Week 7 Flashcards
1
Q
Unusual flexion of the left wrist and thumb and extension of the fingers with cuff blood pressure measurement is a sign of?
A
= 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]
2
Q
Initial presentaiton of painless ulcers with later progression to painful inguinal lymphadenopathy and ulcerations
A
chlamydia trachomatis serotypes L1 through L3 –> lymphogranuloma venerem
Histo: cytoplasmic inclusion bodies
3
Q
Scatter plots…what is the meaning of the correlation coefficient (r)
A
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)
4
Q
What are small nuclear RNAs?
what disease process can affect these protein molecules?
A
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)
5
Q
Cyanide:
toxicity symptoms
antidote (how does it works?)
A
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*
6
Q
Calcineurin:
A
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
7
Q
Complications of prematurity:
A
Respiratory distress symptoms
Patent ductus arteriosus
Bronchopulmonary dysplasia
Intraventricular hemorrhage
necrotizing enterocolitis
retinopathy of prematurity
8
Q
Intraventricular hemorrhage:
A
- 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)
9
Q
Where does the aberrant rate in AFib comes from?
A
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)
10
Q
esophageal squamous cell CA histo:
A
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
11
Q
Adverse effects of secondhand smoke exposure in an embryo/infant:
A
increased risk of low birth wt
asthma
middle ear disease
suddent infant death syndrome
respiratory tract infections (bronchitis, pneumonia)
12
Q
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
A
straining phase of teh valsalva maneuver/ bearing down against a closed glottis = decreases venous return
abrupting standing = decreases left ventricular volume
13
Q
Cushing Triad:
A
Hypertension
Bradycardia
Bradypnea
H/A + impaired consciousness –>
INC intracranial pressure
14
Q
Uncal herniation
A
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
15
Q
what is the most common cause of adrenal insufficiency?
A
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
16
Q
blood smea of DIC?
A
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
17
Q
Brunner glands
histo
location
purpose
A
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
18
Q
Dengue fever:
classical presentation
A
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
19
Q
Chikungunya
A
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]
20
Q
two deficiencies caused by megaloblastic anemia and how to distinguish?
A
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
21
Q
Ketoconazole MOA
A
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
22
Q
VHL
A
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*
23
Q
What is responsible for the HIV high mutability and what type of effect could this have on the immune system?
A
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
24
Q
what do nucleoside analogues require for activation?
what do nucleoside drugs require for activation?
A
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
25
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
26
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
27
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.
28
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.
29
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
30
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**
31
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
32
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
33
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]
34
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
35
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_**
36
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
37
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**
38
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
39
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)*
40
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
41
Signs and symptoms of transtentorial/uncal herniation
1. 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
42
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
43
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_**
44
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
45
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**
46
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
47
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
48
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*
49
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
50
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
51
How can non-virulent strains of corynebacteriam acquire pathogenicity?
acquires virulence via **bacteriophage-mediated "infection" (bacteriophage=corynephage beta)**
**phage conversion** _permiting exotoxin production_
--\> can then cause severe pseudomembranous pharyngitis after acquiring the **_*Tox* gene_ via _lysogenization_ by a temperate bacteriophage**
**(bacteriophage infects a host bacterium and integrates its genome into the host bacterium's genome)**
although chromosomal mutations can theoretically lead to endotoxin production, these mutations more commonly lead to antibiotic resistance
Tox gene codes for AB exotoxin -
52
Mesothelioma:
arises from teh pleura or peritoneum
strongly associated with asbestos exposure
hemorrhagic pleural effusions and plueral thickening are characteristic
histopath: tumor cells with numerous, long slender microvilli and abundant tonofilaments (Tonofilaments are keratin intermediate filaments that make up tonofibrils in epithelial tissue. In epithelial cells, tonofilaments loop through desmosomes)
vs: adenocarcinoma - glandular or papillary elements, have SHORT and PLUMP microvili that distinguish adeno from meso
vs: squamous cell- imaging usually shows hilar mass; characterized by keratinization and intercellular bridges; can present sometimes as cavitary lung lesion
53
Conn's Syndrome
Primary hyperaldosteronism (aldosterone secreting tumor/adenoma)
sx: HTN, HYPOkalemia, metabolic alkalosis, decreased plasma renin activity (no hypernatremia)
tx of unilateral adenoma secreting aldosterone either via surgical resection or by medical therapy with aldosterone antagonist (spironolactone, eplerenone -- most common side effect ability to cause gynecomastia)
(aldosterone, causes resorption of sodium and water, and wasting of potassium and hydrogen ions at the distal portion of the nephron)
54
why do highly lipophilic drugs have a rapid onset of action and short duration?
