Mixed Flashcards
autosomal dominant long QT syndrome
Romano-Ward
mutation in V-gated K channel
autosomal recessive long QT syndrome, sensorineural deafness
Jervell and Lange-Nielson
mutation in long QT involves:
K channel (rectifier current)
mutated cardiac cell cytoskeletal proteins or mitochondrial oxidative phosphorylation proteins
inherited dilated cardiomyopathy
mutated sarcomeric proteins ( B-myosin heavy chain, myosin binding protein C)
autosomal dominant hypertrophic cardiomyopathy
trinucleotide repeat expansion diseases: (5)
fragile X, Huntington’s, myotonic dystrophy, Friedrich ataxia, spinocerebellar ataxia, often have anticipation (offspring earlier onset and worse sx)
Imprinting diseases (2)
Prader-Willi (paternal deletion, maternal inactivation), Angelman’s (maternal deletion, paternal inactivation)
Chromosomal deletion diseases (3)
Cri du chat (5p deletion), Prader-Willi (15q deletion), DiGeorge (22q11 microdeletion)
SE of pulmonary fibrosis and flagellate skin discoloration, chemotherapy drug
Bleomycin
CHF due to chemo drug SE
doxorubicin
SE of hemorrhagic cystitis, chemo drug
cyclophosphamide
stop codons
UAG, UAA, UGA
potency of an inhaled anesthetic is defined by this parameter
MAC
rate of onset of inhaled anesthetic
related to arteriovenous gradient and tissue solubility
hematuria, edema, HTN
PSGN
tea/cola-colored urine, periorbital or generalized edema
UA with protein, blood, RBC casts, low C3 and C4, increased serum creatinine
anti-DNase B and AHase
ASO, anti-NAD if pharyngitis
PSGN histology
granular sub epithelial deposits of IgG, IgM, C3
gram +, bacitration sensitive, beta hemolytic, in chains
GAS
acute oligoarthritis, conjunctivitis, urethritis, caused by deposition of immune complexes after GI or GU infection
reactive arthritis
associated with HLA B27
Prader-Willi
Loss of PATERNAL genes on chromosome 15
paternal micro deletion or maternal UPD
neonatal hypotonia, hyperphagia, short, hypogonadism
Angelman syndrome
Loss of MATERNAL genes on chromosome 15
maternal micro deletion or paternal UPD
epilepsy, ataxic gait/tremors, laughter/smiling
mucosal erythema and neutrophil infiltration of small bowel
IBD, infectious colitis
macrophages with accumulated PAS+ granules
Whipple disease
associated with HLA DQ2 and DQ8, gliadin exposure
Celiac
dermatitis herpetiformis, pruritic, b/c of anti-gliadin IgA Ab cross react with transglutaminase at dermal BM–microabscesses at dermal papillary tips that coalesce to form sub epidermal blisters
confirm with IgA immunofluorescence staining
villous atrophy
increased rate of myosin mRNA synthesis
causes cardiac hypertrophy
elevated CA-125
epithelial ovarian cancer, unilocular cysts with papillary growths in the center lumen of cyst, BRCA increases risk
elevated androgen levels inhibit single follicle from dominance, multiple small follicles instead
PCOS
androgen excess, ovarian dysfunction, insulin resistance, obesity
PCOS
PCOS treatment
wt loss, OCP, metformin for DM
what determines cellular differentiation
transcription factor milieu, allow only certain genes to be expressed, can also induce de differentiation
terminally differentiated cell reverts to less specialized form
dedifferentiation, induced by transcription factors
EGFR over expression predisposes to
colon cancer
HGPRT deficiency
X-linked
Lesch-Nyhan
hyperuricemia and hyperuricuria lead to nephrolithiasis and gout, self-mutilation, dev delay, dystonia
pilocarpine
direct cholinergic muscarinic agonist
atropine
mAch R antagonist
physostigmine
indirect cholinergic agonist, requires functioning neurons to work
phenylephrine
alpha agonist (alpha1>alpha2)
timolol
nonselective BB
pupillary constriction
mAch R
pupillary dilation
alpha 1 adrenergic R
aqueous humor secretion
B2 R
fatigue, peripheral neuropathy, atrophic glossitis, macrocytosis and hyperhsegmented neutrophil
pernicious anemia: AI destruction of gastric mucosa–> chronic atrophic gastritis–> hypochlorhydria that increases gastrin secretion, loss of IF-secreting parietal cells–> depletes B12
what cell type secretes IF
parietal cells
where is B12+IF absorbed
distal ileum
testicular mass, no transillumination with light, enlarge with standing, regress when lying down
varicocele
dilations of spermatic vein pampiniform plexus due to aorta and SMA compression of L renal vein–> retrograde blood flow
bag of worms feeling
testicular atrophy, reduced fertility
acanthosis nigricans (black/velvety thickened plaques in flexural areas)
insulin resistance
GI malignancy or lungs
atrophic glossitis (shiny tongue)
nutritional deficiency: Fe, B12, folate, others
anticoagulation for mechanical heart valve
vitK antagonist
Warfarin MOA
inhibits vitamin K epoxide reductase–> decrease clotting factors
normally vit K helps gamma carboxylate II, VII, IX, X–> converted to inactive form, the epoxide reductase reactivates vit K
eptifibatide, abciximab, tirofiban
GPIIb/IIIa inhibitors, inhibit platelet aggregation and activation
clopidogrel, ticagrelor, prasugrel
P2Y12 R blockers inhibit platelet activation and aggregation
PCSK9 inhibitor
increases degradation of hepatic LDL-R, alirocumab is Ab against PCSK9–> increases LDL clearance
TPA
fibrinolytic, convert plasminogen into plasmin to bind fibrin in thrombus, use in STEMI and stroke
cells that make testosterone
Leydig cells, stimulated by LH
GnRH agonist
leuprolide, inhibits LH and FSH release from ant pit
decreases testosterone synthesis
ketoconazole
decreases conversion of T to DHT
5alpha reductase inhibitors (finasteride)–treat BPH and male pattern baldness
androgen R blockers
flutamide, cyproterone, spironolactone
most prostate cancers are ____ dependent
androgen–so treat with surg orchiectomy or pharm suppression of T–> relieve sx, slow dz
melanocytes are derived from
neural crest, migrate from neural crest to dermis and epidermis
germ cells
migrate from yolk sac to gonadal ridge
oogonia go through mitosis and meiosis and arrest in prophase I
spermatogonia go through proliferation in basal compartment and give rise to primary spermatocytes
anaplasia in skeletal muscle
rhabdomyosarcoma
conotruncal cardiac defects abnormal facies thymic aplasia cleft palate hypocalcemia (CATCH)
DiGeorge
22q11.2 deletion
defective development of pharyngeal pouches 3 and 4
lack of CD40L on CD4 cells
hyperIgM syndrome XR
normally T cell CD40L binds CD40 on B cell
and TCR binds MHCII on B cell
then CD4 T cell releases cytokines to help Ig class switching
IL-13 leads to IgE
low IgG, IgA, IgE
sinopulm, GI inf, OI
low B cells and Ab
X-linked (bruton) agammaglobulinemia
CpG dinucleotide repeats (cytosine-guanine) in promoter region
preferentially methylated, part of epigenetic code, silences transcription
prokaryotes methylate ___
adenine and cytosine residues
UV radiation damages DNA by
forms covalent bonds b/w thymine residues–> thymine dimers
rRNA is synthesized by
RNA polymerase I
mRNA is synthesized by
RNA polymerase II
methylation of histones
represses DNA transcription
Rx for cataplexy
stimulants for narcolepsy, TCA for cataplexy
abdominal viscera, viscera of L hemithroax, all inferior to umbilicus, and L superior to umbilicus–> cancer enlarges what LN
L supraclavicular LN (Virchow’s node) b/c receives all of thoracic duct
tongue malignancy–> what LN
submandibular, submental, deep cervical LN
breast cancer–> what LN
axillary or parasternal
MCA infarct–> what VF defect
homonymous hemianopsia
damage optic radiations (temporal = lower = Meyer’s, upper = parietal)
homonymous hemianopsia caused by infarct of
MCA, PCA, anterior choroidal (lesion distal to optic chiasm)
acute rhinosinusitis most commonly affects
maxillary sinuses b/c poor drainage (drains up to middle nasal meatus)
inferior to each orbit
anion gap metabolic acidosis, flank pain, hematuria, oliguria
ethylene glycol poisoning
metab to glycolate that is cytotoxic to renal tubules–> ATN
glycolate to oxalate–> precipitates in kidneys and obstruct tubules
envelope (square with X in it) or dumbbell shaped Ca oxalate crystals, + birefringent
suspected CO poisoning–measure what?
