferase -> histone deacetylation -> prevention of transcription/gene silencing; also involves a deficiency in GABA, increased dopamine
Elastase
Both macrophages and nuetrophis secrete elastase; macrophage elastase is inhibited by TIMP, neutrophil by _1-antitrypsin; each elastase can degrade the other’s inhibitor -> additive destruction
IFN_/_
Synthesized in response to viral infection –> suppress viral replication/induce apoptosis of infected cells; induce infected neighboring cells to halt protein synthesis in presence of dsRNA
Also induce MHC I expression, stimulate NK/Cytotoxic T-cells
Acute leukemia
Patients typically present with sx’s of pancytopenia
Anemia: fatigue; Leukopenia: oppostunistic infections; Thrombocytopenia: bleeding
Ischemia
Ischemia -> deplation of intracellular ATP stores -> NA+/K+ ATPase dysfuntion -> dissipation of resting transmembrane potential -> extracellular K+/intracellular Ca2+ accumulation
Mcardle Disease
Glycogen storage disease type V; deficiency in muscle glycogen phosphorylase: muscle pain on exertion, rhabdomyolysis -> myoglobinuria; Tx: Vitamin B6
Hypokalemia EKG changes
QT prolongation, U-waves, ST depression, potentially torsades
Kluver-Bucy Syndrom
Primarily involves the amygdala; inappropriate sexual activity, oral fixation, hyperphagia, aphasia, loss of anger/fear reactions, etc.
Associated with HSV-1 encephalitis
Tradive dyskinesia
Results from upregulation of central dopamine receptors, decrease in cholinergic activity in the striatum
Bone remodeling
Osteoclasts resorb bone via carbonic anhydrase
Osteoblasts deposit hydroxyapetite via alkaline phosphatase
Renal artery clamp
Decreased perfusion pressure -> large decreased RPF + small decrease in GFR -> increased filtration fraction
GFR partially preserved via constrx. of efferent arteriole by R/A
Mumps orchitis
Significant swelling of the testes -> seminiferous tubule atrophy -> infertility/Leydig cell atrophy -> decreased testosterone production
Sexual dysfunction tx: exogenous testosterone
Incretins
Glucagon-like peptide-1, gastric inhibitory peptide: GI hormens that stimulate pancreatic insulin secretion in response to sugar-containing meals; response independent to insulin
ACE inhibitor fetopathy (AIF)
Occurs secondary to ACE-I therapy in pregnant women: ATII is required for fetal renal devo.; Presents w/oligohydramnios, pulm. hypoplasia, limb hypoplasia, growth retard., hypoplasia of the skull
PCI w/drug-eluting stent
Paclitaxel prevents microtubule breakdown causing arrest of the cell cycle in the M phase; this prevents intimal hyperplasia/ restenosis
GPCRs
Composed of seven transmembrane _-helical domains
VHL
Pheochromocytoma, Renal cell carcinoma, Cerebellar/retinal hemangioblastoma
Dysplastic nevus syndrome
Architect./cytologic atypia: nests of nevomelanocytes w/ angulated, hyperchromic nuclei and bridging w/ nests; have the potential to evolve into melanoma: CDKN2A on chromosome 9p21 encodes CDK inhibitor 2A which inhibits CDK4, allows advance of cell cycle
Leucine zipper
Short _-helix protein fragment with leucine residues at every 7th position that binds DNA/acts as a transcription factor
Other DNA-binding domains: helix-loop-helix, zinc finger motif, etc.
Anaphylaxis
Mediated by mast cells: tryptase is a specific marker
Degranulation is activated by IgE crosslinking/receptor aggregation
Tumor Lysis Syndrome
Develops during chemotherapy for high-grade cancer; cell destruction -> release of K+, PO4-, nucleic acids -> arrhythmias, obstructive uropathy (hyperuricemia), acute renal failure
Tx: aggressive hydration, allopurinol or rasburicase
Pulsus Paradoxis
Decrease in systolic blood pressure > 10 mmHg w/inspiration; In conditions that impair expansion into pericardial space, increased RV volume d/t increased return during inspiration pushes IV septum toward the left, decreasing LV EDV/SV –> dereased BP during insp.
