depletion of B12 stores? folate?
B12 depletes over years.
folate affected (by alcohol abuse) within weeks
MS: Lhermitte’s phenomenon
shock-like sensation radiating to the feet with neck flexion. also have cognitive defects.
B12 deficiency does this too.
guillain-barre syndrome presentation
acute postinfetious polyneuropathy. nonspecific prodome and nausea followed by progressive ascending paralysis.
sensory stroke presentation
numbness of face, arm, leg on one side of body w/o accompanying motor defect
pathophysiology of myasthenia gravis
acquired autoimmune condition. fluctuating weakness of facial, periocular, bulbar, pelvic girdle muscles.
antibody-mediated, T-cell dependent attach on postsynaptic NMJ.
myasthenia gravis is associated w/ what additional finding
60-70% have hyperplastic thymus tissue. 10-15% have thymomas.
removal of thymus helps.
loss of heterogeneity
inherit mutation in one tumor suppressor, and then develop somatic mutation later. allows for malignant transformation (i.e. Rb)
parental imprinting
preferential transcription of genes from one or the other homologous pair of chromosomes depending on parental origin of chromosome
common causative organisms for infective arthritis by age (children < 2, late adolescence & early adult, older children/older adults, sickle cell.
- children <2: H. flu
- late adolescence & early adult: N. gonorrhea (esp women)
- older children/adult: s. aureus
- sickle: salmonella
third pharyngeal arch
stylopharyngeus muscle, hyoid, glossopharyngeal n.
fourth pharyngeal arch
intrinsic muscles of pharynx + cricothyroid
CN X: superior laryngeal n.
hyperkalemia in DKA? hyponatremia
- acidemia drives K+H+ exchange
- insulin tends to drive K+ into cells
- note: total body K+ low bc osmotic diuresis and GI loss.
hyponatremia:
1. osmotic activity of glucose (serum Na drops 1.6 mEq/L for every 100mg/dl rise in glucose)
2. hyperglycemia-induced osmotic diuresis
arnold chiari malformation
downward displacement of elongated cerebellar tonsils through foramen magnum & into upper cervical canal. CSF flow blocked.
additional findings: small posterior fossa, caudal displacement of medulla, hydrocephalus, lumbar myelomeningocele
dandy-walker malformation
characterized by enlarged posterior fossa.
absent/shrunken vermis replaced by large midline cyst = expanded fourth ventricle
spina bifida cystica (myelomeningocele)
herniation of a sac containing CSF, spinal cord, nerve roots through defect in vertebral arches and dura
syringobulbia
fluid-filled cavities within medulla oblongata
inheritance of androgen insensitivity (testicular feminization syndrome)
rare X-linked disorder. 46 XY.
absence of testosterone receptors in target tissue.
testosterone and LH high (lack of receptors prevents negative feedback)
circulating androgens eventually peripherally converted to estradiol – feminization.
no mullerian duct (MIF from sertoli) so vagina = blind duct
testes: abdomen, inguinal canal, labia majora. make testosterone, but no spermatogenesis
normal testes descent
- transabdominal: MIF
- inguinoscrotal: hCG and androgens
mullerian agenesis
uterus, fallopian tubes, proximal vaginal fail to develop. LH, FSH, estrogen normal.
cause of primary ammenorrhea
when does the germinal matrix subside in prominence
after 32 weeks. decline in cellularity & vascularity.
why is germinal matrix prone to hemorrhage?
highly cellular & vascular (generates neurons & glia during fetal development).
no network fibers present to support vasculature in germinal matrix.
cephalhematoma
hemorrhage within circular region of scalp that inters the lower uterus during childbirth.
associated with sudden delivery, disproportion between diameter of fetal head & birth canal, inappropriate forceps use.
cisplatin toxicity
ototoxicity. damages apical stereocilia on hair cells
amiodarone toxicity in lungs? other toxicity?
insterstitial pneumonitis
dyspnea, cough, dry inspiratory crackles, patchy interstitial infiltration on radiograph.
other: hepatic necrosis, thyroid abnormalities, corneal deposits, bluish-gray skin discoloration
adverse effects of sotalol
TdT and excessive beta blockade
procainamide toxicity
drug-induced SLE (anti-histone)
prostaglandin PGE1
stimulate gastric epithelial cell mucus production & decrease parietal cell acid secretion
misoprostol for GI
PGE1 analog.
stimulate gastric epithelial cell mucus production.
may also decrease parietal cell acid secretion )
submandibular lymphadenopathy suggests
head & neck cancer: vast majority: SQUAMOUS CELL CARCINOMA. associated w/ tobacco and alcohol.
develop in oral cavity: ventral tongue, floor of mouth, lower lip, soft palate, gingiva.
often infiltrates adjacent tissue.
nitroglycerin effect on heart
venodilation predominantely.
reduced preload –> decreased effective circulating blood flow due to venous pooling.
cardiac reflex compensates for drop in SV, CO, MAP w/ sympathetic increase in HR and contractility.
new steady state: decreased preload, afterload, end systolic ventricular volume, CO. TPR relatively unchanged.
overall, myocardial consumption decreased –> relieved angina / ischemia
Liddle syndrome
pseudohyperaldosteronism.
