96 The Cardiovascular System - wps.aw.comwps.aw.com/wps/media/objects/443/454381/Circulation.pdf · 1 1 The Cardiovascular System 97 longer meet tissue demands for oxygen and nutrients

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96 The Body Systems: Clinical and Applied Topics

The CardiovascularSystemThe components of the cardiovascular systeminclude the blood, heart, and blood vessels. Bloodflows through a network of thousands of miles ofvessels within the body, transporting nutrients,gases, wastes, hormones, and electrolytes andredistributing the heat generated by active tissues.The exchange of materials between the blood andperipheral tissues occurs across the walls of tinycapillaries that are situated between the arterialand venous systems. The total capillary surfacearea for exchange is truly enormous, averagingaround 6300 square meters, 50 percent larger thanthe area of a football field.

Because the cardiovascular system plays a keyrole in supporting all other systems, disorders ofthis system will affect virtually every cell in the

body. One method of organizing the many potentialdisorders involving this system is by the nature ofthe primary problem, whether it affects the blood,the heart, or the vascular network. Figure A-34provides an overview of major blood disorders, andFigure A-35 summarizes heart and blood vesseldisorders that are discussed in the text and in latersections of the Applications Manual.

THE PHYSICAL EXAMINATIONAND THE CARDIOVASCULARSYSTEMIndividuals with cardiovascular problems oftenseek medical attention with one or more of the fol-lowing as chief complaints:

1. Weakness and fatigue: These symptoms devel-op when the cardiovascular system can no

ThalassemiasSickle cell anemia (SCA)Hemophilia

Secondary disorders

Congenital disorders

Degenerative disorders

Excessive coagulationTrauma

Tumors

LeukemiaMyeloidLymphoid

Nutritional disorders

Iron deficiency anemiaIron loadingPernicious anemiaVitamin K deficiency

Infection

BacteremiaViremiaSepticemiaPuerperal feverMalariaHemolytic anemia

BLOODDISORDERS

Urinary system: Erythrocytosis

Immune problems: Hemolytic disease of the newborn

Hemorrhagic anemiaAplastic anemia

Figure A-34 Blood Disorders

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The Cardiovascular System 97

longer meet tissue demands for oxygen andnutrients. These symptoms may occur becausecardiac function is impaired, as in heart failure(p. 115) or cardiomyopathy (p. 104), or becausethe blood is unable to carry normal amounts ofoxygen, as in the various forms of anemia (p.102). In the early stages of these conditions, theindividual feels healthy at rest, but becomesweak and fatigued with any significant degree ofexertion because the cardiovascular systemcannot keep pace with the rising tissue oxygendemands. In more advanced stages of these dis-orders, weakness and fatigue are chronic prob-lems that continue, even at rest.

2. Cardiac pain: This is a deep pain felt in thesubsternal region and often radiating down theleft arm or up into the shoulder and neck.There are two major causes of cardiac pain:

Constant severe pain can result frominflammation of the pericardial sac, a condi-tion known as pericarditis. This pericardialpain may superficially resemble the painexperienced in a myocardial infarction (MI),or heart attack. Pericardial pain differs from

the pain of an MI in that (a) it may berelieved by leaning forward, (b) a fever maybe present, and (c) the pain does notrespond to the administration of drugs,such as nitroglycerin, that dilate coronaryblood vessels. Nitroglycerin, which is effec-tive in relieving angina pectoris, does notrelieve the pain associated with pericarditis.

Cardiac pain can also result from inade-quate blood flow to the myocardium. Thistype of pain is called myocardial ischemicpain. Ischemic pain occurs in angina pec-toris and in a myocardial infarction. Anginapectoris (p. 106) most often results fromthe constriction of coronary blood vesselsby atherosclerosis. The associated painappears during physical exertion, whenmyocardial oxygen demands increase, andthe pain is relieved by drugs such as nitro-glycerin, which dilate coronary vessels andimprove coronary blood flow. The painassociated with a myocardial infarction isusually felt as a heavy weight or a constric-tion of the chest. The pain of an MI is alsodistinctive because (a) it is not necessarily

(b)

Patent foramen ovale and ductus arteriosusVentricular septal defectsTetralogy of Fallot

Blood supply problems

Congenital disorders


Cardiomyopathy

Tumors

MyxomaSarcoma

Functional disorders

Inflammation

ArteritisPhlebitis Thrombophlebitis


Arteriosclerosis Focal calcification AtherosclerosisAneurysmVaricose veins

Infection and inflammation

Carditis Endocarditis Myocarditis PericarditisRheumatic heart disease (RHD)

CARDIOVASCULARDISORDERS

Coronary artery disease (CAD)Shock Circulatory Cardiogenic Obstructive Neurogenic Septic Anaphylactic

HypertensionHypotensionEdemaCerebrovascular accident (CVA)

BloodvesselsHeart

Figure A-35 Disorders of the Heart and Blood Vessels


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linked to exertion, (b) it is not relieved bynitroglycerin or other coronary vasodila-tors, and (c) nausea, vomiting, and sweat-ing may occur during the attack.

3. Palpitations: Palpitations are a persons percep-tion of an altered heart rate. The individualmay complain of the heart skipping a beat orracing. The most likely cause of palpitationsis an abnormal pattern of cardiac activityknown as an arrhythmia. The detection andanalysis of arrhythmias are considered in alater section (p. 108).

4. Pain on movement: Individuals with advancedatherosclerosis often experience pain in theextremities during muscle use. The pain maybecome so severe that the person is unwillingor unable to walk or perform other commonactivities. The underlying problem is constric-tion or partial occlusion of major arteries, suchas the external iliac arteries to the lower limbs,by plaque formation.

These are only a few of the many symptomsthat can be caused by cardiovascular disorders. Inaddition, the individual may notice the appearanceof characteristic signs of other cardiovascular prob-lems. A partial listing of important cardiovascularsigns includes the following:

Edema is an increase of fluid in the tissuesthat occurs when (a) the pumping efficiencyof the heart is decreased, (b) the plasma pro-tein content of the blood is reduced, or (c)venous pressures are abnormally high. Thetissues of the lungs and the legs are mostoften affected, and individuals experienceswollen feet and ankles. When edema is sosevere that pressing on the affected arealeaves an indention, the sign is called pittingedema. Edema is discussed in Chapter 13 ofthe text (p. 397).

Breathlessness, or dyspnea, occurs when car-diac output is inadequate for tissue oxygendemands. Dyspnea may also occur with pul-monary edema, a buildup of fluid within thealveoli of the lungs. Pulmonary edema and dys-pnea are often associated with congestive heartfailure (p. 115).

Varicose veins are dilated superficial veins thatare visible at the skin surface. This condition,which develops when venous valves malfunc-tion, can be caused or exaggerated byincreased systemic venous pressures. Varicoseveins are considered further on p. 112.

There may be characteristic and distinctivechanges in skin coloration. For example, palloris the lack of normal red or pinkish color to theskin of a Caucasian or the conjunctiva and oralmucosa of darker-skinned individuals. Palloraccompanies many forms of anemia, but mayalso be the result of inadequate cardiac output,

shock (p. 113), or circulatory collapse. Cyanosisis the bluish color of the skin occurring with adeficiency of oxygen to the tissues. Cyanosisusually results from either cardiovascular orrespiratory disorders.

