Basics of general pathology

1.28: Basics of general pathology

Indumathi Karnan, Geetha Devadas

Cell injury

Cell injury is defined as the effect of a various stresses a cell encounters resulting in changes in its internal and external environment. There are various forms of cellular responses to cell injury as (Fig. 1.28.1)

  1. (1) Adaptations: When the functional demand increases the cell adapts to the changes morphologically which then reverts back to normal when the stress is removed
  2. (2) Reversible cell injury: When the stress is mild to moderate the cell may recover to normal
  3. (3) Irreversible cell injury: When the stress is severe the cell is unable to revert back and end up in permanent damage.

Fig. 1.28.1 Schematic representation of cell injury.


  • Atrophy: Reduction in number and size of the cells in the organ or parts of body which was once normal types of atrophy include ischaemic atrophy, disuse atrophy, neuropathic atrophy, endocrine atrophy and pressure atrophy.
  • Hypertrophy is the increase in the size of cell and hyperplasia is increase in number of cells within the parenchyma.
  • Metaplasia is due to change of cell type either epithelial or mesenchymal from one adult type to another type, most commonly occurs in oesophagus, uterine endocervix and bronchial mucosa. It commonly occurs due to change in the environment and it is totally reversible when the stimulus is removed.
  • Dysplasia is disordered cellular development that occurs in association with hyperplasia or metaplasia and presents with cellular derangements with nucleomegaly and altered nuclear cytoplasmic ratio. They may or may not regress on removing the stimulus.

Morphological changes in reversible cell injury

The common morphological changes in non-lethal reversible cell injury are

  • Hydropic change (Fig. 1.28.2A and B)
  • Hyaline change (Fig. 1.28.3)
  • Mucoid change
  • Fatty change

Fig. 1.28.2 (A) Normal renal tubules with glomerulus(*) and renal proximal convoluted tubule(**), H&E, 100x. (B) Hydropic degeneration of renal tubule seen as edematous tubules with vacuolated appearance, H&E, 100x.

Fig. 1.28.3 Mallory hyaline bodies in alcoholic liver disease, H&E, 100×.

These changes are termed as retrogressive changes.

Irreversible cell injury – cell death and necrosis

  1. 1. Programmed cell death – Apoptosis
  2. 2. Deranged cell metabolism – Intracellular accumulations
  3. 3. After effects of necrosis – Gangrene, pathological calcification.

Reversible cell injury: The changes that happen within the cells are due to certain environmental changes and these changes are totally reversible when the stimulus is removed.

Irreversible cell injury

  • Irreversible cell injury is cell death which can be apoptosis, necrosis or autolysis.
  • Necrosis is localized cell death which is accompanied by inflammatory reaction.
  • Coagulative necrosis are due to cessation of blood flow leading to ischaemic necrosis in infarcts in all solid organs except brain.
  • Liquifactive necrosis happens in brain which is subjected to ischaemia. It is also seen in bacterial and fungal infections due to hydrolytic enzymes involved in tissue degradation.
  • Fat necrosis seen in omentum in case of pancreatitis and also in fat containing organ like breast (Fig. 1.28.4).
  • Caseous necrosis is a combined effect of coagulative and caseous necrosis with granulomatous inflammation classically seen in tuberculous infection (Fig. 1.28.5A and B).
  • Fibrinoid necrosis is seen in autoimmune conditions.
  • Apoptosis is the programmed cell death that can be either physiological (embryologically in formation of fingers) or pathological (viral infections).
  • Molecular mechanism of apoptosis regulated by genetic mechanisms and it can be due to intrinsic pathway mediated through mitochondria with pro- and anti-apoptotic member of Bcl2 family proteins and extrinsic pathway through the FAS-FAS-L and finally activated through caspases and engulfed by phagocytosis.

Fig. 1.28.4 Necrotic fat cells in the right side ( black arrow), with no nuclei and amorphous cytoplasm, compared to the normal adipose clusters in the left. H&E, 40×.

