TABLE 2. Contrasting Features of Apoptosis and Necrosis
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FEATURE
APOPTOSIS
NECROSIS
1. Definition
Programmed and coordinated cell death
Cell death along with degradation of tissue by hydrolytic enzymes
2 Causative agents
Physiologic and pathologic processes
Hypoxia, toxins
3. Morphology
No Inflammatory reaction
Inflammatory reaction always present
Death of single cells
Death of many adjacent cells
Cell shrinkage
Cell swelling initially
Cytoplasmic blebs on membrane
Membrane disruption
Apoptotic bodies
Damaged organelles
Chromatin condensation
Nuclear disruption
Phagocytosis of apoptotic bodies by macrophages
Phagocytosis of cell debris by macrophages
4. Molecular changes
Lysosomes and other organelles intact
Lysosomal breakdown with liberation of hydrolytic enzymes and oncossuppressor genes
DEATH, SIGNS OF DEATH, POSTMORTEN CHANGES
Death is the expression of irreversible stopping of the vital activity of organism. With approach of death a man turns into the dead body or corpse (cadaver).
There are natural (physiologic), violent death and death after diseases.
Natural death takes place in senile persons as a result of physiologic wear of organism.
Violent death is a result of murders, suicides, traumas and accidents.
Death after diseases is a result of incompatibility of the life with changes that were provoked by pathological (unhealthy) processes.
There are clinical and biological death:
1. Clinical death is characterized with stopping of breathing and blood circulation, which are reversible during some minutes (the time of outliving of the brain cortex). Agony precedes clinical death and is the result of uncoordinated actions of homeostatic systems during terminal period (arrhythmia, paralysis of sphincters, convulsions and pulmonary edema).
2. Biological death is irreversible changes of vital activity of organism and beginning of autolytical processes. The central nervous system dies in the fiirst 5-6 minutes. In other organs and tissues this process lengthen out to some hours or even days.
Soon after biological death a number of signs of death and postmorten changes appears. They are the followings:
coolness of the dead body (algor mortis) develops as the result of stopping of warnth’s production in the body and equilization of temperature of dead body and environment;
becoming numb of a corpse (rigor mortis) is manifested as condensation of arbitrary and nonarbitrary muscles because of disappearing of adenosine triphosphate and accumulation of lactic acid in them. Usually it develops in 2-5 hours after death, spreads to all muscles of the body to the end of the first day, is kept during 2-3 days and then disappears;
putrid drying appears because of evaporation of moisture from the surface of the body. It may be localized or generalized (mummification). The dimness of cornea and appearance of dark-brown patches on sclera are connected with this process;
redistribution of blood in the corpse results in repletion of veins with blood, but arteries remain almost empty. The postmorten coagulation of veins and cavities of the right part of the heart takes place. However in the cases of death because of asphyxia the blood does not coagulate (asphyxia of newborns);
putrid patches appear because of redistribution of blood in the corpse and depend on its position. The blood flows down into the veins of the lower parts of the body and accumulates their. That’s why putrid hypostases appear in 3-6 hour after death;
putrifacation of the corpse is connected with processes of autolysis and rotting of the corpse. Postmorten autolysis appears earlier and is more expressed in glandular organs which cells are rich in proteolytic enzymes (liver, pancreas, stomach). Patrifacative processes join quickly to postmorten autolysis because of proliferation of putrifactive bacteria. Putrifacation intestifies postmorten autolysis, leading to fusion of tissues which become to be colored in dirty-green color and exhale characteristic putrid smell. Quickness of corpse’s aulotysis and putrifacation depends on the temperature of environment.
CELLULAR ADAPTATIONS
For the sake of survival on exposure to stress, the cells make adjustments with the changes in their environment (i. e. adapt). Broadly speaking, such physiologic and pathologic adaptations occur by
Decreasing or increasing their size (atrophy and hypertrophy respectively).
By changing the pathway of phenotypic differentiation of cells (metaplasia and dysplasia). In general, the adaptive responses are reversible on withdrawal of stimulus.
Atrophy
Atrophy means reduction of the number and size of cells, tissues and organs in living organism characterized by decrease or stopping their function.
Atrophy may be physiologic and pathologic.
