Random Crap Flashcards
McCune Albright Syndrome pt presentation
unilateral cafe-au-lait spots,
polyostotic
fibrous dysplasia (bone is replaced by collagen and fibroblasts),
precocious puberty
Peutz-Jeghars Syndrome pt presentation
Hamartomatous polyps in the colon,
dark-colored macules on the mouth, hands, feet, and genitals
Patau syndrome pt presentation
Chromosome 13 trisomy holoprosencephaly cutis aplasia midline defect cleft palate polydactyly rocker-bottom feet heart and kidney defects (polycystic kidney disease)
Edwards syndrome pt presentation
Chromosome 18 trisomy intellectual disability overlapping fingers clenched fists micrognathia rocker bottom feet
What is oppositional defiant disorder?
pattern of anger and irritability with argumentative, vindictive, and defiant behavior toward authority figures lasting > or equal to 6 months
Everything about Warfarin
Warfarin causes “war” in placenta!!!
Inhibits VKOR, which will inhibit Factors 2,7,9,10, Protein C and S
Used for DVT prophylaxis and for arrhythmia prophylaxis
Can cause skin necrosis
Must measure INR and PT regularly
Parts of the adrenal gland - what do they produce
GFR
Glomerulosa - Mineralcorticoids
Fasciculata - Glucocorticoids
Reticularis - Androgen
Pathogenesis/presentation for Pemphigus Vulgaris and Bullous pemphigoid:
Pemphigus vulgaris: Auto-Ab to desmoglein 1/3 (structural support)
Older adults, potentially fatal. Flacid intraepidermal bullae. Separation of keratinocytes so + Nikolsky sign. Oral mucosa involved.
Reticular pattern around epidermal cells
Bullous Pemphigoid: Auto-Ab to hemidesmosomes (connects keratin in basal cells to underlying basement membrane)
Less severe, also older adults. Fluid filled blisters containing eosinophils. Oral mucosa spared. Nikolsky sign -
Linear pattern at epidermal-dermal jxn
what is another name for 21-hydroxylase mutation
CYP21A2
everything about vinca alkaloids
Vincristine and Vinblastine are microtubule inhibitors
Vincristine adverse effect: “crisps” nerves
Vinblastine adverse effect: causes bone marrow suppression
Taxane drugs
ex. paclitaxel
“taxes stabilizes the economy”
causes microtubules to bind so tightly that the cell can’t divide
trastuzumab
a drug that targets the HER2 receptor
adverse effect: dilated cardiomyopathy “tracy with the big boobs goes to church”
Lynch Syndrome
Mismatch repair is defective
Autosomal dominant mutation of mismatch repair genes MLH1 and MLH2
around 80% progress to colorectal cancer
associated with endometrial, ovarian, and skin cancers
what are the thionamides and what is their MOA
Propylthiouracil (PTU) and methimazole
MOA: blocks TPO, inhibiting the oxidation and organification of iodine which ultimately leads to inhibition of thyroid hormone synthesis
PTU is used in first trimester of pregnancy due to methimazole toxicity wherease methimazole is used in second and third trimester of pregnancy
AE: skin rash, aplastic anemia, hepatotoxicity
metabolic acidosis NAGMA
NAGMA means that the anion gap is 8-12 mEq/L. Cl is high compared to bicarb.
HARDASS H- hyperailmentation/hyperchloremia A- Addison disease (dec. Aldosterone) R- renal tubular acidosis D- diarrhea A- acetazolamide (CA inhibitor in the PCT) S- spironolactone (aldosterone receptor blocker) S- saline infusion
Explain fetal circulation
Oxygenated blood comes from the mom through the Umbilical v. then goes into the placenta. The blood goes through the ductus venosus into the IVC.
The blood enters the RA then goes through the foramen ovale to enter the LA. Blood then goes to LV and into the aorta to go to the body.
Deoxygenated blood from the SVC passes through the RA into RV into pulmonary artery then takes the ductus arteriosus to get into descending aorta!
YAY
where is a PDA heard best
pulmonic valve
Misoprost
MOA: PGE1 analong that inc. production of gastric mucous
clinically used for: prevention of NSAID-induced peptic ulcers and induces labor (ripens cervix)
Adverse effects: diarrhea
where is a PDA heard best
pulmonic valve
Misoprost
MOA: PGE1 analong that inc. production of gastric mucous
clinically used for: prevention of NSAID-induced peptic ulcers and induces labor (ripens cervix)
Adverse effects: diarrhea
Behcet syndrome - presentation
What HLA is it associated with?
Small vessel vasculitis in Turkish/Mediterranean ppl.
Involved w/ HLA-B51. May be precipitated by HSV or Parvo.
Recurrent ulcers + erythema nodosum.
Flares last 1-4 wks.
Mesoderm derivatives
GONADS
G- genitourinary system (ureters, kidneys)
O- other (muscle, bone, connective tissue, serous lining of body cavities, CV system, parenchyma)
N- notochord (nucleus pulposus)
A- adrenal cortex
D- dura mater
S- spleen
HLA-DR3 associations
diabetes mellitus type 1 SLE Graves Hashimoto Addisons
SLE dIEd in the GRAVE bc she ADDed HASH
HLA-DR4 associations
Diabetes mellitus type 1
Addisons
Rheumatoid Arthritis
HLA-DR3 and B8
Graves
Job Syndrom (Hyper IgE)`
Symptoms: A- cold Abscess B- baby teeth C- coarse facies D- derm problems E- hyper IgE F- fractures
timing on separation anxiety
if kid is less than 3-4 years then its normal
otherwise it has to last for at least 4 weeks
What murmurs INCREASE with the standing valsalva maneuver?
MVP (dec LV volume) with earlier midsystolic click
Less blood coming into heart - easier to regurgitate back into LA
HCM - Stiff hard ventricle which means lots of pressure. Small amount of blood will make a lot of sound whereas if a lot of blood is coming into the ventricle - blood will stretch out ventricle and normalize pressure. this is why HCM murmur is decreased with leg raise and squatting.
Azathioprine MOA
Purine analog - inhibits PRPP and inhibits purine synthesis
Volume of Distribution -
Vd = amount of drug in body / plasma drug concentration
Low Vd - intravascular - plasma bound protein
High Vd - all tissues like fat
Etiologies of PAH:
Often idiopathic. Mostly females. can be from inactivating mutation BMPR2 that normally inhibits cell proliferation,
Endothelial dysfxn which inc vasoconstriction.
Drugs (amphetamines, cocaine)
3 drug classes to treat Pulm HTN
Endothelin antagonists (bosentan) PDE-5 inhibitors (sildenafil) Prostacyclin analogs (epoprsotenol, iloprost)
Specific Prostacyclin analog used for Pulm HTN:
MOA:
Side effects
PGI2 (prostacyclin) Epoprostenol, iloprost
MOA: direct vasodilation and inhibits platelet aggregation. Inc cAMP
Side effect: flushing, jaw pain
MOA of Montelukast, Zafirlukast:
What are these drugs especially good for
blocks leukotriene receptors (CysLT1). Specifically blocks LTC4, D4, E4.
Especially good for aspirin and exercise induced asthma
MOA of Zileuton
Adverse Effect
5-lipooxygenase inhibitor. Decrease the conversion of arachidonic acid to leukotrienes.
Inhibits bronchoconstriction!
Hepatotoxicity
Class 1A antiarrhythmic drugs
The drugs: Quinidine, Procainamide, Disopyramide
MOA: moderate Na channel blocker, inc AP duration, inc QT interval
Clinical Use: both atrial and ventricular arrhythmias
Adverse Effect: cinchonism (quinidine), reversible SLE-like syndrome (procainamide), HF (disopyramide), thrombocytopenia, and torsades due to increased QT interval
Class 1A antiarrhythmic drugs
The drugs: Quinidine, Procainamide, Disopyramide
MOA: moderate Na channel blocker, inc AP duration, inc QT interval
Clinical Use: both atrial and ventricular arrhythmias
Adverse Effect: cinchonism (quinidine), reversible SLE-like syndrome (procainamide), HF (disopyramide), thrombocytopenia, and torsades due to increased QT interval
What is the potency of class 1 antiarrhymics
C>A>B
How to read ECG
- P wave. If present - sinus
- R-R. Rhythym. + rate
- QRS. (< 3 tiny boxes)
- PR interval (< 1 box)
- QT interval (less than 1/2 of the RR)
CYP 450 INHIBITORS
SICKFACES.COM RAG S- sodium valproate I- isoniazid C- cimetidine (H2 blocker) K- ketoconazole (-azoles) F- fluconazole A- acute alcohol C- chloremphenicol E- erythromycin (macrolides) S- sulfonamides C- ciprofloxacin (fluoro) O- omeprazole M- metronidazole
R-ritonavir
A- amiodorone
G- grapefruit
Bismuth, sucralfate MOA and what it is used for
Bismuth binds to the base of an ulcer and allows for increased mucus production, can use as quadruple therapy for H.pylori
Sucralfate requires an acidic environment so can NOT use with PPI
Macrolides MOA (erythromycin, clindamycin)
Used for atypical pneumonia (legionella, mycoplasma, chlamydia) Adverse Effects: MACRO M- motility problems A- arrythmias, QT prolongation C- cholestatic hepatitis R- rash O-eosinophilia
Drugs that cause increased SIADH
cyclophosphamide
carbamazapine
SSRIs
Cyclophosphamide uses
MOA
Adverse Effects
blood cancers and solid tumors, nephritic/nephrotic stuff
MOA; DNA alkylating agent
AE: hemorrhagic cystitis (prevent with MESNA), bladder transitional carcinoma
What is Wolff-Parkinson White Syndrome + treatment
MC pre-excitation ventricular arrythmia
There is an extra bundle of Kent
AV node is bypassed
Delta wave is present–> widened QRS and tiny PR interval
treatment: procainamide
Class IB antiarrhythimcs:
MOA:
Used for:
Lidocaine, Phenytoin, Mexiletine
Na blockade
especially ischemic tissue - binds to partially depolarized cardiac tissue
How do the pulmonary arteries travel relative to the main bronchi
RALS
Right artery is ANTERIOR to the right main bronchus
Left artery is SUPERIOR to the left main bronchus
Triad of Rubella
“eye stuff” (cataracts), “ear stuff” (deafness), and “heart stuff” (PDA)
also can see blueberry muffin rash
Central Venous Catheters should be placed at what location(s) to decrease the risk of infection?
Subclavian V. or
Internal Jugular V.
What is the afferent limb of the cough reflex?
the internal laryngeal n. (travels through the piriform recess)
the internal laryngeal n. is a branch of the superior laryngeal n. which is a part of the vagus nerve
What gene is mutated in Fragile X? And how is it mutated?
FMR1 through methylation, which inactivates FMR1 and inhibits transcription
What are the structures in the retroperitoneum?
