Pathology Book Nursing PDF

INDEX 1-INFLAMMATION……………….. 1 2-REPAIR………………..10 3-CELL INJURY & CELLULAR ADAPTATION………………..17 4-NEOPLASIA & CARCINOGENESIS………………..22 5-CIRCULATORY DISORDER………………..32 6-BACTERIAL INFECTION………………..37 7-GRANULOMA………………..43 8-BILHARZIASIS………………..50 9-ORAL SHEET ...

INDEX 1-INFLAMMATION……………….. 1 2-REPAIR………………..10 3-CELL INJURY & CELLULAR ADAPTATION………………..17 4-NEOPLASIA & CARCINOGENESIS………………..22 5-CIRCULATORY DISORDER………………..32 6-BACTERIAL INFECTION………………..37 7-GRANULOMA………………..43 8-BILHARZIASIS………………..50 9-ORAL SHEET  Inflammation Inflammation Definition: The response of vascularized living tissue to an irritant. Etiology: Agents that cause inflammation may be:- 1. Physical agents: heat, cold and radiation. 2. Mechanical agents: trauma. 3. Chemical agents: acids, alkalies and poisons. 4. Infective: bacteria, viruses, fungi and parasites. 5. Immunologic: Ag-Ab reaction and hypersensitivity reactions. 6. Necrosis as inflammation around infarct. Classification of Inflammation: I. Acute Inflammation: this is characterized by rapid onset and short duration. A. Suppurative Inflammation: - Localized: e.g. abscess. - Diffuse: e.g. cellulitis. B. Non Suppurative Inflammation: - Serous. - Fibrinous. - Catarrhal. - Pseudomembranous. - Haemorrhagic. - Allergic. - Necrotizing. II. Chronic Inflammation: this is characterized by slow onset and long duration. A. Non specific. B. Specific. III. Subacute Inflammation: this is an ill-defined grade which lie between acute and chronic types. 1  Inflammation Cardinal Signs of Inflammation: 1. Rubor (redness). 2. Tumour (swelling). 3. Calor (hotness). 4. Dolor (pain). 5. Loss of function. Systemic Events of Acute Inflammation: 1. Elevation in body temperature: - Mediated by release of Interleukin 1 from macrophages, PGE2, and TNF-α. 2. Leukocytosis and other hematopoietic changes: - Associated with: a- Increased release of mature cells from bone marrow. b- Stimulation of granulopoiesis (colony stimulating factors) released from macrophages and T lymphocytes. Fate of Acute Inflammation: 1. Resolution: this is return of the tissue to its normal state. It occurs when inflammation is limited and tissue damage is minimal. In such cases, neutralization of toxins and mediators, phagocytosis and drainage of the exudate by lymphatics is not accompanied by healing. Examples: resolution of lobar pneumonia. 2. Regression and Healing: inflammation subsides (as described above) but there's tissue damage which is gradually repaired. 3. Progression and Spread: with weak immunity, bacteria may spread. a. Direct spread causing extension and widening of the inflammatory field. b. Lymphatic spread causing lymphangitis and lymphadenitis. c. Blood spread which may lead to serious effect as septicaemia. 4. Chronicity: This occurs if the injurious agent could not be eliminated completely. I- Suppurative Inflammation (Septic, Purulent or Pyogenic Inflammation) - Caused by pyogenic organisms as Staphylococcus aureus, Streptococcus haemolyticus and others. 2  Inflammation - Mechanism of Pus Formation: 1. Pyogenic organisms cause: a- Remarkable necrosis. b- Attraction of huge number of neutrophils. c- Death of many neutrophils due to high virulence of the bacteria. 2. Dead neutrophils (called pus cells) release their proteolytic enzymes, which liquefy necrotic tissue and fibrin. The liquefied material mixed with pus cells and fluid exudate form pus. Characters and Composition of Pus: Pus is a non-coagulable (no fibrinogen) creamy alkaline yellowish or yellowish green fluid composed of: 1- Fluid exudate without fibrin (liquefied). 2- Cells: A large number of pus cells, PMNs, some macrophages and some erythrocytes. 3- Necrotic fragments (sloughs) and liquefied necrotic tissue. 4- Bacteria and bacterial pigments which may be yellowish (as in staphylococcal infections) or greenish (as in pyocyaneous infections). Types of Suppurative Inflammation: I- Localized: Caused by Staphylococcus aureus bacteria, which produce coagulase enzyme that leads to fibrin deposition leading to localization. The most common forms of localized suppurative inflammation are: a. Abscess. b. Boil (furuncle). c. Carbuncle. II- Diffuse: Caused by Streptococcus haemolyticus bacteria, which produce hyaluronidase (the spreading factor) and streptokinase (fibrinolysin) which dissolves fibrin. The most common forms of diffuse suppurative inflammation are: a. Cellulitis. b. Suppurative appendicitis. c. Diffuse septic peritonitis. 3  Inflammation Abscess Abscess is a type of localized suppurative inflammation characterized by the formation of a cavity containing pus. It is commonly caused by staphylococcal infection. It can occur in any organ, but is most common in the subcutaneous tissues. Pathological Features: 1- Early, two zones can be recognized: a. A central zone of necrosis. b. A peripheral zone of inflammation shows many PMNs, macrophages, dilated capillaries and fibrin. 2- Later, progressive liquefaction starts at the margin of necrotic tissue, now the abscess consists of three zones: a. A central necrotic core. b. A mid zone of pus. c. The peripheral zone of inflammation (now called the pyogenic membrane). 3-Further enlargement: The central necrotic core may disappear later by further liquefaction and the abscess may enlarge if the bacteria cause further necrosis and liquefaction. Fate of abscess: 1- Small abscess: pus may be absorbed, followed by healing. 2- Large abscess: because absorption of pus occurs at a very slow rate, a big abscess undergoes pointing and rupture (spontaneous evacuation), followed by healing. Complications of abscess: 1- Complications of evacuation and healing: a. Ulcer: It is a local defect or excavation of the surface (discontinuation of the epithelium). It is due to separation of inflammatory necrotic tissue and defective healing. b. Sinus: It is a blind ended tract between a deep abscess and the surface, e.g. a peritoneal abscess may cause sinuses on the abdominal wall. c. Fistula: It occurs if evacuation of a deep abscess results in a tract communicating between two surfaces or hollow organs, this tract with two openings is called fistula. Ano-rectal fistula complicating a perianal abscess is an example. 4  Inflammation d. Keloid. e. Hemorrhage e.g. hemoptysis when a large abscess opens into a bronchus. 2- Putrefaction: e.g. putrefaction of a lung abscess by saprophytes (a type of bacteria) leading to gangrene. 3- Spread of infection: a. Direct spread leads to abscess enlargement. b. Lymphatic spread leads to lymphangitis and lymphadenitis. c. Blood spread may lead to: i- Toxaemia: Bacterial toxins circulating in the blood. ii- Septicaemia: Large number of virulent bacteria & their toxins circulating in blood. Commonly fatal. iii- Pyaemia: Multiple small abscesses caused by septic emboli derived from septic thrombi due to septic inflammation of veins near the abscess (septic thrombophlebitis). 4- Compression effects: e.g. in case of brain abscess and liver abscess. 5- Chronicity: If the abscess is neither evacuated spontaneously nor surgically, it gets surrounded by fibrosis and becomes a chronic abscess. Pus dries and dystrophic calcification may occur. Examples: a. Chronic breast abscess: May be clinically mistaken for a tumor. b. Chronic lung abscess. 5  Inflammation Cellulitis Cellulitis is an acute diffuse suppurative inflammation, more common in diabetics. The differences between cellulitis and abscess are listed in the following table: Criteria Cellulitis Abscess Acute diffuse suppurative Acute localized suppurative 1- Definition inflammation. inflammation. Caused by Streptococcus Caused by Staphylococcus aureus. 2-Aetiology haemolyticus. 3-Character of Bacteria secrete fibrinolysin & Bacteria secrete coagulase. causative hyaluronidase agent Occurs in loose connective Occurs in any organ or tissue but is most tissues as subcutaneous tissues, common in subcutaneous tissue. 4- Site areolar tissue of orbit, scrotum and pelvis. Pus is characterized by: Pus is characterized by: a. Thin, because fibrinolysin a.Thick due to the presence of large antagonizes fibrin deposition; amount of liquefied fibrin. thus the amount of liquefied 5-Characters fibrin within pus is small. b. Contains few erythrocytes. of pus b. Sanguineous i.e. contains numerous erythrocytes. c. Contains few sloughs. c. Contains many sloughs due to more extensive necrosis. Spread of infection is more Spread of infection is less common. 6- Spread common (direct, lymphatic & blood spread). 6  Inflammation II- Non Suppurative Inflammation 1- Serous Inflammation: Characterized by excessive serous fluid poor in fibrin. Examples: a. Skin blisters due to skin burns. b. Epidermal vesicles due to herpes simplex viral infection. c. Inflammation of serous membranes (pleura, pericardium and peritoneum). 2- Fibrinous Inflammation: Characterized by an exudate rich in fibrin, with a little fluid component. Examples: a. Lobar pneumonia b. Inflammation of serous membranes. 3- Serofibrinous Inflammation of Serous Membranes: Inflammation of serous membranes. 4- Catarrhal Inflammation: Characteristics: A mild form of acute inflammation of mucous membranes characterized by an exudate mixed with mucous secreted by the irritated mucous membrane. Examples: a. Catarrhal rhinitis (common cold). b. Catarrhal appendicitis. 5- Pseudomembranous (Membranous) Inflammation: Characteristics & pathogenesis: a severe form of acute inflammation of mucous membranes characterized by mucosal necrosis and marked submucosal inflammation resulting in formation of false membrane. Examples: a. Diphtheria. b. Bacillary dysentery. 