Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Physiology for Anaesthetists > Genetics and Ageing > Flashcards

Genetics and Ageing Flashcards

(87 cards)

Start Studying
1
Q

What is a chromosome and how does it differ from chromatin

A

Chromatin is compacted into chromosomes during mitosis and meiosis forming 22 pairs of autosomes and 1 pair of allosomes. Chromatin is made up of compacted DNA wrapped around histone proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Classify the four nucleobases and define how this nucleobases are paired in DNA

A

Pyrimidines (CuT Pie or ‘py’)
Cytosine
Thymine

Purines (Pure gold - ‘Ag’ periodic table)
Adenine
Guanine

Pairing
AT
CG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Define DNA

A

Deoxyribonucleic acid or DNA is a polymer of 4 nucleotides in sequence bound to a complementary DNA strand and folded into a double helix. The strands run antiparallel 5’ to 3’.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Simplify the structure of DNA and differentiate nucleotide from nucleoside from nucleobase

A

Posphate - Pentose Sugar - Nucleobase - hydrogen bond - Nucleobase (complementary) - Pentose sugar - Phosphate.

Sugar phosphate backbone attached to nucleobases.

Nucleobase = CTAG
Nucleoside = nucleobase + Pentose sugar
Nucleotide = nucleobase + Pentose sugar + PO4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which pathway forms the sugars found in DNA

A

The pentose phosphate pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is RNA

A

The amino acid sequence of protein is encoded by the DNA sequence in the cell nucleus. When the cell needs to synthesize protein, the code is anchored in the cell nucleus, and protein manufacturing apparatus (ER/Golgi) is located within the cytoplasm. RNA is produced as a copy of DNA genetic code in the nucleus and exported to the cytoplasm, where it is used to synthesize protein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

List the differences between RNA and DNA

A

RNA - extra hydroxyl group on sugars (hence ‘deoxy’)
RNA - has Uracil instead of thymine
RNA - single strand - no antiparallel strand to form double helix

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the 3 types of RNA and what is their function?

A

messenger - mRNA - produced by transcription in nucleus and then transferred to ER for use in protein synthesis

transfer tRNA - 20 types gather 20 aa’s in cytoplasm and transfer to ribosome for protein synthesis

ribosomal rRNA - Aligns tRNA units in their correct positions along the mRNA sequence

The amino acids are joined together and a complete protein released.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Define a codon

A

Triplet of nucleosides that encodes for an individual amino acid - e.g. GCA represents aa alanine

mRNA - codons
tRNA - anticodons
Jigsaw match

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Give three examples of errors may occur during DNA replication/repair. Which of these has to most significant effect on changing protein synthesis and why?

A
  1. Point mutation
  2. Deletion
  3. Insertions

Deletions and insertions are the worst because “frame shift’ can occur with the ensuing DNA encoding a significantly different protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the gene mutation in sickle cell disease and how this mutation leads to the the ‘sickling’ of red blood cells

A

Chromosome 11
Point mutation in the DNA code for the beta chain of Hb
GAG (Glutamic acid) is changed to GTG (Valine)

Glutamic acid - polar
Valine - non-polar

This causes aggregation of Hb and thus shape change of the erythrocyte under conditions of low O2 tension.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the genetic defect in cystic fibrosis and how this manifests clinically

A

Chromosome 7
> 1000 point mutations described of Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene –> encodes a transmembrane Cl- channel
Most common is delta F508 mutation
–> deletion of 3 nucleotides (an entire codon which codes for phenylalanine, F) at the 508th position.