SADPUCKER S- (suprarenal) adrenal glands A- abdominal aorta & IVC D- duodenum (except 1st part) P- pancreas (only head and body) U- ureters C- colon (only ascending and descending) K- kidneys E- esophagus R- rectum (mid-distal)
What is the function of the cricothyroid m.?
what is it innervated by?
what pharyngeal arch is the cricothyroid m. from?
what other muscles are derived from this pharyngeal arch?
helps with vocalization
external branch of superior laryngeal n.
ONLY the 4th arch
pharyngeal constrictors and levator veli palitini
what is the function of the internal laryngeal n.?
mainly sensory, supplies to vocal folds
what muscles are supplied by the recurrent laryngeal nerve?
what pharyngeal arch are these muscles from?
what sensory function is carried out by the recurrent laryngeal n.?
ALL intrinsic muscles of the larynx EXCEPT cricothyroid m.
6th arch
sensory function below the vocal folds
what nerve is deep to the piriform recess?
internal laryngeal n.
function of IL-3
stimulates growth and differentiation of stem cells in the bone marrow
what is the most important cytokine that is released in the setting of sepsis?
TNF-alpha, activated macrophages stimulate TNF-alpha to induce systemic inflammation via recruitment of additional leukocytes and increasing pro-inflammatory cytokine production (ex. IL-1 and IL-6)
what is lipoxin?
lipoxin A and B are anti-inflammatory mediators that come from lipoxygenase
__________ are a special type of dendritic cells that contain intracytoplasmic granules having the shape of a tennis racquet
Langerhans cells
the tennis racquet granules are called Birbeck granules
What and where are Meissner corpuscles
location: glabrous (hairless) skin
used for light touch, low-frequency vibration
What and where are Pacinian corpuscles
location: deep skin layers, ligaments, joints
used for high-frequency vibration, skin indentation
What and where are Merkel discs
location: finger tips, superficial skin
used for pressure, deep static touch (shapes, edges)
rare: Merkel cell carcinoma, highly malignant
What and where are Ruffini corpuscles
location: finger tips, joints
used for stretch and joint angle changes
Ehrlichia chaffeensis stuff
harbored by white-tail deer in the US; transmitted to humans via tick bite.
spreads to tissue that’s rich in mononuclear cells (bone marrow, lymph nodes, liver, spleen)
peripheral blood: MORULAE (intraleukocytic inclusions) that are mulberry-shaped
alpha-synuclein production in Parkinsons drive what kind of problems?
NON-MOTOR problems (autonomic dysfunction- constipation, vascular sympathetic nerves- orthostatic hypotension)
because the motor problems (bradykinesia, cogweel rigidity, shuffling gate etc.) is driven by the loss of dopamine
How do you differentiate between primary polydipsia and central DI
Primary polydipsia is more psychological than pathological as the pt is simply consuming a lot of water.
In primary polydipsia and DI the urine osmolality is dilute.
Normal person - If a water deprivation test is done, this kicks in ADH activity. This should cause the serum osmolality to increase until it plateaus because all of the ADH receptors in the kidneys have been used. If exogenous vasopressin is then administered the graph should remain plateaued because all of the ADH receptors are used, it doesn’t matter that you’ve given them more ADH.
Primary polydipsia essentially looks exactly like a normal person except for the fact that initially their serum sodium levels will be lower than a normal person.
If it was central DI, and a water deprivation test was done then the urine osmolality would increase slightly but not significantly because there is no ADH. So exogenous vasopressin administration would then cause a huge increase in urine osmolality.
how do you calculate relative risk?
What do the values of relative risk mean?
How is RR strengthened by p-value and confidence interval (CI)
relative risk is calculated usually in a cohort study.
Ex. risk of people who have breast cancer due to daily alcohol consumption.
to calculate: add all the people in the risk of an outcome(ex. breast cancer) to the exposure(ex. alcohol use) and divide that by the people in the risk of that same outcome without the exposure
If RR= 1 (null value), there is no association
If RR >1, exposure is associated with increased disease occurrence
If RR<1, exposure is associated with decreased disease occurrence
RR values are strengthened if the risk due to chance/probability is proven to be low.
If there is a 95% CI and that interval does NOT include the null value (always 1.0), then this automatically means that the p-value will be <0.05. This means that the RR is statistically significant.
Page 260 in FA
what is rales?
popping sound in alveoli due to heart failure
Explain linkage equilibrium and what happens in disequilibrium?
In a normal population: linkage equilibrium means that there is physical distance between two alleles so the chances of them being inherited together is smaller
Linkage disequilibrium: tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance. Measured in a population, not in a family, and often varies in different populations.
how to calculate the haplotype frequency of the alleles being linked: (frequency of first allele) x (frequency of second allele)
If this calculated value is lower than the frequency of both alleles being inherited together (what they will give in the question), then the population is said to be in Linkage Disequilibrium
what is pleiotropy?
the occurrence of multiple phenotypic manifestations, often in different organ systems, which result from a mutation in a single gene
What is the function of Apo B48
essential because B48 is placed onto chylomicrons; this is the only way chylomicrons can be secreted from the enterocyte
What is the function of Apo B48
essential because B48 is placed onto chylomicrons; this is the only way chylomicrons can be secreted from the enterocyte
MOA of statins
inhibit HMG CoA Reductase
what are the layers of the heart from inside to out?
which layer is most susceptible to ischemic injury?
endocardium myocardium epicardium (visceral layer of serous pericardium) pericardial cavity parietal layer of serous pericardium fibrous pericardium
myocardium (wall pressures are the highest); area with the least amount of blood flow from coronary arteries during systole
What are the layers of the skin?
from superficial to base
COME LET'S GET SUN BURNED stratum corneum lucidum granulosum spinosum basale
characteristics of Psoriasis
Activation of T helper cells and proliferation of keratinocytes. Epidermal hyperplasia (acanthosis) produces erythematous plaques, hyperkeratosis and confluent parakeratosis of the stratum corneum producing the scaling.
Can see pinpoint bleeding from dermal papillae exposure when scales are scraped off: Auspitz sign
Parakeratosis: when keratinocytes still have their nucleus in the stratum corneum
what are the 4 reasons that may cause Minimal Change Disease
MCD: most common nephropathy in kids 4 I's primarily IDIOPATHIC recent infection immunization immune stimulus
what occurs during N3 sleep and what waveform is it on EEG
Deepest sleep.
Sleep walking, night terrors, and bedwetting (Wee and Flee in N3)
Delta waves (low freq, high amplitude)
Difference in side effects b/w nonbenzo hypnotics for insomnia and benzos?
Nonbenzos (Zolpidem, Zaleplom, Eszopliclone) dont affect sleep cycle as much as regular benzos
Difference between first and second gen H1 blockers?
Second gen has less sedating effects because of decrease entry in CNS
What are the layers of the skin?
from superficial to base
COME LET'S GET SUN BURNED stratum corneum lucidum granulosum spinosum basale
First Gen H1 blockers:
Second gen H1 blockers:
and their clinical use.
first gen: Diphenhydramine (benadryl), dimenhydrinate, chlorpheniramine, doxylamine
for allergy, motion sickness, vomiting in pregnancy, sleep
second gen: Loratadine, Fexofenadine, desloratadine
“adines” - used for allergy
Why can diphenhydramine be used for Acute Dystonia in Parkinson patients?
H1 blockers have sedation and anti-muscarinic effects which help the muscle spasms and stiffness
(also have a1 antagonism)
Diphenhydramine and Benztropine are both used for acute dystonia
characteristics of Psoriasis
Activation of T helper cells and proliferation of keratinocytes. Epidermal hyperplasia (acanthosis) produces erythematous plaques, hyperkeratosis and confluent parakeratosis of the stratum corneum producing the scaling.
Can see pinpoint bleeding from dermal papillae exposure when scales are scraped off: Auspitz sign
Parakeratosis: when keratinocytes still have their nucleus in the stratum corneum
what are the 4 reasons that may cause Minimal Change Disease
4 I's primarily IDIOPATHIC recent infection immunization immune stimulus
What are the two main substances that get stuck in the brain in Alzheimer’s
beta-amyloid plaques (excess beta amyloid from insoluble fibrils that accumulate into extracellular amyloid plaques)
AND
neurofibrillary tangles (aggregates of hyperphosphorylated tau protein form intracellular tangled clumps)
What is Ziehl neelson stain used for
Acid fast bacteria (Mycobacteria, Nocardia, Cryptosporidium)
drug that treats pubic lice
Permethrin
this drug is also used for scabies, which affects interdigital skin but presents with small papules, pustules, and burrows
Variceal hemorrhaging is a direct consequence of __________________
Which vein connects the portal vein to the esophagus to cause varices?
portal hypertension
left gastric vein
Characteristics of PSGN
PSGN is a nephritic syndrome which means that the basement membrane is fucked up
happens 2-4 weeks after a Group A Strep Infection in kids and in adults can also be caused by Staph
LM- hypercellular glomeruli
IF- granular (starry sky) appearance due to IgG, IgM, and C3 deposition along GBM and mesangium
EM- subepithelial IC humps
Acute Kidney Injury is common and therefore leads to fluid and salt retention resulting in edema and hypertension
why are vasodilators (arteriolar/venous) not good for long-term therapy of HTN
vasodilators reduce systemic vascular resistance. Baroreceptors can sense this and cause reflex sympathetic activation:
inc. heart rate, cardiac output, contractility AND
RAAS is activated causing sodium and fluid retention
How do you calculate positive predictive value (PPV)?
calculated as the proportion of subjects who truly have the disease among all those with a positive test result`
Antitumor antibiotics (3 classes) and more or less what they do + major side effect
Bleomycin - radical formation - skin hyperpigmentation, pulm fibrosis
Actinomycin D - intercalates into DNA - myelosuppression
Anthracyclines (Doxorubicin, Daunorubicin) - does both of the above mechanisms - DILATED CARDIOMYOPATHY (prevent with dexrazoxane), alopecia
Biggest adverse effect of dihydropyridines
peripheral edema
Ca2+ channel blocking occurs precapillary, so arteriolar dilation, this allows for increased blood flow which then increases capillary hydrostatic pressure and fluid extravasation into interstitium
MOA and clinical use of Flutamide and Bicalutamide
nonsteroidal competitive inhibitors at androgen receptor (decreases steroid synthesis)
use: prostate cancer
MOA and clinical use of Danazol
synthetic androgen that acts as partial agonist at androgen receptors.
use: endometriosis, hereditary angioedema (the drug increases the amount of C1 esterase inhibitor)
MOA and clinical use of Finasteride
5alpha-reductase inhibitor; decreases the amounts of DHT
use: BPH and male-pattern baldness
Polymyositis/Dermatomyositis - similarities and differences
Both: +ANA, inc CK, +anti-Jo, +antiSRP, +anti-Mi-2(helicase)
Poly: Symmetrical shoulder weakness with ENDOmysial inflammation. CD8
Dermatomyositis: also has gottrons papules, heliotrope rash, “shawl and face rash”. CD4. PERImysial and atrophy. For dermatomyositis look for occult malignancy
Explain what happens after PDA is closed/ligated
there is decreased LA pressure–> decreased LV preload
and there is also an increase in LV afterload, this is because before, blood used to enter the aorta and then immediately be shunted to the pulmonary artery.
