Week 5 Flashcards
what is the most common pathologica cause of unilateral fetal hydronephrosis?
narrowing or kinking of the proximal ureter at the URETEROPELVIC JUNCTION
pathogenesis of UPJ obstruction may involve failure of the canalization of the ureteric bud as it develops into the renal pelvis and ureters through dilation and canalization by 10 weeks
common finding during second trimester, and transiet/clinically insignificant due to fetal renal pelvis having a high compliace and can accomodate large volumes
Newbornds not prenatally diangosed by present iwth a palable abdominal mass reflecting an enlarged kidney
Vesicoureteral reflux can cause NONobstructive fetal hydronephrosis
Flattening of deltoid muscle with acrominal prominence after shoulder injury….
Anterior humerus dislocation
most commonly results from a blow to an externally rotated and abducted arm
Often assocaited axillary nerve injury resulting in deltoid paralysis / flattening of the deltoid prominence, protrusion of the acromion, loss of sensation over the lateral shoulder, ant axillary fullness (humeral head has moved here)
Deltoid muscle
innervates deltoid m, teres minor
sensory innnervation to the skin overlying the lateral shoulder
Isoniazid side effects
direct hepatotoxic, peripheral neuropathy is a potential side effect if not given with pyridoxine/B6
10-20% of pt, causes acute, mild hepatic disfuction, characterized by transient increase in AST/ALT
usually within the first 4-6 months of treatment
liver return to normal
Frank hepatitis can occur in rare cases <1%
how does IgG act as an opsonin?
IgG acts as an opsonin by binding antigens (bacterial surface proteins, etc) at its FAB sites and subsequently binding a phagocyte at is Fc site (to FcR on the phagocyte - neutrophil, macrophage) –> signals for the phagocytosis of the Fab bound antigen by the phagocyte; near the carboxyl terminal
Disorders of fructose metabolism
Essential fructosuria –> deficiency of fructokinase
(hexokinase can compensate for high levels of fructose by converting fructose to fructose6-posphate, which can enter glycolysis) benign condition
Hereditary fructose intolerance –> deficiency of aldolase B
hypoglycemia, vomiting after fructose ingestion; failure to thrive, liver and renal failure
tx: no fructose or sucrose intake
How does an impaired CFTR transmembrane protein cahnge the secretions and electrolyte content?
Does it differ depending on the type of gland??
In respiratory and gastric glands, impaired functioning of the CFTR transmembrane protein:
DEC luminal chloride secretion,
INC sodium and INC net water absorption
–> dehydrated mucus and a more negative transepithelial potential difference
In sweat glands, abnl CFTR function causes
reduced lumnal salt absorption –> hypertonic sweat with high chloride content
*CFTR channel acts opposite at respiratory and gastric glands vs sweat glands**
transepithelial potential difference is MORE NEG that normal due to the chloride ions retained at the mucosal surface
Hawthorne effect
=observer effect tendency of subjects to change their behavior as a result of their awarenss that they are being studied
Berkson’s bias?
refere to selection biased created by choosing hospitalized patients as the control group
Pygmalion effect?
the fact that a researcher’s belief in the efficacy of tx can potentially affect the outcome
innervations of the tongue:
Motor: hypoglossa nerve (CN XII) with the exception of the palatoglossus muscle - CN X/vagus
Generay sensory (touch, pain, pressure temp)
anterior 2/3: mandibular branch of trigeminal
Posterior 1/3: glossopharyngeal nerve iX
Posterior tongue root: vagus nerve X
Gustatory/taste buds:
Anterior 2/3: chorda tympani branch of facial nerve
Posterior 1/3: glossopharyngeal IX
Posterior are of the togue root and taste buds of the larynx and upper esophagus: vagus X
what is the most common cause of infants with Potter sequence?
Respiratory failure due to severe pulmonary hypoplasia
potter sequence results from a renal anomaly that caues secresed fetal urine output leading to oligohydraminos. THe lack of amniotic fluid –> compression of the fetus w/characteristic facies and limb abnormaliteis and pulmonary hypoplasia, which isteh mos common cause of death in affected infants
Elderly abuse:
clinicians have a legal and ethical obligation to report elder abuse, neglect and exploitation. If there is a reason to suspect abuse or neglect, the patient should be interviewed alone to avoid intimidation by possible abusers.
What to ask once alone:
- Do you fee safe where you live?
- Who prepares your meals?
- Who handles your checkbook?
*physica and pschological sings of abuse; interaction btw the elderly pt and teh caregiver should be carefully observed
If there is reason to suspect - prompt reporting is required
What medications have anti-muscarinic effects? (5)
common symptoms?
atropine, antidepresssants (amitriptyline), H1 receptor antagonist (diphenhydramine), neuroleptics, anti-parkinsonian drugs
flushed skin, mydriasis (pupillary dilation)
Recall there are two main forms of cholinergic R - nicotinic and muscarinic; the toxic effects of anticholinergic meds results primarily from blockade of muscarinic R
Nicotinic R - found on postganglionic neurons in sympathetic and parasympatheic ganglia and on skeletal muscle cells at the NMJ – blockade coudl cause respiratory paralysis, and automatic ganglion blockad can cause hypotension and tachycardia
H1 vs H2 receptors?
H1 = found in the vascular endothelium and bronchial smooth muscle where they help to mediate vascular permeability and bronchoconstriction, respectively
H2 = common in parietal cells for gastric acid release
relative risk:
odds ratio:
risk of dz among exposed/risk of dz in unexposed
typically in cohort studies
odds ratio: ad/bc
often calculated in case-control studies where RR cannot be obtained because such studies do not follow patient sover time to determine incidence of a new outcome
how does HBV cause injury to the liver?
The HBV itself does NOT have cytotoxic effect; rather it is teh presence of the viral HbsAg and HbcAg on teh cell surface STIMULATE HOST’s CYTOTOXIC CD8+ T lymphocytes to destroy infected hepatocytes
so the host immune response is that causes the damage
How does the HBV infection progress?
Two phases: proliferative and integrative
1) PROLIFERATIVE: entire virion and all related antigens of the episomal HBV DNA are present – viral HBaAg and HBcAg expressed on MHC I which then activate cytotoxic CD8+ T lymphocytes to destroy the infected hepatocytes (virion itself does NOT have cytopathic effects)
2) INTEGRATIVE: the HBV DNA is incorporated into the host genome of those hepatocytes that survive the immune response – infectivity ceases, liver damage tapers off when the antivirals antibodies appear adn viral rep stops
pregnant mom with rubella
acute viral xanthem (one of them)
maculopapular rash begin on the head and neck and spread downward
generalized lymphadenopathy particularly postauricular and occipital is more prominent in rubella
adult women tend to develop polyarthritis and polyarthralgia as sequeale
fetal infection –> sensorineural deafness, cataracts, cardial malformations like PDA
What deficiency should we be careful about with strict vegans?
Vitamin B12, since its obtained through the diet soley from animal sources
B12 is important for myelin syntehsis and DNA synthesis –> megalopblastic anemia, , subacute combined degereration of teh spinal cord,
This deficiency takes many years to develop (4-5 yrs!!) due to the large hepatic B12 reseve and presents with anemia (megaloblastic), potentially irreversible neurologic deficits (parethesias, weakness, ataxic gait)
note- this could also be seen in pt with total gastrectomy if not given the proper vitamin supplementation though remember ti takes YEARS to develop due to the large hepatic B12 reseve.
What deficiency could isoniazid lead to?
Vitamin B6
sx - dermatitis, atrophic glossitis, siderblastic anemia
which bones are more likely to fracture in a bunch to the eye?
the weakest plates of the orbit = medial and inferior walls
fracture is typically evident in radiographic imaging and fluid (ie-blood) or herniation of the orbital contents can often be visualized in teh adjacent normally air filled sinuses
what is reduced compliance of the lung?
For any given volume, the pressure will be significantly increased
Reduced pulmonary parenchymal compliance is a hallmark of pulmonary fibrosis
[increased compliance seen in emphysema]
atrial fib on ecg and on the venous pulse wave?
irregularly irregular
ecg - ABSENCE of Pwaves, varying R-R intervals
(some pt have fine fibrillatory waves = fwaves, between QRS complexes (often narrow), representing the chaotic atrial activation
Absent a wave on jugular venous pulse
AF is teh most common tachyarrhythmia and is often precipitated by acute systemic illness or increased sympathetic tone, occassionally after excessive alcohol consumption “holiday heart syndrome”
Acute tubular necrosis:
ischemic ATN is one of the most common causes of acute kidney injury in hospitalized pt
ATN can be caused by decreased renal perfusion due to severe hypovolemia, shock or surgery
The straight proximal tubules (PCT) and the thick ascending limb of Henle’s loop located in the outer medulla are the most commonly affected portions of the nephron. (predom the medulla since they have a low blood supply even in nl conditions -pct uses a lot of energy with ATP transport)
clinical pres: inc serum creatinine, inc BUN, norm bun/cr rationoliguria, muddy brown casts
Biliary sludge?
Sludge formation is a known precursor to stone formation, particularly cholesterol stones and may be complicated by biliary colic, acute cholecystitis, cholangitis, and pancreatitis.
Gallbladder functions to actively absorb water from bile. Hypomotility cases bile concentration, which promotes bile precipitation and accumulation of viscious biliary sludge that predisposes to gallstones formation and bile duct obstruction
what are pigment stones?
pigment gallstones can be brown to black and arise from conditions that increase the amt of unconjugated bilirubin in bile.
brown stones – asc w/ biliary tract infections (microbes producting B-glucoronidases)
black stones – setting of chronic hemolytic anemia (SCD), and increase enterocyte cycling of bilirubin (Crohn disease)
electrolyate imabalance of addison’s?
hyponatremia, hyperkalemia, hyperchloremia, non-anion gap metabolic acidosis
2,3 BPG effect on the oxygen saturation:
23PBG is an organophosphate created in erythrocytes during glycolysis
The production of 2,3 BG is increased when oxygen availability is reduced, as occurs in chronic lung disease, heart failure, and chronic exposure to high altitudes
elevated 2,3 BPG dec hemoglobin O2 affinity allowing the release of more O2 in the peripheral tissues
2,3 BPG binds to deoxygenated HB, between 2 beta chains, decreasing the affinity for oxygen (binding pocket increased in positive charge to allow for binding)
Lateral ankle sprain
most often due to inversion of a plantar-flexed foot, ankle is stablized laterally by the
ant inferior tibiofibular, ant talofibular, posterior talofibular and calcaneofibular ligaments
the lateral ligaments are weaker and are injured more often than the medial ligaments
most common ankle sprains involve only the ant talofibular ligament and present with pain, ecchymosis at the anterolateral aspect of the ankle
isoniazid MOA
inhibition of mycolic acid synthesis
side effects: neurotoxicity (give vitamin B6/pyridoxine), hepatotoxicity, could cause drug induced SLE reaction (SHIPPE)
[mycolic acids are essential for proper cell wall structure and virulence factor synthesis-sulfatides, wax D, cord factor; without the mycolic acids, they canot create proper cell walls or divide–also it is what allows them to be acid fast as they retain the carbolfuchsin dye and resist decoloration by an acid alcohol decolrizing agent]
Acoustinc neuromas:
Schwann cell-derived tumors that typically arise from the vestibular portion of the vestibulocochlear nerve (CN VIII) and are commonly located at teh cerebellopontine angle (between teh cerebellum and lateral pons).
Patients present with ipsilateral unilateral sensorineural hearling loss and tinnitus due to impairment of the cochlear portion of the nerve. Damage to the vestibular component may also result in vertigo, dysequilibrium and nystagmus.
most are unilateral but recall that bilateral acoustic neuromas are frequently seen in pt with neurofibromatosis type 2.
how does insulin increase glucose uptake?
IN insulin sensive skeletal and adipose tissue, GLUT4 is the insulin-sensitive transporter; it is sotred in cytoplasmic vesicles, thus when insulin is present, GLUT 4 is incorporated into the cell membrane –> inc # of transporters, inc # of glucose uptake
= carrier mediated transport
stereoselective and preferentially catalyze the entrance of D-glucose rather than L-gluc
what is the time requirement for PTSD?
> 1 month duration of clinical features
- intrusive thoughts, nightmares, flashbacks, avoidance of trauma reminders, hypervigilance and sleep disturbance*
tx: trauma-focused CBT
anti-depressants (SSRIs, SNRIS)
[less than 1 month, more likely to be acute stress disorder- sx may remit within 1 month or progress to PTSD after this time]
What is the first-line treatment for chronic asthma?
corticosteroids have the strongest and most predictable effects on the inflammatory component of asthma
inhaled corticosterods form teh cornerstone of chronic therapy for pt with persistent astham and can reduce the # and severity of acute asthma exacerbations (futicasone)
pronounced anti-inflammatory effects on the respiratory epithelium
used for chronic mgmt (inhaled) and acute exacerbations (systemic)
inhibit the formaiton of inflammatory mediationrs (cytokines, prostaglandins, leukotrienes) implicated in bronchial asthma
reduce leukocyte extravasation
induce apoptosis of inflammatory cells
within a few weeks –> significant reduced airway inflammation; decrease amt of mucus produced by goblet cells further educing airway obstruction
histology of bronchial asthma
condition characterized by chronic airway inflammation and edema leading to bronchial wall thickening and remodeling.
