Transcript Aging: Normal And Abnormal

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 -
Hypovolemic
Septic
-
Clinical Examples
Principal Mechanism
Ventricular rupture
Arrhythmia
Myocardial infarction
Failure of myocardial
pump owing to intrinsic
myocardial
damage,
extrinsic pressure,
or obstruction to outflow
Hemorrhage
Fluid loss, e.g., vomiting,
diarrhea, burns, or trauma
Inadequate
blood
plasma volume
- Overwhelming microbial
infections
- Endotoxic shock
- Gram-positive septicemia
- Fungal sepsis
or
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