Kussmaul’s Sign
Increase in JVP on inspiration; Impaired filling of the RV d/t fluid in pericardial space or poorly compliant myocardium -> increased bloodflow during inspiration to back up into venous system
CREST syndrome
Excessive tissue fibrosis d/t fibroblast proliferation; Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasia;
E.D. presents as heartburn, regurgitation, dysphagia
Myocardial energy
Source: fatty acid oxidation (60%), glucose oxidation (30%), glycolysis (5%); Fatty acid oxidation produces more ATP but has a high oxygen utilization
Hypercalcemia + Nephrogenic DI
PTHrP from squamous cell carcinoma -> hypercalcemia -> dehydration via downregulation of aquaporins -> resistance to vasopressin -> one form of DI
Mitral Regurgitation
Best indicator of severe MR with LV volume overload is the presence of an S3 gallop: reflects increased rate of LV filling d/t a large volume of regurgitant flow re-entering the ventricle during diastole
Cardiac Tamponade
Beck’s triad: hypotension, distended neck veins, distant or muffled heart sounds; combined with tachycardia and pulsus paradoxis is indicative of tamponade
Insulin Resistance
TNF-_ activates serine kinases which phosphorylate insulin receptor serine residues, inhibiting tyrosine phosphorylation by insulin as well as downstream signaling; similar mechanism of action for catecholamines, glucocorticoids and glucagon
Neurophysin
Carrier protein for oxytocin (paraventricular) and ADH (supraoptic nuclei) from the site of their production to the postieror pituitary
Pancreatitis
Acute interstitial: digestion of adipose by lipase -> fatty acids bind Ca2+, precipitate as insoluble calcium salts + necrosis
Acute necrotic: activation of trypsin -> autodigestion -> hemorrhage into necrosis, fat necrosis can spread into abdominal cavity
Vertical transmission of HIV
Presents as oral thrush, interstitial pneumonia, severe lymphopenia during the 1st year of life; Risk of transmission w/no prenatal care is ~40%; prophylaxis with zidovudine (NRTI) reduces risk by 2/3
Carcinoid Tumor
Commonly appear in ileum, appendix, rectum; Eosinophilic cytoplasm, oval/round nuclei, minimal to no variation in shape/size of tumor cells; form glands, nests, rows, sheets; dense core granules seen on EM; malig. transformation of enterochromaffin cells
de Quervain’s thyroiditis
2ndary to viral infection; initially causes thyrotoxicosis without increased readioactive iodine uptake d/t release of stored thyroid hormone; followed by hypothyroid; Histology: mixed cellular infiltrate w/occasional multinucleated giant cells
Central DI
Isolated damage to the posterior pituitary gland produces only transient central DI; damage to hypothalamic nuclei will cause permanent central DI
von Willebrand disease
Often present with a lifelong history of mucosal bleeding; normal platelet count, prolonged bleeding time; Can present with a microcytic anemia caused by iron deficiency d/t bolod loss
P450 monooxygenase
Pro-carcinogens are metabolized by P450 monooxygenase in hepatic microsomes or the ER of other tissues; This renders most substances soluble and easier to excrete; can also convert pro-carcinogens