Now, blood is flowing through the aorta to the rest of the system, so there will be an increase in BP and therefore an increase in LV afterload
MCC of subarachnoid hemorrhage?
MCC of subdural hematoma?
MCC of epidural hematoma?
anterior communicating artery aneurysm that bursts
hemorrhage of bridging veins
tearing of the middle meningeal artery
What is the problem in Open angle glaucoma?
decreased outflow of aqueous humor or increased production
(from uveitis ,RBCs, retinal detachment) all can cause blockages
Medications used to treat open angle glaucoma:
To increase trabecular outflow: (cholinomimetics) Muscarinic agonist
Pilocarpine and Carbachol. both target M3 to contract ciliary muscle leading to pupil constriction. (dec pressure)
To increase uveoscleral outflow: Prostaglandins
Bimatoprost, Latanoprost. inc. outflow of humor via dec. resistance
Side effect: darkens color of iris, eyelash growth
To DEC. Aqueous humor inflow (Production)
Beta (2) blockers: Timolol, betaxolol, carteolol
Alpha agonist: Epinephrine (a1)(works via vasoconstriction of ciliary body), Brimonidine (a2)
Diuretics: Acetazolamide via inhibition of carbonic anhydrase
what is pulmonary alveolar proteinosis?
progressive respiratory dysfunction due to the accumulation of surfactant debris within alveolar spaces.
surfactant is a lipoproteinaceous material that appears pink with PAS staining. It forms lamellar bodies seen on electron microscopy.
debris isn’t being removed because there is impaired alveolar macrophage function.
tx: inhaled GM-CSF replacement therapy
How is atrophy accomplished?
By ubiquitin-proteosome degradation (autophagy of cell components) and then apoptosis
What is apoptosis mediated by and what does this lead to?
Mediated by CASPASES (activated by many different ways) which then activate proteases and endonucleases
Proteases break down cytoskeleton
Endonucleases break down DNA
what are the 4 chronological events/mechanical complications that can happen after an acute MI
- time frame: acute or within 3-5 days
complication: papillary muscle rupture/dysfunction (usually due to RCA occlusion)
findings: acute Mitral Regurg, leading to severe pulmonary edema - time frame: acute or within 3-5 days
complication: interventricular septum rupture
findings: chest pain, hypotension/cardiogenic shock, there will be inc. O2 saturation in Right Ventricle
3.
time frame: within 5 days or up to 2 weeks
complication: free wall rupture (usually due to LAD occlusion)
findings: slit in the Left Ventricle that can lead to cardiac tamponade and sudden death
previous MIs or LV hypertrophy is PROTECTS against rupture!
4.
time frame: up to several months
complication: left ventricular aneurysm
findings: heart failure, angina, ventricular arrhythmias
Why should you NEVER give monotherapy in active TB
Because the bacteria will develop rapid antibiotic resistance
for example: Isoniazid monotherapy would cause 2 forms of gene mutations by the bacteria
1) the bacteria will decrease the amount of catalase-peroxidase enzymes which is what is needed to convert isoniazid to its active metabolite
or
2) the bacteria will modify the protein binding site for isoniazid
therefore, pair Isoniazid with streptomycin, ethambutol and/or pyrazinamide, basically use the RIPE drugs in combination
Why should you NEVER give monotherapy in active TB
Because the bacteria will develop rapid antibiotic resistance
for example: Isoniazid monotherapy would cause 2 forms of gene mutations by the bacteria
1) the bacteria will decrease the amount of catalase-peroxidase enzymes which is what isoniazid needs to kill the bacteria
or
2) the bacteria will modify the protein binding site for isoniazid
therefore, pair Isoniazid with streptomycin, ethambutol and/or pyrazinamide, basically use the RIPE drugs in combination
What are the 4 R’s of Rifampin
RNA Pol Inhibitor
Ramps up P-450
Red/orange body fluids
Rapid resistance if used alone!
drug that is given to help stop serotonin production in serotonin syndrome
cyproheptadine
fyi serotonin syndrome is AMS, neuromuscular excitation, autonomic hyperactivity
What are distinguishing side effects of taking a beta blocker?
Hypoglycemia(no glycogenolysis)
Bronchospasm (no bronchodil)
Heart block
hypotension (if overdose)
What will digoxin toxicity look like?
Hyperkalemia (blocking K from entering cells), “scooped” or depressed ST segments on ECG
+Hypotension/bradycardia
Besides hypotension and bradycardia, what is a major side effect of intoxication from Ca2+ channel blockers
Hyperglycemia (L type calcium channels are found in the pancreas, and blocking them inhibit release of insulin)
What is Recombination?
when 2 chromosomes exchange information via crossing over. Result is having progeny that have mixed traits from both parent viruses. ex.. developing resistance to a medication that one parent virus didn’t have before but the other parent virus did.
Its like a mom and a dad having a baby. Its a complete mix of genetic information and the baby will possess characteristics of both mom and dad. vs reassortment
What is reassortment?
When viruses with segmented genomes (influenza) exchanges genetic material
Ex. a virus that usually infects animals and a virus that normally infects humans end up infecting a cell in a human. Their RNA segments mix together and form a COMPLETELY new virus w/ both RNA. This can lead to antigenic shift and cause pandemics (Spanish flu)
Its like you, a human, mated with a dragon monster and the baby was a weird monster human that had full segments of RNA from you and the dragon monster.
When do you exclude the patients from a study in which they weren’t compliant to, Intention to treat (ITT) or Per Protocol?
Which way is better to avoid bias?
Per protocol is when you remove patients from a study because they weren’t complaint in taking the drug, etc. Reason why researchers want to do this sometimes is because it doesnt’t reflect the rest of the experiment group who is actually complaint. BUT.. ITT is apparently the more fair and unbiased why to conduct research. This is when you dont exclude anyone and leave them in the group they were in. The idea why is that there was some reason why patients weren’t complaint in the study and this needs to be accounted for.
Where does negative selection occur?
Fetal thymus
What is directive counseling and when should a physician do this?
Directive counseling is when you pretty much tell the patient what they need to do. This happens when there is ONLY 1 medically reasonable treatment option.
Ex. Woman wants to keep pregnancy even though it is found to be an ectopic pregnancy and chance of rupture is high. You as physician have to say No because this fetus is sadly not viable and can kill the mother.
What indicates a normal axis on ECG
Lead I and II positive. (-30 to +90)
What causes prolonged QT and why?
Hypocalcemia (Ca enters in phase 2 of A.P.. if no Ca then depolarization/repolarization are prolonged) Drugs (lots of antiarrythmics) Long QT syndrome Levofloxacin Haldol
Etiology of congenital long QT syndrome and 2 different types:
+ Classic presentation of congenital long QT syndrome:
Inherited mutation due to loss of function mutation of Na and K channels. Prolongs depolarization/repolarization and increases risk for ventricular tachyarrhythmias and sudden cardiac death.
Romano-Ward syndrome - aut. dominant, purely cardiac (no deafness)
Jervell and Lange-Nielson syndrome - aut. rec. sensorineural deafness
Young pt. with recurrent seizures(not seizures, just passing out), w/ family history of Sudden cardiac death
What are the 1st, 2nd, and 3rd degree conduction blocks
First degree AV block: Prolonged PR interval (longer than one big box). Can occur with B-blocker use, Ca channel blocker use, and well-trained athletes
tx: nothing
Second degree AV block:
Type 1 (wenckebach)–> progressive lengthening of PR interval until a beat is dropped (P wave not followed by QRS complex). There will also be a variable R-R interval because of this.
tx: nothing
Type 2–> dropped beats that are not preceded by a change in PR interval
tx: pacemaker
Third degree (complete) AV block:
P waves and QRS complex are completely dissociated. Atria and ventricles beat independently of each other. May be caused by LYME DISEASE.
tx: pacemaker
What comprises the Thayer-Martin Agar usually used in Neisseria
vancomycin, polymyxin (colistin), and nystatin
What is Tropheryma whipplei? What disease does it cause? How does it infect? What is the patient’s presentation?
The patient will usually be a middle-aged man with no history of tobacco or alcohol use. The patient will present with diarrhea, malabsorption, weight loss, arthralgia, and in later stages even present with CNS problems (dementia) and heart problems (endocarditis).
The bacteria causes Whipple disease. Basically the bacteria is engulfed by macrophages and then replicates within macrophages. This impairs antigen presentation. Buildup of infected macrophages blocks lymphatic channels which leads to malabsorption.
There will be foamy macrophages that stain PAS (+).
LOL “PAS the FOAMy WHIPped cream in a CAN”
C-cardiac symptoms
A-arthralgias
N-neurologic symptoms
Explain the relationship between these variables in the kidney: FF (filtration fraction), RPF (renal plasma flow), and GFR (glomerular filtration rate)
FF = GFR/RPF
Filtration fraction refers to the amount of “things” that actually get filtered into the lumen from the plasma.
So, how would efferent constriction affect FF?
first the RPF decreases because if there’s vasoconstriction then less amounts of blood plasma goes to the glomerulus in the first place. Then, there is an increase in GFR because pressure to filter the blood increases due to efferent constriction. So finally with an increase in GFR and decrease in RPF, the FF will increase overall.
What is the difference between Iron Deficiency Anemia and Anemia of Chronic Disease
Iron Deficiency Anemia: a microcytic and hypochromic anemia. Decrease in iron due to chronic bleeding, malnutrition, decrease absorption, GI surgery, or increased demand ex. pregnancy.
Labs:
decrease in iron,
increase in TIBC, transferrin saturation will be low,
decrease in ferritin (ferritin is the molecule that stores iron in cells)
Symptoms: fatigue, conjunctival pallor, pica, koilonychia
Anemia of Chronic Disease: a normocytic anemia. This is an anemia due to chronic inflammation (ex. increase in IL-6). This can be due to any chronic infection, neoplastic disorders, chronic kidney disease, and autoimmune diseases.
Labs:
decrease in iron because there is an increase in hepcidin (an inflammatory mediator released by liver, this will bind ferroportin on intestinal mucosal cells and macrophages thus inhibiting iron transport),
decreased release of iron from macrophages
decreased iron absorption from gut
Symptoms: fatigue, mild pallor, prior/current autoimmune condition, etc.
What is the difference between ferritin, transferrin, hepcidin, ferroportin?
ferritin: binds iron in cells
transferrin: transports iron in plasma
hepcidin: inflammatory mediator released by liver
ferroportin: pore within macrophages and mucosal cells to secrete iron when they need to
what are the motor functions and sensory functions of the phrenic nerve?
motor: moves the diaphragm
sensory: sensory fibers to the pericardium, mediastinal pleura, and diaphragmatic peritoneum
How do you calculate true negatives?
How do you calculate false positives?
true negatives = (specificity) x (number of patients confirmed without the disease)
false positives = (1-specificity) x (number of patients confirmed without the disease)
How do you calculate true positives?
How do you calculate false negatives?
true positives = (sensitivity) x (number of patients confirmed with the disease)
false negatives = (1-sensitivity) x (number of patients confirmed with the disease)
what is immune privilege?
there are certain anatomic sites, eyes and testes, in which inflammation is inhibited to limit organ dysfunction.
