Exercise + Health Physiology Flashcards
Define fitness
Ability to perform physical tasks and the state of being physically healthy
How many deaths can be attributed to physical inactivity
Estimated 9.4% worldwide
(Kamada eg al 2017)
What did Taylor et al 1962, focusing on occupational activity + longevity find
Clerks (less active occupation) (11.83 per 1000) are more likely to die than railway workers (7.62 per 1000)
Limitations of Taylor et al 1962
May be a self-selection bias - people may become clerks because they have an illness that prevents them from doing physical jobs
Doesn’t account for confounders- smoking, alcohol, leisure activities
What did the Harvard alumni health study (paffenbarger et al 1986) do
Questionnaire about lifestyle with an estimated calorie expenditure for each activity
Harvard alumni health study key findings
There is a large decrease in mortality in those doing a bit of activity compared to extremely low activity.
Remained significant even after adjusting for various factors eg BP + Smoking
How does intensity of exercise impact mortality
Vigorous activity is associated with a greater mortality risk reduction, minute by minute, than moderate intensity (Samitz et al)
What is the problem with subjective studies about activity
Participants are likely to overestimate the amount of activity they do, therefore results may underestimate true benefits
What was the healthy ABC study?
Objective study following high functioning older adults for 6.5years, using doubly labelled water to quantify daily energy expenditure
Findings + limitations of healthy ABC study
55% decrease in mortality risk between the least active and moderately active
But v expensive and gives no info on intensity of activity
Ekelund et al 2019 metanalysis findings
Largest benefits are seen going from the 1st quartile to the second quartile
5-6mins of moderate activity per day is associated with 30% lower mortality
Impact of strength training on mortality
Decreases risk of all cause mortality
Benefits seen are additive to aerobic exercise
Benefits peaked at 82mins per week
Describe the relationship between sedentary behaviour and mortality
Non linear relationship
The risk of sedentary behaviour is only substantial at >8hrs per day (4% Inc in mortality)
Each additional hour after 8 increases the risk
TV viewing vs General sedentary behaviour
Inc risk of all cause mortality is sharper in TV viewing than general sedentary behaviour because it tends to be associated with other unhealthy behaviours- snacking, alcohol (Patterson et al 2018)
Can you outrun sedentary behaviour?
High physical activity seems to offset negative effects of sedentary time (Ekelund et al 2016)
Does timing of physical activity matter in relation to mortality?
No both ‘weekend warriors’ and those regularly active over 5 days have a similar reduction in mortality. (O’Donovan et al 2017)
How does fitness impact mortality
Higher fitness is associated with lower mortality in patients with and without CVD at baseline, even after accounting for confounders
How does fitness age 18 impact mortality
High fitness aged 18 is associated with decreased risk all cause mortality
(Hogstrom et al 2016)
Limitation - don’t know what the participants did in the 30 years in between
Impact of physical activity on obese populations (mortality)
The risk of mortality is ameliorated but not eliminated
Impact of cardio respiratory fitness in obese individuals
Obese pts with high levels cardio respiratory fitness have similar mortality risk as a fit normal weight adult
Define obesity
Abnormal or excessive fat accumulation that poses a risk to health
BMI >=30 (>=35 very obese)
Why use waist circumference alongside BMI
To get an idea of central obesity + fat distribution as this can have major impact on health
Problem with visceral adipose tissue
Inc risk of health conditions
Adipose tissue compresses organs + can lead to chronic inflammatory state + dyslipideamia which may promote insulin resistance
List some conditions associated with obesity
Osteoarthritis- Inc load on joints
Obstructive sleep apnoea - Inc pharyngeal soft tissue
T2DM - insulin resistance due to inc pro inflammatory cytokines
Heart failure + stroke - atherosclerosis due to dyslipidemia and inc lipid production
Implication of having NO subcutaneous fat
Same metabolic processes that happen in obesity may occur
How do genetics impact obesity
Genetic influence has been confirmed by twin and adoption studies
Monogenic- potent influence by single gene
Polygenic - combination of multiple genes
FTO gene if carry both high risk alleles have Inc risk obesity
Environmental impact on obesity
21st century diet, leisure, transport and work habits have lead to inc obesity
70yrs ago people with high risk genes weren’t fat due to their environment, it is the environment changing that has lead to more obese people
Obesity Mx
Depends on BMI
Overweight may be able to use lifestyle changes alone
Obese - trial medication alongside diet + exercise
Last resort BMI>40 (or 35 with co-morbidities) - surgery - banding or gastric bypass (exercise post surgery for maintenance)
Problems with ozempic
Expensive
Limited availability
Side effects
Effect of physical activity on weight gain over time
Being active helps prevent weight game over time
But most evidence is observational studies - don’t look at diet or consider bidirectional impact
Does regular exercise lead to weightloss
Can induce significant weightloss in a strictly controlled + motivated environment
But very difficult to replicate this is real life so most people won’t see any benefit from exercise alone
Is exercise or diet control better?