Status Epilepticus
Treatment: IV lorazepam followed by phenytoin (prevent recurrent seizures); Still seizing: phenobarbital, followed by general anesthesia
Causes of myopathy
Glucocorticoids: proximal muscle weakness/atrophy without pain; Polymyalgia rheumatica: pain/stifness in shoulders/pelvis; Poly/Dermatomyositis: proximal weakness, rash, arthritis, increased CK; Statins: proximal weakness/pain, increased CK; Hypothyroid: proximal pain/weakness, myoedema, decreased reflexes, incr. CK
HUS-TTP
Opposite ends of a spectrum; HUS: microangiopathic hemolytic anemia following bloody diarrhea; TTP: fever, neurological sx’s, renal failure, thrombocytopenia, microangiopathyic hemolytic anemia
Acid Buffers
Utilized by the kidney to trap H+ and allow the excretion of larger amounts of acid in acioditic states; 2 most important: HPO4 and NH3
Hearing loss
Prolonged exposure to noises > 85dB can cause distortion/fracture of sterocilia d/t shearing forces against the tectorial membrane in the organ of Corti
Primary CNS Lymphoma
Most frequent CNS tumor in immunosuppressed patients; universally associated w/EBV; appears as dense cellular aggregates of unifor, atypical lymphoid cells, commonly B-cells; Diffuse large B-cell lymphoma is the most common subtype
Acute Hemolytic Reaction
Both AHR and hemolytic disease of the newborn are type II antibody-mediated hypersensitivity reactions d/t preformed anti-ABO antibodies fixing complement –> complement mediated cell lysis
Seratnin Syndrome
Sx’s: neuromuscular excitation, autonomic stimulation, AMS
Caused by: SSRIs, SNRIs, MOAIs, Tricyclics, tramadol, 5-HT3 antagonists (ondansetron), Linezolid, Triptans
Pineal Germinoma
Most common tumor of the pineal gland; Originate from embryonic germ cells, secrete _-hCG; present w/parinaud syndrome (impaired upward gaze), precocious puberty, obstructive hydrocephalus
Obstructive Sleep Apnea
In patients w/OSA peritubular cells in the renal cortex sense hypoxia and respond by releasing erythropoietin: 2ndary polycythemia in the presence of chronic hypoxia (OSA, COPD, R->L shunt, high altitude)
Toxoplasmosis
Tx: Pyrimethamine + sulfadiazine + leucovorin
Pure Red Cell Aplasia
Presents as low erythrocyte count w/low percentage of reticulocytes and low Hb + WBC/platelets within normal limits; Pathogenesis: inhibition of erythropoietic precursors by IgG/CTL; when thymoma is present, removal can occasionally cure; also caused by Parvo B19
Nitroprusside toxicity
AMS, seizures, cardio. collapse, lactic acidosis, bright red venous blood, dusky colored skin; d/t cyanide poisoning: mitochondrial toxin that binds Fe3+ in cytochrome c oxidase, inhibiting the ETC; Antidote: Sodium thiosulfate (sulfur donation) sodium/amyl nitrite (methemoglobinemia), hydroxocobalimin (direct binding)
Acute Calculous Cholecystitis
Most common complication of cholelithiasis; results from chemical irritaion/inflammation caused by stones in the gallbladder which disrupt protective mucus layer, allow for damage from bile salts/PGs -> ischemia, bacterial invasion
Smooth ER
Contains enzymes for steroid/phospholipid biosynthesis; high concentration in cells of the adrenal cortex, e.g.
