Deck 5 Flashcards
Tetrolagy of fallot results from failure of what embryologic process?
*what other 2 cyanotic heart disease arise from the same type of error?
- migration of neural crest cells into the truncal and bulbar ridges of the truncus arteriosus and bulbus cordis
- These would normally grow grow in a spiraling fashion to separate the aorta and pulmonary arteries
*Truncus arteriosus and TGA
patau syndrome clinical appearance results from defect in what?
- Prechordal mesoderm development
* Non-disjunction in meiosis 1 is original error
The carotid sinus’ afferent fibers run with the ______ nerve, while the aortic sinus’ afferents run with the _______ nerve. They both end up at the ________ nucleus of the ________.
- glossopharyngeal
- Vagus
- Solitary nucleus
- Medulla
WHat are the specific skin findings in dermatomyositis? What about lab findings?
Pts who develop it after age 50 have incr risk of _______
- Grotton papules = red or violaceous, flat topped papules, often with light scale, OVER BONY PROMINENCES, usually over MCP, PIP, and DIP joints.
- Heliotrope rash = erythematous or violaceous edematous eruption on the upper eyelids and periorbital skin
Labs:
- Incr CK
- Positive ANA (antinuclear antibodies), but not specific
- Anti-Jo1 antibodies = specific!
-Over 50 = incr risk of underlying malignancy
What is the triad in Ménière’s disease and how can you differentiate it from a CPA tumor?
- Tinnitus, Vertigo, Hearing loss (caused by incr volume of endolymph)
- pts often also describe a sensation of “fullness”
-It is episodic with exacerbations and remissions! Vs. CPA tumor which would be progressive and constant
What does a carcinoid tumor look like on microscopy?
- Uniform shape and size of cells
- Kind of looks like a fly’s eye
Incr solubility of a gas in the blood require ________ amounts in order to become saturated and affect the brain maximally
*High solubility = ______ blood/gas partitioning coefficient
- Larger
- takes longer to reach desired effect bc more gas must be administered
- incr solubility = High partitioning coefficient
As mitral stenosis becomes more severe, the S2 to opening snap time interval becomes _______
Shorter!
For each of these virion, what is their virulence ability? (what do they bind to?
- CMV = cellular integrins
- EBV = CD21
- HIV = CD4 and CXCR4/CCR5
- Rabies = Nicotinic AcH receptor
- Rhinovirus = ICAM-1
Other than Flagyl and Vanc, what other drug can you use for C. Diff colitis? What are some of its properties?
- Fidaxomicin
- Oral, bacteriocidal, minimal systemic absorption
- used for recurrent c diff (minimal effect on colonic fluora)
Of the HIV structural genes, which one’s product is glycosylated and cleaved in the ER? What does this create?
- Env
- glycosylated to gp160
- Cleaved to gp120 and gp41 —> facilitate virion absorption by target cells
How can HepA virus be inactivated?
- Water chlorination
- Bleach
- Formalin
- UV irradiation
- Boiling to 85 deg for one minute
- Autoclave at 120 deg for 20 minutes
What is the 5 –> 3 and the 3 –> 5 exonuclease activity responsible for?
- 5 –> 3 = removes RNA primers and damaged DNA segments
- 3 –> 5 = proofreading function that removes and replaces mismatched nucleotides on the newly formed daughter strands
A high _____/_______ ratio in the pancreatic Beta cells results in the closure of the ________ channel, which causes insulin secretion by opening the voltage-gated calcium channels.
- ATP/ADP
- Potassium (KATP)
What enzyme serves as a major glucose sensor for the pancreatic Beta cell? It’s increased activty leads to release of insulin, and it is the major rate limitor
-Glucokinase
When is HCG detectable in maternal serum? why?
- no earlier than 6 days after ovulation (sometimes up to 11 days)
- Because successful impantation in the uterus must occur before HCG is detectable in the serum (which takes a few days)
What is the MDR-1 gene in tumor cells, what does it produce, and what does it accomplish?
