Cells are constantly adjusting to their environment and stresses to maintain homeostasis. Adaptive responses include atrophy, hypertrophy, hyperplasia and metaplasia. If stresses exceed adaptive capabilities, reversible or irreversible cell injury occurs. Causes of injury include oxygen deprivation, chemicals, infections, immune reactions, genetics, nutrition and physical agents. Injuries include ischemic, free radical and toxic injuries. Cells adapt through changes in size, number or cell type to withstand stresses or return to viability.
Biochemistry of Aging
Presented by Shanzay Annum Malik
Aging
Gradual change in an organism that leads to increased risk of weakness, disease, and death over the entire adult life span of any living thing.
There is a decline in biological functions and in ability to adapt to metabolic stress.
Changes in organs include
reduced immunity,
loss of muscle strength,
decline in memory and cognition,
loss of colour in the hair
elasticity in the skin.
Gerontology and Geriatrics
Gerontology is concerned with the changes that occur between maturity and death along with factors that influence these changes.
Geriatrics focuses on health care of elderly people and promote health by preventing and treating diseases and disabilities in older adults.
Factors of Aging
Mitochondria: main unit of chemical power supply
During the synthesis of macroergical bio-molecules(high energy releasing potentials e.g. ATP) free radicals are being produced as the by-product.
Free radicals released in large quantities cause intercellular oxidative stress (e.g. oxidative damage of mitochondria)
damaging mitochondria and cause early apoptosis
Free radical
A molecule that contains one or more unpaired electrons &is capable of independent existence.
Eg : Superoxide H2O2,
hydroperoxy radical (HOO+2 )
lipid peroxideradical (ROO)
Nitric oxide (NO)
Harmful effect of free radicals
Because of their reactive nature, free radical can provoke inflammation or altered cellular function through
Lipid peroxidation
Protein modification
DNA modification
Lipid peroxidation product:
React with amino acid mainly CYS, HIS,LYS to modify protein structure & function.
Can crosslink lipid in cell membrane interrupting structure & fluidity.
Protein modification
DNA modification :
Free radical induced DNA damage includes
strand break.
DNA protein crosslink.
large range of base & sugar modification.
Telomeres
Repetitive DNA sequences at the ends of all human chromosomes
aging cells have shorter telomeres
length differs between species
in humans 8-14kb long
Telomeres are thought to be the "clock" that regulates how many times an individual cell can divide.
Telomeric sequences shorten each time the DNA replicates.
Once the telomere shrinks to a certain level, the cell can no longer divide. Its metabolism slows down, it ages, and dies
Apoptosis and Necrosis
There are two ways that a cell can die:
Necrosis occurs when a cell is damaged by an external force, such as poison, a bodily injury, an infection or getting cut off from the blood supply (which might occur during a heart attack or stroke). When cells die from necrosis, it's a rather messy affair. The death causes inflammation that can cause further distress or injury within the body.
Apoptosis or programmed cell death
When a cell is compelled to commit suicide proteins called caspases go into action.
They break down the cellular components needed for surviva
Mechanism of cell injury
Types of cell injury
Reversible and irreversible cell injury
Etiology of cell injury
Apoptosis, it's types and mechanism
Necrosis, it's types and mechanism
Biochemistry of Aging
Presented by Shanzay Annum Malik
Aging
Gradual change in an organism that leads to increased risk of weakness, disease, and death over the entire adult life span of any living thing.
There is a decline in biological functions and in ability to adapt to metabolic stress.
Changes in organs include
reduced immunity,
loss of muscle strength,
decline in memory and cognition,
loss of colour in the hair
elasticity in the skin.
Gerontology and Geriatrics
Gerontology is concerned with the changes that occur between maturity and death along with factors that influence these changes.
Geriatrics focuses on health care of elderly people and promote health by preventing and treating diseases and disabilities in older adults.
Factors of Aging
Mitochondria: main unit of chemical power supply
During the synthesis of macroergical bio-molecules(high energy releasing potentials e.g. ATP) free radicals are being produced as the by-product.
Free radicals released in large quantities cause intercellular oxidative stress (e.g. oxidative damage of mitochondria)
damaging mitochondria and cause early apoptosis
Free radical
A molecule that contains one or more unpaired electrons &is capable of independent existence.
