STEP1 deck 2 Flashcards
fragile X sx
macroorchidism, intellectual disability, long narrow face with prominent mandible
dopamine agonists
bromocriptine - ergot
pramipexole and ropinerol - non-ergot
1st line for PD - delay need to start L-dopa
St. John’s Wort
Cyp450 inducer
meningioma histo
psammoma bodies
VLCFA metabolixm
degraded in peroxizomes; dysrupted in Zellweger Sy and X-linked adrenoleukodystrophy
hypoxic-ischemic encephalopahty
watershed infarct - wedge-shaped areas of necrosis
haptoglobin
binds circulation hemoglobin, reduces renal excretion of free hemoglobin, preventing tubular injury
decreased in SCD b/c used up
SCD sx in kids
dactylitis (vasoocclusion), increased indirect bilirubin and lactate dehydrogenase, decreased haptoglobin
CYP 450 inhibitors
=> increased warfarin effect acetaminophen/NSAIDs antibiotics/antifungals (metronidazole) - except rifampin Amiodarone Cimetidine Cranberry juice, Ginkgo biloba, vitE Omeprazole Thyroid hormone SSRIs (fluoxetine)
CYP 450 inducers
=> decreased warfarin effect carbamazepine, phenytoin ginseng, St. John's wort OCPs Phenobarbital rifampin
translation initiator
Kozak consensus sequence
(gcc)gccRccAUGG
initiates translation in people - mutated in B-thalassemia
paroxysmal nocturnal hemoglobinuria
hemolytic anemia, hypercoagulability, and pancytopenia exacerbated by any inflammatory trigger
acquired mutation of PIGA gene w/in clonal population of hSCs
PIGA is part os synthesiss of GPI anchor, the attachment for cell-surface proteins like CD55 (DAF) and CD59 (MAD inhibitory factor) which protect self-cells from complement
hemolysis increased at night due to increased complement activation in decreased pH
clotting is from release of clotting factors from lysed cells
cells expressing CD14
monocytes + macrophages
porphyria cutanea tarda
uroporphyrinogen decarboxylase deficiency
earlier deficiencies => neuro changes but not photosensitivity
G6PD
rate-limiting step of pentose phosphate pathway, catalyzed G-6-P -> 6-phosphogluconolactone
needed to generate NADPH and ribose-5-P
multiple myeloma
plasma cell cancer => bone pain, fatigue, anemia, kidney disease, and hypercalcemia
plasma cells secrete tons of Ig, and are thus susceptible to proteasome (recycling center) inhibitors such as bortezomib (boronic acid-containing dipeptide) => pro-apoptosic protein buildup
hereditary spherocytosis
AD cytoskeletal mut => hemolytic anemia, jaundice, splenomegaly (spherocytes stuck in spleen)
labs show increased MCV, spherocytes, negative Coombs, increased osmotic fragility
causes pigmented gallstones and aplactic crisis with parvovirus B19 infection
treat with splenectomy
cardiac tissue conduction velocity
fast - purkinje>atrial>ventricular>AV node - slow
Paget’s disease and association
increased bone turnover with production of disorganized + fragile bone - associated with osteosarcoma
osteopetrosis
oseoclasts fail to resorb bone => decreased remodeling, increased osteosclerosis, fractures
oseltamivir and amantidine fcn
oseltamivir blocks NA which does viral release
amantidine prevents viral envelope assembly via M2, now used for Parkinson dyskinesia
follicular BC lymphoma mutation and progression
t(14;18) => increased BCL2 => evasion of apoptosis
indolent, growing and shrinking
atropine
belladonna - competitive muscarininc R antagonist => action on M3 => decreased smooth muscle contraction
used in MI with bradycardia - prevents parasympathetic from slowing heart without stimulating it too much
ipatropium and tiotropium are inhaled versions
anticholinergics and sx
atropine (belladonna), Jimson weed
hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter
acute promyelocytic leukemia
t(15;17) => pancytopenia, DIC
histo with abnormal promyelocytes with Auer rods
treat will all-trans retinoic acid
IL-2
made by Ag-stimulated TCs to activate more TCs (clonal proliferation of TCs specific for this Ag), BCs, NKcs, and macrophages
Il-1
made by macrophages -> activated lymphocytes; also a primary inflammatory molecule => fever, lethargy, anorexia
TNF-a
made by activated macrophages => systemic inflammatory response (sepsis in v. high doses)
INF-a
made by monocytes, macrophages, BCs, and NKcs - antiviral, makes you sick
GM-CSF
made by everything, stimulated granulocyte and monocyte stem cell production
hemidesmosomes
cell-BM connection
desmosomes
cell-cell connection
made of cadherins
pancreas bicarb secretion
acidic chyme in stomach => gallbladder bile release and stimulates S cells in cryps to Lieberkuehn to release secretin => pancreas => bicarb
knee dislocation
risk of injury to popliteal a, tibial n, and common peroneal n
if ant. or post., popliteal artery is at greatest risk b/c fixed tightly above and below the joint
craniopharyngioma
slow growing suprasellar tumor from Rathke’s pouch - kids and elderly
ptsd cutoff
1 month; less than that = acute stress disorder
schizophrenia time cutoffs
<1mo = brief psychotic disorder <6mo = schizophreniform
HSV encephalitis
most common kind of encephalitis - affects both immunocompetent and immunosuppressed