Hyperinflated lungs, airway mucus plugging, cellular infiltration of bronchial wall
airflow can be compromsied by airway hyperresponsiveness adn increased bronchoconstriction, which occurs in acute asthma exacerbation
methotrexate:
folate antagonist
structually similar to folic acid and competitively and irreversibly inhibits DHF reductase, which inhibits the formation of THF
after entering the cell, MTX udnergoes polyglutamation, which prevents the movement of MTX out fo teh cell, resulting in intracellular accumulation of MTX for later use
Tetrahydrofolate is an integral precursor of DNA synthesis; inhibited
folic acid and DHF polyglutamate will accumulate in cells
Complete mole
is composed of multiple cystic edematous hydropic villi as a result of trophoblast proliferation
serial measurements of B-hCG should be performed following evacuation of a hydratidiform mole!
**persistently elevated or rising levels may signify the development of an invasive mole or choriocarcinoma!
heart abnormalities associated with turner syndrome?
preductal coarctation of the aorta (note diminished femoral pulses)
bicuspid aortic valve
symptoms of chronic renal allograph rejection and histology:
characterized by gradual deterioration in graft function at least 3 months post-transplant in absent of other events
sx: worsening hypertension, progressive rise in serum creatinine, proteinuria with normal urinary sediment
pathogen: graft endothelial damage, low-grade cellular and humoral immune response directed against alloantigens
–> obliterative fibrosis intimal thickening and scattered mononuclear infiltration of the surrounding tissues
–> renal ischemia and chornic inflammation causing shrinkage of the renal parenchyma with tubular atropy and interstitial fibrosis
hyperacute transplant rejection:
minutes to hours
PREFORMED antibodies agasint graft in recipeints circulation
morphology: gross mottling, cyanosis, arterial fibrinoid necrosis and capillary thrombotic occlusion
Acute transplant rejection
usually <6 months
exposure to donor antigens induces humoral and cellular activation of naive immune cells
Humoral: C4d deposition, neutrophilic infiltrate, necrotizing vasculitis
Cellular: lymphocytic interstitial infiltrate and endothelitis
aneurysmal compression of oculomotor nerve vs diabetic opthalmoplegia:
Aneurysmal compression of oculomotor nerve –> takes out the parasympathetics since the efferents are superficial
early: dilated pupil and loss of accomodation
late: ptosis and opthalmoplegia
Diabetic opthalmoplegia –> central infarction, affects teh somatic nerve fibers but spares peripheral parasympathetics (thus pupil ok!)
down and out position (unopposed CN IV, CN VI since CN III is out!)
normal sized, reactive pupil
ptosis (paralysis of levator palpebrae)
cholesteastomas?
collection of squamous cell debris that form a round pearly mass behind the tympanic membrane
can be congenital or may occur as an acquired primary lesion or following infection, trauma or surgery of the middle ear. They can cause hearing loss due to erosion into auditory ossicles
Primary are due to chronic negative pressur ein the middle ear causing retraction pockets in the tympanic membrane that become cystic – as squamous cell debris accmulates -> cholesteatoma formed
secondary – occur after squamous epithelium migrates to or is implanted i the middle ear
commonly cause painless otorrhea, can produce lytic enzymes and are often discovered when they erode through the auditory ossicles causing conductive hearing loss
**despite what the name implies, cholesteatomas do not contain any lipid or cholesterol components**
lamotrigine
anticonvulsant works by blocking voltage gated sodium channels
clinical use: partial and generalized seizures (except status epilepticus), is also effective for bipolar disorder
AE: steven johnson syndrome (<10 % body involvement) or toxic epiderma necrolysis (>30% body involvement) -flu like symptoms, flollwed by extensive cutaneous and mucosal lesions; lesions are characterized by epidermal necrosis and subepiderma bullae
what anticonvulsants are associated with SJS/TEN?
Lamotrigine
carbamazepine
phenobarbital (?)
phenytoin
ethosuximide (?)
Filtration of fluid through glomerulus
depends on renal plasma flow and GFR
FF = GFR / RPF
on avg, aprox 1/5 of the plasma that passes through the glomerulus capillaries is filtered into bowman’s capsule
DEC RPF –> DEC GFR –> reducing distal tubule sodium delivery
this stimulates secretion of renin and increased angiotension II production –> angio II preferentially constricts the efferent glomerular arteriole –> increasing hydrostatic pressure in the glomerular capilaries and attempts to maintain the GFR (autoreg) – the decrease in GFR is thus less pronounces than the decrease in RPF –> increasd in FF
Jervell and Lange-Nielsen syndrome:
one of the most common congenital long-QT syndromes
autosomal RECcessive
other presentation: congenital neurosensory deafness
QT-interval prolongation predispose to syncopal episodes and possible sudden cardiac death due to torsades de pointes / inherited disorder of myocardial repolarization, typically due to ion channel defects; increased risk for sudden cardiac death (k+ ??)
vs: Romano-Ward Syndrome, autosomal Dominant, but a pure cardiac phenotype with no deafness involved
mitral valve prolapse
cardiac auscultation reveals a nonejection, midsystolic click and mid to late systolic murmur of mitral regurg.
MVP is most often casued by defects in mitral valve connective tissue proteins that predispose to myxomatous degeneration of the mitral leaflets and chordae tendinae
click due to sudden tensing of the chordae as they are pulled taut by the ballooning valve leafest
murmur due to malaligment of the valve margins during systole
Squatting increases venous return and LV volume –> help bring the leaflets in a more normal anatomical position and thus delaying onset of click and the murmur shortes/disappears
murmur disappears with squatting (note HCM also disappears with squatting but no midsystolic click will be heard!)
MVP coudl be primary sporadic characterized by myxomatous degeneration of connective tissue
secondary - inherited connective tissue disorders, including marfan’s, ehler’s danlos syndrome and osteogenesis imperfecta
**myxomatous lesions are characterized by proliferation of spongiosa of the valve leafets, fragmentation of elastin fibers with increase in mucopolysac adn type III collage deposits
CVD prophylaxis
Aspirin
or clopidogrel (irreversibly block P2Y12 component of ADP receptors on the platelet and prevents platelet aggregation) with pt who are intolerant of aspirin
what are the watershed areas of the GI tract?
the splenic flexure and rectosigmoid junction lie between regions of perfusion of major arteries.
These watershed areas are susceptible to ischemic damage during hypotensive states, esp in patients underlying arterial insufficiency
(ie-ischemic colitis 0 sx: abdominal pain adn bloody diarrhea following complicated surgery)
colon receives blood from teh marginal artery/artery of drummond, an anastomic system of arteries that is in turn supplied by the SMA and IMA
distal colon also receives blood from the internal iliac artery
noncolusive ischemic coudl occur at the marigins of anastomic distributions
less commonly occlusive ischemic can also be caused by thromboemnolic or atheroembolic events
impaired profusion –> ischemia and necrosis; complications includa cidosis, spepsis, grangrene, performaiton
colonscopy –> pale mucosa and petechial hemorrhages
piolcytic astrocytoma
cystic tumor in teh cerebellum of a child most likley to be a pilocytic astrocytoma
biopsy will show a well-defined neoplasm comprised of spindle cells with hair-like glial processes that are associated with microcysts
these cells are mixed with Rosenthal fibers and granular eosinophilic bodies
which cells are unable to use ketones as a source of energy?
erythrocytes - since they lack mitochondria
Liver - lacks the enzyme succinyl CoA-acetoacetate CoA transferase (thiophorase), which is required to convert acetoacetate to acetoacetyl CoA
12-18 hours of fasting, bodys glycogen sotres are depleted and glyconeogenes is requires to maintian blood gluc levels – if fasting continues, body limits its relaince on gluconeo in an effort to conserve protein and seorts instead to ketone body synthesis
generated in the liver from FA and yield energy when converted to acetyl coA in the mitochondria of target cells
what is the embryologic origin of the following strucutres:
epidermis
dermis
melanocytes
Ectoderm –> epidermis
mesoderm –> dermis
melanocytes –> neural crest cells
cavernous sinus thrombosis:
Infection of the medial face, sinuses (ethmoidal or sphenoidal) or teeth may spread through the valvess facial venous system into the carvenous sinus –> carvenous sinus thrombosis
2° to pituitary tumor mass effect, carotid-cavernous fistula, or cavernous sinus thrombosis related to infection.
typical presentation: h/a, fever, proptosis, ipsilateral deficits in CN III, IV, VI, and V (opthalmic and maxillary branches)
THINK: nerves that control extraocular eye + V1 and V2, cavernous part of internal carotid also here
*CN IV is the most susceptible to injry
Blood from eye and superficial cortex —> cavernous sinus –> internal jugular vein
what is squamous metaplasia?
examples?
REVERSIBLE, adaptive response to chronic irritation, such as smoking
the normal columbar epithelium is replaced by sw epithelium in the lungs, which is more resistant to irritaiton but has reduced mucociliary clearance (increased risk for injuries)
etaplasia also occurs with Barrett esophagus, in which esophageal squamous epithelium is replaced by columnar epithelium in response to chronic acid exposure
Triad of Ataxia Telangiectasia:
Cerebellar ataxia
Telangiectasias (superficial, blanching nest of capillaries)
INC risk of sinopulmonary infections
Also inc risk of hematologic malignacies and causes an immune deficiency consisting of both cell-mediated and humoral dysfunction (primarily IgA deficiency, increasing risk for infections of upper and lower airways)
Autosomal Recessive
due to a mutation of ATM gene (Ataxia Telangiectasia Mutated) - gene responsible for DNA break repair
**hypersensitive to X-ray radiation that causes multiple chromosomal breaks**
Bare lymphocyte syndrome?
Immunodeficiency resulting from a defect in expression of HLA class II antigens on the surface of antigen presenting cells
MHC II is needed to present foreing anteigen to T cells to elicit a cell mediated AND humoral response (because T cells must first activate B cells to mature and undergo class switch)
Collagen synthesis
IN RER:
- synthesis -translation of collagen alpha chains = preprocollage usually GLY-X-Y where X and Y are prolines/lysinnes
- hydroxylation - req vitamin C / scurvy
- glycosylation and formation of hydroxyline resides, formation of procollage via hydronge and disulfied bonds (triple heliz 3 alpha chains) – if probs fomring tirple helix = osteogensis imperfecta
4 exocytosis
outside in fibroblast:
- proteolytic processing - cleavege of disulfied bonds –> insoluble tropocollagen
- crosslinking - reinforcement by covalent lysine-hydroxylysine cross linkage by copper containinglysyl oxidase - ehlers-danlos syndrome, menkes dz
Menkes disease vs wilsons disease
Menkes disease - X linked connective tissue dz caused by impaired copper absorption and transport defect due to defective menkes protein ATP7A –> decrease activity of lysyl oxidase (copper is a necessary factor) –> brittle/kinky hair, growth retardation and hypotonia
Wilsons dz = autosomal recessive defect in ATP 7B, leads to copper accumulation
what inhibits FA beta oxidation / breakdown?
in fed state --> increase amt of ATP –> inhibits isocitrate dehydrogenase (isocitrate –> alpha-ketoglutarate) –> increased citrate levels –> citrate leaves the mitochondrial via citrate shutle, cleaved by ATP citrate lyase to make acetyl CoA –> malonyl-Coa via acetyl-coA carboxylase (CO2 + biotin) –> fatty acid synthesis
malonyl coa inhibits carnitine acyltransferase, which is part of the carnitine carrier that shuttles fatty acyl-coa into the mitcondria. this inhibition prevents the transfer of acyl groups into the mitocondria, thus functions to preven thte breakdown of newly synthesized fatty acids.
