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ICS Abnormal signs and symptoms: Progressive pain right calf; about 5 day, as vague, intermittent pain aggravated

by movement and walking; 2 days PTC: cellulitis, erythema and tenderness, fever and chills Abnormal elements of Patient history: 30 years of DM, HPN and ischemic heart disease Abnormal PE findings: BP 160/100 high (120/80) HR 105/min high (60-100) RR 22/min high (12-18) Temp 38.9 high general: Obese, no ARDS HEENT diabetic retinopathy chronic compli of Dm Heart sounds bounding ( increased stroke volume aortic insufficiency and arterial stiffness, occur with aging) Apex beat left 5th ICS anterior axillary line (normal left 5th ICS MCL): LV and RV enlargement, CHF, Valvular dse. Abnormal Lab results: HB 165 (N: 120-160) HCT 48% (36 48%) WBC 16500 ( 4000-11000) PLT 350000 (200k-400k) neuto 85 (55-60) Lym 10 (20-30) Mono 3-6 Eo 1 FBS 216 / 12mmol (N: <100; Impaired: 100-125; DM: >125) Prothrombin time normal (12-14 secs) D-dimer: 650 ng/ml (for the presence of thrombus: used in dx of DVT, PE and stroke) (positive: (+) fibrin degradation products; NV - <0.4 ug/ml) Chest x-ray: tortuous (twisted) and atherosclerotic aorta; LV enlargment Doppler ultrasound intraluminal lesion in popliteal vein. (with the use of sound waves, it evaluates the blood flow within a vessel) Pathologic process: Disorders of Inflammation, fluid and hemodyanmics: 1. Redness (Rubor) Due to vasodilatation Mediated by prostaglandins like PGE and prostacyclin, resulting in hyperaemia

Also due to stimulation of pain-sensitive nerve endings by prostaglandins and bradykinin

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Loss of Function of the Affected Area (Functio Laesa) Due to pain and immobility E.g. in tonsillitis it is difficult to swallow because it is painful (motion of swallowing is limiting) A. Vasoactive changes in calibre and flow 1. A brief period of vasoconstriction followed by vasodilatation leading to increased blood flow 2. The increased blood flow leads to increased hydrostatic pressure in capillaries and venules 3. As a result, fluid will be driven from the intravascular to the extravascular compartment, forming transudate. The loss of fluid and increased vessel diameter lead to slower blood flow, concentration of red cells in small vessels, and increased blood viscosity. These changes result in stasis, which is seen as vascular congestion. As stasis develops, blood leukocytes (principally neutrophils) accumulate along the vascular endothelium. This results in the adhesion of leukocytes to the endothelium. Afterwards, they migrate through the vascular wall, into the interstitial tissue. B. Increased capillary permeability Occurs through several mechanisms: Endothelial cell contraction o Most common mechanism of intravascular leakage o Also called the immediate transient response, since it occurs rapidly after exposure to the mediator, and is usually reversible and short-lived Direct endothelial injury o Leakage starts immediately after injury and is sustained at a high level for several hours until the dammaged vessels are thrombosed or repaired o Also known as the immediate sustained response o Delayed prolonged leakage/response in some forms of mild injury (e.g. sunburn, type IV hypersensitivity reaction), vascular leakage begins after a delay of 2 to 12 hours, and lasts for several hours to days Leukocyte-mediated endothelial injury via release of toxic oxygen species and proteolytic enzymes Increased Transcytosis due to increased transport of fluids and proteins C. Increased vascular permeability leading to exudate formation The oncotic pressure within the blood vessels is decreased the oncotic pressure outside the blood vessels increased

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Swelling (Tumor) Due to Increased vascular permeability Mediated by vasoactive amines (histamine, serotonin), C3a, C5a, bradykinin, leukotrienes C4, D4, and E4 and Platelet-activating Factor (PAF) Results in edema manifested in the form of swelling Heat/warmth (Calor) Due to increased blood flow (hyperaemia) Pain (Dolor) Due to increased pressure exerted by edema

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the combination of increased intravascular hydrostatic pressure and increase in the extravascular oncotic pressure will create the production of exudates (protein rich fluid)

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Inc. vascular permeability


Hemoconcentration decreased intravenous osmotic pressure (increased hydrostatic pressure due to vasodilatation)

Increased blood Viscosity Stasis (slow blood flow) Disrupts normal axial blood flow cellular events of inflammation

edema or swelling 2.