If there is significant injury to the eye or testes self-antigens from these areas may be released into the lymphatic system where self-reactive T cells (cells that escape negative selection in the thymus) will attack BOTH eyes and testes.
that’s why if there is significant damage to immune privilege organs they are usually removed completely. If it seems curable, then the patient will be started on aggressive steroids.
What is Goodpasture Syndrome?
It is a type of Rapidly progressive (crescentic) glomerulonephritis (RPGN).
there are autoantibodies to GBM and alveolar basement membrane, targeting type 4 collagen. It is a type 2 hypersensitivity reaction.
LINEAR Immunofluoresence!
symptoms: hematuria, hemoptysis
What are the symptoms of Vitamin B12 deficiency?
What 2 “things” are increased in the serum?
Patient will be easily fatigued, exertional dyspnea, gait is unstable, impaired vibratory sensation, pallor of conjunctivae, and nail beds and palms.
1) Vitamin B12 (AKA cobalamin) activates tetrahydrofolate (THF) by removing a methyl group from THF. That methyl group is then transferred onto homocysteine to make methionine. Methionine is used to build proteins and to also make glutathione which can modify DNA. THF is also used in DNA synthesis.
SO, if there is a B12 deficiency then there will be increased amounts of homocysteine and low amounts of THF.
2) Vitamin B12 is also used as a cofactor to the enzyme methylmalonyl-CoA mutase. This enzyme converts methylmalonyl CoA to Succinyl CoA. Succinyl CoA is used for many things in our body, but more importantly if there is a B12 deficiency there will be a buildup of methylmalonyl CoA (methylmalonic acid) which impairs myelin synthesis. This leads to subacute combined degeneration of the dorsal columns and lateral corticospinal tract.
Function of Sertoli and Leyding cells?
Sertoli cells: produce Anti-mullerian hormone (stops female internal genital organs) and Androgen binding protein (concentrates testosterone in the seminiferous tubules).
Leydig cells: produce testosterone which stimulates the Wolffian ducts to develop into internal male genital organs.
Testosterone is peripherally converted to DHT by 5alpha-reductase which develops external male genitalia.
Explain RTA Type IV
Patient will probably be: diabetic and has impaired renin secretion in the setting of juxtaglomerular apparatus destruction from diabetic nephropathy. This means downstream decrease in aldosterone production.
Decreased aldosterone means hyperkalemia and metabolic acidosis (NAGMA); more specifically type 4 RTA.
Serum Sodium CONCENTRATION is unchanged because ADH is still able to function and maintains a normal serum sodium concentration! SO COOL
What is the only pancreatic enzyme that is inactivated by acidic environment?
Pancreatic lipase
This is why if patients have GERD and are on a PPI, it may help them to absorb dietary fats.
Which artery services Wernickes and Brocas area
MCA
What are the symptoms of Acute intermittent porphyria?
How do you treat it?
5 P's: painful abdomen port-wine colored pee polyneuropathy psychological disturbances precipitated by factors that increase ALA synthase (CYP450 inducers)
tx: heme and glucose
This happens because the mitochondrial enzyme ALA synthase, which is responsible for converting [succinyl coA and glycine –> ALA], is over active. Too much ALA is converted into the next intermediate, Porphobilinogen (PBG) and this is what causes the symptoms.
Heme will negatively feedback onto ALA synthase decreasing its activity.
Describe the MOAs and what the following drugs are used for? apixaban (-xaban drugs) cilostazol clopidogrel (-grel drugs) enoxaparin (-parin drugs) eptifibatide, Abciximab, tirofiban drugs naproxen warfarin
-xaban drugs:
MOA-> directly inhibits factor Xa
used for-> treatment and prophylaxis for DVT and PE, stroke prophylaxis in patients with A fib
cilostazol, dipyramidole drugs:
MOA-> blocks phosphodiesterase, which decreases cAMP hydrolysis and increases cAMP within platelets leading to less platelet aggregation
used for-> mainly peripheral vascular disease (claudication)
-grel drugs + ticlopidine:
MOA-> blocks ADP (PDY12) receptor which decreases ADP induced GP2b/3a expression
used for-> same as aspirin use; dual antiplatelet therapy, angina, coronary diseases
-parin drugs:
MOA-> these are LMWH drugs that act mainly on factor Xa
used for-> DVT and PE prophylaxis and MI
eptifibatide, Abciximab, tirofiban drugs:
MOA-> blocks Gp2b/3a (fibrinogen receptor) on activated platelets
used for-> unstable angina, percutaneous coronary intervention
naproxen:
MOA-> NSAID, blocks COX1 and COX2
used for-> analgesic, antipyretic, anti-inflammatory
warfarin:
MOA-> inhibits VKOR enzyme, this inhibits Vitamin K dependent carboxylation of factors 2,7,9,10, protein C and S
clinical use-> chronic anticoagulation, monitor PT/INR
Milrinone
what is it?
MOA?
clinical use?
PDE-3 inhibitor
MOA:
in cardiomyocytes-> increases cAMP and therefore increases Ca2+ influx, increase in inotropy and chronotropy
In vascular smooth muscle-> increase in cAMP leads to MLCK inhibition, that leads to vasodilation and decrease in preload and afterload
clinical use-> acute decompensated HF with cardiogenic shock (inotrope)
What do you use to treat benzodiazepine overdose?
flumazenil
When do you use atropine and when do you use pralidoxime?
If there is a cholinergic excess causing excessive bradycardia, tachypnea, excess salivation, etc. AND there is weakness of muscles…..
then the first thing to give is Atropine because we want to inhibit the Ach at the muscarinic receptors first. We can then give pralidoxime to inhibit the Ach excess at the nicotinic junction and this will help with the muscle weakness.
Pralidoxime MOA: a cholinesterase-reactivating agent that treats both the muscarinic and nicotinic effects in ex. organophosphate poisoning
MOA of Neostigmine and what is it used for
Neostigmine is used for myasthenia gravis, it is a acetylcholinesterase inhibitor
What are neuromuscular blocking drugs used for?
What are the two categories within this drug class?
Clinical use-> used for muscle paralysis in surgery or mechanical ventilation. Selective for nicotinic receptors
1)depolarizing neuromuscular blocking drugs:
Succhinylcholine - produces sustained depolarization and prevents muscle contraction
2)nondepolarizing blocking drugs (-cur drugs):
ex. atracurium, pancuronium, vecuronium, etc.
these are competitive Ach antagonists
what happens if a local anesthetic such as lidocaine is accidentally administered to the internal pudendal artery or inferior gluteal artery instead of the pudendal nerve?
hematoma or arrythmia!
1st pharyngeal arch derivatives:
nerves
muscles
cartilage
nerves-> CNV3, chewing
muscles-> mastication (temporalis, masseter, lateral and medial pterygoids), mylohyoid, tensor tympani, anterior 2/3 of tongue, tensor veli palatini, anterior belly of digastric
cartilage-> maxillary process (maxilla, zygomatic bone) mandibular process (meckel cartilage, mandible, malleus and incus, sphenomandibular ligament)
2nd pharyngeal arch derivatives:
nerves
muscles
cartilage
nerves-> CNVII, facial expression
muscles-> muscles of facial expression, stapedius, stylohyoid, platysma, posterior belly of digastric
catilage-> Reichert cartilage (stapes, styloid process, lesser horn of hyoid, stylohyoid ligament)
3rd pharyngeal arch derivatives:
nerves
muscles
cartilage
nerves-> CNIX, swallow stylishly
muscles->
stylopharyngeus
cartilage->
greater horn of hyoid
Central chemoreceptors in the medulla vs. peripheral chemoreceptors (carotid and aortic bodies)
what do they recognize
central chemoreceptors sense CO2 levels whereas peripheral chemoreceptors sense PaO2(arterial oxygen)
Define the following terms/answer the questions:
1) 5’–> 3’ exonuclease activity does what?
2) 3’–>5’ exonuclease activity does what?
3) primase function?
4) What direction is DNA synthesized?
1) this removes the RNA primers on both the leading and lagging strand
2) this is the inherent proofreading function by DNA polymerase, it allows DNA polymerase to go backwards to remove incorrect bases
3) lays down an RNA primer. This has to be done before DNA daughter strand synthesis
4) always in 5’–>3’ direction
Fibrate drugs (gemfibrozil, fenofibrate, etc.)
MOA and
Adverse Effects
Fibrates are used to decrease the amount of TGs by fatty acid oxidation via upregulating lipoprotein lipase.
Adverse effect of fibrates is gallstones because fibrates also inhibit the enzyme cholesterol 7alpha-hydroxylase. This enzyme is the rate-limiting step in the synthesis of bile acids.
What is the purpose of Interferons?
A part of innate host defense, interferons interfere with both RNA and DNA viruses. Cells infected with a virus synthesize these glycoproteins which act on local cells by priming them for viral defense by down-regulating protein synthesis to resist potential viral replication (interferon alpha and beta)
and by upregulating MHC expression to facilitate recognition of infected cells to improve the intracellular killing ability of macrophages (interferon gamma)
In CF explain how the Cl channel works at the level of sweat ducts and airway/pancreas?
sweat ducts: normally body reabsorbs any NaCl that comes out with sweat, but since the Cl channel is messed up, Cl stays out and because of that even Na doesn’t get reabsorbed leading to salty sweat
airway: normally Cl channel allows for Cl to leave into the lumen of airway and this allows for Na and H20 to be reabsorbed. But in CF, the Cl channel is messed up so there are increased amounts of Cl in epithelial cells and this increases the osmolarity and pulls even more H20 and Na into the epithelium leaving a really sticky and thick mucus.
How do we prevent anthracycline induced cardiotoxicity?
Dexrazoxane - an iron chelator
What do barbiturates and benzos do to cell membrane?
binds to GABA and HYPERpolarizes the cell membrane by allowing Cl- influx. this causes an increased threshold of the excitability
Anti-epileptic drug classes that work post-synaptically
GABA A agonists - Phenobarbital, Topiramate, Benzos
GABA reuptake inhibitor - Tigabine
GABA transaminase inhibitor - Valproic acid, Vigabatrin
What are our accessory muscles used for inhalation?
External intercostals: innervated by thoracic nerve roots T1-T11
Sternocleidomastoid: C1-C4
Scalenes: C4-C8
What muscles are needed for active expiration?
Internal intercostals (T1-T11) Abdominal muscles (innervated by thoracic and lumbar nerve roots)
3 main disease processes that increase Creatine Kinase
Inflammatory myopathies (polymyositis, dermato)
Statin induced myopathy
Hypothyroid myopathy
Right to Left shunts present as early cyanosis and are called “blue babies”
There are 5 of these….
5 T’s
- Truncus Arteriosus
- Transposition
- Tricuspid atresia
- Tetralogy of Fallot
- TAPVR (total anomalous pulmonary venous return)
What are the 4 characteristics of tetralogy of fallot and which one is the most important?
