SHOCK LECTURE OUTLINE I. Hyperemia and Congestion. II. Edema. III. Hemorrhage. IV. Hemostasis and Thrombosis. V. Embolism. VI. Infarction. VII. Shock.
2 BODY FLUID COMPARTMENTS Fluid distribution in a 70 kg man. • The human body consists of 60% water. • The total body water (TBW) is separated into intracellular water (ICW, 66%) and extracellular water (ECW, 33%). • The ECW consists of the intravascular fluid (IVF, 25%) and extravascular fluid (EVF, 75%), mainly interstitial fluid INTRODUCTION • The health of cells and tissues depends on the circulation of blood, which delivers oxygen and nutrients and removes wastes generated by cellular metabolism. • Under normal conditions, as blood passes through capillary beds, proteins in the plasma are retained within the vasculature and there is little net movement of water and electrolytes into the tissues. • This balance is often disturbed by pathologic conditions that alter endothelial function, ↑ vascular pressure, or ↓ plasma protein content, all of which promote edema—accumulation of fluid resulting from a net outward movement of water into extravascular spaces. 4 INTRODUCTION • Depending on its severity and location, edema may have minimal or profound effects. In the lower extremities, it may only make one’s shoes feel snugger after a long sedentary day; in the lungs, however, edema fluid can fill alveoli, causing life-threatening hypoxia.
• Blood vessels are frequently subject to trauma of varying
degrees. Hemostasis is the process of blood clotting that prevents excessive bleeding after blood vessel damage. INTRODUCTION • Inadequate hemostasis may result in hemorrhage, which can compromise regional tissue perfusion and, if massive and rapid, may lead to hypotension, shock, and death.
• Conversely, inappropriate clotting (thrombosis) or
migration of clots (embolism) can obstruct blood vessels, potentially causing ischemic cell death (infarction). •Indeed, thromboembolism lies at the heart of three major causes of morbidity and death in developed countries: myocardial infarction, pulmonary embolism (PE), and cerebrovascular accident (stroke). LECTURE OUTLINE I. Hyperemia and Congestion. II. Edema. III. Hemorrhage. IV. Hemostasis and Thrombosis. V. Embolism. VI. Infarction. VII. Shock.
7 HYPEREMIA AND CONGESTION • Hyperemia and congestion both refer to an increase in blood volume within a tissue but they have different underlying mechanisms.
• Hyperemia is an active process resulting from arteriolar dilation
and increase blood inflow, as occurs at sites of inflammation or in exercising skeletal muscle.
• Hyperemic tissues are redder than normal because of engorgement
with oxygenated blood. 8 HYPEREMIA AND CONGESTION Ø Congestion is a passive process resulting from impaired outflow of venous blood from a tissue. It can occur systemically, as in cardiac failure, or locally as a consequence of an isolated venous obstruction. Ø Congested tissues have an abnormal blue-red color (cyanosis) that stems from the accumulation of deoxygenated hemoglobin in the affected area. Ø In long-standing chronic congestion, inadequate tissue perfusion and persistent hypoxia may lead to parenchymal cell death and secondary tissue fibrosis, and the elevated intravascular pressures may cause edema or sometimes rupture capillaries, producing focal hemorrhages. MORPHOLOGIC FEATURES Grossly: Cut surfaces of hyperemic or congested tissues feel wet and typicaly ooze blood. On microscope: § Acute pulmonary congestion: marked by blood-engorged alveolar capillaries and variable degrees of alveolar septal edema and intraalveolar hemorrhage. § Chronic pulmonary congestion: the septa become thickened and fibrotic, and the alveolar spaces contain numerous macrophages laden with hemosiderin. § Acute hepatic congestion: the central vein and sinusoid distended with blood, and there may even be necrosis of hepatocytes. § Chronic passive congestion of the liver: the central regions of the hepatic lobules are red-brown and slightly depressed. Figure 3–1 Liver with chronic passive congestion and hemorrhagic necrosis. A, In this autopsy specimen, central areas are red and slightly depressed compared with the surrounding tan viable parenchyma, creating “nutmeg liver” (so called because it resembles the cut surface of a nutmeg). B, Microscopic preparation shows centri-lobular hepatic necrosis with hemorrhage and scattered inflammatory cells.
11 LECTURE OUTLINE I. Hyperemia and Congestion. II. Edema. III. Hemorrhage. IV. Hemostasis and Thrombosis. V. Embolism. VI. Infarction. VII. Shock.
12 EDEMA • Edema is an accumulation of interstitial fluid within tissues. • Extravascular fluid can also collect in body cavities and such accumulations are often referred to collectively as effusions. • Such as the pleural cavity (hydrothorax), the pericardial cavity (hydropericardium), or the peritoneal cavity (hydroperitoneum, or ascites). • Anasarca is severe, generalized edema marked by profound swelling of subcutaneous tissues and accumulation of fluid in body cavities. 13 Pathophysiologic Causes of Edema
14 EDEMA Ø Fluid movement between the vascular and interstitial spaces is governed mainly by two opposing forces—the vascular hydrostatic pressure and the colloid osmotic pressure produced by plasma proteins.