7  Inflammation 6- Other Types of Acute Non Suppurative Inflammation: - Haemorrhagic Inflammation: Characterized by excessive erythrocytes within the exudate due to associated vascular damage. Example: small pox. - Necrotizing Inflammation: Characterized by extensive necrosis in association with inflammation. Example: cancrum oris. - Allergic Inflammation: The underlying cause of inflammation is hypersensitivity. There are usually many eosinophils. Examples: urticaria, allergic rhinitis and bronchial asthma. Chronic Inflammation Types: 1. Non specific: a- Lymphocyte, monocyte/macrophage accumulation with occasional plasma cells present. b- Diffuse and/or focal with perivascular cuffing. c- Eosinophils present in parasitic infections or allergic immune reactions. 2. Specific (Granulomatous): - Granulomas are characterized by: a- Spherical accumulation of monocular cells often surrounded by connective tissue. b- Formed mainly of activated macrophages (epithelioid cells) in the central core often around tissue necrosis. c- Then surrounded by rim of lymphocytes, some plasma cells and connective tissue. d- The epithelioid cells unit together and form multinucleated giant cells. 8  Inflammation The Main Differences Between Acute and Chronic Inflammation: Criteria Acute Inflammation Chronic Inflammation 1- Onset & duration Rapid onset and short Gradual onset and long duration. duration. 2- Vasodilatation Marked. Less marked and common endarteritis. 3- Exudate More abundant fluid exudate. Usually scanty fluid exudate. 4- Inflammatory cells: - Main inflammatory cells: Main inflammatory cells: Neutrophils, Macrophages. Macrophages, * Remark : Variations in Lymphocytes, Plasma acute inflammatory cells cells, Giant cells. include: 1- Eosinophils may be seen (mainly in allergic inflammation). 2- Neutrophils may be very few or absent (mainly in cases of infection with bacilli as typhoid). 3- Lymphocytes & plasma cells may be the predominant cells (in viral infections as acute viral hepatitis). 5- Fibrosis No fibrosis. Fibrosis occurs. 9  Repair Repair Definition Repair is defined as replacement of damaged tissue by a new healthy one. It represents the body response to injury in an attempt to restore normal structure and function. Types of Repair: 1- Regeneration: Replacement of damaged tissue by new healthy one of the same type. 2- Healing by connective tissue: Replacement of the damaged tissue by connective tissue, which may be in the form of: a) Fibrosis (scarring) in any part of the body (except CNS) or b) Gliosis in CNS. Types of cells according to their capacity to divide: The type of repair is determined by the type of damaged cells. Depending upon their capacity to divide (proliferate), the cells of the body can be classified into 3 groups (See the table that demonstrates characters of cells of the body): 1. Labile cells 2. Stable cells 3. Permanent cells. Characters of cells of the body: 10  Repair Labile cells Stable cells Permanent cells 1.Capacity to These cells These cells have low These cells can't proliferate continue to divide ability to proliferate proliferate at all. (proliferate) after adolescence but They lose their ability throughout life retain the capacity to to proliferate after under normal multiply in response birth. physiologic to a variety of conditions to stimuli. replace aging of the cell or cell loss 2. Relationship They have short G0 They remain in the These are non- with cell cycle (resting) phase. They resting phase (G0) dividing cells i.e. continuously divide for long times but have no capacity for (enter the cell cycle retain the capacity to mitotic division in and undergo mitosis). proliferate (enter the postnatal life cell cycle) in case of exposure to stimulus 3. Examples 1. Surface epithelium 1.Parenchymal cells 1.Neurons of nervous of skin and mucous of organs like: system. membranes as in: Liver, pancreas, 2.Skeletal muscle cell *Epidermis. kidneys and thyroid. 3.Cardiac muscle cell *Alimentary tract. 2.Mesenchymal cells *Respiratory tract. like: smooth muscle, *Urinary tract. fibroblasts, *Vagina, cervix & endothelium, bone endometrium. and cartilage. 2. Hematopoietic cells of bone marrow and cells of lymph nodes and spleen. 4. Type of Regeneration. 1. Regeneration in Fibrosis or repair in case of small Gliosis (in brain case of cell damage. and spinal cord injury or 2. Fibrosis in case of cord). damage large damage. Regeneration 11  Repair Definition: Regeneration means replacement of damaged tissue by new healthy one of the same type. This is done by proliferation of the surrounding living cells. It usually results in complete restoration of the original tissues. Cells Capable of Regeneration: I. Labile cells II. Stable cells (in case of mild or small damage) Examples of Repair by Regeneration: I. Regeneration of Epidermis of the Skin II. Regeneration of Liver (Hepatic) Cells III. Repair of Bone Fracture IV. Regeneration of Peripheral Nerves I. Regeneration of Epidermis of the Skin: The epidermal cells are labile & can regenerate easily. In case of damage of the dermis, repair occurs by fibrosis. Healing by Fibrosis Definition: It is the replacement of damaged tissue by granulation tissue which matures into fibrous tissue. The Most Common Examples of Healing by Fibrosis: 1. Healing of chronic inflammation as tuberculosis and bilharziasis. 2. Healing of infarctions. 3. Organization (invasion by granulation tissue) of thrombus. 4. Wound Healing. Wound Healing - Healing of skin wounds provides a classical example of combination of regeneration of the epidermis and repair by fibrosis of the dermis. - Types of wound healing: A. Healing by First Intention (Primary Union). B. Healing by Second Intention (Secondary Union). 12  Repair A. Healing By First Intention (Primary Union): - This is defined as healing of a wound, which has the following characteristics: a. Clean incision, non-infected b. Minimal loss of cells and tissue c. Edges of wound are approximated.e.g. by sutures in surgical wounds - The sequence of events in primary union is: 1. Immediately after injury, blood clots and debris fill the small gap between the edges of the wound. 2. Day 1: Three to 24 hours after injury, mild hyperaemia and few neutrophils (PMNLs) accumulate around the edge. 3. Within 2 days: - Epidermal regeneration: epidermal cells proliferate from both sides of the edges, grow across the clot and proliferate to form the whole thickness of the epidermis. - The remnant of the clot at the surface of the growing epidermis is called scab. 4. Day 3: Macrophages replace Neutrophils (PMNLs): Macrophages gradually phaogcytose (remove) clot and products of inflammation and release growth factors. 5. Day 4, 5: The small gap of the wound under the epidermis gets filled with granulation tissue. Collagen fibers begin to appear. 6. Second to fourth Week: - Maturation of granulation tissue into fibrous tissue i.e. mature scar formation is completely formed. - Scab becomes loose and separated within 2 weeks leaving a complete epithelial covering. - The dermal adnexa don't regenerate and healing occurs by fibrosis 7. Second month: Mature scar is covered by intact epidermis B. Healing By Second Intention (Secondary Union) - This is defined as healing of a wound having the following characteristics: a. Widely apart, gapped with a large tissue defect. b. Having extensive loss of cells and tissues. c. Infected e.g. in abscesses and septic wounds - The sequence of events in secondary union is principally similar to healing by first intention but differs in: 13  Repair 1. The cavity or wide gap of the wound is filled with blood clots, fibrin, necrotic debris, neutrophils (PMNLs), pus cells & Macrophages. 2. Epidermal cells start to grow at the margins of the wound but they fail to cover the wound until the gap is filled with granulation tissue. 3. Macrophages remove necrotic tissue debris & products of inflammation and release growth factors 4. The wide gap gets filled from below upward and from the sides with granulation tissue which is large in amount. 5. The epidermal cells continue to proliferate to cover the formed granulation tissue and restore the whole epidermal thickness. 6. Maturation of granulation tissue into large fibrous tissue i.e. mature scar formation occurs. 7. The wound contracts and its size decreases by the action of the myofibroblasts at the edges. The wound starts contracting and the process is completed by the end of the 14th day. The mechanism of wound contraction is: - Dehydration as a result of removal of fluid. - Contraction of collagen. - Presence of myofibroblasts [altered fibroblasts that have ultra-structure characteristics of smooth muscle cells]. 8. Few months later, large thick contracted scar is formed which is covered by regenerated Differences between primary and secondary union of wounds Criteria First intention Second intention 1- Type of wound Incised clean wounds Gapped septic wounds 2- Tissue destruction Minimal Marked 3- Edges Approximated Gaping 4- Rate of healing Rapid Slow 5- Amount of Small Large granulation tissue 6- Scar size Small Large and Keloid may occur 14  Repair Complications of Wound Healing 1. Delayed healing 2. Infection: - Bacterial contamination of an open wound delays the process of healing due to release of bacterial toxins that provoke necrosis, suppuration and thrombosis. 3. Epidermoid (Implantation) cyst: - It is a cyst that is lined by stratified squamous epithelium &filled with keratin - It is formed as a result of trapping of epidermal cells in the depth of the wound 4. Chronic ulcer: - It is persistent discontinuity of the surface epithelium. It occurs either due to persistent infection which destroys the granulation tissue or due to excess collagen deposition at the edges of the wound without filling the whole wound. 5. Chronic Fistula: - It is a persistent double-ended tract of infected granulation tissue that extends between two surfaces or two hollow organs with the two ends opened. 6. Chronic Sinus: - It is a persistent blind-ended tract of infected granulation tissue opening on the surface with one opening 7. Pigmentation. 