Pathology Lecture 3, Cell Injury (Continued) [Lecture Notes]
Pathology, Lecture 2, Cell Injury (slides)
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Transcript of Pathology, Lecture 2, Cell Injury (slides)
Cell Injury:
Cellular Injury (year 2010 )
Dr. Huda M.Zahawi, FRC.Path.
Cell Injury:
Topic Outline
Causes of cell injury Types of Injury Priciples & Mechanisms of cell injury Outcome : ?Reversible ? Irreversible Morphology Adaptation to Injury Patterns & types of Cell Death Process of Aging
Cell Injury:
Cellular Injury & Adaptation
Normal cell is in a steady dynamic state “Homeostasis” :
The ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes.
Cell Injury: Cells are constantly exposed to
stresses.
Normal physiologic stress Severe stresses: injury results, and
alters the normal steady state of the cell, consequently,
It can survive in a damaged state and adapt to the injury
(reversible injury or adaptation) It can die (irreversible injury or cell death).
NORMALCELL
STRESS INJURY
AtrophyHypertophyHyperplasiaMetaplasia
Cellular swellingVacuolar change
Fatty change
Necrosis
Apoptosiss
IrreversibleIrreversibleinjuryinjury
ReversibleReversibleinjuryinjury
AdaptationAdaptation
Cell Injury:
Causes of Cell Injury
Hypoxia and ischemia Free radicals Chemical agents Physical agents Infections Immunological reactions Genetic defects Nutritional defects Aging
Cell Injury:
TYPES OF INJURY
Cell Injury:
Causes of Hypoxia
low levels of oxygen in the air poor or absent Hemoglobin function decreased erythropoiesis respiratory or cardiovascular
diseases, or ischemia (reduced supply of blood)
1- Hypoxia & Ischemia
Cell Injury:
Ischemia & Hypoxia induce mitochondrial
damage.
This results in decreased ATP which in turn reduces energy for all cell functions
!
If persistent CELL DEATH
Cell Injury:
Hypoxia is a common cause of cell injury Result : Cell resorts to anaerobic glycolysis Ischemia is the commonest cause of hypoxia,
& injures the cells faster than pure hypoxia Why ?? Restoration of blood may lead to recovery OR
Ischemia/ Reperfusion injury Progressive cell damage Examples : Myocardial & Cerebral infarction
Cell Injury:
Ischemia/Reperfusion Injury Restoration of blood flow influx of high
levels of calcium Reperfusion increases recruitment of
inflammatory cells free radical injury Damaged mitochondria induce free
radical production & compromise antioxidant defense mechanisms
Dead tissue becomes antigenicAB activation of complement immune
response
Cell Injury:
Recommendation :
In some cases , high oxygen therapy to improve hypoxia is NOT given because
it generates oxygen derived FREE
RADICALS ( Reactive Oxygen Species ROS)
Cell Injury:
2- Free Radicals
Free radicals are chemical species with a single unpaired electron in an outer orbital, they are chemically unstable and therefore readily react with other molecules, resulting in chemical damage.
To gain stability, the radical gives up or steals an electron.
Radicals can bind to proteins, carbohydrates lipids, producing damage.
Cell Injury:Sources of Free Radicals in pathology
Chemical injury Physical injury Inflammation Oxygen toxicity Reperfusion injury Malignant transformation Aging
Cell Injury:
Formation of Free Radicals :
Endogenous from normal metabolism
Reduction Oxidation reaction (REDOX) in mitochondria
Transition metals (Copper, Iron) catalyze Free Radicals formation by donating or accepting free electrons
(Fenton reaction)
Ferric iron Ferrous iron
superoxide
Cell Injury:
Exogenous formation : Ionizing radiation Drug metabolism
Cell Injury:
Free Radicals (Examples) Reactive Oxygen Species (ROS)
generated
by mitochondrial respiration : Oxygen Superoxide H2O2 (Hydrogen peroxide)
OH (hydroxyl group) Inflammation :
Accumulation of leucocytes NO (Nitric oxide) reactive nitrite
Cell Injury:Mechanism of injury by Free Radicals
1-Lipid peroxidation (oxidative degradation of lipids):
Destruction of unsaturated fatty acids by binding to methylene groups (CH2)
that posses reactive hydrogen molecules
Cell Injury:
2-Protein destruction: By cross linking proteins forming
disulfide bonds (S-S) → inactivate enzymes, & polypeptide degradation
3- DNA alteration: By producing single strand breaks in
DNA Induce mutation that interfere with
cell growth
Cell Injury:
Inactivation Free Radicals
Spontaneous decay Enzymes
Superoxide dismutase, glutathione peroxidase, and catalase
Antioxidants Block synthesis or inactivate free radicals
Include Vitamin E, Vitamin C, albumin, ceruloplasmin, and transferrin
Cell Injury:
3- Chemical Agents Chemical agents can cause cellular
injury by:
direct contact of the chemical with molecular components of the cell.