carboxyhemoglobin (pO2 normal)
PTH actions
increase bone resorption, increase renal reabsorption of Ca, decrease reabsorption of phos, increase conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D
vitamin D actions
increase intestinal absorption of Ca and phos (**), increase renal reabsorption of both, decrease PTH, increase bone mineralization
calcitonin actions
decrease bone resorption, decrease renal Ca reabsorption
decreasing ___ increases contraction velocity
afterload
ADH/vasopressin R is a
GPCR, Gs–> AC–> cAMP–> PKA–> AQP2 to luminal membrane
causes of nephrogenic DI
Li, hyperCa, hereditary (AVPR2 mutations–> defect in AQP2)
HOXA13 mutation
hand foot genital syndrome
dominant
malformed distal limbs (hypoplastic digit), mullerian fusion abnl–> miscarriages)
Homeobox genes
encode transcription foactors modulating rostro-caudal, limb, and genital axes–> develop axial and appendicular skeleton, CNS, gut, urogenital tract
HER-2/neu, ERBB2
EGFR overexpressed in BC
PAX (paired box)
for embryologic specification of certain tissues
mutations in PAX6–> ocular defects like aniridia (absent iris)
TP53
tumor suppressor, mutated in Li Fraumeni (BC and sarcomas)
VHL
VHL, retinal, cerebellar, spinal hemangioblastomas
RCC, pheo, panc tumors
HIV nephropathy
FSGS/Collapsing glomerulopathy, FSGS + collapse and sclerosis of whole glomerular tuft, glom epithelial cell proliferation and hypertrophy, marked tubular injury with accompanying microcyst formation
FSGS
heroin addiction, HIV, SCD
crescents, glomerular tuft collapse
anti-GBM or ANCA-associated RPGN
diffuse glomerular capillary wall thickening, spiky subepithelial IgG deposits
membranous glomerulopathy
enlarged, hypercellular glomeruli with infiltration by neuts and monocytes, increased mesangial cellularity causes capillary basement membrane thickening, granular IgG or C3 deposits
membranoproliferative glomerulonephritis
diffuse hyper cellularity of glomeruli, infiltrated with PMN and monocytes, diffuse granular IgG and C3 deposits
PSGN
diffuse mesangial proliferation and expansion of ECM, granular IgA deposits
IgA nephropathy/Berger disease, related to HSP
direct uptake of naked DNA from environment
transformation
one way transfer of chromosomal or plasmid DNA, F factor DNA–> sex pilus = donor, no F factor = recipient
conjugation
transfer of DNA by bacteriophage
transduction
generalized: random bacterial genes into virion during lytic infection
specialized: packaging of specific genes into viral insertion site during lysogenic infection
broom-like fungus on methenamine silver stain
Aspergillus
PCP at CD4 of
<200
cup/disc shaped organisms on silver stain
PCP
gram positive bacterium, mouth or GI tract abscesses after trauma, yellow sulfur granules
actinomyces
umbilical venous catheter passes through
umbilical vein–> ductus venosus–> IVC
ligamentum teres is remnant of
umbilical vein
medial umbilical ligaments are remnants of
umbilical arteries
drains blood from posterior walls of thorax and abdomen into SVC
azygous vein
umbilical artery passes through
umbilical artery, internal iliac, common iliac, aorta
aspirin MOA
irreversibly inhibits COX-1 and COX-2
COX-1 inhibition in platelets–> prevents TXA2 production–> prevent platelet aggr and vasoconstriction
COX-2 inhibition promotes thrombotic events if selective COX-2 (celecoxib) b/c decrease endothelial cell production of PGI2 which normally vasodilates and inhibits platelet aggr
anti TNF alpha
infliximab (Ab to TNF-alpha) and etanercept (recombinant TNF R fusion protein)
TNF alpha
produced by macrophages, inflammatory response by accel neut migration and macrophage phagocytosis, lymphocyte prolif and cytokine synth, can cause fever, anorexia, increase in acute phase reactants, cachexia, septic shock, corticotropin releasing hormone
prednisone
suppress PMN migration, reverse increases in capillary permeability
tacrolimus
suppress T cell activation by binding FKBP-12 (intracellular), used in transplant and severe atopic dermatitis
imatinib
inhibits BCR-ABL tyrosine kinase, CML
methotrexate
folate antimetabolit, inhibit DNA synth in rapidly proliferating cells
Gq
alpha 1 adrenergic R, epi/norepi binds–> activates Gq–> activates PLC–> releases IP3 and DAG from membrane phospholipids
IP3–> Ca release from ER
DAG–> activates PKC
together–> smooth muscle contraction
increased 2,3-BPG
right shift, increased O2 delivery
Gs
Gs activate AC–> cAMP–> PKA activated
Beta agonists, glucagon, PTH, TSH
BNP, ANP, NO R mech
G–> GC—> cGMP–> activate protein kinase G–> smooth muscle relaxation
SAM (S-adenosylmethionine)
methyl group donor, for norepi–> epi via phenylethanolamine-N-methyltransferase in adrenal medulla, increases with cortisol
early: bowel wall with mucosal hemorrhage and pathy necrosis, later: thickened and edematous, transmural infarct
ischemic colitis
mutation in osteogenesis imperfecta
mutated type I collaen, COL1A1 and COL1A2
dystrophin mutation
connects muscle to ECM, causes duchenne muscular dystrophy
fibrillin mutation
Marfan
impaired intestinal copper transport
Menkes syndrome, X-linked recessive, sz, dev delay, skeletal abnl, brittle hair
megaloblastic anemia, yellow skin, smooth shiny tongue, shuffling/broad-based gait
pernicious anemia
megaloblastic anemia, sore tongue, angular stomatitis, GI upset, pain with swallowing, hyperpigmentation
folate deficiency
hypochromic microcytic anemia, glossal pain, dry mouth, atrophy of tongue papilla, alopecia, pagophagia
Fe deficiency
basophilic stippling, hypochromic microcytic RBC
sideroblastic anemia
ring sideroblasts
alcohol, myelodysplastic syndromes
picornavirus family includes
enterovirus (enterovirus, coxsackie, echovirue, polio), parechovirus, hepatovirus (hepA), rhinovirus
picornavirus genome
naked, icosahedral, ss + sense RNA
reovirus
includes rotavirus, ds RNA
paramyxovirus
negative sense, ssRNA, measles, mumps, RSV
coronavirus
+ sense ssRNA, common cold
calcivirus
+ sense ssRNA, norovirus
arenaviruses
- sense ssRNA, Lassa virus (hemorrhagic fever when dirt/dust with rodent urine inhaled)
most common cause of viral meningitis
enteroviruses (picornavirus, ssRNA +)
Standard error (SE)
variability around the mean
= stan dev/ square root (n)
brief psychotic disorder
<1 month
unmyelinated nerves
primary sensory afferent fibers responsible for slow pain, heat sensation (group C nerve fibers), olfaction
postganglionic autonomic neurons
glucose-6-phosphate dehydrogenase deficiency
X=linked, African Asian Mediterranean
inadequate reducing equivalents through pentose phosphate shunt–> oxidant stress e.g. sulfonamides–> methemoglobin and oxygen free radicals that denature Hgb, damage membrane, causes intravascular and extravascular RBC hemolysis
duchenne inheritance
X-linked recessive dystrophin mutation (links actin to skeletal muscle PM)
wide fixed split
ASD
holosystolic murmur over LSB
VSD
thyroid: intense diffuse lympocytic infiltrate, destruction of thyroid follicles, formation of lymphoid germinal centers, Hurthle cells (metaplastic enlarged epithelial cells with prominent nucleoli and abundant eosinophilic cytoplasm surrounding atrophic thyroid follicles
Hashimoto thyroiditis
chronic lymphocytic thyroiditis
thyroid: intact capsule around well-differentiated colloid containing follicles
follicular adenoma
thyroid: relatively uniform cells forming small follicles, nests, or sheets
follicular carcinoma, often hemorrhage, capsular invasion, vascular invasion
thryoid: tall epitheium, crowded with hyperactive resorption causing scalloping around edges of colloid
Graves
fungi SW US, mexico, South america, mild pneumonia, thin walled cavity in lung–> hemoptysis
Coccidio
pontiac fever: self-limited flue like disease
legionella
lobar pneumonia, hemoptysis in alcoholic
current jelly hemoptysis
klebsiella
or COPD or diabetes
togavirus genoma
enveloped, ss RNA +
picornavirus
+ sense ssRNA, naked
poxvirus
linear, dsDNA, ONLY DNA VIRUS NOT REPLICATING IN NUCLEUS
paramyxovirus
enveloped neg sense ssRNA
papillomavirus
replicate in host cell nucleus, nonenveloped, circular dsDNA
recurrent laryngeal innervates
all intrinsic muscles of larynx except cricothyroid (external laryngeal, branch of superior laryngeal)
all the arytenoids
can be damaged by aneursym of aortic arch (L), R near brachiocephalic artery
hereditary cancer syndromes are all caused by ___ mutations EXCEPT MEN2
autosomal dominant inactivating mutation in tumor suppressor, 2nd hit to loss of heterozygosity and malignant transformation
MEN2–autosomal dominant activating (GOF mutation) in proto-oncogene RET–> continuous stimulation of cell division causes tumor growth
MEN2
AD activating mutation of RET
medullary thryroid cancer, pheochromocytoma, parathyroid hyperplasia
MEN1
MEN1 AD inactivating mutation, parathyroid+pituitary+pancreatic adenomas
Li Fraumeni syndrome
