Cellular Injury, Adaptation and Death

ANSC 409

what are the 3 responses to cell injury?

• adaptation

• degeneration

• death

A clear understanding of normal cell structure and function is essential to the study of…

cellular responses to injury

The cell can be visualized simplistically as a ________-_______ structure, subdivided into smaller functional units (organelles)

membrane-enclosed

cell membranes and organelles

are targets for injury by various microbial, genetic, metabolic, and toxic diseases

plasma membrane

• encloses the entire cell and first point of contact with harmful substances (toxins, infectious microbes)

• separates the interior of the cell from the exterior environment, neighboring cells, or the ECM

____________ and _______ are specialized areas of the plasma membrane that are often altered in disease

microvilli and cilia

cytoplasm (cytosol)

The portion of the cell inside the plasma membrane and outside the nuclear envelope (just outside the nucleus)

nucleus

Animals are made of eukaryotic cells, meaning cells that have a nucleus is retained throughout the life of the cell.

exception: erythrocytes (RBCs)

what is readily visible by light microscopy because it contains chromatin?

a nucleus

chromatin

DNA complexed with histones

nucleolus

• A non–membrane-bound structure within the nucleus.

• Can be inconspicuous in inactive cells or quite prominent in cells with high protein production

rough endoplasmic reticulum

• A membrane-bound network of flattened saclike cisternae

• Continuous with the outer nuclear membrane

primary function of rough ER?

protein synthesis

ribosomes

• Found in the cytoplasm and on surface of RER.

• Facilitate the synthesis of proteins in cells

golgi complex

• Series of flattened membrane-bound sacs with its inner face near the RER near the nucleus

• Proteins made in the rER are delivered to the Golgi complex by transport vesicles

• As the proteins traverse the Golgi complex, they are processed and packaged into secretory vesicles to be released from the Golgi complex into the cytoplasm

smooth endoplasmic reticulum

• A membrane-bound network of tubules without surface ribosomes.

• Main function is the synthesis of lipids, steroids, and carbohydrates, as well as the metabolism of exogenous substances, such as drugs or toxins

mitochondria

• Organelles that can change shape and move about within the cell.

• Generate energy for the cell as adenosine triphosphate (ATP) through Oxidative Phosphorylation

lysosomes

Membrane-bound vesicles that contain enzymes that can digest most chemical compounds within the cell or extracellular substances taken up by endocytosis or phagocytosis.

cellular inclusions

• Composed of molecules that accumulate as metabolic by- products or as a result of cell injury.

• Certain infectious microbes, especially viruses, can also produce intranuclear or cytoplasmic inclusions

transmembrane protein receptors

• Central to the pathogenesis of many disorders.

• Receive and interpret extracellular signals from the environment

• Often used by infectious microbes to invade cells or use cell systems during their life cycles, thus initiating a process that can injure the host cell.

intercellular junctions

The cell connects and communicates with neighboring cells of the same type via intercellular junctions

injury to tissues begins at the _________ level

cellular

the visible lesions we see in tissues are preceded by…

biochemical changes within the cell

cells can be damaged functionally (biochemically) yet have no ____________ alterations

morphologic

what are the 4 basic mechanisms of cell injury?

• ATP depletion

• cell membrane damage

• disruption of biochemical pathways (protein synthesis)

• DNA damage

there is often _______ between the 4 mechanisms of cell injury, so it is rarely just 1 mechanism taking place in the cell

interplay

what do the 4 mechanisms of the cell injury look like practically?

banding a bull calf

describe how banding a bull calf affects ATP depletion

• loss of blood supply

• testicular tissue becomes ischemic

• mitochondria can’t perform oxidative phosphorylation

• ATP rapidly decreases

banding causes ischemia → ATP depletion → energy failure

describe how banding a bull calf affects cell membrane damage

with ongoing ischemia:

