4/12/19 Flashcards
Osteocytes are connected by
Gap junctions
Glucagon effects what kind of receptor
Gs coupled actives adenylate cyclase and increases cAMP which activates protein kinase A
Same with TSH and PTH
cGMP activates what
Protein kinase G
SM relaxation, platelet activation, sperm metabolism
CGMP is inactivated by cGMP specific phosphodiesterase (sildenafil)
Janus tyrosine kinase
Cytoplasmic protein activated by ligand binding to non-G protein coupled transmembrane rec that lack intrinsic tyrosine kinase activity
Activate transcription factors called STAT which enter nucleus to promote gene transcription
GH, erythropoietin, cytokines (interferon), prolactin
blueish neoplasm underneath the nail bed
either a glomus tumor or subungal melanoma (produces pigmentation)
Glomangioma
blueish neoplasm underneath nail bed
tumor of modified SM cells
Gloms bodies shunt blood away from skin surface in cold temperatures to prevent heat loss - function in thermoregulation
Caspases
Proteolytic enzymes that cleave proteins
Part of extrinsic (receptor initiated) and intrinsic (mitochondria mediated) pathway for apoptosis
esophageal varices, splenic enlargement, normal liver biopsy
portal hypertension from venous thrombosis - causes obstruction in portal venous flow upstream from liver
increased hydrostatic pressure
normal biopsy = presinusoidal process responsible for portal hypertension
Budd-Chiari syndrome
occlusion of hepatic vein (drains blood from liver and portal circulation into systemic circulation)
liver biopsy shows centrilobular congestion and fibrosis
See the same with constrictive e pericarditis
intrinsic tyrosine kinase
transmembrane receptors with activity in intracellular domain initiating downstream phosphorylation cascade
Insulin and insulin-like growth factor
erythropoietin signal transduction
Janus kinase 2/signal transducers and activators of transcription
Home-canned food
botulinum toxin
nicotinic blockade (dysphagia, ptosis) muscarinic blockage (dry mouth)
botulinum toxin
enters nerve terminals via endocytosis
prevents binding and fusion of acetylcholine containing synaptic vesicles with the plasma membrane through destruction of SNARE proteins
no acetylcholine release
Medicare
65 yo and older
younger with disabilities
ESRD
ALS
Cystic degeneration of the putamen
Wilson’s disease (MC on step)
other progressive neurologic diseases
radio frequency ablation for afib
right femoral vein –>RV –>RA–>interracial septum at foramen ovale
Severe toxicity of mannitol
pulmonary edema esp in CHF and preexisting pulmonary edema
rapid rise in volume that increases overall hydrostatic pressure in vasculature
attrition bias
form of selection bias
systematic differences between group in terms of treatment response or prognosis
lead time bias
when screening test diagnoses a disease earlier than it would have appeared by natural history alone
time from diagnosis to death appears prolonged even though might actually be no improvement in survival
misclassification bias
either exposure or outcome not identified correctly
tetanus toxin
produces metalloprotease exotoxin (tetanospasmin)
migrates by retrograde axonal transport to central inhibitory neurons in spinal cord
tetanospasmin
inhibits release of glycine and GABA –> increased activation of motor nerves causing muscle spasm and hyperreflexia
Vibrio cholera entertoxin
stimulates serotonin release from enterochromaffin cells in GI tract = extreme fluid secretion
Loeffler syndrome
invasion of lungs by roundworm Ascaris = eosinophilic invasion for helminth destruction
pig farmer with cough and dyspnea
Loeffler syndrome - Ascaris roundworm
transpeptidases
form of penicillin-binding-protein that function to cross-link peptidoglycan in bacterial cell wall
cell-wall glycoproteins
vancomycin binds to terminal D-alanine residues of cell wall glycoproteins and prevents transpeptidases from forming cross-links
form of ceftriaxone resistance
