Thomas smith AAA Flashcards
Alpha 1 agonist (sympathomimetic)
Examples
MOA
effect on blood vessels
Example:
Desglymidodrine
Pseudoephedrine
Phenylephrine
MOA:
* post synaptic action
* activates phospholipase C -> increases inositol pathway -> increases diacylglycerol -> increases intracellular calcium
Effect:
*Vasoconstriction/ increases BP.
Alpha 2 agonist (sympathomimetic)
Examples
MOA
Effect of BP
Examples
*Clonidine
MOA
*pre-synaptic action- acts in CVS centre of CNS
*inhibits adenylyl cyclase
*reduces cAMP formation
*reduces activation of calcium channels
*increases potassium efflux
*causes hyperpolarisation and so norepinephrine cant be released
Effect:
*causes vasodilation by preventing catecholamines vasoconstrictive effect - drops BP
Beta 1 agonist (sympatomimetic)
Examples
MOA
Effect
Example:
*Dobutamine
MOA:
*Post synaptic action
*Gs GPCR
*activates adenylyl cyclase
*increases cAMP
*activation of L-type calcium channels via phosphorylation
*increased calcium = increased contractile force
*increases opening of HCN channels in SA node = increased HR
Effect
*Increased rate + contractility of heart.
*no major effect on blood vessels.
Beta 2 agonists (sympathomimetic)
Example
MOA
effect
Example
*Salbutamol
MOA
*post-synaptic
*Gs GPCR
*increases cAMP
*activates PKA
*reduces intracellular calcium influx
*inhibits phosphorylation of myosin light chain kinase.
*prevents constriction
Effects:
Bronchodilation.
Alpha blockers (antagonists)
Sympatolytics
MOA
Example
Effect
Example
Doxazosin
MOA Inhibits phospholipase C
Inhibits inositol triphosphate
Inhibits diacylglycerol
Reduces intracellular calcium
Causes vasodilation
Anti-hypertensive drug
Beta blockers/ antagonists
Propanolol- equal affinity for B1+2
Atenolol - selective to B1
Labetalol - antagonises alpha also
-blocks epinephrine/norepinephrine from binding to cardiac myocytes, SA + AV nodal cells.
- lowers intracellular calcium concentration
Effect: reduces HR and contractility
used for:
-arrythmias
- MI
- hypertension
-congestive heart failure
Define shock and give 4 types.
Shock is the body’s response to systemic hypoperfusion of tissues caused by failure of the cardiovascular system, resulting in impaired tissue perfusion and cellular hypoxia
Hypovolemic
Cardiogenic
Obstructive
Distributive
Causes of hypovolemic shock
(i) Excessive sweating, vomitting, diarrhea
(ii) Hemmorhage (internal/external)
(iii) uncontrolled diabetes mellitus resulting in polyuria
(iv) third space causes e.g. ascites
REDUCED PRELOAD
Causes of cardiogenic shock
(i) MI
(ii) valve dysfunction
(iii) excessive afterload
(iv) cardiomyopathiese.g. Lt ventricle hypertrophy.
REDUCED CO
Causes of obstructive shock
(i) cardiac tamponade
(ii) constrictive pericarditis
(iii) aortic stenosis
(iv) pulmonary embolism
(v) Tension pneumothorax
Distributive/ vascular shock causes
(i) anaphylaxis: histamine induced vasodilation
(ii) Septic shock
(iii) Neurogenic- trauma to head causes damage to CVS centre of medulla
Coarctation of the aorta most commonly occurs at what part of aorta?
List 5 complications of coarctation
Distal ligamentum arteriosum- distal to the left subclavian artery branch point.
Left ventricular hypertrophy
Cardiomegaly
Congestive heart failure
Aortic dissection
Systemic hypotension
Describe the histology of large arteries
Large arteries include Aorta, subclavian, common carotids, iliac arteries.
3 layers:
(i) Tunica Intima
-Endothelial cells (simple squamous epithelium) with tight junctions.
-Sub-endothelial layer
-internal elastic lamina (separates intima from media)
(ii) Tunica media
-Thickest layer in large arteries.