- Multi-drug resistance gene
- Produces P-glycoprotein, a transmembrane ATP-dependent efflux pump, normally expressed in intestinal and renal tubular epithelial cells
- functions to eliminate foreign compounds from the body
Atheromatous plaque stability depends significantly on mechanical strength of _______. This is made primarily out of _______. Inflammatory macrophages in the intima may reduce plaque stability by secreting ________.
- the fibrous cap
- Made mostly of collagen
- metalloproteinases, which degrade collagen —> weaken fibrous cap
Differentiating DIC with TTP/HUS
DIC:
- Bleeding
- Coag cascade involved (incr PT and PTT)
- Low fibrinogen
- high D-dimer
*All opposite for TTP/HUS
Acute intermittent porphyria is an autosomal ________ condition, caused by deficiency of _________.
- Autosomal dominant
- Porphobilinogen deaminase deficiency (PBG deaminase)
How does acute intermittent porphyria present?
What makes it worse? What makes it better?
- Acutely with variable GI and neurological symptoms…abd pain, vomiting, peripheral neuropathy, neuropsych derrangements
- Reddish urine —-> darkens on exposure to light and air via oxidation of excess PBG
- Worsening factors: upregulating ALA-synthase (P450 inducers, alcohol, smoking)
- Improving factors: Heme and glucose, to tx with IV heme and dextrose
how is TPR calculated in vassels arranged in paralell?
1/TPR = 1/R1 + 1/R2 etc…
- Parallel = total body circulation
- Series = individual organ
Which 2 arteries to other tissues branch off from the splenic artery? Which of these tissues is succeptible to ischemia is the splenic artery is occluded?
- Short gastric A. to the fundus of stomach, and Left Gastroepiploic A. to the greater curvature
- The gastric fundus, bc of poor anastamoses of short gastric artery
- L gastroepiploic has good anastamoses with R. gastroepiploic
Gastric EROSIONS are defined as mucosal defects that do not extend through the ________
- Muscularis mucosa
* Gastric ULCERS penetrate mucosa and go into sub-mucosa
HIT is more commonly caused by _______. Treatment is ______
- Unfractionated heparin compared to LMW heparin
- Direct thrombin inhibitors (Argatroban, Hirudin, Lepirudin)…but obviously 1st stepis to stop heparin
What kind of bias occurs when ther eis significant “loss to followup” which is disproportional (i.e: a greater number of one group was lost) ?
-Attrition bias, which is a form of selection bias
How do you define PAH, and What is the genetic cause for inherited pulmonary arterial hypertension?
- PAH defined as PA pressure > 25 mmHg
- Abnormal BMPR-2 (bone morphogenic protein receptor type 2)….then a second insult (infection, drugs, etc ) —-> PAH
Other than back pain, what systems are affected in Ankylosing spondylitis?
- MSK - Also get enthesitis…pain at insetion of muscles
- Respiratory - enthesopathies of costochondral joints, etc…decr chest wall expansion….MONITOR THIS….rarely fibrosis of lung
- Cardiovascular - ascending aortitis –> dilation of aortic ring with aortic insufficiency
- Eye - anterior uveitis in 30-40% (pain, blurred vision, photophobia, conjunctival erythema)
**remember: RF is negative!!
All protease inhibitors have what side effects?
- Lipodystrophy - central obesity, buffalo hump, etc
- Hyperglycemia - from incr insulin resistance
- Inhibition of P450 (dont use rifampin in pts of HAART…it increases P450 and thus decreases protease ……use rifabutin instead)
The Urachus is a remnant of the _______ that connects the ______ to the yolk sac in fetal life. Failure of the urachus to obliterate by birtch results in patent urachus, and presents with _______
- Allantois
- Bladder
- Urine discharge from the umbilicus
How is Attributable risk % calculated?
ARP = (risk in exposed - risk in unexposed) / risk in exposed
Diff in nucleotides in frameshift vs nonsense mutation?
- Frameshift = deletion of non-multiples of 3
- Nonsense = single base substitution —> premature stop codon
Graft vs host dz usually happens ______ after transplant. Most commonly affected sites are _______
- within one week
- can affect anywhere, but most common is skin, Liver, GI tract
Each MHC class 1 molecule is composed of what 2 things? WHat about MHC class 2?
