STEP 1 Week 4 Flashcards
Trastuzimab toxicity
Binds to HER2 receptor
Can have cardiotoxicity, usually just causes a decrease in myoxyte contractility
What happens to endometrial cells when progesterone stimulation stops
Release of prostoglandins that cause vasoconstriction and release of metalloporteases that causes apoptosis
Symptoms of neuroblastoma
Tumor of neural crest origin
Nonrhythmic eye movement and jerking movements of the trunk and limb are high indication
Usually have abdominal mass - adrenal gland
What is punctured during a direct suprapubic cysotomy
Anterior abdominal apeneurosis
Most common site of anal fissures
Posterior midline distal to dentate line
Occurs there because less direct blood supply
How to diagnose tetanus
Clinical diagnosis
Effect of prolactin on sex hormones
High levels of prolactin suppress GnRH so can get lower LH and FSH - ammenorhea
Role of citrate in the urine
Citrate binds excess calcium and prevents the fomration of calcium stones
What does hemoglobin release when it binds oxygen
It becomes more acidic so it releases protons - occurs in the lungs
Common medications associated with constipaption
Most protective drug to give during heart failure
Beta blocker
SX of paroxysmal nocturnal hemoglobinuria
Fatigue and jaundice due to hemolytic anemia
Thrombosis - release of prothrombotic chemicals from lysed RBC
Pancytopenia
Hemosiderinuria after a few days
Biochemical change seen in alzheimers
Not enough Ach signaling in the nucleus basalis
This occurs because a deficiency in choline acetyltransferase
Organisms that can commonly cause eryhteme multiforme and MOA
Herpes and mycoplasma pneumonia
Circulating antigen is phagocytosed by peripheral mononuclear cells and DNA is given to keratinocytes. Cytotixic T-cells then see the foreign DNA and begin an immune cascade that causes epithelial damage
Treatment for pyruvate dehydrogenase deficiency
Ketogenic diet
High intake of the ketogenic AA - lysine and leucine
Causes of vascular calcifications
Metabolic insults that cause epithelial cells to differentiate into osteoblast-like cells
Common in chronic kidney disease becuase:
- Electrolyte imbalance - hyperphsophatemia and hypercalcitemia (from dialysis)
- Chronic inflammation
- Atherosclerosis
What ion does GABA cause to come into the cell
Chloride - has an equilobirum of -75 so hyperpolarizes the cell
Immune change with aging
Fewer production of naive B and T lymphocytes - those that are produced are often turned into memory cells of previously encountered infections
How does rhabdo cause renal damage
Release of myoglobin causes ATN - caused by release of heme pigment
If blood is positive but no RBC, suggestive of Rhabdo
Most common causes of acute bacterial prostatitis
Gram negative bacilli
E.coli, klebsiella, proteus, pseudomonas
Most common cause of increased maternal alpha fetal protein
Incorrect aging - often underestimate age when there is irregular meses
Other causes would be multiple fetuses, open neural tube defect/abdominal defect
What is the first step in the formation of atherosclerosis
Damage to epithelial cells
Allows for entrance of cholesterol and inflammation where monocytes come and become macrophages and eat cholesterol – foam cells. Smooth muscle then migrates to form hard cap
Cascade of Gq receptor
GDP is converted to GTP which allows for conversion of PIP2 by phospholipase C into DAG and IP3. This triggers release of Ca2+ that activates protein kinase C
What kind of bias occurs when loss-to-follwup occurs more in a certain group
Attrition bias - a form of selection bias
Makes it look like no correlation exists when there is
How does glycosuria cause hyperfiltration
Because SGLT2 also brings up Na, there will be less sodium delivered to the macula densa when glucose is high. This triggers renin and ultimately higher angiotension II that constricts efferent arteriole. This causes hyperfiltration
What is the axonal reaction
Occurs in the cell body when a part of the axon has been severed.