Ø Normally, the outflow of fluid produced by hydrostatic pressure at
the arteriolar end of the microcirculation is nearly balanced by inflow due to the slightly elevated osmotic pressure at the venular end; hence there is only a small net outflow of fluid into the interstitial space, which is drained by lymphatic vessels. EDEMA • Either increased hydrostatic pressure or diminished colloid osmotic pressure causes increased movement of water into the interstitium.
• This in turn increased the tissue hydrostatic pressure, and
eventually a new equilibrium is achieved.
• Excess edema fluid is removed by lymphatic drainage and
returned to the bloodstream by way of the thoracic duct. Figure 3–2 Factors influencing fluid movement across capillary walls. Capillary hydrostatic and osmotic forces are normally balanced so there is little net movement of fluid into the interstitium. However, ↑ hydrostatic pressure or diminished plasma osmotic pressure leads to extravascular fluid accumulation (edema). Tissue lymphatics drain much of the excess fluid back to the circulation by way of the thoracic duct; however, if the capacity for lymphatic drainage is exceeded, tissue edema results. 17 EDEMA ØThe edema fluid that accumulates owing to increased hydrostatic pressure or reduced intravascular colloid typically is a protein- poor transudate; it has a specific gravity less than 1.012.
ØBy contrast, because of increased vascular permeability,
inflammatory edema fluid is a protein-rich exudate with a specific gravity usually greater than 1.020 VARIOUS CAUSES OF EDEMA. 1. Increased Hydrostatic Pressure. 2. Reduced Plasma Osmotic Pressure. 3. Lymphatic Obstruction. 4. Sodium and Water Retention. 5. Inflammation.
19 CAUSES OF EDEMA: INCREASED HYDROSTATIC PRESSURE. ØIncreases in hydrostatic pressure are mainly caused by disorders that impair venous return. Ø Local increases in intravascular pressure caused, for example, by deep venous thrombosis in the lower extremity can cause edema restricted to the distal portion of the affected leg. ØGeneralized increases in venous pressure, with resultant systemic edema, occur most commonly in congestive heart failure and liver failure (leading to ascites). Ø Several factors ↑ venous hydrostatic pressure in patients with congestive heart failure. The ↓ cardiac output leads to systemic venous congestion and resultant increase in capillary hydrostatic pressure. At the same point, this reduced in cardiac output results in hypo-perfusion of the kidneys, triggering the renin- angiotensin-aldosterone axis and inducing sodium and water retention (secondary hyperaldosteronism). 20 Figure 3–3 Pathways leading to systemic edema due to heart failure, renal failure, or reduced plasma osmotic pressure.
21 CAUSES OF EDEMA: INCREASED HYDROSTATIC PRESSURE. ØUnless cardiac output is restored or renal water retension is reduced (e.g., by salt restriction or treatment with diuretics or aldosterone antagonist), this downward spinal continues.
ØBecause secondary hypoaldosteronism is a common feature of generalized
edema, salt restriction, diuretics and aldosterone antagonists also are of value in the management of generalizad edema resulting from non- cardiac causes. CAUSES OF EDEMA: REDUCED PLASMA OSMOTIC PRESSURE. Ø Under normal circumstances albumin accounts for almost half of the total plasma protein. Therefore conditions in which albumin is either lost from the circulation or synthesized in inadequate amounts are common causes of reduced plasma osmotic pressure.
Ø In nephrotic syndrome, damaged glomerular capillaries become leaky, leading to
the loss of albumin (and other plasma proteins) in the urine and the development of generalized edema. o Nephrotic syndrome, is the most important cause of albumen loss from the blood.
Ø Reduced albumin synthesis occurs in the setting of severe liver disease (e.g., cirrhosis) and protein malnutrition.
23 CAUSES OF EDEMA: REDUCED PLASMA OSMOTIC PRESSURE. Ø Regardless of cause, low albumin levels lead in a stepwise fashion to edema, reduced intravascular volume, renal hypoperfusion, and secondary hyperaldosteronism.
Ø 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. Figure 3–3 Pathways leading to systemic edema due to heart failure, renal failure, or reduced plasma osmotic pressure.
25 CAUSES OF EDEMA: LYMPHATIC OBSTRUCTION.
Impaired lymphatic drainage and consequent lymphedema usually result from a
localized obstruction caused by an inflammatory or neoplastic condition. Ø For example, the parasitic infection filariasis can cause massive edema of the lower extremity and external genitalia (so-called elephantiasis) by engendering inguinal lymphatic and lymph node fibrosis. Ø Infiltration and obstruction of superficial lymphatics by breast cancer may cause edema of the overlying skin; the characteristic finely pitted appearance of the skin of the affected breast is called peau d’orange (orange peel). Ø Lymphedema also may occur as a complication of therapy. One relatively common setting for this clinical entity is in women with breast cancer who undergo axillary lymph node resection and/or irradiation, both of which can disrupt and obstruct lymphatic drainage, resulting in severe lymphedema of the arm. 26 CAUSES OF EDEMA: SODIUM AND WATER RETENTION.
