Deck 6 Flashcards
What meds for diabetes act on SGLT-2 receptors and what is the result? What lab do you need to check before admin?
What are some side effects?
- Canagliflozin and dapagliflozin
- Decr proximal tubule reabsorption of glucose via SGLT-2 transporter
- Check BUN/creatinine first
-SE: UTI and genital mycotic infections 2/2 glucosuria, HoTN from osmotic diuresis
What is the mechanism of digoxin toxicity leading to Vtach and death?
-Delayed after-depolarizations from high intracellular calcium
In an adult with nephrotic syndrome and a malignancy, suspect _______
membranous glomerulopathy
What are the histologic features of membranous glomerulopathy?
- uniform, diffuse thickening of glom. capillary wall, without hyperplasia
- EM = irregular dense deposits that form spikes when stained with silver (IgG and C3)
Positive Latex agglutination test detects the presence of ______.
- Cryptococcal polysaccharide capsular antigen
- LM = budding yeast
What happens to Mitral valve prolapse murmur with squatting?
- diminishes
* Incr venous return and incr afterload –> incr LV volume –> brings valve leaflets into more normal arrangement
What are 2 drugs used to treat HepC?
- IFN-alpha
- Ribavirin
What is the mechanism of action of Ribavirin?
Nucleoside antimetabolite with the following actions
- lethal hypermutation
- inhibits RNA polymerase and IMP DH (depleting GTP)
- defective 5’cep formation
- Modulates more effective immune response
Describe the entire process of Insulin release following Glucose entry into pancreatic beta cells:
- glucose enters via GLUT-2
- undergoes metabolism –> glycolysis –> TCA
- generates ATP
- high ATP/ADP ratio –> closure of K+ channels by ATP-binding
- K+ cannot leave the cell –> cell depolarization
- opening of voltage-gated Calcium channels
- Incr intracellular calcium –> Insulin release
Manifestations of vitamin E deficiency
Normally protects membranes from oxid. damage:
- skeletal myopathy
- spinocerebellar ataxia
- pigmented retinopathy
- Hemolytic anemia
What is the most common cause of aseptic meningitis? How is it transmitted?
- Enteroviruses (echovirus, coxsackie, polio)
- Fecal-oral transmission (ENTERO-viruses)
How does rifampin work?
What about fluoroquinolones?
- Blocks RNA synthesis (not via ribosomes)
- Bind to and inhibit DNA gyrase in bacterial cells —> DNA chain fracture
Why do you have to wait 2 weeks following MAOi d/c to start an SSRI? What happens during this time?
- Avoid serotonin syndrome
- MAOi is re-generated
What is responsible for the delayed clinical effects of antidepressants?
-Down-regulation of post-synaptic Monoamine receptors, decreasing their density within the synaptic cleft
What intubation induction agent can cause life threatening hyperKalemia? In what patient populations especially?
- Succinylcholine
- Burn victims, myopathies, crush injuries, denervating injuries or disease
*happens bc nACh receptors are non selective, so allow K+ efflux as well when acted upon by succinylcholine
What feature in herpes virus confers resistance to nucleoside analogs?
-What are tx options in those cases?
- Absence of viral thymidine kinase (phosphorylating enzyme) –> resistant to Acyclovir, Gancyclovir, Valacyclovir, Famciclovir
- Cidofovir or foscarnet
*cedofovir requires only a cellular kinase rather than a virally-encoded kinase
How is status epilepticus treated?
- First = IV Lorazepam )or other fast-acting benzo)
- simultaneously administer IV Phenytoin (acts on Na channels to reduce their ability to recover from inactivation)
Other than insulin resistance, what can cause acanthosis nigricans?
- Malignancy (GI and GU tracts especially)
- most common is gastric adenocarcinoma
What are some clinical features of a glucagonoma?
- Diabetes
- NECROLYTIC MIGRATORY ERYTHEMA: face, groin, extrem….elevated painful and pruritic rash. Papules/plaques coalesce to form large lesions with central clearing of BRONZE-colored induration
- glossitis, chelitis
- Normocytic, normochromic anemia
- incr glucagon in serum
How would a somatostatinoma present?