See swelling of the body with pushing of the nucleus and nissl substance to the periphery as more protein is produced for regeneration
What systemic effect is often seen in autosomal dominant PKD
Cysts and vessel abnormalities - especially berry aneurysm
How is lithium excreted
In the kidneys, filtered and absorbed in the proximal tubule
Diuretics cause volume depletion that lead to resorption of sodium and lithium in the proximal tubule - can cause overdose
Cancer that can be caused by celiac disease
T-cell lymphoma
caused by chornic activation. of T cells with monoclonal expansion
How does pregnancy cause gall stones
Increased estrogen induces HMG-CoA to produce more cholesterol
Progesterone causes reduced bile acid synthesis and gall bladder hypomotility
How does pregnancy impact the intestine
Progesterone causes small bowel hypomotility - less smooth muscle activated and less motilin
Uterus can also impede the small intestine
Salicylate poisoning acid/base levels
Should see about normal pH
There is a metabolic acidosis because salicylic acid uncouples oxygen phosphorylation so get lactic acidosis
There is respiratory alkalosis because of stimulation of the medullary respiratory center
What is seen in peripartum cardiomyopathy
The heart expands with eccentric hypertrophy due to an increase volume, which allows for an increase in compliance. However, over time there is left ventricular failure with reduced ejection fraction
What is occuring during the first few weeks of TB infection
Bacteria are able to grow unchecked inside macrophages due to cord factor
How does CF predespose for bacterial infections
Thick, viscous secretions allow for a good environment for colonization of gram negative rods like pseudomonas - formation of macrocolonies
What is achondroplasia
Autosomal dominant mutation in fibroblast growth factor receptor 3 (FGFR3) that causes dwarfism
How do opioids cause hypotension
Release of histamines
What is subclavian steal
Occurs when there is is stenosis of the subclavian artery proximal to the entrance of the vertebral artery. The vertebral artery on the ipsalateral side will reverse flow to supply blood to the arm
How to diagnose giant cell arteritis
Apparently you can use an elevated sed rate and c-protein
Then if those. are positive would do anartery. biopsy
Why does trisomy 21 predispose for early alzheimers
The amyloid precursor. protein gene is on chromosome 21 - get accumulation of beta amyloid plaques
What is myotinic dystrophy
Autosomal dominant CTG nucleotide repeat in DMPK gene - abnormal myotonin protein kinase
Myotonia (difficulty relaxing muscles), cataracts, baldness, gonadal atrophy
Effect of TMP/SMX on electrolytes
Can cause hyperkalemia
Impairs sodium/potassium exchange in the distal tubule, can have worse side effects if diuretics, ACEi, ARB, elderly
Diagnosis of. narcolepsy
Low levels of hypocretin-1 in CSF or lack of sleep latency (rapid entrance into REM)
How to diagnose anklyosing sponylitis
X-ray of pelvis (see inflammatory arthritis) and spine (fusion of syndesmophytes - bamboo spine)
Side effects of low-potency vs high-potency antipsychotics
MOA of n-acetylcysteine in acetopminophen toxicity
Serves as a source of glutathione which can metabolize NAPQI
Risk factors for esophageal adenocarcinoma
Barret’s esophagus, obesity (increased gasric pressure), smoking, smoked meats
What is seen on liver biopsy in biliary atresia
Inflammation and proliferation of small bile ducts - caused by fibrous destruction of the extrahepatic tree
Greatest risk factor for pancreatic cancer
Smoking
Most common sites for cholesterol emboli
Vessels in the kidney, skin, GI, and CNS
What is lambert-eaton
Autoantibodies to presynaptic Ca2+ channels causes a drop in Ach release - proximal muscle weakness, autonomic sx, hyporeflexia
Improves with use
Associated with small cell lung cancer
Lab changes seen after starting chemo with high cell turnover
Hyperkalemia, hyperphosphatemia, increaased uric acid, increased lactate dehydrogenase
All spill out of cell
Changes in testosterone levels with aging
Drop in free and total testosterone
Compensatory increase in in LH
Increase in sex-hormone binding globulin
