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Aging:

Normal And Abnormal


By Dr. Tarek Atia

Definition of Aging:

A decreasing ability to survive"


Aging: Cellular aging, and aging changes in organs and systems.

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.

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

Aging changes in organs and systems

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.

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.

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.

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.

Aging and the Lungs Less elastic and compliant with aging Tend to become expanded secondary to

qualitative changes in elastin and collagen


fibers.

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.

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.

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.

Aging Related Diseases Hemodynamic Disorders

Changes in vascular volume, pressure, or


protein content, or alterations in

endothelial function, will affect the net

movement of water across the vascular


wall.

THROMBOSIS
Three primary factors predispose to thrombus formation, the so-called Virchow triad: (1) Endothelial injury (2) Slowing of blood flow

(3) Blood hypercoagulability

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.

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.

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.

Thrombosis

Fate of the Thrombus.

Propagation.
Fragmentation and embolus formation.

Dissolution.
Organization and recanalization.

Potential outcomes of venous thrombosis.

Lines of Zahn: alternating


layers of platelets and

fibrin.

Embolism

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

Types of embolism

1- PULMONARY THROMBOEMBOLISM

95% of instances,
venous emboli originate from deep

leg vein thrombi

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

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.

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.

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.

Infarction

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.

Infarcts are classified on the basis of their color

(reflecting the amount of hemorrhage) and the


presence or absence of microbial infection

Red

(hemorrhagic)

infarcts
(1) with venous occlusions (such as in ovarian torsion);

(2) in loose tissues (such as


lung) (3) in tissues with dual

circulations (e.g., lung and liver)

White (anemic) infarcts

1. with arterial occlusions


in solid organs with endarterial circulation (such as
heart, spleen,

and

kidney)

2. Solid tissues (muscles).

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

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.

Shock

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.

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.

Type of Shock Cardiogenic -

Clinical Examples
Ventricular rupture Arrhythmia Myocardial infarction

Principal Mechanism
Failure of myocardial pump owing to intrinsic myocardial damage, extrinsic pressure, or obstruction to outflow

Hypovolemic

Hemorrhage Fluid loss, e.g., vomiting, diarrhea, burns, or trauma

Inadequate blood plasma volume

or

Septic

- Overwhelming microbial infections - Endotoxic shock - Gram-positive septicemia - Fungal sepsis

Peripheral vasodilation and pooling of blood; endothelial activation/injury; leukocyte-induced damage; disseminated intravascular coagulation; activation of cytokine cascades

Less commonly:
1.Neurogenic shock
2.Anaphylactic shock

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.

Thank You