Acute Inflammation The survival of all organisms requires that they eliminate foreign invaders, such as infectious pathogens, and damaged tissues. These functions are mediated by a complex host response called inflammation. Definition of inflammation Inflammation is fundamentally a protective response, the ultimate goal of which is to rid the organism of both the initial cause of cell injury (e. g. , microbes, toxins) and the consequences of such injury (e. g. , necrotic cells and tissues) The process of inflammation is usually described by the suffix “itis” The components of the inflammatory reaction that destroy and eliminate microbes and dead tissues are capable of also injuring normal tissues. Therefore, injury may accompany entirely normal, beneficial inflammatory reactions, and the pathology may even become the dominant feature if the reaction is very strong (e. g. , when the infection is severe), prolonged (e. g. , when the eliciting agent resists eradication), or inappropriate (e. g. , when it is directed against self-antigens in autoimmune diseases. r against usually harmless environmental antigens in allergic disorders). Some of the most vexing diseases of humans are disorders in which the pathophysiologic basis is inappropriate, often chronic, inflammation. This is why the process of inflammation is fundamental to virtually all of clinical medicine. ] ACUTE INFLAMMATION Acute inflammatory reactions are triggered by a variety of stimuli: • Infections (bacterial, viral, parasitic) and microbial toxins • Trauma (blunt and penetrating) • Physical and chemical agents (thermal injury, e. . , burns or frostbite; irradiation; some environmental chemicals) • Tissue necrosis (from any cause) • Foreign bodies (splinters, dirt, sutures) • Immune reactions (also called hypersensitivity reactions Cardinal signs of inflammation Celsus, a Roman writer of the first century AD, first listed the four cardinal signs of inflammation Rubor, Calor, Dolor, Tumour & Functio laesa Rubor- redness Calor – heat (Increased blood flow can be visualized as redness (rubor) and felt as heat (calor) Tumor – swelling (due to edema)Order now
Dolor – pain The fourth cardinal sign of inflammation is pain (dolor). This is the result of increased pressure in the interstitium due to edema. Pain fibers are stimulated through pressure receptors but also may be stimulated by the direct effects of bradykinin, a plasma protease end product of the kinin system A fifth clinical sign, Functio laesa- loss of function was later added by Virchow. Acute inflammation has two major components: Vascular events The 2 major vascular changes are: 1) Alterations in vascular caliber that lead to an increase in blood flow (vasodilatation) (2) Structural changes in the microvasculature that permits plasma proteins and leukocytes to leave the circulation (Increased Vascular Permeability) Cellular events 1. Leukocyte extravasation 2. Chemotaxis 3. Phagocytosis Vascular events Vascular changes play an important role in acute inflammation. Normally, plasma proteins and circulating cells are sequestered inside the vessels and move in the direction of flow. laminar flow) In inflammation, the blood vessels undergo a series of changes to maximize the movement of plasma proteins and circulating cells, out of the circulation and into the site of injury. The 2 major vascular changes are: 1. Changes in vascular flow and caliber (vasodilatation) • Vasodilation is one of the earliest manifestations of acute inflammation. Sometimes, it follows a transient constriction of arterioles, lasting a few seconds. • Vasodilation first involves the arterioles and then results in opening of new capillary beds in the area.
Thus comes about increased blood flow, which is the cause of the heat and the redness. • Vasodilation is induced by the action of several mediators, notably histamine and nitric oxide, on vascular smooth muscle. Histamine causes dilation of arterioles and contraction of endothelial cells in the venule 2. Increased Vascular Permeability (Vascular Leakage) Hallmark of acute inflammation is increased vascular permeability leading to the escape of a protein-rich fluid (exudate) into the extravascular tissue. Alterations in the anatomy and function of the microcirculation are among the earliest responses to tissue injury and may promote fluid accumulation in tissues- “OEDEMA” Formation of transudates and exudates. | |A, Normal hydrostatic pressure (blue arrows) is about 32 mm Hg at the arterial end of a capillary bed and 12 mm Hg at the venous | |end; the mean colloid osmotic pressure of tissues is approximately 25 mm Hg (green arrows), which is equal to the mean capillary | |pressure. Therefore, the net flow of fluid across the vascular bed is almost nil. | |B, A transudate is formed when fluid leaks out because of increased hydrostatic pressure or decreased osmotic pressure. |C, An exudate is formed in inflammation | The loss of fluid results in concentration of red cells in small vessels and increased viscosity of the blood, reflected by the presence of dilated small vessels packed with red cells and slower blood flow; a condition termed as stasis. As stasis develops, leukocytes, primarily neutrophils, accumulate along the vascular endothelium, stick to the endothelium and eventually escape into the interstitial tissue via the vascular wall.