What organs contain high levels of smooth er
Helps produce steroid hormones
Gonads, adrenals, liver
Adverse effects of SERMS
Hot flashes, venous thromboembolism
Tamoxifen: Uterine hyperplsia, uterine sarcome
Most common tracts impacted in cobalamin deficiency
DCML, lateral corticospinal, spinocerebellar
Structure most likely injured in posterior hip dislocation
Sciatic nerve
What is DiGeorge Syndrome
Microdeletion of 22q11
Defective development of pharyngeal pouches
What is buspirone
Anxiolytic
Serotonin (5Ht1) and Dopmaine (D2) agonsit
Wont cause dependence like benzos
What is Charcot-Marie-Tooth disease
Group out autosomal dominant progressive hereditary nerve disorders related to defective myelin proteins - PMP22 gene duplication
Foot deformities (pes cavus, hammer toe), lower extremity weakness, sensory deficits
How do SNRIs reduce neuropathic pain
Increase norepinephrine in central synpases which allows for inhibiution of pain pathways
What kind of receptor does glucagon use
Gs
Effects mediated through protein kinase A
What can reduce gynecomastia in men who take GnRH and testosterone inhibitors
Tamoxifen - SERM that will work to block a relative increase in estrogen in the breast
Cytokines associated with atopic dermatitis
Hyper Th2 response: IL-4 and IL-13 – increases IgE, increase vascular permeability, impair further immunity
Most likely brain areas affected in thiamine defiency associated wernicke korsakov
Mammilary bodies
thalamus, periaqueductal gray, locus ceruleus
Metabolism of sublingual nitro vs oral isosorbide dinitrate
Nitro - directly into venous circulation, quick onset
Isosorbide dinitrate - GI absorbption, high first pass metabolism (higher dose)
What is the benefit of a polyclonal immune response
Different Ig from different plasma cells can bind to different epitopse on the same antigen, so multiple Igs can be against a single antigen
Affinity vs avidity
Affinity - How strong the bond of a single binding site is with the antigen
Avidity - How strong the entire Ig binds (so usually higher for IgM)
How is accuracy measured
Area under the curve
Basically number of true positives and true negatives / all measured
What accumulates in pseudogout
Calcium PYROPHOSPHATE
Features of drug induced liver injury
Basically looks like viral hepatitis - fever, jaundice, anorexia, nausea, RUQ pain, rash, myalgia
Liver will be atrophied and shrunken with centrilobular necrosis and inflammation of the portal tracts and parenchyma
High ALT/AST, prolonged PTT (low factor VII)
Where are NADH, FADH2, and GTP produced?
What is icthyosis vulgaris
Dry and cracking skin due to fillagrin mutation that causes defective keratinocyte desquamation
Also see many palmar creases
Why is SIADH euvolemic
When an increase in BV is seen, the RAAS system is suppressed and natreuretic peptide is produced that leads to higher GFR with loss of sodium - see more hyponatremia
Path of CSF
Lateral ventricles, interventricular foramen of monro, third ventricle, cerebral aquedcut, fourth ventricle, formane of luschka and megende, subarachnoid space
Drugs with a lower dose that are given more frequently have:
Lower average drug and peak levels and lower level of side effects
Where does the quadriceps femoris attach
To the tibial tubercle
Osler-Schattler syndrome occurs in young athletes when there as an avulsion at the tibial tubercle because bone grows too fast and tendons cant keep up
Milrinone MOA
PDE3 inhibitor
Increases inotropy and vasodilates
What is food induced allergic proctolitis
Usually seen in neonates, painless bloody/mucus stools thaat are caused by non-IgE mediated allergy to certain food - just avoid that food
Inflammation of the distal colon with eosinophils
How can giant cell arteritis cause blindness
Ischemic optic neuropathy, central retinal occlusion, cerebral infarct
Mannitol MOA
Rapidly increases tubular or plasma osmolality which causes fluid to shift out of cells - can be good as a diuretic or in cerebral edema (from tissues to plasma)
Can be dangerous in CHF or pulmonary edema
What do muscle biopsies look like in duchenes muscular distrophy
Muscles are replaced by fat and fibrour tissue - firbofatty muscle replacement
SX of short bowel syndrome