Diet control as you can control 100% of your input but only 20% of energy expenditure
+ it takes longer to expend energy than to consume it
Therefore easier to induce negative energy balance through diet
Impact of aerobic training alongside weightloss diet
One study showed additional weightloss of =1.5kg
Best way to prevent regaining weight
Combination of exercise and Liraglutide facilitated weightloss maintenance better than either alone
Define T2DM
Disorder of carbohydrate metabolism caused by combination of hereditary and environmental factors. Characterised by inadequate secretion or utilisation of insulin leading to sustained hyperglycaemia
T2DM S+S
Fatigue
Weightloss
Thirst
Excessive urination
Hunger
T1DM v T2DM
T1 - autoimmune condition, can’t produce insulin, typically occurs younger
T2 - often due to obesity, resistant to insulin (may eventually stop producing it)
What is HbA1c
Glycated haemoglobin
Gives a measure of the amount of sugar in the blood over a 2-3 month period
>=6.5% (48mmol) = Diabetes (2 measures over 2 days)
Blood sugar pattern in T2DM
High fasting glucose
Postprandial hyperglycaemia
Describe the OGTT
Oral glucose tolerance test
Measure plasma glucose 120 mins after consuming 75g glucose
If >7.8 suggests impaired glucose tolerance
Often used in pregnancy to dx gestational diabetes
Impact of T2DM on mortality
Diabetics have a 15% higher risk of death than general population
Each 1% increase in HbA1c is as 12% increased risk of Mortality
Macro vascular complications T2DM
Stroke
CVD
Micro vascular complications T2DM
Diabetic retinopathy, nephropathy and neuropathy
Describe normal glucose metabolism in a fasted state
Want glucose to enter circulation
Liver increases glucose output through glycolysis and gluconeogenesis
Describe normal glucose metabolism in fed state
High levels of insulin, want to remove glucose from circulation
Increased glucose uptake and glycogen synthesis in skeletal muscle
Increased glucose uptake, Inc de novo lipogenesis and dec lipolysis in adipose tissue
Inc glycogen synthesis, Inc de novo lipogenesis and dec glucose output from liver
Metabolism of glucose in insulin resistance
Decrease glucose uptake into muscle - more glucose remains in circulation
Dec glucose uptake and inc lipolysis in adipose tissue
Inc glucose output and glycogen synthesis in liver
Define gluconeogenesis
New formation of glucose from non carb sources including glycerol
Goals of diabetes management
Glycemic control
Weight management
Cardiovascular and renal risk management
Lifestyle management for T2DM
Physical activity and diet can be very effective
26% reduction if meet weekly exercise guidelines
Best exercise for T2DM Mx
Combination of aerobic and resistance training is most effective
The more intense the exercise the greater the improvement in Hba1c
Why can you only put diabetes into remission in the first 6 year
Pancreatic beta cells have often died after 6 years of hyper secretion of insulin, therefore pt is dependent on insulin injections
DARE Study results
HbA1c decreased significantly over a 6 month Period with exercise session 3x weekly
Combination training had the biggest effect
How does exercise impact pancreas for T2DM
Increased beta cell mass
Increased insulin
Decreased glucagon
How does exercise impact adipose tissue (T2DM)
Decreased inflammation
Decreased fat mass
Increased insulin sensitivity
Impact of exercise on muscle tissue (T2DM)
Inc glucose uptake, Inc glucose and fatty acid oxidation, Inc insulin sensitivity
Impact of exercise on liver (T2DM)
Inc insulin sensitivity, dec hepatic glucose production, dec triglyceride accumulation
Impact of exercise on circulation (T2DM)
Dec blood glucose, Dec BP, dec serum triglycerides
What happens to glucose in acute exercise
Contractions cause increased glucose uptake independent of insulin
Muscles remain more sensitive to insulin for up to 2 days after
5S’s in T2DM
Sitting - break up long periods of sitting with short walks every 30 mins
Sweating - do at least 150 min moderate intensity activity weekly
Strengthening - 2-3 resistance training sessions a week improve insulin sensitivity
Sleep - aim for consistent uninterrupted sleep 6-8hrs per night
Stepping - increasing daily steps by 500 is associated with a 2-9% decreased risk of CVD
When does risk of sudden cardiac events increase
During and shortly after exercise
Describe relative and absolute risk of sudden cardiac event during exercise
Relative risk increases during exercise (you are more likely to have SCR/MI during exercise than at rest) but absolute risk remains very low
How to measure manual BP
Find brachial artery
Wrap BP cuff around bicep + put bell of stethoscope on brachial artery
Pump up cuff
Release cuff until you can hear pulse - systolic
Slowly release more until can no longer hear pulse - diastolic
Smoking + CVD
Smoking is a well know risk factor for CVD
Damages lining of arteries, increases BP, + thickens blood
Describe bland Altman plot
Compares 2 sets of measurements to identify any systematic bias or random error in date
Factors contributing to differences between venous sampling and finger prick
Air bubbles in sample
