Pathology Quiz 2 PDF

Intended learning objectives Types of acute non suppurative inflammation Types of acute suppurative inflammation Chronic inflammation: Define granuloma Localized suppurative inflammation: Abscess, Carbuncle Diffuse suppurative inflammation: Cellulitis  {A} Acute Non suppurative...

Intended learning objectives Types of acute non suppurative inflammation Types of acute suppurative inflammation Chronic inflammation: Define granuloma Localized suppurative inflammation: Abscess, Carbuncle Diffuse suppurative inflammation: Cellulitis  {A} Acute Non suppurative inflammation Catarrhal inflammation Fibrinous inflammation Membranous inflammation Allergic inflammation Necrotizing / hemorrhagic inflammation  Catarrhal inflammation A mild acute inflammation affecting the mucous membrane results in exudates rich in mucous. Examples: inflammation of nose, larynx, trachea, stomach, appendix and gall bladder.  Fibrinous inflammation Acute inflammation with exudate rich in fibrin. Examples: Inflammation of serous cavities as pericardium, pleura and peritoneum. Inflammation of alveoli of the lung in acute lobar pneumonia.  Membranous inflammation A severe type of inflammation affecting mucous membrane with formation of pseudomembrane. Examples: Diphtheria and bacillary dysentery.  Allergic inflammation Acute inflammation caused by antigen-antibody reaction with excessive edema fluid, large number of eosinophils and necrosis. Examples: Eczema-Urticaria-Allergic rhinitis.  Necrotizing- hemorrhagic inflammation A severe acute inflammation due to high virulent bacteria, virus and fungi with marked necrosis and hemorrhage. Examples: Plague and herpes simplex encephalitis {B} Acute Suppurative inflammation -Localized suppurative inflammation: abscess, boil and carbuncle. -Diffuse suppurative inflammation: cellulitis  {C} Chronic inflammation Granuloma: Chronic specific inflammation. It is collection of immune cells mainly macrophages and giant cells around a pathogen or foreign body in a circular form  Pathogenesis of fibrinous inflammation (Bread and butter) Pathogenesis of membranous inflammation  Feed back quiz Mention characters of allergic inflammation Analyze the formation of pseudomembrane Suppurative inflammation  Suppurative inflammation Definition: Inflammation which form pus Causes: Pyogenic or suppurative organism as Staphylococcal aureus Inflammatory cell: Large number of neutrophils that secretes proteolytic enzymes and form pus  Abscess Definition Sites Pathogenesis Treatment Complications Component of pus Mechanism of pus formation  Abscess: Acute localized suppurative inflammation. It is a cavity contains pus  Sites of abscess Subcutaneous tissue, liver, lung, brain  Abscess Pathogenesis of abscess: Bacteria and toxin, liquefactive necrosis of tissue, localization by fibrin threads Pyogenic membrane: peripheral zone of abscess cavity contains congested blood vessels, bacteria, neutrophils and fibrin threads Large number of neutrophils Pus: fluid contains dead and living bacteria and neutrophils, exudate and necrotic tissue Abscess  Localized suppurative inflammation Boil (furuncle) Carbuncle  Carbuncle A large suppurative lesion which develops usually in diabetic patients due to low resistant to infection. The commonest site is the back of the neck, scalp, and buttocks because the subcutaneous tissue in this area is tough and is divided into compartments by fibrous septa. The lesion is made of multiple cavities which communicate with each other and open through multiple points in the skin. Carbuncle  Treatment of abscess: Surgical excision with removal of abscess cavity and pyogenic membrane. Complications of abscess: Spread of inflammation to lymph nodes Chronic abscess Ulcer, sinus, fistula Bacteremia, sepsis, pyemia Ulcer: Loss of surface epithelium Sinus: Tract formed of infected granulation tissue and connects between abscess cavity and outside. Sinus has a closed blind end. Fistula: Tract formed of infected granulation tissue and connects between abscess cavity and other cavity or between the two cavities and outside. Fistula has open end. Ulcer- Sinus- Fistula  Cellulitis Diffuse suppurative inflammation caused by streptococci which produce: Streptokinase which liquefies fibrin. Hyaluronidase which liquefies the fibrous tissue. These enzymes allow the streptococci to spread very rapidly in the infected tissue Sites: Mostly subcutaneous tissue of lower limb Different from abscess: Large, diffuse, red and release serosanguinous fluid Cellulitis  Fate of inflammation 1- Resolution: subsidence of inflammatory changes and return of the tissue to normal: - Clearance of injurious stimuli - Clearance of mediators and acute inflammatory cells - Replacement of injured cells - Normal function 2- Suppuration and pus formation. 3- Chronic inflammation - Angiogenesis - Chronic inflammatory cell infiltrate - Fibrosis 4- Spread of inflammation.  