Cell adaptation, injury, pathophysiology, and death

How stress affects normal cell function visual

Glucose vs. insulin release visual

General adaptation syndrome (GAS)

1) Systemic adaptation to exposure to a stressor resulting in physical manifestations that are coordinated and interdependent

2) The three stages include:

• Alarm

• Resistance

• Exhaustion

Disease

1) Any process that causes the inability of an individual to adapt to their environment and maintain homeostasis

• threatens the survival of the organism

• causes impaired bodily function, cellular changes, inflammation, and pain

2) Results in similar cluster of symptoms per disease state

• EX: chicken pox

• EX: asthma

Disease: pathophysiology

The study of disease processes that change the normal structure and function of the human body

• symptoms

• morphological cellular changes

• changes in tissue and organ function

• outcomes

Disease: Etiology

1)The cause of a particular disease

2) includes both intrinsic and extrinsic factors

3) knowing the etiology of a condition can help with:

• disease prevention: (early identification/screening- early treatment and/or cure and design a therapeutic strategy)

• sometimes may be idiopathic (EX: alzheimers disease)

Epidemiology

1) study of disease occurrence in populations

2) Looks for patterns and tries to make predictions

Incidence VS prevalence

1) the # of new cases in a population at risk during a specific time

VS

2) the # of cases of a disease/current population

Morbidity VS mortality

• Effects the disease has on a person’s life

• looks at the persistence of a disease and the long term consequences

VS

• the death-causing ability of a disease

Patient notes must consist of:

• patient demographics

• chief complaint

• history of present illness

• past medical history

• drug allergies

• current medications

• personal and social history

• review of systems (ROS)

Disease categories

Infectious:

• caused by pathogens

Degenerative:

• caused by wear and tear, aging or trauma

Neoplasia:

• Abnormal, uncontrolled growth of tissue

Immune disorders:

• Immune system deficiencies

• allergies

• autoimmune disorders

Metabolic disorders:

• caused by lack of enzymes

• hereditary disorders

Malnutrition

Hormonal disorders

• Imbalance of hormones

Mental and emotional disorders

Cellular adaptations

• Cells can alter their structure and/or biochemical processes in order to achieve a new “steady state”

• Cell injury=disease

Types of cellular adaptation

1) Atrophy

2) Hypertrophy

3) Hyperplasia

4) Metaplasia (may be associated with increased cancer risk)

5) Dysplasia

• Malignancy

6) Anaplasia

• Malignancy

7) Intracellular accumulations

Atrophy

1) Cells decrease in size

2) Tissues “waste away”

3) Causes:

• inactivity

• denervation

• inadequate nutrition

• actions (or lack) of hormones

• aging

• decreased blood flow

4) Cell organelles decrease in size and number

5) cytoskeleton breaks down via the ubiquitin-proteasome system

6) apoptosis may be triggered

EX: muscle atrophy after prolonged immobility

Hypertrophy

1) individual cells increase in size and tissue mass increases

2) Causes:

• increased workload

• excessive hormonal stimulation

EX: body builders

Hyperplasia

1) Increase in cell # only, not an increase in cell size

2) results in an increase in tissue mass

3) causes:

• may be compensatory mechanism for increasing metabolic demands

• excessive hormonal stimulation

Metaplasia

1) one mature cell type is replaced by another mature cell typle

2) Reversible

• EX: ciliated columnar epithelium- replaced by stratified squamous epithelium in the airway

3) Causes:

• chronic inflammatory irritation

• adaptive mechanism to replace a more vulnerable cell type for a stronger cell type- due to abnormal stimulus

Dysplasia

1) cells mature abnormally within a tissue such that cells vary in size, shape, and organization

2) Large nuclei

3) increased rate of mitosis

4) Causes:

• chronic irritation

• pre-cancerous change

Anaplasia

• cells become undifferentiated- immature

• nuclei are variable (large and stain very dark)

• multiple cells undergoing mitosis

• associated with malignancy

Intracellular accumulations

1) build up of substances in:

• the cytoplasm- lysosomes

• the nucleus

2) accumulation may be transient or permanent

3) harmless or toxic

4) substances that accumulate:

• normal substances produced in excess (ex: lipids, proteins, melanin, bilirubin, etc)

• EX: tay-sachs disease

• Abnormal endogenous products resulting from errors in metabolism

• Exogenous substances taken in from the environment

5) Stressed cells may fill up with:

• Unused foods (lipids, glycogen)

• abnormal proteins

• pigments

• calcium salts

Neoplasms

• “new growth”

• causes a lump or tumor

• when a cell ignores the normal controls of cell division (EX: contact inhibition) and multiplies excessively

• can either be benign or maligant

cells under attack: causes of injury and sublethal morphological changes

ells under attack: causes of injury and sublethal morphological changes (cont.)