A. Physiologic atrophy. It is a normal process of aging in some tissues:
1. Atrophy of lymphoid tissue in lymph nodes, appendix and thymus.
2. Atrophy of gonads after menopause.
3. Atrophy of brain.
4. Atrophy of bones.
It may be obliteration of the umbilical arteries and arterial duct (Botallow’s) after birth.
B. Pathologic atrophy may be general and local.
General atrophy is observed in cachexia due to
Oncologic and chronic diseases.
Starvation.
Injury of hypophysis (endocrine cachexia).
Injury of hypothalamus (cerebral cachexia).
Gross appearance of patients occurs:
Sharp exhaustion.
Adipose tissue is decreased and it has brown color.
Muscles are atrophied; skin is dry and flabby.
Internal organs are small, brown color and often shrunken.
Osteoporosis takes place.
Histologically:
Cells become smaller in size but are not dead cells.
Shrinkage in cell size is due to reduction in cell organelles.
Accumulation of lipofuscin around nucleus takes place. Lipofuscin (“wear and tear” pigment) is a golden yellow pigment representing undigested lipid material derived from cellular metabolism.
Local atrophy has several types:
1. Ischemic atrophy develops due to insufficiency of the blood supply. Hypoxia stimulates of the proliferation of fibroblasts and forms sclerosis. For example: small atrophic kidney in atherosclerosis of renal artery, atrophy of brain in cerebral atherosclerosis.
2. Disuse atrophy (dysfunctional) develops due to reduction of the function of organ: atrophy of muscles due to immobility, atrophy of the pancreas in obstruction of pancreatic duct.
3. Neuropathic atrophy due to interrupted nerve supply: poliomyelitis, motor neuron disease, nerve section, and inflammation of facial nerve.
4. Endocrine atrophy: hypopituitarism may lead to atrophy of thyroid, adrenal and gonads; hypothyroidism may cause atrophy of the skin and its adnexal structures.
5. Pressure atrophy: compression of spine by tumor in nerve root, compression of skull by meningioma arising from pia-arachnoid, compression of sternum by aneurysm of arch of aorta, compression of renal tissue by dilated renal pelvic in hydronephrosis, compression of brain tissue by dilated ventricles in hydrocephalus.
6. Atrophy due to chemical and physical influences. For example: action of the radiation lead to atrophy of bone marrow and genital organs.
7. Idiopathic atrophy: myopathies, testicular atrophy.
The atrophic tissue may be replaced by fatty ingrowths. Atrophy is reversible provided the cause is eliminated or deficiencies restored.
Hypertrophy and hyperplasia
Hypertrophy refers to an increase in the size of parenchymal resulting in enlargement of the organ or tissue, without any change in the number of cells.
Hyperplasia is an increase in the number of parenchymal cells resulting in enlargement of the organ or tissue. Quite often, both hyperplasia and hypertrophy occur together.
Mechanisms of hypertrophy
Hypertrophy of tissue arises due to increase of size of functional cells. Thus, the hypertrophied organ has no new cells, just larger cells.
Hypertrophy of tissue arises due to increase of number of functional cells (hyperplasia of cells).
Hypertrophy of cells arises due to both increase of size of functional cells and increase of number of ultrastructural elements. Thus, the increased size of the cells is due not to an increased intake of fluid, called cellular swelling or edema, but to the synthesis of more structural components. It is called true hypotrophy.
False hypertrophy is the increase of the size of organs due to growth of connective tissue, accumulation of the fluid or fatty tissue. It results in atrophy of organ (hydronephrosis, hydrocephalus, obesity of heart).
True hypertrophy (hyperplasia) has adaptative and compensative characteristics and may be physiologic and pathologic:
A. Physiologic hypertrophy (hyperplasia).
1. Neurogumoral (hormonal) hypertrophy: hypertrophy of female breast at puberty, during pregnancy and lactation, hypertrophy of pregnant uterus, proliferative activity of normal endometrium after a normal menstrual cycle, prostatic hyperplasia in old age.
2. Working hypertrophy of skeletal muscle: hypertrophied muscles in athletes and manual labour.
B. Pathologic hypertrophy (hyperplasia).
1. Neurogumoral hypertrophy develops due to impairment of endocrine functions. Endometrial glandular hyperplasia following estrogen excess which it occurs by metrorrhagia; atrophy of testis leads to increase of breast (gynecomastia); hyperfunction of anterior lobus hypophisis (adenoma) leads to increase skeleton (acromegaly).
