Lifestyle, Health and Risk

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Why have a circulation?

  • Overcome the limits of diffusion

  • Diffusion too inefficient in large organisms as the surface area to volume ratio is too small - so would be too slow to sustain life

  • Mass flow (movement of fluid down a pressure or temperature gradient) more efficient than diffusion

  • Heart - pump allows a fast flow of blood - movement of blood quickly too and from cells

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Why Double Circulation system?

  • Double circulation system - more efficient
  • Prevents the mixing of oxygenated and deoxygenated blood
  • Tissues receive purely oxygenated blood via mass flow
  • Allows a higher pressure to be maintained - blood is pressurised twice per cycle - causing a higher flow rate than otherwise possible
  • Mammals are large - sufficient pressure needs to be maintained to get the blood back to the heart for the next cycle
    • Generally need blood to be supplied quickly because of their relatively high basal  metabolic rates (basic energy required to sustain only vital organs when one is at rest, bmr)
    • Need to maintain a relatively high body temperature, which requires sufficient blood flow, necessary for homeostasis
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Importance of water

  • Water is dipole - Slight e- charge of the oxygen attracts the slightly positive charge of the hydrogen creation an easily broken/made bond 
    • So water is liquid at room temperature  - H+attracted to O- of surrounding molecules, which will form hydrogen bonds slowing down the water by holding the molecule together
  • Solvent for ionic and polar molecules - important tranport medium 
    • Water molecules are attracted to them, collect around them, and separate them, so that they dissolve 
    • Most processes happen in solution because of this as chemicals are free to move around and react with other chemicals 
    • Non-polar molecules like lipids therefore tend to be pushed together by water - important for hydrophobic interactions in protein structure and in membrane structure 
  • Thermal Properties
    • High heat capacity - 1oC/gram change in temperature with every change of 1 cal of energy 
    • Excellent protector against thermal variation (70-90% of cell mass is water so bodies of organisms also slow to change temperature 
    • Requires a relatively high amount of energy to become a gas - effective means of cooling the body 
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Structure and function of arteries

Arteries - built for high and fluctuating pressure - strength and elasticity needed to withstand the pulsing of blood, preventing bursting and maintaining a pressure wave

  • Outer layer - collagen - tough - able to withstand high pressure and maintain its shape
  • Smooth muscle - autonomous contracts  allowing the arteries to constrict and dilate
  • Internal elastic membrane - stretch and constrict to withstand high and changing pressure and to maintain its shape and pressure
  • Small lumen - helps create high blood pressure
  • Conducting (elastic) artery - allows pulse
  • Distributing (muscular) artery - vasoconstriction/vasodilation
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Veins and Capillaries

Veins - transport low pressure, deoxygenated blood back to the heart

  • Thin outer walls - enables the veins to be pressed flat against muscles, which are then used to push the blood upwards towards the heart + little danger of bursting as no pulse
  • Thin muscle and elastic layer - low pressure of blood after flowing through capillaries muscle/elastic not needed
  • Large lumen - wide passageway to allow for a large quantity of slow moving low pressure blood
  • Veins have semilunar valves to prevent the backflow of blood

Capillaries - site of exchange of requirements and waste of metabolic reactions

  • Cell walls only one cell thick - ease of diffusion
  • Very narrow - only 10 um, lies close to the cells and slows down the flow of blood - decreases diffusion distance and allows time for efficient exchange
  • Capillary networks - allows exchange with tissue - large surface area to volume ratio
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Blood movement?

Arteries - Aorta, Pulmonary Artery - stretch and recoil - pulsing of blood flow 

  • Heart contracts (systole) - blood forced through arteries and their artery walls stretch to accomodate blood - thick artery walls can withstand high hydrostatic pressure generated as the blood is forced against the walls 
  • Heart relaxes (diastole) - elasticity of artery walls allow them to recoil behind the blood helping to push the blood forward and smoothing blood flow 
  • Semilunar valves at base which base which prevents backflow 

Veins - Vena Cava, Pulmonary vein 

  • Low pressure in the thorax when breathing in helps to draw blood back into the heart from the veins 
  • Skeletal muscles - contraction also assists movement of blood 
  • Semilunar valves 
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Cardiac Cycle

Phase 1: Atrial systole 
Blood under low pressure flows into the left and right atria from the pulmonary veins and vena cava
Increasing blood pressure as atria fill - opening the the AV valves - blood flows into the ventricles 
The atria walls contract forcing more blood into the ventricles (atrial systole) 

Phase 2 Ventricular systole 
Slight delay
Ventricles contract - SL valves open and pushes blood up and out of the coronoary arteries 
The pressure against the AV valves closes them preventing backflow of blood 

Phase 3 Cardiac Diastole - Atria and ventricles relax
Elastic recoil of the relaxing heart wall lowers pressure in the atria and ventricles 
Blood under higher pressure in the pulmonary arteries and aorta is drawn back towards the ventricles, closing the semilunar valves preventing further backflow of blood
Coronary arteries fill during diastole 
Low pressure in the atria helps draw blood into the heart from the veins 

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What happens in atherosclerosis?

