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uWorld 30 Flashcards

1
Q

how does nucleotide excision repair of UV damaged DNA work

A

UV expires creased PYRIMIDINE DIMERS
ENDONUCESE complex recognizes the deformed helix
single strand NICKS on both sides of segment
damage DNA discarded (excised)
synthesis of replacement segment (DNA POLYMERASE)
remaining gap sealed (DNA LIGASE)

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2
Q

ionizing radiation does what to DNA and how is it fixed

A

double stranded DNA breaks

fractured ends can be joined by NONHOMOLOGOUS END JOINING

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3
Q

deamination of DNA bases (cytosine conversions of uracil, adenosine to hypoxanthine) can occur how and how is that fixed

A

spontaneously or secondary to chemical exposure

BASE EXCISION REPAIR- abnormal bases are recognized by specific GLYCOSYLASES without disruption of the phosphodiester backbone

the APURINIC and APLYRIMIDINIC residues are then removed by specific ENDONUCLEASE and replaced with the correct base by DNA POLYMERASE

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4
Q

what is MATURITY-ONSET DIABETES of the YOUNG

A

heterozygous mutations in GLUCOKINASE GENE cause a decrease in beta cell METABOLISM of GLUCOSE, LESS ATP FORMATION, and DIMINISHED INSULIN secretion

mild, non progressive hyperglycemia that often worsens with pregnancy-induced insulin resistance

homozygous mutations lead to fetal growth retardation and severe hyperglycemia at brith

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5
Q

what is special about glucokinase

A

lower glucose affinity than other hexokinases

allows it to function as a glucose sensor in beta cells by varying the rate of glucose entry into the glycolytic pathway based on blood glucose levels

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6
Q

how does glucose-induced insulin release from beta cells wotk

A
  1. glucose enters the beta cell through GLUT-2
  2. glucose metabolism by glucokinase to G-6-P
  3. G-6-P is further metabolized by glycolysis and the krebs cycle to produce ATP
  4. a high ATP to ADP ratio within the beta cell results in the closure of ATP-sensitive K channels
  5. depolarization of beta cells results in opening of voltage-dependent calcium channels
  6. high intracellular calcium causes insulin release
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7
Q

what do deficiencies in pyruvate carboxylase cuase

A

lactic acidosis

fasting hypoglycemia

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8
Q

what is raltegravir

A

INTEGRASE INHIBITOR- disrupts the ability of double-strafed HIV DAN to integrate into host cell’s chromosomes, thereby preventing host cellular machinery from transcribing viral mRNA

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9
Q

what does C3a do

A

split product ANAPHYLATOXIN that is derived from C3

stimulates mast cell HISTAMINE release- increase d vascular permeability and vasodilation

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10
Q

what does platelet activating factor do

A

causes platelet aggregation, vasoconstriction, bronchoconstriction, and increased leukocyte adhesion to endothelium

at ver low concentrations it causes vasodilation and increases the permeability of venules

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11
Q

what does IL-5 do

A

eosinophil stimulation
IgA stimulation
B-cell stimualtion

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12
Q

what characterizes acute eczematous dermatitis

A

SPONGIOSIS
accumulation of EDEMA FLUID in the intercellular spaces of the epidermis
intercellular bridges become more distinctive in an edematous background
epidermis often described as “spongy”

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13
Q

what is seen in acute allergic contact dermatitis

A

Type IV hypersensitivity reaction to antigen on the skin surface

erythematous, papulovesicular, weeping lesion

characterized by spongiosis, accumulation of edema fluid int he intercellular spaces of the epidermis

w/ chronic exposure, lesions become less edematous, with thickening of the stratum spinosum and stratum corneum

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14
Q

what happens in lactate dehydrogenase deficiency

A

glycolysis is inhibited in strenuously exercising muscle as muscle cells cannot regenerate NAD+

high-intensity physical activity leads to muscle breakdown, pain, and fatigue as insufficient amounts of energy are being produced in the exercising muscle