Sample contamination
Length of time taken to get sample
Blood volume
What is Q risk 3
Calculates persons risk of having MI or stroke in next 10 years
Benefits of Q Risk
Includes additional risk factors compared to Framingham CVD risk prevention, providing greater risk prediction accuracy
Additional risk factors in Q risk
Ethnicity
Townsend deprivation score
Migraine
CKD stage 3+
SLE
RA
A Fib
BP treatment
Angina/MI in 1st degree relative under 60
Erectile dysfunction
Antipsychotics/ steroids
Severe mental illness
Framington CVD risk predictor variables
Age
HDL
Total cholesterol
Untreated systolic BP
Treated systolic BP
smoker
Diabetes
What is the Townsend deprivation score
Measure of material deprivation in a population based on unemployment, non car ownership
Non home ownership, household overcrowding
What risk factors are there that you can’t change for MI/Stroke
Male
Asian ethnicity
Family history
Aims of ACSM pre-participation screening algorithm
Identify Individuals who require medical clearance before initiating an exercise programme
Identify individuals who may benefit from partaking in a medically supervised exercise programme
Identify individuals with medical conditions who should be excluded from exercise until medical condition improves
3 factors that the ACSM pre participation screening is based on
Current exercise participation
Desired exercise intensity
Hx + Sx of CV, Metabolic or renal disease
When is medical clearance recommended for exercise
No regular exercise + S+S of CV/Metabolic/Renal disease
No regular exercise + Known CV/Metabolic/Renal disease
Currently active, known disease + want to engage in vigorous activity
Currently active + new onset of S+S (discontinue exercise until medically cleared)
What does detailed evaluation for medical clearance include
Hx, examination, bloods, resting ECG, Exercise ECG
Define CVD
Collective term for diseases affecting heart and circulatory system
List 8 cardiovascular diseases
Stroke
Angina
MI
Heart failure
Peripheral arterial disease
Congenital heart defects
Arrythmias
CHD
DVT
Number of CVD Deaths
27% of UK deaths 2022
Active jobs v sedentary jobs CVD risk
Sedentary 2x more likely to have MI
But self selection bias
Impact of cardio respiratory fitness on CVD deaths
1 met increase in baseline cardio respiratory fitness was associated with 18% decrease in CVD deaths after adjustment for confounders
Cardio respiratory fitness vs genetic components CVD
Increased cardio respiratory fitness decreases risk of CVD even in people with high genetic risk for CVD
What increases risk of CVD mortality
Low physical activity
Poor cardio respiratory fitness
Define atherosclerosis
Thickening and hardening of artery caused by build up of plaque in the inner layer of the artery wall
Harder for blood to flow through so Inc risk of MI + Stroke
Describe development of atherosclerosis
- RFs cause endothelial damage increasing permeability of endothelial layer
- Initimal smooth muscle proliferation stimulated by various mechanisms
- Plasma LDL enters intima and is oxidised
- Oxidised LDL is taken up by scavenger receptors on monocyte transforming it into lipid laden foam cells
- Fatty streaks are formed from lipid filled foam cells
- Atherosclerotic plaque forms over many years
- Plaques are susceptible to rupture, haemorrhage, athero-embolism + anneurysm formation
Contents of atherosclerotic plaque
Cells - smooth muscle, macrophages, T cells
Extra cellular contents - collagen, elastic fibres
Intra+ extra cellular lipid
Role of hyperlipidemia in atherosclerosis
Can increase endothelial permeability
Inc serum conc of LDL + VLDL, can promote formation of foam cells
Modifiable atherosclerosis RF
Hyperlipidemia
Hypercholestroaemia
HTN
Smoking
Diabetes
Obesity
Low physical activity
Chylomicron function
Transport dietary fat from intestines to adipose tissue, muscle + liver
VLDL function
Made in liver, transports triglycerides to tissues
Contributes to build up of atherosclerotic plaque
LDL function
Predominate carrier of serum cholesterol to tissues
Contributes to build up of atherosclerotic plaque
HDL function
Transports excess cholesterol from blood + peripheral tissues to liver
Protective against CVD
Effect of exercise on lipoproteins
Regular exercise elevates HDL and lowers VLDL + triglycerides
The changes are more likely if exercise also causes weight loss
Findings for LDL less consistent
Effect of walking on BP
Both accumulated + continuous walking lead to post exercise hypotension, in healthy individuals and those at risk of CVD
Effects lasted = 24hrs
Impact of exercise alongside anti hypertensive meds in African Americans
Significant decrease in diastolic BP
Significant decrease in intraventricular septum thickness + left ventricular mass
Mean arterial pressure calculation
MAP = CO*Systemic vascular resistance
How does aerobic exercise decrease systemic vascular resistance
Vasodilation
Histamine released during vasodilation increases endothelial dependant vasodilation
Arterial baroreceptor reflex is reset - decreased noradrenaline - less vasoconstriction
Adaptations to training that decrease systemic vascular resistance
Vascular structural changes