- abd pain
- gallstones
- constipation
- hyperglycemia
- steatorrhea
What 3 mutations are associated with early-onset alzheimers?
- Amyloid precursor protein on chromosome 21
- Presenelin 1 on chromosome 14
- Presenilin 2 on chromosome 1
*late onset alzheimers = ApoE4
What are some features of myotonic dystrophy?
- Autosomal dominant
- Trinucleotide CTG repeats with anticipation
- early childhood to late adulthood varied presentation
- Difficulty relaxing handgrip or doorknob
- Cataracts
- Frontal balding
- gonadal atrophy
- Biopsy = Atrophy of muscle fibers, type 1 more affected
WHat is mutated in Li-Fraumeni syndrome? Most common cancers?
- p53…AD…inherited p53 mutation in one allele, need second hit for dz
- Breast, brain, adrenal cortex, sarcomas and leukemias
How do primary CNS lymphomas appear microscopically? most common type
- dense, cellular aggregates of uniform, atypical lymphoid cells
- majority arise from B cells
- diffuse large B-cell lymphoma is most common type
What mutation is associated with MEN2A and 2B? Cells affected by this have what embryological origin?
- RET proto-oncogene
- Neural crest cells!
- these migrate to several locations, including the 4 pharyngeal pouches and adrenal meculla (hence medullary thyroid cancer of parafollicular C-cells, and pheo of mesothelial adrenal cells in medulla)
What translocation is associated with Burkitt lymphoma? What is the function of the resultant protein?
- t(8;14) –> c-myc
- c-myc phosphoprotein is transcriptional activator, controls cell proliferation, diff, apoptosis, etc
What are some derivitive of the 1st pharyngeal arch?
- Trigeminal nerve
- Mandible
- Malleus
- incus
- maxilla
- zygoma
- vomer
- palatine
Which neoplasm has an indolent course, causing waxing and waning painless LAD?
-Follicular lymphoma t(14;18) bcl-2
What is seen in pancreatic cells of pts with type 2 diabetes?
-Amyloid deposition (amylin)
What causes pigmented stones in someone who had recent cholecystitis?
- infection –>release of Beta-glucoronidase by injured hepatocytes and bacteria
- Beta-glucoronidase –> hydrolysis of bili glucoronides –> incr amount of unconjugated bili in the bile –> brown pigment stones
*common in rural asian populations, and usually E. Coli, Ascaris lumbricoides, Opisthorchis sinensis
Kid presenting with fever, gingivostomatitis, and lymphadenopathy….diagnosis? histo findings?
- Primary HSV-1 infection
- Intranuclear inclusions (replicate within host cell nucleus)
How do bisphosphonates work?
Alendronate, risedronate, ibandronate:
- structural analogues of pyrophosphate, an important component of hydroxyapetite
- makes hydroxyapetite more insoluble
- decr bone resorption by interfering with osteoclasts
- poor mucosal absorption…take on empty stomach with lots of water….causes reflux
- unchanged renal excretion
How can nitrates cause a paradoxical increase in myocardial O2 demand? What can overcome this?
- Vasodilation can cause reflex tachycardia, increasing demand
- Beta blockers by slowing AV conduction
- selective CCBs like diltiazem or verapamil may also work, but not as well
What is the pathology of Polyarteritis nodosa? What arteries are SPARED?
- segmental, transmural, necrotizing inflammation of medium to small sized arteries in any organ
- —> ischemia, infarction, hemorrhage
-PAN spares the pulmonary arteries and rarely involves bronchial arteries
What do you give someone with exposure to radioactive isotopes and why?
- Potassium-Iodide
- thyroid takes up Iodine, including radioactive…..so give them normal iodine to compete with radioactive form for absorption in the thyroid gland
WHat is the diagnosis in a kid with “differential cyanosis”, where his lower extremities are affected, but not his upper extremities?
-PDA…..bc happens after branches for UE come off the aorta
Name 3 things that cause LEFT shift of O2-Hgb dissoc. curve, and 3 things that cause RIGHT shift?
Left:
- decr H+ (incr pH)
- Decr 2,3-BPG
- Decr temperature (hypothermia)
Right:
- incr H+ (decr pH)
- incr 2,3-BPG
- incr temperature
How do you calculate clearance in order to calculate FF?