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15
Q

during glycolysis glyceraldehyde-3-phosphate is converted to 1-3-bisphosphoglycerate (BPG) by the enzyme G3P dehydrogenase. This enzyme reduces NAD+ to NADH. NAD+ is in limited amounts in most cells, how is it regenerated from NADH for glycolysis to continue

A

under aerobic conditions: NAD+ is converted to NADH int eh TCA cycle and NADH is the reconverted to NAD+ in the ETC as the energy in NADH is used to synthesize ATP

under anaerobic conditions: NAD+ is regenerated from NADH when pyruvate is converted to lactate via lactate dehydrogenas

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16
Q

what does carnitine do

A

amino acid derivative that transports fatty acids into the mitochondria for beta oxidation

synthesized from lysine and methionine (via C essential for this)

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17
Q

what is citrates effect on glycolysis

A

decreased glycolysis

citrate is powerful allosteric inhibitor of PFK-1

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18
Q

what is required for glyceraldehyde-3-phosphate to 1-3-bisphosphoglycerate in glycolysis, and where does it come from in anaerobic conditions (exercise)

A

NADH transfers electrons to pyruvate to form lactate and regenerate NAD+

NAD+ is required to convert glyceraldehyde-3-phosphate to 1-3-bisphosphoglycerate

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19
Q

what is ECTOPY

A

functionally normal cells/tissues found in an abnormal location due to EMBRYONIC MALDEVELOPMENT

different from metaplasia which happens during life

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20
Q

red blood cell fragments, burr cells, and helmet cells are associated with what

A

microangiopathic hemolytic anemia (DIC, TPP/HUS)

mechanical red cell destruction

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21
Q

what are the first signs of alcohol withdrawal (6-24 hours after last drink)

A

MILD WITHDRAWL:

TREMULOUSNESS, anxiety, insomnia, diaphoresis, palpations, gastrointestinal upset, intact orientation

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22
Q

what is seen 12-48 hours after the last drink

A

SEIZURES:
single or multiple generalized tonic-clonic

ALCOHOLIC HALLUCINOSIS:
visual, auditory, or tactile; intact orientation; stable vital signs

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23
Q

what is seen 48-96 hours after an alcoholics last drink

A

DELIRUIM TREMENS:

confusion, agitation, fever, tachycardia, hypertension, diaphoresis, hallucinations

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24
Q

chronic ethanol use causes down regulation of what

A

GABA receptos

also weakly inhibits NMDA receptor in the brain, chronic exposure leads to upregualtion of these receptors

