Week 7 Flashcards
Unusual flexion of the left wrist and thumb and extension of the fingers with cuff blood pressure measurement is a sign of?
= carpal spasm
Trousseau sign
sign of hypocalcemia
hypocalcemia in DGS (ex: 22q11.2 microdeletion, neural crest fials to migrate into the derivatives of the third and fourth pharyngeal/brachial pouches) –> increased neuromuscular excitability, which may manifest as tetany, carpopedal spasms or seizures
[another sign would be chvostek sign = twitching of the nose and lips]
Initial presentaiton of painless ulcers with later progression to painful inguinal lymphadenopathy and ulcerations
chlamydia trachomatis serotypes L1 through L3 –> lymphogranuloma venerem
Histo: cytoplasmic inclusion bodies
Scatter plots…what is the meaning of the correlation coefficient (r)
mathematically describes how well a “line of best fit” would correspond to the data points plotted
value ranges from -1 to +1
decribes 2 impt characteristics: strength and polarity
(closer the value is to the poles, the stronger the association)
What are small nuclear RNAs?
what disease process can affect these protein molecules?
SnRNA is synthesized by RNA polymerase II in the nucleus and complexes with specific proteins to form small nuclear ribonucleoproteins (snRNPs)
snRNPs are essential component of splicesomes, which remove introns from pre-mRA to form mature mRNA.
Pt with SLE can have autoantibodies directed against snRNPs (anti-smith antibody)
Cyanide:
toxicity symptoms
antidote (how does it works?)
sx: reddish skin discoloration, tachypnea, headache, tachycardia, often with n/v, confusion and weakness; develop quickly and can progress to seizures adn cardiovascular collapse
labs: lactic acidosis, in conjunction with narrowing of hte venous-arterial PO2 gradient, resulting from the inability of tissue to extract arterial oxygen
CN- toxicity is dependent on its ability to bind ferric iron (Fe3+) with high affinity, inhibiting cytochrome c oxidase in the mitochondria
–> severe lactic acidosis adn death as a result of cell switching to anaerobic metabolism
Antidote: Nitrate + thiosulfate, hydroxycobalmine
- inhaled amyl nitrite oxidez ferrous iron Fe2+ present on hemoglobin to ferric iron Fe3+ –> methemoglobin (incapable of carrying oxygen but high affinity for cyanide – binds and sequesters*
- thiosulfate adn hydroxycobalamin –> generally nontoxic metaboites that are esily excreted in the urine*
Calcineurin:
essential protein in teh activation of IL2, which promotes teh growth and differentiation of T-cells
Immunosuppresenats such as cyclosporine and tacrolimus owrk by inhibitng calcineurin activation
Calcineurin then activates NFAT –> IL-2 gene transcription –> IL2 goes onto IL2 R –> mTOR (inhibited by sirolimus + FKBP) –> cell growth and proliferation
Complications of prematurity:
Respiratory distress symptoms
Patent ductus arteriosus
Bronchopulmonary dysplasia
Intraventricular hemorrhage
necrotizing enterocolitis
retinopathy of prematurity
Intraventricular hemorrhage:
- common complication of premature
(RF: <32 wks gestation and/or birth weight <1500 g)
sx: alt consciousness, hypotonia, dec sponatneous movements, catastrophic bleeding including a buldging anterior fontanelle, hypotension, decerebrate posturing, tonic-clonic seizures, irregular respirations and coma
- Usually originates from teh germinal matrix (highly cellular and vascularized layer in teh subventricular zone from which neurons and glial cells migrate out during brain development; btw 24-32 weeks of gestation, the germinal matrix becomes less prominent and its cellularity and vascularity decreases, reducing the risk for IVH)
Where does the aberrant rate in AFib comes from?
