Chapter 3 Hemodynamic Disorders
The most common cause of increased vascular permeability is inflammation. Inflammatory edema results from the action of mediators such as histamine, complement fragments (C3a and C5a), bradykinin, platelet-activating factor (PAF), and leukotrienes.
Retention of sodium plays a major role in the pathogenesis of cardiac edema. Heart failure is accompanied by reduced perfusion of the kidneys, which stimulates the juxtaglomerular apparatus to secrete renin. Renin activates the angiotensin system, resulting in an increased secretion of aldosterone from the adrenal cortex. Aldosterone acts on the distal convoluted tubules of the kidney, stimulating them to retain sodium. Retention of sodium is accompanied by water retention, which expands the intravascular volume, leading to increased hydrostatic pressure and hydrostatic edema.
Transudate is an ultrafiltrate of plasma that contains few, if any, cells and does not contain large plasma proteins, such as fibrinogen. Transudate results from increased hydrostatic or reduced oncotic pressure. Exudate, on the other hand, is a sign of inflammation and is typically a consequence of increased vascular permeability. Vascular changes permit diapedesis of white blood cells and the passage of large-molecular-weight proteins of the plasma. Accordingly, transudate resembles serum, whereas exudate resembles cell-rich plasma. Transudates do not coagulate, whereas exudates do. The main differences between transudate and exudates are listed in Table 2-1
Pitting edema is a clinical term used for subcutaneous leg edema typically found in patients suffering from heart failure. The name refers to the “pit” that can be induced by pressing the skin over the shin.
Pulmonary edema is most often caused by increased pulmonary venous pressure secondary to left-heart failure. In adult respiratory distress syndrome, shock, or infections (pneumonia), pulmonary edema is caused by increased permeability of pulmonary capillaries. Pulmonary edema may also occur in generalized edema caused by hypoalbuminemia of end-stage liver disease or nephrotic syndrome.
In hyperemia, which is an active process, the increased blood influx into the tissues results from dilatation of arterioles. Typically this occurs in inflammation. Adrenergic stimuli cause dilatation of arterioles of the face during blushing. Increased blood flow through the muscles during exercise is another example of active hyperemia.
Congestion, also known as passive hyperemia, results from stagnation of blood in the capillaries caused by impeded outflow of blood on the venous end. Obstruction of veins with thrombi or backward pressure caused by heart failure is typically accompanied by congestion.
Hyperemic tissues contain increased amounts of oxygenated blood, and therefore such tissues appear bright red. In contrast, congested tissues contain increased amounts of deoxygenated venous blood and therefore appear dusky red or bluish. Hyperemic tissues are warm, whereas the congested tissues are clammy and cold.
In acute congestion, the blood is inside the dilated veins and capillaries. Such an accumulation of blood may pass without serious consequences, but if it occurs rapidly, the ensuing hypoxia and mechanical compression of tissue around the dilated blood vessels may cause necrosis. In chronic passive congestion, there is invariably ischemia accompanied by loss of parenchymal cells, which are usually replaced by fibrosis.
Acute congestion leads to centrilobular stasis of blood that fills the central vein and the sinusoids around it. If the congestion develops suddenly and a large amount of blood is retained in the liver, the centrilobular hepatocytes will undergo necrosis. In chronic passive congestion, the hepatocytes die off and are replaced by fibrous tissue. The cut surface of the liver in such cases has the appearance of a nutmeg. The fibrosis may progress, and the nutmeg liver may transform into cardiac cirrhosis.
Chronic passive congestion of the lungs is typically a consequence of left heart failure. It is accompanied by extravasation of red blood cells (RBCs) into the alveolar spaces. These RBCs fall apart and are taken up by macrophages, which can be expectorated as “heart failure cells.” Macrophages also enter the interstitial spaces, where they may die or stimulate fibroblasts to produce collagen. On gross examination at autopsy, such lungs appear brownish red, due to hemosiderin, and fibrotic, due to the deposition of collagen. The technical term for these changes is brown induration of the lungs.
Prolonged stagnation of blood leads to dilatation of veins (varicose veins) and capillaries. RBCs leak out of the capillaries and die in the interstitial tissues of the subcutis. Hemosiderin formed from hemoglobin accounts for the brownish discoloration of the skin. Chronic ischemia of the skin impedes healing of minor traumatic injuries, and ulcers form. Such stasis ulcers tend to heal slowly or not at all.
All three terms refer to hemorrhages into the skin and mucosae. Pinpoint hemorrhages smaller than 1 mm are called petechiae; those measuring 1 mm to 1 cm in diameter are called purpura; and those larger than 1 cm are called ecchymoses. This classification is arbitrary and has survived only by tradition. Note that petechiae often become confluent and become purpura or ecchymoses. To complicate matters, the term purpura is also used for several diseases characterized by widespread cutaneous hemorrhages (e.g., thrombotic thrombocytopenic purpura and Henoch–Schönlein purpura).
Hematoma is a grossly visible accumulation of extravasated blood in the tissue. First it is red, and then as the blood is deoxygenated, it becomes dusky and bluish red. As the RBCs fall apart, biliverdin forms, and the hematoma will appear greenish. Bilirubin formed from biliverdin will give it a yellow hue. After that, the remnants of the RBC may be resorbed and the tissue resumes its normal color, or the iron portion of heme pigment is taken up by macrophages and degraded into hemosiderin, which gives the tissues a brownish color.
Hemorrhage can occur into any of the preexisting body cavities. Such hemorrhages are named by combining the prefixes hem or hemato (from Greek haima, “blood”) and the anatomic site involved. Accordingly, most of these terms are self-explanatory. For example, terms such as hematopericardium, hematothorax, and hemarthrosis can be easily understood as denoting bleeding into the pericardial, pleural, or intraarticular space, respectively. Other terms are not so intuitively obvious. For example, hematocephalus denotes accumulation of blood in the ventricles of the brain. Hematocolpos signifies accumulation of blood in a vagina occluded by an imperforate hymen.
Hematuria is appearance of blood in urine. It may be classified as microscopic (i.e., detectable by microscopic examination of urine) or macroscopic if visible to the naked eye. Hematuria may be a sign of kidney or urinary tract disease.
Hematemesis is vomiting of blood. Typically, it is a sign of esophageal and gastric hemorrhage. Common causes of hematemesis are ruptured esophageal varices and peptic ulcer of the stomach and duodenum.
Melena or black blood presenting as “coffee-ground” material in the stool is a sign of upper gastrointestinal bleeding. Such blood is partially digested by hydrochloric acid of the gastric juice and transformed into a black pigment called hematein. This pigment is not digested in the intestines and is passed in the feces.
Both processes are based on the coagulation of blood. Hemostasis (“stopping of hemorrhage”) is the physiologic process designed to stop the bleeding from ruptured blood vessels. Thrombosis is a pathologic form of coagulation of circulating blood inside intact vascular spaces.
Coagulation factors are a group of plasma proteins that are activated by acting upon each other in a sequence known as the extrinsic and intrinsic pathway. These proteins lead to activation of thrombin, which plays a crucial role in the polymerization of fibrinogen into fibrin. Fibrin formed at the end of the coagulation cascade represents the meshwork skeleton of the clot and also serves as the glue that holds together platelets and other components of the clot. Deficiency of coagulation factors results in bleeding disorders.
The intrinsic pathway is so called because it can be activated by pouring the blood into a test tube without adding any extrinsic material. The coagulation cascade is activated by the binding of Hageman factor (F XII) to negatively charged glass. The extrinsic pathway is activated by adding tissue factor, which activates factor VII.