2. Working hypertrophy develops in tissues consisting of stable undivided cells due to increase of size it one. It may be often in cardiac muscle at some cardiac diseases, such as: systemic hypertension, aortic valve disease (stenosis and insufficiency), mitral insufficiency; hypertrophy of smooth muscle: cardiac achalasia (in esophagus), pyloric stenosis (in stomach), and intestinal stricture; hypertrophy of urine bladder in adenoma of prostatic glands.
3. Compensatory reparative hypertrophy: regeneration of the liver following partial hepatectomy, regeneration of epidermis after skin abrasion; hypertrophy of myocardium in postinfarctional cardiosclerosis.
4. Vicarious (substitutional) hypertrophy: following nephrectomy on one side in a young patient there is compensatory hypertrophy as well as hyperplasia of the nephrons of the other kidney.
5. Hypertrophic vegetations develop due to chronic inflammation in mucous membranes (polyps and condilomas); lymphostasis leads to ingrowth of connective tissue, examples of false hypertrophy. In wound healing, there is formation of granulation tissue.
According to stage of adaptation two types of myocardial hypertrophy have been described:
Concentric. In concentric hypertrophy (clinically, no insufficiency) the musculature is clearly enlarged, measuring till 1.8 cm, but chambers of the heart are not dilated.
Eccentric. In eccentric hypertrophy myocardium is enlarged but chambers of the heart are dilated. This leads to hemodynamic disorder with cardiac insufficiency. It is called myogenic dilatation.
The affected organ is enlarged and firm. For example: a hypertrophied heart of a patient with systemic hypertension may weight 700-800 g as compared to average normal adult weight of 350 g. There is enlargement of muscle fibers as well as of nuclei. At ultrastructural level, there is increased synthesis.
Metaplasia
Metaplasia is defined as a reversible change of one type to another type of adult epithelial or mesenchymal cells, usually in response to abnormal stimuli, and often reverts back to normal on removal of stimulus. Metaplasia is broadly divided into 2 types:
A. Epithelial metaplasia. This is the more common type. The metaplastic changes may be patchy or diffuse and usually result in replacement by stronger but less well-specialized epithelium. Some common types of epithelial metaplasia following:
Squamous metaplasia: in bronchus in chronic smokers, in uterine endocervix in prolapse of the uterus and in old age, in gall bladder in chronic cholecystitis with cholelithiasis, in prostate in chronic prostatitis and estrogen therapy, in renal pelvis and urinary bladder in chronic infection and stones; in vitamin A deficiency, apart from xerophthalmia, there is squamous metaplasia in the nose, bronchi, urinary tract, lacrimal and salivary glands.
Columnar metaplasia in which there is transformation to columnar epithelium: intestinal metaplasia in healed chronic gastric ulcer, conversion of pseudostratified columnar epithelium in chronic bronchitis and bronchiectasis to columnar type, in cervical erosion.
B. Mezenhymal metaplasia. Less often, there is transformation of one adult type of mesenchymal tissue to another.
Osseous metaplasia. Osseous metaplasia is formation of bone in fibrous tissue, cartilage or myxoid tissue: in arterial wall in old age, in soft tissues in myositis ossificans, in cartilage of larynx and bronchi in elderly people, in scar of chronic inflammation of prolonged duration, in the fibrous stroma of tumor.
Cartilaginous metaplasia. In healing of fractures, cartilaginous metaplasia may occur where there is undue mobility.
Dysplasia
Dysplasia means “disordered cellular development”, often accompanied with metaplasia and hyperplasia, it is therefore also referred to as atypical hyperplasia. Epithelial dysplasia is characterized by cellular proliferation and cytological changes, which include:
Hyperplasia of epithelial layers.
Disorderly arrangement of cells from basal layer to the surface layer.
Cellular and nuclear pleomorphism.
Increased nucleocytoplasmic ratios.
Nuclear hyperchromatism.
Increased mitotic activity.
The two most common examples of dysplastic changes are the uterine cervix and respiratory tract.
Healing
Healing is the body response to injury in an attempt to restore normal structure and function. The process of healing involves 2 distinct processes:
Complete regeneration (restitution), denoting the replacement of injured cells by cells of the same type, sometimes leaving no residual trace of the previous injury, and
Incomplete regeneration (substitution) or replacement by connective tissue, or fibroplasia, which leaves a permanent scar. In most instances, both processes contribute to repair. In addition, both regeneration and fibroplasia are determined by essentially similar mechanisms involving cell migration, proliferation, and differentiations, as well as cell-matrix interactions.
