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Before going through studying pathology, we have to review the normal structure and function of cell. The normal cell is a highly complex unit consists of various organelles and enzymes, which carry out the metabolic activities, that maintain cell viability and support its normal function. It consists of a mass of protoplasm divided into nucleus and cytoplasm. The cytoplasm consists of cytoplasmic matrix and cytoplasmic organelles. The cytoplasmic matrix (cytosol) is the non-organelle component of the cytoplasm occupying the intracellular spaces between organelles and inclusions. The cell membrane is the outer membrane of the cell that acts as a barrier between its internal and external environment. With electron microscope (EM) it appears as a trilaminar structure consisting of outer and inner electron-dense layers, believed to consist of protein, separated by an intermediate electron-lucent lipid layer. The primary function of cell membrane is regulating the exchange of molecules and ions between its internal and external environment. Mitochondria are membranous organelles involved primarily in cell respiration and energy production. It is ovoid or elongated structures bounded by outer smooth membrane and inner membrane, which thrown into folds (cristae) into the inner cavity. It contains enzymes involved in catalyze reactions that provide the cells with most of its ATP. Due to their role in energy production, the mitochondria are likened to powerhouses of the cells. Moreover, it participates in regulation of calcium level within the cytosol. The Endoplasmic reticulum is an irregular network of branching and anastomosing tubules, cisternae and vesicles. Two types of ER are recognized: rough and smooth endoplasmic reticulum. The rough endoplasmic reticulum is a membranous organelle concerned principally with synthesis and secretion of proteins. The smooth endoplasmic reticulum is participated in steroid hormone synthesis, drug detoxification in liver cells, lipid synthesis in the intestinal absorptive cells, release and storage of Ca ++ ions in striated muscle cells and production of H CL in gastric parietal cells. The Golgi apparatus is a membranous organelle concerned principally with synthesis, concentration, packaging and release of the secretory products. Lysosomes are membrane-bounded vesicles containing hydrolytic enzymes that degradation of any exogenous macromolecules (phagocytosis and pinocytosis). Free ribosomes are responsible for synthesis of proteins for internal use (cytoplasmic proteins and enzymes). Attached ribosomes are responsible for synthesis of proteins for external use (secretory or lysosomal enzymes). The nucleus is the archive of the cell that carries the genetic information necessary to regulate the different cell functions. It consists primarily of DNA, DNA-binding proteins, and some RNA. Most commonly nuclei are spherical or ovoid but they may be spindle-shaped, bean or kidney-shaped or multilobulated. The nucleus consists of nuclear envelope, chromatin, nucleolus and nuclear sap. The Normal function is depend on (1) the environment of the cell; (2) nutritional supply; and (3) constant removal of the products of metabolism.
Figure 1: Ultra structure of cell membrane, EM.
Figure 2:: Ultra structure of mitochondria, EM.
Figure 3: Rough endoplasmic reticulum (rER), EM.
Figure 4: Smooth endoplasmic reticulum (sER), EM.
Figure 5: Golgi apparatus, EM.
Figure 6: Lysosome and peroxisome, EM.
Figure 7: Free and attached (fixed) ribosomes, EM.
Figure 8: EM of the nucleus.
There are a wide number of etiological agents, which lead to cellular injury and death
It is a common cause of cell injury and death. Depending on the severity cell may be adapted, undergo injury or die as in case of Loss of blood supply (ischemia.), inadequate oxygenation of blood due to cardio-respiratory failure and loss of oxygen carrying capacity of blood as in anemia or carbon monoxide poisoning.
It includes mechanical trauma, temperature (burns and deep cold), radiation and electric shock.
Concentrated simple chemicals, poisons substance as arsenic, cyanide or mercuric, insecticides, environmental and air pollutants alcohol and narcotic drugs are example for chemical substances induced cell injury
These agents include viruses, bacteria, fungi and parasites.
It may be life saving or lethal. The anaphylactic reaction to foreign antigen is an example.
An enzyme lack is excellent example for cell damage due to DNA alteration.
It occurs in case of deficiency in protein, vitamins and minerals.
