Aging: Normal And Abnormal

1. Aging: Normal And Abnormal By Dr. Tarek Atia

2. Definition of Aging: �A decreasing ability to survive" Aging: Cellular aging, and aging changes in organs and systems.

3. I. Cellular Aging Aged mitochondria have a decreased ability to survive hypoxic insult. Oxidative phosphorylation decreased progressively. DNA and RNA synthesis of structural and enzymatic proteins decreased progressively. Senescent cells have a decreased capacity for uptake of nutrients and for repair of chromosomal or genetic damage. Cells disclose morphologic features with increasing age.

4. Theories Of Cellular Aging "Wear and Tear" Theories Free radical theory Post-translational modifications (cross-linkage theory) Accumulation of waste products theory Error-catastrophe theory Genome-Based Theories Finite doubling potential of cells somatic mutations programmed aging

5. Aging changes in organs and systems

6. Immunity and Senescence There is a progressive quantitative and qualitative diminution in the capacity to produce antibodies. There is a tendency for aggregates of lymphocytes to appear in the bone marrow and other sites, and an increase in the development of autoimmune reactions and diseases. There is a profound decline in T-lymphocyte function with age.

7. Neuroendocrine and Senescence Age-related development of hypertension possibly related to increased sympathetic system activity. Impaired glucose intolerance. Diminished thyroid function. Decline in gonadal function.

8. The Brain and Senescence Selective loss of isolated neurons No evidence that the function of the brain significantly deteriorates with aging Benign senescent forgetfulness vs. dementia.

9. Aging and the cardiovascular system Diminished heart rate Cardiac output is maintained by adaptive mechanisms such as cardiac dilatation and greater stroke volume Isolated cardiac muscle appears to suffer little age dependent change in function Progressive rise in basal systolic blood pressure, possibly due to a loss of compliance of the aorta and major arteries with age.

10. Aging and the Lungs Less elastic and compliant with aging Tend to become expanded secondary to qualitative changes in elastin and collagen fibers.

11. Aging and Body Composition Loss in muscle and bone mass, accompanied by an increase in fat mass. Elderly who remain physically active have only moderate loss of skeletal muscle, mainly type II "fast twitch" fibers. Ligaments and tendons stiffen. Bone loss occurs in almost all postmenopausal women and elderly men. Magnitude of bone loss is dependent on physical activity, nutrition, and hormonal changes.

12. Aging and other systems Liver mass decreases with age, as does hepatic blood flow. Loss of melanocytes in hair follicles ------ white hair Skin changes: thinning, random decrease in melanocytes, atrophy of subcutaneous fat, and loss of elasticity and wrinkling.

13. Diseases of aging Age dependent disease: direct consequence of physiologic senescence Age related disease: occurs with increasing frequency with age. The three leading causes of death in people 75 to 84 years of age are heart disease, cancer, and cerebrovascular disease.

14. Aging Related DiseasesHemodynamic Disorders

15. Changes in vascular volume, pressure, or protein content, or alterations in endothelial function, will affect the net movement of water across the vascular wall.

16. Three primary factors predispose to thrombus formation, the so-called Virchow triad: Endothelial injury Slowing of blood flow Blood hypercoagulability

18. Virchow triad in thrombosis. Endothelial integrity is the single most important factor. Note that injury to endothelial cells can affect local blood flow and/or coagulability; abnormal blood flow (stasis or turbulence) can, in turn, cause endothelial injury. The elements of the triad may act independently or may combine to cause thrombus formation.

19. Thrombi may develop anywhere in the cardiovascular system, but they are commonly seen in veins. The propagating tail may not be well attached and, particularly in veins, is prone to fragmentation, creating an embolus.

20. Mural thrombi. (A) Thrombus in the left and right ventricular apices, overlying a white fibrous scar. (B) Laminated thrombus in a dilated abdominal aortic aneurysm.

22. Fate of the Thrombus. Propagation. Fragmentation and embolus formation. Dissolution. Organization and recanalization.

23. Potential outcomes of venous thrombosis.

26. Embolism

27. An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin. Emboli lodge in vessels too small to permit further passage, resulting in partial or complete vascular occlusion

28. Types of embolism

29. 1- PULMONARY THROMBOEMBOLISM 95% of instances, venous emboli originate from deep leg vein thrombi

30. 2- SYSTEMIC THROMBOEMBOLISM emboli traveling within the arterial circulation. Most (80%) arise from intra-cardiac mural thrombi. two thirds of which are associated with left ventricular wall infarcts

31. 3- FAT EMBOLISM Microscopic fat globules may be found in the circulation after fractures of long bones (which have fatty marrow) or, rarely, in the setting of soft tissue trauma and burns.

32. 4- AIR EMBOLISM Gas bubbles within the circulation can obstruct vascular flow. enter the circulation during obstetric procedures or as a consequence of chest wall injury.

33. 5- AMNIOTIC FLUID EMBOLISM Characterized by sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures and coma. Underlying cause is the infusion of amniotic fluid or fetal tissue into the maternal circulation via a tear in the placental membranes or rupture of uterine veins.

34. Infarction

35. An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue. Nearly 99% of all infarcts result from thrombotic or embolic events, and almost all result from arterial occlusion.

36. Infarcts are classified on the basis of their color (reflecting the amount of hemorrhage) and the presence or absence of microbial infection

37. Red (hemorrhagic) infarcts with venous occlusions (such as in ovarian torsion); in loose tissues (such as lung) in tissues with dual circulations (e.g., lung and liver)

38. White (anemic) infarcts with arterial occlusions in solid organs with end-arterial circulation (such as heart, spleen, and kidney) Solid tissues (muscles).

39. Examples of infarcts. (A) Hemorrhagic, roughly wedge-shaped pulmonary infarct. (B) Sharply demarcated white infarct in the spleen.

40. Septic infarctions may develop when embolization occurs by fragmentation of a bacterial vegetation from a heart valve or when microbes seed an area of necrotic tissue.

42. Shock

43. Shock, or cardiovascular collapse, is the final common pathway for a number of potentially lethal clinical events, including severe hemorrhage, extensive trauma or burns, large myocardial infarction, massive pulmonary embolism, and microbial sepsis.

44. gives rise to systemic hypoperfusion caused by reduction in: 1.cardiac output 2.the effective circulating blood volume. The end results are hypotension, followed by impaired tissue perfusion and cellular hypoxia.

46. Less commonly: Neurogenic shock Anaphylactic shock

47. Clinical Course The clinical manifestations depend on the precipitating insult. In hypovolemic and cardiogenic shock, the patient presents with hypotension; a weak, rapid pulse; tachypnea; and cool, clammy, cyanotic skin. In septic shock, the skin may initially be warm and flushed because of peripheral vasodilation.

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