Also involved in detoxification of drugs (hepatoytes), specializes as sarcoplasmic reticulum in striated muscle cells
Schwanoma
Tumor of the PNS; appear biphasic with highly cellular areas (Antoni A - spindle cells) intermixed with myxoid regions of low cellularity (Antoni B); S-100 + d/t neural crest cell origin
Hydrocephalus
Long term complications include irritability, poor feeding, muscle hypertonicity and hyperreflexia –> d/t upper motor neuron damage caused by stretching of the periventricular pyramidal tracts
Elevated AFP
Most common cause is underestimation of gestational age
Also associated with neural tube/abdominal wall defects
Blood Transfusion
Large volume transfusions can lead to hypocalcemia d/t elevated plasma levels of citrate, which is added to stored blood as an anticoagulant; Citrate chelates calcium/magnesium -> parasthesias
Galstones in pregnancy
Estrogen increases cholestrol synthesis by upregulating hepatic HMG-CoA reducatse -> supersaturation of bile; Progesterone induces gallbladder hypomotility
Neonatal hypoglyemia
Poor glucose control in mother -> increase BG in fetal circulation -> increased insulin release -> beta cell hyperplasia -> overproduction of insulin in the neonate, macrosomia
Anti-nausea/emesis
Visceral nausea (GI insults): 5-HT3 antagonists
Vestibular nausea: Antigistamines/anticholinergics
Nausea assocaited w/migraines: Dopamine antagonists
Respiratory Compensation
PaCO2 = (1.5 x HCO3-) + 8 +/- 2
Hemachromatosis
HFE protein mutataions are most common cause; Inactivation –> decreased hepcidin synthesis by hepatocytes (stored Fe regulation), increased DMT expression by enterocytes (intestinal absorption)
Hemolytic Uremic Syndrome
Caused by shiga toxin producing organisms; endothelium injury -> platelet activation/aggregation -> microthrombi -> AKI, microangiopathic hemolytic anemia
Arteriovenous Shunt
Abnormal connection between artery/vein; congenital, trauma related, aneurysm rupture, etc.; decreased TPR –> increased CO, decreased afterload, increased prelaod (d/t shunting of blood)
Area postrema
Responsible for vomiting that resuts from administration of systemic chemotherapy; located on the dorsal surface of the medulla at the base of the 4th ventrical where it can sample circulating chemicals
Digoxin toxicity
Fatigue, blurry vision, changes in color perception, nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, confusion, hyperkalemia, delerium, bradycardia, vtach
Resistance in parallel
1/R = 1/R1 + 1/R2 + 1/R3 + € 1/Rn
Menopause
Average age = 52; Ovarian failure –> decreased estrogen production, therefore elevated FSH d/t loss of feedback inhibition is diagnostic
Glucagonoma
Presents with dermatitis, diabetes, DVT, depression; dermatitis = necrolytic migratory erythema –> erythematous papules/plaques on face, perineum, extremities that coalesce forming a bronze-colored central indurated area w/peripheral blistering and scaling
Rheumatoid Arthritis
Cartilage components serve as autoantigens that activate CD4+ T-cells, which in turn stimulate B-cells to secrete rhematoid factor –> IgM Ab specific for the Fc component of self IgG
Marcus Gunn Pupil
Afferent pupillary defect cause by a lesions involving the optic nerve; a relative afferent pupillary defect can occur due to a lesion of the optic tract, as the nasal portion of the retina contribues more input to the pretectal nucles than the temporal portion
Chemotherapeutic resistance
Human multidrug resistance (MDR1) gene –> P-glycoprotein: transmembrane protein, ATP-dependent efflux pump; normally expressed in intestinal/renal tubular cells, blood/brain barrier
Topical steroids
Decrease the production of extracellular matrix collagen/ glycosaminoglycans -> atrophy of dermis, loss of dermal collagen, drying/cracking of the skin, telangiectasias, ecchymoses, striae
M™llerian Agenesis