Effects of bacterial infection Bacteremia: is the presence of bacteria in the blood as a severe complication of infections. Septicemia: is the presence of large amount of virulent bacteria in the blood that may trigger sepsis. Sepsis: is a life-threatening condition that arises when the body's response to infection injures its own tissues and organs. Pyemia: it is the formation of multiple abscesses in different organs. Pyemia is a type of sepsis that caused by pus- forming organisms in the blood as staphylococcus aureus. The multiple abscesses occur in lungs in systemic pyemia and in liver in portal pyemia.  Cell injury Intended learning objectives Define homeostasis and cell injury List causes of cell injury. What are types of cell injury. Explain fatty change Analyze the mechanisms of hemochromatosis and pathologic calcification Describe amyloidosis, necrosis and  Cell injury Homeostasis: is the ability of the cells to adjust their functions with different environmental stress. Cell injury: is a condition when the changes in the environmental stress exceed the ability of the cell to adapt. Causes of cell injury (Stress): - Hypoxia: chronic heart failure and anemia. - Physical agents: trauma and burns. - Chemical agents: poisons and industrial chemicals. - Inflammation: bacteria and viruses. - Antigen-antibody reaction. - Genetic abnormality: gene mutations. - Nutritional imbalances: deficiencies of vitamins.  Types of cell injury - Reversible cell injury (degeneration): they are pathological changes in which the cells can return to normal state when the stimulus stops. Degeneration: It is a reversible deterioration in the cell function leads to change of tissue to less functionally active one. - Irreversible cell injury: The injury cannot adapt by the cells and the cells cannot return to normal state. Irreversible injuries lead to cell death either by necrosis or apoptosis.  Fatty change (steatosis) Definition: It is a reversible intra- cytoplasmic accumulation of triglycerides either due to excessive entry or defective metabolism and release. Sites: liver, heart, muscles and kidney. Causes: Alcohol- Diabetes- Obesity  Fatty change (steatosis) Gross picture: The organ is enlarged, yellow, soft and greasy. Microscopically: H&E stain: The affected cells appear vacuolated. The fat droplets push the nucleus to one side giving signet ring appearance. Complications: fatty change is a reversible condition but it can lead to inflammation and Fatty change  Primary hemochromatosis (Bronzed diabetes) Definition: iron overload due to an inborn error characterized by increase absorption of dietary iron. It mainly affects males and is rare in females (due to physiological loss of iron in menses and pregnancies). Sites: The pigment is deposited in the cells of liver, pancreas, heart and skin. Gross: the organs appear enlarged, brown and hard. Microscopically: the affected cells undergo necrosis and fibrosis. Effects: Liver: cirrhosis and liver cell carcinoma. Pancreas: fibrosis replaces islet cells leads to diabetes mellitus. Heart: fibrosis leads to heart failure. Skin: bronzed color due to increased melanin and hemosiderin deposition.  Pathological calcification: Abnormal soft tissue deposition of calcium salts. 1- Dystrophic calcification: Definition: it is calcification of dead or damaged tissues in spite of a normal blood calcium level. Psammoma bodies: single necrotic cells around which calcium is deposited. Psammos is Greek for sand. Psammoma bodies are common in papillary carcinomas of thyroid glands. 2- Metastatic calcification: Definition: it is calcification of normal tissues due to hypercalcemia. It occurs widely throughout the body: (metastatic) Examples: gastric mucosa, kidney tubules (nephrocalcinosis) and lung alveoli.  Amyloidosis Definition: It is extracellular deposition of an insoluble protein substance in between cells and walls of blood vessels. Amyloid deposition leads to pressure atrophy to adjacent tissue. Characters: Stains positively with Congo red. Causes: Multiple myeloma- Rheumatoid arthritis Congo red  Necrosis Definition: it is a form of cell injury which results in premature death of cells in a living tissue by autolysis or heterolysis. Autolysis: digestion of cell by its own lysosomal enzymes. Heterolysis: digestion of cell by lysosomal enzymes of leukocytes.  Types of necrosis 1- Coagulative necrosis: necrotic tissue remains firm. Examples: Infarction of heart, kidney, and spleen 2- Liquefactive necrosis: digestion of tissues by proteolytic enzymes. Examples: A) Infarction of brain: lysosomal enzymes from microglial cells or necrotic cells liquefy the brain. B) Abscess and cellulitis (proteolytic enzymes from neutrophils liquefy infected tissues forming pus).  