Indirect injury formation of free radicals, or lipid
peroxidation.
Cell Injury:
Examples of injurious chemicals
Cyanide disrupts cytochrome oxidase. Mercuric chloride binds to cell
membrane in cell resulting in increased permeability.
Chemotherapeutic agents & antibiotics may act in the same way.
Carbon Monoxide (CO) Ethanol Lead
Cell Injury:
Action of Carbon Monoxide :
Has a very high affinity to hemoglobin (carboxyhemoglobin: COHb) The effect of large quantities of
COHb is death (carbon monoxide poisoning).
Smaller quantities of COHb leads to tiredness,dizziness & unconsciousness.
Cell Injury:
Action of Ethanol :
The conversion of ethanol to acetaldehyde leads to formation of free radical.
Acetaldehyde initiates changes in liver Fatty change Liver enlargement Liver cell necrosis.
Cell Injury:liver enlargement with deposition of fat
Cell Injury:
Action of Lead :
Mimics other metals (calcium, iron and zinc) which act as cofactors in many catalyzing enzymatic reactions.
Acts on the CNS by interfering with neurotransmitters, blocking glutamate receptor.
(May cause wrist, finger,&foot paralysis).
Affects hemoglobin synthesis
Cell Injury:
Indirect injury of some chemicals :
Activation in the liver by the P- 450 mixed function oxidases in SER . CCL4 CCL3 (FR) membrane
phospholipid peroxidation & ER destruction:
↓ protein ↓ lipid No apoproteins for lipid transport Fatty liver
Mitochondrial injury ↓ATP Failure of cell function increased cytosolic Ca+ cell death
Acetaminophen may act similarly
Cell Injury:
4- Physical agents
Mechanical injury resulting in tearing, or crushing of tissues.
e.g.: blunt injuries , car accidents….
Ionizing Radiation Water and DNA are the most
vulnerable target
Cell Injury:
Physical agents (cont……) Extreme temperatures
Hypothermia Hyperthermia
Atmospheric Pressure Blast injuries Water pressure – increased or
decreased
Cell Injury:
5-Infectious Agents Bacteria: produce toxins
Endotoxin Exotoxin
Viruses : Decrease the ability to synthesize
proteins Change host cell’s antigenic
properties
Cell Injury:
5-Immunological reactions
Cell membranes are injured by contact with immune components such as lymphocytes, macrophages….etc
Exposure to these agents causes changes in membrane permeability
Cell Injury:
6- Genetic Diseases
Genetics play a substantial role in cellular structure and function.
A genetic disorder can cause a dramatic change in the cell’s shape, structure, receptors, or transport mechanisms.eg : Enzyme deficiencies Sickle Cell Anemia
Cell Injury:
7- Nutritional Imbalances Adequate amounts of proteins, lipids,
carbohydrates are required. Low levels of plasma proteins, like
albumin, encourages movement of water into the tissues, thereby causing edema.
Hyperglycemia, hypoglycemia, Vitamin deficiencies (vitamins E, D, K,
A, and folic acid) Excess food intake is also classified as
a nutritional imbalance
Cell Injury:
Mechanism of cell injury & sites of damage
Cell Injury:
Function is lost before morphological changes occur
EM changes Microscopic changes Gross changes
General Considerations:
Cell Injury:
Result of injury depends on : Injury : Type
Duration Severity
Type of cell: Specialization Adequacy of blood supply,
hormones, nutrients Regenerative ability or adaptability Genetic make up
Cell Injury:
Steps & Cellular targets in Injury :
Cell Injury:
1- Mitochondria: Interruption of oxidative
metabolism Loss of energy due to formation of mitochondrial permeability transition pore (MPT) loss of membrane potential prevents ATP generation (ATP depletion)
Cytochrome c released into cytosol activates apoptosis.