Atrial fibrillation occurs due to irregular, chaotic electrical activity within the atria and presents with absent P waves, irregularly irregular R-R intervals and narrow QRS complexes
AV node refractory period regulates the number of atrial impulses that reach the ventricle and determines the ventricular contraction rate in conditions where the atria undergo rapid depolarization; AF is initiated by aberrant electrical impulses tha tarise within regions of heightened atrial excitability (most often the pulmonary veins). ONce trigered, AF leads to electrical remodeling of the atria with the development of shortened refractory periods and increased conductivity. This facilitates the creation and persistence of multiple ectopic foci and re-entrant impulses wtihin the atria, increasing the risk and chronicity of subsequetn epsidoes (AF begets AF)
esophageal squamous cell CA histo:
solid nests of neoplastic squamous cells with abundant eosinophilic cytoplasm and distinct borders.
Areas of keratinization (keratin pearls!) and the presence of intercellular bridges are also characteristic of squamous differentiation
sx: pt typically present with progressive solid adn eventually liquid dysphagi and wt loss.
Prognosis is generally poor as many pt present with incurable locally advanced or metastatic disease
Adverse effects of secondhand smoke exposure in an embryo/infant:
increased risk of low birth wt
asthma
middle ear disease
suddent infant death syndrome
respiratory tract infections (bronchitis, pneumonia)
What does the following maneuver do the blood volume / cardiac cycle:
straining phase of teh valsalva maneuver/ bearing down against a closed glottis
abrupting standing
straining phase of teh valsalva maneuver/ bearing down against a closed glottis = decreases venous return
abrupting standing = decreases left ventricular volume
Cushing Triad:
Hypertension
Bradycardia
Bradypnea
H/A + impaired consciousness –>
INC intracranial pressure
Uncal herniation
transtentorial herniation of the uncus
could be due to space occupying lesions within the temporal lobe, which can tehn cause elevated intracranial pressures
may result in compression of the ipsilateral CN III as it exits the midbrain at the same level –> ispilat oculomotor nerve palsy with fixed dilated pupil due to damage to the preganglionic parasympathetic fibers running on the outer portion of the third cranial nerve
advanced symptoms: mid-positioned and fixed bilateral pupils; advanced transstentorial herniation include loss of vestibular ocular reflexes and decorticate followed by decerebrate posturing
what is the most common cause of adrenal insufficiency?
Suppression of the hypothalamus-pituitary-adrenal axis by glucocorticoid therapy is the most common cause of adrenal insufficiency
In these patients, adrenal crisis can be precipitated by stressful situations (ie-infections, surgery) if glucocorticoid dose is not increased appropriately.
sx include: N/V. abdominal pain and dizziness after stressful situation
Patients wtih exogenous glucocoritcoids will not have a normal physiologic response to stress, and their HPA acivity will be:
CRH- decreased
ACTH- decreased
Cortisol - decreased
blood smea of DIC?
schistocytes = fragmented erythrocytes will be seen on peripheral smear
for example - in DIC due to gram negative sepsis, the coagulation cascade is activated by bacterial endotoxins, leading to widespread firbin deposition and consumption of coagulation factors and plateltes –> bleeding. Excess fibrin strans exerts shearing forces on circulating erythrocytes, resulting in schiztocytes on peripheral smear
LAB valules:
decreased platelet count, fibrinogen, factor V and VIII levels, with prolonged prothomib and partial thromboplastin times
Brunner glands
histo
location
purpose
Submucosal/Brunner glands- secrete copious amounts of alkaline mucus into the duodenum; glands are most numerous at the pylorus but may be found intermittently up to the ampulla of vater; galnds pass through the muscularis mucosa and terminate in the mucosa crypts (crypts of lieberkuhn)
Histo: branched, tubular submucosal glands containing alkaline secretions
chronic overproduction of gastric acid can lead to hyperplasia of the submucosal glands
Dengue fever:
classical presentation
virus transmitted by the Aedes aegypti mosquito
prevalent in tropical and subtropical regions (south adn southeast asia, pacific islands, caribbean, americas)
presentation: acute febrile illness with h/a, retro-orbital pain, and joint and muscle pain
hemorrhage (petechia, purpura, epistaxis, melena), thrombocytopenia, leukopenia, hemoconcentration
Chikungunya
virus transmitted by the Aedes mosquito
sx: febrile illness with flulike symptoms, prominent polyarthralgia/arthritis (hands, wrists, ankles) and diffsue macular rash
[note- many areas have simulatenous outbreaks of both dengue and chikungunya]
two deficiencies caused by megaloblastic anemia and how to distinguish?
