PathologyPathology: is the study of diseases.Diseases are the deviations from normal.The concept of diseases:For the pathologist: structural changes that are accompanied by functional changes. For a patientFor a physician

The Scope of Human PathologyPathology deals with recognition of diseases, their causes (aetiology), and their progression.Pathologists study structural changes (gross, or microscopic), etiology and mechanisms of diseases (pathogenesis)Most diseases can be placed in one of these categories: Inflammatory Neoplastic Degenerative conditions Developmental conditions

InflammationInflammation: Local defense and protective response against cell injury or irritation or Local vascular and cellular reaction, against an irritant.Irritating or injurious agents (Irritant)Living: Bacteria, Fungi, Virus, Parasite or their toxinsNon-Living: Chemical Physical MechanicalInflammation is designated by adding the suffix (itis) to the end of the name of the inflamed organ or tissue.

Types of inflammationAcute inflammation3) Chronic inflammation2) Sub acute inflammation: rarely occur.

1. Acute inflammationMicroscopic signs:Inflammatory response

Macroscopic signs:Symptoms1)Redness: 2)Hotness: 3)Swelling: 4)Pain and tenderness: 5)Loss of function:1. Local vascular change2. Formation of inflammatory exudate

Inflammatory response: (microscopic signs)Normal InflammationFirst: Local vascular changes:1. Initial temporary vasoconstriction for few seconds.2. Active vasodilatation of arterioles and capillaries (by chemical mediators: Histamine) and passive dilatation of venules. Increase in capillary permeability (fluid exudate to the extravascular tissue) thus concentration of blood cells, slowing of blood flow (stasis)3. Pavmentation: the margination of leukocytes.

Second: Formation of inflammatory exudates: Immigration or infiltration of the various leukocytes, fluid and plasma proteins outside the blood vessels into the surrounding tissue without injury of the blood vessels. Leukocytes seem to leave the smallest blood vessels by inserting pseudopodia into the interendothelial junctions and sliding through the wall by amoeboid movement. This is also due to the increased capillary permeability caused by the high osmotic pressure of the surroundings. The early stages are marked by the predominance of polymorphs especially neutrophils migration, particularly when the inflammation is caused by pyogenic cocci, later on monocytes infiltration occurs.

****In some cases RBCs may also pass (Diapedesis)

Function of inflammatory exudates1-Dilute the invading microorganism and its toxins.2-Bring antibodies through the plasma to the inflamed area.3-Bring leukocytes that engulf the invading microorganisms.4-Bring fibrinogen through the plasma, which is converted, to fibrin mesh, helping in trapping the microorganism and localize the infection.

Blood stem cell

Cells of inflammatory response1)Polymorphonuclear leukocytes: are basophils, neutrophils and eosinophils; lobed nucleus and grainy cytoplasm (granulocyte). Microphages (small eaters)2)Monocytes or histocytes: macrophages. (big eaters)3)Lymphocytes: leukocyte of fundamental importance; they determine the specificity of the immune response to infectious microorganisms and other foreign substances. 4)Plasma cells: A type of immune cell that makes large amounts of a specific antibody, developed from activated B cells (Derived from lymphocytes originate in the bone marrow). It is a type of WBCs and also called plasmacyte.

NeutrophilEosinophilBasophilLymphocytePlasma cellMonocyte

MonocytesPlasma cellPlasma cell

Name NeutrophilEosinophilBasophilMonocyteLymphocytePlasma cellMicrophageAcidophileBasophilMacrophage = Histocytes>Polymorphs and < RBCsPlasmacyteShape Pale pink to blue,Minimal granulation.Red with eosin,Coarse granulation.Blue with eosin,Coarse granulation1.5 to 2 times larger, Abundant fine granulationAgranular: non-granulated, Large round nucleusBasophilic, Encentric nucleus% of WBCs60-70%1-2% (50% in allergy)1%4-6%30%Found in tissue onlyFunction Phagositic1st defense Unknown but could neutralize histamine, serotonin and other kininsUnknown but contain histamine &heparinPhagocytic2nd defense elementengulf bacteria, dead cells, debris & dead neutrophils (pus cells) Antibodies productionLate stage of the inflammation

Primary source of specific Antibodies

PhagocytosisProcess by which Phagocytic cell (microphages and macrophages) engulf and kill foreign particles (bacteria)Two main types of phagocytes:

1- Motile phagocytes found in the blood stream and migrate to the inflamed area (microphages)

2- Histocytes (macrophages) of the reticuloendothelial system (RES) which remove bacteria that escapes from the inflamed area.

Normal cell

Phagocytosis

Phagocytosis

Steps of Phagocytosis1. Recognition 2. Ingestion- pseudopods engulf microbe through endocytosis3. Vacuole Formation- vacuole contains microbe4. Digestion- vacuole merges with enzymes to destroy microbes 5. Exocytosis- microbial debris is released

It occurs in two subsequent stages1. Ingestion of the m.o.2. Intracellular killing of the m.o. (digestion):Increased glycolysis and the PH drop to 4 -4.5 As a result, the proteolytic enzymes, phagocytin, lysozyme and other hydrolytic enzymes (lipase, esterase, nuclease etc.) are released and digest the ingested microorganism. Some species of bacteria e.g. tuberculosis are not killed within the phagocyte and even multiply within it.

Ingestion stageMethods of Intracellular killing of the m.o. (digestion)

Oxygen-dependent intracellular killing: Production of a superoxide. Use of the enzyme myeloperoxidase from neutrophil granules

Oxygen-independent intracellular:1. electrically charged proteins 2. lysozymes 3. lactoferrins 4. proteases and hydrolytic enzymes

ChemotaxisPositive directional response to chemical stimuli (chemotactic subs)The migration of leukocytes (by amoeboid movement) toward the injurious agent and the injured cells due to chemical stimuli (chemotactic subs).

Chemotactic subs: Exogenous (Specific): Polysaccharide secreted by m.o. Endogenous (General): Reaction product of the antigen-antibody reaction .

Chemotaxis

Types of acute inflammation(based on type of exudates)1-Catarrhal inflammation: 2-Serous inflammation: 3-Fibrinous inflammation: 4-Membranous inflammation: 5-Hemorrhagic inflammation: 6-Gangrenous inflammation: 7-Allergic inflammation: 8-Suppurative or purulent inflammation:

NameOccur inCharacterized byCatarrhal Mild inflammation in mucous membrane of respiratory or alimentary tracts e.g. common cold and catarrhal appendicitis Exudates rich in mucousSerousMild inflammation in serous surface such as pleural cavity, joint cavity where no damage in endothelium ex. Tuberculosis pleurisy and Common blistersExtensive watery low protein exudatesFibrinousOutpouring of exudates with high protein and less volume ex. in lobar pneumonia due to Streptococcus pneumonia & pericardium inflammationExudates rich in fibrinogenMembranousFibrinous inflammation in which network of fibrin entangling inflammatory cells and bacteria forms pseudo-membrane. Example: Diphtheria , Bacillary dysentery. Yellowish grey pseudo membrane rich in fibrin , polymorphs & necrotic tissues HemorrhagicIn blood vessels e.g. in plague Exudates rich RBCsGangrenousAcute appendicitisNecrotic tissues resulting from thrombi or emboliAllergicResult to Ag Ab reaction HypersensitivityPresence of edema & increase in vascularity.SuppurativeCaused by pyogenic bacteria and is characterized by pus formation Example: Abscess. Large amount of Pus & Purulent exudates produced

Lobar Pneumonia due to Streptococcus pneumonia is associated with massive fibrinous exudates in the lung alveoli. Pseudomembranous inflammation in diphtheria showing network of fibrin entangling inflammatory cells. Bacteria forming pseudo-membrane (left).3. Fibrinous type:4. Membranous type5. Suppurative or purulentPyemic abscess in myocardium. Abscess containing necrotic cell debris, colonies of bacteria, and large number of neutrophils, many of them degenerate. Myocardium is on the right.

Suppurative or purulent inflammationPus: thick fluid containing viable and necrotic polymorph and necrotic tissue Localized: ex. Abscess: Abscess is the localized collection of pus, commonly seen solid block of tissue - Example: dermis, liver, kidney, brain etc. Pus consists of partly or completely liquefied dead tissue mixed with dead or dying neutrophils and living or dead bacteria, formed of 3 zones Small abscess is called boil or furuncle Large one carbuncle Fistula2. Diffused: Spreading of pus to adjacent areas e.g. cellulites occurring in subcutaneous tissue . Usually caused by streptococci.

Abscess:

Fate of acute inflammation1- Resolution: exudates are reabsorbed and tissue becomes normal again.2- Healing: by repair and regeneration.3- Spread: through lymphatics or blood stream.4- Chronicity

Chronic inflammation: (granulomatous)Results from increased resistance of the causative agent to phagocytosis or the body defense mechanism is depressed. Shows lower vascular and exudative response The inflammatory cells are mainly macrophages, plasma cells, giant cells, lymphocytes, fibroblasts.Occurs in the form of granuloma.Chronic inflammation usually occur with granulomatous infections; e.g. leprosy, tuberculosis and fungal infections.

Phagocytosis

Acute inflammation