uWorld 30 Flashcards
how does nucleotide excision repair of UV damaged DNA work
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)
ionizing radiation does what to DNA and how is it fixed
double stranded DNA breaks
fractured ends can be joined by NONHOMOLOGOUS END JOINING
deamination of DNA bases (cytosine conversions of uracil, adenosine to hypoxanthine) can occur how and how is that fixed
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
what is MATURITY-ONSET DIABETES of the YOUNG
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
what is special about glucokinase
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
how does glucose-induced insulin release from beta cells wotk
- glucose enters the beta cell through GLUT-2
- glucose metabolism by glucokinase to G-6-P
- G-6-P is further metabolized by glycolysis and the krebs cycle to produce ATP
- a high ATP to ADP ratio within the beta cell results in the closure of ATP-sensitive K channels
- depolarization of beta cells results in opening of voltage-dependent calcium channels
- high intracellular calcium causes insulin release
what do deficiencies in pyruvate carboxylase cuase
lactic acidosis
fasting hypoglycemia
what is raltegravir
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
what does C3a do
split product ANAPHYLATOXIN that is derived from C3
stimulates mast cell HISTAMINE release- increase d vascular permeability and vasodilation
what does platelet activating factor do
causes platelet aggregation, vasoconstriction, bronchoconstriction, and increased leukocyte adhesion to endothelium
at ver low concentrations it causes vasodilation and increases the permeability of venules
what does IL-5 do
eosinophil stimulation
IgA stimulation
B-cell stimualtion
what characterizes acute eczematous dermatitis
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”
what is seen in acute allergic contact dermatitis
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
what happens in lactate dehydrogenase deficiency
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
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
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
what does carnitine do
amino acid derivative that transports fatty acids into the mitochondria for beta oxidation
synthesized from lysine and methionine (via C essential for this)
what is citrates effect on glycolysis
decreased glycolysis
citrate is powerful allosteric inhibitor of PFK-1
what is required for glyceraldehyde-3-phosphate to 1-3-bisphosphoglycerate in glycolysis, and where does it come from in anaerobic conditions (exercise)
NADH transfers electrons to pyruvate to form lactate and regenerate NAD+
NAD+ is required to convert glyceraldehyde-3-phosphate to 1-3-bisphosphoglycerate
what is ECTOPY
functionally normal cells/tissues found in an abnormal location due to EMBRYONIC MALDEVELOPMENT
different from metaplasia which happens during life
red blood cell fragments, burr cells, and helmet cells are associated with what
microangiopathic hemolytic anemia (DIC, TPP/HUS)
mechanical red cell destruction
what are the first signs of alcohol withdrawal (6-24 hours after last drink)
MILD WITHDRAWL:
TREMULOUSNESS, anxiety, insomnia, diaphoresis, palpations, gastrointestinal upset, intact orientation
what is seen 12-48 hours after the last drink
SEIZURES:
single or multiple generalized tonic-clonic
ALCOHOLIC HALLUCINOSIS:
visual, auditory, or tactile; intact orientation; stable vital signs
what is seen 48-96 hours after an alcoholics last drink
DELIRUIM TREMENS:
confusion, agitation, fever, tachycardia, hypertension, diaphoresis, hallucinations
chronic ethanol use causes down regulation of what
GABA receptos
also weakly inhibits NMDA receptor in the brain, chronic exposure leads to upregualtion of these receptors
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
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+
what is a major risk factor ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
PANCREATITIS
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
elevated pulmonary capillary wedge pressure is suggestive of what
cariogenic pulmonary edema (decompensated left ventricular failure)
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
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
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