- pulmonary artery stenosis (most important determinant for prognosis)
- RVH
- overriding aorta shifted to the right
- VSD
*the reason this is happening is because the embryologic tubular structure, infundibulum (gives rise to pulmonary artery), is displaced to the right. This allows for overriding of aorta and VSD formation.
Because of the infundibular stenosis (pulmonic stenosis), the pressure is too high for blood to go from RV into Pulm. A., instead it uses the VSD to go into LV. This makes baby cyanotic.
“tet” spells: mild obstruction of pulmonary artery
L-> R shunt is beneficial to help oxygenate blood (PDA)
systolic ejection murmur (crescendo-decrescendo), single S2 heard (if the pulmonic valve is diseased, no sound heard)
squatting improves symptoms because this increases afterload/TPR and less blood is shunted from RV-> LV
CXRAY: boot-shaped heart
When is a VSD murmur heard?
VSD produces a holosystolic murmur that is only heard if the VSD is SMALL, the bigger the VSD the more inaudible it becomes
Where is the position of the aorta relative to the pulmonary artery in a NORMAL heart
aorta is posterior to pulmonary artery
What happens in D-transposition of the great arteries?
The aorta forms anterior and rightwards of the pulmonary artery, the aorta arises from the R ventricle while the Pulmonary artery arises from the L ventricle
Problem: there are two separate circulations going on and therefore this is incompatible with life
Fix: have to have a VSD or PDA so that there is at least some oxygenated blood going into circulation
CXRAY: normal cardiac silhouette but a narrowed mediastinal shadow.
Difference between schizophrenia, schizophreniform disorder, brief psychotic disorder, schizoaffective disorder, bipolar disorder with psychotic features
Schizophrenia is having at least 2 positive symptoms (delusions, hallucinations, disorganized speech) for greater than 6 months.
schizophreniform disorder is having everything in schizophrenia but only lasting 1-6 months.
brief psychotic disorder is at least 1 positive symptom lasting no more than 1 month, usually precipitated by stress.
schizoaffective disorder has symptoms of both schizophrenia and mood disorders (MDD or bipolar disorder). Patient must have > 2 weeks of psychotic symptoms without a manic or depressive episode.
bipolar disorder with psychotic features is either MDD or manic episodes with hallucinations or delusions. The psychotic features occur EXCLUSIVELY during a manic or MDD episode.
Where do the gluteus medius and minimus insert?
What are the functions of these muscles?
insert into greater trochanter, that’s why if something hurts near the hip, it could be something to do with medius and minimus.
these muscles do hip abduction and external rotation and internal rotation (if the hip is flexed)
What is heteroplasmy
describes the condition of having different mitochondrial genomes within a single cell. The severity of mitochondrial diseases is often directly related to the proportion of abnormal to normal mitochondria within a patient’s cells.
Angiogenesis is primarily driven by which two factors
VEGF and FGF (fibroblast growth factor)
Where are B1 receptors found
on the heart AND juxtaglomerular cells of the kidney
MOA of Ribavarin
this is an antiviral drug, inhibits IMP dehydrogenase so that GMP can not be made.
MOA of mycophenolate
this is an immunosuppressant that inhibits IMP dehydrogenase
Alzheimer disease: altered proteins: Change in neurotransmitters: What does brain look like? What type of plaques and tangles? What bodies do we see?
ApoE-2 Dec. risk of sporadic form
ApoE-4 Inc. risk of sporadic form
App, presenilin 1 and 2.
Dec. ACh
Widespread cortical atrophy especially hippocampus. , narrowing of gyri and widening of sulci.
Senile plaques w/ B amyloid core.
Neurofibrillary tangles (intracellular hyperphosphorylted tau proteins.) # of tangles correlates with severity
Hirano bodies in hippocampus (intracellular eosinophilic proteinaceous rods)
What are tangles and which diseases have them
Neurofibrillary tangles are hyperphosphorylated Tau proteins. Found in Alzheimers and Pick’s
Most common cause of encephalitis outbreaks in US? Can you see these on brain scan?
Arboviruses (west nile, St. louis virus, Eastern/western equine viruses)
Must eliminate arthropods to stop outbreaks due to no vaccines available
Sx: Confusion, tremors, focal deficits.
Small viruses so might not be seen on gram stain
Don’t cause any lesions on brain scan
MOA of Ribavarin
this is an antiviral drug, inhibits IMP dehydrogenase so that GMP can not be made.
MOA of mycophenolate
this is an immunosuppressant that inhibits IMP dehydrogenase
MOA of 6-mercaptopurine (6-MP) and azathioprine
mimics hypoxanthine and guanine, it gets incorporated during DNA synthesis but makes non-functioning “DNA”
azathioprine is a prodrug that gets converted into 6-MP in the body
If we have elevated Alk Phos - cholestatic problem – what do we want to do and why
RUQ to determine if it is Intrahepatic or extrahepatic
Causes of intrahepatic cholestasis vs extra:
Extra:
Gallstones, pancreatic mass, biliary strictures
Intra: Primary biliary cholangitis, Cholestasis of pregnancy, contraceptives, erythromycin
Where are parietal cells found vs delta and chief
Parietal - upper glandular layer
Delta/chief - Deeper aspect of gastric glands
Acute gastritis vs chronic
Acute is from Burns,brain injury (cushing ulcer), NSAID use.
Chronic is from H. pylori (more common) or autoimmune (ab attacking parietal cells and intrinsic factor)
Is acute or chronic gastritis a risk factor for gastric carcinoma?
Chronic - from metaplasia
In benign fructosuria, what enzyme is deficient so what enzyme will be utilized instead?
No fructokinase! so.. some fructose can be shunted over to glycolysis via hexokinase and it will turn to fructose 6 phosphate.yay.
Why is hereditary fructose intolerance more severe than essential fructosuria?
Pts are stuck with fructose 1-phosphate which cant get shunted to anything to make energy. In addition, we have wasted a phosphate making fructose 1 phosphate so glycogenolysis and gluconeogenesis are inhibited.
Presents in babies after weaning from breast milk.
No sorbitol, sucrose, or fructose
How does a disseminated gonococcal infection (DGI) present?
DGI is one of the most common causes of septic arthritis in young, sexually active individuals. It is dues to the spread of N. gonorrhoeae from a (usually asymptomatic) genitourinary infection into systemic circulation.
Patients will present with either purulent arthritis or the triad of polyarthralgia, dermatitis, and tenosynovitis.
What is “jersey finger”
happens with someone ruptures their flexor digitorum profundus tendon (FDP).
This tendon originates from the FDP muscle in the forearm, travels through the carpal tunnel, palm, and flexor tendon sheath and then inserts onto the base of the distal phalynx.
The tendon pops when someone hyperextends the DIP joint. Complete tendon rupture results in absent DIP flexion.
function of Flexor Carpi Ulnaris
primary flexor of the wrist
Where is alcohol/ethanol metabolized?
liver
Process of ethanol metabolism
step 1:
ethanol is converted to acetaldehyde via [alcohol dehydrogenase]; this process simultaneously reduces NAD+ to NADH–> this all happens in the cytosol
OR
ethanol is converted to acetaldehyde via [catalase]; this process simultaneously converts H2O2 to H20–> this all happens in the peroxisome
step 2:
acetaldehyde is converted to acetate via [acetaldehyde dehydrogenase]; this process simultaneously reduces NAD+ to NADH–> this happens in the mitochondria
what happens to the liver with increased alcohol consumption?
Hepatosteatosis!
Excess NADH production inhibits free fatty acid oxidation and instead enhances fatty acid formation and increased triglycerides.
It makes more triglycerides by converting DHAP to Glycerol-3-phosphate which requires NADH. Since there is excess NADH via alcohol metabolism, there will be increased Glycerol-3-phosphate.
The glycerol-3-phosphate then accumulates to make triglycerides.
lipids can be stained with oil red O or Sudan black
What is the Hawthorne effect
this is also called observer effect and is the tendency of study subjects to change their behavior as a result of their awareness that they are being studied. This can impact the observed outcomes, thereby seriously affecting the validity of the study.
What is Berkson’s bias
this is also called selection bias which is created by choosing certain people to be the control group
What is the Pygmalion effect
this describes the fact that a researcher’s beliefs in the efficacy of treatment can potentially affect the outcome.
classic example-> teacher is told that a set of students have a high IQ score (they actually don’t). Teacher then has higher expectations for these students and teaches them in a way that facilitates their success. Because of this those students actually performed better.
How does hydrostatic and oncotic pressure affect GFR?
Increase in Glomerular capillary hydrostatic pressure or increase in Bowman’s space oncotic pressure INCREASES the GFR.
Increase in Bowman’s space hydrostatic pressure or Glomerular capillary oncotic pressure DECREASES the GFR.
what are the Z line, M line, A band, H band, and I band in a sarcomere?
Z line: actin filaments are bound to proteins at the Z line
M line: myosin filaments are bound to proteins at the M line in the middle of the sarcomere.
A band: corresponds to myosin filaments in the sarcomere. The size does not change.
H band: region where myosin does not overlap with actin. This area gets smaller with contraction.
I band: region where actin does not overlap with myosin. This area gets smaller with contraction.
Pathogenesis of hepatic encephalopathy
Too much ammonia in the liver that can be converted to urea because of liver damage, cirrhosis, etc.
Ammonia travels to brain where astrocytes convert ammonia to glutamine via glutamine synthetase. The glutamine is then passed into neurons where it uses glutaminase to turn glutamine into glutamate. This is how excitatory NT glutamate is released into the synapse.
If there is too much ammonia, then there is increasing glutamine production in astrocytes. There is an increased intracellular osmolarity causing the astrocyte to swell up and is unable to release the glutamine. This disrupts excitatory neurotransmission. Hence, asterexis.
What artery branches does the splenic a. give off as it makes its way to the spleen?
it gives off the short gastric artery and the left gastroepiploic artery.
The short gastric goes to the stomach and has poor ansastamoses, so the tissue it supplies is vulnerable to ischemia.
The tissue supplied by the L gastroepiploic artery can alternatively be supplied by the Right one.
What artery branches does the splenic a. give off as it makes its way to the spleen?
it gives off the short gastric artery and the left gastroepiploic artery.
The short gastric goes to the stomach and has poor ansastamoses, so the tissue it supplies is vulnerable to ischemia.
The tissue supplied by the L gastroepiploic artery can alternatively be supplied by the Right one.
What occurs in a blunt aortic injury (traumatic aortic rupture) most common in an MVC?
Sudden deceleration results in extreme stretching and injury to the aortic isthmus which is tethered by the ligamentum arteriosum.
Widened mediastinum seen on chest x-ray
Explain the three main steps in De Novo Purine Synthesis
1) Ribose-5-P comes from HMP shunt and is converted to PRPP via [PRPP synthetase]
2) PRPP is converted to IMP
3) IMP is converted to either AMP or GMP via [IMP dehydrogenase]
some facts that go with this process:
- the nitrogenous base in IMP is hypoxanthine
- AAs that donate nitrogens to make purines: glycine, aspartate, and glutamine
- Carbon source to make purines: THF, glycine, CO2
How do we salvage Purines?