Occurs after bowel resection or in crohns
Diarrhea after meals, weight loss, B12 deficiency (loss of distal illeum)
What is posttransplant lymphoproliferative disorder
Immunosuppression leads to less cytotoxic T cell surveillance so EBV can trigger unchecked proliferation of B cells
WIll get B cell symptoms - night weats, lymphadenopathy, weight loss and will see monoclonal B cell proliferation
What would pyruvate kinase deficiency look like
Pyruvate kinase converts phosphoenolpyruvate into pyruvate and yields one molecule of ATP
RBC dont have mitochondria so rely on this reaction to make pyruvate which eventually becomes lactate, their major source of energy. Without pyruvate kinase, ATP cant be produced so RBC lose ability to maintain membrane and transport cations - leads to hemolysis
Would see splenomegaly due to red pulp hypoplasia - removing damaged RBC
Changes in renal blood vessels due to malignant hypertension
- Fibrinoid necrosis - amorphous pink material due to cell death and fibrin deposition. Smudged necrotic endothelial cells
- Hyperplastic arteriolosclerosis - activated platelets and injured cells release growth factors that lead to layers of smooth muscle cell and collagen with a narrows lumen - onion skinning
What is an acute dystonic reaction
Occurs after giving a antipsychotic - acute, involuntary contraction of a major muscle group
Occurs due to dopamine antagonism in the nigrostriatial pathway
Function of hormone sensitive lipase
Converts triglycerides in adipose tissue into glycerol and free fatty acids
Sx and findings of cerebral palsy
Motor delay, hypotonia, hyperreflexia, early hand preference
Will see periventricular focal necrosis becuase of sparse blood flow (if premature)
Which binds both Xa and thrombin - heparin or LMWH
Heparin - it has a longer pentasaccharide sequence so can bind antithrombin and then either Xa or thrombin
SX of ALS
Anterior horns affected - LMN signs
Lateral corticospinal tracts affected - UMN signs
What are the indirect and direct pathway
SX of secondhand smoke in children
Recurrent infections - pneumonia, otitis media due to impaired mucociliary and macrophage function
Asthma
What fetal cells does zika target
Neural progenitor cells
Where is the most common site of aortic rupture during traumatic injury
The aortic isthmus - it is thethered by the ligamentum arteriosum
Why are diabetics at risk of hypoglycemia with exercise
In non-diabetic people, exercise leads to uptake of glucose by muscles and a subsequent reduction in insulin and release of glucagon. This leads to gluconeogenesis and glycogenolysis
In diabetics, there is no insulin regulation
How can fibrates cause gall stones
They inhibit cholesterol 7 alpha hydroxylase which is the enzyme that catalyzes the formation of bile acids - cholsterol accumulates in the bile undesolved
What CN exits the brain at the. cerebellar peduncle
CN V
What enzyme and regulator regulate the first state in conversion on pyruvate for gluconeogenesis
Pyruvate carboxylase to oxaloacetate (in mitochondria) - activated by increased Acetyl-coa
What are the steps in de novo purine synthesis
Starts with Ribose 5-phosphate which is converted to PRPP
PRPP to 5-phosphoribosylamine then to IMP
At what levels does the psoas msucle attach to the spine
T12-L5
How can administration of O2 lead to hypercaprnia in COPD exacerbation
Before O2, pulmonary vessels constrict in areas of low ventilation
When O2 is given, these vessels dilate but there is still low ventilation so there is a perfusion-ventilation mismatch
Pemphigus vulgaris vs bullous pemphigoid age difference
Pemphigus is 40-60
Phemphigoid is over 60
What is presbyopia
The age related hardening of the lens - loss of accomodation with far vision - the image is focused behind the retina
If the person had myopia before then this can be helpful
SX of phenylketonuria
Lack of pigment - hair, sking, brain
Seizures
Musty odor
Intellectual disability
What are the final branches of the brachial plexus
MARMU
musculocutaneos
axillary
radial
median
ulnar
How can those with 17 alpha hydroxylase deficiency survive
In the mineralcorticoid pathway (unblocked), there is increased production of coricosterone, a weak glucorticoid
