GERIATRICS - unideb.hu · As a function of age our nervous system gets old as well. This normal...

IMRE SEMSEI PhD

Faculty of Health

University of Debrecen

Hungary

GERIATRICS Alterations with age, diseases, handling II

Nervous system, cardio-vascular system, immune system

Alterations with age, diseases, handling

A little genesis

200 millions: mammals

300 millions: amphibians

500 millions: plants, fungi

530 millions: cambrium blast

1 milliard: multicellular organisms

3-4 milliards: prokaryotes


A little evolution


A little biology


Nervous system; cardiovascular system, immune system

Alterations

of the

nervous

system with

age and

diseases of

old age

Alterations of the nervous system

with age and diseases of old age

As a function of age our nervous system gets old as well. This normal process can be accompanied by neurological diseases such as Alzheimer’s disease, Parkinson disease or strokes of vascular origin (brain infarct, „apoplexy”).

1. Physiological aging of the nervous system

• 1. 1. Macroscopic structural changes of the brain The weight of the brain decreases by 2 - 3% in every ten

years above 50 years of age.

• 1. 2. Microscopic structural changes of the brain Even at healthy aging the number of neurocortical nerve

cells decreases by 10 % by the age of 90. In contrast to that in the hippocampus there is only a

very little or no changes in the number of neurons. The volume decrease originates from the decrease of the number of synapses.

1. 3. Neurological symptoms accompanying aging

Changes of cognitive functions

Primitive reflexes

Disturbances of vision and eye movement

„Aging” of the moving system

Alterations of the perceptions

Changes of deep reflexes

Alterations of walking and balance

1. Physiological changes of the nervous

system



• 2. 1. Alzheimer’s disease

• 2. 2. Parkinson’s disease

• 2. 3. Strokes (bleeding, ischemic)

• 2.4. Epilepsy

• 2. 5. Polineuropathy

• 2. 6. Intracranial tumors

2. Frequent neurological diseases of old age



2. 1. Alzheimer’s disease • Frequency of the disease is 2 – 3 %

below 60 years of age but it is doubled in every 5 years after the age of 65. At the age of 85 the frequency can reach 30 %.

• The disease is characterized by disorientation in space and time and loss of cognitive functions.

• There are characteristic structural changes observed; there are more senile deposition and neurofibrillar bundles than during normal aging.

• Number of neurons could be decreased even by 60 %.



2. Frequent neurological diseases of old age

2. 2. Parkinson’s disease • Only 1 % of the elderly has this disease below 65,

nevertheless, 2.5 % of the elderly suffers from the diseases above 80 years of age.

• Symptoms of the disease originate from the parish of nigrostriatal dopaminerg lines.

• Symptoms: hypo- or akinesis, which is accompanied by spontaneous or active slowing

down of moving, mimicry-arm face, lack of the coordination of the two arms or legs, small steps at walking, hard movements at start and turn or stop of walking, instability of poise (body)

Rigor i.e. resistance of muscle against passive movement Resting tremor i.e. rhythmic quick movements of agonist and antagonist

muscles (tremble) that ceases during active movements (characteristic rolling movements of fingers)

Still, monotone speaking micrography (writing with small letters) Among the vegetative symptoms the plentiful secretion of saliva is common

(hypersalivatio) and the face is shining (seborrhoea). The orthostatic hypotonia is also common(fall of blood pressure at sitting up and standing up)

Neuropsychiatric disturbances: demencia, hallucination, distraction and disturbance of sleep could also develop.



2. 3. Stroke • There are two types of the stroke: the bleeding type consists of 10 - 20

% while the ischemic type is 80 – 90 % of the strokes . Main symptoms are: paralysis of the half of the body (full paralysis: plegia; partial paralysis: paresis) and disturbance of the senses.

• Classical risk factors of the blood vessel sclerosis are: smoking, overweight, hyperlipidaemia, hypertension and diabetes.

• 1. Bleeding type It usually originates from hypertension, which harms

the wall of the blood vessels in a long time.

• 2. Ischemic type Blood supply is suddenly worsening after the

obstruction if a blood coagulant joins the deposition at the blood wall and blocks the blood stream by blocking the lumen. Symptoms depend on which parts of the brain is blocked by the pinched or blocked blood vessels.



2. 4. Epilepsy • Frequency of epilepsy increases with age as well. The focal (it

originates from a well defined part of the brain) and the secondarily generalizing (generalizing after a focal beginning) epilepsy is characteristic of old age.

• The most dominating cause of the epilepsy is the disturbance of the circulation of brain.

2. 5. Polineuropathy • Function of the peripheral sensing and moving system

gradually decreases as a function of age. • As disturbance of the deep sensing is frequent with age

(sensing of vibration and location of joints is disturbed) the pathological nerve damage could be deduced from the decrease of sensing of heat and pain.

2. 6. Intracranial tumor • Incidences of all the tumors (new cases) increases with age. • Fortunately the benignant tumors are more frequent

(meningeoms, hipophysis adenomes, acoustic neurinoms). If these can be eliminated the chances to survive are good.



Alterations of

cardio-vascular

system with

age, and

diseases

Blood vessels • Wall of the blood vessels thickens with age the lumen

becomes wider and more rigid. The tissues are altered as well.

Heart • The resistance of circulation increases with age

therefore the after-load effect on the heart increases and the systolic blood pressure increases as well.

• The heart rate is slower in old age. • In case of physical load the maximal heart frequency

decreases meanwhile the maximal volume/minute does not alter (because of the Frank-Starling compensation).

• Even the old but healthy heart is capable of compensation in many respects.

• The number of working muscle cells and other nerve cells decreases even physiologically with age.

• These alteration could cause both brady- and tachyarrhythmias.