Decreased inflammation
Decreased adiposisity
Increased insulin sensitivity
Describe endothelial dysfunction
Endothelium should be able to interact with vascular smooth muscle to influence blood flow
Atherosclerosis hardens and thickens blood vessels- harder for this to happen
Get turbulent flow and thrombus formation
Describe NO induced vasodilation
Exercise
Increased endothelial shear stress
Increased endothelial nitric oxide synthesis
Inc nitric oxide availability
Nitric oxide vasodilates blood vessels
Improved endothelial function
Impact of regular exercise on cardiovascular system
Enlarged coronary artery diameter, lower BP, Dec risk blood clots, improved endothelial function, dec chronic inflammation
Therefore potential for it to contribute to cardiovascular health
Define inflammation
Local immune response to physical injury/ damage or infection
Inflammation signs
Rubor, Dolor, calor, tumour, loss of function
Inflammation functions
Phagocytic cells engulf and destroy infected or damaged tissues
Stimulate tissue repair
How does inflammation stimulate tissue repair
Causes cytokine release from tissues which stimulates liver to release acute phase proteins eg CRP
Describe interleukins
Group of cytokines released by immune cells that play important role in regulating immune response including inflammation, proliferation, differentiation + activation
What is bad inflammation
Chronic low grade inflammation
Dysfunction of immune response leading to LT release of inflammatory cytokines by immune cells
Causes of chronic low grade inflammation
Obesity - FFA uptake by immune cells
Smoking - high levels of toxins in circulation
Unresolved infection
Autoimmune response
Local tissue hypoxia
Describe how obesity/ high levels visceral fat cause chronic long term inflammation
Adipocyte hypertrophy
Blood supply therefore stretched over larger area
Hypoxic areas cause Inc metabolic stress
Cytokine release
Obesity can’t be beaten in 2-3 days so stimulus remains + cytokines constantly released
List conditions associated with chronic inflammation
Diabetes
CKD
Heart disease
Inflammatory arthritis
Dementias
Stroke
IBD
Endometriosis
Role of pro-inflammatory cytokines in chronic inflammation
Mediates inflammation
Eg IL6, TNF-alpha
What are elevated pro inflammatory cytokines, fibrinogen + CRP associated with
Inc prevalence of multiple inflammation related diseases
Inc risk all cause mortality
Inc CVD RF
Impact of inflammation on liver
Insulin resistance
Sustained acute phase protein release
Impact of inflammation on adipose tissue
Adipokine production + immune cell infiltration
Impact of inflammation on brain
Build up of amyloidogenic proteins (IL6 can cross BBB)
Impact of inflammation on endothelial cells
Endothelial dysfunction + arteriosclerosis
Impact of inflammation on skeletal muscle
Sarcopenia, insulin resistance
Inflammation + CVD
Chronic inflammation is a RF for CVD
IL6 is increases as number of other CVD RFs increase in otherwise healthy women
Impact of using monoclonal antibodies to target inflammatory pathways
Dec incidence of atherosclerotic pathogens
Lowered CRP, NOT lipids
Dec incidence of having another CVD event/death over 4years
Can exercise be ani-inflammatory
Yes
Study showed more active people had lower inflammatory markers
But same trend seen - more active people had less adipose tissue
Impact of sedentary time on inflammation
People with higher sedentary time had higher inflammation levels even if also physically active
List 4 mechanisms why LT physical activity is anti inflammatory
1.Decreased adipose tissue - biggest source of circulating IL6
2. Decreased numbers of inflammatory immune cells entering adipose tissue
3. Altered cytokine production from inflammatory immune cells
4. High intensity exercise + counter action of anti-inflammatory response
How is decreasing numbers of inflammatory immune cells entering adipose tissue anti-inflammatory
Migration of immune cells from circuit tissues is a key event in chronic inflammation
Studies show monocyte migration decreases in obese individuals who move more
Mice studies show decreased inflammatory macrophages per gram adipose tissue in obese mice that exercise compared to obese mice
How does altered cytokine production from inflammatory cells make LT physical activity anti inflammatory
Regular brisk walking in pts with CKD decrease inflammatory immune cell activation and release of pro inflammatory proteins into blood
How is higher intensity activity anti-inflammatory
Causes skeletal muscle to release large amounts of IL6 as an acute response.
Stimulus leads to release of counter active anti-inflammatory response - IL10
Regular performance of higher intensity/longer duration activity can lead to persistent elevation of IL10
Anti-inflammatory effects of regular physical activity
Reduced circulating levels of anti-inflammatory markers at rest
Lower pro-inflammatory cytokine release from immune cells at rest
What is the gold standard measure of cardio respiratory fitness
VO2 max (maximum oxygen uptake)
What is a low VO2 max indicative of
Inc risk CVD + Premature mortality
Why is direct determination of VO2 max not always possible?
