Al-Esra’a University College of Pharmacy Pathophysiology Lecture 3 PDF

Al-Esra’a University College of Pharmacy 3rd Grade 2024-2025 PATHOPH YSI O L O G Y Lecture 3 Disorders O f The Cardiovascular System Dr.Mohammed Hassan Kadhum BSc.Ph/PGY1/F.I.B.M.S/CP  C...

Al-Esra’a University College of Pharmacy 3rd Grade 2024-2025 PATHOPH YSI O L O G Y Lecture 3 Disorders O f The Cardiovascular System Dr.Mohammed Hassan Kadhum BSc.Ph/PGY1/F.I.B.M.S/CP  Content of this lecture - Thrombus and embolus - Ischemia and infarction - Hyperemia and edema - Aneurysm and varicose veins - Heart failure - Hypertension and its type - Shock and its type A thrombus is a blood clot that forms in a vein. An embolus is anything that moves through the blood vessels until it reaches a vessel that is too small to let it pass. When this happens, the blood flow is stopped by the embolus. An embolus is often a small piece of a blood clot. It may also be fat, air, amniotic fluid, or a foreign substance such as talc, iodine, cotton, or a tiny piece of catheter tube. Drugs causes VTE ;estrogen , oral contraceptive , cisplatin. VTE risk factors A genetic predisposition to VTE or a family history of VTE (especially in a first- degree relative like a parent or sibling) Obesity. Immobilization, such as bed rest and long-distance travel. Cancer Diabetes mellitus Ischemia is a restriction in blood supply to tissues, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue. It also means local anemia in a given part of a body sometimes resulting from constriction (such as vasoconstriction, thrombosis or embolism). Ischemia comprises not only insufficiency of oxygen, but also reduced availability of nutrients and inadequate removal of metabolic wastes. Ischemia can be partial (poor perfusion) or total. The blood vessel supplying the affected area of tissue may be blocked due to an obstruction in the vessel (e.g., an arterial embolus, thrombus, or atherosclerotic plaque), compressed by something outside of the vessel causing it to narrow (e.g., tumor, volvulus, or hernia), ruptured by trauma causing a loss of blood pressure downstream of the rupture, or vasoconstricted, which is the narrowing of the blood vessel by contraction of the muscle wall rather than an external force (e.g., cocaine vasoconstriction leading to myocardial infarction). Infarction is tissue death (necrosis) due to inadequate blood supply to the affected area. It may be caused by artery blockages, rupture, mechanical compression, or vasoconstriction. Classification I infarctions are divided into two types according to the amount of blood present: 1 White infarctions (anemic infarcts) Usually results when there is arterial occlusion and stoppage of blood flow to an area of tissue ,most often seen in solid organ like liver , kidney ,spleen.also seen in organ with end arterial circulation 2 Red infarctions (hemorrhagic infarcts) Occurs when there is venous occlusion , blockage of outflow of venous blood ,blood congestion so its appear red , seen in testicular occlusion.occurs specially in areas with dual blood supply , eg brain ,intestine ,lung. Red infarction White infarction is wedge shaped By location : Heart: Myocardial infarction (MI), commonly known as a heart attack Brain: Cerebral infarction is the ischemic kind of stroke due to a disturbance in the blood vessels supplying blood to the brain Lung: Pulmonary infarction or lung infarction Spleen: Splenic infarction occurs when the splenic artery or one of its branches are occluded L imb: L imb infarc tion is an infarc tion of an arm or leg. C a uses include arterial embolisms and skeletal muscle infarction Bone: Infarction of bone results in avascular necrosis. Testicle: an infarction of a testicle may be caused by testicular torsion. Eye: an infarction ca n occur to the central retinal artery which supplies the retina causing sudden visual loss. Bowel: Bowel infarction is generally caused by mesenteric ischemia due to blockages in the arteries or veins that supply the bowel Hyperaemia is the increase of blood flow to different tissues in the body. allowing change in blood supply to different tissues through vasodilation. Clinically, hyperaemia in tissues manifest as erythema (redness of the skin) because of the engorgement of vessels with oxygenated blood. Functional hyperaemia Functional hyperaemia, metabolic hyperaemia, arterial hyperaemia or active hyperaemia, is the increased blood flow that occurs when tissue is active. more blood in the digestive system after a meal, more blood in the muscles after exercise, and more blood in the face when a person blushes. Reactive hyperaemia Reactive hyperaemia, a sub-category of arterial hyperaemia, is the transient increase in organ blood flow that occurs following a brief period of ischaemia. Following ischaemia there will be a shortage of oxygen and a build-up of metabolic waste.eg Raynaud's phenomenon. E dema also known as fluid retention, or swelling, is the buildup of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area may feel heavy, a nd affected joints may be hard to move. Other symptoms depend on the underlying cause. Causes may include:  heart failure  kidney problems  low protein levels  liver p roblems  deep vein thrombosis  Infections  Angioedema  cer tain medications  lymphedema  It may also