Review of the Normal Cell and Causes of Cell Injury

Lecture 2

Define a cell.

a membrane bound structure which can be divided into functional units which is interconnected by a fluidic system of fusing and blebbing of these membrane bound structures

What is the cytocavitary network?

fluidic system of fusing and blebbing of membrane bound structures in a cell

The cell is enclosed by a phospholipid bilayer which forms what?

a selective barrier

What helps determine the cell function?

the selective barrier formed by the phospholipid bilayer

Define selective barrier

keep certain items in selective spaces

Membrane bound vesicles are shuttled in which direction?

from the ER to Golgi apparatus to other organelles or the plasma membrane

Organelles and membrane bound vesicles are embedded within what?

the cytosol

What is the cytosol?

cytoplasmic matrix containing water, dissolved ions, and macromolecules like proteins

Membrane bound structures interact with what?

the cytoskeleton

What is the cytoskeleton?

the structural network of the cell which helps in movement, cell division, and many biochemical pathways

What are the three types of filaments within a cell?

• microfilaments

• intermediate filaments

• microtubules

What is the purpose of microfilaments?

facilitate cell motility

What is the purpose of intermediate filaments?

provide physical strength to the cells, often via junctional complexes

What is the purpose of microtubules?

move organelles and vesicles within the cytosol, and chromosomes via the mitotic spindle

The nucelus is composed of what?

chromatin surrounded by a bilayered nuclear membrane with pores

What is chromatin?

DNA coiled around histones

What are the two types of chromatin?

• euchromatic nuclei

• heterochromatic nuclei

Which type of chromatin is loosely coiled and involved in active transcription to mRNA?

Euchromatic

Which type of chromatin is tightly coiled and is inactive?

heterochromatic

Is the nucleus membrane bound?

Yes

Which non membrane bound structure is found within the nuclei?

nucleoli

What is the function of nucleoli?

synthesis of ribosomal RNA

The prominence of nucleoli measures what?

the cells synthetic activity

What are the two types of endoplasmic reticulum?

• rough

• smooth

Which type of endoplasmic reticulum is continuous with the nuclear membrane and is lined by ribosomes?

rough

Which type of endoplasmic reticulum lacks ribosomes?

smooth

What is the function of the rough endoplasmic reticulum?

• protein syntehsis

• basophilia (staining with H&E) of a cell’s cytoplasm

What is the function of the smooth endoplasmic reticulum?

metabolizing drugs, lipids, steroid, carbohydrates, glycogen

Cells with adbundant smooth endoplasmic reticulum will have what appearance of cytoplasm?

pink, finely vacuolated

Give an example of cells that have adbundant smooth endoplasmic reticulum.

endocrine cells

What is the function of the golgi apparatus?

synthesizes and packaging center for proteins to be exported out of the cell

The Golgi apparatus is not always visible by light microscopy within a cell. When it is viible, it is often due to what?

a large production of proteins such as immunoglobulins (plasma cells)

What are the functions of the mitochondria?

• produce ATP through oxidative phosphorylation

• involved in apoptosis

• cell signaling

• cell differentiation

• cell growth

Are lysosomes membrane bound?

Yes

Lysosomes contain what type of enzymes?

hydrolytic

The enzymes found in lysosomes digest what?

most chemical compounds taken up through endocytosis or phagocytosis

What is the function of lysosomes?

aid in intracellular digestion

Enzymes in lysosomes are synthesized by what?

rough endoplasmic reticulum

Enzymes in lysosomes are process and packaged where?

in Golgi

Enzyme in lysosomes are released in vesicles from the golgi into where?

cytosol

What are the different types of junctional complexes?

• tight junction

• gap junction

• adherens junction

• desmosome junction

• hemidesmosome junction

What type of junctional complex is this?

tight junction

What type of junctional complex is this?

gap junction

What type of junctional complex is this?

adherens junction

What type of junctional complex is this?

desmosome junction

What type of junctional complex is this?

hemidesmosome junction

Can a cell be damaged functionally with no apparent morphologic alterations?

Yes

What are the four major mechanisms of cellular injury?

• depletion of ATP

• permeabilization of cell membranes

• disruption of biochemical pathways, especially protein synthesis pathways

• DNA damage

There are too many causes of cell injury to count, what list can be used to make sure you cover all bases? (Hint: DAMNITV)

• degenerative

• anomalous/aging

• metabolic

• nutritional/neoplastic

• infectious/inflammatory

• trauma/toxic

• vascular

What is the most common and important cause of cell injury?

hypoxia

Explain the pathway for cell damage caused by hypoxia.

no oxygen —> no oxidative phosphorylation —> anaerobic glycolysis (long term) or reversible injury or no ATP production —> no ATP production causes no ATPase pump function —> no ion stabilization in cell / no homeostasis / cells fill with water and burst —>reversible injury or point of no return (death)

What are the four causes of hypoxia?

• cardiac or respiratory failure

• reduced vascular perfusion (ischemia)

• reduced oxygen transport by erythrocytes

• inhibition of respiratory enzymes within the cell

What can cause reduced oxygen transport by erythrocytes?

• anemia

• carbon monoxide poisoning

What can cause inhibition of respiratory enzymes within the cell?

cyanide toxicosis

Ischemia can result in what?

reperfusion injury

What is reperfusion?

the restoration of blood flow to a site

Reperfusion injury can result in what?

Formation of free radicals (reactive oxygen species)

What are the reactive oxygen species (free radicals)?

• superoxide anion (O2-)

• hydrogen peroxide (H2O2)

• hydroxyl radical (HO-)

Free radicals are commonly formed during what?

oxidative phosphorylation

Free radicals function as what?

cell signaling molecules which affect cell proliferation and survival

Where are reactive oxygen species generated?

• nucleus

• mitochondria

• peroxisomes

• endoplasmic reticulum

• other organelles

Imbalances in reactive oxygen species (increased numbers) causes what?

counteracts antioxidants resulting in oxidative stress and damage to DNA, RNA, cell membranes, proteins, and deactivation of specific enzymes

What is the main enzyme responsible for catalyzing free radicals?

superoxide dismutase

Other than superoxide dismutase, what other components can help catalyze free radicals?

• glutathione peroxidase

• vitamin E/selenium

• vitamin C

When cell injury in irreversible, what will happen?

death

If a cell responds to reversible cell injury, what occurs?

adaptation

What is the response to both reversible and irreversible cell injury, making it difficult to distinguish cells that will recover or die?

acute cell swelling

What is the most common cause of acute cell swelling?

hypoxia

Other than hypoxia, what else can cause acute cell swelling?

direct injury to cell membrane

What can cause direct injury to cell membrane?

• lipid peroxidation from reactice oxygen species

• binding of toxins

• damage to ion channels

• transmembrane pores

What do we term cell swelling in hepatocytes and renal epithelial cells?

hydropic degeneration

What do we term cell swelling in keratinocytes?

ballooning degeneration

What do we term cell swelling in astrocytes?

cytotoxic edema

Grossly, cell swelling can appear as what?

• increased volume and weight of an organ (increased organ/tissue size)

• increased pallor (pale appearance)