- Heavy chain
- Beta-2-microglobulin
-Alpha and beta polypeptide chains
WHat is the histology seen in lacunar infarct areas?
- Small vessel Lipohyalinosis and atherosclerosis
- grossly = small cavities filled with clear fluid (5-6 mm)
Dx for someone with fixed segmental loss of UE pain+T sensation, UE lower motor neuron signs, and/or LE upper motor neuron signs….in the setting of SCOLIOSIS?
-Syringomyelia
What is the mechanism of staph scalded skin syndrome?
-Exotoxin acting as protease in the superficial epidermis by cleaving desmoglein in desmosomes
WHat conditions are associated with carpal tunnel syndrome?
- Hypothyroid
- DM
- RA
- dialysis-associated amyloidosis
What is a common mutation in non-small cell lung carcinoma that results in constitutively active tyrosine kinase activity?
-EML4-ALK fusion gene
Integrin-mediated adhesion of cells to basement membrane and ECM involves the binding of integrins to what 3 molecules?
- Fibronectin
- Collagen
- Laminin
Which anti-arrythmics have been implicated with QT prolongation and torsades?
- Quinidine
- Procainamide
- Disopyramide
- ibutilide
- dofelitide
- Sotalol
Describe the findings seen in Pulm Silicosis
CXR:
- Nodular densities, most prominently in Apical region
- Calcified Hilar lymph nodes (eggshell)
Node sampling:
-Birefringent particles surrounded by dense collagen fibers
From what cells does RCC usually originate from?
What are RCC risk factors?
- PCT
- Smoking and obesity
What appetite suppressants have been shown to cause pulmonary hypertension?
- Fenfluramine
- dexFenfluramine
- phentermine
Which drugs for BPH work on the dynamic component of obstruction (muscular tension)? And which work on fixed component (decreasing prostate size)?
- Dynamic = alpha 1 antagonists (terazosin, tamsulosin) –> work in days to weeks
- Static = 5-a-reductase inhibitors (finasteride, dutasteride) –> can take up to 6-12 months to work
What drug is used to treat Hairy-cell leukemia? What class is it in, how does it work, etc?
- Cladribine
- purine analog, resistant to degradation by adenosine deaminase
- able to reach high intracellular concentrations –> incorporated into DNA and causes DNA strand breaks
- Can penetrate the CNS well, excreted in the urine
What structures are in the retroperitoneum?
- major vessels - abd aorta, IVC and their branches
- solid organs - Pancreas (except tail), kidneys, adrenals
- Hollow organs - parts 2,3 of duodenum (part of 4 too), ascending and descending colon, rectum, ureters, bladder
- Vertebral column and spinal muscles
What enzyme is relatively specific to Mast cells, and can be used as a marker of mast-cell activation?
-Tryptase
How is Menotropin useful in the treatment of infertility in women? WHat else is needed after menotropin administration and why?
- Menotropin acts like FSH and forms a dominant follicle
- hCG is then needed in a large dose in order to induce an LH surge –> Ovulation
What is seen in the brain (at autopsy) of a child with PKU?
-pallor of the substantia nigra, locus ceruleus, and vagal nucleus dorsalis
What is seen on muscle biopsy in Polymyositis? WHat lab value is specific?
- inflammation, necrosis, regeneration, fibrosis of muscle fibers
- infiltration of endomysium by macrophages and CD8+ T cells
Lab: Anti-Jo-1 antibodies
When looking at a near object, the lens accommodates….this happens when the the ciliary muscles ______, causing ______ of the zonular fibers, allowing the lens to relax and assume a more ________ shape
- contract
- relaxation of zonular fibers
- Convex shape (lens thickening)
*with age, lens gets less elastic and ciliary muscles weaker —> harder to see close objects
What segment of bowel is ALWAYS involved in Hirschsprung’s disease?
- Rectum and anus
* sigmoid is 75% of the time
The chemotherapeutic effect of methotrexate is overcome by _______ supplementation. This is not true for what similar drug?