Fig. 1.28.5 (A) Hilar lymphnode showing caseous necrosis. (B) Central caseous necrosis surrounded by epitheliod granuloma, H&E, 40×.

Intracellular accumulations can occur with normal cell constituents like lipid, protein and carbohydrates or abnormal substances in the absence of certain enzymes or accumulation of pigments. Fatty liver is due to increased free fatty acids either from dietary metabolism or from the adipose tissues and leads to accumulation of triglycerides within the liver parenchyma as cytoplasmic vacuoles.

Pigment accumulation

  • Pigments can be endogenous or exogenous.
  • Melanin is the most common endogenous pigment.
  • Next is the heme-derived pigment which accumulates as haemosiderin, bilirubin or porphyrin.
  • Haemosiderin is the iron-containing pigment which stains for perls Prussian blue (Fig. 1.28.6A and B).
  • Bilirubin is the non-iron containing pigment, its increase causes jaundice.
  • Lipofuscin is an intralysosomal golden brown pigment accumulates as a wear and tear pigment (Fig. 1.28.7).
  • Exogenous pigments are carbon particles and pigments that accumulate due to tattooing.

Fig. 1.28.6 (A) Golden brown haemosiderin pigments in hepatocytes. H&E, 100×. (B) perls Prussian stain highlights the haemosiderin as blue granules. H&E, 100×.

Fig. 1.28.7 Lipofuscin pigment in liver parenchyma. H&E, 100×.

After effects of necrosis

  • Gangrene occurs in dead tissue with superadded putrifaction in any ischaemic injury. The main types are dry gangrene which occurs in the distal limb or digits following an ischaemia commonly due to atherosclerosis. Here the line of demarcation is clearly made out between the viable and gangrenous tissue – diabetic foot (Fig. 1.28.8). The other type is the wet gangrene that occurs in moist tissues and organs where the line of demarcation is not clearly made out – gangrenous bowel.
  • Pathologic calcifications are accumulations of calcium in tissues other than osteoid and enamel. It can be dystrophic calcification were the calcium salts are deposited in the necrotic and dead tissue. The other type is the metastatic calcification were the calcium accumulates in normal tissue due to hypercalcaemia due to excessive calcium metabolism from bones or increased absorption from intestines.

Fig. 1.28.8 Dry gangrene with clear demarcation between the normal and gangrenous skin.

Inflammation and healing

Inflammation is the protective response of the living organism to the injury produced by any exogenous or endogenous agents. The agents can be infective agents like bacteria, virus, fungi, toxins and parasites or immunological agents like cell-mediated immunity and antigen antibody reaction or physical agents like heat, cold, radiation and trauma or chemical agents like inorganic or organic poisons or inert elements like foreign bodies. Though they are protective mechanisms, sometimes they are eligible of causing considerable damage to the body in setting up of the inflammation, e.g. anaphylaxis in insect bites.

Inflammation is of two types: Acute when the response is short and is characterized by accumulation of fluids with activation of platelets and neutrophils, at times it can be so severe and called as fulminant acute inflammation. The other one is chronic inflammation that is characterized by the presence of chronic inflammatory cells such as lymphocytes, plasma cells and granulation tissue formation. The chronic active inflammation is the type of chronic inflammation in which there are acute exacerbations of disease activity.

Granulomatous inflammation

Granulomas are collection of epitheliod cells which are nothing but modified macrophages and are rimmed in the periphery by lymphoid cells and forms a circumscribed tiny inflammatory mass. It is an example of type IV hypersensitivity reaction. It starts as a protective defence mechanism by the host around the non-digestible antigen may be infectious particle like mycobacterium or non-infectious particle like suture material or any foreign body or even associated with autoimmune conditions.

