Lipids/ cardiovascular pathophysiology & Pathophysiology of thyroid glands Flashcards
What other disorders of the body are affected by vascular disease?
- Stroke- Strokes are caused by blocked BV in the brain
2.Angina- caused by restricted blood supply to the heart Muscle
- Coronary heart disease- BV to heart , reducing the blood supply to heart muscle
4.Heart failure- Heart cannot pump properly and supply to the body
5.Rheumatic heart disease - Damage to the heart from rheumatic fever
- Birth heart defects- Defects heart structures existing at birth
- Deep vein thrombosis- Blood clots formed in the leg veins which move to the heart and lungs
Epidemiology of Vascular Disease?
-Worldwide effected
- Low social economic
Risk factors of CVD
Non-modifiable factors:
1. Age
2.Gender
3. Race & Ethnicity
4. Genetic factors
Modifiable factors:
1. High BP
2. Smoking
3. Obesity
4. High blood cholesterol
5. Diabetes
6. Physical inactivity
What is the old and new concept of the Atherogenesis?
Old= Healthy -> Subclinical- Small plague (Lipid deposit)-> Symptomatic- Plague takes over the whole shape (Mths- Days)
New= Healthy -> Arterial wall bulges outward with the deposition of the collateral deposits -> Endothelial cells are disrupted causing activation of platelets, platelet puck the endothelial lining and case formation of blood clot and thrombus
What is the information about cholesterol?
Structural component (30%) of Cell membranes.
Precursor for steroid hormone synthesis.
Structural component of lipoproteins
What is the information about LDL cholesterol?
- Strongly associated with atherosclerosis and CHD events
– 10% increase results in an approximate 20% increase in CHD risk
– Most of the cholesterol in plasma is found in LDL particles
– Smaller denser LDL are more atherogenic than larger, less dense particles
– Risk associated with LDL-C is increased by other risk factors such as Low serum [HDL-C] Smoking Hypertension & Diabetes
LDL Receptor Structure
*Best characterised lipoprotein receptor
- Membrane bound
- 5 major domains
- Internalises LDL into cell
- Recognises apoE & apo-B100
- Binds:
VLDL, IDL, Chylomicron remnants & LDL
HDL cholesterol?
- HDL has a protective effect for risk of atherosclerosis and CHD
- Epidemiological studies show the lower the HDL level, the higher the risk for atherosclerosis and CHD
- HDL tends to be low when triglycerides are high
- HDL is lowered by smoking, obesity and physical inactivity
- ApoA-I is the major apolipoprotein in HDL and an elevatedapoA-I is linked to reduced CVD risk
Key info on Triglycerides?
1.May be associated with increased risk of CHD event
- Link with increased CHD risk is complex
- May be direct effect of smaller TG-rich lipoproteins and/or
- May be related to: low HDL concentrations, hyperinsulinaemia/insulin resistance, hypertension and abdominal obesity
What are lipoproteins?
- Molecular complexes that consist of lipids and proteins.
- They function as transport vehicles for lipids in blood plasma
- Lipoproteins deliver the lipid components (cholesterol andtriglyceride etc.) to various tissues for use.
Structure of lipoproteins
Phospholipid
triglyceride
free cholesterol9i
Info about Apolipoproteins
- The protein composition differs from one lipoproteinclass to another
- Activate enzymes involved in lipid metabolism (LCAT,LPL)
3.Maintain structural integrity of lipid/protein complex 4. Delivery of lipids to cells via recognition of cell surface receptors
What are the different types Apolipoproteins?
apoA-I- HDL structural protein;
apoA-II-HL activation
apoA-IV - Tg metabolism; LCAT activator; diet response
What are the two thyroid hormones and why are they important?
Thyroxine (T4) and triiodothyronine (T3)
* For normal growth and development and have many effects on metabolic processes
- Effect on metabolism to stimulate the basal metabolic rate
Key information about Thyrotropin-releasing hormone (TRH)?
*3 amino acid peptide hormone
* glu-his-pro
* Reference range 24 – 138 pg/mL
* Half-life 4 – 5 minutes
* Receptors embedded in anterior pituitary cell membranes
* Binding of hormone = activates of G protein-phospholipase C - Ca2+-protein kinase-phosphorylated protein cascade
What is the Mechanism of thyroid hormone action?
- All cells have intracellular receptors for thyroid hormones.
- Thyroid hormones enter cells through membrane carrier proteins ,enter the nucleus, T4 T3, T3 nucleus and binds to the thyroid hormone repressor, conformational change enables transcription.
what is the action of the thyroid hormone?
Regulate maturation and metabolism of all cells in the body
* Foetal and neonatal brain development
* Foetal growth
* Regulation of mitochondrial activity
* Stimulate heart rate and heart contraction
* Stimulate protein synthesis
* Stimulate carbohydrate metabolism
* Bone growth and development Stimulate erythropoiesis
What does Too much thyroid hormone – hyperthyroidism lead to?
*Palpitations
* Weight loss
* Sweating and heat intolerance
* Nervousness
* Fatigue
* Muscle weakness
* Angina and heart failure
What does Too little thyroid hormone – hypothyroidism lead to?
- Tiredness
- Cold intolerance
- Weight gain
- Dryness and coarsening of hair and skin
- Hoarseness
- Slow relaxation of muscles and tendon reflexes
- Constipation
- Anaemia
What are the causes of hyperthyroidism?
*Graves’ disease (toxic diffuse goitre)
* Toxic adenoma (unregulated hormone production by portion of the thyroid glands, single nodule)
* Thyroiditis
* Iodine-induced hyperthyroidism (e.g. with amioderone therapy)
* TSH-induced hyperthyroidism (pituitary adenoma)
* Excessive ingestion of thyroid hormone
Causes of hypothyroidism?
- Surgical removal of thyroid gland
2.Radioactive iodine treatment
3.Iodine organification defect
4.Lymphoma replacing thyroid gland - Drugs e.g. lithium and interferon
Tests for thyroid antibodies
1.Anti-thyroglobulin antibody, anti-thyroid peroxidase antibody, anti-TSH receptor antibody
2. Most Grave’s disease patients have elevated anti-TSH receptorantibody
Key information about Thyroid nodules?
1.One or more lumps in the thyroid gland
2. Detected by palpitation, may be visible on neck
3.Common problem, 8% women, 2% men in the UK
4. 95% of all nodules are benign
5.Patients given small dose of radioactive iodine and then undergo thyroid scan