March 27 Flashcards
cytokines attributing to elevated ESR
IL-1, IL-6, TNF-alpha
elevate acute phase reactant in the liver –> fibrinogen –> erythrocyte stacks (rouleaux) –> increased ESR
lung particle clearance in respiratory bronchioles and alveolar ducts
phagocytosis via alveolar macs
lung particle clearance in bronchi and proximal bronchioles
mucociliary clearance
Succinylcholine
depolarizing blocker @ NMJ (neuromuscular junction)
prevent depolarization of the motor endplate
@ phase I blockade: show content but diminished signal
persistent exposure –> Phase II Blockade: ACh receptors become desensitized and inactivated –> Fade response
Phase II looks like non depolarizing NMJ blockers like vecuronium and pancuronium
Nondepolarizing Neuromuscular junction blockers
vecuronium, pancuronium, tubocurarine
competitive inhibitors of postsynaptic ACh receptor
stimulation demonstrates Fade = progressive reduction of signal strength
due to less ACh release with each subsequent impulse
reversal with Neostigmine!
Dantrolene
relaxes skeletal muscle by blocking Ca++ release from SR
tx for malignant hyperthermia
Mesothelioma
dyspnea and chest pain (Asbestos Exposure) also hemorrhagic pleural effusions
nodular or smooth pleural thickening
histopath: epithelia-type cells joined by desmosomes, abundant monofilaments, long slender microvilli, psammoma bodies
IHC shows +pancytokeratin / cytokeratin
+ calretinin
remember that bronchogenic carcinoma is more common outcome of asbestos exposure than mesothelioma
Pancoast Tumor
Tumor at the lung apex, often in the Superior Sulcus (groove @ subclavian vessels)
shoulder pain radiating toward axilla and scapula
horner syndrome due to involvement with cervical sympathetic ganglia (ptosis, mitosis, anhyrosis)
upper extremity edema due to compression of subclavian vessels
spinal cord compression and paraplegia due to tumor extension into intervertebral foramina
Mechanism of cavitary lesion in TB
macrophages grab bugs -> present on MHCII to CD4+ T-cells –> TNF and IFN-gamma
macrophages release proteases NO and ROS to try and destroy TB –> tissue damage!
macrophages (and neutrophils) also release their lysosomal content (!) in an attempt to digest pathogens but also damage parenchyma
granuloma of macrophages and T-cells –> caseous necrosis and cavitary lung lesion.
Mycoplasma
Lack peptidoglycan cell walls
they are resistant to penicillins, cephalosporins, carbapenems, vancomycin
treat with anti ribosomal agents: tetracyclines, macrolides)
Pulmonary Edema
causes increased alveolar surface tension (opposite of surfactant which decreases the tension and makes inflation easier)
causes decreased lung compliance due to fluid in the interstitial –> swelling.
Reduced pulmonary compliance (causes)
pulmonary edema
surfactant insufficiency
pulmonary fibrosis
Non-maligant results of Asbestos exposure
pleural thickening with calcification of there posterolateral middling zones and diaphragm
calcified lesions = pleural plaques esp @ parietal pleura, esp @ ribs 6-9
generally asymptomatic
oxygen induced hypercapnia
COPD patients have main respiratory drive based on hypoxemia instead of hypercapnia
when you give them a bunch of oxygen their respiratory drive goes down
decreased RR causes hypercapnia (increased CO2)
causes confusion and lethargy - increased dead space ventilation
Cold agglutinins
mycoplasma pneumonias infection
also EBV and hematologic malignancy
Small cell carcinoma
most aggressive
produce ACTH, ADH, and can cause myasthenia syndrome (Lambert-Eaton syndrome)
express neural cell adhesion molecule (NCAM aka CD56) enolase, chromogranin, synaptophysin
metyrapone stimulation test
investigates HPA axis
blocks cortisol synthesis by inhibiting 11-beta-hydroxylase –> reduced cortisol –> ACTH spike
ACTH –> increased production of 11-deoxycortisol –> 12-hydroxycorticosteroids in the urine
DNA viruses
DNA viruses are HHAPPPy
Hepadna Herpes Adeno Pox Parvo Papilloma Polyoma
Herpesviruses
Nuclear Membrane (bud through and acquire the lipid bilayer envelope of the host cell nuclear membrane)