8. Incisional hernia due to the presence of weak scar. 9. Keloid formation. - It is a large protuberant (bulging) scar which is covered by thin stretched epidermis. - It is formed due to excess collagen formation leading to raising of the epidermis at the site of the wound. - It may be formed due to foreign body reaction caused by inclusion of hair, keratin, debris, etc in the wound. - It may occur in healing of burns and healing by second intention. - People with dark skin are more susceptible. It has a hereditary tendency. - It recurs after surgical removal but it shrinks by irradiation. 10. Functional troubles due to excessive contraction of the scar tissue. 11. Cosmetic deformities due to excessive scarring. 12. Neoplasia (squamous cell carcinoma) may develop rarely. 15  Repair 16  Cell Injury and Cellular Adaptations Cell Injury and Cellular Adaptations Definition: - The cellular response to injury varies and depends on the type of cell and tissue involved as well as on extent and type of cell injury. Cellular responses to injury may be as follows: 1- The cell may adapt to the changes and then revert back to normal after the stress is removed (cellular adaptations). 2- The residual effects may persist in the cell as evidence of cell injury. 3- The injured cell may recover (reversible cell injury) or die (irreversible cell injury). Etiology of Cell Injury: A. Genetic defect B. Acquired causes that include: 1. Hypoxia 2. Physical agents 3. Chemicals agents 4. Microbial agents 5. Immunologic agents 6. Nutritional imbalance 17  Cell Injury and Cellular Adaptations I- Reversible Cell injury (Degeneration) 1- Cellular Swelling - This is the commonest, earliest and mildest form of cell injury. - Other synonyms of cellular swelling include: cloudy swelling, hydropic change, vacuolar degeneration (due to cytoplasmic vacuolation). Etiology: - The common causes include: bacterial toxins, chemicals, poisons, burns, high fever. Gross picture: -The affected organ such as kidney, liver or heart muscle is enlarged. The cut surface bulges outwards and is pale. Microscopic picture: - The cells are swollen and the surrounding capillaries are compressed. - Small clear vacuoles are seen in the cells. Examples -Cloudy swelling of renal tubules in cases of nephritis and liver cells in viral hepatitis. 2- Fatty Change (Steatosis) - It is accumulation of neutral fat within parenchymal cells. - Common in liver but may occur in heart, skeletal muscle, kidneys. Fatty Liver - Liver is the commonest site for accumulation of fat because it plays central role in fat metabolism. 18  Cell Injury and Cellular Adaptations - Depending upon the cause and amount of accumulation: Fatty change may be mild and reversible, or severe producing irreversible cell injury and cell death. Etiology: 1- Excess alcohol consumption (most commonly). 2- Starvation: mobilize fat from its stores. 3- Malnutrition. 4- Obesity. 5- Diabetes mellitus. 6- Chronic illnesses (e.g. Tuberculosis). 7- Hypoxia (e.g. Anemia). 8- Hepatotoxins (e.g. Carbon tetrachloride. Chloroform, ether, aflatoxins). 9- Certain drugs (e.g. Oestrogen, steroids, tetracycline). 10- Liver diseases as hepatitis C. Gross picture: - The fatty liver is enlarged with rounded margins. The cut surface bulges slightly, pale-yellow and is greasy to touch. - It may be diffuse in severe injury or spotty in mild injury with mottled nutmeg appearance. Microscopic picture: - Numerous lipid vacuoles in the cytoplasm of hepatocytes. The vacuoles are initially small (microvesicular), then vacuoles become larger pushing the nucleus to theperiphery of the cells (signet ring appearance). - The cells then rupture and lipid vacuoles coalesce to form fatty cysts. - Fat in the tissue can be seen by special stains such as Sudan III (stain fat orange), Osmic acid (stain fat black). II. Irreversible Cell injury (Cell Death) 19  Cell Injury and Cellular Adaptations - It includes autolysis, necrosis and apoptosis. A- Autolysis Definition: - Self-digestion of the cell by its own hydrolytic enzymes liberated from lysosomes. Causes: - Occur in the living body with inflammation. - Occur as postmortem change with absence of inflammation. B- Necrosis Definition: Necrosis is a focal death of a group of cells within a living body. Causes: Necrosis can be caused by various agents such as hypoxia, chemical and physical agents, microbial agents and immunological injury. Types of necrosis: 1. Coagulative Necrosis - This is the most common type of necrosis. - It results from ischemia, and less often from bacterial and chemical agents. - It occurs in infarction of all organs except CNS. Gross picture: - Early stage, there is protein denaturation. Foci of coagulative necrosis are pale, firm and slightly swollen. - With progression, lysis of necrotic cells occurs. The necrotic area becomes more yellowish, softer, and shrunken. Microscopic picture: - The hallmark of coagulative necrosis is that outlines of the cells are maintained so cell type can still be recognized but their cytoplasmic and nuclear details are lost. 20  Cell Injury and Cellular Adaptations - The necrosed cells are swollen and appear more eosinophilic than the normal, with nuclear changes. - Later, the necrotic tissue becomes structureless. 2. Liquefactive Necrosis 3. Caseous Necrosis 4. Fat Necrosis 5. Fibrinoid Necrosis C- Apoptosis Definition: - Apoptosis 'dropping off' is a form of programmed cell death to remove diseased and unnecessary tissue (Cell sucide). - It occurs in both physiologic and pathologic conditions. Examples of Apoptosis: a- Physiologic conditions: 1. During development of embryo. 2. Physiologic involution of cells in hormone-dependent tissues e.g endometrial shedding, regression of lactating breast. 3. Involution of the thymus in early age. 4- Normal turnover of cells. b- Pathological conditions: 1. Cell death in tumors exposed to chemotherapeutic agents. 2. Cell death by cytotoxic T cells in immune mechanisms such as rejection reactions. 3. Cell death in viral infections such as hepatitis. 4. Cell death in response to injurious agents involved in causation of necrosis. 5- Cell death in malignant tumors. Difference between necrosis and apoptosis 21  Cell Injury and Cellular Adaptations Criteria Necrosis Apoptosis 1- Definition Cell death with degradation Programmed cell death of tissue 2-Stimulus Pathologic stimulus Pathologic or physiologic 3- Nucleus Disruption Chromatin condensation 4-Cytoplasm Swelling Shrinkage 5-Mitochondria Swelling Compaction 6-Lysosomes Break down Intact 7-Cell membrane Loss of integrity Intact with blebbing 8-Inflammatory Present Absent response 9-Chemical mediators Present Absent 22  Neoplasia Neoplasia Definition: It is a mass of tissue formed as a result of abnormal, excessive, uncoordinated, autonomous and purposeless proliferation of cells. Classification of the tumours: - According to their behavior : 1- Benign tumour 2- Malignant tumour 3- Locally malignant - According to tissue of origin: 1- Epithelial 2- Mesenchymal 3- Others The basic components of tumours: All tumours, benign as well as malignant, have 2 basic components: 1. Parenchyma: It is comprised of proliferating tumour cells; parenchyma determines the nature of the tumour. 2. Supportive stroma: - It is composed of fibrous connective tissue and blood vessels; it provides the framework on which the parenchymal tumour cells grow. - The tumours derive their nomenclature on the basis of the parenchymal component comprising them. - The suffix '-oma' is added to denote benign tumours. - Malignant tumours of epithelial origin are called carcinomas, while malignant tumours of mesenchymal origin are named sarcomas (sarcos = fleshy). - Some malignant tumours are composed of highly undifferentiated cells and are referred to as undifferentiated malignant tumours. - Rarely, combinations of carcinoma and sarcoma are called carcinosarcoma. - Although, this broad generalisation regarding nomenclature of tumours are usually true in majority of instances, some examples contrary to this concept are: melanoma for carcinoma of the melanocytes, hepatoma for carcinoma of the hepatocytes, lymphoma for malignant tumour of the lymphoid tissue, and seminoma for malignant tumour of the testis. 22  Neoplasia Characteristics Of Benign and Malignant Tumours: Criteria Benign Tumours Malignant Tumours Rate of growth Often slow. Often rapid. Mode of growth Expansile i.e compressing the Invasive, i.e infilterating and surrounding tissues without destroying the surrounding invasion. normal tissues. Some degree of expansion also exists. Macroscopic a. Margins of the tumour are a. Tumour margins are picture well defined irregular or ill-defined. b. Cut section of the tumour is b. Cut section of the tumour commonly uniform with no often shows areas of hemorrhage or necrosis. hemorrhage and necrosis. c. When the tumour occurs in a c. A tumour inside as solid solid organ it appears globular or organ appears as an irregular ovoid and often becomes or non-capsulated mass. surrounded by Fibrous capsule composed of a rim of condensed connective tissue. d. When the tumour arises from d. Tumours arising from surface epithelia it forms a non- surface epithelia appears as capsulated polyp (papilloma). non-capsulated masses assuming different patterns: - Polypoid fungating cauliflower-like masses bulging over the surface. The base of the mass shows some infilterations under the surface. - Ulcerative pattern The ulcer is irregular, with raised everted edges, rough necrotic floor & indurated base fixed to nthe surrounding tissue due to inflteration. -Irregular infilterative growth below the surface. In tubular organs as intestine. This infilterative pattern may be localized to a segment causing annular stricture. Microscopic a. Cellular differentiation: a. Cellular Anaplasia: picture Cellular differentiation is the (abnormal differentiation): extent to which tumour cells Malignant cells show grades 23  Neoplasia resemble comparable cells. of cellular atypia referred to In benign tumours the cells are as anaplasia ranging between perfectly differentiated i.e mild anaplasia and marked closely mimic the corresponding anaplasia characterized by : normal cells. 