Question Log Flashcards
Acute onset CVP elevation, together with HOTN and tachycardia, can occur with what conditions?
cardiac tamponade or tension pneumothorax
Acute onset HF following viral illness should make you think?
dilated cardiomyopathy caused by viral myocarditis, which manifests as LV/RV dilation, mitral/tricuspid regurg, inc. ESV/EDV in LV
*unless there’s a high systolic pressure gradient between LV and aorta, because then that suggests LV outflow obstruction
Acute transplant rejection time frame and histopathology
1-4wks post-transplant; dense lymphocytic infiltrate in the interstitium of the organ
Aldolase B is part of what pathway?
Fructose (and Sucrose which can become fructose); Fructose to F-1-P is by Fructokinase, then F-1-P to Glyceraldehyde or DHAP is by Aldolase B
Alveolar transmural pressure and Intrapleural pressure
ATP is always positive; at FRC the airway pressure is 0 and there’s no force for bringing air in or out; at FRC the chest wall tendency to open and the lung tendency to collapse results in intrapleural pressure being about -5 cmH2O
Anti-Smith Ab - what does the Smith protein do?
Ab associated with SLE; the Smith protein complexes with snRNA to form a spliceosome, which cuts out introns from mRNA before it leaves the nucleus
Aortic stenosis, Afib, and Pulmonary edema
AS –> LVH –> dependent on atrial strength to fill up LV
Afib –> less likely to fully fill LV –> blood backs up into lungs –> pulmonary edema
Bilirubin metabolism pathway
Heme –[Heme Oxygenase]–> Biliverdin (green) –[Biliverdin reductase]–> Unconj Bilirubin –[Glucoronyl transferase]–> Conj bilirubin (liver) –[bacterial dehydrogenase]–> Urobilinogen (gut) –> Stercobilin –> brown color to feces
Bleeding from the nipple, think -
intraductal papilloma
Calculating resistance in parallel circuits
1/Rt = 1/R1 + 1/R2 + … 1/Rn
Can histamine antagonists be used in asthma?
Histamine antagonists are ineffective in asthma
Causes of dilated cardiomyopathy
Coxsackie B viral myocarditis, peripartum, alcoholism, thiamine def/wet beriberi, cardiotoxic drugs, chronic SVT
Causes of polyhydramnios
“decreased swallowing: esophageal/duodenal obstruction, intestinal atresia, or anencephaly
increased fetal CO: fetomaternal hemorrhage, Parvo infxn, alloimmunization”
CCBs’ effect on pacemaker cells vs. cardiac myoctes
“PM cells: will decrease/slow the Ca channel opening and thus Ca deolarization; this decreases the rate of firing of the SA and AV nodes
Myocytes: will decrease the opening of Ca channels, decrease the IC [Ca], and thereby reduced the excitation-contraction coupling”
Cells of bronchial epithelium
distal to terminal bronchioles = MPs; proximal is all lined with ciliated epithelium
Characteristics of mesothelioma
epithelioid neoplasm of the serosa, joined by desmosomes and have abundant tonofilaments with long slender microvilli; hemorrhagic pleural effusions are frequent and on CXR will see nodular or smooth pleural thickening
Cherry-red macula - ddx?
Hyphenated: Niemann-Pick (HSM; foam cells) and Tay-Sachs (tay-six; NO HSM; onion skin lysosome)
Clinical Triad: acute neuro abnormalities, hypoxia, and petechial rash on chest (following long bone fracture/surgery)
fat embolism to lungs
Common cause of pigmented stones
excretion of large amounts of conjugated bilirubin into bile, which is then deconjugated by beta-glucuronidase, causes pigmented stones; large amounts of bilirubin may result from chronic hemolysis, and lots of deconjugation (making it available for stones) is done by beta-glucuronidases which often come from bacteria and HCs injured in infection
COPD causes increase or decrease in FRC/TRV?
increase - because air is trapped
Cystic fibrosis - effects on pancreas and absorption
pancreas is damaged in CF, so ADEK are less absorbed; avitaminosis A is most likely to contribute to squamous metaplasia of the exocrine ducts in pancreas
DDx for painful thyroid nodules
De Quervain granulomatous thyroiditis - follows infection, self-limited, may start as hyperthyroid but ends up hypothyroid; will see early inflammation but the main thing is granulomas
Medullary thyroid carcinoma may also present as neck pain; pain here is more likely than in papillary thyroid carcinoma
Describe Myeloma cast nephropathy
when a pt has MM, there’s an overproduction of Bence Jones proteins (light chains) which are filtered by the glomerulus then reabsorbed in the tubule, but when it reaches limit for reabsorption the light chains are stuck in the tubule and end up forming casts with Tamm Horsfall proteins; when peed out these casts stain intensely pink (eosinophilic)
*Not to be confused with eosinophils in the urine (drug-induced interstitial nephritis)
Describe the shape and pH of the 4 types of kidney stones
- Ca oxalate - acidic pH, square envelopes (if Ca phosphate then basic pH)
- AMP - basic pH, coffin lids, from infxn with urease+ bugs (staghorn in adults)
- Uric acid - acidic pH, rhomboid or rosettes (radiolucent - unique)
- Cystine (aa) - acidic pH, hexagonal (staghorns in kids)
Differentiating between coarctation of the aorta and PDA?
coarctation will present with BP discrepancy, PDA will present with distal extremity cyanosis
DNA polymerase III has what activity? DNA pol I has what activity?
“Pol III: 5’–>3’ synthesis; 3’–>5’ exonuclease
Pol I: same as pol III but also removes RNA primer and replaces with DNA”
Does Cushing’s/excess ACTH cause hypertrophy or hyperplasia of (what level of the adrenal cortex)?
Hyperplasia of the fasciculata and reticularis (can be diffuse or nodular)
Doxorubicin AE on heart?
dose-dependent cardiotoxicity that produces dilated cardiomyopathy
Eccentric vs Concentric LVH
both are types of hypertrophy in response to an increased load; concentric is when the muscular wall gets bigger and thicker in order to pump against inc. afterload (like Aortic stenosis); eccentric is when the ventricle gets bigger and dilated in order to deal with the increased preload (like aortic regurgitation)
Effect of sex steroids on bone growth
Initially increase linear growth; also encourage closure of the epiphyseal growth plates
Effects of insulin
“promotes synthesis of TGs, glycogen, nucleic acids, and proteins
inhibits gluconeogenesis and glycogenolysis”
Explain endothelium-dependent vasodilation
“1. stimulus (including ACh, bradykinin, shear stress, substance P, and serotonin) induces rise of IC Ca
- inc. Ca induces ENOS which converts Arginine + O2 –> NO + citrulline
- NO diffuses over to smooth muscle where it stimulates GC
- active GC converts GTP to cGMP which activates pKG which reduces IC Ca and causes relaxation of the smooth muscle”
Explain hormones involved in anovulatory cycles
without ovulation there’s no progesterone, there’s just a cyclical rise/fall in estrogen; this means that the endometrium is perpetually proliferating, and bleeds whenever it become unstable and outgrows its own blood supply, instead of on a regular cycle. Results in irregular/longer menses.
Fabry’s Disease
XLR deficiency of alpha-galactosidase A; ceremide trihexosidase accumulates; angiokeratomas, peripheral neuropthy, hypohydrosis, and eventually renal failure; differentiate from Krabbe by the angiokeratomas
Factors that make a LVOT murmur louder
“decreasing the preload or afterload - this decreases the size of the LV and brings the mitral and aortic valves closer which is part of the LVOT obstruction; this is what causes SCD in pts with HCM
*Anything that increases preload or afterload - like squatting, passive leg raise, or sustained hand grip - would decrease murmur intensity”
Fate of K+ in the renal tubules
All of it is filtered; 65% reabsorbed in the PCT; 35% reabsorbed in the TAL (NaKCC); DCT/CD regulates final concentration of K - if low then it will reabsorb, if normal/high it will secrete K+
For a patient in afib, what is the determining factor for ventricular rate?
