2. Cell Injury: Review of the Normal Cell & Causes of Cell Injury

The cell is a ________ structure.

complex

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

cell

the fluidic system of fusing and blebbing of the membrane bound structures that is interconnecting the functional units of the cell

cytocavitary network

What encloses the cell? What does this form? What does this do?

phospholipid bilayer; selective barrier; keeps certain items in selective spots, which helps determine cell function

Where are proteins made in the cell?

endoplasmic reticulum

Where are proteins packaged to other organelles or the plasma membrane?

the golgi

Where are organelles and membrane bound vesicles embedded within?

the cytosol

cytoplasmic matrix containing water, dissolved ions, and macromolecules (proteins, etc)

cytosol

The membrane bound structures interact with the ________, which is the structural network of the cell that helps in movement, cell division, and other biochemical pathways.

cytoskeleton

What are the 3 types of filaments within a cell?

M
I
M

1. microfilaments

2. intermediate filaments

3. microtubules

facilitate cell motility

microfilaments

provide physical strength to the cells, often via junctional complexes

intermediate filaments

move organelles and vesicles within the cytosol and chromosomes via the mitotic spindles

microtubules

place where DNA is stored, translated, and transcribed into RNA and is composed of chromatin surrounded by a bi-layered nuclear membrane with pores

nucleus

DNA coiled around histones

chromatin

What are the two types of chromatin?

E
H

• euchromatic nuclei

• heterochromatic nuclei

loosely coiled chromatin that is active transcription to mRNA

euchromatic nuclei

tightly coiled chromatin that is inactive

heterochromatic nuclei

What type of chromatin is present in very active cells?

euchromatic nuclei

found within the nuclei and is non membrane bound

nucleoli

What is the function of the nucleoli?

synthesis of rRNA

What does the prominence of nucleoli measure?

the cell’s synthetic activity (the more rRNA it is making)

ER that is continuous with the nuclear membrane and is lined by ribosomes

rough ER

What is the rough ER responsible for?

P
B

• protein synthesis

• basophilia of a cell’s cytoplasm

ER that has no ribosomes

smooth ER

What is the smooth ER important for?

metabolizing drugs, lipids, steroids, carbohydrates, and glycogen

What is significant about the cytoplasm of cells with abundant smooth ER, such as endocrine cells?

they will have pink, finely vacuolated cytoplasm

synthesizes and packing center for proteins to be exported out of the cell that takes the protein made by the ER and puts them into membrane bound vesicles

golgi apparatus

True or false: The golgi apparatus is not always visible by light microscopy within a cell. When it is visible, it is often due to a large production of proteins such as immunoglobulins.

true

What are the functions of the mitochondria?

P
I
C
C
C

• produce ATP through oxidative phosphorylation

• involved in apoptosis

• cell signaling

• cell differentiation

• cell growth

What do lysosomes contain?

hydrolytic enzymes

Enzymes in lysosomes are synthesized by ________, processed and packaged in ________, released in vesicles from the ________ ________ into ________.

rER; golgi; golgi complex; cytosol

What do lysosomes aid in? How?

P
B

intracellular digestion

• phagocytized particles

• breakdown of organelles within the cell

True or false: A cell can be damaged functionally with no apparent morphologic alterations. This means they can be damaged but not see any damage microscopically.

true

What are the 4 major mechanisms of cellular injury?

1. D

2. P

3. D

4. D

1. depletion of ATP

2. permeabilization of cell membranes

3. disruption of biochemical pathways, especially protein synthesis pathways

4. DNA damage

Which mechanism of cellular injury typically begins the cascade?

depletion of ATP

True or false: There can be multiple mechanisms of injury at the same time, and it is often an interplay between these mechanisms.

true

While causes of cell injury are too numerous to count, what is a scheme to think of?

D
A
M
N
I
T
V

• degenerative

• anomalous/aging

• metabolic

• nutritional/neoplastic

• infectious/inflammatory

• trauma/toxic

• vascular

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

hypoxia

state of decreased O2

hypoxia

Describe what happens when in an hypoxic state, leading to death.

no oxygen → mitochondria have to shift from aerobic to anaerobic respiration → less ATP is made → less ATP causes the Na+/K+ ATPase to not function properly → causes Na+, H2O, and Ca2+ in and K+ out → this will lead to death

if long term, anaerobic glycolysis will lead to death

Describe another route that can happen in hypoxia.

no oxygen → mitochondria have to shift from aerobic to anaerobic respiration → can lead to reversible injury, where if the insult is removed, the cell will live

What are causes of hypoxia?

C
R
R
I

What is the main causes that begins the cascade?

• cardiac or respiratory failure

• reduced vascular perfusion (ischemia)

• reduced oxygen transport by erythrocytes (anemia, carbon monoxide poisoning)

• inhibition of respiratory enzymes within the cell (cyanide toxicosis)

cardiac or respiratory failure

form of hypoxia due to reduced vascular perfusion

ishcemia

What is this an example of?

reduced vascular perfusion/ischemia

What can ischemia result in?

reperfusion injury

restoration of blood flow to a site, especially when there was a lot of anaerobic respiration

reperfusion injury

What can reperfusion injury result in?

the formation of free radicals, also known as reactive O2 species (ROS)

What are examples of reactive oxygen species?

S
H
H

• superoxide anion (O2-)

• hydrogen peroxide (H2O2)

• hydroxyl radical (HO-)

Free radicals are commonly formed during ________ ________ and function as ________ ________ molecules, which affect cell ________ and ________.

oxidative phosphorylation; cell signaling; proliferation; survival

Where are ROS generated in?

N
M
P
E
O

• nucleus

• mitochondria

• peroxisomes

• ER

• other organelles

True or false: Imbalances in these ROS, such as high numbers, counteracts the antioxidants resulting in oxidative stress and damage to DNA, RNA, cell membranes (lipid peroxidation), proteins (oxidation of AA), and deactivation of specific enzymes.

true

What are the free radical’s arch enemy?

superoxide dismutase

What are other things that will counteract free radicals?

G
V
V

• glutathione peroxidase

• vitamin E/selenium

• vitamin C

What will the free radical’s arch enemies turn them into?

water

What will happen if a cell responds to reversible cell injury?

adaptation will occur and can sometimes improve or benefit the cell

What happens if irreversible cell injury occurs?

cell death will ensue

What is a response to both reversible and irreversible cell injury?

acute cell swelling

True or false: It can be difficult to distinguish between cells which will recover or die both grossly and microscopically.

true

What is the most common cause of acute cell swelling?

hypoxia

What are other causes of acute cell swelling?

D
B
D

• direct injury to the cell membrane (from lipid peroxidation from ROS)

• binding of toxins

• damage to ion channels or transmembrane pores

when hepatocytes and renal epithelial cells swell

hydropic degeneration

cell swelling that occurs in keratinocytes/skin

ballooning degeneration

cell swelling in astrocytes/brain

cytotoxic edema

What is this an example of? What are the arrows pointing to?

ballooning degeneration in skin; cytoplasmis eosinophilic viral inclusions due to pox virus

Grossly, how can cell swelling appear?

I
I

• increased volume and weight of an organ

• increased pallor

What is this an example of?

hydropic degeneration

What is this an example of?

cytotoxic edema