all encephalitis => fever, HA, malaise
affects temporal lobe => CT changes and also sz, personality changes, and psychosis
acute intermittent porphyria
porphobilinogen deaminase def => intermittent AP, neuro sc, dark urine, but no photosensitivity
Lhermitte’s phenomenon
shock-like sensation radiating to the feet with neck flexion, cognitive dysfunction
caused by MS or cobalamin deficiency
ca cause of myasthenia gravis
thymoma
Eaten-Lambert Sy
autoimmune disorder of the NMJ acquired with small cell lung ca - more extremity weakness> ptosis
septic arthritis histo
PNMs and bacteria in the joint space
DKA Na and K changes
pseudohyponatremia happens to maintain osmolar balance - Na pulled into cells b/c so much glucose outside
hyperkalemia b/c K/H antiporter pulling H into cells to reduce acidemia (note total body K stores depleted)
pheochromocytoma medications
treatment is designed to avoid hypertensive crisis
start with long-acting alpha blocker such as phenoxybenzamine
then add beta blocker (propranolol) but don’t give it alone because unopposed alpha-stimulation causes vasoconstriction and life-threatening hypertensive crisis
medications causing interstitial lung disease
amiodarone (class III antiarrythmic), nitrofurantoin, MTX, bleomycin
side effects of amiodarone
interstitial pneumonitis, arrythmias, hepatic injury, thyroid, blue/gray skin discoloration
ASA-induced asthma
ASA blocks Cox1+2, blocking prostaglandins => increased LOX pathway and increased leukotrienes, which are pro-inflammatory
nitrates effects on heart and vessels
cause systemic vasodilation => reflex tachycardia
pseudohypopartathyroidism
type 1a = Albright hereditary osteodystrophy (AD GNAS1 mut FROM MOM) => short stature, short metacarpal and metatarsal bones, plus PTH resistance
GNAS1 mut FROM DAD => developmental defects with normal PTH (pseudopseudohypoparathyroidism)
allelic heterogeneity v. polygenic
allelic heterogeneity - diff types of mutations at same gene cause same disease
polygenic - muts of diff genes cause same disease
pleiotropy
mut of one gene has multiple effects
exercise-induced asthma and tx
exercise => eosinophils and mast cells make leukotrienes (especially D4) which => bronchospasm and increased mucus secretion
tx with anti-leukotriene (montelukast)
bronze diabetes
hemochromatosis => hyperpigmentation, arthalgias, liver damage, diabetes, cardiomyopathy, increased susceptibility to listeria, vibrio, and yersinia enterocolitica
cirrhosis pressure changes
cirrhosis => portal HTN => splenic vein HTN (b/c splenic vein empties into portal system) => splenomegaly (cause of hepatosplenomegaly)
causes of impetigo
GAS, staph aureus
efflux pumps
bacterial resistance via exporting drug is usually via a H+/drug symporter and thus can be dysrupted by increased extracellular H+
achonroplasia
FGFR3 pt mut => nl head circumference but decreased cartilage => shortening of the long bones and digits, midface hypoplasia, frontal bossing
osteogenesis imperfecta
COL1A1 mut => defective type I collagen (procollagen), short stature, femoral bowing and recurrent fractures, blue sclerae, dearing difficulties (abnl ossicles) and tooth cavities (no dentin)
fragile X
FMR1 mutation => intellecutal disability (subtle physical changes at birth => prominent forehead, chin, macroorchidism in adolescence)
fetal alcohol syndrome
smooth philtrum thin vermilion border, short palpebral fissure, CNS changes
maternal isotretinoin use
ear anomalies, micrognathia, depressed nasal bridge, transposition of the great arteries, hydrocephalus, microcephaly
Red safranin O
colors cartilage, mast cell grnules, and mucin red
vanillylmandelic acid
metabolite of epi and NE
PE ABGs
V/Q mismatch => hypoxemia (low PaO2) but not hypercapnia b/c we have excess CO2 elimination capacity
hypoxemia => hyperventilation => low PaCO2 and respiratory alkalosis
carcinoid tumor sx and tx
sx: flushing, HoTN, diarrhea, ronchospasm, valve lesions
tx: octreotide (somatostatin analogue which +> reduced secretion of bioactive peptide)
translation of proteins needed for apoptosis
eukaryotic initiation factors (eIFs) are degraded during apoptosis, so proteins needed for apoptosis are translated via internal ribosome entry
IRES (different nucleotide sequence in the 5’ UTR) lets translation start in the middle of the mRNA sequence
thiazolidinediones
TZDs - oral DM2 meds (pioglitazone, rosiglitazone) - increase transcription of insulin-responsive genes => GLUT4 upregulation and increased adipocyte differentiation => increased insulin sensitivity
most frequent site of Crohn disease
terminal ileum
lactulose
treats hepatic encephalopathy by acidifying intestinal contents => NH4+ (ammonia)production which then gets pooped out
beta agonist biochem
bind seven transmembrane G protein-couple receptors that activate Gs=>adenyl cylcase => cAMp => smooth muscle relaxation
osteomalacia
vit D def => hypophosphatemia => decreased mineralization of newly deposited osteoid => fractures
peripheral artery disease
PAD - caused by arterial atherosclerosis => claudication, rest pain, skin thinning, loss of leg hair
