Aging:

Normal And AbnormalBy

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.

• Three primary factors predispose to thrombus

formation, the so-called Virchow triad:

(1) Endothelial injury

(2) Slowing of blood flow

(3) Blood hypercoagulability

THROMBOSIS

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 end-

arterial 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 Clinical Examples Principal MechanismCardiogenic - Ventricular rupture 

- Arrhythmia   - Myocardial infarction

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 or plasma volume

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