Fever Due to pyrogens that stimulate prostaglandin synthesis in vascular and perivascular cells of the hypothalamus Exogenous pyrogens (bacterial products such as LPS) stimulate leukocytes to release endogenous pyrogens cytokines (TNF & IL-1) increases enzyme cyclooxygenase that converts amino acid into Prostaglandins In the hypothalamus, prostaglandins (esp. PG2) stimulate production of neurotransmitters (cAMP) reset temperature set point at a higher level. Changes in the peripheral blood a) Leukocytosis o count of above 10k per cubic mm o Normal 5k-10k per cubic mm Due to colony stimulating factors that stimulate leukocyte from bone marrow pool Differs from leukemoid reaction - count of above 100k per cubic mm; resemble leukemia; no blast cells shift to the left appearance of immature forms in the differential count Neutrophilia - indicative of bacterial infection Absolute lymphocytosis (I.M., mumps, German measles) Eosinophilia (bronchial asthma, hay fever, parasitic infestation) b) Leukopenia o Decreased WBC count o Below 5k o Seen in typhoid fever, viral, rickettsia, protozoan infection Increased acute phase proteins o C-Reactive Protein o Fibrinogen o serum amyloid A protein (SAA) Elevated serum levels of CRP have been proposed as a marker for increased risk of MI in patients with coronary artery disease Fibrinogen binds to red blood cells and cause them to form stacks (rouleaux) that sediment more. Prolonged production of SAA causes secondary amyloidosis Chronically elevated plasma concentrations of hepcidin reduce the availability of iron anemia Increased blood coagulability Sticky due to platelet, coagulation factors Increased pulse and blood pressure Decreased sweating Due to redirection of blood flow from cutaneous to deep vascular beds, to minimize heat loss through the skin Rigors (shivering), chills (search for warmth), anorexia, somnolence, and malaise

*Normal axial blood flow is when the cellular component of blood occupies the central portion of the blood stream while the fluid component of blood occupies the periphery of the blood stream. This is disrupted during stasis; wherein the cell components now occupy the periphery. Note: Injurious stimulus vascular events cellular events
Role of Inflammation Vasodilation Mediators Prostaglandins Nitric Oxide Histamine Histamine & serotonin (Vasoactive amines) C3a & C5a (by liberating vasoactive amines from mast cells, other cells) Bradykinin Leukotrienes C4, D4, E4 PAF (platelet activation factor) Substance P TNF, IL-1 Chemokines C3a, C5a Leukotriene B4 (Bacterial products, e.g. Nformyl methyl peptides) IL-1, TNF Prostaglandins Prostaglandins Bradykinin Lysosomal enzymes of leukocytes Reactive oxygen species Nitric oxide

Increased vascular permeability

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Chemotaxis, leukocyte recruitment and activation

Fever Pain Tissue damage

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Acute Phase Responses or Systemic Inflammatory Response Syndrome (SIRS) 7.

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Probably due to the actions of cytokines on brain cells

Sepsis Presence of large amounts of bacterial toxins in the blood Septic shock (triad of disseminated intravascular coagulopathy widespread thrombosis, hypoglycemia and cardiovascular system failure) Multiple organ failure Normal fluid homeostasis is maintained by: 1. Endothelial / vessel wall integrity - Endothelial wall must be free of trauma - The normal blood vessel is fenestrated or interrupted - When the endothelial wall is disrupted, there is a great volume of water that may go out of the blood vessel resulting to edema Intravascular pressure -Function of hydrostatic pressure - The major pressure that allows the exit of water at the arterial end Plasmaosmolarity - Function of osmotic pressure - Predominant plasma protein contributing to plasma osmolarity is albumin -The pressure that tends to draw fluid back to the intravascular space

Due to increased vascular permeability: damage in the endothelium as a result of an active inflammatory process causes fluid to escape into the interstitial space Fluid (exudate) has high inflammatory specific gravity because cells and proteins leak out with the fluid Can be caused by infection, vasculitis Also known as EXUDATIVE EDEMA Protein-rich fluid because of altered permeability of endothelial cells Fibrin-rich fluid Inflammatory cells are typical Specific gravity > 1.020 Usually a localized process

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NON-INFLAMMATORY Due to changes in hemodynamic forces intravascularly Represents an interplay between changes in hydrostatic pressure or osmotic pressure which leads to outflow of fluid Non-inflammatory fluid (transudate) has a low specific gravity because only the fluid moves out Also known as TRANSUDATIVE EDEMA Lower protein content because of no alteration in endothelial permeability No fibrin in fluid No inflammatory cells in fluid Specific gravity < 1.012 Often a generalized process PATHOPHYSIOLOGIC (MECHANISMS) CATEGORIES OF EDEMA 1. 2. 3. 4. 5. 6. Increased hydrostatic pressure - due to increased venous return Reduced plasma osmotic pressuredue to low serum albumin Lymphatic obstruction the reabsorbing capacity of the lymphatic channel is removed Sodium retention causes hypervolemia, leading to increased hydrostatic pressure Inflammation Leaky vessels

TWO TYPES OF FORCES THAT DRIVE THE NORMAL FLUID EXCHANGE: 1. Hydrostatic pressure - Function of the arteriolar pressure - Affected by: cardiac output, vessel wall elasticity, vascular tone, and blood volume. 2. Oncotic or osmotic pressure - Function of serum albumin - The differential osmotic force is maintained by the higher protein level in the blood - The most important force that promotes reabsorption of water from the interstitium back to the intravascular space

EDEMA Increased accumulation of fluid in the interstitium and body cavities May also be caused by low serum albumin, in which the reabsorbing power of the bloodvessel into the circulation is low Fluid tends to accumulate in very loose connective tissues; usually starts in the periorbital area and in the dependent portions of the body Should be differentiated from CLOUDY SWELLING wherein water accumulates inside the cell Inflammatory vs. Non- inflammatory INFLAMMATORY

-HEMORRHAGE PATHOGENESIS Trauma, laceration Atherosclerosisdamage of endothelial linings along with fat deposition on endothelial wall 3. Inflammatory- weakening of blood vessels potential to rupture 4. Neoplastic erosion of blood vessel- problem with clotting network 5. Hemorrhagic diathesis - there is an increased tendency to hemorrhage from usually insignificant injury bleeding tendencies/clotting anomaly (hemophiliacs) 1. 2.

Thrombus 1. Simply put, a blood clot. Derived from blood elements: vessel wall particularly the endothelium, platelets and clotting factors A.K.A antemortem clot (formed before death) Predisposing Factors/Virchows Triad

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Injury to endothelium Major cause of thrombosis in acute myocardial infarction (AMI), atherosclerosis, cigarette smoking (nicotine is endotheliotoxic), vasculitis (inflammation of the vessel wall), hypertension, hypercholesterolemia. This factor is particularly important in thrombosis in the heart or in arteries because in such areas, there is high flow rate of blood that prevent platelet adhesion and wash out active coagulation factors. However, imbalance in the production of pro- and anticoagulation substances may also lead to thrombosis. Alteration in normal blood flow (Stasis/Turbulence) Stasis, aneurysm (abnormal dilatation of blood vessel wall), valvular stenosis/regurgitation, vascular obstructions. Turbulence: contributes to arterial and cardiac thrombosis by injuring the vessel wall and by forming countercurrents Stasis: major contributor in venous thrombosis Laminar flow is disrupted, so there is increase contact of platelets with wall; no washout and dilution of active clotting factors Hypercoagulability/thrombophilia Immobilization, malignancy (pancreatic CA: release of TF-like substances), APAS (Antiplatelet antibody syndrome), DIC, nephritic syndrome, oral contraceptive use. Any alteration of the coagulation cascade that predisposes to thrombosis Less frequent contributor, but may predominate sometimes. May be primary (genetic) or secondary (acquired) EMBOLISM Process by which a detached intravascular solid, liquid or gaseous mass (embolus) is carried via blood stream to a site distant from its point of origin. Unless otherwise specified, emboli should be considered thrombotic in origin. INFARCTION An area of ischemic necrosis of organ/tissue as a result of arterial or venous occlusion SHOCK Final common pathway for potentially lethal clinical events like severe hemorrhage, extensive trauma or burns, large MI, massive PTE, and microbial sepsis.

Characteristic: systemic hypotension due to reduction of CO or effective circulating blood volume. Outcome of the characteristic: impaired tissue perfusion and cellular hypoxia Produces hypotension, anoxia, and cellular death. 1. Septic elaboration of toxins by bacteria (endotoxemia) peripheral vasodilation leading to pooling of blood (reduced venous return) reduced CO Septic shock: factors contributing to its pathophysiology Inflammatory mediators: massive release triggered by microbial cell wall constituents; result in activation of endothelial cells Endothelial cell activation and injury: leads to thrombosis (may lead to DIC), increased vascular permeability, and vasodilation. Microthrombi form all over the body. Edema is present. NO synthetase expression by endothelium is increased, releasing more NO, causing vasodilation. Metabolic abnormalities: insulin resistance due to proinflammatory cytokines that impair expression of GLUT-4; presence of hyperglycemia Immune suppression: hyperinflammatory state triggers counter-regulatory immununosuppressive mechanisms. Organ dysfunction: end result -DEEP VENOUS THROMBOSIS Conditions that favour development of DVT: - stasis (CHF) - injury and inflammation infection -hypercoagulability - advanced age -sickle cell disease Most of the venous thrombi begin in calf veins, frequently in the sinuses above the venous valves. Homan sign claf tenderness often associated with forced dorsiflexion of foot. Risk factors: -sepsis -advanced age -CHF -obesity Presentation: -pain, swelling, (+) homan sign,redness, fever, tachycardia Cellulitis VS DVT Temperature Cellulitis > DVT Lymphadenopathy (+) in cellulitis Skin color DVT is normal or cyanotic; Red in cellulitis Potential fates of venous thrombi -lysis -organization canalization -propagation venous thrombi serve as nidus for further thrombi -embolization