Myasthenia gravis
most commonly caused by autoantibodies against postsynaptic nicotinic acetylcholine receptors (striated muscle)
—> blockade of the receptors active site, receptor internalization and dedegration, and damage to the motor endplate due to complement fixation
–> decrease number of functional acetylcholine R
–> DEC available cation channels –> reduction of end-plate potential following acetylcholine release
–> threshold potential not reach = muscle cells do not repolarize = no contraction
NL absolute refractory period
BUT actual synaptic concentrations of acetylcholine are UNAFFECTED (unlike botulism or lamber-eaton syndrome)
treatment of myasthenia gravis
how could you treat a common side effect
typically involved a cholinesterase inhibitor, an immunosuppresive agent and/or thymectomy
cholinesterase inhibitors example pyridostigmine
common side effect is GI symptoms due to excessive cholinergic stimulation of the gut
could give scopolamine, hyoscyamine (selective muscarinic acetylcholine R antagonist) that will reduce the effects of cholinesterase inhibitors at muscarinic R (ie- GI) without affecting the one on skeletal muscles since its nicotinic R!
enoxaparin:
low-molecular wt heparin that fxns like heparin (enoxaparin) in that it binds and activates anti-thrombin III (AT III) –> binds to factor Xa and stops factor Xa from converting prothrombin to thrombin
DUe to its fewer molecules, LMWH acts primarily on factor Xa, not thrombin
low molecular wt heparins are more effective at blocking AT III than thrombin/IIA directly.
Risk factors for suicide
+ protective factors
RF: pre-existing psychiatric disorders, hopelessness and impulsivity, previous attempts/threats, divorced/separated, elderly white man, unemployed/unskilled, physical illness, fam hx, fam discord, access to firearms (individuals with access have3x risk of suicide completion as sucide by firearm is asc with higher fatality rates vs other methods –> where direct intervention can help!), substance abuse
protective factors: suicide support/family connectedness, pregnancy, parenthood, religion adn participation in religious activities
piriformis syndrome
the piriformis passes through the greater sciatic forament and is involved with external hip rotation. muscle injury or hypertropy can compress the sciatic nerve in the foramen 00>
The sciatic foramen - pelvic opening for structures of the lower limbs
divided into greater and lesser by the sacrspinous ligament
piriformis originates on the anterior aspect of the sacrum and occupies most of the psace in teh greater sciatic foramen –> inserts on teh greater trochanter of the femur
common cause of meningitis in the newborn (up to 6 mo)
SEL
strep group B
E. coli
listeria
cephalosporin-resistant organisms
Resistant to penicillin-binding proteins:
listeria (not covered by 3rd degree cephalosporins), MRSA, enterococci
No cell wall:
atypicals - mycoplasma, chlamydia
how can listeria avoid the immune system
treatment
LIsteria is a gram-positive facultative intracellular organism that is able to avoid phagocytosis and spread intracellularly (actin rockets!)
requires cell-mediated immunity
humoral response does not play a role
–> listeria is most common among pt with deficient cell-mediated immunities such as infants and those receiveing chemotherapy, or HIV positive, pregnant women
Tx: ampicillin
NOT covered by third gen cephalosporins
most common congenital breast anomalie in women and men?
accessory nipples ie- polythelia, supernumerary nipple
due to failure of involution of the mammary ridge
asympto
may well or become tender during inc hormones
occur anywhere along the embryonic milk line btw axilla and perineum
bilateral in 50%
findings: hyperpig, epidermal thickening, pilsebacous structure of montgomery areolar tubercles, smooth muscle bundles, possib mammary glands and multiple ducts
solar lentigines vs solar lentigo?
solar lentigines = “freckles” aka ephelides..
increased melanin production by melanocytes
solar lentigo = increased proliferation of melanocytes themselves
both hyperpigmented and flat but solar lentigines are often larger and occur in adults
Buspirone
partial agonist of 5HT1a receptor
nonbenzo anxiolytic used to treat general anxiety disorder
NO muscle relaxant or anticonvulsant properties (vs benzos)
NO RISK dependence
ok with alcohol (vs benzos and barbs)
not useful for acute anxiety or tx panic disorder due to its SLOW ONSET OF ACTION (clinical response is up to 2 weeks)
Heteroplasmy
= different mitochondrial genomes within a single cell
(each cell has tons of mitochondrai, and defects in their own genome may occur in any # of mit within the cell)
variable clinical expression in affected members, due to the coexistence of distinct verisions of mitochondrial genomes in an individual cell
severity often directly related to the proportion of abnormal to normal mitochondria within a pt cell
*think about when a mitochondrial dz; ie- presence of lactic acidosis and ragged skeletal muscle fibers ~ myopathy (recall mitco responsible for ATP production, thus tend to cause lactic acidosis nad primarily affect tissues with the highest metabolic rates!)
uniparental disomy
when both members of a chromosomal pair are inherted from one parente, which causes problems due to genomic imprinting
ie) although most often due to chromosoal deletions, uniparental disomy can also cause prader willi and angelmann syndromes due to loss of expression of maternalparental imprted components of a critical region of chrom 15
Aminocaproic acid
anti-fribinolytic agent that inhibits plasminogen activators and to a lesser degree antiplasmin activity
helps achieve hemostasis when firbinolysis is the casue of bleeding
cryoprecipitate
contains only cold-soluble proteins (Factor VIII, fibrinogen, vWf, vitronectin)
vs fresh frozen plasma contains all the coag factors
drug of choice for paroxysmal supraventricular tachycardia?
adenosine
rapid acting drug with a half-life of only less than 10 seconds
acts by slowing the conduction through the AV node by HYPERPOLARIZING the nodal pacemaker and conducting cells
Also, drug used for chemical stress test!
side effects: flushing, chest burning(due to bronchospasm), hypotension and high grade AV block
Charcot-Marie-Tooth disease
Also known as hereditary motor and sensory neuropathy (HMSN).
Group of progressive hereditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath.
Typically autosomal dominant inheritance pattern and associated with scoliosis and foot deformities (high or flat arches).
often present with weakness of foot dorsiflexion due to involvement of the common peroneal nerve
Positive trendelenburg sign would indicate injury to what nerve?
superior gluteal nerve injury
most often caused by peliv trauma or iatrogenic damage occuring during hip surgery or buttock injections (superior medial)
the superior gluteal nerve innervates the gluteus medius, gluteus minimus and tensor fasciae latea muslces –> fucntion to stablized the pelvis and abduct the thigh
weakness –> pelvis will sag towards the unaffected/contralateral side when the pt stands on the affected leg to compensate for the hit drop (gluteus medius lurch)
Femoral nerve
innervates muscles responsible for flexion of the thigh at the hip (iliacus and sartorius) and extension of the leg at the knee (quads)
Also supplies sensory innervation ot the skin on the anterior thigh and medial leg
injury —> knee buckling and loss of patellar reflex
Injury to obturator nerve
–> impairment thigh adduction and medial thigh sensory loss
Sciatic nerve
innervates the muscles in the posterior comparment of the thigh (hamstrings)
subsequently divides into the tibial and common fibular/common peroneal nerves –> motor and sensory innervation to the leg and foot TIP and PED
Hartnup disease
Autosomal recessive
Deficiency of neutral amino acid (e.g., tryptophan)
transporters in proximal renal tubular cells and on enterocytes –> neutral aminoaciduria and absorption from the gut –> tryptophan for conversion to niacin –> pellagra-like symptoms (diarrhea, dementia, dermatitis). Treat with high-protein diet and nicotinic acid.
** Niacin is made from tryptophan (which is essential!!)
Labs: aminoaciduria, restricted to the neutral amino acids
Note- the urinary excretion of proline, hydroxyprolife and arigine remians unchanged - impt to differentialte hartnup from other causes of genearlized aminoaciduria as fanconi syndrome
tx: nicotinic acid or nicotinamide and high protein diet generally results in significant improvement of symptoms
* Recall - Na+-dependent transporters in PCT reabsorb amino acids.*
Tryptophan is a precursor for what?
essential amino acid and precurosf for nicotinic acid (–>niacin), serotonin and melatonin
thiamine is important for:
is maximal in states of accelerated carbohydrate metabolism b/c it acts as a cofactor for the enzyme transketolase in the pentose pathway
Obesity hypoventilation syndrome-
characterized by chronic fatigue, dyspnea, difficult concentrating and evidence of hypoventilation (partial pressure of carbon dioxie >45 mmHg while awake) in an obse person!
it is one of hte important causes of hypoxemia with a normal alveolar to arterial oxygen gradient
normal Aa gradient
what conditions could cause hypoxemia with a normal Aa gradient?
nl: 5-15 mmHg
hypoxemia wiht a normal Aa gradient indicates that both the alveolar and the arterial partial pressure of oxygen are low
this can occur with: alveolar hypoventilation or inspiriration of air at high altitude
major processes that maintain plasma glucose between meals?
Glycogenolysis and gluconeogenesis
First 12-18 hours: glycogenolysis
first step: breakage of 1-4 glycosidic linkage to form glucose-1-hosphate
Once the glycogen stores become depleted: gluconeogenesis becomes the major process used by the body to keep blood glucose levels within the normal range
oxalocacetate –> phosphoenolpyruvate one of the steps
D-xylose
monosaccharide (remember that monosacs can be absorbed directly and don’t need to be degraded)
absorption is NOT affected by exocrine pancreatic insufficiency, and can be used to differentiate between pancreatic versus mucosal causes of malabsorption
exocrine pancreas can undergo how much destruction before malabsorption is seen?
exocrine pancreas has significant secretory reserve and >90% of the glandular tissue must be destroyed before a patient wil develop clinical malabsorption
can use the D-xylose test to observe if malabsorption is occuring without the pancreatic enzyme or if it due to the brush border
How does AVP increase water absorption in the collecting duct?
AVP attaches to its membrane receptor V2 –> acts on G2 –> AC –> increase cAMP –> inc protein kinase A –> phosphorylation of aquaporin 2 vesicles, to increase the # of aquaporin 2 channels in the apical membrane –> increasing H20
What is the length constant?
Aka space constant = measure of how far along an electrical impuse can proproage / distance at which the og potenital decreases to 37% of its original amplitude
DEC can be due to: decrease of myelin (fxn is to increase membrane resistance to decrease the charge dissipation and thus increasing length constant - ie like an insulation); myelinaiton also decreases the time constant (time it takes for a charge in the membrane potential to achieve 63% of the new value; reduction in time constant = faster / decrease membrane capacitance)
What is the clinical presentaiton of obliteration of the processus vaginalis?
During decent of teh testes (located in the peritoneal cavity and sub decend into the scrotum before birth), the testes are accompanied by an envagination of the peritoneum = processus vaginalis, which is suppose to oblieterate after descent is complete
failure –> persistent connection btwn the scrotum and the peritoneal cavity through the inguinal canal
if the opeing is small –> fluid leakage –> hydrocele (transillumination of the scrotum, and scrotal ultrasound reveals fluid surround the affected testicle)
if large –> could allow for pasage of abdominal organs, an indirect inguinal hernia develops
[indirect hernias are common in children, as they pass through teh deep inguinal ring, are covered by internal spermatic fascia and are located lateral to the inferior epigastric blood vessels]
hydroceles and indirect inguinal hernias both can present as an asymptomatic scrotal mass that increase in size during valsalva maneuvers
learning disorder
characterized by difficulties with key academic skills (reading, writing, math - it could be in only one subject, does not have to be all ), resulting in performace well below expectations for age level
children commonly display symptoms of axiety, inattention or hyperactivity when under stress.
If a child is showing these symptoms a learing disorder should be ruled out (need to rule out intellectual disability, hearing, vision orneurological disoder)
what influence do the following hormones have on male sexual development?
testosterone
DHT
testosteron: development of internal male genitalia (except prostate), spermatogenesis, male sexual differentiation at puber (muscle mass, libido)
DHT: developmet of external male genitalia, prostate, male-patter hair growth; also amplified effects of testosterone due to high affinity for testosterone receptors
T –> DHT requires 5alpha-reductase
male pseudohermaphorditism could occur if 5alpha-reductase type 2 deficiency (type 2 is predom found in genitals, where type 1 is found in postpubercent skin)
small phallus with hypospadias are common
The presence of a central vascular catheter, receiving parenteral nutrition puts a pt at risk for what infection?
Candidemia- candida can colonize teh catheter, and the lipid emulsion in the parenteral nutrition solution is thought to promote the growth of some candida sp
Candida dispaly psudeohyphae with blastocondida
most susceptible to echinocandis and nearly always to fluconazole
CYP 450 enzymes
group of heme-containing proteins that are responsible for the majority of drug metabolism, predom in the liver but also found in the gut and elsewhere
various CYP exitgenerally deactivate drugs and faciliate excretion from the body by improving water solubility, and also metabolize certain compounds to their acrive forms
Polymorphisms: genes could alter their expression/activity
three impt: poor, intermediate, rapid
what disease could be caused by an exotoxin released by S. aureus?