Vascular skin lesions were introduced in the dis-cussion of skin disorders on p. 38. Characteristicvascular lesions may occur in primary clottingdisorders (p. 104) and as a result of leukemia(p. 102). For example, abnormal bruising maybe the result of a disorder affecting the clot-ting system, platelet production, or vesselstructure. Petechiae, which appear as purplespots on the skin surface, are often seen incertain types of leukemia or other diseasesassociated with low platelet counts.

CARDIOVASCULAR DISORDERSAND DIAGNOSTIC PROCEDURESOften the initial detection of a cardiovascular disor-der occurs during the assessment stage of a physi-cal examination.

1. When the vital signs are taken, the pulse ischecked for vigor, rate, and rhythm. Weak orirregular heart beats will often be noticed atthis time.

2. The blood pressure is monitored with a stetho-scope, blood pressure cuff, and sphygmo-manometer. Unusually high or low readingscan alert the examiner to potential problemswith cardiac or vascular function. However, adiagnosis of hypotension or hypertension is notmade on the basis of a single reading, but afterseveral readings over a period of time.Hypertension and hypotension are discussed indetail on p. 112.

3. The heart sounds are monitored by ausculta-tion with a stethoscope:

Cardiac rate and rhythm can be checkedand arrhythmias detected.

Abnormal heart sound, or murmurs, mayindicate problems with atrioventricular orsemilunar valves. Murmurs are noted inrelation to their location in the heart (asdetermined by the position of the stetho-scope on the chest wall), the time of occur-rence in the cardiac cycle, and whether thesound is low or high pitched.

Nothing is usually heard during ausculta-tion of normal vessels of the circulatorysystem. Bruits are the sounds resultingfrom turbulent blood flow around anobstruction within a vessel. Bruits are typi-cally heard where large atheroscleroticplaques have formed.

Functional abnormalities of the heart andblood vessels can often be detected through physi-


cal assessment and the recognition of characteris-tic signs and symptoms. The structural basis forthese problems is usually determined through theuse of scans, X-rays, and the monitoring of electri-cal activity in the heart. For problems with a hema-tological basis, laboratory tests performed on bloodsamples usually provide the information necessaryto reach a diagnosis.

Polycythemia EAP p. 347An elevated hematocrit with a normal blood volumeconstitutes polycythemia (po-l-s-TH-m-uh).There are several different types of polycythemia.Erythrocytosis (e-rith-r|-s-T-sis), a polycythemiaaffecting only red blood cells, will be consideredlater in the chapter. Polycythemia vera (truepolycythemia) results from an increase in thenumbers of all blood cells. The hematocrit mayreach 8090, at which point the tissues becomeoxygen-starved because red blood cells are block-ing the smaller vessels. This condition seldomstrikes young people; most cases involve patientsage 6080. There are several treatment options,but none cures the condition. The cause of poly-cythemia vera is unknown, although there is someevidence that the condition is linked to radiationexposure.

Thalassemia EAP p. 349The thalassemias are a diverse group of inheritedblood disorders caused by an inability to produceadequate amounts of the normal protein subunitsof hemoglobin. Each hemoglobin molecule has twoalpha ()chains and two beta () chains. A specificcondition is categorized as an alpha-thalassemiaor beta-thalassemia depending on whether the or hemoglobin subunits are affected. Normal indi-viduals inherit two alpha chain genes from eachparent, and alpha- thalassemia develops when oneor more of these genes are missing or inactive. Theseverity of the symptoms varies depending on howmany normal alpha chain genes remain functional.For example, an individual with three normal alphachain genes will not develop symptoms at all, butthis person can be a carrier, passing the defect tothe next generation. A child born of parents whoare both carriers is likely to develop a more severeform of the disease:

Individuals with two copies of the normal alphachain gene, rather than four copies, havesomewhat impaired hemoglobin synthesis. Thered blood cells are small and contain less thanthe normal quantity of hemoglobin. This condi-tion, known as alpha-thalassemia trait, affectsroughly 2 percent of African Americans andmany Southeast Asians.

Individuals with one copy of the alpha chaingene have very small (microcytic) red blood cellsthat are relatively fragile.

Individuals with no functional copies of thealpha chain gene usually die shortly after birth,because the hemoglobin synthesized cannotbind and transport oxygen normally. The inci-dence of fatal alpha-thalassemia is highestamong Southeast Asians.

Each person inherits only one gene for the betahemoglobin chain from each parent. If an individ-ual does not receive a copy of the normal gene fromeither parent, the condition of beta-thalassemiamajor, or Cooleys disease, develops. Symptoms ofthis condition include severe anemia; microcytosis;a low hematocrit (under 20); and enlargement ofthe spleen, liver, heart, and areas of red bone mar-row. Potential treatments for those with severesymptoms include transfusions, splenectomy (toslow the rate of RBC recycling), and bone marrowtransplantation. Inheriting one normal gene resultsin beta-thalassemia minor, or beta-thalassemiatrait, which seldom produces clinical symptoms.The rates of hemoglobin synthesis are depressed byroughly 15 percent, but this decrease does notaffect their functional abilities, and no treatment isnecessary.

Sickle Cell Anemia EAP p. 349Sickle cell anemia (SCA) results from the produc-tion of an abnormal form of hemoglobin. The chains are involved, and the abnormal subunit iscalled hemoglobin S. Sickle cell anemia affects60,00080,000 African Americans today; this rep-resents roughly 0.14 percent of the African-American population.

An individual with sickle-cell anemia carriestwo copies of the abnormal gene, one from eachparent. If only one copy is present, the individualhas a sickling trait. One African American in 12 car-ries the sickling trait. Although it is now knownthat the genes are present in Americans ofMediterranean, Middle Eastern, and East Indianancestry, statistics on the incidence of sickling traitand SCA in these groups are as yet unavailable.

In individuals with the sickling trait, most ofthe hemoglobin is of the normal form and the ery-throcytes function normally. But the presence ofthe abnormal hemoglobin gives the individual theability to resist the parasitic infections that causemalaria, a mosquito-borne illness. The malariaparasites enter the bloodstream when an individualis bitten by an infected mosquito. The microorgan-isms then invade and reproduce within the ery-throcytes. But when they enter an erythrocyte froma person with the sickling trait, the cell respondsby sickling. Either the sickling itself kills the para-site, or the sickling attracts the attention of aphagocyte that engulfs the RBC and kills the para-site. In either event the individual remains unaf-fected by the disease, while normal individualssicken and often die.

Symptoms of sickle cell anemia include painand damage to a variety of organs and systems,


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depending on the location of the obstructions. Inaddition, the trapped red blood cells eventuallydie and break down, producing a characteristicanemia. Transfusions of normal blood can tem-porarily prevent additional complications, andthere are experimental drugs that can control orreduce sickling. Hydroxyurea is an anticancerdrug that stimulates production of fetal hemoglo-bin, a slightly different form of hemoglobin pro-duced during development. It is effective, but hastoxic side effects (not surprising in an anticancerdrug). The food additive butyrate, found in but-ter and other foods, appears to be even moreeffective in promoting the synthesis of fetalhemoglobin. In clinical trials it has been effectivein treating sickle cell anemia and other condi-tions caused by abnormal hemoglobin structure,such as beta-thalassemia.

