Pathophysiology

Challenge 2010
propound

Lecture Notes

Lecture Title : CVS disorders Prof name : Dr.Mostafa Shihebat Done by : Pharmacy students Corrected by : Dentistry students

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CVS disorders

Today's lecture about CVS disorders (Ischemia): -Anatomical and Physiological Introduction:
Heart arteries are mainly 2 arises from the ascending aorta (which is the largest art. In human) and supply the oxygenated blood to the myocardium : 1- Left Coronary art. Divides into : -anterior interventricular branch. -circumflex branch. 2- Right Coronary art. Divides into : - posterior interventricular branch. -marginal branch( left and right). Drainage of veins through the Coronary sinus ( a vascular sinus which's thin-walled that has no smooth muscle ) which enters the blood in the right atrium. ( Note : that these art. or this system of art. referred to as the vascularity of the heart so thats why we explained them to get the idea about how ischemia occurs). Normal coronary blood flow: The resting coronary blood flow= 225 ml/min (relaxed situation e.g sleeping ) In strenuous exercise = increase three to four folds. ( sometimes up to 7 folds)
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Now the question is when perfusion occurs during the systole or the diastole? Systolic pressure created from the contraction of the left ventricle(phase of contraction) . Diastolic pressure created from the recoil of the aorta (phase of relaxtion) . During systole: arteries( the subendocardial arteries) of the heart will be compressed so most of the perfusion of heart occurs during diastole.

As you see in the following diaghram:

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Systole BF is 100 ml/minute. Diastole BF is 300 ml/minute. Which controls the coronary blood flow and all arteries of the body in general ? Need or increased demand in order to increase the blood supply. Otherwise ( if there's imbalance between the supply and the demand) it's going to be assumed a disorder (defect ) which is called Ischemia. -Blood flow is controlled mainly by : Metabolic (activities) regulation : if it increased then bf will increase.( Blood flow through coronary system is regulated almost entirely by local arterial vasodilatation in response to cardiac muscle need for nutrients which leads to increased contraction so Increase in rate of coronary blood flow) .

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Nervous regulation : sympathetic stimulation increase the heart rate and contractility so it will increase the cardiac output which means increased coronary blood flow.

-Now let us start with pathophysiology:

Ischemia : There are two important subjects placed under or related to ischemia generally : -Ischemia. -Necrosis.

Now what do we mean by Ischemia? Lack of oxygen due to inadequate perfusion of the myocardium, which causes imbalance between oxygen supply and demand. Specificly : when there's a constriction , narrowing or subdivision(partial occlusion) in the arteries which supply the heart(coronary arteries ). The other part is necrosis(myocardial infarction ): When there's complete occlusion of the blood vessel ( not partial).
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Then the myocytes beyond the occlusion will die and it might be fatal (this leads to a state of necrosis) . Ischemia equation :

e.g u need 10 liter and blood supply only 8 ltrs ( this leads to ischemia). -causes of myocardial ischemia : The most common cause is Coronary atherosclerosis( which means blockage of arteries ): Thickening or narrowing of the wall of the arteries due to accumulation of fatty material such as cholesterol ( most common in old people ). Epicardial coronary arteries are the major site.
Major risk factors that causes atherosclerosis (precipitating factors) : Increase in LDL( low density lipoprotein) . Decrease in HDL( high density lipoprotein) . Cigarette smoking. Hypertension.
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DM (Diabetes mellitus).
*Additional note : low density lipoprotein means bad cholesterol and HDL means good cholesterol.

all of us know that smoking ,hypertension..etc are common causes , but what the mechanism? Because all these things leads to destruction or injury to the endothelial (has to be smooth) layer of the arteries which leads to aggregation of clotting factors ( platelets) due to the fragility of its surface ( no luminar flow) . This mechanism similar when we got injured or had an external cut this leads to rough (fragile) surface and aggregation of clotting factors.
*remember that blood vessels consists of 3 layers : tunica interna(endothelial) , tunica media ,tunica externa . *there are 2 type of blood flow : luminar flow( steady or smooth state ) and turbulent flow.

Normal function of vascular endothelium : -Local control of vascular tone. -Maintenance of an anticoagulant surface. -Defense against inflammatory cells. Loss of these defenses leads to: -Inappropriate constriction. -Luminal clot formation. -Abnormal interactions with blood monocytes & platelets.
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- Now the occlusion caused either by Thrombosis or Embolism, but what the difference ? The thrombosis is local formed clot , but in the embolism the clot could be transferred to other sites (from artery to another artery) & may follow deep venous thrombosis. The Dr started to talk about angina(to know that it differs from local spasm) it occurs in people who has neither embolism , thrombosis nor any problem but they develop signs and symptoms that resemble the angina ( when they get angry, sad or stressed.) they could feel a pain in their chest ( thorax) this case is due to spasm of the coronary arteries ( angina-like symptoms) that occurred because of the deffientcy of blood perfusion (low or less) due to over sympathetic stimulation . And if the patient brought to ER and had an examination it would be a normal ECG without angina.

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Partial occlusion CVS disorders (ischemia) may develop to complete

Complete occlusion (necrosis) death of the area supplied by the artery

The Location of the obstruction Influence the quantity of myocardial ischemia ,Determines the severity of the clinical manifestations which means that if the occlusion where in major artery then the effect will be major ( the heart will be affected so much , massive destruction of cells leads to massive dead myocytes) but if the artery is small the complication will be less( why? Because there's a less amount of dead cells).

Collateral circulation:

Before that there's a question : if where young man had a myocardial infarction he would die but an old or middle- aged man wouldn't? Due to Collateral circulation that only formed in old people and athletes . Which means that an area(the same one) supplied by many arteries ( network of blood vessels) it is
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not opened in young people (except athletes) but opens when we get older. *in athletes because they have a high demand (cardiomegaly ). If heart rate less than 60 it's a disorder which is called brady cardi but in athletes not ( their heart size is larger = cardiomegady) normal to had HR <60. -Effects of ischemia : Disturbances of myocardial functions: Mechanical function. Biochemical function. Cell membrane function. Electrical function. 1)Mechanical function: -Failure of normal muscle contraction & relaxation. -Ischemia of large portions of ventricle : left ventricular failure. -Regional disturbances: Systolic stretch. 2) Biochemical function:
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-Fatty acid cant be oxidized. -Glucose is broken down to lactate. -Reduced intracellular PH and ATP stores. 3) Cell membrane function: -Leakage of potassium and uptake of sodium by myocytes. 4) Electrical function: -ECG changes: Repolarization abnormalities. Transient ST segment depression. -Electrical instability: Ventricular tachycardia and fibrillation. Later on when we discuss arrythimia we will know that one of its important causes is ischemia and massive myocardial infarction ( it may lead to ventricular fibrillation which is fatal). -angina there are 2 types : -unstable angina : which is misdiagnosed between
unstable angina and acute MI(myocardial infarction
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)both of them are Acute coronary syndrome(symptoms: retrosternal severe chest pain near to the left hand). We can differentiate between them by ecg ,we have to do blood tests, ckmp, troponine (will be +ve for MI patients and ve for unstable angina patients) next lecture we will discuss it in detail .

-stable angina: chronic artery disease,

Characteristics: Heaviness,Pressure, Squeezing, Smothering and Choking pain.

Causes: - CAD ( coronary artery disease). - Aortic valve disease. - Hypertrophic cardiomyopathy.
History: A man > 50 years. A woman > 60 years. Pain with physical & emotional exertion.
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Last to 5-10 min (relieved by vasodilators). But how does the pain occurs or start? Radiating pain to the left shoulder, both arms, back, interscapular region, root of the neck, jaw and teeth but you need to know that any other symptoms that are not related to the heart in diagnosing angina or MI ( e.g abdominal pain) otherwise if you didn't you might kill the patient because you will forget or misdiagnose that he has angina and you will give him another treatment for other disease ( that you thought) .

Both types have the same cause(narrowing and constriction of the coronary artery) but the stable is relieved by Vasodilators(nitro-peceline sublingual, nitrates,-adrenergic blockers,Calcium,antagonist,Antiplatelet drugs.) occurs mainly after doing exercises specially when the demand become more than the supply which leads to a severe chest pain but signs and symptoms will be subsided by Vasodilators .

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But in unstable pain will not be subsided by Vasodilators.

*tread-mill or stress test : to know if that your heart doing well ( 220- the age) e.g ( your age is 20 then 220-20=200 this means that your HR after doing exercise should reach 200 without feeling any chest pain otherwise there would be a disorder .

Why are these patient given analgesics (morphine or opium) or we call them painkillers? Because heart pain is very severe (painful).

THE END

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