Both deficiencies in vitamin B12 and folate could be assocaited with megaloblastic anemia
vit B12 deficiency –> associated with both megaloblastic anemia and neurologic dysfunction
folate deficiency –> associated with megaloblastic anemial alone
moderate improvement in the hemoglobin level often occurs when a deficiency in vitamin B12 is treated with folate or vice versa BUT vitamin B12 deficiency with folate alone can actually worsen neurological dysfunction
Ketoconazole MOA
weak anti-androgen that decreases synthesis of testosterone in leydig cells of the testes
As with all azole antifungal agents, ketoconazole works principally by inhibiting the enzyme cytochrome P450 14α-demethylase (P45014DM). This enzyme participates in the sterol biosynthesis pathway that leads from lanosterol to ergosterol –> inhibits steroid hormone production by the adrenal glands
VHL
autosomal dominant disorder caused by a deletion or mutation of the VHL tumor suppressor gene on chromosome 3p
characterized by: cerebellar hemangioblastomas, clear cell renal carcinomas, pheochromocytomas
RCC develops in nearly 40% of pt with VHL and is a major cause of death
- although VHL disease is rare, alt of the VHL gene and chromosome 3P are found in the majority of pt with sporadic RCC*
- thus pt with BOTH sporadic and hereditary (asc with CHL disease) renal cell carcinomas are found to have deletions or mutations involving the VHL gene on chrom 3p*
What is responsible for the HIV high mutability and what type of effect could this have on the immune system?
Drug resistance is associated with the prolong use of highly active antiretroviral therapy. High mutability of HIV-1 allows for the evasion of host humoral and cellular immune responses and development of resistance to anti-retroviral drugs
drug resistance has been attributed to the high mutation rate of the HIV genome and selective pressures exerted by antiretroviral drugs
- Pol* gene mutations –> responsible for acquired resistance to HIV reverse transcriptase inhibitors adn HIV protease inhibitors
- Env* gene mutations enable escape from teh host neutralizing antibodies
what do nucleoside analogues require for activation?
what do nucleoside drugs require for activation?
Nucleoside drugs: acyclovir, valacyclovir, famciclovir, ganciclovir
require both herpes and cellular kinases for conversion to their active nucleoside triphosphate form; absence of viral thymidine kinase in a herpesvirus strain confers resistance to nucleoside analog antiviral drugs [isolates with thymidine kinase-deficiency almost always obtained from AIDS pt]
Nucleoside monophosphate- cidofovir, tenofovir, require only cellular kinases for activation
name the properties of statins
inhibit the rate-limiting enzyme in hepatic cholesterol synthesis HMG-CoA reductase
–> hepatocytes increase the surface expression of the LDL R
High intensity statin therapy reduces the risk of actue coronary events, also have anit-inflammatory properties, improved endothelial dysfunction and appear to stabilize atheroscleortic plaques
biliary excetion of cholesterol decreases in pt on statins due to decreased de novo hepatic synthesis of cholesterol
Why is the genetic code consdered “degenerate”
because more than 1 codon can code for a particular amino acid. some of this degeneracy is explained by the wobble hypothesis, which states that the first 2 nucleotide positions on the mRNA codon require traditional (watson-crick) base pairing, whereas the third “wobble” nucleotide position may udnergo less stringent/non-traditional base pairing
note- there are 61 codon that code from amino acids, but only 20 amino acids are used in protein syntehsis
thus certain tRNA molecules can recognize multiple different codons coding for the same amino acid, a phenomenon explained by the wobble hypothesis
What is train of four stimulation:
TOF is used during anesthesia to assess the degree of paralysis induced by NMJ blocking agents
a peripheral nerve is stimulated 4 times in quick succession and the muscular response is recorded.
