NBME Flashcards
What is apoptosis characterized by
cell shrinkage, nuclear shrinkage, (pyknosis) and basophilia, and membrane blebbing, nuclear fragmentation (karyorrhexis) and formation of apoptotic bodies which are then phagocytosed
pyknosis
nuclear shrinkage
karyorrhexis
nuclear fragmentation
basophilia
a dye (basic or positive) that stains DNA/RNA in the nucleus, RNA in ribosomes, which are acidic and negatively charged
what is the intrinsic pathway?
involved in tissue remodeling in embryogenesis
occurs when a growth factor is withdrawn from a proliferating cell population,
occurs after exposure to injurious stimuli radiation, toxins hypoxia
changes in proportions of anti and pro apoptotic factors lead to increased mitochondria permeability and cytochrome C release
extrinsic pathway
FAS ligand binding to FAS
immune cell 9perforin and granzyme B
necrosis
enzymatic degradation and protein denaturation resulting from irreversible injury
intracellular components extravasate
inflammatory process
coagulative necrosis characteristics
eosinophilia, loss of cytoplasmic and nuclear detail, blurring of cytoplasmic membranes, cell otherwise intact preservation of tissue architecture
reversible with O2
decreased ATP synthesis
cellular swelling ( no ATP —> impaired Na+/K+ pump)
nuclear chromatin clumping
decreased glycogen
fatty change
ribosomal detachment (decrease protein synthesis)
irreversible cell injury
nuclear pyknosis, karolysis, karyorrhexis, Ca2+ influx, –> Capsase activation
Plasma membrane damage
lysosomal rupture
mitochondrial permeabillity
red infarcts
red infarcts occur in tissues with collateral circulation,
liver lungs, intestine
pale infarcts
sold tissues with single blood supply
heart kidney and spleen,
Clinical presentation of hypovolemic and cardiogenic shock
low output failure
increase TPR
low cardiac output
cold clammy patient, vasoconstriction
Clinical presentation of septic shock
high-output failure
decreased TPR
dilated arterioles, high venous return,
hot patient (vasodilation)
atrophy
decrease hormones (uterus/vagina) decrease innervation (motor neuron damage) decrease blood flow decrease nutrients increase pressure (nephrolithiasis) occlusion of secretory ducts
Clinical Presentation of Inflammation
redness, dolor, calor, tumor, loss of function
vascular component of inflammation
increase vascular permeability, vasodilation, endothelial injury
cellular components of inflammation,
neutrophils extravasate and participate in inflammation, phagocytosis, degranulation and inflammatory mediator release
acute inflammation
rapid onset
lasts minutes to days
key players in acute inflammation
neutrophils
chronic inflammation
lymphocytes and macrophages
characterized by persistent destruction and repair
blood vesel proliferation and fbirosis
granuloma
nodular connections of epithiliods and giant cells, outcomes include scarring and amyloidosis,
outcomes of acute inflammation
complete resolution abscess, or progression to chronic inflammation
causes of acute inflammation
infection
necrosis
physical injury
causes of chronic inflammation
autoimmune disease
chronic irritation
viral infecton
systemic inflammation of acute inflammation
chills,
fever,
myalgias
From blood to sites of tissue injury, neutrophils via 4 steps
rolling,
adhering,
diapedsis,
migration
which protein allows neutrophils to roll?
selectins
which protein allows neutrophils to adhere
integrins
what do leukocytes use to travel through interstitium
chemotatic signals`
free radicals damage ]
membrane lipid peroxidation,
protein damage
and DNA breakage
where do free radicals come from?
gamma rays and x rays, metabolism of drugs redox reactions NO transition metals, leukocyte oxidative burst
Elimination of free radicals
catalase superoxide dismutase, glutathione peroxidase spontaneous decay antioxidants
retinopathy of prematurity
abnormal blood vessels grow in the retina, retinal detachment –>causing blindness
bronchopulmonary dysplasia
in premature infants, chronic lung disease caused by mechanical ventilation and oxygen supply.
wound healing
three stages
inflammatory
proliferative
remodeling
inflammatory key mediators
platelets, neutrophils, and macrophages
proliferative key mediators
fibroblasts, myofibroblasts, endothelial cells, keratinocytes, and macrophages.
remodeling key players
fibroblasts
what occurs during inflammation
increased vascular permeability, clot formation, neutrophil migration, macrophage clean up debris 2 days later
what occurs during proliferation
deposition of granulation tissue and collagen, angiongenesis, epithelial cell proliferation, dossolution of clot and wound contraction mediated by myofibroblasts.