We use the enzymes HPGRT (hypoxanthine-guanine phosphoribosyltransferase) and APRT (adenine phosphoribosyltranserase).
Based on the name of the enzyme, we combine either
Guanine (recycled)+ PRPP to make GMP OR
hypoxanthine (recycled) + PRPP to make IMP OR
using the enzyme APRT
Adenine (recycled)+ PRPP to make AMP
Difference between Allopurinol, Febuxostat, and Rasburicase drugs
Allopurinol and Febuxostat both inhibit Xanthine Oxidase to inhibit Uric Acid synthesis
Rasburicase converts Uric Acid into Allantoin. Allantoin is a more easy metabolite to excrete.
De Novo Pyrimidine Synthesis Steps
1) glutamine + CO2 -> carbomyl phosphate via [carbomyl phosphate synthetase II]
2) carbamoyl phosphate + aspartate -> orotic acid
3) orotic acid + PRPP -> UMP via [UMP synthase]
4) UMP -> UDP
5) UDP is either converted to CTP OR
is converted to dUDP via [ribonucleotide reductase]
6) dUDP -> dUMP
7) dUMP -> dTMP via [thymidylate synthase]
*thymidylate synthase requires N5N10methylene THF as a cofactor
What is a Leukemoid Reaction?
it means reactive neutrophilia
the neutrophils will have toxic granulation, cytoplasmic vacuoles, and Dohle bodies (blue cytoplasmic inclusions of rough endoplasmic reticulum)
there will be an increase in LAP (leukocyte alkaline phosphatase, this is an enzyme found in maturing neutrophils)
Patient will be a normal person who suddenly gets very sick. They will have a fever, dyspnea, has an underlying infection like pneumonia. They will have increased neutrophils and bands.
How does the insulin receptor work?
Insulin travels in the blood and binds to insulin receptors on insulin-dependent tissue (muscle and fat).
This leads to two different things->
-RAS/MAP kinase pathway which leads to cell growth and DNA synthesis
OR
-phosphoinositide-3 kinase pathway which ultimately will lead to increased GLUT-4 receptors on cell membrane
How is insulin secreted from B cells?
Glucose is the major regulator of insulin release. When glucose is present in the gut, incretins (GLIP-1 and GIP) are also released which increases B cell sensitivity to glucose.
1) Glucose will enter the B cell via GLUT2 receptor.
* remember GLUT2 is BI-directional*
2) the glucose will undergo glycolysis and hence increase ATP
3) The increase in ATP, will CLOSE the K+ inward rectifying channels, and this keeps K+ within the B cell
4) increase K+ leads to depolarization
5) depolarization leads to increased Ca2+ influx
6) increased Ca2+ leads to exocytosis of insulin granules
What are the diabetes drugs that increase insulin sensitivity?
MOA?
Adverse Effects?
1) Biguanides (Metformin)
MOA: increases AMPK, and inhibits glycerol-3-phosphate dehydrogenase (mGPD) increases glycolysis, increases peripheral glucose uptake, inhibits hepatic gluconeogenesis and the action of glucagon–> all done to increase insulin sensitivity
Adverse effects: lactic acidosis (decrease hepatic uptake of lactate) and B12 deficiency, weight loss (desired)
2) Thiazolidinediones (-glits, pioglitazone)
MOA: Activates PPAR-y (nuclear receptor) which increases insulin sensitivity and levels of adiponectin
Adverse effects: weight gain, edema (ENaC increased, leads to water absorption), HF, increase risk of fractures.
there is a delay in onset of action (several weeks)
What are the diabetes drugs that increase insulin secretion?
MOA?
Adverse Effects?
1) Sulfonylureas (-ides, tolbutamide, glyburide)
MOA: closes the K+ channels in pancreatic B cells-> increased insulin release
Adverse effects: hypoglycemia, weight gain
2) Meglitinides (-glins, nateglinide, repaglinide)
MOA: same as sulfonylureas but act fast, shorter duration, bind on a different site on the K+ channel
What are the diabetes drugs that increase glucose-induced insulin secretion?
MOA?
Adverse Effects?
1) GLP-1 analogs (-glutides, liraglutide, semaglutide, and exenatide)
MOA: decrease glucagon release, decrease gastric emptying, increase glucose-dependent insulin release
Adverse effects: nausea, vomiting, pancreatitis, weight loss, increased satiety
2) DPP-4 inhibitors (-gliptin, linagliptin, sitagliptin)
MOA: inhibits DPP-4 enzyme that deactivates GLP-1, decrease glucagon release, decrease gastric emptying, increase glucose-dependent insulin release
Adverse effects: respiratory and urinary infections, increased satiety
What are the diabetes drugs that decrease glucose absorption?
MOA?
Adverse Effects?
1) Sodium-glucose co-transporter 2 inhibitors (-gliflozin, dapagliflozin)
MOA: blocks reabsorption of glucose in PCT
Adverse Effects: glucosuria, UTIs, vulvovaginal candidiasis, weight loss, use with caution in renal problems like low GFR
2) alpha-glucosidase inhibitors (acarbose, miglitol)
MOA: inhibit intestinal brush-border alpha-glucosidases, this delays carbohydrate hydrolysis and glucose absorption, decreases postprandial hyperglycemia
Adverse Effects: bloating, whoo! LOL
function of amylin
amylin released with insulin from B-cells and inhibits glucagon release and decreases gastric emptying
MOA and Adverse Effect of
Pramlintide
MOA: decrease glucagon release, decrease gastric emptying
Adverse Effect: hypoglycemia, increased satiety
What are the differences between the following anesthetics:
1) Propofol
2) Etomidate
3) Ketamine
1) propofol is a GABA agonist thats used for long-term sedation. Adverse effect is hypotension.
2) Etomidate is a GABA agonist that has the advantage of being the most hemodynamically neutral sedative. Adverse effect is decreased cortisol synthesis. Because of this, it is often avoided in patients with septic shock and should not be used as maintenance of sedation after induction.
3) Ketamine is an NMDA antagonist. This is a good sedative because it preserves the respiratory drive during induction of anesthesia AND it also provides an analgesic effect compared to etomidate and propofol.
Ketamine stimulates release of catecholamines which can cause bronchodilation, but also increase HR, contractility of the heart, which potentially puts patients at risk for CV events.
Extrapyramidal Symptoms of using high potency antipsychotics and how do you treat them?
ADAPT
1) Acute Dystonia: treat with benztropine and diphenhydramine
2) Akathisia: treat with benztropine, B-blocker, benzodiazepine
3) Parkinsonism: treat with benztropine, amantadine
4) tardive dyskinesia: treat with benzodiazepines, botulinum toxin injection, valbenazine (inhibits VMAT2), deutetrabenazine
Extrapyramidal Symptoms of using high potency antipsychotics and how do you treat them?
ADAPT
1) Acute Dystonia: treat with benztropine and diphenhydramine
2) Akathisia: treat with benztropine, B-blocker, benzodiazepine
3) Parkinsonism: treat with benztropine, amantadine
4) tardive dyskinesia: treat with benzodiazepines, botulinum toxin injection, valbenazine, deutetrabenazine
Epoprostenol, iloprost MOA, clinical use, side effects
Prostacyclin (PGI2)
for PAH
flushing, JAW pain
Fxn of PGI2 and TXA2:
PGI2 (prostacyclin)- vasodilation, dec. platelet aggregation
TXA2 (stored in platelets) - vasoconstriction, inc. platelet agg.
In restrictive lung diseases - what is the main form of resistance that we experience and how does the body compensate for this?
Elastic resistance -
Less work is required at low tidal volumes - so rapid, shallow breathing is used.
In obstructive lung diseases, what type of resistance is present and how does the body compensate for this?
Airflow resistance - Work is minimized when these pts. have low respiratory rates with high tidal volumes (slow, deep breathing) Bc if fast breathing - worsens resistance.
2 maneuvers that increase preload and 2 that increase afterload
Preload: passive leg raise and squatting
Afterload: squatting and hand grip
What enzyme is deficient in orotic aciduria?
What happens in this disease?
Inheritance?
UMP synthase
Cant convert orotic acid to UMP. Children have FTT, developmental delay, megaloblastic anemia due to no folate or B12 being incorporated into thymidine.
B12 nor folate helps symptoms!
Treat the kids with Uridine Monophosphate (UMP)
Aut. rec.
What does hydroxyurea do and who cares?
inhibits ribonucleotide reductase (converts UPD to dUDP)
Used in myoproliferaive disorders(CML, polycythemia vera) and sickle cell (inc. HbF)
How does 5-fluorouracil halt DNA synthesis? WHat is its prodrug? and what is it used for?
It forms into fdUMP and inhibits thymidylate synthase
mimics uracil
How does flucytosine work?
Converts itself to 5-fluorouracil by cytosine deaminase .
5 fluorouracil pretends to be uracil and halts dna synthesis
:) hehehehe
Folate becomes ____ that becomes ____ via dihydrofolate reductase.
What meds inhibit this enzyme
End result?
DHF —- THF
Methotrexate, TMP.
Less dTMP bc folate is needed to convert dUMP to dTMP
Urea cycle disorder that results in excess orotic acid?
Ornithine transcarbamylase deficiency -
excess carbamyl phosphate is converted to orotic acid. Ammonium builds up bc halted urea cycle and child will have mental changes or coma.
What is hyperthyroid induced bone loss?
Hyperthyroidism causes increased bone turnover with net bone loss. T3 stimulates osteoclast differentiation, increased bone resorption, and release of calcium.
BUT, as calcium is released from bones into circulation, it suppresses PTH secretion, which leads to decreased reabsorption of calcium in the renal tubules and gut.
SO, at the end this maintains a normal blood calcium level.
Meniere disease triad
- recurrent vertigo
- ear fullness/pain
- unilateral hearing loss and tinnitus
caused by increase pressure and volume of endolymph in the inner ear
Otosclerosis features
conductive hearing loss, no vertigo, mainly in middle aged people
caused by sclerosis of ossicles particularly bony overgrowths of the footplate of the stapes
What is a left atrial appendage and what is it associated with?
An atrial appendage is a small saclike structure that comes off of the atria (like Romeo’s little ear pouch hehehe)
These appendages are susceptible to thrombus formation. Approximately 90% of left atrial thrombi are found within the left atrial appendage in patients with nonvalvular atrial fibrillation..
What are the cellular components/findings between acute atopic dermatitis and chronic atopic dermatitis?
acute atopic dermatitis:
dermal perivascular lymphocytosis and epidermal intercellular edema (spongiosis) manifests clinically as small vesicles
chronic atopic dermatitis: epidermal hyperkeratosis (thickening of the stratum corneum) and epidermal hyperplasia (increased cellularity in the stratum spinosum) manifests clinically as lichenification and scales
Protein synthesis is a process involving the following steps:
- Transcription of DNA into pre-mRNA within the nucleus
- Posttransciptional modification (pre-mRNA processing), including splicing of introns and the addition of a 5’ cap and poly-A tail
- Translation of mRNA to protein at the ribosomes
- Folding of the amino acid chain into a protein structure
- Posttranslational modification and trafficking to the correct destinations
What is Cushing triad?