the height of each bar representes the strength of each twitch; higher bars indicate the activation of increasing numbers of individual muscle fibers/myocytes
nondepolarizing NMJ blockers (vecuronium), competitive inhibition of postsynaptic acetylcholine R at the motor endplate r_epvent some of tehse fibers from activatin_ –> decreasing strength of the twitch. the TOF shows a PROGRESSIVE reduction in each of hte 4 responses/fading pattern as a result of less acetylcholine being released with each subsequent impublse (due to additional effect of presynaptic ach receptor blockade)
depolarizing blockers (succinylcholine) initially function by preventing repolarization of the motor endplate and show equal reducation of all 4, during phase I; the response remains equal becuase the presynaptic ACh receptor simulation helps to mobilize presynaptic ACh vesicles for release. Persistent exposure to SC results in eventual transition to phase II blockade – as the ACH R become desensitized and inactivates/functionally similar to non-depolarizing blockade; during phase IIthere is a progressive reduction in each of hte 4 twitches.
Deficiency of what vitamin could increase the rate of complications from a pt with measles.
Think of measles when you see: fever, cough, congestion and conjunctivitis followed by a maculopapular rash [starts on the face and spreads in a cephalocaudal and centrifugal pattern, erythematous, blanching, maculopapular lesions often progress to a deep red or brown, nonblanching, coalesced rash]
VITAMIN A supplementation is recommended; acute measles depeltes vitamin A stores, resulting in a risk of keratits and corneal ulceration; vitamin A helps prevent and treat these ocular complications; it reduces the risk of other comorbidities (pneumonia, encephalitis), recovery time and length of hospital stay.
what is neonatal abstinence syndrome (NAS)?
Withdrawal from transplacental opiates due to maternal drug use
Clinical manifestations:
neuro- irritability, hypertonia, jittery movements, seizures (rare)
cardipulm - tachypnea, sneezing, crying
GI - diarrhea, vomiting, feeding intolerance
Autonomic - sweating, sneezing, pupillary dilation
tx: opiod therapy (morphine, methadone) dose is gradually INC until symptoms are controleld – then pt is weaned off over several weeks
[NOT naloxone. this is a pure opiod R antagonist that is used for ACUTE intoxication or OD or diagnosing dependence. using it for a pt in withdrawal can make withdrawal sx more severe and potentially cause seizures]
at risk: newbords born to mothers with poor mental health, no prenatal care and hep C
Varicose veins
causes and common complications
dilated, tortuous veins resulting from impairment of the venous valves and refulx of venous veins. This leads to venous stasis/congestion, edema, and an increased incidence of SUPERFICIAL venous thrombosis (not deep venous thrombosis, which is the leading cause of pulmonary emboli) thus thromboemobbolism is rare.
common complications result from poor blood flow –> painful thromboses, stasis dermatitis, skin ulcerations (especially medial malleolus), poor wound healing and superficial infections
What is the most common inherited thrombophilia?
Factor V leiden
with heterozygote prevalence of this genetic mutation ranging from 1-9% in caucasian populations
heterzygotes have 5-10X risk of developing a thrombosis, while homozygotes have 50-100X risk
two pathophysiological mechansims:
1) Factor Va Leiden has reduced susceptibility to cleavage by activated protein C..factor Va is a cofactor for the conversion of prothrombin –> thrombin, increased factor Va –> increased trhombin production
2) factor V leiden is unable to support APC anticoagulant activity
–> increased coagulation + decreased anticoagulation produced the HYPERCOAGULABLE state seen in pt with factor V leiden
Diphenoxylate?
opioid anti-diarrheal agent structurally related to meperidine.