O2 depletion ROS
Cell Injury:
2- Cell Membranes
Important sites of damage : Mitochondrial membrane ATP Plasma membrane failure of Na
pump leads to cellular amounts of water
Lysosomal membrane enzyme release,
activation & digestion of cell components
Cell Injury:
3- Influx of Calcium:
Ca stability is maintained by ATP Loss of Ca homeostasis cytosolic
Ca+ activation of:
phospholipases proteases ATPases Endonucleases
Cell Injury:
4-Protein synthesis:
High fluid levels cause ribosomes to separate from the swollen
endoplasmic reticulum protein synthesis, glycolysis Metabolic acidosis
5- Genetic apparatus DNA defects & mutations
Cell Injury:
Injury at one locus leads to wide ranging secondary effects
Cascading effect
Cell Injury:
Subcellular response to injury
Cell Injury:
1- Hypertrophy of Smooth Endoplasmic Reticulum in liver induced by some drugs
e.g. barbiturates , alcohol…. etc.2-Mitochondrial alterations in size &
number e.g. in atrophy, hypertrophy, alcoholic
liver3-Cytoskeletal abnormalities
e.g. microtubule abnormality involved in cell mobility
Cell Injury:
4- Lysosomal Catabolism: Enzymatic digestion of foreign
material (Heterophagy / pinocytosis & phagocytosis) or intracellular material (Autophagy).
Persistent debris → residual body (Undigestible lipid peroxidation products → Lipofuscin pigment.
Cell Injury: Morphology of reversible cell injury:
Ultrastructurally :• Generalized swelling of the cell and
its organelles • Blebbing of the plasma membrane• Detachment of ribosomes from the endoplasmic reticulum• Clumping of nuclear chromatin.
Cell Injury:Transition to irreversible cell injury :
• Increasing swelling of the cell• Swelling and disruption of lysosomes• Severe swelling & dysfunction of
mitochondria with presence of large calcium rich densities
in swollen mitochondria• Disruption membranes→ phospholipase• Irreversible nuclear changes
Ultra structural changes in irreversible injury
mitochondria
Breaks in cell & organelles membranes
Nucleus
Cell membrane
Endoplastic retic
lysosomes
Amorphous density,bizarre forms,calcification
rupture
fragmentation
See by light mic
Nuclear changes in irreversible changesby light microscopy
Pyknosis
Nuclear shrinkage+Increasedbasophilia
Pyknotic nucleus
karyolysis karyorrhexis
Anucleated cell
Cell Injury:
After death Cellular constituents are digested by
lysosomal hydrolases → enzymes & proteins leak into
extracellular space → useful in diagnosis Myocardial Infarction ( creatine kinase &
troponins) Liver injury (biliary obstruction): Alkaline
phosphatase Dead cells converted to phospholipid masses (Myelin Figures) → Phagocytosis or degraded
to fatty acids → calcification
Summary
Cell Injury:
IF INJURED CELLS DON’T DIE, THEY MAY ADAPT TO PROTECT
THEMSELVES !
Cell Injury:
Cellular Adaptations
Cells change to Adapt to a new environment Escape from injury Protect themselves
Cell Injury:
Cellular Adaptations: Growth adaptations:
Hyperplasia, Hypoplasia, Hypertrophy, Atrophy, Metaplasia , Dysplasia.
Degenerations: (Accumulations) Hydropic change (water collection in cell
/edema) Fatty Change Hyaline Change Pigment storage – wear & tear..
Cell Injury:Cellular Adaptation to Injury
The most common morphologically apparent adaptive changes are
– Atrophy (decrease in cell size)– Hypertrophy (increase in cell size)– Hyperplasia (increase in cell number)– Metaplasia (change in cell type)
Cell Injury:
Atrophy
Decrease in cell size due to loss of cell
substance (protein degradation & lysosomal
proteases digest extracellular endocytosed
molecules )
Often hormone dependent (insulin, TSH,
etc…).
Atrophic cells have diminished function.