Causes vaginal agenesis: no upper vagina development, combined with variable uterin development; patients have normal ovaries and thus develop 2nd sexual character.s, but are unable to menstruate
Friedreich Ataxia
Autosomal recessive mutation in the frataxin gene on chromosome 9; Presentation: Spincerebellar tract degeneration (ataxia), Dorsal column/DRG degeneration (position/vibration loss), kyphoscoliosis and foot abnormalities, hypertrophic cardiomyopathy, DM
Malignant Hyperthermia
D/t hypersensitivity of skeletal muscles to inhalation anesthetics + succinylcholine; autosomal dom. defect of ryanodine receptors causing incr. release of Ca2+ during muscle contraction; Excess free Ca2+ is taken up via ATP, consumption generates heat and induces muscle damage; Tx: Dantrolene -> inhibits ryanodine receptors
PCOM stroke
Common site of saccular aneurysm; causes CN III palsy: eye is “down and out” with ptosis and mydriasis
Acetaminophen Toxicity
Acetaminophen has three pathways for metabolism: glucuronidation, sulfation, formation of NAPQI –> toxic byproduct: mst be conjugated by glutathione for elimination; alcoholics have depleted glutathione which increases risk for acetaminophen toxicity
Aspergillus flavus
Fungi grows on grains/foodstuffs with high humidity/temperature; high levels of aflatoxin consumption assocatied w/a G:C -> T:A transversion in codon 249 of p53; increases risk for HCC
Congenital Hypothyroidism
6 P’s: pot-bellied, pale, puffy-faced child with protruding umbilicus, protuberant tongue, poor brain development; Also include jaundice, constipation, hypotonia, hoarse cry, myxedema, coarse facial feature
Traumatic aortic rupture
Caused by rapid deceleration, i.e. MVA; the most common site of injury is the aortic isthmus: tethered by the ligamentum arteriosum, fixed and immobile compared to descending aorta
Halogenated inhaled anesthetics
Can cause severe liver damage; hepatitis presents in 2 days to 4 weeks after surgery under general anesthesia; liver tenderness, hepatomegaly, increased LFTs; widespread centrilobular hepatic necrosis; shrunken liver on autopsy; 80% mortality rate
Nitrates
Around the clock administration rapidly results in development of tolerance; nitrate-free interval must be provided every day; patients don’t take a night-time dose;
Ischemic insult
Myocardial stunning: ischemia-induced reversible loss of contractile function that takes hours to days to recover; Hibernation: persistent or repetitive ischemia/stunning that can be reversed by reperfusion (reverses upon perfusion)
Necrotizing enterocolitis
Occurs in preterm infants secondary to GI/immunologic immaturity; enteral feeding intrduces bacteria into bowel where they proliferate excessively; impaired mucosal barrier function –> ischemic necrosis, intramural gas collections: pneumatosis intestinalis
Lupus
Circulating antiphospholipid Ab’s cause aPTT prolongation in vitro, but act in vivo to produce hypercoagulable state; cause false-positive results on VDRL test; incr. risk for DVT, PE, TIA, recurrent miscarriage
Primary Hyperaldosteronism
Mineralocorticoid excess -> increased Na+ reabsorption -> incr. fluid retention, hypertension -> increased ANP, pressure naturesis -> limited increase in extracellular fluid volume w/o hypernatremia (aldosterone escape)
Melanoma
Commonly presents with a mutation in BRAF V600E: involved in activation of proliferation signals (Ras pathway); responds to Vemurafenib
Nongonococcal urethritis
Most commonly caused by chlamydia trachomatis or ureaplasma urealyticum; Azithromycin is treatment of choice: chlamydia lacks muramic acid/peptidoglycan in cell wall, ureaplasma lacks cell wall entirely; thus, anti-cell wall antibiotics are ineffective
Psoriasis treatment
Calcipotriene/calcitriol/tacalcitol are topical vitamin D analogs that active the vitamin D receptor: inhibits keratinocyte proliferation, stimulates differentiation, inhibits T cell proliferation; Other tx: cyclosporin, etanercept, methotrexate, ustekinumab
Atheroembolic disease