- Toxic shock syndrome
- staph scalded syndrome
- gastroenteritis (usually mayonnaise containing products, heat stable exotoxin that causes rapid-onset nausea, vomiting and abdominal cramping)
Duchenne muscle dystrophy:
X-linked recessive
deletion of the dystrophin gene (structural protein of muscle fibers and its absence casues muscle fiber destruction = myonecrosis)
on light microscopy - variation in muscle fiber shape and size, regenerating fibers and increased amounts of connective tissue are seen on light microscopy
disease onset: 2-5 years
muscles of the proximal lower extremities, back adn peliv and shoulder girdles are affected first
look for: abulation difficulties, gower sign, calf pseudophypertropy (calf muscles hypertropy initially but later replaced by fat and connective tissue/fibrofatty), asymmetric weakening of the paraspinal muscles –> kyphoscoliosis
wheelchair bound by 12
scolisosi progresses rapidly due to muscle imbalance and body positional changes –> complicated by restricted pulmonary function (dec vital capacity and total lung capcity)
What is the function of BRCA 1 and BRCA 2?
tumor suppressor genes, involved in repair of double-stranded DNA breaks
mutations results in genetic instability, predispoding cells to an increased risk of malignancy transformation
Both BRCA mutations are inhereted in AUTOSOMAL DOMINANT manner with VARIABLE PENETRANCE
70-80% lifetime risk for developing BCA,
40% of developing ovarian (> BRCA1)
Naltrexone is used for…
mu-opioid receptor, blocks the rewarding and reinforcing effects of drugs…
used for:
alcoholicim, show to reduce craving and ok to be initiated while the pt is still drinking
heroin - Long-acting opioid antagonist used for relapse prevention once detoxified
wilson’s antidote
wilson’s disease
aka- hepatolenticular degeneration
autosomal recessive mutaiton of ATP7B gene –> impaired cellular transport of cooper –> decrease incorporation into ceruloplasmi, reduced biliary copper excretion –> copper accumulation in liver, brain and eyes
–> injury by binding to sulfhydryl groups of cellular protines
sx: hepatic, neurologic, psychiatric, kayer-fleishcer rings
low ceruloplasmin, elevated transaminase
antidote: D-penicillamine (contains free sulfhydryl group and functions as a copper chelator)
What type of defense mechanism is reaction formation?
Reaction formation is a defense (immature) mxn in which an individual transforms unacceptable feelings or impulses into teh extreme opposite
(ie-being a sex addict then becoming a nun)
causes of polyuria (urine output >3L/day) and polydipsia?
diabetes mellitus
diabetes insipidus (central/nephrogenic)
primary polydipsia (PP)
primary polydipsia?
psychological disorder characterized by increased intake of free water –>
usually pt have hyponatremia with low initial urine osmolarity w/large volume
urine osmo increases after water depriviation
but there is not additional increase in urine osmolarity with vasopressin injection
tx: restriction of water intake
selective IgA deficiency
usually asmpto
recurrent sinopulmonary and GI infections
asc with other AI diseases
anaphylaxis during transfusion (potentially fatal! IgE mediated)
dx: low or absent serum IgA levels, nl IgG and IgM levels
pt can form IgE antibodies to IgA (anti-IgA antibodies)
due to failure of B cells to differentiate inot IgA-secreting plasma cells
C1 inhibitor deficiency
causes hereditary angioedema that can be triggered by transfusions. affected pt have angioedema but DO NOT have urticaria or wheezing
alpha 1 adrenergic antagonist
use
side effects
ex- terazosin, doxazosin
–> decrease in systemic vascular resistance
reflex increase heart rate
used for symptomatic BPH
side effects: orthostatic hypotension – lightheadedness and syncope due to cerebral hypoperfusion upon standing
alpha 1 blockers-
–> increase release of NE from peripheral nerve terminals –
increase blood pressure and heart rate
symptoms of neuroleptic malignant syndrome
and causes
NMS is an adverse reaction to anti-psychotic medication characterized by severe “lead-pipe” rigidity, hyperthermia, autonomic instability, and mental status changes
Fever
Fever, Encephalopathy, Vitals unstable, Enzymes inc, Rigidity of muscles
potentially life-threatening adverse reaction to neuroleptics (antipsychotics)
**although symptoms overlap with those of serotonin syndrome, pt wtih NMS do not exhibit hyperreflexia and clonus characteristic of serotonin syndrome
What is serotonin syndrome?
SSRI + any additional drug that will increase the serotonin
hyperthermia, confusion, myoclonus, cardiovascular instability, flushing, diarrhea, seizures.
Treatment: cyproheptadine (5-HT2 receptor antagonist).
what type of infarction does the lung undergo?
hemorrhagic, because there is dual blood supply to the lungs
Cauda equina syndrome:
typically results from a massive rupture of a intervertebral disk that is capable of compressing two or more of the 18 spinal nerves roots of the cauda equina
but can occur due to any trauma or space-occupyin glesion of hte lower vertebral column
these nerve roots provide the senosry and motor innervation of most of the lower extremities, the pelvic floor and the sphincters
sx: low back pain rading to one or both legs
saddle anethesia
loss of anocutaneous reflex
bowel and baldder dysfunction (S3-S5)
loss of ankle-jerk reflex with plantar flexion weakness of the feet
major side effects of calicum channel blockers
dihydropyridine -dipines
h/a, flushing, dizziness, peripheral edema
effective anti-hypertensive agents commonly used as monotherapy or in combination with other agens for treatmetn of hypertension
pt get peripheral edema due to its preferential dilation of precapillary vessels (arteriolar dilation), which leads to increased capillary hydrostatic pressure and fluid extravasation into the intersititum vs ARBs and ACE inhibitrs cause post-capillary venodilation adn can normalize teh increasd capillary hydrostatic pressure, reducing risk for peripheral edema in pt taking CCB
what causes genomic imprinting?
genomic imprinting = phenomenon in whcih an offsprings genes are expressed in a parent manner
it is caused by DNA methylation, an epigenetic process in which genes can be silenced by attaching methyl groups to cytosine residues in the DNA molecule
enzyme: DNA methytransferase, uses S-adenosyl-methionine (SAM) as the methyl group donor
- modify gene expression without altering the genetic code
cytosine methylation is also used, as a means that the genes expressed are parent-specific (ie-parent is methylated/imprited so that only the mother’s is expressed)
what is epistasis?
the phenomenon in which the allel of one gene affects the phenotypic expression of alleles in another gene
Avitaminosis A:
Vitamin A maintains orderly differentiation of specialized epithelia, inclduing the mucus-secreting columnar epithelia of the ocular conjunctiva, respiratory and urinary tracts adn pancreatic adn other exocrine ducts
it can also cause squamous metaplasia of such epithelia to a keratinizing epithelium, when a deficiency state exits!
drugs that cause aplastic anemia:
“can’t make new blood cells properly”
Carbamazepine, Methimazole, NSAIDs, Benzene, Chloramphenicol, Propylthiouracil
Aplastic Anemica
pathogen
cause
clinical findings
dx
bone marrow failure due to hematopoietic stem cells (CD 34+)
Histo: hypocellular marrow filled with fat cells adn amrrow stroma
causes: autoimmune, infections (parvo, EBV), drugs (carbamazepine, chloramphenicol, sulfonmides), exposure to radiation or toxins (benzene, solvents)
clinical findings: pancytopenia and sx associated w/it
anemia
thrombocytopenia
leukopenia
dx: biopsy showing hypocellular bone marrow composed mainly of fat and stromal cells
Define the following movement disorders:
dystonia
myoclonus
cogwheel
bradykinesia
chorea
hemiballism
dystonia: sustained, unvoluntary muscle contractions, force certain parts of the body int abnl, sometimes painful movements or postures; affect single muscle or group of muscles or entire body (cervical dystonias = spasmodic torticollis - most common focal dystona; blepharospams - involuntary, forcible closure of the eyelids, writers cramp)
myoclonus - sudden, brief, sometimes shock-like muscle contraction. both physiologic ( hiccups, hypnic jerks when falling asleep) or pathological (epilepsy, creutzfeldt-jakob dz)
cogwheel - resistent to passive extension/flexion on a parkinsonian limb
bradykinesia- slow movement, parkinson
chorea- involuntary muscle activity that flows from one muscle group to another; appear fragmented or jerkey; pt may display a dancing gait; huntington dz-
hemiballism- flinging of hte limbs (arms and/or leg) on one side of the body; occurs due to contralater injury in or near the subthalamic nucleus
what is the single most important measure to reduce the risk of transmission of hospital acquired infections?
hand hygiene
pathogenesis of MS:
MS = AI demyelinating disease of teh CNS that typically presents in young women age <50, with neurologic deficits disseminated in time and space. A common initial manifestation of MS is optic neuritis,
MRI findings - include white matter lesions scattered through the brain and/or spinal cord with a predilection for hte subcortical periventricular regions
involves autoimmune response (T cell and antibody-mediated) targeting oligodendrocytes and myelin in the central nervous system –> release of cytokines that promote infiltration of destructive macrophages/microglia and leukocytes, be cells play a role as most pt have oligoclonal immunoglobulin bands in teh CSF–> myelin destruction–> slowed nerve conduction with neurologic deficits!
Risk factors for cervical cancer:
infection with high risk HPV strains (16, 18) **strongest**
hx of STI
early onset of sexual activity (before 18- 2x)
multiple or high-risk sexual partners
immunosuppression (INC esp w/HIV!)
history of vaginal or vulvar cancer
low socioeco status
tobacco use (note-alcohol does NOT inc for cervical although it does for breast ca)
C. neoformans
yeast that has antiphagocytic polysac capsule, its major virulence factor
methenamine silver stain – narrow based buds
india ink – capsules appear clear
mucicarmine – capsules appear red
affects immunocomp
transmitted via respiratory route, most commonly preesnts with subacute or chronic meningoencephalitis; lung disease cause pneumonia like symptoms, including cough with scant sputum production, pleuritic chest pain, dyspnea and hempotysis
chest x-rays are nonspecific
dx-identify in sputum, bronchoalveolar washing or tissue sampling
findings for diastolic HF
LVEDP
LVEDV
LV ejection fraction
diastolic heart failure is caused by decreased ventricular compliance
LVEDP- increased
LVEDV- normal
LV ejection fraction - normal / near nl >50%
in the setting of increased LV filling pressures
due to conditions that decrease LV compliance:
impaired myocardia relaxation (ie-from ischemia)
inc intrinsic ventricular wall stiffness (amyloid deposits)
Inc LV wall hypertrophy (long stanidng HTN), impairing myocardial relaxation and increase intrinsic wall stiffness
LV diastolic pressure- determined by blood volume in the lV cavity and compliance of the LV, reduced ventricular compliance –> increased LVEDP at teh same LVED volumes; this casues a shift in teh pressure-volume curve that goes upward and to the left
as diastolic dysfunction worsens, LVEDP continues to rise as the heart attempts to maintain a near normal stroke volume and CO…decompensation occurs when the increased LVEDP (transmitted to teh left atrium and pulmonary veins) casues PE and dyspnia…cardiac reserve also diminished as teh stiffened ventricle becomes less effective at accomondating incread blood volumes, limiting the ability of frank-starling mxn
findings for systolic HF
LVEDP
LVEDV
LV ejection fraction
systolic HF is caused by primary decrease in myocardial contractility rather than ventricular compliance. as a result, systolic HF is characterized by
reduced LV ejection fraction <50%
along with progressive chamber dilation with,
increased LV volume
increased LVEDP
Osgood-Schlatter disease (OSD)
overuse injury of the secondary ossification center/apophysis of the tibial tubercle
common key pain in young adolescentatheltes after recent growth spurt
presents with pain and swelling at the tibial tubercle, the insertion point of the patellar ligament…patellar ligament conects the tibia to the patella, which in turn is connected to the quad muscles
decreased maternal serum AFP?
aneuploidies
TRISOMY 21 + others
increased maternal fetal AFP?
multiple gestations
incorrect date
anencephaly
neural tube defects (NOT spina bifina oculta)
ventral wall defects (omphalocele, gastroschisis)
Multiple gestations
Down’s syndrome screening:
in the quadruple screen,
LOW AFP and unconjugated estriol levels associated with DS
w/INCREASE h-HCG and inhibin A
chromosome 21 nondisjunction occurs during oogenesis and is significantly associated with advanced maternal age; could also result from an unbalanced Robertsonian translocation, during which the entire long arm of one chrome 21 is translocated to the long arm of an acrocentric chromosome, thus individuals have 46 chromosomes but one with a long arm.
Polycythemia vera
myeloproliferative disorder characterized by uncontrolled erythrocyte production. Virtually all patients with polycythemia vera have a mutation in JAK2, a non-receptor cytoplasmic tyrosine kinase associted with the erythropoietin receptor –> constitutivea activation of its kinase domain, resulting in clonal proliferation of myeloid cells
clinical presentation: nonspecific systemic symptoms, aquagenic pruritus, facial plethora, splenomegaly
other conditions include peptic ulcer dz (due to alt mucosal blood flow due to increased viscosity- recall that blood helps to buffer the acidity), gouty arthritis (higher red cell turnover –> inc uric acid)
labs: increased erythrocyte mass, thrombocytosis, leukocytosis and low erythropoietin levels
other erythorcyte indices are usually normal
Protease inhibitors
Name Drugs
MOA
Adverse Effects
Protease inhibitors reversibly inhibit viral protease, an enzyme responsible for HIV polyprotein cleavage to form mature viral proteins
NEVER USED as monotherapy
side effects: fat distribution!