-Smooth muscle cells.
-These SMCs produce collagen, proteoglycans and elastin forming lamellae sheets.
- External elastic lamina
(iii) Tunica Adventitia
-connective tissue
-Fibroblasts
-Macrophages
-Collagen fibres
-Vasa Vasorum
list 5 functions of endothelium
- Exchanging of nutrients between blood and surrounding tissue.
- Converts angiotensin I -> II in order to cause vasoconstriction to raise BP
- Nitric oxide synthesis
- Lipolysis - fat break down to prevent accumulation in intima
- Conversion of inflammatory, clotting and vasoconstriction mediators to an inert form to dampen their effects i.e. bradykinin, serotonin, thrombin
In capillaries, what is the only layer to form their walls? List 3 types of capillaries.
They are surrounded by pericytes, list 3 functions of pericytes. What is their origin?
Tunica intima is the only layer present; Its walls are made of the following
-Endothelium
-Basal lamina
-Pericytes
3 types of capillaries
(i) Continuous - continous endothelial layer and basement membrane BBB, lungs, lung, exocrine glands
(ii)Fenestrated - endothelial layer fenestrated but basement membrane is continuous Intestine, endocrine glands, Glomeruli
(iii)Sinusoids/Discontinuous - both endothelial layer and basement membrane fenestrated. Liver, bone marrow, spleen
3 Functions of pericytes
-Regulate blood flow through contraction
-Help mediate vessel permeability as acting as a barrier to influx/efflux of molecules.
-Can contribute to vessel repair by differentiating into endothelial or SMC’s
They are undifferentiated mesenchymal cells.
What layer of vein wall is the largest? How can you differentiate them from arteries?
Tunica adventita
-Their walls are not well defined
-Thinner walls
-There is no internal or external elastic layer
surrounding muscle layer
-They contain valves
Outline the 3 stages of shock
- Non-progressive
- normal body compensatory mechanisms allow for full recovery - Progressive
-Requires intervention to prevent death. - Irreversible
-Loss of ATP -> death
Outline 5 effects of shock on the cellular level
- Reduction in active transport of sodium + potassium
- results in accumulation of sodium + chloride in cell, potassium is lost to the ECF -> cells swell - Reduction in mitochondrial activity
-impaired liver function
-loss of detoxification mechanisms - release of hydrolases from lysosomes -> damages cell
- increased production of lactic acid from anaerobic glycolysis
- Depletion of ATP -> excess adenosine diffuses into blood forming uric acid
outline 4 complications of massive blood transfusion
- Hypocalcaemia
- Citrate within the blood product can bind the calcium thereby reducing the concentration of ionized calcium. - Coagulopathy
-Dilution of platelets and clotting factors, hypothermia and platelet dysfunction. - Hypothermia
-rapid infusion of cold products - can lead to coagulopathy - Hyperkalemia
-Lysis of RBC’s while in storage -> increased extracellular potassium.
How does hypothermia cause coagulopathy?
- Reduces the release of Thromboxane A2
- leads to reduction in platelet stimulation and aggregation and so affects platelet plug formation.
*Can affect the normal function of essential clotting enzymes.
Why are infra-renal AA’s more common than supra-renal?
Poorer vascularisation via vasa vasorum in infra-renal aorta making it more prone to ischemic damage. Relies more so on direct diffusion of nutrients from blood passing through its lumen.
The infra-renal aorta also has less lamellar sheets making it less elastic so less able to distribute stress.
Define an abdominal aortic aneurysm
AAA is a localised dilation of the aorta which is > 50% larger than the normal diameter ( >3cm diameter).
5 risk factors for AAA
- Atherosclerosis
- Smoking
- Diabetes
- Hypertension
- Age > 65
How does smoking contribute to AAA
- Endothelial damage, chronic inflammation and expression of cytokines, chemokines + leukocyte (mostly macrophage) infiltration.
- Degrades elastin + collagen through oxidative stress (mainly via superoxide dismutase)
- Increases activity of metalloproteinases -> elastin + collagen break down.
- Can cause increased LDL’s and reduced HDL’s -> atherosclerosis