Normal fluid exchange and microvascular permeability are critically dependent on an intact endothelium. How then does the endothelium become leaky in acute inflammation? Following mechanisms have been proposed: 1. Gaps due to endothelial contraction Endothelial cell contraction leads to intercellular gaps in venules. It is the most common form of increased vascular permeability and is elicited by histamine, bradykinin, leukotrienes and many other classes of chemical mediators. Its action is fast and short lived. 2. Direct Injury
Direct endothelial injury results in vascular leakage by causing endothelial cell necrosis and detachment. This effect is usually seen after severe injuries like burns, toxins and chemicals. Venules, arterioles, and capillaries can all be affected depending on site of injury. Its action is fast and may be long lived (hours to days). 3. Leukocyte-dependent injury Leukocyte dependant endothelial injury usually happens in venules and pulmonary capillaries, the vascular sites where leukocytes can adhere to the endothelium. This is a late response and is long lived. 4. Increased transcytosis
Increased transcytosis also augments venular permeability, especially after exposure to vascular endothelium derived growth factor. This occurs in venules. 5. New blood vessel formation New blood vessel formation at sites of angiogenesis also increases vascular permeability. This persists till intercellular junctions form. Cellular Events The next requirement for the inflammatory response is to get the inflammatory cells (leukocytes) to the site of injury. Vascular dilatation increases the volume of blood to the tissue site but also changes the flow characteristics within the vessel.
The cells are normally contained in the central or axial part of the blood column. Dilatation increases cross sectional area of the vessel and decreases the net flow rate per unit area. This causes cells to fall out of the central region of the vessel; they begin to tumble along the epithelial surface. Sequence of cellular events in journey of leukocytes from vessel lumen to interstitial tissue is divided to 3 phases, in the lumen, diapedesis, and migration in interstitial tissue towards chemotactic stimulus.
A: In the lumen: B: Diapedesis The next step is migration of cells through the endothelium, called diapedesis . Therefore the process of transmigration across the endothelium, also known as diapedesis which happens after adhesion Diapedesis occurs predominantly in the venules. PECAM-1 (platelet endothelial cell adhesion molecule-1, CD31) in intercellular junctions of endothelium is involved in the migration of leukocyte towards site of infection.
Leukocytes pierce the basement membrane by secreting collagenases, insert pseudopods into the junction between endothelial cells and then squeeze through interendothelial junction. In extravascular connective tissue, leukocytes adhere to extracellular matrix by ? 1 and CD44. Eventually they traverse the basement membrane and escape into extravascular space. Leukocyte adhesion and transmigration is regulated by chemical mediators and binding of complementary adhesion molecules on leukocytes and endothelial surfaces. The adhesion receptors involved belongs to 4 families: ) selectins b) immunoglobulin super family c) integrins d) mucin like glycoprotein a) Selectins are proteins which function in the adhesion of leukocytes to endothelial cells. P-selectin (CD62P) – present in platelets and endothelium (Wiebel-Palade bodies) mediates binding of neutrophil, lymphocyte, and monocytes. L-selectin (CD62L) -which are expressed on most leukocyte types, serve as homing receptors for lymphocytes to enter lymph nodes. It also serves to bind neutrophil to endothelial cells t sites of inflammation.