AV node refractory period - this is the RLS since they will get signals and pass them on, it just won’t be organized signals, so they pass them on as fast as they can
bronchogenic carcinoma is #1 malignancy and
for asbestos exposure:
mesothelioma is rare; can also see pleural plaques, pulmonary fibrosis, and asbestos bodies
Gallstones in pregnancy
high estrogen causes upregulation of HMG-CoA reductase and thus the bile is hypersaturated with cholesterol, plus progesterone causes gallbladder hypomotility – resulting in cholesterol stone formation; can have same effect from OCPs
Gaucher’s disease
deficiency of glucocerebrosidase; glucocerebroside accumulates; triad = HSM, avascular necrosis of femur (severe hip/knee pain, aka Legg-Calve-Perthes disease) and osteoporosis, specific finding of MPs that look like crumpled tissue paper (Gaucher cell), yellow-brown skin pigmentation (non-specific); “young patient with easy bruising and anemia/pancytopenia, joint pain, MASSIVE liver and/or spleen, diffuse petechiae”
von Gierke disease
GSD type I - missing G-6-phosphatase, can’t get glucose OUT of the liver
Respiratory/metabolic changes in high alititude
high altitude –> hyperventilation –> blow off CO2 –> respiratory alkalosis –> kidneys secrete bicarb
Gout presents as what type of joint reaction?
acute inflammatory process; therefore treat with NSAIDs aimed at reducing PGs/NTs or Colchicine which inhibits NT activation and migration
Hepatosplenomegaly - ddx?
Gaucher (hip/knee pain), Niemann-Pick (cherry red macula), Hurler’s (gargoylism, cloudy corneas) and Hunter’s (gargolyism + aggression, no cloudy corneas)
Hgb subunits? Myoglobin? O2 dissociation curve of each
Hbg subunits = 2 alpha and 2 beta, each has a heme group; Myoglobin = monomer, 1 heme (so basically just like 1 beta subunit of Hgb); O2 dissociation curve is sigmoidal for Hgb because of the multi-heme interactions while it’s straight up and asymptote near 100% for myoglobin/monomer
High estrogen comes from where and causes what?
“thickened endometrium” - think high estrogen; if ovarian mass too - granulosa cell tumor; then look for Call-Exner bodies (description: cuboidal granulosa cells in a rosette pattern with coffee bean nuclei)
Histological presentation of kidneys following RAS
the one with the stenotic artery will be smaller and the other one will be bigger due to compensatory hypertrophy
Holosystolic murmur that increases in intensity during inspiration
tricuspid regurgitation
How are parasites killed by eosinophils?
the parasites are first covered by Abs; the eo’s then bind those Abs with their Fc receptors and that causes them to degranulate their MBP; this is a form of ADCC
How do you get neurological sx from hyperventilation?
tachypnea –> hypocapnia –> vasoconstriction (has to do with pH) –> decreased ICP
hypocapnia during hyperventilation causes neuro sx, it also causes vasoconstriction (related? dunno)
How does CHF affect lungs?
well of course you get a transudate into the interstitium, but the real effect of this is that the lung compliance is decreased because there’s distortion and swelling in the tissue and it’s harder to open the lung; creates the same net effect as pulmonary fibrosis and insufficient surfactant
How does depolarization happen in the 3 major muscle types?
“Cardiac: depolarization opens L-type CaCh, influx opens the RyR2 receptor in the SR which releases more Ca to bind troponin to let actin and myosin interact
Smooth: same as cardiac except instead of Ca binding troponin, Ca binds calmodulin and this lets actin and myosin interact
Skeletal: L-type CaCh interact directly with the RyR1 receptors and don’t need an influx of Ca to open it, then Ca binds troponin and actin/myosin interact”
How does GH make someone taller?
It acts to increase the IGF being released from the liver, which has the direct growth effects
How does PAH get cleared?
majority is filtered in glomerulus but then a lot is secreted by the PCT; none is reabsorbed
How does silicosis affect MPs?
damages them; thought that the MP eat the silicon fibers and break
How long does it take after birth for PVR to decline enough to hear a left-to-right shunt murmur?
4-10d
How to calculate the RBF using PAH?
RBF = PAH clearance = (Urine PAH * Urine Flow rate) / [PAH in plasma]
–> be careful if they give you a serum concentration; then you have to convert: Plasma = 1 - Hct
How to differentiate an Granulosa cell tumor and a Sertoli-Leydig cell tumor?
GCT –> Estrogen which will produce ABNORMAL uterine bleeding 2/2 endometrial hyperplasia, and precocious puberty
SLCT –> Testosterone which will produce virilization meaning AMENORRHEA, deep voice, hirsutism, clitoromegaly
How to differentiate dermatitis herpetiformis from atopic dermatitis that is triggered with eating certain foods?
DH is going to occur in 4-5th decade; AD typically presents in infants and usually before age 5
DH usually affects the buttocks/extensor surfaces; AD in infants will involve scalp/extensor surfaces but spare the diaper area, then in older kids will affect the flexor surfaces
DH is associated with Celiac disease, which also has LC infiltration, crypt hyperplasia (not crypt abscesses - that’s UC), and loss of villi which would make for malabsorption/steatorrhea.
AD is associated with asthma and allergic rhinitis = allergic triad.
How to recognize a pulmonary abscess
if the abscess communicates with an air passage there will be partial drainage enough for an air cavity to form which can be seen on CXR; this abscess is forming because of release of lysosomal enzymes from the dying NTs/MPs; there can also be an air-fluid level on imaging.
Symptoms = night sweats, fever, weight loss, and productive cough with foul-smelling sputum
Hypocapnia implies
alveolar hypoventilation (assuming constant rate of CO2 production)
In a patient with dementia, prior stroke, and PNA, what is the most likely cause of the PNA?
aspiration (can lead to septic shock, lactic acidosis)
Incontinence and DM1
think diabetic autonomic neruopathy–affecting detrusor muscle; also don’t feel the urge and can’t empty completely, with difficulty starting/stopping
Ivabradine
selectively inhibits funny sodium channels in the SA node cells, thereby slowing HR; it’s the only drug that has NO effect on contractility or relaxation; used in treatment of HF (reduces the risk of hospitalization)
Kidney stones and Calcium levels
#1 reason for kidney stones is hypercalciuria - makes sense because if you have too much Calcium then your body tries to dump it in the kidneys, instead of leaving it in circulation for that reason there's normal serum calcium levels
Know what direction glycolysis goes when you have high Fructose
down glycolytic pathway
Law of Conservation of Mass - as applied to a blood vessel that gets smaller
Qin = Qout --> V1*A1 = V2*A2 Q = flow; V = velocity; A = diameter of vessel
Mainstem bronchus lesion
from obstruction of the bronchus you get air trapped in the lung, then it all gets absorbed into the blood; when no more air in the alveoli –> atelectasis; trachea deviates toward side of lesion because of lower pressure when lung collapses
Major basic protein is for
for parasites, as it’s “anti-helminth”
Man with testicular tumor and hyperthyroidism - likely diagnosis?
Choriocarcinoma - because this tumor secretes hCG, the alpha subunit of which is similar between hCG, TSH, FSH, and LH (may also see gynecomastia)
Midline episiotomy will involve what structures?
vaginal lining/mucosa and perineal body
MOA of the CFTR
CFTR uses ATP hydrolysis
most common benign pulmonary lung tumor:
hamartoma - “popcorn calcifications” with islands of mature hyaline cartilage
Most frequent mechanism of SCD following MI/coronary artery occlusion
V-fib
Neurophysins
carrier proteins for ADH/oxytocin to move them down to the nerve terminal for release in posterior pituitary
Normal Pressures in cardiac cath
SVC/RA: 1-6mmHg RV: systolic is 15-30mmHg PA: diastolic is 6-12mmHg Pulm wedge: 6-12mmHg (~PA diastolic) LA: 10mmHg (higher in mitral regurg) LV: ~120mmHg (same as aorta)
Pancoast tumor is also called:
Superior Sulcus tumor
Pancreatitis is a major risk factor for what lung disease?
ARDS
What size particle are dealt with by mucociliary transport in the respiratory tract?
2.5-10 micrometers = mucociliary transport
Pentad of sx makes you think:
fever, neuro sx, RF, anemia, thrombocytopenia in the setting of GI illness
TTP-HUS or another thrombotic microangiopathy
Peripheral neuropathy (LSD) - ddx?
“EE”: Fabry (angiokeratoma) and Krabbe (optic atrophy)
Phenylalanine metabolism pathway
Phenylalanine –> Tyrosine* –> DOPA (–>melanin)
Can’t convert to Tyrosine = PKU
Can’t convert to DOPA = Albinism
*Tyrosine –> Homogentisate ->->-> Fumarate
Can’t convert Homogentisate = Alkpatonuria
Problems limited to the right heart - think
carcinoid syndrome (and most commonly, serotonin/bradykinin)
PRPP is an enzyme where?
in the purine/pyrimidine synthesis pathway; without it you get gout (deposition of needle-shaped, negatively birefringent crystals in joints)
Ras-Raf-Mek-Erk-TF - what activates Ras?
Ras is a G-protein that gets activated when it binds GTP; it’s inactivated form is when GTP is cleaved into GDP and it hangs out like that; a mutated Ras may never again cleave GTP into GDP and thus would be constitutively active always, leading to continuous proliferation/cancer
Rate of Inulin clearance best approximates ?