readily diffuse across membranes --\> accumulate in tissues receiving high blood flow --\> rapid onset
redistributed to organs receiving less blood flow --\> short duration
ex) propofol (used for induction and maintenance of general anesthesia, and procedural sedation) onset ~ 30 sec with \<10 min duraction --\> rapid decrease in level of consciousness and global amnestic effect
cleared -- first to organs receiving high blood flow (brain) accounting for rapid onset of sedation
over time redistrbuted to organs receiving less blood flow (fat and muscle) --\> since site of action is the brain, redistrubution --\> termination of drug action
55
What is hoffmann elimination
spontaneous dedegration in plasma and organ tissues of non-depolarizing neuromuscular blocking agents
ie- atracurium
56
What is the lymphatic drainage of the following:
testes
scrotum
glans penis
testes --\> para-aortic/retroperitoneal lymph nodes
scrotum --\> superficial inguinal lymph nodes
* drain all the cutaneous strucures inferior to hte umbilicus, including the external genitalia and the anus up to the pectinate line*
* except: dorsal lateral foot and posterior calf (popliteal lymph) and*
* testes, kidneys and ureters (para-aortic lymphs)*
glans penis, superficial nodes --\> deep inguinal nodes
lower rectum to anal canal above the pectinate line, bladder, middle third vagina and prostate --\> internal iliac lymph nodes
57
Class III antiarrhythmic drugs?
amiodarone, sotalol, dofetilide
predominantely block potassium channels and inhibit the outward potassium currents during phase 3 of the cardiac action potential, --\> prolonging repolarization and total action potential duration
58
What coenzymes are required by brancehd-chain alpha-ketoacid dehydrogenase??
reuquires pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase
**requires 5 cofactors**
Tender Loving Care For Nancy
Thiamine
Lipoate
Coenzyme A
FAD
NAD
59
**Absolute risk reduction =**
event rate in the control group - event rate in the treatment group
60
Post-strep glomerulonephritis
LM: enlarged hypercellular glomeruli on light microscopy
w/hematuria, proteinuria and urine RBC casts
Lba findings: elevated titers of anti-streptococcal antibodies (anti-streptolysin O, anti-DNase, anti-cationic proteinase)
LOW C3 concentration
cryoglubulins may also be present in serum
\*hypercellularity involved all lobules of all glomeruli, result of leukocyte infiltration adn endothelial and mesangial cell proliferation
EM: electron-dense deposits "humps" on the _epithelial_ side of the BM (composed of immune complexes)
IF: coarse granular deposits of IgG and C3 with the characteristic "stary sky" appearance
low C3 suggest activation of the alternative complement pathway
C4 usually normal (maybe slightly low, significant for classical pathway activation)
61
what is secreted by the paraventricular and supraoptic nucleus?
Neurosecretory cells in the hypothalamus sends hormones to the neurohypophysis / posterior pituitary (neuroecoderm derived)
paraventricular --\> oxytocin
supraoptic --\> ADH/AVP/vasopressin
hormones released into the circulation from axon terminals in the posterior pituitary
**_neruphysins_ are involved in posttranslational processing and stabilization** of oxytocin adn vasopressin *_within neurosecretory vesicles during transport to the posterior pituitary_*
62
what does HIV use to infect cells?
HIV virus uses the CD4 protein as a primary receptor and the chemokine receptor CCR5 as a coreceptor.
both are bound by the HIV viral outer envelop protien gp120 --\> virus enters the cell via fusion with the cell membrane
\*if CCR5 is not expressed on the cells, hte HIV binds CD4 but unable to enter teh cell
thus deletion of both alleles that code for CCr5 R renders teh individual resistance to HIV infection while heterzygous individuals can be infected but develop clinical smptoms later than pt with two copies fo the CCr5 gene
63
What is required to activate acyclovir?
Acyclovir is a guanosine analog
once acyclovir enters a virally infected host cell, it is phosphorylated to acyclovir monophsoate, principally by a **VIRALLY encoded thymidine kinase (TK)**
*_RATE LIMITING step in acyclovir activation_*
acyclovir monophosphate is then phosphorylated by CELLULAR enzymes into the active triphophate form, which IMPAIRES VIRAL DNA polymerase-mediated replication of the virus
note: this is effective for HSV and VZV, wherease EBV and CMV infected cells cannot easily convert acyclovir into its pharmacologically active form
64
calcium-channel blockers:
blcok L-type calcium channels
decrease phase 0 depolarization adn conduction velocity in the SA and AV nodes
--\> slowing of the sinus rate and conduction through the AV nodes, which can cause bradycardia and varying degrees of AV block.
NEG inotropic effect
relatiely contraindicated in pt with CHF due to left ventricular systolic dysfunction
SE: constipation major side effect of nondihydropyridine CCBs (verapamil \> diltiazem)
65
which vaccines are LIVE attenuated?