Clearance = Urine conc x Urine flow rate / plasma conc
FF = Creatinine clearance / PAH clearance
What is the clinical presentation of ataxia-telangiectasia? and what are they at great risk for?
- Autosomal recessive
- Cerebellar atrophy –> ataxia early in life (toddler)
- Telangiectasias later
- repeated sinopulmonary infections***
- Great risk of cancer due to inefficient DNA repair –> HYPERSENSITIVITY OF DNA TO IONIZING RADIATION
Who is at risk for psoas abcess and what is the clinical presentation?
- infection of adjacent tissues (appendix), diabetics, IVdu, HIV, immunosuppression
- Fever, back or flank pain, inguinal mass, difficulty walking
- patients will avoid stretching Psoas (psoas sign) so will have hip flexed, externally rotated, etc
What class of antiarrythmics specifically bind rapidly depolarized cells, and is especially good for ischemic tissue (i.e ventricular arrythmias following MI)?
- Class 1B
- Amiodarone, Lidocaine
For prevention of ischemic strokes, ACS, and periph vascular disease…..if a patient cant take Aspirin or clopidigrel due to allergy, what is the next option?? What is a dangerous side effect of this drug?
- Ticlopidine
- Neutropenia (fever and mouth ulcers)
What patients get reactive arthritis with sterile joint aspirates?
- HLA-27 serotypes
- usually after infection with chlamydia, CJ, salmonella, shigella, or yersinia
- Triad: arthritis, conjunctivitis, urethritis
What is the cause of intestinal atresias distal to the duodenum?
- Vascular accidents in utero
- example: SMA obstructed –> apple peel atresia with blind-ending proximal jejunem with absence of a large portion of small bowel and mesentery.
- terminal ileum distal to the atresia assumes spiral formation around the ileocolic vessel
What GI condition would reveal distended macrophages in the intestinal lamina propria on biopsy?
What about Neutrophil collections within the crypt lumina?
- Whipple disease
- UC
After how long of total ischemia to cardiac myocytes does contractility cease? At what point does it become irreversible?
- 60 seconds! –> due to depletion of ATP bc of switch to anaerobic glycolysis, accumulating lactate, etc
- 30 minutes
DCIS is also known as _______, and on histology shows _______
- Comedocarcinoma
- ducts distended by pleomorphic cells with prominent central necrosis
- lesion does not extend beyond the basement membrane
Why dont calcium channel blockers affect the skeletal muscle?
- bc skeletal muscle does not require influx of extracellular calcium for excitation-contraction coupling
- cardiac and smooth mucle cells, however, depend on extracellular calcium entering through voltage gated L-typre calcium channels
In the brain, the putamen lies ______ to the globus palidus?
Lateral
What area of the brain can cause vomiting, ex-when exposed to chemotherapy?
- Area postrema
- chemoreceptor trigger zone, dorsal surface of the medulla at the caudal end of the 4th ventricle
What agent that can be used for depression can also be used to delay the progression of parkinson’s dz? How?
- Selegiline
- MAOi –> type B is inibited –> prevention of MPTP-induced damage of dopaminergic neurons
*lots of times PD tx starts with Selegiline, anticholinergics, and amantadine until they dont work anymore….before starting Levodopa/carbidopa
Other than colon cancer…what other malignancies are associated with Lynch syndrome (HNPCC)?
-type 2 can be assoc. with: endometrial, ovarian, stomach, pancreas, and urothelial tract (carcinomas)
how/why can someone with acute GI bleeding and liver failure develop subsequent hepatic encephalopathy?
- GI bleed –> incr Nitrogen delivery to gut in the form of Hemoglobin
- converted into ammonia –> absorbed into bloodstream
- Ammonia enters liver thru portal vein, where it is normally converted to urea….but liver failure –> failure to convert to urea –> incr serum ammonia –> encephalopathy
Which AAs are ketogenic?
Ketogenic:
-Leucine and Lysine
*phenylalanine, isoleucine, and tryptophan are ketogenic and glucogenic
What is the difference between type 1 and type 2 arnold chiari malformations?