The evolution of granuloma

  1. 1. Engulfment by macrophages: The monocytes and macrophages engulf these antigen and when they are poorly degradable they fail to digest them and chronically undergo morphological changes and are transformed into epitheliod cells.
  2. 2. CD4 T cells: Upon its failure to digest they present the antigen to the CD4 T lymphocyte and they elaborate lymphokines that include IL-1, IL-2, Interferon Gamma, TNF-Alpha.
  3. 3. Inflammatory cytokines: Both activated macrophages and CD4-T lymphocytes elaborate cytokines like IL1 and stimulate the proliferation of more T cells, interferon gamma activates macrophages, TNF alpha promotes fibrosis and vascular response.

Thus the granuloma is formed by collection of modified epitheliod cells in the centre and surrounded by T lymphocytes, multinucleated giant cells, healing fibroblasts or collagen depending upon the age of the granuloma (Fig. 1.28.9).

Fig. 1.28.9 Evolution of granuloma.

Granulomatous conditions

The most common granulomatous inflammation in India is by Mycobacterium tuberculosis which presents with central caseation and well-formed epitheliod granulomas and other caseating granulomas are seen with tuberculoid type of leprosy. Non-caseating granulomas rae associated with a variety of bacterial infections as syphilis, donovanosis, brucellosis, cat scratch disease, tularemia, fungal infections like actinimycosis, blastomycosis, cryptococcosis, coccidiomycosis, parasitic infestations by schitosomiasis and non-infectious causes like sarcoidosis, crohn disease, silicosis and foreign body granuloma (Fig. 1.28.10).

Fig. 1.28.10 Types of granulomas.

Mantoux test – tuberculin intradermal test

This test is performed by injecting 0.1 mL of purified protein derivative of Tuberculin protein as intradermal injection. Following that a delayed hypersensitivity develops and is identified as indurated area measuring more than 15 mm in 72 h, in individuals who are having or have been previously infected with tuberculous infection; patients with disseminated tuberculosis may not elicit an immune response as already they would have released a large amount of tuberculoproteins endogenously, masking the response to hypersensitivity test. A positive test is indicative of cell-mediated hypersensitivity but does not distinguish between disease and infection.

  • False-positive result:

    • A typical mycobacterial infection
    • Previous BCG vaccination

  • False-negative result

    • Cutaneous energy (due to weakened immune system)
    • Sarcoidosis
    • Hodgkin disease
    • Recent tuberculous (8–10 weeks of exposure) infection
    • Fulminant tuberculosis.

Wound healing

Healing of skin wounds is a combination of regeneration and repair, It can by first intention (primary union) or second intention (secondary union).

Healing by first intention

It happens in clean uninfected clear cut margins as surgically incised wounds without much loss of cells and tissue and in wounds were the edges are approximated. Here the space between the wounds are filled with haemorrhage and the site attracts the polymorphs and macrophages. The basal layer of the epithelium starts proliferating and migrating towards each other and along with the clot and inflammatory cells they form the scab. It gets organized by new collagen fibrils and fibroblasts proliferation and gives strength to the wound and by the end of 4 weeks are completely replaced with scar tissue (Fig. 1.28.11).

Fig. 1.28.11 Phases of cutaneous wound healing.

Healing by secondary intention

Any wound with large tissue defect at times infected, having extensive loss of tissue and not approximated by surgical sutures heal by secondary union. Healing takes a longer process and results with ugly scars as compared to the primary union. Initial haemorrhage, inflammatory exudates and epithelial changes are similar to primary healing but they have florid fragile granulation tissue with neovascularization and wound contraction takes place by excess proliferation of myofibroblasta and hence leads to contractures.

Wound contractures and strength by extracellular matrix

Following an injury the wound starts contracting after the initial inflammatory response and the contraction process is completed by 14th day. By the end of second week the wound is contracted to 80% of its original size. During the process there is proliferation of fibroblasts and myofibroblasts which gives structural support. The extracellular matrix has five components that include the collagen, adhesive glycoproteins which include fibronectin, tenascin and thrombospondin, basement membrane, elastic fibres and proteoglycans. Collagen is synthesized and secreted by ribosomes. Their synthesis is stimulated by various growth factors and degraded by collagenase. This balance is maintained by various local and systemic factors so that the normal content of collagen is maintained. When there is defective regulation of collagen synthesis it leads to hypertrophied scar, fibrosis and organ dysfunction (Fig. 1.28.12).