ENaC overexpression in CT
CFTR in sweat glands?
reabsorb Cl- and enhance Na+ resorption.
defect: excessive Cl- and Na+ in sweat
CFTR in respiratory and intestinal epithelium
active secretion Cl-.
defect: no Cl- secretion, increased Na+ resorption. passive H20 resorption
albright hereditary osteodystrophy (AHO)
autosomal DOMINANT
end organ resistance to PTH
pseudohypoparathyroidism.
skeletal and developmental defects (short stature, short metacarpal and metatarsal bones). end-organ resistance to PTH, TSH, and LH/FSH. (all G-s-alpha-mediated pathways)
allelic heterogeneity vs genetic heterogeneity vs. phenotypic heterogeneity
allelic heterogeneity: DIFFERENT mutations
SAME gene locus
SIMILAR phenotypes.
(i.e. complete loss of fxn vs. partial loss of protein)
genetic heterogeneity: mutations of DIFFERENT genes SIMILAR phenotypes
phenotypic heterogeneity: mutations in SAME gene
DIFFERENT phenotype
duchenne vs. becker
duchenne: complete loss of fxn in dystrophin
becker: structurally abnormal but partially fxn dystrophin.
inheritance of type II DM
polygenic
hemochromatosis
autosomal recessive.
excessive GI absorption of iron.
hemosiderin in dermis and various parenchymal organs.
silent until at least 20 grams accumulated.
hepatomegaly, skin hyperpigmentation (hemosiderin deposit in dermis, DM (pancreatic islet destruction), impotency, arthropathy, cardiac dysfunction & enlargement.
elevated plasma iron w/ >50% saturation of transferrin, elevated ferritin.
defects in melanocyte proliferation & migration
Piebaldism (partial albininism) and Waardenburg syndrome.
blue-gray macules referred to Mongolian spots, arise when melanocytes are halted in dermis as they migrate from neural crest to epidermis.
Menke’s disease
abnormally pigmented, kinky hair, hypopigmented irises.
latex agglutination
detect for presence of antigen.
add sample to collection of specific of antibodies fixed to latex beads
erythema with yellow “honey” crush on cutaneous wound is.. caused by?
IMPETIGO.
most common cause: s. aureus and group A strep.
note: s. aureus can lead to bullous impetigo (toxin production)
s. epidermis?
normal skin flora. not commonly associated w/ skin disease. regarded as contaminant if found in wound culture.
hypoparathyroidism sign
Chvostek sign: tap cheek (facial n) –> contract facial muscle
Trousseau sign: take BP (occlusion of brachial artery, cuff Triceps) –> carpal spasm.
tetany due to hypocalcemia (due to accidental surgical excision of parathyroid glands, autoimmune destruction or DiGeorge
drug effux pumps often use
derivive energy from H+ gradient or Na+ gradient or direct ATP
achondroplasia mutation
point mutation FGFR3 (substitute Arg for Gly) in 375 position, chr 4p.
increased function. severely restricted chondrocyte proliferation in the growth plate.
mutation in marfan’s
fibrillin-1, chromosome 15q
mutation in osteogenesis imperfecta
COL1A1 chr 17q
COL1A2 chr.7q
ewing’s sarcoma translocation
t(11,22) joins EWS gene from chr 22 to FLI1 gene
brutton’s agammaglobulinemia
X-linked. defect BTK. poor maturation of B cells, can’t leave bone marrow. no CD19 in circulation.
chr 7 diseases
cystic fibrosis, ehlers-danlos, osteogenesis imperfecta
chr 16 diseases
polycystic kidney disease, tuberous sclerosis
signal sequences for synthesis into ER
N-terminal HYDROPHOBIC
maple syrup urine disease
defective branched chain alpha-keto acid dehydrogenase complex.
can’t degrade leucine, isoleucine, and valine –> CNS toxicity.
life threatening if untreated.
rx: early restriction of isoleucine, leucine, valine.
normally:
valine, isoleucine —> prionyl-CoA
leuine —> acetyl-CoA
via branched-chain alpha-keto acid dehydrogenase
hydrops fetalis with thalassemia
Hb Barts, severe form of alpha thalassemia characterized by four nonfunctional alpha globin loci
microcytic, hypochromic RBCs. occasional target cells.
high concentration of local testosterone
maintained by androgen-binding protein (ABP) within the seminiferous tubule. made by sertoli cells.
makes them less lipophillic, concentrating them within the luminal fluid.
glucagon signalling via
Gs protein
adencylate cyclase (in hepatocytes, myocardiocytes, and adipocytes)
increased cAMP
activate glycogen phosphorylase
like B2 – Gs
glycogenolysis and gluconeogenesis in hepatocytes.
intracellular mediator for growth factor & insulin
intrinsic tyrosine kinase activity
Ras is related to..
