Cell injury 2

Cell injury, Intracellular accumulations & Pathological calcification Dr. Banan B. Al-Abady Lecturer in pathology department


Irreversible cell injury: occurs when the injury persist or when it is severe from the start. Here the cell reaches the point of no return and progression to cell death is inevitable. It is of 2 types: 1) Necrosis 2)Apoptosis Necrosis: it is a sequence of morphologic changes that follow cell death in the living tissue or organs due to action of degradative enzymes or protein denaturation on irreversibly injured cells.


It is a passive processAssociated with inflammationRandomly occurs Involve a group of cells Always pathologicCauses : ischemia, chemical injury or infarction( cell death due to cut of blood supply), nutritional….etcMechanisms of necrosis:Denaturation of proteinsEnzymatic digestion of the cell: either by its own enzymes (autolysis) or the cell digested by proteolytic enzymes secreted from invading inflammatory cells, this is called (heterolysis)

Liver cell necrosis: Nuclear changes

normal
pyknosis
karyorrhexis
karyolysis

Types of necrosis

coagulation necrosis liquifactive necrosis fat necrosis caseous necrosis fibrinoid necrosis gangrene


Coagulative necrosis: The commonest type of necrosis. Occur Any where in the body except C.N.S Usually due to hypoxia Grossly: Whitish-gray or red-hemorrhagic firm wedge shape area of infarction Histology: Preservation of the tissue architecture & cellular outline for sometime loss of internal details including nuclei. It Results from denaturation of proteins

Myocardial infraction, the cells become more eosinophilic , loss of striation, absence of nucleus & their outline are preserved

infarction

It is an ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage. Necrosis is of coagulative type (except brain: liquifactive).

Grossly : wedge-shaped ,(the occluded vessel at the apex and the periphery of the organ forming the base), the border tends to be dark red, reflecting hemorrhage into surrounding viable tissue. Microscopically, a pale infarct exhibits coagulative type (except brain: liquifactive).

Coagulative necrosis(infarction)-Spleen

Coagulative necrosis(infarction)-kidney


Liquefactive necrosis:Seen in Ischemic necrosis (infarction) of CNSAbscess formation in pyogenic infection. Enzyme digestion & autolysis ˃ protein denaturation so the area become soft  cystic.Grossly: softening & liquefaction of the necrotic tissue (Soft liquid like)Microscopically : complete loss of tissue architecture(Loss of original tissue) , the area contains necrotic debris & macrophage,.

Liquefactive necrosis(Lung Abscess)

Liquefactive necrosis- Brain infarction

Caseous necrosis:

Caseous necrosis (TB), yellow white appears as cheese-like

Caseous necrosis (Lung TB), amorphous structureless granular eosinophilic material

Fat necrosis:
1- Enzymatic fat necrosis: which usually follow acute pancreatitis due to release of pancreatic enzyme(lipases)  necrosis of pancreatic tissue & release of free fatty acid which combined with calcium to produce grossly visible chalky-white areas (fat saponification), 2- Traumatic fat necrosis: occur in the breast after trauma which caused release of fatty acid from cell this stimulate macrophage infiltration which engulf fat, inflammation  massive fibrosis so the lesion grossly become hard mimic carcinoma.

Fat necrosis The areas of white chalky deposits represent foci of fat necrosis with calcium soap formation (fat saponification)


Fat necrosis Eosinophilic cytoplasm, shadowy outlines of necrotic fat cells, with basophilic calcium deposits, surrounded by an inflammatory reaction

Fibrinoid necrosis:

Fibrinoid necrosis (is caused by immune-mediated vascular damage).It is marked by deposition of fibrin-like proteinaceous material in arterial walls, which appears eosinophilic on light microscopy.