Bilirubin Tests and JaundiceEAP p. 349

When hemoglobin is broken down, the heme units(minus the iron) are converted to bilirubin.Normal serum bilirubin concentrations rangefrom 0.1 to 1.2 mg/dl. Of that amount, roughly85 percent will be metabolized and removed bythe liver. Several different clinical conditions arecharacterized by an increase in the total plasmabilirubin concentration. In such conditions,bilirubin diffuses into peripheral tissues, givingthem a yellow coloration that is most apparent inthe skin and over the sclera of the eyes. This com-bination of signs (yellow skin and eyes) is calledjaundice (JAWN-dis).

Jaundice can have many different causes, butblood tests that determine the concentration of dif-ferent forms of bilirubin can provide useful diagnos-tic clues. For example, hemolytic jaundice resultsfrom the destruction of large numbers of red bloodcells. When this occurs, phagocytes release massivequantities of one form of bilirubin (unconjugated)into the blood. Because the liver cells accelerate thesecretion of bilirubin in the bile, the blood concen-tration of another form of bilirubin (conjugated) doesnot increase proportionately. A blood test from apatient with hemolytic jaundice would reveal (1) ele-vated total bilirubin, (2) high concentrations ofunconjugated bilirubin, and (3) conjugated bilirubincontributing much less than 15 percent to the totalbilirubin concentration.

These results are quite different from thoseseen in obstructive jaundice. In this condition,the ducts that remove bile from the liver are con-stricted or blocked. Liver cells cannot get rid ofconjugated bilirubin, and large quantities diffuseinto the blood. In this case, diagnostic tests wouldshow (1) elevated total bilirubin, (2) unconjugatedbilirubin contributing much less than 85 percentto the total bilirubin concentration, and (3) highconcentrations of conjugated bilirubin.

Iron Deficiencies and ExcessesEAP p. 350

If dietary supplies of iron are inadequate, hemoglo-bin production slows down, and symptoms of irondeficiency anemia appear. This form of anemia canalso be caused by any condition that produces ablood loss, since the iron in the lost blood cannot berecycled. As the red blood cells are replaced, ironreserves must be mobilized for use in the synthesisof new hemoglobin molecules. If those reserves areexhausted, or dietary sources are inadequate,symptoms of iron deficiency appear. In iron defi-ciency anemia, the red blood cells are unable tosynthesize functional hemoglobin, and they areunusually small when they enter the circulation.The hematocrit declines, and the hemoglobin con-tent and oxygen-carrying capacity of the blood aresubstantially reduced. Symptoms include weaknessand a tendency to fatigue easily.

Women are especially dependent on a normaldietary supply of iron, because their iron reservesare smaller than those of men. The body of a nor-mal man contains around 3.5 g of iron in the ionicform Fe2+. Of that amount, 2.5 g are bound to thehemoglobin of circulating red blood cells, and therest is stored in the liver and bone marrow. Inwomen, the total body iron content averages 2.4 g,with roughly 1.9 g incorporated into red bloodcells. Thus a womans iron reserves consist of only0.5 ghalf that of a typical man.

Because their reserves are relatively small,women are dependent on a reliable dietary supplyof iron. When the demand for iron increases out ofproportion with dietary supplies, iron deficiencydevelops. An estimated 20 percent of menstruatingwomen in the United States show signs of iron defi-ciency. Pregnancy also stresses iron reserves, forthe woman must provide the iron needed to pro-duce both maternal and fetal erythrocytes.

Good dietary sources of iron include liver, redmeats, kidney beans, egg yolks, spinach, and car-rots. Iron supplements can help prevent iron defi-ciency, but too much iron can be as dangerous astoo little. Iron absorption across the digestivetract normally keeps pace with physiologicaldemands. When the diet contains abnormallyhigh concentrations of iron, or hereditary factorsincrease the rate of absorption, the excess irongets stored in peripheral tissues. This is callediron loading. Eventually cells begin to malfunctionas massive iron deposits accumulate in the cyto-plasm. For example, iron deposits in pancreaticcells can lead to diabetes mellitus; deposits incardiac muscle cells lead to abnormal heart con-tractions and heart failure. (There is evidence thatiron deposits in the heart caused by the overcon-sumption of red meats may contribute to heartdisease.) Liver cells become nonfunctional, andliver cirrhosis may develop.

Comparable symptoms of iron loading mayappear following repeated transfusions of whole


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blood, because each unit of whole blood containsroughly 250 mg of iron. For example, as notedabove, the various forms of thalassemia result froma genetic inability to produce adequate amounts ofone of the four globin chains in hemoglobin.Erythrocyte production and survival are reduced,and so is the oxygen-carrying capacity of the blood.Individuals with severe untreated thalassemia usu-ally die in their twenties, but not because of theanemia. These patients are treated for severe ane-mia with frequent blood transfusions that prolonglife, but the excessive iron loading eventually leadsto fatal heart problems.

Erythrocytosis and Blood Doping EAP p. 351

In erythrocytosis (e-rith-r|-s-T-sis), the bloodcontains abnormally large numbers of red bloodcells. Erythrocytosis usually results from the mas-sive release of erythropoietin by tissues (especiallythe kidneys) deprived of oxygen. People moving tohigh altitudes usually experience erythrocytosisfollowing their arrival, because the air contains lessoxygen than it does at sea level. The increasednumber of red blood cells compensates for the factthat individually each RBC is carrying less oxygenthan it would at sea level. Mountaineers and thoseliving at altitudes of 10,00012,000 feet may havehematocrits as high as 65.

Individuals whose hearts or lungs are function-ing inadequately may also develop erythrocytosis.For example, this condition is often seen in heartfailure and emphysema, two conditions discussedin later chapters. Whether the blood fails to circu-late efficiently or the lungs do not deliver enoughoxygen to the blood, peripheral tissues remain oxy-gen-poor despite the rising hematocrit. Having ahigher concentration of red blood cells increasesthe oxygen-carrying capacity of the blood, but italso makes the blood thicker and harder to pusharound the circulatory system. This increases thework load on the heart, making a bad situationeven worse.

The practice of blood doping was temporari-ly widespread among competi t ive athletesinvolved with endurance sports such as cycling.The procedure entails removing whole blood fromthe athlete in the weeks before an event. Thepacked red cells are separated from the plasmaand stored. By the time of the race, the competi-tors bone marrow will have replaced the lostblood. Immediately before the event the packedred cells are reinfused, increasing the hemat-ocrit. The objective is to elevate the oxygen-car-rying capacity of the blood, and so increaseendurance. The consequence is that the athletesheart is placed under a tremendous strain. Thelong-term effects are unknown, but the practiceobviously carries a significant risk. Once EPObecame available, its ease of use replaced blooddoping. Both have been banned in amateur

sports. Attempts to circumvent this rule by theuse of EPO in 19921993 resulted in the tragicdeaths of 18 European cyclists.

Blood Tests and RBCs EAP p. 351This section describes several common blood teststhat assess circulating RBCs.