Fig. 1.28.12 Stages of wound healing.


Mechanisms of fibrosis

Following a wound contraction there is excessive accumulation of collagen which is produced by fibroblasts leading to a permanent fibrotic scar

  • In the pathogenesis of fibrosis the most important effector cells are reactive macrophages and proliferating.
  • Pro-fibrotic inflammatory mediators that include TGF-b and IL-13 amplify the process of fibrosis.
  • The liver normally heals by regeneration. It can regenerate perhaps 75% of its volume. Scarring occurs when the extracellular matrix of the liver is damaged by repeated or severe injury. Bile ducts then proliferate, regenerative nodules form and collagenous scars become evident. This scarring process is commonly called cirrhosis (Fig. 1.28.13A and B).

Fig. 1.28.13 (A) Gross appearance of liver showing cirrhotic nodules separated by fibrous septa. (B) Microscopic appearance of cirrhotic nodules in liver. Masson trichrome stain. 40x.


Our human body has an internal environment that comprises of cells, tissue, plasma and interstitial fluid, all together maintain the normal functionality of the system. The mechanism by which this system is constantly maintained is called the homeostasis.

Normal composition of internal environment

Water: Water is the principle and essential constituent of the body. The total body water in a normal adult male comprises 60%–70% of the total body weight. Total body water is distributed into two compartments separated by membranes freely permeable to water.

Electrolytes: The concentration of electrolytes are different in extracellular and intracellular compartments. In the intracellular fluid, the main cations are magnesium and potassium and the phosphates and proteins are the main anions. Sodium and chloride are less in concentration. In the extracellular fluid, the predominant cation is sodium and the principle anions are chloride and bicarbonates, along with these diffusible nutrients and metabolites as glucose and urea are present in the ECF.

Normal water and electrolyte balance (Gibbs donnan equilibrium)

Normally there exist a balance between the amount of water absorbed into the body and the amount eliminated. The water is absorbed through the intestines and eliminated as urine through kidneys, as sweat through skin and insensible losses through exhaled air, faeces and body secretions. The two main subdivisions of extracellular fluid – the blood plasma and interstitial fluid – are separated from each other by capillary wall which is freely permeable to water but does not allow free passage of plasma proteins resulting in higher concentration of protein content in the plasma.

Acid base balance

Besides changes in the volume of fluids in the compartments, changes in the ionic equilibrium affect acid base balance of the fluids.

An acid is a molecule which gives off a hydrogen ion and a base is a molecule that takes up a hydrogen ion. During normal metabolic activity a number of acids as carbonic, phosphoric, sulphuric, lactic, hydrochloric and ketoacids are formed, but still the pH of the blood is constantly maintained at 7.4 in health and this balance is regulated by

  1. 1. Buffer System: Buffers are substances which have weak acids and strong bases and limit the change in H+ ion. The most important buffer is bicarbonate–carbonic acid system.
  2. 2. Pulmonary System: During respiration the CO2 is removed by the lungs depending upon the partial pressure of CO2 in the arterial blood. Hyperventilation leads to alkalosis.
  3. 3. Renal System: The renal tubular cells excrete the H+ in the urine and they are buffered by combining with phosphates to form phosphoric acids; bicarbonate ions to form carbonic acid, and with ammonia to form ammonium ions in the glomerular filtrate.

Hyperemia and congestion

Increased volume of blood from the arterial and arteriolar dilatation is referred to as hyperemia which is effected through sympathetic neurogeneic mechanism or release of vasoactive substances and the affected organ is red in appearance, whereas impaired venous drainage is called venous congestion or passive hyperemia and the affected tissue is bluish in colour. The obstruction to the venous flow can be either systemic or local. Systemic venous congestion is caused mainly due to heart failure. Left-sided heart failure presents as chronic venous congestion of lung and right-sided heart failure as chronic venous congestion of liver and spleen (Figs

Fig. 1.28.14 Microscopic picture of chronic venous congestion of lung showing thickened fibrous septa and numerous haemosiderin laden macrophages.

