Cellular Aging

Cellular Aging: cellular dysfunction, tissue atrophy and an increased loss of cells are noted with normal chronological aging. Widely held theories point to aging and longevity as multifaceted events.

Aging theories Wear and tear Autoimmunity Free radical Programmed Somatic mutation Homeostatic Generic related – programmed change  Error theories – environmental or random damage to cells	Programmed Change Theories: Genetic related. Genetic influences that determine physical condition, occurrence of disease, age of death cause of death contributing to longevity. Activation of gene or genes after a number of cell divisions
Cell changes with Aging Dysfuntion, tissue athrophy Telomeres become too short, can no longer divide Older cells have more DNA damage, more free radicals	Error Theories: Environmental or random damage to sells. Aging is caused by random damage to vital cell molecules and the damage eventually accumulates the level sufficient to result in the physiological decline associated with aging. Somatic mutation theory – longevity and function of the cells are determined by the DNA molecule and its specific repair enzymes.

Cellular Death

Necrosis: cell death in an organ or tissue that is still part of a living person.

Liquefactive:	Such as the liquid exudates from the center of an abscess. – some cells catalogic enzymes still there, swollen pussy, draining
Coagulative:	Gray, firm mass– tissue hardens withers grey
Caseous	a form of coagulative necrosis with a “distinctive cheese-like center”. Cheesy material from fat-like infiltrate. Fat found in the breast pancre abd structures, spec cell dissolution caused by lipase
Gangrene:	A considerable amount of tissue death (necrosis).
Dry gangrene:	A form of coagulation necrosis usually from an interference of arterial blood flow.
Wet Gangrene:	Dry can be converted to wet. Wet is an interference of venous return and is a form of liquefactive necrosis. – venous
Gas Gangrene:	Special type of gangrene that results form infection of already devitalized tissues or from Clostridium bacterium. -an aerobic bacteria clostridia perfringens
Apoptosis :	“Cell suicide” eliminating cells that are worn out, in excess, have developed improperly or have genetic damage. – cell suicide

Apoptotic Cell Removal:

Shrinking of the cell à Condensing and fragmenting of chromatin à separation of nuclear fragments and cytoplasmic organelles into apoptotic bodies à engulfment of apoptotic fragments by phagocytic cells.

It is induced by tightly regulated intracellular program in which cells destine-to-die activate enzymes that degrade the cell zone nuclear DNA and cytoplasmic proteins. The cells plasma membrane remains intact but its structure is altered in such a way that the apoptotic cell becomes an avid target for phagocytosis.  The dead cell is rapidly cleared before its contents leaked out, therefore cell death by this pathway does not elicit an inflammatory response. It is a normal process.

 Examples of apoptosis

• Separation of webbed fingers and toes in the embryo
• Development of neural connections
• Removal of cells from intestinal villa
• Removal of senescent blood vessels. 

 

Brain Death General Criteria

Absence of breathing and movement

Absence of cranial nerve reflexes

Iunresponsiveness and unreceptivenes to any level of painful stimuli

Absent cerebral blood flow

Flat EEG - electroencephalogram

Tests must be done with patient at body less than 90 F

No CNS depressants

Free Radicals

Formation of Free Radicals and Effects of Free Radicals on the Cell

Free radicals are highly reactive chemical species are rising from an atom that has a single unpaired electron in the outer orbit. In this state the radical is highly unstable and can enter into reaction with cellular constituencies particularly key molecules in cell membranes and nucleic acids.

Free radical formation is a byproduct of many normal cellular reactions in the body including energy generation, breakdown of lipids and proteins, and inflammatory processes. E.g. free radical generation is the main mechanisms for killing microbes by phagocytic white blood cells

Under normal conditions most cells have chemical mechanisms that protect them from the injurious effect of free radicals.

These mechanisms commonly breakdown when the cell is deprived of oxygen or exposed to certain chemical agents, radiation or other agents

Free radical formation is particularly threatening to tissues in which the blood flow has been interrupted and then restored. During the period of interrupted flow the intracellular mechanisms that control free radicals are inactivated or damaged. That is one of the reasons we have giving warning we should include Vitamin E, A and C in our diet which are scavengers.

