Pathology-2(cell Injury & Healing)

Cell Injury and Repair (2) DURGE RAJ GHALAN

Morphology of cell injury

• Degeneration/Intracellular Accumulations • Cell death

Degeneration and Intracellular Accumulations • Cellular swelling • Fatty change • Hyaline change • Amyloidosis • Pigments • Pathologic calcification

Fatty change (Steatosis) •

The terms fatty change and steatosis describe abnormal accumulations of triglycerides within parenchymal cells.

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Fatty change is often seen in the liver because it is the major organ involved in fat metabolism, but it also occurs in heart, muscle, and kidney.

Fatty metamorphosis of liver, gross

. Fatty metamorphosis of liver, microscopic

Fatty change, liver, microscopic

Hyaline Change •

The word “Hyaline” means glassy (hyalos = glass).

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Hyaline is a descriptive histologic term for glassy, homogeneous, eosinophilic appearance of material in H.E stained sections and does not refer to any specific substance.

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Hyaline change is associated with heterogeneous pathologic conditions and may be intracellular or extracellular.

Intracellular Hyaline •

Intracellular hyaline is mainly seen in epithelial cells. For example: 1. Hyaline droplets in the proximal tubular epithelial cells in cases of excessive reabsorption of plasma. 2. Mallory’s hyaline represents aggregates of intermediate filaments in the hepatocytes in alcoholic liver cell injury. 3. Russel’s bodies representing excessive immunoglobulins in the RER of the plasma cells.

Hyaline droplets in the renal tubular epithelium

Mallory's hyaline, liver, microscopic

Extracellular Hyaline •

Extracellular hyaline is seen in connective tissues. A few examples of extracellular hyaline change are: 1. Hyaline degeneration in leiomyomas of the uterus. 2. Hyalinised old scar of fibrocollagenous tissues. 3. Hyaline arteriosclerosis is renal vessels in hypertension and diabetes mellitus. 4. Hyalinised glomeruli in chronic glomerulonephritis.

Uterus, leiomyoma, microscopic

Renal hyaline arteriolosclerosis with diabetes melli

Amyloidosis •

Amyloidosis is the term used for a group of diseases characterised by extracellular deposition of fibrillar proteinaceous substances called amyloid having common morphological appearance, staining properties and physical structure but with variable protein (or biochemical) composition.

Amyloidosis •

By light microscopy with H.E staining, amyloid appears as extracellular, homogeneous, structureless and eosinophilic hyaline material, which is positive with Congo red staining.

Amyloid deposition, Congo red stain, microscopic

Pigments •

Pigments are coloured substances present in most living beings including humans.

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There are 2 broad categories of pigments: endogenous exogenous

Pigments •

Haemosiderin Haemosiderin is formed by aggregates of ferritin and is identifiable by light microscopy as golden-yellow to brown, granular pigment, especially within the mononuclear phagocytes of the bone marrow, spleen and liver where break down of senescent red cells takes place.

. Hemosiderin in pulmonary macrophages, microscopic

. Hemosiderosis of liver, iron stain, microscopic

Hemosiderin deposition in renal tubules, iron stain, microscop

Pigments •

Lipofuscin (Wear and Tear Pigment) Lipofuscin or lipochrome is yellowish-brown intracellular lipid pigment. The pigment is often found in atrophied cells of old age and hence the name “wear and tear pigment”. It is seen in the myocardial fibres, hepatocytes, Leydig cells of the testes and in neurons in senile dementia.

Lipochrome in hepatocytes, microscopic

Pigments •

Melanin Melanin is the brown-black, nonhaemoglobin-derived pigment normally present in the hair, skin, choroid of the eye, meninges and adrenal medulla. It is synthesized in the melanocytes and dendritic cells.

Melanoma

Pigments •

Bilirubin Bilirubin is the normal major pigment found in bile. It is derived from hemoglobin but contain no iron. Its normal formation and excretion are vital to health, and jaundice is a common clinical disorder caused by excesses of this pigment within cells and tissues.

Bilirubin in liver (cholestasis), microscopic

Pigments •

Coal dust The lungs of most individuals, especially of those living in urban areas due to atmospheric pollutants and of smokers, show a large number of inhaled pigmented materials. The most commonly inhaled substances are carbon or coal dust; others are silica or stone dust, iron or iron oxide, asbestos, and various other organic substances.

Anthracotic pigmentation seen on surface of lung, gross

Anthracotic pigment in macrophages of hilar lymph node, microscopic

Pathologic calcification •

Deposition of calcium salts in tissues other than osteoid or enamel is called pathologic calcification.

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Two distinct types of pathologic calcification are recognised: Dystrophic calcification Metastatic calcification

Dystrophic calcification It is characterized by deposition of calcium salts in dead or degenerated tissues with normal calcium metabolism and normal serum calcium levels.

Dystrophic calcification, stomach, microscopic

Metastatic calcification Metastatic calcification occurs in apparently normal tissues and is associated with deranged calcium metabolism and hypercalcaemia.

Metastatic calcification of lung with hypercalcemia, microscopic

Cell death • Cell death is a state of irreversible injury. • It may occur in the living body as a local or focal change (i.e. necrosis and apoptosis) and the changes that follow it (i.e.gangrene and pathologic calcification), or results in end of the life (somatic death).

Cell death • Necrosis • Apoptosis

Necrosis • Definition of necrosis • Morphology of necrosis • Types of necrosis

Necrosis • Necrosis is defined as focal death along with degradation of tissue by hydrolytic enzymes liberated by cells. • It is invariably accompanied by inflammatory reaction.