TP53 inactivting mutation AD, sarcomas, BC, brain tumors, adrenocortical carcinoma, leukemia
VHL
AD inactivation of VHL, hemangioblastomas, CC renal carcinoma, pheochromocytoma
FAP
APC mutation AD, inactivating, colorectal cancer, desmoids and osteomas, brain tumors
Lynch
MSH2/MLH1/MSH6/PMS2 inactivating AD, CRC, endometrial, ovarian cancer
osteomalacia pathophys
decreased mineralization of osteoid (inadequate Ca and phos) b/c of vitD deficiency, malabsorption, CKD, RTA
bone pain, muscle weakness
bony fibrocartilage callus
early fx repair, fibroblast and chondroblast deposit firm flexible hyaline, that is mineralized
osteoporos pathophys
bone resorption> bone formation, otherwise normal mineralization, affect compact and trabecular bone, increased risk of fracture but no bone pain/muscle weakness
woven bone vs lamellar bone
woven bone immature, from fetal osteogenesis and after fracture, remodeled to lamellar bone that is stronger and has regular parallel collagen fibers in sheets
Paget disease
abnormal lamellar bone formation
CYP450 inhibitors
increase warfarin effect
acetaminophen, NSAIDs, -azoles, amiodarone, cimetidine, cranberry juic, ginkgo, vitE, omeprazole, thyroid hormone, SSRI
CYP450 inducers
decrease warfarin effect
carbamazepine, phenytoin, ginseng, St. John’s wort, OCP, phenobarb, rifampin
competitive inhibition of renal tubular drug secretion
probenecid (gout med) increases penicillins and fluoroquinolones
lactulose MOA
for hepatic encephalopathy
nonabsorbable disaccharide, colonic bacteria degrade to lactic and acetic acid–> acidifies GI tract–> NH3 trapped as NH4+ in GI tract–> osmotic and peristalsis to move along stuff
fluconazole affect on warfarin
inhibits CYP450 so increases INR
rifampin affect on warfarin
induces CYP450 so decreases INR
bowel most affected by celiac
distal duo and proximal juju
chronic atrophic gastritis
chronic inflamm of gastric body and fundus–> AI parietal cell destruction
antral destruction = H pylori
acarbose MOA
alpha-glucosidase inhibitor, decreases postprandial hyperglycemia by decreasing GI glucose absorption
oral antidiabetic meds bad for CHF
TZD (because of fluid retention)
TZD MOA
activate PPAR gamma which upregulate insulin responsive genes to decrease insulin resistance increased GLUT4 (increased glucose uptake in adipocytes and skeletal muscle), increases adiponectin (cytokine from fat that increases number of insulin-responsive adipocytes and stimulates FA oxidation
must have __ for penicillin sensitivity
cell wall, inhibit peptidoglycan cross linking in cell wall
prokaryotes have ___ genomes
haploid genomes, no nuclei
haploid genome, peptidoglycan cell wall between outer and inner plasma membrane, no nuclear membrane
gram negative bacteria
treatment of carcinoid syndrome
octreotide (somatostatin analog) inhibits release of bioactive peptide
aspirin pretreatment prevents flushing in patients taking
niacin
fexofenadine
nonsedating antihistamine
chlorpropamide
sulfonylurea, decrease blood glucose by stimulating insulin release
phentolamine
blocks alpha R, decrease HTN in pheos
deficiency associated with carcinoid
pellagra b/c niacin deficiency from deleted tryptophan (from excess serotonin production)
Ras
oncoprotein, MAP kinase signal transduction, GTP binding protein–> nucleus to promote mitogenesis, active when phos
protooncogene (1hit GOF)
1 hit GOF mutations, proto-oncogenes
RAS (GTP-binding protein, cholangio, panc adeno), MYC (transcription factor, Burkitt), ERBB1/EGFR (RTK, lung adeno), ERBB2/HER2 (RTK, BC), ABL (nonRTK, CML), BRAF (Ras signal transuction, hairy cell leukemia, melanoma)
2 hit LOF, tumor suppressors
BRCA1/2 (DNA repair, BC and ovarian cancer), APC/B-catenin (Wnt signaling, colon/gastric/panc cancer, FAP), TP53 (genomic stability, most cancers, Li Fraumeni), RB (G1/S transition inhibitor, RB, osteosarcoma), WT1 (urogenital differentiation, Wilms tumor), VHL (ubiquitin ligase component, RCC, VHL)
hypoketotic hypoglycemia
medium chain acyl CoA dehydrogenase (MCAD) deficiency (most common beta oxidation defect)
n/v, sz, liver dysfunctio, first few years of life, prolonged fast (after glycogen used in 24 hr)
muscle weakness, cardiomyopathy, hypoketotic hypoglycemia, elevated muscle TG
primary carnitine deficiency
if hypoglycemic w/o ketones
fatty acid oxidation defect
glucose 6 phosphatase deficiency
von gierke disease, glycogen storage disease type I, fasting hypoglycemia, excessive glycogen in liver and kidneys, nl ketones
glycogen phosphorylase deficiency
cannot cleave alpha 1,4 links between glycogen to liberate glucose 1 phosphate
McArdle disease, type V glycogen storage disease, exercise intolerance and muscle pain
fibrinoid necrosis and neutrophl infiltration of arteirioles, glomeruli, and peritubular capillaries
hyperacute rejection (minutes), preformed Ab against graft in recipient’s circulation
linear C3 and IgG deposits on GBM
type 1 RPGN (goodpasture)
crescents on light microscopy
RPGN, glomerular parietal cells, monocytes, macrophages, FIBRIN in bowman’s space, sclerose–> disrupt glomerular function, irreversible renal injury
chi-square test
test association b/w two categorical variables, compare proportions
two sample z test and t test
compare 2 group means
ANOVA (analysis of variance)
compare 2 or more group means
acetylation of histones
weakens DNA histone bone–> DNA more accessible for transcription
abnormal huntingtin acts to ____ (acetylate or deacetylate) histones
increased histone deacetylation–> silences genes–> neuronal survival genes silenced–> neuronal death
deacetylating histones
silences genes by binding DNA more tightly
huntington disease genetics
AD, GOF in huntingtin protein (CAG trinucleotide repeats)
bloody nipple discharge w/o mass or skin changes
intraductal papilloma, proliferation of papillary cells in duct/cyst wall with fibrovascular core can have some foci of atypia or DCIS
ductal spread of malignant cells to nipple/areola–> eczematous exudate
Paget dz of nipple
cysts lined by metaplastic apocrine cells
fibrocystic changes, cyclic breast pain
positive selection on T cells
thymic cortex
negative selection on T cells
thymic medulla
OCP MOA for hirsutism
suppress LH release–> decrease androgen prod
ambiguous genitalia in girls, salt wasting
21 hydroxylase deficiency
high 17 hydroxyprogesterone, low cortisol and aldo, high testosterone
ambiguous genitalia in girls, salt and fluid retention with HTN
11beta hydroxylase deficiency
low cortisol and aldo, high testosterone, high 11 deoxycorticosterone (weak mineralocorticoid) and deoxycortisol
phenotypically female (all), fluid and salt retention with HTN
17 alpha hydroxylase
low cortisol, low T, high mineralocorticoids, high corticosterone
exfoliative toxin
exotoxin from SSSS, protease that cleaves desmoglein in desmosomes–> epidermolytic blistering
similar mechanism with bullous impetigo
endotoxin-mediated inflammatory response
septic shock
gram - and gram +(listeria) with lipid A in cell membrane, not actively secreted, released by bacteriolysis during abx treatment/immune mechanisms
contact dermatitis, TB skin test, anergy test with candida antigen
Th1 response, type IV cell mediated hypersensitivity, Th1 secrete cytokines attracting macrophages
sickle cell patients (autosplenectomy) are susceptible to
osteomyelitis from staph and salmonella
encapsulated bacteria: H flu, Strep pneumo, N meningitidis, Salmonella typhi
cholestyramine MOA
increase hepatic cholesterol (block this with a statin synergistically) and bile acid synthesis (uses cholesterol) to reduce LDL
bile acid binding resin (sequestrant)
statins MOA
inhibit HMGCoA reductase, decreases hepatic cholesterol synthesis, upregulates LDLR–> decrease LDL
actinic keratoses
hyperkaratosis (hyperplasia of stratum corneum), parakeratosis (nuclei retained in stratum corneum), atypical keratinocytes
risk of invasive SCC
most common skin cancer
BCC, nests of basaloid cells and peripheral palisading of nuclei
benign proliferation of fibroblasts
LE solitary nodule, dermatofibroma
CKD effects on vitD/PTH/Ca/Phos
low vitD, high phos and low Ca, secondary hyperPTH
hypercapnia
central chemoreceptors sense increase PaCO2–> increased RR
hypoxemia
peripheral chemoreceptors in carotid and aortic bodies sense–> increased RR
regulate duration of inspiration depending on degree of lung distension (hering-breuer reflex)
pulmonary stretch fibers (myelinated and unmyelinated C fibers in lungs/airways)
in COPD, response to PaCO2 is___
blunted, so hypoexemia is main respiratory drive
complement mediated destruction of RBC
paroxysmal nocturnal hemoglobinuria
paroxysmal nocturnal hemoglobinuria
defective PIGA, no CD55 or CD59 so hemolysis b/c normally protect from complement
leukopenia, thrombocytopenia (pancytopenia)
Rx eculizumab
RBC fragments, burr cells, helmet cells
nl platelets = mechanical
low platelets = MAHA
obstruct/constrict ureter–> GFR? FF?
