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190 Cards in this Set
- Front
- Back
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Most common mutation
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point mutations
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Silent mutation
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altered DNA codes for the same amino acid without changing the phenotypic effect
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Missense mutation
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altered DNA codes for different amino acids, which changes the phenotypic effect
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what type of mutation is sickle cell disease/trait
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missense mutation
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describe the missense mutation that occurs to cause sickle cell anemia disease
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a missense mutation occurs when adenine replaces thymidine causing valine to replace glutamic acid in the 6th position of the b-globulin chain. As a result the RBCs spontaneously sickle in the peripheral blood if the amount sickle hemoglobin is greater than 60%
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NONsense mutation
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altered DNA codes for stop codon that causes premature termination of protein synthesis
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b-thalassemia major
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nonsense mutation with stop codon
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what does the mutation that causes b-thalasemia do?
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nonsense mutation produces a stop codon that causes premature termination of the DNA transcription of the b-globulin chain. Consequently there is no synthesis of hemoglobin A resulting in microcytic anemia
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frameshift mutation
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Tay-Sachs disease
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describe a frameshift mutation
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insertion or deletion of one or more nucleotides shifts the reading frame of the DNA strand
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What is Anticipation?
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additional trinucleotide repeats increase the disease severity in future generations
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what is the MC type of mendelian disorder?
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autosomal recessive
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describe the inheritance pattern of an autosomal recessive disorder
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individuals must be homozygous for the mutant recessive gene to express the disorder
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if you have an AR disease when are you symptomatic?
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early in life
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T/F
Heterozygous individuals of AR disorders are Asymptomatic |
True
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T/F
AR inheritance both parents must have the mutant gene |
True
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what type of disorder is CF?
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Autosomal recessive
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what is the likely hood of passing an AR mutation to your child if both parents have the mutation?
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25% without disorder
50% asymptomatic 25% with disorder |
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Hereditary angioedema
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C1 esterase inhibitor deficiency
Autosomal dominant |
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Glucose 6 phosphate dehydrogenase deficiency
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Glucose 6 phosphate dehydrogenase deficiency
X-linked recessive |
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Sickle cell disease
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specific protein effected: sickle hemoglobin
inheritance pattern: autosomal recessive |
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Hereditary spherocytosis
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Ankyrin defect
Autosomal dominant |
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Duchenne's muscular dystrophy
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Dystrophin defect
X-linked recessive |
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Cystic fibrosis
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Cystic fibrosis transmembrane regulator defect
Autosomal recessive |
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Familial hypercholesterolemia
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LDL receptor
Autosomal dominant |
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neurofibromatosis
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Neurofibromin
autosomal dominant |
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Hemophilia A
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Factor VIII deficiency
X-linked recessive |
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Alkptonuria
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there is a deficiency of HOMOGENTINSIC OXIDASE with proximal accumulation of homogentiisic acid which turns black upon oxidation
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T/F most AR disorders involve enzyme deficiencies
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true
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Phenylketonuria
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deficiency of phenylalanine hydroxylase
causes increase in substrate phenylalanine and decrease in product tyrosine phenylalanine is further metabolized into neurotoxic phenylketones and acids that produce mental retardation and urine with a musty odor |
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Von Gierke's disease
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glucose-6-phosphatase deficiency
fasting, hypoglycemia, heptaomegaly |
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MC AR disorder
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hemochromotosis
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Autosomal dominant disorders
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heterozygotes with dominant mutant gene express disease
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describe the inheritance pattern of AD disorders
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one dominant mutant gene is required to express disorder
Heterozygotes express the disorder Homozygotes are often spontaneously aborted |
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Alkaptonuria deficient enzyme
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homogentisate oxidase
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accumulated substrate in alkaptonuria
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homogentisate
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describe clinical findings in Alkaptonuria
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black urine when exposed to light and cartilages, degenerative arthritis
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what reaction is inhibited by the homogentisate oxidase deficiency in alkaptonuria
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homogentisate > Maleylacetoacetate
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deficient enzyme in Galactosemia
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GALT
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reaction the deficient GALT in Galactosemia inhibits
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Galactose 1-P > Glucose-1-P (Glucose)
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accumulated substrates in Galactosemia
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Galactose-1-phosphate (toxic to liver, CNS)
Galactose (in urine) Galactitol (alcohol sugar increase produces osmotic damage) |
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what are the clinical findings in Galactosemia
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mental retardation, cirrhosis, hypoglycemia (decreased gluconeogenic substrate), cataracts (osmotic damage), avoid dairy products (galactose derives from lactose
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what is the deficient enzyme in Hereditary fructose intolerance?