RETICULOCYTE COUNT. Reticulocytes are imma-ture red blood cells that are still synthesizinghemoglobin. Most reticulocytes remain in the bonemarrow until they complete their maturation, butsome enter the circulation. Reticulocytes normallyaccount for around 0.8 percent of the erythrocytepopulation. Values above 1.5 percent or below 0.5percent indicate that something is wrong with therates of RBC survival or maturation.

HEMATOCRIT (Hct). The hematocrit value is thepercentage of whole blood occupied by cells.Normal adult hematocrits average 46 for men and42 for women, with ranges of 4252 for men and3747 for women.

HEMOGLOBIN CONCENTRATION (Hb). This testdetermines the amount of hemoglobin in the blood,expressed in grams per deciliter (g/dl). Normalranges are 1418 g/dl in males and 1216 g/dl infemales. The differences in hemoglobin concentra-tion reflect the differences in hematocrit. For bothsexes, a normal RBC contains 2733 picograms(pg) of hemoglobin.

RBC COUNT. Calculations of the RBC count, thenumber of RBCs per microliter of blood, are basedon the hematocrit and hemoglobin content, andcan be used to develop a better picture of the con-dition of the RBCs. Values often reported in bloodscreens include

Mean corpuscular volume (MCV), the averagevolume of an individual red blood cell, in cubicmicrometers. It is calculated by dividing thevolume of red cells per microliter by the RBCcount, using the formula

Normal values range from 80 to 98. For a rep-resentative hematocrit of 46 and an RBC countof 5.2 million, the mean corpuscular volumewould be

Cells of normal size are normocytic, whereaslarger-than-normal or smaller-than-normalRBCs are called macrocytic or microcytic,respectively.

MCV =Hct 10

RBC count (in millions)

MCV =465.2

10 = 88.5 m3


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Mean corpuscular hemoglobin concentration(MCHC), the amount of hemoglobin within asingle RBC, expressed in picograms. Normalvalues range from 27 to 31 pg. The MCHC iscalculated as

RBCs containing normal amounts of hemoglobinare termed normochromic, while hyperchromicand hypochromic indicate higher or lower thannormal hemoglobin content, respectively.

Anemia (a-N-m-uh) exists when the oxygen-carrying capacity of the blood is reduced, diminish-ing the delivery of oxygen to peripheral tissues.Such a reduction causes a variety of symptoms,including premature muscle fatigue, weakness,lethargy, and a general lack of energy. Anemia mayexist because the hematocrit is abnormally low orbecause the amount of hemoglobin in the RBCs isreduced. Standard laboratory tests can be used todifferentiate between the various forms of anemiaon the basis of the number, size, shape, and hemo-globin content of red blood cells. As an example,Table A-20 shows how this information can be usedto distinguish among four major types of anemia.

1. Hemorrhagic anemia results from severeblood loss. Erythrocytes are of normal size,each contains a normal amount of hemoglobin,and reticulocytes are present in normal con-centrations, at least initially. Blood tests wouldtherefore show a low hematocrit and low hemo-globin, but the MCV, MCHC, and reticulocytecounts would be normal.

2. In aplastic (-PLAS-tik) anemia, the bone mar-row fails to produce new red blood cells. The1986 nuclear accident in Chernobyl (USSR)caused a number of cases of aplastic anemia.The condition is fatal unless surviving stemcells repopulate the marrow or a bone marrowtransplant is performed. In aplastic anemia thecirculating red blood cells are normal in allrespects, but because new RBCs are not beingproduced, the RBC count, Hct, Hb, and reticu-locyte count are extremely low.

3. In iron deficiency anemia, normal hemoglo-bin synthesis cannot occur, because ironreserves are inadequate. Developing red bloodcells cannot synthesize functional hemoglobin,

and as a result they are unusually small. Ablood test therefore shows a low hematocrit,low hemoglobin content, low MCV, and lowMCHC, but a normal reticulocyte count. Anestimated 60 million women worldwide haveiron deficiency anemia. (See the discussion oniron deficiencies and excesses on p. 100.)

4. In pernicious (per-NISH-us) anemia, normal redblood cell maturation ceases because of an inad-equate supply of vitamin B12. Erythrocyte pro-duction declines, and the red blood cells areabnormally large and may develop a variety ofbizarre shapes. Blood tests from a person withpernicious anemia indicate a low hematocrit witha very high MCV and a low reticulocyte count.

Hemolytic Disease of the NewbornEAP p. 354

Hemolytic disease of the newborn results from thematernal production of anti-Rh antibodies thatcross the placenta to attack fetal Rh-positive redblood cells. Within 6 months after delivery, roughly20 percent of Rh-negative mothers who were preg-nant with Rh-positive children have become sensi-tized and produce anti-Rh antibodies. For theentire sequence of events, see Figure A-36. Withouttreatment, the fetus will probably die before deliv-ery or shortly thereafter.

A newborn with severe HDN is anemic, and thehigh concentration of circulating bilirubin pro-duces jaundice. Because the maternal antibodiesremain active for 1 to 2 months after delivery, theinfants entire blood volume may need to bereplaced by an exchange transfusion. Bloodreplacement removes most of the maternal anti-bodies as well as the affected erythrocytes, reduc-ing the complications and the chance the infantwill die.

When there is a danger that the fetus may notsurvive to full term, premature delivery may beinduced after 7 to 8 months of development. In asevere case affecting a fetus at an earlier stage, oneor more transfusions can be given while the fetuscontinues to develop within the uterus.

To avoid the problem, the maternal productionof Rh antibodies is prevented by administering Rhantibodies (available under the name RhoGam)after delivery or miscarriage or abortion. Theseforeign antibodies quickly destroy any fetal redblood cells that enter the maternal circulation.Thus there are no exposed antigens to stimulatethe maternal immune system, sensitization doesnot occur, and Rh antibodies are not produced.This relatively simple procedure could almostentirely prevent HDN mortality caused by Rhincompatibilities.

The Leukemias EAP p. 356

Leukemias characterized by the presence of abnor-mal granulocytes or other cells of the bone marroware called myeloid; leukemias that involve abnor-

Table A-20 RBC Tests and Anemias

Reticu-locyte

Anemia type Hct Hb count MCV MCHC

Hemorrhagic low low normal normal normalAplastic low low very low normal normalIron deficiency low low normal low lowPernicious low low very low high high

MCHC =Hb

10RBC count (in millions)


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mal lymphocytes are termed lymphoid. The firstsymptoms appear as immature and abnormalwhite blood cells appear in the circulation. Astheir numbers increase, they travel through thecirculation, invading tissues and organs through-out the body.

These cells are extremely active, and theyrequire abnormally large amounts of energy. As inother cancers, described in Chapter 3 of the text andelsewhere in this Applications Manual (p. 33), invad-ing leukemic cells gradually replace the normal cells,especially in the bone marrow. Red blood cell, nor-

mal WBC, and platelet formation decline, withresulting anemia, infection, and impaired blood clot-ting. Untreated leukemias are invariably fatal.

Leukemias are classified as acute (short andsevere) or chronic (prolonged). Acute leukemias maybe linked to radiation exposure, hereditary suscep-tibility, viral infections, or unknown causes.Chronic leukemias may be related to chromosomalabnormalities or immune system malfunctions.Survival in untreated acute leukemia averagesabout three months; individuals with chronicleukemia may survive for years.