Cell Injury:
Atrophy
Physiologic: Uterus following parturition Pathologic:
Decreased workload (Disuse atrophy) Loss of innervation (Denervation
atrophy) Decreased blood supply (Brain atrophy) Malnutrition (Marasmus). Lack of hormonal stimulation.
Ageing: Senile atrophy
Cell Injury:
Disuse atrophy of muscle fibers
Cell Injury:
Atrophy of frontal lobe
Cell Injury: Atrophy: Undescended testes
Cell Injury:
Hypertrophy
Hypertrophy is an increase in cell size by gain of cellular substance
With the involvement of a sufficient number of cells, an entire organ can become hypertrophic
Hypertrophy is caused either by increased functional demand or by specific endocrine stimulations
With increasing demand, hypertrophy can reach a limit beyond which degenerative changes and organ failure can occur
Cell Injury:
Hypertrophy
Physiological & Pathological
Skeletal muscles in manual workers & athletes
Smooth muscles in pregnant uterus (Hyperplasia accompanies hypertrophy
here) Cardiac muscles in hypertension Remaining kidney after
nephrectomy
Cell Injury:Left ventricle hypertrophy -
HPTN
Compare normal & pregnant uterus
Cell Injury:
Hyperplasia
Hyperplasia is an increase in the number of cells of a tissue or organ, from an increased rate of cell division.
If cells have mitotic ability and can synthesize DNA, both hyperplasia and hypertrophy can occur.
Hyperplasia may be a predisposing condition to neoplasia
Cell Injury:
Cells differ in their capacity to divide :
High capacity: Epidermis, intestinal epithelium hepatocytes, bone marrow, fibroblasts.
Low capacity: Bone cartilage, smooth muscles
Nil capacity: Neurons, cardiac muscle, skeletal muscle….
Cell Injury:
Types of Hyperplasia
Physiological Hyperplasia (hormonal or compensatory),
Examples:
Uterine enlargement during pregnancy
Female breast in puberty & lactation Compensatory hyperplasia in the
liver
Cell Injury:
Pathological
Hyperplasia of the endometrium (excessive hormone stimulation).
Wound healing (Effects of growth factors). Infection by papillomavirus
Cell Injury:
Endometrial Hyperplasia
Cell Injury:
Metaplasia Metaplasia is a “reversible” change
(adaptation ) in which one adult cell type is replaced by another adult cell type that are better suited to tolerate a specific abnormal environment.
May occur in epithelial or mesenchymal tissue. e.g. Bronchial , gastric, & cervical epith., and bone in injured soft tissue
Cell Injury:
Some disadvantages occur :
Because of metaplasia, normal protective mechanisms may be lost.
Persistence of signals that result in metaplasia often lead to progression from metaplasia to dysplasia and possibly to adenocarcinoma.
Cell Injury:
Example of Metaplasia Replacement of ciliated columnar
epithelium with stratified squamous epithelium in respiratory tract of a smoker.
Cell Injury:Columnar (gastric) metaplasia in esophageal squamous epithelium
Cell Injury:
Dysplasia
Abnormal changes in size, shape, appearance, and organizational structure of the cells
Sometimes atypical hyperplasia can progress to neoplasia
Caused by persistent injury or irritation
Cervix, oral cavity, gallbladder, and respiratory tract“Cells having disordered arrangement”
Cell Injury:
Cervical dysplasia
Cell Injury:
Intracellular Accumulations & Deposits
Cell Injury:May occur in any one of the following ways :
Excessive production of a normal product
but metabolic function is inadequate
Normal or abnormal substance accumulates but there is genetic or acquired defective enzyme mechanism for removal
Abnormal exogenous substance accumulates because the cell does not possess a mechanism for removal
Cell Injury:
Accumulations include
Water ( Hydropic degeneration/cloudy swelling)
Fatty change Cholestrol & cholestrol esters Proteins Glycogen Pigments Calcium Amyloid deposition
Cell Injury:
Hydropic degeneration
Cell Injury:
1- Fatty change
Accumulation of excessive lipid in cells
The liver is the main organ involved, to lesser extent heart and kidney
Fatty acids → hepatocytes → triglyceride + apoproteins → lipoprotein → exit liver
Excess accumulation may result from defect in any of the above steps
Cell Injury: Causes of fatty change :
Toxins including alcohol Starvation and protein malnutrition Diabetes mellitus Oxygen lack (anemia & ischemia ) Drugs, Complicate pregnancy &
Obesity
Cell Injury:
Morphology of fatty liver
Gross appearance in liver depends on severity Normal to large size, looks yellow and
greasy when severe Histology
Fat accumulates in hepatocytes as small vacuoles in cytoplasm with nucleus in the center (Microvesicular fatty change ).