innervation by recurrent laryngeal n
branches from the vagus and innervates intrinsic muscles of larynx responsible for sound production (have arytenoid in name) - except the cricothyroid - can be damaged by aortic aneurysm
hashimoto v. graves histo
hashimoto (hypoT) diffuse lymphocytic infiltration of thyroid by BCs and TCs, with germinal centers and Huerthle cells (enlarged epithelial cells with eosinophilic cytoplasm and prominent nucleoli
graves (hyperT) tall, crowded follicular epithelium with scalloped colloid
right-way eyes
destruction of frontal eye fields => ipsilateral deviation
unmyelinated nerves
(group C) postganglionic autonomic nerves, afferent heat sensation, afferent slow-onset dull, burning, or visceral pain, first order biporal sensory olfactory nerves
invariant chain
sits between a and B chains of MHCII in antigen-binding site; degraded and replaced by antigen during macrophage antigen processing
prader-willi
microdeletions on paternal copy or maternal uniparental disomy
PCOS
increased LH:FSH ratio => increased androgen production by theca interna cells => anovulation
cellular dedifferentiation
driven by TFs
cause pupillary constriction
muscarinic cholinergic agonists (pilocarpine)
nl RBC size
should be able to fit 5 RBCs in one neutrophil
pernicious anemia
autoimmune destruction of parietal cells => decreased IF production and B12
also => decreased HCL production => hypochloridia and alkalinization of gastric juice => increased gastrin production
acanthosis nigricans
associated with insulin resistance and obesity
can also signal GI malignancy if sudden growth
Peutz-Jeghers Sy
rare AD disease => pgmented mucocutaneous macules and hamartomatous GI polyps which can eventually => malignancy
DiGeorge
Catch 22 Conotruncal (outflow tract) cardiac defects Abnormal facies Thymic aplasia Cleft palate Hypocalcemia
Gaucher
(couch) - most common lysosomal storage disorder (AR) => B-glucocerebrosidase accumulation in macrophage lysosomes (wrinkled tissue paper) => hepatosplenomegaly, pancytopenia, osteopenia (lysosome buildup => release of inflammatory enzymes)
infliximab
anti-TNFa mab
cox1 v cox2
cox1 - (TXA2) plt aggregation
cox2 - proinflammatory
transduction v. transformation
transduction: phage transfers genetic information
transformation: bacteria take up naked DNa from the environment
FSGS
HIV-associated, => nephrotic sy (high proteinuria) - some glomeruli collapse and sclerose - BM collapse, hyalinosis, (in HIV, get collapsing glomerulopathy => tubular injury and microcyst formation)
causes of anion gap metabolic acidosis
MUDPILES Methanol Uremia DKA Propylene glycol Isoniazid/Iron Lactic acidosis Ethylene glycol (antifreeze) Salicylates (ASA)
ethylene glycol poisoning
anion gap metabolic acidosis
sudden-onset flank pain, hematuria, and oliguria
metabolized to oxalate => envelope/dumbbell-shaped calcium oxalate crystals (positively birefringent on polarization)
maxillary sinuses
most common site of acute rinusinusitis; live below each orbit, empty into the middle nasal meatus
osteocyte communication
long intracanalicular processes linked via gap junctions allow nutriend and waste exchange
also able to sense mechanical stress and modulate osteoblast activity
bisphosphonates
(alendronate, risedronate) - used for osteoporosis tx
chemical structure similar to pyrophosphate - bind hydroxyapatite binding sites on bone surfaces, preventing osteoclast adhesion
also => osteoclast apoptosis
atropine SEs and complications
mydriasis (acute angle-closure glaucoma)
loss of accommodation
sedation, psychosis
tachycardia (used in MI with bradycardia)
decreased tears, sweat, saliva, GI, bronchial secretions
detrusor relaxation
bronchodilation
fat embolism sx
respiratory distress
neuro sx
petechial rash
Huntington pathogenesis
AD CAG repeat expansion => huntingtin gain-of-fcn mutation => histone deacetylation => silencing of genes needed for neuron survival
babesiosis
transmitted by Ixodes tick (sames as lyme) => intraepithelial ring inclusions (looks like malaria) and Maltese crosses
found in NE US, => flu-like sx, ARDS, CHF, DIC, splenic rupture
labs show anemia, thrombocytopenia, increased LFTs
motor innervation of the tongue
CN XII (hypoglossal) except for palatoglossus muscle which is CNX (vagus) 10, 12
general sensory innervation of the tongue
touch, pain, pressure, temp ant. 2/3: mandibular branch of trigeminal n (CN V3) post. 1/3: glossopharyngeal n. (CN IX) tongue root: vagus n (CN X) V3, 9, 10
taste innervation of the tongue
ant. 2/3: chorda tympani branch of facial n. (CN VII)
post. 1/3: glossopharyngeal n. (CN IX)
tongue root, larynx, upper esophagus: vagus n. (CN X)
7, 9, 10
adjustable gastric banding
inflatable, goes around cardiac part of stomach (upper 1/3, including LES), has to pass through lesser omentum (hepatogastric portion)
analgesic nephopathy
large amts of NSAIDs over a long time concentrate in medulla and papillae => glutathione depletion and tubualr and endothelial cell damage => chronic interstitial nephritis