Rh

Rh Rh

Rh

Rh+

Rh+ Rh+

Rh+

Rh Rh

Rh

Rh+

Rh+

Rh+

Rh+

Rh+

Rh+

Rh

RhRh

Rh

Rh

RhRh

Rh

Rh+ Rh+

Rh+

First pregnancy

Maternalblood

Maternaltissue

Fetaltissue

Fetalblood

Placenta

Maternaltissue

Fetaltissue

Maternaltissue

Maternaltissue

Fetaltissue

Rh

Second pregnancyMaternal agglutinin production

(anti-Rh)

Hemorrhagingat delivery

FIGURE A-36 Rh Factors and Pregnancy

When an Rh-negative woman has her first Rh-positive child, mixing of fetal and maternal blood occurs at delivery when the placentalconnection breaks down. The appearance of Rh-positive blood cells in the maternal circulation sensitizes the mother, stimulating theproduction of anti-Rh agglutinins. If another pregnancy occurs with an Rh-positive fetus, maternal agglutinins can cross the placentalbarrier and attack fetal blood cells, producing symptoms of HDN (hemolytic disease of the newborn).


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Effective treatments exist for some forms ofleukemia and not others. For example, when acutelymphoid leukemia is detected early, 8590 percentof patients can be held in remission for 5 years orlonger, but only 1015 percent of patients withacute myeloid leukemia survive 5 years or more.The yearly mortality rate for leukemia (all types) inthe United States has not declined appreciably inthe past 30 years, remaining at around 6.8 per100,000 population. However, new treatments arebeing developed that show promise when usedagainst specific forms of leukemia. For example,administration of -interferon, a hormone of theimmune system, has been very effective in treatinghairy cell leukemia and chronic myeloid leukemia.

One option for treating acute leukemias is toperform a bone marrow transplant. In this proce-dure, massive chemotherapy or radiation treatmentis given, enough to kill all the cancerous cells.Unfortunately, this also destroys the patientsblood cells and stem cells in the bone marrow andother blood-forming tissues. The individual thenreceives an infusion of healthy bone marrow cellsthat repopulate the blood and marrow tissues.

If the bone marrow is extracted from anotherperson (a heterologous marrow transplant), caremust be taken to ensure that the blood types andtissue types are compatible (see Chapters 11 and14 of the text). If they are not, the new lymphocytesmay attack the patients tissues, with potentiallyfatal results. Best results are obtained when thedonor is a close relative. In an autologous marrowtransplant bone marrow is removed from thepatient, cleansed of cancer cells, and reintroducedafter radiation or chemotherapy treatment.Although there are fewer complications, the prepa-ration and cleansing of the marrow are technicallydifficult and time consuming.

Bone marrow transplants are also performed totreat patients whose bone marrow has beendestroyed by toxic chemicals or radiation. Forexample, heterologous transplants were used suc-cessfully in the USSR to treat survivors of theChernobyl nuclear reactor accident in 1986.

Testing the Clotting SystemEAP p. 359

Several clinical tests check the efficiency of theclotting system:

BLEEDING TIME. This test measures the time ittakes for a small skin wound to seal itself. Thereare several variations on this procedure, with nor-mal values ranging from 1 to 9 minutes. The non-prescription drug aspirin prolongs the bleedingtime by affecting platelet function and suppressingthe extrinsic pathway.

COAGULATION TIME. In this test, a sample ofwhole blood is allowed to stand under controlledconditions until a visible clot has formed. Normalvalues range from 3 to 15 minutes. The test hasseveral potential sources of error, and so is not

very accurate. Nevertheless, it is the simplest testthat can be performed on a blood sample.

PARTIAL THROMBOPLASTIN TIME (PTT). In thistest, a plasma sample is mixed with chemicals thatmimic the effects of activated platelets. Calcium ionsare then introduced, and the clotting time is record-ed. Clotting normally occurs in 3550 seconds if theenzymes and clotting factors of the intrinsic pathwayare present in normal concentrations.

PLASMA PROTHROMBIN TIME (PROTHROMBINTIME, PT). This test checks the performance of theextrinsic pathway. The procedure is similar to thatin the PTT test, but the clotting process is triggeredby exposure to a combination of tissue prothrombi-nase (formerly called thromboplastin) and calciumions. Clotting normally occurs in 1214 seconds.

Infection and Inflammation of the Heart EAP p. 369

Many different microorganisms may infect hearttissue, leading to serious cardiac abnormalities.Carditis (kar-D-tis) is a general term indicatinginflammation of the heart. Clinical conditionsresulting from cardiac infection are usually identi-fied by the primary site of infection. For example,those affecting the endocardium produce symp-toms of endocarditis. Endocarditis primarilyaffects the chordae tendineae and heart valves, andthe mortality rate may reach 2135 percent. Themost severe complications result from the forma-tion of blood clots on the damaged surfaces. Theseclots subsequently break free, entering the circula-tion as drifting emboli (see p. 361 of the text) thatmay cause strokes, heart attacks, or kidney failure.Destruction of heart valves by infection may lead tovalve leakage, heart failure, and death.

Bacteria, viruses, protozoa, and fungalpathogens that either attack the myocardiumdirectly or release toxins that do, producemyocarditis. The microorganisms implicatedinclude those responsible for many of the condi-tions discussed in earlier chapters, includingdiphtheria, syphilis, polio, and malaria. The mem-branes of infected heart muscle cells become facili-tated, and the heart rate may rise dramatically.Over time, abnormal contractions may appear, theheart muscle weakens, and these may eventuallyprove fatal.

The Cardiomyopathies EAP p. 370The cardiomyopathies (kar-d-|-m-OP-a-thz)include an assortment of diseases with a commonsymptom: the progressive, irreversible degenerationof the myocardium. Cardiac muscle fibers are dam-aged and replaced by fibrous tissue, and the mus-cular walls of the heart become thin and weak. Asmuscle tone declines, the ventricular chambersbecome greatly enlarged. When the remainingfibers cannot develop enough force to maintain car-diac output, symptoms of heart failure develop.


Chronic alcoholism and coronary artery diseaseare probably the most common causes of cardiomy-opathy in the United States. Infectious agents,including viruses, bacteria, fungi, and protozoans,can also produce cardiomyopathies. Diseases affect-ing neuromuscular performance, such as musculardystrophy (discussed elsewhere in this manual),can also damage cardiac muscle fibers, as can star-vation or chronic variations in the extracellular con-centrations of calcium or potassium ions.

There are also several inherited forms of car-diomyopathy. Hypertrophic cardiomyopathy(HCM) is an inherited disorder that makes the wallof the left ventricle thicken to the point at which ithas difficulty pumping blood. Most people withHCM do not become aware of it until relatively latein life. However, HCM can also cause a fatalarrhythmia; it has been implicated in the suddendeaths of several young athletes. The implantationof an electronic cardiac pacemaker has proved tobe beneficial in controlling these arrhythmias.

Finally, there are a significant number of casesof idiopathic cardiomyopathy, a term used when theprimary cause cannot be determined.

