Lecture 29 Flashcards
Define obesity
excess accumulation of body fat
Obesity and its associated metabolic syndrome change the function of the heart in two general ways. What are they?
Intrinsic and extrinsic ways
What do intrinsic changes refer to?
This refers to altered substrate metabolism:
- increased FS oxidation
- decreased glucose utilisation
- reduced cardiac efficiency
- oxidative stress
- mitochondrial dysfunction
- apoptosis
- lipotoxicity
- altered Ca2+ dynamics
- inflammation
- fibrosis
What is the metabolic syndrome?
This is the presence of 3 or more of risk determinants such as increased waist circumference, high triglycerides, low HDL, high blood pressure, high fasting glucose
What do extrinsic changes refer to?
- hyperlipidemia
- increased coronary atheroscleoris
ischemic heart disease - volume expansion
- increased cardiac output
- hypertension
- sleep disorders
- changes to the renin angiotensin system
- increased vascular tone
- decreased NO availability
- increased FFA, triglycerides
- hypoadiponectinemia
What are the 4 main mechanisms contributing to cardiac dysfunction in obesity?
- haemodynamic load (volume expansion)
- heart fat (affecting the conduction system)
- adipocytes - adipokines - myocardial fibrosis
- microangiopathy (endothelial dysfunction)
How does the haemodynamic load change during obesity?
There is an increased mass due to the increase in the overall body blood flow (there is more tissue to perfuse with blood).
How does the haemodynamic load change during obesity?
There is an increased mass due to the increase in the overall body blood flow (there is more tissue to perfuse with blood).
How much more blood flow does 100kg of excess body fat require? What are the cardiac outputs for someone that is 70kg, 120kg and 170kg?
100 kg of excess body fat requires an extra 3 L/min blood flow
Subject of 70 kg: 6.0 L/min
Subject of 120 kg: CO 7.5 L/min
Subject of 170 kg: CO 9.0 L/min CO
Increased mass results in an increase in what? Why is this?
An increase in preload because there is more filling required.
How does an increase in body weight effect the HR, SV (and CO) and TPR? What does this mean in terms of output and resistance state?
CO is increased because HR due to an increase int eh sympathetic activation of the heart and SV are both increased but TPR will decrease because there is more tissue to perfuse.
This means we are in a high output, low resistance state
What is the cardiac remodelling that happens in obesity?
Because there is the volume overload, there is eccentric remodelling of the heart (significant LV dilation)
Explain the eccentric remodelling of the heart during obesity. What else can happen?
There is an increase in the size of both the LV and LA (hypertrophy) when there is the volume overload. However, when you have an increase in body mass, there is also an increase in blood pressure. Because of this pressure overload, there is LV concentric hypertrophy
Morbidly obesity is associated with mild systemic hypertension and you get ______ overload.
Mild obesity associated with severe systemic hypertension is related to ________ overload
volume
pressure
Combination of obesity and hypertension results in mix of
eccentric and concentric hypertrophic remodelling.
yes
What are the two types of heart fat? Which one is more important?
- there can be epicardial fat which is fat in the epicardial tissue (this one is more important)
- there can be pericardial fat which is fat in the pericardial sac
fat going into the myocardium is also a problem
What is and what is the issue wth fat infiltration?
This is when fat accumulates as lipid pools in the myocytes. This affects the function of the heart
What are 4 main consequences of heart fat deposition and infiltration?
- mechanical impairment
- thermoregulation (higher body core temperature)
- cardiac conduction
- endocrine effects (adipokines and cytokines)
How does heart fat affect the conduction system? What are the risks of this?
If you are obese, there is LV and can be RV hypertrophy and both eccentric and concentric remodelling. The heart gets bigger and the conduction system has to grow with this.
The fatty infiltration means that there is electrical conduction and so the electrical activity is affected (slowed down). There is prolongation of the QT interval. Also, adipokines and cytokines released may also have an effect.
This can result in sleep apnea, cardiac arrhythmias and sudden death
How do adipocytes and adipokines and myocardial fibrosis affect the cardiac function?
Fat cells use fatty acids for energy. They secrete factors such as adipokines. As you gain more wright, there is more fat and so you release more adipokines. Adipocytes attract macrophages and an inflammatory response is triggered which is bad. The insulin response is also affected
What is the consequence of more adipokines being released?
The ECM with the collagen and fibronectin and elastin. With hypertension, there is an increase in the formation of these structures.
When you have many adipokines being released, they have effects on lots of cells such as the fibroblast which makes the ECM proteins. This means you get remodelling of the ECM and this leads to changes in isoform and crosslinking and this leads to heart failure
What is the consequence of more adipokines being released?
The ECM with the collagen and fibronectin and elastin. With hypertension, there is an increase in the formation of these structures.
When you have many adipokines being released, they have effects on lots of cells such as the fibroblast which makes the ECM proteins. This means you get remodelling of the ECM and this leads to changes in isoform and crosslinking and this leads to heart failure
What is microangiopathy?
This is a disease of the small blood vessels (fat in the smaller vessels)
What happens when adipocytes gets into the blood vessels?
The vessels are different sizes in different places in the tissue instead of being nice and uniform and straight
What happens with the vessels are exposed to adipocytes around the vasculature (perivascular)?
There are adipocytes surrounding the vasculature. If they are exposed to high levels of FFA, they will take them up and grow bigger and then they will attract microphages and they will release the factors such as leptin adiponectin, cytokines and inflammatory markers (same as in the heart).
What is the long term effect of adipose on vascular regulation?
Normally there is a balance between constriction and dilation by endothelin and NO respectively.
Non-esterified FA and changes in insulin have effects between the balance between endothelin and NO. This can cause Microangiopathy - Retinopathy - Nephropathy - Neuropathy
