Flashcards in Cardiovascular system Deck (50)
What are the 3 functions of blood?
Transport - oxygen, co2
Regulation -pH and temp
Protection - platelets and immune cells
What is blood plasma made up off?
water, proteins (albumin, globulins) and solutes (electrolytes, nutrition, gases)
What are the 5 main types of blood vessels?
arties (elastic and muscular), arterioles, capillaries, venules, veins
Describe the structure of an artery.
intima is the inner layer made of endothelial cells
Media is the middle layer made of smooth muscle
Adventitia is the outer layer with elastic and collagen fibres
What is the vasa vasorum?
the blood vessels that provides nutrients to the endothelial layer
What are 5 functions of vascular endothelium?
maintain tone and structure via vasodilation and constriction
regulate cell growth
regulate thrombosis and fibrinolysis
mediation of inflammation, oxidative stress
regulation of leukocytes and platelet adhesion
What are the 3 main receptors on the vascular endothelium?
Hormone receptors = angiotensin II promotes vasodilation and bradykinin II promotes vasoconstriction
Pattern Recognition Receptors (PRR) = detect damage exposure and pathogens
Toll Like Receptor 4 (TLR4) = detects Lipopolysaccharides (endotoxins from bacteria)
What are the 2 types of risk factors for CVD?
Non-modifiable = age, gender and family history
Modifiable = blood cholesterol, increased TGL and low HDL, high blood pressure, diabetes, smoking, overweight, inactive, excessive alcohol, excessive stress
List 5 symptoms for CVD.
Shortness of breath
Loss of consciousness
What is the glycocalyx?
Surface layer of glycoproteins that protects endothelial cells. Glycoproteins bind anti-oxidant enzymes to limit oxidative stress and prevent adhesion of transport protein and blood cells to endothelium.
List 5 substances that can damage the glycocalyx.
Acetaldehyde (from alcohol), PAHs (smoking and charred meat), Inflammatory cytokines, Advanced glycation end protects (AGEs) from high sugar levels, Leptin, free radicals
Explain how hyperglycaemia is a risk factor for endothelial dysfunction.
Sugar is very sticky and if insulin sensitivity is not optimal or cells are less responsive to insulin then sugar remains trapped in blood stream increasing risk of glycosylation reactions (sugar sticking to proteins). If glycosylation reactions happen the Advanced Glycation End products form (AGEs). Receptors called RAGE are activated by AGEs trigger inflammatory processes.
How does insulin work in the endothelium?
Insulin binds to receptors by activating glucose transport protein (GLUT4) to uptake glucose into cells. GLUT4 only appears in cell membrane when insulin is present but stored in vesicles when insulin is absent.
Why do GLUT4 only appear when insulin is present?
It protects cells from being flooded with sticky glucose
Explain how insulin signals GLUT4 to be inserted into membranes.
Insulin signaling triggers phosphates to be added to membrane phospholipids (phospholylation). Phosphorylation of inositol dependent phospholipids triggers GLUT4 insertion to cell membranes.
Why is vitamin C levels in cells at risk during insulin resistance?
Vitamin C uses the same GLUT4 transporter so if the cells are resisting insulin then they are also not up taking vitamin C so loosing anti-oxidant protection
What are some external signs of insulin resistance?
Ancanthosis nigricans and skin tags
Explain how hyperglycaemia causes inflammation.
High blood sugar binds to proteins forming Advanced Glycation End products (AGEs) which bind to RAGE on endothelium. Rage triggers NF-KB to be released which trigger cytokines (TNF, IL-1 and IL-6 to be released promoting inflammation.
How does RAGE alter NADPH oxidase and eNOS (endothelial Nitric oxide Synthase)?
Normally NADPH oxidase and eNOS react together with L-arginine to form Nitric oxide (vasodilator). But RAGE triggers uncoupling of these enzymes so NADPH oxidase reacts with oxygen to form SuperOxide (a free radical) and eNOS creates its own free radical (Peroxynitrite - ONOO). Also less NO is formed so that increases blood pressure.
Explain how the glycocalyx is an antioxidant.
Glycocalyx binds to antioxidant enzymes (SOD) and converts SuperOxide into O2 and H2O2 which are less toxic but AGEs damage glycocalyx so SuperOxide is not converted
Describe the Renin-angiotensin system.
Renin reacts with angiotensinogen into Angiotensin I (a mild vasoconstrictor, and increases BP). Then angiotensin converting enzymes (ACE) converts angiotensin I to angiotensin II ( a stronger vasoconstrictor and raises BP). Angiotensin II stimulates aldosterone release increasing vasoconstriction by stimulating endothelial receptor for angiotensin II called AT-1r. Aldosterone also initiates renal sodium and water retention which increase blood vol and blood pressure.
What mechanisms are involved with cardio metabolic syndrome?
hyperinsulinaemia due to insulin resistance stimulates SNS activity which stimulates renal renin release and increases blood pressure. People with CMS also have visceral adiopocytes which produce inflammatory cytokines which stimulate the HPA (adrenal) axis in hypothalamus. Leptin from adiopocytes increases SNS activation.
Explain how C-reactive protein increases BP.
CRP activates RAGE receptors so AGEs bind to these receptors which increase NF-KB expression leading to production of inflammatory cytokines. CRP-RAGE also decreases eNOS and nitric oxide while increasing ONOO free radical.
What are the consequences of high homocysteine levels?
stimulates atherosclerosis causing oxidative endothelial damage.
Explain how shear stress can cause more endothelial dysfunction.
Glycocalyx protects endothelium from the stress of a high volume of blood travelling through narrow blood vessels. AGEs, inflammatory cytokines and oxidative stress disturb the glycocarlyx as well as NO metabolism is decreased increasing hypertension. High blood pressure causes shear stress to increase
Whats the difference between primary and secondary hypertension?
primary - age, earlier menopause, family history, lack of exercise, smoking and alcohol
Secondary - renal disease, diabetes, medications, Autoimmune conditions
Explain what is meant by the DASH diet?
reduces blood pressure as well as reduces total cholesterol and low density lipoprotein (LDL). It involves high vegetable and fruit, low fat dairy and low fat generally as well as low sodium.
What are the core DASH principles?
8-10 servings of fruit and vege; eat food higher in potassium, mg, ca and fibre; replace red meats with fish and white chicken, replace high fat dairy with unprocessed low fat dairy; replace sat and trans fat rich food with nuts, seeds, avo and restrict sodium intake
How does salt act on the NS?
stimulates dopamine and glutamate receptor activity increasing reward pathways making food taste nicer.