Binds to mu opiate receptors in the GI tract and SLOWS MOTILITY
high doses can produce the morphine-like euphoria and physical dependence. To discourage abuse, it is combined with ATROPINE, which produces adverse symptoms (dry mouth, blurry vision and nausea) if taken in high doses.
other similar drugs: loperamide
dont give for diarrhea due to toxin-producing or invasive organisms (shigella, salmonella) or C diff
common side effects- rebound constipation and mild sedation
how to confirm celiac dz?
Screening test will show elevated level of IgA against tissue transglutaminase (intestinal enzyme required for gluten metabolism); others: increased anti-endomysial antibodies
Duodenal biopsy is CONFIRMATORY, showing villus flattening and INTRAepithelial LYMPHOCYTE infiltration
[duodenum and jejunum are exposed to the highest concentration of gliadin thus biopsy of these ares is required for diagnosis]
What 2 substances predominantly drive angiogensis:
angiogenesis is predominately driven by:
1) Vascular endothelial growth factor (VEGF):
* stimulates angiogen. in a variety of tissues (nl, chronic inflammed, healing or neoplastic), helps new capillaries to sprout by increasing endothelial cell motility and proliferation [dont confuse with epidermal growth factor EGF]*
2) Fibroblast growth factor (FGF): FGF-2 produced in a wide range of cells and is invoved in endothelial cell proliferation, migration and differentiation. appears to play an impt role in embryogenesis, but also to embryonic development, hematopoiesis and wound repair (via the recruitment of macrophages, fibroblast, and endothelial cells to damanged tissue)
** laminin in basement membrane may pose a physical barrier to the sprouting of new blood vessels **
proinflammatory cytokines (IL-1, interferon-gamma) can INDIRECTLY promoate angiogen through increased VEGF expression
Erythema multiforme:
EM = acute inflammatory disorder that can involve the skin of extremities, face, trunk and neck; severe cases can also affect oral mucous membranes and the tongue
rash appearance can vary but pt typically develop erythematous round papules that evolve into target lesions with a dusky central area, a dark red inflammatory zone surrounded by a pale ring, and an erythematous halo in the lesion’s periphery
cell-mediated immune process, with an inflammatory infiltrate predominante by cytotoxic CD8+ lymphocytes
most frequently associated with infections - esp HSV and mycoplasm, and may be due to an immune response against antigens deposited in the skin; could also be seen with certain medications (sulfonamides), but is a systemic immune response to a localized infection
what conditions are associated with renal papillary necrosis?
RPN classically presents with gross hematuria, acute flank pain and passage of tissue fragments in urine. It is most commonly see in pt with SCD or train, DM, analgesic nephorpathy or severe obstructive pyelonephritis
sickle cell disease or trait
analgesic nephropathy- (NAIDS! inhibit renal blood flow by decreasing prostaglanding synthesis and vasoconstricting the afferent arterioles. certain analgesics can cause ischemia in pt predisposed to renal hypoperfusion)
diabetes mellitus –> renal vasculopathy and subsequent hypoperfusion
pyelonephritis and urinary tract obstrution –> edematous interstitum of the pyelonephritic kidney compresses the medullary vasculature, leading to ischemia
sx: gray-white or yellow necrosis of the distal 2/3 of the renal pyramids is seen macroscopically and corresponds microscopically to coagulation necrosis with preserved tubular outlines; cortical surface scars can develop subsequently as inflammatory foci are replaced by fibrous depressions.
sx are DUE TO sloughed papillae (sometimes visible in urien as tissue flecks) and include dark/rusted-colored or bloody ruine or acute and colickly flank pain/uteral obstruction
chronic RPN may present with subtle reccurent hematuria
Echinococcus granulosus
tapeworm
endemic @: eastern mediterranean, middle east, south america, sub-suharan africa, former soviet union, western china or those residing in SW US with sheep and dog (participate in tapeworm life cycle) exposure
most common cause of hydatid cysts
the liver is often affected –> hepatomegaly or right upper quadrant pain but others can be invovled
infection –> larvae implant within the capillaries, triggering an inflammatory reaction involving monocytes and eosinophils; some larvae encyst
microscopic exam - encapsulated and calcified cysts “eggshell calcification” containing fluid and budding cells that will eventually become daughter cells. outer wall is composed of gelatinous sheets surrounded by a thick fibrous capsule.