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Aldolase B
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what reaction is inhibited in Hereditary fructose intolerance
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Fructose 1-P > G-3P + DHAP > Glucose
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what is the accumulated substrate in hereditary fructose intolerance
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fructose-1-phosphate (toxic substrate)
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describe the clinical findings in hereditary fructose intolerance.
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cirrhosis, hypoglycemia (decrease in gluconeogenic substrate), hypophsophatemia (used up in phosphorylating fructose), Avoid fructose and sucrose
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deficient enzyme in homocystinuria
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cystathione synthase
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accumulated substrate in homocystinuria.
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homocystine and methionine
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clinical findings in homocystinuria
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mental retardation, vessel thrombosis; lens dislocation, arachnodactyly (similar to Marfan syndrome; genetic heterogeneity)
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Deficient enzyme in maple syrup urine disease
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branched chain a-ketoacid dehydrogenase
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what are the accumulated substrates in maple syrup urine disease?
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Leucine
Valine Isoleucine their ketoacids |
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what are the common clinical findings in maple syrup urine disease
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mental retardation
seizures feeding problems sweet smelling urine |
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what is the deficient enzyme in Phenylketonuria
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Phenylalanine hydroxylase
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what is the accumulated substrate in phenylketonuria?
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Phenylalanine
Neurotoxic by products |
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what are the clinical findings with phenylketonuria
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Mental retardation, microcephaly, mousy odor, decreased pigmentation
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what must occur for phenylalanine to accumulate in a patient with Phenylketonuria?
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Must be exposed to Phenylalanine (milk) before it can be increased
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how do your treat patients that have phenylketonuria?
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restrict phenylalanine: avoid sweeteners containing phenylalanine
Add tyrosine to diet Pregnant women with PKU must be on a Phy-free diet or newborns will be mentally retarded at birth |
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what enzyme is deficient in "Malignant" phenylketonuria?
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dihydropterin reductase (doesn't produce 5-HT)
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describe "malignant" phenylketonuria.
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accumulation of Phy
similar findings to PKU inability to metabolize tryptophan or tyrosine, which both require BH4. This decrease synthesis of NT (serotonin/dopamine) Neurological problems occur despite adequate dietary therapy restrict Phy in diet Administer L-dopa and 5-HT to replace NT Administer BH4 |
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what is McArdle's disease
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Glycogen storage disease Type IV
deficient enzyme: muscle phosphorylase accumulated: Glycogen Glycogenosis, muscle fatigue; no lactic acid increase with exercise |
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what is Pompe's disease?
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Glycogen storage disease type II
deficient enzyme: a-1,4-Glucosidase (lysosomal enzyme) Accumulated: Glycogen CF: Glycogenolysis, cardiomegaly with early death |
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what is Von Gierke's disease?
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Glucose-6-phosphate deficiency
Accumulated Glucose-6-Phosphate CF: Glycogenosis, enlarged liver and kidneys, hypoglycemia - no response to Glucagon or other gluconeogenesis stimulators Glucose cannot get out of the liver/kidney to be used |
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Gaucher's disease
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lysosomal storage disease
Deficient enzyme: Glucocerbrosidase accumulated substrate: Glucocerebroside CF: hepatosplenomegaly, fibrillar-appearing macrophages in liver, spleen, and BM |
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Hurler's disease
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deficient enzyme: a-L-Iduronidase
accumulated substrate: dermatan and heparan sulfate CF: mental retardation, coarse facial features, short neck, corneal clouding, CAD X-linked recessive form is milder |
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Neimann-Pick disease
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deficient enzyme: Sphingomylinase
accumulated substrate: sphingomyelin CF: mental retardation, hepatospleenomegaly, foamy macrophages |
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Tay-Sachs disease
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4-nucleotide insertion
Deficient enzyme: Hexosaminidase Accumulated substrate: GM2 ganglioside CF: mental retardation, muscle weakness, CHERRY RED MACULA, blindness |
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what type of disease has reduced penetrance?