Cost, lack of specialised equipment, lack of trained personnel
May be dangerous in some people
List 4 methods to estimate VO2 max
Bruce treadmill protocol - maximal graded exercise test
Astrand-ryhming cycle ergo meter test - submaximal
Chester step test - submaximal
Questionnaire
Guidelines for safe conduct of laboratory exercise test
Physical activity readiness questionnaire should be completed
Ensure treadmill/ ergometer is safe
Fully describe all procedures to pt and provide participant info sheet
Familiarise participants with all equipment
Give participants opportunity to ask Qs
Watch participants closely in test + for 10 mins after
Provide opportunity for warm up/cool down
Describe Bruce treadmill protocol
Maximal graded exercise test performed until exhaustion or til termination is indicated by S+S
3 minute stages of increasing treadmill speed and gradient
Duration of test sustained can be used to estimate VO2 max
What variables are measured in the Bruce treadmill protocol
HR, BP, Ratings of perceived exhaustion
ECG if done in clinical practice
Describe Astrand-rhyming cycle ergometer test
Single stage test lasting 6 minutes
Individuals pick a work rate based on sex and fitness status
Pedal rate set at 50
HR measured min 5 + 6 and mean is used to estimate VO2 max from a nomogram
Must then adjust value for age
What assumptions are made when estimating VO2 max using sub-maximal tests
Steady state HR is obtained for each exercise work rate
Linear relationship exists between HR + work rate
Difference between actual + predicted maximum HR is minimal
Mechanical efficacy is the same for everyone
The participant is not affected by other factors that may affect HR - Caffiene, stress, hot environment
Benefits + limitations of the Chester step test
Cheap and easy
May be difficult for people with balance issues
Few points for plotting- line of best fit less accurate
Describe Chester step test
Step up and down in time with metronome which increases in pace as test stages progress
Stop when HR reaches 80% of max or feel breathless, overtired or dizzy
Maximal O2 uptake estimated based off of HR response to submaximal exercise stages
How to decide what size step participants should use in the Chester step test
30 cm = under 40, regularly active, used to moderate-vigorous exertion
25cm = over 40, regularly active, used to moderate-vigorous exertion
20cm under 40 little active/ moderately overweight
15cm over 40 little active
How to calculate max HR
220-age
Benefits and limitations for estimating VO2 max from questionnaires
Quick, simple + easy
Rely on prior knowledge
People unlikely to be totally accurate
What questionnaires are used in estimating VO2 Max
Perceived functional ability (PFA)
Physical activity rating (PA-R)
What is the difference between RMR and basal metabolic rate
RMR is slightly higher (measured at rest, 3-4hrs post light meal)
BMR - minimum level of energy required to sustain vital functions. Measured at rest in post-absorbative state 12 hours after food
How is RMR Measured
Indirect calorimetry
Direct calorimetry
Predictive equations provide an estimate
What Are the four most common equations used to predict RMR?
Harris-Benedict
Owen
Who/FAO/UNU
Miffed St Jeor
How are predictive equations developed
Based Off off measurements of direct and indirect calorimetry
How Are predictive equations, validated
Used On a diverse population with a variety of weights ages And ethnicities
How Much variation exists between the different productive equations
A fair bit, but Owens tends to be roughly 200kcal lower than the other 3
What are The key limitations when using predictive equations
They are based off of a generalised population, which might not be representative of the individual
Maybe Unreliable for certain ages and ethnicity , particularly older adults and non-white
Risk Of individual error in calculations and measurements
Individual Variation
Energy expenditure calculation
Energy expenditure = RMR * physical activity level
Physical activity level associated with sedentary existence during work and leisure
1.4
Physical activity level associated with very high PA levels during work and pleasure
2.5
Estimated Physical activity level that is the maximum level of sustainable in humans
5 (Before body weight is lost)
Physical Activity level associated with moderate activity levels
1.6 women
1.7 men
Physical activity level associated with high activity levels
1.8 women
1.9 men
What Is a MET
A multiple of the resting metabolic rate
What Is 1met equivalent to?
Energy Expenditure of the body, at rest quantified as one kcal, per kilogram, body mass per hour
Oxygen Consumption equivalent to one met
3.5mL/kg/min
How Does exercise, intensity, affect energy expenditure?
Higher intensity equals higher energy expenditure
What is exercise, intensity, dependent on
Physical Fitness and individual needs a good level of cardiovascular fitness to work at high exercise intensity
How Many calories are expended for each litre of oxygen consumed
5kcal (21kJ)
Why Does low energy intake cause a decline in energy expenditure?