1-Cellular Pleomorphism: Rare mitoses. Malignant cells vary in size and shape. However, some tumours are monomorphic. 2-Nuclear pleomorphism: Nuclei may be irregular or bizarre shaped. 3-Nuclear enlargement and hyperchromatism: Due to increased synthesis of DNA, the nuclei appear dark (hyperchromatic) & nucleo- cytoplasmic ratio is increased approaching 1:1 (Normally N/C ratio is approximately 1: 5). 4- Nucleoli may be prominent. 5- Abundant mitoses and sometimes abnormal mitotic figures (e.g tripolar spindles). 6- Tumour giant cells containing a single large polypoid nucleus or multiple nuclei. b. Structural (histological ) b. Structural (histological ) Differentiation: Differentiation: In benign tumours the tumour -This is the degree of cells exhibit structural patterns resemblance of the structural similar to the normal tissue. pattern of the tumour that of Thus adenoma of thyroid the normal tissue. consists of acini similar to those - Carcinoma may be graded of normal thyroid as Well-differentiated (grade 1) Moderately-differentiated (grade 2) Poorly-differentiated (grade 3) Undifferentiated (grade 4 ) 24  Neoplasia Better differentiated tumours tend to show less marked cellular anaplasia & grow slower. On the other hand undifferentiated show great cellular anaplasia & grow faster. Undifferentiated (grade 4 ) carcinoma is sometimes termed Anaplastic c. Other features: carcinoma - The tumour has stroma c. Other features: containing few vessles. - The tumour stroma is rich - Secondary changes are myxoid in vessles, which may be or hyaline changes may occur, sometimes thin-walled (as in but necrosis and hemorrhage are sarcoma) extremely exceptional. - Secondary changes may occur and foci of hemorrhage and necrosis are common. Metastases No metastases Sends metastases. Prognosis a. Benign tumours don't spread. a. Malignant tumours spread b. Benign tumours don't recur if b. Recurrence after surgical well excised. excision is very common c. Benign tumours are not either from tumour cell dangerous unless: remnants they were not -They arise in vital organs as the removed with the excised brain. tissue or from a new -They arise in hollow organs (as neoplastic transformation. intestine causing obstruction). c. Malignant tumours are -They produce hormones as in serious & cause death. tumours of endocrine glands. Causes of death include: -They may change malignant 1. Local organ destruction (this may be evident clinically due to direct spread. by elevated rate of growth and 2. Destruction of distant pathologically by change of organs by metastases (distant gross pattern including : capsular spread). invasion, necrosis & hemorrhage 3. Cerebral tumours → and change of microscopic destruction of vital centers. pattern including loss of cellular 4. tumours of hollow organs &histological differentiation). as intestine → lumern obstruction. 5. Organ failure e.g * Renal failure due to urinary obstruction (or bilateral renal 25  Neoplasia tumours). * Liver failure & jaundice in case of primary or metastatic liver tumours. 6. Malnutrition due to : *Loss of appetite. * interference with food intake (in cancer of GIT) 7. Chronic toxemia due to secondary bacterial infection. 8. Anaemia is common due to several causes including: *Recurrent hemorrages from the tumour. *Bone marrow destruction by metastases. *High tumour cell metabolism may lead to folic acid deficiency. Iron deficiency may also occur. *Autoimmune hemolysis occur in some cases. 9. Cachexia This is marked wasting & weakness (due to anemia, toxemia, malnutrition, organ failure ) It's manifested by marked decrease of body weight accompanied by profound weakness, anorexia & anemia. The body resistance is lowered & infections as pneumonia may terminate the patient's life. Remark: Recently, it has been shown that TNF (released from activated macrophages) may play an important role in cachexia because it both suppresses the patient's appetite and interferes with fat metabolism. 10. Paraneoplastic Syndromes occur in 10% of 26  Neoplasia cases. They are caused by abnormal products of the tumour e.g ACTH causing Cushing syndrome. Spread of Malignant tumors Metastasis (Distant Spread): - Metastasis (meta = transformation, stasis = residence) is defined as spread of tumour by invasion forming discontinuous secondary tumour mass/masses at the site of lodgement. - Metastasis is the most important feature to distinguish malignant from benign tumours. - Benign tumours do not metastasise while all the malignant tumours can metastasise with a few exceptions like gliomas of the central nervous system and locally malignant tumours. Routes oF Spread: Spread of tumours classified into: I- Local spread II- Distant spread I. Local spread: - Malignant cells can spread along lines of least resistance. - Some structures as cartilage, periosteum delay direct spread. - Direct spread to surface leading to ulceration. - Direct spread from one hollow organ to another adjacent one causes a malignant fistula. II. Distant spread (Metastasis): Distant spread can occurs through many routes 1. Lymphatic spread 2. Blood (Haematogenous) spread 3. Other routes (transcoelomic spread, spread along epithelium-lined surfaces, and spread via cerebrospinal fluid, implantation). 1. Lymphatic spread: - In general, carcinomas favor to metastasize by lymphatic route while sarcomas favor haematogenous route. However, sarcomas may also spread by lymphatic pathway. 27  Neoplasia - The lymphatic spread occurs by two methods: a. Lymphatic permeation: The walls of lymphatics are invaded by malignant cells and form a continuous growth in the lymphatic channels called lymphatic permeation. b. Tumour emboli: the malignant cells may detach to form tumour emboli so as to be carried along the lymph to the next draining lymph node. The tumour emboli enter the lymph node at its convex surface and are lodged in the sub capsular sinus - Later of course, the whole lymph node may be replaced and enlarged by the metastatic tumour. Gross picture: Affected lymph nodes are enlarged, firm, grayish white cut surface and adherent capsule. Microscopic picture: Metastatic deposit resembles the primary tumors. 2. Blood spread: - The common sites for blood-born metastasis are the liver, lungs, brain, bones and kidneys, than are the unfavorable sites like the spleen and muscles. - The cancer cells invade the walls of capillaries, venules and veins more than the arteries which have thick walled and contain elastic tissue resistant to invasion. - Also malignant cells can reach the circulation through thoracic duct after lymphatic spread. - Emboli detached from primary tumours of organs drained by systemic veins e.g. kidney, brain, breast causing lung metastases through pulmonary arteries. - Emboli detached from tumours of lungs causing metastases in different organs through pulmonary veins which reach left side of the heart and then the systemic circulation. - Emboli detached from tumours of organs drained by portal veins (Tumours of GIT) are carried to liver causing liver metastases. Further spread from liver may give rise to emboli reach the systemic circulation then to lung. 3. Other routes of metastasis: a. Transcoelomic spread: Certain cancers invade through the serosal wall of the coelomic cavity so that clusters of tumour cells detached to be carried in the coelomic fluid and are implanted elsewhere in the body cavity. 28  Neoplasia Transcoelomic spread includes: - Transperitoneal spread from carcinoma of the GIT causing peritoneal and omental nodules with hemorrhagic ascites. - Transpleural and transpericardial spread from lung and breast carcinoma causes metastases on diaphragm associated with hemorrhagic pleural or pericardial effusion b. Spread along epithelium-lined surfaces: A malignant tumour may spread through the fallopian tube from the endometrium to the ovaries or vice-versa, through the bronchus into alveoli, and through the ureters from the kidneys into urinary bladder. c. Spread via cerebrospinal fluid: Malignant tumour of the ependyma and leptomenjnges may spread by release of tumour cells into the CSF and produce metastases at other sites in the central nervous system. d. Implantation: Rarely, a tumour may spread by implantation by surgeon's scalpel, needles, sutures, or be implanted by direct contact such as transfer of cancer of the lower lip to the opposing upper lip. 29  Neoplasia Characteristics of Carcinoma and Sarcoma Criteria Carcinoma Sarcoma 1- Definition Malignant tumour of epithelium Malignat tumour of the mesenchyme 2- Incidence Most common Less common 3- Growth rate Rapid but slower than sarcoma Faster than carcinoma 4- Mode of growth: More infiltrative Less infiltrative 5- Gross picture 1- Size: less bulky 1- Size: bulky 2- Haemorrhage and necrosis are 2- Haemorrhage and necrosis are less severe marked 3- Consistency: hard 3- Consistency : soft 4- Color; greyish 4- Color; pink 5- If arised in solid organ: 5- If arised in solid organ: irregular irregular mass mass 6- If arised from the surface or 6- Not arised from the surface or hollow organ: ulcerative, hollow organ. fungating and infiltrative pattern. It can arise from subepithelial mesenchyme and appear as bulky expansile growth. 6- Terminology: Carcinoma is derived from the Sarcoma is derived from the Greek Greek Carcinos meaning a crab Sarc which means flesh to describe to describe their infiltrative their fleshy consistency. mode. 7-Microscopic 1- Cellular anaplasia: less 1- Cellular anaplasia: marked. picture: marked 2- Diffrentiation; depends on the 2- Diffrentiation; depends on the arrangement of the tumor cells. secretion of the tumor cells which may be intracellular as in liposarcoma or ex 3- Less haemorrhage and 3- Less haemorrhage and necrosis necrosis. 