histo: patchy interstitial inflammation with fibrosis, tubular atrophy, papillary necrosis and scarring, and distortion of caliceal architecture
papillary calcifications may be visible on renal imaging
can also => decreased prostaglandins => constriction of vasa recta => ischemic papillary necrosis
asthma sputum histo
eosinophils (granule-containing) and Charcot-Leyden crystals; eosinophils are recruited and activated by IL-5 from Th2 cells
medications used in stress testing
adenosine, dipyridamole (coronary vasodilators)
can => coronary steal syndrome
arteries damaged by stomach ulcers
most stomach ulcers form along the lesser curvature, so the R and L gastric arteries are at greatest risk
primary biliary cholangitis
chronic autoimmune destruction of hepatic bile ducts => cholestasis
causes fatigue, itching, hepatomegaly, increased alk phos, and antimitochondrial antibodies
biopsy shows pathcy lymphocytic inflammation with destruction of intrahepatic bile ducts, necrosis, and micronodular regeneration - looks similar to GVHD b/c both immune
mostly middle-aged women, associated with other autoimmune diseases
base excision repair
fixes single-base DNA defects
glycosylase removes defective base
endonuclease and lyase remove empty sugar-phosphate site
DNA polymerase replaces missing nucleotide
Ligase seals remaining nick
11-hydroxylase deficiency
CAH => females with ambiguous genitalia, HTN 2/2 buildup of 11-deoxycorticosterone (weak mineralocorticoid)
timeline of cardiomyocyte ischemia
seconds - transition to anaerobic glycolysis
<60 sec - loss of contractility
<30 min - contractility gradually recovers over hrs to days
>30 min - cellular adenine stores depleted => irreversible injury
hypertensive emergency tx
IV fenoldopam (short acting, selective, peripheral D1 - receptor agonist) => systemic arteriolar vasodilation, most pronounced in kidneys
x-linked SCID
most common cause of SCID
mutation of IL-2RG (common gamma chain) => no T or B lymphocyte growth
alpha-1 blockers
doxazosin, prazosin, terazosin => smooth muscle relaxation in arterial and venous walls (used for HTN)
also => smooth muscle relaxation in bladder neck and prostrate (used for urinary retention in BPH)
start at low dose to avoid HoTN
antiphospholipid antibody syndrome
=> recurrent miscarriage, placental insufficiency, preeclampsia; DVT, PE, stroke
labs: lupus anticoagulant effect (paradoxical PTT prolongation not reversed with mixing study), antiphospholipid (anticardiolipin, anti-beta2-glycoprotein-1) antibodies - these can => false-positive RPR and VDRL
methylmalonic acidemia
methylmalonyl-CoA mutase deficiency => newborn with lethargy, vom, tachypnea
labs; hyperammonemia, ketotic hypoglycemia, metabolic acidosis, high methylmalonic acid and propionic acid
thoracic outlet syndrome
2/2 cervical rib, scalene muscle anomalies, or repetitive overam movements
compression of lower trunk of brachial plexus => UE paresthesias and weakness
can also compress subclavian vein => UE swelling or subclavian artery => exertional arm pain
disseminated gonorrheal infection and VF
arthritis, dermatitis, and tenosynovitis - from n. gonorrhoeae
VF: makes IgA protease which cleaves IgA at its hinge region, preventing it from binding bacterial membrane proteins and keeping them from adhering to mucosa
IgA is not a good opsonin
developmental field defect
initial embryonic disturbance => multiple malformations by disrupting the development of adjacent tissues and structures (holoprosencephaly => facial defects)
CD 31
PECAM1 - immunoglobulin expressed on endothelial surface which functions in leukocyte migration through the endothelium
liver angiosarcoma
rare malignant vascular ca associated with arsenic (pesticide), thorotrast (radioactive contrast), or polyvinyl chloride (industry) exposure
expresses CD31 (PECAM1)
intraductal papilloma
most common cause of bloody nipple discharge
papillary cells in duct wall with fibrovascular core; may contain DCIS foci (cancer)
G1->S transition
proliferation signals activate ADK4 => Rb protein phosphorylation, releasing E2F transcription factor, initiating S phase
influenza A resistance
via either exposure or vaccination - anti-HA Abs (anti-NA Abs have mild protective effect)
pathogenesis of HBV-related HCC
integration of viral CNA into cellular genome => neoplastic changes
chronic inflammation and regeneration also => accumulation of mutations
capitation v. global payment
capitation: payor pays a fixed, predetermined fee to cover all the medical services required by a patient or group of patients (common in HMOs)
global payment: insurer pays a single payment to cover all the expenses associated with an incident of care, including follow-up visits (common in elective surgeries)
centriacinal emphysema pathogenesis
smoking => oxidative injury to respiratory bronchioles => activation of alveolar macrophages => inflammatory recruitment of neutrophils
macrophages and neutrophils release proteases and generate free radicals which block protease inhibitors => protease-antiprotease imbalance => acinar wall destruction and airspace dilation