GFR
Ratio of phosphatidylcholine (aka lecithin) to sphingomyelin in amiotic fluid?
approximately 1:1 until week 35 (3rd trimester) when lecithin will rise sharply as fetal lungs start to produce surfactant; will rise to 2:1 or higher
Reactive arthritis - how to recognize it?
since it’s a seronegative spondyloarthropathy, look for a single involved joint about 1-4wks following an infection; may also have the other symptoms of conjunctivitis and urethritis; associated strongly with HLA-B27, but not serum markers
*Reactive arthritis may also involved sacroiliitis, dactylitis, hyperkeratotic vesicles on palms/soles, dermatitis of glans penis (circinate balanitis), and oral ulcers
Relationship between Ca and granulomatous disease
activated MPs (in granulomas) can express 1-alpha-dehydroxylase which will activate Vit D and increase Ca, independent of PTH
Relationship between PTH, Vit D, Ca, PO4, and Mg
low serum Ca or Mg will inc. PTH; really high Mg will dec. PTH; when PTH is secreted it will tell kidney to retain Ca and dump PO4 because PO4 likes to bind up free Ca; diarrhea will cause low Mg
Retinopathy of prematurity
when a baby is born premature and they have hypoplastic lungs they will be treated with O2 and/or CPAP; the hypoxia however will induce angiogenic factors in the retina, which start neovascularization when there is sufficient O2 (like when the nurse gives it) and all the neovascularization will increase the risk of retinal hemorrhage/detachment, hence retinopathy (this is a major cause of blindness in developed countries)
Roles of HGPRT and PRPP in purine synthesis
HGPRT is purine salvage and PRPP is de novo synthesis; so in the case of Lesch-Nyhan when you’re missing HGPRT you can’t keep up with all the purines that need recycling and they get shunted/stuck as Hypoxanthine/Guanine, Xanthine, and Uric acid
Signs of normal aging in the heart
sigmoid shaped ventricular septum, increased interstitial collagen/CT, and accumulation of brown cytoplasmic granules containing lipofuscin (wear and tear pigment)
Sorbitol pathway
“Glucose –> Sorbitol –> Fructose
Aldose reductase / Sorbitol dehydrogenase”
Theca cells make?
Granulosa cells make?
TAGE
Theca –> Androgens
Granulosa –> Estrogen
Thionamide induced agranulocytosis
both methimazole and PTU can produce agranulocytosis; so if a patient has fever and sore throat get a WBC with differential to rule out agranulocytosis and probably stop the drug asap; this side effect makes radioactive iodine the preferred treatment for hyperthyroidism (including Grave’s disease)
Thoracic outlet syndrome
presents as numbness, tingling, weakness, and maybe swelling (if vein involved) of the upper extremity; outlet is most commonly obstructed at the scalene triangle (formed by ant and middle scalenes and the first rib)
Thymomas or thymic hyperplasia is associated with what disease of bone marrow?
pure red cell aplasia - the thymus makes T cells that then develop a destructive affinity for RBCs only (via IgG or CTLs); this could also be due to Parvovirus B19 infection
Total PVR is lowest at ?
lowest = FRC; at max inspiration the alveoli are full of gas and put pressure on the capillaries; at max expiration there’s lots of intrathoracic pressure on the capillaries; so happy medium is where you’re not breathing in or out
Transient myocardial ischemia causes cells to increase in size. What happens?
decreased O2 causes cell to switch to anaerobic metabolism, but can’t make as much ATP so the Na/K ATPase in the membrane fails, as well as the Ca-ATPase in the mitochondrial membrane; this build up of IC Na and Ca is bad for the cell and causes swelling - the primary cause of the increased size
Failure of the SR to sequester Ca results in decreased contractility of the muscle
What aa’s anchor a protein into the cell membrane?
nonpolar, hydrophobic aa’s like: ala, val, leu, phe, tryp, met, pro, gly
What are the 2 ways to represent CO?
CO = SV * HR = O2 consumption / arteriovenous O2 difference
What are the cardinal veins?
in utero they are the veins that eventually become the systemic veins; in contrast to the umbilical and vitelline veins which degenerate and form the portal system, respectively
What are the normal partial pressures for O2 and CO2?
Normal PaO2=75-105, PAO2=105
Normal PaCO2=33-45, PACO2=40
What are the vascular changes that occur in malignant HTN? DM? atherosclerosis?
- malignant HTN - onion skinning/concentric hypertrophy of small vessels
- DM - hyaline arteriosclerosis/homogenous acellular pink material; stains pink with PAS stain
- atherosclerosis - lipid-filled intimal plaque covered by fibrous cap (ECM and fibrous cap made by VSMCs)
What cell types line the female reproductive tract?
Ovary - cuboidal; Fallopian tubes and Uterus - simple columnar; Cervix - simple columnar to stratified squamous (NK); Vagina - stratified squamous (NK)
What cofactor is most often required for transfer of groups between/to amino acids?
B6 - required for decarboxylation and transamination of amino acids, as well as for gluconeogenesis
What do hemosiderin laden MPs look like and how do they stain?
golden cytoplasmic granules within MPs that stain blue with Prussian blue (stains the iron in the blood)
What do the enzymes PNMT, COMT, and MAO do?
“PNMT: converts NE to Epi
COMT: breaks down NE –> normetanephrine; Epi –> metanephrine
MAO: breaks down NMN/MN into vanillylmandelic acid (VMA)”
What do the Purkinje PM cells do?
they are ectopic PM cells that can assume pacemaker activity during bradycardia
What does Buerger disease look like?
they’ll tell you it’s an Asian male (young) who has something to do with smoking/tobacco - could be hypersensitivity rxn to tobacco component; and they have vascular insufficiency in the extremities, and this segmental vasculitis is unique in that it extends into contiguous veins and nerves
What does left dominant circulation mean?
That the PDA is fed primarily by the Left coronary circulation, specifically the L circumflex artery.
The PDA also gives rise to the AV nodal artery; so whichever coronary is dominant, that the one that feeds the AV node.
What factors affect airway resistance?
airway resistance is increased by smaller diameter and turbulent airflow (in larger diameter); it’s decreased by total cross sectional area which is maximal in small bronchi and beyond
What form of O2 in blood doesn’t change?
partial pressure of dissolved O2
What happens to C peptide?
it gets cleaved from the proinsulin molecule by beta-peptidases but is secreted alongside, so it ends up in circulation
What happens to the thyroid pool when you take Estrogen/Progesterone?
estrogen increases the amount of TBG, so more thyroid is bound up and less free T3/T4 - this feeds back to pituitary to increase TSH; TH then saturates the TBG and repletes the free T3/T4; so net effect is that the total TH goes up while free T3/T4 stays the same
What is a glomangioma and where is it found?
a tumor of the modified smooth muscle cells of a glomus body, which is a small encapsulated neurovascular organ found in the dermis of the nail bed, finger/toe pads, and ear; the glomus body functions to sense the temp and dilate or constrict to let heat out/in
What is PFK1 and PFK2 and when are they active?
PFK1 converts F-6-P to F-1,6-BP in glycolysis.
PFK2 converts F-6-P to F-2,6-BP in the side path that is going to sense whether you need to run glycolysis or not.
Fed state: inc. F-2,6-BP will push PFK1 to run glycolysis.
Fasting state: Glucagon has inc. cAMP/pKA which drives PFK2 backwards to make more F-6-P to turn into glucose (MAIN GOAL = GLUC)
What do Homeobox genes code for?
transcription factors that alter expression of genes that will result in the cranio-caudal segmentation of the embryo; mutations in these genes will result in improperly placed organs and limbs and skeletal abnormalities
Amitryptiline
a TCA with strong anticholinergic properties
Clinical features of Vitamin A deficiency
night blindness, coarse/itchy skin, eye dryness +/- corneal ulceration, growth retardation, immune impairment
What does antiphospholipid antibody syndrome look like?
venous/arterial thromboembolism, miscarriages, premature birth 2/2 placental insufficiency or preeclampsia, paradoxical prolonged aPTT that doesn’t reverse, and false-positive RPR/VDRL
PLUS
symptoms of lupus: glomerulonephritis, skin photosensitivity, and arthralgias
What does the 95% confidence interval indicate?
that is the value falls in that range, you can be 95% sure it’s statistically significant
Calculated: Mean +/- 1.96*SD
To account for variability when not measuring the entire population, incorporate standard error: SE = SD/(square root of n)
So when trying to find the CI of the mean of a population sample, calculate:
CI = mean +/- 1.96SE
CI = mean +/- 1.96(SD/sqrt[n])
How is copper absorbed, carried, and excreted?
absorbed: stomach and duodenum
carried: ceruloplasmin
excreted: hepatic excretion via bile/stool; 5-15% via renal but that’s minority
What do neurons look like 12-24hr post-ischemic stroke?
