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Is For DR Raed Al Ani
Is For DR Raed Al Ani
Is For DR Raed Al Ani
EDEMA
Increased fluid in the interstitial tissue spaces Massive edema is called Anasarca. Fluid may also accumulate in body cavities These collections of fluid are referred to based on location as:
Hydrothorax, hydropericardium, hydroperitoneum (Ascites )
maintained by opposing effects of vascular hydrostatic pressure and plasma colloid osmatic pressure
Fluid Homeostasis
Homeostasis is maintained by the opposing effects of vascular hydrostatic pressure and plasma colloid osmotic pressure
Either increased vascular hydrostatic pressure or decreased plasma colloid osmotic pressure can lead to EDEMA
I. Increased Hydrostatic Pressure Increased Hydrostatic Pressure II. Reduced Plasma Oncotic Pressure III. Inflammation IV. Other
I.
Increased Hydrostatic Pressure: Generalized increases in venous pressure, with resultant SYSTEMIC EDEMA, occur MOST COMMONLY in CONGESTIVE HEART FAILURE Thus, Congestive Heart Failure is the most common cause of EDEMA due to Increased Hydrostatic Pressure Types of disease causing Edema:
A. Congestive Heart Failure B. Portal Hypertension C. Venous Thrombosis
Blood backs up, first into the lungs, then into the venous circulation - increasing Central Venous Pressure (CVP) Increased CVP leads to increased capillary pressure (Hydrostatic Pressure) leading to Edema
EDEMA
EDEMA
EDEMA
Renal Perfusion
ADH Renal Vasoconstriction
Portal Hypertension
Portal Hypertension is Increased resistance to portal blood flow The most common cause of Portal Hypertension is CIRRHOSIS. Pathogenesis of Ascites is complex
Increased Portal Pressure (hydrostatic pressure) leads to increased liver sinusoidal hypertension. Fluid moves into the Space of Disse then into lymphatics
Portal Hypertension
Sinusoidal Hypertension
Hepatic Lymph
Cirrhosis
Serum
Albumin
Renal Perfusion
Aldosterone
ASCITES
Venous Thrombosis
Impaired venous outflow increases hydrostatic pressure
Inflammation
Both Acute and Chronic Inflammation are associated with EDEMA
Lymphatic Obstruction
Impaired lymphatic drainage with resultant lymphedema, usually localized
Usually due to INFLAMMATION or NEOPLASTIC OBSTRUCTION Inflammatory (Filariasis - A parasitic infection affecting inguinal lymphatics resulting in elephantiasis
Picture of Elephantiasis
Neoplastic
Resection and/or radiation to auxiliary lymphatic can lead to arm edema Carcinoma of breast with obstruction of superficial lymphatic can lead to an unusual appearance of the breast - peau dorange (orange peel)
Edema Morphology
Edema of the Subcutaneous Tissue is most easily detected Grossly (not microscopically) Push your finger into it and a depression remains
Edema Morphology
Dependent Edema is a prominent feature of Congestive Heart Failure Facial edema is often the initial manifestation of Nephrotic Syndrome
The Lungs are typically 2-3 times normal weight Cross sectioning causes an outpouring of frothy, sometimes blood-tinged fluid
Normal
Pulmonary Edema
Edema of the Brain : Trauma, Abscess, Neoplasm, Infection (Encephalitis), etc. The big problem is: There is no place for the fluid to go!!! The skull is the limit. Herniation into the foramen ovale will kill Subcutaneous Edema : Annoying but Points to Underlying Disease
However, it can impair wound healing or clearance of Infection.
Pulmonary Edema : May cause death by interfering with Oxygen and Carbon Dioxide exchange Creates a favorable environment for infection
Culture Media
Hyperemia
Hemorrhage
extravasation of blood due to rupture of blood vessels
Rupture of a large vessel: Trauma, Atherosclerosis, Inflammatory or Neoplastic Erosion Rupture of small vessels: hemorrhagic diathesis.