Alterations of cardio-vascular

system with age, and diseases

The common governing pathological process, which causes cardio-vascular diseases is the atherosclerosis.

The physiological changes could be accompanied by harms caused by genetic determination, environmental or life style-governed processes, infection and oxidative stress.

The results is: impairment of the endothelium and small damages of the local humoral defense systems. Plasma proteins and macrophages can enter the sub-endothelial space causing a sequence of inflammation.

A sub-endothelial formation a so called pluck is formed from cell debris, cartilage matrix and free cholesterol

Risk factors are: dyslipidemia, diabetes, overweight, smoking, etc.



Atherosclerosis in old age and patomechanisms of diseases



Hypertension in old age • Frequency of high blood pressure elevates with

increasing age.

• In the elderly population of the EU 60-75% of the people have a 140/90 Hgmm blood pressure or even higher and about 50% of the elderly has a 160/95 Hgmm blood pressure or even higher!

Peripheral arterial disease (PAD) in old age • This is a very frequent disease of the elderly. Insufficient

supply of the peripheries with blood is caused primarily by the atherosclerosis of the middle sized blood vessels. The small sized blood vessels would try to compensate this effect, however, it is hampered by the arteriosclerosis of these small vessels too.



Acute stroke • Status before stroke: TIA (transitory ischemic attack)

Basic strategy of handling the acut stroke: Speed up the process of

reaching the hospital Support of the most important life parameters (optimal position of the head, free air ways, support of vein, infusion) Determination of the type of stroke (CT examination: ischemic<vs>bleeding type) Thrombolysis (in 3 hrs, if the institute is prepared for that) Early rehabilitation Secondary prevention (35% probability of preventing a new stroke)

Most frequent clinical pictures of the stimulus production or stimulus conduction of the heart: high frequency of arrhythmias, auricular fibrillation (AF)

Insufficiencies of heart • One third of the population of 80 years of age suffers from this

disease. • The death risk of people suffering from this diseases is 4–8 higher

comparing to the healthy old ones.



Angina – Myocardial infarct • It is heart disease of coronary artery origin the

base of this ischemic heart disease lies is the atherosclerosis of the coronary artery.

• The stricture formed this way or an even more dangerous way i.e. distal acute strictures caused by emboli of plakks origin results in the temporal (angina) or final (heart infarct) insufficiency of the blood supply of the given part of heart. This situation is even hampered by the elevation of the tone of coronary artery.



Aging of

immune

system and

its

disorders

The cardio-vascular and the

immune systems

Types of the immune system:

existing at birth or acquired immunity.

Parts of the immunity existing at

birth are the cellular (macrophages,

polimorphonuclear cells (PMN), natural

killer cells (NK) and dendrite cells (DC),

etc.) and the non cellular part (C

reactive protein (CRP), complement

system, mannose-binding protein etc.).

Acquired immunity is characterized

by an ability of specific response to the

antigen, i.e. cellular (cytotoxic) and/or

humoral (antibody) response, memory -

which provides a quick response by the

repeated antigen stimuly - T-cell

dependent cell mediated and humoral

immune response.

Aging of immune system and

its disorders

Aging is accompanied by the

changes of the immune system. The

most important alteration happens in

the functioning of T-cells.

Antigen and non antigen specific

functions of monocytes decrease.

Antigen production of the B cells

caused by infection or vaccination

decreases but that of the number

and quantity increases with age.


its disorders

T-cells

B-cells

NK-cells

Phagocytes

Alterations with age

oActivation signals

oAlteration of life time of cells

o Clinical importance of

immune response


its disorders

T-cells • Number of circulating lymphocytes slightly decreases with age. • Beside the decrease of naive T cells (CD45RA+) the number of

both CD4+ and CD8+ memory T cells (CD45RO+) increases. • During aging the Th1 dominant (IL-2, IFN) cytokine

production changes to a Th2 (IL-4, IL-5, IL-10) dominancy. (Immune response of TH1 type is protective against the most important infectious agents the TH2 type response is connected to allergic and parasite infections.)

• Activity of cytotoxic T lymphocytes decreases with age.

B-cells • Production of antibody decreases after infection or vaccination;

the ration of classes or subclasses of immunoglobulins alters; the amount of circulating IgG and IgA increases but the affinity of antibodies decreases; deregulation of the network of anti-idiotype can be noticed and the number and titer of antibodies elevates.

• Neutralization capacity of antibodies is not so effective as it was before.


its disorders

NK cells • The ratio of NK cells increases according to the

results of investigation of CD16/CD56 markers in old age.

• Decrease in activity of NK cells can be assumed.

Phagocytes • Absolute number of neutrophyl granulocytes,

monocytes, macrophages does not remain constant during life at all.

• Fungicide capability decreases. • Number of dendritic cells (DC, the most

effective APCs) is higher.


its disorders

Activation signals • There is no significant change in complex number and activity of TCR-

CD3 receptors in old age. • Functions coupled to cytoskeleton decreases. • There is a decrease in cytoplasm Ca2+ concentration and activity both

in T and B cells with age. • The amount of transcription factors (AP-1, NF-AT, és NF) in cell

nucleus also decreases. Expression of all the genes that are connected to these factors decreases too.

Alteration of cell life time • The increase of numbers of aged, dysfunctional and auto reactive cells

is due to the decreased age-dependent expression of CD95. • Elevation of apoptosis can be assumed in old age.

Clinical importance of the immune response in old age • There is a substantial heterogeneity in immune reactivity in the old

population. • The details of the reasons of this heterogeneity is unknown yet. • Morbidity and mortality caused by malignancies and infections can be

increased by immune-scenescens and other physiological alterations in old age.


its disorders

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