- Lipodystrophy –> buffalo hump, with central obesity and peripheral wasting
- hyperglycemia –> increased insulin resistnace and may lead to diabetes
- inhibition of cytochrome P450 (ritonavir)
vitamin D synthesis:
On exposure from sunlight, &-dehydrocholesterol (provitamin D) in the skin absorbs uvB rays –> opens the B ring of 7-dehydrocholesterol, forming previtamin D3, which then undergoes thermal isomerization to form Vitamin D3
D3 hydroxylated in the liver to 25-hydroxyvitamin D
–> 1,25 hydroxyvitamin D
treatment for symptomatic gallstones:
- cholecystectomy
- Medical tx: hydrophilic bile acids (ursodeoxycholic acid) –> reduce biliary cholesterol secretion and increased biliary bile acid concentration –> gallstone dissoluation by improving cholesterol solubility (high rate of recurrence)
What are the two exceptions to sympathetic NS regulation?
- adrenal medulla-
stimulated by sympathetic cholinergic preganglionic neurons (ACh on a nicotinic R)
- eccrine sweat glands
pre and post innervated by cholinergic innervation
(pre = ACh on nicotinic R / post is ACh on muscarinic R)
with normal nerve stimulation, what would decreasing muscular change indicate?
–> progressive weakening during contraction
could indicate NMJ pathology (MG) and/or abnormally rapid muscle fatigue due to some restriction / fibrosis or disease
what muscle is injured in whiplash?
trapezius
serves to elevate, rotate and stabilize the scapula
innervation: CN XI
how do MHC class I molecules fxn?
antigens are presented to cytotoxic CD8+ T lymphocytes on MHC I
Structure: heavy chain and B2 microglobulin
location: all nucleated cells
fxn: present antigen to cd8+ T cells
type of antigens: viruses, tumor proteins
antigens are processed in the cytoplasm (RER and golgi app); endogenously synthesized!
Antigen is presented (first signal), activating CD8+ T cell via B7/CD28 second signal –> apoptosis of the presenting cell
how do MHC class II molecules fxn?
antigens are presented to cytotoxic CD4+ T lymphocytes on MHC II
Structure: beta and alpha polypep chains (+invariant chain)
location: APCs (b-cells, macros, dendritic, langerhans)
fxn: present antigen to cd4+ T helper cells
type of antigens: bacterial
antigens phagocytosed, digested by lysosomes within which antigen binds MHC II
Antigen is presented (first signal), activating CD4+ T cell via B7/CD28 second signal –> activated and produces cytokines
Most common site of hematogenous osteomyelitis in children vs adults?
children - metaphysis of long bones (due to slower blood flow and capillary fenestrae in the region)
adults - vertebral body
Effects of desmopressin?
AVP:
hemophilia A (increase circulating factor VIII)
type 1 Vonwillebrand (increases endothelial secretion of vWF)
Pressor – central diabetes insipidus, noctunral enuresis (bindsV2 receptors in rental tubular cells, leading to increased aquaporin channels, increased water reabsorption and decreased urine output)
which clotting factors are NOT produced in the liver?
vWF and factor VIII
produced in the endothelial cells
attributable risk percentage in the exposed=
the excess risk in the exposed population that can be attributed to the risk factor
ARPexposed = 100 x [(rel risk -1)/RR]
direct factor Xa inhibitors
Directly inhibit Xa
examples- rivaroxaba, apixaba
prolong both aPTT and PT with NO effect to TT
guillain-barre syndrome (GBS)
demyelinating syndrome of the peripheral nerves characterized by ascending muscle weakness and paralysis
Pulmonary arterial hypertension
defined as mean pulm arterial pressure > 25 mmHg at rest
follows a 2 hit hypothesis:
an abnormal BMPR2 (auto dom) gene acts as the first insult and predisposes to excessive endothelial and smooth muscle proliferation
A second insult (drugs, infections, channeld defects..) is then thought to activate the dz process: increase endothelin, decrease prostacyclin, decreased NO–> resulting in vascular remodeling, elevated pulmonary vascular resistance and progressive pulmonary hypertension
clinica pres: dyspnea, fatigue, can be heard as an accentuation of the second heart beat; eventualy leads to right ventricular failure (cor pulmonale) which can present with exertional angina, elevated JVP, hpatic congestion and peripheral edema
what reaction are the following enzymes involved in:
G6PD
gluthione reductase
pentose phosphaste pathway - fxn is to generate teh reducing agent NADPH, which is then essential to reduce oxided gluthaione, that will then convert hydrogen peroxide –> water
G6PD: NADP+ –> NADPH
Gluthione reductase: oxidized gluthione –> reduced glu
what do fibrates pre-dispose pt for?
cholesterol gallstones
Fibrate medications (fenofibrate, gemfibrozil) INHIBIT cholesterol 7alpha-hydrxylase, which catalyzes the rate limiting step in the synthesis of bile acids
Reduced bile acid production results in decreased cholesterol solubility in bile–> super saturate and favors the formation of cholesterol gall stones
also upregulate LPL, resulting in increased oxidation of fatty acids
what part of the intestinal tract is always affected with hirschsprung dz?
Hirschsprung dz is a result of abnl migration of neural crest cells druing embryogenesis.
these cells are the precurosors of ganglion cells of intestinal wall plexi
since neural crest cells migrate caudally, the RECTUM is always involved
histological finding of acute viral hepatitis:
hepatocyte necrosis (cellular swelling and cytoplasmic emptying / balloon degeneration), apoptosis with mononuclear infiltration
in severe cases, adjacent lobules are interconnected with swaths of dead hepatocytes called bridging necrosis
hepatocyte apoptosis is characterized by cellular shrinkage adn nuclear fragmentation with intense eosinophilia (councilman bodies), likely caused by mitochondiral oxidative damage
what test should be done immediately if giant/temporal cell arteritis is suspected
erythrocyte sedimentaiotn rate or C-reactive protein
- nonspecific but highly sensistive and almost always highlly elevated in GCA –> then must undergo temporal artery biopsy for definitive diagnosis
what drug could be used to treat both bipolar and seizure disorder?
Valproate - used for seizure prophylaxis and bipolar disorder
blocks voltage-gated sodium channels adn enhaces GABA synthesis and release. As an anti-convulsant, valproate effectively treats absence (2nd line), myoclonic (DOC) and generalized tonic-clonic sezures.
Wheal
single lesion of urticaria which is classically described as an erythematous papule/plaque with central pallor
a bee sting is a hypersensitivity type I
release of histamine and heparin + other vasoactive mediators occurs when tehre is IgE crosslinke and degranulation on mast cells and basophils –> increase local vascular permeability, but can also cause systemic vasodilation, bbronchoconstriction and inflammation leadsin to anaphylactic shock and potential death
(there must have been a primary exposure that allowed for class swithching to IgE, that in which subsequent exposure results in degranulation)
TNF-alpha
cytokine produced by macrophages and mast cells
functions to signalf or apoptosis of tumor cells and activation of inflammatory cells such as CD4+ T lymphocytes, neutrophils, fibroblasts, endothelial cells and hematopoietic stem cells
elevated in inflammatory conditions
can be elevated in type IV hypersensitivity rxn
What reactions within glucose metabolism and other co-factor does Thiamine (vit B1) participate in?
how could you diagnose thiamine deficiency?
- pyruvate dehydogenase cofactor, gyclolysis –> TCA
pyruvate –> acetyl-CoA
- alpha-ketoglutarate dehydrogenase, TCA
ketoglutarate –> succinyl
- branched chained alpha ketoacid dehydrogenase, essential for catabolism of brancehd chain amino acids (lecuine, isoleucine, valine)
- transketolase, enzyme of the pentose pathway pathway
ribulose 5P (from glucose) –> glycolysis intermediates
deficiency - LOW baseline erythrocyte transketolase activity but increases after the addition of thiamine pyrophosphate
*ensure to give thiamine supplemenation with glucose infusion; if not, acute cerebral damage could occur
case-fatality rate =
of fatal cases / total # of people with disease
what parameters is likely to be most similar between systemic and pulmonary circulation?
blood flow per minute
the circulatory system is a continuous circuit and therefore the volume output of the left ventticle must closely match the output of the right ventricle
This balance is necessary to maintian continuous blood flow through the body and exits both at rest and during exercise
what does tetrodotoxin block?
Tetrodotoxin is a potent neurotoxin found in pufferfish
functions by blocking the VOLTAGE GATED SODIUM CHANNELS in nerve cell membranes – inhibits passive transport of sodium
Lesions to CN III –>
recall CN III innnervates: all except superior oblique and lateral rectus
fxn: adduction, depresison, elevation and external rotation
Lesion findings: eye deviated doward and laterally, diagonal diplopia, dilation of pupil and loss of accomodation, ptosis
2nd generation sulfonylureas:
Sulfonylureas bind to their receptors on pancreatic beta cells to inhibit the ATP-dependent potassium channels –> alters cell’s resting potential, allowing calcium influx and leading to exocytosis of insulin
–> insulin secretion oby beta cells independent of blood gluc levels
thus, high risk of hypoglycemia risk..
risk increase with exercise, missed meals, chronic malnourshiment, organ dysnfuction or after a hospital admission
all 2nd gen sullfonylureas are equally as effective to lower blood glucose levels BUT they have different durations of action
Glyburdie and glimerpiride are long acting, and a higher incidence of hypoglycemia, espeically in the lederly!
vs: glipizide is short acting thus lower incidence of hypoglycemia
acarbose moa:
alpha-glucosidase inhibitor –> decrease intestinal glucose absorption and blunts the postprandial rise in serum glucose
not associted with significant hypoglycemia
sitagliptin moa
dipeptidyl peptidase 4 (DPP-4) inhibitor that decrease glucose utilization by peripheral cells and incerase beta cell insulin release
effect is glucose-dependent!!
thus effect diminishes as glucose levels approach normal –> no big risk of hypoglycemia
thiazolidinediones (pioglitaones)
Binds to PPAR-γ nuclear transcription regulator –>
increase insulin sensitivity by increasing glucose untilization and decreasing glucose production in adipose, muscle and liver.
have been associated with CARDIAC side effects (HF) but do not cause significant hypoglycemia
what are the effects of gestation diabetes mellitus:
embrypathy: congeital malformations (heart, neuro tube defects)
placental vasculopathy: asphyxia, growth restriction, polycthemia
increased fetal insulin: macrosomia, hypertrophic cardiomyopathy, hypoglycemia after birth (beta cell hyperplasia and hyperinsulinism –> increasd fat deposition and enhanced fetal growth, resulting in macrosomia; req frequent feedings or parenteral glucose to prevent hypoglycemia and subsequent neurologic injry - most of the time, the hyperplasia willl resolve over time)
Caudal Regression Syndrome
Transposition of Great Vessels
What effect do thiazide diuretics have on distal tubular calcium reabsorption?
Thiazides increase calicum reabsorption through 2 mechansims:
- inhibit the Na+/Cl- contransporter on the apical side of the distal convulouted tubel –> decrease intraceullar sodium –> activated the basolater na/ca antipoter, whcih pumps Na into the cell and Ca out –> decrease intraceullar caclium concentration, enhances teh lumina calcium reabsorption across the apical membrane
- hypovolemia induced by thiazides increases Na+ adn H2O reabsorption in the proximal tubule, leading to a passive incrase in paraceullar calcium absorption
–> thiazides can help prevent stone fromation be decreasing urine calcium excretion
indicated in pt with nephrolithiasis secondary to hypercalciuria adn contraindicated in hypercalcemia
Chronic rejection is a major problem in lung transplat recipients -
what histology is seen?
Chronic rejection of lung transplant mostly affects the small airways, causing bronchiolitis obliterans.
It is charactetrized by first a lymphocytic inflammation and destruction of the epithelium of the small airways
subsequently, fibropurulent exudate and granulation tissue are found in the lumen of the bronchioli, which ultimately results in fibrosis, scaring and the progressive oblietration of small airways
Small cell CA
aka: undifferentiated/oat cell CA
10-20% of malignant lung tumors
strong association with smoking
usually centrall located
arises from primitive cells of hte basal layer of the bronchial epithelium
ligh microscopy: round or oval cells with scant cytoplasm and large hyperchromatic nuclie; may resemble lymphocytes but typicall larger
can form sheets or cluters, abundat mitosis
could be seen to have secretory granules in cytoplasm
immunohistochem stains are frequently positive for neuroendocrine markers (chromogranin, neuron-specific enolase, synaptophysin)
histological features of HCM:
massive myoctye hypertrophy predominately affecting the septal region
myofiber dissary (irregular arrangement of abnormally shaped myocytes with bizarre nuclei and areas of increased connective tissue)
primary cartinite deficiency vs medium chain acyl CoA dehydronase (MCAD) deficiency
Primary: muscle weakness, cardiomyopathy, hypoketotic hypoglycemia, elevated muscle triglycerides
MCAD deficieny: hypoglycemia, hypoketotic hypoglycemia
deficient synthesis of ketone bodies (acetoacetate) in the liver, decrease ATP generation from FA in cardiac and skeletal myocytes
In a pt with breast cancer, what causes skin retraction? what can cause lymphedema with finey pitted apperance ie- peau d’orange?