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Autosomal dominant
- individual with mutant gene does NOT express the disease - transmits to children |
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what is the MC AD disorder?
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von Willebrand disease
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what is the inheritance pattern of X-linked recessive disorders?
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males must have the mutant recessive gene on the X chromosome to express the disorder
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is a female symptomatic in XR inheritance?
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asymptomatic female carrier transmits mutant gene to 50% of sons
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what is the most common X-linked disorder?
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Fragile X syndrome
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what disease may manifest with self-mutilation?
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Lesch-Nyhan syndrome
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what is the inheritance pattern of XD disorders?
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female carriers are symptomatic
- the dominant mutant gene causes disease in males and females |
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what is an example of XD disorder?
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Alport's syndrome
Vitamin D-resistant rickets |
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what is a Barr body?
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inactivated X chromosome
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when does inactivation of the X chromosome that makes the Barr body occur?
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embryonic period of development
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where is the Barr body found?
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The Barr body is attached to nuclear membrane of cells
they are visible in squamous cells obtained from scraping the buccal mucosa |
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how do you calculate the number of Barr bodies an individual should have?
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number X chromosomes - 1
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T/F
normal females have one Barr body, and normal males have none |
True
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what is a nondisjunction?
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unequal separation of chromosomes in meiosis
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what is Mosaicism?
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nondisjunction in mitosis
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describe Down syndrome with (14:21).
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the mother of affected child has 45 chromosomes because of a robertsonian translocation between the long arms of chromosomes 21 and 14.
This produces one long chromosome (14;21) the mother also has one chromosome 12 and one chromosome 21. The father has the normal 46 chromosomes. The affected child has 46 chromosomes with 3 functional 21 chromosomes including (14;21) and 21 from the mother and 14 and 21 from the father |
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what causes Cri du chat syndrome?
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deletion short arm chromosome 5
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what causes most cases of Down syndrome?
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nondisjunction
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what is risk factor for bearing offspring with trisomoy syndromes?
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advance maternal age
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what is the MCC genetic mental retardation?
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Down syndrome
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what are the lab findings in a pregnant mother carrying a child with downs syndrome?
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decreased AFP
decreased estradiol increased b-hCG |
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what are some common clinical findings with Downs syndrome?
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duodenal atresia
Hirschsprung's Epicanthic folds, flat facile profile, macroglossia simian crease |
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what is Edwards syndrome?
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Trisomy 18
CF: mental retardation clenched fist with overlapping fingers VSD Early death |
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what is Patau's syndrome?
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trisomy 13
CF: mental retardation Cleft lip and palate Polydactyly, VSD, cystic kidneys Early death |
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what is the MCC of Turners syndrome?
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Nondisjunction
45, X karyotype |
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what causes the webbed neck observed in Turner's syndrome?
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cystic hygroma
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"Menopause before Menarche" what does this describe?
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Turner's sydnrome
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In a patient that has Turner's syndrome, will they have a Barr body?
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NO
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what are the lab findings in a Turner's syndrome patient?
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decreased estradiol
decreased progesterone increased FSH Increased LH |
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MCC genetic cause of primary ammenorrhea?
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Turner's syndrome
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what characterizes Klinefelter's syndrome?
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female secondary sex characteristics
gynecomastia female hair distribution legs disproportionately long |
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what are the lab findings in Klinefelter's syndrome?
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Leydig cell hyperplasia > loss of Sertoli cells
decreased testosterone, decreased inhibin increased LH & FSH > increased aromatase in Leydig cells increased estradiol > femenization |
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If there is a paternal nondisjunction what may occur?
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XYY syndrome
associated with aggressive behavior (sometimes criminal) normal gonadal function |
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T/F
Polygenic disorders are more common than mendelian and chromosomal disorders. |
True
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what are mitochondrial DNA disorders associated with?