E-selectin (CD62E) – expressed on endothelium mediates homing of effector and memory T-cells to peripheral sites of inflammation, particularly the skin. b) Immunoglobulin superfamily includes 2 endothelial adhesion molecules: a) ICAM-1 (intracellular adhesion molecules 1) b) VCAM-1 (vascular cell adhesion molecule 1) They both serve as ligands for integrins found on leukocyte c) Integrins are transmembrane heterodimeric glycoproteins that promote cell-cell, or cell-matrix interactions. Integrins are expressed on many cell types. 2 integrins, LFA-1 and Mac-1 bind to ICAM-1. ?1 integrins, VLA-4 binds to VCAM-4 d) Mucin like glycoproteins is found in extracellular matrix and on cell surface. For example heparan sulphate serves for ligand for leukocyte adhesion molecule CD44. Chemotaxis After extravasation, leukocytes emigrate in tissue towards site of injury in a process called chemotaxis. It’s defined as locomotion along a chemical gradient. Both exogenous and endogenous substances can act as chemo attractants a) Exogenous – components of bacterial products. ) Endogenous – components of complement system, C5a – products of lipoxygenase pathway, leukotriens B4 – Cytokines like IL-8 All the chemotactic agents bind to 7-transmembrane G-protein coupled receptors on leukocyte surface. v Signals initiated from these receptors result on recruitment of G-protein and activation of several effector molecules, phospholipase C, phophonositol-3-kinase, and protein tyrosine kinase. v PLC? and phophonositol-3-kinase act on membrane inositol phospholipids to generate lipid 2nd messenger that increases cytosolic calcium and activates small GTPases. GTPases cause polymerization of actin, leading to increased amount of polymerized actin at leading edges of the cell. Leukocyte moves by extending filopodia that pull the back of the cell to the direction of extension. (3)Phagocytosis Leukocytes ingest offending agents, kill bacteria and other microbes, and get rid of necrotic tissue and foreign substances. Phagocytosis involves three distinct but interrelated steps • (1) recognition and attachment of the particle to be ingested by the leukocyte (2) its engulfment, with subsequent formation of a phagocytic vacuole • (3) killing or degradation of the ingested material (a) Recognition and attachment of the particle to be ingested by the leukocyte. Phagocytosis of microbes and dead cells is initiated by recognition of the particles by receptors expressed on the leukocyte surface. (1)Mannose receptors (2) Scavenger receptors are two important receptors that function to bind and ingest microbes. The mannose receptor is a macrophage lectin that binds terminal mannose and fucose residues of glycoproteins and glycolipids. These sugars are typically part of molecules found on microbial cell walls, whereas mammalian glycoproteins and glycolipids contain terminal sialic acid or N-acetylgalactosamine. Therefore, the macrophage mannose receptors recognize microbes and not host cells • The process of coating a particle, such as a microbe, to target it for phagocytosis is called opsonization • The efficiency of phagocytosis is greatly enhanced when microbes are opsonized by specific proteins (opsonins) for which the phagocytes express high-affinity receptors Major opsonins are IgG antibodies • C3b breakdown product of complement, • Certain plasma lectins, notably MBL (mannose binding lectin ) (b)Engulfment with subsequent formation of a phagocytic vacuole • During engulfment, extensions of the cytoplasm (pseudopods) flow around the particle to be engulfed, • Eventually resulting in complete enclosure of the particle within a phagosome created by the plasma membrane of the cell. The limiting membrane of this phagocytic vacuole then fuses with the limiting membrane of a lysosomal granule, resulting in discharge of the granule’s contents into the phagolysosome. • (c) Killing or degradation of the ingested material The ultimate step in the elimination of infectious agents and necrotic cells is their killing and degradation within neutrophils and macrophages, which occur most efficiently after activation of the phagocytes
Oxygen-dependent mechanism Microbial killing is accomplished largely by oxygen-dependent mechanism leading to production of reactive oxygen intermediates also called reactive oxygen species. These reactive oxygen species are converted into hydrogen peroxide (H2O2), which along with enzyme myeloperoxidase (MPO) liberated from Azurophilic granules of neutrophils form the H2O2-MPO-halide system which is the most efficient bactericidal system Mechanism
The generation of reactive oxygen intermediates is due to the rapid activation of an oxidase (NADPH oxidase), which oxidizes NADPH and, in the process, reduces oxygen to superoxide anion • Superoxide is then converted into hydrogen peroxide (H2O2), mostly by spontaneous dismutation • Hydrogen peroxide can also be further reduced to the highly reactive hydroxyl radical (OH) • Most of the H2O2 is eventually broken down by catalase into H2O and O2, and some is destroyed by the action of glutathione oxidase The H2O2 generated by the NADPH oxidase system is generally not able to efficiently kill microbes by itself therefore other agents take over • Azurophilic granules of neutrophils contain the enzyme myeloperoxidase (MPO),which converts in the presence halide such as Cl- H2O2 hypochlorite (HOCl) Myeloperoxidase (MPO) (potent antimicrobial agent) The H2O2-MPO-halide system is the most efficient bactericidal system in neutrophils.