Killed vaccines?
Herpes zoster/shingles, varicella, yellow fever, small pox, rotavirus, sabin polio, MMR, influenza (nasal)
--\> cellular + humoral response
Rabies, influenza (injected), polio (salk K=killed), HAV
--\> humoral response
66
What drugs should NOT be used when using bezodiazepines?
alcohol
barbiturates
neroletics
1st generation antihistamines = first gen H1 receptor antagonist (chlorpheniramine, diphenhydramine, promethazine, hydroxyzine)
--\> can lead to high sedation because they easily penetrate the BBB and accumulate in the CNS; blcok both central and peripheral H1 receptors
67
Pernicious anemia
autoimmune disease
characterized by CD4+ T cells / cell-mediated destruction of parietal cells --\> progressive destruction of oxyntic/acid-producing mucosa --\> loss of parietal cell mass --\> dec IF (dec vitb b12 + megaloblastic anemia), achlorhydria --\> inc intraluminal pH, stimulating gastrin secretion by gastric G cells
B cells --\> autoantibodies against: H+/K+ATPase, intrinsic factor (also produced, useful for diagnosis but not significantly involved in the pathogen)
as parietal cells are destroyed, ability to secrete HCl decreases, resulting in an elevated intraluminal pH --\> upregulation of gastrin secretion
(parietal cells are found in the body and fundus of the stomach)
develop vitamin B12/cobalamin deficience as a result of decreased intrisic factor secretion
68
Brachial plexus anatomical location
Describe the effects of an interscalene nerve block
originates from C5-T1 spinal nerves, branching network of nerves innervating the upper limb (controls all motor activity in the _upper extremity_ except the trapeziues and scm - CN XI)
nerve roots combine into 3 trucks (superior, middle and inferior) and pass btw the middle adn anterior scalene muslces (scalene triangle) in the posterior neck
trunks then differentiate into divisions, cords and terminal nerve branches
INTERSCALENE NERVE BLOCK - regional anesthesia techique used for procedures involving the shoulder and upper arm
administered in teh scalene triangle
affects brachial plexus roots and trunks
also causes transient ipsilateral diaphgramatic paralysis in nearly all pt by anesthezing the roots of the phrenic nerve (C3-C5) as it passes through the interscalene sheath
\*\*avoid this nerve block in pt with chronic lung disease or with contralateral phrenic nerve dysfunction\*\*
69
How is EBV detected
relies on detecting a heterogenous group of hetrophile IgM antibodies that react wtih antigens on horse erythrocytes / sheep erythrocytes in the classic Paul Bunnell test
agglutination of these erythrocytes by human serum is a sensitive and highly specific test for EBV infection in human B cells
mechanism remains unclear- EBV either induces a humoral response to heterophile antigens or stimulates non-specific polyclonal activation of B cells
EBV infects B cells -- simulating them to enter to cell cycle and proliferat continuously/transformation/immortalization
--\> immortalized B cell is still able to secrete immunoglobulins and B-cell activation products(CD23), with few releasing virus particles at any one time
EBV is an oncogenic virus that promotes POLYCLONAL B cell proliferation adn heterphile antibody production
70
Testicular torsion
usually due to inadequate fixation of the lower pole of the testis to the tunica vaginalis -- twsiting of the spermatic cord, resulting in compression of the pampiniform plexus of the testicular vein and reduced venous outflow; arterial blood flow in the testicular arteries is initially preserved, leading to engorgement and eventual hemorrhagic infarction
sx: acute, severe pain with n/v, an asymmetrically high-riding testis and absent creamasteric reflex (elevation of testis while pinching hte skin in upper thigh)
71
pathophys of HUS
hemolytic uremic syndrome
usually do to shiga/verotoxin-toxin producing bacteria
(E. coli O157:H7, Shigella)
clinical features: antecedent diarrheal illness (often bloody), hemolytic anemia with schistocytes, thrombocytopenia (platelet consumption), acute kidney injury
Toxins injry the endothelium of preglomerular arterioles and glomerular capillaries --\> platelet activation and aggregation adn the formation of micrthrombi -- consumption of patelets --\> thrombocytopenia (typically no purpura or active bleeding vs HSP has palpable purpura)
erythrocytes passing through damaged capillaries suffer shear injury and are broken down to schistocytes --\> microangiopathic hemolytic **anemia** w/conjnctival pallor (not seen in PSGN)
extensive damage to the renal vasculature --\> acute kidney injury (oliguria/anuria, hematuria, increased creatinine)
72
what is seen in light microscopy of guillain-baree infected cells?