Heart Transplants and AssistDevices EAP p. 370

Individuals with severe cardiomyopathy may beconsidered as candidates for heart transplants.This surgery involves the complete removal of theweakened heart and its replacement with a hearttaken from a suitable donor. To survive thesurgery, the recipient must be in otherwise satis-factory health. Because the number of suitabledonors is limited, the available hearts are usuallyassigned to individuals younger than age 50. Outof the 8,00010,000 U.S. patients each year whohave potentially fatal cardiomyopathies, only about1,000 receive heart transplants. After successfultransplantation, there is an 8085 percent one-year survival rate and a 5070 percent five-yearsurvival rate. These rates are quite good, consider-ing that these patients would have died if thetransplant had not been performed.

Many individuals with cardiomyopathy who areinitially selected for transplant surgery succumb tothe disease before a suitable donor becomes avail-able. For this reason there continues to be consid-erable interest in the development of an artificialheart. One model, the Jarvik-7, had limited clinicaluse in the 1980s. Attempts to implant it on a per-manent basis were unsuccessful, primarilybecause of the formation of blood clots on themechanical valves and infections involving itsexternal power source. When the clots broke free,they formed drifting emboli that plugged peripheralvessels, producing strokes, kidney failure, andother complications. In 1989 the federal govern-ment prohibited further experimental use of theJarvik-7 as a permanent heart implant. Modifiedversions of this unit and others now under devel-opment may still be used to maintain transplant

candidates while awaiting the arrival of a donororgan. These are called left ventricular assistdevices (LVAD). As the name implies, these devicesassist, rather than replace, the damaged heart. Amechanical left ventricular assist device has beenused to support a patient awaiting a transplant.

An experimental approach, which has yet to betried with human patients, involves the insertion offetal heart muscle cells in a damaged adult heart.The fetal cells appear to adapt to their surroundingsand differentiate into functional contractile cells.

RHD and Valvular StenosisEAP p. 373

Rheumatic (roo-MA-tik) fever is an inflammatorycondition that may develop following untreatedinfection by streptococcal bacteria (strep throat).Rheumatic fever most often affects children of age515 years; symptoms include high fever, jointpain and stiffness, and a distinctive full-body rash.Obvious symptoms usually persist for less than 6weeks, although severe cases may linger for 6months or more. The longer the duration of theinflammation, the more likely it is that carditis willdevelop. The carditis that does develop in 5060percent of patients often escapes detection, andscar tissue forms gradually in the myocardium andthe heart valves. Valve condition deteriorates overtime, and valve problems serious enough to affectcardiac function may not appear until 1020 yearsafter the initial infection.

Over the interim the affected valves becomethickened and often calcified to some degree.This thickening narrows the opening guarded bythe valves, producing a condition called valvularstenosis (ste-N-sis; stenos, narrow). The result-ing clinical disorder is known as rheumaticheart disease, or RHD. The thickened cuspsstiffen in a partially closed position, but thevalves do not completely block the circulation,because the edges of the cusps are rough andirregular (Figure A-37). Regurgitation may occur,and much of the blood pumped out of the heartmay flow right back in. The abnormal valves arealso much more susceptible to bacterial infection,a type of endocarditis.

Mitral stenosis and aortic stenosis are themost common forms of valvular heart disease.About 40 percent of patients with RHD developmitral stenosis, and two-thirds of them are women.The reason for the correlation between gender andmitral stenosis is unknown. In mitral stenosis bloodenters the left ventricle at a slower than normalrate, and when the ventricle contracts, blood flowsback into the left atrium as well as into the aortictrunk. As a result, the left ventricle has to workmuch harder to maintain adequate systemic circu-lation. The right and left ventricles discharge identi-cal amounts of blood with each beat, and as theoutput of the left ventricle declines, blood backsup in the pulmonary circuit. Venous pressuresthen rise in the pulmonary circuit, and the right


12


ventricle must develop greater pressures to forceblood into the pulmonary trunk. In severe cases ofmitral stenosis, the ventricular musculature is notup to the task. The heart weakens, and peripheraltissues begin to suffer from oxygen and nutrientdeprivation. (This condition, called heart failure, isdiscussed in more detail in a later section.)

Symptoms of aortic stenosis develop in roughly25 percent of patients with RHD; 80 percent ofthese individuals are males. Symptoms of aorticstenosis are initially less severe than those ofmitral stenosis. Although the left ventricle enlargesand works harder, normal circulatory function canoften be maintained for years. Clinical problemsdevelop only when the opening narrows enough toprevent adequate blood flow. Symptoms thenresemble those of mitral stenosis.

One reasonably successful treatment for severestenosis involves the replacement of the damagedvalve with a prosthetic (artificial) valve. Figure A-37ashows a stenotic heart valve; two possible replace-ments are a valve from a pig (Figure A-37b) and asynthetic valve (Figure A-37c), one of a number ofdesigns that have been employed. Pig valves do notrequire anticoagulant therapy, but may wear outand begin leaking after roughly 10 years in service.The plastic or stainless steel components of the arti-ficial valve are more durable but activate the clottingsystem of the recipient, leading to inflammation, clotformation, and other potential complications.Synthetic valve recipients must take anticoagulantdrugs to prevent strokes and other disorders causedby embolus formation. Valve replacement operationsare quite successful, with about 95 percent of thesurgical patients surviving for 3 years or more and70 percent surviving over 5 years.

Coronary Artery Disease EAP p. 374The term coronary artery disease (CAD) refers todegenerative changes in the coronary circulation.Cardiac muscle fibers need a constant supply of

oxygen and nutrients, and any reduction in coro-nary circulation produces a corresponding reduc-tion in cardiac performance. Such reducedcirculatory supply, known as coronary ischemia(is-K-m-uh), usually results from partial or com-plete blockage of the coronary arteries. The usualcause is the formation of a fatty deposit, or plaque,in the wall of a coronary vessel. The plaque, or anassociated thrombus, then narrows the passage-way and reduces blood flow. Spasms in the smoothmuscles of the vessel wall can further decreaseblood flow or even stop it altogether. Plaque devel-opment and growth are considered in Chapter 13.

One of the first symptoms of CAD is often angi-na pectoris (an-JI-nuh PEK-tor-is; angina, painspasm + pectoris, of the chest). In the most com-mon form of angina, temporary insufficiency andischemia develop when the workload of the heartincreases. Although the individual may feel com-fortable at rest, any unusual exertion or emotionalstress can produce a sensation of pressure, chestconstriction, and pain that may radiate from thesternal area to the arms, back, and neck.

Angina can often be controlled by a combina-tion of drug treatment and changes in lifestyle.Lifestyle changes to combat angina include (1) lim-iting activities known to trigger angina attacks,such as strenuous exercise, and avoiding stressfulsituations; (2) stopping smoking; and (3) modifyingthe diet to lower fat consumption. Medications use-ful for controlling angina include drugs that blocksympathetic stimulation (propranolol or metoprolol);vasodilators such as nitroglycerin (n-tr|-GLIS-er-in); and drugs that block calcium movement intothe cardiac muscle cells (calcium channel blockers).