MAP kinase cascade – control of cell ENTRY into CELL CYCLE
alpha 1 and V1 work on..
Gq, PLC, IP3
sympathetic innervation of sweat glands in axilla
T2 sympathetic ganglion
superior cervical sympathetic ganglion provides sympathetic innervation to…
tarsal muscle, lacrimal gland, radial muscle of iris, and all salivary glands
greater, lesser, least splanchnics
sympathetic preganglion neurons into abdomen, synapse on postganglionic cell bodies within celiac and aorticorenal ganglia (sympathetics to abdominal viscera)
can also pass to adrenal medulla without synapsing.
vagus nerve parasympatics
all parasympathetic preganglion fibers to viscera of thorax, foregut, midgut.
red safranin O stain
colours cartilage, mast cell granules, and mucin red
dystrophin location
cytoplasmic! intracellular anchor
round ligament of the uterus
derivative of gubernaculum.
connects uterus fundus to labia majora THROUGH (round) inguinal canal
broad ligament
wide fold of peritoneum that connects uterus to pelvis side wall.
contains ovaries, fallopian tubes, round ligament of uterus & uterus
infundibulopelvic ligament (suspensory ligament of the ovaries
connects ovaries to lateral pelvic wall. carries ovarian vessels.
cardinal ligament
connects cervix to side wall of pelvis, contains uterine vessels
(ureters at risk of injury during ligation of uterine vessels)
ovarian ligament
medial pole of ovary to lateral uterus
latches to lateral uterus
conversion of NE to E?
conversion of E to metanephrine?
metanephrine to vanillylmandelic acid?
NE –> E
phenylethanolamine-N-methyl transferase (PNMT) uses S-adenosyl methionine (SAM)
E –> metanephrine
catechol-O-methyltransferase
metanephrine –> VMA
MAO
COMT is important for
degradation of epinephrine to metanephrine
MAO is important for
degradation of metanephrine to VMA
rate limiting step in catecholamine synthesis
tyrosine to DOPA (tyrosine hydroxylase)
DOPA decarboxylase requires what cofactor
vitamin B6
primary respiratory issue with PE
hypoxemia secondary to pulmonary V/Q mistmatch.
hypoxemia –> hyperventillation and respiratory alkalosis.
increased pH, reduced PaO2 and PaCO2.
primary respiratory issue with COPD
slightly decrease pH, increased PaCO2, decreased PaO2.
platelet activating factor
phospholipid inflammatory mediator. causes severe bronchoconstriction, vasoconstrition, and platelet aggregation (with microthrombus formation).
low dose -> relatedd to NO production with eNOS. vasodilator, promotes leukocyte adhesion to endothelium, diapedesis (transmigration), degranulation, and oxidative bursts.
made by platelets, basopphils, mast cells, neutrophils, monocytes, macrophages, and endothelial cells.
Gq -> PLC -> IP3 -> calcium
prostacyclin signalling
Gs: adenylate cyclase, cAMP.
inhibit platelet function
thromboxane and PAF signalling
Gq –> PLC, IP3, Ca2+
activate platelets
cilastozol and dipyrimidole
PDE III inhibitor, increase cAMP in cells –> vasodilation and inhibit platemet activation
which agents directly promote healing of peptic ulcer
bismuth subsalicylate & sucralfate
which agents directly promote symptom relief of peptic ulcer
calcium carbonate, proton pump inhibitors, H2 blockers
why are antibiotics used in PUD?
treat disease recurrence.
2 or more of the following required for diagnosis of NF1 (chr 17)
6+ cafe au lait spots, intertriginous freckling, 2+ cutaneous neurofibromas or 1 plexiform neurofibroma, optic nerve glioma, characteristic bony lesions, iris Lisch nodules, 1st degree relative
CA NN OT FAI L2 B 1st
cafe au lait 2+ neurofibromas optic glioma freckling of axilla or inguinal 2 Lisch nodules
bone abnormality: kyphoscoliosis, tibia dysplasia (bowing), sphenoid dysplasia
1st degree relative
neurofibromas = benign growth of schwann cells
epidermoid cysts
sebaceous cysts, keratin-filling, cystic papules, central punctum. not actually from sebaceous glands
what side of heart do IV drug users mess up?
right side! tricuspid and pulmonary
important adverse reaction to vancomycin
- “red main” syndrome
- nonspecific mast cell degranulation when vanc is infused too rapidly
- NOT an IgE mediated reaction
increases with RATE of infusion.
pencillin G adverse reaction
IgE mediated hypersensitivity reaction. not directly related to RATE of infusion.