Gangrene
It is coagulative necrosis plus putrefaction by saprophytes (anaerobic bacteria). It can be classified into two types: Primary gangrene Secondary gangrene

Primary gangrene

Secondary gangrene
This type of gangrene is characterized by necrosis due to some other causes , usually loss of blood supply from vascular obstruction or tissue laceration & saprophytic bacteria then digest the dead tissue , there are two types : Dry gangrene Wet gangrene


It occurs in the distal part of the limb due to gradual cut of blood supply as in old patient due to arteriosclerosis or in patient with vasculitis). The line of demarcation between dead and living tissue is clear. The lesion remains localized . the affected part is dry ,shrunken with black discoloration
Dry gangrene


Wet gangrene occurs due to venous block & less commonly due to arterial obstruction as a gangrene of bowel due to mesenteric vascular occlusion and in diabetic limb. The line of demarcation between dead and living is indistinct . May extend proximally beyond the site of infective. the affected part is soft moist swollen & dark.
Wet gangrene

It is a form of a necrosis of the tissue with superadded putrefaction.

Dry gangrene -Ischemia
Wet gangrene –D.M


Fate of necrotic tissue:

Effect of necrosis: it is variable depending on the: type of the cell involved extent of necrosis (small, large) the involved organ the proliferation capacity of the cell involved .

Mechanisms of apoptosis: Include 4 steps

Signaling: apoptosis will be initiated by different signals, intrinsic as ( embryogenesis signal), or extrinsic as( injury ,radiation, toxin….) or due to withdrawal of growth factor.Control and integration: which is caused by certain type of proteins that carry the signal death to the execution.

3-Execution: characterized by formation/or activation of a no. of catabolic enzymes (caspases) → protease(degrade cytoskeleton & nuclear proteins)endonuclease (cleavage the DNA into fragments of double stranded DNA)transglutaminase cause cross linking of cytoplasmic proteins causing shrinkage of the cells.4-Removable of apoptotic bodies by phagocytes.

Genetic basis of apoptosis: bax, bcl-x & bad genes are apoptotic genes P53 stimulate apoptosis by stimulating synthesis of bax gene bcl-2 is antiapoptotic gene . Microscopically: in H&E staining section, apoptotic cell appears reduced in size and contains brightly eosinophilic cytoplasm and a condensed nucleus.

Apoptosis of an epidermal cell. The cell is reduced in size and contains brightly eosinophilic cytoplasm and a condensed nucleus.


鐂ҥ(鐀ѭ鐂ȠēЋǯЂᯀЃ攰‚늘ѓ攰„늘…‡€їƿǿ́〃̿쎀(οعنصر نائب للمحتوى 2ﾠᙼฐt௃￿￿ Examples where apoptosis occurs include: a-Physiologic apoptosis 1-During embryogenesis. i.e. it is responsible for shaping of various organs and structures . 2- Hormone- dependent involution. e.g. endometrium during the menstrual cycle & lactating breast after weaning. 3-Proliferating cell populations: e.g. intestinal epithelium, skin & blood cells. b-Pathological: 1-Atrophy of the prostate after castration. 2-Virally infected cells as in acute viral hepatitis 3- Neoplasia. 4-Radiation 5-Cytotoxic drugs

Differences between apoptosis & necrosis

Apoptosis
Active process Occur in single cells Physiological & pathological No inflammatory reaction Programmed process Mechanism; Gene activation Caspases activation causing activation of endonuclease, proteases & transglutaminase
Necrosis
Passive process Affects mass of cells Always pathological Stimulate inflammation Random process Mechanism; ATP depletion Cell membrane injury

Differences between apoptosis & necrosis

Apoptosis
Morphology: Cell shrinkage Nuclear condensation & fragmentation Formation of apoptotic bodies Apoptotic bodies engulf by macrophages
Necrosis
Morphology Cell swelling Nuclear changes (pyknosis, karyorrhexis & karyolysis) Eosinophilic cytoplasm Necrotic area infiltrate&cleaned by inflammatory cells

Intra cellular accumulation : Excess storage of substances inside the cells, can be seen in many conditions include : Upset of normal metabolism results in accumulation of normal substance e.g fatty changes (reversible cell injury) . Genetic defect in the enzyme lead to accumulation of its substrate ( abnormal substance). Some materials are incapable for digestion or transport to other place so it will accumulate e.g. pigments


Hyaline change: It refers to an alteration within cells or in the extracellular space that gives a homogeneous, glassy, pink appearance in routine histologic sections stained with H&E . Example of intracellular hyaline Alcoholic hyaline in hepatocytes Viral inclusion Example of extracellular hyaline Hyaline arteriolosclerosis, Amyloid, Scar.