4- Blood vessels are less and 4- Blood vessels are more better formed. numerous and thin walled. 5- Cell cohesion: malignant cells 5- Cell cohesion: is often absent show variable grades of and tumor cells are singly. cohesion which is poor in undifferentiated carcinoma 8- Spread - Usually slower than sarcoma - Usually faster - Early by lymphatic then by - Early by blood then by lymphatic blood 30  Neoplasia Classification Of Tumours: The currently used classification of tumours is based on the histogenesis (i.e. tissue of origin) and on the anticipated behavior. Histological classification of the tumours. Tissue of origin Benign Malignant A – Epithelium Surface epithelium 1-stratified squamous Squamous cell papilloma Squamous cell carcinoma 2-transitional Transitional cell papilloma Transitional cell carcinoma 3- Ducts of glands Duct papilloma Duct carcinoma 4-Mucosa of GIT Adenomatous polyp adenocarcinoma Glandular Epithelium Endocrine &exocrine glands Adenoma Adenocarcinoma B-Mesenchyme 1-Connective tissue Fibrous Fibroma Fibrosarcoma Adipose Lipoma Liposarcoma Primitive mesenchyme Myxoma Myxosarcoma Bone Osteoma& osteoblastoma Osteosarcoma Cartilage Chondroma Chondrosarcoma 2- Smooth muscle Leiomyoma Leiomyosarcoma 3-Striated muscle Rhabdomyoma Rhabdomyosarcoma 4-endothelium Angioma Angiosarcoma Mesothelium Mesothelioma Synovium Synovial sarcoma C-Others Lymphoid &hemopoeitic Lymphoma& leukemia Pigmented cell Nevus Malignant melanoma Trophoblast Vesicular mole Choriocarcinoma Embryonic cells Mature Teratoma Immature Teratoma 31  Circulatory System Disturbances Circulatory System Disturbances Hyperaemia and Congestion Hyperaemia 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 is referred to as hyperaemia or active hyperaemia, whereas the impaired venous drainage is called venous congestion or passive hyperaemia. I. Active Hyperaemia: - The affected tissue or organ is pink or red in appearance (erythema). - Examples: 1- Inflammation. 2- Menopausal flush. 3- Muscular exercise. 4- High grade fever. II. Passive Hyperaemia (Venous Congestion): - The dilatation of veins and capillaries due to impaired venous drainage results in passive hyperemia or venous congestion, which is commonly referred to as congestion. - Congestion may be acute or chronic, the latter being more common and called chronic venous congestion (CVC). - Venous congestion is of 2 types: 1- Local venous congestion results from obstruction to the venous outflow from an organ or part of the body e.g. portal venous obstruction in cirrhosis of the liver. 2- Systemic (General) venous congestion is engorgement of systemic veins e.g. in left-sided and right-sided heart failure and diseases of the lungs, which interfere with pulmonary blood flow, like pulmonary fibrosis, emphysema etc. A few common examples are considered below. CVC Lung Chronic venous congestion of lung occurs in cases of left-sided heart failure, especially in rheumatic mitral stenosis which leads to consequent rise in pulmonary venous pressure. Gross picture: - The lungs are heavier than normal and firm in consistency. - The sectioned surface is dark brown in color referred to as brown induration of the lungs. Microscopic picture: 32  Circulatory System Disturbances - The alveolar septa are widened due to the presence of interstitial edema as well as due to dilated and congested capillaries. - Rupture of dilated and congested capillaries may result in minute intra-alveolar hemorrhages. -The breakdown of erythrocytes liberates hemosiderin pigment, which is taken up by alveolar macrophages, so called heart failure cells, present in the alveolar lumina. Oedema Definition: Oedema is the pathological accumulation of excess fluid in the interstitial tissue spaces and serous sac. Classification of edema: I- Localized. II- Generalized. I- Localized Oedema: - Abnormal accumulation of fluid in the tissue spaces of a part of the body. - Causes of localized oedema are: 1- Inflammatory edema 2- Oedema due to venous obstruction 3- Lymphatic oedema (lymphoedema) caused by: 4- Allergic oedema II. Generalized Oedema (anasarca): 1. Cardiac oedema 2. Renal oedema 3. Nutritional oedema 4. Hepatic oedema Another Classification of Oedema: I. Non pitting oedema II. Pitting edema III. Myxoedema: Thrombosis Definition: 33  Circulatory System Disturbances It is the process of formation of a compact mass (solid or semi-solid) from the constituents of the blood within the vessels or the heart during life. Types of thrombi: 1- Pale thrombus: formed mainly of platelets and fibrin, small, grayish white, firm and adherent to the intima. Example: cardiac vegetations. 2- Red thrombus: formed mainly of RBCs and fibrin, dark red in colour, soft and loosely attached to the vessel wall. It is very rare. 3- Mixed thrombus: the most common type formed of platelets + fibrin + blood cells. 4- Propagating thrombus: 5- Presence or absence of bacteria: infected or non-infected. Fate of thrombus: 1- Very small thrombus undergoes lysis and becomes absorbed. 2- Big thrombus undergoes: a. Organization: the thrombus is invaded by capillaries, fibroblasts (derived from vascular wall) and the thrombus is transformed into fibrous mass. b. Organization and canalization: the fibrosed thrombus may shrink leaving a space from the vascular wall allowing passage of blood. c. Detachment: forming aseptic emboli causing infarction of the affected organ. d. Propagation of the thrombus: spread of the thrombus leads to propagated thrombus. e. Dystrophic calcification: may occur and form phlebolith. Embolism Definition: It is partial or complete obstruction of some part of cardiovascular system by an undissolved material (solid, liquid or gaseous). Types of Emboli: A. Depending upon physical state, the emboli may be: 1. Solid: a. Detached thrombus. b. A mass of tumour cells. c. Parasites. 34  Circulatory System Disturbances 2. Liquid: a. Fat globule. b. Amniotic fluid. 3. Gas-Air. Gangrene Definition: Gangrene is tissue necrosis followed by putrefaction. Differences between dry and moist gangrene: Criteria Dry Gangrene Moist Gangrene 1- Cause - Gradual arterial occlusion. -Sudden arterial& venous occlusion. 2- Site - Exposed part (limb). -Internal organs (intestine). 3- Rate of putrefaction - Slow putrefaction. -Rapid putrefaction. 4- State of tissue - Tissue mummification. -Tissue oedema. 5- Toxaemia - Mild toxaemia. - Severe toxaemia. 6- Auto separation - Auto separation may occur. - Auto separation absent. 7- Line of demarcation - Marked line of demarcation. - Poor line of demarcation. 8- Spread - Slow spread. - Rapid spread. 35  BACTERIAL INFECTION Bacterial infection Definition: Infection is defined as invasion of a living tissue or organ by harmful organisms (bacteria, viruses, ricketessiae, chlamydia, mycoplasma, fungi, protozoa and helminths). Types of bacteria: 1- Saprophytic bacteria: They are non-pathogenic and can be present in the body without producing infection or disease under normal circumstances. 2- Pathogenic bacteria: These can produce disease and are divided into endogenous and exogenous microorganisms. Routes of infection: 1. Exogenous organisms: These bacteria invade the tissues from outside the body such as from the enviroment, from a diseased patient or from a healthy carrier. They enter the body from the following routs: a. Direct contact through skin and mucous membrane. b. Inhalation through the respiratory tract. c. Ingestion through the GIT. 2. Endogenous organisms: These are pathogenic bacteria that are normally present in the body without producing a disease unless the defensive mechanisms of the body are overcomed e.g. streptococcus viridans and hemophilus influenza which are normally present in the mouth, pneumococci in the nasopharynx and E.coli, Cl. Welchii in the intestine. Mechanisms of cell injury in bacterial infections: 1- Bacterial adhesion to host cells can directly cause cell death. 2- Bacterial exotoxins produced mainly by gram +ve bacteria. 3- Bacterial endotoxins liberated by gram –ve bacteria. 4- Hypersensitivity reactions initiated by bacterial antigens. 37  BACTERIAL INFECTION Effects of bacterial infection: 1- bacteremia 2- toxemia 3- pyemia 4- septicemia I. Bacteraemia Definition: It is transient invasion of the blood by bacteria without significant toxemia. Sources of bacteremia: These bacteria are usuallty derived from a septic focus somewhere in the body. a. Bacteremia following tooth extraction or tonsillectomy, nasal sinuses (streptococcus viridans). b. Bacteremia following procedures e.g catheterization. c. Bacteremia occurring during the incubation period of some bacterial disease as typhoid. Effects and fate of bacteremia: 1- In most cases when small numbers of bacteria reaches the blood, they are rapidly eliminated and destroyed by members of lymphoreticular system. 2- When large numbers of bacteria enter the blood, one of the following effects may result: a. Low grade fever, chills as occur in bacteremia following catheterization. b. Renal infection may occasionally result following filtration of blood with bacteremia. c. In children, a septic skin lesion by staphylococci such as boil or subcutaneous abscess may give rise to bacteremia. d. Streptococcus viridans bacteremia following tooth extraction or tonsilectomy may lead to subacute infective endocarditis in-patients predisposed by a rheumatic valve or congenital heart diseases. II. Toxaemia 38  BACTERIAL INFECTION Definition: It is the circulation of bacterial toxins in the blood with the production of clinical and pathological manifestations. Types of toxemia: 1. Endotoxic toxemia: Bacterial endotoxin is a lipopolysaccharide that is a structural component in the outer cell wall of gram negative bacteria. These endotoxins are liberated only after the death of bacteria and have the following effects: a. Fever. b. Injury of parenchymal cells of different organs as liver, kidneys and heart leading to degenerative changes as cloudy swelling. c. Septic endotoxic shok. d. Disseminated intravascular coagulation (DIC). e. Acute respiratory distress syndrome. f. Bone marrow depression leading to normocytic anemia, particullarly in prolonged toxemia. g. Hemorrhahge and necrosis of adrenal glands resulting in acute adrenal cortical insufficiency. 