edrophonium
short-acting AChE inhibitor used in “Tensilon test” to differentiate between worsening of MG due to undertreatment (sx improve with edrophonium, tx: increase pyridostigmine dose) or cholinergic crisis (sx don’t improve, tx: temporarily discontinue pyridostigmine)
insulin action on hepatocytes
tyorsine kinase receptor activates MAP K and PI3K pathways
MAP K => cell growth, DNA synthesis
PI3K => glycogen, lipid, and protein synthesis, increased GLUT-4 expression via activation of protein phosphatase, which activates glycogen synthase
key steps in glucagon signalling
GPCR/adenylate cyclase pathway => PKA => activated glycogen phosphorylase => glycogen breakdown
renal osteodystrophy
CKD => hyperphosphatemia + hypocalcemia => secondary hyperparathyroidism => increase osteoclast activity => osteopenia
can also => PTH resistance => low bone turnover + osteomalacia (inadequate mineralization)
hepatic pyruvate metabolism
either pyruvate dehydrogenase -> acteyl-CoA-> CAC
or pyruvate carboxylase -> oxaloacetate -> glucose
high Acetyl-CoA feedback-inhibits pyruvate dehydrogenase and activates pyruvate carboxylase => increased gluconeogenesis
this allows hepatocytes with enough energy to make glucose to release into the blod
minimal change disease
most common cause of nephrotic syndrome (hematuria and proteinuria) in kids
immune dysregulation (post-URI) => podocyte damage => loss of BM anions + loss of charge barrier => albuminuria
tx: corticosteroids
POMC
proopiomelanocortin (polypeptide precursor) modified to form beta-endorphins, ACTH, and MSH (melanocytes stimulating hormone)
anticholinergic toxicity
Mad as a hatter (AMS)
hot as a hare (hyperthermia)
red as a beet (flushing)
dry as a bone (decreased saliva and sweat)
blind as a bat (mydriasis)
the bowel and bladder lose their tone (constipation, urinary retention)
and the heart runs alone (tachycardia)
mucormycosis
facial pain, HA, and nasal eschar in pt with DKA
can go to brain => AMS and death
histo shows ribbon-like nonseptate hyphae with right-angle branching
tx: amphotericin B, surgery
innervation to the external auditory canal
mostly trigeminal (CN V3) posterior portion is from vagus (CN X)
major blood supply to femoral head/neck
medial femoral circumflex a.
injury via femoral neck fx can => osteonecrosis of the femoral head
diastolic heart failure
from decreased LV compliance (restrictive cardiomyopathy)
caused by transthyretin mut => amyloid accumulation (infiltrative cardiomyopathy), sarcoidosis, HTN, and obesity
sertoli and leydig roles in development
Sertoli -> AMH => loss of mullerian ducts
Leydig -> testosterone => development of Wolffian ducts and male secondary sex characteristics
losing Sertoli => dual internal genitalia and male external genitalia
losing Leydig => no internal genitalia (except testes), female external genitalia
Alzheimer’s MRI and tx
MRI: cortical atrophy (worst in hippocampus and temporoparietal lobes) without other reversible cause to sx
tx: 1) increase cholinergic neurotransmission (donepezil)
2) protect neurons via antioxidants (vitamin E)
3) NMDA R antagonists (memantine)
IL-4
made by Th2 cells => growth of BCs and Th2 cells, => isotype switching to IgE
PSGN
edema, hematuria, hx GAS infection
type III hypersensitivity reaction => immune complex deposition (anti-strep Abs bound to strep Ags)
EM shows subepithelial humps; IF (anti-IgG and C3) shows granular depositions in mesangium and capillary walls
PTT v PT
PTT - intrinsic + common
PT - extrinsic + common
Addison disease
chronic primary adrenal insufficiency - adrenal atrophy or destruction (autoimmune or TB) => decreased aldosterone and cortisol => hyponatremia and HoTN, hyperkalemia, metabolic acidosis, hyperpigmentation (MSH is byproduct of ACTH production as ACTH goes up to try to stimulate cortisol release)
aldosterone
increased Na reabsorption and K and H secretion - in response to low volume or hyperkalemia
sympathomimetic overdose
tachycardia, tachypnea, temp 102-104, big pupils (mydriasis), increased bowel sounds and secretions
agitation, AMS, sz
cocaine, meth, MDMA (also thirsty), bath salts, pseudoephedrine, epi, NE
opiod overdose
bradycardia, slow RR, cold, miosis (pinpoint pupils), no bowel sounds, clammy
decreased level of counsciousness
heroin, etc
anticholinergic overdose
tachycardia, hot, dry, big pupils (mydriasis), decreased bowel sounds
altered (mad as a hatter)
belladonna, Jimson weed, plants, TCAs, antihistamines, AChR blockers
cholinergic overdose
bradycardia, bronchospasm, increased secretions and sweat, fasciculations, increased bowel sounds, miosis
decreased level of consciousness
paralysis if nicotinic
carbamates, organophosphates, sarin gas, shrooms
tx: atropine and pralidoxine, intubation
sedative/hypnotic overdose
low RR, otherwise nl vitals
alcohol, benzos, barbs, antiepileptics, date rape drugs
no response to narcan
tx: intubation, time
sodium correction in hyperglycemia
increased serum glucose pulls water out of the cells => relative dilutional hyponatremia