segmental demyelination and endoneural inflammatory infiltrate in the peripheral nerves
GB syndrome manifests with ascending muscle weakness that starts after recoery of respiratory of GI infection; disappearance of deep tendon reflexes (areflexia); paralysis may ascend to the cranial nerves (CN VII - bells palsy), paralysis of respiratory muscles is fatal without supportive care
strong association with Campylobacter jejuni
Beriberi, is similar but due to thiamine deficiency - it also can cause demyelination of peripheral nerves; but there is _no perineural inflammation._ sx include muscle weakness and arefelxia, pain and parethesia; involvement of distal lower limbs is characteristic
73
Schwannomas
Histo: biphasic pattern of cellularity (Antoni A - high and Antoni B- low cellularity
Atoni A areas are composed of spindle cells (enlongated cells with regular, oval nuclei) that form _palisading patterns_ with interspersing nuclear-free zones called Verocay bodies
Universally S-100 positive (due to neural crest cell origin; melanoma is also S100 positive)
could occur within the cranial vault and spinal canal
\*\* schwannomas may arise from any CN except the optic nerve, which is covered by oligodendrocytes instead of schwann cells\*\*
most common at teh cerebellopontine angle at CN VIII - at this spot called acoustic neuromas (tinnitus, vertico and sensorineural hearing loss)
74
regulation of gastic acid secretion:
cephalic (cholinergic mediated and vagal mx, triggered by thougth, sight, smell and taste of food) inc gastric release
gastric, mediated by the presence of gastrin -- stimulates histamine secretion and acid secretion, triggered by the chemical stimulus of food adn distension of hte stomach
sfd phasesdf
protein stimulates gastric secretion but most effective in down-regulating gastric acid secretion via peptide YY, which is secreted by the ileum and colon -- bind to endocrine, histamine-containing cells = enterochromaffin-like cells (ECL) --? inhibit gastrin-stimulated release of acid
75
how would you test for attention and concentration deficits/impariment such as in demetia, head injury, depression?
COUNTING DOWN or backwords
- reciting months of the year backwards
- counting down from 100 by intervals of 3 or 7
- spelling "world" backwords
Mini-mental staet examinaiton- screening tool for cognitive impariment (does not test for executive function - must test by other measures such as clock drawing)
for dementia- pt must demonstrate impairment across several cognitive domains during testing as well as functional impairment in activites of daily living
76
what does HER2/neu oncogene encode for?
encodes for a 185 kD transmembrane glycoprotein that has intracellular tyrosine kinase activity
it is one of the peidermal growth factor receptors, which know to play a role in the activation of epiderma transduction pathway that control epithelial growth and differentiation
overexpression associated with increased rates of breast and ovarian, gastric and endometrial CA
77
most common type of kidney stone?
RF?
what are the serum and urine labs look like?
calcium tones = 75-80% of all renal calculi and include calcium oxalate and calcium phosphate stones
hypercalciuria most common risk factor
mostly idiopathic; other include- hyperoxaluria (high oxalate in diet, low calcium diets / intestinal malabsoprtion syndromes ie-Crohns), hyeruricosuria, low urine volume, hypocitraturia
YET normocalcemic due to intact regulation of serum calcium levels by vitamin D and parathyroid
78
describe the potassium filtration throughout the kidney:
Most of the k+ filtered by the glomeruli (freely filtered) is resorbed in the proximal tubule (aprox 2/3) and loop of henle
the late distal and aortical collecting tubules are the primary sites for regulation of K+ concentration in the urine
K+ depletion stimulates alpha-intercalacted cells to reabsorb extra potassium;
principal cells secrete K+ under conditions of nomral or increased K+ load
high dietary K+ intake can cause the amt of K+ in the collecting tubules to actually exceeded that of the filtered load
79
In stats, what detects a study's ability to detect a difference when one exist?
= statistical POWER = (1-b)
* probability of rejecting the null hypothesis when it is truly false (probability of finding a true relationship)*
* b=probability of committing a type II error (when researches fail to reject the null hypothesis when it is truly false, causing investigators true relationships)*
depends on sample size and difference in outcome between the groups being tested
typically set at 80%
80
what is type I and type II errors?