Thickened secretions that prevent clearance by ciliated epithelium resulting in blockages of:

  1. Small airways (pneumonia)
  2. Pancreatic ducts (malnutrition)
  3. Vas deferens (incomplete development and infertility)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the genetic defects in Huntingdon’s disease

A

Chromosome 4
Insertion of repeated segments of DNA
Codon for glutamine (CAG) is repeated multiple times within the Huntingdon gene on chromosome 4 = trinucleoside repeat disorder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is haploid and diploid

A

haploid - cell containing 23 chromosomes (gametes)

diploid - cell containing 46 chromosomes (human cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is an allele

A

A gene that codes for a specific trait e.g.blue alleles and brown eye alleles. (Mendelian).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Give 3 examples of autosomal dominant diseases

A
  1. Hypertrophic cardiomyopathy
  2. Polycystic kidney disease
  3. Myotonic dystrophy
  4. Malignant hyperthermia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Give 3 examples of autosomal recessive diseases

A
  1. Sickle cell disease
  2. Wilson’s disease
  3. Cystic fibrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Give 3 examples of X-linked recessive diseases

A
  1. Haemophilia A
  2. Duchenne muscular dystrophy
  3. Red-green colour blindness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Define functional reserve

A

The difference between maximum and basal levels of function - safety margin for trauma/disease/surgery/healing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the hypothesized mechanisms of aging

A
  1. Stochastic -> dependent on time and probability - due to random errors in protein synthesis
  2. Non - stochastic -> “biological clock for each species dependent on neuroendocrine or immune mechanisms

Progressive imbalance between oxidative stress and metabolic protection of oxidative stress –> increased ROS –> damaged membranes/proteins/DNA –> decreased antioxidant scavenging capacity –> progressive cycle –> decreased bioenergetic capacity –> loss of functional reserve –> susceptibility to disease and infection –>Increased probability of death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What happens to the heart with age

A
  1. Decreased myocytes
  2. Decreased conduction fibre density
  3. Decreased sinus node number
  4. LV wall thickening
  5. Interstitial fibrosis
Systolic dysfunction (reduced contractility)
Diastolic dysfunction (reduced compliance)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Why is sinus rhythm vital in aged patients

A

Reduced LV compliance –> decreased earl diastolic filling with compensatory increase in late diastolic filling of LV to maintain EDV and SV –> therefore strong reliance on LA filling of LV in the aged.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does cardiac output change with age

A

An 80 year old has 50% CO at aged 80 (vs CO at 30 yrs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How is the vasculature affected by age