causes of cell injury

1) physical injury

• mechanical: crushing, cutting, or any disruption of cell integrity

• thermal: burns, freezing, and fevers

2) toxic exposure

3) changes in pH- acidosis and alkalosis

4) bacteria, viruses, and fungal infections

5) injury from nutritional imbalances

• excess

• deficiencies

6) radiation

Sublethal morphological changes

1) Biochemical changes- hard to see or detect

2) morphological changes- can be seen under a microscope

• cellular swelling due to loss of volume control

• 2 types: hydropic changes (or vacuolar changes), fatty changes

3) these changes result in changes in tissue size, weight, and appearance

4) may be reversible or irreversible upon d/c of stimulus

Tissue repair

1) regeneration- replacement of dead or damaged cells by the same type of cell as before

• restores normal function

• skin injuries and liver regenerate

2) fibrosis- replacement of damaged cells with scar tissue

• holds organs together

• does not restore normal function

Cell death visual

2 Mechanisms:

1) Necrosis: associated with a disease process

• injured beyond repair by toxins, infection, hypoxia, or other injury

2) Apoptosis: programmed cell death, not associated with a disease process

• induced to commit suicide

Necrosis

1) cell death in a tissue/organ of a living person

2) unregulated

3) process:

• cells and their organelles swell

• cell then ruptures and contents leak out

• release of intracellular contents into the extracellular space triggers an inflammatory cascade

• see inflammation in the surrounding tissue

4) necrosis interferes with the replacement of cells and healing

Apoptosis

1) controlled self-digestion of cellular components by enzymes

2) does not interfere with cell replacement or tissue regeneration

3) requires ATP

4) process:

• cells shrink

• develop bubbles/blobs on their surface

• have the chromatin (DNA and protein) in their nucleus degraded

• have their mitochondria break down with the release of cytochrome c- triggers caspases

• break into small, membrane wrapped, fragments

• may be triggered by increased intracellular calcium- activates nuclear enzymes- DNA breakdown

• phosphatidylserine, which is normally hidden within the plasma membrane, is exposed on the surface

• this “eat me” signal is bound by receptors on phagocytic cells like macrophages engulf the cell fragments

Apoptosis visual

Why would a cell want to commit suicide?

there are 2 different reasons:

1) programmed cell death is as needed for proper development

• EX: the formation of the fingers and toes of the fetus

• EX: menstration

• EX: the formation of the proper connections (synapses) between neurons in the brain

2) Programmed cell death is needed to destroy cells that represent a threat to the integrity of the organism

Types of necrosis

All necrotic tissue is hypoxic

1) Liquefaction of necrosis:

• cells die, but their lysosomal enzymes are not destroyed

• they are released and liquefy the tissue

2) coagulative necrosis: acidosis develops and cell proteins are denatured and coagulate (or congeal)

• Forms a firm gray mass

3) fat necrosis: fat tissue is broken down into fatty acids

4) caseous necrosis: a form of coagulation necrosis that has a yellow, cheesy look

• infiltration of fat-like subtances

5) infarction: area of cell death caused by a lack of O2

6) gangrene: a considerable area of necrotic tissue is present- due to hypoxia. Three types:

• dry gangrene: tissue is dry and turns dark brown or black. Spreads slowly, mostly affecting extremities. creates a line of demarcation between the dead and healthy tissue. Usually does not involve bacterial invasion

• Wet gangrene: area is cold, swollen, pulseless, and skin is moist. skin appears black, may have blobs. no clear line of demarcation. spreads quickly, and may affect extremities or organs. bacterial infections are almost always present. may have a foul odor.

• Gas gangrene: deadly form of gangrene where necrotic tissue is invaded by anaerobic, spore forming bacteria. most commonly clostridium perfringens. bacteria produce toxins that destroy tissue and form hydrogen sulfide gas as a byproduct. Infection spreads very rapidly and needs to be treated as a medical emergency.

types of necrosis: treatment

• Antibiotics

• debridement of necrotic tissue or amputation

• maggots

Sequelae of necrosis

1) Loss of function

• depending on the size or proportion relative to the organ, loss of organ function

2) infection:

• sepsis if the organism spreads

3) inflammation and fever (local and/or systemic)

4) leaking of cell enzymes into the bloodstream

• CPK: creatine phosphokinase

• lactic dehydrogenase (LDH)

5) replacement of functional tissue with scar tissue

6) somatic death

Pathologic calcification

1) when the necrotic tissue is not cleared or removed from an organ or tissue

2) deposition of fibrous connective tissue- then calcium deposits over the necrotic area

3) types:

• dystrophic or necrotic calcification

• metastatic calcification

• stone formation (calculi)

4) result from imbalances in the make up of secretions such as bile acids in bile- galstones

5) calculi contain calcium + other salts

6) tend to block ducts and cause pain

Aging

Is it programmed into the cells?

• telomeres become too short; cells can no longer divide

is it the result of accumulated damage?

• older cells have more DNA damage

• older cells have more free radicals

• cells can lose the ability to repair their telomeres

Biological theories

• cross link theory

• degenerative extracellular changes or the free radical theory

• neuroendocrine theory

• genetic and environmental lifestyle factors or the wear and tear theory

Somatic death

• death of the entire organism

• when electrical activity in the brain stops- the person is declared dead

• not all cells in the body die at once- why transplantation is possible

• post- mortem changes (rigor mortis)

• body temp drops and acclimates to ambient temp.

• blood coagulates and pools

• autolysis

• putrefaction