CV System and Aging (PDF)

Drugs and Aging (The Cardiovascular System) 2X- Fundamental topics in Biology Prof. Simon Kennedy [email protected] Physical changes related to “normal” aging ARE NOT diseases. As we age: We all change physically, as we grow older. Some systems slow down, while other...

Drugs and Aging (The Cardiovascular System) 2X- Fundamental topics in Biology Prof. Simon Kennedy [email protected] Physical changes related to “normal” aging ARE NOT diseases. As we age: We all change physically, as we grow older. Some systems slow down, while others lose their "fine tuning." Lifestyle changes can influence aging- smoking, exercise, diet alcohol use etc. Changes tend to be slight, often barely noticed and not problematic. Steps can be taken to help prevent illness- often through use of drugs to maximise quality of life. Drugs effects (and their side effects) can be influenced by age. Aging Theories Not all diseases increase: Prevalence of selected chronic conditions, expressed in percentages, as a function of age for the US population (2002-2012 dataset). All forms of cancer and heart disease are featured. Source: CDC/NCHS, National Vital Statistics System, Mortality Some changes are cosmetic The skin wrinkles and sags The dermal layer thins. Less collagen is produced. The elastin fibers that provide elasticity wear out. --------- Decrease in the function of sebaceous & sweat glands contributes to dry skin. The fat cells get smaller- wrinkles become more noticeable and skin can sag. Skin Changes How does Botox work? After injection- binds to Internalised into Several proteins required surface of nerve cell small vesicles in neve for Ach release. Botox Affects SNAP-25 Hair Many men (and a few women) suffer from pattern baldness Increased hair growth in ears, nostrils and eyebrows Loss of body hair elsewhere Hair transplant Minoxidil 5% Opens KATP channels to hyperpolarise the membrane of vascular smooth muscle cells- less sensitive to constriction Not a first line drug for hypertension Side-effect of hypertrichosis- bad for some patients- good for the pharmaceutical/cosmetic industry!  Aging & the Cardiovascular System Difficult to differentiate between age-related changes and those related to an inactive lifestyle or “abuse” Are the changes normal 'wear and tear' or cardiovascular disease? Normal Heart Muscle Changes Anatomical changes Thickening of the left ventricular wall  collagen,  elastin Heart becomes less efficient Supply of O2 to the body is reduced Fatigue, lower exercise tolerance Normal Heart Rate Changes  cardiac responsiveness rate with exercise Heart may take longer to return to baseline rate Valve changes  thickness  flexibility Aortic & mitral valve calcification Can lead to heart murmur Long-term hypertrophic changes Can be treated by valve replacement Changes to the conduction system  number of pacemaker cells Fibrous tissue infiltration of conductive system Can lead to conduction abnormalities (arrhythmias) More prone to arrhythmias after an ischaemic event Normal SA Node & Intranodal Atrial Tract Changes Irritability of the myocardium may result in extra systoles, along with sinus arrhythmias & sinus bradycardia Changes to heart contraction Excitation-contraction coupling is what makes the heart contract Relies on the conducted impulse depolarising the membrane of the cardiac muscle cells (cardiomyocytes) Calcium enters the cells and causes contraction Rate and force of contraction can lower in the elderly- can lead to heart failure! Heart failure and treatment Cardiac output falls- leading to fatigue, cyanosis, peripheral oedema, distensed jugular vein, pulmonary oedema. Treatment is not curative- trying to either make the heart work harder to cope with demand or unload the heart in other ways such as: -correcting hypertension -blocking endogenous constrictor agents -modulating return of blood to the heart  What causes oedema in HF patients?- fluid transport imbalance Determined by Starlings Forces- hydrostatic pressure vs. osmotic pressure Hydrostatic pressure forces fluid out at the arteriolar end and osmotic pressure draws fluid back in at the venous end. Imbalance leads to net outward filtration = oedema. ARTERIAL END CAPILLARY HYDROSTATIC HYDROSTATIC PRESSURE PRESSURE =35mmHg =15mmHg COLLOID O.P. COLLOID O.P. =28mmHg =28mmHg COLLOID O.P. COLLOID O.P. =3mmHg =3mmHg VENOUS END  Pulmonary Hydrostatic pressures are much lower than systemic pressure Colloid pressure are equivalent Therefore have a net fluid transfer at both ends Prevents pulmonary oedema What would induce pulmonary oedema? Heart failure drugs Nitrates- release a vasodilator called nitric oxide which dilates veins- lowers blood return to the heart and reduces workload. Positive inotropic agents- block pumps in the cardiac muscle to increase calcium in the cells- heart contracts more strongly. ACE inhibitors- inhibit an enzyme so body produces less AngII- blood pressure goes down and reduced water retention by kidney. Normal Blood Pressure Changes Systolic blood pressure may rise disproportionately higher than diastolic Blood pressure and aging BP creeps up gradually with age. Related to structural changes in the arteries and especially with large artery stiffness. Isolated systolic hypertension most common in patients over 50 Increases CV risk- MI, HF, stroke etc Risk is predicted by pulse pressure = systolic – diastolic pressure WHO global risk factors 2012 DEFINING HYPERTENSION Causes of hypertension Primary (Essential) hypertension (~90%) multifactorial: smoking obesity diet (e.g. salt) exercise (lack of) genetic Secondary hypertension (