decrease GFR and FF
Hib vaccine
meningitis, pneumonia, bacteremia, epiglottitis
severe intellectual disability, sz, musty body odor, hypopigmentation of skin/hair/eyes/brain nuclei
AR mutation in phenylalanine hydroxylase or BH4 cofactor
burnt sugar smell of urine
branched chain ketoacid dehydrogenase cannot dearboxylate 3 branched chain amino acids (leucine, isoleucine, valine)
connective tissue hyperpigmentation and degenerative joint disease
alkaptonuria
AR tyrosine degradation disorder b/c deficiency in homogentisic acid oxidase–> accumulate homogentisic acid
albinism mutation
AR tyrosinase deficiency
isoniazid MOA
anti TB, inhibit mycolic acid synthesis
treatment of crypto meningoencephalitis (often in HIV)
HIV patients, amphotericin B and flucytosine, long term fluconazole
gram + rod with tumbling motility
listeria
listeria meningitis treatment
ampicillin
ionizing radiation for cancer treatment mechanism
causes dsDNA breaks, free radical formation (from ionization of water–> cellular and DNA damage)
direct dopamine agonists
ergot: bromocriptine
nonergot: pramipexole and ropinirole
don’t need to be metabolized to be active
bromocriptine uses
for hyperprolactinemia, direct dopa agonist, also PD
selegiline
inhibit MAO-B, decreasing central dopa degradation
amantadine
indirect and direct dopa agent, enhances endogenous dopamine
entacapone, tolcapone, carbidopa
COMT inhibitors and dopa decarboxylase inhibitors decrease breakdown of levodopa in peripheral tissues, increase amount of levodopa that can cross BBB
trihexyphenidyl and benztropine
anticholinergic, antimAch centrally, for drug-induced PD and tremor of PD
bisphosphonates MOA
similar to pyrophosphate, attach hydroxyapatite binding sites to block bone resorption by mature osteoclasts (can’t adhere to bone), decrease osteoclast activity, induce osteoclast apoptosis, decrease dev/recruitment of precursors
teriparatide
recombinant PTH–> maturation of preosteoblasts, increased GI absorption of Ca and renal reabsorption of Ca
raloxifene
SERM, inhibit osteoclast differentiation
denosumab
Ab bind RANKL and block RANKL/RANK interaction, preventing pre-osteoclast maturation
osteoporosis: PTH, Ca, phos levels
normal, mostly cancellous bone (vertebral fractures), then cortical bone (long bone shafts and outer envelopes of all bones–> hip fx)
pancytopenia, increased risk of AML, hypo/hyperpigmented patches, short stature, hypoplastic thumbs
fanconi anemia, inherited aplastic anemia
EBV findings on peripheral blood smear
atypical lymphocytes
parvovirus B19 can cause aplastic crisis in
SCD, hereditary spherocytosis
treatment of restless leg syndrome
dopamine agonist (pramipexole), check for Fe deficiency
treatment of cataplexy
mACH antagonists
treatment of akathisia
SE of antipsychotics, use propanolol
hypercalcemia, cough, dyspnea, b/l hilar adenopathy, noncaseating granulomas on bx
sarcoidosis, PTH-independent formation of vitD by activated macrophages–> increased intestinal Ca absorption
elevated ACE
sarcoidosis
electrolytes in primary adrenal insufficiency
hyponatremia, hyperK, hyperCl, non anion gap met acidosis
anemia, constipation, bone pain, elevated serum protein, renal failure with glassy casts that stain intensely eosinophilic
MM
constipation from hypercalcemia, renal bence jones proteins that precipitate with tamm horsafall protein–> casts that cause tubular obstruction and epithelial injury
can also cause AL amyloidosis –> renal failure
proximal tubular vacuolar degeneration
aminoglycoside Abx causing ATN when accumulate in renal cortex
sterile pyuria, eosinophilia and eosinophiluria
hypersensitivity interstitial nephritis
chronic tubulointerstitial nephritis (interstitial fibrosis and tubular atrophy)
chronic lead
interscalene nerve block SE
anesthesia for shoulder and upper arm, anesthetizes brachial plexus, transient diaphragmatic paralysis b/c phrenic nerve roots pass through interscalene sheath
sun sensitive facial rash, ashkenazi jew, small stature, infertility, predisposition to malignancy
bloom syndrome, AR, chromosomal instability
diarrheal illness, then hemolytic anemia, thrombocytopenia, AKI
HUS, no bleeding (nl coags)
palpable purpura, abd pain, arthralgias, acute GN
NORMAL platelets and coags
HSP
systemic leukoclytoclastic vasculitis caused by IgA IC deposition
chlamydia
obligate intracellular, unusual peptidoglycan cell wall that doesn’t stain well with gram stain and makes Blactam abx useless, treat with azithro or doxy
acyclovir MOA
inhibit viral DNA polymerase, nucleoside analog that terminates DNA synth
activated by virus
protease inhibitors treat
HIV, hep C
viral RNase H
removes RNA primer–>complete newly synth DNA
HIV
viral reverse transcriptase
HIV
asymmetric polyarthritis, neutrophilic joint aspirate with intracellular organisms
neisseria gonorrhoeae, disseminated
triad of polyarthralgias, skin lesions, tenosynovitis
OR
purulent arthritis w/o skin lesions
testicular malignancy secreting hCG
nonseminomatous germ cell tumor or gestational trophoblastic disease
can cause paraneoplastic hyperthyroidism (same alpha subunit as TSH)
liver cancer with elevated AFP
hepatocellular carcinoma
placenta-like alk phosphatase
testicular seminoma
inhalation of thermophilic actinomycetes
hypersensitivity pneumonitis
respiratory and systemic sx after exposure to moldy hay or contaminated compost
DNA polymerase with 3’ to 5’ exonuclease activity
all 3 prokaryotic DNA poly, proofreading
only DNA poly I has 5’-3’ exonuclease activity for removing RNA primer
direct arteriolar vasodilators
hydralazine, minoxidil
cause reflex sympathetic activation, stimulating RAAS–> tachy and edema, can give with sympatholytics/diuretics to avoid this effect
atenolol
B1 blocker (cardiac, renal) NO smooth muscle
NRTI SE
lactic acidosis, lipodystrophy
zidovudine bone marrow suppression
didanosine pancreatitis
abacavir hypersensitivity
NNRTI SE
SJS/rash, hepatotox, neuropsych and teratogenicity (efavirenz)
PI SE
metabolic syndrome-like, inhibit CYP450
integrase inhibitor
myopathy
doluteGRAVIR, ralteGRAVIR
integrase inhibitor
atazaNAVIR, daruNAVIR, indiNAVIR, lopiNAVIR, ritoNAVIR
protease inhibitors
efaVIRenz, neVIRapine
NNRTI
SE of acyclovir
renal toxicity (crystal nephropathy)
also neurotox
Rx and PPx of MAI
azithromycin
CMV treatment
foscarnet, pyrophosphate analog, does not require intracellular activation
ganciclovir requires intracellular activation
foscarnet SE
nephrotoxicity, hypoCa, Mg, K
chelates Ca, renal Mg wasting causes hypoPTH, low Ca–> hypoCa and Mg–> risk of sz
PCP PPx and treatment
TMP-SMX
TMP-SMX SE
megaloblastic anemia, SJS, TEN
zidovudine
NRTI, bone marrow toxicity
HIV treatment regimen
3 drugs: 2 NRTI + integrase inhibitor
comma shaped oxidase positive gram negative bacillus, watery diarrhea, grows on TCBS agar (highly alkaline)
vibrio cholerae, highly acid sensitive
dsDNA virus, enveloped
hepadna (hepB), herpes, pox
dsDNA virus, nonenveloped
APP
adenovirus, papova (HPV), polyoma (JC & BK)
ssDNA virus, nonenveloped
parvovirus
DNA hypersensitivity to ionizing radiation
ataxia telangiectasia
AR defect in dsDNA repair ATM gene, cerebellar ataxia, oculocutaneous telangiectasias, repeated sinopulmonary infections (B and T cell deficient), increased risk of malignancy
4A’s: ataxia, IgA deficiency, ATM gene, angiomas (spider)
hypersensitivity of DNA to cross-linking agents
fanconi anemia
hypersensitivity of DNA to UV radiation
xeroderma pigmentosum, premature skin aging, increased risk of melanoma and SCC
northern blot
noRthern blot
mRNA
southern blot
DNA
southwestern blot
DNA binding proteins
western blot
proteins (gel electrophoresis first, vs ELISA directly tests serum)
wolffian ducts
mesonephric ducts (epididymis, ductus deferens, seminal vesicles, ejaculatory duct)
mullerian ducts
paramesonephric ducts, fallopian tubes, uterus, cervix, upper vag
lower vag is dervied from
urogenital sinus, failure to fuse vertically with paramesonephric ducts–> transverse vaginal septum
phenylalanine hydroxylase deficiency
PKU, cannot convert phenylalanine to tyrosine
cystathionine synthase deficiency
AR, homocystinuria
cannot convert homocysteine–> cysteine
cysteine is essential AA
give cysteine, restrict methionine, B6 supplementation
elevated methionine
elevated homocysteine is prothrombotic
ectopic lentis, marfanoid habitus, intellectual disability
branched-chain alpha ketoacid dehydrogenase deficiency
maple syrup urine disease
toxic buildups of branched chain amino acids leucine, isoleucine, valine, and their metabolites–> feeding difficulties, sz, cerebral edema, sweet odor of urine
1st gen antipsychotic MOA
2nd gen MOA
1st gen block dopa R
2nd gen block dopa R and 5HT R to decrease EPS SE
carbamazepine MOA
block Na channels to stabilize neuron membranes
benzos MOA
potentiate GABA, increased frequency of Cl channel opening
gastric varices only in fundus, prior pancreatitis
short gastric veins drain fundus and drain into splenic, can get splenic vein thrombus from chronic pancreatitis/panc cancer/other abd cancer
drains upper stomach and lower esophagus into portal vein
left gastric
gastric and esophageal varices if elevated pressure
drains esophageal veins into SVC
azygos vein, collateral drainage from portal venous system to azygos system
varices in lower stomach
blockage of SMV (where pancreaticoduodenal veins drain into)
resistors in series, like blood flow resistance in an individual organ
add R to get total R
resistors in parallel like total body circulation
1/totalR = 1/R1+1/R2….