“red neurons” - intensely eosinophilic cytoplasm, loss of Nissl substance, and pyknotic nuclei.
Beyond 2 wks there’s glial scar formation, >1mo there’s a cystic area surrounded by dense glial fibers
“glycoprotein” in the context of cancer cells - think
P-glycoprotein, the ATP-dependent efflux pump that makes the cells resistant to chemo drugs (MDR1 gene)
Redistribution of thiopental takes it where?
mostly to skeletal muscle and adipose tissue, but also to other organs.
it’s fat-soluble
Aortic arch derivatives
1 - maxillary artery (portion) 2 - hyoid and stapedial arteries 3 - CCA, ICA 4 - L: aortic arch; R: prox R subclavian 5 - nothing 6 - prox PA, ductus art
Elevated MMA in urine - ddx?
MMA –> MM-CoA –> Succinyl-CoA –> TCA cycle
= B12 deficiency - would lead to inability to convert MMA to Methylmalonyl-coA, from MMA build-up get impaired myelin synthesis
OCFA/AA –> Propionyl-CoA –> MM-CoA –> Succinyl-CoA –> TCA cycle
= Congenital MM-CoA mutase deficiency - would lead to inability to convert MM-CoA to succinyl-CoA meaning build up of propionyl-CoA (from OCFA, threonine, methionine, isoleucine, and valine) which causes elevated MMA, PPA, and ketones in urine; plus hypoglycemia, metabolic acidosis (from ketone production), and hyperammonemia
Common MOA of drug infusion followed by diffuse pruritis
medication-induced (IgE-independent) mast cell degranulation
–> opioids, radiocontrast agents, and some abx (e.g., vanc)
Anti-mitochondrial antibody, association with Sjörgen syndrome, and liver issues - condition? histology?
Condition: most likely primary biliary cirrhosis (PBC)
Histology: destruction of small/mid intrahepatic bile ducts with lymphocytic infiltrate, results in cholestasis; may also see Mallory-Denk bodies
Findings: fatigue, itching (esp. at night), hepatomegaly, xanthomas, jaundice; elevated serum Alk-Phos, IgM, and cholesterol; then confirm dx with anti-Mi Abs
Histopathology of acetaminophen overdose
central lobar necrosis, can extend to entire lobule; liver failure
Alcoholic hepatitis - histopathology
cellular swelling, necrosis, Mallory-Denk bodies (damaged intermediate filaments within HCs), NT infiltration, fibrosis
Vasopressin acts to increase reabsorption of what in the kidney?
water and urea
Friederich ataxia
(AR) GAA trinucleotide repeats in Chr 9 makes for mutated frataxin
- means problems with Fe and free radical formation in mitochondria
- results in degeneration of spinocerebellar and lateral corticospinal tracts –> gait ataxia, spastic muscle weakness
- presents as young person with kyphoscoliosis, high plantar arch (pes cavus), HCM/CHF
Pathogens most often responsible for bacterial PNA following influenza infxn
- S. pneumo
- S. aureus
- H. flu
Baclofen
GABA-A agonist
useful for spasticity 2/2 brain/spinal cord disease such as MS
Timeline for brain cell changes following ischemic stroke
0-48hr = red neurons 3-5d = NTs then microglia move in and phagocytose the broken down cells then = cystic space replaces area of necrosis; astrocytes forms a glial scar
MOA of ANP/BNP
binds ANP receptor which stimulates GC, increases cGMP, and causes vasodilation
Histone proteins
H1 = outside the core
H2A/B, H3, H4 = make up the core
How to differentiate T-ALL from B-ALL in a kid with leukemia?
First of all - general sx of ALL include fever, fatigue, pallor, petechiae, and bleeding
T-ALL more likely to present with mediastinal mass that causes SVC syndrome, compress the esophagus leading to dysphagia, or compress the trachea leading to dyspnea
Then on staining both will have TdT+ (indicated lymphoid lineage) and T cells will have CD2/3/4/5/7/8 and B cells will have CD10/19/20
Effects of prolonged glucocorticoid use on: skeletal muscle adrenals bone liver adipose skin immune system
skeletal muscle - atrophy
adrenals - atrophy
bone - osteoporosis
liver - increased gluconeogenesis/glycogenesis (increased protein synthesis to keep up with demand)
adipose - fat redistribution, lipolysis
skin - striae, thinning, impaired wound healing
immune system - suppression, T cell apoptosis
Antibodies in erythroblastosis fetalis/hemolytic disease of the newborn (HDN)
Mother O, will have IgG anti-A/B
Mother A/B, will have IgM anti-B/A
*If the mother is blood type A or B - the abs will be IgM, and therefore won’t cause problems because they can’t cross the placenta
Most common site for compartment syndrome in the leg
Anterior compartment - includes the foot extensor muscles (dorsiflexion), deep peroneal nerve, and anterior tibial artery and veins
Fenoldopam
short-acting D1R agonist rapidly vasodilates (inc. cAMP), especially renal arterioles --> inc. renal perfusion and natriuresis
What med is best to reduce airway inflammation in asthma?
glucocorticoids:
- inhaled for long-term use
- systemic for acute exacerbations
*LTs (e.g. montelukast) are also used long-term to reduce airway inflammation but they are not nearly as efficacious nor as anti-inflammatory as steroids
What is the significance of ether and viruses?
ether (and other organic solvents) can inactivate a lipid bilayer; therefore enveloped viruses can be inactivated by ether; this is because the bilayer is derived from the last cell it left and is needed for entry into the next cell
Inhibin
hormone secreted by Sertoli cells in the seminiferous tubules responsible for negative feedback to hypothalamus to say, we have enough FSH
Look out for low inhibin when the testes are undescended as the higher temps will damage the seminif. tubules, and no inhibin means really high FSH that falls on nonfunctional sertoli cells
*also inc. risk of cancer in undescended testes
What spinal cord levels do these reflexes come from:
Biceps
Bracioradialis
Triceps
Biceps - C5-6
Brachioradialis - C5-6
Triceps - C7-8
Phenylephrine
administered for pupil dilation -
selective a1 agonist for the pupillary dilator muscle (causes contraction which results in pupil dilation)
Myopathy and statins
- statins, which inhibit HMG-CoA reductase, has main side effects of myopathy and hepatitis
- can see a myopathy seen by increased serum CK levels and also muscle weakness relieved by stopping the statin
- the myopathy is worsened when fibrates (especially gemfibrozil) are taken concurrently because they impair hepatic clearance of the statins, allowing them to achieve higher serum levels
Categories of hypoglycemic symptoms
- Neurogenic - SNS in control: releases NE/Epi and causing tremulousness, anxiety, palpitations; also releases ACh causing sweating, hunger, paresthesias
- Neuroglycopenic - behavior changes, confusion, visual disturbances, stupor, and seizures
3 treatment options for C. diff and their indications
- Metronidazole (IV) - the most systemic absorption; used for mild to moderate cases, 1st and 2nd infections – but not subsequent
- Vancomycin (PO) - SEVERE infection, first or recurrent; is only bacteriostatic at employed doses
- Fidoxamicin (PO) - oral drug with bacteriocidal activity, minimal systemic absorption, and a narrow spectrum (hits on C. diff only); best choice for multiple recurrent infections because it has a better cure rate than the others
Deficiency of what enzyme would cause maternal virilization in pregnancy with a female fetus?
aromatase deficiency - will give high androgen and low estrogen levels, the excess androgens spill over to mom
Normally aromatase will convert androstenedione to estrone, and testosterone to estradiol
Majority should happen in the placenta, thus if it’s broken it’s close to mom in the placenta
What nerve is most commonly injured at the lateral head of the tibia and what symptoms would it cause?
Common peroneal nerve (which splits into deep and superficial peroneal nerves)
Would cause foot drop and inability to extend the toes upward (DPN); also inability to evert the foot (SPN) with loss of sensation over the foot dorsum and lateral leg (SPN)
Takes a long time to slough umbilical cord - what’s the problem?