Eg : Superoxide H2O2,
hydroperoxy radical (HOO+2 )
lipid peroxideradical (ROO)
Nitric oxide (NO)
Harmful effect of free radicals
Because of their reactive nature, free radical can provoke inflammation or altered cellular function through
Lipid peroxidation
Protein modification
DNA modification
Lipid peroxidation product:
React with amino acid mainly CYS, HIS,LYS to modify protein structure & function.
Can crosslink lipid in cell membrane interrupting structure & fluidity.
Protein modification
DNA modification :
Free radical induced DNA damage includes
strand break.
DNA protein crosslink.
large range of base & sugar modification.
Telomeres
Repetitive DNA sequences at the ends of all human chromosomes
aging cells have shorter telomeres
length differs between species
in humans 8-14kb long
Telomeres are thought to be the "clock" that regulates how many times an individual cell can divide.
Telomeric sequences shorten each time the DNA replicates.
Once the telomere shrinks to a certain level, the cell can no longer divide. Its metabolism slows down, it ages, and dies
Apoptosis and Necrosis
There are two ways that a cell can die:
Necrosis occurs when a cell is damaged by an external force, such as poison, a bodily injury, an infection or getting cut off from the blood supply (which might occur during a heart attack or stroke). When cells die from necrosis, it's a rather messy affair. The death causes inflammation that can cause further distress or injury within the body.
Apoptosis or programmed cell death
When a cell is compelled to commit suicide proteins called caspases go into action.
They break down the cellular components needed for surviva
Mechanism of cell injury
Types of cell injury
Reversible and irreversible cell injury
Etiology of cell injury
Apoptosis, it's types and mechanism
Necrosis, it's types and mechanism
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
The Indian economy is classified into different sectors to simplify the analysis and understanding of economic activities. For Class 10, it's essential to grasp the sectors of the Indian economy, understand their characteristics, and recognize their importance. This guide will provide detailed notes on the Sectors of the Indian Economy Class 10, using specific long-tail keywords to enhance comprehension.
For more information, visit-www.vavaclasses.com
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
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Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
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Model Attribute Check Company Auto PropertyCeline George
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2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
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1. OVERVIEW OF CELL INJURY
• Cells are active participants in their environment,
• constantly adjusting structure and function to accommodate
• changing demands and extracellular stresses.
• Cells
• preserve their immediate environment and
• intracellular milieu within a relatively narrow range of physiologic
parameters- > normal homeostasis.
• physiologic stresses or pathologic stimuli -> adaptation, achieving
a new steady state and preserving viability.
1
2. • adaptive responses are atrophy, hypertrophy, hyperplasia, and
metaplasia.
• If the adaptive capability is exceeded, cell injury develops.
• Within certain limits, injury is reversible, and cells return to a
stable baseline;
• with severe or persistent stress, irreversible injury results, and
the affected cells die.
2
3. • The relationships between normal, adapted, and reversibly
and irreversibly injured cells.
• Myocardium
• in hypertension or with a stenotic valve,
• hypertrophy.
3
4. • Prolonged starvation or in cachexia
• myocardium -> atrophy.
• If Coronary Artery occlusion is incomplete or sufficiently brief,
• Myocardium - reversible injury
• complete or prolonged occlusion.
• Myocardium – irreversible injury
4
5. • stresses and injury - affect the morphologic appearance &
functional status of cells and tissues.
• reversibly injured myocytes are not dead and,
• resemble normal myocytes;
• transiently noncontractile and
• a potentially lethal clinical impact.
• Whether a specific form of stress induces adaptation or causes
reversible or irreversible injury depends not only on
• the nature and severity of the stress but also on several other
variables, including
• specific cellular vulnerability,
• differentiation,
• blood supply, and
• nutritional status.
5
6. CAUSES OF CELL INJURY
• The stresses that can induce cell injury range from
• physical trauma of a motor vehicle accident to
• the single gene defect.
• Grouped into the following broad categories.
6
7. Oxygen Deprivation.
• Hypoxia, or oxygen deficiency,
• interferes with aerobic oxidative respiration and
• common cause of cell injury and death.
• oxygen deficiency
1. Ischemia
2. inadequate oxygenation of the blood,
• pneumonia, or
3. reduction in the oxygen-carrying capacity of the blood,
• anemia or CO poisoning.
7
8. • Chemical Agents.