treatment of hyperemesis gravidarum
promethazine (antihistamine)
scopolamine
antimuscarinic, for motion sickness
meclizine
antihistaminic for motion sickness
mononeuritis multiplex, late-onset asthma, rhinosinusitis, eosinophilia
eosinophilic GPA (churg-strauss) small-med vessel vasculitis
eosinophilic GPA associated with what Ab
p-ANCA (neutrophil myeloperoxidase), perinuclear staining
antitopoisomerase I
systemic scleroderma
Scl-70, also associated with anticentromere and anti-RNA polymerase III
Ab in anti-GBM
Ab against collagen 4 (alveolar and glom BM)
pseudopalisading necrosis brain tumor
glioblastoma multiforme, commonly crosses midline (butterfly glioma), areas of hemorrhage and necrosis grossly
most common primary brain tumor in adults
glioblastoma multiforme
adult brain tumors
glioblastoma, oligodendroglioma, meningioma, hemangioblastoma, pituitary adenoma, schwannoma
psammoma
meningioma, mesothelioma, papillary cancers
whorled pattern and psammoma bodies brain cancer
meningioma
most common childhood brain tumors
pilocytic astrocytomas and medulloblastomas, usually infratentorial
HIV virus
+ ssRNA, diploid, glycoprotein envelope with gp120 and gp41
herpesvirus characteristics
enveloped dsDNA, linear
acquire envelopes from budding from nuclear membrane
includes CMV, EBV
coxsackie virus
picornaviridae family, +ssRNA
PCA supplies
occipital, thalamus, putamen globus pallidus aka lentiform nucleus
ACA supplies
anterior limb of internal capsule, head of caudate
ACA stroke
contralateral leg and foot motor and sensory function, spares arm and face
bilateral ACA stroke
behavioral sx, urinary incontinence
ramelteon
melatonin agonist, treatment for insomnia in elderly with few SE (benzos, antihist, sedating antidep are bad in elderly)
antipsychotic in elderly SE
falls, cardiac mortality
duodenal bulb ulcer causing GI bleed
damaged gastroduodenal artery
febrile neutropenia
ANC<500, most commonly gram + but also at risk of viral and fungal infections (aspergillus if respiratory infection, consider candida if line infection, crypto if meningoencephalitis, PCP if diffuse b/l interstitial infiltrates, rhizopus if sinus inf)
septate narrow hypae branching at acute angles
aspergillosis
degenerative changes in myenteric plexus of esophagus, impaired LES relaxation
achalasia
diminished relaxation of cricopharyneal muscles
zenker diverticulum
febrile, rash, confusion, flaccid paralysis
west nile virus
west nile virus
+ssRNA flavivirus
arboviruses (transmitted by insect bites)
togaviridae (eastern, western, venezuelan equine encephalitis), bunyaviridae (california encephalitis)–most in summer and fall
west nile virus (flavivirus)–most in summer
APC mutation
FAP, chromosomal instability pathway
MLH1 or MLH2 mutation
HNPCC (lynch), microsatellite instability pathway, impaired DNA repair
overexpression of COX-2 is linked to
CRC (some protection with NSAIDs)
sporadic CRC adenom-carcinoma sequence
AK-53
APC inactivation and beta-catenin accumulation–> colon at risk–> KRAS–> adenoma–> p53–> carcinoma
amplified NMYC oncogene
neuroblastoma
multiple unrelated phenotypic manifestations b/c of single genetic defect
pleiotropy, most syndromic genetic illnesses
RF for pancreatic cancer
smoking, obesity
RF for renal cancer
smoking, obesity, HTN
RF for gastric cancer
dietary nitrates, alcohol, smoking, H pylori
RF for bladder cancer
smoking, occupational (rubber, aromatic amine-containing dyes, textiles, leather)
RF for liver cancer
hepB and C, cirrhosis, hemochromatosis, aflatoxin
RF for CRC
IBD, obesity, charred/fried food
RF for prostate cancer
age, AA race
gross hematuria
transitional cell carcinoma of bladder (multifocal sessile or papillary tumors on cystoscopy, esp elderly male, plastic/rubber/dyes/textiles/leather), RCC
hemorrhagic cystitis
SE of cyclophosphamide, isofosfamide
metabolite of these is acrolein–> irritates bladder mucosa
pepsinogen
released by chief cells, converted to pepsin by HCl–> start protein digestion
secretin
produced by S cells of duodenum, stimulates bicarb secretion from duodenum, inhibits gastric acid secretion from stomach
bile salt formation
bile acid conjugation with glycine and taurine–> increased solubility to aid lipid digestion and absorption through micelles
trypsinogen
released by pancreas, activated by enteropeptidase in jejunal brush border–> trypsin–> activate pancreatic enzymes like chymotrypsinogen, procarboxypeptidase, proelastase–> degrade dietary proteins
enteropeptidase deficiency
protein and fat malabsorption b/c cannot activate trypsin–> cannot activate enzymes
diarrhea, FTT, hypoproteinemia
statins
decrease LDL
fibrates
decrease TG
activate PPARalpha, increases LPL activity
niacin
increase HDL
SE flushing, hyperglycemia
ezetimibe
decrease LDL by decreasing cholesterol absorption in GI tract
liver will increase LDLR expression
exercise/wt loss effect on lipids
decrease TG
HDL mechanism
remove cholesterol from peripheral tissues
direct pathway–HDL to SCARB1 on liver
indirect pathway–HDL to LDL to VLDL by cholesteryl ester transfer protein
telangiectasias in skin, mucous membranes of lips, oronasopharynx, respiratory tract, GI, urinary tract
epistaxis, GI bleed, hematuria
Osler-Weber-Rendu syndrome
(hereditary hemorrhagic telangiectasia)
AD
neurofibroma, optic nerve glioma, pigmented nodules of iris, hyperpigmented cutaneous macules
lisch nodules (iris), cafe au lait spots (macule)
NF1 aka von Recklinghausen’s disease, AD
b/l CN VIII schwannomas, multiple meningiomas
NF2, AD
mutation associated with melanoma
BRAF
mutation associated with prostate cancer
BRCA1 and 2
BRAF inhibitor
vemurafenib
improves outcomes in melanoma
normal melanocyte growth
serum growth factors (KIT R kinase–inhib by imatinib, nilotinib, dasatinib) activate NRAS–> activate BRAF–> activate nuclear DNA replication–> cyclin D, growth/diff/survival
melanoma growth
mutated BRAF–> NRAS-independent and uncontrolled BRAF activation–> uncontrolled DNA replication/cell growth/survival–> metastasis
uremia:
PT, aPTT, plt count, BT
all normal except elevated bleeding time
qualitative platelet disorder (uremic toxins impair platelet function), improves with dialysis
isolated aPTT prolongation
hemophilia A, Xlinked, factor VIII deficiency
hemophilia B
heparin (associates with antithrombin to inhibit factor II and X)
warfarin effect on PT and aPTT
increases both, but increases PT much more than aPTT
vWF
bridge b/w glycoprotein1B and collagen in damaged vessels–> platelets BIND damaged vessels
prolonged bleeding time with NORMAL platelet count
also protects factor VIII from degradation so can have prolonged aPTT
DIC coags
elevated PT, aPTT, BT, low plt
HIIT
normal PT, elevated aPTT and low platelets,
immune thrombocytopenia
normal PT and aPTT, low platelets, increased bleeding time
mitral stenosis severity indicated by
A2-opening snap
shorter = more severe stenosis
diastolic rumbling murmur with presystolic accentuation from LA contraction
moving rostral (to head), spinal cord has____ and less ___, is more ___-shaped
more white matter, less gray matter, more oval (esp C spine)
C spine
no lateral horns, gracile and cuneate fasciculi, mostly white, little gray, oval
cuneate fasciculus starts at
T7 and up
below T7, only gracile fasciculus
sacral spinal cord
no lateral horns, mostly gray, little white
large ventral horns
lower cervical and lumbosacral spinal cord (arms and legs)
lateral gray matter horns are present in
thoracic and early lumbar (intermediolateral cell columns)
low OPG/RANKL ratio
increased osteoclast formation and activity
high OPG/RANKL ratio
decreased osteoclast formation and survival
osteoprotegerin
decoy receptor, binds RANKL so RANK cannot, decreases osteoclasts
how low estrogen causes osteoporosis
low estrogen decreases osteoprotegerin–> increases RANKL–> increased RANK expression in osteoclast precursors–> low OPG/RANKL ratio increases osteoclasts
RANKL
receptor for activated nuclear factor kappa B ligand
M-CSF
important in osteoclast differentiation
denosumab
postmenopausal osteoporosis, binds RANKL (works like osteoprotegerin aka OPG)
phenoxybenzamine
irreversible alpha1 and 2 adrenergic antagonist–> decreases arterial vasoconstriction (can treat pheo–when adrenal medulla overproduces NE)
noncompetitive inhibitor or irreversible competitive inhibitor effect on Vmax
reversible competitive inhibitor effect on Vmax
noncom/irreversible decreases Vmax, reversible competitive doesn’t change Vmax
treatment of cocaine intoxication
labetalol (reversible competitive antag of alpha 1, both beta)
norepinephrine
agonist at alpha 1 and beta 1, little effect at beta 2 so potent vasoconstrictor
phentolamine
reversible competitive antagonist of alpha, use in pheo, MAOi toxicity, cocaine intox)
Conn syndrome
primary hyperaldo
hypertension, hypokalemia, met alk, decreased renin
wasting K and H
if unilateral, treat with aldo antag or surg
type IV RTA
hypoaldosterone
sertoli cells produce
MIF–> involution of paramesonephric ducts
leydig cells produce
testosterone–> makes wolffian duct into male internal genitalia, made into DHT which makes genital tubercle and urogenital sinus into male external genitalia
oseltamivir
neuraminidase inhibitor
prevent release of virus from infected cells
influenza to treat and prevent, impairs viral penetration of mucous secretions of resp tract
elevated urinary 5-HIAA
carcinoid syndrome, byproduct of serotonin
endocardial thickening and fibrosis of tricuspid and pulmonary valves (R>L)
carcinoid heart disease
also flushing, watery diarrhea, bronchospasm
treatment of carcinoid syndrome
octreotide, surg for liver mets
elevated VMA (vanillylmandelic acid)
byproduct of epi and norepi, neuroblastoma
holosystolic murmur that increases with inspiration
tricuspid regurg
loud holosystolic murmur best heard at L 3rd and 4th intercostal spaces, thrill
VSD
number needed to harm
NNH = 1/attributable risk
attributable risk = event rate in treatment - event rate in placebo
ganciclovir SE
for CMV, severe neutropenia
AI destruction of platelets, after viral infection, petechiae, mucosal bleeds
ITP
immune thrombocytopenic purpura
terminal ileum resection
bile acids lost–> fat malabsorption–> ADEK deficiencies
HCV lacks ___ giving
no 3’-5’ proofreading exonuclease activity
has hypervariable regions in envelope glycoprotein sequences
strep pneumo main virulence factor
capsular polysaccharides
w/o capsule, not pathogenic
taking up exogenous DNA, integrating into genome
transformation
irritation of parietal pleura from mediastinum? from diaphragm? from intercostals?