Types of necrosis 3- Gangrenous necrosis: it starts as coagulation necrosis due to cut of blood supply leads to dry gangrene. By time, liquefaction of necrotic tissue occurs due to the action of putrefactive bacteria resulting in wet gangrene. 4- Caseation necrosis: the necrotic tissue is soft, friable and cheesy. Causes: reaction between macrophages and T lymphocytes with bacterial antigen. Example: Tuberculosis. Gangrenous necrosis Caseation necrosis  Types of necrosis 5- Fat necrosis: it is seen in adipose tissue. Examples: 1- Enzymatic necrosis of omental fat: In acute hemorrhagic pancreatitis. Causes: It is due to lipase enzyme released from injured pancreatic cells. 2- Traumatic fat necrosis of female breast. 6- Fibrinoid necrosis: Pattern of necrosis occurs in: A- Deposition of immune complex protein (Ag-Ab) and fibrin in arterial wall Examples: immune vasculitis as in SLE B- Deposition of non-immune protein (plasma proteins). Examples: malignant hypertension. Fibrinoid necrosis  Apoptosis Definition: it is an energy dependent genetically programmed cell death that involves single cells. Characters: 1- Apoptosis is a cell suicide program. 2- This type of cell death is under the influence of hormones, growth hormone and cytokines. 3- Apoptosis is not harmful to the host and doesn’t result in inflammation. The died cell doesn’t rupture and intracytoplasmic granules are not released outside the cell. Tissue Renewal, Regeneration and Repair Introduction and objectives: to gain knowledge about: Types of tissue renewal Types of cells according to division power Stem cells: definition- characters- division Cell cycle: characters and functions Angiogenesis and granulation tissue Types, steps and complications of wound healing Bone healing Nervous tissue repair Tissue Renewal, Regeneration and Repair The process by which the body forms new cells to replace structures damaged in pathological process. Two types of tissue renewal: Regeneration: Healing by same type of cells Repair: Healing by mixture of same cells and fibrosis  Conditions for regeneration Tissue composed of labile or stable cells Presence of good number of stem cells Less amount of tissue damage Intact connective tissue matrix Ex: very superficial skin wound- bone fracture  Conditions for repair Tissue composed of permanent cells Small number of stem cells by tissue damage Severe tissue damage Destruction of connective tissue matrix Chronic inflammation st nd Ex: Wound healing (1 & 2 intention)  Labile cells Ex: Epidermis, GIT, Endometrium and blood cells Characters: short life span- continuous proliferation- large number of stem cells  Stable cells Ex: liver- fibroblast-osteoblast Characters: replicate until reaching the adult size then stop Most of their life in G0 of cell cycle Can be active and replicate again if stimulate (bone fracture)  Permanent cells Ex: nerve cells, cardiac muscle and skeletal muscle fibers Don’t replicate in post natal life Under tissue stress, they tend to increase in size (hypertrophy) of functional capacity (CNS cells) In damage condition they are replaced by fibrous tissue (glial tissue)  Stem cells Undifferentiated cells that can: Turn into many types of differentiated cells Self renewal: divide to make more stem cells They maintain their numbers and population through two types of divisions: - Symmetric division: one stem cell can replicate itself and create two stem cells. - Asymmetric division: one stem cell can divide into one similar stem cell and differentiated cell. Stem cell division Stem cell division A: stem cell B: progenitor cell C: differentiated cell 1: symmetric stem cell division 2: asymmetric stem cell division 3: progenitor division 4: terminal differentiation  Adult stem cells Adult (somatic) stem cells: they have been identified in many mature tissues as bone marrow, GIT, skin, liver, pancreas, and adipose tissue. Typically they have a more limited capacity to differentiate. Sources of stem cells: bone marrow, adipose tissue, blood and umbilical cord blood.  Cell cycle It is the ordered sequence of events that occurs in a cell in preparation for cell division. The cell cycle is a four stage process in which the cell 1- Increase in size (G1: growth) stage 2- Copies its DNA (S: DNA Synthesis) stage 3- Prepare to divide (G2: growth and preparation for mitosis) stage 4- Divides (M: mitosis) stage Cell cycle and regulation of cell replication Cyclin and cyclin dependent kinases (CDKs)  Characters of cell cycle Continuously dividing labile cells can enter G1 phase directly after completing mitosis (M) phase. Stable cells can re-enter the cycle from G0 to G1 when needed. Cell cycle has two check points (G1-S) and (G2-M) which act as surveillance for any DNA damage. The cell cycle progression is controlled by a family of proteins named cyclin and cyclin dependent kinases (CDKs). The main role of these complexes are controlling and signaling the cells that are ready to pass into the next phase during the cell cycle.  