Cellular Injury

Cellular Injury

• Cells are complex units and can be injured in many ways. 
•  A person’s state of wellness and disease is reflected in cells. Injury to any of the cells’ components can lead to illness. 
•  The mechanisms responsible for cell injury leading to necrotic cell death are numerous and interrelated.  They are dependent on a delicate balance between intracellular and extracellular events.  Whether the cell is reversible or irreversible is dependent on intensity and duration of the injury and the type of cell involved.

Stresses damage cells by DNA damage, damage to vital cell proteins including enzyme

Lipid peroxidation and injury to cell membranes

Remember TIPD

Toxic injury – endogenous exogenous

Infectious injury – viral bacterial

Physical – thermal - mechanical

Deficit injury –  water oxigen nutrients

Causes: 

Hypoxia:	oxygen deprivation resulting in interruption of oxidative metabolism and generation of ATP.
Physical Agents:	responsible for cell and tissue injury from mechanical forces, extremes of temperature and electrical injuries. cellular membrance are injured by direct contact with cellular and chemical components of immune and inflammatory responces, temp extreme, electrical ionizing rad, illumination of florescent lighting, mechanical injury and noise, AC more dangerous violent muscle contrations
Chemical Agents and Drugs:	Multiple chemical agents are found in the environment. Drugs such as ethylene alcohol (ETOH), prescription or “over the counter” drugs and street drugs can be injurious cells and tissues. – deficit alcohol
Biologic Agents:	Virus’, bacteria and parasites can replicate and continue tissue disruption. – infection,  produce injury by invading and destroying cells producing toxins inducing hypersensitivity
Ionizing Radiation:	Can cause ionization of atoms or molecules in the cell, directly hit target molecules in the cell or aid in the production of free radicals that interact with critical cell function
Nutritional Imbalances:	Excess and deficiencies predispose the cells to injury

Mechanisms: Complex and varied. Most injuries fall under one of three major categories.

Depletion of ATP:	Usually associated with hypoxia and chemical cellular injury.
Free Radical Injury:	Formation: Unstable chemical species with a unpaired electron in the outer orbit. Effects: Wide ranging effects including lipid perioxidation, oxidative modification of proteins, and DNA effects. Defenses against Free Radicals: Under normal circumstances cells have chemical mechanisms that protect against the effects of free radicals. Free radical scavengers include Vitamins E, A and C.
Impaired calcium homeostasis:	ischemia and certain toxins disrupt the normally low intracellular calcium levels predisposing damaging effects on the cell.

Somatic Death

Algor mortis	cooling of the body
Livor mortis (Lividity)	gravitational pooling of blood
Rigor mortis	stiffening of the body

 

 Illustration of Livor mortis

 

 

 

Cellular Adaptation

Cell membrane- controls the space they enclose, help with cellular mobility and maintain the cell’s shape. The cell membrane is the gateway into and out of the cell. Only certain sub stances are allowed to pass in or out through the membrane.  Cell membranes are made up of phospholipids and proteins.

Cells adapt to their environment to protect themselves from injury.  Cellular adaptations are common and central parts of many disease states

 

Cellular Adaptation

Atrophy:	a decrease in cell size or number, with a corresponding decrease in number and size of cellular constituents. caused by denervation, paralysied, decreased sized decreased organelles
Hypertrophy:	an increase in cell size and tissue mass, as opposed to cell number.   workout just bigger cell no new cell
Hyperplasia:	an increase in cell number, as opposed to cell size. Doesnt improve function Compensatory - allows some organs to regenerate– breast feeding Hormonal - allows some tissues (usually reproductive) to enlarge– uterus grows Pathologic - abnormal proliferation– abnormal proliferation Physiologic - can occur as a result of compensation, hormonal stimulation or increased functional demand Non-Physiologic - usually due to hormonal stimulation or effects of growth factors on target tissues.
Dysplasia or Atypical Hyperplasia	abnormal changes in cell size, shape and appearance. Minor dysplasia is associated with chronic irritation/inflammation. Dysplastic cells may be found adjacent to neoplastic (cancer) cells. As an adaptive process, dysplasia does not necessarily lead to cancer. all kind of abnormal forms not normal cells
Metaplasia	conversion of one cell type to another usually caused by chronic   inflammation/irritation and can be reversed if the irritant is removed. Continued exposure to the irritant may predispose to cellular neoplastic transformation reversable if removed, callus allowes the good ones to survive, caused by chronic infections
Neoplasia	growth of a neoplasm is uncoordinated and autonomous lacking regulatory controls governing cellular growth and division. – cancer growth, uncoordinated cellular growth