Type 1:
- can present later (adulthood)
- low-lying cerebellar tonsils extend below foramen magnum into vertebral canal
- headaches and cerebellar symptoms
Type 2:
- more serious, presents in neonatal period
- abnormally formed cerebellum and medulla
- both cerebellar vermis and medulla extend into foramen magnum
- medulla compression Sx: diff. swallowing, dysphonia, stridor, apnea
- Lumbar myelomeningocele and hydrocephalus almost always present
What does actinic keratoses look like on histology?
- Hyperkaratosis
- parakeratosis (retention of nuclei in stratum corneum)
- atypical keratinocytes
- may also be pigment or blood vessel irregulaities
*pre-malignant–> small % transform to SCC
What are epinephrine’s effects on adrenergic receptors?
-agonist of a1, B1, B2
- Low doses = predominance of B2 in vasculature –> vasodilation
- High doses = a1 predominates –> vasoconstriction
What are the actions of Isoproterenol on adrenergic receptors? What effects does this have physiologically?
- Non-selective Beta agonist
- Incr HR and contraction force from B1
- Decr vascular resistance from B2
What are the histological characteristics of acute vs chronic renal tpx rejection?
Acute:
-Dense interstitial mononuclear infiltrate
Chronic:
- Obliterative vascular fibrosis (fibrous intimal thickening)
- shrinking of renal parenchyma
- tubular atrophy
- interstitial fibrosis
Describe theophylline intoxication and its treatment:
-Abd pain, vom/diarrhea, arrhythmias (no QT prolongation), SEIZURES (major cause of mortality)
Tx:
- Gastric lavage + activated charcoal and cathartics
- Beta-blockers for arrhythmia
- Benzos or barbiturates for seizures
a majority of pts with acute HepC go on to develop ________
- Stable chronic hepatitis
* closely followed by cirrhosis
Work done against elastic resistance of the lung is increased when the tidal volume is ___________. Therefore, pts with incr elastic force (fibrosis) will _______ tidal volume and have a ________ baseline RR
- increased
- reduce
- higher RR
*Opposite is true for obstructive dz….lower RR with bigger TV
The vascular reaction to endothelial and intimal injury is _________. This is predominantly mediated by ___________ cells that migrate from the media to the intima.
- intimal hyperplasia and fibrosis
- reactive SM cells
*stimulated by injured endothelial cells who release PDGF
What enzyme converts glucose to sorbitol? What about sorbitol to fructose?
CLinical significance?
- Aldose reductase
- Sorbitol dehydrogenase (polyol DH)
- normal pts = normal glucose levels –> ability to convert sorbitol to fructose in the lens–> allows escape
- Diabetes = high glucose –> high Sorbitol which cant leave cells –> sorbitol DH is overwhelmed –> accumulation and incr osmotic pressure –> incr water entry –> cataracts from lens destruction etc
The chemotherapeutic agent _______, causes hemorrhagic cystitis. This happens when it is metabolized in the kidneys to _______, which is excreted in the urine and is toxic to uroepithelial cells.
Administration of _______ along with aggressive hydration, prevents this by _______
- Cyclophosphamide
- Acrolein
- Mesna (2-mercaptoethanesulfonate)
- binds and inactivates the toxic metabolites found in the urine
NE administration causes vascular vasoconstriction via __________, and ++chronotropy and inotropy in the heart via ________.
However, there is reflex bradycardia from vasoconstriction. The end result is _____
- alpha-1 –> IP3 pathway
- Beta-1 –> Gs cAMP pathway
-Combined effect = no change or slight decr in HR
What 2 classes of antiarrythmics cause QT prolongation? Which drug within this class has the lowest risk?
- class 1A and class 3
- Amiodarone (class 3)
What skin lesion, when examined microscopically, shows microabcesses at the tips of dermal papillae?
-Dermatitis herpetiformis
What is the mechanism responsible for Desmopressin/DDAVP’s effects in stopping bleeding?