Usually occurs due to increase in intracranial pressure due to space-occupying lesions (ex. hemorrhage, hematoma)
- hypertension
- bradycardia
- irregular respirations
What is the most common cause of a transtentorial herniation of the uncus?
Lesions in the temporal lobe!
Symptoms: ipsilateral oculomotor nerve palsy with a fixed dilated pupil due to preganglionic parasympathetic nerve fiber damage
What are the symptoms of an uncal herniation?
This kind of herniation will compress the cerebral peduncles, resulting in corticospinal tract injury with contralateral hemiparesis.
Patients will have hyporeflexia and flaccid paralysis
When is nystagmus present?
lesions to the pons, medulla, or cerebellum due to disruption of vestibular pathways
When does an upward gaze palsy occur?
Anything that causes compression of the dorsal midbrain (superior colliculus, pretectal area); usually occurs due to hydrocephalus and dilation of the third ventricle
Everything about Celiac disease
Celiac disease is a chronic malabsorptive disorder caused by a hypersensitivity to gluten, a protein found in wheat, barley, and rye.
Gliadin (a gluten component) triggers an immune-mediated reaction causing villous atrophy, crypt hyperplasia, and intraepithelial lymphocyte infiltration.
Classic celiac disease presents after introduction of gluten into the diet (between 6-24 months old) with symptoms of malabsorption (ex. diarrhea, steatorrhea, flatulence, nutrient deficiencies, weight loss).
Serology: elevated IgA anti-endomysial and anti-tissuetransglutaminase antibodies.
Diagnosis is confirmed by endoscopic biopsy.
Features of necrotizing fascitis:
What bacteria does it come from?
Pathogenesis?
Clinical Manifestations?
Treatment?
Strep Pyogens (GAS)
Staph Aureus
Clostridium perfringens
Pathogenesis:
bacteria spread rapidly through subcutaneous tissue and deep fascia, undermining the skin;
most commonly involves the perineal region and extremities
Clinical Manifestations: erythema of overlying skin swelling and edema pain out of proportion to exam findings systemic symptoms (fever and hypotension)
Treatment:
requires surgical debridement and broad-spectrum antibiotics
3 main “things” seen in hemolytic anemia
- increased reticulocytes
- spherocytes
- nucleated erythrocytes
reticulocytes are larger than mature RBCs, lack central pallor and have a bluish color (polychromatic RBCs) due to the presence of ribosomes which are NOT found in mature RBCs.
spherocytes are erythrocytes with reduced cell membrane, which makes the cell spherical rather than biconcave. Spherocytes generally arise in the setting of immune mediated hemolytic anemia. IgG-coated erythrocytes are partially phagocytized by splenic macrophages, whcih reduces the surface area of the erythrocyte cell membrane, thereby causing the erythrocyte to assume.a spherical shape.
nucleated erythrocytes are very immature RBCs. The presence of nucleated RBCs in the peripheral blood indicates a strong bone marrow response to compensate for the anemia
In chronic transplant rejection, which type of T cells are reacting to APCs presenting DONOR peptides?
What type of hypersensitivity is this?
CD4 (CD8 cytotoxic T cells are involved in the hyperacute/ acute)
Both cellular and humoral - Type II and IV
Everything about Celiac disease
Celiac disease is a chronic malabsorptive disorder caused by a hypersensitivity to gluten, a protein found in wheat, barley, and rye.
Gliadin (a gluten component) triggers an immune-mediated reaction causing villous atrophy, crypt hyperplasia, and intraepithelial lymphocyte infiltration.
Classic celiac disease presents after introduction of gluten into the diet (between 6-24 months old) with symptoms of malabsorption (ex. diarrhea, steatorrhea, flatulence, nutrient deficiencies, weight loss).
Serology: elevated IgA anti-endomysial and anti-tissuetransglutaminase antibodies.
Diagnosis is confirmed by endoscopic biopsy.
What is the response in a chronic transplant reaction?
Proliferation of vascular smooth muscle(arteriosclerosis), parenchymal atrophy, interstitial fibrosis.
WHen does bronchiolitis obliterans (cryptogenic organizing pneumonia) happen?
What is happening?
Classically in chronic transplant rejection reaction. (from lung)
Could be from virus, other etiologies not known.
Fibrosis in small bronchioli
Drugs for TB and thei MOA and side effects
Rifampin - RNA polymerase inhibitor Ramps up CYP-450 (so use rifabutin if liver disease) Red/orange body fluids Rapid resistance if used alone
Isoniazid - inhibition of mycolic acid - neurotoxicity
Pyrazinamide - MOA unclear (:)) hyperuricemia
Ethambutol - blocks arabinosyl transferase (carb polymerization of cell wall) - optic neuropathy
What is a sequence?
A sequence occurs when a single developmental defect causes a cascade of additional malformations
What is the Pierre Robin sequence?
Hypoplasia of the mandibular prominence leads to micrognathia.
Severe micrognathia causes posterior displacement of the tongue (glossoptosis) and this then blocks fusion of the palatine shelves, resulting in a cleft palate that is characteristically U-shaped.
tx: put patient in prone position because gravity pulls the tongue anteriorly, opening the airway
What is an association?
A collection of malformations that are often seen together and do not have a known, common cause
Ex. VACTERL association vertebral anomalies anal atresia cardiac defects tracheoesophageal fistula renal anomalies limb anomalies
Features of polymyalgia rheumatica
Symptoms: pain and stiffness in proximal muscles (shoulders, hips), often with fever, malaise, weight loss. Does not cause muscular weakness. More common in females > 50 years old; associated with giant cell (temporal) arteritis (anterior ischemic optic neuropathy, AION)
findings: increased ESR and CRP, normal CK
Treatment: rapid response to glucocorticoids
Most common cause of Lacunar Stroke and where does it occur?
due to longstanding HTN and diabetes mellitus
near the subthalamic nucleus, causes damage at that area which results in contralateral hemiballism
REVIEW the basal ganglia pathways! pg 516 in book
MCC of atrophy of the lentiform nucleus
Wilson disease!
The lentiform nucleus (globus pallidus and putamen) degenerate. Characterized by liver (hepatitis, cirrhosis), psychiatric (depression, personality changes), and neurologic abnormalities (dysarthria, movement disorders)
Difference between Mifepristone and Progestins (ex. levonorgestrel)
Mifepristone is a progesterone antagonist. When progesterone levels are high during pregnancy, it is used for medical abortion because it causes necrosis of the uterine decidua and stimulates uterine contractions.
Progestins are used as oral contraceptives. They decrease LH secretion, thereby inhibiting ovulation and preventing pregnancy.
Primary hemochromatosis (heriditary hemochromatosis) features
Pathogenesis:
mutations in HFE protein; this protein interacts with the transferrin receptor complex that functions as a sensor of iron stores.
If HFE is mutated, it becomes inactivated and causes enterocytes and hepatocytes to detect falsely low iron levels.
Enterocytes respond by increasing apical expression of DMT1 increasing iron absorption
Hepatocytes respond by decreasing hepcidin synthesis, so low hepcidin results in increased ferroportin expression on basolateral surface of enterocytes. This leads to increased iron secretion into circulation-> iron overload.
i’ve put a picture of this on our document
Symptoms: micronodular cirrhosis, diabetes mellitus, skin pigmentation (bronze diabetes).
Patients at risk for hepatocellular carcinoma, heart failure, and testicular atrophy/hypogonadism.
Polymyositis features
Pathology:
It is an inflammatory myopathy triggered by unknown, possibly viral, antigens. It likely represents a cell-mediated immune response against myocytes. Increased expression of MHC I antigens leads to presentation of autoantigens to CD8+ T cells that then initiate myocyte destruction.
Infiltration of the ENDOMYSIAL by macrophages and CD8+ lymphocytes is typically seen.
Labs: + ANA, increased CK, + anti-Jo-1, + anti-SRP, + anti-Mi-2 (helicase)
Dermatomyositis features
Similar to polymyositis, but also involves Gottron papules, photodistributed facial erythema (ex. heliotrope edema of the eyelids), “shawl and face” rash, hyperkeratosis of fingers “looks dirty/mechanical worker hands”
PERIMYSIAL inflammation with CD4+ cells
Labs: + ANA, increased CK, + anti-Jo-1, + anti-SRP, + anti-Mi-2 (helicase)
Mnemonic for the different blotting techniques
SNOW
DROP
Southern blot is for DNA
Northern blot is for RNA
OOOOOOOOOOOOOOO
Western blot is for Protein
What does equilibrium potential mean?
Equilibrium potentials of cellular ions reflect how they affect the membrane potential if the membrane were permeable solely for that ion.
What are the most important opsonins that promote phagocytosis?
IgG and C3b
What is the main blood supply to the ACL and PCL
middle geniculate artery
What are the symptoms of B2 (riboflavin) deficiency?
What process is affected due to B2 deficiency?
Symptoms: Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth), “magenta” tongue, corneal vascularization
Riboflavin is used in the TCA cycle and ETC!
SO, first riboflavin is phosphorylated to become flavin mononucleotide (FMN), which can then be further phosphorylated to flavin adenine dinucleotide (FAD).
FMN and FAD participate in numerous red-ox reactions, and are also converted to energy carrying states like FADH2 or FMNH2.
FAD is important for the enzyme Succinate Dehydrogenase in the TCA cycle.
FMN serves as a component of Complex 1 in the ETC.
What are the antibiotics that are notorious for causing C. diff infections
clindamycin (most important one imo)
fluoroquinolones
cephalasporins
penicillins
Where is type 1 collagen located
Skin, Bone, tendons, ligaments, dentin, cornea, blood vessels, SCAR tissue
What are the symptoms of B2 (riboflavin) deficiency?
What process is affected due to B2 deficiency?
Symptoms: Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth), “magenta” tongue, corneal vascularization
Riboflavin is used in the TCA cycle and ETC!
SO, first riboflavin is phosphorylated to become flavin mononucleotide (FMN), which can then be further phosphorylated to flavin adenine dinucleotide (FAD).
FMN and FAD participate in numerous red-ox reactions, and are also converted to energy carrying states like FADH2 or FMNH2.
FAD is important for the enzyme Succinate Dehydrogenase in the TCA cycle.
FMN serves as a component of Complex 1 in the ETC.
What are the antibiotics that are notorious for causing C. diff infections
clindamycin (most important one imo)
fluoroquinolones
cephalasporins
penicillins
How do babies with symptomatic VSDs present?
Babies will present with signs of heart failure (poor feeding, sweating/tachypnea with feeds) and failure to thrive due to left-sided volume overload with inability to maintain adequate cardiac output.
cardiac exam: holosystolic murmur at the left lower sternal border; a palpable thrill might also be present at the left sternal border
DiGeorge syndrome/velocardiofacial syndrome features
CATCH-22
Conotruncal abnormalities (tetralogy of fallot, truncus arteriosus, interrupted aortic arch)
abnormal facies
thymic hypoplasia/aplasia (T-cell deficiency)
craniofacial deformities (cleft palate)
hypocalcemia/hypoparathyroidism
What are the thrombolytics?
