Cell Injury, Death, and Adaption - Human Pathology & Physiology

Pathology

Understanding of cells, tissues, and organs as a whole

-Associated to Signs & Symptoms

Signs

Observable by another person

Symptoms

Patient experiences by themselves

Pathogenesis

Mechanism of disease

-Biochemical changes in cell and/or structural changes

What leads to Pathogenesis?

Disease

What are the 2 ways in which one can identify the change in cells and tissues?

Gross and Microscopic

Gross

Physical things that we can see and measure

-IE: color or size

Microscopic

Changes in cell size or shape

-Can be on a Microscopic scale (production of proteins, enzymes, lipids, etc)

Homeostasis

Process by which organisms maintain a relatively stable internal environment

What occurs when the body is out of Homeostasis?

Adaptation

Adaptation

Achievement of a new, steady state to preserve viability and function

Is Adaptation a long-term fix?

NO

Cell Injury

Adaptive capacity exceeded and external stress is harmful

What is the basis for all disease?

Cell Injury

List the Classifications of Injurious Stimuli (8)

1. Hypoxia & Ischemia

2. Toxins

3. Infectious Agents (Bacteria or Viruses)

4. Immunologic Reactions

5. Genetic Abnormalities

6. Nutritional Imbalances

7. Physical Agents

8. Aging

If you have Hypoxia, you will not have Ischemia

YES

If you have Hypoxia, you will have Ischemia

NO

If you have Ischemia, you will have Hypoxia

YES

If you have Ischemia, you will not have Hypoxia

NO

Hypoxia

Oxygen Deficiency

Ischemia

Reduced blood flow

Examples of Toxins

-Air pollutants, CO, smoke, Ethanol

-Too much or too little of Glucose, Oxygen, Salt, Water, etc.

Immunologic Reactions

Excessive reactions to agents

Example of Genetic Abnormalities

Mutations

Examples of Physical Agents

pH, temperature, radiation

Senescence

Cells that do NOT divide or replicate

What happens to the Plasma Membrane as the cell is under Adaptation for an extended period of time?

Plasma Membrane forms blebs

Bleb

Bumpy surface on the Plasma Membrane

What happens to the Endoplasmic Reticulum as the cell is under Adaptation for an extended period of time?

rough ER loses its Ribosomes

-No longer able to produce Proteins for Plasma Membrane or excretion

Eosinophilic

Characteristic of cell as it is exposed to Adaptation for too long, cell will appear to be redder than normal because the cell is taking up more Iron

What happens to the Lipids within the cell as it is exposed to Adaptation for too long?

It congregates together to form Myelin Figures within the cell

Cell Death

If stimulus is NOT removed or becomes excessive

List the 3 characteristics of the point of no return

1. Inability to restore Mitochondria

2. Loss of Plasma Membrane structure and function (includes intracellular membranes)

3. Loss of DNA and Chromatin

What happens when the Plasma Membrane continues to lose its structure and function when the cell is approaching Cell Death?

Glebs that previously formed begin to fall off

What happens to the Nuclei as the cell's situation continues to worsen?

Nuclei becomes smaller

-In staining, it becomes redder and appears darker

Why does the Nuclei look darker in staining process?

Due the denseness of the structure

List the two types of Cell Death

1. Necrosis

2. Apoptosis

Necrosis

Occurs if SEVERE disturbance occurs

-Rapid, uncontrolled cell death

List the causes of disease that are needed for Necrosis

Ischemia, Toxins, and Infections

Apoptosis

Less severe disturbances

-Normal cellular elimination

-Controlled cell death

How often does Apoptosis occur?

Daily basis

Why is Apoptosis a controlled cell death?

Helps with intrinsic abnormalities, such as unrepairable DNA and or proteins

Pyknosis

Chromatin becomes highly condensed

Karyorrhexis

Chromatin starts to shear itself (AKA breaks apart)

Within the process of Necrosis, what happens to the contents of the cell?

The contents are released out of the cell

-Enzymes that are released will digest the original cell and its neighbors and friends

Within the process of Apoptosis, what happens to the components of the cell?

The contents remain within the cell, but everything is reduced

Does Necrosis or Apoptosis trigger Inflammation?

Necrosis

Which process occurs to fix a pathological issue? Necrosis or Apoptosis?

Necrosis

Which process occurs when there is a physiological change? Necrosis or Apoptosis?

Apoptosis

Purpose of Inflammation

Helps clear cellular debris and begins process of healing

List types of Necrosis (6)

1. Coagulative Necrosis

2. Ligue factive Necrosis

3. Gangrenous Necrosis

4. Caseuous Necrosis

5. Fat Necrosis

6. Fibrinoid Necrosis

Coagulative Necrosis

When the architecture of the tissue remains, but the cell itself is dead & hardens

-Due to the denaturation of proteins and enzymes

-Seen in organs, EXCEPT BRAIN

Infarct

Lack of blood flow to a region

Within Coagulative Necrosis, which cells persist?

Anucleated cells persist, but are eventually destroyed by Leukocytes

Ligue Factive Necrosis

Found in BRIAN !!

-Result of Bacterial & Fungal Infections

What type of Brain tissue does Ligue Factive Necrosis target?

Hypoxia which is liquid-like material

Puss

Infectious & Inflammatory cells

Gangrenous Necrosis

Combination of Necroses

-Refers to limbs that have lost blood

In relation to the limbs that have lost blood, do they still have an immune response?

NO, so they may develop cracks within the tissues which will promote the presence of Bacteria which may instill Liguefactive Necrosis

When there is a bacterial infection within a cell undergoing Gangrenous Necrosis, what occurs?

Liguefactive Necrosis

Caseous Necrosis looks like...

Cheese--yellow, white

Where can Caseous Necrosis be found?

Tuberculosis Infections and Fungal Infections of Lung

Which type of Necrosis has Giant Cells and what are they?

Caseous Necrosis

-Several Immune Cells join together to engulf on a larger scale

-They have multiple Nuclei

Fat Necrosis

Pancreatic Enzymes are released into the Pancreas or Peritoneal Cavity

Lipase

Chews up fat cells

Functions of Pancreatic Enzyme (2)

1. Lyse fat cells

2. Breakdown Triglycerides

Fat Saponification

When Triglycerides and Fatty Acids combine with Calcium to become a chalky-like substance

-NOT GOOD!

Fibrinoid Necrosis

Immune reaction occurring within blood vessel walls

-Bunch of Fibroid-like material shows up within the blood vessel walls

When does Fibroid-like material tend to appear within the walls of blood vessels?

In High Blood Pressure or Hypertension

Is the Fibrinoid-like material stretchy?

NO

What does the Heart release into the bloodstream when it undergoes a heart attack?

Cardiac Creatine Kinase and Cardiac Troponin

What does the Gallbladder release into the bloodstream when it undergoes disease?

Alkaline Phosphatase

What does the Liver release into the bloodstream when it undergoes disease?

Transaminases (ALT and AST)

Apoptic Body

When the blebs fall off the Plasma Membranes during Apoptosis and become free-floating within the Cytoplasm

What engulfs an Apoptic Body?

Phagocytes

p53

Guardian to Genome

Function of p53

Sense damage to DNA -> triggers pro-apoptotic factors -> factors will travel to Mitochondria to accumulate an outer membrane to form a pore -> release of Cytochrome C -> activation of Apoptosome -> activation of Caspade Cascade -> Caspase 3 activation

What marker states that Apoptosis is occurring?

Caspase 3

Death Signal is also known as...

Pro-Apoptotic Signal

What is the Extrinsic Pathway to signal Apoptosis?

The Pro-Apoptotic Signal binds to the Death Receptor, which is found on the surface of cells, which then triggers the Cascade of Caspases which denotes that Apoptosis is occuring

Necroptosis

Cell signals, like apoptosis, but results in cell death like Necrosis

-Has Inflammation

Pyroptosis

Apoptosis with a fever

Autophagy

Results from Nutrient Deprivation

-Lysosomal degradation of its own components

-Cell eats itself

What can cell do if it does not have ATP?

Nothing

Ischemia-Reperfusion

Restoring blood flow to Ischemic tissues that were still viable can lead to increased cell injury

-Cell has adapted to Ischemic event, so it can run with little Oxygen present

-Thus, when re-introduction of Oxygen occurs, the cell is not adequately prepared

What happens to cell when Oxygen is re-introduced after a period of little to no Oxygen is present?

1. Increase Reactive-Oxygen Species (ROS)

2. Induction of Inflammation

3. Immune Response

Oxidative Stress

Too much O2 or re-introduction of Oxygen to cells after deprivation

Reactive-Oxidative Species (ROS)

Radicals, such as supra oxide or hydroxyl groups

-Produced in Mitochondria or Phagocytic cells

Is ROS harmful to cells?

YES

-They damage DNA, proteins, lipids, and macromolecules which leads to death

Latent Toxins

Innert molecules

-We convert it to reactive metabolites which are harmful

What do viral medicines utilize and why?

Latent Toxins

-Due to the inert molecules, the antiviral does not harm our healthy cells, instead, they are able to target and harm viral cells

Inert Cells

Does not do anything to our cells, needs to be converted to actually do something

Endoplasmic Reticulum Stress

Occurs when you have an accumulation of misfolded proteins

What happens when ER Stress is a mild condition?

-ER will produce more proteins to help the proteins fold correctly

-Increase protein degradation within the cell

What happens when ER Stress is at a point past mild?

ER sends a signal to activate the Caspase Cascade which signals Caspase 3 and Apoptosis

What phase must the DNA be repaired to prevent Apoptosis?

S Phase

If S Phase occurs and DNA is still not fixed, what occurs?

Apoptosis

What can damage DNA?

Radiation, Chemotherapeutics, ROS, and Mutations

Cellular Adaptations

Changes to number, size, phenotype, metabolic state, or function

-Reversible

Physiological Adaptation

Could have certain hormones released or new demands in a tissue that could show up