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.

• Fatty change is often seen in the liver because it is the major organ involved in fat metabolism, b

ut 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).

• 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.

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

Intracellular Hyaline• Intracellular hyaline is mainly seen in epithelial ce

lls. 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 mellitus, microscopic

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 prese

nt in most living beings including humans.

• 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, microscopic

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, non-haemoglobin-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.

• 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 appar

ently normal tissues and is associated wit

h deranged calcium metabolism and hyp

ercalcaemia.

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 (pykno

sis)

• 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, microscopic

Coagulative necrosis, renal infarction, microscopic

Liquefaction Necrosis • Liquefaction or colliquative necrosis occu

rs 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, microscopic

Liquefactive necrosis, cerebral infarction, microscopic

Caseous Necrosis

• Caseous necrosis is found in the centre of

foci of tuberculous infections.

• It combines features of both coagulative a

nd liquefactive necrosis.

Caseous necrosis, a tuberculous lung, gross

Caseous necrosis, hilar lymph node, gross

Lung, granulomas

, medium power microscopic

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

• Regenerationwhen 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 proliferat

e 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.

• Repairwhen 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 woundsThe 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 healingHealing 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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