Dx: imaging (US, CT, MRI) and serology testing
tx: depend on size; surgery and adjunctive chemotherapy (albendazoles) are the tx of choice for symptomatic pt. Cyst manipulations should be performed with caution, as spilling of cyst contents can cause anaphylactic shock
what are the hemodynamic changes that occur with exercise?
stimulation of mechano and chemo R in the exercising muscles –> sympathetic activation and withdrawal of vagal tone –>
INC: HR, stroke volume, CO (at higher levels of exercise, HR is predominately responsible for most of the increase in CO)
contraction of: arterioles in all tissues except the actively working muscles, splanchnic vasoconstriction –> shunting blood towards the exercising muscles
INC SBP
rise in mean arterial pressure is much lower due to an overall decrease in systemic vascular resistance due to substantial arteriolar vasodilation in active skeletal muscles mediated by adenosine, potassium ions, ATP, CO2, lactate
LVED volume and pressure rise due to increased venous return (peripheral vasoconstriction and pumping actions of actively contracting muscles)
pulmonary artery systolic pressur erises but like systemic smaller than increase in blood flow across the pulmonary circulation due to a fall in pulmonary vascular resistance
Gallstone ileus:
sx: intermittent abdominal crampy pain, vomiting and bloating
exam shows - signs of small bowel obstruction such as abdominal distension, tenderness and high-pitched/tinkling bowel sounds.
Imaging- dialted bowel loops with air-fluid levels, pneumobilia (air in the biliary tree due to retrograde passage of intestinal gas through the fistula)
Not a true ileus, since its a mechanical obstruction, that occurs when a large gallstone (>2.5 cm in diameter) erodes into the intestinal lumen through a cholecystoenteric fistula
–> travels down the intestine, and as it intermittently obstructs the lumen, causes episodic sx and eventually can become stuck at the ileum since it has the smallest lumen in the intestinal tract
note although the bowel wall is disrupted in gallstone ileus, the cholecystoenteric fistula is usually associated with fibrotic adhesions btw the biliary tree and the bowel - no free communication with teh peritoneal cavity thus not common to see free air in the periotneal cavity (which is suggestive of bowel perforation)
What should all pt with major depression be screened for prior to starting tx?
past history of manic episodes
- need to differentiate between major depressive disorder (unipolar depression) and bipolar disorder
if history is suggestive of bipolar - antidepresant monotherapy should be avoided due to risk of inducing mania; bipolar pt in teh depressed phase may be misdiagnosed with unipolar MDD when there is a neglect to obtain hx of past manic sx for a variety of reasons
question: history of distinct periods of elevated mood and increased energy, decreased need for sleep, hyperactivity, racing thoughts and uncharacterized risk-taking behavior
Signs and symptoms of transtentorial/uncal herniation
- affects the oculomotor nerve –> fixed, dialted pupil on the ipsilateral side
with time –> contralateral or ipsilateral hemiparesis, ipsilateral paralysis of oculomotor muscles, contralateral homonymous hemianopsia with macular sparing
What is the cause of subacute sclerosis panencephalitis?
SSPE is due to mutated or absent matrix proteins of the measles virus. this prevents mature viron envelop viruses from forming –> persistent noninvading infection that continues to replicate while evading the immune system
it is the accumulation of viral nucleocapsids within neurons and oligodendrocytes that–> formation of intranuclear inclusions –> inflammation, demyelination and gliosis in many cerebral areas
sx: ataxia, myoclonus, visual issues YEARS after infection, personality changes, poor school performance
(clue in with immigrant / nonvaccinated child)
high titers of measles antiboides in serum and CSF (detectable as oligoclonal bands)
Measles:
matrix (M) protein for viral assembly
2 glycoproteins: hemagglutinin, and fusion
what is the pathogen of chronic myelogenous leukemia?
the classic and most common cause is a translocation between chromosome 9 and 22.