Lower Metabolic rate due to lower metabolically Active tissue mass
Adaptive Thermogenesis an involuntary compensatory mechanism to conserve energy
Why Are patients given new energy intake targets for body weight maintenance once their goal weight is achieved
To ensure they are in energy balance
It Is lower than pre-weight-loss maintenance calories, because lean mass is increased compared to Fat mass
Define ectopic fat
Fat stored in places not designed for mass storage eg intraorgan
How does accumulation of ectopic fat occur
1.positive energy balance
2. Inc inflammation, hypoxia, pro inflammatory cytokines and insulin resistance
3. Fat spillover occurs leading to more free fatty acids in circulation
4.FFA deposit within organs
Stages of non alcoholic fatty liver disease
- Healthy
- Fatty liver (32% population)
- Non alcoholic steatohepatitis (NASH)
- Cirrhosis (+ Inc risk HCC)
MASLD diagnostic criteria
Metabolic dysfunction related steatotic liver disease
= steatotoic liver disease plus 1 of
BMI>25/waist circumference >94(M) or >80 (f)
Fasting serum glucose >5.6 or 2hr glucose >7.8 or T2DM
BP >130/85
Plasma triglycerides >1.7
HDL cholesterol <1(m) or <1.3 (f)
Gold standard Ivx for MASLD
Liver biopsy
Visible liver droplets in >5% hepatocytes
Able to identify different stages of MASLD
But invasive + specialised
Gold standard non invasive Ivx for MASLD
MR spectroscopy
Liver fat% >5.56
Allows repeat measures
But expensive + specialised
MASLD prevalence
Affects 32% adults
Most common form of liver disease worldwide
Often co-exists with other diseases T2DM(60%),Obesity (70%)
Individuals with MASLD 2x more likely to develop T2DM
Strongest predictor of insulin resistance
Intra-organ liver fat
Lipid supply to liver mechanisms
Adipose tissue lipolysis
Dietary fat
De novo lipogenesis
Lipid disposal from liver mechanisms
Fat oxidation
VLDL-TAG export
Hepatic steatosis pathogenesis
Inc dietary fat - Inc lipolysis - Inc FFA - Inc TAG synthesis
Inc dietary fat - Inc TAG rich chylomicrons, chylomicron remnants left, Inc TAG synthesis
Inc dietary fructose + glucose - Inc de novo lipogenesis
Why does hepatic steatosis occur
Lipid supply to liver exceeds disposal due to over nutrition and insulin resistance
Disposal routes may also increase but not enough to offset Inc supply
MASLD Mx
Resmetrion - 1st drug approved this year, some anti obesity drugs also look promising
Lifestyle modifications - exercise + hypocalorific diet.
5% weightloss - dec hepatic steatosis, 7% weightloss NASH resolution, 10% weightloss fibrosis regression
Impact of exercise alone on MASLD
No change body weight
Significant decrease in liver fat
Significant increase in peripheral insulin sensitivity
Why does exercise improve MASLD - adipose tissue
Improved adipose tissue insulin sensitivity
Decreased adipose tissue lipolysis
Why does exercise improve MASLD - Skeletal muscle
Inc glucose uptake as enhanced insulin sensitivity
Leading to less substrate for de novo lipogenesis
Why does exercise improve MASLD - liver supply
Dec uptake of lipids from circulation, decreased hepatic lipase activity
Dec de novo lipogenesis
Why does exercise improve MASLD - liver disposal
Inc lipid oxidation
(Rodent studies showed Inc markers of B-oxidation + mitochondrial biogenesis)
Impact of resistance exercise on MASLD
Similar improvements in BMI and liver fat between aerobic + resistance exercise despite lower intensity and energy consumption with resistance training.
May complement aerobic training by modulating liver fat through different mechanisms
Resistance exercise mechanisms to dec liver fat
Hypertrophy of Type 2 muscle fibres
Activation of GLUT 4 + AMPK
Alteration in myokines
How does hypertrophy of type 2 muscle fibres improve MASLD
Hypertrophy of skeletal muscle = increased glycotic demand by muscle
Decreased circulating glucose = less substrate for de novo lipogenesis
What is GLUT 4
Insulin regulated transporter protein, responsible for glucose uptake into muscle.
What is AMPK
Energy sensing kinase that promotes insulin sensitivity
How does activation of GLUT 4 + AMPK improve MASLD
Inc insulin sensitivity so Inc GLUT 4 mediated uptake into muscle
Decreased circulating glucose + insulin, less substrate for de novo lipogenesis
What is a myosin’s
Cytokine produced and secreted by skeletal muscle
How does alteration in myokine improve MASLD
Irisin = myokine increased in resistance exercise, believed to inhibit key regulators and enzymes in de novo lipogenesis
What is the athletes paradox
Skeletal muscle lipids are elevated in endurance athletes and T2DM compared to lean sedentary counterparts
But athletes remain insulin sensitive so this may be beneficial for them due to high fuel demand
Therefore believed the form in which lipids are stored is important
PUFA better than SFA and intermediates
Describe inspiration
Process of breathing in
Diaphragm moves down, external intercostals move up and out
Chest cavity is increased therefore pressure in lungs is lower than atmospheric pressure
Air pulled into lungs
Describe expiration
Process of removing CO2 from body through the lungs
Diaphragm relaxes, moving up, external intercostals move down + in
Intra thoracic pressure increases above atmospheric pressure
Air passively flows out
Define tidal volume
Amount of air that moves in and out of lungs with each respiratory cycle
Typically 500ml ish
Define inspiratory reserve volume
Amount of air that can be taken into the lungs after tidal volume, upon forced inspiration
Define expiratory reserve volume
Extra volume of air that can be expired with maximal effort, beyond the level reached at the end of normal quiet breathing
Define residual volume
Vol of air remaining in lungs after maximal forceful expiration
Define vital capacity
Total vol of air that can be displaced from lungs following maximal inspiration
Define ventilation
Movement of air in and out of airways
Define asthma
Chronic inflammatory disease of airways that causes reversible airway obstruction + hypereactivity