A similar enzyme system generates reactive nitrogen intermediates, notably nitric oxide, which also helps to kill microbe Oxygen-independent mechanisms Is through the action of substances in leukocyte granules like • Bactericidal permeability increasing protein (BPI), a highly cationic granule-associated protein that causes phospholipase activation, phospholipid degradation, and increased permeability in the outer membrane of the microorganisms • Lysozyme, which hydrolyzes the muramic acid-N-acetyl-glucosamine bond, found in the glycopeptide coat of all bacteria • Lactoferrin, an iron-binding protein Major basic protein, a cationic protein of eosinophils, which has limited bactericidal activity but is cytotoxic to many parasites • Defensins, cationic arginine-rich granule peptides that is cytotoxic to microbes • Neutrophil granules contain many enzymes, such as elastase,which contribute to microbial killing After killing, acid hydrolases, which are normally stored in lysosomes, degrade the microbes within phagolysosomes .
The pH of the phagolysosome drops to between 4 and 5 after phagocytosis, this being the optimal pH for the action of these enzymes. After phagocytosis, neutrophils rapidly undergo apoptotic cell death and are ingested by macrophages. The predominant cell type of acute inflammation is the neutrophil Lymphocytes, plasma cells & macrophages are the cells found in chronic inflammation Special macroscopic appearances of acute inflammation
Serous inflammation – marked by outpouring of thin fluid that, depending on the size of injury,is derived from either the plasma or the secretions of mesothelial cells lining the peritoneal pleural, pericardial cavities The skin resulting from burns and acute synovitis are good examples Catarrhal inflammation – Mucus hypersecretion accompanies acute inflammation of a mucus membrane common cold
Fibrinous inflammation – Sever injury leading to outpouring of larger molecules like fibrinogen outpouring from the vasculature . e. g. pericarditis in rheumatic fever Hemorrhagic inflammation – acute pancreatitis Suppurative inflammation – characterized by production of large amounts of pus or purulent exudate consisting of neutrophils, necrotic cells, and edema fluid .
Eg: acute appendicitis Abscess – localized collection of purulent inflammatory tissue caused by suppuration buried in tissue, an organ or confined space Membranous inflammation – An epithelium is coated by fibrin, desquamated epithelial cells and inflammatory cells-diphtheria Pseudo membranous inflammation – Pseudo membranous colitis – clostridium difficile Superficial mucosal ulceration with overlying slough or disrupted mucosa, fibrin, mucus and inflammatory cells Necrotizing (gangrenous) inflammation –A combination of necrosis and putrefaction E. g. gangrenous appendicitis
Effect of inflammation Beneficial effects • Dilution of toxins produced by bacteria are carried away in the lymphatics • Entry of antibodies -Due to increased vascular permeability, destruction by microorganisms • Transport of drugs to the site where bacteria is multiplying • Fibrin formation – impedes the movement of micro-organisms • Stimulation of immune response • Delivery of nutrients and oxygen required for the cells Harmful effects • Digestion of normal tissue- enzymes such as collagenases and proteases may digest normal tissues, resulting in their destruction E. . glomerulonephritis • Swelling – epiglottis swelling leading to airway obstruction as in Heamphilus influenza • Inappropriate inflammatory response – In Hypersensitivity reaction type I, the inflammatory responses appear inappropriate, where the provoking agent otherwise poses no threat Summary of Clinical and Laboratory Evaluation of Acute Inflammation Systemic features • Fever/ Pyrexia: produced in response to pyrogens that act by stimulating PG synthesis in hypothalamus.
Endogenous pyrogens which act on the hypothalamus to set the thermoregulatory mechanisms at higher temperature. IL-2 • Constitutional symptoms – malaise/anorexia/ somnolence • Reactive hyperplasia of reticulo-endothelial system – lymph node enlargement/splenic enlargement • Other manifestations :Increased pulse rate& BP, decreased sweating, rigors and chills • Sepsis: due to severe bacterial infection. Septic shock – can lead to DIC , Hypoglycemia, Cardiovascular failure, ARDS, Renal failure Local features (cardinal clinical signs; seen at site of injury only) Redness, swelling, heat, pain, and loss of function
Laboratory evaluation • Changes in peripheral white blood cell count Leukocytosis: Normally climbs to 15000 – 20000 Neutrophilia – bacterial infections Lymphocytosis – viral infections ( Infectious Mononucleosis , Mumps) Eosinophilia – allergic or parasitic infestation Leucopenia – Typhoid, virus, rickettsia Lymphocytosis and neutropenia in acute viral infections • Examination of inflammatory infiltrate Changes in plasma proteins Characteristic high protein levels and high specific gravity Presence of acute inflammatory cells
Elevated levels of acute phase reactants (C-reactive protein, 1 antitrypsin, Fibrinogen, Serum amyloid protein (SAA) and haptoglobin) • CRP and SAA bind to microbial cell walls , act as opsonins and fix complement • Fibrinogen causes erythrocytes to form rouleaux • Prolonged production of these proteins results in secondary amyloidosis in chronic inflammation • Elevated levels of CRP is a marker of increased risk of myocardial infarction in patients with coronary artery disease • Increased erythrocyte sedimentation rate Biopsy and microscopic examination of tissue; Hyperemia, edema, neutrophil infiltration and fibrin Lymphatics in inflammation • Much of the emphasis in the discussion of inflammation is on the reactions of blood vessels, but lymphatics also participate in the response. • As is well known, the small amount of interstitial fluid formed normally is removed by lymphatic drainage. • In inflammation, lymph flow is increased and helps drain edema fluid from the extravascular space. • Because the junctions of lymphatics are loose, lymphatic fluid eventually equilibrates with extravascular fluid. In addition to fluid, leukocytes and cell debris may also find their way into lymph. • In severe inflammatory reactions, especially to microbes, the lymphatics may transport the offending agent. • The lymphatics may become secondarily inflamed (lymphangitis), as may the draining lymph nodes (lymphadenitis). • Inflamed lymph nodes are often enlarged, because of hyperplasia of the lymphoid follicles and increased numbers of lymphocytes and phagocytic cells lining the sinuses of the lymph nodes. This constellation of pathologic changes is termed reactive, or inflammatory, lymphadenitis • For clinicians, the presence of red streaks near a skin wound is a telltale sign of an infection in the wound. • This streaking follows the course of the lymphatic channels and is diagnostic of lymphangitis; it may be accompanied by painful enlargement of the draining lymph nodes, indicating lymphadenitis. Sequelae of inflammation – The possible outcomes of acute inflammation are Resolution
When the injury is limited or short-lived and when there has been no or minimal tissue damage, the usual outcome is restoration to histologic and functional normalcy. This involves the clearance of injurious stimuli, removal of chemical mediators and acute inflammatory cells, replacement of the injured cells, and eventually, the restoration of normal function of cells. Events in the resolution of inflammation. Phagocytes clear the fluid, leukocytes and dead tissue, and fluid and proteins are removed by lymphatic drainage.
Organization – Scarring or fibrosis Scarring or fibrosis results after substantial tissue destruction or when inflammation occurs in tissues that do not regenerate. Extensive fibrinous exudates may not be completely absorbed and are organized by ingrowth of connective tissue with resultant fibrosis. Abscess formation may occur in the setting of extensive neutrophilic infiltrates or in certain bacterial or fungal infections. Due to the extensive underlying tissue destruction, the nly outcome of abscess formation is scarring. Abscesses may form in some bacterial infections Progression to chronic inflammation- Progression to chronic inflammation may follow acute inflammation, although signs of chronic inflammation may be present at the onset of injury. Depending on the extent of the initial and ongoing tissue injury as well as the capacity of the affected tissues to regrow, chronic inflammation may be followed by regeneration of normal structure and function or may lead to scarring.
Defects in Leukocyte Function Since leukocytes play a central role in host defense, it is not surprising that defects in leukocyte function, both acquired and inherited, lead to increased susceptibility to infections, which may be recurrent and life-threatening • The most common causes of defective inflammation are bone marrow suppression caused by tumors and chemotherapy or radiation (resulting in decreased leukocyte numbers), and metabolic diseases such as diabetes (causing abnormal leukocyte functions). The genetic disorders, although individually rare, illustrate the importance of particular molecular pathways in the complex inflammatory response. Some of the better understood inherited diseases are the following: a. Defects in leukocyte adhesion. In leukocyte adhesion deficiency type 1 (LAD-1), defective synthesis of the CD18 ? subunit of the leukocyte integrins LFA-1 and Mac-1 leads to impaired leukocyte adhesion to and migration through endothelium, and defective phagocytosis and generation of an oxidative burst.
Leukocyte adhesion deficiency type 2 (LAD-2) is caused by a defect in fucose metabolism resulting in the absence of sialyl-Lewis X, the oligosaccharide on leukocytes that binds to selectins on activated endothelium. Its clinical manifestations are similar to but milder than those of LAD-1. b. Defects in microbicidal activity. An example is chronic granulomatous disease, a genetic deficiency in one of the several components of the phagocyte oxidase responsible for generating ROS. In these patients, engulfment of bacteria does not result in activation of oxygen-dependent killing mechanisms. . Defects in phagolysosome formation. One such disorder, Chediak-Higashi syndrome, is an autosomal recessive disease that results from disordered intracellular trafficking of organelles, ultimately impairing the fusion of lysosomes with phagosomes. ] d. Rare patients with defective host defenses have been shown to carry mutations in Toll-like receptor signaling pathways. |Clinical Examples of Leukocyte-Induced Injury: Inflammatory Disorders | Disorders |Cells and Molecules Involved in Injury | |Acute | |Acute respiratory distress syndrome |Neutrophils | |Acute transplant rejection |Lymphocytes; antibodies and complement | |Asthma |Eosinophils; IgE antibodies | |Glomerulonephritis |Antibodies and complement; neutrophils, monocytes | |Septic shock |Cytokines | |Vasculitis |Antibodies and complement; neutrophils | |Chronic | |Arthritis |Lymphocytes, macrophages; antibodies | |Asthma |Eosinophils, other leukocytes; IgE antibodies | |Atherosclerosis |Macrophages; lymphocytes? | |Chronic transplant rejection |Lymphocytes; cytokines | |Pulmonary fibrosis |Macrophages; fibroblasts | |Defects in Leukocyte Function | |Disease |Defect | |Acquired |Bone marrow suppression: tumors, radiation, and |Production of leukocytes | |chemotherapy | | |Thermal injury, diabetes, malignancy, sepsis, |Chemotaxis | |immunodeficiencies | | |Hemodialysis, diabetes mellitus |Adhesion | |Leukemia, anemia, sepsis, diabetes, neonates, |Phagocytosis and microbicidal activity | |malnutrition | | |Genetic | |Leukocyte adhesion deficiency 1 |? hain of CD11/CD18 integrins | |Leukocyte adhesion deficiency 2 |Fucosyl transferase required for synthesis of sialylated | | |oligosaccharide (receptor for selectins) | |Chronic granulomatous disease |Decreased oxidative burst | | X-linked |NADPH oxidase (membrane component) | | Autosomal recessive |NADPH oxidase (cytoplasmic components) | |Myeloperoxidase (MPO) deficiency |Absent MPO-H2O2 system | |Chediak-Higashi syndrome |Protein involved in organelle membrane docking and fusion |
At the end of reading – try to answering these questions – if you can then you are thro if not go back and read 1. Define inflammation and discuss the causes of inflammation 2. List and explain the cardinal signs of inflammation 3. List and explain the stimuli for inflammation 4. Explain the vascular changes that occur during inflammation 5. Explain the cellular events during inflammation 6. Explain phagocytosis in detail 7. Describe with illustrations how the endothelium becomes leaky in acute inflammation? 8. Discuss the cells that are involved in inflammation 9. Explain in detail the adhesion receptors involved in adhesion and transmigration 10. Explain Diapedesis and chemotaxis 11. Explain the clinical genetic deficiencies due to phagocytosis 12.
Explain the regulation of endothelial and leukocyte adhesion molecules 13. Briefly explain the outcomes of acute inflammation 14. Explain the various special macroscopic appearance of acute inflammation 15. Explain the harmful, beneficial and systemic effects of inflammation 16. Define Exudate, Transudate, Edema , Pus 17. Tabulate the differences between exudate and transudate 18. Write briefly on chemoattractants involved in chemotaxis during inflammation 19. Write briefly on inflammatory oedema 20. Explain the various Defects in Leukocyte Function 21. Tabulate and list the Clinical Examples of Leukocyte-Induced Injury: Inflammatory Disorders 22.
Tabulate and list Defects in Leukocyte Function 23. Explain the role of lymphatics in inflammation 24. Explain the Clinical and Laboratory Evaluation of Acute Inflammation CAUTION ? If your incredible short-term memory got you through “Organic Chemistry”, it probably won’t get you through “Pathology”, which is a quantum leap with more material. ? Find some way to organize the material to suit your learning style. ? Adopt active learning (read text books) ? Passive learning (others notes) is not recommended in the medical curriculum ? Don’t memorize without understanding ? MY NOTES ARE THERE TO GUIDE YOU BUT CERTAINLY NOT A SUBSTITUTE TO READING TEXTBOOK