May be external, into a body cavity or into a tissue hematoma: accumulation of blood enclosed or confined within tissue petechiae: minute hemorrhages into skin or lining surface
Hemorrhage
Purpura (slightly larger hemorrhages than petechia) Ecchymoses (over 1-2 cm subcutaneous hematoma aka bruise). Accumulation of blood in a body cavity:
Hemothorax Hemopericardium Hemoperitoneum Hemarthrosis
hemoglobin (red) bilirubin (blue-green) hemosiderin (golden-brown) Thats why bruises change color as they resolve
Hemostasis
Normal - blood is flowing and not clotting Injury - blood is clotting and not flowing This works due to a daily interaction between the vascular wall, platelets and the coagulation cascade
Thrombosis
Abnormal activation of the normal hemostatic process Thrombosis is Pathologic
Hemostasis
after initial injury, there is a brief period of arteriolar vasoconstriction (neurogenic reflex augmented by local factors such as endothelin)
Vasoconstriction
A transient effect
Hemostasis
Endothelial injury exposes the blood to the extracellular matrix (ECM)
The ECM is highly thrombogenic Platelets adhere, flatten and then activate To form hemostatic plug (primary hemostasis)
summary
Flatten Adhere Activate Recruit
Hemostatic
Plug
Secondary Hemostasis
Tissue factor together with platelet factors activate the coagulation cascade with fibrin deposition. Thrombin activation induces further platelet recruitment and granule release (secondary hemostasis)
Secondary Hemostasis
Polymerized fibrin and platelet aggregates to form permanent plug
Anti-thrombotic Regulation
Endothelium
Anti-thrombotic and Procoagulant Properties
Anti-thrombotic - Anti-platelet, anti-coagulant and fibrinolytic effects Procoagulant - Tissue Factor, vWF attachment
Endothelial production of prostacyclin and nitric oxide inhibits platelet adhesion to normal endothelium
Pro-thrombotic Properties
- Normal endothelium produces : von Willebrand factor (vWF) facilitates adhesion of platelets to ECM - Tissue Factor secretion by endothelium is induced by cytokines or bacterial endotoxin
Tissue Factor activates the extrinsic clotting pathway.
- Endothelial cells secrete plasminogen activator inhibitors (PAIs) which depress fibrinolysis thus promoting thrombosis
Platelets
When circulating are (membrane-bound smooth discs) They contain two specific types of granules: alpha granules and delta granules. 1- Alpha: contain fibrinogen, fibronectin, factors V and VIII, platelet factor 4, platelet-derived growth factor (PDGF), and transforming growth factor (TGF- ) . 2- Delata: contain adenine nucleotides (ADP and ATP), ionized calcium, histamine, serotonin and epinephrine
Platelet Activation
On contact with ECM, platelets undergo:
(1) (2) (3) Adhesion and shape change Secretion (release reaction) Aggregation
Platelet Adhesion
Adhesion to ECM is mediated largely via interactions with vWF which acts as a bridge between platelet surface receptors and exposed collagen.
Platelet Secretion
Both granules Explode soon after adhesion Calcium and ADP: potent mediators of coagulation and platelet aggregation
Platelet Aggregation
ADP and thromboxane A2 (TXA2) stimulate further platelet adhesion This sets up an autocatalytic reaction leading to an enlarging platelet mass(the primary hemostatic plug) This is a reversible collection of platelets
Platelet Aggregation
With activation of the coagulation cascade, thrombin is generated, causing further aggregation then platelet contraction constituting the secondary hemostatic plug This is an irreversible fusion of platelets
TXA2 (platelets)
vasoconstriction Stimulates platelet aggregation
Activates
Thrombin
Fibrinogen
Fibrin
Coagulation Cascade
Conversion of Pro-Factors to Activated Factors , ending in the formation of Thrombin, Thrombin converts Fibrinogen to Fibrin, Fibrin is critical for hemostasis. Each reaction is the result of the assembly of:
Enzyme (activated) coagulation factor Substrate (pro-enzyme form of a coagulation factor) Co-Factor (reaction accelerator).
Thrombosis
Pathogenesis Of Thrombosis
Virchows triad
endothelial injury stasis or turbulence of blood flow blood hypercoagulability
Endothelial Injury
exposure of subendothelial collagen and other platelet activators adherence of platelets release of tissue factor local depletion of postacyclin (prostaglandin) and plasminogen activator (PA)
Retard the inflow of clotting factor inhibitors and permit thrombi build-up Promote endothelial cell activation Aneurysms, mitral valve stenosis, hyperviscosity syndromes (e.g. polycythemia)
HYPERCOAGULABILITY
any alterations of the coagulation pathways that predispose to thrombosis primary (genetic) or secondary (acquired) disorders
HYPERCOAGULABILITY (contd)
mutation of factor V gene with functional deficiency of protein C, and other anticoagulants (protein S, antithrombin III). Patient will have venous thrombosis and recurrent thromboembolism smoking, obesity, lupus anticoagulant with lupus erythematosis (arterial and venous thrombosis)
ARTERIAL THROMBI
usually begin at site of endothelial injury and grow in a retrograde direction from point of attachment typically are firmly adherent to the injured arterial wall (atherosclerotic plaque) and are gray-white and friable (mesh of platelets, fibrins, RBC, and leukocytes)
Arterial thrombi
Usually begin at site of endothelial injury and grow along flow of blood Typically are firmly adherent to the injured arterial wall (atherosclerotic plaque)
Morphology of Thrombi
Arterial Thrombi Are Usually Occlusive Venous Thrombi Are Almost Always Occlusive
85-90% of Venous Thrombi Form in Lower Extremities
Walkers Law :-)
Superficial venous thrombi, usually occur in saphenous system, may cause local congestion, swelling, and pain; rarely embolize Deep thrombi, usually in large leg veins at or above knee joint (e.g. popliteal, femoral, and iliac veins); cause edema of foot and ankle; may embolize
Characteristically occur at site of stasis and extend in the direction of blood flow (towards heart); contains more enmeshed erythrocytes (red)
Thrombi in Deep Veins (Femoral, Iliac) More Likely to show emobolization About 50% Are Asymptomatic (Formation of Collaterals) May Produce Edema, Pain and Tenderness
Valvular Thrombi
Infective Endocarditis Non-bacterial Thrombotic Endocarditis Verrucous Endocarditis (Libman-sacks)
Lupus Related
FATE OF THROMBOSIS
Propagation and obstruction Embolization Dissolution Organization and recanalization
Dissolution of Thrombi
Recent Thrombi Can Undergo Total Lysis After the First 2-3 h, Thrombi wont undergo Lysis
Thus the Use of TPa Is Only Effective in the First 13 Hours
Organization/Recanalization
Granulation Tissue Followed by Capillary Channel Formation or may heal so totally As to Leave Only a Small Fibrous Lump As Evidence of a Previous Thrombus
EMBOLISM
An embolus is a detached intravascular solid, liquid or gaseous mass that is carried by the blood to a site distant from its point of origin 99% are dislodged thrombus potential consequence: ischemic necrosis (infarction)
PULMONARY THROMBOEMBOLISM
Generally originates from deep leg veins Usually pass through the right heart into pulmonary vasculature and may occlude main pulmonary artery, across the bifurcation (saddle embolus) or pass into the smaller, branching arterioles; multiple emboli may occur
Paradoxical Embolism
An embolus pass through an interarterial or intraventricular defect to gain access to the systemic circulation( from vein to artery) Most pulmonary emboli (60-80%) are clinically silent because of small size
PULMONARY THROMBOEMBOLISM
When 60% or more of the pulmonary circulation is obstructed, sudden death may occur as caused by right heart failure . Embolic obstruction of medium-sized arteries may result in hemorrhage without infarction because of intact bronchial circulation (unless bronchial circulation is compromised - left heart failure). multiple pulmonary emboli over time may cause pulmonary hypertension and right heart failure
SYSTEMIC THROMBOEMBOLISM
emboli traveling within the arterial circulation 80% arise from intracardiac mural thrombi, others from ulcerated atherosclerotic plaques, aortic aneurysm, or from fragmentation of valvular vegetation major sites are lower extremities (75%), brain (10%), intestines and kidneys
AIR EMBOLISM
gas bubbles within the circulation can obstruct vascular flow to cause distal ischemic injury
air may enter circulation in chest wall injury or in individuals exposed to sudden atmospheric pressure changes (decompression sickness)
Embolism
Potential Consequences
Ischemic Necrosis (Infarction) Though Pulmonary Emboli Are Common and Important, Secondary Pulmonary Infarction Is Not Common Lung Is Protected by a Dual Blood Supply The Brain Is Not So Protected and Gets Infarcts (Stroke) LIQUEFACTIVE NECROSIS
INFARCTION
An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or venous drainage in a particular tissue
nearly 90% of all infarcts result from thrombotic or embolic events in arterial vasculatures
Venous infarcts are more likely in organs with a single venous outflow channel (testis, ovary) All infarcts tend to be wedge-shaped, with the occluded vessel at the apex
RED INFARCTS
Occur:
with venous occlusions (e.g. ovarian torsion) in loose (spongy) tissues (e.g. lung) that allow blood to collect in the infarcted zone in tissues with dual circulations (e.g. lung and small intestines) in tissues that were previously congested when the occluded site is re-perfused
SHOCK
Constitutes systemic hypoperfusion due to reduction either in cardiac output or in the effective circulating blood volume. The end results are hypotension, followed by impaired tissue perfusion and cellular hypoxia Three main categories: cardiogenic, hypovolemic, and septic Others: neurogenic shock and anaphylactic shock
CARDIOGENIC SHOCK
Results from myocardial failure (infarction), ventricular arrhythmia, extrinsic compression [cardiac tamponade, or outflow obstruction pulmonary embolism)]
HYPOVOLEMIC SHOCK
Results from loss of blood or plasma volume (hemorrhage, fluid loss from severe burns or trauma)
SEPTIC SHOCK
Caused by systemic microbial infection, most often by gram-negative infection (endotoxic shock) but can also occur with gram-positive and fungal infections
ANAPHYLATIC SHOCK
IgE mediated hypersensitivity response associated with systemic vasodilatation and increased vascular permeability
NEUROGENIC SHOCK
Occur in esthetic accident or spinal cord injury with loss of vascular tone and peripheral pool of blood
STAGES OF SHOCK
1- Initial non-progressive stage: compensatory reflex, perfusion of vital organs maintained 2- Progressive stage: characterized by tissue hypoperfusion and onset of circulatory and metabolic imbalance 3- Irreversible stage: tissue and organ damage