Angina can also be treated surgically. A single,soft plaque may be reduced with the aid of a slen-der, elongate catheter (KATH-e-ter). The catheter, asmall-diameter tube, is inserted into a large arteryand guided into a coronary artery to the plaque. Avariety of surgical tools can be slid into thecatheter, and the plaque can then be removed with


12

(b) (c)(a)

Figure A-37 Artificial Heart Valves

(a) A stenotic semilunar valve; note the irregular, stiff cusps. (b) Intact BioprostheticTM heart valve,which uses the valve from a pigs heart. (c) Medtronic HallTM prosthetic heart valve.


laser beams or chewed to pieces by a miniature ver-sion of the Roto-Rooter machine. Debris createdduring plaque destruction is sucked up by thecatheter, preventing blockage of smaller vessels.

In balloon angioplasty (AN-j-|-plas-t;angeion, vessel) the catheter tip contains an inflat-able balloon. Once in position, the balloon is inflat-ed, pressing the plaque against the vessel walls.This procedure works best in small (under 10 mm)soft plaques. Several factors make this a highlyattractive treatment: (1) The mortality rate duringsurgery is only around 1 percent; (2) the successrate is over 90 percent; and (3) it can be performedon an outpatient basis. Although in about 20 per-cent of patients the plaque deposit returns to itsoriginal size within 6 months, the process can berepeated as needed.

A coronary artery bypass graft (CABG) involvestaking a small section from either a small artery(often the internal thoracic artery) or a peripheral vein(such as the great saphenous vein of the leg) andusing it to create a detour around the obstructedportion of a coronary artery. As many as four coro-nary arteries can be rerouted this way during a sin-gle operation. The procedures are named accordingto the number of vessels repaired, so one speaks ofsingle, double, triple, or quadruple coronary bypassoperations. The mortality rate during surgery foroperations performed before significant heart damagehas occurred is relatively low (12 percent). Underthese conditions the procedure completely eliminatesthe angina symptoms in 70 percent of the cases andprovides partial relief in another 20 percent.

Although it does offer certain advantages,recent studies have shown that for mild angina,coronary bypass surgery does not yield significant-ly better results than drug therapy. Current recom-mendations are that coronary bypass surgery bereserved for cases of severe angina that do notrespond to other treatment.

Heart Attacks EAP p. 375

In a myocardial (m-|-KAR-d-al) infarction (MI), orheart attack, the coronary circulation becomesblocked and the cardiac muscle cells die from lack ofoxygen. The affected tissue then degenerates, creat-ing a nonfunctional area known as an infarct. Heartattacks most often result from severe coronaryartery disease. The consequences depend on the siteand nature of the circulatory blockage. If it occursnear the base of one of the coronary arteries, thedamage will be widespread and the heart will proba-bly stop beating. If the blockage involves one of thesmaller arterial branches, the individual may survivethe immediate crisis, but there are many potentialcomplications, all unpleasant. As scar tissue formsin the damaged area, the heartbeat may becomeirregular and other vessels can become constricted,creating additional circulatory problems.

Myocardial infarctions are most often associat-ed with pre-existing fixed partial blockages, such as

those seen in CAD. When the crisis developsbecause of complete blockage by a thrombus (clot)formation at a plaque, the condition is called coro-nary thrombosis. A vessel already narrowed byplaque formation may also become blocked by asudden spasm in the smooth muscles of the vascu-lar wall. The individual then may experience intensepain, similar to that of an angina attack but persist-ing even at rest. However, pain does not alwaysaccompany a heart attack. These silent heartattacks may be even more dangerous, because thecondition may not be diagnosed and treated beforea fatal MI occurs. Roughly 25 percent of heartattacks are not recognized when they occur.

The cytoplasm of a damaged cardiac musclecell differs from that of a normal muscle cell. Asthe supply of oxygen decreases, the cells becomemore dependent on anaerobic metabolism to meettheir energy needs. Over time the cytoplasm accu-mulates large numbers of enzymes involved withanaerobic energy production.

As the cardiac muscle cell membranes deterio-rate, these enzymes leak into the surroundingintercellular fluids. The appearance of suchenzymes in the circulation thus indicates that aninfarct has occurred. The enzymes tested for in adiagnostic blood test include lactate dehydroge-nase (LDH), serum glutamic oxaloacetictransaminase (SGOT, also called aspartate amino-transferase), creatine phosphokinase (CPK, orCK), and a special form of creatine phosphokinasefound only in cardiac muscle (CK-MB).

Roughly 25 percent of MI patients die beforeobtaining medical assistance, and 65 percent of MIdeaths among those under age 50 occur within anhour after the initial infarct. The goals of treatmentare to limit the size of the infarct and prevent addi-tional complications by preventing irregular con-tractions, improving circulation with vasodilators,providing additional oxygen, reducing the cardiacworkload, and, if possible, eliminating the cause ofthe circulatory blockage. Anticoagulants may helpprevent the formation of additional thrombi, andclot-dissolving enzymes, such as t-PA, may reducethe extent of the damage if they are administeredwithin 6 hours after the MI has occurred. Follow-up treatment with heparin or aspirin or both is rec-ommended; without further treatment thecirculatory blockages will reappear in roughly 20percent of patients.

A number of factors increase the risk of a heartattack: smoking, high blood pressure, high bloodcholesterol levels, high circulating levels of low-density lipoproteins (LDL), diabetes, increasing age,male gender (below age 70), and obesity. The role oflipoproteins and cholesterol in plaque formationand heart disease are considered in Chapter 13.Hereditary factors may also predispose an individ-ual to coronary artery disease. Although the rate ofheart attacks of women under age 70 is lower thanthat of men, their mortality rate is actually high-erperhaps because heart disease in women is


12


neither diagnosed as early nor treated as aggres-sively as is heart disease in men.

The presence of two risk factors more thandoubles the risk, so eliminating as many risk fac-tors as possible will improve ones chances of pre-venting or surviving a heart attack. Changes in dietto limit cholesterol, exercise to lower weight, notsmoking, and seeking treatment for high bloodpressure are steps in the right direction. As publichealth knowledge and education about risk factorsfor heart disease and treatment for hypertensionand high cholesterol have improved death rateshave declined. Data from the CDC shows a drop ofdeath rates from coronary artery disease from over200 per 100,000 to 134 per 100,000 between 1963and 1996. In 1996, they estimate there were621,000 fewer deaths from CAD than would havebeen expected had the rates stayed as high.

Diagnosing Abnormal Heartbeats EAP p. 378

Damage to the conduction pathways caused bymechanical distortion, ischemia, infection, orinflammation can affect the normal rhythm of theheart. The resulting condition is called a conduc-tion deficit, or heart block. Heart blocks of vary-ing severity are illustrated in Figure A-38. In afirst-degree heart block (Figure A-38b), the AVnode and proximal portion of the AV bundle slowthe passage of impulses heading for the ventricularmyocardium. As a result, a pause appears betweenthe atrial and ventricular contractions. Although adelay exists, the regular rhythm of the heart con-tinues, and each atrial beat is followed by a ven-tricular contraction.

If the delay lasts long enough, the nodal cellswill still be repolarizing from the previous beatwhen the next impulse arrives from the pacemak-er. The arriving impulse will then be ignored, theventricles will not be stimulated, and the normalatria-ventricles, atria-ventricles pattern will dis-appear. This condition is a second-degree heartblock (Figure A-38c). A mild second-degree blockmay produce only an occasional skipped beat, butwith more substantial delays the ventricles willfollow every second atrial beat. The resulting pat-tern of atria, atria-ventricles, atria, atria-ventri-cles is known as a two-to-one (2:1) block.Three-to-one or even four-to-one blocks are alsoencountered.