Fig. 1.28.15 Microscopic picture of chronic venous congestion of liver showing congestion around central veins.

Fig. 1.28.16 Schematic representation of blood flow in arteriovenous channel leading to hyperemia and congestion.

Fig. 1.28.17 Right- and left-sided heart failure leading to congestion of various organs.


Haemorrhage is the escape of blood from a blood vessel. It may occur externally as traumatic injury or internally into the serous cavities or into the hollow viscus or into the skin and mucous membranes. Rapid loss of 33% of blood volume is more serious than gradual blood loss of 50% in 24 h. The blood loss may be large and sudden or as small repeated bleeds over a period of time. It can be due to trauma to the vessel wall, spontaneous rupture of an aneurysm, associated with bleeding diathesis, neoplastic invasion of vessel, vascular diseases or elevated blood pressure leading to vessel rupture.

Thrombosis and infarction

Definition: Thrombosis is an inappropriate activation of normal haemostasis, resulting in formation of a blood clot (thrombus) in uninjured vasculature.

Both hemostasis and thrombosis depend on three general components (Fig. 1.28.18)

  1. 1. Vascular wall
  2. 2. Platelets
  3. 3. The coagulation cascade.

Fig. 1.28.18 Schematic representation of Virchow triad involving endothelial injury, turbulence of blood flow and hypercoagulable state.

High risk for thrombosis

  • Prolonged bed rest/immobilization
  • Atherosclerosis (Fig. 1.28.19A–C)
  • Myocardial infarction, atrial fibrillation
  • Tissue damage (e.g. surgery/burns)
  • Cancer, prosthetic cardiac valves
  • DIC, Heparin-induced thrombocytopenia
  • Antiphospholipid antibody syndrome

Fig. 1.28.19 (A) Gross picture of coronary thrombus occluding the vessel. (B) Microscopic picture of coronary vessel lumen completely occluded by the thrombus formed on atherosclerotic plaque, H&E, 40×. (C) Microscopic picture of remote thrombus showing recanalization of the lumen, H&E, 40×.

Low risk for thrombosis

  • Cardiomyopathy,
  • Hyperestrogenic states,
  • Oral contraceptive pills,
  • Smoking,
  • Sickle cell anaemia.

Deep vein thrombosis

  • Deep vein thrombus are seen in 35% of patients after major surgery and most frequently associated in recent myocardial infarction. The incidence is greatest in the older age, but young people immobilized for any prolonged period of time are also prone for deep vein thrombosis. It is one of the common postoperative hazards of splenectomy, hip joint surgery, hysterectomy for carcinoma and retro pubic prostatectomy.

Five stages in the thrombus formation

  • Primary platelet thrombus: the primary clot forms by platelet aggregation
  • The coralline thrombus: platelet aggregation and activation attracts fibrin and RBC along with other leukocytes gets entrapped to form the coraline thrombus
  • Occluding thrombus: the vessel is completely occluded by the formed thrombus
  • Consecutive clot: once completely occluded the stagnant blood gets clotted and forms a consecutive clot
  • Propagated clot: the consecutive clot can detach or progressively block the entire vessel.

Fate of the thrombi

The fully formed thrombus can undergo complete lysis or can retract, organize and recanalize or can get infected and form septic emboli. If the thrombus gets detached from the site of attachment it forms an emboli and it occludes the travelling vessel at a distant site (Fig. 1.28.20).

Fig. 1.28.20 Fate of the thrombi.

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Mar 25, 2024 | Posted by in CARDIOVASCULAR IMAGING | Comments Off on Basics of general pathology

Full access? Get Clinical Tree

Get Clinical Tree app for offline access