Rx 316 Exam 1

7 properties of life

• Order

• Reproduction

• Growth and development

• Energy processing

• Response to environment

• Regulation

• Evolutionary adaptation

Order

the highly ordered structure that exemplifies life

Reproduction

the ability of organisms to reproduce their own kind

Growth and development

consistent growth and development controlled by inherited DNA

Energy processing

the use of chemical energy to power an organism's activities and chemical reactions

Response to environment

an ability to respond to environmental stimuli

Regulation

an ability to control an organism's internal environment within limits that sustain life

Evolutionary adaptation

adaptations evolve over many generations as individuals with traits best suited to their environments have greater reproductive success and pass their traits to offspring.

2 types of chromatin

heterochromatin and euchromatin

Heterochromatin

condensed chromatin and is therefore genetically inactive (transcription is not occurring).

Euchromatin

extended chromatin and is therefore genetically active transcription is occurring).

Micro-RNA

short RNAs (22 nucleotides on average) that modulate the translation of mRNAs into their corresponding proteins (functions in post-transcriptional regulation of gene expression).

Cell membrane structure

Phospholipids form a two-layer sheet called a phospholipid bilayer in which the hydrophilic heads are exposed to water and the hydrophobic fatty acid tails point inward away from water. Some proteins form channels or tunnels that transport substances into and out of the cell

Cell membrane function

1. Maintain the ionic content of the cell for proper osmotic balance and membrane potential.

2. Regulate entry of nutrients and the exit of wastes.

3. Uptake of macromolecules from the environment (endocytosis) and the discharge of macromolecules from the environment (exocytosis).

4. Receive chemical messages from other cells (receptor-ligand interactions) and initiate a response leading to specific cellular reactions.

Cytoskeleton structure

1. Microfilaments (actin filaments) support the cell's shape and are involved in motility.

2. Intermediate filaments reinforce cell shape and anchor organelles (e.g.

Cytoskeleton function

structural support and motility

The nuclear envelope

layer of two membranes that surrounds the nucleus of a cell

Smooth endoplasmic reticulum (ER)

Lacks attached ribosomes. It produces enzymes important in the synthesis of lipids

Rough endoplasmic reticulum (ER)

Has ribosomes attached. It makes additional membrane for itself

Golgi apparatus

Post-translational modification of proteins and sorting and packaging of modified proteins

Lysosomes

two primary functions:

1. Degradation of extracellular material ingested from the environment

2. Degradation of intracellular material no longer useful to the cell. Leakage of hydrolytic enzymes can result in undesirable destruction of cell components (autolysis).

Peroxisomes

three major activities:

1. H2O2 is utilized in certain reactions by phagocytic cells to kill ingested microorganisms.

2. Detoxification of lipids and alcohol in liver cells.

3. Beta-oxidation of fatty acids

endosomes

transport

plasma membrane

A selectively-permeable phospholipid bilayer forming the boundary of the cells

Mitochondria

central roles in anabolic metabolism

Extracellular signals determine what?

whether a cell lives or dies

Errors in intracellular signaling are responsible for what?

diseases such as cancer

Cell communication steps

1. Reception (signaling molecule attaches to receptor)

2. Transduction (relay molecules in a signal transduction pathway)

3. Response (activation of cellular response

What stem cells give rise to all types of differentiated tissues?

Totipotent

What stem cells are the most undifferentiated?

Embryonic

Why are hematopoietic stem cells the most extensively studied?

these stem cells can be used to repopulate marrows depleted after chemotherapy (e.g.

Regenerative medicine

the ability to identify

Yamanaka factors

Reprogram somatic cells to achieve "stem-ness" of ES cells. Oct3/4

Why is Yamanaka factors important in biomedicine?

iPS cells are derived from the patient

Adaptive cellular response to stress

Atrophy

Decrease in the size of a cell that has at one time been of normal size.

Physiologic atrophy

Occurs due to a normal stressor (e.g.

Pathologic atrophy

Occurs due to an abnormal stressor. In general

Normal vs Atrophic kidney (picture)

Hypertrophy

Increase in the size of the cell.

Physiologic hypertrophy

Occurs due to a normal stressor (enlargement of skeletal muscle with exercise)

Pathologic hypertrophy

Occurs due to an abnormal stressor (e.g.

Both hyperplasia and hypertrophy result in what?

an increase in organ size

therefore

both cannot always be distinguished grossly

Normal vs Heart with hypertrophic cardiomyopathy (picture)

Normal vs Atrophied muscle (picture)

Hyperplasia

Increase in the number of cells.

Physiologic hyperplasia

Occurs due to a normal stressor (e.g.

Pathologic hyperplasia

Occurs due to an abnormal stressor (e.g.

What cells will undergo hyperplasia?

Only cells that can divide (hyperplasia of the myocytes in the heart and neurons in the brain does not occur.)

Normal vs Hyperplasia of Bone Marrow (picture)

Normal vs Epidermal hyperplasia (picture)

Metaplasia

Change of epithelium at a site

Mechanisms of metaplasia

The epithelium normally present at a site cannot handle the new environment so it converts to a type of epithelium that can adapt (reversible).

Glandular metaplasia (picture)

Resistance-induced hypertrophy molecular mechanism

1. IGF-1 goes into receptor

2. This causes an increase in Akt

3. Increased AKT causes an increase in TORC 1 and TORC 2 4A. TORC 1 increases protein synthesis

Atrophy molecular mechanism

1. Myostatin goes into receptor

2. Increase in Smads production

3. An increase in Smads production inhibits Akt and increases production of FOXO

4. FOXO increases ubiquitin ligases

5. Which increase protein degration

6. which causes an atrophic fiber

Provide examples of metaplasia that occur as a response to cellular injury.