ABL from 9 (proto-oncogene) transported to chrome 22 near BCR –> oncogene, BCR-ABL which code for a FUSION PROTEIN with constitutitve tyrosine kinase activity
stimualtes the proliferation of granulocytic precursors and leads to the development of CML
kinase activity of this fusion protien is a target of the protein kinase inhibitor, imatinib
which amino acid is found in greatest quantity in collagen?
glycine
collagen is the most abundant protein in the body
synthezised by fibroblast, osteblast and chorndoblast
3 polype alpha chains, held together by hydrogen bonds, forming a rope-like triple helix
self-assemble into fibrils –> crosslink to form collagen fibers
gly-X-Y is the typical sequence of collagen, its simple and repetitive AA se within each alpha chain helps the helical conformation
X usually hydroxyproline or hydroxylysine - good for rigidity of the helical structure by introducing kinks
Y - usually hydroxylysine, good for cross-linking, which greatly increases the tensile strength of assembled collagen fibers
Maple syrup disease
AR disorder characterized by the defective breakdwon of branched-chained amino acids
“i love vermont maple syrup”
isoleucine (a metabolite gives sweet odor to urine)
leucine
valine
mutations of BCKDC –> accumulation of branched-chain amino acids in serum and peripheral tissues –> NEUROTOXICITY (seizures, irritability, lethargy and poorfeeding)
life-threatning if untreated; brain swelling –>death
dietary restriction + some pt improve with high dose thiamine B1 treatmemt
Analgesic nephropathy
if NSAIDS taken for a prolong period of time could lead to renal failure
modest elevation in serum creatinine, mild proteinuria, evidence of tubular dysfunction (polyuria, nocturia)
microscopic heamturia and serile pyuria on UA
NSAIDs concentrate on renal medulla along medullary osmotic gradient, with higher levels in the papille
–> uncouple oxidative phosphorylation and are thought to cause gluthione depletion with subsequent lipid peroxidation, resulitng in damage to ubular and vascular endothelial cells
–> chronic interstitial nephritis (pathy interstitial inflammation with subsequent fibrosis, tubular atrophy, paillary necrosis and scaring and caliceal architecture distortion
because NSAIDS decrease prostaglandin synthesis, can cause constriction of medullary vasa recta and ischemic papillary necrosis
insulin synthesis and secretion
DNA –> mRNA
hydrophobic N terminal signal peptide directs translocation of preproinsulin to rough ER
by interacting with cytosolic signal recognition peptide – halts protein synthesis until the ribosome translocated to the RER
@ RER, signal peptide is cleaved, converting preproinsulin –> proinsulin –> undergoes confirmational changes and addition of 3 disulfied bonds into the RER
sent to golgi for packaging
Prosinulin is cleaved to insulin and c-peptide in secretory granule (beta cell endopeptidases) BOTH are relased in equimolar amounts
requirements to decision-making capacity:
Communicates a choice
understands infomraiton provided
appreciates consequences/acknowledges
Rationale given for a decision
principle of autonomy; need to be assessed for decision-making capacity if refusing tx
Heroin withdrawals:
sx: n/v, abdominal cramping, muscle aches
PE: dilated pupils, yawning, piloerection, lacrimation, hyperactive bowel sounds
starts 6-12 hrs
peaks 24-48 hrs
users or pt who take opiod
SSRI common side effects
Sexual dysfunction is a common side effect of SSRI that can leads to nonadherence
overall, improved toelrability and better side effect profile compared to TCAs - SSRIs have minimal activity at alpha-adrenergic, cholinergic and histaminic R
other: can prolong QT slighlty but rare cause of arrythmia (unlike with TCA overdse-serious side effect is cardiac arrythmia), seizures, wt gain