The whole cytoplasm is replaced by fat and nucleus is pushed to one side of the cell (Macrovesicular fatty change).
Cell Injury:
Fatty Liver (Alcoholism)
Cell Injury:2- Cholestrol & Cholestrol esters
Accumulate in macrophages ( foam cells ) & in foreign body giant cells : Atherosclerosis Hereditary & Acquired
hyperlipidemia → Xanthomas (a yellow nodule or plaque, especially of the skin, composed of lipid-laden histiocytes).
Cell Injury:
3- Protein accumulation:
kidney in the nephrotic syndrome. Plasma cells as immunoglobulins. Mallory Bodies: Alcoholic liver
disease as (Eosinophilic intracellular hyaline body)
Glycogen accumulation in Glycogen Storage Diseases.
Liver - Mallory hyaline - Alcoholism
Cell Injury:
4- Pathologic Calcification
A- Dystrophic calcification : Abnormal deposition of calcium
phosphate in dead or dying tissue Dystrophic calcification is an
important component of the pathogenesis of atherosclerotic disease and valvular heart disease.
Areas of caseous, coaggulative or fat necrosis.
Dead parasites & their ova
Cell Injury:
cont… B- Metastatic calcification : Calcium deposition in normal tissues
as a consequence of hypercalcemia: Increased PTH with subsequent
bone resorption Bone destruction: METASTATIC
BONE CANCERS Vitamin D disorders Renal failure
Organs affected: Kidney, stomach, lungs….
Cell Injury:
Dystrophic calcification - Stomach.
Cell Injury:
5-Pigments
Pigments
EXOGENOUS
Hb-derived Non Hb -derived
ENDOGENOUS
Bilirubin
IronTattooing
Anthracosis
Lipofuscin
Melanin
Cell Injury:
Exogenous pigment :
Anthracosis :
Accumulation of carbon, black pigment Smokers Tatooing
Cell Injury:Exogenous pigment : Anthracosis
Cell Injury:
Endogenous pigments : 1- Melanin pigment : Brown pigment synthesized in
melanocytes. Melanin protects the nuclei of cells in
basal layer of epidermis against effects of UV light
Lesions associated with melanocytes Moles (nevi)…..benign Melanoma…….malignant
Lesions can occur anywhere e.g.rectum,eye.
Cell Injury:
2- Lipofuscin pigment Brown pigment in cytoplasm of cells,
represents residue of oxidized lipid derived from digested membranes of organelles.
It is called “wear and tear”pigment accumulates as a part of the aging process and atrophy, in which lipid peroxidation take part in it.
It is harmless to the cell. Large amounts in atrophic organs
gives rise to “Brown atrophy” e.g brown atrophy of the heart.
Cell Injury:
Lipofuscin
Cell Injury:
3- Bile pigment (Bilirubin ) Derived from heme of Hb from destroyed
RBC in reticuloendothelial system. Conjugated in hepatocytes with glucuronic
acid and excreted as bile. Hyperbilirubinemia may present clinically
as jaundice Causes may be hemolysis, liver diseases or
obstruction to the outflow of bile
Cell Injury:
4- Excess iron accumulation Total body iron….. 2 - 4gm. Functional pool
Hb, myoglobin, cytochromes & catalase Storage pool
in macrophages of RES in the ferric form as ferritin & / or hemosiderin which is golden brown.
Potasium ferrocyanide + hemosiderin = ferric ferrocyanide. This is known as ” Prussian Blue reaction” or Perl`s reaction.
Cell Injury: Iron overload: Localized or systemic
Local increase of iron in tissues Localized hemorrhage in tissues Chronic venous congestion of lung in
heart failure Systemic increase of iron
Hemosiderosis ….. Iron in RES without much damage
Occurs in: Excessive hemolysis Multiple blood transfusions Intravenous administration of iron
Cell Injury:Hemosiderin granules in liver cells. A- H&E section showing golden-brown, finely granular pigment. B- Prussian blue reaction, specific for iron.
