1. H EMODYNAMIC DISORDERS

2. EDEMA Normally, 60% of lean body weight = water  (2/3) intracellular.  (1/3)extracellular (interstitial fluid)  5% blood plasma. edema = an accumulation of interstitial fluid within tissues. Edema ≠ Extravascular fluid collection in body cavities: - pleural cavity (hydrothorax) - the pericardial cavity (hydropericardium) - peritoneal cavity (hydroperitoneum, or ascites). Anasarca is severe, generalized edema marked by profound swelling of subcutaneous tissues and accumulation of fluid in body cavities.

3. 1- Increased Hydrostatic Pressure Impaired Venous Return Congestive heart failure; Constrictive pericarditis; Ascites (liver cirrhosis); Venous obstruction or compression; Thrombosis; External pressure (e.g., mass); Lower extremity inactivity with prolonged dependency Arteriolar Dilation Heat; Neurohumoral dysregulation 2- Reduced Plasma Osmotic Pressure (Hypoproteinemia) Protein-losing glomerulopathies (nephrotic syndrome) Liver cirrhosis (ascites); Malnutrition; Protein-losing gastroenteropathy 3- Lymphatic Obstruction Inflammatory; Neoplastic; Postsurgical; Postirradiation 4- Sodium Retention Excessive salt intake with renal insufficiency Increased tubular reabsorption of sodium; Renal hypoperfusion; Increased renin-angiotensin-aldosterone secretion 5- Inflammation Acute inflammation; Chronic inflammation; Angiogenesis causes of edema

5. I NCREASED H YDROSTATIC P RESSURE - CAUSES Local : -impaired venous return- e.g. DVT Generalized: -congestive heart failure (most common): - reduced cardiac output leads  hypoperfusion of the kidneys  renin-angiotensin-aldosterone axis  sodium and water retention (secondary hyperaldosteronism). - fluid retention  increased venous hydrostatic pressures  worsening edema=(vicious circle) - Treatment of generalized edema includes: salt restriction, diuretics, aldosterone antagonists.

6. R EDUCED P LASMA O SMOTIC P RESSURE common causes: 1- albumin is lost from the circulation e.g. nephrotic syndrome  loss of albumin (and other plasma proteins) in the urine. 2- albumin synthesized in inadequate amounts e.g. severe liver disease (e.g., cirrhosis) e.g. malnutrition Unfortunately, increased salt and water retention by the kidney not only fails to correct the plasma volume deficit but also exacerbates the edema, since the primary defect (low serum protein) persists.

7. L YMPHATIC O BSTRUCTION = LYMPHEDEMA Causes : 1- localized obstruction by an inflammation or infection (e.g. filariasis =elephantiasis) 2- neoplastic conditions (e.g. breast cancer: Infiltration and obstruction of superficial lymphatics cause edema of the breast’s overlying skin  peau d'orange (orange peel)). 3- post surgical (e.g. breast cancer after axillary lymph node resection and/or irradiation  upper limb lymphedema 4- irradiation

8. S ODIUM AND W ATER R ETENTION leads to edema by increasing hydrostatic pressure (due to expansion of the intravascular volume) and reducing plasma osmotic pressure. causes: diseases that compromise renal function, including poststreptococcal glomerulonephritis and acute renal failure

9. C LINICAL C ORRELATION OF EDEMA Subcutaneous edema: -the most common -it signals potential underlying cardiac or renal disease -Can impair wound healing or the clearance of infections. Pulmonary edema  Common causes: -LVF- renal failure - ARDS –lung infections or inflammation.  can cause death if impeding oxygen diffusion Brain edema - life-threatening   brain herniation through the foramen magnum.

10. HEMORRHAGE Hemorrhage is extravasation of blood from vessels into the extravascular space. May be: 1. External hemorrhage. 2. Within a tissue (= hematoma ) 3. hemorrhage into body cavities ; a. Hemothorax : Blood in the pleural cavity. b. Hemopericardium : Blood in pericardium. c. Hemarthrosis : Blood in joints. 4. Small bleeds I. Petechiae are minute 1-2 mm bleeds in skin or mucous membranes II. Purpura are 3 to 5 mm bleeds III. Ecchymoses : Larger (1- to 2-cm) subcutaneous hematomas (bruises).

12. C LINICAL SIGNIFICANCE OF HEMORRHAGE DEPENDS ON : 1. The volume of and Rate of bleeding a. Rapid loss of < 20% of the blood volume, or slow losses of even of larger amounts, may be insignificant. b. Greater losses can cause hemorrhagic (hypovolemic) shock. 2. Site of bleeding : -Bleeding that would be trivial in the subcutaneous tissues can cause death if located in the brain. - Note: Chronic or recurrent external blood loss ( peptic ulcer or menstrual bleeding) may result in iron deficiency anemia.

13. HEMOSTASIS AND THROMBOSIS Hemostasis : tightly regulated processes that maintain blood in a fluid, clot-free state in normal vessels while inducing the rapid formation of a localized hemostatic plug at the site of vascular injury. The pathologic form of hemostasis is thrombosis. Thrombosis: blood clot (thrombus) formation in uninjured vessels or thrombotic occlusion of a vessel after relatively minor injury. Both hemostasis and thrombosis involve three components: the vascular wall, platelets, and the coagulation cascade.

14. C AUSES OF THROMBOSIS Virchow's triad: (1) endothelial injury (2) stasis or turbulence of blood flow (3)hyper- coagulability

15. 1- Causes of Endothelial injury 1. Valvulitis (heart valve inflammation) 2. MI (myocardial infarction) 3. Atherosclerosis 4. Traumatic or inflammatory conditions 5. Increased Blood Pressure 6. Endotoxins (infections) 7. Hypercholesterolemia 8. Radiation 9. Smoking

16. 2- Stasis and turbulence - Stasis is a major factor in venous thrombi. - Normal blood flow is laminar (platelets flow centrally in the vessel lumen, separated from the endothelium by a slower moving clear zone of plasma). - Stasis and turbulence cause the followings:

17. 3- H YPERCOAGULABILITY A- Inherited causes of hypercoagulability: Mutations in the factor V gene and the prothrombin gene are the most common. Deficiencies of anticoagulants such as protein C or protein S (rare) B. Acquired hypercoagulability 1.Oral contraceptive use and hyperestrogenic state of pregnancy. 2.Prolonged bed rest or immobilization. 3.Myocardial infarction. 4. Disseminated cancers (e.g. release of mucin in adenocarcinoma predisposes to thrombus formation (migratory thrombophlebitis, or Trousseau's syndrome).

18. F ATE OF THE T HROMBUS 1. Propagation: accumulation of additional platelets and fibrin. 2. Embolization: Fragment of thrombus is transported elsewhere in the vasculature. 3. Dissolution: In newly formed thrombus, due to activation of fibrinolysis. 4. Organisation and recanalization: Older thrombi become fibrosed and capillary channels may form and establish the continuity of the original lumen. 5. Bacterial seeding of thrombus serve as a culture medium, and the resulting infection may weaken the vessel wall, leading to formation of a mycotic aneurysm

19. C LINICAL C ORRELATIONS : V ENOUS VERSUS A RTERIAL T HROMBOSIS 1- Venous thrombi by obstructing the venus drainage can cause swelling and edema, but are most worrisome because they can embolize to the lungs and cause death. 2- Arterial thrombi can embolize. However, they mainly obstruct vessels (in coronary and cerebral arteries ) to cause myocardial and cerebral infarction. Also cardiac thrombi in the setting of myocardial infarction can give systemic embolization (brain, kidneys, and spleen).

20. V ENOUS THROMBOSIS 1. Superficial venous thrombi: - Arise in the saphenous vein particularly in varicose veins; these rarely embolize but can cause edema from impaired venous outflow, leading to varicose ulcers. II. Deep venous thromboses ("DVTs") : Occur in the larger leg veins at or above the knee ( popliteal, femoral, veins). May be asymptomatic. Serious because they can embolize.

21. E MBOLISM An embolus = a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin. 99% of all emboli = a dislodged thrombus (thromboembolism). 1% = Air embolism, fat embolism, amniotic fluid embolism. The consequences of thromboembolism include ischemic necrosis (infarction) of downstream tissue. Two forms of thrmoboembolism: 1.Pulmonary thromboembolism. 2.Systemic thromboembolism

22. P ULMONARY T HROMBOEMBOLISM In 95% of cases, venous emboli originate from DVT. They are carried through progressively larger channels and pass through the right side of the heart before entering the pulmonary vasculature. clinical features of pulmonary thromboembolism: a. Clinically silent: 60% to 80% of emboli esp. small ones. b. Sudden death or right sided heart failure (acute cor pulmonale):A large embolus that blocks a major pulmonary artery or pulmonary trunk (saddle embolus) c. Pulmonary hemorrhage d- Pulmonary hypertension and chronic right ventricular failure (chronic cor pulmonale): Multiple emboli occurring over long time.

23. S YSTEMIC ( ARTERIAL )T HROMBOEMBOLISM -80% arise from intra-cardiac thrombi. -The remainder originate from aortic aneurysms and thrombi overlying ulcerated atherosclerotic plaques. Common arterial embolization sites : a. The lower extremities (75%). b. Central nervous system (10%). c. Intestines, kidneys, etc : are less common. -Arterial emboli often cause infarction

24. INFARCTION An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue. 99% of all infarcts result from thrombotic or embolic events. Infarcts are classified on the basis of their color (reflecting the amount of hemorrhage) and the presence or absence of microbial infection. Therefore, infarcts may be either: 1- Red (hemorrhagic) 2- White (anemic) also, infarcts may be septic or bland.

25. Red infarcts (1) With venous occlusions (such as in ovarian torsion). (2) In loose tissues (such as lung). (3) In tissues with dual circulations such as lung and small intestine. (4) In tissues that were previously congested because of sluggish venous outflow. (5) When flow is re-established to a site of previous arterial occlusion. White infarcts Arterial occlusions or in solid organs (such as heart, spleen, and kidney), where the solidity of the tissue limits the amount of hemorrhage

26. S HOCK -is the final common pathway for several potentially lethal events, including hemorrhage, extensive trauma or burns, MI, pulmonary embolism, and sepsis, characterized by systemic hypoperfusion of tissues - shock initially is reversible, however, prolonged shock eventually leads to irreversible tissue injury that often proves fatal. -The typical signs of shock are low blood pressure, rapid heart rate, and signs of poor end- organ perfusion (i.e.: low urine output, confusion, or loss of consciousness).low blood pressurerapid heart rateperfusion

27. T HE MOST COMMON FORMS OF SHOCK 1- Cardiogenic shock: results from low cardiac output due to myocardial pump failure. It may be caused by myocardial damage (infarction), ventricular arrhythmias, extrinsic compression (cardiac tamponade) 2- Hypovolemic shock: most common type. Results from low cardiac output due to loss of blood or plasma volume (e.g., due to hemorrhage or fluid loss from severe burns 3- Septic shock: results from arterial vasodilation and venous blood pooling that stems from the systemic immune response to microbial infection.