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)