Overlying skin retractions such as dimiling slignal invovlement of suspensory ligaments of teh breast (cooper ligament) –> causing fibrosis and shortening, leading to traction on teh skin with distortion in breast contour
most commonly with invasive breast carcinoma presenting with an irregularly shaped adherent breast mass
apendicitis pain:
causes dull visceral pain at the umbilicus due to afferent pain fibers entering at the T10 level in the spinal cord. Progressive inflammation in teh appendix irritated the pareital peritoneum and abdominal wall to cause more severe somatic pain shifting from teh umbilicus to McBurney point.
– rebound tenderness is a “peritoneal sign”
Explain the key defense mechanism of projection
vs displacement
isattributing one’s own uncoscious, undesired thoughts or feelings to another person who does not actuall have them
“a son is upset his parents are getting a divorce but he believes they are upset with him
Projection is an immature defense mxn involving the malattribution of one’s unacceptable feelings or thoughts to anothe rperson who does not actually have them
vs displacemet = redirecting unacceptable thoughts, feelings and impulses inteded for one person to a more neutral person (if the son was mad at his sibling)
what drugs have a high hepatic clearance tendency?
high lipophilicty
high volume of distribution
high CNS penetration
recombination
vs
reassortment?
Reassortment only occurs in segmented viruses! Capable of genetic shifts via this mechanism
it involved teh exchange of entire genomic segments –>epidemics or pandemics; more dramatic process than the point mutations responsible for genetic drift
ReCombination undergo Crosing over
all viruses
what are the segmented viruses? 4
orthomyxovirus
reoviruses
bunyaviruses
arenavirues
Medulloblastoma
second most common brain neoplasm in children
located in the cerebellum, often times in the vermis and consist of small, blue cells
like other PNET (primitive neuroectodermal tumors- sheets of small cells with deeply basophilic nuclie and scant cytoplams, abundant mitoses) tumors medulloblastomas are poorly differentiated and have a bad prognosis
**sheest of primitive cells with many mitotic figures**
undifferentiated and aggressive tumors
clinical pres: gait instability, limb ataxia - symptoms of cellular involvement, increased intracranial pressure (morning headaches, vomiting lethary)
What antibiotic can percipitate serotonin syndrome?
Linezolid (used to tx infections caused by gram-positive bacteria, particularly vancomycin-resistant enterococcus and methicillin-resistant S. Aureus) has MAOI activity thus can precipitate serotonin syndrome when used cocomitantly with an SSRI
Serotonin syndrome is characterized by a triad of autonomic instability, alt metal status, neuromuscular irritability
MAOI or non-antidip with MAOi activity (linezolid), with serotonergic med: SSRI, serotonin-NE reputake inhibitor or TCA
what is photoaging due to?
excessive exposure to UVA wavelenths and is characterized by epidermal atropy with flattening of rete ridges
additionally, there is decreased collagen fibril production and
upregulation of matrix metalloproteinases (including collagenases) –> increased degradation of collagen and elastin in the dermis
atrophic dermis and increased collagen crosslinking, along with desiccation of the stratum corneum, produce the characteristic wrinkling of photoaged skin
What artery provides the primary blood supply to the ACL?
middle geniculate artery
injuries are characterized by rapid-onset hemarthrosis and knee swelling
what is the characteristic genotype of a complete mole?
gestational trophoblastic disease
A complete mole usually results when an empty ovum (no x, no y) is fertilized by a haploid sperm –> then there is duplication of the paternal genetic complement resulting in characteristic 46,xx genotype (YY has not been observed; and less commonly 2 sperm can fertilize an empty ovum to create a 46, XY)
- no fetal structures
- composed of large, edematous, disorderd chrionic villi that appear grossly as clusters of vesicular structures “bunch of grapes”
- high b-hCG, due to trophoblastic hyperplasia
- ultrasound demonstartes a central heterogenous mass with multiple cystic areas and is classically described as a “swiss cheese” or “snowstorm” pattern
rf: gestational age, prior molar pregnancy, prior miscarriage or infertility
IL2 fxn
produced by helper T cells adn stimulates growth of CD4+ and CD8+ T cells and B cells.
activates NK cells and monocytes
increased activity of T cells adn natural killer cells is thought ot be responsible for IL2’s anticancer effect on metastatic melanoma and renal cell CA.
why are pt with high-oxygen affinity hemogloblins typically asymptomatic?
high-O2 affinity hemoglobin mutations reduce the ability for hemoglobin to release oxygen in the tissues –> low perfusion of the kidney, stimulate to increase erythropoietin synthesis, which results in a compensatory erythrocytosis that helps maintain oxygen delivery
What is ebstein’s anomaly
what drug causes this?
what is the indication of this drug?
Ebstein anomaly is characterized by apical displacemet of hte tricupsid valve leafets, decreased volume of the right ventricle and atrilization of the right ventricle
caused by gestation use of lithium
lithium is used to treat bipolar disoder, acute mania, hypomania, bipolar and unipolar depression
what is a significant adverse effect of ganciclovir therapy?
neutropenia
incidence increased when co-administered with zidovudine or trimethoprim-sulfamethoxazole
how does CO affecting oxygen binding?
competitively bind iron present in heme protiens, with a higher affinity than oxygen –> carboxyhemoglobin
any remaining site opened for oxygen to bind will have increased oxygen affinity –> leftward shift of oxygen dissociation curve, impeding oxygen delivery to tissues.
CO can also bind cardiac myoglobin –> imparied use of oxygen and decrease cardiac output
CO binds cytochrome oxidase, inhibiting aerobic metaboilsm adn exacerbating tissue hypoxia
tx: high-flow or hyperbaric oxygen therapy
what are the side effects that diphenhydramine?
First-generation antihistamine are signed to relieve allergic symptoms BUT have can have prominent side effects due to blockade of other receptors, includign alpha-adrenergic, serotonergic and cholinergic receptors
anticholinergic effects on the ocular ciliary muscle impair accomodation and cause blurring of visison for close objects
How does accomodation occur in the eye?
ciliary muscle attaches to the lens via the zonular fibers
contraction of the muscle reduces tension of the fibers –> allowing the lens to becoe more spherical and increase its refractive power
ciliary muscle is under teh parasympathetic control from teh Ediner-Westphal nucleus/ciliary ganglion
light comes in, synapses on the pretectal nucleulus –> synapses on each of the edinger-westphal nucleus –> ciliary ganglion to synpase on ciliary muscle
inhibting the parasympathetic agents limit accomodation adn cause blurring of vision for close objects
(pupillary sphinceter also receives parasympathetic innervation from teh edinger-westphal nuclues – pt on antimuscarinic agents may have mydriasis/pupillary dilation as well
pudenal nerve injury
pudenal nerve provides motor and sensory innervation to the perinal region
it originates from ventral rami S2-S4 and passes between the piriformis and coccygeus muscles as it exits the pelivs through the greate sciatic foramen, then reenters the pelvis near teh ischial spin through the lesser sciatic foramen prior to dividing into its termianl branches
sensory branches innervate the external genitalia as well as teh skin around the anus and perinuem
motor branches innervate the peliv floor muscles as wellas teh external urethral and anal sphinceters
**vulnerable to stretch injury, due to its curved course around the ischial spine**
sx: fecal and urinary incontinence, perineal pain and sexual dysfunction
of the major vascular beds, which are most susceptible to atherosclerosis?
Lower abdominal arteries followed by the coronary arteries, popliteal arteires, internal cartoid arteires adn the circle of willis
what could happen to pt who receive more than one body blood volume (5-6 L) of whole blood transfusions or packed RBC overa a 24 hour period??
may develop elevated plasma levels of citrate (a substance added to store blood)…citrate chelated calicum and mangesium, and may reduce their plasma levels –> paresthesias
acute rhematic fever
due to molecular mimicry: anti-group A strep antibodies attach host antigens on cardiac and neuronal tissue approx 2-4 weeks acter acute pharyngitis
clinical featuers: JONES critera
Joints - migratory arthritis
O - pancarditis, mitral regurg
N -nodules
E- erythemam margiatum
S -sydenham chorea
anti-group A strep antibodies (anti-M protein, anti-N-acetyl-beta-D-glucosamine) cross react and attack cardiac and CNS antigens
prevent with promt treatment of strep pharyngitis w/penicillin
what are undesirable effects of volatile anesthetics?
almost all increase cerebral blood flow –> could result in increased ICP
other impt effects of inhalation anesthetics are myocardia depression, hypotension, respiratory depression and decreased renal function
confounding bias
vs effect modification
confounding = exposure-disease relationship is muddied by the effect of an extraneous factor that has correlations with boht the exposure and the disease; it can result in the false association of an exposure with a disease
- confounding effects can be negated by running separeate analyses for the smokers and non-smokers - both have an RR close to 1; larege pvalues suggest small difference in RR from the null value is due to chance alone –therefore the RR disappears an dno true association (stratified analysis)*
- ie) increased alcohol use is associated with increased smoking, and perhaps not alcohol alone leads to increase in bladder cancer in people who use alcohol*
Effect modification results when an external variable positively or negatively impacts the observed effect of a risk factor on disease status – stratified analysis will reveal a significant difference in risk between the stratified groups p-values >0.05
ie) smoking would modify the effect of alcohol consumption on bladder cancer
Lung abscess
risk factors
moa
sx
Lung absences usually have a presentaiton of indolent symptoms, fever, night sweats, wt loss and a cough productive of foul-smelling sputum (indiciative of anaerobes); usually there is a vacitary lesion with identifiable air-fluid level on imaging
RF: anything that increases aspiration risk - alcoholism, drug abuse, seizure disorder, stroke, dementia, prolong anesthesia, severe neurologic diseases
MOA:
1) oropharyngeal aspirations most common cause
- watch for mixed aerobic and anaerobicm oral flora in the absecess (peptostreptococcus, prevotella, bacteroides, fusobacterium sp) anything that is associated with increased aspiration puts ppl at riks, loss of consciouness or dysphagia
2) lung abscess may occur as a complication of bacterial pneumo. predisposing facotrs - immunocompromised, old age, nderlying chornic lung disease; necrotizing pneumonias are usually nosocomial and caused by A. aureus, E.coli, Klebsiella, pneumo and pseduo
3) in with septicemia or infectious endocarditis,
histo of takayasu and temporal arteritis?
temporal - granulomatous inflammation of the media
both invovle arterial vessesl of different sizess and locations (aorta and proximal aortic arterial branch invovlement vs more distal carotid artery branch invovlement, respectively) and have diff clinical presentaitons
they both have common pathologic morphology: granulomatous inflammation of the media
caudal repgression syndrome
agenesis of the sacrum and occasionally lumbar spine and experience resultant flaccid paralysis of hte legs, dorseflexed contractures of the feet and urinary incontinence
can range from isolated anal atresia –> sirenomelia
rare 1:60,000 births
related to poorly controlled maternal diabetes
what effect could overdose of vitamin A have on a developing fetus?
can cause craniafacial abnormalities, psoterior fossa CNS defects, auditory defects and abnormalities of the great vessels
(similar to those in DiGeorge Syndrome)
What are signs of NE extravation?
what therapy should be started?
blanching of a vein into which NE is being infused together with induration and pallor of the tissues surrounding the IV site are signs of NE extravation
NE leak causes intense alpha 1 receptor mediated vasoconstriction, which can lead to local tissue necrosis
Necrosis can be prevted by infiltration throughout the affected area with 10-15 cc of sodium chloride solution containing 5-10 mg of phentolamine mesylate, an alpha receptor blocker –? must be given within 12 hours of extravation to be effective
**phentolamine / other alpha receptor blockers lead to vasodilation, countering the alpha1 receptor mediated vasoconstriction of NE
*beta receptor activation will not be effective because these receptors are not found in subcutaneous tissue blood vessles as compared to alpha 1 receptors; beta are more likely found in striated muscle, renal and mesenteric vascular beds
bohr and haldane shifts:
In the lungs = haldane effect
oxygenation of Hb promoates teh dissociation of H+ from Hb; this shifts teh equilibrium towards the formation of CO2 –> CO2 is released from RBC at the lung (chloride shift IN!)