Corrected Sodium = Measured sodium + 0.016 * (Serum glucose - 100)
DKA effects on potassium
acidosis pushing H+ into cells which is exchanged for K+ => hyperkalemia but total body K depletion
Wiskott-Alrich syndrome
X-linked WASp (RBC cystoskeleton protein) mut => eczema, recurrent infections, and thrombocytemia
BC and TC defect => encapulated and opportunistic infections starting at 6mos
tx: bone marrow transplant
melanocyte developmental origin
neural crest
TMP and sulfa targets
TMP - bacterial DHFR (same as MTX - ppl and pyrimethamine - fungi)
sulfa - dihydropteroate synthetase
renal blood flow calculation
(urine[PAH] * urine flow rate) / (plasma[PAH]*(1-hematocrit))
neoplastic and non-neoplastic colon polyps
neoplastic: villous >tubular >serrated
non-neoplastic: hyperplastic, submucosal, inflammatory, mucosal
trigeminal nerve brainstem level
CN V exits the brainstem at the pons at the level of the middle cerebellar peduncles
damage to CN V => facial paresis including forhead muscles
if forehead muscles are spared it’s a lesion of the corticobulbar cract
amphotericin B side effects
nephrotoxicity => anemia, hypokalemia, and hypomagnesemia
hypokalemia => weakness and arrythmias (PVCs, VT, VF)
hypokalemia EKG
T wave flattening, ST depression, prominent U waves, arrythmias
hyperkalemia EKG
tall peaked T waves, P wave flattening, PR interval lengthening, QRS widening
=> sine wave pattern => VF
muddy brown casts
acute tubular necrosis (ATN) - from acutely decreased renal perfusion - usually affects thich ascending loop of Henle and proximal tubules
increased creatinine and BUN, nl BUN/cre ratio, oliguria
usually regenerates in about 3 wks
renal papillary necrosis
from UTI/obstruction, analgesic ingestion, DM2, or SCD
=> gross hematuria, flank pain, tissue fragments in urine
RPGN
nephritic - HTN, hematuria, moderate proteinuria
anti-GBM IgG targets type IV collagen => C3 deposition => crescentic glomerulonephritis on light microscopy and linear Ig deposits on IF
Goodpasture syndrome: RPGN + pulmonary hemorrhage from anti-GBM Abs cross-reacting with alveolar BM
sudden cardiac death
in first 48 hrs after MI, most likely from VF
pseudogout
calcium pyrophosphate crystals - mostly knee joint
rhomboid-shaped positively birefringent
class 1C antiarrythmic effects on EKG
(flecainide) - block Na channels which cause phase 0 (rapid depolarization) of cardiac AP, which => wide QRS without long QT
normal tracheal pO2, alveolar pO2, and alveolar pCO2
effects of perfusion and diffusion defects
normal tracheal pO2 = 150 mmHg
normal alveolar pO2 = 104 mmHg
normal alveolar pCO2 = 40 mmHg
if alveolar pO2 rises to match tracheal that’s due to a failue of equilibration with venous blood
if drops Co2 and raises O2, it’s usually due to perfusion defect, but if it only raises O2 that’s from a diffusion limitation
hormones that signal via cAMP
FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2), MSH, PTH, calcitonin, GHRH, glucagon, histamine (H2)
(Gs and Gi receptors)
hormones that signal via cGMP
BMP, ANP, EDRF (NO)
vasodilators
hormones that signal via IP3
GnRH, Oxytocin, ADH (V1), TRH, histamine (H1)
Gq receptors
hormones that signal via intracellular receptor
progesterone, estrogen, testosterone, cortisol, aldosterone, T3/T4, vitamin D
(adrenal cortex products + T and D)
hormones that signal via receptor tyrosine kinase
(MAP K pathway)
insulin, IGF-1, FGF, PDGF, EGF
(growth factors)
hormones that signal via nonreceptor tyrosine kinase
(JAK/STAT pathway)
prolactin, cytokines, GH, G-CSF, erythropoietin, thrombopoietin
aortic arch derivatives
1 - maxillary artery (branch of internal carotid)
2 - stapedial and hyoid arteries
3- common carotid and proximal internal carotid
4 - L aortic arch, R proximal subclavia
6 - proximal pulmonary arteries and ductus arteriosus
branchial cleft derivatives
(clefts = outside ridges)
1 - external auditory meatus
2-4 - temporary cervical sinuses
if persist, => immobile cyst in lateral neck
branchial arch derivatives
1 - maxilla, mandible, malleus, incus, muscles of mastication, CN V2, V3
2 - stapes, styloid process, stylohyoid ligament, muscles of facial expression, stapedius, stylohyoid, CN VII
3 - greater horn of hyoid, stylopharyngeus, CN IX
4-6 - arytenoids, cricoid, corniculate, thyroid, pharyngeal constrictors and intrinsic larynx muscles, 4-> CN X, 6 -> recurrent laryngeal (CN X)
chew, smile, swallow stylishly, simply swallow, then speak
branchial pouch derivatives
(pouches = inside ridges)
1 - middle eat, eustacian tube (endoderm)
2 - epithelial lining of palatine tonsil
3 - inferior parathyroids, thymus
4 - superior parathyroids, parafollicular (C cells) of thyroid (make calcitonin)
ear, tonsils, bottom to, top
sperm pathway
seven up seminiferous tubules epididymis vas deferens ejaculatory ducts (nothing) urethra penis
sperm precursors
-gonium is going to be a sperm; -zoon is zooming to the end
gestational HTN
BP>140/90 after 20th wk without pre-existing HTN
tx: hydralazine, a-methyldopa, labetalol, nifedipine (hypertensive moms love nifedipine)