structural changes in penicillin binding proteins
changes of 5 bands in radioautography to 2
change of 5 radioautography to zero with ceftriaxone
beta-lactamase action that degrade ceftriaxone
MM tumor cells secrete
osteolytic cytokines = TNF alpha that liberate calcium from bone
multiple myeloma labs
Hypercalcemia decreased PTH increased urinary calcium decreased 1,25-dihydroxyvitamin D normal PTHrp
Hepatitis A exposure
shellfish
coagulase negative staph
staph epidermis
one of MC infections associated with foreign bodies (VP shunts)
staph epidermidis most important virulence factor
synthesis of extracellular polysaccharide matrix = biofilm
encases the bacteria, barrier to Abx penetration and interferes w/host defenses (opsonization, neutrophil migration, T-cell activation)
biofilms eventually can disperse individual pathogen “seeds” (planktonic cells) into bloodstream
Obligate intracellular organisms
Chlamydiae and Rickettsiae
Facultative intracellular
Legionella, listeria, mycobacterium, neisseria, salmonella
encapsulated bacteria
pneumococcus, H.flu type B, neisseria meningitides
Protein A
cell wall of staph aureus
binds to Fc region of immunoglobulins = inhibits opsonization and phagocytic engulfment
exotoxin production
staphylococcal enterotoxins (food poisoning), botulinum toxin, diphtheria toxin, tetanus, pertussis
Arsenic poisoning
insecticide ingestion, contaminated water from wells, pressure treated wood
binds sulfhydryl groups (bad cellular respiration via inhibition of pyruvate dehydrogenase)
disrupts cellular respiration and gluconeogenesis and glutathione metabolism
treat with Dimercaprol or DMSA
severe watery diarrhea, hypotension, QTc prolongation (maybe torsades), garlic odor of breath, abdominal pain, N/V
arsenic poisoning
Tx: dimercaprol (chelating agent) - increases urinary excretion of heavy metals
psoriasis
activation of T helper cells and proliferation of keratinocytes
Auspitz sign
See in psoriasis
epidermal cell later superficial to dermal papillae is thinned and contain dilated blood vessels that can lead to pinpoint bleeding when scale removed
Tx of mild to moderate psoriasis
corticosteroids (diflorasone) first line - anti-inflammatory/antiproliferative properties
Vitamin D analog, first line (calcipotriene, calcitriol) - activate vitamin D rec –> nuclear transcription factor –> inhibition on T-cell and keratinocyte proliferation and stimulation of keratinocyte differentiation
Tx of severe psoriasis
systemic treatment better than topical tx
methotrexate and cyclosporine
virchow triad
endothelial injury, venous stasis, hyper coagulable state
VTE
Denosumab
one of medications for osteoporosis
binds RANK-L and inhibits binding to RANK
reduces differentiation and survival of osteoclasts
treatments for osteoporosis
Calcium and vitamin D
Bisphosphonates
Denosumab
Recombinant PTH analog
Bisphosphonates MOA
attach to hydroxyapatite binding sites on bone surfaces
inhibit osteoclast mediated bone resorption
Herpain-induced thrombocytopenia and thrombosis
5-10 days post heparin exposure
large drop in platelets
MC after unfractionated heparin but can happen w/LMWH
HITT mechanism
Generation of IgG antibodies for heparin and PF4 complexes –> Fc of IgG Abs binds additional platelets –> further PF4 release and widespread Plt activation –> Prothrombotic state –> arterial and venous thrombosis
TTP mechanism
decreased vWF-cleaving protease ADAMTS13
fever, thrombocytopenia, MAHA, renal insufficiency, neurologic dysfunction
TTP pentad
Cryoglobulinemia
AI diseases or viral infection (hepatitis C) = systemic vasculitis, fatigue, arthralgia, purpuric rash
usually no thrombocytopenia
Idiopathic thrombocytopenic purpura mechanism
splenic destruction of Plt labeled by IgG Abs to glycoprotein IIb/IIIa receptors
inter scalene nerve block
procedures for shoulder and upper arm
affects brachial plexus roots and trunks (C5-T1) and transient ipsilateral diaphragmatic paralysis by anesthetizing roots of phrenic nerve (C3-5)