Pigmentations :

There are two types : Exogenous pigmentations : Carbon (coal dust), accumulation of carbon particles in the lung give its black color called (anthracosis). if there is excess deposition of carbon in the lung it may cause extensive fibrosis & the condition is called pneumoconiosis Tattooing, the pigment inoculated is taken by dermal macrophages (harmless).

Accumulation of carbon particles in the lung & LN (anthracosis)

Endogenous pigmentation : 1- Lipofuscin : yellow brown pigment seen inside the cell of the liver , heart & brain ,seen in old ages ( wear & tear pigment) & it is a marker of damage by free radicals and in pateints with sever malnutrition and cancer cachexia.

Lipofuscin pigment within hepatocytes

2-Melanin: This is an endogenous non-hemoglobin-derived brown-black pigment. The skin pigment is produced from tyrosin by the action of tyrosinase enzyme within the melanocytes.Lesions associated with melanocytes areMoles (nevi) …….benign lesionMelanoma………..Malignant

3-Bilirubin: Yellow-brown pigment . It is derived from the heme portion of hemoglobin. The conversion to bile occur in the liver. Excess accumulation of bilirubin pigment will lead to a clinical condition called jaundice which characterized by yellow discoloration of skin & mucous membrane. .

Bilirubin deposition within the liver

4-Hemosidrin: Is a hemoglobin-derived, golden-yellow to brown granules. Excess iron in the body causes hemosiderin to accumulate within the cells.Special stain for iron is Prussian blue or Perl’s stain Excess deposition is termed as hemosiderosis which is either localized or systemic.A-Localized hemosiderosis: result from local hemorrhage e.g. bruise, cerebral hemorrhage.

Hemosiderin pigment in the alveolar macrophages

Prussian blue or Perl’s stain

B- Systemic hemosiderosis : Primary: idiopathic hemosiderosis Characterized by excess absorption of the iron from the gut. Liver cirhosis Diabetes mellitus Skin pigmentation causing bronzed diabetes Liver cancer.

Secondary : occurs whenever there is systemic iron overload, this is associated with1-Increased dietary iron absorption.2-Impaired utilization of iron.3-Hemolytic anemia.4-Excessive blood transfusion.In systemic hemosiderosis, hemosiderin accumulation →tissue damage→ the disease called hemochromatosis.

Pathological calcification : is the abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium, and other mineral salts & it is of two types : 1-Dystrophic calcification : Deposition of calcium in non viable or dying tissues in the presence of normal serum level of calcium with normal calcium metabolism. such as Areas of necrosis wall of artery in atherosclerosis Disease of valve ( aging or damage valve) Dead parasites & their ova.

dystrophic calcification

Fine, white granules or clumps, often felt as gritty deposits.


Dystrophic calcification


Pathogenesis : is not well known , it could be due to one of the followings : Increase in the PH of the tissue i.e. become alkaline . Release of alkaline phosphates which stimulate the deposition of calcium . The presence of cellular product which act as a nucleus that stimulate the deposition of calcium around it .

2-Metastatic calcification : deposition of calcium salts in otherwise normal tissues, and it almost always results from hypercalcemia secondary to some disturbance in calcium metabolism. Causes :(1) increased secretion of parathyroid hormone (PTH), as in hyperparathyroidism due to parathyroid tumors,(2) resorption of bone tissue, as prolong immobilization or in destructive disease of the bone such as multiple myeloma, leukemia & secondary deposit in the bone (e.g. breast cancer)(3) vitamin D–related disorders, including vitamin D intoxication (4) renal failure, which causes retention of phosphate, leading to secondary hyperparathyroidism.Less common cause milk-alkali syndrome, which is due to excessive ingestion of antacids such as milk or calcium carbonate.Organs affected are: kidneys, stomach, lungs , pulmonary veins& systemic arteries.

metastatic calcification lung

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