1. Cardiovascular System
Gilead -Topics in Human Pathophysiology Fall Drug Safety and Public Health
Todays topic is the cardiovascular system. We’ll start by reviewing what we learned about blood.

3. Blood Consists of: Plasma Erythrocytes Leukocytes
platelets– thrombocytes
Vitamin K is required, as is Calcium. Vitamin K is made by bacteria in the gut, and is absorbed as a fat soluble vitamin with other digested fats. Damage to the liver may cause decreased bile production, thus interfering with Vit. K absorption. Vit K is also required for bone deposition and anticoagulation.
The liver also makes many of the clotting proteins, so liver disease can directly inhibit clotting, causing excessive bleeding and anemia.
Thrombocytopenia is the name for a low platelet count.
Also important are those drugs that prevent clotting, the anticoagulants. Much of the risk in CVD is that clots may form at narrowed lesions in blood vessels – “thrombus”, or a clot that forms elsewhere and travels to location where it gets stuck “embolism”

4. Figure 7.8
Thrombocytes and clotting :
Vitamin K is required, as is Calcium. Vitamin K is made by bacteria in the gut, and is absorbed as a fat soluble vitamin with other digested fats. Damage to the liver may cause decreased bile production, thus interfering with Vit. K absorption. Vit K is also required for bone deposition and anticoagulation.
The liver also makes many of the clotting proteins, so liver disease can directly inhibit clotting, causing excessive bleeding and anemia.
Thrombocytopenia is the name for a low platelet count.

5. Blood Production and Disorders
Overview of blood production
Disorders of erythrocytes
Disorders of platelets
Disorders of leukocytes

6. Blood Cell Production Occurs in bone marrow
Also called hemopoiesis (hematopoiesis)
Stem cells are rapidly dividing
Requires iron, Vitamin B12 (and other B vitamins), other trace minerals, vitamins
Controlled by chemical messengers
Has 5 lines of production
Lack of oxygen carrying capacity is called anemia

7. Blood Cell Formation Slide 13 Stem cells are located in red
bone marrow
Stem cells multiply and
become specialized
Mature blood cells
Erythrocyte
(red blood cell)
Erythroblast
Nucleus
lost
Neutrophil
Granular
leukocytes
Eosinophil
Myeloblast
White
blood
cells
Basophil
Stem cell
Monoblast
Monocyte
Agranular
leukocytes
Lymphocyte
Lymphoblast
Megakaryoblast
Megakaryocyte
Platelets

8. Blood Disorders Anemias Thrombocytopenia Leukocytopenia, leukocytosis
Clotting factor disorders
Lipid disorders
Lack of oxygen carrying capacity is called anemia - problem is with RBC and hemoglobin. AIDS is also associated with anemia; CMV – cytomegalo virus is also a cause of anemia, as is hepatitis. The mechanisms are sometimes known, sometimes multifactorial
Lack of platelets or clotting factors causes bleeding disorders
Leukocytopenia – low WBC count, seen in AIDS
Reference Viroj Wiwanitkit Tropical Anemia, Nova Science Publishers, 2007
Clotting factor disorders often caused by liver disease – hepatitis
Lipid disorders like hypercholesteremia can be related to HAART- HIV therapy,and HIV is associated with iron deficiency anemia
Many problems with nutrition or the digestive system can lead to deficits in hematopoiesis

9. Heart and Disease Structure and function Ischemic Heart Disease
Lexiscan, Ranexa
Heart Failure

10. Heart lives in thoracic cavity between the lungs
It is surrounded by a double layered pericardium that protects it and provides lubrication

11. Heart is a double pump R side to lungs(pulmonary circuit), L side to systemic circuit
Atria are filling chambers, ventricles are pumping chambers. Atrioventricular valves keep blood moving into large arteries (aorta and pulmonary trunk) during ventricular contraction (systole). The R AV valve is also “tricuspid”, the L AV valve is “mitral”, or “bicuspid”
Semilunar valves prevent blood in aorta (aortic semilunar) and pulmonary trunk (pulmonic) from falling back into ventricles after contraction (diastole)

12. Figure 8.7b
A closer look showing valves and chambers. Wall of ventricles is thick, the L side more so, for providing pressure on the blood to push it into arteries. Thus creating arterial blood pressure. Muscle is myocardium, specialized to beat in coordinated fashion, autorhythmic

13. Cardiac Cycle
Cardiac cycle 3 minute video

14. Figure 8.14
The conduction system of the heart that stimulates the muscle to contract. The sequence needs to be precise and coordinated. Arrythmias may occur as a result of hypoxia, or disease.
The rate of contraction and strength of contraction is controlled by the NS sympathetic and parasympathetic nerves, as well as other chemical messengers that bind to receptors on heart tissue.

