Brainscape's Knowledge GenomeTM

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


See full index

MOD 1: DR > Chapter 2 > Flashcards

Chapter 2 Flashcards

1
Q

def of pathology

A

Pathology = study of _structural, bchmal, functional c_hanges in cells, tissues, organs that underlie dis

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

def of disease

A
  • – any deviation /interruption of the normal structure or function of a part, organ, sys of the body as manifested by characteristic symptoms and sign
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

def of disorder

A
  • Disorder – a derangement from abnormality of fucntion; a morbid physical or mental state
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Neoplasm

A

NEW ABNORMAL grth; specifically new grth of tissue in which the grth is uncontrolled and progressive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q
  • 4 aspects of dis process
A
  1. Etiology: cause
  2. Pathogenesis: sequence o_f cellular, biocehmical or molecular even_ts that occur after a tissue is damaged. Can be different in different population
  3. Morphologic changes: s_tructural alterations that occur_ in cells and organs that are characteristic of a disease or diagnostic of an etiologic process
  4. Clinical manifestations = fctal consequences of the changes that lead to clinical manifestations (signs and symptoms)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q
  • Defining the ______ and _____ is essential to understand the dis and the tx
A

etiology

pathogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q
  • Injury to ___ and to the ____ lead to tissue and organ injury, which determines the morphologic and clinical patterns of the disease.
A

cells and ECM

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

Our organs are in homeostasis with the stress placed on it. Increases, decreases or changes in stress on the organ can result in ________\_

A

Our organs are in homeostasis with the stress placed on it. Increases, decreases or changes in stress on the organ can result in growth adaptations.

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

what are adaptiations?

A

adaptations are REVERSIBLE responses to REPEATED pathologic or physioglic stress, where NEW STEADY states are acheived to allow the cell to continue to survive and function.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are our growth adaptations?

A
  • Increase in stress => Hyperplasia/hypertrophy
  • Decrease in stress => Atrophy
  • Changes in stress=> Metaplasia
    1. Dysplasia
    1. Aplasia
    1. Hypoplasia

REMEMBER THESE ARE REVERSIBLE

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

What is cell injury?

A

a cell is going to undergo injury when it can no longer normally adapt to to stress, is deprirved of nutrients or mutations affect the cell

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

Is cell injury reversible?

A

is reversible up to a certain point, but if the stimulus persists or is severe enough from the beginning, the cell suffers irreversible injury => cell death.

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

Cell death is usually d/t

A
  • ischemia (reduced blood flow),
  • infection,
  • toxins
  • or it can be a normal process in embryogenesis/dev/homeostasis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q
  • Pathways of cell death: ____, ____ or ______
A
  1. necrosis
  2. apoptosis
  3. nutrient deprivation can trigger adaptive responses that can cause cell death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the stages of progressive impairment following insults

A

Adaptatation => cell injury (3) => cell death (3)

cell injury: can not longer adapt, deprived of nutrients or mutations affect parts of cell. irreversible at first, but if stimilus is severe enough or persists long enough=> cell death, which is irreversible (via necrosis, apoptosis, nutrient deprivation triggers adaptations that cause CD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q
  • _____________ colors myocardium magenta to see stages of progessive impairment after insults
    • how did the myocardium adapt
      • what can we see on histology that will tell us that injury is reversible?
A

Tri phenyl tetrazolium colors myocardium magenta to see this

  • Hypertrophy d/t increase WL
  • Cell swelling and fat accumulation: NO gross/microscopic changes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe

hypertrophy and hyperplasia

these are adaption to _______ in stress

What types of cells can undergo each?

Describe subcategories

A

Both types of adaptations to INCREASE IN STRESS:

  • Hypertrophy: increase in the size of the cells => increase in the size of the organ by activating genes to increase PROTEIN SYNTHESIS of the cell (increase size of cytokeleton) and make new organelles. Dividing cells undergo both hyperplasia nad hypertophy. Non-dividing cells can ONLY undergo hypertropphu.
    • Physiologic hypertropgy: occurs d/t increase demand (working out), _mechnical stretch o_r hormones and GF
    • Pathologic hypertrophy: occurs d/t excessive GF and hormones
  • Hyperplasia: increase in number of cells that occurs in cell that are capable of DIVIDING cells via making new cells from stem cells OR proliferation of mature cells by GF.
    • Physiologic hyperplasia: occurs d/t :
      • GF/hromones in hormone sensitive organs that need to increase fx
      • damaged/resectied tissue that needs to recover
    • Pathologic hyperplasia: occurs d/t excessive hormones/GF and viruses. reversible if imbalance is fixed but can lead to CANCER/DYSPLASIA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q
  • Cells that can divide may respond to stress by undergoing …
A

hyperplasia

hypertrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Physiologic hypertrophy example

A
    1. Working out => causes muscle fibers to hypertrophy
    1. Uterus undergoes hypertophy d/t hormones in pregnancy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Generally, hyperplasia and hypertrophy occur together. An example would be a uterus during pregnancy.

There is an exception

A
  • permanent tissues (skeletal and cardiac muscle and nerves). These ONLY undergo hypertrophy because they cannot make new cells.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

The most common stimulus for cardiac muscle hypertrophy is

A

FAULTY VALVES AND HTN THAT CAUSE AN increase in hemodynamic load

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

_________ is reversible if ____________ is fixed and can lead to cancer and dysplasia

A

Pathological hyperplasia

hormone imbalance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Ex of pathologic hyperplasia

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q
  • __________are the main trigger for physiologic hypertrophy
  • ________ are the main trigger for pathologic hypertrophy.
A
  • Mechanical sensors are the main trigger for physiologic hypertrophy
  • GF and hormones are the main trigger for pathologic hypertrophy.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the molecular pathogenesis for cardiac hypertrophy?

A
    1. PAthological stressors: Mechanical sensors (+ by increased WL), GF (TGF-B, IGF1 and FGF) and physioligical stresstors: vasoactive agonists (a-adrenergic AGO, endothelin-1 and angiotensin II) => detect pathologic => +
      • Hypertrophic signal transduction pathways:
        * A. GCPR G-proteins (+ in pathologic hypertrophy)
        * B. P13K/AKT (+ in physioloic hypertrophy, like working out)
    1. Pathways activate transcription factors (GATA4, NFAT, and MEF2) =>
    2. Increase the synthesis of m proteins = hypertrophy!
    3. Switch of adult contractile proteins -> fetal or neonatal forms
      1. The genes can be switched back to the fetal form: alpha isoform of the myosin heavy chain is replaced by B isoform => producing slower, energy saving contractions
    4. express genes only expressed during early development => products participate in the cellular response to stress (ANP, ANF, cardiac alpha actin) => increases mechanical performance and decreases workload
    5. Increase production of growth factors to postively regulate hypertrophy
  • Adaptive changes can non longer keep up with the stress and the heart begins to give up => regressive changes in the myocardial fibers (lysis and loss of contractile elements) and myocyte death occur
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

how can we prevent hypertrophy of <3

A
  • NFAT, GATA4, MEF2 inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What cause hyperplasia?

A

1. Make new cells from stem cells

2. GF-driven proliferation of mature cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are examples of physiologic hyperplasia?

A
  1. female breast (glandular epithelial cells) is an example of hormonal hyperplasia and hypertrophy at puberty/preg in response to hormonal cues.
  2. Compensatory hyperplasia in liver regeneration and bone marrow
    1. BM: blood loss/hemolysis=> causes activation of EPO => increase in the red cell progenitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Examples of

  • Pathologic hyperplasia
A
    1. Endometrial hyperplasia: balance between estrogen and progesterone fucks up => increase estrogen production => pathologic hyperplasia of endometrial glands => a_bnormal menstrual bleeding_
    1. BPH: d/t too many androgens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Decrease stress causes atrophy (an adaption). Describe this process.

A
  • Decreased nutrient supply or disuse => leads to loss in the metabolic needs to maintain the cells at their current size => cell decreases protein synthesis and increases protein degradation
  • => reduction in the size of an organ or tissue by decreasing cell size and number =>
    • To decrease size (2):
        1. Ubiquitin-proteosome degradation of cytoskeleton:
          * + ubiquitin ligases => attach Ub to cell proteins => degraded in proteasomes
        1. Autophagy of cellular components
        2. Cell consumes its own components in vacuoles to reduce nutritional demand to match supply -> fuse with lysosomes -> lysosomes have hydrolytic enzymes necessary to break the organelles down.
    • To decrease number of cells:
      • 1. Apoptosis
  • loss of intracellular organelles. Atrophy can be physiologic or pathologic.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Types of atrophy

A
    1. Physiological atrophy common during development:
      * notochord
      * thyroglossal duct
      * Uterus after partuition
    1. Pathological atrophy has many causes and can be local or generalized:
      * decreased WL
      * Denervation atrophy
      * Ischemia (decreased BS)
      * Malnutrition
      * Loss of endocrine stiumulation
      * Pressure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q
  1. Pathological atrophy has many causes and can be local or generalized:
  • decreased WL
  • Denervation atrophy
  • Ischemia (decreased BS)
  • Malnutrition
  • Loss of endocrine stiumulation
  • Pressure
A
  • Decreased WL: no longer use muscle from BR or cast
    • initially reversible but if prlonged, skeletal m fibers decrease in number and size => atropgy and bone resorption=> osteoporosis of disuse
  • Denervation atrophy:The loss of innervation to muscle fibers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q
  1. Pathological atrophy has many causes and can be local or generalized:
  • decreased WL
  • Denervation atrophy
  • Ischemia (decreased BS)
    • ​give example
  • Malnutrition
  • Loss of endocrine stiumulation
  • Pressure
A

Ischemia (decreased BS)

  • Senile atrophy: arthersclerosis in BV to brain and heart => atrophy of brain

Malnutrition:

  • Profound protein-calorie malnutrition (marasmus): the body eating the skeletal muscle for NRG after using other resrouces (fat tissue), resulting in cachexia
    • In chronic inflammatory diseases, too much of inflammatory cytokines (TNF) suppresses appetite and lipid depletion and => muscle wasting.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q
  1. Pathological atrophy has many causes and can be local or generalized:
  • decreased WL
  • Denervation atrophy
  • Ischemia (decreased BS)
  • ​give example
  • Malnutrition
  • Loss of endocrine stiumulation
  • Pressure
A
  • Loss of endocrine stiumulation
    • Loss of hormones to hormone- responsive tissues like the breast, uterus, and vagina=> atrophy
      • Ex. menopause
  • Pressure
    • Tissue compression can cause atrophy and compress surrounding uninvolved tissues. May be d/t ischemia.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

conseques of menopause are d/t what?

A

pathological atrophy: loss of endocrine stimulation of the boobs, uterus and vagina cause ATROPGY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

pressure (or compression of tissue) can cause what

A

pathological atrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q
  • .__________ can be seen inside atrophic cells.
A

LIPOFUSCIN GRANULES/residual bodies (d/t autophagy that occurs to decrease cell size in atrophy), which makes tissue look brown

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

what is Metaplasia

how does it occur

most commonly involves?

A
  • Change in stress and and most commonly, chronic irritation, on an organ leads to a REVERSIBLE change to a new cell type (metaplstic cell) to better handle stress by reprogramming of stem cells or undifferentiated mesenchymal cells in CT => become new cells anme make new ones
  • Most commonly involves surface epithelium: (squamous, columnar or transitional/urothelium)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

The metaplastic changes that occur can leads to what?

A

Cell that can better protect against irritation and insult, BUT

Reduced function

Increase risk of cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Most common type of metaplasia

A
  • : epithelium changing from columnar => stratified squamous (which protects:
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What adaption occurs in the respiratory tract d/t

  1. chronic irritation (smoking)
  2. Vit A deficiency
  3. stones in salivary, bile and pancreatic glands
A

from columnar => stratified squamous,

stratified squamous can better handle irritation and insult but it looses its specialized job (muscus secretion and ciliary action)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What cellular adaptation is most common in

Barrett esophagus

A
  • Barrett esophagus = goblet cell Metaplasia (_squamous to columnar typ_e)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Baretts ESO can lead to what?

A

glandular cancers (adenocarcinomas)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q
  • Connective tissue metaplasia
    • ​what is it?
    • What is an example
A
  • CT metaplasia: The creation of cartilage, bone, or adipose tissue in tissues that do not normally contain these elements.
  • Myositis ossificans , an adaptation that occurs after intramuscular hemorrhage in where skeletal muscle -> makes bone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What is the mechanism metaplasia occurs?

A
  • the reprogramming of stem cells or undifferentiated mesenchymal cells in CT.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What 2 types of adaptations can lead to cancer?

A

1. Metaplasia

2. Pathologic hyperplasia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What adaptation occurs in mesenchymal cells?

A
  1. Mesenchymal tissues (CT like bone, fat, BV, cartilage) can undergo metaplasia.

Ex. Myositis ossificans: bone is made from skeletal muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Q: When does injury occur to a cell?

A

Injury occurs when a cell cannot adapt to stress.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Reversible cell injury

  • Occurs when?
  • Reversible?
A

Reversible cell injury

  • Occurs in the early stages or mild forms of cell injury.
  • Reversible if damaging stimulus is removed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Likelihood of injury depends on what?

A

1. Type of stress

2. How severe the stress is

3. Cell that is affected.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q
  • Neurons are _____ susceptible to hypoxia; skeletal muscle, on the other hand, __________.
A
  • Neurons are very susceptible to hypoxia; skeletal muscle, on the other hand, can withstand hypoxia for longer periods of time.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q
  • Hallmarks of reversible injury include:
A
    1. Reduced Oxphos => decrease in ATP
    1. Decrease in ATP causes cellular swelling bc Na/K ATPase channels stop working => Na+ cannot move out of cell and water moves in.
    1. Alters intracellular (mT and cytoskeleton) organnels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What cells are VERY sensitive to cell death?

A

heart

CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

There are 2 types of cell death: what is the difference between the two?

A
  1. Necrosis: when damage to MEMBRANES is severe, lysomal enzymes NTR cytoplasm => digest cell=> contents leak out => _acute inflammatio_n due to damage of the cell membrane and a disruption in the homeostasis of ions => death of a LARGE group of cells.
    * ALWAYS pathologic: never normally occurs
  2. Apoptosis: NRG-dependent,**genetically programmed cell death of single cells or a SMALL GROUP of cells that occursd/t damage to cells DNA/ misfolded proteins/ infections, pathological atrophy in paranchymal organs after duct obstruction. Characterized by nuclear dissolution, fragmentation of the cellwithout complete loss of membrane integrity**, and rapid removal of the cellular debris
  • No inflammation
  • Pathologic OR physiologic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What is the process of necrosis?

A

Process: ischemia, exposure to toxins, infection, trauma => damages cell membrane -> lysosomal enzs enter cytoplasm => digest cell => morphologic changes (mito damage, destruction ATP) => cellular contents leak into ECM > inflamm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

APOPTOSIS is characterized by:

A
  1. Apoptosis: a form of cell death characterized by nuclear dissolution, fragmentation of the cell without complete loss of membrane integrity, and rapid removal of the cellular debris; SAVING THE DAY FROM INFLAMMATION :)
    2.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q
  1. Which cell death process can BOTH pathologic and physiologic?
  2. Which CD process involves death of a large group of cells?
  3. Which CD process is followed by acute inflamation and why?
  4. Why CD process ocurs d/t damage of cells DNA or proteins?
A
  1. Apoptosis
  2. Necrosis
  3. Necrosis because membrane is damage -> lysomal enzymes to leak into cytoplasm -> digest cell -> damage mT and destroy ATP => causing cell contents to leak into ECM => inflammation
  4. Apoptosis occurs d/t damage of cell DNA/proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What are causes of cell injury?

A
    1. Hypoxia (ischemia, decrease O2 content in blood d/t cardioresp failure, Hb has a decrease O2 carrying capacity (occurs in anemia and CO poisoning) and s_evere blood loss_).
    1. Genetic problems (def of functional proteins, damaged DNA or misfolded proteins)
    1. Chemicals/drugs
    1. Infectious agents
    1. Immunological reactions (autoimmune diseases)
    1. Nutritional excess (obesity, high cholesterol) or defieincy (protein-cal def), vit def, self-imposed (anorexia)
    1. Physical agents (radiation, trauma, extreme temps, pressure changes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

how does hypoxia cause cell injury?

A

Hypoxia is low O2 delivery to tissue. However, Tissues are dependent on O2 because O2 is the electron-acceptor in the ETC. Accepting of electrons by O2 allows us to make ATP

  • Thus; low O2 -> impair oxidative phosphorylation -> low ATP -> cellular injury.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

How are the effects different if hypoxia occurs gradually or sudden/if severe?

A
  • If gradual, the cell can adapt and atrophy,
  • But it it is sudden or severe, the cell can die.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Morphological alterations in cell injury

  • All stresses and noxious influences exert effects FIRST at the ______ and then they progress to be able to be seen at the______
A

Morphological alterations in cell injury

  • All stresses and noxious influences exert effects FIRST at the molec/bchm level and then they progress to be able to be seen at the structural level.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q
  • Cells may become rapidly nonfctal after the onset of injury, but may still be viable (rever).

T or F?

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

When do morphological changes become apparent when a cell is injured

A

Injury leads to loss of cell function BEFORE we can see morphological changes.

  • Morpholoical changes are detected ONLY after biochemical alterations have caused cell death. t
  • he interval between injury and morphological changes depend on method of detection.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Which methods of detection detect injury first -last?

A
  1. Ultrastructural changes
  2. Light microscope changes
  3. Gross morphologic changes are seen last.

All of these occur after biochemical reactions have occured that can cause cell death.

65
Q

What morphological changes do we see with REVERSIBLE CELL INJURY on a LIGHT MICROSPE and Ultrastructural changes

A

Light microscope=> cell swelling and fattty change

  1. Cell swelling: if the first manifestation of all forms of injury because lack of ATP causes the cell not to maintain proper ion grandient, which then causes water flows INTO the cell.
  • Hydropic change or vacuolar degeneration: peices of ER that are released as small vacules in the cytoplasm
  • Increase eosinophillic staining (d/t loss of cytplasmic staining, which binds blue) and increased denatured cytoplasmic proteins (binds red)

Ultrastructural changes include:

  1. Changes in plasma membrane: blebbing, loss of microvillus
  2. ER swells: causing ribosomes to pop off
  3. mT swells
  4. Changes in nucleus: chromatin clumps, granular and fibrrilar elements break up.
  5. Fatty change: lipid vaculous appear in cytoplasm in cells mainly dept on fat metabolism (liver cells and heart cells)
66
Q

Cell sweling is best seen on what level?

What does it look like?

A

ORGAN LEVEL, hard to see with light microscope

=> organ is swollen causes some pallor, increased turgor, an_d increased weight._

67
Q

What is a morphological pattern of non-lethal injury we see in REVERSIBLE CELL INJURY.

A

hydropic change or vacuolar degeneration:

  • small clear vacuoles may be seen in the cytoplasm which are from pieces of the ER that have been pinched off and released.
68
Q

If myelin figures are present in ultrastructural changes of cell injury: is it reversible or irreversible?

A

IRREVERSIBLE!

is not assx with reversible cell injjury

69
Q

Reversible injury shows increased _______ staining (more pronounced in necrosis)

A

EOSINOphillic; d.t

  • Loss of cytoplasmic RNA (which binds blue dye, hematoxylin)
  • Denatured cytoplasmic proteins (bind red dye, eosin)
    *
70
Q

A cell with alot of microvillus and no blebbing is?

A

normal

71
Q

what stage of injury:

swollen mT

blebbing

lipid vaculous in cytoplasm

A

EARLY cell injury (early because reversible)

72
Q

What is the characteristic signs of atrophy?

A

Autophagy and decreased protein synthesis

73
Q

What processes underlie m_orpholical changes_ seen in necrosis?

What is the hallmark?

A

Necrosis: when damage to membrane is severe, lysosomal enzymes enter the cytoplasm, causing:

  1. Cells protein denaure
  2. Lethal injured cell undergoes enzymatic digestion

Membraen is destroyed, causing => contents leak out of leaky membranes and enzymes from its own lysosome that digest cell => acute inflammation (hallmark)

74
Q

How soon can we detect necrosis?

A

Histologically= hours (4-12

but, because contents leaked, within 2 hours we can detect ezymes and proteins in BLOOD

75
Q

What are distinctive morphological featuers of necrosis?

A

1. NEctrotic cells are more eosinophiliic on HE stain

2. Appear glassy d/t glycogen loss

*** Cell size: enlarged d/t swelling

3. Cytoplasm is vacuolated

  1. Dead cells are replaced by large masses of phospholipid called myelin figures that come from damaged cell membranes.
    * Then, eaten by other cells => broken down into FA, which can be calcified into calcium soaps

5. Breakdown of membranes

  1. Leakage and enzymatic digestion of cellular contents
  2. changes in nucleus
76
Q

what changes in morphological changes in nucleus do we see in necrosis?

A

Nuclear changes occur d/t breakdown of DNA.

  1. Karyolysis (nuclear fading): endonucleases (DNAase/RNAse) degrade DNA=> causing basophila of chromatin to fade”
  2. Pyknosis (nuclear shrinkage): nucleus shrinks => chromatin condenses into a solid, shrunken mass=> basophil increases. This is also seen in apop.
  3. Karyorrhexis (nuclear fragmentation) the pyknotic nucleus fragments and then w/in a day or 2 the cell disappears.
77
Q

Cmopare morphological changes of necrosis and apoptosis

Cell size:

Nucleus:

PM:

Cell contents:

Inflammation

Physiologic or pathologic?

A
78
Q

What are the 4 patterns of tissue necrosis?

A
  1. Coagulative necrosis
  2. Liquifactive necrosis.
  3. Caiseous necrosis
  4. Fibrinoid necrosis.
79
Q

Coagulative necrosis

faetures and typically caused by

A
  • Coagulative necrosis
    • Tissue remains firm and preserved for a few days to weeks d.t coagulation.
    • Structure proteins AND degradative enzymes are affected, therefore, the tissue is able to remain for a while
      • eosinophilic**, **anucleate cells observed
    • Dead cells are eventually removed by via: phagocytosis from leukocytes & lysosomal enzy.
    • Typically caused by an obstruction of a blood vessel that leads to the tissue – except brain. The affected area is called an infarct.
      *
80
Q

where is one place coagulative necrosis does not occur

A

brain

81
Q

a localized area of coagulative necrosis is called what

A

infarct

82
Q
  • Liquefactive necrosis is characterized by what?
A
  • Characterized by digestion of the dead cells that turns the dead tissue into a YELLOW liquid viscous mass (pus) typically from bacterial and fungal infections, bc they recruit alot of leukocytes
83
Q
  • Liquifactive necrosis is characteristic of what?
A
  1. bacterial and fungal infection
  2. Hypoxic death of CNS cells: only one that occurs in brain
84
Q
  • Caseous necrosis
    • aka
    • Often seen in:
A
  • aka cheese like
  • Soft, friable necrotic tissue that looks like cheese
  • Often seen in: granulomatous inflammation of TB (most common) or a fungal infection.
85
Q

On microscopic examination, caseous necrosis looks like?

A

fragmented and lysed cells and granular debris inside of a distinct inflammatory border called a granuloma

86
Q

What is helpful in fat necrosis to allow the surgeon localize the lesion

A

White-chalky fat saponification formed from FA-Ca2+.

87
Q
  • Fibrinoid necrosis
    • characteristic of:
    • How is it formed?
A
  • Characteristic of: : malignant HTN or vasculitis
  • Fibrinoid necrosis is is a special type of necrosis seen in immune reactions that involve blood vessesls: Ag- Ab complexes deposit in the walls of the arteries (type 3 hypersensitivity
  • Deposits of immune complexes + fibrin that leaked out => a bright pink staining in H/E stains called fibrinoid.
88
Q
  • Fat necrosis
A
  • NOT A PATTERN OF NECROSIS!
  • Adipose tissue that undergoes necrosis
  • In acute pancreatitis, pancreatic lipases or MO are released into pancrease or peritoneal cavity -> cause the release of TAGS from FA , which then combine with Ca2+ to produce a chalke white appearance (saponification)
89
Q

What is Gangrenous necrosis

A

Not A PATTERN, but coagulative necrosis that occurs in a extremity/limb and involves many tissue.

90
Q

When is gangraneous necrosis considered “wet gangrene”?

A

If gangrenous tissue becomes infected w bacteria, it can cause liquefactive necrosis as well => wet gangrene

91
Q
  • ______: thought to be most important in physiologic muscle hypertrophy
A
  • PI3K/AKT: thought to be most important in physiologic muscle hypertrophy
92
Q
  • EXAM QUESTION: A 68 year old obese, post-menopausal women experiences abdominal pain. A biopsy of her uterus is obtained and shows increased proliferation of endometrial tissue and presence of glands. What is the underlying mechanism of this hyperplasia?
A
  • : increased levels of estrogen; NOT GF
93
Q
  • In cancer and chronic infections, it is the ___ that suppresses appetite and depletes lipid stores, thus causing there to be wasting of the muscle tissue => atrophy
A

TNF

94
Q
  • What happens if necrotic cells are not taken back up by leukocytes?
A

dystrophic calcification: Ca2+ and other minerals deposit => calcified

95
Q

Parts of cell damaged most freq:

A
  • mT, cell mems, machinery of protein synth/packaging, DNA
96
Q
  • Responses to injurous stimilu depend on what:
  • Consequences of injury depend on:
A
  • Responses to injurous stimilu depend on what: type, severity and duration of injury
  • Consequences of injury depend on: type, state and how well the injured cell can adapt
97
Q

Cell injury occurs d.t one of 5 essential elements:

A
  1. ATP production via aerobic respiration in mT
  2. Integrity of mT (indep on ATP production)
  3. Integrity of plasma membrane, which maintains ion and osmotic homeostsis
  4. Protein synthesis, folding, degradation and refolding
  5. Genetics
98
Q

In general, what happens if you have a decreased of ATP?

A

Decreased ATP => _failure of NRG-dependent function_s => reversible injury=> fundamental cause of necrosis; associated with hypoxic and toxic injury,

99
Q

How is ATP made?

A
  • Oxidative phosphorylation of ADP (via reducing O2 in the ETC) in mT
  • Glycolytic pathway: uses glucose from body fluids or hydrolysis of glycogen to make ATP (no O2 needed)
100
Q
  • Depletion of ____ of ATP has profound effects on the critical cellular systems:
A

5-10%

101
Q
  • Hypoxia or toxic injury causes a decrease of oxidative phosphorylation -> decreases ATP production->

Depletion of ATP causes what?

A
  1. Activity of Na/K ATPase pump is reduced.
    1. Allows influx of H20 and Na+ and K+ efflux=> causes the cell to swell, dilation of the ER, loss of microvilli and blebs.
  2. Cellular energy metabolism is altered: increase in anaerobic glycolyis
    1. Decrease in ATP => Increase of AMP => anerobic glycolysis: makes ATP by metabolizing glycogen -> glucose (depleting glycogen stores), increases lactic acid production and decreases pH => causes clumping of nuclear chromatin & decrease activity of enzymes
  3. Activity of Ca pump is reduced
    1. => increased influx of Ca => many damaging effects.
  4. With greater amounts of ATP loss: ribosomes detach from ER=> decrease in protein synthesis
  5. Misfolding of proteins
    1. These then accumulate in the ER = cause an unfolded stress response => causes _ER stress response => c_auses cell injury and death
102
Q

What happens if ATP depletion persists

A

If ATP depletion goes on long enough, there will be enough damage to the mito and lysosomal membranes that will cause the cell to go into necrosis.

103
Q

How can we damage the mT?

A
  • 1. Oxygen deprivation
  • 2. Increase Ca2+ in cytosol
  • 3. ROS

Thus, they mT is sensitive to ALL types of injury (hypoxia and toxins

104
Q

What are the 3 major consequences of mito damage?

A
    1. Formation of a mitochondrial permeability transition pore: disrupts electrical potential of the mT, so that we cannot make ATP via Oxphos => which can then lead to necrosis.
    1. Creation of ROS d/t problem with oxphos
    1. Outer mitochondrial membrane increases in permeability, releases Cytochrome C, which can then activate caspases and + intrinsic pathway of apoptosis.
105
Q

Influx of Ca and Loss of Ca homeostasis: how does it cause cell injury?

A

Usually, cytoplasm has low concentrations of Ca2+ because it is stored in ER and mT, protecting us from damage.

  1. When toxins or ischemia is detected, intracellular Ca2+ is released from the mT and ER at first, then later there is an extracellular influx of Ca2+ into the cell d/t a leaky plasma membrane. Increased cytosolic Ca2+ then causes:
    1. Causes mitochondria permeability transition pores to open –> failure to generate ATP
    2. Activate enzymes that damages the cell
      1. Phospholipases –> membrane damage
      2. Proteases –> breaks down membrane and cytoskeleton proteins
      3. Endonucleases –> DNA and chromatin fragmentation
      4. ATPases –> faster loss of ATP
    3. Direct activation of apoptosis via caspases
106
Q

What is

  • One of the structural components of the mitrochondrial permeability transition pore?
A

Cyclophillin D

107
Q

Barrett’s esophagus is an example of what kind of metaplasia?

A

Squamous to columnar (columnar metaplasia)

*Metaplasias are named for what it turns into

108
Q
  • Mechanisms of membrane damage
A
  • ROS and lipid peroxidation
  • Decreased phospholipid synthesis
    • Via hypoxia or mitochondrial dysfunction.
    • Affects all cellular membranes including the membranes of the organelles.
  • Increased phospholipid breakdown
    • Via activation of Ca dependent phospholipases by increased levels of calcium.
    • Phospholipid breakdown leads to an increase in lipid breakdown products (Free fatty acids, Acyl carnitine, Lysophospholipids) which have a detergent effect on the membrane. They can also insert/exchange into the membrane and change the permeability and electrophysiologic alterations.
  • Cytoskeletal abnormalities
    • Increased Ca++ levels cause proteases to attack the cytoskeleton and allow it to detach from the membrane.
    • This allows the expanding membrane to detach and stretch/rupture while it is expanding.
109
Q

In reversible cell injury: there is cell swelling, membrane blebbling and swelling of the RER, decreasing protein synthesis.

Eventually, once the membrane is damaged, the cell undergoes IRREVERSIBLE DAMAGE.

  • Consequences of membrane damage
    • mt
    • plasma membrane
    • lysosome
A
  • Mitochondrial membrane damage –> Opening of the transition pore
    • Decreased ATP generation and release of Cytochrome C that trigger apoptosis
  • Plasma membrane damage –> Loss of osmotic balance and cellular contents including the compounds needed for making ATP again.
    • Leaky plasma membranes are bad
  • Injury to lysosomal membranes –> leakage of enzymes into cytoplasm and activation of acid hydrolases in the acidic intracellular pH of the injured cell
    • RNAses, DNAses, proteases, phosphatases, glucosidases.
    • Leads to necrosis.
110
Q

What IDAble morphalogical/biochemial changes to we see with irreversible injury?

A

none because no definition

111
Q
  • What 2 morphological changes consistently represent irreversible changes in cell injury?
A
  • Inability to reverse mitochondrial dysfunction (lack of oxidative phosphorylation and ATP generation) even after resolution of the original injury and profound problems with membrane function. Injury to lysosomal membranes results in the enzymatic dissolution of the injured cell that is characteristic of necrosis.
  • Leakage of intracellular proteins through the damaged cell membrane and ultimately into the circulation provides a means of detecting tissue-specific cellular injury and necrosis using blood serum samples.
112
Q
  • What are the biomarkers that are released from cardiac muscle when there is membrane damage?
A
  • Cardiac specific isoform of creatine kinase and troponin.
113
Q
  • What are the biomarkers that are released from liver and bile duct epithelium when there is membrane damage?
A
  • Alkaline phosphatase
114
Q
  • What are the biomarkers that are released from hepatocytes when there is membrane damage?
A
  • Transaminases
115
Q

What provides a means for the detection of tissue-specific cellular injury and necrosis using blood serum samples?

A

Leakage of intracellular proteins through the damaged cell membrane and ultimately into the circulation

116
Q

Accumulation of damage DNA and misfolded proteins triggers what kind of cell death?

A

Apoptosis

117
Q
  • In ______ tissue damage, have a narrow window in until the irreversible phase
A

cardiac tissue

118
Q
  • If having an MI, troponin IDd in blood w/in ______
A

2-4 hours

119
Q
  • Pt presentation:
    • Smoker, long hx of HTN
    • Chest pain, radiation down L arm
    • ST segment elevation
  • Having an MI
    • Cardiac cells deplete ATP quickly (bc mito damage) à lose contractility quickly
    • In cardiac tissue damage, have a narrow window in until the irreversible phase
  • If present w MI, cardiac biomarkers should be measured at presentation
    • If having an MI, troponin IDd in blood w/in 2-4 hrs

After he dies, what do we see on autopsy?

A

cardiomegaly because of longstanding HTN

120
Q
  • ATP depletion:
  • mT damage:
  • Influx if Ca2+
  • Accumulation of ROS:
  • Increased permeability of CM:
  • Accumulation of damaged DNA:
A
  • ATP depletion: failure of NRG dependent processes -> reversible injury -> eventually, necrosis
  • mT damage: failure of NRG depent processes bc no ATP -> ultimately necrosis; you can also have leakage of cytochrome C which can cause apoptosis
  • Influx if Ca2+: active enzymes that damage cell and damages mT by cauing pore to open
  • Accumulation of ROS: covalent modification of cell ptorins, lpipids and nucleic acids
  • Increased permeability of membrane: affects plasma membrane, lysosome membrane and mT membrane => typically causes necrosis
  • Accumulation of damaged DNA and misfolded proteins => triggers apoptosis
121
Q

What happens in a pt having a MI?

A

MI=> infarction => damage to mT => decrease in ATP and increase in ROS=> contraciility decreases

122
Q

most common type of cell injury in clinical medicine?

What does it result from?

A

ISCHEMIA=> decrease in blood flow => preventing blood from bring substrates, taking away waste products => decrease in O2 delivery to tissue => hypoxia.

123
Q

Ischemia is most often due to what?

A

1. Mechanical arterial obstruction

2. Reduced venous drainage

124
Q
  • [Q:] How is ischemia different from hypoxia?
A
  • Hypoxia NRG can be made by anaerobic glycolysis,
  • In ischemia, no blood flow thus the substrates for glycolysis cannot be delivered. Thus, aerobic AND anerobic metabolism cannot occur.
125
Q
  • ______ tends to cause more rapid and severe cell and tissue injury than does ______.

Fill in blank with: ischemia and hypoxia in the absence of ischemia

A

Ischemia: decrease in BF causes a decrease in arrival and leaving of dedation substances, which does not allow aerobic or anaerobic glycolysis.

126
Q

<3 muscle ceases to contract within 60 seconds of coronary artery occulusion. Are the cells dead or alive?

A

ALIVE. loss of contraction does not mean they are dead

127
Q
  • [Q:] What are the sequences of events that follow hypoxia or ischemia?
A
    1. Low O2 in cell = no oxphos = decreased ATP
    1. à No Na+ pump = K efflux, Na/H2O influx =swelling
      * There is also an influx of Ca2+
    1. Loss of glycogen and decreased protein synthesis
    1. If ischemia persists: irreversible injury and necrosis begin: associated with:
      * severe swelling of mT,
      * Extensive damage to PMs (giving rise to myelin figures)
      * Swelling of lysosomes.
      • Large flocculent amorphous densities develop in the mitochondrial matrix
      • These changes can be seen as early as 30-40 min in cardiac tissue after ischemia
128
Q

Mammalian cells have developed protective responses to deal with hypoxic stress, the best defined is what TF and what does it do?

A

- Hypoxia-inducible factor 1: a transcription factor used for protection and helps to:

  • BV formation
  • Stimulates cell survival pathways
  • Enhance anaerobic glycolysis
129
Q

Large, flocculent, amorphous densities develop in the mitochondrial matrix, what are these an indication of in myocardium and how quickly can they be seen?

A
  • Indication of irreversible injury
  • Seen as early as 30-40 mins. after ischemia
130
Q

What is the best known strategy for treating ischemia (and traumatic) brain and spinal cord injury?

A

Inducing hypothermia (CBT < 92 F)

    • Reduces metabolic demands of stressed cells,
  • decreases cell swelling,
  • suppresses formation of free radicals,
  • inhibits the host inflammatory response
131
Q

What does restoration of blood flow do?

A
  1. Promote recovery in cells that have been reversibly injured
  2. Promote damage to cells that have been IRREVERSIBLY injured
132
Q

What are the 4 mechanisms that contribute to ischemia-reperfusion injuries?

A

1) Oxidative stress :reoxygenation may increase ROS’s and reactive nitrogen species; also a decrease in activity of antioxidants

2) Intracellular Ca2+ overload:

  • Increase in Ca2+ Begins during acute ischemia.
  • Continues to get worse when the reperfusion happens and the blood brings lots more Ca to the cell and the membrane is damaged and unable to keep it out.
  • Remember that Ca causes the pores to open in the mito that makes shit go down in the cell. (depletes ATP à further injury)

3) Inflammation: surrounding cells are dying from necrosis and releasing factors that attract immune cells. neutrophils brought to site of inflammation by reperfusion and exacerbate initial insult
4) Complement system activation: some IgM antibodies have propensity to deposit in ischemic tissues, and when blood flow resumes, complement proteins bind the Ab’s and cause more cell injury and inflammation

133
Q
  • __________ == #1 contributor to cell death
A
  • Depletion of ATP == #1 contributor to cell death
134
Q
  • Chemical injury is a frequent problem in clinical medicine and is a major limitation to drug therapy. The liver metabolizes many drugs, making it a frequent target of drug toxicity. Actually, toxic liver injury is the MOST COMMON reason for ending use/development of a drug.
  • Chemicals induce cell injury by 1 of 2 mechanisms: wjat are they
A
    1. Direct toxicity to cells
    1. Indirect: conversion from inactive toxic chemical => reactive toxic metabolic
135
Q

What is the most frequent reason for terminating the therapeutic use or development of a drug?

A

Toxic liver injury

*Many drugs are metabolized in liver

136
Q

What 2 chemical can cause direct toxicity to cells?

and how?

A
  • 1. Mercury (mercuric chloride)
    • Binds to sulfhydryl groups of the cell membrane proteins => increases membrane permeability and inhibition of ion transport.
    • Greatest damage occurs to cells that concentrate, absorb, or excrete the chemicals like the _GI and kidne_y.
  • 2, Cyanide
    • Cyanide poisons cytochrome oxidase and inhibits oxphos.
137
Q

Which drugs therapeutic drugs induce cell damage by direct cytotoxic effects?

A

Many antineoplastic chemotherapy agents and antibiotics

138
Q

[SUMMARY Q:] What events occur in mild ischemia vs severe and prolonged ischemia?

A
  • Mild (reversible): Decreased oxphos => decrease ATP production => breaks Na/K ATPase => swelling.
  • Severe/prolonged ischemia (irreversible): severe swelling of mT => Ca2+ influx inside the mT and into the cell with rupture of lysosomes and plasma membrane => release of cytochrome C from mT => necrosis or apoptosis => DEATH.
139
Q

how do we get rid of cells undergoing apoptosis?

A
    1. They break up into apop bodies, which contains portions of cytoplasm and nucleus. However, PM remains intact.
    1. PM becomes a target for phagocytes, which devour it berore contents leak out so there is NO inflammation.
140
Q

Apoptosis can be physiological or pathological.

when does physiological apoptosis occur?

A
  1. Embryogenesis (destruction of cells during implantation, organogenesis, dev involution, and metamorphosis)
  2. Shrinkage of hormone sensitive dependent organs with hormone withdrawal.
    1. Exs. Endometrial shedding during menstration, ovarian follicle atresia in menopause, regression of lactating breast after weaning, and prostatic atrophy after castration
  3. Cell loss in proliferating populations
    • Ex. immature lymphocytes in bone marrow, thymus/B lymphocytes in germinal centers w/o useful Ag receptors, and epitlelial cells in intestinal crypts
  4. Elim of harmful, self-reacting lymphocytes
    • Either before or after they have matured.
  5. Death of host cells that have served their purpose: neutrophils in a acute inflammatory response and lymphocutes at the end of a immune response
141
Q

Apoptosis can be physiological or pathological.

when does physiological apoptosis occur?