occur due to prolonged sitting or standing and during menstruation or pregnancy. The condition is more concerning if it starts suddenly, or pain or shortness of breath is present. Treatment depends on the underlying cause. Cutaneous edema is referred to as "pitting" when, after pressure is applied to a small area, the indentation persists after the release of the pressure. Peripheral pitting edema, is the more common type, resulting from water retention. It can be caused by systemic diseases, pregnancy in some women, either directly or as a result of heart failure, or local conditions such as varicose veins, thrombophlebitis, insect bites, and dermatitis. Non-pitting edema is observed when the indentation does not persist. It is associated with such conditions as lymphedema, lipedema, and myxedema. A neurysm An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus (starting point) for clot formation (thrombosis) and embolization. As an aneurysm increases in size, the risk of rupture increases, leading to uncontrolled bleeding. Although they may occur in any blood vessel, particularly lethal examples include aneurysms of the Circle of Willis in the brain, aortic aneurysms affecting the thoracic aorta, and abdominal aortic aneurysms.. Classification Aneurysms are classified by type, morphology, or location. True and false aneurysms A true aneurysm is one that involves all three layers of the wall of an artery (intima, media and adventitia). A false aneurysm, or pseudoaneurysm, is a collection of blood that forms between the two outer layers of an artery , the media and adventitia. Morphology Aneurysms can also be classified by their macroscopic shapes and sizes and are described as either saccular or fusiform. Saccular aneurysms, or "berry" aneurysms, are spherical in shape and involve only a portion of the vessel wall; they usually range from 5 to 20 cm (2.0 to 7.9 in) in diameter, and are often filled, either partially or fully, by a thrombus.Saccular aneurysms have a "neck” that connects the aneurysm to its main ("parent") artery, a larger, rounded area, called the dome. Fusiform aneurysms ("spindle-shaped" aneurysms) are variable in both their diameter and length; their diameters can extend up to 20 cm (7.9 in). They often involve large portions of the ascending and transverse aortic arch, the abdominal aorta. L ocation Aneurysms can also be classified by their location: Arterial and venous, with arterial being more common. And their location could be in : -The heart, including coronary artery aneurysms, ventricular aneurysms, and aneurysms following cardiac surgery. -The aorta, namely aortic aneurysms -The brain, including cerebral aneurysms, berry aneurysms - The legs, including the popliteal arteries. - The kidney, including renal artery aneurysm and intraparechymal aneurysms. Pathophysiology Aneurysms form for a variety of interacting reasons. Multiple factors, including factors affecting a blood vessel wall and the blood through the vessel, contribute. The pressure of blood within the expanding aneurysm may also injure the blood vessels supplying the artery itself, further weakening the vessel wall. Without treatment, these aneurysms will ultimately progress and rupture. Infection. A mycotic aneurysm is an aneurysm that results from an infectious process that involves the arterial wall, resulting in the formation of an aneurysm. The most common locations include arteries in the abdomen, thigh, neck, and arm. A mycotic aneurysm can result in sepsis, or life- threatening bleeding if the aneurysm ruptures. Less than 3% of abdominal aortic aneurysms are mycotic aneurysms.Most common pathogen staphylococcus aureus C opper deficiency, A minority o f aneurysms are caused by copper deficiency, which results in a decreased activity of the lysyl oxidase enzym e, af fec ting elastin, a key comp onent in vessel walls. Varicose veins is a medical condition in which superficial veins become enlarged and twisted. Typically they develop in the legs, just under the skin. Usually, varicose veins cause few symptoms, but some individuals may experience fullness or pain in the area. Complications can include bleeding or superficial thrombophlebitis. varices in the scrotum are known as a varicocele while those around the anus are known as hemorrhoids. Due to various physical, social and psychological effects varicose veins can affect quality of life. Varicose veins have no specific cause. Risk factors include obesity, lack of exercise, leg trauma, and family history of the condition. They also develop more commonly during pregnancy. Occasionally they result from chronic venous insufficiency. Underlying causes include weak or damaged valves in the veins. Diagnosis is typically by examination and may include ultrasound. Epidemiology This condition is most common after age 50. It is more prevalent in females. There is a hereditary role. It has been seen in smokers, those who have chronic constipation, and in people with occupations which necessitate long periods of standing such as lecturers, nurses, conductors (musical and bus), stage actors, the Queen's guard, lectern orators, security guards, traffic police officers, surgeons.  