The high-energy phosphate bonds of ATP are very important for cells to perform its activities. The loss of APT synthesis lead to: a. An defect in energy dependent ionic pump lead to accumulation of intracellular sodium and diffusion of potassium outside. The earliest results due to the dysfunction of energy depending sodium potassium pump in the plasma membrane resulting in entrance of sodium, calcium and water into the cells which leads to cloudy swelling and hydropic degeneration. b. The same mechanism lead to swelling of cell organelles c. Switch to anaerobic metabolism, which led to production of lactic acid and decrease pH. Chromatin clumping and disruption of organelle membranes then occur which lead to release of lysosomal enzyme into the cytoplasm and damage vital intracellular molecules
Hypoglycemia which result in deficient ATP production Hypoxia which result from respiratory diseases, ischemia, anemia and alteration of hemoglobin Enzyme inhibition as in case of cyanide poisoning which inhibits cytochrome oxidase causing acute ATP deficiency Uncoupling of oxidative phosphorylation as in case of mitochondrial injury
Plasma membrane damages and impaired it s functions lead to: Loss of structural integrity, which lead to rupture and necrosis of the cell, while less severe lead to localized reversible damage. Loss of function, which lead to abnormal entry of water and sodium and loss of potassium causing cloudy swelling. Deposition of lipofuscin pigment
Free radicals are highly unstable particles with an odd number of electrons in their outer shell. It produces by chemicals, radiation, oxygen toxicity, aging process and phagocytosis of microbial agent by inflammatory cells. The reaction with the cell membrane lipids result in excess energy and membrane damage.
Activation of complement lead to phospholipase like effect that can enzymatically damage the plasma membrane
Enzyme with lipase like activity damage cell membrane as pancreatic lipase with acute pancreatitis. Also clostridium perfringens produce enzymes that cause damage of plasma membrane.
Viruses cause lysis by direct insertion into the cell membrane or indirect through immune response to the viral antigen on infected cell surface
As extremes heat, cold or certain chemicals cause direct lysis
It leads to failure of mitosis, synthesis structural and growth regulating proteins and enzyme.
A. Inherited genetic abnormalities B. Acquired genetic abnormalities is a somatic mutation due to ionizing radiation, viruses and mutagenic drugs and chemicals
Many exogenous and endogenous agents including alcohol, drugs heavy metals and infectious agents causing degenerative changes or necrosis by interfering directly with various specific biochemical reactions. Before we will discus cell death, we kwon that the cell injury is depend on severity or duration of stimuli. Not all-injurious stimuli causing cell death. So we have to turn our attention to the adaptive changes that occurs in cells and tissue suffering from less severe injurious agents. The pathological adaptation allows the injured cells to ideally modulate their environment to escape the effect of stimuli. The adaptive process in cell growth and adaptation (atrophy, hyperplasia, hypertrophy, metaplasia and dysplasia) will discus in section of disorders of development and growth.
Cell death is occurs when the insult is causing irreversible cell injury or reaching the point of no return. Cell death occurs in two distinct patterns, accidental cell death (necrosis) and programmed cell death (apoptosis).
The mechanism of apoptosis can be explained in the following points:
There are several signaling that initiate apoptosis. The signals may be intrinsic, lack of growth factors and release of enzymes from toxic T cells. The transmembrane signal acts either through suppresses preexisting death program or initiate a death cascade.
It occurs through specific proteins that carries and connect the apoptotic signal to the final execution program.
It is results from activation or synthesis of number of catabolic enzymes leading to morphological changes.
The apoptotic cell has surface marker molecules that facilitate phagocytosis of the dead cells or fragments by adjacent cells or phagocytes.
Apoptosis usually involves single cells or group of cells. The cells appear firstly as round or oval with deeply eosinophilic cytoplasm. After that the cell shrinkage and the chromatin aggregate under the nuclear membrane. After that the chromatin fragmented and the cell fragmented into apoptotic bodies consist of membrane bound fragment of cytoplasm and nucleus. The apoptotic bodies then phagocytize by adjacent cells or phagocytic cells without inflammatory reaction.
Figure 10: Liver cell
shows apoptotic body. H&E.
Figure 11: Liver shows apoptosis H&E.
Necrosis is the death of cells or tissue in the living animal resulting from enzymatic degradation of the nucleus and cytoplasm. Necrosis may occurs directly or follow degeneration.
The changes occur in dead tissue are collectively known as necrosis
It is the best evidence and common manifestation of cell necrosis and every nucleus goes through each of these stages before finally disappear. The nucleus becomes shrunken but round dense and deeply basophilic or nearly black homogenous mass and lack nucleolus (Pyknosis). The pyknotic nuclei may be break up into numerous small basophilic granules with rupture of nuclear membrane (Karyorrhexis). The fragment may be remain in the original place or scattered in the cytoplasm. Moreover, the nucleus may be lysis as a result of the action of lysosome enzymes of dead cells and appear as a hollow sphere surrounded by faint outline nuclear membrane (Karyolysis). Finally complete loss of the nucleus is seen.