A
  1. DNA damage
  2. Acummulation of misfolded proteins
  3. Virus-induced cell death via virus itself or the host immune response (T-cells)
  4. Pathological atrophy in parenchymal organs after duct obstruction.
142
Q
  • Apoptosis morphology
A
    1. Cell shrinkage; Dense cytoplasm with tightly packed organelles.
      * NO cell swelling.
    1. Chromatin condensation into oddly shaped masses in the periphery and then even the nucleus may fragment into pieces.
    1. Formation of cytoplasmic blebs and apoptotic blebs
      * First shows surface blebbing, then fragments into compact membrane bound apoptotic bodies (w organelles, and w or wo nuclear fragments
  • 4 The apoptotic cells or cell bodies are then eaten by Mfs then degraded by lysosomal enzs
    1. Apoptotic cells/bodies are very eosinophilic (and see dense chromatin)
    1. Bc shrinkage and quickly phagocytized and no inflamm, may not see on mico
143
Q

What is the most characteristic feature of apoptosis seen with electron microscope?

Describe it

A
  • Chromatin condensation
  • Chromatin aggregates peripherally, under the nuclear membrane, into dense masses and then may fragment
144
Q

What happens to the size of the cell in necrosis vs. apoptosis?

A

Necrosis the cell swells

Apoptosis the cell shrink

145
Q

Whhat are the 2 stages of apoptosis?

What are they guided by?

A
  • Guided by caspases
    1. Initiation phase: caspases are enzymatically activated
    1. Execution phase: other caspases trigger degradation of cellular components.
146
Q

Which pathway is the major mechanism of apoptosis in all mammalian cells?

A

Intrinsic Mitochondrial pathway; however, malignant cells have learned to avoid it

147
Q
  • What are the anti-apoptotic proteins in the that prevent activation of intrinsic mT pathway?
  • What domains do they contain?
  • What do they prevent?
A
  • BCL2, BCL-XL, MCL1
  • BH1-4 (four BH domains)
  • Cytochrome c leakage
148
Q

What are the pro-apoptotic proteins in the intrinsic mT pathway?

What domains do they have?

What do they promote?

A
  • BAX and BAK
  • BH1-4
  • Promote mitochondrial outer membrane permeability, allows leakage of Cytochrome C
149
Q

What are the major sensors of apoptosis in the intrinsic mT pathway.

Domains?

Function?

A
  • BAD, BIM, BID, Puma, Noxa
  • BH3 ONLY
  • Sensors of cellular stress and damage, regulate the balancebetween the anti-apoptotic and pro-apoptotic proteins
150
Q

Describe the intrinsic mT pathway.

A
    1. Cell viability is maintained when surviving signals (growth factors_)_ produce anti-apoptotic proteins like BCL2, BCL-XL and MCL-1, which make outer mT membrane impermeable and prevent leakage of cytochrome C.
      * Have 4 BH domains
      * Found in the outer mT membrane, cytosol and ER membrane
    1. Loss of survival signals, DNA damage and other insults => activate sensors (BH3-only proteins like BAD, BIM, Puma and Noxa), which balance the activity of the pro and anti-apoptotic proteins and detect damage=>
      * Sensors have only 1 BH domain
    1. Sensors block anti-apoptotic protein and activate pro-apoptotic proteins BAX and BAK, which form pores in mT membrane.
    1. Cytochrome C and other mT proteins leak
    1. Cytochrome C binds to APAF-1, forming an apoptosome
    1. Apoptosome binds caspase-9, the critical initiator caspase
    1. Caspase-9 cleaves adjacent caspase molecules, creating an auto-amplification process which activates the executioner caspases (caspase-3/6).
    1. ALSO Smac/Diablo (mito proteins) enter the cytoplasm and neutralize proteins (IAPs) that inhibit apoptosis.
      * IAPs usu block caspase activation to keep the cell alive
151
Q

Whatis another name for the extinsic pathway of apoptosis?

A

Death-receptor initated apoptotic pathway

152
Q

What are the BEST KNOWN death receptors of the extrinsic pathway of apoptosis?

A

- Fas (CD95)

- TNFR1

153
Q

What is the adaptor protein that begins the pathway of apoptosis once Fas binds FasL?

A

FADD

154
Q
  • Extrinsic (death-receptor initiated) apoptotic pathway
  • What is it?
    *
A
    1. Fas ligand (FasL), located on T cells that kill self-Ag and cytotoxic T cells that kill virus infected tumors, binds to Fas receptor, located on ALL cells.
      * Fas is located on all cells
    1. => 3+ Fas proteins come together and create a binding site for FADD (Fas-associated death domain), adaptor protein that initiates pathway.
    1. FADD then binds inactive caspase 8 (caspase 10 in humans) => activates, which will activate executioner caspases 3 and 6
155
Q

What protein is capable of inhibiting the death receptor pathway of apoptosis?

How?

What contains this protein?

A

FLIP

  • Binds pro-caspase-8, but cannot cleave and activate because it lacks protease domain. “locks it”

- Viruses and normal cells use this inhibitor to protect themselves from Fas-mediated apoptosis

156
Q

How are the extrinsic and intrinsic pathways of apoptosis interconnected in tissues like hepatocytes and pancreatic β cells?

A
  • In hepatocytes and pancreatic-B-cells, caspase 8 activated the BH3 protein -> feeding into the mito pathway
  • Activation of both pathways delivers a fatal blow to the cells
157
Q

What are the proteins in the execution phase of apoptosis (both pathways)?

A

- Caspase 3 and 6 are the executioner caspases

  • Cleave an inhibitor of cytoplasmic DNase, chops up DNA
  • Degrade the nuclear matrix
158
Q

What are the most prominent (“eat me”) signals for apoptotic cells ready to be engulfed by phagocytes?

A

- Phosphatidlyserine(ligand for macrophage receptor)

- Thrombospondin (adhesive glycoprotein recognized by phagocytes)

  • C1q (antibody of the complement system, recognized by phagocytes)
159
Q
A

MOD 1: DR (11 decks)

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