A

Arteriosclerosis –> AAA/Carotid artery stenosis etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
How is the autonomic nervous system affected by age?
SNS - beta receptors less sensitive --> 2% loss of HR response during dynamic exercise. PSNS - Reduced vagal tone --> therefore can't reduce vagal tone below an already reduced baseline.
26
What happens to elastic recoil of the lungs and chest wall compliance with age --> how does this affect the pressure volume curve
Elastic recoil decreases --> increased static compliance Chest wall compliance decreases Pressure-volume curve shifts to the left. Lest change in pressure required for same volume change.
27
What happens to static lung compliance with age?
Increases
28
What happens to dynamic lung compliance with age?
Becomes more frequency dependent
29
How does residual volume change with age
Increases by 10% per decade after 50
30
How is vital capacity changed by increasing age?
Decreases
31
How does closing volume change with age
Increases
32
How does FEV1 change with age and why
Chest will stiffens with age - calcification of costo-chondral cartilage/costo-vertebral joints and progressive weakening of the auxiliary musculature of ventilation ---> decreased FEV 1 and increased WOB
33
Describe the changes to the pulmonary vasculature that occur with aging
Decreased cross-sectional area of pulmonary capillary bed --> increased PVR --> higher pulmonary artery pressure. Hypoxic pulmonary vasoconstriction is blunted in the elderly which may cause difficulty with one lung ventilation.
34
What happens to mean PaO2 with age and why?
PaO2 = 102 - (0.498 x Age) 1. CC encroaches FRC 2. Closing volume is more --> V/Q mismatch 3. Deteriorating parenchymal integrity --> decrease surface area --> increased (A - a)dO2. 4. Decreased sensitivity of respiratory centres to hypoxia and hypercapnoea --> diminshed or delayed response to injury
35
How is Nervous system effected by aging
Reduced functional reserve Nerves - high O2 utilization --. altered mitochondiral bioenergetics with age compromise reserve --> alters the response to anaesthetic agents and perioperative stress. Brain weight at 20 yrs = 1400 g Brain weight at 80 yrs = 1200 g
36
How are the kidneys affected by age
Progressive reduction in renal mass 1. Glomerulosclerosis 2. Thickening of vascular intima 3. Fibrosis of stoma 4. Chronic infiltration by inflammatory cells RPF decreases more than GFR FF increases to a state of hyperfiltration (adapatation for loss of functioning glomeruli) Reduced ability to concentrate urine Reduced ability to excrete acid load Sodium loss in the face of adequate sodium intake
37
How is liver function affected by age
1. Decreased hepatic blood flow --> but large reserves 2. Reduced hepatic drug clearance 3. Reduced hepatic synthesis of plasma cholinesterase
38
How does body composition change with age
Increased abdominal fat mass Increased obesity Decreased resting BMR Decreased energy expenditure (1% per year after 20yrs)
39
How is glucose metabolism affected by age
Plasma glucose higher due to glucose intolerance
40
How is the locomotive system affected by age
Reduction in height (atrophy of spinal muscles etc. - spinal anaesthesia more difficult) Osteoporosis --> positioning patient in theatre.
41
Which plasma protein binds acidic drugs and how is it affected by age. Which plasma protein binds basic drugs and how is it affected by age?
Acidic drugs --> Albumin --> decreases with age --> Increase free fraction Basic drugs --> alpha 1 - acid glycoprotein --> increases with age --> decrease free fraction
42
How does body composition change with age and how does this affect
Decreased lean body mass Increase body fat Decrease in total body water EFFECT 1. Smaller central compartment with increased serum concentrations after bolus administration 2. Increased Vd --> prolonged effect
43
Do elderly patients need more or less volatile and why
``` MAC falls by 6% per decade 1. Decreased cell density 2. Lower Cerebral O2 consumption 3. Lower CBF Alterations in ion channels/synaptic activity or receptor sensitivity ```
44
Does age directly affect the duration of neuraxial anaesthesia
No
45
Define elderly
>65 years
46
By how much does perioperative mortality increase per decade after 65 years of age
35% per decade
47
What are the two theories of aging
Extrinsic (Stochastic = random) - cellular damage / ROS / Radiation / Errors protein synthesis Intrinsic - Pre-programmed genetically determined process Whatever the underlying cause, the process occurs at very different rates between individuals and between organ systems within an individual
48
What is the ultimate effect of aging