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25
what is the major stimulator of respiration in healthy people, how does this change in COPD
PaCO2- even slight raises resits in increased pulmonary ventilation in COPD response to PaCO2 is blunted and hypoxemia becomes an important contributor to the respiratory drive PERIPHERAL CHEMORECEPTORS are primarily responsible for sensing arterial PaO2 and can be suppressed with oxygen administration
26
the cardiac myocyte action potential has increased membrane permeability to what and decreased permeability to what ions
increased membrane permeability to Na+ and Ca++ decreased permeability to K+
27
what is a major risk factor ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
PANCREATITIS
28
what characterizes ARDS (acute respiratory distress syndrome)
diffuse injury to pulmonary microvascular endothelium and alveolar epithelium, resulting in increased pulmonary capillary permeability and a leaky alveolar capillary membrane leads to decreased lung compliance, oxygen diffusing capacity decreases, increased work of breathing, and worsened ventilation to perfusion mismatching PULMONARY CAPILLARY WEDGE PRESSURE is NORMAL
29
elevated pulmonary capillary wedge pressure is suggestive of what
cariogenic pulmonary edema (decompensated left ventricular failure)
30
what are peroxisomal diseases
rare inborn errors of metabolism where peroxisomes are either absent or nonfunctional very long chain and some branched chain fatty acids cannot undergo mitochondrial beta-oxidation these FAs are metabolized by a special form of beta oxidation (VLCFA) or by alpha oxidation (branched chain fatty acids such as phytanic acid) within PEROXISOMES
31
what is Zellweger syndrome
an example of peroxisomal disease infants are unable to properly form myelin in the CNS hypotonia and seizures w/ hepatomegaly, mental retardation, and early death within months of initial presentation
32
Refuse disease results from a defeat in what
peroxisomal alpha oxidation and leads to neurologic disturbances in response to accumulation of phytanic acid within the body stick avoidance of chlorophyll in diet
33
where are very long chain fatty acids and fatty acids with odd numbered branch points metabolized
PEROXISOME
34
what goes down in the mitochonidra
``` beta oxidation ketogeneiss TCA cycle ETC initial steps of urea ```
35
patient presenting with progressive headache caused by an expanding neoplasm in the left CEREBELLAR HEMISPHERE, this lesion would result in what
IPSILATERAL DYSDIADOCHOKINESIA, LIMB DYSMETRIA, and INTENTION TREMOR
36
what doe the cerebellar vermis modulate
ataxial/truncal posture and coordination via connection with the medial descending motor systems (anterior corticospinal, reticulospinal, vestibulospinal, and tectospinal tracts) lesions result in TRUNCAL ATAXIA, vertigo and nystagmus can also occur due to the disruption of the inferior vermis and the flocculonodular lobe (vestibulocerebellum)
37
what is a budding yeast with a thick capsule
Cryptoccus neoformans grows abundantly in soil containing bird (pigeon droppings) causes meningoencephalitis and pulmonary disease in immunocompromised
38
small cell carcinomas can display varying degrees of NEUROENDOCRINE differentiation, what immunohistochemical stains do they frequently test positive for
neuron-specific enolase chromogranin synaptophysin
39
what is seen in lung adenocarcinoma
glandular differentiation tubules or papillae may produce mucin
40
what si seen in bronchioloalveolar carcinoma
tall, columnar cells that spread along the alveolar septa and may form papillary projections into the alveolar spaces underlying architecture is usually preserved
41
what is seen histologically in squamous cell carcinoma
polygonal cells with eosinophilic cytoplasm and distinct borders well-differentiated- keratin pearls
42
what is seen histologically in papillary thyroid cancer
branching papillae (fibrovascular stalk covered by neoplastic cuboidal cells) "ground glass" nuclei psammoma bodies
43
what is the coarse of the ulnar nerve
branch of medial CORD of the brachial plexus (C8-T1) psoteromedially in the upper arm passes posterior to the MEDIAL EPICONDYLE of the humerus to enter the anterior compartment of the forearm passes between HOOK of the HMATE and the PISIFORM BONE within GUYON'S CANAL
