Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

General Pathology > Cell Death > Flashcards

Cell Death Flashcards

1
Q

Four Aspects of a Disease Process

A

1) ETIOLOGY or CAUSE (either genetic or acquired)
2) PATHOGENESIS
3) MORPHOLOGICAL CHANGES (structural alterations in cells or tissues that are characteristic of a disease or diagnostic etiologic process)
4) FUNCTIONAL DERANGEMENT AND CLINICAL MANIFESTATIONS (signs/symptoms)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is Pathogenesis?

A

A sequence of events in cell’s response to etiologic agent, from initial stimulus to the ultimate expression of the disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Stages of the Cellular Responses to Stress and Injurious Stimuli

A

1) Normal Cell (homeostasis)
2) if the cell under goes stress, than it can undergo ADAPTATION or if it is unable to adapt or simply undergoes injurious stimulus, cell injury occurs.
3) Cell injury can either be reversible or irreversible and if it is IRREVERSIBLE, cell death occurs
4) Cell death is either NECROSIS or APOPTOSIS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Types of Cellular Adaptations

A
  • Hypertrophy
  • Hyperplasia
  • Atrophy
  • Metaplasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Hypertrophy

A

Reversible INCREASE IN CELL SIZE leading to INCREASED SIZE OF ORGAN or TISSUE

**NO NEW CELLS, JUST BIGGER ONES

Examples:
> normal production of sex hormones at puberty/pregnancy

> exogenous stimuli like anabolic steroid use

> endogenous stimuli (internal) such as overproduction of Thyroid stimulating hormone

> PATHOLOGICAL HYPERTROPHY (non-physiological) from excessive or prolonged stress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Hyperplasia

A

A reversible increase in the NUMBER of cells in an organ or tissue resulting in an increase in the size of an organ or tissue

may be precancerous and are often see concurrently in proliferating cells

Examples:
> hormonal increase in estrogen leads to increase in # of endometrial cells (pathologic if excessive)

> compensatory increase in mass after damage/resection

> increased functional demand - secondary polycythemia (like with sleep apnea)

> persistent cell injury - epithelial hyperplasia/hyperkeratosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Mechanism of Hyperplasia

A

growth factor driven proliferation of mature cells

increased output of new cells from tissue stem cells

DILANTIN AND CYCLOSPORIN lead to hyperplasia in the CT of gums

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Atrophy

A

Adaptive response to stress in which the cell/tissue shrinks in volume and shuts down its differentiated functions – reducing its energy needs

Results in a decrease in cell size and function (clinically seen as a decrease in the size or function of a tissue or organ)

Causes can be physiologic – due to decreased work load or endocrine stimulation (immobilized by cast, decreased size of uterus following child birth or disease)

Pathological – primarily due to denervation of muscle, diminished blood supply, nutritional deficiency. chronic injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Mechanisms of Underlying Atrophy

A

Decreased metabolic activity reduces protein synthesis and increased protein degradation in cells

Shrinkage of cells/tissue/organ due to
- nutrient deficiency: activates a ubiquitin/proteasome pathway: ligases attach ubiquitin to proteins which target them to degradation in proteasomes

  • autophagy: starved cell “eats” its own content to attempt to reduce nutrient demand to match supply
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Metaplasia

A

Reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type

Most common replacement is glandular columnar epithelium by squamous epithelium

IS A RESPONSE TO PERSISTENT INJURY
(smoking, GERD, chronic infection)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Mechanism underlying Metaplasia

A

Arises from re-programming stem cells or undifferentiated mesenchymal cells present in adult tissue due to local effectors (cytokines, growth factors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Reversible Changes Induced by Injury

A

(reversible if damage is removed)

CHANGES IN ION CONCENTRATION AND WATER INFLUX

HYDROPIC SWELLING (light microscopic change)

FAT DROPLET FORMATION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Ultrastructural changes in Reversible injury

A

Plasma Membrane: blebs (outpouches) appear and there is a lose of microvili

Mitochondria: swells and may develop small amorphous densities

ER; dilates and ribosomes detach

Nucleus: chromatin clumping, break down of granular and fibrillar elements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Examples of Nuclear Changes

A

PYKNOTIC - nuclear condensation
(clumping) increases as the cell dies

KARYORREHEXIS - small pieces of the nucleus breaking off

KARYLOYSIS - breaking up of the nucleus totally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Hydropic Swelling

A

increase in cell volume characterized by a large amount of pale CYTOPLASM and a normally located nucleus

accumulation of sodium is what leads to increase in water content and the organ often becomes heavier and firmer

IS A REFLECTION OF ACUTE. REVERSIBLE, CELL INJURY (however can be irreversible if injury continues)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Necrosis

A
  • Cells are unable to maintain membrane integrity
  • Contents leak out
  • Elicits an inflammatory response

• Cell contents are digested by cellular lysosomal enzymes and
inflammatory process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Coagulative Necrosis

A

The outline of the dead cells and architecture are maintained and the tissue is somewhat firm

  • Protein denaturation (low pH) is the primary pattern
  • Example: myocardial infarction
  • Earliest tissue microscopic or gross evidence 4-12 hours after cell death, enzymes released immediately ~2hrs
18
Q

Liquifactive necrosis

A

The dead cells undergo disintegration and affected tissue is liquefied

  • Enzyme digestion by leukocyte hydrolases dominates
  • Example: cerebral infarction or bacterial infection
  • Evoked by bacterial or fungal infection
  • White blood cells (neutrophils) have hydrolases which digest dead cells
  • Abscess is formed when cells are killed and digested faster than
    the repair process, leaving a cavity filled with leukocytes and fluid (pus = dead stuff and white blood cells )
  • Also seen in cerebral infarcts – brain tissue liquefies – without an inflammatory response
19
Q

Gangrenous necrosis

A

clinical term often involving both coagulative (due to ischemia) and liquifactive (due to infection) necrosis

20
Q

Caseous necrosis

A

a form of coagulative necrosis (cheese-like)
associated with tuberculosis lesions
- Microscopic: granuloma

21
Q

Fat necrosis

A

Enzymatic digestion of fat associated with pancreatitis
and leakage of enzymes into abdomen

  • Occurs when activated pancreatic lipases are released into the pancreas and the peritoneal cavity
  • Microscopic: necrotic fat cells
22
Q

Fibrinoid necrosis

A

immunologically-mediated vasculitis in blood vessel

walls

23
Q

Mechanisms of cell injury

A

ALL LEAD TO CELL DEATH DETECTABLE AT THE TISSUE LEVEL

Decrease in ATP production and mitochondrial damage

Entry of Ca2+ leading to an increase in mitochondrial permeability and/or activation of multiple cellular enzymes

Increase in ROS (reactive oxygen species) leads to damage to lipids, proteins, DNA

Membrane damage of either plasma membrane or lysosomal membrane leading to loss of cellular components (plasma) or enzymatic digestion of cellular components (lysosomal)

Protein Misfolding/DNA damage leading to activation of pro-apoptotic proteins

24
Q

Mechanism of Cell Injury

A
  • Cellular response to injury depends upon the nature of the injury, duration and severity
  • Consequences of cell injury depend on the type, state, and adaptability of the injured cell

• Cell injury results from different biochemical mechanisms acting on
several essential cellular components

25
Q

Sequence of Events in Ischemic Injury

A

Ischemia - no blood to an area (vessel blocked so there is blood on one side but not the other; causing ischemia on the side with no blood)

There is a switch to anaerobic glycolysis which results in increased lactic acid and acidic pH.

Reduced OX PHOS and ATP levels have a central role and ischemia can cause membrane damage

CARDIAC CELLS CEASE TO BEAT AFTER 60 SECONDS OF ISCHEMIA

26
Q

Functional and morphologic consequences
of decreased intracellular
ATP during cell injury

A

• Decrease of ATP during cell injury is related to
ischemia (lack of blood
supply)

• Initial event is in the
mitochondria, which
decreases ATP, and can
eventually lead to ischemic necrosis

• These changes are reversible in the beginning, but if lack of oxygen continues, it will lead to complete disruption of the cell

27
Q

Consequences of

Mitochondrial Damage

A
  • mPTP: mitochondrial permeability transition pore
  • MAC: mitochondrial apoptosis-induced channel
  • Damage to mitochondria can cause both necrosis and apoptosis
28
Q

Loss of Calcium

Homeostasis

A

• Increased cytosolic calcium – opening of
mitochondrial pores – failure of ATP generation

  • Activated damaging enzymes
  • Induction of apoptosis
29
Q

Membrane Damage

A

• Swelling can lead to rupture

• Lysosomes, plasma membrane,
mitochondria

30
Q

Reactive Oxygen Species (ROS)