mediastinum and diaphragm pleura–> phrenic–> C3-C5 felt over neck and shoulder, intercostals to intercostal nerve
oseltamivir
sialic acid analog inhibitor of influenza neuraminidase
saquinavir
HIV protease inhibitor, prevents cleavage of polyprotein precursors
sofosbuvir
inhibits NS5B, RNA dependent RNA polymerase needed for hep C replication
lamivudine
cytosine analog, NRTI
acyclovir
nucleoside analog
NSAID chronic renal injury (analgesic nephropathy)
chronic interstitial nephritis and papillary necrosis
NSAIDs concentrate in renal medulla, uncouple ox phos and deplete glutatione–> damage tubular and vascular cells
rifaximin MOA
inhibits bacterial RNA synthesis
decrease intestinal production and absorption of ammonia
lactulose
catabolized by intestinal bacteria to short chain FA to lower colonic pH–> increase ammonia to ammonium
posteromedial papillary muscle blood supply
PDA
typical rupture 3-5 days after MI
pure red cell aplasia
erythro precursors inhibited by IgG autoAb or cytotoxic T cells, associated with thymomas, lymphocytic leukemias, parvovirus B19
normal white count and plt
epinephrine effects at different doses
lower doses–> renal and mesenteric vasodilation (dopa)
then beta1–> increase contractility, pulse pressure, SBP, then alpha1–> systemic vasoconstriction with decreased CO b/c of afterload increase
bowel most susceptible to ischemic injury (watershed areas)
splenic flexure (SMA and IMA), rectosigmoid junction (sigmoid and superior rectal)
abd pain and bloody diarrhea after hypotension
pale mucosa, petechial hemorr on colonoscopy
colon blood supply
artery of drummond/marginal artery that is supplied by SMA and IMA, distal colon gets some blood from internal iliac
alcoholic, old, megaloblastic anemia, neuro sx
cobalamin B12 deficiency
folate if no neuro sx, folate faster (weeks)
cancer associated with anemia or erythrocytosis, hepatic dysfunction, hypercalcemia, cachexia, amyloidosis, polymyalgia rheumatica
RCC (hypernephroma)
lambert eaten syndrome is associated with
small cell lung cancer
extremity weakness
beta 2 integrin mutation
leukocyte adhesion problem
severe leukocytosis, delayed umbilical cord separation, sterile abscesses, poor wound healing
CD3+ cell
T cell
CD20+ cell
B cell
candida infections and tetany
digeorge, T cell deficiency (cellular immunity defect causes fungal), hypoplastic thymus, hypoparathyroid causes low Ca
defective lymphoid progenitor cells
adenosine deaminase deficiency–> lymph cells die b/c toxic buildup, SCID
XR CD40 L defect
hyper IgM CD40L normally on T cells--> w/o, cannot help B cells class switch, no IgG, increased susceptibility to encapsulated bacteria
XR NADPH oxidase deficiency
CGD
recurrent bacterial infections with catalase +, like staph aureus
DKA Na, ketones, glucose, K, Na
met acid, ketonemia, hyperglycemia, hyperK, hypoNa
can have hyperammonemia from muscle degradation
hyperK b/c acidemia–> drives K/H exchange in cells, insulin not there to drive K into cells, but total body K is depleted from urine/GI loss
serum Na decreases ___ for every 100 rise in blood glucose
1.6
occipital headaches, cerebellar dysfunction (dizziness with Valsalva), adolescent/adult
chiari I malformation, downward displacement of elongated cerebellar tonsils
b/f surgical removal of pheochromocytoma, give ___ to prevent intraop hypertensive crisis
phenoxybenzamine, long acting alpha blocker
beta blockers alone in pheo can cause severe vasoconstriction (unopposed alpha) and hypertensive crisis
isoproterenol
nonselective B agonist used for bradycardia and heart block
phenylephrine
alpha agonist, decongestant and vasopressor
pheochromocytomas, 25% inherited
Chromaffin cells of adrenal medulla
VHL, RET (MEN2), NF1
10% bl, extra-adrenal, malignant
pheo dx
elevated urine/plasma metanephrines and catechols
intraventricular hemorrhage in premature infant, sz/AMS, hydrocephalus, apnea
increased risk if resp distress/mech vent/CPR b/c changes cerebral blood flow
germinal matrix fragility
dense, cellular, vascularized layer of brain that starts disappearing at 28 weeks and involutes by term, hemorrhage or clot into ventricular system
ruptured subperiosteal blood vessels in newborn, does not cross suture lines
cephalohematoma
tearing of bridging veins
subdural hemorrhage
ototoxic chemo drug
cisplatin, damage hair cells in cochlear membranous labyrinth, esp high frequencies
chemo drug with alopecia, GI irritation, myelosuppression
etoposide
hydroxychloroquine SE
pigment changes, retinopathy
drug causes interstitial lung disease
medical causes of ILD
amiodarone, also arrhythmias, hepatic injury, hypothyroid, blue/gray skin–reverse if decrease or d/c drug
nitrofurantoin, methotrexate, bleomycin
RA, sarcoid, vasculitis, amyloidosis all associated with ILD
misoprostol
PGE1 analog, binds prostaglandin R
in upper GI, stimulates gastric epithelial cell mucus production to decrease parietal cell acid secretion
stimulate parietal cells to produce gastric acid
Ach (M3), histamine (H2), gastrin (CCK2)
H2 blockers
cimetidine, ranitidine
aspirin-exacerbated airway disease
dysregulated arachidonic acid metabolism b/c of COX inhibition–> AA diverted so increased 5-lipooxygenase action–> increased leukotrienes C4,D4, and E4–> bronchoconstriction
treat with montelukast
most head and neck cancers are
squamous cell carcinomas, associated with tobacco and alcohol use, met to cervical or mediastinal LN, lung, liver, bone
genetic heterogeneity
disease phenotype can be caused by one of several DIFFERENT mutated genes (e.g. osteogenesis imperfecta caused by COL1A1 or COL1A2 mutations in type 1 collagen)
multiple genotypes to one phenotype
FBN1 mutation
marfan syndrome, AD
variable expressivity
one genotype, multiple phenotypes
CFTR in sweat ducts vs in resp mucosa
sweat ducts Na and Cl in
resp mucosa Na in and Cl out
CFTR deltaF508 mutation
abnl protein folding and processing–> aberrant protein degraded b/f reaches cell surface
Class II mutation
ENaC overexpression in renal collecting tubules
Liddle syndrome
increased Na reabsorption–> HTN, hypoK, met alk
hypocalcemia, hyperphosphatemia, elevated PTH
pseudohyperPTH, end organ resistance to PTH b/c PTH R/downstream pathway defects
albright hereditary osteodystrophy = pseudohyperPTH type 1a, AD GNAS1 mutation (alpha Gs subunit of GPCR of PTH), and short stature, short metacarpal and metatarsal bones, also end organ resistance to TSH, LH, FSH
kidneys only express maternal GNAS1, paternal transmission causes dev defects but nl Ca/phos/PTH = pseudopseudohypoPTH
elevated calcitonin, cancer
medullary thryroid carcinoma (calcitonin producing parafollicular C cells of thyroid), sporadic or MEN2A or 2B
bone pain, nephrolithiasis, osteoporosis, GI, neuropsych
primary hyperPTH
hyperCa, high/inappropriately normal PTH, nl/low phos
posttranscriptional modification (mRNA processing) to mature mRNA
5’ capping to stabilize mRNA in cytosol: 7 methylguanosine added to 5’ end with 5’-5’ link
polyA tail addition, stabilizes 3’ end in cytosol
splicing out introns via snRNPs
allelic heterogeneity
different mutatations at the SAME genetic locus causes similar phenotypes
e.g. beta thal can be caused by three different mutations in the gene
phenotypic heterogeneity
mutations of the same gene causes very different phenotypes
epistasis
interactions b/w multiple genes–> new phenotype or modify phenotype of one gene
pleoitropy
1 genetic defect–> multiple seemingly unrelated phenotypic manifestations
expressivity
different phenotypic severity in people with the same mutation
synthesizes leukotriene D4
eos, mast cells, important in asthma by inducing bronchospasm and increasing bronchial mucus secretion, treat with anti-leukotriene like montelukast (antag cysteinyl-leukotriene R)
indomethacin
antag PGE2, close PDA
thromboxane A2
promote plt aggregation
hemochromatosis
AR, excessive GI Fe absorption, store excess iron in dermis and other organs as hemosiderin
hyperpigmentation, joint pain, liver cirrhosis, diabetes, cardiomyopathy, pit deficiencies
increased susceptibility to listeria, vibrio vulnificus, yersinia enterocolitica
test for Ab against specific Ag in serum
ELISA
known Ag fixed, then patient serum, then anti-human Ig Ab coupled to enzyme like peroxidase, then chromogen substrate–> enzymes produce color change
impetigo
GAS or staph aureus
if bullous, staph aureus
bacterial abx efflux pumps
use energy, most commonly from proton gradient (or Na gradient or ATP) to pump abx out of the cell
macrocephaly, frontal bossing, midface hypoplasia, shortened limbs (rhizomelia), trident hand (space b/w 3rd and 4th finger), bowing of tibia, spinal stenosis often
achondroplasia
AD FGFR3 point mutation, GOF, normally inhibits cartilage proliferation in long bones, too inhibition of cartilage–> restricted growth plate cartilage–> decreased endochondral ossification
mostly unaffected parents, 10% inherited
FMR1 gene mutation
fragile X
XL, defect in cytoplasmic tyrosine kinase
Bruton agammaglobulinemia
XL, bruton tyr kinase defect–> cannot mature B cells–> no Ab
recurrent bacterial infections (esp resp)
normal T cell, low CD19/20+ lymphos
mutation on chromosome 7
CF, Ehlers Danlos, osteogenesis imperfecta
mutation of chromosome 16
PKD, TS
mutation on chromsome 20
maturity onset diabetes of young type 1
chromosome 22 mutation
digeorge
directs mRNA to ER
N terminal peptide sequence, recognized by SRP (signal recognition proteins)–> target to RER, once in RER then SRP dissociates and translation continues into RER through membrane pore
alpha-ketoacide dehydrogenase coenzyme?
B1 (thiamine), mutated in maple syrup urine disease (branched chain ketoaciduria)
transketolase cofactor
B1
acetyl coA carboxylase, pyruvate carboxylase cofactor
Biotin
which cells produce androgen binding protein
sertoli cells
increase concentration of T and DHT to keep them in the seminiferous tubules and epididymis for spermatogenesis
synthesized in response to FSH
exogenous androgen use
inhibit leydig cell function–> infertility with testicular atrophy, low LH
glucagon R
GPCR Gs, increase AC/cAMP
epinephrine R
B2 is GPCR Gs, cAMP
insulin R
RTK, P3K (phosphoinositide 3 kinase path, NOT PIP which is Gq)
key enzymes in glycogenolysis
glycogen phosphorylase, phosphorylase kinase
gluconeogenesis key enzymes
pyruvate carboxylase, PEP carboxykinase
sweating
cholinergic postganglionic fibers of symp NS, can ablate thoracic symp trunk for severe axillary hyperhidrosis
parasympathetic NT
pregang Ach to nAch, postgang Ach to mAch
sympathetic NT
pregangl Ach to nAch, postgang NE to alpha beta EXCEPT sweat is postgang Ach to mAch
red safranin O stains
cartilage (type II collagen), mast cell granules, mucin–> red
gubernaculum remnant in women
round ligament of the uterus, from uterus through inguinal canal into labia majora
superior part persists as proper ovarian ligament (connects ovary to ute)
gubernaculum remnant in males
scrotal ligament (attach testes to scrotal floor)
epinephrine and norepi metabolism
metab to metanephrine and normetanephrine by COMT
then to vanillylmandelic acid by MAO
tyrosine–> dopa–> dopamine–>norepi–> PMNT to epi
elevated VMA
pheo/catechol secreting tumors like paraganglionoma
elevated 17-hydroxyprogesterone
21-hydroxylase deficiency (CAH)
elevated 17 ketosteroids (androstenedione, androsterone)
androgen-secreting adrenal tumors
elevated 5-hydroxyindoleacetic acid
breakdown of serotonin, carcinoid tumors
VIPomas
in pancreas, watery diarrhea
pulmonary embolism pH, pO2, pCO2
increased pH, decreased PaCo2 (resp alk), pO2 decreased (hypoxemia)
mesangial expansion, GBM thickening, glomerular sclerosis (can be nodular)
if nodular = Kimmelstiel wilson lesion, dense hyaline deposits
diabetic nephropathy
cardiac tissue conduction velocity
fastest purk, atrial, vent, AV slowest
LA near pulmonary veins
prone to PAC and AFib
RA near SVC
SA node
interatrial septum near tricuspid orifice
AV node
interventricular septum
bundle of His and R and L BB
destroyed normal trabecular bone pattern, mixed radiodense and radiolucent areas, periosteal new bone formation, lifting of cortex, Codman’s triangle, adjacent soft tissue with sunburst ossification
osteosarcoma
associated with Paget’s disease
crescent sign, subchondral collapse
avascular necrosis
osteophytes, joint space narrowing
osteoarthritis
hyperPTH bone disease, osteomalacia, mixed uremic osteodystrophy, aplastic bone
associated with chronic renal failure
renal osteodystrophy
generalized osteosclerosis and fx
osteopetrosis
vit A in pregnancy
retinol
teratogenic, esp 1st trimester
fetal microcephaly, cardiac anomalies, early epiphyseal closure, growth retardation, SAB
maraviroc
block viral attachment
posttranslational cleavage
proteins for export from cell, cleave protective/signaling sequences
e. g. collagen N and C terminal propeptides are cleaved by procollagen peptidases in extracellular space
trypsinogen: enterokinase in duodenal brush border cleaves–> trypsin–> cleaves other proenzymes like proelastase and procarboxypeptidase
DNA fragments in multiples of 180bp on gel electrophoresis
DNA laddering, sensitive for apoptosis
overexpression of BCL2
evade apoptosis
follicular B cell lymphoma–overexpress BCL2 (antiapoptosis), t(14;18)
competitive blocker of mAch
atropine, ipratropium, tiotropium (bronchodilate)
SE benzo in elderly
conf, anterograde amnesia, psychomotor retardation
fever, dry skin and mucous membranes, flushing, blurred vision, AMS
anticholintergic intoxication, similar to atropine OD, hyoscyamine, scopolamine
also if OD antihist, antipsych, antispamodic (dicyclomine, hyoscyamine), TCA (amitriptylene)
jimson weed
unit of analysis is populations
ecological studies, e.g. frequency of vitD intake and frequency of outcome studied using population (not individual) data
cohort study
individuals w/ and w/o exposure followed to see incidence of disease
case control study
individuals w/ and w/o disease compare don exposure in past
cardiac defects, clenched fists, rocker bottom feet, omphalocele, low set ears
trisomy 18 (edward) meiotic nondisjunction
de novo partial deletion of short arm of chromosome 5
cri du chat
round face, cat-like cry, microcephaly
neonate with lymphedema and cystic hygromas
turner, loss of paternal chromsome x
sharp intermittent pain at lateral hip and thigh, pain with lying on side of hip and with walking, normal joint motion
trochanteric bursitis
wedge-shaped zone of dead bony trabeculae, empty lacunae, fat necrosis
AVN femoral head
glomerular crescent, no Ig or complement deposits (pauci immune). renal failure, hemoptysis, URI sx. dz? assoc Ab?
RPGN
ANCA vasculitis–GPA, microscopic polyangiitis
low C3 and C4 renal disease
PSGN, SLE (IC RPGN), anti-GBM RPGN, membranoproliferative glomerulonephritis
B6 (pyridoxine) required for
transamination reactions (amino acid and alpha ketoacid), e.g. glutamate + oxaloacetate to make aspartate and alpha-ketoglutarate; pyruvate and glutamate to form alanine and alpha ketoglutarate
halothane SE
drug-induced liver injury, fulminant hepatitis, looks the same as viral hepatitis, massive hepatocellular injury (high ALT and AST), prolonged PT b/c depleted factor VII (shortest half life)
rapid atrophy and shrunken liver, widespread centrilobular necrosis, inflamm of portal tracts
hypersensitivity rxn
fish oil
decrease VLDL and apoB synth
decrease TG, increase HDL
6 mercaptopurine and 6 thioguanine activated by? inactivated by?
activated by HGPRT–> inhibit purine synthesis
inactivated by thiopurine methyltransferase (TPMT) and xanthine oxidase, block with allopurinol to increase concentration
blocks dihydrofolate reductase
methotrexate, blocks conversion of dihydrofolate to tetrahydrofolate–> disrupt thymidine synthesis
cyclophosphamide must be activated by
CYP450 2B
topoisomerase II is inhibited by
etoposide, teniposide
catalase + organisms
problem in CGD (NAPDPH oxidase deficiency)
staph aureus, burkholderia, serratia, nocardia, aspergillus
aortic arch vascular derivatives
1st: maxillary artery
2nd: hyoid, stapedial arteries
3rd: common carotid, proximal internal carotid
4th: L becomes aortic arch, R becomes proximal R subclavian
6th: proximal pulmonary arteries, L becomes ductus arteriosus
pharmacologic closure of PDA
indomethacin (inhibits PGE2 synthesis)
bulbus cordis forms
ventricular outflow (smooth L and R V near Ao and PA)
primitive atria
rough L and R atria
sinus venosus
smooth RA (sinus venarum), receives blood from venae cavae
bethanecol
cholinergic agonist, postop ileus and atonic bladder
carbachol, pilocarpine
cholinergic agonists, glaucoma (miosis widers angle for better outflow of aqueous humor)
cytokine produced (mostly) by Mphage
IL-1, also from other WBC
endotoxin
lipopolysaccharide, part of gram - cell wall
IL-2
released ONLY by Ag-stimulated T cells, stimulates differentiation and growth of T, B, NK and mphage, can bind T cell IL-2R in autocrine fashion to cause clonal proliferation
if IL-2 present for too long–> Fas mediated apoptosis
IL-1
produced by mononuclear phagocytes, to activate lymphocytes and trigger fever/lethargy/anorexia
TNF-alpha
prod by activated macrophages
SIRS, septic shock, cachexia
IFN alpha
monocytes, mphage, B, NK cells
antiviral (inhibit replication and protect uninfected cells from viruses, stim cytotoxic lymphocyte and NK cell antiviral)
GM-CSF (granulocyte mphage colony stimulating factor)
mphage, T, NK, mast, endothelial, fibroblasts
stimulates granulocyte and monocyte production
neutralization of chyme
acidic chyme in duo triggers GB bile release, stimulates S cells of crypts of LIeberkuhn to release secretin–> stim panc to release bicarb rich fluid
knee dislocation risks injury of
popliteal artery (ant and post–continuation of femoral, would disrupt post tib and dorsalis pedis pulses), tibial nerve, common peroneal nerve
blunt trauma to lateral knee
common peroneal nerve injury, wraps around head of fibula
EGFR R type
RTK (RAS)
EPO R type
nonRTK (JAK STAT)
corticosteroid or retinoid R type
translocates to nucleus
pancreatic cells that produce enzymes
acinar cell
pancreatic cells that produce aqueous part
ductal cell, have bicarb/Cl exchanger with increased action in presence of secretin (more bicarb secreted) and depending on flow rate, if high flow then high bicarb, if low flow then more Cl
false positive rate (FPR)
= 1-specificity
doesn’t change with prevalence (just like specificity)
relative risk (RR)
= risk in exposed/risk in unexposed
NNT (number needed to treat)
= reciprocal of absolute risk reduction (risk in exposed - risk in unexposed)
viral encephalitis
herpesvirus
can happen in normal patients
temporal lobe, sz, personality change, psychosis
Rx with IV acyclovir
acanthamoeba
prozoan, fatal encephalitis in AIDS, space-occupying lesion
bunyavirus
encephalitis, california, mosquito transmission, transient infection with fever and headache
carbon dioxide effect on brain vasculature
oxygen’s effects?