1. Endothelial Dysfunction - injury to the aterial endothelium (delicate layer of cells that lines the inside of the artery and separates the blood that flows in the artery from the muscular wall0 

- causes of endothelial dyfunction; high blood pressure - extra strain on the layer of cells, exposure to toxins - cigarette smoke, high lipid concentration, diabeters 

2. Inflamatory response - once the inner lining of the artery is breached - white blood cells leave the blood vessel and move into the artery wall, accumulating chemicalls from the blood e.g. cholesterol. A fatty deposit builds up called an atheroma 

3. Plaque - calcium salts and fibrous tissues also build up at the site resulting in a hard swelling on the inner wall of the artery - causing the artery to lose some of its elasticity 

4. Lumen narrows - due to plaquwa making it more difficult for the heart to pump blood around the body and can lead to a rise in blood pressure 

5. Positive Feedback loop - atherosclerosis and plaques increase blood pressure which makes damage to the endothelial lining more likely making it more likely that further plaques form 

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Blood clotting process and CVD

Blood clotting - seals the break in a damaged blood vessel  limiting blood loss and preventing entry of pathogens 
Platelets - when they come into contact with damaged walls there cell surfaces chanfe causing them to stick to the exposed collagen in thw wall and to each other to form a temporary platelet plug 

Clotting Cascade

  • Platelets and damaged tissue release a protein called thromboplastin
  • Thromboplastin activates an enzyme which catalyses the conversion of prothrombin protein into thrombin enzyme. a number of other protein factors must be present (vitamin K and calcium) 
  • Thombin catalyses the conversion of fibriongen (soluble) into fibrin (insoluble) 
  • Fibrin mesh traps blood cells forming a clot (thrombosis) 

Atherosclerosis causes blood clots as platelets attach to exposed collagen - A blood clot can block the flow of blood preventing vital oxygen and nutrients from passing and preventing the removal of waste products (usually endothelium very smooth and has substances that repel platelets) 

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Consequences of Atherosclerosis?

Coronary Heart Disease 

Angina - narrorwing of the coronary arteries limits the amount of oxygen-rich blood reaches cardiac muscle - resulting in chest pain (angina) - cardiac muscle forced to respire anaerobically 
Myocardial infarction (heart attack) - if blood supply is blocked completely (ischemic - without blood) - if the affected cells are starved for oxygen long enough they will be permenantly damaged (heart attack) 
Arrythmia - CHD causes the heart to bear irregularly which can lead to heart failure 

Stroke - supply of blood to the brain interrupted - the more extensive the damage the less likely the chance of a full recovery 

Aneurysm - block in the artery can cause blood to build up behind it - can be fatal if it burst due to blood loss and shock 

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High blood pressure - measure

High blood pressure - Hypertension (elevated blood pressure) - one of the most common factors in the development of CVD - increases the risk of atherosclerosis

Measure

  • systolic and diastolic pressure 
  • Sphygmomanometer - measures blood pressure, measured in mmHg (millimeters of mecury)
  • systolic pressure (the maximum pressure when the heart contracts)/diastolic pressure 
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Tissue fluid, Oedema and high bp

Tissue Fluid (interstitial fluid)

1. High hydrostatic pressure in arteries pushes some blood fluid out of the capillary wall through tiny gaps - tissue fluid (plasma, allows exchange of substances by surrounding body cells) 
2. The tissue fluid itself has some hydrostatic pressure and is pushed against the capillaries allowing it to re-enter 
3. Water potential of blood more negative than that of the tissue fluid so water tends to move into the blood via osmosis along the water potential gradient 
4. Hydrostatic pressure of tissue fluid and osmotic force of plasma proteins is sufficient to move 5. tissue fluid back into the blood (as blood at venous end has lost hydrostatic pressure) 
20% of the fluid drains into the lymph capillaries,flows through the lymph vessels and returns the lymph fluid to the blood via the thoracic duct in the neck which empties into the vena cava 