Cyanotic toe discoloration + renal failure in elderly patient following invasive vascular procedure is characteristic of atheroembolic disease of the renal arteries causing cholesterol emboli
Lung transplant rejection
Acute: CD8+ T-cell mediated vascular damage; presents w/dyspnea, dry cough, low-grade fever
Chronic: Inflammation/fibrosis of small bronchiolar walls –> narrow/ obstruction; presents w/dyspnea, non-productive cough, wheezing
SVT Treatment
Vagal stimulation: valsalva maneuver, carotid massage –> increase refractory period in the AV node, prevent reentrant circuits; If these fail, administration of adenosine
Lung abscess formation
Pulmonary abscess: local suppurative collection within parenchyma, causes necrosis of surrounding tissue; If connected to air passage –> air-fluid level seen on radiograph; d/t release of lysosomal enzymes by neutrophils/macrophages
Thoracocentesis
Pleural borders: Midclavicle - 7th rib; paravertebral - 12th rib; midaxillary - upper border of 10th rib (right), lower border of 10th rib (left); Lower border of the lung is 2 intercostal spaces above the pleural border; thus, thoracocentesis should be performed above 7th, 9th, or 11th rib respectively
Opoid Tolerance
Mechanism: activation of NMDA receptors by glutamate -> phosphorylation of opioid recetors; Ketamine is an NMDA blocker, can be used to decrease morphine tolerance
Cholesterol stones
Estrogen -> incr. HMG-CoA reducatse -> incr. biosynthesis of cholesterol; Suppression of cholestrol 7a-hydroxylase by fibrates reduces cholesterol to bile acids –> cholesterol stone formation
RDS complications
Temporary local hyperoxia in the retina d/t O2 supplimentation -> upregulation of VEGF upon return to RA -> neovascularization/retinal detachment (retinopathy of prematurity)
Myasthinia Gravis
Associated with abnormalities of the thymus: thymoma, thymic hyperplasia; embryologically derived from the 3rd pharyngeal pouch
Paraneoplastic Cerebellar Degen.
Small cell lung cancer, brest, ovarian, uterine: progressively worsening dizziness, limb/trunk ataxia, dysarthria, visual disturbances; tumor cells cross-react with Purkinje neuron antigens; Anti-Yo, anti-P/Q, anti-Hu are sometimes detectable
Ankylosing spondylitis
HLA B27 assiated; presents as low back pain in a young man; progressive course with exaserbation/remission: inflammation at tendon insertion, hypoventilation d/t decr. Chest expansion, ascending aortitis, uveitis; routinely monitor chest expansion
Verapamil
Cardiac muscle specific; skeletal muscle contraction occurs via membrane depolarization causing physical RyR opening in the SR -> intracellular calcium release: this is not associated with extracellular Ca2+ influx; In cardiac muscle calcium-induced Ca2+ release occurs
Osteitis fibrosa cystica
Most characteristic skeletal manifestation of 1 hyperpara: subperiosteal resorption with cystic degeneration; presents with bone pain,subperiosteal erosions affecting the phalanges, “salt-and-pepper skull”, brown tumor bone cysts
Juvenile Myoclonic Epilepsy
Form of idiopathic geeralized epilespy that may be familial; presents with moyclonic seizures: sudden-onset jerking movements involving both arms e.g.; Aggravated by sleep depreivation, no loss of consciousness; Tx: Valproic acid
Systemic Mastocytosis
Abnormal proliferation of mast cells, increased histamin seretion; foci within the gstric mucosa –> hastric hypersecretion
Atherosclerosis
Release of PDGF by locally adherent platelets, endothelial, cells, macrophages promotes proliferation/migration of smooth muscle cells from media into the intima
Neonatal narcotic withdrawal
Sx’s: puplliary dilation, rhinorrhea, sneezing, nasal stuffiness, diarrhea, nausea, vomiting, chills, tremors, jittery movements, seizures; Tx: tincture of opium, followed by tapering
Glands
Apocrine: secrete membrane bound vessicles into hair folicles; secretions can become malodorus d/t bacterial decomposition
Holocrine: entire secretory cells break down to release product
Eccrine/Merocrine: secrete sweat directly to skin surface
Paracrine: secretions reach target cells by diffusion
Uremic bleeding
Significant renal dysfunction –> uremic toxin buildup in the circulation –> impiared platelet aggregation – qualitative disorder –> prolonged bleeding time
Vitamin E Deficiency
Manifests as hemolytic anemia, neuromuscular disease: skeletal myopathy, spinocerebellar ataxia, pigmented retinopathy; d/t incr. oxidative damage to axons and erythrocytes; mimics Friedreich ataxia (degeneration of posterior columns/spinocerebellar tracts)
Cystic Fibrosis CFTR
Respiratory/gastric glands: secretes Cl- ions into the lumen, inhibits Na+ reabsorption –> increased salt/water content of mucus
Sweat glands: absorbs lumenal Cl-, increases Na+ abosrption –> reduced salt content of sweat
Opportunistic prophylaxis
P. jirovecii: TMP-SMX when CD4+ count
Colorectal Carcinoma
In contrats to spontaneous CRC, CRCin IBD is more likely to: affect younger patients, progress from flat/non-polypoid dysplasia, appear mucinous/signet ringed, develop early p53 and late APC gene mutations, affect the proximal colon, be multifocal in nature
Serum Sickness
Type III hypersensitivity: immune complex deposition –> decreased serum C3; fever, pruritic skin rash, arthralgias, lymphadenopathy, proteinuria 7-14 days after exposure; Histology shows small vessel vasculitis w/fibrinoid necrosis and intense neutrophil infiltration
Native Valve Bacterial Endocarditis
Most often involve mitral valve: prolapse is most common predisposing abnormality; Platelet + fibrin deposition occus spontaneously acting as a nidus; High velocity blood streams and turbulant flow contribute microinjury promoting infection
Lead Poisoning
Exposure: batteries, ammunition, mining, chemical processing, etc. Presentation: “lead colic”, constipation, headaches, short-term memory loss, “lead lines” on the gums, wrist/foot drop, anemia, basophilic stipling
Iron Poisoning
Stage 1: nausea, diarrhea, abdominal pain, hemorrhage, hypovolemia, shock; Stage 2: apparent recovery; Stage 3: metabolic acidosis, hepatic dysfunction, hypoglycemai; Stage 4: scarring of the GI tract
Abetalipoproteinemia
Impaired formation of apoB: causes accumulation of lipis in intestinal villi; autosomal recessive mutataion in MTP gene; presents as malabsorption, low plasma TG/cholesterol, lack of chylomicrons, VLDL’s, apoB; fat-soluble vitamin deficiency; acanthocytes
Infarction
Cerebral amyloid angiopathy: d/t alzhemiers, most common cause of spontaneous lobar hemorrhage; Charcot-Bouchard aneurysm: d/t chronic HTN, causes hemorrhage in deep brain structires; Hypertensive arteriolar sclerosis: d/t chronic HTN, causes ischemic lacunar infarcts in deep brain structures
Microscopic polyangitis
Assocaited with antibiotic use: small vessle vasculitis that results from a type III immune reaction to a medication such as penicillin
Caudal Regression Syndrome
Presents with agenesis of the sacrum/lumbar spine, flaccid paralysis of the legs, dorsiflexed foot contracture, urinary incontincence; d/t poorly controlled maternal diabetes
Lipotoxicity
Induction of insulin resistance and beta cell dysfunction caused by free fatty acids/triglycerides; lowering FFA’s impreoves beta cell function and insulin resistance
Anesthetic Potency
Potency: 1/MAC
Onset of action: 1/blood-gas partition coefficient
Onset of action: arteriovenous concentration gradient
Incr. AV concentration gradient means incr. uptake by peripheral tissues, thus longer time to saturation
Clearance: rate of exhalation (or hepatic metabolism for halothane)
MRSA treatment
Vancomycin: blocks glycopeptide polymerization, causes nephrotoxicity/red man syndrome; Daptomycin: depolarizes cell membrane, causes myopathy; Linezolid: inhibits 50S subunit, caues optic neuritis, thrombocytopenia, serotonin syndrome
Osmotic diuresis