Reduced functional reserve of organ systems with a threat to homeostasis in the face of stress.
49
Summarise the change in body composition in the elderly
Decreased % lean body mass from 1. Cell loss in solid organs 2. Decrease body water 3. Loss of muscle mass 4. loss of bone mass 5. Loss of skin an SC tissue Body fate % increases, with a shift in distribution from peripheral to visceral sites
50
Why do the elderly develop isolated systolic hypertension and what haemodynamic effects result from this
After 40 years: - Collagen accumulates whilst elastin production falls - Collagen also accumulates damage over time with stiff, non-enzymatic cross-linking between fibers. - Connective tissue thus stiffens in the arteries, veins and the myocardium Haemoodynamic effects 1. Isolated systolic hypertension 2. Widened pulse pressure (reduced diastolic pressure too) 3. Increased afterload (Aorta cannot accommodate SV) 4. LVH (increased afterload) 5. Reduced LV compliance with diastolic dysfunction 6. Increased dependence on atrial contraction due to diastolic dysfunction 7. Reduced DBP --> compromise coronary perfusion
51
How do SV, HR and LVEF vary in the elderly vs younger individuals at rest
Actually unchanged However, there is reduced beta-adrenergic sensitivity and reduced cell numbers in the SA node ``` Reduced maximum heart rate (SA cells down) Reduced contractility (myocyte numbers down) ---> Result in reduction in maximum CO in response to exercise or stress ```
52
Describe the pattern of decline of maximum cardiac output in the elderly
Maximum cardiac output declines by 1% per year after 50. So by 80 years --> Max CO is 30% less than at 50 years.
53
How is the conducting system of the heart affected by age
Fibrosis in the conducting system may cause conduction abnormalities
54
Summarise the changes in the blood vessels in the elderly
1. Reduced elastin and increased damaged + stiff collagen (stiffer arterial walls even in the absence of atherosclerosis) 2. Intimal thickening 3. Media calcification 4. Endothelial dysfunction (less NO) Venous stiffening --> impairs venous capacitance and ability to maintain stable preload
55
Summarise the changes to autonomic tone in the elderly
Increased SNS tone Reduced PSNS tone Diminished baroreceptor responses
56
Summarise the changes to respiratory mechanics in the elderly
1. Reduced chest wall compliance - Calcification costal cartilage - Arthritis costovertebral joints - Stiffness intercostal muscles - Reduction height thoracic spine (osteoporosis) 2. Reduced respiratory muscle mass - Intercostals and diaphragm weaker Overall --> Increased WORK of breathing - Breathing rapid and shallow 3. Lung parenchyma - Loss elastic tissue --> dilatation/enlargement airways + increased alveolar size + fusion adjacent alveoli -->reduction in alveolar surface area and a decrease in surface tension inward recoil
57
How do the physiological changes associated with aging affect lung function tests?
1. RV - increase 5% - 10% per decade 2. FRC - increase 1 - 3 % per decade 3. Closing capacity increase --> airway closure --> V:Q mismatch during tidal ventilation 4. TLC - unchanged 5. VC - Reduced as RV increased 6. FEV1 - falls by 25 ml/year after age 20 7. FVC - falls by 20 ml/year after 20 8. FEV1 : FVC ratio therefore falls 9. Diffusing capacity - decreased due to thickened alv-capillary barrier
58
Why does arterial oxygenation decrease with age
1. Decrease diffusing capacity (thickened alv-cap barrier) 2. Reduced alveolar surface area --> V:Q mismatch 3. Small airways close prematurely (Increased closing capacity) 4. Increased shunting of blood due to alveolar destruction
59
Give one formula to predict PaO2 in the elderly
Predicted PaO2 = 13.3 - (Age/30) kPa
60
How does age affect the respiratory response to hypercapnoea and hypoxia
There is a 50% decrease in the response to hypercapnoea and hypoxia
61
What are the airway considerations in the elderly
1. No teeth 2. Collapsed cheeks - difficult BVM 3. Cervical spondylosis - reduced ROM 4. Pharyngeal muscle weakness (POPC + OSA + aspiration risk)
62
Why is the risk of post-operative pulmonary complications increased in the elderly
The physiological changes with ageing result in a significant increase in the required work of breathing
63
Summarise the anatomical changes in the kidneys that occur with age
Kidneys enlarge until 50 years 25% of their mass then lost over 30 years - Cortical tissue lost --> glomerulosclerosis - Acellular obliteration of glomeruli with vascular shunts forming around the lost units
64
How does renal blood flow change with age?
RBF decreases 10% per decade Increased proportion of blood flow to the medulla (GS) Intrarenal blood vessels show the same changes seen in the blood vessels in the rest of the body with age