Depending upon their capacity to divide, the cells of the body can be divided into 3 groups:
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, hematopoietic cells of bone marrow and cells of lymph nodes and spleen.
Stable 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.
Forms:
Cellular: bones, epidermis, mucous membrane, connective tissue, endothelium, hemopoetic system, and limfoid tissue.
Intracellular: myocardium, skeletal muscles, ganglious cells and central nervous system (CNS).
Mixed: liver, kidneys, lungs, pancreas, endocrine organs, smooth muscles, vegetative nervous system (VNS).
Types:
1. Physiological regeneration is the process of replacement that occurs due to physiologic necrosis (erythrocytes, mucosa).
2. Reparative regeneration (complete, incomplete with regenerative hypertrophy) is the regeneration after some pathologic necrosis.
3. Pathologic regeneration is the slow (hyporegeneration) or pathologically absence one, hyperregeneration or metaplasia (change in cell type).
Repair
Repair is the replacement of injured tissue by fibrous tissue. Two processes are involved in repair:
1. Granulation tissue formation.
2. Contraction of wounds.
Repair response takes place by participation of mesenchymal cells (consisting of connective tissue stem cells, fibrocytes and histiocytes), endothelial cells, macrophages, platelets, and the parenchymal cells of the injured organ.
Granulation tissue formation
The following 3 phases are observed in the formation of granulation tissue.
1. Phase of inflammation. There is acute inflammatory response with exudation of plasma, neutrophils and some monocytes within 24 hours.
2. Phase of clearance. Combination of proteolytic enzymes liberated from neutrophils, autolytic enzymes from dead tissues cells, and phagocytic activity of macrophages clear of the necrotic tissue, debris and red blood cells.
3. Phase of ingrowth of granulation tissue. This phase consists of 2 main processes: angiogenesis or neovascularisation and formation of fibrous tissue.
Angiogenesis (neovascularisation).Formation of new blood vessels at the site of injury takes place by proliferation of endothelial cells from the margins of severed blood vessels. The process of angiogenesis takes place under the influence of the following:
1. Endothelial cell growth factors.
2. Some components of matrix like type IV collagen.
Fibrous tissue formation.The new fibroblasts originate from fibrocytes as well as by mitotic division of fibroblasts. Some of these fibroblasts have morphologic and functional characteristics of smooth muscle cells (myofibroblasts). Collagen fibrils begin to appear by about 6th day. As maturation proceeds, more and more of collagen is formed while the number of active fibroblasts and new blood vessels decreases. This results in formation of inactive looking scar known as cicatrisation.
Contraction of wounds. The wound starts contracting after 2-3 days and the process is completed by the 14th day. In order to explain the mechanism of wound contraction, a number of factors have been proposed:
1. Dehydration as a result of removal of fluid.
2. Contraction of collagen.
3. Discovery of myofibroblasts.
Wound healing
Healing of skin wounds provides a classical example of combination of regeneration and repair described above.
Two types of factors influence the wound healing: those acting locally and those acting in general.
Local factors: infection, poor blood supply to wound, foreign bodies including sutures interfere with healing and cause intense inflammatory reaction and infection; exposure to ionizing radiation; exposure to ultraviolet light; type, size and location of injury.
Systemic factors: age, nutrition, systemic infection, uncontrolled diabetes, hematological abnormalities.
This can be accomplished in one of the following two ways:
1. Healing by first intention (primary union).
2. Healing by second intention (secondary union).
Healing by first intention (primary union)
This is defined as healing of a wound, which has the following characteristics:
Clean and uninfected.
Surgically incised.
Without much loss of cells and tissue.
Edges of wound are approximated by surgical sutures.
The sequence of events in primary union is described below:
1. Initial hemorrhage.Immediately after injury, the space between the approximated surfaces of incised wound is filled with blood, which then clots and seals the wound against dehydration and infection.
2. Acute inflammatory response.This occurs within 24 hours with appearance of polymorphs.
3. Epithelial changes.The basal cells of epidermis from both the cut margins start proliferating and migrating towards incisional space in the form of epithelial spurs.
4. Organization.By 3rd day, fibroblasts also invade the wound area. By 5th day, new collagen fibrils start forming. In 4 weeks, the scar tissue with scanty cellular and vascular elements, a few inflammatory cells and epithelialised surface is formed.