**type I error** = when researches reject the null hypothesis when teh null hypothesis is really true; study finds a statistical significance btw both groups when one truly doesn't exist
**alpha** = maximum probability of making a type I error that a researcher is willing to accept; generally alpha is compared to p-value, the probability of observing a given result due to chacne aloneassuming the null is true; typically, p is set to 0.05 = researchers are willing to accept up to a 5% chance of making a type I error, thus in such a scenario, if **p \<0.05, the result is said to be statistically significant**
**type II error=** when researchers fail to reject the null hypothesis when the null is truly false
**beta** = probability of committing a type II error
what to minimize B to maxamize the **power** (1-b)
81
name the approx location of the following:
IVC
L atria
L ventricle
R ventricle
Pulmonary trunk
IVC - right side of the central tendon of the diaphgram at the level of T8 (injured by a penetrating wound to the back, immediate right of the vertebral bodies)
L atria - base of heart, posetrio surface, opposite teh apez, makes up most of hte hearts posterior surface; only the auricle of the left atrium is visble anteriorly between the pulomnary trunk and left ventricle
L ventricle- left lateral aspect of the heart; stab wound in the fourth intercostal space in the midclavicular line could strike the left ventricl bu tonly after passing through the bulk of the left lung
R ventricle- most of hte hearts anterior surface
Pulmonary trunk- pierced if penetrating injury to the second intercosta psace at the left sternal border
82
I-cell
inclusion cell disease
Auto Recessive lysosomal storage disorder, occurs due to defects in protein targeting
proteins targeted for **lysosomes** req the **golgi** body **phosphotransferase enzyme that** catalyzes teh phosphorylation of mannose residues on lysosome-bound proteins; allowing them to traverse the golgi network and ultimately be transported to the lysosome, where they serve as a catalyst for degradation of cellular components
defect of enzyme --\> extracellular secretions of tehse proteins and accumulation of cellular derins in teh lysosome, forming the characteristic inclusion bodies seen in I-cell dz
clinical pres: failure to thrive, cogn defects in first year of life + coarse facial features, corneal clouding; typically fatal in childhood
83
What could cause coronary sinus dilation?
most venous drainage from the myocardium traverses teh CS -- delivering deoxy blood to the right atrium
CS travels in the atrioventricular groove on the posterior aspect of the heart, opens into the right atrium btwn the IVC and tricuspid valve
Most common cause of CS dilation is elevated right sided heart pressure secondary to pulmonary hypertension; also can occur in pt with anomalous venous drainage into the CS, including persistent left superior vena cava, and total anomalous pulmonary venous retrun
84
what is tetrahydrobiopterin BH4 a cofactor for?
hydroxylase enzymes in teh synthesis of tyrosine (from phenylalanine), dopamine and serotonin (from tryptophan)
BH4 deficiency --\> phenylketonuria (PKU, intellecula disbility, neurotransmiter deficiency and hyperpheylalanemia)
tx: low phenylalanine diet + BH4 supplementation
85
Daptomycin MOA and indication
disrupts bacterial membrane by creating transmembrane channels that cause intracellular ion leakage --\> cellular membrane depolarization adn macromolecular synthesis inhibition --\> cell death
used for: gram positive ogranisms including skin and skin structure infectiosn and bacteremia due to S Aureus, and MRSA
Not used for: gram negative (cannot permeat the outer membrane)
pneumonia (inactivated by pulmonary surfactant)
SE: increased creatine phosphokinase (CPK) and an increased incidence of myopathy
\*cpk level monitoring with assessment for muscle pain and weakness should be performed regularly in pt
86
hCG is common to what hormones?
hCG is produced by the synytiotrophoblast
fxn: maintain corpus luteum/progesterone during the first 8-10 weeks of pregnancy by acting like LH (otherwise, no luteal cell stimulation --\> abortion)
after this time, placenta produces its own estradiol and progesterone, allowing CL to degenerate
hCG is alpha and beta subunit
alpha is identical to LH, FSH and TSH
beta is unique, and used in pregnancy test
87
what can cause torsades the pointes?
=form of polymorphic ventricular tachycardia characterized by QRS complexes of varying amiplitude and cycle length giving the appearance that the tip of the QRS is twsing around the ECG baseline)
always associated with prolong QT interval
long QT syndrome...caused by certain congential, **drugs, DEC K+, DEC Mg2+**
**drugs: anti-ABCDs**
Anti-**A**rrythmics (class IA, III - sotalol, quinidine)
anti-**B**iotics (macrolides, fluoroquinolones)
anti-**C**ycotics (haloperidol)
anti-**D**epressants (TCAs)
anti-**E**metics (odancetrone)
(note- digoxin causes QT interval shortening not prolongation)
88
What is spliting?
defense mechanism that involved experiencing the self or others as ALL BAD or ALL GOOD
commonly seen in borderline personality disorder and can contribute to teh unstable relationships and mood instabilties that characterize teh disorder
89
what infections are transmitted by the ixodes tick?
**babesiosis** (babesia microti)
**Lyme** (borrelia burgdorferi)
co-infection is common since they are both endemic in similar geographic regions
Also ixodes is responsible for **human granulocytic anaplasmosis** (granulocytes with morulae / deep blue/purpule grape-like structures)
90
what is the virulence of salmonella?