4 Ts cancers found in the anterior mediastinum
Thymoma
Teratoma (and other germline tumors)
Terrible (lymphoma)
Thyroid neoplasm
What enzyme takes over in fructose metabolism in a fructokinase deficiency
Hexokinase - shunts fructose to glycolysis
What areas are most affected by Alzheimers
Temporoparietal lobes and hippocampus, but it is diffuse
Landmarks for a pudendal nerve block
Ischial spine and sacrospinal ligament
Location most likely to cause intraventricular hemorrahge in newborns
The germinal matrix - doesnt have as many supporting cells
How does nitroprusside affect heart function
Equally dilates arteries and veins so leads to a decrease in preload and afterload - same SV
Area of heart conduction from fastest to slowest
Purkinje, atrial muscle, ventricular muscle, AV node
What is eosinophilic esophagitus
TH2 hyperactivity that lead to eoisinophils invading the esophageal mucosa
Rings, linear furrows, whitish papules
Phases of cells in stroke
What is lipofuscin
Accumulates with age
Lysosomal breakdown products = lipid polymers, phospholipids from lipid peroxidation
Most often cause of atrial flutter
Re-entrent circuit in the travocuspid isthmus - area between the tricuspid and inferior vena cava
What is hidradenitis suppurative
Obstruction of folliculopilosebaceous units that leads to large ulcers and nodules in the axilla, groin, medial thighs
Damage to the radial nerve at what muscle is caused by repetitive pronation/suppination
Supinator muscle - see finger drop (loss of extension)
What do eosinophils look like
Bi-lobed and have orange-pink granules (major basic protein)
What can cause forward slippage of a vertabra
Sponylolisthesis - break of the pars interarticularis
Which steps of the TCA cycle require thiamine
Pyruvate dehydrogenase (to make succinyl-coA) and alpha-ketoglutarate dehydrogenase
What nerve lies below the piriform recess
internal branch of the superior laryngeal nerve - carries sensory innervation above the vocal cords
Important for cough reflex
FIndings for pericarditis
Pleural chest pain
Can cause a pericardial effusion that causes decreased stroke volume so get tacchycardia, low voltage ECG (blocking heart), electrical alternans (swinging heart)
What does metastatic melanoma look like
Cells of variable pigments with abnormal nuclei (multiple)
Simulation of what nerve would help in obstructive sleep apnea
Hypoglossal - would push the tongue forward
What enzyme deficiency can cause diabetes
Glucokinase
It is necessary to turn glucose into ATP which triggers release of insulin
Interpretation of Weber and Rhinne tests
Weber - on forhead, should be the same. If conductive hearing loss, heard best in affected ear. If sensorineural, head best in unaffected ear
Rhine - place on mastoid then shift to ear, should be heard longer through air. If heard better through bone, then conductive on affected ear. Sensorineural would have AC>BC bilaterally
How to tell primary vs secondary polycythemia vera
Primary PV will have an increase in plasma volume with luekocytosis, thrombocytosis, and splenomegaly
What is seen on biopsy in rheumatic fever
Large group of multinucleated giant cells (aschoff body) and cells with linear “caterpillar” chromatin (Anitchskow cells)
What are some conditions with polygenetic inheritence
Function of HFE and transferrin
They serve as a receptor that monitors iron loads
Mutation in hemachromatosis leads to chronic actication and uptake of iron from the intestines (DMT 1)
Also leads to less hepcidin release by the liver which allows for increased ferrorportin levels - higher circulating iron
Is GFR v creatine linear?
No, at the steady state, large changes of GFR wont impact creatinine
But at the extreme low of GFR, creatinine is greatly impacted
What is abetalipoproteinemia
A defect in the MTP (microsomal transport protein) gene that causes a lack of ApoB-100 and ApoB-48 so no chylomicrons or VLDL
Get no fat absoprtion - steattorhea, failure to thrive, intellectual disability, retinitis, ataxia
Biopsy shows lipid laden enterocytes
What is sorbitol usually degraded into
Fructose
What is the first thing to measure in metabolic alkalosis
Urine chloride
Low chloride can cause a defect in secretion in bicarb