5. Suture tracks. Each suture track is a separate wound and incites the same phenomena as in healing of the primary wound.
Healing by second intention (secondary union)
This is defined as healing of a wound having the following characteristics:
Open with a large tissue defect, at times infected.
Having extensive loss of cells and tissues.
The wound is not approximated by surgical sutures but is left open.
The sequences of events in secondary union are as under:
Initial hemorrhage.
Inflammatory phase. There is an initial acute inflammatory response followed by appearance of macrophages, which clear off the debris as in primary union.
Epithelial changes. As in primary healing, the epidermal cells from both the margins of wound proliferate and migrate into the wound in the form of epithelial spurs.
Granulation tissue. The main bulk of secondary healing is by granulations. Granulation tissue is formed by proliferation of fibroblasts and neovascularisation from the adjoining viable elements.
Wound contraction. Contraction of wound is an important feature of secondary healing, not seen in primary healing.
Presence of infection. Bacterial contamination of an open wound delays the process of healing due to release of bacterial toxins that provoke necrosis, suppuration and thrombosis.
Complications of Wound Healing
Infection.
Implantation (epidermal) cyst.
Pigmentation.
Deficient scar formation.
Incisional hernia.
Hypertrophied scars and keloid formation.
Excessive contraction.
Neoplasia.
Hematological abnormalities.
HEMODYNAMIC DISTURBANCES
These are considered 2 broad headings
Disturbances in the volume of the circulating blood. These include hyperemia and congestion, hemorrhage and shock
Circulatory disturbances of obstructive nature. These are thrombosis, embolism, ischemia and infarction.
Hyperemia and congestion
Hyperemia and congestion are the terms used for increased volume of blood within dilated vessels of an organ or tissue the increased volume from arterial and arteriolar dilatation being referred to as hyperemia or active hyperemia, whereas the impaired venous drainage is called venous congestion or passive hyperemia. The capillaries and veins are dilated paralytically and filled with blood.
Arterial or active hyperemia is caused by an increased supply of blood from arterial system. The affected tissue or organ is pink or red in appearance (erythema).
I. Common arterial or active hyperemia is a result
Of increasing volume of circulating blood (pletora).
Of increasing of amount of erythrocytes.
Vacatic (lat. – vacuum) because of decreased atmospheric pressure.
II. Local arterial hyperemia can be
Angioneurotic – because of dilatation of arteries and arterioles.
Collateral.
Hyperemia after anemia.
Vacatic.
Inflammatory.
In arterio-venous fistula.
Venous, or passive hyperemia, or congestion is caused by impediment to the exit of blood through venous pathway. The dilatation of veins and capillaries due to impaired venous drainage results in passive hyperemia or venous congestion, commonly referred to as congestion.Congestion may be acute or chronic, the latter being more common and called chronic venous congestion.
I. Common congestion or Systemic (General) venous congestionis engorgement of systemic veins. It can be a result of
left-sided and right-sided heart failure
diseases of the lungs which interfere with pulmonary blood flow, like pulmonary fibrosis, emphysema, etc.
cardiac decompensation.
II. Local congestion can be a result of
venous obstruction because of its thrombosis,
compression of venous vessel with tumor or ingrowth of connective tissue,
development of collateral blood circulation.
Morphology of congestion
Because of the increase in venous blood, organs become swollen and purplish. With long continued over-distension, the wall of the venules shows reactive thickening and there is mild intestinal fibrosis of the organs, giving them a very firm consistency. These changes are seen typically in the kidney and spleen. Important additional changes are found in the lungs and liver.
Lungs. The lungs are burcly, congested and brownish in color. Pulmonary venous engorgement leads to alveolar hemorrhage. Hemoglobin from intra-alveolar blood is transformed into hemosiderin, which is then phagocytized by macrophages. These macrophages are known as heart failure cells. Phagocytes full of brown pigment migrate into intestinal tissue and to the lymph nodus. The sectioned surface is dark brown. It process in lungs is named as “brown induration”of the lungs.