Salmonella is a nonlactose-fermenting, oxidase-negative, motile gram negative organism with a special capsule called Vi antigen -- capsule protects it from opsonization and phagocytosis (contributes to osteomyelitis)
can also produce an exotoxin that may contribute to typhoid fever not osteomyelitis
* salmonella is a common cause of osteomyelitis in pt with SCD but not in patients without SCD*
* sickling in the intestinal vasculature leads to areas of necrosis, with the potential for transient mucosal breakdown and bacterial seeding in patients with SCD who may have subclinical or undiagnosed salmonella infection*
* vaso-occlusive crises cause focal areas of bone necrosis within which bacteria can easily establish infeciton*
* also --\> spleen infarction (functional asplenia) -- puts patients at an increased risk for infection by encapsulated organisms such as s. pneumo, N. haemophilus, salmonella spp.*
91
Midline episiotomy?
used to enlarge the vaginal outlet to faciliate delivery and reduce the risk of severe perinel laceration
vertical incision from the posterior vaginal opening to the perineal body
transects teh vaginal lining and teh submucosal tissue but NOT the external anal sphincter or the rectal mucosa
improper repair of a midline episiotomy may result in pelvic organ prolapse or dyspareunia
the perineal body is a fibromuscular tissue between the urogenital and anal triangle'
92
major difference between infertility of a pt with primary ciliary dyskenesia and CF
diagnosis
Infertility in PCD is due to immotile spermatozoa
dx: low nasal NO levels, bronchoscopy and electron microscopic visulaization of ciliary abnormalities, genetic testing
vs in CF, due to absent vas deferns bilaterally (azoospermia) - CFTR mutation likely responsible for abnormal development of Wolffian structures, resulting in vasal agenesis and defective sperm transport
dx: elevated sweat chloride levels, abnl nasal transepithelial potential difference, genetic testing
93
What are teh pentad of symptoms associated with TTP-HUS
thrombocytopenic thrombotic purpura-hemolytic uremic syndrome is one of the thrombotic microangiopathy synrdomes
pentad: fever, neurologic symptoms, renal failure, anemai and thrombocytopenia in the setting of a GI illness
platelet activation in arterioles and capillaries, diffuse microvascular thrombosis (commonly affecting the brain, kidney and heart), microangiopathic hemolytic anemia with schistocytes, thrombocytopenia
NORMAL PT and apTT (unlike DIC which have increased)
94
Aspirin MOA
aspirin/acetylsalicylic acid is a NSAID that IRREVERSIBLY inhibits Cox1 and cox2 enzymes via acetylation
otehr nsaids reversible inhibit cox1 and cox2
95
causes of gout
presentation - uptake of urate crystals by neutrophils leads to free radical release, cytokine production and joint inflammation
- monosodium urante cystals in the joints and soft tissues. urate crystales under polarized light apepar needle-shaped, negatively birefringent
causes: idiopathic (primary gout), increased urate production (myeloproliferative/lymphoproliferative disorder, tumor lysis syndrome, hypoxanthine guanine phosphoribosyl transferase deficiency), or decreased urate clearance by the kidneys (chronic kidney disease, thiazide or loop diuretics)
96
what portions of the lung are suscepitble to aspiration pneumonia?
while supine - posterior segments of the upper lobes and superior segments of the lower lobes
right main bronchus \> left main brochus due to larger diameter, shorter lengthe and more vertically orientted than teh left
*(swallow a bite, goes down the right)*
upright/semi-recumbent tend to aspirate into the basilar segments of the lower lobes
97
What area of lymph node is more highly populated by the T-lymphocytes
paracortex is the region of the lymph node propulated primarily by T-lymphocytes and dendritic cells
lies in the internal to the cortex, between the follicles and medulla
(area where dendritic cells present antigens from the blood and lymph to teh aggregated T lymphocytes in this region)
becomes enlarged by the proliferation of T lymphocytes during adaptive cellular immune responses (viral infections)
poorly developed in DiGeorge syndrome, due to deficiency of mature T lymphocytes
98
where are B cells located in lympho nodes??
In the outer cortex, the follicles are sites of B lymphocyte localization and proliferation
primary follicles are dense and dormant
secondary follicles have a pale germinal center containing proliferating B cells and follicular dendritic cells
\*in agammaglobulinemia, germinal centers and primary lyphoid follicles do not form due to an absence fo B cells
99
log dose-response curve change with reversible competitive antagonist and noncompetitive antagonist?