2- Exotoxic toxemia: These toxins are produced by living bacteria. Most exotoxins are produced by gram+ve organisms. Exotoxins have more potent effects than endotoxins. Their effects are selective (each toxin has affinity for specific tissues). Examples: a. Exotoxins of cholera act on intestinal epithelial cells causing excessive secretion of fluid resulting in voluminous watery diarrhea and consequently loss of water and electrolytes. b. Diphteria toxins cause neural and myocardial dysfunction. c. Clostridium botulinum toxins block the release of cholinergic neurotransmitters particularly at the neuromuscular junctions resulting in progressive paralysis of the limbs, respiratory muscles and cranial motor nerves. d. Clostridium tetani toxins (tetanospasmin) act on the presynaptic terminals of the spinal interneurons. This interferes with the release of inhibitory transmitter substance, thus inducing the violent muscle contractions that characterize tetanic spasms. 39  BACTERIAL INFECTION III. Pyaemia Definition: It is the condition in which multiple small abscesses (pyaemic abscesses) develop within one or more organs as a result of impaction of septic emboli (derived from septic thrombi) or due to arrest of pyogenic organisms circulating in the blood in various organs. Pathogenesis:  The condition starts by the development of septic thrombi , most commonly in veins in cases of septic thrombophlebitis and less commonly in the heart from aseptic valve thrombi (septic vegetations ) in case of acute infective endocarditis.  The causative bacteria are usually Staphylococcus aureus.  Proteolytic enzymes derived from inflammatory cells will cause fragmentation of the septic thrombus → septic emboli.  Septic emboli (multiple) will circulate in the blood, until they get impacted in the small blood vessels of organs. These small vessels are peripherally located in organs (while larger vessles are central or hilar).  Multiple small abscesses (pyemic abscesses) will develop in the vicinity of impacted emboli i.e. adjacent to small vessels in the peripheral parts of organs. Types of pyaemia: 1- Pulmonary pyaemia: In which pyaemic abscesses are found inside the lung. They are derived from septic emboli originating from septic thrombophlebitis of one of the systemic veins as occurs in: a. Abscesses or cellulitis. b. Acute hematogenous osteomylitis. c. Purperal sepsis. 2- Systemic pyaemia: Causes: a. The same causes of pulmonary pyaemia if some septic emoli are too small and could bypass the lungs to reach the left side of the heart and then various organs. 40  BACTERIAL INFECTION b. Septic thrombophlebitis of pulmonary veins in cases of pulmonary infections. c. Septic vegetations of mitral or aortic valves in cases of acute infective endocarditis. 3- Portal pyaemia: It is due to septic thrombophelibitis of one of the venous tributaries of the portal vein as in cases of acute cholecystitis or acute appendicitis or infected piles. Sites of pyaemic abscesses: 1- Pulmonary pyaemia: lunges. 2- Systemic pyaemia: lungs, liver, brain, kidneys, spleen and others. 3- Portal pyaemia: liver. Characters of pyaemic abscesses: Grossly: They are usually numerous, small, superficial, nearly of the same size, usually peripheral containing some pus and surrounded by a zone of congestion. Microscopically: Debris, neutrophils, pus cells, macrophages, congested capillaries. Manifestation of toxaemia  Signs & symptoms of toxaemia  Degenerations  Acute adrenal insufficiency  Bone marrow depression  Acute respiratory distress syndrome IV. Septicaemia Definition: It is a serious and may be fatal condition in which large numbers of virulent bacteria circulate and multiply in the blood with the production of manifestatuions and accompanied by severe toxemia. Etiology: Septicemia can complicate infections with pyogenic organisms particularly if the immunity is lowered so it is more common in extremes of age (neonates, infants and elderly). Examples: Severe infections as meningiococcal meningitis, neonatal umbilical sepsis, lobar and bronchopneumonia, post operatiove infections and neglected infected wounds. 41  BACTERIAL INFECTION Pathological features: 1- Peticheal haemorrhage all over the body including the skin, mucous and serous membranes. It is due to destruction of the endothelial lining of the capillaries by bacterial toxins. 2- Hemolysis of blood produced by circulating bacteria as streptoccoci. 3- Dissiminated intravascular coagulation (DIC). 4- Inflammation of the serous membranes (pleura, pericardium and peritoneum). 5- Toxic myocarditis and acute infective endocarditis as a result of invasion of the valves and formation of septic vegetations followed by pyaemia. 6- Toxic injury and degeneration of parenchymal cells of liver, kidney…etc. 7- Acute respiratory distress syndrome due to damage of the alveolar walls. 8- Bone marrow depression. 9- Acute adrenal cortical insufficiency. 10- Septic shock. 11- Acute splenic swelling in which the spleen is moderately enlarged, very soft and friable. The cut section shows a semifluid dark red pulp, which can be easily washed out by tap water. Microscopic picture: The sinusoids are filled with neutrophils and macrophages & lymphoid follicles early show hyperplasia but later on may under necrosis and necrosis. 42  Granulomatous Inflammation Granulomatous Inflammation Definition: - It is a particular form of chronic inflammatory reaction characterized by the formation of nodular aggregates of particular types of inflammatory cells such as macrophages (or cells derived from them), lymphocytes, plasma cells, giant cells and sometimes neutrophils. - The essential components of a granuloma are collections of modified macrophages, termed epithelioid cells, usually with a surrounding zone of lymphocytes. - Granulomas may represent type IV hypersensitivity reaction. Morphological types of granulomatous inflammation: 1- Diffuse granulomatous reaction is seen in lepromatous leprosy. 2- Tuberculoid granulomatous reaction in three variants which are: a- Non-caseating tuberculoid reaction: as seen in sarcoidosis, Crohn’s disease and tuberculoid leprosy. b- Caseating tuberculoid reaction: as seen in tuberculosis. c- Suppurative tuberculoid reaction: as seen in cat-scratch disease. Types of Granulomas According to the Etiological Cause: 1- Infectious Bacterial: Mycobacteria (tuberculosis, leprosy), syphilis, brucellosis. Fungi. Parasites (e.g. Schistosoma). 2- Foreign bodies Endogenous: e.g. keratin, uric acid crystals (gout). Exogenous: e.g. silica, asbestos dust, suture material and foreign bodies trapped in tissue as pieces of glass, wood and metals. 3- Unsettled etiology Sarcoidosis, Crohn's disease. Tuberculosis (T.B) 43  Granulomatous Inflammation Definition: -Tuberculosis is a chronic infectious granulomatous disease. - It is common in communities with low standard of nutrition and housing. - Tuberculous lesions may occur in almost any organ of the body. The most common sites are the lungs and lymph nodes. Etiology and mode of infection: a. Human tubercle bacilli (Mycobacterium tuberculosis) are the etiologic agent of tuberculosis in humans. Bacteria are expectorated with sputum from patient with pulmonary T.B. and contaminate dust: 1- Inhalation of contaminated dust causes T.B. of lung and tonsils. 2- Ingestion of contaminated dust causes T.B. of intestine and tonsils. 3- Inoculation through the skin is uncommon. b. Bovine tubercle bacilli (Mycobacterium bovis) are the etiologic agent of TB in cows and rarely in humans. - Both cows and humans can serve as reservoirs. - Humans can be infected by the consumption of unpasteurized milk. Disease course and progression depends on: Dose and virulence of the organism. Immunity status and hypersensitivity of the host. Innate immunity and general health, acquired immunity and delayed hypersensitivity. Clinical Identification and Diagnosis of Tuberculosis: - The diagnosis of tuberculosis requires detection of acid-fast bacilli in sputum via the Ziehl- Neelsen stain. - The organisms must then be cultured from sputum using conventional media as Lowenstein-Jensen Medium. - Skin testing is performed as the tuberculin or Mantoux test. PPD (purified protein derivative) is employed as the test antigen PPD is intradermally injected in the forearm. The test is read within 48-72 hours. The reactions to the tubercle bacillus: 1. Proliferative lesions (the tubercle): 44  Granulomatous Inflammation Gross picture: - Tubercles are microscopic in size (1-2mm in size). When they fuse, they form small yellowish grayish nodules. - Firm in consistency. May appear soft and cheesy due to caseation. Microscopic picture: A central caseation surrounded by epithelioid and giant cells, which in turn are enclosed in a wide zone of lymphocytes and fibroblasts. 2. Exudative lesions: - Occur in case of large dose of bacilli, low degree of immunity and high degree of hypersensitivity. - It is characterized by the out-pouring of inflammatory exudates rich in fibrin. There are numerous lymphocytes and often polymorphs but epithelioid and giant cells are scanty. - These lesions are typical of tuberculosis of serous membranes. The Fate of tuberculous lesion: 1- Localization: - Healing produced by fibrosis. -Small lesions are totally replaced by fibrosis. - Larger caseous lesions may be surrounded by fibrosis (encapsulation). Some bacilli may remain alive and dormant within capsulated lesions. If body resistance is lowered, reactivation of tuberculosis may occur. 