- Leucovorin (N-5-formyl-THF)
- 5-FU
What is the presentation of an infant with testicular feminization syndrome?
- Aka androgen insensitivity syndrome
- 46XY infants appear to be phenotypically normal females with blind-ended vaginal pouch and no uterus
How do you calculate maintenance dose of a drug?
Maint dose =
(steady state plasma conc mg/L x Clearance mg/L) / Bioavailability
- for IV drugs, bioavailability can be assumed to be 1
- answer is in mg/min….so need to multiply accordingly (ex: for drug given every 3 hours…..multiply by 60 for 1 hr, then by 3)
What happens on a molecular level to cause Factor 5 Lieden mutation?
-Single AA substitution of glutamine for arginine near the protein C cleavage site on factor 5 gene product
What are treatment options for pts on anti-psychotics who develop Akithisia?
- Decrease dose of antipsychotic
- Beta blockers or Benzos
Describe the steps involved in dysplastic cells eventually invading basement membrane –> carcinoma.
- Detachment
- decr expression of adhesion molecules such as E-Cadherins - Adherence to Basement membrane
- incr expression of Laminin and others - Invasion
- secretion of proteolytic enzymes such as metalloproteinases
- also Cathepsin D protease
Crohn’s dz inflammation is mediated mostly by ______ cells and ______ cytokines
What about UC?
Crohn’s:
- Th-1 T cells
- IL-2, IFN-gamma, macrophages secrete TNF
UC:
- Th-2 T cells
- IL-4, IL-5, IL-6, IL-10
What are the histological findings associated with Hydronephrosis?
grossly:
- dilation and deformation of calices and renal pelvis
- atrophy and scarring or renal parenchyma and distortion of architecture
LM:
- interstitial fibrosis with patches of mononuclear infiltration
- tubular atrophy
- What nerve is damaged in pts with positive trendellenbug sign?
- WHat muscles are innervated by this nerve?
- What does positive trendellenburg look like?
- Superior Gluteal nerve
- Gluteus medius and minimus, tensor fascia latae (stabilize pelvis and Abduct thigh)
- Pelvis sags down on UN-affected side….patients will often lean toward affected side when walking to maintain a level pelvis
What is the clinical presentation of Granulomatosis with polyangitis (aka Wegner’s)?
- Pulmonary
- cough and/or hemoptysis
- focal necrotizing granulomas…sometimes coalesce into nodules and cavitate - Upper resp tract
- chronic sinusitis
- mucosal ulcers and/or granulomas - Renal disease
- RPGN (crescenteric GN)
- no immunoglobs or complement deposits…unlike Goodpastures
What elevated serum marker is diagnostic for Wegner’s?
-c-ANCA
In atelectasis, the trachea deviates ________ the affected side, and in Pleural effusion the trachea deviates ________ the affected side
- Towards
- away from
How do patients with familial Hyperchylomicronemia present? What is the pathology? Associated complications?
- Presents in childhood: marked hypertriglyceridemia, recurrent acute pancreatitis, and milky plasma appearance. Also eruptive xanthomas
- Autosomal recessive, LPL deficiency—> body is unable to clear dietary lipid loads due to defective hydrolysis of serum triglycerides
- No incr risk of premature CAD!! Pancreatitis
What is a common cause of unilateral nasal hemianopia?
-Aneurysm or atherosclerotic calcification of the internal carotid artery —> laterally impinges on optic chiasm
What type of hemoglobin binds poorly with 2,3-BPG?
HgF
-allows it to bind oxygen more avidly
What is the underlying mechanism of a BRAF mutation and what is the result?
What drug targets BRAF mutation?
- Valine replaced by glutamate at position 600 (V600E)
- protein kinase overactivation –> incr signaling pathway stimulus for melanocyte proliferation
-Vemurafenib
What should yu suspect in a pt with sore throat and fever who has Hx of Hyperthyroid?
- Rule out agranulocytosis (caused by PTU and methimazole)
- D/c those meds and check CBC with diff
Why are NSAIDS an inappropriate choice for fever tx in a pt with hyperthyroid?
-They can displace thyroid hormones from binding proteins, thereby worsening thyrotoxic state
Clinical presentation of homocystinuria?