Spleen. Chronic venous congestion of the spleen occurs in right heart failure and in portal hypertension from cirrhosis of liver. The spleen in early stage is moderately enlarged while in long-standing cases there is progressive enlargement and may weigh up to 500 g to 1000 g. The organ is deeply congested, tense and cyanotic (“cyanotic induration of the spleen”). Sectioned surface is gray tan.The red pulp shows congestion and marked sinusoidal dilatation with areas of recent and old hemorrhages. These hemorrhages may get organized. This advanced stage seen more commonly in hepatic cirrhosis is called congestive splenomegalyand is the commonest cause of hypersplenism.
Liver. Chronic venous congestion of the liver occurs in right heart failure and sometimes due to occlusion of inferior vena cava and hepatic vein. The liver is enlarged and tender and the capsule is tense. Cut surface shows characteristic “nutmeg liver”due to red and yellow mottled appearance. The changes of congestion are more marked in the centrolobular zone due to severe hypoxia than in the peripheral zone. The centrolobular hepatocytes undergo degenerative changes, and eventually centrolobular hemorrhagic necrosismay be seen. The peripheral zone of the lobule is less severely affected by chronic hypoxia and shows some fatty changein the hepatocytes. If the patient has periods of remission, the remaining liver cells may undergo compensatory hyperplasia. This results in small, irregular, pale nodules alternating with areas of fibrosis – so-called cardiac cirrhosis. It’s not true cirrhosis and does not causes hepatic failure.
Outcomes of congestion:
Edema.
Stasis.
Hemorrhage.
Thrombosis.
Induration of organs.
Atrophy of organs.
Hemorrhage
Hemorrhage (i.e. bleeding) is a discharge of blood from the vascular compairtment to the exterior of the body or into nonvascular body spaces.
Mechanisms of hemorrhages
1. By destruction of the blood vessel’s wall (f.e. trauma, rupture of aneurysm).
2. By diapedesis of erythrocytes because of the increased permeability of the vascular wall (f.e. intoxication, hypoxia).
3. By ulceration of the vessel’s wall (f.e. ulcer of stomach, necrosis of tumor, pulmonary tuberculosis).
Thus a severe decrease in the number of platelets (thrombocytopenia) or a deficiency of a coagulation factor (e.g., factor VIII in hemophylia) is assosiated with spontaneous hemorrhages unrelated to any apparent trauma.
Types of hemorrhages according to the site of origin
1. Cardiac, as following a penetrating heart wound.
2. Arterial, due to trauma and rupture of a dissecting aneurysm.
3. Capillary, which is usually due to trauma, inherent vessel wall weakness, or a coagulation defect.
4. Venous, which is usually caused by trauma or surgical operation, from esophageal varices.
Types of internal hemorrhages
Petechia – a small mucosal or serosal hemorrhage or minute punctate hemorrhage usually in the skin or conjunctiva.
Purpura or hemorrhagic infiltration - the accumulation of some erythrocytes in tissue between cells.
Ecchymoses or bruise - the superficial large extravasations of blood into the skin and mucous membranes. Following a bruise in association with coagulation defect, an initially purple discoloration of the skin turns green and then yellow before resolving, a sequence that reflects the progressive oxidation of bilirubin released from the hemoglobin of degraded of red blood cells. A good example of an eccxymosis is a “black eye”.
Hematoma - a grossly visible localized accumulation of the blood in the soft tissue.
Types of hemorrhages in body cavities
Hemothorax – hemorrhage in the pleural cavity.
Hemopericardium – hemorrhage in the pericardium cavity.
Hemoperitoneum – hemorrhage in the abdomen cavity.
Hemoarthrosis – hemorrhage in the joint cavity.
External hemorrhages may be such as:
Melena is deposition of the blood in the faces (excrement or stool) due to hemorrhage from ulcer of stomach, polip or ulcer of intestines.
Hemoptyesis is hemorrhage from lungs.
Metrorrhagia is hemorrhage from uterus.
Outcomes of hemorrhages
Coagulation of the blood.
Organization and incapsulation of the hematoma.
Brown cystic formatiom (in cerebral hematoma due to accumulation of hemosiderin).
Purulent fusion of the hematoma.
In cases of death from acute massive hemorrhage, the most significant postmorten changes are gross rather then microscopic and consists in generalized pallor of tissue, collapse of the great veins, and a flabby, shrunken, gray spleen.
A sudden loss of 33% of blood volume may cause death, while loss of upto 50% of blood volume over a period of 24 hours may not be necessarily fatal. However chronic blood loss generally produces an iron deficiency anemia, whereas acute hemorrhage may lead to serious immediate consequences such as hypovolemic shock.