2- Spread of tuberculosis as bacilli are carried by macrophages into the surrounding lymphatics and tissue spaces. The hallmark of healing is fibrosis. The hallmark of activity is caseation and softening. Spread of Tuberculosis in the body: 1- Local spread: to surroundings by macrophages. 2- Lymphatic spread: the result is a regional tuberculous lymphadenitis. 3- Blood spread: It may produce: a- No effect: if small dose of bacilli enter the blood and destroyed by phagocytic cells in different organs. b- Isolated organ tuberculosis: The organism settles in one or few organs causing tuberculous lesions. 45  Granulomatous Inflammation c- Miliary tuberculosis: If large number of organisms reach the blood stream to produce miliary tuberculosis. The lungs, spleen, liver, kidney and other organs are seeded by tubercle bacilli which produce numerous granulomas of millet seed size. It is rapidly fatal condition. 4- Intracanalicular spread (Spread along epithelial lined surfaces): e.g. Tuberculosis of the larynx can spread through intrabronchial spread. Tuberculosis of kidney can spread down the ureter to the trigone of the urinary bladder. Patterns of Infection: There are two major patterns of disease with TB: 1- Primary tuberculosis: seen as an initial infection, usually in children. 2- Secondary tuberculosis: seen mostly in adults as a reactivation of previous infection (or reinfection), particularly when health status declines. Difference between primary and secondary T.B. Criteria Primary Tuberculosis Secondary Tuberculosis 1-Definition Tuberculous infection for the Tuberculous infection of first time sensitized individuals. 2-Age Children Adults 3-Sites Lungs, tonsils intestine and Any site skin 4-Tissue Less marked More marked due to destruction hypersensitivity 5-Tissue reaction Slow Accelerated 6-Spread More common Less common 7-Factors affect the Innate immunity - Innate immunity course of infection - Acquired immunity - Hypersensitivity Primary Tuberculosis Develops in Lungs, tonsils intestine and skin. In these organs tubercle bacilli are present in 3 sites: 1- Infected organ (primary focus). 2- Draining lymphatics (TB lymphangitis). 46  Granulomatous Inflammation 3- Draining LNs (TB lymphadenitis). I. Primary pulmonary tuberculosis: Typically affects the lungs of a child. This takes the form of a Ghon’s complex comprising: 1. A peripheral parenchymal subpleural lesion (the Ghon’s focus) usually just above or just below the interlobar fissure. 2. Tuberculous lymphangitis, a chain of tubercles along the course of lymph vessels. 3. Enlarged hilar lymph nodes draining the parenchymal focus show caseating tuberculous reaction. Fate of primary pulmonary tuberculosis: 1- Localization and healing by fibrosis. 2- Reactivation of dormant bacilli in capsulated or healed lesions. 3-Spread due to failure of localization. Routes of spread: Direct spread leads to tuberculous pneumonia, pleurisy, pericarditis. Lymphatic spread. Blood spread: - No effect, isolated organ tuberculosis or miliary tuberculosis Bronchial spread: through intrabronchial spread: e.g. tuberculous bronchopneumonia, tuberculosis of larynx. Tuberculous lymphadenitis: Occurs as a part of primary complex: - Hilar LNs in primary TB of the lung. - Cervical LNs in primary TB of tonsils. - Mesenteric LNs in primary TB of the intestine. - LNs elsewhere in primary TB of the skin. Gross picture: - LNs are enlarged and discrete. - Later, they become matted and soft (cold abscess) due to caseation. Microscopic picture: Tubercle formation and caseation. Fate and complications: 1- Localization. 47  Granulomatous Inflammation 2- Reactivation if immunity is lowered. 3- Spread. a. Direct: - Cervical LN causing skin sinus. - Hilar LN causing tuberculous pericarditis. - Mesenteric LN causing tuberculous peritonitis. b. Lymphatic spread. c. Blood spread. d. Bronchial spread: hilar LN may erode the bronchus and cause bronchial spread. Secondary Tuberculosis: Secondary Pulmonary Tuberculosis: Chronic fibrocaseous pulmonary tuberculosis: -Occurs in patients with moderate level of immunity and hypersensitivity. It has slow chronic course. Gross picture: 1- Apical lesions: - The pulmonary focus is present at sites of high oxygen tension, especially the apices (Assmann focus). - The bacteria cause progressive caseation, bronchial erosion, evacuation of caseous material in the eroded bronchus forming cavities. - Areas of caseous necrosis tend to be walled off by fibrous tissue (fibrocaseous TB). 2- Basal lesions small caseous foci due to transbronchial spread. 3- Insignificant lesions within hilar LNs: uncommon due to acquired immunity. 4- The pleura is usually involved. Microscopic picture: Large areas of caseous necrosis surrounded by few tubercles and fibrosis. Complications: 1- Haemoptysis due to erosion of blood vessels traversing the tuberculous cavity. 2- Rupture of cavity in the pleural sac results in pneumothorax. 3- Spread: 48  Granulomatous Inflammation - Direct to the pleura leading to tuberculous pleurisy, tuberculous empyema, tuberculous pericarditis. - Blood spread leading to miliary tuberculosis. - Bronchial spread with coughing of infected sputum lead to tuberculosis of larynx, tonsils, and tongue. If the sputum is swallowed causes secondary intestinal tuberculosis. 4- 2ry (reactive) systemic amyloidosis. 5-Right side heart failure due to lung fibrosis. 49  Granulomatous Inflammation Schistosomiasis (Bilharziasis) Etiology: It is a very common endemic parasitic disease in Egypt, especially among farmers. It is chronic granulomatous disease caused by: - Shistosoma hematobium, affecting the genito-urinary system. - Shistosoma mansoni, affecting digestive system. Although mixed infestation by the two species may occasionally occur. Reaction of the body to various stages of Bilharzial Infestation: - The reaction of the body is the same for both species. - Bilharzial lesions are mediated by type I and IV hypersensitivity reactions. 1- Reaction against cercariae: - Acute allergic dermatitis at sites of skin penetration by cercariae. The lesion is in the form of erythematous papules and appears few hours after penetration and lasts for about one week. 2- Reaction against adult worm: - Living adult worms inside the veins excite little or no reaction in the surrounding tissue. However, they produce: 1-Bilharzial pigment They ingest red blood cells and the incompletely digested hemoglobin is excreted by them as granules of brown to blackish pigment (bilharzial pigment). 2-Bilharzial ova - Dead worms produce: 1-Severe venous wall necrosis and inflammation characterized by tissue necrosis and marked cellular infiltration formed mainly of eosinophils together with neutrophils and macrophages. 2- Thrombophlebitis. 3- Reaction against the ova: -This is the main and constant reaction present in bilharzial infestation. -The ova may be trapped in the wall of the bladder and intestines or may be carried by the blood to other organs. - Miracidia within the ova are antigenic leading to type IV hypersensitivity reaction with immune-mediated inflammatory response. Inflammation is commonly (but not always) in the form of granulomas (bilharziomas). 50  Granulomatous Inflammation - Phases of Bilharzial granuloma: a. These perioval granulomas are formed of ova that are surrounded by macrophages, eosinophils, lymphocytes, occasionally giant cells and fibroblasts (cellular granuloma). b. The cellular granuloma are surrounded by granulation tissue (fibrocellular granuloma). c- The end result of this inflammation is fibrosis and the lesion may be represented by fibrosis surrounding bilharzial ova with minimal inflammatory cells (fibrous granuloma). - The ova in this reaction may be living (with refractile shells), dead (containing amorphous or finely granular material of dead miracidia) or calcified (appearing bluish). 4- Bilharzial antigens: Released from worms and ova induce hyperplasia of lymphoid and reticuloendothelial cells. Bilharziasis of The Urinary Tract - It is mainly caused by S. hematobium and rarely by S.mansoni. A. Bilharziasis of The Urinary Bladder (Bilharzial Cystitis): - Bilharzial infestation occurs mainly and primarily in the submucosa of the trigone and posterior wall of the bladder, as it is the most vascular part. - However, in severe long-standing cases, all layers of the bladder wall are affected by bilharzial ova deposition. Pathological Lesions and Pathogenesis: 1- Hyperemia, petechial hemorrhages and granularity of the mucosal surface: - These are early lesions that result from early inflammatory response associated with congestion. 2- Sandy Patches: - They are very common bladder lesions. - They result from heavy submucosal deposition of large numbers of ova associated with dystrophic calcification. The overlying mucosa undergoes pressure atrophy and ischemic atrophy. Gross Picture: They appear as irregular grayish yellow patches covered by thin atrophic mucosa. Microscopic picture: Heavy submucosal deposition of large numbers of ova associated with dystrophic calcification and mucosal atrophy. 3- Bilharzial Polyps: 51  Granulomatous Inflammation - They are less common lesions than sandy patches. - These polyps result from repeated submucosal deposition of bilharzial ova surrounded by inflammation leading to mucosal elevation and mucosal hyperplasia leading to polyp formation. Gross picture: They appear as single or multiple sessile, pedunculated or complex branching pinkish lesions with granular surface. They vary in size from 0.5-2cm. Microscopic picture: - The polyps consist of a fibrovascular core showing bilharzial ova surrounded by chronic inflammatory cells and a covering of hyperplastic epithelium. 