Heart failure it describes the clinical syndrome that develops when the heart cannot maintain adequate output, or can do so only at the expense of elevated ventricular filling pressure. In mild to moderate forms of heart failure, symptoms occur only when the metabolic demand increases during exercise or some other form of stress. In severe heart failure, symptoms may be present at rest. In clinical practice, heart failure may be diagnosed when a patient with significant heart disease develops the signs or symptoms of a low cardiac output, pulmonary congestion or systemic venous congestion at rest or on exercise. Three types of heart failure are recognised. 1 left sided heart failure 2 right sided heart failure 3 Biventricular heart failure Pathogenesis Heart failure occurs when cardiac output fails to meet the demands of the circulation. Cardiac output is determined by preload (the volume and pressure of blood in the ventricles at the end of diastole), afterload (the volume and pressure of blood in the ventricles during systole) and myocardial contractility. Causes of heart failure : - Common causes of heart failure include coronary artery disease, including a previous myocardial infarction (heart attack), high blood pressure, atrial fibrillation, valvular heart disease, excess alcohol use, infection, and cardiomyopathy of an unknown cause.  Hypertension Blood pressure is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. Blood pressure is taken using two measurements : - Systolic ( measured when the heart beats, when blood pressure is at its highest). - Diastolic ( measured between heart beats , when blood pressure is at its lowest). Blood pressure that is too low is called hypotension, pressure that is consistently too high is called hypertension, and normal pressure is called normotension. Pathogenesis Five factors influence blood pressure: Cardiac output. Peripheral vascular resistance. Volume of circulating blood. Viscosity of blood. Elasticity of vessels walls 1Essential hypertension: (Primary) 95% of cases, no specific underlying cause of hypertension can be found. Hypertension is more common in some ethnic groups, particularly African Americans and Japanese, and approximately 40–60% is explained by genetic factors. 2 Secondary hypertension : (5%) of cases , causes : Cushing syndrome ,, hyperaldosternoism , pheochromocyroma , stenosis of renal artery 3- Refractory hypertension Refractory hypertension refers to the situation where multiple drug Treatments do not give adequate control of BP. Although this may Be due to genuine resistance to therapy in some cases, a more Common cause of treatment failure is non-adherence to drug Therapy. can also be caused by failure To recognize an underlying cause, such as renal artery stenosis Or phaeochromocytoma. 4- Accelerated hypertension Accelerated or malignant hypertension is a rare condition that can complicate hypertension of any aetiology. It is characterised by accelerated microvascular damage with necrosis in the walls of small arteries and arterioles (fibrinoid necrosis) and by intravascular thrombosis. The diagnosis is based on evidence of high BP and rapidly progressive end-organ damage, such as retinopathy , renal dysfunction (especially proteinuria) and/or hypertensive encephalopathy. Left ventricular failure may occur and, if this is untreated, death occurs within months. The British Hypertensive society classify blood pressure and hypertension as follow :( Similar thresholds have been published by the European Society o f Hypertension and the WHO–International Society o f Hypertension) :  Shock I is defined as a state of cellular and tissue hypoxia, where oxygen delivery is decreased relative to oxygen consumption.it is most commonly occurs from inadequate tissue perfusion due to low or unevenly distributed blood flow. Classification of shock : 1 Hypovolemic shock : - decreased in circulating blood volume - example : (hemorrhage , severe dehydration) - pathophysiology : Decreased circulating blood volume  decreased preload decreased stroke volume  decreased cardiac output  decreased DO 2 2 Obstructive Shock : - physical impediment of blood flow in large vessels - example : cardiac tamponade ,pulmonary embolism - pathophysiology : Physical blockage  blood tapped distal to obstruction  decrease preload  decrease stroke volume  decreased cardiac output  decreased DO 2 3 distributive shock : - inappropriate changes in vascular resistance - examples : septic shock , anaphylactic shock - vasodilation maldistribution of blood volume decreased preload  decreased stroke volume  decreased cardiac output  decreased DO 2 Multifactorial , distributive shock may also cause : Increased vascular permeability  fluid leaks from vasculature  hypovolemia Release of cytokine mediators  decreased contractility  decreased cardiac output decreased DO 2 A c tivation of the coagulation system  clot formation  vessel occlusion  decreased preload  decreased cardiac output  decreased DO 2 4- Cardiogenic shock : - decrease in forward flow from the heart - example : cardiomyopathy , arrhythmias - pathophysiology : lack of contractility  decreased cardiac output decreased DO 2 May be complicated by : increased afterload  decreased cardiac output  decreased DO 2 5- Hypoxemia : - decreased in O2 content in arterial blood - anemia , C O poisoning 6- Metabolic : - deranged cellular metabolism - ex : hypoglycemia The EN D