Ø Excessive retention of salt (and its obligate associated water) can
lead to edema by increasing hydrostatic pressure (due to expansion of the intravascular volume) and reducing plasma osmotic pressure.
Ø Excessive salt and water retention are seen in a wide variety of
diseases that compromise renal function, including post- streptococcal glomerulonephritis and acute renal failure.
27 MORPHOLOGY o Edema is easily recognized on gross inspection.
o Microscopic examination shows clearing and separation of the
ECM elements.
o Although any tissue can be involved, edema most commonly in
encountered in subcutaneous tissues, lungs and brain. SUMMARY OF EDEMA. Edema is the result of the movement of fluid from the vasculature into the interstitial spaces; the fluid may be protein-poor (transudate) or protein-rich (exudate). Edema may be caused by: 1) ↑ hydrostatic pressure (e.g., heart failure). 2) ↑ vascular permeability (e.g., inflammation). 3) ↓ colloid osmotic pressure (oncotic pressure), due to ↓ plasma albumin: a) ↓ synthesis (e.g., liver disease, protein malnutrition). b) ↑ loss (e.g., nephrotic syndrome, renal failure).
4) Lymphatic obstruction (e.g., inflammation or neoplasia).
5) Sodium retention (e.g., renal failure). 29 LECTURE OUTLINE I. Hyperemia and Congestion. II. Edema. III. Hemorrhage. IV. Hemostasis and Thrombosis. V. Embolism. VI. Infarction. VII. Shock.
30 HEMORRHAGE § Hemorrhage simply means bleeding § Bleeding may occur due to clotting disorders (defective clot formation), or from trauma (damage to blood vessels) § Capillary bleeding can occur in chronically congested tissues. § Bleeding may be external or internal (within the tissues) § Collection of blood within a tissue is called hematoma. (Large hematomas can be fatal). HEMORRHAGE Ø Hemorrhage, defined as the extravasation of blood from vessels, occurs in a variety of settings. Ø The risk of hemorrhage (often after a seemingly insignificant injury) is ↑ in a wide variety of clinical disorders collectively called hemorrhagic diatheses. Ø Trauma, atherosclerosis, inflammatory or neoplastic erosion of a vessel wall also may lead to hemorrhage, which may be extensive if the affected vessel is a large vein or artery. 32 HEMORRHAGE Hemorrhage may be manifested by different appearances and clinical consequences: 1- Hemorrhage may be external or accumulate within a tissue as a hematoma, which ranges in significance from trivial (e.g., a bruise) to fatal (e.g., a massive retroperitoneal hematoma resulting from rupture of a dissecting aortic aneurysm). Larger accumulations of blood: ü Hemothorax: blood in the pleural cavity ü Hemopericardium: blood in the pericardial cavity ü Hemarthrosis: blood in the joint ü Hemoperitoneum: blood in the peritoneal cavity. HEMORRHAGE 2-Petechiae are minute (1 to 2 mm in diameter) hemorrhages into skin, mucous membranes, or serosal surfaces causes include low platelet counts (thrombocytopenia), defective platelet function, and loss of vascular wall support, as in vitamin C deficiency.
3- Purpura are slightly larger (3 to 5 mm) hemorrhages. Purpura can
result from the same disorders that cause petechiae, as well as trauma, vascular inflammation (vasculitis), and ↑ vascular fragility. HEMORRHAGE 4- Ecchymoses are larger (1 to 2 cm) subcutaneous hematomas (colloquially called bruises). Extravasated red cells are phagocytosed and degraded by macrophages; the characteristic color changes of a bruise are due to the enzymatic conversion of hemoglobin (red-blue color) to bilirubin (blue-green color) and eventually hemosiderin (golden-brown). PETEACHIAE VS. PURPURA VS. ECCHYMOSIS HEMATOMA VS. BRUISE
Bruise Muscle hematoma
HEMORRHAGE Ø The clinical significance of any particular hemorrhage depends on the volume of blood lost and the rate of bleeding. Rapid loss of up to 20% of the blood volume, or slow losses of even larger amounts, may have little impact in healthy adults; greater losses, however, can cause hemorrhagic (hypovolemic) shock . Ø The site of hemorrhage also is important; bleeding that would be trivial in the subcutaneous tissues can cause death if located in the brain. HEMORRHAGE
A, Punctate petechial hemorrhages of the colonic mucosa, a
consequence of thrombocytopenia. B, Fatal intracerebral hemorrhage. 39 HEMMORRHAGE AND IRON Ø Chronic or recurrent blood loss ( e.g., due to peptic ulcer or menstrual bleeding) frequiently culminates in iron deficiency anemia as a consequence of loss of iron in hemoglobin.
Ø By contrast, iron is efficiently recycled from phagocyted red blood
cells, so internal bleeding (e.g., hematoma) does not lead to iron deficiency.
