BLD 204 Exam 1

What is the cell membrane composed of?

Phospholipids, proteins and some cholesterol

3 functions of the cell membrane

1. Keep toxic substances out of cell
2. Allows for specific molecules into and out of the cell (or organelle) using receptors and channels.
3. Separate vital metabolic processes conducted within organelles

Function of mitochondria

Make ATP via oxidative phosphorylation and ETC

Function of lysosome

"Clean up the mess" (Used in catabolic processes)

Function of nucleus

House genetic information (DNA)

Function of ER

Assist with making proteins, protein folding and shipping to the golgi

Function of Golgi Apparatus

Packaging and secretion of macromolecules

Function of microtubules

Used to move "stuff" around the cell

Function of microfilaments

(AKA Actin) Thinnest fiber of cytoskeleton and used for movement of molecules

Function of ribosomes

Translate RNA --> Proteins (polypeptides)

Define etiology

Cause of the disease

Falling on ice and getting a subdural hematoma

Etiology

Genetic abnormality

Etiology

Toxins, Trauma

Etiology

Define pathogenesis

Progression or development of the disease

What a bacteria or virus does that causes the disease to continue

Pathogenesis

Brain swelling due to subdural that lead to coma

Pathogenesis

How disease is progressing

Pathogenesis

Hypertrophy

Increased cell (organ) size in response to stress. Increased work load on cells that can't divide

Uterus increasing in size during pregnancy

Hypertrophy

Hyperplasia

Increased number of cells in response to stress, found in cells that are capable of division

Callus on finger to protect against blistering

Hyperplasia

Atrophy

Cells shrink by loss of cell substance ( removal of activity or nutrients)

Do atrophied cells still have function?

Yes, the function is diminished but it is not gone. They are NOT DEAD. The cells can be restored with increase in nutrients or activity.

Muscular wasting of the patient who is in a coma

Atrophy

Metaplasia

Reversible change in one adult cell type that is replaced by another. Improves function of the cell (organ) in light of stress.

Smokers lung cells changing from columnar to squamous epithelial cells (loose cilia)

Squamous cells are tougher than columnar.
Metaplasia

Homeostasis

A steady state within the cell that requires ATP to be maintained. Stress on a cell (organ) can tip the balance and cause different pathology to occur.

Major causes of stress (9)

Hypoxia
Chemical damage
Genetic problem
Physical damage
Irradiation
Infection
Immune system reactions
Nutritional causes
Aging

Hypoxia

Oxygen deficiency

3 forms of hypoxia

1. Ischemia - Not adequate perfusion
2. Inadequate blood oxygenation - CO
3. Low blood oxygen carrying capacity - anemia

Substances that cause damage to cells, often through membrane damage

Chemical damage - Toxins

Examples of chemical toxins

1. Poisons
2. Ethanol
3. Asbestos

Genetic Problems

Congenital (present at birth) or later mutations

Accumulation of damaged DNA or proteins, Mutated proteins that can't be eliminated

Genetic problems

Temperature, mechanical damage, electric shock, barometric pressure, radiation

Physical damage

Irradiation

S/S worsen depending on strength of dose, duration of exposure and body part thats exposed

Toxins released by microorganisms (fungi, bacteria, viruses, parasites)

Infection

Autoimmunity, allergy, chronic inflammation

Immune system reactions

Calorie deficiency, Obesity, Vitamin deficiency

Nutritional causes of disease

Cells are less able to respond to damage and stress than a younger persons cells

Aging

6 Major biochemical mechanisms of cell injury

1. ATP Depletion
2. Mitochondrial damage
3. Oxidative stress
4. Calcium Influx
5. Membrane damage / Increased membrane permiability
6. DNA damage

Dysfunction that occurs with hypoxia, lack of nutrients, damage to mitochondria and some toxins (CN-)

ATP Depletion

What will not function properly in ATP depletion?

Pumps that require ATP to function, protein synthesis

What increases in ATP depletion?