• any chemical substance can cause injury
1. glucose or salt - derange the osmotic environment injury or
cell death.
2. Oxygen at sufficiently high partial pressures is also toxic.
3. poisons - severe damage at the cellular level
• altering membrane permeability,
• osmotic homeostasis, or
• the integrity of an enzyme or cofactor
• the death of the whole organism.
8
9. 4. potentially toxic agents in our environment;
• air pollutants,
• insecticides,
• carbon monoxide,
• asbestos, and
• social "stimuli" such as ethanol.
5. Therapeutic drugs
• cell or tissue injury in a susceptible patient or in the
appropriate setting.
9
10. • Infectious Agents.
• submicroscopic viruses to meter-long tapeworms;
• the rickettsiae, bacteria, fungi, and protozoans.
10
11. • Immunologic Reactions.
• immune reactions intended or incidental.
• Anaphylaxis to a foreign protein or a drug.
• autoimmune diseases .
11
12. • Genetic Defects.
• congenital malformations associated with Down syndrome or
• the single amino acid substitution in the hemoglobin S of sickle cell
anemia.
• inborn errors of metabolism
• cell and tissue damage
• "trivial" alterations in deoxyribonucleic acid (DNA).
12
13. • Nutritional Imbalances.
• nutritional deficiencies remain a major cause of cell injury.
• Protein-calorie insufficiency.
• specific vitamin deficiencies
13
14. • Excesses of nutrition are also important
• obesity increases the risk for type 2.
• diets rich in animal fat
• atherosclerosis
• cancer.
14
15. • Physical Agents.
• Trauma,
• extremes of temperatures,
• radiation,
• electric shock, and
• sudden changes in atmospheric pressure
• all have wide-ranging effects on cells.
15
16. • Three common forms of cell injury:
• ischemic and hypoxic injury,
• free radical-induced injury, and
• toxic injury.
16
17. • Anaerobic energy generation also ceases in ischemic tissues after
• substrates are exhausted or
• glycolysis is inhibited by metabolites.
• Ischemia injures tissues faster than does hypoxia.
17
18. • hypoxia is on the cell's aerobic respiration,
• reduced oxygen tension -> generation of ATP is markedly reduced.
• depletion of ATP has widespread effects.
18
19. • Activity of the plasma membrane ATP-driven "sodium pump" is
reduced,
• accumulation of intracellular sodium and the diffusion of potassium
out of the cell.
• net gain of sodium solute -> isosmotic gain of water, -> acute
cellular swelling.
• Exacerbated
• inorganic phosphates,
• lactic acid, and
• purine nucleosides.
19
20. • Anaerobic glycolysis increases.
• the cell's energy by generating ATP from glycogen, and
• activation -> rapid depletion of glycogen stores,
• apparent histologically.
20
21. • accumulation of lactic acid and inorganic phosphates -> lowering
the intracellular pH.
21
22. • Decreasing pH and ATP levels cause
• ribosomes to detach from the rough endoplasmic reticulum (RER) and
• polysomes to dissociate into monosomes,
• reduction in protein synthesis.
22
23. Ischemia/Reperfusion Injury
• If cells are reversibly injured, the restoration of blood flow can
result in cell recovery.
• under certain circumstances, the restoration of blood flow to
ischemic but otherwise viable tissues results, paradoxically, in
exacerbated and accelerated injury.
23
24. • tissues sustain the loss of cells.
• called ischemia/reperfusion injury
• myocardial and
• cerebral infarctions
24
25. • the exact mechanisms are unclear,
• reperfusion into ischemic tissues may cause further damage :
• blood flow bathes compromised cells in high concentrations of
calcium -> increased intracellular calcium activates enzymes -> a
loss of cellular integrity.
25
26. • locally augmented recruitment of inflammatory cells -> release
high levels of oxygen-derived reactive species -> additional
membrane damage as well as the mitochondrial permeability
transition.
26
27. • Damaged mitochondria in compromised but viable cells yield
• incomplete oxygen reduction -> increased production of free radical
species;
• compromised antioxidant defense mechanisms.
27
28. Free Radical-Induced Cell Injury
• Free radical damage also underlies
• chemical and
• radiation injury,
• toxicity from oxygen and other gases,
• cellular aging,
• microbial killing by phagocytic cells,
• inflammatory cell damage,
• tumor destruction by macrophages, and
• other injurious processes.
