Week 10 - Geriatric Pharmacology Flashcards
Why do cardiovascular changes occur as we age?
- Mutations: somatic mosaicism (mutations on top of mutations)
- Discovered CHIP (clonal hematopoiesis of indeterminate potential) – have mutations but we don’t know what they are going to cause
- Association between CHIP and CV disease incidence and ischemic stroke
- All cause mortality increased (looking to understand why)
What genetic mutations increase the risk of CV disease? (3)
TET2: accelerate atherosclerosis by generating a large pool of macrophages with proinflammatory cytokines: ILB-1, leading to a marked increase in plaque size – accelerates adverse cardiac remodeling leading to HF
JAX2: increase in thrombosis may account for the increase in the incidence of CV disease observed in JAKV617F-positive carriers
DNMT3A: loss of function within hematopoietic cells promotes inflammatory processes and HF
What are the CV changes with age?
- Decreased response to atropine (lower basal parasympathetic tone – removal = less response)
- Loss of SA node cells – slowed conduction (increased incidence of 1st/2nd degree heart blocks, sick sinus syndrome, and a-fib)
- Myocyte death without replacement (senescence) – due to necrosis and apoptosis
- Connective tissue changes (increase in cardiac connective tissue)
- Decreased response to beta-receptor stimulation
- Strength of contraction does not decrease significantly
- Peripheral vasoconstriction slightly enhanced – enhanced SNS activity at rest and with stimulation, vascular response to alpha stimulation may decrease, HoTN with loss of sympathetic tone (happens with GA and RA)
- Decreased vascular growth factor (leads to HTN)
- Increased remodeling –> macular degeneration
Why does the heart increase in size during aging?
It is a result of concentric ventricular hypertrophy that occurs in response to the increase in LV afterload
*increase in afterload occurs as the result of fibrosis and endothelial damage –> increases arterial stiffness and reduce the capacity for nitric oxide induced vasodilation
What is age-related endothelial dysfunction?
Decrease in the ability of the endothelium to dilate or contract blood vessels in response to physiologic and pharmacologic stimuli
*accelerated by smoking, diabetes, HTN, and hyperlipidemia
What are the effects of the elderly having increased systolic pressure at the end of ejection?
Stiff arteries = increased velocity of blood flow (not increased flow – just increased velocity)
Reflected waves of increased pressure = increased pressure on the aortic root
- in the young this happens in early diastole with no effect on ejection
- in the elderly this happens in late systole making it harder to eject
- Causes ventricular hypertrophy –> slower contraction/relaxation –> impairs early diastolic filling
- Increases importance of Atrial Kick to fill the ventricle
- Requires increased atrial pressure which leads to CHF –> diastolic dysfunction
Why is the elderly heart markedly dependent on the atrial “kick”?
Active diastolic relaxation is significantly impaired in the elderly (Ca++ is removed from troponin-C binding sites, triggering the dissociation of actin and myosin facilitating isometric relaxation) – uses approximately 15% of the energy consumed during the cardiac cycle
-atrial kick is needed for adequate ventricular preload
Contributes to approximately 30% of ventricular filling in the elderly vs 10% in younger individuals
*loss of atrial kick is poorly tolerated because of decreased capacitance of the LV – causes them to be more sensitive to hypovolemia
Why is there a decreased venous capacitance with aging? What is the effect of it?
Veins stiffen with age – can’t buffer changes in blood volume like pliable veins
- shifts the distribution of the body’s fluid/blood volume (produces exaggerated changes in cardiac filling pressure)
- changes in SNS tone also affect filling pressure
Why is there a decrease in absolute number of myocytes in the elderly?
Cardiac Myocyte Death – myocardial cells die over time and don’t divide (significantly)
- increased apoptosis, necrosis, decreased cardiac stem cell reserve
- more susceptible to oxidative stress from increased ROS production
*Remaining cells hypertrophy to compensate – this exacerbates the filling issues
What is cardiac dysfunction in aging largely related to?
Impaired diastolic LV function with increased prevalence of diastolic HF
- Age related increase in cardiac connective tissue that when combined with ventricular hypertrophy, increases wall stiffness and reduces diastolic compliance
- Slowed ventricular contraction prevents rapid ventricular relaxation and early diastolic filling predisposing the heart to diastolic dysfunction/failure
When is ventricular filling typically complete in the elderly?
Typically not complete until very late in diastole
- because of the importance of atrial contraction and delayed filling due to reduced ventricular compliance
- late filling depends on left atrial pressure and atrial kick = high left atrial pressures
What changes occur to the large vessels in the elderly?
They become elongated, tortuous, and dilated
They are less distensible due to thickening
Impaired cushioning function leads to lower diastolic pressure, increased systolic and pulse pressure, and elevated LV afterload
Why is there a decreased response to beta receptor stimulation in the elderly?
- Downregulation of post-receptor signaling — responsible for the age-related decline in max HR during exercise
- Number of beta adrenergic receptors in the myocardium is reduced
*decreased chronotropic (HR)/inotropic (contractility) response has a contribution from downstream changes in the mechanism by which binding at the receptor is coupled to cyclic adenosine monophosphate
At what ages do lung changes and CV changes start to occur?
Lung Changes = mid 40s
CV Changes = >65
What are the effects of lung tissue becoming more compliant with age?
More compliant due to the loss of elastin (not chest wall – just lung tissue)
Airways NOT held open:
- patchy lung collapse (increasing risk of pneumonia)
- higher work of breathing (hypercarbia increases strain on heart)
- lower blood O2 levels (need supplemental O2)
- hypoxia more likely with GA than SAB
Lungs need to be overinflated to keep open: increased closing capacity (use PEEP and increase tidal volumes)
Residual volume increases
Increased V/Q mismatching = Decreased resting PaO2 (elderly have lower baseline PaO2 levels)
What is the effect of the chest wall becoming less compliant with aging?
Noncompliant thoracic cage makes intercostal muscle activity less efficient – diaphragm and abdominal muscles assume a greater role in tidal breathing
*diaphragmatic function declines with age, predisposing elderly to respiratory fatigue when required to significantly increase minute ventilation
Presumable related to changes in the thoracic skeleton and a decline in costovertebral joint mobility – cause restrictive functional impairment
What are the functional consequences of aging of the respiratory system?
- Decrease in lung elastic recoil
- Increase in lung compliance
- Decrease in oxygen diffusing capacity
- Premature airway closure causing V/Q mismatch and increased alveolar-to arterial oxygen gradient
- Small airway closure and gas trapping
- Decreased expiratory flow rates
What are the lung volume and capacities changes with aging?
- Vital capacity
- Residual volume
- Total lung capacity
- Functional residual capacity
- Closing capacity
- Expiratory flow
- Vital Capacity: progressive loss resulting from increased chest wall stiffness, decreased lung elastic recoil, and decreased respiratory muscle strength
- Residual Volume: progressive increase due to dynamic airway closure limiting expiration (up to 10% per decade)
- Total Lung Capacity: remains relatively constant (sum of VC and RV)
- Functional Residual Capacity: progressive increase – result of decreased elastic recoil force
- Closing Capacity: airway closure occurs at progressively greater lung volumes – gas exchange impairment due to shunting in regions of airway closure is typical in the elderly during normal tidal breathing (airway closure is greater when supine)
- Expiratory Flow: progressively decreased