Oedema - fluid building up in tissues and causing swelling, associated with high blood pressure, kidney or liver disease, and restricted body movement
If blood pressure rises above normal, more fluid may be forced out of the capillaries, and the fluid accumulates as it does not re-enter the blood

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Risk factors for CVD

Obesity - raises blood pressure. elevated blood lipid levels, increases risk of type II diabetes, increases risk without other factors being present 

Diabetes - high levels of glucose in blood increases hydrostatic pressure 

Cholesterol - 50% of CVD events can be attributed to cholesterol level over 3.8 mmol/l 

- LDLs (low density lipoproteins - triglycerides + cholesterol + protein) - transports cholesterol to cells, where it is involved in synthesis and maintenance of the cell membrane, excess LDLs overwhelm cell receptors, and hence increases cholesterol levels in the blood where it may be despoited in artery walls causing atheromas 
- HDLs (high density lipoproteins - higher percentage of protein and less cholesterol) - transports cholesterol from body tissues to the liver to be broken down - lower cholesterol in bloodstream and so lower risk of plaques 
- Ideal - low overall level of cholesterol and high HDL:LDL ratio in blood 
- Saturated fats increase LDLs more than HDLs, unsaturated fats decreased LDLs and HDLs 

Salt - high salt diet causes the kidneys to retain water - higher fluid levels in blood - increased blood pressure 

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Risk factors for CVD

Alcohol - raises blood pressure, contributes to obesity (calorific), can cause an irregualar heart rate, potential damage to liver tissue - Alcohol - Ethanol - LDLs, impaired ability to remove cholesterol, glucose and lipids from the bloodstream
Radicals -  antioxidants such as Vitamins can protect against radical damamge by providing a hydrogen atom that stabilises the radical - radicals are highly reactive and can damage cells
Inactivity - activity prevents high blood pressure, type II diabetes and obesity 

Genetic Inheritance - Apolipoprotein gene cluster - APOA - protein in HDL, mutation - lower HDL  - APOB - protein in LDL - high LDL - higher suceptibility to CVD - APOE - major component in HDL and in LDL - APOE4 - slows removal of cholesterol 

Age 
Gender - males at higer risk, oestrogen protects against CVD

Smoking - CO binds to haemoglobin instead of oxygen, reduces O2 supply to cvells so increased heart rate and blood pressure to provide enough oxygen - nicotine - stimulates adrenaline which increases blood pressure 

Stress - raises blood pressure, overeating, poor diet, higher alcohol consumption 

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Types of studies

Cohort Studies- can take years and be very expensive as it may take a long time for a condition to develop 

Population -followed over time-> group who develop condition, group who do not develop a condition - compare exposure to risk factors, look for correlations and draw conclusions
Population exposed/not exposed to risk factor --> groups who develop condition, groups who don't - compare outcomes and draw conclusions 

Case Control Studies - retrospective, control group must me reresentative of the population from which the case group was drawn 

Cases with condition/without condition - take histories of exposure to risk factors in the past, compare, look for correlations and draw conclusion 

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Features of a good study?

Order of Validity (worst to best) - laboratory work, case report, case-control study, cohort study, randomised controlled trial, systematic review and meta-analysis 

Good studies 

  • Clear aim - clearly stated aim or hypothesis, design must be appropriate to the stated hypothesis and aim and produce results that are valid and reliable 
  • Representative sample - must be selected from the wider population that the study's conclusion will be applied to, without selection bias, minimise drop outs to experiments (especially cohort studies), and after drop outs ensure still representative 
  • Valid (measures what it is supposed to be measuring) and Reliable (results are repeatable and reproductible) results aand disease diagnosis must be clearly definied 
  • Sample size - large enough that results couldn't have occured by chance = large sample size means more accurate data 
  • Controlling variables - potential effect of all variables must ve considered when designing the study, matching case and control groups on variables that are known to correlate with the disease being studied will ensure only the factor under investigation will be influencing the outcome 
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Why do people over/underestimate risk?

