Week 7 inflammatory response

Cause of Redness

occurs from increased amount of blood via vasodilation

Cause of Swelling

Occurs from increased permeability of blood vessels

Mast Cells

Abundant alongside the blood vessels that supply connective tissue. They produce histamine (dilates small blood vessels) and can also bind to, ingest, and kill bacteria

Aparin

*Administration* orally *Site & action* inhibits generation of thromboxane A2, a powerful inducer of platelet aggregation *side effect* hemorrhage (asparin is a blood thinner)

Coumarin

*site & action*inhibit liver synthesis of vitamin K dependant coagulation factors *stage* Interferes with stages 1-3 (inhibits synthesis of factor X and prothrombin, among others, which will prevent the synthesis of prothrombinase and activation of prothrombin into thrombin *time period in treatment* long term prophylaxis *administration* by mouth as its polarity and size allow it to cross the membrane into the digestive system *coagulation test* PT *side effect* Hemorrhage

Inappropriate Clot Formation

*Dangers* A blood clot can form in any blood vessel in your body. It can end up in the lungs, heart, brain and other locations if it breaks away and travels through the blood. These migrations can lead to serious complications as the clot disrupts the flow of blood to important organs. *Action of fibrin* a clot does not extend beyond a wound site into the general circulation because fibrin absorbs thrombin which activates fibrinogen into fibrin threads. *Chemicals contained in endothelials and WBC's* prostacyclin, a prostaglandin, opposes actions of thromboxane A2, stopping it from activating other platelets

Bruno's Stages of Wound Healing

*Defensive stage* begins at time of injury, lasts 4-6 days, and consists of three major mechanisms: hemostasis (formation of fibrin and clots), inflammation (debridement of wound; inflammatory response also contributes to fibrin thread formation), and cell migration (epithelisation - re-establishing the primary barrier). *Reconstructive stage* begins during the last phase of the defensive stage and will last 2-4 weeks depending on the size and character of the wound. Involves regeneration of the damaged tissue cells, repair and formation of scar tissue. *Maturative stage* may continue for months to years and involves shrinkage and remodeling of scar tissue, which will increase the new tissue's strength and ability to resist stress. After a couple of weeks the scar area will have approximately 70% of its final strength. As the collagen production and deposition slows the capillaries begin to disappear. The final scar will thus be fibrous due to large quantities of collagen, and white due to reduced vascularization.

Platelet Plug Formation

*Examples of the contents in the platelet cytoplasm:* Within many vesicles are clotting factors, ADP, ATP, Ca2+ and serotonin. Also present are enzymes that produce thromboxane A2, a prostaglandin; fibrin-stabilizing factor (which helps to strengthen a blood clot), lysosomes; some mitochondria; membrane systems, glycogen and platelet growth factor (PDGF). *Platelet adhesion:* Initially, platelets contact and stick to parts of a damaged blood vessel, such as collagen fibres of the connective tissue underlying the damaged endothelial cells. *Platelet release reaction:* Due to adhesion, the platelets become activated and their characteristics change dramatically. They extend many projections that enable them to contact and interact with one another, and they begin to liberate the contents of their vesicles. *Platelet plug:* The accumulation and attachment of large numbers of platelets forms this mass.

Intrinsic Pathway

*Stage 1* Damaged epithelial cells activates activators in contact with or in the blood. Also causes damage to platelets which release phospholipids. Contact with collagen fibers activates clotting factor XII which begins a sequence of reactions to activate clotting factor X (also activated by phosophlipids and Ca) It combines with clotting factor V to form prothrombinase

Extrinsic Pathway

*Stage 1* tissue trauma causes release of thromboplastin (tissue factor) into the blood. In the presence of Calcium, TF activates clotting factor X which combines with clotting factor V in the presence of calcium to form Prothrombin

Common Pathway

*Stage 2* Prothrombinase and calcium catalyze the conversion of prothrombin to thrombin *Stage 3* Thrombin, in the presence of calcium converts fibrinogen (soluble) to loose fibrin threads (insoluble). Thrombin also actibates clotting factor XIII (fibrin stabilizing factor) which strengthens and stabilizes fibrin threads into a sturdy clot. Plasma also contains some clotting factor XIII

Four Systemic Signs of Inflammation

*Temperature:* increased temperature *White blood cell count:* increased number of white blood cells usually indicate an infection/inflammation *Pulse:* increased pulse *Respirations:* increased