Cell Injury:
Idiopathic Hemochromatosis
Abnormality is lack of regulation of iron absorption & defect in the monocyte - macrophage system.
Iron accumulates in liver, pancreas, other parenchymal cells & to lesser extent in RES.
Induce fibrosis, secondary diabetes, cirrhosis & liver cancer
Cell Injury:
5- Amyloidosis
Extracellular deposition of an abnormal fibrillar proteins in various tissues and organs (kidney, heart, brain, liver…etc.)
The abnormal protein is called Amyloid. Many types associated with different
diseases or primary forms H & E … Hyaline-like acellular eosinophilic
material Congo red stains amyloid pink or red and
under polarizing microscopy gives apple green birefringence .
Cell Injury:
Amyloid deposition in kidney
Cell Injury:
Congo Red Stain
Cell Injury:
Classification of amyloidosis Localized amyloid deposition
larynx,lungs,urinary bladder,etc.. Systemic amyloidosis
multiple myeloma associated …. AL amyloid Reactive (secondary amyloidosis) … AA amyloid
RHEUMATOID ARTHRITIS, INFLAMMATORY BOWEL DISEASE, OSTEOMYELITIS, HODGKIN’S DISEASE AND RENAL CELL
CARCINOMA. Hereditary amyloidosis
Cell Injury:
CELL DEATH
Cell Injury:
CELL DEATH
Ultimate result of injury, following ischemia, infection, toxins, immune reactions……
Physiologically seen in embryogenesis, lymphoid tissue development, hormonally induced involution.
Therapeutically in cancer radiotherapy and chemotherapy.
Cell Injury:
Types :
Necrosis: Morphologic changes seen in dead cells within living tissue.
Autolysis: Dissolution of dead cells by the cells own digestive enzymes. (not seen)
Apoptosis: Programmed cell death. Physiological, cell regulation.
Cell Injury:
NECROSIS
Irreversible
Necrosis is local cell death and cellular dissolution in living tissues.
Necrosis involves the process of self/auto digestion and lysis.
Cell Injury:
Morphologic changes :
Increased eosinophilia of cells Pyknosis of nuclei Karyorrhexis Karyolysis: dissolution of the
nucleus from hydrolytic enzymes Release of catalytic enzymes from
lysosomes cause either autolysis or heterolysis
Cell Injury: Morphologic appearance of necrosis
is due to: Enzymic digestion of the cell Denaturation of proteins
Types: coagulative, liquefactive, caseous, fat necrosis, gummatous necrosis and fibrinoid necrosis.
Sequels of Necrosis: Autolysis Phagocytosis Organization & fibrous repair Dystrophic calcification
Cell Injury:
1- Coagulative necrosis
Commonest type of necrosis, usually ischemic Infarction specially in heart (Myocardial
Infarction) Also in kidney & in adrenals…. Variable appearance mostly firm texture. It is suspected that high levels of intracellular
calcium plays a role in coagulative necrosis. Results from denaturation of all proteins
including enzymes .
Cell Injury:
Histology:
Preservation of the tissue architecture & cellular outlines.
The necrotic area stains more eosinophilic, often devoid of nuclei.
Cell Injury:
Renal Infarction: Coagulative Necrosis
Cell Injury:
2- Liquefactive Necrosis Autolysis predominates and results in
liquefied mass e.g. hypoxia in brain, bacterial infections (abscess). Brain cells have a large amount of
hydrolytic digestive enzymes (hydrolases). These enzymes cause the neural tissue to become soft and liquefy.
Liquefactive necrosis is what causes pus to form.
Hydrolytic enzymes are released from neutrophils to fight an invading pathogen.
E. Coli, Staphylococcus, and Streptococcus
Cell Injury:
Stroke- Liquifactive necrosis
Cell Injury:
Lung abscess: Liquefactive necrosis
Cell Injury:Liver abscess: Liquefactive necrosis
Cell Injury:
3- Caseous Necrosis
Grossly “cheese-like”, appearance, being soft and white.