1. Barrett esophagus is due to reflux of gastric contents into the esophagus

Steps of hypoxia

1. Interruption of blood supply decreases delivery of O2 and glucose.

2. Distortion of the activities of pumps in the plasma membrane skews the ionic balance of the cell.

3. Anaerobic glycolysis leads to overproduction of lactic acid and decreased pH.

4. Activation of phospholipase A2 (PLA2) and proteases disrupts the plasma membrane and cytoskeleton.

5. Calcium also activates a series of proteases that attack the cytoskeleton and its attachments to the cell membrane.

6. Lack of O2 impairs mt electron transport chain. Decreasing ATP synthesis and facilitating ROS production.

7. Mitochondrial damage promotes release of Cytochrome C to the cytosol.

8. The Cell Dies.

Reversible cellular injury

The decreased production of ATP causes sodium to enter the cell

How can cell injury be reversible?

These changes are reversible. If ATP is once again produced by the cell

Irreversible cellular injury

This type of injury occurs with damage to the plasma or lysosomal membranes

What are the two most important factors determining irreversible damage?

1. Membrane disturbances

2. The inability to reverse mitochondrial dysfunction.

Reversible injury

Cellular swelling (hydropic) and fatty change.

Necrosis

Uncontrolled cell death due to one of the various causes of cell injury (swelling

The two main types of necrosis

1. coagulative necrosis

2. liquefactive necrosis (Note: several other variants exist).

What happens to the cell during necrosis?

• Increase in cell volume

• Loss of plasma membrane integrity

• Leakage of cellular contents

Coagulative necrosis

Coagulative necrosis is the type of necrosis in which protein denaturation is more prominent than enzymatic breakdown.

Histology impressions of coagulative necrosis

There is increased eosinophilia of the cytoplasm and decreased basophilia of the nucleus

both are associated with preservation of the general cellular architecture (the organ type is identifiable).

Organs affected by coagulative necrosis

Coagulative necrosis may occur in any organ. In organs with a high fat content

Liquefactive necrosis

occurs in situations in which enzymatic breakdown is more prominent than protein denaturation or in organs that lack a substantial protein-rich matrix (e.g.

Histology impressions of liquefactive necrosis

Loss of organ cell architecture. In the brain

Organs affected by liquefactive necrosis

Liquefactive necrosis is most commonly associated with organs that have a high fat and low protein content (e.g.

Fat necrosis

a change in adipose tissue due to trauma or the release of enzymes from adjacent organs (e.g.

Caseous necrosis

a "cheesy-looking" necrosis associated with tuberculosis infections and other granulomatous disease processes. Granulomas are a form of chronic inflammation due to some infections (e.g.

Cell death by necrosis

1. Ischemia reduces O2 and glucose

2. Anaerobic glycolysis produces lactate/lactic acid --- 2A.Reduced pH --- 2B. Reduced ATP

3. Reduce plasma membrane ion pump function -> ionic imbalances

4. Ca2+ accumulates in cell

5. Ca2+ activates phospholipase A2 ---5A. Plasma membrane disrupted ---5B. Cell swelling

6. Impaired mitochondrial electron transport ---6A. Reduced ATP ---6B. ROS formation

7. Cell dies

Apoptosis

Programmed cell death.

Patterns of occurrence of apoptosis

During growth and development

in adults

however

Phases of apoptosis

1. Initiation is the phase in which caspases (cysteine aspartic acid proteases) become catalytically active.

2. Execution is the phase in which the action of caspases causes the death of the cell.

Initiation phase of apoptosis

the phase in which caspases (cysteine aspartic acid proteases) become catalytically active.

Execution phase of apoptosis

the phase in which the action of caspases causes the death of the cell.

Apoptosis Initiation of extracellular pathway

The Fas ligand (FasL) binds to a member of the tumor necrosis factor family known as the Fas receptor. The activated Fas receptor in turn activates FADD (Fas associated death domain)

Apoptosis Initiation of intracellular pathway

The mitochondria release cytochrome c

Is there inflammation with apoptosis?

No

How is apoptosis different from necrosis?

Apoptosis does not generate an inflammatory reaction as necrosis does. Fragments of cells express phosphatidyl serine

therefore

fragments can be engulfed without generating an inflammatory reaction.

Necrosis vs Apoptosis: Cell Size

N: Enlarged A: Reduced

Necrosis vs Apoptosis: Nucleus

N: Discoloration A: Shrinkage and fragmentation

Necrosis vs Apoptosis: Plasma membrane

N: Disrupted A: Intact with altered orientation of phospholipids

Necrosis vs Apoptosis: Cellular contents

N: Leakage

Necrosis vs Apoptosis: Inflammation

N: Yes A: No

Necrosis vs Apoptosis: Role

N: Pathologic A: Usually physiologic

Increased mitochondrial matrix Ca2+ activates what?

apoptosis

Progerias

Rare diseases that seem to resemble accelerated aging

Two conditions of progeria diseases

Werner Syndrome (WS) and Hutchinson-Gilford progeria syndrome (HGPS).

Werner Syndrome (WS)

caused by recessive mutations in the WRN gene (a DNA helicase involved replication and telomere maintenance). Succumb to MI or cancer by their 40s or 50s.

Hutchinson-Gilford progeria syndrome (HGPS)

is caused by autosomal dominant mutation in the LMNA gene (codes for lamin A

Five cardinal signs of inflammation

1. Redness (Rubor)

2. Swelling (Tumour)

3. Heat (Calor)

4. Pain (Dolor)

5. Loss of function (Functio laesa)