Rev competitive antagonist- req higher doses of the full agonist to be present to achieve the same effect at each point along the curve --\> maximum effect does not change, BUT right shift of the response cruve, due to an increase in the ED50 (decrease potency)
Non-competitive --\> shift down
ED50 unchanged / unchanged potency
E max are reduced b/c the non-competitive antagonist has effectively reduced the number of receptors available for binding; depend on teh dose of noncompetitive antagonist
100
what is the association with thymomas?
paraneoplastic syndromes, many autoimmune or endocrine
most common are: myasthenia gravis, pure RBC aplasia, hypogammaglobinemia
101
nitrates MOA?
nitrates --\> NO, which activate guanyl cyclase --\> increase intracellular cGMP --\>
decrease intracellular calcium (deactivate ML kinase)
activation of ML phosphaase --\> dephosphorylation of ML --\> relaxation
102
actions of mifepristone and misopristol in a pregnancy termination?
mifepristone - progesterone antagonist --\> blocking progesterone --\> apoptosis and necrosis of uterine decidua, preventing further development of first trimester
misopristol - prostaglandin E1 anolog --\> cervical softening and uterine contractions
103
what are the important SE of anti-psychotic meds?
1. **extrapyramidal** - acute dystonia (sustained muscle contractions), akathsia (restlessness, inability to sit still), drug-induced parkinsonism (TRAPE)
2. **Tardative dyskinesia** -involutary movements after chronic use (lip smacking, choreatheroid movements)
3. **neuroleptic malignant syndrome** - fever, autonomic dysregulation, mental status changes, rigidity
104
what is the main effect of muscarine toxin?
muscarine is a toxin found in mushroom that acts as muscarinic agonist - its main effects are exerted on M2 and M3 receptors
In the blood vessels, this ---\> vasodilation. Although M receptors are not found on vessles, M3 receptors are found on endothelial surface, which promote NO synthesis, which then diffuses into vascular smooth muscle walls --\> vasodilation and hypotension
In other sites, M3 --\> contraction via activation of G-protein
105
What is DRESS syndrome?
Drug Reaction with Eosinophilia and Systemic Symptoms
sx: fever, generalized lymphadenopathy, facial edema, diffuse rash, eosinophilia and internal organ dysfunction (liver, kidney, lungs), elevated ALT, atypical lymphocytosis
typically occurs 2-8 weeks after exposure to high-risk drugs:
anti-convulsants (phenytoin, carbamazepine), allopurinol, sulfonamides and antibiotics (minocycline, vancocycline)
106
what drugs most commonly cause drug-induced antineutrophilic cytoplasmic-associated antibody vasculities?
hyperthyroidism (PTU, MMI)
hydralazine
sx: constiutional symptoms, athralgias/arthritis, cutaneous vasculitis
107
histology of medullary thyroid CA:
neuroendocrine tumor that arises from parafollicular calcitonin-secreting C cells
characterized by nests or sheets of polygonal or spindle-shaped cells with extracellular amyloid deposits derived from calcitonin (stain congo red)
20% are familial: Men 2 sydromes or Ret germ-line mutation of proto-onco gene
108
gastrinoma etiology?
most are sporadic but 20-30% are associated with MEN 1 (gastrinoma from pancreatic tumor secreting gastrin, zollinger-ellison sydnrome)
109
what is the replication of HBV?
(partially ds-DNA)
double stranded DNA ("repaired") --\> transcription into + RNA template --\> translation of viral proteins and reverse transcription into a ss-intermediate DNA, converted back into a partial ds-DNA, double stranded DNA progeny
*although HepB is a DNA virus, replicated via reverse transcriptase*
110
presentation of fulminant hepatitis / acute viral hepatitis?
significantly elevated aminotransferase levels, increased prothrombin time (due to dec synthesis and function of VII - shortest half life), leukocytosis and eosinophilia
rapid atrophy and shrunken appearance
wide spread centrilobular necrosis
inflammation of the portal tract and parenchyma
\*drug-induced liver injury could be due to inhaled anestheics such as halothane
111
5-aminosalicylates (mesalamine, sulfasazizine)
used to treat inflammatory bowel diseases (crohns, ulcerative colitis)
inhibit cytokine, prostaglandin, leukotriene production during inflammatory states
112
what is the most common cause of E coli bacteremia?
UTIs (both male and female)
Ecoli is the most common cause of UTI's in both healthy adults and elderly pt
special adhesive proteins / fimbriae allow it to colonize and ascend the urinary tract
normal part of GI flora
113
rod shaped intracytoplasmic inclusions?