HSV, EBV, CMV, KSV
Cholestasis
dilated bile canaliculi and green-brown plugs and yellow-green accumulation of pigment in the hepatic parenchyma
+striking increase in serum all pos, elevated bili, elevated hepatic transaminases
intrahepatic due to: PBC, PSC, cholestasis due to pregnancy/contraceptives (estrogen), also erythromycin
extra hepatic: choledocholithiasis or malignancy (gallbladder or pancreas)
can cause malabsorption of fats and fat soluble vitamins
Competitive inhibitors
bind at active site
increase Km
Vmax is unchanged, just requires more substrate to get there
GLUT4
glucose transporter on adipose cells
carrier-mediated transport of D-glucose - form of facilitated diffusion
Bacterial Toxin Matching
Inactivates EF-2
C. diphtheria - Diphtheria toxin
Pseudomonas aeruginosa - Exotoxin A
Bacterial Toxin Matching
Inactivates 60S
Shigella - Shiga toxin
EHEC - Shiga-like toxin
Bacterial Toxin Matching
cleave SNAREs
Clostridium tetani - tetanospasmin
Clostridium botulinum - botulinum toxin
Bacterial Toxin Matching
increases cAMP
ETEC - heat labile toxin
Bacillus anthracis - edema toxin
Vibrio cholerae - cholera toxin
Bordetella pertussis - pertussis toxin (microbial survival) –> whooping cough
Bacterial Toxin Matching
massive T-cell activation
Staph aureus - Toxic Shock Syndrome Toxin
Strep pyogenes - Exotoxin A
inter scalene nerve block
gets brachial plexus + phrenic nerve –> ipsilateral diaphragmatic paralysis
S3
filling against stiff ventricle
normal in kids, abnormal in adults
provoked by left lateral decubitus @ end expiration
Side Effects of systemic Glucocorticoids
muscle weakness skin thinning impaired wound healing osteoporosis immunosuppresion
increased hepatic gluconeogenesis and glycogenesis + peripheral insulin antagonism –> hyperglycemia
Primary carnitine deficiency
mild motor delay, hypoglycemia with fasting, muscle weakness, cardiomyopathy, elevated muscle TGs
no carnitine, no fatty acid shuffle from cytoplasm –> mitochondria (via carnitine shuttle)
–> no beta oxidation of fact acids –> liver is unable to synthesize ketones (acetoacetate is a ketone)
extra medullary hematopoiesis (cause)
chronic hemolytic anemia (beta-thalassemia)
Flutamide
competitive testosterone receptor inhibitor (glutamine, cyproterone, spironolactone)
used in the treatment of prostate cancer
tumor size reduction and reduction in symptoms (bony pain and urinary obstruction)
Proximal Convoluted Tubule
resorption of Glucose, Amino Acids, Bicarb
secretion of PAH, Cr, Inulin > urea > Cl-
Osteoprotegerin
blocks interaction of RANK and RANK-L by binding RANK-L –> decreased differentiation and survival of osteoclasts –> decreased bone resorption and increased bone density
(blocks activation of osteoclasts by osteoblasts)
estrogen increases osteoprotegerin - protects the bones
Denosumab does the same thing, binds RANK-L and blocks interaction with RANK
Deficit in N-terminal propertied removal @ collagen processing
Ehler-Danlos variant - deficient in procollagen peptidase
fragile, hyper extensible skin, easy bruising, umbilical herniation
prevents proper collagen cross linking
Collagen Synthesis
Starts in RER
1. hydroxylation @ proline and lysine - VitC dependent
2. Glycosylation of hydroxylysine
3. assembly into pro collagen triple helix
Triple helix pro collagen is then processed in the golgi and secreted into extracellular matrix
4. N and C terminal pro peptides are cleaved off by pro collagen peptidases (pro collagen –> tropocollagen)
5. Tropocollagen fibrils are covalently corsslinked by lysol oxidase
increased cross linking, decreased production, increased breakdown without clearance
produce less and what is there is broken down and left
Ecthyma gangrenosum
Pseudomonas aeruginosa bacteremia
cutaneous necrotic lesions from perivascular invasion and release of tissue destroying exotoxins –> decreased blood flow and patches of necrosis
seen in neutropenia, burns, indwelling catheters
Chronic allograft rejection
obliterative fibrous intimal thickening with scattered mononuclear infiltrate