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maternal inheritance
ova have mutant gene |
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what is the inheritance pattern of mitochondrial DNA disorders?
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affected females transmit the mutant gene to all their children
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when does Genomic imprinting take place?
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before fertilization
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what does Genetic imprinting rely on?
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inheritance pattern depends on whether the mutant gene is of maternal or paternal origin
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Prader-Willi syndrome
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microdeletion on paternal chromosome 15
mental retardation, short stature, hypotonia at birth, obesity, hypogonadism |
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Angelman syndrome
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microdeletion on maternal chromosome 15
mental retardation wide based gait inappropriate laughter |
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what determines the genetic sex of an individual?
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Y chromosome
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what occurs with absence of the Y chromosome?
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germinal tissue differentiates into ovaries
Wolffian duct structures undergo apoptosis |
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what occurs with presence of the Y chromosome?
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Germinal tissue differentiates into testes
MIF causes mullerian tissue to undergo apoptosis |
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what is the function of fetal testosterone?
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develops the wolffian duct structures
Epididymis, seminal vesicles, vas deferns |
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what are the functions of fetal DHT?
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develops prostate gland
develops external male genitalia |
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T/F
Genitalia is phenotypically female before DHT is produced |
True
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describe a true hermaphrodite.
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fetus has both male and female gonads
Karyotype is usually 46 XX |
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what is a pseudohermaphrodite?
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phenotype and genotype doe NOT match
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Male pseudohermaphrodite
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Genotypic male (XY with testes)
Phenotypic female - the vagina ends in a blind pouch |
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Female pseudohermaphrodite
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Genotypic female (XX with ovaries)
Phenotypic male |
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what is the MCC of male pseudohermaphroditism?
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testicular feminization
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describe testicular feminization
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defective androgen receptors
loss of function mutation XY genotype Testicles present Mullerian and Wolfian structures: both not present vagina ends in a blind pouch testicles present in the inguinal canal or abdominal cavity |
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when do Malformation disturbances occur?
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disturbances in morphogenesis in embryonic period
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what are some examples of malformation defects?
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open neural tube defect, cleft lip/palate
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when does a deformation defect occur?
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extrinsic disturbance in fetal development
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what is Oligohydraminios a cause of?
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it is a deformation causing problem
causing Potter's facies, clubfeet |
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what causes congenital anomalies
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genetic + environmental factors
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what can Maternal DM cause?
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macrosomia
hyperinsulinemia increases muscle mass and fat |
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what is the MC teratogen?
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alcohol
- fetal alcohol syndrome |
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what is the MC pathogen causing congenital infection?
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CMV
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TORCH syndrome?
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Toxoplasmosis
other agents rubella CMV Herpes simplex virus |
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what does retinoic acid cause in pregnancy?
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disrupts HOX gene function
- craniofacial, CNS, CV defects |
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what is the MCC of stillbirth?
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abruptio placenta
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what is spontaneous abortion commonly caused by?
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trisomy 16
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when do the majority of deaths occur due to SIDS?