Risk - the probability of occurance of some unwanted event or outcome 

Overestimate Risk - Involuntary, not natural, unfamiliar, dreaded, unfair, very small

Underestimate risk - voluntary, natural, familiar , not dreaded, fair, large risk 

Overestimate the risk of a sudden, imposed danger with severe consequences and underestimate the risk of a long term effect in the future where the risk is uncertain 

Estimating risk to health i.e. 19900 died of injuring or poisoning, total population 6226200

19900 in 6226200 -- 1 in 62,26200/19900 -- 1 in 3129 - 0.0032% 

Identifying Risk - Null hypothesis - assume no difference between control and case group 

Correlation - when a change in one variable is accompanied by a change in another variable 
Causation - when a change in one variable causes a change in another variable 
Causation doesn't equal correaltion - control variables to see if altering one reall does alter the other 

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What are the various energy units

1 calorie - the number of joules needed to raise 1cm of water by 1oC
1 calorie = 4.18 joules 
kilocalories or Calories = 1000 calories (food labels) 
kilojoules - 1000 joules (reference to weight ) 

DRVs - dietary reference values 

  • EAR - estimated average requirement 
  • LRNI - lower reference nutrient uptake and HRNI - higher reference nutrient uptake 
  • Provide a range of values within which a healthy balanced diet should fall 

Basal Metabolic Rate - energy needed for essential proccesses - higher in males, heavier people, younger people, more active people
BMI - Body Mass Index = body mass (kg)/height^2 (m^2) - not accurate for athletes, children, those with long term health conditions 

Waist to Hip Ratio - much better indicattion of obesity than BMI and shows significant association with risk of heart attack  - waist circumference/hip circumference (under 0.9 for men and under 0.85 for women) 

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Monosaccharides - draw structures

General formula C(H2O)n 

Glucose - two isomers draw them? 

-  main sugar used in respiration 

B-Glactose

- part of lactose 

a-fructose 

- occurs naturally in fruit, honey and some vegetables

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Disaccharides - how formed, types?

Condensation reaction - joins sugar units releasing a water molecule

Glycosidic bond 

What are the three types 

Sucrose - transports sugar in plants - a-glucose - a-fructose 

Lactose - milk sugar - a-glucose and B-galactose

Maltose - malt sugar, formed when amylase breaks down starch - a-glucose - a-glucose - 1,4 glycosidic bond 

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Polysaccharides, types, which bonds, what is it?

Starch 

  • 20% amylose -straight chain of between 200 and 5000 glucose molecules, 1,4 glycosidic bond, chain coils into a spiraled shape
  • 80% amylopectin -  side branches which have a 1,6 glycosidic bond to main branch 
  • Plant storage of glucose 
  • Insoluble and tightly packed 

Glycogen - storage of glucose in animals, plants and fungi

  • numerous side branches means it can be rapidly hydrolysed giving easy access to stored energy 
  • Stored in humans in the liver and msucles

Cellulose (dietary fibre, non-starch polsaccharide) 

  • Up to 10000 glucose are joined together to form a straight chain with no branches 
  • B-glucose and B-glucose 
  • Cell walls - indigestible and tough 
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Structure and types of lipids and health

Triglyceride; three fatty acids joined to one glycerol thorugh condensation reaction and the reomval of three H2O to form ester bonds 
Saturated fat - contains the maximum number of hydrogen atoms, are solid at room temperature, no carbon to carbon double bonds, packed together closely, 

Unsaturated fats
Monounsaturated fats - have one double bond in each fatty acid chain 
Polyunsaturated fats - have a larger number of double bonds 
Double bonds causes a kink in the hydrocarbon chain. these kinks prevent the unsaturated fats from packing closely together which weakens the intermolecular forces between the unsaturated triglycerides resulting in oils that are liquid at room temperature 

Trans-fats - Unsaturated fats with hydrogen added to be made more solid at room temperature. worse than saturated fats for you 

Cholesterol - essential for good health - bile salts, steroid sex hormones, some growth hormones made from cholesterol 

Essential fatty acids - essential fatty acids that the body cannot synthesise itself 

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CVD Drugs and their side effects

  • Lowers Blood Pressure 
  • ACE inhibitors -  which reduce the synthesis of angiotensin II which causes vasoconstriction of the blood vessels 
    • Reduction in kidney function, arrythmia 
  • Calcium channel blockers - prevents calcum from moving into the muscle cells which do not contract and therefore the blood vessels do not constrict and this lowers blood pressure 
    • Swollen ankles, headaches, can be fatal in those who have/have had heart failure 
  • Diuretics - increase the volume of urine and therefore rids the body of excess fluids and salts
    • Dizziness, nausea and muscle cramps, and eating salt counteracts its effects 

Cholesterol -lowering drugs - Statins inhibit the enzyme involved in the synthesis of LDLs by the liver - ongoing debate on the effecacy and health benefits of statins

  • Reduces the risk of heart attack by 33% in patients with CVD 
  • Quickly reduces the risk of heart attack and stroke 
  • Tiredness, nauseass, vomiting, diarrhoea, headache 
  • May increase the risk of death by non-vascular causes, increased risk of developing some cancers 
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