28
29. • Free radicals -a single unpaired electron.
• readily react with inorganic or organic chemicals;
• attack and degrade
• nucleic acids,
• membrane molecules.
• free radicals initiate autocatalytic reactions;
• molecules that react with free radicals are in turn converted into free
radicals.
29
30. • Free radicals may be generated within cells by
• The reduction-oxidation (redox) reactions
• superoxide radicals
• hydrogen peroxide (H2O2), and
• OH·.
30
32. • Nitric oxide (NO) - can act as a free radical or can be converted
into highly reactive nitrite species.
• The absorption of radiant energy
• Ionizing radiation - hydrolyze water into hydroxyl (OH·) and hydrogen
(H·) free radicals.
• The enzymatic metabolism of exogenous chemicals
• carbon tetrachloride.
32
33. • Three reactions are relevant to cell injury mediated by free
radicals:
o Lipid peroxidation of membranes.
33
35. CELLULAR ADAPTATION TO
INJURY
• under normal conditions, cells constantly adapt to changes in
their environment.
• Physiologic adaptations
• responses of cells to normal stimulation by hormones or
endogenous chemical mediators
• the enlargement of the breast and
• induction of lactation by pregnancy.
35
36. • Pathologic adaptations often
• share the same underlying mechanisms, but they allow the cells
to modulate their environment and ideally escape injury.
• cellular adaptation is a state that lies between the normal,
unstressed cell and the injured, overstressed cell.
36
37. • the adaptive changes in cell growth and differentiation:
• atrophy,
• hypertrophy,
• hyperplasia, and
• metaplasia.
37
38. Atrophy
• Shrinkage in the size of the cell by the loss of cell substance is
known as atrophy.
• the entire tissue or organ diminishes in size, becoming
atrophic.
• atrophic cells may have diminished function, they are not
dead.
• apoptotic death may also be induced by the same signals that
cause atrophy.
38
39. • Causes of atrophy
• a decreased workload,
• a loss of innervation,
• a diminished blood supply,
• inadequate nutrition,
• a loss of endocrine stimulation, and
• aging.
39
40. • physiologic
• the loss of hormone stimulation in menopause and
• pathologic
• denervation
• the fundamental cellular changes are identical.
• represent a retreat by the cell to a smaller size at which survival is
still possible.
40
41. • Atrophy represents a reduction in the structural components of
the cell due to;
Decreased synthesis,
increased catabolism, or
both may cause atrophy.
41
43. • may progress to the point at which cells are injured and die.
• If the blood supply is inadequate even to maintain the life of
shrunken cells , injury and cell death may supervene.
• The atrophic tissue may then be replaced by fatty ingrowth.
43
44. Hypertrophy
• Hypertrophy is an increase in the size of cells and consequently
an increase in the size of the organ.
• bigger cells, enlarged by an increased synthesis of structural
proteins and organelles.
• Hypertrophy can be physiologic or pathologic
• caused by increased functional demand or by specific
hormonal stimulation.
• Hypertrophy and hyperplasia can also occur together.
44
45. • massive physiologic hypertrophy of the uterus during
pregnancy
• estrogen stimulation.
• weight lifter hypertrophy of individual skeletal muscle cells
• an increased workload.
• pathologic cellular hypertrophy
• cardiac enlargement - hypertension or aortic valve disease , and
myocardial infarction.
45
46. Hyperplasia
• Hyperplasia constitutes an increase in the number of cells in an
organ or tissue.
• Hypertrophy and hyperplasia are closely related and often
develop concurrently.
• the gravid uterus.
• In certain instances, even potentially dividing cells , undergo
hypertrophy but not hyperplasia.
46
47. • Hyperplasia can be physiologic or pathologic.
• Physiologic hyperplasia
• (1) hormonal hyperplasia,
• the proliferation of the glandular epithelium of the female breast.
• (2) compensatory hyperplasia,
• occurs when a portion of the tissue is removed or diseased. E.g.
partial hepatectomy.
47
48. • Hyperplasia is also a critical response of connective tissue cells
in wound healing.
48
49. • Pathologic hyperplasia - excessive hormonal or growth factor
stimulation.
• the balance between estrogen and progesterone is disturbed,
endometrial hyperplasia ensues, a common cause of abnormal
menstrual bleeding.