Leukocyte adhesion deficiency (LAD) - low expression of integrins from absence of CD18 (AR)
Candida spreads and the cells that contain them
- Superficial - T cells
- Hematogenous/Disseminated - NTs
* So someone with HIV will probably get cutaneous candida, but won’t get disseminated infection unless they have a neutropenia (as in hematologic malignancy/chemo)
Surface marker for monocyte/MP lineage
CD14
Target(s) of GVHD
a particular organ may be the target but the most common are skin, GI, and liver
Look for patient with recent transplant and within a week or two gets a diffuse rash and N/V/D, ulcerations of intestinal mucosa
Predispositions to developing chronic giardiasis
- IgA deficiency
- X-linked agammaglobulinemia (BTK)
- CVID
Acute respiratory distress syndrome
“Diffuse Alveolar Damage”
Alveolar walls get proteinaceous fluid leakage which becomes hyaline membranes.
This causes decreased gas exchange/hypoxemia/cyanosis, as well as diffuse lung collapse because the hyaline membranes are “sticky”.
Etiology is many, all converge on activating NTs which let out proteases and free-rads, these factors damage type I AND II pneumocytes - makes it harder to regenerate lung tissue (Type 2 PC’s are stem cells) and get interstitial fibrosis instead.
Neonatal respiratory distress syndrome
- lecithin (phosphatidylcholine) increases after week 36, when it’s 2x sphingomyelin then the lungs are mature
- the following increases risk of NRDS: maternal diabetes (baby pancreas produces lots of insulin to keep up; insulin inhibits surfactant production); C-section (no stress –> cortisol –> no lung opening)
- placing baby on 100% O2 will create lots of free radicals, can damage lungs and retina
Major inducers of CYP3A4
CROPP GGGAS: Carbamazepine Rifampin OCPs Phenobarbital Phenytoin
Griseofulvin Ginseng Green vegetables Alcohol, chronic use St. John's Wort
–> decrease Warfarin effect
Crop gas makes crops grow = inducers
Major inhibitors of CYP3A4
Say No To CRACK AMIGGOSS:
SSRIs/Fluoxetine
NSAIDs/Acetaminophen
Thyroid hormone
Cimetidine Ritonavir/Protease inhibitors Amiodarone Ciprofloxacin, Erythromycin/Abx Ketoconazole/Azoles/Metronidazole
Acute Alcohol use Macrolides Isoniazid Grapefruit/Cranberry juice Gingko Biloba Omeprazole Sulfonamides
+Vit E
–> inc. Warfarin effect
“Say No” = inhibition
Drugs that can cause QT Prolongation
“Some Risky Meds Can Prolong QT”
Sotolol, Risperidone, Macrolides, Chloroquinolone, Protease inhibitors, Quinidine, Thiazides
**Amiodarone can prolong the QT interval but it has little risk of becoming torsades
Medications to avoid in pts with HCM
vasodilators and diuretics - because anything that decreases preload or afterload (ultimately decreasing the LV volume) will worsen the LVOT obstruction by allowing the LV to collapse
*HCM can cause chest pain by producing a sort of ischemia during exertion, whenever the preload or afterload decreases you get increased LVOT obstrucion and thus less coronary supply
What kind of splitting do ASDs cause?
wide and fixed splitting of S2
because increased volume makes its way to the R heart with every contraction
Pulsus paradoxus
A drop in SBP >10 on inspiration (normally increased)
Caused by diseases affecting R ventricle expansion into the pericardium, like cardiac tamponade.
During inspiration the R heart is super-filled and won’t normally compress the left ventricle, but if there’s something else pushing on it (like cardiac tamponade) then the only option is to decrease the size of the left ventricle, thereby decreasing outflow - hence drop in SBP.
In the absence of pericardial disease, the MCC is obstructive pulmonary disease (asthma/COPD exacerbation). Treat with bronchodilators - B2R agonists
Lymph drainage - scrotum, testes, glans penis, posterior cutaneous calf
Superficial inguinal LNs drain nearly all cutaneous lymph from umbilicus and below, including external genitalia and anus, below dentate
*Exceptions = testis, glans penis, cutaneous post calf
Scrotum –> superficial inguinal LN
Testes –> para-aortic (RP) LNs
Glans penis, post cutaneous calf –> deep inguinal LNs
Superficial Inguinal LN –> Deep Inguinal LN
Ureteral circulation
Proximal ureter - branches off renal artery
Middle ureter - gonadal artery
Distal ureter - common iliac artery, internal iliac artery, vesical artery
Where is a transplanted kidney placed?
retroperitoneal in the right iliac fossa
What organs are located retroperitoneally?
SAD PUCKER S - suprarenal glands A - aorta/IVC D - duodenum (except 1st part) P - pancreas (except tail) U - ureters C - colon (asc/desc) K - kidneys E - esophagus R - rectum
What predisposes to drug-induced lupus?
slow-acetylators
Hydralazine, Isoniazid, Procainamide
Minocycline, TNF-alpha inhibitors
Guillan-Barre syndrome - MOA
ascending weakness/paralysis following a URI (Campylobacter); an immune-mediated demyelination of spinal cord and peripheral nerves - get segmental demyelination on LM along with endoneural inflammatory infiltrate (LCs/MPs)
HPV of head/neck likes to infect what locations?
like basal epithelial cells - so stratified squamous cells in the true vocal cords
Most common congenital heart defect in Turner and Down’s syndrome
Turner - bicuspid aortic valve
Downs - no/bad AV valves, ASD, and VSD (endocardial cushion defects)
MCC of IVH in pre-term infants?
Hemorrhage from germinal matrix (origin of migrating neurons)
Bleed will occur within 5d post-natal and appear as bulging fontanel, HOTN, decerebrate posturing, tonic-clonic seizures, irregular respirations, coma
*Pre term = before 32wks and/or
MOA of bisphosphonates
Inhibition of mature osteoclast-mediated bone resorption
*Note the cells are already mature, the meds don’t inhibit maturation or anything
Outcomes of HBV infection
Most resolve completely (>95%).
4-5% will become chronic, and only 20-50% of those will get cirrhosis, of those 10% will get HCC.
Fulminant hepatitis happens in
Persistent lymphedema will increase the risk for
lymphangiosarcoma
Cavernous hemangioma
benign neoplasm of endothelial cells of small blood vessels
- MC benign tumor of the liver
- in the brain they are usually in the parenchyma and can cause seizures
MCC of ED
SSRIs (50% of pts on them have sexual dysfunction)
Atherosclerosis
?
Antibodies against PRP is protective against what?
H. influenza (B)
Treatment for peripheral artery disease
- platelet inhibitor
- arteriole dilator - need this to stop the claudication
Cilostazol - inhibits PDE, thereby inhibiting plt aggregation and causing vasodilation
Most common catalase-positive organisms that afflict pts with CGD
Aspergillus, Burkholderia cepacia, Nocardia, Serratia marcescens, and S. aureus,
Fifth disease - pathogenesis
Caused by Parvo B19 (ssDNA linear - the only one)
enters by respiratory droplets, causes congestion, HA, low-grade fever, then you get a lace-like, erythematous rash that starts as flushed cheeks then spreads down to include the trunk
The virus replicates in erythrocytes, and thereby can cause aplastic anemia in SCD
How to treat widened QRS interval?
Sodium bicarbonate
Potential causes of prolonged QRS = something that binds Na channels and prevents the influx of sodium
- Flecainide, Class IC anti-arrhythmic
- TCA overdose, which blocks the fast sodium channels causing seizures, delirium, cardiac abnormalities, severe HOTN, and signs of ACh toxicity
NaHCO3 good for treating ventricular arrhythmias, basically by providing so much Na that some will leak in past the block.
How to recognize a manic episode?
DIG FAST:
Distractibility, Impulsivity, Grandiosity, Flight of Ideas, Activity increase, Sleep decrease, Talkativeness
+/- delusions or hallucinations
–> Should make you think Bipolar I because depressive episodes are not needed for diagnosis
Organ of Corti vs. Cochlear cupula
Organ of corti - the steroeciliated hair cells that transduces the sound from the vibrating tectorial membrane
Cochlear cupula - located at the apex of the cochlea, registers low-frequency sound
Edema and hemorrhagic necrosis of the temporal lobe - infection?
HSV-1 encephalitis; results from oropharyngeal infection that spreads via olfactory tract, or latent viral infection in trigeminal ganglion
Osteocytes connect to each other in lamellae by…?
gap junctions - so they can continue to communicate
MCC of Turner syndrome
paternal non-disjunction in gametogenesis
Fishy odor plus clue cells
Gardnerella - Clindamycin or Metronidazole
Pain in appendicitis
Starts out as generalized because of luminal distention carried by general visceral afferents.
Later becomes localized due to somatic irritation of the parietal peritoneum.
Pathogenesis of SIADH
tumor cell secretes ADH, causing a transient increase in ECF volume; this stimulates enough ANP/BNP to cause salt wasting, which ultimately results in hyponatremia.