• cell membrane loses integrity

• ion gradients collapse

• Ca enters the cell

• lysosomal membranes rupture

• results in digestive enzymes leaking into the cytoplasm

• cell undergo necrosis

testicular and scrotal tissues become cold swollen, and eventually necrotic

describe how banding a bull calf affects disruption of biochemical pathways

without oxygen and ATP

• protein synthesis stops

• ribosomes detach from rER
  enzymatic reactions fail

• metabolic pathways collapse

cells can no longer maintain normal function and begin to degenerate

describe how banding a bull calf affects DNA damage

during prolonged ischemia:

• activated enzymes

• free radical production

• loss of repair mechanisms

this leads to irreversible cell injury and death

final outcome of banding a cull calf?

• all these mechanisms together cause tissue to:

  • die

  • dries out

  • eventually sloughs off

cells respond to stress or injury along a _________

spectrum

Whether the injury is reversible or irreversible depends on the ______ and ______ of the insult.

severity and duration

cells are constantly trying to maintain _______

homeostasis

when exposed to stress of damaging stimuli, cells respond in two main ways:

• cell recovery

• cell death

If the cell responds to injury with either an Adaptive Response or a Degenerative Response, the cell injury is termed ________

reversible

If the cell response to injury progresses into Cell Death Response, the cell injury is termed ________

irreversible

Reversible Pathways = Recovery

• Adaptive Response

• Degenerative Response

Irreversible Pathways = No Recovery

• Cell Death

…

adaptive responses of reversible pathways

• Cell responds to injury by making controlled structural or functional adjustments to survive the injury

• Examples: Hypertrophy, Hyperplasia, Atrophy

degenerative response of reversible pathways

• Cell undergoes noticeable structural changes but still can recover

• Examples: Cell and Organelles Swell, Lipids accumulate in cytoplasm

If the injury or insult stops, the cell will eventually return to normal or _____-_____ structure and function.

near-normal

cell death in irreversible pathways

• Cell responds to injury by progressing from degenerative stage into death

• The nature of the injury is so severe or prolonged that the cell is unable to survive

common causes of cell injury

• Oxygen Deficiency (Hypoxia)

• Physical Agents

• Infectious Agents

• Nutritional Imbalances

• Genetic Derangement

• Chemicals, Drugs, Toxins

• Immunologic Dysfunction

oxygen deficiency (hypoxia)

A reduction in O2 supply to cells

one of the most common and most important causes of Hypoxia?

• Low Blood O2 Levels

  • Heart Disease, Respiratory Failure

• Reduced Vascular Perfusion

• Reduced O2 Transport by RBC’s

  • Anemia, CO Toxicosis

physical agents (trauma)

may include any direct or indirect trauma

• Crushing or tearing of cells / tissues

• Disruption of Blood Supply to cells or

tissues. (Ischemia)

• Extreme Heat denatures enzymes

and proteins in cells.

• Extreme cold freezes cells

• Radiation (UV)

infectious agents

• Bacteria

  • Produce toxins

• Viruses

  • Subverts host cell’s DNA synthesis in the production of own gene products

• Parasites

  • Rob host of vital nutrients

nutritional imbalances

• Nutritional deficiencies, excesses, and imbalances all predispose the cell to injury.

  • long-term starvation leads to atrophy of cells and tissues

  • caloric excess can overload cells with glycogen and lipids and lead to obesity with metabolic disturbances that predispose the obese animal to a variety of diseases

genetic derangement

Selective breeding of domestic animals for a particular conformational or dispositional phenotype has resulted in decreased genetic diversity in purebred animals and increased prevalence of inherited diseases

chemicals, drugs and toxins

• Chemicals, including drugs and toxins, can alter cellular homeostasis

• Chemicals affect cells by binding receptors, inhibiting or inducing enzymes or otherwise altering metabolic pathways, producing free radicals, increasing membrane permeability, or damaging chromosomes or structural components of the cell.

Immune reactions

• the immune system is attacking normal cells of the body