• Increased sensitivity to normal levels of growth factors may also
underlie pathologic hyperplasia.
49
50. • the common skin wart.
• any minor trophic stimulation of the cell by growth factors
results in an overexuberant mitotic activity.
• the hyperplastic process remains controlled; if hormonal or
growth factor stimulation abates, the hyperplasia disappears.
50
51. • This differentiates these processes from cancer, in which cells
continue to grow despite the absence of hormonal stimuli.
• pathologic hyperplasia constitutes a fertile soil in which
cancerous proliferation may eventually arise.
• hyperplasia of the endometrium are at increased risk of
developing endometrial cancer, and
• papillomavirus infections predispose to cervical cancers.
51
52. Metaplasia
• Metaplasia is a reversible change in which one adult cell type
(epithelial or mesenchymal) is replaced by another adult cell
type.
• cells sensitive to a particular stress are replaced by other cell
types better able to withstand the adverse environment.
52
53. • Epithelial metaplasia - squamous change in the respiratory
epithelium.
• Vitamin A deficiency , ciga. Smoking.
• important protective mechanisms are lost,
• mucus secretion and
• ciliary clearance.
53
54. • if persistent, may induce cancer transformation in the
metaplastic epithelium.
• squamous cell ca
54
55. • chronic gastric reflux
• Columnar metaplasia
• Osseous metaplasia- mesenchymal cells but less clearly as an
adaptive response.
• bone is occasionally formed in soft tissues, particularly in foci of
injury.
55
56. Intracellular Accumulations
• harmless or may cause varied degrees of injury.
• either in the cytoplasm(typically lysosomes), or in the nucleus.
• The substance may be synthesized by the affected cells or may
be produced elsewhere.
56
57. • three general pathways by which cells can accrue abnormal
intracellular accumulations :
1. A normal substance is produced at a normal or an increased
rate, but the metabolic rate is inadequate to remove it.
57
58. 2. A normal or an abnormal endogenous substance accumulates
because of genetic or acquired defects in its metabolism,
packaging, transport, or secretion.
58
59. • An abnormal exogenous substance is deposited and
accumulates because the cell has neither the enzymatic
machinery to degrade the substance nor the ability to
transport it to other sites.
59
60. Fatty Change (Steatosis).
• Fatty change refers to any abnormal accumulation of
triglycerides within parenchymal cells.
60
61. • seen in the liver, heart, skeletal muscle, kidney, and other
organs.
• may be caused by toxins, protein malnutrition, diabetes
mellitus, obesity, and anoxia.
• alcohol abuse is the most common cause of fatty change in the
liver (fatty liver) in industrialized nations.
61
62. • may result from defects at any step from fatty acid entry to
lipoprotein exit.
• Hepatotoxins (e.g., alcohol) alter mitochondrial and SER
function;
• CCl4 and protein malnutrition decrease the synthesis of
apoproteins;
62
63. • anoxia inhibits fatty acid oxidation; and
• starvation increases fatty acid mobilization from peripheral
stores.
63
65. • The significance of fatty change depends on the cause and the
severity of accumulation.
• mild - no effect on cellular function.
• severe fatty - transiently impair cellular function.
• fatty change is reversible.
• In a severe form, fatty change may precede cell death.
65
68. carbon
Anthracosis
• Inhaled carbon -> phagocytosed by alveolar macrophages and
transported through lymphatic channels to the regional
tracheobronchial lymph nodes -> aggregates of the pigment ->
blackenening the draining lymph nodes and pulmonary
parenchyma.
• Heavy accumulations may induce coal workers'
pneumoconiosis.
68
69. Melanin
• an endogenous, brown-black pigment formed by melanocytes when
the enzyme tyrosinase catalyzes the oxidation of tyrosine to
dihydroxyphenylalanine.
• synthesized exclusively by melanocytes.
• Freckles – accumulation in basal keratinocytes.
• Nevus
• melanoma
69
70. Hemosiderin
• a hemoglobin-derived granular pigment that is golden-yellow
to brown.
• represents large aggregates of ferritin micelles.
• accumulates in tissues when there is a local or systemic excess
of iron.
70
71. • Local excesses of iron - hemorrhage.