Anaerobic glycolysis to try and increase ATP

Causes of Mitochondrial damage

Hypoxia, toxins, radiation, Reactive oxygen species (ROS which cause oxidative stress)

What happens due to increased mitochondrial membrane permiability?

ATP depletion

What causes oxidative stress on cells?

ROS that contain free radicals (*** Follow the electrons)

3 outcomes of oxidative stress on cells

1. Lipid peroxidation - Membrane damage
2. Protein modification - Breakdown of peptide and protein misfolding
3. DNA damage - Mutations

Where is most cellular calcium contained to?

Mitochondria and ER

How can ischemia and toxins create an increase in cytosolic calcium concentrations

1. Release of calcium stores
2. Increased flux across plasma membrane

4 enzymes activated by calcium influx

1. Phospholipase - Break down phospholipids
2. Protease - Break down proteins
3. Endonuclease - Break down DNA
4. ATPase - Break down ATP

3 negative outcomes of calcium influx

1. Membrane damage
2. Nuclear damage
3. Decreased concentrations of ATP

Membrane damage and increased membrane permeability cause

Bacterial toxins, complement, chemical toxins, physical damage, ischemia

Biochemical explanation of membrane damage

1. Phospholipids - Decreased synthesis or increased breakdown
2. ROS release
3. Damaged cytoskeleton
4. Lipid breakdown products act as detergents and form micelles

What happens with too much DNA or protein damage?

Apoptosis

6 major types of necrosis

1. Coagulative necrosis
2. Liquefactive necrosis
3. Gangrenous necrosis
4. Caseous necrosis
5. Fat necrosis
6. Fibrinoid necrosis

Coagulative necrosis

Architecture of cell still visible, firm texture, cells own enzymes are denatured so leukocytes are needed to degrade the cell.

Where is coagulative necrosis seen?

Seen in infarcts of solid organs

What are the solid organs?

Liver, spleen, kidneys, adrenals, pancreas, ovaries and uterus

Liquefactive necrosis

Tissue actually liquefies

Where is liquefactive necrosis seen

Bacterial and fungal infections. Also seen in CVA's

Gangrenous necrosis

Usually lower limb or gut tissue with no blood supply and coagulative necrosis that has occured

Type of infection often related to gangrenous necrosis?

Anaerobic bacterial infection, can see gas bubbles in tissue with clostridia infections causing gangrene

Caseous necrosis "cheese like"

Fragmented or lysed cells seen, no visible architecture

When is caseous necrosis commonly seen?

In granulomas found in TB patients

Fat necrosis

Due to traumatic injury in high fat areas (breast) or by release of activated pancreatic enzymes into the peritoneum.

What occurs during fat necrosis

Lipolysis - Breakdown of lipids into glycerol and free F.A.

How do pancreatic enzymes in the peritoneum cause fat necrosis

Saponification (form soaps) and cells start to look like shadows with basophilic (blue) calcium deposits.

This necrosis happens when Ab/Ag immune complexes get deposited and stuck in tissues

Fibrinoid necrosis

What type of diseases show this?

Immune mediated diseases

What does fibrinoid necrosis look like under the microscope?

Looks like fibrin

Change to nucleus during apoptosis

Condensation of chromatin and blebbing of the cell membrane

Changes to nucleus that occur during cell death (Necrosis) - 3

1. Pyknosis - Nucleus shrinks, basophilic (blue color)
2. Karyorrhexis - Fragmentation of the nucleus
3. Karyolysis - No nucleus (DNA nucleases)

Apoptosis and inflammation

Cellular contents are packed into apoptotic bodies so the cellular contents are contained and not spilled into the open so there is no inflammation.

What degrades apoptotic bodies?

Phagocytes

Necrosis and inflammation

All active enzymes, contents of lysosomes and ROS are released into the surroundings and cause inflammation at the site.

Intrinsic pathway of apoptosis also known as?

The mitochondrial pathway

Activation of intrinsic apoptotic pathway (AKA mitochondrial pathway)

Cell injury due to decrease in amount of growth factor, DNA damage, protein misfolding

What starts the intrinsic apoptotic pathway

Cytochrome C is released from the mitochondrial membrane to start the pathway.