The cytoplasm of necrotic cells is usually more eosinophilic attributable in part to degradation of RNA, which usually give a degree of basophilia to cytoplasm, and denaturation of cytoplasmic protein. The cytoplasm appears homogenous due to loss of glycogen particles. The cytoplasm appears vacuolated due to digested cell organelles by lysosomal enzyme. Finally the cytoplasm tend to become less and less dense and finally disappear.
Loss of cell outline. When the changes of necrosis are advanced it is impossible to see the form and outline of cell. Later on, loss of differential staining and finally loss of cells occur.
The dead tissue is paler than healthy one due to hemolysis of erythrocytes and diffusion of pigments from cytoplasm of necrotic cells. Moreover, the necrotic tissue is less strength than normal due to enzymatic digestion of cytoskeleton and cell membrane. The necrotic tissue may be friable (caseous necrosis), firm (coagulative necrosis) or liquid (liquifactive necrosis). The odors of putrefaction from necrotic tissue colonized by saprophytic bacteria.
It is the most common pattern of necrosis and characterized by maintenance of cell out line and tissue architecture. It results from denaturation of cellular proteins and enzymes, which block cell autolysis. It is not observed in diseases where large number of neutrophils is present.
Local ischemia as infarction. Toxic products of certain bacteria as in calf diphtheria.Certain locally acting poisons as mercuric chloride. Necrosis of muscle (Zenker's necrosis) as in virus infection or vitamin E deficiency.
The necrotic tissue is firm, gray or white and depressed compared with the surrounding tissue.
Figure 14: Muscle showing Coagulative necrosis (Zenker's necrosis)
infiltrated with inflammatory cells, H&E.
Figure 16 : Kidney of rat showing coagulative necrosis of the epithelium
lining, H&E.
Figure 17 :Liver
showing coagulative necrosis (right) and normal one (Left).
It is usually associated with granulomatous diseases as in tuberculosis. It is consist of a mixture of coagulated protein and lipid. It is resulted from death of macrophages and eosinophils or dehydration of pus.
Loss of tissue architecture and cellular details which replaced by granular eosinophilic and basophilic debri (blue chromatin fragment and red material derived from the cytoplasm). The caseous necrosis surrounded by granulomatous wall.
Soft friable, whitish gray debri resembling cheesy material.
Figure 18 :Lymph node
of cattle infected with tuberculosis showing caseous necrosis
characterized by replacement of the lymphoid tissue with eosinophilic
and basophilic debri. H&E.
Figure 20 :
Sheep
lymph node suffering from caseous lymphadenitis showing caseous
necrosis. The lymph node replaced by caseated materials in the form of
lamellated layers.
It is resulted from the action of powerful hydrolytic enzymes. It associated with abscesses formation or necrosis in the central nervous system (rich in non-coagulable lipoidal material and poor in coagulable albumin)
In suppurative inflammation characterized by loss of tissue architecture and cellular details which replaced by structure less basophilic substance (dead and life neutrophils and bacteria) surrounded by numerous neutrophils and dilated blood vessels. In the central nervous system characterized by empty cavities or containing pink staining material.
Large or small cavities containing yellowish or whitish fluid are seen in CNS. Pus of various colors and consistencies are seen.
Figure 21 :
Lung
showing liquifactive necrosis represented by replacement of the
pulmonary tissue with structureless basophilic materials. H&E.
Figure 22 :Lung
showing liquifactive necrosis represented by replacement of the
pulmonary tissue with structureless basophilic materials. H&E. Figure 23 :
Uterus showing
accumulation of pus in its lumen.
Figure 24 :
Lung of cattle
showing cavities filled with mucopurulent materials.
It is the necrosis of adipose tissue. The fat decomposed by lipase enzyme into fatty acid and glycerin. The fatty acid combines with sodium, potassium and calcium to form soap like compounds. Fat solvents used during tissue processing do not dissolve these compounds. The fat necrosis could be: Traumatic or external fat necrosis Enzymatic or pancreatic fat necrosis
The necrotic adipose tissue appear as foci of shadow outline of necrotic fat cell containing blue, pink or purple crescentic crystals depending on the presence of sodium, potassium or calcium respectively. The nuclei are pyknotic and the necrotic area surrounded by inflammatory reaction.
The necrotic tissue appear opaque, whitish solid or slightly granular. Figure 25 :
Adipose tissue showing fat necrosis represented by
foci of shadow outline of
necrotic fat cell containing pink crescentic crystals. Moreover,
the nuclei
are pyknotic and the necrotic area surrounded by inflammatory
reaction. H&E
It is a type of connective tissue necrosis occurs in autoimmune diseases. It is involve smooth muscle and collagen fibers especially media of blood vessels. It characterized by loss of tissue architecture, which replaced by homogenous bright pink staining material resembling fibrin.