65
Why does GFR decline with age. Why can Creatinine be decreased despite this
1. Glomerulosclerosis 2. Thickened basement membrane Reduced creatinine production (loss of muscle mass)
66
Which formula should be used to calculate GFR
CKD-EPI formula
67
What is tubular senescence
With age comes reduced tubular length, interstitial fibrosis and basement membrane changes resulting in disruption of tubular function - -> Impaired ability to reabsorb sodium - -> Impaired ability to excrete K and H Reduced ability to regulate electrolytes
68
How is the renal response to aldosterone and ADH affected by age?
Renin production is reduced --> reduced response to aldosterone Response to ADH is reduced Reduced ability to regulate fluid
69
Why are elderly patients more susceptible to dehydration
Decreased thirst response
70
How do elderly patients excrete drugs differently from younger patietns
Reduced capacity to clear drugs by the renal route and are more susceptible to injury for nephrotoxic agents
71
What happens to the volume and weight of the brain after age 40. why does this occur? And where do the losses predominate. Which area of the brain is mostly affected by this
It decreases by 5% per decade after age 40 - cell loss - decrease dendritic density Losses more pronounced in white matter vs. grey matter. Not uniformly distributed throughout the brain. Most affected: prefrontal cortex
72
What changes occur with regard to neurotransmitters and nerve conduction in the elderly
Reduced - Dopamine - Serotonin - Brain derived neurotrophic factor Increased - Monoamine levels --> free radical release SLOWING of nerve conduction in the PNS and CNS
73
What happens to the blood brain barrier with age
Permeability increases possibly leading to increased neuroinflammation and inapprpriate modulation of CNS function
74
Describe the vascular changes in the brain in the elderly
1. Same as everywhere else 2. Capillary density decreases 3. Microvessel deformities increase 4. CMRO2 and CBF decrease with age
75
Discuss the observable neurological deficits often present in the elderly
1. Cognitive impairment (memory loss) 2. Auditory impairment 3. Visual impairment 4. Decreased mechanoreceptor and proprioceptor density increases risk of falls Post operative delirium is common in the elderly
76
How is autonomic function altered in the elderly
It is decreased. 1. Impaired thermoregulation (shivering, VC 2. Reduced beat to beat variation in response to postural changes 3. Reduced baroreceptor reflex sensitivity
77
What are the requirements for analgaesics and anaesthetics in the elderly population
The requirements are diminished
78
Summarise the age related changes in the GIT
Oesophagus - Decrease contraction amplitude and number. Increased number of disordered contractions Stomach - Slowed gastric emptying - Atrophic gastric mucosa --> decreased acid and IF production - Reduced gastrin secretion Pancreas - Normal exocrine function Small and large bowel - minimal (polyps / diverticuli)
79
How is Hepatic function affected by age
Liver mass and hepatic flow decrease by 20 - 40%. Decline in phase 1 drug metabolism (loss of endoplasmic reticulum)
80
How does age affect the sex hormones
Decreased secretion from endocrine glands and diminished tissue responsiveness to hormones. E.g. Menopause - bone loss - Loss of oestrogen cardioprotective effects E.g. Testosterone levels decline with age (?significance)
81
How does age effect thyroid
E.g. Thyroid levels decreased (?clinical effects)
82
How does age effect parathyroid
E.g. Parathyroid levels increased (--> osteoporosis)
83
How does age effect GH and ILGF-1
E.g. GH and ILGF-1 decreased | - loss of lean body mass and increased % body fat)
84
How does age effect Insulin
E.g. Insulin - Decreased and insulin resistance (abdominal fat) - glucose intolerance
85
How are circadian rhythms affected in the elderly
Shifted -->Cortisol release earlier in the day
86
How are secretion and levels of adrenalin and noradrenalin affected in the elderly. why is this important in the perioperative period
Baseline levels are elevated but secretion in response to stress is diminished NB as inability to regulate temp/HR/CO/BP in the face of surgical stress
87
how is immune function affected by age
Immune function declines with age - Impaired T cell mediated immunity - Increased susceptibility to infection - T-cell response to IL-2 diminished - Blunted increase in NK cells to infection Markers of SIRS are elevated in the elderly - IL6 / TNF alpha / CD 11b/ CD 18 expression

Physiology for Anaesthetists (61 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions