Cell Injury Flashcards
1
Q
What is Etiology?
A
Why disease arises
2
Q
What is pathogenesis
A
How disease develops
3
Q
In **reversible **cell injury, what changes you can see? And why?
A
Become Swollen because water gets inside as a result of the failure of energy-dependent pumps
4
Q
What are the two main morphological changes in REVERSIBLE cell injury?
A
Cellular Swelling and Fatty Change
5
Q
Repercussions of multiple cell swelling or the whole organ? [Macroscopic]
A
Pallor (as a result of compression in capillaries), Turgor and Weight increase.
6
Q
Repercussions of multiple cell swelling or the whole organ? [Microoscopic]
A
Small clear Vacuoles within Cytoplasm. (Distended segments of the ER)
7
Q
Non-Lethal Injury caused of cellular swelling is named…?
A
Hydropic Change or Vacular Degeneration
8
Q
In reversible cell injury, Fatty Change is manifested by?
A
The appearance of Triglyceride-Containing lipid vacuoles in the Cytoplasm (typically in the liver).
9
Q
Name of the red stain that appears in injury cells?
A
Eosinophilic
by H&E
10
Q
Intracellular changes associated with cell injury include…?
Inflated and broken furry red balloon
A
- Redder
- Blebbing
- Distortion of microvilli
- Loosening of intracellular attachments
- Mitochondrial swelling
- Dilation of ER
- Detachment of ribosomes in ER.
- Nuclear alterations (chromatin clumping)
- Myelin Figures
11
Q
Although there are no definite morphological correlations of Irreversibility, how is characterized?
A
-Inability to restore mitochondrial function (OP and ATP prod.)
-Loss of structure and functions of intracellular and plasma membrane.
-Loss of DNA and chromatin structural integrity.
12
Q
The injury of lysosomal membranes result in…?
A
Enzymatic dissolution of the injured cell, which is the culmination of NECROSIS
13
Q
Commonly types of injuries (or causes) in Necrosis
A
-Ischemia
-Toxins
-Various infections
-Trauma
(To severe to be repaired)
14
Q
Features of A) Necrosis and B) Apoptosis in [ Cell size ]
A
A) Enlarged (Swelling)
B) Reduces (shrinkage)
15
Q
Features of A) Necrosis and B) Apoptosis in [ Nucleus ]
A
A) Pyknosis-> Karyorrhexis->Karyolisis
B) Fragmentation in very small fragments
16
Q
Features of A) Necrosis and B) Apoptosis in [** Plasma Membrane** ]
A
A) Disrupted
B) Intact; Altered structure. (Especially orientation of lipids)
17
Q
Features of A) Necrosis and B) Apoptosis in [ Cellular Contents]
A
A) Enzymatic Digestion; may leak out of the cell
B) Intact; (released in apoptotic bodies)
18
Q
Features of A) Necrosis and B) Apoptosis in [** Adjacent Inflammation**]
A
A) Frequent
B) No
19
Q
Features of A) Necrosis and B) Apoptosis in [ Physiologic or pathologic role]
A
A) Invariably pathologic
B) Often physiological (elimination of unwanted cells) or maybe pathologic after some types of injury
20
Q
What is Apoptosis?
A
Is a process that eliminates cells with abnormalities and promotes clearance of the fragments of the dead cells without eliciting an inflammatory reaction.
21
Q
Apoptosis or Necrosis?
Occurs in healthy tissues. It serves to eliminate unwanted cells during normal development and to maintain constant cell numbers, so it is not necessarily associated with pathologic cell injury.
A
Apoptosis
22
Q
Myocardial cells become noncontractile after how many minutes of ischemia?
A
1 to 2 minutes
23
Q
Myocardial cells die until how many minutes?
A
20 to 30 minutes of
ischemia
24
Q
Morphologic features indicative of the death of ischemic myocytes appear by electron microscopy within…?
A
2 or 3 hours after the death of the cells
25
Morphologic features indicative of the death of ischemic myocytes appear by **light Microscope** in how many hours?
6 to 12 hours
26
What is Necrosis?
is a form of cell death in which cellular membranes fall apart,
and cellular enzymes leak out and digest the cell. Also inflammation
27
Morphological Necrotic Cytoplasm changes?
- increased eosinophilia (red)
- glassy homogeneous appearance
-vacuolated and appears “moth-eaten" (polilla)
28
Morphologic Nuclear changes by: **Pyknosis**
Nuclear shrinkage and increased basophilia; the DNA condenses into a dark shrunken mass
29
Morphologic Nuclear changes by: **Karyorrhexis**
The pyknotic nucleus can undergo fragmentation
30
Morphologic Nuclear changes by: **Karyolysis**
The basophilia fades because of the digestion of DNA by DNase activity.
31
After **Karyolysis,** in how many days does the nucleus disappear in the dead cell?
1-2 days
32
Process of dead cell calcification?
Dead cells-> Myeline Figures-> degraded to Fatty Acids -> Bind to Ca Salts
33
Fibrinoid necrosis is detected ONLY by?
Histologic examination
34
Morphologic Patterns of Tissue Necrosis for: **Coagulative necrosis** ?
The underlying tissue architecture is preserved for at least several days after death of cells in the tissue. Eosinophilic and anucleated cells may persist for days or weeks
35
Type of Necrosis that is typicall in **infarcts** in solid organs (Except for the brain)
Coagulative necrosis
36
Morphologic Patterns of Tissue Necrosis for: **Liquefactive necrosis** ?
It is seen in focal bacterial and,occasionally, fungal infections because they stimulate rapid accumulation of inflammatory cells, and the enzymes of leukocytes digest (“liquefy”) the tissue. Cells are completely digested,transforming the tissue into
a **viscous liquid** creamy yellow and is called **pus**
37
**Hypoxic death** of cells within the **central nervous system** often evokes...? (Type of necrosis)
Liquefactive necrosis
38
Morphologic Patterns of Tissue Necrosis for: **Gangrenous necrosis** ?
| Not an official pattern (only in clinical practice)
Condition of a limb that has lost its blood supply and has undergone coagulative necrosis and liquefactive necrosis involving multiple tissue layers
39
What is known as "**wet Gangrene**"
After by liquefactive necrosis + Coagulative necrosis. The Pus generated by the destructive contents of the bacteria and the attracted leukocytes
40
Morphologic Patterns of Tissue Necrosis for: **Caseous necrosis** ?
Most often encountered in foci of tuberculous infection. Caseous means “**cheeselike**,” referring to the friable yellow-white appearance of the area of necrosis on gross examination. In H&E are granulomas
41
Morphologic Patterns of Tissue Necrosis for: **Fat necrosis** ?
**Focal areas of fat destruction**, typically resulting from the release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity (Acutepancreatitis)
42
The released fatty acids combine with calcium to produce **grossly visible chalky white areas (fat saponification)** are characteristics of..?
Fat necrosis
43
Morphologic Patterns of Tissue Necrosis for: **Fibrinoid necrosis ** ?
It usually occurs in immune reactions in which complexes of antigens + antibodies are deposited in the walls of blood vessels, but it also may occur in severe hypertension.
44
Deposited immune complexes and plasma proteins that leak into the wall of damaged vessels produce a bright pink, amorphous appearance on H&E called **fibrinoid** (fibrinlike)
Fibrinoid necrosis ((e.g., polyarteritis nodosa))
45
**Irreversible injury and cell death** in these tissues elevate the serum levels of these proteins in **Cardiac muscle**
A unique isoform of the enzyme **Creatine kinase (CK)** and contractile protein **Troponin**
46
**Irreversible injury and cell death** in these tissues elevate the serum levels of these proteins in **Hepatic
bile duct epithelium**
Alkaline phosphatase (ALP)
47
**Damage** in these tissues elevate the serum levels of these proteins in **Hepatic Cells**
**ALT and AST **(Alanine transaminase and Aspartate transaminase)
48
Pathway of cell death in which cells activate enzymes that degrade the cells’ own nuclear DNA and nuclear and cytoplasmic proteins
Apoptosis
49
During normal development of an
organism, some cells die and are replaced by new ones
Physiologic apoptosis
50
**Mechanism of Apoptosis** for a **Physiologic** condition during: [Embryogenesis]
Loss of growth factor signaling
51
**Mechanism of Apoptosis** for a **Physiologic** condition during: [Turnover of proliferative tissues
(e.g., intestinal epithelium,
lymphocytes in bone marrow,
and thymus)]
Loss of growth factor signaling
52
**Mechanism of Apoptosis** for a **Physiologic** condition during: [Involution of hormonedependent tissues (e.g., endometrium)]
Decreased hormone levels lead
to reduced survival signals
53
**Mechanism of Apoptosis** for a **Physiologic** condition during: [Decline of leukocyte numbers at the end of immune and inflammatory responses]
Loss of survival signals as stimulus for leukocyte activation is eliminated
54
**Mechanism of Apoptosis** for a **Physiologic** condition during: [Elimination of potentially harmful self-reactive lymphocytes]
Strong recognition of self antigens induces apoptosis by both the mitochondrial and
death receptor pathways
55
**Mechanism of Apoptosis** for a **Pathologic** condition during: [DNA damage]
Activation of proapoptotic
proteins by **BH3-only sensors**
56
**Mechanism of Apoptosis** for a **Pathologic** condition during: [Accumulation of misfolded proteins]
Activation of proapoptotic proteins by **BH3-only sensors**, possibly **direct activation of
caspases**
57
**Mechanism of Apoptosis** for a **Pathologic** condition during: [Infections, especially certain viral infections]
Activation of the mitochondrial pathway by viral proteins Killing of infected cells by
**cytotoxic T lymphocytes**, which activate **caspases**
58
Caspases are activated by...?
Apoptosis
59
Which pathway is more common for caspase (and apoptosis) activation
Mitocondrial (Intrinsic) pathway
60
Explain step by step **Miochondrial (intrinsic) pathway**
->Cell injury
->Activate BH3 prt Sensors -> Bak and Bax dimerize
-> Form channels in mitocondria
-> Cytochrome c and other prt escape
->Caspase Activation
->Nuclear fragmentation (by endonucleases) and apoptotic bodies
61
Explain step by step **Death Receptor (extrinsic) Pathway**
->Receptor-Ligand interaction ( Fas CD95, TNF receptor)
-> Death domain binding
->Caspase activation
->Nuclear fragmentation (by endonucleases) and apoptotic bodies
62
How Macrophages recognize a apoptotic cell?
Phosphatidylserine is inverted opposite to cytoplasm and also cells secret soluble factors for recruiting phagocytes
63
Explain Necroptosis
Initiated by TNF receptors but Kinases called rceptor-interactin Protein (RIP) are activated for dissolution of the cell like Necrosis.
64
Explain Pyroptosis
Assosiated with activation of Inflammasomes for activation of Caspases for some infected cells.
Apoptosis + Fever
65
Autophagy is?
Lysosomal digestion of the cell own components.
Starved cells can live by eating its own contens and recycling them for nutrients and energy.
66
Pathway of Autophagy
-> Straving
->Autophagy genes activation
->Formation of autophagy vacuole (with cytosolic ocntent inside)
->Fusion of vacuole with lysosomes
->Enzyme digestion
->Use them as a source of nutrients
67
How much time do striated skeletal muscle cells resist with complete ischemia without irreversible injury?
2 to 3 hours
68
Hoy many Kg of ATP does a heathy human burn every day?
50-75 Kg/day
69
What is HIF-1?
**Hypoxia Inducible Factor 1** (A family of transcription factors)
70
Function of HIF-1
| Hypoxia inducible factor 1
Stimulates the synthesis of several proteins that help the cell to survive with low oxygen such as VEGF for angiogenesis to increase blood flow. Also stimulates the uptake of glucose and glycolysis.
| Vascular Endothelial Growth Factor
71
What is the result of the reduced activity of plasma membrane ATP-dependent sodium Pumps?
Intracellular acumulation of Na and efflux of K. Gain of solutes is accompanied by isoosmotic gain of water causing swelling and ER dilatation
72
Consecuence of prolonged anaerobic glycolysis?
Lactic Acid accumulation, decreased intracellular pH, and cellular enzymes.
73
Hypoxia increase ROS?
Probably, but it is not been fully understanded
74
Ischemia-Reperfusion Injury increased injury? why?
Sometimes, New damage may be initiated by **ROS** and also the **leukocytes** produce it. **Complement and antibodies** are also activated **more inflammation**
75
Oxidative stress refers to...?
Cellular abnormalities that are
induced by ROS
76
Causes of **ROS in cell Injury**
| Free Radical-mediated injury
->Chemical and Radiation injury
-> Hypoxia,
-> Cellular aging
-> Tissue injury caused by inflammatory cells
-> Ischemia-reperfusion injury.
77
What are Free Radicals
Are chemical species with a single unpaired electron in an outer orbit
78
Why are Free Radicals are dangerous?
their chemical states are **extremely
unstable**, and readily **react with inorganic and organic molecules**; when generated in cells, they avidly
**attack nucleic acids** as well as cellular **proteins and lipids**. Also initiate reactions in which molecules that react with the free radicals are themselves converted into other types of free radicals, thereby **propagating the chain** of damage.
79
What is Respiratory Burst
| or Oxidative Burst
The ROS generated in the Phagolysosomeand phagosomes by the leukocytes. They also produce Hypoclorite, peroxynitrite and others...
80
How cells remove ROS?
->Some by itself **spontaneously**
-> By the action of **Superoxide dismutase** (**SOD**) (Removes Superoxide)
->**Glutathione Peroxidase**s (GSH) (Degrade peroxide and Hydroxyl radical)
->**Catalases** (degrade peroxide)
->**Other enzymes** in the cytosol remove peroxynitrite
->Endogenous and exogenous **anti-oxidants ** (e.g., vitamins E, A, and C and β-carotene)
81
ROS causes cell injury by damaging multiple components of cells, which ones?
->**Lipid peroxidation of membranes**. (Damage to plasma membranes as well as mitochondrial and lysosomal membranes)
-> **Crosslinking and other changes in proteins** (resulting in enhanced degradation or loss of enzymatic activity)
->**DNA damage** (reactions with thymine residues in nuclear and mitochondrial DNA produce singlestrand breaks)
82
Define what happens when there's Endoplasmic Reticulum Stress
The accumulation of misfolded proteins in a cell can stress compensatory pathways in the ER and lead to cell death by apoptosis.
If unfolded or misfolded proteins accumulate in the ER, they first induce a protective cellular response that is called the **unfolded protein response**
83
What happens in the **unfolded protein response**?
This adaptive response activates signaling
pathways that increase the production of chaperones and decrease protein translation, thus reducing the levels of
misfolded proteins in the cell.
84
What happen when a large amount of misfolded protein accumulates and cannot be handled by the adaptive response "unfolded protein response"?
the signals that are generated result in
**activation of proapoptotic sensors of the** **BH3-only family** as well as **direct activation of caspases,** leading to **apoptosis by the mitochondrial (intrinsic) pathway**
85
What could cause the accumulation of misfolded proteins?
-Mutations
-Aging
-Infections (specially viral)
-Ischemia
Hypoxia
86
Damage of DNA lead to the accumulation of which sentinel protein?
p53
87
What **p53 protein** does?
-> Arrest cell cycle G1 (allows the DNA be repaired before mitosis)
-> Triggers apoptosis (if the damage can't be repaired) (Stimulating BH3-only
88
Repercussions of a **mutation in p53**
**Cancer **(can't undergo to apoptosis)
89
What causes the **mitochondrial permeability transition pore**?
**Damage to mitochondria** lead the formation of a** high-conductance channel** in the membrane this leads to the loss of mitochondrial membrane potential and pH changes, further compromising oxidative phosphorylation.
90
Increased permeability of the plasma membrane and lysosomal membranes is a feature of apoptosis?
**ABSOLUTELY NOT**
91
What is **Hypertrophy?**
Increase in size of cells (Resulting in an increase in the size of the organ) by the increased amoints of structural proteins and organells
| NO NEW CELLS, JUST BIGGER CELLS
92
What is **Hyperplasia?**
Hyperplasia is an increase in the number of cells in an organ that stems from increased proliferation, either of differentiated cells or, in some instances, less differentiated progenitor cells.
| Increase in Cell Number
93
Adaptive response in cells **capable of replication** that increase cell number
Hyperplasia
94
Adaptive response in cells **with limited capacity of replication** that increase their size.
Hypertrophy
95
During pregnancy, there is Estrogen stimulated smooth muscle _______?
a) Hypertrophy
b) Hyperplasia
c) both
C)
96
In response to **increased workload**, the **striated muscle cells **in both the **skeletal muscle** and the** heart** undergo only?
**a) Hypertrophy
b) Hyperplasia
c) both**
Hypertrophy
| Because adult muscle cells have a limited capacity to divide
97
Cardiac enlargement that occurs with hypertension or aortic valve disease is an example of?
a) Pathologic Hypertrophy
b) Pathologic Hyperplasia
c) both
A)
| Is for generate a higher contractil force
98
Mechanisms driving cardiac hypertrophy
**Mechanical triggers,** such as stretch, and soluble mediators that stimulate cell growth, such as **growth factors and adrenergic hormones**.
The outcome is the induction of genes for the synthesis of more proteins and myofilaments per cell, which increases
the force generated with each contraction, enabling the cell to meet increased work demands
99
An adaptation to stress such as hypertrophy can progress to functionally significant cell injury if the **stress is
not relieved**?
True or False?
True
100
When mycardial fibers get a lot of hypertrphy (fragmentation and loss of myofibrillar contractile elements) what happens?
| Not fully understand
There may be finite **limits on the** abilities of the **vasculature **to adequately supply the enlarged fibers, the **mitochondria to supply ATP**, or the biosynthetic machinery to provide **sufficient contractile proteins or other cytoskeletal elements.** The net result of these degenerative changes is ventricular dilation and ultimately cardiac failure.
101
The proliferation of the glandular epithelium of the female breast at puberty
and during pregnancy
a) Hypertrophy
b) Hyperplasia
c) both
Hyperplasia
| (hormonal)
102
The residual tissue grows after removal or loss of part of an organ is?:
a) Hypertrophy
b) Hyperplasia
c) both
Hyperplasia
| compensatory hyperplasia
103
When part of a liver is resected, mitotic activity in the remaining cells begins as early as 12 hours later, eventually restoring the liver toits normal size, is?
a) Hypertrophy
b) Hyperplasia
c) both
Hyperplasia
| compensatory hyperplasia
104
When part of a liver is resected and for restoring the liver to its normal size, The stimuli for hyperplasia in this setting are?
**Polypeptide growth factors** produced by uninjured hepatocytes as well as nonparenchymal cells in the liver.
105
Endometrial hyperplasia, which is a common cause of abnormal menstrual bleeding is caused because?
Pathologic hyperplasia caused by
excessive hormonal or growth factor stimulation.
106
Most forms of pathologic hyperplasia are caused by?
Excessive hormonal or growth factor stimulation.
107
Benign prostatic hyperplasia is another common example of?
** Pathologic hyperplasia ** (induced in
responses to hormonal stimulation by androgens)
108
Papillomaviruses cause skin warts and mucosal lesions that are composed of masses of?
**Hyperplastic epithelium**. Here the growth factors may be encoded by viral genes or by the genes of the infected host cells
109
Pathologic Hyperplasia could cause Cancer?
**ABSOLUTELY YES**
110
Which disease is related to the **growth control mechanisms become permanently dysregulated or ineffective** in hyperplasia
Cancer
111
What is **Atrophy**?
Atrophy is shrinkage in the size of cells by the loss of cell substance. Although atrophic cells may have diminished function, they are **not dead**
112
Causes of Atrophy
->**Decreased workload** (e.g., immobilization of a limb to permit healing of a fracture)
->**Loss of innervation**
->**Diminished blood supply**
->**Inadequate nutrition**
->**Loss of endocrine stimulation**
->**Aging **(senile atrophy).
113
Atrophy means cell dying?
Survival is still possible; a **new equilibrium is achieved **between cell size and diminished blood supply, nutrition, or trophic stimulation.
114
Results from a combination of decreased protein synthesis and increased protein degradation.
Cellular Atrophy
115
Atrophy also is associated with
autophagy?
Yes! with resulting increases in the number of autophagic vacuoles.
116
What is Metaplasia
is a change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type. A cell type sensitive to a particular stress is replaced by another cell type better able to withstand the adverse environment. Metaplasia is thought to arise by the** reprogramming of stem cells**
117
Name of the change that occurs in the respiratory epithelium of habitual cigarette
smokers, in whom the normal ciliated columnar epithelial cells of the trachea and bronchi often are **replaced by stratified squamous epithelial cells**
Epithelial **Metaplasia**
118
chronic gastric reflux, the normal stratified squamous epithelium of the lower esophagus may undergo __________ to gastric or intestinal-type columnar epithelium
**Metaplasia or Metaplastic transformation**
119
The influences that induce metaplastic change in an epithelium, if persistent, may predispose to?
**Malignant Transformation **
| Cancer
120
Under some circumstances, cells may accumulate abnormal amounts of various substances, which may be harmless or may cause varying degrees of injury. The substance may be located in the
| INTRACELLULAR ACCUMULATIONS
In the **cytoplasm, within organelles
(typically *lysosomes*)**, or in the **nucleus**, and it may be synthesized by the affected cells or it may be produced
elsewhere.
| LYSOSOMEEEEEEES
121
How is the IntracellularAccumulation of: **Fatty Change**?
Fatty change, also called **steatosis**, refers to any accumulation of triglycerides within parenchymal cells. It is most often seen in the liver, since this is the major
organ involved in fat metabolism, but also may occur in heart, skeletal muscle, kidney, and other organs.
122
Causes of Statosis
toxins (like alcohol), protein malnutrition, diabetes mellitus, obesity, or anoxia.
| Loss of oxygenation of brain tissue is called anoxia or hypoxia.
123
How is the IntracellularAccumulation of: **Cholesterol and Cholesteryl Esters**
**Phagocytic cells may become overloaded with lipid** (triglycerides, cholesterol, and cholesteryl esters) in several different pathologic processes, mostly characterized **by increased intake or decreased catabolism of lipids.** Of these, **atherosclerosis** is the most important
124
How is the IntracellularAccumulation of: **Proteins**
**Occur when excesses are presented to the cells or if the cells synthesize excessive amount. **
i.e. Nephrotic Syndrome with heavy
protein leakage across the glomerular filter much more of the protein is reabsorbed, and vesicles containing this protein accumulate, giving the histologic appearance of pink, hyaline cytoplasmic droplets
125
How is the IntracellularAccumulation of: **Glycogen**
Excessive intracellular deposits of glycogen are associated with abnormalities in the metabolism of either **glucose or glycogen**. In** poorly controlled diabetes mellitus**, the prime example of abnormal glucose metabolism, glycogen accumulates in renal tubular epithelium, cardiac myocytes, and β cells of the islets of Langerhans.