preeclampsia
gestationl hypertension + proteinuria or end0organ dysfunction
from abnormal placental spiral arteries => endothelial dysfcn, vasoconstriction, and ischemia
tx: hydralazine, a-methyldopa, labetalol, nifedipine
IV magnesium sulfate, delivery
eclampsia
preeclampsia + maternal sz
tx: IV magnesium sulfate, antihypertensives, delivery
HELLP syndrome
Hemolysis, Elevated Liver enzymes, Low Platelets
schistocytes on blood smear; => hepatic subcapular hematomas => rupture and severe HoTN
tx: delivery, antihypertensives, magnesium sulfate, corticosteroids
Ca from DES exposure in utero
clear cell adenocarcinoma
HPV ca mech + histo
HPV 16+18 make E6 (blocks p53) and E7 (blocks Rb) => proliferation => cervical cancer
koilocytes (dark nucleus with halo) are pathognomonic for HPV
drugs => gynecomastia
Spironolactone, Hormones, Cimetidine, Ketoconazole
some hormones create knockers
Peyronie disease
Louis XIV
fibrous plaque in tunica albuginea => abnormal curvature of penis and erectile dysfcn
tx: surgical repair once curvature stabilizes
falciform ligament connection and structures contained
liver to ant. abdominal wall
contains ligamentum teres (from umbilical vein)
hepatoduodenal ligament \ connection and structures contained
liver to duodenum
contains portal triad (proper hepatic a, portal v, common bile duct)
can pinch to control bleeding
part of lesser omentum
gastrohepatic ligament connection and structures contained
liver to lesser curvature of stomach
contains gastric arteries
separates greater and lesser sacs
part of lesser omentum
gastrocolic ligament connection and structures contained
greater curvature of stomach and transverse colon
contains gastroepiploid arteries
part of greater omentum
gastrosplenic ligament connection and structures contained
greater curvature of the stomach and spleen
contains short gastric a.s, left gatroepiploic v.s
separates greater and lesser sacs
part of greater omentum
splenorenal ligament connection and structures contained
spleen and post. abdominal wall
contains splenic a. and v., tail of pancreas
kupffer cells
specialized liver macrophages
form lining of sinusoids
Ito cells
hepatic stellate cells
in space of Disse (lymph drainage)
store vitA when quiescent
produce ECM when activated
primary sources of damage to liver zones
zone I (portal triad) - ingested toxins and viral hepatitis zone II (canalliculus and sinusoid) - yellow fever zone II (central vein) - ischemia, metabolic toxins, alcoholic hepatitis
sites of Fe, B9, and B12 absorption
Iron Fist, Bro
Fe2+ (iron) in duodenum
B6 (folate) in small bowel
B12 (cobalamin) in terminal ileum via IF
3 causes of gastric ulcers
NSAIDS -> decreased PGE2 -> decreased protection
Burns -> hypovolemia -> mucosal ischemia
Brain injury -> increased vagal stimulation -> increased ADh -> increased acidity
adenomatous polyps
can => neoplasia via chromosomal instability pathway (APC -> KRAS -> p53 muts)
villous more malignant than tubular
serrated polyps
can => neoplasia via microsatellite instability pathway (BRAF, mismatch repair mut)
familial adenomatous polyposis
(FAP) AD APC mut (chromosome 5) => thousands of colorectal polyps after puberty => CRC
tx: prophylactic colectomy
Gardner syndrome
(FAP-plus)
thousands of colorectal polyps after puberty => CRC
osseous and soft tissue tumors, congenital retinal pigment epithelium hypertrophy, impacted/supernumerary teeth
Turcot syndrome
FAP/Lynch syndrome plus malignant CNs tumor
FAP - colon polyps/CRC
Lynch - CRC and endometrial, ovarian, and skin ca
Peutz-Jeghers syndrome
AD, => numerous GI hamartomas, hyperpigmented mouth, hands, genitalia
increase risk of breast and GI ca
Juvenile polyposis syndrome
AD - numberous GI hamartomatous polyps <5 yo => CRC
Lynch syndrome
(HNPCC) AD mismatch repair mut => microsatellite instability => CRC, endometrial, ovarian, and skin ca
ischemic stroke histo
12-24 hrs - red neurons
1-3 days - neutrophilic infiltration
3-7 days - macrophages and microglia
1-2 wks - reactive gliosis and vascular proliferation (liquefactive necrosis macroscopically)
>2 wks - glial scar formation, macroscopically cystic area surrounded by fibrosis
H. influenzae
G- coccobacilli
can’t grow on sheep blood agar - require hematin and NAD+ (released by S. aureus => satellite colonies if plated together)
oocyte arrests
after birth to ovulation - prophase of Meiosis I
until fertilization - metaphase of Meiosis II
pancreatic beta cell receptors
M3, glucagon, B2, and GLP-1 receptors all => increased insulin secretion (Gq and Gs)
a2 and somatostatin 2 receptors => decreased insulin secretion (Gi)
selective IgA deficiency
mild, recurrent URIs and GI infections (giardia), autoimmunity
anaphylaxis during blood transfusion (due to anti-IgA IgE recognizing donor IgA)
low or absent IgA; normal IgG and IGM
skeletal v. cardiac and smooth muscle Ca source
cardiac and smooth: extracellular Ca influx through L-type Ca channels (blocked by CCBs)
skeletal: Ca release from sarcoplasmic reticulum via RyR linked to L-type Ca channels (resistant to CCBs)
