w12 Flashcards

1
Q

Normal metabolism

A

maintains homeostasis, converts food to energy and removes waste products of metabolism

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2
Q

Metabolic disorders can disrupt

A

the ability of enzyme/cell or organ to perform critical biochemical reactions

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3
Q

Metabolic disorders can interfere with

A

1) growth (2) energy production & distribution to organs and tissues (3) waste product elimination

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4
Q

consequences of metabolic imbalances

A

: brain dysfunction (intellectual disability or siezures) sensory and motor dysfunction (HL, blindness, decreased muscle tone) organ failure

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5
Q

Metabolic pathways

A

: many including transporting or processing proteins (amino acids) carbohydrates (sugars and starches) or lipids (fatty acids)

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6
Q

what causes metabolic disorders

A

Genetic: deficiency can be at molecular/cell level or organ/tissue level
Environment & lifestyle

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7
Q

Hereditary metabolic disorders:

A

common disorder- as a group affect 1/1000 but individually rare >1300 different types of rare metabolic disorders
- Onset congenital or early childhood

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8
Q

acquired metabolic disorders

A

diabetes mellitus type 2 * MOST common acquired disorder affecting >2 million Canadians

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9
Q

metabolic disorder: complex

A

Genetic factors: inherited susceptibility
Environmental/lifestyle factors: lack of physical activity, smoking, excess alcohol consumption, nutrient deficits, toxic exposures
Organ/tissue disease affecting (liver, cardiovascular system, pancreas, endocrine gland, other organ involved in metabolism

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10
Q

Site of lesion of metabolic disorders

A

cochlea, auditory nerve, CANS may be affected

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11
Q

Primary auditory damage metabolic disorders

A

disease process which directly target both inner ear and another tissue/organ system
- Both are primary targets & share same underlying pathophysiology (e.g., gene mutation)

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12
Q

Secondary auditory damage metabolic disorders

A

metabolic derangement primarily targeting non-auditory tissues/organs (e.g, hyperlipidemia: Cardiovascular & blood vessel disease)
- Metabolic derangement then has secondary effects disrupting auditory system

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13
Q

mitochondrial disorders

A

damaged mitochondria cause loss of energy supply to cochlear cells (ATP) and excessive ROS generation- disrupts stria vascularis, hair cells & neurons leading to degeneration

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14
Q

metabolic syndrome

A
  • quite complex and a number of different factors: Genetics, Lifestyle
  • rates of recovery from SSNHL were lower among patients with metabolic syndrome and prognosis is poorer in patients with a greater # of metabolic syndrome factors (central obesity, impaired glucose metabolism, insulin resistance, inflammation, dyslipidemia etc.)
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15
Q

Type 1:

A

cause unknown (autoimmune & genetic factors) develops in childhood or adolescence, associated with peripheral and CAS dysfunction

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16
Q

Type 2

A

acquired, develops in adulthood, ongoing research to examine effects on hearing

17
Q

Pathology responsible for permanent SNHL varied

A
  • Generation of excess “free radicals” caused by metabolic disorder> damage cochlear and brain tissues
  • Primary neuropathy affecting auditory nerve
  • Small blood vessel disease: compromise vascular perfusion of cochlea
    o Ohc and stria vascularis very sensitive
  • Central auditory damage and auditory processing (biological mechanisms poorly understood)
18
Q

Diabetes audiological assessment

A

Audiometry: abnormal thresholds especially high frequencies but low frequency decline also observed (ultra-high freq. range)
Objective tests: DPOAE and ABRs abnormal
Suprathreshold & auditory processing: SIN tests abnormal, temporal processing abnormal

19
Q

what is DNA

A

a double helix structure made up of A, T, C, G (A binds with T, C binds with G)

20
Q

dNA described

A

Each nucleus contains 23 pairs of chromosomes
22 autosomal (1-22) and 1 pair of sex chromosomes (XX= female XY=male)
- Autosomal tend to not be related to sex
- Most of information is on X chromosome, not lots on Y
- More males tend to be affected then it would be an X linked hearing loss

21
Q

What is a gene

A

Approx 30 000 genes in the human body
- Portion of DNA that code for proteins
- Different etiologies have different forms of inheritance

22
Q

RNA and proteins

A

Information gets translated from DNA to RNA
RNA is single stranded and contains Uracil (U) instead of thymine (T)

23
Q

Mutation in promotor-

A

part of gene that initiates transcription: possible outcome ‘;transcription process may not be initiated or may have up regulation if binds with additional affinity; results in change in protein level (can have none, too much or not enough)

24
Q

Mutation in exon

A

wrong peptide coded, change protein, can have premature stop, can result sometimes in no change

25
Mutation in intron
- will get spliced out often, no issues, can occasionally change splicing, can have truncated or elongated MRNA transcript which would then change the peptide and protein function
26
Gene expression
- Every cell contains 100% of genetic information - Approx.. 20% of genes are expressed in each cell type (not always on or off can have different levels of expression)_ - Can have mutations causing HL, syndromes or HL + other impairments
27
types of mutation
Substitution Inversion Deletion Insertion
28
autosomal traits
- Traits controlled by 1 gene - Inherited by dominant or recessive pattern Dominant: 1 copy of the allele required to show trait Recessive: 2 copies of the allele required to show trait
29
Polygenic traits
multiple alleles that contribute to phenotype Shows different probabilities of exhibiting certain phenotypes Ex., 6 copies of darker skin allele - more likely to have darker skin vs 6 copies of lighter skin allele more likely to have lighter skin
30
genetics and hearing
- Approx.. 50% hearing impairments due to genetic factors - Genetic HL categorized into 2 major forms: (1) syndromic 30% (2) non-syndromic 70% - Genetic HL caused by various mutations in various genes, resulting in various phenotypic presentations. Over 100 genes identified (ex. GJB2, Cadherin 23, Otoferlin)
31
1997 DFNB1: GJB2
- DNA codes for connexin 26 protein – protein in gap junctions which connect adjacent cells and regulate the flow of small molecules between cochlear cells (not present in hair cells) - Most common form of non-syndromic deafness - GJB2 mutations: different errors in gene code >100 identified
32
Cadherin 23
Function: allows cells to stick together Expression: stereocilia, retina Phenotype: deafness or Deafness and blindness - Difference depends on type of mutation in cdh23
33
Cadherin 23 mutation 1
nonsense mutation (premature stop-shorter protein) Phenotype1: hearing loss + vision impairment
34
Cadherin 23 Mutation 2
missense mutation (Change in amino acid) Phenotype 2: hearing loss only
35
Otoferlin (OTOF)
Function: unknown Expression: brain, cochlea Phenotype: auditory neuropathy 16 different mutations identified within OTOF - Unique mutation (deletion) results in “deafening fever” severe- profound HL only when fever present, only mild HL when no fever present
36
Why bother familiarize with genetics
HL can have genetic etiology, improved counselling, better understanding of HL, potential for new treatments (e.g., gene therapy)
37
X-linked in newfoundland family
mutation on X chromosome causes HL phenotype WFs1: autosomal dominant mutation 28 affected individuals KNCQ4: autosomal dominant mutation 13-16 affected individuals FOXL1: autosomal dominant otosclerosis
38
future opportunity for audiology
1. Identification (do I have genetic HL and what type) 2. Surveillance (have gene but hl fine, or have HL will it get worse) 3. Counselling 4. Treatment/monitoring