A

Can damage cell either way (pathologic or removal of free radicals)

31
Q

Hypoxia vs. Ischemia vs.
Ischemia-Reperfusion
Injury

A

• HYPOXIA is a deficiency of oxygen, which causes cell injury by reducing aerobic oxidative respiration

  • Cardio-respiratory failure (CHF, COPD) leads to inadequate oxygenation

• ISCHEMIA is a loss of blood supply from impeded arterial flow and compromises the supply of oxygen and metabolic substrates, including glucose

-Ischemic tissues are injured more rapidly and severely than are hypoxic tissues

• ISCHEMIA-REPERFUSION INJURY: paradoxically, restoration of blood flow induces additional cell death because of ROS generation, activation of complement by IgM antibodies and cytokines that induce an inflammatory response

32
Q

Three Ways Cells Can DIE

programmed cell death

A

• PCD I: APOPTOSIS – induced to commit suicide
- DNA damage

• PCD II: AUTOPHAGY – starve to death
- Lack of food

• PCD III: NECROSIS – killed by injurious agents
- Membranes are damaged or ATP levels are not restored

• Necrosis, autophagy, and apoptosis have different underlying mechanisms

33
Q

Irreversibly cell injury occurs when?

A

Membranes are damaged or ATP levels not restored….death by necrosis

DNA damage…death by apoptosis

Lack of food….death by autophagy

34
Q

Apoptosis

A
  • A pathway of cell death
  • Induced by a tightly regulated suicide program
  • Cells destined to die activate intrinsic enzymes that degrade the cells’ own nuclear and cytoplasmic proteins
  • Estimated 50-70 billion cells die each day
35
Q

Physiological Apoptosis

A
  • Tissue homeostasis balance proliferation
  • Embryogenesis
  • Involution hormone withdrawal (lactating breast)
  • Eliminate self-reactive lymphocytes
  • Eliminate inflammatory neutrophils
36
Q

Pathological Apoptosis

A
  • DNA damage (p53)
  • Unfolded protein response (neuro-degeneration)
  • Some infections (viral)
37
Q

MECHANISMS of apoptosis

A

Apoptosis results from the activation of enzymes called CASPASES

  • Exist as inactive proenzymes that must undergo enzymatic cleavage to become activated
    - Activation is a balance between pro-apoptotic and anti-apoptotic proteins

Two phases:

  • Initiation phase: some caspases become active
  • Execution phase: other caspases trigger the degradation of cellular components
38
Q

Two pathways converge on caspase activation

A

Intrinsic mitochondrial pathway (major mechanism in mammalian cells)

  • growth factor withdrawal
  • DNA damage (by radiation, toxins, free radicals)
  • protein misfolding (ER stress)

Death receptor pathway
- receptor- ligand interactions (Fas and TNF receptor)

39
Q

Key players in apoptosis

A

• Mitochondria: intrinsic pathway
• Caspases
• Endonucleases: degradation of cellular components
• p53: guardian of genome – DNA damage too great for repair – triggers
apoptosis
• Bcl-2 family proteins: cell death rheostat

o Control release of mitochondrial pro-apoptotic proteins
• Death receptors: extrinsic pathway (tumor necrosis factor, Fas ligand)

40
Q

Can kill other cells by

inducing apoptosis

A
  • Fas ligand generating cells kill cells that have Fas receptor by extrinsic pathway
  • Tumor necrosis factor (TNF) secreted by macrophages, for example, binds TNF
  • Killer lymphocytes inject granzyme through perforin
41
Q

Features of apoptosis
essential to the immune
response

A
  • Cells autodigest (including intracellular pathogens, e.g. viruses)
  • Loss of plasma membrane integrity is the last step – therefore, intracellular pathogens are destroyed before integrity is lost
  • What would happen if the cells died by necrosis instead?
42
Q

Why are cell responses

important to us?

A
  • Cell responses to injury can be reversible given appropriate treatment
  • Disrupted cell death program is associated with cancer
  • Early stage oral cancer is primarily detected by dentists
  • Most chemotherapies turn on the cell death program – may adversely affect oral tissues
  • Immunosuppressant drugs interfere with cell death and may cause a tissue response
  • Turning off the cell death program can reduce volume of cells that die during trauma

General Pathology (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions