Pathology Hemodynamic Disorders PDF

PATHOLOGY 08/20/2024. MOD 1: HEMODYNAMIC DISORDERS 1 Dr. Renan...

PATHOLOGY 08/20/2024. MOD 1: HEMODYNAMIC DISORDERS 1 Dr. Renan B. Navarro Trans Group/s: __ I. EDEMA AND EFFUSIONS severe nutritional disorders. EDEMA EFFUSION Inflammatory edema fluid/effusion is an EXUDATE, Accumulation of abnormal Accumulation of fluid in while the Non-inflammatory edema fluid/effusion is a amounts of fluid in the the body cavities TRANSUDATE. tissues B. DIFFERENCES BETWEEN TRANSUDATE AND Under normal conditions, there is a balance between the EXUDATE tendency of vascular hydrostatic pressure to push water and salts out of the capillaries into the interstitial TRANSUDATE EXUDATE space and the tendency of the plasma colloid osmotic pressure to pull water and salts back into the vessels. Specific Small net movement of the fluid into the interstitium < 1.012 > 1.020 Gravity drains into the lymphatic vessels and returns to the bloodstream via thoracic duct. Protein Low; < 3.0 g/dl High; >/= 3.0 g/dl Conc. Cellularity Low High Non-inflammatory Mechanism Inflammatory (Hemodynamic) Pleural effusion in Pleural effusion in Example CHF pneumonia II. PATHOPHYSIOLOGIC CATEGORIES OF HEMODYNAMIC EDEMA A. INCREASED HYDROSTATIC PRESSURE Increases in hydrostatic pressure is a result of focal impairment in the venous return as seen in deep Factors affecting fluid balance across capillary wall. venous thrombosis of the leg, causing localized edema. Likewise, when the increase in the hydrostatic pressure Either increased capillary pressure or diminished is generalized, this may result in a systemic or colloid osmotic pressure can result in increased generalized edema as seen in congestive heart failure. interstitial fluid. Examples: If the movement of water into tissues (edema) or the ○ Congestive heart failure body cavities (effusions) exceeds lymphatic drainage, ○ Constrictive pericarditis fluid accumulates. ○ Ascites ○ Venous obstruction or compression A. TYPES OF EDEMA B. REDUCED PLASMA OSMOTIC PRESSURE INFLAMMATORY EDEMA NON-INFLAMMATORY Conditions leading to inadequate synthesis or OR EFFUSIONS EDEMA OR EFFUSIONS increased loss of albumin from the circulation caused by reduced plasma osmotic pressure. Protein-rich fluids are called Protein-poor fluids are The major plasma protein is the albumin. exudates. called transudates. ○ Reduced albumin may be caused by: Inadequate synthesis as seen in liver Due to increase in vascular Due to hemodynamic problems permeability caused by alterations. May be lost due to a protein loss in inflammatory mediators. glomerulopathies like nephrotic syndrome where the glomerulus becomes leaky. Examples: They are common in many ○ Protein losing glomerulopathies diseases including heart ○ Liver cirrhosis failure, liver failure, renal ○ Malnutrition disease, and even among ○ Protein-losing gastroenteropathy Pathology - Mod 1 Hemodynamic Disorders 1 1 of 16 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited. C. SODIUM AND WATER RETENTION 1. EXCESS SALT INTAKE WITH REDUCED ANAL FUNCTION (RENAL INSUFFICIENCY) Increased salt retention with obligate retention of associated water causes both: ○ Increased hydrostatic pressure due to intravascular fluid volume expansion. ○ Diminished vascular colloid osmotic pressure due to dilution. Sodium and water retention is common among conditions that cause renal hypoperfusion like CHF or heart failure. 2. INCREASED TUBULAR REABSORPTION OF SODIUM Bipedal Edema (in CHF). 2.1 Reduced Renal Perfusion In heart failure, there is an inadequate cardiac output B. PERIORBITAL EDEMA: FACE AND PERIORBITAL and therefore, causes renal hypoperfusion. EDEMA (IN RENAL DISEASE) This situation activates the renin-angiotensin-aldosterone axis. 2.2 Increased Renin-Angiotensin-Aldosterone Secretion (RAAS) Such activation causes salt and water retention, increased vascular tone, and elevated levels of antidiuretic hormone or ADH. In effect, cardiac output is improved and normal renal perfusion is restored. ○ However, this pathway or mechanism is beneficial only in the early stage of CHF because later on, as the heart failure worsens and the cardiac output diminishes, the retained fluid nearly increases the hydrostatic pressure, leading to edema and effusions. D. LYMPHATIC OBSTRUCTION Disruption of lymphatic vessels and impairment of the Black arrows pointing toward the edema in the periorbital clearance of the interstitial fluid can result in areas on the face of a patient with renal disease. lymphedema in affected body parts. Trauma, fibrosis, invasive tumors, and infectious C. SUBCUTANEOUS EDEMA: PITTING EDEMA agents can all disrupt lymphatic vessels and impair the When the skin and underlying soft tissues of a leg with clearance of interstitial fluid edema are compressed with fingers, the impressions Examples: remain. ○ Inflammatory disease — Filariasis Most commonly associated with heart failure, usually a ○ Post-mastectomy left-sided heart one. ○ Edema of upper extremity may occur among breast cancer patients after axillary lymph node removal and irradiation. E. INFLAMMATION It is always accompanied with resultant edema. Examples: ○ Acute inflammation ○ Chronic inflammation ○ Angiogenesis III. MORPHOLOGY A. SUBCUTANEOUS EDEMA: BIPEDAL EDEMA (IN CHF) It can be diffused or more conspicuous in regions with high hydrostatic pressures. This is often influenced by gravity, hence, dependent Pitting Edema. edema. Tissue involved becomes loosened. D. FILARIASIS It can be seen among cases of congestive heart Marked edema of the lower extremities due to failure. lymphatic obstruction caused by the filarial worm. ○ Hence, the disease is called filariasis or elephantiasis. Pathology - Mod 1 Hemodynamic Disorders 2 of 16 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Filariasis. E. ANASARCA Microscopically, the alveolar walls are congested (arrow A) Edema can be generalized such that the entire body is and the alveolar spaces are filled with pink fluid (arrow B). A edematous. few alveolar macrophages (arrow C) are present, but there ○ This type of edema is called anasarca. is NO significant inflammation. This is a condition called hydrops fetalis. ○ The baby developed generalized edema, wherein G. CEREBRAL (BRAIN) EDEMA almost all regions of the body are edematous. It can be localized or generalized depending on the ○ Hydrops fetalis is due to a severe red blood cell nature and extent of the pathological process or injury. rhesus incompatibility. Narrow sulci and gyri are distended. Microscopically, there are loosened parenchyma, swelling of glial cells and neurons, and widened Virchow-Robin space. Anasarca. F. PULMONARY EDEMA The lungs are often 2 to 3 times heavier than normal weight. The lungs are baggy and cut sections will show frothy sanguineous fluid. Brain Edema. H. HYDROTHORAX Effusion involving the pleural cavity. Pulmonary Edema. Hydrothorax. I. HYDROPERICARDIUM Effusion involving the pericardial cavity Yellow arrow: opened pericardial sac, exposing the fluid contained within the pericardial cavity. Pathology - Mod 1 Hemodynamic Disorders 3 of 16 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  hypertension), Chronic Passive Congestion (CPC) of the lungs A. HYPEREMIA (ACTIVE HYPEREMIA) Due to arterial and arteriolar dilatation with increased capillary blood flow. B. CONGESTION (PASSIVE HYPEREMIA) 1. CHRONIC PASSIVE CONGESTION, LUNG CHRONIC PASSIVE CONGESTION, LUNG Hydropericardium. The lung is heavy, and baggy. Cut sections: Surface is reddish-blue J. ASCITES or HYDROPERITONEUM Gross due to high levels of deoxygenated Effusion involving the peritoneal cavity. blood Massive collection of fluid within the peritoneal cavity. ○ This is common among ovarian malignancy. Chronically congested tissue, with presence of hemosiderin laden Microscopic macrophages (heart failure cells) ally These are macrophages that have engulfed intravascular red blood cells, or hemorrhages. Ascites. IV. HYPEREMIA AND CONGESTION Both stem from locally increased blood volumes in Chronic Passive Congestion, Lung. affected tissues but have different mechanisms. HYPEREMIA CONGESTION Sympathetic Due to impaired neurogenic or venous outflow release of resulting in an Mechanism vasoactive increased volume substances leading and pressure, thus to engorgement of consequently blood vessels. leading to edema. Blue-red (deoxygenated blood) due to red Bright red Color cells stasis, and (oxygenated blood) accumulation of deoxygenated blood Chronic Passive Congestion, Lung under the microscope. Muscular exercise, Congestive heart Examples febrile state, early failure, cirrhosis 2. CHRONIC PASSIVE CONGESTION, LIVER acute inflammation (portal Pathology - Mod 1 Hemodynamic Disorders 4 of 16 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  ○ Thrombosis CHRONIC PASSIVE CONGESTION, B. HEMORRHAGIC DISORDERS LIVER Characterized by excessive bleeding, where hemostatic mechanisms are either blunted, or The liver appears in reddish-brown, insufficient to prevent abnormal blood loss. slightly depressed centrilobular regions, that are accentuated against the zones of the C. THROMBOSIS Gross Pathologic counterpart of hemostasis which involves uncongested liver. Compared to a cut surface of a blood clot formation within the intact blood vessels. nutmeg (upper left of image above), hence the term “nutmeg liver” VI. SEQUENCE OF EVENTS LEADING TO HEMOSTASIS Centrilobular congestion, and A. ARTERIOLAR VASOCONSTRICTION hemorrhage, with the presence of Occurs immediately in markedly reduced blood flow hemosiderin laden macrophages. to the site of injury. Since the centrilobular area is at the It is mediated by a reflex neurogenic mechanism. Microscopic distal end of the blood supply to the Augment by endothelin which is a potent ally liver, it is prone to undergo endothelium-derived vasoconstrictor hemorrhage, and necrosis, whenever the blood supply is compromised. Vasoconstriction. B. PRIMARY HEMOSTASIS A platelet plug is formed. Destruction of endothelium exposes subendothelial Von Willebrand Factor (vWF), and collagen. Platelet surface receptor, Glycoprotein 1b interacts Chronic Passive Congestion, Liver. with vWF in the subendothelial matrix. ○ This then promotes platelet adherence and activation. Platelets undergo aggregation to form a primary hemostatic plug. During the formation of this plug, adenosine diphosphate (ADP) and thromboxane A2 (Tx A2) are released, inducing more platelet aggregation through platelet GP2B3A receptors, and binding to fibrinogen. 1. BLEEDING DISORDERS Genetic deficiency of: ○ vWF → Von Willebrand Disease ○ GP1B → Bernard-Soulier Syndrome. Chronic Passive Congestion, Liver under the microscope. V. HEMOSTASIS, HEMORRHAGIC DISORDERS, AND THROMBOSIS A. HEMOSTASIS A consequence of tightly regulated processes that maintain blood in a fluid state in normal vessels. A process by which blood clots form at sites of vascular Primary Hemostasis. injury that is essential for life. Derangement in Hemostasis can be divided into two: ○ Hemorrhagic Disorders C. SECONDARY HEMOSTASIS Deposition of fibrin occurs. Pathology - Mod 1 Hemodynamic Disorders 5 of 16 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Tissue factor is exposed to the site of injury. 1. ANTI-PLATELET Tissue factor binds, and activates factor VII, which Prostacyclin (PGI2), Nitric Oxide (NO) are potent triggers a cascade of reactions that culminates vasodilators, preventing platelet adhesion on the site of thrombin generation. vascular injury. Thrombin then cleaves circulating fibrinogen into Adenosine diphosphatase degrades the ADP, thus insoluble fibrin, creating a fibrin meshwork. inhibiting platelet aggregation. ○ It is in this space where consolidation of initial platelet plug occurs. 2. ANTI-COAGULANT Heparin-like molecule, Thrombomodulin, and Tissue Factor Pathway Inhibitor aid in the activation of several coagulation factors. 3. FIBRINOLYTIC Endothelial cells themselves synthesize tissue type plasminogen activator (TPA), which cleaves plasminogen to form plasmin. Plasmin then cleaves fibrin to degrade the thrombi. B. PLATELETS After vascular injury, platelets are exposed to extracellular matrix (ECM) proteins, especially collagen Secondary Hemostasis. and von Willebrand factor. This induces adhesion and shape change, especially the D. THROMBUS AND ANTITHROMBOTIC EFFECTS platelet surface, GpIIb-IIIa. Clot stabilization and resorption. As platelets change in shape, secretion of Ca2+, Where polymerized fibrin, and platelet aggregates adenosine diphosphate and thromboxane-A2 also undergo contraction to form a solid and permanent happens. plug that prevents further hemorrhage. These events lead to platelet activation, inducing more platelet aggregation and this is made possible by the binding of fibrinogen between platelets that have undergone shape change. Thrombus and Antithrombotic Events. VII. FACTORS INVOLVED IN HEMOSTASIS Works tightly close together so that hemostasis is achieved. A. ENDOTHELIUM/VASCULAR WALL Endothelium has anti-thrombotic properties: ○ Anti-platelet ○ Anti-coagulant ○ Fibrinolytic Platelet. 1. GLANZMANN THROMBASTHENIA Bleeding disorder that is a result from the deficiency of GpIIb/IIIa C. COAGULATION CASCADE Involves a series of enzymatic conversions of inactive proenzymes to active enzymes, thus, culminating in the formation of thrombin. 1. THROMBIN Most important coagulation factor in the coagulation cascade. Converts the soluble plasma protein fibrinogen into Endothelium / Vascular Wall. fibrin monomers that polymerize into an insoluble fibrous protein fibrin (insoluble gel). Pathology - Mod 1 Hemodynamic Disorders 6 of 16 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  2. DEFECTS IN SECONDARY HEMOSTASIS Coagulation factor defects Often present with bleeds into soft tissues or joints 2.1 HEMARTHROSIS Bleeding into joints Hemarthrosis. 3. GENERALIZED DEFECTS INVOLVING SMALL VESSELS Often present with hematoma and ecchymoses GENERALIZED DEFECTS INVOLVING SMALL VESSELS ECCHYMOSES HEMATOMA Coagulation Cascade. Also known as bruises Palpable mass of VIII. HEMORRHAGIC DISORDERS extravasated blood Disorders associated with abnormal bleeding inevitably stem from primary or secondary defects in vessel walls, Present with hemorrhages platelets or coagulation factors – all of which must of 1-2 cm in size function properly to ensure hemostasis. A. GENERAL PRINCIPLES RELATED TO ABNORMAL BLEEDING AND ITS CONSEQUENCES 1. DEFECTS OF PRIMARY HEMOSTASIS Platelet defects or von Willebrand disease Affects the platelets or the von Willebrand factor Lesion presents with small bleeds in skin or mucosal membranes Hemorrhages presents usually as petechiae or purpura DEFECTS OF PRIMARY HEMOSTASIS Ecchymoses (L), Hematoma (R). PETECHIAE PURPURA B. HEMOTHORAX Hemorrhage can also take in the form of blood Minute hemorrhage (1-2 Slightly larger (≥ 3mm) accumulation in large spaces or cavities such as mm) than petechiae hemothorax (blood accumulation in the pleural cavity) Hemothorax (Blood accumulation in the pleural cavity) is Petechiae (L), Purpura (R). pointed by the yellow arrow. Pathology - Mod 1 Hemodynamic Disorders 7 of 16 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited. C. HEMOPERICARDIUM 2. IRON DEFICIENCY ANEMIA (IDA) Hemorrhage accumulate in the pericardial