Auer rods
characteristic of many forms of acute myeloblastic leukemia (AML)
M3 variant of AML associated with (15,17) translocation [PML/RAR fusion --\> abnl retinoic acid R]
114
pathogen of acne:
| (4 major causes)
1. follicular epidermal hyperproliferation
2. excessive sebum production
3. inflammation
4. P. acnes
\*\*note: androgens stimualte both follicular epidermal hyperproliferation and excessive sebum production; **anabolic steroid misuse is a known cause of acne** - suspect in a competitive athlete
115
hypophosphorylated retinoblastoma -\>
prevention of G1/S cell-cycle transition
Rb = tumor suppressor gene that codes for RB/nuclearphospho protein
active Rb = HYPOphosphorylated, preventing damaged cells from proceding from G1 --\> S phase
inactive RB = hyperphosphorylated, allows the cells to go from G1--\> S
Mutations to RB have been linked to: osteosarcoma, retinoblastoma, breast adenocarcinoma, small cell carcinoma of lung, bladder carcinoma
116
What selective medium is required to grow Neisseria spp?
Thyer-Martin
contains: **vancomycin** (inhibits gram pos growth), **colistin** (polymixin, inhibits gram neg growth), **nystatin** (inhibit fungal growth), **trimethoprim** (inhibit gram neg)
117
abusive head trauma (AHT) of a child / shaken baby syndrome
due to vigorous shaking or blunt force
--\> subdural hemorrhage (tearing of bridging veins) and bilateral retinal hemorrhages
additional red flags: posterior rib fracture, inconsistent action (baby rolling) vs age (doesn't really happen unitl like 4 months)
*infants have large heads, enlarged subarachnoid spaces, increased brain water content, decreased cervical muscle tone --\> increased movement of immature brain vs skull --\> tearing of bridging veins and subdural hematoma*
118
what are the four stages of lobar pneumonia:
1. congestion (first 24 hours, lobe is red, heavy and boggy; vascular dilation, exudate includes mostly bacteria)
2. Red hepatization (days 2-3): red, firm-lobe/liver like, airless; alveolar exudate contains mostly neutrophils, fibrin, RBC
3. Gray hepatization (4-6): grey-brown, airless firm lobe; alevolar exudate contains mostly neutrophils, firbin and disintegrated RBCs
4: Resolution : resoration of nl architecture, enzymatic digestion of exudate
119
What part of hearing is lost first with normal aging?
high-frequency, at organ of corti, in the proximal portion of the basilar membrane / closest to the ossicles and oval window
thinnest and least compliant (resp. for high freq)
hair cells here - presbuycusis -
classic for sensorineural loss in older pt
high pitch sounds heard less vs low pitch sounds
120
benzodiazepines vs barbituate action of GABA receptors/chloride channels?
benzos increase frequency
Barbituates increase the duration on the opening of the channels
121
what are TB granulomas made of?
primary granulomas --\> gohn complex with medialstinal hilar adenopathy
primary TB at lower lobe
reactivation TB at upper lobs
made of: aggregations of activated leukocytes - macrophages, CD4 T helper, multinucleated giant cells
122
Ortner syndrome?
when the left atria enlarges to the point of impringing on the left recurrent laryngeal nerve
could be due to mitral stenosis
123
what are the different pericarditis that could occur post-MI?
Pericarditis is a sharp pleuritic chest pain, that could be exacerbated by swallowing and alleviated by leaning forward
Pericarditis within a week could be due to the overlying necrotic segment of the myocardium
after a week could be due to Dresslers syndrome - AI polyserositis provoked by antigens exposed to or created by cardiac muscle injury; pericardium is diffusely inflammed
124
what conditions are usually associated with carpal tunnel?
conditions that reduce the carpal space
pregnancy (fluid accumulation), hyperthyroidism (glycosaminoglycan build up), DM (connective tissue thickening), RA (tendon inflammation), long hx of dialysis (dialaysis-induced amylodosis, as the as the B2-microglobulin accumulate)
Tinel sign- tapping of the flexor surface of wrist produces sx
Phalen sign- flexion of the wrist reproduces sx
125
Whipple sx?
disease that causes joint, GI and CNS symptoms
gram positive actinomycetes
classic histo: small intestine mucosa containing enlarged foamy macropahges packed with rod-shapped bacilli and PAS-positive, diastase-resistant granules (lysosomes with partially digested bacteria)
126
HSP:
IgA-mediated Type III hypersensitivity rxn
systemic vasculities as IgA-immune complex depsities in small vessels
--\> activation of neutrophils and lymphocytes, activation of the complement via the alt/lectin pathway
tx; supportive unless complication arises
self-limiting
127
Hairy Cell Leukoplakia:
lymphocytes with cytoplasmic projections
indolent B-cell neoplasm infiltrate bone marrow and RDS
fibrosis and bone marrow failure --\> pancytopenia
dry tap, splenomegaly
dx: bone marrow biopsy and flow cytometry, which has replaced TRAP (tartate-resistant acid phosphase)
\> middle-aged men