for kidney: tubular atrophy and interstitial fibrosis
Haptoglobin
serum protein, brings free hemoglobin and promotes clearance
decreases with hemolysis
Protein A
in cell wall of Staph aureus, binds Fc portion of IgG to prevent complement activation, opsonization, phagocytosis
Vessel posterior to duodenal bulb (prox 1/4)
gastroduodenal artery
CYP Inhibitors
Cimetidine Ciprofloxacin Erythromycin Azole antifungals grapefruit juice Isoniazid Ritonavir / Protease Inhibitors
CYP inducers
carbamazepine phenobarbital phenytoin rifampin griseofulvin
Porphyria cutanea tarda
deficiency in Uroporphyrinogen decarboxylase
vesicles and erosions on the dorsum of the hands
Acute intermittent porphyria
deficiency in Porphobilinogen deaminase
accumulated porphobilinogen, ALA
Painful abdomen Port-wine colored urine Polyneuropathy Psychological disturbances Precipitated by drugs
Proteasome inhibitors
bortezomib - moronic acid dipeptide
tx for multiple myeloma
cause accumulation of toxic intracellular proteins that can no longer be degraded by the proteasome
inhibition of proteasome –> induced apoptosis (of malignant plasma cells)
Huntington’s Disease
trinucleotide repeat disease at CAG
atrophy of caudate nucleus > putamen and frontal lobes
striatum = caudate + putamen
atrophy of caudate and putamen
Huntingtons
atrophy of substantia nigra
Parkinsons
Polymyositis
symmetrical proximal muscle weakness
increased expression of MHC-I on the sarcolemma –> CD8+ infiltrate
biopsy shows: inflammation, patchy necrosis and areas of fibrosis + infiltration with macrophages and CD8+ T-cells
+ANA and anti-Jo-1
Arachnoid granulations
site of CSF reabsorption
subarachnoid space –> arachnoid granulations –> venous sinuses
Flow of CSF
lateral ventricles inter ventricular foramen of monro third ventricle cerebral aqueduct fourth ventricle foramina of Luschka and Magendie Subarachnoid space arachnoid granulations venous sinuses
CYP oxygenase (aka)
microsomal monooxygenase
responsible for metabolism of steroids, alcohol, toxins, foreign substances
Associated condition with Downs
duodenal atresia, hirschprung, imperforate anus, tracheoesophageal fistula, celiac disease
AV septal defect (endocardial cushion)
VSD and ASD
ALL, AML (15:17)
Alzheimers
Rosenthal fibers
Pilocytic Astrocytoma
well circumscribed, posterior fossa tumors with solid+cystic components
GFAP+
“spindle cells with hair-like glial processes associated with micro cysts”
Homer-Wright rosettes
Medulloblastoma
highly malignant cerebellar tumor from neuroectoderm
compresses 4th ventricle and causes obstructive hydrocephalus
Stress incontinence
urethral sphincter dysfunction
Primary Biliary Cirrhosis
Middle-aged women - associated with other autoimmune conditions (Sjögren, CREST, RA, celiac)
autoimmune reaction –> lymphocytic infiltrate + granuloma –> destruction of interlobular bile ducts
pruritus, fatigue, HSM, xanthomatous lesions @ eyelids/skin/tendons –> jaundice, steatorrhea, portal HTN
Clozapine
second gen antipsychotic for treatment-resistant schizophrenia +/- suicidality
ARD: agranulocytosis - Monitor WBC!
seizures, myocarditis, metabolic syndrome
Analgesic Nephropathy
NSAID induced
Chronic interstitial nephritis: patchy interstitial inflammation, fibrosis, tubular atrophy, papillary necrosis, calcium deposition
bilateral shrunken and irregular kidneys with papillary calcifications
Argatroban
Direct thrombin inhibitor
Ticlopidine and Clopidogrel and Prasugrel
inhibit ADP mediated platelet aggregation
ADP induces expression of GpIIb/IIIa (binds fibrinogen)
Dipyridamole and Cilostazol
inhibit PDE activity and increase cAMP - decreased platelet aggregation
Abciximab, eptifibatide, tirofiban
inhibit GpIIb/IIIa directly
alpha-helix –> beta-pleated sheet
hydrogen bonding
HSV1 cencephalitis
edema and hemorrhagic necrosis of the temporal lobe
headache, fever, mental status changes, seizures, aphasia, *personality changes: hyper sexuality, aggression
bilateral hemorrhagic necrosis of temporal lobes
Rituximab
anti-CD20
Infliximab
anti-TNF-alpha
Abciximab
anti-GPIIb/IIIa
Ulcer in the distal duodenum
Neoplasm!