what occurs during remodeling
type III collagen replaced by type I collagen
increase tensile strength of tissue
transudate
hypocellular
protein poor
specific gravity < 1.012
exudate
cellular
protein rich
specific gravity >1.020
cause of exudate
lymphatic obstruction
inflammation
causes of transudate
increased hydrostatic pressure
decreased oncotic pressure
Na+ retention
caseating granuloma
Dx
TB
noncaseating granuloma
Tb sarcodoisis other infections foreign material fungal infections
Increase erythrocyte sedimentation rate
is an indicator of?
infections, inflammation cancer pregnancy SLE
decrease erythrocyte sedimentation rate
sickle cell
polycythemia
CHF
Symptoms of iron poisoning
acute, gastric bleeding
chronic metabolic acidosis, scarring leading to GI obstruction
metaplasia often the result
secondary to irritation and/or environmental exposure
dysplasia
abnormal growth with loss of cellular orientation, shape, and size in comparison to normal tissue, maturation; commonly preneoplastic.
which plasia’s are reversible
hyperplasia,
metaplasia,
dysplasia
anaplasia
abnormal cells lacking differentiation, resemble primitive cells of same tissue, often equated with undifferentiated malignant neoplasms, little or no resemblance to tissue of origin.
neoplasia
a clonal proliferation of cells that is uncontrolled and excessive.
may be benign or malignant
Barret’s esophagus,
change from squamous cell adenocarcinoma to esophageal adenocarcinoma.
BCL2
follicular lymphoma and undifferentiated lymphoma,
anti apoptotic molecule,
BCL2 sensors,
BCL2 inhibit the sensors, which prevents mitochondria from releasing cytochrome C and activates capsases.
aflatoxins are associated
with what cancer
hepatocellular carcinoma
Asbestos
mesothelioma
how is volume of distribution impacted with kidney or renal disease
Vd is increased
describe the characteristics of a drug with high Vd
lipid soluble, low protein binding, low rates of ionization
equation for half life
.7x Vd/Cl
Bioavailability
fraction of drug that reaches systemic circulation unchanged
Equation for the volume of distribution
total amount of drug/ plasma drug concentration
Acetaminophen toxicisity
classical presentation
hepatoxicisity
hepatoxicisty what lab value would indicate liver damage
ALT
What is the cause of acetaminophen toxicisity
N-Acetyl Para Benzoquinoneimine
acetaminophen overdose situation
more drug is available for CYP metabolism to a toxic metabolite.NAPQI
what metabolizes the toxic metabolite of acetaminophen
glutathione,
glutathione is a combination of
glutamate, cysteine, and glycine
what enzyme catalyze formation of glutathione conjugates?
glutathione S transferase
what increases
the risk of acetaminophen hepatotoxicity?
alcohol inducible CYP2E1 which rapidly forms NAPQI’
malnutrition decreases GSH and UDP glucoronic acid levels
high acute doses, >10grams in adults
Stages of Acetaminophen toxicisity
stage 1
stage 1 (0-24 hours)
patients are often asymptomatic,
nonspecific symptoms,
nausea vomiting, lethargy, drowsiness, diaphoresis,
Stages of Acetaminophen toxicisity
stage 2
patients are often asymptomatic,
mild increases AST
and some right upper quadrant pain
Stages of Acetaminophen toxicisity
stage 3
AST, ALT levels > 10,000IU/ml fulminant hepatic failure encepholapthy, coma hemorrhage, jaundice liver transplantation may be needed renal changes usually less prominent.
Stages of Acetaminophen toxicisity
stage 4
liver regernates, near normal laboratory values often observed within a week.
complete recovery may take months
what’s the treatment of acetaminophen toxicisity
NAC
acute management
of acetaminophen
activated charcoal, if you know its toxic
get blood samples, >4 hours and less than 24 hours after dose,
give it if its above treatment line in the Rumack matthew noomogram
Why NAC works
it’s a source of systeine to form glutathione
some binds directly to NAPQI
source of sulfate for sulfate conjugation
list the following G proteins and what’s it linked to
alpha 1—> Gq
alpha 2 —> Gi and Go
B1 B2 B3, D1—> Gs
D1
produce dialtion of renal arteries
LOCATION OF B1 RECEPTORS
heart and kidneys
B2
heart and produce inhibitory effects of sympathetic stimulation
B3
lipolysis
competitive antagonists
on efficcacy grraphs
shifts curve to the right, decrease potency, no change in efficacy
noncompetitive antagonist
shifts curve down, decreases efficacy.
can’t be overcome by increasign agonist substrate concentration,
what is a great example of noncompetitive antagonists
phenoxybenzamine on alpha receptors
partial agonsits,
decreases efficacy
therapeutic index
a comaprison of hte amount of therapeutic agent that causes the therapeutic effect to the amount that causes toxicisity
analogy to remember the equation for TI
TILE
Therapuetic index= LD50/ ED50
lethal dose/ effective dose
therapeutic window
refers to range of doses which optimize between eficacy and toxicisity
what does higher TI values?
SAFER DRUGS
which receptor causes mydriasis
alpha 1
what causes vascular smooth muscle contraction
alpha 1
what causes intestinal and bladder sphincter muscle contraction
alpha 1
what works in the CNS and decreases sympathetic outflow
alpha 2
what causes increase in platelet aggregation
alpha 2
what causes bronchodilation
Beta 2
what causes vasodilation
beta 2
phenelyphrien is use to treat
mydriatic agent and decongest agent
albertorl terbutaline metaproterenol, salmeterol
formoterol
act on what receptor and are used for what?
Beta 2,!!!!!!
bronchodiltion, in asthma and COPD
Norepinephrine treats
acute hypotension HYPO
adverse side effects of alpha agonists
hypertension and cerebral hemorrhage
adverse side effects of beta agonists
tremor and nervousness, tachycardia, and palpitations
main use of reserpine
blocks VMAT, ultimately depleting NE from terminals,
main use is to treat hyperkinetic movement disorders,
main use of ephedrine
releases NE and is a direct agonist
treats hypotension and nasal congestion
pseudophedrine
nasal decongestant
phenoybenzame
only noncompetitive blocker
phentolamine
prototype
alpha 1 selective
prazosin, doxazosin, terazosin
to manage pheochomocytoma
phenozybenzamin
to treat BPH,
urinary obstruction BPH!!!
why with alpha antagonists do you get tachycardia
excess norepinephrine release
but mainly, you lose the control found on alpha 2 receptors which are autoreceptors.
what increases outflow of aqueous humor
alpha agonist
what decreases secretion of aqueous humor?
beta blockers
beta blockers that reduce the production of aqueous humor
timolol betaxolol
What’s used to reduce the myocardial infarction?
propanolol
metaprolol
timolol.
what’s used to treat congestive heart failure
metoprolol carvedilol
adveser effects of beta blockers
heart failure
arrythmias
don’t use with patients iwth asthma
ganglionic blockers
blocks nicotinic receptors in ANS ganglia,
Destroys ANS,
choline esters
ACh, methacholine, carbachol, bethanechol
characteristics of choline esters
poorly absorbed from GIT and doesn’t cross BBB
which ones excite nicotinic receptors
ACh, and carbachol
which drugs have a longer duration of AChE?
carbachol and bethanechol
what are alkaloids?
pilocarpine,
alkaloids are better than cholines
because they are well absorbed from GIt, and they do cross BBB
Pilocarpine,
selective for muscarinic receptors.
two mechanisms of muscarinic agonists
direct stimulation of muscarinic receptor
stimulation of muscarinic receptors on presynaptic terminal to reduce release of neurotransmitter
direct acting cholinometics on the vasculature
dilation via nitric oxide
methacholine
diagnosis of asthma
pilocarpine
xerostomia and glaucoma
Bethanecol
postoperative ileus and urinary retention
carbachol
glaucoma
contraindications of muscarinic directing acting drugs
asthma or cOPD
obstruction in GIT or urinary system
bradycardia hypotension
hyperthyroidism
what’s the good thing about edrophonium
lasts only 2-10 minutes
what’s good about carbamic acid esters?
neostigmine, physostigmine pyridostigmine, block up to 6 hours of ACHE
organophosphates?
echothiopate and malathion
echthiopate
glaucoma
physostigmine
glaucoma, antimucarinic drug intoxication
edrophonium
diagnosis of MG , reversal of neuromucular blockade
pyrdistigmine and ambenonium
treatment of MG
neostigmine
postoperative ileus and urinary retention, MG, reversal of neuromuscular blockade
muscarinic adverse effects
weakness or paralysis increased sweating diarrhea vomiting miosis bronchial constriction?