Mannitol is an osmotic diuretic used to manage cerebral edema /increased intracranial pressure; Increased intravascular volume can exaserbate pulmonary edema in patients w/preexisting condition –> dilutional hyponatremia, metabolic acidosis, hyperkalemia, death
First Dose Effect
ACEIs reduce venous return to the heart which activates Bezold- Jarisch reflex, causing vagally mediated hypotension and bradycardia; predisposing factors include hyponatremia, hypovolemia, low BP, high renin/aldosterone, renal impairment, HF; caution in patients taking thiazide or loop diuretics
Alcohol + Acetaminophen
Alcohol induces CYP 2E1 which activates acetaminophen to a hepatotoxic metabolite (NAPQI); N-acetylcysteine regenerates gluatione (GSH) which metabolizes NAPQI to a non-toxic form
16S RNA
Only piece of rRNA found in the prokaryotic 30S subunit; essential for initiation of protein synthesis:expresses a sequence complementary to the Shine-Dalgarno sequence in all prokaryotic mRNA (located 10 bp upstream from the start codon)
Hepatic Encephalopathy
Occurs d/t failure of the liver to metabolize ammonia; GI bleeding leads to incr. nitrogen delivery to the get in the form of hemoglobin; converted into ammonia and absorbed into the bloodstream
Angisarcoma
Infiltration of the dermis with slit-like abnormal vascular spaces; risk factors include chronic lymphedema, radical mastectomy with axillary lymph node dissection; poor prognosis
Neurotransmitter Nuclei
Nucleus ceruleus: NE; Raphe nuclei: Serotonin; Nucleus basalis of Meynert: ACh; Substantia nigra: dopamine
Bone Descriptions
Osteoid matrix accum. around trabeculae: Rickets/Osteomalacia
Trabecular thinning with fewer interconnections: Osteoporosis
Subperiosteal resorption with cystic degeneration: Hyperparathyroid
Lamellar bone structure resembling a mosaic: Paget’s Disease
Spongiosa in medullary canal w/o mature trabeculae: Osteopetrosis
Mushroom Toxins
Amatoxins are found in a variety of poisonous mushrooms e.g. death cap mushrooms; potent inhibitors of RNA polymerase II, halthing mRNA synthesis
Pauci-Immune RPGN
Associated with granulomatosis with polyangiitis: high serum level of c-ANCA is diagnostic, no Ig or complement deposits found by immunofluorescent studies
Crohn’s Disease
Assocaited with HLA-DR1, mutations in NOD2: triggers the NF-kB pathway –> cytokine production
Pompe Disease
Deficiency of acid _-glucosidase/acid maltase: responsible for breaking down glycogen w/i acidic environment of lysosomes; cardiac and skeletal muscle are particularly susceptible: interfere w/contractile function
Neuroblastoma
Develops from neuroblasts in the adrenal medulla; presents with non-rhythmic conjugate ee movements associated with myoclonus (opsoclonus-myoclonus syndrome); histology: aolid sheets of small cells with dark nuclei and scant cytoplasm
MELAS
Mitochondrial encephalopathy with stroke-like episodes and lactic acidosis
Drug Induced Lupus
Anti-histone Ab’s commonly seen; occurs with agents that are metabolized by liver acetylation; slow acetylators are at greater risk
Gancyclovir + Zidovudine
Neutropenia
Calcium Oxalate Stones
Tx: Thiazide diuretics; decrease urine Ca2+ excretion
Hemolytic Uremic Syndrome
Classic triad: microangiopathic hemolytic anemia, acute renal failure, thrombocytopenia; presents in a 5-year old male with fever, abdominal pain, bloody diarrhea, pallor, oligura
RPGN
Type 1: anti-GBM Ab’s; linear deposits; Goodpasture syndrome
Type 2: immune-complex mediated; “lumpy bumpy” deposits; post-strep, SLE, IgA, Henoch-Schonlein
Type 3: Pauci-immune; no Ig or complement; Wegner’s
Lithium Toxicity
Drigs that increase lithium levels: thiazide diuretics, ACE inhibitrs, NSAIDs
Micturition
Sacral micturition center: S2-S4, bladder contraction; Parasymp. fibers travel w/pelvic nerves -> cholinergic receptors on bladder wall
Pontine micturition center: PRF, relaxes external urethral sphincter
Cerebral cortex: inhibits sacral micturition center