cavity Chronic or recurrent external blood loss may cause Seen in cases of cardiac tamponade iron loss and may lead to iron deficiency anemia. E.g., peptic ulcer, menstrual bleeding 3. HERNIATION Internal bleeding may cause death if it is located in the brain ○ The skull is unyielding and intracranial hemorrhage may increase intracranial pressure → brainstem herniation → compromised cardiorespiratory center. E.g., cerebrovascular accident (stroke) Hemopericardium. D. HEMOPERITONEUM Blood accumulates in the peritoneal cavity Such as in the case of a ruptured ectopic pregnancy in the fallopian tube Intracerebral hemorrhage is fatal when left untreated. IX. THROMBOSIS Pathological counterpart of hemostasis Involves blood clot formation within intact blood vessels 1. VIRCHOW TRIAD Hemoperitoneum. Summarizes the pathogenesis of thrombosis 3 primary factors of abnormalities that lead to the SUMMARY OF HEMORRHAGES ACCORDING TO BODY pathogenesis of thrombosis: CAVITY AFFECTED 1. Endothelial injury 2. Abnormal blood flow (turbulence or stasis) HEMOTHORAX HEMOPERICARD HEMOPERITON 3. Hypercoagulability IUM EUM Blood Blood Blood accumulation in the accumulation in accumulation in pleural cavity pericardial cavity peritoneal cavity E.g., cardiac E.g., ruptured tamponade ectopic pregnancy E. CLINICAL CORRELATION 3 FACTORS THAT DETERMINE THE SIGNIFICANCE OF ANY TYPE OF HEMORRHAGE 1 Amount of blood loss Virchow Triad. 2 Rate of blood loss (sudden or slow) A. ENDOTHELIAL INJURY 3 Site of hemorrhage (brain, pericardial, external) Single most important factor of Virchow triad Injury to endothelial cells can affect the local blood flow Rapid loss of up to 20% of blood volume may have lethal and coagulability effects on healthy adults. Triggers thrombosis by exposing vWF and tissue factor Inflammation and noxious stimuli can cause 1. HEMORRHAGIC OR HYPOVOLEMIC SHOCK endothelial activation or dysfunction by shifting the May be caused by greater losses of blood volume pattern of gene expression in endothelium to one that is E.g., laceration of large caliber blood vessel, “prothrombotic”. ruptured ectopic pregnancy B. ALTERATIONS IN NORMAL BLOOD FLOW Recall: Normal blood flow is laminar. Pathology - Mod 1 Hemodynamic Disorders 8 of 16 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Turbulence in the blood flow contributes to arterial and ○ Pregnancy complications such as recurrent cardiac thrombosis by causing endothelial injury or miscarriages, unexplained fetal death and dysfunction, as well as by forming counter currents premature birth that contribute to local pockets of stasis. Abnormal blood flow causes thrombosis by: ○ Disrupting the laminar flow and bringing PRIMARY APS SECONDARY APS platelets in contact with the endothelium. ○ Preventing dilution and clearance of Exhibit only Individuals with a coagulation factors by blood flow. manifestations of a well-defined ○ Retarding inhibitors of clotting factors and hypercoagulable autoimmune disease, permit build-up of thrombi. state such as systemic ○ Promoting endothelial cell activation, Lack of evidence of lupus erythematosus predisposing to local thrombosis and leukocyte other well-defined adhesion. autoimmune disorders Stasis: major contributor in the development of venous thrombi Clinical manifestations: C. HYPERCOAGULABILITY OF BLOOD ○ Recurrent thromboses Also called thrombophilia ○ Repeated miscarriages Refers to an abnormally high tendency of the blood ○ Cardiac valve vegetations to clot ○ Thrombocytopenia Typically caused by alterations in coagulation factors. ○ Pulmonary embolism Can be divided into ○ Pulmonary hypertension ○ Primary (genetic) disorders ○ Stroke ○ Secondary (acquired) disorders ○ Bowel infarction ○ Renovascular hypertension Inherited hypercoagulability must be considered in HYPERCOAGULABILITY STATE patients