• systemic overload of iron (hemosiderosis)
• (1) increased absorption of dietary iron,
• (2) impaired utilization of iron,
• (3) hemolytic anemias, and
• (4) transfusions
71
72. hemosiderosis
• first - the mononuclear phagocytes of the liver, bone marrow,
spleen, and lymph nodes and macrophages in other organs.
• Later - parenchymal cells ( the liver, pancreas, heart, and
endocrine organs)
• No organ dysfunction.
72
73. • extensive accumulations of iron + tissue injury (liver fibrosis,
heart failure, and diabetes mellitus) -> hemochromatosis.
73
74. Pathologic Calcification
• a common process in a wide variety of disease states.
• it implies the abnormal deposition of calcium salts, together
with smaller amounts of iron, magnesium, and other minerals.
74
75. • deposition in dead or dying tissues - dystrophic calcification.
• occurs in the absence of calcium metabolic derangements
(i.e., with normal serum levels of calcium).
• the deposition of calcium salts in normal tissues - metastatic
calcification.
75
76. clinically
• Silent.
• extensive calcifications in the lungs may produce respiratory
deficits, and
• massive deposits in the kidney -> nephrocalcinosis-> renal
damage.
76
77. Necrosis - refers to a sequence of morphologic changes that
follow cell death in living tissue.
• is the gross and histologic correlate of cell death occurring in
the setting of irreversible exogenous injury.
77
78. • The morphologic appearance of necrosis is the result of two
essentially concurrent processes: (1) enzymatic digestion of the
cell and (2) denaturation of proteins.
78
79. 79
• Common pattern
• preservation of basic outline of the coagulated cell for some days
-intracellular acidosis
– protein denatured
– proteolysis inhibited
-e.g. myocardial infarction (ischemia) the myocardial cells will be replaced by
acidophilic, coagulated, anucleate cells
-latter the necrotic cells are removed by fragmentation and phagocytosis by
leukocytes
-coagulative necrosis is characteristic of hypoxic death of cells in all tissues
except the brain
Coagulative necrosis
80. LiquefactiveNecrosis
• focal bacterial (or fungal) infections
– accumulation of inflammatory
cells
-Dominant enzymatic digestion
-transformation of the necrotic tissue in to liquid
viscous mass (pus)
NB :hypoxic death of cells within CNS
80
83. *Gangrenousnecrosis
–not a distinctive type of necrosis but commonly used in clinical
practice to a limb that has lost its blood supply and undergone
coagulative necrosis
-when bacterial superinfection is superimposed coagulative
necrosis is modified by the liquefactive action of the bacteria
and the attracted leukocytes (so-called wet gangrene).
83
85. 85
*Caseousnecrosis
• distinctive form of coagulative necrosis
• encountered most often in foci of tuberculous
infection
-The term caseous- ‘cheesy white’ gross
appearance of the area of necrosis
-microscopically-amorphous granular debris with
distinctive inflammatory border known as
granulomatous reaction
88. 88
Fatnecrosis
• it is descriptive of focal areas of fat destruction,
• typically occurring as a result of release of activated
pancreatic lipases into the substance of the pancreas
and the peritoneal cavity in acute pancreatitis
• activated pancreas enzymes liquefy fat cell
membranes and release fatty acids
• fatty acids combine with calcium to produce
grossly visible chalky white areas (fat saponification)
90. • Non enzymatic fat necrosis
• In the breast following trauma
• In subcutaneous tissue
90
91. *Fibrinoidnecrosis
• special form
• usually seen in immune reactions involving
blood vessels
• when complexes of antigens and antibodies are
deposited in the walls of arteries
• Deposits of these "immune complexes,"
together with fibrin that has leaked out of
vessels, result in a bright pink and amorphous
appearance in H&E stains, called "Fibrinoid"
(fibrin-like).
• e.g., in polyarteritis nodosa, rheumatic fever
91
93. Apoptosis
• is a distinctive and important mode of cell death .
• Apoptosis ( meaning "a falling away from")
• the programmed cell death in several physiologic processes,
• embryogenesis,
• implantation,
• organogenesis, and
• developmental involution
93
94. • involution of the endometrium during the menstrual cycle, or
• involution of lactating breast ; or
• pathologic atrophy,
• Cell deletion in proliferating populations
94
95. • The cells shrink, form cytoplasmic buds, and fragment into
apoptotic bodies composed of membrane-bound vesicles of
cytosol and organelles.
95