In the periphery = bohr effect
increased hydrogen from the tissue metaolism shfits curve to the right, unloading O2
drug interactions of lithium?
thiazide diuretics
NSAIDS (except aspirin)
ACE inhibitors
toxicity:
ACUTE - GI, late neurologic sequela
CHRONIC - confusiong, agitation, ataxia, tremors/fasiculations
explain noise-induced hearing loss
results from trauma to teh sterociliated hair cells of the organ of corti.
acoustic refelx normally dampens the effects of loud noise by causing the stapedius and tensor tympani muscles to contract, which lessens the responsiveness of hte ossicles to sound. HOwever, prolong noise exposure can cause distortion or fracture of the sterocilia due to shearing forces against the tectorial membrane. High frequency hearing is lost first, reglardss of the freq of teh sound causing the damage
[hearing loss due to the auditory nerve is most commonly due to an vestibular schwannoma; pt develop high freq sensorineural hearing loss, but symptoms are usually unilateral]
Langerhan cells:
dendritic cells found in the skin that act as professional antigen presenting cells
they are derived from the myeloid cell line and they possess characteristic racquet-shaped intracytoplasmic granules known as Birbeck granules
Difference between oppositional defiant disorder and conduct disorder:
COnduct disorder, the problem behaviors are more severe and agressive.
In conduct disorder, often there is physical aggression or cruelty towards people or animals, destruction of property or the typical pattern of stealing or deceit seen in conduct disorder. Think of violations of the basic rights of other sseen in conduct disorder
ODD, may precede the development of conduct disorder and increases the risk of adult antisocial behavior, impulse-control problems, substance abuse, anxiety and depression. pattern of angry/irritable mood, argumentative anddefiant behavior for more than 6 months
oppositional behaviors must be excessive compared to normative age-apprpriate behaviors and observed during interactions with individuals other than siblings
DDX: HIV pt with multiple ring-enhancing lesions:
- Toxo
give pyrimethamine and sulfadiazine (+leucovorin/folinic acid) or use clindamycin if sulfa drug hypersensitivity
- Primary central nervous system lymphoma
diffuse, large-cell non-hodgkin lymphoma of B-cell origin that usually cocurs as a late complication of HIV infeciton; EBV is identified in almost all cases
+ EBV polymerase PCR in CSF is diagnosis
why is hypernatremia and pedal edema hardly seen in primary hyperaldosternism?
Hypernatremia and pedal edem are rarely observed in PH due to the phenomenon of aldosterone escape
The high aldosterone levels lead to increased intravascular volume and therefore cause increased renal blood flow with resulting pressure natriuresis and augmented release of ANP –> results in increased sodium excretion by the renal tubules, which limits net sodium retention and prevents the development of overt volume overload and significant hypernatremia.
what is the most sensitive marker for diagnosis of hypothyroidism?
serum TSH (often times will rise before low thyroid hormone level is seen)
important exception - TSH will not be elevated in pt with secondary or tertiary (central) hypothyroidism. Central hypothyroidism is uncommoon an dpt usually have other clinical features that suggest hypothalamic or pituitary dysfunction
symptoms of hypothyroidism: fatigue, bradycardia, wt gain, constipiation, slowed relaxation of deep tendon reflexes
Dapsone side effects:
fever, rash, methemoglobinemai
dapsone also can put oxidative stress on the body ,so G6PD levels should be checked before administrating dapsone in order to prevent hemolytic anemai in pt with this enzyme deficiency
common factors precipitating factors of G6PD deficiency anemia
- infections
- drugs - dapsone, antimalarials, TMP-SMX
- diabetic ketoacidosis
- favos, (ingestion of fava beans)
note: anemail, reticulocytosis, jaundice and dark urine can occur; red cell fragments, microps
Corticosteriods could –> osteoporosis. What are the blood levels seen?
Osteoporisis is characterized by decrease bone strengt from low bone mass and microarchitectural deterioration of bone tissue but normal bone mineraliztion. Increased susceptibility to fragility fractures (minimal to no trauma).
in primary osteoporosis (not caused by a medical disorder), serum calcium, phosphorus and parathyroid hormones levels are NORMAL!
what are renal angiomyolipoma?
beign tumor composed of blood vessels, smooth muscle adn fat
bilateral renal angiomyolipomas are assocaited with tuberous sclerosis (autosomal dominant)
MOA of thionamides?
Methimazole and propylthiouracil
DEC teh formation of thyroid hormones via inhibition of thyroid peroxidase, the enzyme responsible for both iodine organification and coupling of iodotyrosine
PTU also decreases the peripheral conversion of T4 – T3
DNA pol I and DNA pol III activity
DNA pol I:
- proofreading: 3’-5’ exonuclease activity
- DNA repair: 5’-3’ polymerase activity
- RNA primase removal: 5’-3’ exonuclease activity
DNA pol II:
- DNA repair: 5’-3’ polymerase activity
DNA pol III:
- DNA synthesis: 5’-3’ polymerase activity
- proofreading: 3’-5’ exonuclease activity ONLY
What are the different forms of inheritence observed in Down Syndrome?
Meiotic nondisjunction (95%) - extra copy of chrome 21 present in every cell; based on maternal age
Unbalanced translocation/robertsonian - all or part of additional chrome 21 attached to another chrome; high if balanced translation is presnet in one parent
Mosaicism - some (not all) cells have an extra copy of chrome 21; nondisjuntion event in early embryonic life; based on maternal age
what is uniparental disomy?
when a person receives 2 copies of a chromosome from teh same parent and no copy from the other parent
side effects of Amphotericin B:
most toxic antifungal med
most dangerous toxicity is nephrotoxicity – due to both a decrease in glomerular filtration rate adn direct toxic effects on the tubular eipthelium
–> anemia (dec erythropoietin production), electrolyte abormalities such as hypokalemia, and less often hypomagnesmi due to an increase in the membrane permeability of the distal tubule
hypokalemia –> weakness and arrhytmias
ECG findings in hypokalemia include T wave FLATTENING, ST seg depresison prominent U waves, premature atrial and ventricular contractions.
Profound hypokalemia can cause ventricular tachycardia or fibrillation
what are the two types of gastric adenocarcinomas?
Intestinal type: forms solid mass that projects into the stomach, composed of glandular forming cubodial or columnar cells
Diffuse carcinoma - linitis plastica, infiltrates teh stomach wall and displays signet ring cells on light microscopy
How can bacteria form resistance against aminoglycocsides
-micin’s are the amingoglycoside drugs
bacteria could form resistance by aminoglycoside-modifying enzymes that transfer different chemical groups (acetyl groups, adenyl groups, phosphate groups) to AGs molecule outside the bacterium, decreasing the ability of the AG to bind to ribosomes and exert its antimicrobial effects
- it is acquired resistance mediated by plasmids or transposons NOT chromosomally mediated
What is an ecological study?
Unit of analysis is POPULATIONS not individuals
the frequency of a given characteristic and a given outcome are studied using population data!
useful to generate hypotheses but should not be used to make conclusions regading indivudals within these populations (ecological fallacy)
what is a nested case-control study design?
Start with cohort studies in which participants are followed over time, and those participates who develop an outcome of interest become cases for a case-control study
hypercalcemia of malignancy
caused by secretion of parathyroid hormone-related protein (PTHrP), closely resembles PTH at the bioactive amino-terminal region. PTHrP causes increased bone resorption and decreased renal excretion of calcium
- no focal bone lesions
- very servere, serum calicum levels are usually higher than in primary hyperparathyroidism alone
- complications: polyuria, nephorlithiasis, GI and neuropsychiatric symptoms
80% of malignancy-induced hypercalcemia
tumors: squamous cell cancers ( lung, head, neck, esophagus)
renal and bladder
ovarian and endometrial
breast CA
[can also occur in CA pt due to ostelytic bone mets, excess prod of 1,25-hydroxvit D or rarely ectopic PTH secretion]
what are the test used for cryptococcus neoformans
latex agglutination test detects polysach capsule antige of Crypto, used for diagnosis
India ink staining of CSF shows round or oval budding yeast
culture (sabouraud’s agar)
Methenamine (GMS), mucicarmine stains of tissue
tx: amophtericin B + flucytosine (acute meningitis)
Fluconazole for lifelong prophylaxis
** C. neoformans casues meningoencephalitis in HIV+
Biotin
Vitamin B7
essential for carboxylase enzymes
CO2 carrier
impt role in carboyhydrate, lipid and AA metabolism
deficiency sx: nonspecific, changes in mental status, myalgias, anorexia, chronic dermatologic changes such as macular dermatitis; can also develop metabolic acidosis as a result of increased conversion of pyruvate to lactic acid
associated with excess ingestion of avidin, found in egg whites
DDX for fluid-filled cavity in the liver
fluid filled cavity in the liver + fevers, chills, right upper abdominal paint –> heaptic abscess
In UNDERdeveloped countries – relatively high incidence, primarily caused by parasitic infections (Entamoeba histolytica - scending from teh colon through the portal venous systmem since its a foodborne parasite, echinococcal)
In DEVELOPED countires, hepatic absceens are uncommong, caused by bacterial infection (S. aureus via hematogenous spread, gram negative bacilli from enteric route/ascending cholangitis, mixed aerobic and anaerobic flora from penetrating trauma)
tx for insomnia in the elderly
AVOID when possible benzodiazepines, antihistamines and sedating antidepressants for the use of insomnia in the elderly due to their adverse effects.
For initial mgmt: non-pharacologic intervents - sleep hygiene, CBT
Pharmacologic can be considered shorte term - Ramelteon (melatonin agonist, bind to melatonin R in the suprachiasmatic nucleus - sale for older adults!)
What is the purpose of the invariant chain on MHC II?
peptide framgent that is bound the the MHC II antigen binding site
acts to guide the molecuing during sortin gin the golig and occupies the site until teh molecule enters an acidified endosome where it can bind foreing porinte. FUsion of the vesicle contianing MHC Class II to the acidified phagolysosomes contianign foreign antigen molecule leads to the degradation of the invariant chain and loading of antigen onto the MHC class II
[withouth lysosomal acidification, antigen processing in associated MHC class II antigens won’t occur, and the MHC class II would be unable to bind antigen and thus bind TCR for activaiton]
neural tube defects:
Lab findings!
occurs when the neural tube fials to fuse in the region of the anterior or posterior neuropores @4th week
This leads to a persistent communication betwen the spinal canal and amniotic cavity
leakage of alpha-fetoprotien and acetylcholinesterase occurs, which allows for prenatal diagnosis of NTDs
HIGH AFP and Acetylchonlinesterase appear in amniotic fluid adn also elevated in maternal serum
both used for prenatal diangosis of NTDS
Decreased AFP
Down’s syndrome and other chromosomal abnormalities
down = afp is down
in vitamin D deficient states due to malabsorption, what are the serum values of calcium, phosphorous, PTH
decreased calcium
increased serum PTH (secondary hyperparathyroidism)
decreased phosphorous (dec absorption @ GI and increased secretion @ kidney due to PTH)
sx: bone pain, muscle weakness
GFR and FF changes with vasoconstriction of efferent arteriole in the kidney
vasoconstriction of efferent arteriole (up to an exent) –> increased hydrostatic pressure in the gomerula capillaries –> INC GFR
FF always increases with increasing efferent arteriole constriction!
efferent arteriolar constriction also reduces renal plasma flow RPF
FF = GFR / RPF
** note when RPF is so low, that is secondary to SEVERE efferent arteriolar constriction, the flow becomes so slow that there is an increase in capillary hydrostatic pressure and capillary oncotic pressure begins to oppse –> substantially increased capillary oncotic pressure results in an overall decrease in GFR
metabolism of 1 go of the following yields how many Calories?
protein
carbohydrates
fat
protein: 1 g –> 4 calories of energy
carbohydrates: 1 g –> 4 calories of energy
fat: 1 g –> 9 calories of energy
What are beta-endorphins and how are they derived?
Enkephalins, endorphins, dynsorphins are endogenous opioid peptides part of our body’s natural sysmte, released in response to noxious stimuli and bind to different opiod receptors to allow physiologic modulation of pain
Different types… beta-endorphis is one that is dervied from proopiomelanocortin (POMC)
recall that this is a polypeptide repcursor that goes through enzymatic cleavage and modification to produce not only beta-endorphins but also ACTH and MSH
there may be a close physiological relationship between teh stress axis and opioid system
Rabies encephalitis clinical presentation:
agitation, disorientaiton, pharyngospasm and photobonia –> coma, death
w/ nonspecific, flu-like prodrome, followed by an acute neurologic syndrome taht includes agitation, persistent fever, variable consciousness, photophobia, and painful spasms with swallowing and/or inspiration
pharyngeal muscle spasms –> dysphagia
dysphagia + hypersalivation due to autonomic dysfunction “mouth foaming”
generalized FLACID paralysis and coma follow the acute neurologic phase, with most pt dying within 2 weeks of becoming comatose
rabies are SS RNA virsues envelped by a bullet shaped capuse- which is studded by glycoprotein spikes that bind to nicotinic acetylcholine receptors.
bding to acetylcholine R on peripheral NS axons and travel retrograde to the central CNS
**once the sxs of rabies encephilits appear, post-exposure prophylais is no longer effective**
mitochondrial disease shows what type of clinical presentation?
whta are impt mitochondrial syndromes?