44
what does the ulnar nerve innervate
FLEXOR CARPI ULNARIS MEDIAL portion of FLEXOR DIGITORUM PROFUNDUS sensation to MEDIAL 1.5 DIGITS and HYPOTHEYNAR EMINENCE most of INTRINSIC MUSCLES of HAND
45
injury to the ulnar nerve can result in what
weakness on WRIST FLEXION/ADDUCTION FINGER ABDUCTION/ADDUCTIOn FLEXION of the FOURTH/FIFTH DIGITS weakness of the lumbricles in the fourth/fifth digits may produce an "ULNAR CLAW" deformity during finger extension
46
what nerve is injured at the wrist in GUYONS CANAL
ULNAR | between HOOK of the HMATE and the PISIFORM BONE
47
axillary nerve injury typically presents how
loss of sensation over the lateral upper arm | deltoid weakness
48
what are the ergot and non ergot dopamine agonists
ergot: BROMOCRIPTINE non-ergot: PRAMIPEXOLE and ROPINIROLE
49
the THORACODORSAL nerve (C6-C8) innervates what muscle and what does it do
LATISSIMUS DORSI origin: broad area spanning from the iliac crest and lumbar fascia to the spinous processes of T7-12 and lower ribs insertion: BICIPITAL GROOVE of the HUMERUS action: EXTENSION,, ADDUCTION, and INTERNAL ROTATION of the HUMERUS
50
why is the LATISSIMUS DORSI vulnerable to injury from external trauma, when else is it injured
broad area and exposed location frequently injured in sports requiring forceful downward movement of the humerus, such as THROWING, CLIMBING, or SWINGING a tennis racket OVERHEAD
51
what innervates the DELTOID, what is its primary action, when is it injured
AXILLARY nerve abduction of the arm injured due to SUDDEN or FORCEFUL LOADING of the ARM while ABDUCTION
52
what innervates the INFRASPINATOUS, what is its primary action, when is it injured
SUPRASCAPULAR nerve externally rotate the arm most commonly injured in association with the supraspinatous due to FALLS or OVERUSE in older patients
53
what innervates the TRAPEZIUS, what is its primary action, when is it injured
cranial nerve XI elevate, rotate, and stabilize the scapula injured in REAR-END ("WHIPLASH") motor vehicle accidents
54
REDUCTION in LEFT VENTRICULAR COMPLIANCE in the setting of DECOMPENSATED congestive heart failure (CHF) indicates what
DIASTOLIC DYSFUNCTION
55
conditions that decrease compliance lead to what changes in LVED pressures
decreased compliance leads to INCREASED LVED (LV end-diastolic) PRESSURES at the SAME LVED VOLUMES shifts pressure volume curve UPWARD and to the LEFT higher LV filling pressures are transmitted back to pulmonary vasculature, leading to PULMONARY EDEMA
56
what is a cause of DIASTOLIC HEART FAILURE (heart failure with PRESERVED EJECTION FRACTION)
RESTRICTIVE CARDIOMYOPATHY: idiopathic or infiltrative disorders like amyloidosis, sarcoidosis, hemochromatosis hypertension obesity
57
what is TRANSTHYRETIN (TTR)
protein tetramer produced in the liver (acts as a carrier of thyroxine and retinol) mutations in TTR gene can increase the tendency of TTR to misfold, producing AMYLOID PROTEIN that infiltrates the myocardium (INFILTRATIVE/RESTRICTIVE CARDIOMYOPATHY)
58
what is the most common cause of death in marfan patients
AORTIC DISSECTION (from cystic medial degeneration of the aorta resulting in dilation) 2nd most common cause is cardiac failure secondary to mitral valve prolapse and/or aortic regurgitation
59
what are some differences in the presentation of marfan and homocystinuria
homocystinuria also has intellectual disability and increased risk of thrombotic evens (MI, stroke), eye is down and in marfan eye is up and out
60
what is ACAMPROSATE
ABSTINENCE-promoting drug modulates GLUTAMATE neurotransmitters at the NMDA receptor and is recommended ONCE abstinence HAS BEEN ACHIEVED
61
what can be used to stop someones CRAVING for alcohol
NALTREXONE (mu-opioid antagonist) it blocks the REWARDING and REINFORCING EFFECTS of alcohol can be initiated while individual is still drinking
62
what is VARENICLINE
paritail neuronal NICOTINIC recetor AGONIST and prevents nicotine stimulation of the MESOLIMBIC DOPAMINE system associated with NICOTINE ADDICTION
63
what are the toxicities of amphotericin B