126
How is the IntracellularAccumulation of: **Pigments**
Pigments are **colored substances** that are either exogenous, coming from outside the body, such as carbon, or are endogenous, synthesized within the body itself, such as **lipofuscin, melanin, and certain derivatives of hemoglobin.**
The **most common** exogenous pigment is **carbon**, a ubiquitous air pollutant of urban life. When inhaled, it is phagocytosed by alveolar macrophages and transported through lymphatic channels to the regional tracheobronchial lymph nodes
127
How is the IntracellularAccumulation of: **Pigment: Lipofuscin**
is an **insoluble brownish-yellow granular intracellular material** that accumulates in a variety of tissues (particularly the heart, liver, and brain) with aging or atrophy. It is not injurious to the cell but is** a marker of past free radical injury**
| complexes of lipid and proteins
128
How is the IntracellularAccumulation of: **Pigment: Melanin**
Is an endogenous, brown-black pigment that is synthesized by melanocytes located in the epidermis. Although melanocytes are the only source of melanin, **adjacent basal keratinocytes in the skin can accumulate the pigment (e.g., in freckles), as can dermal macrophages**
129
How is the IntracellularAccumulation of: **Pigment: Hemosiderin**
Is a hemoglobin-derived granular pigment that is golden yellow to brown and **accumulates in tissues ****when there is a local or systemic excess of iron**. The iron can be unambiguously identifiedby the Prussian blue histochemical reaction.
130
What is Pathologic Calcification
**Is a common process in a wide
variety of disease states, is the result of an abnormal deposition of calcium salts**, together with smaller amounts
of iron, magnesium, and other minerals.
131
Which ways can undergo in the process of Pathologic Calcification?
Dystrophic calcification and Metastatic calcification.
132
Define **Dystrophic calcification**
| PATHOLOGIC CALCIFICATION
**It deposits ininjured or dead tissue, such as areas of necrosis ofany type**. It is virtually ubiquitous in the arterial lesions of advanced atherosclerosis. Although dystrophic calcification may be
an incidental finding indicating insignificant past cell injury, it also may be a cause of organ dysfunction. For example, calcification can develop in aging or damaged heart valves, resulting in severely compromised valve motion.
133
Define Metastatic Calcification and Causes of it
| PATHOLOGIC CALCIFICATION
This form is associated with hypercalcemia and can occur in normal tissues. Major caises are:
1) Increased secretion of parathyroid hormone.
2) destruction of bone
3) vitamin D–related
disorders including vitamin D intoxication and sarcoidosis
4) renal failure, in which phosphate retention leads
to secondary hyperparathyroidism.
134
How dystrophic calcification is initiated?
| Pathologic Calcification
Is initiated by the **extracellular deposition of crystalline calcium phosphate in membrane-bound vesicles**, which may be **derived from injured cells**, or the intracellular **deposition of calcium in the mitochondria of dying cells**. It is thought that the extracellular calcium is concentrated in vesicles by its affinity for membrane phospholipids, whereas phosphates accumulate as a result of the action of membranebound phosphatases. The crystals are then propagated, forming larger deposits.
135
Causes of Metastatic calcification **by bone destruction**:
Due to the effects of accelerated turnover (e.g., Paget disease), immobilization, or tumors (increased bone catabolism associated with multiple myeloma, leukemia, or diffuse skeletal metastases).
| Turnover ~Rotation
136
Abnormalities that contribute to cell aging.
- Accummulation of mutations in DNA
- Decreased Cellular Replication
-Decreased Protein synthesis and damaged proteins
137
What is Replicative Senescence?
All cells (other than stem cells) have a limited replication capacity and divisions. So in this process they **become arrested in a terminally nondividing state**
138
Why the replicative senescence happens?
Progressive shortening of telomeres that results in cell cycle arrest.
139
What does the telomerase does?
Is a specialized RNA-protein complex that uses its own RNA as a template for **adding nucleotides to the ends of chromosomes.** Telomerase is
expressed in germ cells and is present at low levels in stem cells, but absent in most somatic cells.
| Telomere
shortening also decrease capacity of stem c. contributing aging
140
Cancer cells can reactivate telomerases?
Yes
141
Calorie restriction and exercise could reduce aging?
Yes, in many ways but principally by reducing chronic inflammation and probably by reducin IGF-1 Signaling that leads to lower rates of cell growth and metabolism.