Heteroplasmy - variable degrees of severity dependent on the variablity of the distributio ofmitochondrail between the daughter cells; exclusively inherited from one’s mother
Mitochondrial syndromes:
- leber hereditary optic neuropathy –> bilateral vision loss
- Myoclonic epilepsy with ragged-red fibers –> myoclonic seizures and myopathy associated with exercise; skeletal bipsy shows irregular shaped muscle fibers / ragged red fibers
- mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS): sezisure disorder with stroke like episdoes + neurological deficits; muscle weakness, inc lactate levels at rest and post-exercise
what leads to gestational diabetes?
human placental lactogen (hPL) decreases maternal fatty acid stores and increases maternal serum glucose in order to provide adequate glucose to the growing fetus. The actions of hPL result in physiologic insulin resistance in the latter half of pregnancy
- usually seen second and third trimesters due to shunting of carbohydrate metabolism toward supplying glucose and amino acids to fetus
- insulin resistance isn primarily due to action of hPL aka chorionic somatomammoropin, a peptide hormone secreted by the syncytiotrophoblast
insulin resistance leads to increased gluocse levels in maternal circulation - glucose can freely cross into fetus and is continuously consumed for fetal energy
maternal lipolysis and protelysis are also increasd by hPL
hPL also stimualtes pancreatic beta cell insulin porduction
–> gestational diabtes mellitus results when the pancreatic funciton is not sufficient to overcome the pregnancy-related icnrease in insulin resistance
**gestational diabetes is more accurate third trimseter doen via orgal glucose
what path does the ureters travel in relation with the gonadal arteries and veins?
The ureters pass posterior to the gonadal vessles within the retroperitoneum (water under the bridge) and anterior to the common/external iliac arteries to reach the true pelvis–
within the true pelvins, the ureters lie antoerior to the internal ilial artery and medial to the gonadal vessels.
The uterine artery crosses over teh anterior surface of the ureter (water under teh bridge)
how does glucose stimualte teh release of insulin from beta cells?
glucose enters beta cells by facilitated diffusion via glucose transport 2 - (glucose + glucokinase –> G-6-P) undergoes oxidative phosphorylation –> increases ATP
ATP –> binds to ATP-sensitive K+channel (K+ in normalluy exiting the cell) –> CLOSES CHANNEL –> decreaes K+ efflux => membrane depolarization –> opening of VG-calcium channels –> increased calcium –> exocytosis of insulin
vitamin B6 / pyridozine is a co-factor for what part of the synthesis of heme?
Vitamin B6 —> active form pyridoxal 5’ phosphate via pyridozine phosphokinase –> pyridoxal 5’ phosphase is a co-factor for gamma-aminolevulinic acid (ALA) synthase, which is the first enzyme that catalyzes the rate limiting step in heme synthesis
**isoniazid is a direct inhibitor of the activation of vitamin B6
–>sideroblastic anemia
microcytic hypocrhomic anemia
iron is transported to developing erythrocytes that are developing but cannot form heme, thus iron accumulates around the nuclues –> ring siderblasts
pyridoxal 5’ phosphate is a co-factor for numerous enzymes thus it can also lead to: dermatitis, stomatitis, neuropathy, confusion
schizoid vs schizotypal?
schizoid = longer, detached, unemotional
schizotypal - eccentric, odd thoughts, perceptions and beavhior; magical thinking, superstitiouness and odd perceptual disturbances that are sub-threshold for a psychotic disorder; do not experience the persistent, fized delusions or frank hallucinations seen in schizophrenia. rarely sustain close interpersonal relatioships due to excessive social anxiety that does not diminish with familiarity
DOC for trigeminal neuralgia:
first line: carbamazepine
others: baclofen, valproic acid - not first line!
what is the reason Hep C has so many genotypes and subtypes and why its genomic composition could vary as much 30-35%??
Due to the fact that the virion-encoded RNA-dependent RNA polymerase has
NO proofreading 3’ –> 5’ exonuclease acivity –> many errors during replication
variant strains differ primarily at hypervaribale genomic regions, such as those encoding glycoproteins;
Prevents host antibodies from mounting an effective immune response
Motion sickness drugs1
Best are antimuscarinic agents and antihistamine with antimuscarinic action
perception of motion and orientation is determined by input from the vestibular, visual and somatosensory systems – conflicting info from teh 3 cause –> motion sickness
integration of tehse sensory pathway occurs in the vestibular nuclei via muscarinic M1 and histaminic H1 neurotransmission
side effects: blurry vision, dry mouth, urinary retention and constipation
Given a positive test result, what is the probablility that a patient has a disease?!
= find positive predictive value
*PPV varies with disease prevalance (unlike specificity and sensitivity)
venous drainage of the gonadal veins?
RIght drains directly to the IVC
Left drains first to the left renal vein then the left real vein IVC
Kaposi’s Sarcoma
where does the tumor derived from?
what virus is it associated with?
Kaposi sarcoma typically presents as blue-violet or brownish skin plaques on the extremities and mucous membranes of HIV-positive patients. This tumor arises from primitive mesenchyma cells and is strong associated with HHV8
There’s a nuclea accident/war….
readioactive material such as iodine-131 can be released into the environment following nuclear reactor accidents, breach of contaimnet waste disposal or atomic bomb blasts…
non reactive radioactive iodine is preferentaily taken up and concentrated within the thyorid gland – an lead to hypothyroidism and thyroid carcinoma
give POTASSIUM IODINE prophylactically to protect the thyroid from excessive accumulation of radioactive 131I
competitively inhibits thyroid uptake of radioactive iodine isotopes and is often administered following nuclear accidents to protect the thyroid and prevent development of radiation-induced thyroid CA (prevents from entering thyroid follice cells - large increases in serum iodine levels also inhbit iodine organification Wlff-chaikoff effect and reduce thyorid hormone releease
How can you gague the severity of mitral stenosis?
The best and most reliable auscultatory indicator of the degree of mitral stenosis is the A2-opening snap interval (becomes shorter because atrial pressures increase with severity; measurement of transvalvular pressure gradients via 2D doppler echocardiograph is a means to diagnose MS severity)
shorter intervals = more severe stenosis
other auscultatory findings can include diastolic rumbling murmur with presystolic accentuation due to left-atrial contraction
CMV histology would show..
enlarged cells with basophilic or eosinophilic INTRANUCLEAR inclusion bodies
sx: odynophagia (pain with swallowing) or dysphagia (difficulty swallowing) and can be accompanied by fever or buring chest pain if CMV esophagiits [think of immunocompromised pt]
What paraneoplastic syndromes are assocaited with subacute cerebellar degeneration?
small cell lung CA,
breast, ovarian and uterine CA
Etiology: Anti-Yo, anti-P/Q, anti-Hu antibodies
sx: progressively worsening dizziness, limb and trucal ataxia, dysarthria and visual disturbances + cerebellar symptoms
due to an immune response agasint tumor cells that cross-reacts with purkinje neuron antigens –> acute-onset rapid degeneration of teh cerebellum
paraneoplastic cerebellar degeneration is diagnosed clinically after exclusing other conditison since antibodies are not always detectable
Neonatal vitamin K deficiency
presentation: intracranial, GI, cutaneous, umbilica and surgical site BLEEDING
etiology: LOW vitamin K stores at birth (poor placental transfer, sterile guyt, low content in breast milk), neonatal liver cannot use vitamin K efficienty
(usually vitamin K is given at birth because of those reasons! but parents could refuse and could lead to this!)
vitamin K importance in clotting:
essential co-factor for gamma-glutamyl carboxylase, enzy responsible for conversion of glutamyl residues for gamma-carboxyglutamates. Carboxylation is critical for the function of clotting factors II (prothrombin), VII, IX, X as it allows for the creation of calcium-binding sites. THe calicum binding sites attract the clotting factors to negatively charged phospholipds on platelets and endothelial cells, encouraging coagulation and thrombin formation
What drugs are indicated in pt with both hypertension and diabetes?
ACE inhibitors then ARBS
reduce the risk of CKD
ACE inhibitrs additionall raise levels of bradykinin (by blocking ACE, which normally degrades bradykinin), thus inhibition leads to increased levels of bradykinin and substance P –> nonproductive cough (not seen in ARBs)
live attenuated vs killed vacciens?
live attenuated vaccines generally produce stronger immune response than killed by acting as a persistent stimulus that better activates helper and cytotoxic T cells
THsu live attenualted orgal vacciens generate a much more robus oropharyngeal and interstial mucosal IgA response thatn intramusucalr inactivates vaccines
[oral sabin vs inactivates Salk]
How is secretory IgA in the GI mucosa sitmulated?
SECRETORY IgA is the major ab associated with mucosal immunity
upon exposure to antigen, B cells fond in Peyer’s patches and mesenteric lymph nodes become activated and preferentially migrate to the lamina propria underlying the interstinal mucosa –> become fully differentiated plasma cells that begin to synthesize IgA dimers (linked by J chain)…IgA dimers then bind the polymeric immunoglobulin receptor (plgR) found on teh basolateral
Narcolepsy tx:
Modafinil
non-amphetamine stimulant
MOA is is not well described but it is thought to enhance dopaminergic signaling
Amphetamines are second line agents due to their sympathomimetic side effects (HTN, arrhythmia, psychosis) and risk for dependence
Tumor Lysis Syndrome
Where can kindey stones occur?
Prophylaxis?
TLS developes due to rapid cell turnover and high sensitivity to chemotherapy. When a large amount of cells are destroyed –> ions, such as potassium, phosphorous, uric acid (a metabolite of tumor nucleic acids) are released into the serum and are then filtered by the kindey…
Uric acid is soluble at physiologic pH but precipitates in acidic environment –> lowest pH in the nephron is at the distal tubules and collecting ducts thus tehse are the segments of the nephron that can become obstructed by ric acid crystals
–> obstructive uropathy and actue renal failure
Prophylaxis: urine alkalinization and hydration
allopurinol can be used to reduce uric acid production during breakdown of tumor cells
Medullary thyroid CA
tumors of PARAFOLLICULAR CALCITONIN-secreting C-CELLs
spindle shaped cells in an amorphous background
80% sporadic, 20% familial (MEN 2 syndrome)
germline RET proto-oncogenes codes for a membrane-bound tyrosine kinase receptor involved in cell cycle regulation
KRAS gene activations…
Activating mutations at the KRAS gene lead to constitutive activation of the epidermal growth factor receptor (EGFR) pathways, promoting increased cell proliferation adn growth
tumors harboring these mutations are resistant to chemotherapy with anti-EGFR drugs (cetuximab, panitumumab)
bisphosphonate MOA:
inhibiting MATURE osteoclast-mediated bone resportion
chemical structure similar to pyrophosphate and attach to hyroxyapatite binding sites on bony surfaces - thus osteoclast that resorb the bone take up the bisphosphonate and are unable toa dhere to more bony surfaces to continue resorption
- decrease osteoclast activity
- induce osteoclast apoptosis
- decrease teh development/recruitment of osteoclast precursor cells
slow bone loss and some pt may experience small increase in bone mineral density
symptoms of myasthenia gravis vs lambert-eaton myasthenic syndrome
MG - fluctuating weakness that WORSENS over the course of the day and most often involved the extraocular and bulbar (chewing, dysphagia) muscles –> decreasing force of muscle contraction with repetitive stimulation
[most pt have thymic abnormalities which may appear as an anterior mediastinal mass on chest imaging]
Lambert-eaton: presents with proximal extremity weakness that IMPROVES with USE
[small cell lung CA due to antibodies direct agasint presynaptic calcium channel, which causes reduced acetylcholine release]
silicosis:
a type of pneumoconioses, mostly asymptomatic but can present with dyspnea on exertion and productive cough 10-20 years after initial exposure
Distinguished by calcification on the rim of hilar nodes (eggshell calcificaiton) and birefringent silica particles surrounded by fibrous tissue on histology
transposition of the great arteries etiology
LINEAR RATHER THAN SPIRAL development during septation of the truncus arteriosus of the aorticopulmonary septum in utero, resulting in an anteriorly positioned aorta connected to the right ventricle and a posteriorly positioned pulomnary artery connected to the left ventricle
–> pulmonary and systemic circulations are abnormally separated and exist as 2 paralel circulations
incompatible with life unless other connection ie)PDA
platelet plug problem
what are the lab values
NL: PT, aPTT and platelet count
with PROLONG BLEEDING TIME
example: uremic toxins accumulate due to significant renal dysfunction – impairing platelet aggregation and adhesion –> qualitative platelet disorder