Can present as normal volume hyponatremia with HA, weakness, AMS, and seizures
What bug is PYR positive?
S. pyogenes (GPC)
What is the RLS for bile acid synthesis?
cholesterol 7a-hydroxylase
converts free cholesterol into acids; the acids are then conjugated to glycine/taurine to form bile salts (more soluble and emulsifiable)
Clasp-knife spasticity
initial resistance to passive extension, followed by a sudden release of resistance; indicates UMN disease, such as a stroke in M1/IC/CST, or any level on down to the LMN
*IC strokes commonly present as pure motor weakness
What bacteria are among the most infectious?
Shigella
Campylobacter
Entamoeba histolytica
Giardia lamblia
Triad of disseminated gonococcal infection
- polyarthralgias
- skin lesions
- tenosynovitis
* Can also present as purulent arthritis WITHOUT skin lesions
What muscle is attached on the medial clavicle?
What muscle is attached on the lateral clavicle?
Medial - SCM
Lateral - pect major, deltoid
Long-acting BZDs
Short-acting BZDs
Best BZDs in impaired hepatic metabolism
Long: diazepam, lorazepam, temazopam, alprazolam, chlordiazepoxide
Short: midazolam, oxazepam, triazolam (MOT)
Best in impaired hepatic metabolism: lorazepam, oxazepam, temazepam (LOT)
Symptoms of pancreatic adenocarcinoma of at the head of the pancreas compressing the common bile duct?
- weight loss
- palpable/enlarged but nontender gallbladder (Courvoisier sign)
- obstructive jaundice = pruritus, dark urine, pale stools
Angiogenesis is driven by what 2 major factors?
- VEGF - stimulates endothelial cell motility and proliferation
- FGF - promotes endothelial cell proliferation, migration, and differentiation; also attracts MPs and fibroblasts for healing
What’s the most common presenting symptom of post-procedure atheroembolism?
acute kidney injury (oliguria, azotemia); frank infarction with pain/hematuria won’t occur because the emboli are caused by cholesterol, and they are small so you will just find cholesterol clefts in the renal arteries (arcuate or interlobar)
What virus causes immortality in cells it infects?
EBV - causes B cells to activate and proliferate indefinitely; they continue to produce Ig’s (including heterophiles) and very few release virus particles at a time
*This may increase risk of c-myc translocation and Burkitt lymphoma, or other lymphomas
How to differentiate C. botulinum from TCA overdose?
C. botulinum - affects both nicotinic and muscarinic; classic 3Ds = diplopia, dysphagia, dysphonia within 12-26hrs of ingestion; +dry mouth
TCA overdose - muscarinic blockade predominates, thus there’d be no effect on NMJ (no diplopia/dysphagia)
How to test the NMJ? - CMAP test, which tests nerve conduction velocities and muscle AP; repetitive stimulation can overcome the botulinum toxin effect and let ACh out (of course this wouldn’t change in TCA OD because there’s no effect on NMJ)
Symptoms of organophosphate poisoning
Inhibition of AChE, basically ACh overdose:
- depolarizing blockade - weakness, paralysis, fasciculations
- CNS effects - lethargy, seizures
- muscarinic overstimulation - miosis, bradycardia, inc. lacrimation/salivation
How to differentiate serotonin syndrome from neuroleptic malignant syndrome? Causes of each?
- NMS consists of 4: generalized “lead-pipe” rigidity, hyperthermia, ANS instability, and AMS
- Serotonin syndrome will usually have hyperactive muscles (instead of rigid, so shivering, clonus, and hyperreflexia) and the hyperthermia/rigidity are way less severe
- Causes: neuroleptics, aka antipsychotics, cause NMS; serotonergic medications cause SS
What’s the first-line treatment for essential tremor?
propanolol
What’s the most effective antagonist for chemotherapy-induced vomiting?
Serotonergic antagonists (-setrons)
These act via 2 mechanisms:
1. inhibit vagus-mediated stimuli coming in from GI tract
2. block the 5-HT3 Rs in the area postrema/NTS
Remember: area postrema has CTZ; projects to NTS which collects info from AP, GI via CN10, vestibular system, and CNS (i.e., meninges); NTS projects to other nuclei to coordinate vomiting reaction
The other main players in the vomiting center signaling system are M1, D2, H1, and NK1 receptors/substances.
Vertical diplopia - described how and indicates what?
Described as double vision particularly when looking down and toward the nose, like climbing stairs or reading.
Indicates CN4 palsy, because the SO can’t turn the eye down and in toward the nose.
May see improvement on head tilt away from the side of the lesion.
Histologic and clinical appearance of acute viral hepatitis
Acute viral hepatitis due to HepA:
Histo: “spotty necrosis” with balloon degeneration, Councilman bodies (eosinophilic apoptotic HCs), and mononuclear cell infiltrates
Clinically: prodrome is fever, malaise, anorexia, N/V, RUQ pain; then within a week later the prodrome goes away and you get signs of cholestasis: jaundice, pruritus, dark urine, and acholic/pale stools; the infection is self-limited and doesn’t progress to chronic hepatitis, cirrhosis, or HCC
Vitiligo is caused by
a loss of epidermal melanocytes and thereby loss of melanin; etiology is unclear but may be autoimmune
Cushing’s vs. Curling’s ulcers
These are 2 types of ulcers due to physiologic stress; secondary to impaired mucosal protection against local ischemic injury from HOTN and splanchnic vasoconstriction following shock/severe injury
Cushing = due to intracranial injury, stimulating vagus nerve with acid hypersecretion, causing ulcer in esophagus, stomach, or duodenum that are particularly prone to perforation
Curling = these ulcers arise in the proximal duodenum secondary to severe burns
Interstitial myocardial granuloma
- aka Aschoff body
- pathognomonic for acute rheumatic fever (ARF)-related myocarditis, follows untreated GAS inxn
- it’s seen on biopsy of the heart and looks like interstitial fibrosis with MPs and LCs plus scattered multinucleated giant cells
- over time the bodies are replaced by fibrous scar tissue leading to chronic mitral valve regurgitation and stenosis
- *If you see a myocardial tissue section and there’s a granuloma-like thing in between the myocytes, think Aschoff body
Anitschkow cells
aka caterpillar cells
- plump MPs with abundant cytoplasm and slender chromatin ribbons
- sometimes seen in Aschoff bodies in ARF-myocarditis
DDx for cardiac granuloma
- ARF-related Aschoff body
- sarcoidosis
- TB, fungal infxn
- metabolic disorders including Farber’s, gout, and CGD
Non-granulomatous histiocyte infiltration can also occur in Whipple’s disease, Niemann-Pick disease, hyperlipoproteinemias, and Gaucher’s
What drugs are used to treat status epilepticus?
First line acute: BZDs (diazepam, lorazepam)
First line prophylaxis: phenytoin
Drugs used to treat absence seziures
First line: ethosuximide
Also: valproate
Signs and Ex of small intestine bacterial overgrowth (SIBO)
- high Vitamin K and Folate (DJ Ill has an Iron Fist, Bro)
- Nausea, bloating, abdominal discomfort, malabsorption
Relationship between beta-endorphin and ACTH
both are produced from POMC precursor
beta-endorphin is an endogenous opioid peptide, and this may be basis of association between stress axis and opioid system
How does desmopressin work to treat hemophilia?
it increases release of vWF and factor 8 from endothelial cells; really only works on mild hemophilia A, also works on von Willebrand disease
Components of the ECM and their functions
Hyaluronic acid, Glycosaminoglycans - absorb water and determine stiffness
Fibronectin, Collagen, Laminin - EC structural proteins to which integrins bind
Cast nephropathy - think
protein
- seen in multiple myeloma from large amounts of bence jones light chain proteins
Painless red serpiginous ulcerative lesions - STD?
Granuloma inguinale (Donovonosis) caused by Klebsiella granulomatis
- these are progressive lesions without LAD
- dx with Gram stain and culture (difficult) or biopsy (donovan bodies)
- differentiate from syphilis because this won’t have LAD
PDGF mutations are in what cancer?
Chronic myelomonocytic leukemia
Action; site of release of: Gastrin Somatostatin CCK Secretin GIP Motilin
Gastrin - acid secretion; G cells (antrum, duodenum)
Somatostatin - stop secretions of GI hormones; delta cells (pancreatic islet, gut mucosa)
CCK - release of pancreatic enzymes and bicarb; I cells (SI)
Secretin - panc. bicarb release, stop secreting acid; S cells (SI)
GIP - insulin release, stop secreting acid; K cells (SI)
Motilin - GI motility; M cells (SI)
Elderly man with insomnia. What drug class to avoid? Best drug to prescribe?
Avoid: BZDs and those with anticholinergic AEs (1st gen Histamine blockers and TCAs)
Good: Ramelteon, melatonin agonist
Systemic mastocytosis - common associated mutation and symptoms
mutation = KIT (GOF in TK)
Symptoms are derived from the excess histamine released by the mast cells; this causes syncope, flushing, HOTN, pruritus, urticaria, and gastric hypersecretion/ulceration
Other GI sx can include N/V and cramps
What does cryptococcus look like under LM?
yeast form only with narrow-based buds
*it’s heavily encapsulated (sarcophagus)
Adenocarcinoma of the lung
Most common
Peripherally located; associated with k-ras, EGFR, and ALK mutations.
In-situ is considered a preinvasive but still malignant mass, it consists of many columnar epithelial cells (w/wo lots of IC mucin) that makes an apparent thickening of the alveolar wall.
Patient may present with copious amounts of expectorate; CXR can have infiltrates that resemble PNA; may also see hypertrophic osteoarthropathy.
Causes of aplastic anemia
most are direct toxic insult to BM or a T-cell response:
- drugs: chemo, benzene, carbamazepine
- virus: hepatitis, EBV, Parvo B19
In kids the etiology is usually idiopathic.
- Myelodysplastic syndrome (not really aplastic anemia because there’s many abnormal blasts on BM biopsy) normally occurs in adults >65yo.
- *Won’t see splenomegaly in AA because there’s no HSCs for extra-medullary hematopoiesis
Alcohol withdrawal symptoms and treatment
- Mild sx present within 24hrs: tremulousness, anxiety, insomnia, tremor, diaphoresis, palpitations, GI upset; still orientated
- Seizures (tonic-clonic) later
BZDs are first-line to prevent DTs and seizures; long-acting BZDs with active metabolites are good choices: diazepam and chlordiazepoxide
Cancers associated with Downs Syndrome
- Myelodysplastic syndrome
- Leukemia: ALL, and AML (and subtype of AMkL, a variant of which can be transient myelocytic leukemia)
- Germ cell tumor
Non-bacterial thrombotic endocarditis - what is it, and what condition it is associated most with?
NBTE aka marantic endocarditis = platelet-rich thrombi attached to mitral valve leaflets
Most commonly associated with advanced malignancy, as well as chronic inflammatory conditions (SLE, antiphospholipid Ab syndrome, and DIC in sepsis)
Types of exocrine glands
- Merocrine - exocytosis; salivary, epocrine, apocrine sweat glands
- Apocrine - membrane-bound vesicle secretion; mammary glands
- Holocrine - suicide secretion (cell lysis releases everything); sebaceous and meibomian glands (eyelid)
What does the Wright-Giemsa stain see when used on blood smear?
It will stain blue the remaining nuclear material in reticulocytes - which is actually a reticular network of residual ribosomal RNA
Only fungus that can survive intracellularly and cause disease
Histoplasmosis
- will see the small ovoid bodies within MPs
Appropriate treatment to initiate when someone first shows up with RA
- Start glucocorticoids/NSAIDs for immediate anti-inflammatory effects
- Start DMARD for long-term control; it does take a few weeks to take effect though
* DMARDs include MTX, Sulfasalazine, Hydroxychloroquine, Minocycline, and TNF-a inhibitors
What are the substances that are catabolized into propionic acid?
Isoleucine, valine, methionine, threonine, cholesterol, and LCFA
*valine and isoleucine undergo oxidative decarboxylation
Propionyl is then converted to MM-CoA by propionyl CoA carboxylase (uses biotin)
What does the suprachiasmatic nucleus do?
Supraoptic?
Arcuate?
SCN - senses light, talks to pineal body
Supraoptic - ADH and oxytocin
Arcuate - dopamine, GHRH, and GnRH
Where does the gastroduodenal artery run?
Where doe the gastroepiploic arteries run?
GD - right behind the duodenum
GE - inferior side of the stomach
Does Rifampin act on blocking DNA, RNA, or protein?
RNA
- blocks DNA-dependent RNA polymerase
- comes with GI side effects, rash, red-orange body fluids and cytopenias
DRESS syndrome - what drugs cause it and how does it present?
Can be caused by phenytoin, carbamazepine, allopurinol, sulfonamides, minocycline, and vancomycin.
Pts develop fever, LAD, facial swelling, and diffuse morbilliform skin rash, with Eosinophilia and elevated ALT (also atypical lymphocytosis).
Symptoms of a VIPoma
WDHA syndrome: Watery Diarrhea, Hypokalemia, Achlorhydria
(AKA pancreatic cholera)
VIP binds to epithelial cells–>activates AC–> causes secretory diarrhea; also causes pancreatic bicarb and chloride secretion.
Somatostatin is the inhibitor (just like ‘statins’ inhibit HMG CoA reductase)
What happens to Rb in tumor cells?
RB gets broken - when active it inhibits G1/S transition; if inactivated by mutation it won’t inhibit the transition
Someone has longstanding gallstones; what can happen?
cholecystenteric fistula can form between the gallbladder and the small bowel (usually duodenum); the gallstone then gets stuck at the ileocecal valve (usually)
May see air in the gallbladder on imaging (“pneumobilia”) with SBO (abdominal distention, pain, high pitched bowel sounds; and N/V)
How to recognize SLE
Clinically:
- fever, fatigue, weight loss,
- migratory arthralgias, butterfly rash, photosensitivity, serositis
- thromboembolic events, cognitive dysfunction, seizures
Lab Findings:
- hemolytic anemia, thrombocytopenia, leukopenia, low C3/C4
- Anti-smith, Anti-dsDNA
- proteinuria, elevated creatinine
Reaction formation
defense mechanism where unacceptable feelings are transformed to the exact opposite
NF1 - recognition? genetics?
- patient will have lots of fibromas on the skin, cafe-au-lait spots, optic nerve gliomas, lisch nodules, sphenoid dysplasia, scoliosis, other brain tumors, and pheo’s
- single mutation, AD, in Chr 17
What is the red cell index measure most specific for hereditary spherocytosis?
mean corpuscular hemoglobin concentration (MCHC)
Why must HepB be there for HepD infection?
HepD needs HepB’s surface antigen to get into the hepatocytes
Leukemoid reaction - when does it occur, why, and how does it present?
- occurs in the setting of severe infection/sepsis, hemorrhage, malignancy (leukemia), or acute hemolysis
- it occurs because the bone marrow is spitting out many more mature cells (as opposed to blasts in leukemia) in order to combat the attack
- presents as LCs >50,000 in the setting of another illness (e.g., pt is febrile with septic PNA)
On blood smear:
- Dohle bodies - blue/basophilic granules in mature NTs
- Increased bands (left shift)
- Toxic granulation
- Cytoplasmic vacuoles
Difference between fractionated and unfractionated heparins?
Unfractionated = real heparin, longer; binds AT3 and lets it inactivate Factor Xa; still has extra binding sites for Thrombin so the complex can inactivate it
Fractionated/LMWH = synthetic, shorter, binds AT3 and lets it inactivate Factor Xa; no binding sites for thrombin though (too short)
Primary impairment in osteogenesis imperfecta
(AD) defective bone matrix formation
- matrix is formed from collagen and hydroxyapatite crystals
- the matrix is then mineralized by VitD/Ca process
- Endochondral ossification = endochondral happens with first a cartilage template, later filled in by deposition of osteoid matrix, then remodeling from woven bone into compact bone
- intramembranous = no cartilage matrix, straight to osteoid and remodeling
Pelvic fracture is most likely to cause injury to the urethra where?
At the bulbo-membranous junction (also the post-ant junction) - the weakest portion of the urethra
This is right around the external urethral sphincter, which is like the first 90deg turn, under the prostate
Leptin
decreases food intake
Hibernating myocardium vs. Ischemic pre-conditioning
Basically, Hibernating is when there’s prolonged decreased O2 flow to myocardium and it resets. Preconditioning is repeated episodes of angina and that is protective later when there’s a complete occlusion
Features of back pain worrisome for metastasis/neoplasm
- pain that is not relieved by rest, position changes, or analgesics
- worse at night
- elderly
- Strong predictor = known history of malignancy
Secondhand smoke increases the risk of what in infants?
- SIDS
- prematurity/low birth weight
- otitis media
- asthma
- URIs, bronchitis, PNA
Uremic bleeding
- bleeding due to build-up of toxic products that should be filtered/excreted by the kidney but can’t because of renal failure, such as in a patient on dialysis
- the toxins prevent platelet aggregation and adhesion, so there’s normal platelet count and coag studies (PT, PTT) but prolonged bleeding time
What gives you wrinkles?