What is another name for the apoptotic pathway?

Caspase Cascade

Extrinsic apoptotic pathway also known as?

The death receptor pathway

Activation of extrinsic pathway

Cells produce surface receptors that trigger apoptosis. Receptor - ligand interactions with factors like TNF or Fas result in activation of the caspase cascade

Apoptotic pathway

Cell damage to normal cell --> Condensation of chromatin and membrane blebs --> Cellular fragmentation (Apoptosis) --> Phagocytosis of apoptotic bodies --> No Inflammation

Necrosis pathway

Reversible injury ( with possibility of recovery) --> Myelin appears, swelling of mitochondria and ER, membrane blebs --> (Progressive injury) --> Breakdown of plasma membrane, organelles, nucleus and leakage of cellular contents, amorphous densities in mitochondria ( Necrosis) --> Inflammation

5 Cardinal signs of inflammation and cause

Heat and redness - Increased blood flow
Swelling and pain - Increased vascular permeability
Loss of function - Cells are not able to do their normal function during the immune response so they technically loose their normal function

The healthy, physiological outcome of inflammation

Eliminate the cause and damaged tissues and initiate repair (healing)

When can inflammation be a problem?

When the inflammatory response is severe, prolonged or inappropriate

Prolonged Inflammatory response

(Chronic) Unable to get through the repair process

Ex of inappropriate inflammatory response

Autoimmunity, hypersensitivity

The difference between acute and chronic inflammation

Resolution, with acute inflammation there is resolution and which chronic there is no resolution

The two main components of inflammation

1. Vascular changes
2. Cellular participation

The two types of vascular changes during an inflammatory response

1. Increased vasodilation - Increased blood flow to the affected area to bring the components of the inflammatory response.
2. Increased vascular permeability - Increased leakage, release of proteins and cells into the surrounding tissues

Five other vascular changes that occur during an inflammatory response

1. Stasis - Concentration of RBC's due to vascular permeability increases the viscosity of blood and slows circulation which then allows for the WBC's to stop and then diapedese into the extravascular space.
2. Margination - PMN's concentrate along the vessel walls
3. Lymph flow is increased
4. Chemical mediators cause the endothelial cells in the venules to contract leaving gaps that allow leakage of protein rich fluid
5. Increased transcytosis of proteins

Protein rich solution that leaks out into the tissue

Exudate

Fluid pushed out of the capillary due to high hydrostatic pressure within the capillary, NO PROTEINS

Transudate

Steps of leukocyte recruitment to inflammed tissues

Macrophages phagocytize a microbe within the tissue → Release of IL-1/TNF (Pro-inflammatory cytokines, cause migration of other WBC's that follow the chemical gradient) → Change to endothelium so endothelial cells express selectins → WBC's marginate and roll to the edges of blood vessels → Sialyl-Lewis X-modified glycoprotein (SLX) on WBC's interact with selectins → WBC's interact with proteoglycan on endothelial surface → Integrin on WBC changes from the low affinity state to the high affinity state → I-CAM 1 helps the cell stop (adhesion) → PCAM 1 helps pull the cell into the extravascular space (Transmigration/extravasation) → Neutrophils follow chemokines (chemotaxis)

Which ligand interacts with integrin on wbc's?

I-CAM 1

What are the 3 principal steps in phagocytosis

a. Recognition and attachment - Microbes bind to phagocyte receptors
b. Engulfment - Phagocyte membrane zips up around the microbe → Phagosome with microbe is ingested → Phagosome and lysosome fuse to form the phagolysosome
c. Killing and degradation - Killing of the microbe by ROS and Nitric oxide → Degradation of the microbes by lysosomal enzymes

What is the mechanism for how phagocytic cells deal with ingested material?

a. Most important - ROS and Lysosomal enzymes in phagolysosome (low pH plays a role)
b. Extracellular products like elastase in the lungs (protease) and antimicrobial peptides in the gut