sternalcleidomastoid muscle innervation
CN XI
PCR
amplify small fragments of DNA
what you need for PCR
DNA template w/target region
flanking sequences adjacent to target sequence (makes primers to start PCR)
Thermostable DNA polymerase (replicate DNA template)
Steps of PCR
Denaturing
Annealing
Elongation
Hypersensitivity pneumonitis
exposure to environmental irritant
Histo: lymphocyte-predominate, interstitial inflammation, sometimes with necrotizing granulomas and loose fibrotic tissues within small airways
Neutrophil elastase
released by neutrophils and macrophages
primary protease for extracellular elastin degradation
Neutrophil elastase is inhibited by
alpha-1 antitrypsin
TATA box is
promoter region that binds transcription factors and RNA polymerase II during initiation of transcription
approx 25 bases upstream of beginning of coding region
Hypertension, hematuria, moderate proteinuria, linear appearance on IF
anti-GBM disease = rapidly progressive (crescentic) glomerulonephritis
Rapidly progressive glomerulonephritis (crescentic)
Anti-GBM Abs target collagen type IV leading to complement deposition
Anti-GBM Abs can cross react w/collagen IV in palm alveolar BM –> pulm hemorrhage (hemoptysis)
can occur with:
granulomatosis with polyangiitis
microscopic polyangiitis
renal failure + pulmonary hemorrhage + anti-GBM Abs
Goodpasture syndrome
Type II hypersensitivity
Glomerular crescents
proliferating parietal cells, lymphocytes, macrophages, fibrin on light microscopy diagnostic for RPGN
attributable risk percent in the exposed (ARPexposed)
excess risk in an exposed population that can be explained by exposure to particular risk
ARPexposed = 100 x [(risk in exposed - risk in unexposed)/risk in exposed]
or
ARPexposed = 100 x [(RR - 1)/RR]
where RR = risk in exposed/risk in unexposed
Relative risk
risk in exposed/risk in unexposed
HBV vaccination works by
impairing vision entry into hepatocytes
utilizes recombinant HBsAg to generate protective immunity
HBV acute infection overcome by
polyclonal cytotoxic T-cell (CD8+) response that destroys infected hepatocytes
HIV and HCV treatment
disrupt viral genome replication
Sofosbuvir
Tx for HCV that targets viral RNA-dependent RNA polymerase
disrupts replication of viral genome
Ledipasvir
N5SA inhibitor for HCV, block virus replication and assembly of visions within cytosol
Phenotypic frequency
p^2 + 2pq + q^2 = 1
Hardy-Weinberg analysis
Calculate mutant allele frequency from disease prevalence
sq.rt. of q^2 = q
q = mutant allele frequency
Beta-oxidation of FA inhibited by
well fed state = increase of Malonyl-CoA
Well fed state biochem
increase in ATP inhibits isocitrate DH –> increase citrate in mitochondria
increase in insulin and citrate = upregulation of acetyl-coA carboxylase
Citrate lyase cutes citrate to form acetyl-coA in cytosol
acetyl-coa carboxylase converts acetyl-coA to malonyl-coA (rate-limiting step of de novo FA synthesis)
fatty acid synthase combines malonyl-coA and acetyl-coA to make 4 C molecule to add to others to make 16C FA
Acetoacetate
ketone body
made in starvation state when oxaloacetate in short supply and acetyl-coA in excess
fuel for muscle, brain, cardiac tissue
Malonyl-CoA inhibits
carnitine acyltransferase
prevents transfer of acyl groups into mitochondria
prevents breakdown of newly made FA’s
Citrate
intermediate in TCA cycle
can be exported out of mitochondria to cytosol and broken down to acetyl-CoA for de novo FA synthesis
Carnitine
AA essential for transport of FAs into mitochondria membrane for FA oxidation
NADPH
reducing molecule needed for FA synthesis
beta oxidation of FA produces
FADH2 and NADH-reducing equivalents
Decreased C1 esterase (+/- C4) inhibitor levels in kid
hereditary angioedema (AD)
Meds contraindicated in hereditary angioedema
ACE inhibitors
angioedema mediated by
bradykinin, C3a, C5a
vasodilation and vascular permeability
Glutamate (AA) + alpha-ketoacid (oxaloacetate) = ?
Aspartate (AA)
transamination reaction
requires vitamin B6 (pyridoxal phosphate)
Maple syrup disease needs supplementation of
thiamine to help with transamination w/branched chain alpha-ketoacid DH
Valine/isoleucine –> propionyl coA
Maple syrup urine disease
AR
defective breakdown of branched chain AA (leucine, isoleucine, valine)
build up of branched chain AA in serum and peripheral tissues
seizures, irritability, lethargy, poor feeding
Branched chain alpha kitoacid DH
pyruvate DH
alpha ketoglutarate DH
all require 5 things
thiamine lipoate coenzyme A FAD NAD
(Tender loving care for nancy)
Most disorders of the urea cycle require
Arginine
makes downstream water soluble intermediates (ornithine, citrulline)
lead to nitrogen disposal and decreased plasma ammonium levels
Lower homocysteine levels with
Cobalamin B12 and B6
Tetrahydrobiopterin deficiency results in
PKU
phenylalanine levels can be decreased with THB supplementation
Tetrahydrobiopterin is cofactor for
phenylalanine hydroxylase
nicotinic (diplopia, dysphagia) and muscarinic (dry mouth) blockage =
C. Botulinum toxin (preformed toxin)
Home canned food
inhibits acetylcholine release from presynaptic terminals at NMJ
decrease in compound muscle action potential (CMAP)
TCA overdose affects only
muscarinic (dry mouth) blockade w/no effect on NMJ (no alterations of CMAP)
Signs of trapezius weakness
drooping of the shoulder
impaired abduction about horizontal
winging of scapula
weakness of SCM (if proximal portions of nerve injured)
painless solid testicular mass is
testicular cancer until proven otherwise
Dx of EBV
heterophiles IgM antibodies that react with antigens on horse/sheep erythrocytes
agglutination of these erythrocytes is sensitive and highly specific test for EBV in human B cells
Secretory phase of menstrual cycle
between ovulation and menses
days 15-28
Progesterone high/plateau
uterine glands coil and secrete glycogen rich mucus in prep for embryo implantation
endometrial stroma is edematous and tortuous spiral arteries extend to deeper layers of uterine lumen
Proliferative phase of menstrual cycle
first day of menses to ovulation
days 1-14
Progesterone low, LH and estrogen increasing
pertussis main virulence factors
tracheal cytotoxin - destroys ciliated epithelial cells = loss of airway protection, develop of whooping cough
pertussis toxin - AB toxin enters cell and activates adenylate cyclase alters cell signaling and inhibit phagocyte activity
pertussis is a
small gram negative coccobacillus
spreads via air droplets
Auer rods
t(15:17)
AML, M3 variant - acute APML
Atypical lymphocytes in infectious mononucleosis represent
activated CD8+ cytotoxic T cells
kill virally infected B cells
pigmented neurons in posterior rostral pons at the lateral flow of fourth ventricle
locus ceruleus
makes NE
role in arousal (reticular activating system)
panic attacks
Dopamine produced in
ventral tegmental area
substantia nigra pars compacta
in midbrain
Poorly soluble gas anesthetic =
decreased blood/gas partition coefficient
partial pressure of drug increases quickly then plateaus
brain saturation (induction) quickly
ex: Nitrous oxide
highly soluble gases in blood require
larger amounts of drug to be absorbed before blood is saturated
partial pressure rises slowly and levels out brain saturation (induction) slower
ex: halothane
most important factors influencing coronary blood flow
adenosine (ATP metabolism) and NO (endothelial cells)
Nitric oxide made in
endothelial cells from arginine and oxygen