Supplementation with what can significantly improve outcomes?
- Marfanoid, lens dislocation, developmental delay, THROMBOEMBOLIC EPISODES
- Vitamin B6 (required cofactor for cystathionine synthetase) which turns homocysteine into cystathionine
How can you tell EHEC (O157:H7) in the lab compared to other strains?
- Does not ferment sorbitol
- does not produce glucoronidase
*remember: toxin is encoded by a phage
What do the HIV structural genes, gag, pol, and env code for?
gag- nucleocapsid proteins p24 and p7 (group specific antigens in the virion core)
pol - Reverse transcriptase, integrase, protease
env - indirectly encodes envelope glycoproteins gp120 and gp41
What markers are commonly seen in Small cell carcinoma of the lung?
What about non-small cell?
Small cell:
-Neurofilaments, synaptophysin, neuron-specific enolase, chromogranin
Non-small cell:
-EGF-receptors, mucin, surfactant-associated proteins
Do not give _______ to patients with Hyperkalemia from Digoxin toxicity.
- Calcium gluconate
* remember: HYPOkalemia worsens Digoxin toxicity, bc digoxin competes with K+ for Na/K/ATPase
Most common presentation of MEN type 1 is _______
- Hypercalcemia from hyperparathyroidism
- 70% also have endocrine pancreatic tumors, usually gastrin…..but occasionally insulin or VIP
- some will have pituitary adenoma
In acute hepatitis B, what are some of the histologic changes seen?
- ballooning degeneration
- hepatocyte necrosis
- portal inflammation
- cytoplasm filled with spheres and tubules of HBsAg –> cytoplasm takes on FINELY GRANULAR, EOSINOPHILIC APPEARANCE
What are the 3 main groups of veins in early embryonic development, and what do they form?
- Umbilical = degenerate
- Vitelline = veins of the portal system
- Cardinal = systemic circulation
WHat is the histological appearance of Medullary thyroid cancer?
- Uniform polygonal or spindle-shaped cells
- extracellular Amyloid deposits —> stain with congo red
Other than for reducing glutathione, what else is NADPH used for?
- as an electron donor for anabolic reactions like making cholesterol, FA, steroids……also drug metabolism
- High need in liver and adrenals
Why do certain adenocarcinomas cause a hypercoagulable state?
-They produce a thromboplastin-like substance capable of causing chronic intravascular coagulations that are disseminated and tend to migrate
Injections given in the superomedial part of the buttock risk injury to the ______ nerve.
Injections in the superomedial, inferomedial, and inferolateral regions of the buttock risk injury to the ______ nerve
- Superior gluteal
- Sciatic
WHich nerve provides cutaneous sensation to the posterior external auditory canal? What nerve does the rest of the ext aud. canal?
- Vagus nerve
- Trigeminal (V3)
WHat is the pathophysiology involved in formation of an aortic aneurysm from syphyllis?
-Vasa vasorum endarteritis and obliteration –> inflammation, ischemia, weakening of aortic adventitia
In an atheromatous plaque, what provides stimulus for SM to migrate from the media into the intima and for proliferation?
- PDGF
* released locally by platelets, endothelial cells, and macrophages
Which anti-epileptic can cause an exaggerated response to vasopressin?
- Carbamazapine
- dizziness, confusion, hyponatremia
What gives Elastin its characteristic elastic properties? And what are the primary amino acids used for its production?
- Interchain crosslinks involving Lysine
- NO TRIPLE HELIX unlike collagen
- Non-polar AAs glycine, alanine, valine (also proline and lysine…but a lot less than collagen)
What is the progression of EKG changes seen in acute transmural MI?
- Peaked T waves are first sign
- ST elevations within minutes to hours
- Q-waves appear within hours to days
Particles entering the respiratory tract are cleared by different mechanisms based on their size….what are the size categories and how is each one removed?
- 10-15 um –> upper airway trapping
- 2.5 - 10 um –> mucociliary transport
- less than 2 um —> reach terminal bronchiolo and alveoli –> phagocytosis by macrophages