Histology: Central cheesy material , rimmed by chronic
inflammatory cells, epitheloid cells & Langhans giant cells ( GRANULOMA)
Typical of tuberculosis, may be seen in others Is a distinctive form of coagulative necrosis
modified by capsule lipopolysacchride of TB bacilli
Cell Injury:
Caseous necrosis in Tuberculosis
Cell Injury:
Caseous necrosis - Tuberculosis
Cell Injury:
4- Fat Necrosis Two types :
Traumatic fat necrosis → foreign body giant cells → calcification → hard lump
Enzymatic fat necrosis due to acute pancreatitis
Acute Pancreatitis : Medical emergency Enzymes released, digests fat
Adipose tissues → triglycerides & fatty acids → saponification & calcification
Cell Injury:
Foci of fat necrosis with saponification in the mesentery
Cell Injury:
Fat Necrosis - Peritoneum.
Cell Injury:
Gangrene Necrosis plus putrefaction (rotting) by
saprophytes. Wet gangrene: Coagulative necrosis due to
ischemia and liquifactive necrosis due to superimposed infection.
Dry gangrene: Drying of dead tissue, is a form of coagulative necrosis, applied to necrosis of the lower limbs distally, associated with peripheral vascular disease.
Necrosis is separated by a line of demarcation from viable tissue.
Gas gangrene: This caused by wound contamination by anaerobic bacteria (Clostridia perfringes)
Cell Injury:
Toes - Dry Gangrene
Cell Injury:
Wet Gangrene Amputated Diabetic foot
Cell Injury:
APOPTOSIS Programmed cell death by suicide The cell’s membrane remains intact Apoptosis is characterised by death of
single cells or clusters and results in cell shrinkage, not lysis and swelling without an inflammatory reaction, unlike necrosis where there is death of
large amounts of the tissue and there is an associated inflammatory reaction.
Cell death involved in normal and pathologic conditions.
Cell Injury:
APOPTOSIS Apoptosis depends on cellular signals, these
signals cause protein cleavage (proteases) within the cell, causing cell death.
Programmed and energy dependent process designed to switch cell off and eliminate them Cell shrinkage Chromatin condensation- most characteristic Formation of cytoplasmic blebs and
apoptotic bodies Phagocytosis of apoptotic cells or bodies
Cell Injury:
Two main pathways
Intrinsic ‘mitochondrial’ pathway: Increased permeability of mitochondrial
membrane results in release of pro-apoptotic factors (cytochrome c and AIF) that activate downstream caspases death .
Extrinsic ‘death receptor pathway’: FAS and TNF1 receptor families with death
domain.
Cell Injury:
Cell Injury:
Physiologic apoptosis
During development, embryogenesis. Homeostatic mechanism to maintain cell
population(Cell turnover in intestinal crypts).
Immune reaction - defense mechanism. In aging. Shedding of menstrual endometrium. Involution of breast after weaning.
Cell Injury:
Pathologic apoptosis Prostatic ‘atrophy’ after castration. Death of inflammatory cells after
inflammation When cells are damage by disease or
injurious agents DNA damage e.g. radiation,
chemotherapy, Cytotoxic drugs Viral infections e.g. viral hepatitis Neoplasia: tumours that regress or
involution Deletion of autoreactive T cells in thymus Others including rejection of transplants
Cell Injury:
A, Apoptosis of epidermal cells in an immune-mediated reaction. The apoptotic cells are visible in the epidermis with intensely eosinophilic cytoplasm and small, dense nuclei. H&E stain. B, High power of apoptotic cell in liver in immune-mediated
hepatic cell injury.
Cell Injury:Comparison of apoptosis with necrosis
Apoptosis Active process
Occur in single cells
Physiological & pathological
No inflammatory reaction
Necrosis Passive process
Affects mass of cells
Always pathological
stimulates Inflammation
Cell Injury:
Aging and Cellular Death Theories
Aging is caused by accumulations of injurious events
Aging is the result of a genetically controlled developmental program.
Mechanisms Genetic, environmental, and behavioral Changes in regulatory mechanisms Degenerative alterations
Cell Injury:
Cellular aging Genetic e.g. failure of repair mechanisms ,
Clock genes overexpression of antioxidative enzymes Telomerase activity …….etc
Telomerase activity stops in somatic cells, but
continues in stem cells & germ cells Environmental: generation of FR, diet Accumulation of multiple defects Aging Aged cells show Lipofuscin pigment ,
abnormally folded proteins & advanced glycosylation end products ( AGES’s)