CO2 vasodilates cerebral vasculature, if hypocapnic–> cerebral vasoconstriction, useful for decreasing cerebral blood volume and intracranial pressure
oxygen little effect until < 50, then potent vasodilator
cerebral perfusion pressure
MAP - ICP
clinical disinfectants MOA
alcohols disrupt cell membrane and denature proteins
chlorhexidine disrupt cell membranes and coagulate cytoplasm
NOT sporicidal (alc and chlorhex)
H2O2 produces destructive free radicals that oxidize cellular components
Iodine halogenates proteins and nucleic acids
SPORICIDAL (H2O2 and I)
PAH estimates
RPF
filtered and secreted by glom and PT
filtration can’t be saturated, PT secretion (carrier enzyme mediated) can be saturated
obstructive hydrocephalus + dorsal midbrain syndrome aka limited upward gaze, b/l eyelid retraction, light-near dissociation
pineal gland mass
aqueductal stenosis
perinaud syndrome from compression of pretectal part of midbrain, eyelid contraction = Collier sign, light-near dissociation = pupils that react to accommodation but not light
most common pineal mass is germinoma, midline malignant tumor from germ cells, can also arise in gonads or mediastinum, more in young boys, can also be in suprasellar region (no perinaud, then endocrinopathies)
most common cerebellar tumor, gait and limb ataxia, intention tremor, nystagmus
medulloblastoma
contra pain and temperature loss, ipsi loss of V, IX, X, XI
lateral medullary (wallenberg) syndrome
contra spastic paralysis, contra vibration and proprioception loss, ipsi CN XII loss
medial medullary syndrome
thrombocytopenia, ecchymoses, petechiae, normal RBC and WBC counts, normal PT and PTT
ITP (immune thrombocytopenic purpura)
IgG against GPIIb/IIIa
typically self limited in kids, chronic in adults
Rx with steroids
secondary ITP associated with HIV and HCV
fever, fatigue, splenomegaly, atypical lymphocytosis
no sore throat, no LAD
serum fails to agglutinate horse erythrocytes
CMV
most infectious mono is EBV associated with serum heterophile Ab that agglutinate with erythrocytes from other species, can be negative early so repeat
can get CMV from blood transfusion (in leukocytes), decreased risk with irradiation
other causes of heterophile neg mono is HHV6, HIV, toxo
aseptic meningitis, herpangina (fever, posterior pharyngeal gray ulcers/vesicles), kid
coxsackie A
immunocompromised
hemiparesis, VF defects, cognitive impairment
JC virus causing PML
microcytic anemia with normal iron studies, constipation, periph neuropathy, cognitive change, blue pigment on gum-tooth line
lead poisoning
elevated zn protoporphyrin (inhibits ALA dehydratase and ferrochelatase, inhibiting heme synth), basophilic stippling on peripheral smea
flattened deltoid muscle
deltoid paralysis and loss of sensation on lateral shoulder
acromial prominence
blow to externally rotated and abducted arm (throwing football)
anterior humerus dislocation
axillary nerve injury
fall on outstretched hand, what nerve is injured if midshaft humerus fx
radial nerve
hereditary angioedema
C1 inhib def
RBC Cl content in venous blood
high, low in art (make HCo3 that diffuses out, cl enters to neutralize)
Chloride shft
hemophilia A and B BT and PTT
BT normal, PTT prolonged
XR factor VIII and factor IX deficiency
factor VIII deficiency
transglutaminase, crosslinks fibrin, stabilizing clots
spontaneous/excessive bleeding
normal BT, PT, long PTT
vWD
most common inherited bleeding disorder, AD, variable penetrance, impaired platelet function and coag abnl (decreased VIII) so long BT and PTT
invades M cells over Peyer’s patches then spreads laterally through actin polymerization
non lactose fermenting, doesn’t produce H2S, GNR
shigella
cells that produce CCK
I cells in small intestine
increase panc enzyme secretion and bicarb
cells that produce GIP
small intestinal K cells increase insulin release and decrease H secretion in stomach
makes motilin
M cells in SI, increase GI motility
prolonged bleeding due to hemophilia
mutation?
treatment?
decreased factor VIII or IX (XR) causes failure to convert prothrombin into thrombin
give thrombin to help clot, give VIII or IX, give desmopressin if hemophilia A (VIII)
oculomotor dysfunction, ataxia, confusion
wernicke syndrome, resolves with B1 (thiamine)
permanent memory loss, confabulation
korsakoff syndrome, damaged anterior and dorsomedial thalamic nuclei, anterograde amnesia
rate of conversion of fibrinogen to fibrin
thrombin time, prolonged if deficient/defective fibrinogen (liver disease)
anterior compartment of leg
anterior tibial, deep peroneal (fibular) nerve (dorsiflexion of foot, 1st web space sensation)
MOST COMMON COMPARTMENT SYNDROME
deep posterior compartment of leg
post tib artery and veins, tibial nerve, peroneal artery and veins
lateral compartment of leg
deep peroneal nervesation of lower leg, foot drop, sen
S-100 + cells
neural crest, schwannoma, melanoma
biphasic cellularity, at cerebellar pontine angle
schwannoma, esp CN8, antoni A/B, S-100 +
AMS, sz, CV collapse, LACTIC acidosis, bright RED venous blood
cyanide tox, nitroprusside
CN binds Fe3+ in cytochrome c oxidase–> inhibit ETC–> halt aerobic respiration
Rx cyanide tox
hydroxycobalamin (direct binding of CN by cobalt–> excrete in urine), induce methemoglobinemia (na nitirite, combines with Cn to form cyanomethemoglobin), detoxifying sulfur donors (Na thiosulfate, sulfur donor to promote hepatic rhodanese-mediate conversion of CN to thiocyanate–> exctete in urine)
quad screen
AFP, beta hCG, inhibin A, estriol
increased AFP
decreased AFP
inc: open NT defects, ventral wall defects, multiple gest
dec: aneuploidies
low estriol
placental abnl, IUGR
mitochondrial disease leading to bilateral vision loss
leber hereditary optic neuropathy
maternal interheritance, myoclonic sz, myopathy associated with exercise, irregular shaped muscle fibers
myoclonic epilepsy with ragged red fibers
sz, stroke-like episodes with residual neuro deficit, muscle weakness, elevated lactate at rest
mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes
mitochondiral disease
MELAS
mix of two types of genetic material, responsible for variability in clinical mito dz
heteroplasmy (some cells inherit all good mito, some with mostly damaged mito DNA–> different clinical dz)
anti-Jo-1
dermatomyositis, gottron papules (red/violacious papules esp on hands), heliotrope rash, proximal muscle weakness with elevated muscle enzymes
theophylline overdose
sz, tachyarrhtyhmias, give activated charcoal, BB, benzo/barb
acetaminophen overdose
liver tox, give acetylcysteine (glutatione donor)
brady, hypotension, hypoglycemia in OD
BB, glucagon to Rx b/c increases caMP and cardiac contractility
OD with melena and hematemesis
Fe
cystic medial degeneration of aorta, MVP
most common cardiac problems with Marfan’s fibrillin 1 mutation, COD
retroperitoneal abd organs
SAD PUCKER
suprarenal (adrenals)
aorta and IVC
duo (except 1st)
pancreas (head and body) ureters and bladder colon ascending and descending kidneys esophagus rectum (mid to distal)
tongue sensory innervation
posterior 1/3 glossopharyngeal
anterior 2/3 chorda tympani (VII) taste, V3 sensation
temporal arteritis is associated with
high ESR
polymyalgia rheumatica (pelvic/shoulder girdle weakness)
intracerebral hemorrhage vs subarachnoid hemorrhage
intracerebral has focal neuro deficits
great lakes
blasto
dimorphic fungi
sporothrix, coccidiodes, histoplasma, blastomyces, paracoccidiodes
hypertrophic cardiomyopathy, high arched feet (pes cavus), kyphoscoliosis, ataxia (degeneration of spinocerebellar tracts), dorsal column loss, anterior motor horn and corticospinal tract, lose DTR
friedrich ataxia
vit E deficiency can present similarly (antioxidant), vitB12 deficiency similar from subacute combined degeneration
kid irritable, losing dev milestones or learning problems, GI sx
lead poisoning
poliomyelitis
asymmetric flaccid paralysis, spares sensation
thrombocytopenia in cirrhosis
splenic sequestration of platelets
t(8;14) translocation
high mitotic index (Ki67)
Burkitt lymphoma
overexpression of c-MYC–> controls cell proliferation
systemic B cell lymphomas and all primary CNS lymphomas in HIV
EBV
EBV appearance on histopath
starry sky
benign macrophages and high Ki-67
requires cholesterol to grow in medium
mycoplasma
requires cell culture to grow, inhaled spores from animal hides
coxiella burnetti
Q fever
obligate intracellular parasite
requires chocolate agar with X and V (hematin and NAD+)
haemophlus
L-cysteine supplemented agar
Legionella
bile soluble, optochin sensitive
strep pneumo
congenital infection, mom with arthralgias and postauricular/occipital LAD, baby with deaf, cataract, PDA
rubella
maple syrup urine disease supplementation
branched chain alpha ketoacid dehydrogenase complex (BCKDC) supplement Tender Loving Care For Nancy = thiamine, lipoate, coenzyme A, FAD (B2), NAD (B3).
ESP THIAMINE, restrict isoleucine/valine/leucine
urea cycle disorders–> supplement?
arginine to increase urea production
homocysteinemia–> supplement with?
B12, B6 (homocysteine prothrombotic)
transamination and decarboxylation of AA during metabolism
also heme and NT synthesis
cofactor needed?
B6
phenylketonuria supplement
with tetrahydrabiopterin (cofactor for phenylalanine hydroxylase, BH4/BH2)
mutated phenylalanine hyroxylase
TYROSINE IS ESSENTIAL