Asthma Sx
Cough, wheeze, chest tightness, SoB
Sx typically worse at night
Multiple triggers - exercise, cold weather, allergies etc
Asthma prevalence
> 300 million affected worldwide
10% 6+7yr olds - greater incidence in children
60,000 uk hospital admissions per year
Asthma attack pathophysiology
Airway Smooth muscle tightens
Air becomes trapped in alveoli
Define COPD
Umbrella term for chronic bronchitis + emphysema
Chronic progressive lung disease characterised by persistent respiratory symptoms + airflow obstruction that’s not fully reversible
Define emphysema
Enlargement of air spaces and destruction of lung parenchyma
Define chronic bronchitis
Increased sputum production, obstruction of major and minor airways, chronic productive cough
COPD Sx
“Air hunger”, exertional dyspnoea, chronic cough, decreased exercise tolerance, sputum production, Inc respiratory effort
COPD Mx
Smoking cessation
Vaccines
Meds - SABA/LABA/LAMA/ICS
Oxygen therapy
Pulmonary rehab
Describe pulmonary rehab
6-12week programme with twice weekly sessions (both exercise + educational)
Aims to improve exercise tolerance and lung function
Does pulmonary rehab work
Yes - overwhelming evidence
Improves mood, dyspnoea, mastery, emotional function, functional + maximal exercise capacity
Pulmonary rehab outcome measures
Strength
Exercise capacity
Quality of life
Mood
Dyspnoea + fatigue
Describe COPD cycle of inactivity
Dec activity
Muscles weaker
Weaker muscles have increased oxygen consumption as less efficient
Feel breathless
Become fearful of tasks making you breathless
Avoid activities making you breathless
Decreased activity
Describe COPD positive cycle of activity
Inc activity
Muscles stronger
Use O2 more efficiently
Decreased breathlessness- tasks feel easier
Feel better
More motivated to continue activity
Increased activity
What is GOLD score
Global initiative for chronic obstructive lung disease
GOLD IV is worst
Effect of physical activity on COPD
Some level activity = decreased risk COPD admissions + mortality
2hrs walking/cycling per week = 30-40% decrease in admission/ mortality
Asthma + physical activity
Mixed results
Most studies suggest physical activity improves lung function, quality of life + asthma control
3 studies showed no improvement. No studies showed worsening
describe trabecular bone
inside
network of cross bridges filled with bone marrow
more rapid turn over
describe cortical bone
on the outside (very outer layer = periosteum)
dense strong structure
longitudinal cylindrical osteons
what is bone tissue composed of
2/3rd ground substance
1/3rd portions
2% bone cells
describe ground substance
predominately hydroxyapatite crystals + other Ca salts and ions
allows storage and release of Ca
describe the protein component of bone
most abundant is type 1 collagen fibres
describe bone cells
osteoblasts - develop from messenchymal stem cells, build bone by recreating osteoid protein which matures to osteocytes
osteocytes = mature bone cells, role in signalling
osteoclasts - resorb bone using acids and enzymes
How is bone mineral distribution measured
DEXA scan - 2D image
pQCT - 3D scan of peripheral bones eg shin + forearm
Clinical QCT - 3D image
describe trends in Bone mineral density
higher in men throughout life
significant drop in post menopausal women - due to decreased oestrogen
both men and women decrease slowly with age
define osteoporosis
systemic skeletal disease characterised by low bone mass + microarchitectural deterioration of bone tissue, with consequent increase in bone fragility and fracture risk
lifetime fracture risk in over 50s
1 in 2 women
1 in 5 men
common fragility fracture sites
NOF, vertebrae, forearm
why does osteoporosis increase risk fragility fracture
thinning of cortical bone and loss of trabeculae
osteoporosis RF
older age
female
smoker
low BMI
FH
decreased oestrogen
cancer Tx
glucocorticoid use
T2DM
high falls risk
describe mechanostat theory
bone adapts to its level of loading
1. Habitual loading - stress causes strain within bone
2. Moderately increased loading - increased strain
3. osteocytes detect additional strain -bone adapts
4. inc loading on adapted bone - less strain
why is it important to not extremely overload bone
causes micro damage and fractures
describe targeted remodelling
old bone undergoes osteocyte apoptosis + is replaced by new bone
total bone mineral density unchanged
describe disuse mediated remodelling
build less bone than resorbed - lose bone mineral density
describe formation modelling
increased load
leads to new bone being build independent of resorption
describe resorption modelling
osteocyte apoptosis and osteoclast resorption occur without osteoblasts building new bone
effect of exercise on children’s bones
regular jumping(impact activity) increases bone mineral density
effects long lasting - seen up to 7 yrs later
effect of exercise on adolescent bones
thickens cortical bone
type of exercise impacts what bone is thickened
eg hockey - multidirectional impact - all-round thickening
running thickened at front and back
effect of exercise on pre-menopausal women
spine - high load resistance training increased BMD
hip - high impact exercise increased BMD
effect of exercise on fracture risk
observational studies suggest decreased 38% women + 45% in men
factors contributing to fracture risk
bone strength - Bone mineral density + bone structure
falls risk - neuromuscular function + environmental hazards
fall prevention exercise
most effective = challenges balance, includes lower limb strength training. > 3 hrs per week tailored to individual
UK recommendations for exercise for osteoporosis
progressive resistance exercise, loading the hip = spine 2-3 days per week
build to 3 sets of 8-12 rep max
include impact exercise - 50 moderate impacts per day with rest breaks
if falls risk prioritise strength and balance training 2-3 days per week
What Is cancer
Uncontrolled mitosis cells can metastasise to another part of the body
How Does the thymus impact cancer incidence?