Zollinger-Ellison syndrome = Gastrinoma
secretin paradoxically stimulates gastrin release from gastrinomas
Complications of Wilson’s Disease
neuro disease (atrophy of basal ganglia, dysarthria, dystonia, premier, parkinsonism)
liver disease (hepatitis, acute liver failure, cirrhosis, hepatocellular carcinoma)
hemolytic anemia
renal disease (Fanconi syndrome = defect in resorption at PCT, lose amino acids, glucose, HCO3- which are normally resorbed)
low serum ceruloplasmin
Neuron Markers
Synaptophysin: found in presynaptic vesicles of neurons
neurons are GFAP NEGATIVE
(glial cells are GFAP +, glioblastoma, oligodendroma, ependymoma)
GFAP = glial fibrillary acidic protein
Esophageal Varicies and normal liver biopsy
Portal vein thrombosis
Elevated PT
Factor VII - Extrinsic pathway issue
Elevated PTT
Factor VIII and IX, XI
Hemophilia A, B, C
Li-Fraumeni Syndrome
TP53 dysfunction
Sarcoma
Breast Cancer
Brain Tumor
Leukemia
Autosomal Dominant LOH disease
Acute Neuronal Injury
Red Neuron
shrinkage of cell body
Pyknosis of the nucleus
Loss of Nissl substance
Eosinophilic cytoplasm
results in cell death due to trauma
Axonal Reaction
Enlargement of cell body
eccentric nucleus
enlargement of nucleolus
dispersion of Nissle substance
loss of axon
Neuronal Atrophy
loss of neurons and functional groups of neurons
reactive gliosis
degenerative disease
extensive lymphocytic infiltration and granulomatous destruction of interlobular bile ducts
Primary Biliary Cirrhosis
long history of pruritus and fatigue with pale stools and xanthelasma
Lesion to cerebellar vermis
truncal ataxia
deep inguinal ring
transversals fascia
superficial inguinal ring
external oblique muscle aponeurosis
Jugular Foramen
CN IX
CN X
CN XI
Jugular vein
Hemolytic Uremic Syndrome
elevated serum indirect bilirubin
Ankylosing spondylitis
HLA-B27
low back/hip/buttock pain
anterior uveitis –> pain, blurred vision, photophobia
monitor disease with degree of chest expansion (disease limits chest expansion and spinal mobility)
How to calculate bioavailability (F)
F = Bioavailability AUC = area under curve
F = (AUC oral x dose IV) / (AUC IV x dose oral)
E. coli Virulence Factors
LPS
K1 capsular polysaccaride
Verotoxin = Shiga-like toxin
P Fimbriae
LPS –> IL-1, IL-6, TNF-alpha - bacteriemia & septic shock
Capsule –> prevents phagocytosis and complement lysis - neonatal meningitis
shiga-like toxin –> inactivates the 60S rRNA - bloody gastro
fimbriae –> adhesion to uroepithelium - UTI
Why do alcoholics get fatty livers?
increased NADH
decreased free fatty acid oxidation
Effects of inhalation anesthetics
decrease hepatic blood flow decrease GFR, decrease RPF increase cerebral blood flow respiratory depression mucociliary clearance decrease decreased CO and increased atrial and ventricular pressures
cause hypotension
Wiskott Aldrich
WATER
Wiskott Aldrich Thrombocytopenia Eczema Recurrent infections
ANP and BNP
cause vasodilation by binding ANP receptors –> guanylyl cyclase –> increased cGMP
Main mechanism of combined OCPs
reduce serum gonadotropins
suppress GnRH –> inhibition of ovulation
poor platelet aggregation in the presence of ristocetin
decreased vWF (like in vWD)
MOA pulmonary HTN due to LV hypertrophy?
vasoconstriction due to pulmonary venous congestion
high pressure –> endothelial damage and capillary leakage –> decreased NO –> increased endothelin –> vasoconstriction and increased vascular tone –> remodeling and smooth muscle proliferation
IL-10
anti-inflammatory
inhibits TH1
reduces MHC-II
suppression of activated macrophages and dendritic cells
CREST
Calcinosis Raynaud Esophageal dysmotility - fibrous replacement of muscular in the LES --> heart burn Sclerodactyly Telangiectasia
Charcot-Bouchard aneurysm
due to HTN
at basal ganglia, cerebellum thalamus, pons
intracerebral
neuro deficits –> headache
Saccular (berry) aneurysms
due to ADPKD, Ehlers-Danlos, HTN
at circle of willis
subarachnoid
sudden severe headache; focal deficits UNCOMMON
Sign of Leser-Trélat
sudden onset multiple subhorrheic keratoses –> GI/Visceral malignancy
Manifestations of Thymoma
Myasthenia gravis
pure RBC aplasia - anemia with low retics
good syndrome= hypogammaglobunlinemia