What do they do?
And how do you reverse the effects of thrombolytics?
Thrombolytics are drugs that lyse a clot by converting plasminogen to plasmin, which cleaves thrombin and fibrin clots. These are the drugs that they call tPA activators
which are: alteplase, reteplase, streptokinase, tenecteplase
To reverse the effects of thrombolytics, give antifibrinolytics.
Which are: aminocaproic acid and tranexamic acid
What is the preferred treatment plan after a STEMI
- Several medications are given to protect heart and relieve pain
- beta blocker
- nitroglycerin
- morphine
- aspirin tablet to chew - PCI (percutaneous coronary intervention) is the first choice for the treatment of STEMI. The goal is to open the artery within 90 minutes of the patient receiving care.
- If the hospital doesn’t have a PCI program, transfer the patient to the nearest PCI hospital. This should be done within 2 hours of the patient first receiving care.
- IF options 2 and 3 are NOT possible, that’s when fibrinolytics/thrombolytics are give. The goal is to infuse clot-busting medications within 30 minutes of a patient’s arrival at the hospital.
What is the #1 adverse effect of giving a fibrinolytic/thrombolytic?
Intracerebral hemorrhage
What is the antiviral given for HSV and VZV?
What is its MOA?
Valacyclovir (prodrug) that gets converted to acyclovir.
MOA: guanosine analogs that are monophosphorylated by the viral thymidine kinase. The virus then tries
to incorporate these guanosine analogs during DNA replication. BUT, DNA replication is terminated! YAY!
Antiviral used for Herpes Zoster
famciclovir
same MOA as valacyclovir/acyclovir
What are some extra-intestinal manifestations of Crohn’s/UC?
Rash (pyoderma gangrenosum, erythema nodosum), eye inflammation (episcleritis, uveitis), oral ulcerations (apthous stomatitis), arthritis (peripheral, spondylitis)
What is the antiviral given for HSV and VZV?
What is its MOA?
Valacyclovir (prodrug) that gets converted to acyclovir.
MOA: guanosine analogs that are monophosphorylated by the viral thymidine kinase. The virus then tries
to incorporate these guanosine analogs during DNA replication. BUT, DNA replication is terminated! YAY!
Antiviral used for Herpes Zoster
famciclovir
What is recall bias and when does this most often occur?
How do we minimize it?
Recall bias results from inaccurate recall of past exposure and many times occurs in RETROspective case control studies. People who have experienced something bad are more likely to remember what happened years ago.
Minimize it by performing a prospective study (begin study by taking exposed and unexposed ppl)
Difference b/w hydralazine and Nitrates
Hydralazine dilates arteries and Nitrates dilate veins.
Hydralazine is for Hypertensive emergencies, HF
Nitrates is for angina, pulm edema. it decreases preload and lets the heart relax :)
What are some extra-intestinal manifestations of Crohn’s/UC?
Rash (pyoderma gangrenosum, erythema nodosum), eye inflammation (episcleritis, uveitis), oral ulcerations (apthous stomatitis), arthritis (peripheral, spondylitis)
Microscopic morphology of Crohn’s
noncaseating granulomas and lymphoid aggregates. Th1 mediated.
Microscopic morphology of Ulcerative Colitis
crypt abscesses and ulcers, bleeding, no granulomas. Th2 mediated.
non selective alpha 1/beta 1/ beta 2 blockers?
Which receptor is more stimulated
Carvedilol
Labetalol
a1 - so DECREASED systemic vascular resistance rather than it just being evened out bc blocking B2
thoracodorsal nerve innervates what -
Nerve root?
Fxn of muscle it innervates?
Latissimus dorsi
C6-8
extension, adduction. internal rotation of humerus
Loop diuretics adverse effects
ototoxicity, sulfa allergy, metabolic alkalosis (loss of K+), gout (because diuretic competes with uric acid transporter leading to increased uric acid in blood)
Sulfa drug allergy Loop Diuretic is ______________
ethacrynic acid,
BUT has more ototoxicity compared to regular loops
Thiazide diuretics Adverse effects
hypokalemia (metabolic alkalosis), hyperuricemia (gout), hypercalcemia, sulfa allergy
Drugs that inc. risk of PML (progressive multifocal leukoencephalopathy)
Natalizumab(a4 integrin blocker), rituximab(CD20)
Features of Glycogen storage disease type V
Called McArdle disease.
Deficient enzyme: skeletal muscle glycogen phosphorylase
Findings: increase glycogen in muscle, but muscle can’t break it down, leads to painful muscle cramps, myoglobinuria (red urine) with strenuous exercise, and arrhythmia from electrolyte abnormalities.
Features of Glycogen storage disease type IV
Called Andersen disease.
Deficient enzyme: branching enzyme
Findings: most commonly presents with hepatosplenomegaly and failure to thrive in early infancy. Other findings include infantile cirrhosis, muscular weakness, hypotonia, cardiomyopathy early childhood death.
Features of Glycogen storage disease type III
Called Cori disease.
Deficient enzyme: Debranching enzymes (alpha-1,6-glucosidase and 4-alpha-glucotransferase)
Findings: similar to von Gierke but milder symptoms and normal blood lactate levels. Can lead to cardiomyopathy. Limit dextrin-like structures accumulate in cytosol. Gluconeogenesis is intact.
Features of Glycogen storage disease type II
Called Pompe disease.
Deficient enzyme: lysosomal acid 1,4- glucosidase (acid maltase) with alpha-1,6-glucosidase activity
Features:cardiomyopathy, hypotonia, exercise intolerance, and systemic findings lead to early death.
Features of Glycogen storage disease type I
Called Von Gierke disease.
Deficient enzyme: glucose-6-phosphatase
Features: severe fasting hypoglycemia, increased glycogen in liver and kidneys, increase in blood lactate, increased TG, increase in uric acid (Gout), and hepatomegaly, renomegaly. The liver DOES NOT regulate blood glucose. Impaired gluconeogenesis and glycogenolysis.
tx: frequent oral glucose/cornstarch; avoid fructose and galactose
Pancreatic ductal adenocarcinoma presentation?
What is the activating mutation?
What other cancers have similar mutations?
Invades common bile duct, therefore increased amounts of conjugated bilirubin in blood, increased Alk Phos, acholic stools
mutation: KRAS-activating mutation
other cancers with KRAS: colorectal and non-small cell lung cancers
Which gene mutation leads to FAP (familial adenomatous polyposis)?
germline mutations in APC tumor suppressor gene
What cancer is strongly associated with BRAF mutations?
malignant melanoma
What cancer is associated with cMYC?
c-MYC protooncogene overexpression is in Burkitt lymphoma, which presents as a facial mass (endemic African form) or with ascites and multi-organ involvement (sporadic form)
Hirschsprung disease presentation
patients do not pass meconium by 48 hrs of life, poor feeding, bilious vomiting, abdominal distension, forceful expulsion of gas and/or stool with a digital rectal exam, and megacolon in the aganglionic segment
What is the most common inherited bleeding disorder?
Presentation?
treatment?
von Willebrand disease.
Presentation: prolonged mucosal bleeding, easy bruising
- vWF carries factor 8 with it, so we would measure bleeding times with PTT*
tx: Desmopressin, apparently this releases vWF from endothelial cells and then would also simultaneously release factor 8
Marijuana intoxication effects
conjunctival injection (red eyes), tachycardia, increased appetite, and dry mouth
What is the SPIKES protocol
This is what is used to deliver serious news. S-> set the stage P-> perception I-> invitation K-> knowledge E-> empathy S-> summary and strategy
How do you know if melanocytes are regressing in melanoma?
The skin will turn white.
The drug is working YAY.
Melanoma uses the PD-1 inhibitor, ex. pembrolizumab
Why would someone be more predisposed to getting Addison disease (primary adrenal insufficiency)?
PAI most commonly results from autoimmune destruction of bilateral adrenal cortex and often occurs in patients with a preexisting history of autoimmune disease (hypothyroidism, T1DM)
Patients will present with salt wasting and hypovolemia and orthostasis (decrease in aldosterone) and hypoglycemia, normocytic anemia, and eosinophilia (decrease in cortisol)
Non-REM stage 1 (N1) Features
EEG- theta waves (4-7.9 Hz)
characteristics- easy to wake; wakefulness-sleep transition
Non-REM stage 2 (N2) Features
EEG- theta waves (4-7.9 Hz) and K complexes and sleep spindles
characteristics- largest percentage of sleep
Non-REM stage 3 (N3) Features
EEG- delta waves (<4 Hz)
characteristics- prominent 1st half of night, difficult to wake, sleepwalking and night terrors
REM Features
EEG- resembles wakefulness, occasional sawtooth waves
characteristics- prominent 2nd half of night, dreams, REMs, muscle atonia, REM sleep behavior disorder and nightmare disorder
Difference between premotor cortex and primary motor cortex
premotor cortex- selection of motor plans for voluntary movements
motor cortex- actually executes the voluntary movements
What happens to our body’s metabolism after a burn injury?
Hypermetabolic state!
increased temperature, hypertension, tachycardia, perisistent hyperglycemia
this is likely triggered by the profound release of inflammatory mediators from damaged tissue which leads to increased levels of catecholamines and glucocorticoids
tx: testosterone analog (oxandrolone), this decreases muscle wasting and enhances protein synthesis
How to calculate Relative Risk Reduction (RRR)?
[Rcontrol - Rtreatment]/Rcontrol
OR
RRR= 1- RR (relative risk-> Rtreatment/Rcontrol)
What is semantic memory? What part of the brain is impaired if there is a loss in semantic memory
Semantic memory refers to memory made from general knowledge (words, pictures, objects). This information is stored in the anterior temporal lobe.
Initial therapy of cryptococcus neoformans and then long-term maintenance therapy
Initial therapy- amphotericin B and flucytosine
Long-term maintenance- fluconazole
What is germline mosaicism
occurs when an unaffected parent has gametes with a mutated allele that is passed to offspring;
it is typically suspected when multiple siblings have an autosomal dominant disorder with phenotypically normal parents
what is genetic heterogeneity?
describes different genetic mutations causing the same disease, so same symptoms/manifestations
When is parental consent NOT required for minors?
- Legal or situational emanicpation (ex. parent, married)
- Emergency care in which delay of care could result in significant harm to life or limb
- Specific conditions (ex. STI, pregnancy, substance abuse) that are potentially serious, sensitive, or stigmatizing
What is the function of Bcl-2
Bcl-2 is an apoptosis inhibitor. When Bcl-2 is overexpressed, cell death is delayed and an accumulation of indolent malignant cells occurs.
Morphine toxicity
Morphine is cleared by kidneys, if there is a problem with the kidneys and they can’t undergo renal clearance, monitor carefully.
Morphine metabolites that are made from hepatic glucuronidation are ACTIVE metabolites.
What binds to the Fc region of antibodies?
Macrophage Fc receptor CD16
What is the receptor on leukocytes and macrophages that bind to and clear complement C3b
CR1