4- Bilharzial Ulcers: - They are relatively common lesions that result from: a. Mucosal damage due to penetration of large numbers of ova in their way to urine. b. Ulceration of a polyp or shedding of atrophic mucosa of sandy patches. Gross picture: These ulcers may be single or multiple, superficial, deep or very deep (fissure ulcer), of variable size with sharp edges, granular floor and firm base. Microscopic picture: The edges, floor and base of ulcers show ova surrounded by chronic inflammatory cells and fibrosis. 5-Dense fibrosis: In long standing severe cases. 6- Urothelial Changes: - They are very common lesions due to chronic irritation. These changes are in the form of: a. Hyperplasia of transitional epithelium. b. Brunn’s nests c. Cystitis cystica d. Cystitis glandularise. e. Squamous metaplasia and leukoplakia f. Dysplasia and carcinoma in situ Effects and complications of urinary bladder bilharziasis: 1- Recurrent terminal hematuria: 52  Granulomatous Inflammation Is a common complication of bilharzial cystitis. It is terminal due to muscular contraction of the bladder at the end of micturition leading to more ova penetrating and damaging the mucosa with subsequent hemorrhage. If persistent, it may be complicated by anemia. 2- Bladder neck obstruction (BNO): The condition results from localized fibrosis due to bilharziasis in the region of bladder neck. BNO has the following effects: a. Diffuse hypertrophy and dilatation of the urinary bladder. b. Diverticulum formation: it is a herniated mucosal pouch through a weakened fibrotic area of the bladder wall, particularly at sites of vessel perforation or entry. c. Urinary stasis with subsequent backpressure manifestation leading bilateral hydroureter and hydronephrosis. Secondary infection may lead to pyoureter and pyonephrosis. d. Chronic renal failure is the end result of bilateral hydroureter and hydronephrosis. 3- Secondary bacterial infection results in: -Fistula formation. -Urinary calculi: They may result from: a. Bilharzial ova with epithelial debris may form the nucleus of stones. b. Secondary bacterial infection may lead to alkaline pH which favors calcium phosphate stone formation. 4- Carcinoma of the urinary bladder: Squamous cell carcinoma, transitional cell carcinoma and adenocarcinoma. 5- Spread leads to pulmonary bilharziasis. Bilharziasis of The Intestinal Tract - It is mainly caused by S. mansoni and rarely by S. hematobium. - The rectum is the commonest site to be involved particularly the submucosa. Rarely, small intestine and stomach are affected. Pathological features: 1- Early hyperemia and granularity of the mucosal surface. They are not so apparent as those of bladder mucosa as the intestinal mucosa is thick. 2- Sandy patches are less common than in urinary bladder. 3- Bilharzial polyps are the commonest bilharzial lesions, particularly in the rectum and sigmoid colon. 53  Granulomatous Inflammation - Secondary changes include ulceration, secondary infection leading to bilharzial dysentery, fibrosis. 4- Bilharzial ulcers are also common lesion in the large intestine. -It is caused by mucosal damage by penetrating ova, polyp avulsion or shedding of atrophic mucosa over sandy patches. 5- Fibrosis. Effects and Complications of Intestinal Bilharziasis: 1- Bilharzial dysentery: - Characterized by recurrent attacks of diarrhea with passage of mucous and blood. - Recurrent bleeding per rectum may lead to anemia. 2- Bilharzial pericolic mass (pericolic bilharzioma): - Bilharzial peritoneal nodule or pericolic mass may result from extensive fibrosis of the colonic wall and compression of the venous radicles within the intestinal wall leading to deposition of ova outside the wall in the surrounding peritoneum. -In these cases ova may not be detected in their stool (closed intestinal Bilharziasis). 3- Intestinal stenosis due to fibrosis: Chronic intestinal obstruction may rarely occur as a result of localized band of intestinal fibrosis so that the patient may suffer from recurrent attacks of intestinal colic, distension and constipation. 4-Intstinal obstruction may rarely results from: - Large polyp. - Intussusception due to abnormal peristalsis. 5- Spread causing bilharziasis of the liver and sometimes to the lung. 6- On the contrary to urinary bladder, intestinal bilharziasis is not complicated by carcinoma. Bilharziasis of The Liver (Bilharzial Hepatic Fibrosis) Etiology: - It is a common disease in Egypt. - The condition may result from marked fibrosis of the intestinal wall that blocks the way for freshly coming ova, which instead may get access to the portal vein branches as parasitic emboli to produce Bilharziasis of the liver. 54  Granulomatous Inflammation - Emboli of ova and dead worms reach the liver via the portal circulation. Pathogenesis: 1. Portal Tract Lesion: - Ova may penetrate the wall of small portal veins into the portal tract and excite bilharzial granulomas ending in fibrosis with thickening of the portal tracts. - Dead worm may be trapped inside venules of coarse portal tracts causing severe inflammation, tissue necrosis and thrombosis. - Angiomatoids: represent dilated collateral vascular channels between the branches of hepatic artery and portal vein. 2. Hepatic Cell Lobule Lesion: - Hepatic lobular architecture is preserved. - Most of liver cells within the lobules are normal but minimal fatty change may occur. - Kupffer cells engulf brown bilharzial pigment. Gross Picture: - In early cases, the liver is enlarged, firm with mild thickening of the portal tracts. - In chronic cases, the liver is shrunken and firm (due to excessive fibrosis) with irregular outer surface. Cut sections have sharp edge and brown or blackish color (due to bilharzial pigment). The portal tracts are thickened and whitish in color. Fibrosis of the big portal tracts is called coarse or pipe-stem fibrosis, while fibrosis of the small portal tracts is called fine or diffuse fibrosis. Microscopic picture: - The capsule is irregularly thickened and fibrosed. - The main pathology is present in the portal tracts. - The portal tracts are thickened with increased fibrosis and bilharzial granulomas in addition to small proliferated bile ducts and many dilated capillaries (angiomatoids) that represent dilated collateral vascular channels between the branches of hepatic artery and portal vein. - The architecture is preserved. Most of liver cells within the lobules are normal but minimal fatty change (steatosis) may occur. - Kupffer cells engulf brown bilharzial pigment. Effects and Complications of Bilharzial Hepatic Fibrosis: 1. Portal hypertension: Causes: a. Portal tract fibrosis that compress portal veins. b. Angiomatoids that convey the high pressure from hepatic artery to portal veins. 55  Granulomatous Inflammation Portal hypertension may lead to: a. Chronic venous congestion in the portal drainage area in the gastrointestinal tract. b. Splenomegaly. c. Ascites. d. Opening and varicosities at the portosystemic venous collaterals leading to: - Esophageal varices at the lower end of the esophagus and upper end of the stomach. - Hematemesis (vomiting of blood). - Piles------ bleeding per rectum. - Caput medusae----- varicosities in the anterior abdominal wall radiating from the umbilicus. 2. Portal vein thrombosis: It may occur as result of chronic congestion and stasis. 3. Mild affection of liver functions and lowering of plasma proteins. 4. Ascites due to portal hypertension and lowering of plasma proteins. 5. Hepatic encephalopathy: - A state of deteriorated brain functions including level of consciousness that may result from absorption of toxic products that are normally detoxified in the liver especially ammonia that are produced by normal bacterial flora in the intestine and normally does not reach the systemic circulation as it is detoxified into urea by the liver. - Hepatic ammonical encephalopathy may complicate bilharzial hepatic fibrosis due to: a. Portal hypertension with opening of portosystemic shunts, so ammonia reach systemic circulation and produce toxic effects on the brain. b. Also, if bilharzial liver is superimposed by hepatitis viruses infection (HBV &HCV), liver cell failure occurs with inability of liver cells to detoxify ammonia and great amounts of ammonia reach the systemic circulation unchanged leading to deterioration of brain function. Bilharzial Splenomegaly - Enlargement of the spleen always develop with bilharzial fibrosis of the liver. - Bilharzial splenomegaly is the commonest cause of huge splenomegaly in Egypt. Etiology and Pathogenesis of Bilharzial Splenomegaly: a. Hyperplasia of the lymphoreticular cells of the spleen in response to bilharzial antigens. (In early cases). b. Portal hypertension leads to red pulp congestion with progressive enlargement of the spleen (In chronic cases). 56  Granulomatous Inflammation Gross picture: - In early cases, the spleen is mildly enlarged (up to 300 gm). - In chronic cases, the spleen is markedly enlarged and may weigh 1-3kgm. - The enlarged spleen is firm, grayish brown due to bilharzial pigment, the capsule is thickened and fibrosed with thick fibrovascular adhesions between the spleen and adjacent structures. - Cut sections have sharp edge and show deeply congested red pulp with areas of hemorrhage. Microscopic picture: - The capsule and trabeculae are thickened, fibrosed and hyalinized. - The red pulp is congested. Rupture of congested sinusoids may lead to interstitial hemorrhages and hemosiderin deposition. Fibrosiderotic or Gandy-Gamna nodules may be formed from hemosiderin deposits and surrounding fibrosis. - The lymphoid follicles of white pulp early show lymphoid hyperplasia by later pressure atrophy of the follicles occurs. - Mononuclear phagocytic cells of the spleen (Littoral cells) contain brown bilharzial pigment granules in their cytoplasm. Effects and Complications of Bilharzial Splenomegaly: 1. Compression of adjacent structures as diaphragm (leading to dyspnea) and stomach causing epigastric discomfort and dysphagia. 2. Hypersplenism leading to anemia, leucopenia and thrombocytopenia. 57