Nuclear changes in necrotic cell • Condensation of nuclear chromatin (pyknosis) • Fragmentation into many granular clumps (karyorrhexis) • Dissolution (karyolysis)

Cytoplasmic changes in necrotic cell • The cytoplasm appears homogeneous and intensely eosinophilic. • Occasionally, it may show vacuolation or dystrophic calcification.

Types of Necrosis 1. Coagulative necrosis 2. Liquetaction (colliquative) necrosis 3. Caseous necrosis 4. Gangrene

Coagulative Necrosis • This is the most common types of necrosis caused by irreversible focal injury, mostly from sudden cessation of blood flow (ischaemia), and less often from bacterial and chemical agents. • The organs commonly affected are the heart, kidney, and spleen.

Coagulative necrosis, renal infarction, gross

Coagulative necrosis, splenic infarctions, gross

Coagulative necrosis, myocardial infarction, micros

Coagulative necrosis, renal infarction, microscopic

Liquefaction Necrosis • Liquefaction or colliquative necrosis occurs commonly due to ischaemic injury and bacterial or fungal infections. • It occurs due to degradation of tissue by the action of powerful hydrolytic enzymes. • The common examples are infarct brain and abscess cavity.

Liquefactive necrosis, lung abscesses, gross

Liquefactive necrosis, cerebral infarction, gross

Liquefactive necrosis, cerebral infarction, gross

. Liquefactive necrosis, liver abscess, microscopic

Liquefactive necrosis, cerebral infarction, microsco

Liquefactive necrosis, cerebral infarction, microsco

Caseous Necrosis • Caseous necrosis is found in the centre of foci of tuberculous infections. • It combines features of both coagulative and liquefactive necrosis.

Caseous necrosis, a tuberculous lung, gross

Caseous necrosis, hilar lymph node, gross

Gangrene • Gangrene is a form of necrosis of tissue with superadded putrefaction. • There are 3 main forms of gangrene --Dry gangrene Wet gangrene Gas gangrene

Gangrene • Dry gangrene This form of gangrene begins in the distal part of a limb due to ischaemia. The typical example is the dry gangrene in the toes and feet of an old patient due to arteriosclerosis.

Dry gangrene of foot

Gangrenous necrosis, foot, gross

Gangrene • Wet gangrene This occurs in naturally moist tissues and organs such as the the mouth, bowel, lung, cervix, vulva etc. Wet gangrene usually develops rapidly due to blockage of venous and less commonly arterial blood flow from thrombosis or embolism.

Wet gangrene of small bowel

Gangrenous necrosis, lower extremity, gross

Gangrene • Gas gangrene Gas gangrene is a special form of wet gangrene caused by gas-forming clostridia (gram-positive anaerobic bacteria) which gain entry into the tissue through open contaminated wounds, especially in the muscles, or as a complication of operation on colon which normally contains clostridia.

Apoptosis • Apoptosis is a form of “coordinated and internally programmed cell death” which is of significance in a variety of physiologic and pathologic conditions. • The term was first coined in 1972 as distinct from necrosis.

Ultrastructural features of apoptosis

Mechanisms of apoptosis

Chapter 3 Healing of Cell Injury

Healing • Injury to tissue may result in cell death and tissue destruction. Healing on the other hand is the body response to injury in an attempt to restore normal structure and function. • The process of healing involves 2 distinct processes: Regeneration and Repair

Healing • Regeneration • Repair • Wound healing

• Regeneration when healing takes place by proliferation of parenchymal cells and usually results in complete restoration of the original tissue.

The cells of the body can be divided into 3 groups (depending upon their capacity to divide): labile cells stable cells permanent cells

Labile cells • These cells continue to multiply throughout life under normal physiologic conditions. • These include: surface epithelial cells of epidermis, alimentary tract, respiratory tract, urinary tract, vagina, cervix, uterine endometrium, haematopoietic cells of bone marrow, cells of lymph nodes and spleen.

Stabile cells • These cells decrease or lose their ability to proliferate after adolescence but retain the capacity to multiply in response to stimuli throughout adult life. • These include: parenchymal cells of organs like liver, pancreas, kidneys, adrenal and thyroid; mesenchymal cells like smooth muscle cells, fibroblasts, vascular endothelium, bone and cartilage cells.

Permanent cells • These cells lose their ability to proliferate around the time of birth. • These include: neurons of nervous system, skeletal muscle and cardiac muscle cells.

• Repair when the healing takes place by proliferation of connective tissue elements resulting in fibrosis and scarring.

Repair is the replacement of injured tissue by fibrous tissue. Two processes are involved in repair: 1. Granulation tissue formation 2. Contraction of wounds

Granulation tissue formation The following 3 phases are observed in the formation of granulation tissue: 1. Phase of inflammation 2. Phase of clearance 3. Phase of ingrowth of granulation tissue

Contraction of wounds The wound starts contracting after 2-3 days and the process is completed by the 14th day. During this period, the wound is reduced by approximately 80% of its original size. Contracted wound results in rapid healing since lesser surface area of the injured tissue has to be replaced.

Granulation tissue formation

• Wound healing Healing of skin wounds provides a classical example of combination of regeneration and repair described above. This can be accomplished in one of the following two ways: Healing by first intention (primary union) Healing by second intention (secondary union)

Primary union of skin wounds

Secondary union of skin wounds

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