parvovirus B19 clinical course
ss DNA virus
kids: erythema infectiosum (5th disease - slapped cheek rash, fever, reticular rash on arms, legs, trunk) - ICs
adults: acute symmetric arthropahty - ICs
chronic hemolytic anemia: transient aplastic crisis
cholesteatoma
round pearly mass behind TM
collections of squamous cell debris from cysts due to chronic negative pressure
=> discharge + TM rupture
reassortment v. recombination
reassortment: mixing of genome segments in 2 segmented viruses infecting same host cell
recombination: gene exchange via corssing over of 2 ds DNA molecules
washout period for antidepressants
when switching from MAOI to SSRI need 2 wk washout period to prevent serotonin syndrome - this allows production of new MAO which was irreversibly inhibited by the MAOI
compensation for metabolic acidosis
Winter formula
PaCO2 = 1.5 (serum bicarb) + 8 +/- 2
compensation for metabolic alkalosis
PaCO2 should increase by 0.7 mmHg for every 1 mEq/L rise in serum bicarb
compensation for acute respiratory acidosis
serum bicarb should increase by 1 mEQ/L for every 10 mm Hg rise in PaCO2
compensation for acute respiratory alkalosis
serum bicarb should fall by 2 mEq/L for every 10 mmHg decrease in PaCO2
Ascending v. descending colon cancer sx
Ascending: bleeding, Fe deficiency anemia
Descending: obstruction
salk v. sabin
Sabin = oral live attenuated => stronger mucosal secretory IgA response thank Salk (only IgG)
Bipolar I
manic episode
depression common but not required
Bipolar II
hypomanic episode and at least one major depressive episode (>2 wks)
cyclothymic disorder
at least 2 yrs of fluctuating mild hypomanic and depressive sx that don’t meet criteria for hypomanic or major depressive episodes
etoposide
inhibits topoisomerase II (makes ds breaks to resolve + and - supercoiling)
prevents ability to seal breaks
used in testicular cancer and small cell lung cancer
koilocytes
HPV
multinucleated giant cells
(+ Tzanck smear)
VZV
chemoreceptor trigger zone location
(CTZ) - responsible for chemo-induced nausea
area postrema of the dorsal medulla (near the 4th ventricle)
arm abduction muscles and nerves
0-15 degrees - supraspinatus - suprascapular n
15-100 degrees - deltoid - axillary n
>90 degrees - trapezius - accessory n
>100 degrees - serratus anterior - long thoracic n
axillary n spine levels, causes of injury, and function
C5-C6
humeral neck fracture or anterior dislocation
innervation to deltoid, sensation to deltoid and lateral arm
musculocutaneous n spine levels, causes of injury, and function
C5-C7
upper trunk compression
forearm flexion and supination, lateral forearm sensation
radial n spine levels, causes of injury, and presentation
C5-T1
midshaft humerus fracture, acillary compression
damage => wrist drop, decreased grip strength, and loss of sensation over posterior arm/forearm and dorsal hand
median n spine levels, causes of injury, and function
C5-T1
supracondylar humerus fracture, carpal tunnel, wrist lac
wrist flexion, lateral finger flexion, thumb opposition, sensation over thenal eminense and lateral 3 1/2 fingers
ulnar n spine levels, causes of injury, and function
C8-T1
medial epicondyle humberus fracture, hook of hamate fracture from FOOSH injury
wrist and medial finger flexion, interossei, medial 2 lumbricals, sensation over medial 1 1/2 fingers and hypothenar eminence
recurrent median n spine levels, causes of injury, and function
C5-T1
palm lac
opposiition, abduction, thumb flexion - no sensation
Erb palsy injury, muscle deficit, and presentation
upper trunk tear
deltoid, supraspinatus, infraspinatus, biceps brachii
=> waiter’s tip
Klumpke palsy injury, muscle deficit, and presentation
lower trunk tear
intrinsic land muscles
=> total claw hand
thoracic outlet syndrome injury, muscle deficit, and presentation
compression of lower trunk and subclavian vessels
intrinsic hand muscles
=> total claw hand plus ischemia, pain, and edema
winged scapula injury, muscle deficit, and presentation
long thoracic nerve
serratus anterior
winged scapula, can’t abduct arm above horizontal
thenar muscles and innervation
opponens pollicis, abductor pollicis brevis, flexor pollicis brevis
median n
hypothenar muscles and innervation
opponens digiti minimi, abductor digiti minimi, flexor digiti minimi brevis
ulnar n.
L3-L4 herniation n. affected and sx
femoral n
weak knee extension, loss of patellar reflex
L4-L5 herniation n. affected and sx
common peroneal n. (from sciatic)
weakness of dorsiflexion (foot drop), difficulty with heel-walking
L5-S1 herniation n. affected and sx
tibial n. (from sciatic)
weakness of plantar flexion, difficulty with toe-walking, decreased achilles reflex
benign and malignant bone tumors
benign: oesteochondroma, giant cell tumor (osteoclastoma)
malignant: osteosarcoma, ewing sarcoma
osteochondroma
common, benign, M<25 - bony “skin tag” with cartilaginous cap
giant cell tumor
20-40 yos, benign but locally aggressive => “soap bubble” on XR, epiphysis of long bones
multinucleated giant cells expressing RANKL (osteoclastoma