acute INFUSION RELATED reaction: fevers, chills, giros, hypotension (initial infusion- stop w/ antipyretics and antihistamines) dose-dependent NEPHROTOXCICTY: decreased GFR, permanent loss thought to be due to cumulative total dose significant ELECTROLYTE ABNORMALITIES (hypomagnesemia and hypokalemia): first week of therapy (monitor electrolytes DAILY) ANEMIA- due to suppression of the renal erythropoietin synthesis (can be worse in HIV on zidovudine) THROMBOPHLEBITIS- site of injection
64
what is glaucoma
type of OPTIC NEUROPATHY characterized by atrophy of the optic nerve head usually associated with increased intraocular pressure (IOP) from ↑ production or ↓ outflow of aqueous humor DIAGNOSTIC features: ↑ IOP, abnormal visual field testing with decreased PERIPHERAL vision, ↑ CUP-toDISC-RATIO due to loss of ganglion cells
65
where is aqueous humor produced
ciliary body epithelial cells secreted into POSTERIOR chamber of eye and transferred the PUPIL into the ANTERIOR eye chamber goes through trabecular meshwork (in the anterior chamber angle aka iridocorneal angle) and diffuses into Schlemm's can; (scleral venous sinus) and then into episcleral and then conjunctival veins
66
what drugs decrease intraocular pressure by increased OUTFLOW of aqueous humor
PROSTAGLANDIN F2alpha (LATANOPROST, TRAVOPROST) and cholinomimetics (PILOCARPINE, CARBACHOL)
67
what is amisfostine
cytoprotective free-radical scavenger sued to decrease nephrotoxicity associated with platinum-contianing and alkylating chemotherapeutic agents used to decrease xerostomia (dry mouth)
68
what is dexrazoxane
IRON-CHELATING agent used to prevent anthracycline(doxorubicin)0induced cardiotoxiciity
69
what is filgastim
G-CSF | used to stimulate the proliferation and differentiation of granulocytes in patients with neutropenia
70
how does meson work
binds acrolein, the toxic metabolites formed by cyclofosphamide or ifosfamide that cause hemorrhagic cystitis
71
what is seen in an optic tract lesion
contralateral homonymous hemianopsia | contralateral Marcus Gunn Pupil (fucked up pupillary light reflex)
72
what is involved in the pupillary light reflex
retina, optic nerve, optic chasm, optic tract fibers, pretectal nucleus in midbrain
73
what is MARCUS GUNN PUPIL
a relative afferent pupillart defect often occurs with lesions of the OPTIC NERVE (optic neuritis MS) patients pupils constrict less (and therefore appear to dilate) when a bright light is swung to the pupil CONTRALATERAL to the tract lesion on the SWINGING FLASHLIGHT test
74
what are the frontal eye fields
regions located bilaterally in the prefrontal cortex RIGHT EYE FIELD generates CONJUGATE gaze movements to the LEFT LEFT EYE FIELD generates CONJUGATE gaze movements to the RIGHT lesion = eyes deviate TOWARD LESION
75
Meyers Loop lesions produce what
contralateral upper quadrantanopia "pie in the sky" defect
76
what are the most common causes of acute pancreatitis, what are the other causes
ALCOHOLISM GALLSTONES ``` GETSMASHED Gallstones Ethanol Trauma Steroids Mumps (coxsackie and mycoplasma too) Autoimmune Scorpion sting Hypercalcemia/Hypertriglyceridemia ERCP procedure Drugs (NRTIS, protease inhibitor, sulfa) ```
77
how does hypertriglyceridemia cause acute pancreatitis
fi the serum concentration is over 1000mg/dL the FFA concentration exceeds the binding capacity of albumin and leads to direct injury of pancreatic acinar cells
78
what is seen on HandE of acute tubular necrosis
loss of columnar epithelium denudation of basement membrane epithelial cell vacuolization
79
what are the passes of acute tubular necrosis (ATN)
INITIATION PHASE- corresponds w/ original ischemic or toxic insult and lasts about 36 hours (slight ↓ in urine output) MAINTENCANCE PHASE: tubular damage is fully established- oliguria, fluid overload, electrolyte imbalances (hyperkalemai, metabolic acidosis) for about 1-2 weeks -↓GFR and ↑ creatinine RECOVER PHASE: characterized by RE-EPITHELIZATION of TUBULES (transient polyuria and loss of electrolytes), most patients get complete restoration of renal function
80
defects in what underlie some specific forms of palmoplantar keratoderma or deafness-assocaited ichthiosis
CONNEXINS
81
autoantibodies against cutaneous basement membrane proteins are characteristic of what
``` epidermolysis bullosa acquisita (forms tense aural bull) cicatricial pemphigoid (causes chronic conjunctivitis and scarring) ```

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