UVA getting to the cells and producing ROS, which then activate TFs and decrease collagen fibril production - hence less structural support, hence aging
- also activates MMPs which secondarily degrade Type I/II collagen and elastin
Obesity gives you what kind of lung disease?
Obesity-Related Restrictive Lung Disease
- this means you have decreased TLC, decreased lung and chest wall compliance due to microatelectasis and increased fat, resp.
- hallmark is huge reduction in ERV, but no change in RV
Traumatic aortic rupture
usually from MVCs, it’s a large deceleration that push/pulls the aorta; the ligamentum arteriosum will hold the arch still and allow greater shear forces, which may rupture the aorta at this segment
BZDs and Barbiturates on GABA receptor
BZDs increase frequency of opening
Barbiturates increase duration of opening (barbiDURATes)
Kussmaul sign
A rise in JVP on inspiration.
Similar to pulsus paradoxus, it’s a sign of constrictive pericardial disease because normally on inspiration the venous return increases, but if constricted the R heart can’t open to accommodate the increased volume, and thus it backs up into the jugular.
How to recognize Lipofuscin
the wear and tear pigment - it’s yellow-brown intracytoplasmic, perinuclear granules; the product of free-radical and lipid peroxidation
** “Lipo” = lipid
Industrial exposure to rubber, aromatic amine dyes, textiles, leather increases risk of what cancer?
transitional cell carcinoma of the bladder
How does spironolactone cause gynecomastia?
It’s an aldosterone antagonist
But it also acts as an androgen receptor antagonist (structurally similar to androgens), and thereby inhibits testosterone synthesis; without the testosterone to be converted to DHT, breast tissue will grow
*Eplerenone is a newer spironolactone type drug that has fewer side effects
What do neurons look like after an axon is severed?
- proximal portion of the neuron = Neuronal Reaction; the cell body swell, nucleus and Nissl moves to the side (central chromatolysis), seen 24-48hrs after injury and peaks around 12d
- distal/severed axon = Wallerian degeneration; swelling and irregularity of the axon, then w/in 7d the Schwann cells and MP digest the fragments
Hemosiderin
coarse yellow-brown pigment that comprises iron complexes from the blood; can be in Kupffer cells like in chronic hemolysis, or in MPs in the lungs like in heart failure
Pathophys difference between gastric and duodenal ulcers
Both are the result of damage to the segment’s defense against acid:
Gastric = damaged mucus layer (and associated inflammation) allows acid to hurt to gastric cells; acid amount will be low to normal
Duodenal = used to having lots of acid dumped, so ulcers here will appear if there’s decreased somatostatin (D cells) or pancreatic bicarb released
*H. pylori and NSAIDs are MCC of duodenal ulcers, but keep in mind ZE syndrome from gastrinoma
Kidney disease and c-ANCA+ - think:
Wegener’s, and rapidly progressive GN (so crescents)
*May also see: necrotizing granulomas in the lungs (so cough/hemoptysis) and ulcerating granulomas in the URT (chronic sinusitis, ENT)
Ristocetin
activates Gp-Ib receptors on platelets for them to bind vWF
Heroin/Opioid withdrawal
Specific = lacrimation and yawning Others = dilated pupils, piloerection, hyperactive bowels, N/V, abdominal cramps
Alcohol vs. BZD withdrawal
Both will have tremors, anxiety, psychosis, tachycardia, palpitations, and seizures.
Alcohol will also have delirium.
BZDs will also have perceptual disturbances and insomnia.
How long does ischemic myocardial tissue last?
30min - after that the damage is irreversible
What cancers are most commonly associated with paraneoplastic syndrome causing Dermatomyositis?
ovarian, lung, and colorectal adenocarcinoma, and non-Hodgkin lymphoma
**Remember Dermatomyositis = proximal muscle weakness with heliotrope rash and rash on knuckles (whereas SLE will affect skin in between knuckles)
What is stimulus control in sleep therapy?
it’s re-associating the bedroom with sleep only and nothing else
How does Vitamin K help babies?
Vit K is a cofactor needed for gamma-glutamyl carboxylase, which is the enzyme that synthesizes Factors 2,7,9,10
- without it working babies will bleed, i.e. ICH, GI, cutaneous, umbilical, and surgical bleeding
Which enzymes give what information about the following:
liver
biliary tree
Liver functionality - PT, albumin, bilirubin, cholesterol
Livers structural integrity/cellular intactness - ALT, AST
Biliary tree structural integrity/cellular intactness - Alk-phos, gamma-glutamyl transferase
*When there’s an elevated Alk-phos, you can’t tell if it’s from biliary tract or bone; check GGT because if elevated then you know the problem is in the biliary tree/biliary epithelium
VPN is a growth medium containing what? used for what?
Used for Neisseria species - Vancomycin - inh. GP bacteria - Polymixin, aka Colistin - inh. other GN bact - Nystatin - inh. yeast \+/- Trimethoprim - inh. Proteus species
Chocolate agar can also grow Neisseria, but not regular blood agar
Cancer from Ulcerative Colitis - development, mutations, risk factors
Develops from flat, dysplastic lesions (not polypoid, as in other types or sporadic CRC).
Mutations include p53 early on, leading to a less differentiated form at presentation (classic sporadic pathway goes APC –> k-ras –> p53).
Pancolitis has the highest risk of CRC, and extent and duration of colitis are the strongest risk factors for development of CRC.
Food-related areas of Hypothalamus
Ventromedial - mediates satiety; destroy and won’t be satisfied, will get fat
Lateral - mediates hunger; destroy and won’t be hungry, will get skinny
Anterior and Posterior Hypothalamus
Anterior - regulates heat dissipation; destroy and all heat will be kept, get hyperthermia
Posterior - mediates heat conservation; destroy and all heat wil be lost, get hypothermia
Most important risk factor for intimal tears leading to aortic dissection
HTN
Watershed areas of the large bowel
splenic flexure and rectosigmoid junction
How long does it take to reach steady-state?
ABout 4-5 half lives for a first-order kinetics drug
That’s because in 1 HL –> 50% of steady state
2 HL –> 75%
3 HL –> 87.5%
etc.
What is the Periodic Acid stain good for?
highlighting glycoproteins, such as those found in fungal cell walls, mucosubstances secreted by epithelia, and basement membranes
Cystic medial degeneration
the process of myxomatous change in the media of blood vessels that weakness the CT and can lead to aneurysm formation; a major cause of which is Marfan syndrome
Causes/Associations of:
SCC of esophagus
Adenocarcinoma of esophagus
SCC - associated with alcohol and smoking in US; associated with chewing betel nuts and foods with N-nitroso compound in Asia
Adenocarcinoma - associated with GERD and Barett’s (fatty diets and obesity) in the US; hot beverages in Asia
What are the 3 types of PNA, and of the lobar type what are the 4 stages?
3 types = bronchopneumonia, interstitial, lobar
Lobar 4 stages =
1. congestion (24hr) - alveolar exudate just bacteria
2. red hepatization (2-3d) - red and firm with RBCs, NTs, and fibrin in exudate
3. gray hepatization (4-6d) - RBCs go away (“disintegrate”, “fragmented”)
4. resolution - restoration of normal, exudate is digested
What’s the main pathophysiology in PCV?
the activating mutation in the JAK2 gene renders HSCs more responsive to growth factors like EPO/TPO
People with SCD or SCT - what infections will they get? What kind of kidney damage?
They will get infected with encapsulated organisms (SHiNE SKIs - MC is Strep pneumo, #2 is H. flu).
They will get renal papillary necrosis which presents as gross hematuria (passage of blood clots) without pain.
What two substances will be elevated in NTD?
AFP
AChE
How does Acetyl-CoA help with gluconeogenesis?
it serves as an allosteric activator of the first step – which is pyruvate carboxylase (converts pyruvate to oxaloacetate for going back to PEP)
Beta-blocker OD:
What’s happening and How to treat
Happening: blocked beta-receptors means myocardial contractility depression, bradycardia, and heart block
Treatment: glucagon, will act on GPCRs, increase IC cAMP and restore cardiac contractlity
Where are dietary fats absorbed?
in the jejunum!!
not the duodenum - in duodenum they are just chopped up by pancreatic lipases and emulsified by bile salts; it’s not until the jejunum that they’ve mixed enough and get into close contact with the wall for passive absorption
Immature myeloid cells + low fibrinogen makes you think
APL (M3 subtype of AML) with t(15;17) translocation
*may also have description of immature myeloid precursors in BM biopsy
The low fibrinogen is a consumptive bleeding because the patient will be in DIC
Don’t forget the Auer rods