Characters of cell cycle Positive regulators of cell cycle like growth factors typically increase the activity of cyclins and Cdks Epidermal growth factor receptors (EGFR) are family of four different transmembrane proteins. Mutation and over expression of EGFR1 is associated with different malignancies. EGFR2 is also called HER-2 neu receptor. It’s over expression is associated with poor prognosis of breast cancer.  Characters of cell cycle Negative regulation like DNA damage typically decreases or blocks the activity of cyclins and Cdks. P53 is a tumor suppressor protein works to ensure that cells with DNA damage do not pass through cell division by triggering the production of Cdk inhibitor.  Objectives to gain knowledge about: Angiogenesis and its role in repair process Granulation tissue Types of wound healing Steps of wound healing Complications of wound healing Bone healing  Angiogenesis Definition: it is the formation of new blood vessels (neovascularization) Importance: - Formation of granulation tissue. Vascularization of ischemic tissues. Granulation tissue is a new tissue that is formed of fibroblasts, collagen , newly formed blood vessels and inflammatory cells. It is used for replacement of damage tissues that can not regenerate. It ends in fibrosis and scar formation  Steps of angiogenesis 1- Vasodilatation of preexisting vessels by nitric oxide. 2- Increased permeability by vascular endothelial growth factor. 3- Breakdown of basement membrane by metalloproteinase. 4- Disruption of endothelial cells contact by plasmin. 5- Proliferation of endothelial cells. 6- Maturation of endothelial cells. 7- Recruitment of peri-endothelial cells as pericytes and vascular smooth muscle. Angiogenesis Granulation tissue Healing by first intention Healing by second intention (Primary union) (Secondary union) clean cut wounds as surgical incision septic wounds, ulcers and abscesses. minimal cell death and minimal marked cell death and basement membrane damage marked basement membrane damage The edges of the wound are closely A wide gap is present. The approximated by suture edges are not in contact There is no foreign body or infection. Foreign body or infection may be present. minimal fibrosis and good re- Dense fibrosis, greater epithelialization (minimal scar). angiogenesis and abundant collagen deposition (dense No scar contracture scar) Significant scar contracture Types of wound healing  Steps of wound healing Formation of blood clot Formation of granulation tissue Cell proliferation and collagen deposition Scar formation Wound contraction Connective tissue remodeling Complications of wound healing Infection Inadequate granulation tissue formation leads to ulceration Keloid formation: excessive formation of granulation tissue that produces a hypertrophic scar covered by thin epidermis. Keloid is due to overdone repair. Wound contracture: reduction in the size of the scar due to excessive contraction Keloid and wound contructure  Bone healing Bone healing is an example of regeneration Steps of bone healing Formation of hematoma Polymorphs, macrophages, fibroblasts and new blood vessels Osteoprogenitor cells, osteoblasts and osteoclasts. Osteoid tissue: collagen- fibroblasts- little amount of calcium Osteoblasts secrete alkaline phosphatase leading to more calcification The osteoid tissue acts as fixator and is arranged in three layers termed calli  Steps of bone healing A) External callus: to the outside under the periosteum. B) Internal callus: in medullary canal. C) Intermediate or permanent callus: found in between the two ends of fractured bones. The osteoblasts of the intermediate callus will form the bony callus by progressive mineralization The external and internal calli will be gradually removed by osteoclasts Steps of bone healing  Repair of nervous system 1- The central nervous system: The nerve cells are permanent cells. Injury to the central nervous system is not followed by extensive regeneration. It is limited by the inhibitory influences of the glial and extracellular environment. Steps of CNS repair: - Necrosis and liquefaction of injured area. - Microglia (Macrophages of CNS) removes debris. - Astrocytes (supporting cells) proliferate and replace the lost area (Gliosis or glial scar). 2- The peripheral nerves: The peripheral nervous system has an intrinsic ability for regeneration. Steps of peripheral nerve regeneration: - The axon distal to injury becomes irregular and myelin sheath breaks into droplets up to the level of the first node of Ranvier (Wallerian degeneration). - Macrophage and Schwann cells remove debris. - The Schwann cells (supporting cell) in both the proximal and the distal ends proliferate and unite together forming a tube in which new myelin is formed by oligodendroglia. - A new axon grows from the proximal segment (axonal sprouts) and elongates gradually until it reaches the required length.