Ischemia
Ischemia is a loss of blood supply, which occurs when arterial flow is impeded by atherosclerosis or by thrombi, or by some other causes. Ischemia is the most common cause of hypoxia.
Types of ischemia
Angiospastic (reflex).
Obstructive.
Compressive.
Because of redistribution of blood.
Morphologic features
The primary response of acute ischemia is cellular swelling or edema with dilation of the endoplasmic reticulum, dissociation of polysomes into monosomes, swelling of mitochondria, and also increased concentration of water, sodium, and chloride and decreased concentration of potassium into the cytoplasm. If the duration of ischemia is short, the structure and the function of tissue may be restored.
If ischemia persists, irreversible injury ensures with severe vacuolization of the mitochondria including their christae, extensive damage to cytoplasm membranes, and swelling of lysosomes. When the lesion is continuous, infarction, atrophy or sclerosis may develop.
Infarction
Infarction is an area of ischemic necrosis within a tissue or an organ, produced by occlusion of either its arterial supply or its venous drainage.
Types of infarctions:
Ischemic (white) infarction is encountered with arterial occlusion and in solid tissues (spleen).
Red (hemorrhagic) infarction is encountered with venous occlusion, in tissue as with double circulation, and in tissue previously congested (lung, intestinum).
White infarction with hemorrhagic halo (kidneys, heart).
According to their age, infarcts are classified as:
Recent or fresh.
Old or healed.
According to the propagation it may be
Total (when the whole organ is affected).
Subtotal (when only a part of the organ is affected).
Microinfarct (when observed only microscopically).
Pathogenesis
The process of infarction takes place as follows:
Localised hyperemia due to local anoxemia.
Within a few hours, the affected part becomes swollen due to edema and hemorrhage.
Cellular changes such as cloudy swelling and degeneration appear early.
There is progressive autolysis of the necrotic tissue and hemolysis of the red cells.
An acute inflammatory reaction and hyperemia appear at the same time in the surrounding tissues.
Blood pigments, hematoidin and hemosiderin, liberated by hemolysis is deposited in the infarct.
Following this, there is progressive ingrowth of granulation tissue from the margin of the infarct.
Morphologic manifestations
Myocardial infarction usually develops due to thrombosis of coronary artery. This infarction shows coagulative necrosis of myocardial cells. Almost no blood is seen in the vessels. The nuclei of muscle’s fibers and stroma cells are absent. The peripheral portion of the infarction has been invaded by acute inflammatory cells, which act as scavengers and remove the dead cells.
It is white infarction with hemorrhagic halo. It is classically irregular shape with hemorrhagic infiltration.
Infarction of the lungs. Embolism of the pulmonary arteries may produce pulmonary infarction, though not always.The pulmonary infarcts are classically wedge-shaped with base on the pleura, hemorrhagic, variable in size, and most often in the lower lobes. Fibrinous pleuritis usually covers the area of infarct. Cut surface is dark purple and may show the blocked vessel near the apex of the infarcted area. Old organized and healed pulmonary infarcts appear as retracted fibrous scars.The characteristic feature is coagulative hemorrhagic necrosis of the alveolar walls.
Renal infarction is common, found in upto 5% of autopsies. Renal infarcts are often multiple and may be bilateral. Characteristically, they are pale or anemic and wedge-shaped with base resting under the capsule and apex pointing towards the medulla. Generally, a narrow rim of preserved renal tissue under the capsule is spared because it draws its blood supply from the capsular vessels.The affected area shows characteristic coagulative necrosis of renal parenchyma i.e. there are shadows of renal tubules and glomeruli without intact nuclei and cytoplasmic content.
Infarction of the spleen is one of the common sites for infarction. Splenic infarction results from occlusion of the splenic artery or its branches. Splenic infarcts are often multiple. They are characteristically pale or anemic and wedge-shaped with their base at the periphery and apex pointing towards hilum. Coagulative necrosis and inflammatory reaction are seen.
Occlusion of an artery or vein may have little or no effect on the involved tissue or it may cause death of the tissue and, indeed, of the individual. The major determinates include:
The nature of the vascular supply.
The rate of development of the occlusion.
The vulnerability of the tissue to hypoxia.