Small necrotic masses are liquefied by autolysis or heterolysis and the fluid removed by blood or lymph. Liquefaction with abscess formation when necrosis is caused or infected by pyogenic Bacteria. Encapsulation without liquefaction as in tuberculosis and dead helminth. Desquamation or sloughing as in case of epithelial lining. Replacement of necrotic tissue by fibrous tissue scare or regeneration. Calcification and gangrene.
It is extensive tissue necrosis complicated to a variable degree by secondary bacterial infection. It may be dry, moist or gas gangrene If the cause of necrosis is the same of putrefaction of the tissue it called primary gangrene, while in secondary gangrene the necrosis and gangrene caused by different type of bacteria.
It is the same as necrosis plus exposure to putrefactive bacteria. In the intestine and extremities the interference of blood supply in the most common cause. In the other hand the most common cause of gangrene in udder and lung is the toxic product of highly fatal bacteria.
It is a condition of which necrotic tissue is invaded putrefactive bacteria. It occurs in extremities but more common in the internal organ; due to rich blood supply, moisture and warmth which is suitable media for rapid bacterial growth.
Mixture of coagulation and Liquefactive necrosis with bacterial bacilli are seen. Numerous gas bubbles, recognizable as empty space of variable size having no wall are seen. The line of defense is not clear.
The affected part is black-greenish, swollen and soft. The affected tissue is cold and insensitive to touch or pain. It has a fetid odor due to liberation of hydrogen sulfide There is no sharp line of demarcation between the living and gangrenous tissue
It occur inn tissues that have limited blood and fluid content, so it occur mostly in external tissue as skin and limbs. The bacterial growth is slower than moist one due to little moisture, heat and blood supply.
The gangrenous tissue shows coagulative necrosis beside bacterial bacilli and few gas bubbles. Sharp line of demarcation is seen between the healthy and gangrenous tissue and consists of numerous leukocytes and congested blood vessels.
The gangrenous part appear dry, cold and wrinkled. It is dark reddish or black in color with fetid odor. Sharp line of demarcation (reddish or bluish area) are seen.
Moist gangrene is more fatal than dry one due to it spread rapidly into the surrounding tissue with production of highly toxic substances that absorbed by blood and affected other tissues.
Animal usually survive due to secondary bacterial infection is insignificant. Treatment consist of surgical removal of dead tissue.
It is characterized by extensive necrosis with production of gas by invasive bacteria. It is usually caused by the genus clostridium as in malignant edema and black leg diseases. The gross appearance is similar to that of wet gangrene in addition to presence of gas (crepitating).
Figure 28: Muscle of cattle
infected with clostridium .You
can find the hematoxylin-stained bacilli and nearby the
dead voluntary muscle fibers. There are a few nuclei visible
in the lesion and the cells are very eosinophilic.
Figure 29: Calf feet showing
dry gangrene.
Figure 30:
Tail of cattle showing dry
gangrene.
It is the chemical and morphological changes that occur in tissues between the time of death and necropsy. The rapidity of postmortem changes depends on environmental temperature and humidity plus the condition of the animal.
It occurs 2-4 hours after death. It begins earliest in cardiac muscle and expressed blood from left ventricle. Failure indicates antemortem degeneration. Rigor disappear after 1-2 days depending on the surrounding environment.
It is usually seen inside heart and large blood vessel.
It is due to lysis of erythrocytes with release of hemoglobin, which stained the intema of large arteries with pink color.
It is the discoloration of liver and intestine with yellowish and green color when they come in contact gallbladder
It is the black or greenish discoloration of internal organs resulting from reaction between hemosiderin (lysis of erythrocytes) and hydrogen sulfide of putrefactive bacteria.
It includes all postmortem changes which alter the tissue color.
It is the general cooling of the body after death.
It is the congestion of the most lower part of the body due to gravity.
It is the presence of gas bubbles in the parenchymatous organ produced by putrefactive bacteria that enter the blood stream from intestine after death.
It is the presence of gas in the stomach and other parts of digestive tract produced by fermentation.
It is due to the postmortem peristaltic movement. There is no inflammation
Autolysis means self-digestion by the tissue's enzymes that released into the cytoplasm of the cell after death. It depends on the content of proteolytic enzymes, so autolysis occurs early in liver, pancreas and kidneys.
It is the decomposition of the cells by enzymes other than those present in the cells as enzymes come from putrefactive microorganisms.
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Copyright © Faculty of Veterinary Medicine, Mansoura University |