- Increases release of vWF from endothelial cells
* only helpful for pts with mild vWF deficiency
Squamous cell keratinization is tumors is a sign of _________
-Well-differentiation
What are common lab abnormalities in pancreatitis? (other than lipase/amylase)
- incr WBC
- Hypocalcemia (saponification)
- hyperglycemia from islet destruction
- Hypernatremia (large 3rd space fluid loss and decr fluid intake)
What increases MORE in obstructive lung disease (asthma, COPD, emphysema)…..RV or TLC?
- RV due to air trapping
* TLC does increase too, but in large part bc of incr in RV
In what conditions is holoprosencephaly seen? WHat type of embryologic defect is this?
- Trisomy 13, trisomy 18, FAS
- MALFORMATION (primary defect in the cells/tissues that form an organ)
Mnemonic for cardiac tissue conduction speed?
“Park At Ventura Avenue”
-Purkinje –> Atrial muscle –> Ventricular muscle –> AV node
(fast to slow)
Where are 90% of anal fissures located?
Posterior midline, distal to the dentate line
*longitudinal tear in the mucosa
Which antifungal drugs inhibit ergosterol synthesis, and also inhibit P450?
-Azoles
What hematologic abnormalities can lupus cause? What is the renal pathology in Lupus most commonly look like?
Heme:
- can cause pancytopenia (decr plt, wbc, rbc)
- formation of warm IgG Abs vs cells
Most common nephritis is Diffuse proliferative
The presence of erythroid precursors in liver and spleen is indicative of _______. Bones would show _______
- Extramedullary hematopoesis
- EPO-stimulated marrow cell invasion of organs
- usually from severe chronic hemolytic anemia (e.g = Beta thalassemia)
-Bones = deformities, thinning of cortex, pathologic fractures
Cisplatin chemotx works by _________. Its main toxicity is _______.
How can you prevent its toxicity?
- forming reactive O2 species that can form DNA crosslinks
- Nephrotoxicity!
Prevention:
- Amifostine (free rad scavenger)
- Chloride diuresis
The nerves, arteries, veins, and lymphatics to/from the ovaries are carried in the ________.
The uterine artery is within the _________
- Suspensory ligament
- Transverse cervical (aka cardinal) ligament
Lab abnormalities in DIC?
- decr Platelets
- decr Fibrinogen
- decr factor 5 and 8
- prolonged PT and PTT
Acanthocytes are seen in what disease?
-Spiky RBCs seen in Abetalipoproteinemia
What to suspect in a patient with diffuse pruritic papulopustular rash….with an oxidase positive GNR on culture?
- Pseudomonas
- Hot tub folliculitis
Sympathetic ANS neurons use NE at synapses….what are 2 exceptions to this rule?
- Adrenal glands are directly innervated by pre-ganglionic neurons using AcH
- Sweat glands are innervated by a 2 neuron efferent system using AcH
How are gallstones formed in pregnancy?
- Estrogen –> incr cholesterol synthesis by up-reg HMG-CoA reductase –> bile gets supersaturated with cholesterol
- Progesterone –> reduces bile acid secretion and slows gallbladder emptying
Treatment options for legionella PNA?
Azithro or Fluoroquinolones like Levofloxacin
What are the effects of vit A toxicity?
Acute:
-N/V , vertigo, blurred vision
Chronic:
-alopecia, dry skin, hyperlipidemia, hepatotoxicity, HSM, visual probs, possible papilledema
Teratogenic:
-Microcephaly, cardiac anomalies, fetal death
What is the cause for the following histological findings in arteries/arterioles?
- Transmural inflammation with fibrinoid necrosis
- Medial band-like calcification
- Homogenous acellular thickening of arteriolar walls
- onion-like concentric thickening of arteriolar walls
- Granulomatous inflammation of the media
- Polyarteritis nodosa
- Monckeberg’s medial calcific sclerosis
- Hyaline arteriolosclerosis (is this from DM? HTN?)
- Malignant hypertension
- Temporal arteritis….can also be Takayasu if in the aorta
Which monosaccharides enter glycolysis at each of the following steps:
- G6P
- F6P
- Glyc-3-P or DHAP
- Galactose
- Mannose
- Fructose (bypasses PFK –> faster metab)
What heart murmur may be heard with delayed closure of the tricuspid valve?
-Wide splitting of S1….accentuated by inspiration