causes vascular SM relaxation by guanylate cyclase-mediated cGMP second messenger system
Integrase inhibitor for HIV inhibits
Raltegravir
production of viral messenger RNA
dsHIV DNA cannot integrate into host cell chromosomes
Viral meningitis MCC
enterovirus MC
arbovirus
herpes simplex 2
bacterial meningitis MCC
adults: pneumococcus and neisseria
babies: GBS and gram negative bacilli
difference between polymyositis and PMR
PMR does not have weakness and usually patients >50 yo
polymyositis symptoms
symmetric muscle weakness (painless of painful)
elevated CK
ANA, anti-jo
Increased expression of MHC I antigens
Self attacking CD8 cytotoxic cells for myocyte destruction
can occur independently or as paraneoplastic of malignancy
similar to dermatomyositis but no skin findings
PMR symptoms
myalgia of shoulder and pelvic girdle
systemic symptoms (fever, weight loss)
older patients >50 yo
Drugs that can lead to lithium toxicity
HCTZ
NSAIDs
ACE inhibitors
all cause decreased renal perfusion
Myasthenia graves pathogenesis similar to
Goodpasture syndrome
type II hypersensitivity
If unilateral renal artery thrombosis d/t HTN and PVD, other kidney will show
significant arteriolosclerosis to compensate for lost kidney function
PSGN immune complexes
granular deposits of IgG, IgM, and C3 on GBM and mesangium
“starry sky appearance”
amniocentesis for phospholipid content checks for
fetal lung maturity
NF1 symptoms
cafe au lait spots cutaneous neurofibromas ancillary or inguinal freckling optic glioma iris hamartomas
NF2 symptoms
bilateral acoustic neuromas
brain meningiomas
schwannomas of dorsal roots in spinal cord
Classic galactosemia is inherited
AR
Hemophilia B (Christmas disease) is inherited
XR
Huntington disease is inherited
AD
Leber hereditary optic neuropathy is inherited
mitochondrial
Rett syndrome is inherited
XD
Niacin is a cofactor for which TCA cycle stuff
isocitrate DH
alpha-ketoglutarate DH
malate DH
Niacin is a precursor for
NAD and NADP
important for dehydrogenase and reductase enzymes
COPD developed decrease in RR as a result of O2 supplementation d/t ?
peripheral chemoreceptors in carotid and aortic bodies (main site for sensing PaO2 and stimulated by hypoxemia)
rapid increase in PaO2 can reduce peripheral chemoreceptor stimulation = decrease the RR
Celiac disease can present with deficiency of what
dietary fats and fat soluble vitamins
Positive transflutaminase antibody assay
celiac disease
NE and DA are made in
CNS and PNS
Epinephrine is made in the
adrenal medulla
First rate limiting step in catecholamine synthesis
tyrosine –> dihydroxyphyenylalanine (DOPA)
by tyrosine hydroxylase
In the medulla, NE is converted to epinephrine by
phenylethanolamine-N-methyltransferase (PNMT)
phenylethanolamine-N-methyltransferase (PNMT) is unregulated by
cortisol
Catechol-O-methyltransferase and monoamine oxidase are responsible for
catecholamine inactivation
catecholamines are made from
tyrosine
strenuous exercise leads to inhibition of glycolysis in skeletal muscle bc intracellular _______ is depleted
NAD+
in anaerobic glycolysis, NAD+ is regenerated from NADH when
pyruvate is converted to lactate by lactate DH
NADH transfers electrons to pyruvate to make lactate and regenerate NAD+
in aerobic conditions, NAD+ is converted to NADH in the
TCA cycle
in aerobic conditions, NADH is reconverted to NAD+ in the
electron transport chain as the energy in NADH is used to make ATP
in aerobic glycolysis, NAD+ is needed to convert
G3P to 1, 3-BPG
Lab test for suppurative parotitis in adults
elevated serum amylase without pancreatitis
which hepatitis virus usually completely resolves
HBV
labs for cholesterol gallstone formation
increased cholesterol
decreased bile acids
decreased phosphatidylcholine
bile becomes super saturated with cholesterol
high levels of bile salts and phosphatidylcholine increase
cholesterol solubility and decrease risk of gallstones
new eye pain after treatment for acute inferior MI
was treated with atropine to fix bradycardia –> muscarinic receptor blockade = mydriasis (dilated pupil) and narrowing of anterior chamber angle and diminished outflow of aqueous humor
can precipitate angle-closure glaucoma
CI in those with glaucoma
atropine can be used for bradycardia bc it
decreases vagal influence on SA and AV nodes
common AE is increased intraocular pressure
MC community acquired pneumonia in healthy and HIV patients
pneumococcus
the ciliary muscle is under PNS control from
Edinger-Westphal nucleus/ciliary ganglion
inhibition of Edinger-Westphal nucleus/ciliary ganglion
blurry vision with accommodation causing trouble seeing up close
inhibition by antimuscarinic pathway w/1st gen antihistamines
Pramiprexole MOA
directly stimulates DA receptors
ergot DA agonists
bromocriptine
Tx for hyperprolactinemia
non ergot DA agonists
pramipexole and ropinirole
delays use of levodopa in Parkinsons
Selegiline MOA
inhibits MAO-B in the brain = decreased central DA
used to delay clinical progression of Parkinsons
Amantadine works for Parkinsons by
indirect and direct DAnergic agent
alleviates motor symptoms by enhancing endogenous DA
some anticholinergic properties to reduce tremors
Tx for drug induced parkinsonism or idiopathic PD
anticholinergics inhibit central muscarinic receptors
trihexyphenidyl
benztropine
During muscle contraction, ATP attaches to the sarcomere causing immediate
myosin head detachment from actin filament
Pauci-immune RPGN
no Ig or complement deposits on BM
increased ANCA
Three kinds of RPGN
antiglomerular BM (IgG and C3 linear deposits, Goodpasture)
Immune-complex (granular pattern of IgG and IgA and complement, PSGN, SLE, IgA nephropathy, Henoch-Schlonlein)
Pauci-immune (no Ig or complement, increased ANCA, granulomatosis with polyangiitis, microscopic polyangiitis)
Complications of prolactinoma in premenopausal women
galactorrhea estrogen deficiency (oligo/amenorrhea, decreased bone density, vaginal atrophy)
Complications of prolactinoma in men
infertility
decreased libido
impotence
complications of prolactinoma in children/adolescents
delayed puberty
growth impairment
prolactinoma effects on other hormones
suppressed GnRH from hypothalamus reduced LH (FSH to lesser extent) - hypogonadism, an ovulation, amenorrhea estrogen deficiency
deltaF508 mutation
cystic fibrosis
mutation in CFTR protein
cystic fibrosis MC electrolyte disturbances
hyponatremia from excessive salt wasting in sweat
hypochloremia same
Vitamin E deficiency can happen in
fat malabsorption
abetalipoproteinemia
Vitamin deficiency that causes hemolysis and neurologic dysfunction (due to free radical damage of cell membranes, mimics Freidrich ataxia)
Vitamine E
Patient looks like Freidrich ataxia but asking for deficiency
Vitamin E
Thiamine deficiency seen in
alcoholics and malnourished
thiamine deficiency associated with
peripheral neuropathy
high output HF
Wernicke encaphalopathy (ataxia, confusion, ophthalmoplegia)
Polio causes damage to
anterior horn cells = asymmetric flaccid paralysis and hyporeflexia
sensation intact