Thrombolytics - Tissue Plasminogen Activator

*administration* through an IV line within 3 hours of the beginning of a stroke or MI symptoms, only to patients who meet strict criteria *Site & action* binds with fibrin within a clot and converts trapped plasminogen into plasmin *side effects* hemorrhage, especially in patients with hemorrhagic stroke

Heparin

*site & action* interacts with antithrombin III to increase inhibition of specific clotting factors within the blood *stage* interferes with stages 1-3 (at low concentrations inhibits factor X and at higher concentrations inhibits almost all clotting factors) *time period in treatment* When rapid onset of anticoagulant effects are required (prevention of pulmonary embolism or DVT) *administration* By injection as its polarity and size prevent it from crossing the membrane in the digestive system *coagulation test* APTT *side effect* hemorrhage

Tissue Repair Factors

*vitamin A* maintains general health and vigor of epithelial cells *Vitamin B* folic acid is essential for normal RBC and WBC production *Vitamin C* promotes protein synthesis including laying down of collagen in formation of connective tissue. Promotes wound healing *Vitamin D* essential for absorption of calcium which is required for many steps in the blood clotting process *Vitamin E* may promote wound healing, prevent scarring, and protect liver from toxic chemicals *Vitamin K* coenzyme essential for synthesis of four clotting factors *Blood circulation* increased circulation means more blood flow to site of tissue damage, and an increased presence of platelets, clotting factors, and associated enzymes. *Age* collagen becomes fragile and disorganized, macrophages become less efficient and less numerous, decreased size of sebaceous glands leads to dry and broken skin that is more susceptible to infection.

Stage 2 of Inflammatory Response (Phagocyte Migration)

-chemotaxis -leukocytosis (increased WBCs in blood) -phagocytes migrate to damaged area through leaky wall of blood vessels

Stage 3 of Inflammatory Response (Release of Nutrients)

-neutrophils phagocytose invading microbes -monocytes follow neutrophils to area of infection, becoming macrophages to phagocytose damaged tissue, worn out neutrophils, & invading microbes

Stage 5 of Inflammatory Response (Pus Formation)

-pus is the collection of dead phagocytes and damaged tissue -continues until infection subsides -may reach surface of body and drain or remains until infection is terminated

Thrombus

A blood clot in an unbroken blood vessel

Embolus

A blood clot, bubble of air, fat from broken bones, or a piece of debris transported by the blood stream

Antihistamine

A drug that inhibits effects of histamine. It prevents inflammation symptoms, vasoconstricion of bronchi, and stimulation of mucous secretion. If they are working for a mild allergic reaction, then the patient should feel no pain, have no swelling, increased temperature or redness. They should also have easy breathing and not be itching.

Hemostasis

A sequence of responses that stops bleeding and reduces blood loss involving 1. vasoconstriction, 2. platelet formation (temporary measure), and 3. blood clotting (coagulation) [multiple steps, doesn't need platelets]

Approximation

A value or quantity that is nearly but not exactly correct

Keloid

An area of irregular fibrous tissue formed at the site of a scar or injury

Activated Partial Thromboplastin Time

An assay in which a negatively charged contact activator (eg. Kaolin), phospholipids and calcium are added to citrated plasma and the time to clot formation is measured to determine APTT in seconds; the assay is used to assess the function of the intrinsic pathway of coagulation and to monitor agents such as heparin and hirudin/hirulog. 25 - 39 seconds

Anticoagulent Therapy

Anticoagulant therapy is used prophylactically and/or to treat intravascular clotting problems by decreasing the coagulation of the blood.

Antiplatelet Drug Therapy

Antiplatelets are used prophylactically and/or to treat patients with acute myocardial infarction (heart attack) or ischemic stroke by preventing further platelet aggregation and clotting in the coronary or brain blood vessels.

Blockage of Common Bile Duct

Blockage of the common bile duct prevents the delivery of bile (fat emulsifying agents) to reach the small intestines to digest fats, thus resulting in inadequate or no absorption of vitamin K from large intestines. This prevents the stage 2 of clotting process from happening. Inadequate release and delivery of bile into small intestine leads to lower than normal levels of lipid absorptions which results in vitamin K defiency means there is little or no syntheses of the clotting factors produced by vitamin K (factors II (prothrombin), VII, IX, and X)

Platelets

Break off magakaryocytes in red bone marrow and then enter blood circulation. *Stage 3 blood clot formation* their granules contain chemicals that once released promote blood clotting.

Pus Formation

Collection of dead phagocytes and damaged tissue that is either drained or remains in site of infection

Exudate Formation

Composed of serum, fibrin, and WBC's. It is a fluid that filters from blood vessels to the area of inflammation, appearing pus like or a clear liquid

Thrombocytopenia

Decrease in platelet numbers result in a tendency to bleed from the capillaries (or where blood vessels are damaged). ] b) They help stop blood loss from blood vessels by forming a platelet plug. Their granules also contain chemicals that once released promote blood clotting

Stage 4 of Inflammatory Response (Fibrin Formation)

Fibrinogen released from the liver, creates an insoluble, thick mesh of fibrin threads that localizes and traps invading microbes to block their spread

Fibrin

Fibrinogen turns to fibrin by thrombin *Stage 3* forms the threads of the clot

Fibrin Formation

Formation of fibers and other components to make up the extracellular matrix, done by fibroblasts

Parenchyma

Functional parts of any organ as opposed to stroma tissues

Thrombin

In stage 2 prothrombinase and calcium catalyze conversion of prothrombin to thrombin *stage 3* In the presence of calcium it converts fibrinogen into loose fibrin threads and also activates clotting factor XIII

Chronic Inflammation

Inflammation that may have a rapid or slow onset but is characterized primarily by its persistence and lack of clear resolution; it occurs when the tissues are unable to overcome the effects of the injuring agent

Vitamin K Deficiency

It is required for the synthesis of four clotting factors by hepatocytes: factors II (prothrombin), VII, IX, X...the deficiency results in no factors present to promote clotting formation may result in excessive bleeding. No factors to promote clotting formation may result in excessive bleeding. Vitamin K is needed for the synthesis of the factors which play a vital role in the clotting formation.

Inflammation

Non specific, defensive response of the body to tissue damage due to pathogens, abrasions, chemical irritations, distortion or disturbance of cells, and extreme temperatures. It is characterized by redness, pain, heat and swelling. The purpose is to attempt to dispose microbes, toxins or foreign material at the site of an injury, to prevent their spread to other tissues and to prepare the site for tissue repair in an attempt to restore tissue homeostasis

Liver Damage

Liver damage prevents the liver from producing needed plasma proteins (fibrinogen and prothrombinase). Prothrombinase which is needed with Ca2+, converts prothrombin to thrombin, which in the presence of Ca2+ converts fibrinogen (soluble) into loose insoluble fibrin threads to form the clot

Cause of Loss of Function

May be caused by inflammation from kinins affecting nerve endings, depending on site and extent of injury

Granulation Tissue

New vascular tissue ingranular form on an ulcer or healing surface of a wound

Platelet Count

Platelets can be counted directly or numbers can be estimated from the blood smear (>5 per oil immersion field.). Decreased platelet numbers (thrombocytopenia) occur with disseminated intravascular coagulation, bone marrow depression, autoimmune haemolytic anemia, systemic lupus erythematosus and severe hemorrhage. Thrombocytosis (increased platelet numbers) is caused by excessive bleeding from trauma, blood sucking parasites or neoplasia, iron deficiency anemia and myeloproliferative syndromes. 150000 - 400000 platelets present in each uL of blood.

Blood Coagulation Positive Feedback

Platelets cling to damaged blood vessel and release chemicals to attract more platelets until a clot is formed. This escalating process is a positive feedback loop that ends with the formation of a blood clot which patches the vessel and stops the bleeding

Kinins

Polypeptides formed in blood from inactive precursors called kinogens. It is involved in Stage 1 and induces permeability and increased permeability of blood vessels

Repair

Process by which skin or other body tissue heals itself after trauma

Neutrophils

Produced and released by red bone marrow and involved in stage 2: phagocytes migration. An hour after inflammatory process starts, phagocytes appear on scene. As large amount of blood accumulates, neutrophils begin to stick to inner surface of endothelium (lining) of blood vessels. Neutrophils squeeze through lumen of blood vessel to reach damaged area. This is known as emigration which depends on chemotaxis. Neutrophils attempt to destroy invading microbes by phagogytosis. Pnedominate in early stages of infection but die rapidly.

Fibrinogen

Produced by liver (circulates blood plasma) involved in Stage 4 fibrin formation and plays an important role in blood clotting, localize and trap invading microbes and block their spread. By the action of thrombin it becomes activated fibrin

Monocytes

Produced in red bone marrow and involved in stage 2. Monocytes follow neutrophils to damaged area, once in tissue, monocytes transform into macrophages that add to phagocytic activity of fixed macrophases present. They large and engulf damage tissue, worn out neutrophils and large microbes.

Prostaglandins

Released by damaged cells and involved in stage 1 and 2. They intensify effects of histamine and kinins and may stimulate emigration of phagocytes through capillary walls. Also, intensify and prolong pain associated with inflammation.

Leucocytosis Promoting Factor

Released from damaged tissue cells and involved in Stage 2. Promotes release of leukocytes at red bone marrow

Histamine

Released from mast cells in connective tissue, and from basophils and platelets in blood. Also neutrophils and macrophages attracted to site of injury stimulate release. Cause vasodilation and increased permeability of blood vessels. Causes vasoconstiction of smooth muscle of bronchioles and stimulates neurons creating itch and pain and also stimulates mucous secretions.

Tissue Thromboplastin

Released from plasma membrane of damaged cells *Stage 1 extrinsic pathway* In the presence of calcium it begins a series of reactions that ultimately creates clotting factor X

Debridement

Removal of damaged tissue or foreign objects from wound

Cause of Heat

Results from increased amount of blood that accumulates in the damaged area and metabolic reactions proceed more rapidly

Cause of Pain

Results from injury to neurons and from toxic chemicals released by microbes, kinins affect some nerve endings, prostaglandins which intensify and prolong the pain, and from increased pressure from edema

Stroma

The supportive tissue of an epithelial organ consisting of connective tissue and blood vessels

Scar Tissue

The connective tissue forming a scar and composed of fibroblasts recent scars and largely of dense collagenous fibers in old scars

Fibrinolysis

The fibrinolytic system dissolves small, inappropriate clots. It prevents blood clots that occur naturally from growing and causing problems. Primary is the normal breakdown of clots; secondary is the breakdown of blood clots due to a medical disorder *Plasminogen* an inactive plasma enzyme incorporated into the clot *Plasmin* both body tissues and blood contain substances that activate plasminogen to plasmin, and active plasma enzyme. It breaks down fibrin *Events which trigger process* Once a clot has enlarged and created an impairment of blood flow through undamaged vessels. Dissolves clots at a site of damage once damage is repaired

Coagulation

The process of gel formation (clotting) by a series of chemical reactions that culminates in formation of fibrin threads

Vasoconstriction

When arteries or arterioles are damaged, the circularly arranged smooth muscle in their walls contracts immediately. Such a vascular spasm reduces blood loss for several minutes to several hours, during which time the other hemostatic mechanisms to into operation.

Chemotaxis and Emigration of Phagocytes

Within an hour of the inflammatory processes start, phagocytes appear on the scene. As large amounts of blood accumulate, neutrophils begin to stick to the inner surface of the endothelium of blood vessels. Then the neutrophils begin to squeeze through the blood vessel to reach the damaged area. This process of emigration depends on chemotaxis, a chemically stimulated movement of phagocytes to an area of damage. Neutrophils attempt to destroy the invading microbes by phagocytosis. A steady stream of neutrophils is ensured by the production and release of additional cells from red bone marrow (leukocytosis)

Vitamin K

a fat soluble vitamin produced by bacteria in large intestine required for synthesis of factors II (prothrombin), VII, IX and X by hepatocytes

Prothrombinase

formed by end of extrinsic and intrinsic stage 1 pathways and converts prothrombin into thrombin

Calcium

ion found in body in bones, teeth and platelets *stage 1* allows clotting factor X to combine with clotting factor V to form prothrombinase *Stage 2* with prothrombinase it catalyzes prothrombin to thrombin *Stage 3* Thrombin with Ca converts fibrinogen to loose fibrin threads

Prothrombin

plasma protein produced by liver *stage 2* and gets converted to thrombin

Prothrombin Time

sensitive to changes in vitamin K dependant factors, especially prothrombin. approximately 12 seconds

Hemostatic Drug

special type of antihemorrhagic agent that works by contracting tissue to seal injured blood vessels

Stage 1of Inflammatory Response (Vasodilation and Increased Permeability of Blood Vessels)

vasodilation allows for more blood to flow through damaged area, increased permeability permits defensive proteins such as antibodies & clotting factors to enter the injured area from the blood histamine, kinins, prostaglandins, leukotrienes, and complement all contribute to vasodilation and increased permeability. Heat and redness result from the large amount of blood accumulating to the damaged area; swelling (edema) results from the increased permeability of blood vessels