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before age of 6 months
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Cigarette smoking
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nicotine is an addictive chemical that attaches to nicotinic cholinergic receptors
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Motor vehicle accidents
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MCC of accidental death between 1-39
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Cigarette smoking
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MCC of increased morbidity and mortality in the US
Yes, also leading cause of premature death in the US |
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Passive smoking
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increased risk in children for otitis media, respiratory infection, and cancer
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Powder tattooing
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this occurs with intermediate wounds
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Wet drowning
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lung injury and hypoxemia are the most common cause of death in wet drowning
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Drowning in fresh water
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water enters the circulation causing dilution of plasma and hemolysis of RBCs
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Salt water drowning
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Lungs have pulmonary edema
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Third degree burns
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painless and have extensive scarring
Healing occurs for residual epithelium along the margins of the burn and from adnexal structures |
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Second degree burns
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painful and have blisters
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contact wounds stellate shaped
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contains soot and gunpowder
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Long range wounds
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no powder tattooing
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Exit wounds
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typically larger and more irregular than entrance wounds
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Heat cramps
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patients are afebrile and the skin is cool and moist
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heat stroke
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body temperature > 40C
No sweating Cerebral dysfunction Skin hot and dry Volume depletion NO sweating Elderly and untrained amateurs are prone to this |
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Heat exhaustion
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temperature < 40C
profuse sweating minimal mental status changes Volume depletion |
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Frostbite
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painless and vasodilation with thrombosis is cause of ischemia
Ice crystallization in cells directly damages the cells |
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Electrocution
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current is more important than voltage
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Dry skin
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increases resistance, which decreases current, while wet skin decreases resistance causing an increase in current
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Current left arm to right leg
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Most dangerous route since it crosses the heart
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COD in electrocution
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cardiorespiratory arrest with ventricular fibrillation is the MC COD
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Non-ionizing radiation
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corneal scarring in skiing
UVB related injury |
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Ionizing radiation
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DNA is most susceptible to direct injury and hydroxyl FRs
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Radiosensitvity
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lymphocytes are most sensitive
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Total body irradiation
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lymphopenia is the first sign
since lymphoid tissue is most susceptible to radiation |
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UV light
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UVB light reflected from the snow is the primary culprit
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UVB light
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thymidine dimers predisopose to basal cell carcinoma of the skin
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Laser radiation
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resembles third degree burns
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heat stroke
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body temperature > 40'C
no sweating, cerebral dysfunction, presence of cerebral dysfunction. Elderly and untrained amateurs are prone to this |
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heat exhaustion
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temperature < 40C
profuse sweating minimal mental status changes Volume depletion |
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Frostbite
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painless and vasodilation with thrombosis is cause of ischemia.
Ice crystallization in cells directly damage the cells |
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Electrocution
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current is more important than voltage
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High altitude
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respiratory alkalosis is essential for oxygenation
a lower alveolar CO2 increases the alveolar oxygen and increases arterial PO2 and arterial saturation |
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acute mountain sickness
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descent to a lower altitude is useful therapy
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acute mountain sickness
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acetazolamide may be useful for acclimatization since it produces the compensation for respiratory alkalosis
- blocking reclaiming of bicarbonate in the proximal tubule, it produces metabolic acidosis, which would normally take a couple of days for the kidneys to accomplish |
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High altitude
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increase synthesis of 2,3-BPG
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sideroblastic anemia: Vitamin ?
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Pyroxidine deficiency
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Perifollicular hemorrhage
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Vitamin C deficiency
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Wernickes
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thiamine deficiency
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Craniotabes
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Vitamin D deficiency
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Follicular hyperkeratosis
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Vitamin A
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Alopecia
lacitic acidosis |
Biotin
(think weight lifter) |
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Anticoagulated
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decreased vitamin K
increased vitamin E |
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Diarrhea
Dermatitis Dementia |
Niacin deficiency
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Bleeding Diathesis
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Vitamin K decreased
Vitamin C decreased |
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Subacute combined degeneration
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Vitamin B12
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Nicotinic acid
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lowers cholesterol and TGs
flushing relieved by taking 30 minutes prior to using drug cheapest lipid lowering agent |
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Pt being treated for TB develops a microcytic anemia
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Pyroxidine deficiency
would have sideroblastic anemia |
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Muscle builder eats 20 raw eggs
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Biotin deficiency
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Dermatitis
Alopecia Lactic acidosis |
Biotin deficiency
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Pure Vegan is most likely deficient in ________.
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Vitamin B12
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Drinking unfortified goats milk.
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Folate deficiency
Pyroxidine deficiency |
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Copper deficiency
|
microcytic anemia
cofactor for ferroxidase which converts ferric to ferrous for binding transferrin |
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Fluoride excess
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mottled teeth and brittle bones
can lead to calcification of ligaments |
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Vitamin E toxicity
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decreases synthesis of vitamin K dependent factors in the liver but doesn't interfere with synthesis of Vitamin K
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Cooper deficiency
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poor wound healing
iron deficiency aortic dissection |
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Chromium deficiency
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glucose intolerance
peripheral neuropathy |
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Vitamin C deficiency
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poor wound healing
bleeding diathesis Glossitis |
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Vitamin E deficiency
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hemolytic anemia
peripheral neuropathy posterior column degeneration myopathy |