Thymus Produces t cells
Thymus Shrinks as you get older, less t cells produced
Greater Incidence of cancer as you get older
Describe Non-specific cancer immunity
Natural Killer cells kill abnormal cells - identified as they have lost MHC class 1 receptors
2 Methods
Cytolytic activity - secrete granzymes- enzymes enter through pore and cause cells to lyse
Cytokine release- indirect method through recruiting specific immune cells
Describe Specific antitumour immunity
Dendritic Cells such as macrophages do phagocytosis
B Cells produce specific antibodies, causing a humeral immune response
T cells - work with CD8 to induce apoptosis via cytotoxic cells
T cells work with CD4 to prime B cells
Describe the 3 Es of immunosurveillence
Eliminatation - immune System destroys, weakest cancer cells
Equilibrium, small sub population of cancer cells, survive and lie, dormant
Escape - Clonal outgrowth of surviving cancer cells
Define clonal
Every cell in the population has original mutation
Describe Metastasis
Cancer Cells spread to other parts of the body
2/3 of cancer related deaths are due to mets
Metastasis are made of different cell types, including stem cells which are harder to treat
Cancer RF
Nearly 50% preventable
Pathogens - EBV infection - nasopharyngeal ca + Burkitt lymphoma
Obesity
UV damage
Toxin exposure - asbestos, smoking
How to reduce cancer risk
Exercise
Eat well
Healthy body weight
Limit UV a exposure
Don’t smoke
Avoid infectious agents
Effect of exercise on cancer overview
Dec primary cancer risk
Improves chemo response
Improved recovery
Dec secondary cancer risk (probably, hard to research)
Effect of leisure time PA on Ca risk
Dec risk oesophageal Adenocarcinoma, liver, lung, kidney, myeloma,colon, H+N
But Inc risk malignant melanoma- Inc UV exposure (outside more)
How to exercise help prevent cancer
Sex hormones - breast cancer often driven by oestrogen, oestrogen produced by adipose cells, exercise decreases adiposity.
Metabolic hormones - exercise improves insulin sensitivity, dec risk T2DM, associated with some cancers
Chronic inflammation promotes cancer - exercise dec chronic inflammation (4 mechanisms)
How does exercise effect existing Cancer
Can decrease cell growth - voluntary wheel running in mice decreased tumour growth 67%
Cancer cells incubated with exercised serum produced fewer tumours in mice
Exercise decreased breast cancer cell viability, proliferation + tumourogenic potential in vitro
BUT
Can’t shrink tumours
Effect of exercise on tumour metabolism
Cancer cells more susceptible to exercise induced energy stress
Cancer cells use up lots of glucose - always metabolise through lactate producing pathway - therefore adapted to inc number of GLUT 1 transporters to counteract quick build up of lactate.
Why shouldn’t you completely cut out sugar if have cancer
Cancer cells have more GLUT 1 transporters therefore can use any available sugar faster
Cutting out majority of sugar will starve healthy cells as cancer cells will monopolise any available
Effect of exercise on chemo
Cancer cells cause angiogenesis (new blood vessels, these tend to be more leaky + tortuous)
Exercise promotes this and makes the new blood vessels stronger
Therefore chemo can be delivered deeper into the tumour - better effects
Increased drug tolerance - able to withstand higher dose - more like likely to kill tumour
Effect of exercise on immune cell function (Cancer)
Exercise mobilises cells involved in immune response
Natural killer cells first to be mobilised by exercise- as express more B-adrenergic receptors
Patients with Inc NK + Cytotoxic T cells = better prognosis
Effect of exercise on NK cells
Inc NK cell cytotoxic activity
Inc lymphocytic production
Inc number of granulocytes
Which cancer patients is exercise most beneficial for
Compromised immune function
What can effect ability to exercise in Ca pts
Type + stage Ca
Ca Tx
Stamina, strength + fitness level
Exercise + metastasis
Cancer stem cells are more chemo resistant
Exercise may alter cancer stem cell phenotypes
Research ongoing