15. Figure 8.15
The ECG is how clinicians monitor the conduction system. Non invasive

16. Figure 8.11
The coronary arteries are what supply the heart with oxygen rich blood. Narrowing of these vessels by spasm or plaque is known as cardiovascular disease, and causes ischemia

17. Ischemic Heart Disease
Coronary artery disease
Myocardial ischemia
Myocardial hypoxia
Myocardial infarct
Myocardial necrosis
Most of the time there are no symptoms before a sudden death event, but some may experience angina, dizziness, shortness of breath, heart palpitations, nausea, feeling of pressure

18. Coronary Angiogram
Narrowed spot in L coronary artery

19. Progression of atherosclerosis
From wikipedia

20. Risk Factors for Cardiovascular Disease
Age
Male sex
Heredity
Smoking
Diabetes mellitus
Hypertension
High cholesterol
Obesity
Lack of exercise

21. Diagnosis and Treatment of Ischemic Heart Disease
BP monitoring
Symptoms
ECG
Angiogram
Stress Test
Nuclear myocardial perfusion tests
Symptoms include angina, dizziness, shortness of breath, heart palpitations, nausea, feeling of pressure

22. Lexiscan For myocardial perfusion imaging (MPI)
A2A adenosine receptor agonist
Vasodilates coronary arteries as if exercising
Injected into blood stream prior to gamma camera scan
Can give a good indication of myocardial perfusion
Used as a testing method if the patient can not do stress test on treamill. Lexiscan is 2nd generation drug, after adenosine itself. It binds specifically to the A2A adenosine receptor. Adenosine is chemical messenger with actions in the brain and heart. Adenosine is given for severe tachycardia emergencies.
“In humans, there are four adenosine receptors. Each is encoded by a separate gene and has different functions, although with some overlapping.[3] For instance, both A1 receptors and A2A play roles in the heart, regulating myocardial oxygen consumption and coronary blood flow, while the A2A receptor also has broader antiinflammatory effects throughout the body.[4] These two receptors also have important roles in the brain,[5] regulating the release of other neurotransmitters such as dopamine and glutamate,[6][7][8] while the A2B and A3 receptors are located mainly peripherally and are involved in processes such as inflammation and immune responses.
Most older compounds acting on adenosine receptors are nonselective, with the endogenous agonist adenosine being used in hospitals as treatment for severe tachycardia (rapid heart beat),[9] and acting directly to slow the heart through action on all four adenosine receptors in heart tissue,[10] as well as producing a sedative effect through action on A1 and A2A receptors in the brain. Xanthine derivatives such as caffeine and theophylline act as non-selective antagonists at A1 and A2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a stimulant effect and rapid heart rate.[11] These compounds also act as phosphodiesterase inhibitors which produces additional antiinflammatory effects, and makes them medically useful for the treatment of conditions such as asthma, but less suitable for use in scientific research.[12]
Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, which is now resulting in a new generation of more selective drugs with many potential medical uses. Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands which are entirely structurally distinct, giving a wide range of possible directions for future research.[13][14]” from wikipedia

23. Diagnosis and Treatment of Ischemic Heart Disease
Coronary bypass surgery
Angioplasty
Stents
Cholesterol lowering agents
Anticoagulents
Antianginal medications

24. Ranexa
For angina
Probably changes ion channels in walls of blood vessels serving the heart
Can be taken with other anti-anginal meds
Very effective
Suggested for pts for whom the other antianginal meds don’t work.

25. Congestive Heart Failure
Heart becomes weak
Blood backs up in veins and capillaries
Fluid excess in tissues
Symptoms include shortness of breath, edema, difficulty breathing (especially when lying down,) difficulty exercising
Causes include hypertension, lung disease, coronary artery disease, previous myocardial infarction, valve disease, cardiomyopathy

26. Congestive Heart Failure

27. Congestive Heart Failure
Patient tissues fill with fluid, treatment is often diuretics to make sure the lungs stay clear of excess fluid. These only treat the edema, not the underlying cause. But also drugs to decrease the workload of the heart (ACE inhibitors, AgII blockers, B blockers, etc.)