Clinical significance of infarction
Most of the cardiovascular deaths result from myocardial and cerebral infarction. Pulmonary infarction is an extremely common complication in a variety of clinical settings. Ischemic necrosis (gangrene) of the lower extremities is a relatively unusual clinical problem in the population at large but is a major concern in diabetes melitus.
Stasis
Stasis (stasis - stop) is arrest of blood flow in the vessels of microcirculatory system (capillaries). The capillaries and veins are dilated paralytically and filled with blood. In the lumen of some capillaries the homogenous eosinophilic masses can be seen. They are columns of erythrocytes sticked together, which is called prestasis. Sludge syndrome (phenomenon) is regarded as a type of stasis. It is characterized by sticking of erythrocytes, leukocytes and thrombocytes to each other, which is accompanied by blood viscosity increase.
Stasis may be discirculatory as a result of venous hyperemia or ischemia. Causes of stasis:
Physical factors (temperature elevation, cold).
Chemical factors.
Infection.
Infectious-allergic factors.
Autoimmune factors.
Short stasis is reversible, long one causes hyaline thrombi formation, vascular permeability increase, edema, bleeding.
Isolated vein spasm may cause leukostasis, accumulation of erythrocytes within venules (small veins) and capillaries. It is observed in hypoxia. In shock, leukostasis may be generalized, but as a rule it is localized in the venules.
Microcirculation disturbances. There are four links in microcirculation:
1. The link of inflow and distribution of the blood (arterioles and precapillaries).
2. Intermediate (exchange) link (capillaries).
3. Depot link (postcapillaries and venules).
4. Drainage link (lymphatic capillaries and postcapillaries). The function of microcirculation is exchange between the blood and tissue. Pathology of microcirculatory system is formed of vascular, intravascular and extravascular changes.
Vascular changes are those in the thickness and shape of the vessels, angiopathies with disturbance of vascular permeability as a result of hypoxia.
Intravascular changes manifest as different disturbances of blood rheology (sludge, prestasis, stasis). They are observed in shock of different origin.
Extravascular changes are perivascular edema, hemorrhage, lymphostasis on the lymph vessels.
Thrombosis
Thrombosis is a pathologic process, which denotes the formation of a clotted mass of blood within the noninterruptured vascular system.
Influences predisposing to thrombosis:
1. Injury to endothelium;
2. Alterations in the normal blood flow;
3. Alterations in the blood coagulation system (hypercoagulability).
Mechanisms of formation
Agglutination of platelets. Platelets adhere to the endothelium and to each other forming a projecting mass;
Agglutination of erythrocytes. If the rate of the blood flow is slow, as in veins, red cells are entangled so that the lumen is occluded;
Coagulation of fibrinogen. In front and behind the platelet mass the blood stagnates. Further formation of fibrin takes place resulting in a large solid coagulum. The thrombus extends in either direction to the nearest junction;
Precipitation of plasma proteins. With a slow blood flow in the joining vessel more fibrin is formed by the platelets at the tip of the thrombus, thus occluding the joint vessel. Blood stagnates in the joining vessel and thrombosis forwards to the next joining vessel. There may be a succession of thrombotic episodes – a propagating thrombus.
Types of thrombi
According to the degree of the lumen obstruction, thrombi may be:
Occlusive thrombi most commonly develop in small arteries and veins.
Wall-attached or parietal thrombi develop in large arteries and heart cavities.
Axial.
Globe-shaped (in the heart).
According to the morphology
Thrombi may be of various shapes, size and composition depending upon the site of origin and it is attached to the vascular wall; it is dense, with corrugated surface. It is composed of branching bars of stuck thrombocytes and bands of fibrin with erythrocytes and leukocytes located between them.
Morphological types of thrombi
White thrombus – consists mainly of platelets, fibrin and leukocytes; forms slowly in rapid circulation of the blood (usually in the arteries);
Red thrombus – consists of platelets, fibrin and excessive amount of erythrocytes; forms rapidly at slow blood circulation (usually in veins). Venous thrombi are dark-red colored dry masses with dim surface.
Mixed or laminated thrombus – has laminated structure, contains white and red elements of thrombus (usually forms in veins, aneurysms of aorta and heart). Mixed thrombus consists of core or head (white thrombus), body (white and red) and tail (has construction of red thrombus). Core is connected with endothelium. Mixed thrombus is of gray-red color with rough dim surface, fixed to the intima of the vessel. Body and tail are located freely in the vessel’s lumen
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