ZOOL-1073 Module 4: Altered Cells and Tissues

When a cell is injured, what are its only TWO choices?

Adapt or die

Why look at disease at the level of cells and tissues?

Cells and tissues are the basic building blocks of organs and organ systems

List the 9 common causes of cell injury.

1) Inadequate oxygenation

2) Physical, thermal, or chemical agents

3) Ionizing radiation

4) Toxins

5) Microbes

6) Inflammation and immune reactions

7) Nutritional imbalance

8) Genetic and metabolic defects

9) Aging

Inadequate oxygenation is usually the result of ______

Ischemia (inadequate blood flow)

Besides oxygen delivery, what 2 things does inadequate blood flow disrupt?

1) Transport of glucose to fuel cells

2) Removal of metabolic waste products like carbon dioxide (CO2)

How fast do neurons die without oxygen?

2–3 minutes

Ionizing radiation: what damage do they cause?

damage DNA or cause proteins to misfold

Toxins: what 2 kinds of damage can they cause?

1) Damage enzyme pathways in cells

2) Destroy cell membranes

Which microbes can injure cells?

Bacteria, yeasts, moulds, and viruses

How do inflammation and immune reactions injure cells?

your own antibodies cross-react and attack your own cells

How do genetic and metabolic defects injure cells?

Some genetic diseases cause accumulation of abnormal products, which damage cells

How does aging injure cells?

Progressive, mild injury that leads to cell death directly, or makes cells not able to withstand other forms of injury

What are 3 key principles of cell injury?

1) Injury happen anywhere in the body's structural hierarchy

2) Genes influence how we react to injury

3) Impaired health result from inflammation and repair process that follows injury

what 'program' runs when the CYTOSKELETON is damaged?

The cell makes an enzyme to repair it

what 'program' runs when DNA is damaged?

The cell makes a different enzyme to detect the change and correct it

When can a cell NOT fix itself, and what is the result?

When damage is too extensive OR there aren't enough raw materials

Result: inflammation or cell death

Do all injured cells die?

Some survive but show physiological changes, which can be reversible or permanent depending on the TYPE and EXTENT of injury

Whether cell injury is reversible depends on what 2 factors?

Duration and severity of the injury or stress

What happens to the visible changes of mild injury when the cause disappears?

They go back to normal

What happens with LONG-TERM mild injury or stress?

Changes continue until cause of the injury disappears

ACUTE mild injury: timeframe

Minutes to days

ACUTE mild injury: 2 cell responses?

1) Hydropic change

2) Steatosis

CHRONIC mild injury: timeframe

Weeks to years

CHRONIC mild injury: 2 cell responses?

1) Intracellular accumulations

2) Altered growth and differentiation

Most common cause of acute mild injury?

hypoxia or anoxia

Hydropic change

Cell swelling with water caused by a rise in intracellular sodium

Is Hydropic change reversible?

if the injurious situation is corrected

example of hydropic change

Cardiomyocytes in congestive heart failure

is sodium higher inside or outside the cell?

Outside

What maintains the normal sodium gradient?

The sodium pump in the cell membrane, which pumps sodium out as fast as it seeps in

Hydropic change: explain the mechanism step by step

Hypoxia/anoxia → no ATP → sodium pump fails → sodium seeps into cytoplasm → solutes attract water → water enters → cell swells.

In hydropic change, why does water enter the cell?

Solutes attract water, so the rise in intracellular sodium draws water into the cytoplasm

Steatosis

Fat accumulation inside cells (fatty liver)

Why is steatosis most common in liver cells?

Because of the liver's role in fat metabolism.

Who commonly develops steatosis?

People who abuse alcohol. Now common in young adults and even children due to obesity

Steatosis is reversible, but chronic liver steatosis can progress to what?

Cirrhosis and liver failure ( chronic → lose more cells → scar tissue → decreased liver function)

Short-term mild injury causes accumulation of ______

water and fat

prolonged injury causes accumulation of ______

cholesterol, protein, pigment, environmental particles

What are the 4 types of intracellular accumulations?

1) Cholesterol

2) Protein

3) Pigment

4) Environmental particles

LDL

low-density lipoproteins

VLDL

very-low-density lipoproteins

What do LDL and VLDL do?

carry cholesterol from the liver to fat cells

What happens when there is too much LDL/VLDL in the bloodstream?

They bind and build up where they shouldn't, narrowing arteries = atherosclerosis

Why do proteins accumulate in cells?

When damaged and misfolded, they may clump together

What is the NORMAL function of tau protein?

Stabilizes microtubules (form the cytoskeleton)

What happens to tau in Alzheimer's disease?

misfolds and binds to other tau, causing clumps

What happens when too many tau clumps form inside a cell?

The cell can't function and dies via apoptosis.

diseases caused by protein accumulation?

• Huntington's

• Parkinson's

• ALS

• alpha-1-antitrypsin deficiency

Alpha-1-antitrypsin deficiency

Genetic mutation causing buildup of alpha-1-antitrypsin in the liver

Alpha-1-antitrypsin deficiency can cause?

COPD and liver cirrhosis

Most occurring pigment accumulation?

Lipofuscin

Lipofuscin: colour and where it's found?

Golden brown

Lipofuscin: where it's found?

Found in long-lived cells

Lipofuscin's presence indicates what?

Wear and tear

Lipofuscin is the end result of what process?

Fatty acid oxidation in lysosomes

Lipofuscin: associated diseases and what damage it may signal?

Associated with many diseases, from Parkinson's to COPD

Lipofuscin: what damage it may signal?

membrane damage, or damage to mitochondria and lysosomes

Bilirubin accumulation causes what?

Jaundice

Common causes of bilirumin accumulation

liver diseases, gallstones, pancreatic tumours.

Melanin: what uses it

Skin keratinocytes use it to protect against UV damage

Environmental particle accumulation: sources

Inhaled particles from cigarette smoke or air pollution

Environmental particle accumulation: location

accumulate in respiratory cells and bronchial lymph nodes

Environmental particle accumulation: effect

contribute to a variety of respiratory diseases

What are the 5 types of altered growth and differentiation?

1) Atrophy

2) Hypertrophy

3) Hyperplasia

4) Metaplasia

5) Dysplasia.

Altered growth/differentiation adaptations respond to what

Chronic mild injury or stress (including the GOOD stress of exercise)

Atrophy

Decrease in cell NUMBER, cell SIZE, and work output

Why does a cell atrophy?

Adaptive response to decreased demand or increased stress: the cell shuts down metabolic processes to conserve energy

what happens to muscle when you stop exercising?

Skeletal muscle cells break down excess sarcomeres and organelles → decreased cell size and function → whole muscle smaller and weaker

Disuse atrophy

atrophy from decreased workload

Pathologic atrophy

Disuse or lack of normal physiological support

4 examples of pathologic atrophy

1) Bodies of underfed children

2) Organs deprived of blood and its nutrition

3) Paralyzed limbs

4) Thyroid and adrenal glands denied hormonal support from the pituitary

In atrophy, do muscle cells die?

Not really, they just shrink

What are the 6 causes of atrophy?

1) Disuse

2) Denervation (neurogenic)

3) Hormones

4) Malnutrition

5) Ischemia

6) Aging

Denervation atrophy affects the ______

NERVES connected to muscles

Why is denervation atrophy harder to treat than disuse atrophy?

Nerve damage is harder to treat and does NOT reverse

Common causes of nerve damage (denervation atrophy)?

Alcohol abuse, toxins, injury

Diseases that cause denervation atrophy?

ALS, polio, carpal tunnel syndrome, spinal cord injury

Hormonal atrophy cause

A significant drop in estrogen levels

Malnutrition causing atrophy can be due to what 2 things?

1) Insufficient total caloric intake (starvation)

2) Insufficient intake of a particular nutrient (e.g., protein)

Effects of malnutrition?

• Changes in body mass

• poor wound healing

• severe weight loss

• organ failure

Cachexia

Severe weight loss

Arteriovenous (AV) fistula

Abnormal connection or passageway between an artery and a vein

example of ischemia causing atrophy?

Peripheral artery disease

Aging atrophy: what changes, and why?

body composition, energy, protein metabolism

Loss of lean body mass with aging is associated with what?

increased disability and mortality.

Hypertrophy

Increase in cell SIZE (only) and work output

What causes hypertrophy

Adaptation to increased workload and/or increased endocrine stimulation

Is hypertrophy reversible or irreversible

Reversible

What is the opposite of atrophy?

Hypertrophy

Why is hypertrophy most often seen in muscle?

Muscle can't grow new cells so it has to adapt by enlarging existing cells

What happens to muscle when you lift weights?

Muscle builds more sarcomeres and organelles → cells enlarge and contract with more force → bigger, stronger muscles.

Why do males tend to have more skeletal muscle mass than females?

Testosterone stimulates skeletal muscle hypertrophy

Afterload

The work the left ventricle must do to force open the aortic valve and eject blood into the aorta

How does the left ventricle respond to hypertension?

LV cardiomyocytes hypertrophy → contract with greater force → generate enough pressure to overcome afterload

Difference between regular hearts and hypertensive hearts?

Hypertensive hearts have thicker left ventricles

Cardiac hypertrophy: short-term

Short-term: adaptive, keeps blood pumping

Cardiac hypertrophy: long-term effect

cells stop hypertrophying → left heart failure = can be fatal

Can non-muscle cells hypertrophy

epithelial and connective tissue cells can

Example of non-muscle cells hypertrophy

One kidney is removed or inactive, the remaining kidney enlarges to compensate

Hyperplasia

Increase in cell NUMBER in an organ or tissue