In a third-degree heart block, or completeheart block, the conducting pathway stops func-tioning altogether (Figure A-38d). The atria andventricles continue to beat, but their activities areno longer synchronized. The atria follow the paceset by the SA node, beating 7080 times perminute, and the ventricles follow the commands ofthe AV node, beating at a rate of 4060 per minute.A temporary heart block can be induced by stimu-lating the vagus nerve. In addition to slowing therate of impulse generation by the SA node, such

stimulation inhibits the AV nodal cells to the pointthat they cannot respond to normal stimulation.Comments such as my heart stopped or myheart skipped a beat usually refer to this phenom-enon. The pause typically lasts for just a few sec-onds. Longer delays end when a conducting cell,usually one of the Purkinje fibers, depolarizes tothreshold. This phenomenon is called ventricularescape because the ventricles are escaping fromthe control of the SA node. Ventricular escape canbe a lifesaving event if the conduction system isdamaged. Even without instructions from the SA orAV nodes, the ventricles will continue to pumpblood at a slow but steady rate.

Tachycardia and FibrillationAdditional important examples of arrhythmias areshown in Figure A-39. Premature atrial contrac-tions (PACs), indicated in Figure A-39b, oftenoccur in normal individuals. In a PAC the normalatrial rhythm is momentarily interrupted by a sur-prise atrial contraction. Stress, caffeine, and vari-ous drugs may increase the frequency of PACincidence, presumably by increasing the perme-abilities of the SA pacemakers. The impulse


12

P T P

SQ QS

R

T

R

(a) Normal

2:1 Block (ventricles follow every other atrial beat)

3:1 Block(ventricles follow every third atrial beat)

(c) Second-degree blocks

(d) Complete block (third-degree block) (atrial beats occur regularly, ventricular beats occur at slower, unrelated pace)

(b) First-degree heart block (long P-R interval)

P P

R R

T T

QS QS

Skipped ventricular beat

P P P

1 2 1 2

1 2 3 1 2 3

p p p p p p p

Figure A-38 Heart Blocks (ECG tracings)



12

(a) Normal

(b) Premature atrial contraction (PAC)

(c) Paroxysmal atrial tachycardia (PAT)

(d) Atrial fibrillation

(g) Ventricular fibrillation (VF)

(f) Ventricular tachycardia (VT)

(e) Premature ventricular contraction (PVC)

Q S Q S

P PT T

R R

P P P

P P P P P

P PT T

P

Figure A-39 Cardiac Arrhythmias (ECG tracings)

spreads along the conduction pathway, and a nor-mal ventricular contraction follows the atrial beat.

In paroxysmal atrial tachycardia (par-ok-SIZ-mal), or PAT (Figure A-39c), a premature atrialcontraction triggers a flurry of atrial activity. Theventricles are still able to keep pace, and the heartrate jumps to about 180 beats per minute. In atrialflutter the atria are contracting in a coordinatedmanner, but the contractions are occurring veryfrequently. During a bout of atrial fibrillation (fi-bri-L-shun), Figure A-39d, the impulses are mov-ing over the atrial surface at rates of perhaps 500beats per minute. The atrial wall quivers instead ofproducing an organized contraction. The ventricu-lar rate in atrial flutter or atrial fibrillation cannotfollow the atrial rate, and may remain within nor-mal limits. Despite the fact that the atria are nowessentially nonfunctional, the condition may gounnoticed, especially in older individuals leadingsedentary lives. PACs, PAT, atrial flutter, and evenatrial fibrillation are not considered very dangerousunless they are prolonged or associated with some

more serious indications of cardiac damage, suchas coronary artery disease or valve problems.

In contrast, ventricular arrhythmias may beserious and even fatal. Because the conductionsystem functions in one direction only, a ventricu-lar arrhythmia is not linked to atrial activities.Premature ventricular contractions (PVCs;Figure A-39e) occur when a Purkinje cell or ven-tricular myocardial cell depolarizes to thresholdand triggers a premature contraction. The cellresponsible is called an ectopic pacemaker. The fre-quency of PVCs can be increased by exposure toepinephrine and other stimulatory drugs or toionic changes that depolarize cardiac muscle fibermembranes. Similar factors may be responsible forperiods of ventricular tachycardia, also known asVT, or V-tach (Figure A-39f).

Multiple PVCs and VT often precede the mostserious type of arrhythmia, ventricular fibrilla-tion (VF; Figure A-39g). The resulting condition,known as cardiac arrest, is rapidly fatal becausethe heart quivers and stops pumping blood.During ventricular fibrillation, cardiac musclefibers are overly sensitive to stimulation and theimpulses are traveling from cell to cell around andaround the ventricular walls. A normal rhythmcannot become established, because the ventricu-lar muscle fibers are stimulating one another at arapid rate. The problem is exaggerated by a sus-tained rise in free intracellular calcium ion concen-trations, due to massive stimulation of alpha andbeta receptors following sympathetic activation.

A defibrillator is a device that attempts toeliminate ventricular fibrillation and restore nor-mal cardiac rhythm. Two electrodes are placed incontact with the chest, and a powerful electricalshock is administered. The electrical stimulusdepolarizes the entire myocardium simultaneously.With luck, after repolarization the SA node will bethe first area of the heart to reach threshold. Thusthe primary goal of defibrillation is not just to stopthe fibrillation, but to give the ventricles a chanceto respond to normal SA commands. Early defibril-lation can result in dramatic recovery of an uncon-scious cardiac arrest victim.

In treating arrhythmias there are several med-ications that can slow down rapid heart rates, orthe abnormal portions of the conducting systemcan be destroyed. Pacemakers are used to acceler-ate slow heart rates. Implantable pacemakers ableto sense ventricular fibrillation and deliver animmediate defibrillating shock have been success-ful in preventing sudden death in patients withprevious episodes of ventricular tachycardia andventricular fibrillation.

Aneurysms EAP p. 391An aneurysm (AN--rizm) is a bulge in the weak-ened wall of a blood vessel, usually an artery.This bulge resembles a bubble in the wall of atire, and like a bad tire, the affected artery may


suffer a catastrophic blowout. The most danger-ous aneurysms are those involving arteries of thebrain, where they cause strokes, and of the aorta,where a blowout will cause fatal bleeding in amatter of seconds.

Aneurysms are most often caused by chronichigh blood pressure, although any trauma or infec-tion that weakens vessel walls can lead to ananeurysm. Some aortic aneurysms have beenlinked to inherited disorders, such as Marfanssyndrome, that have weakened connective tissuesin vessel walls. It is not known whether othergenetic factors are involved in the development ofother aneurysms.

An aneurysm usually forms gradually, as ves-sel walls become less elastic. When a weak pointdevelops, the arterial pressures distort the wall,creating an aneurysm. Unfortunately, because theyare often painless, they are likely to go undetected.

When aneurysms are detected by ultrasound orother scanning procedures, the risk of rupture cansometimes be estimated on the basis of their size.For example, an aortic aneurysm larger than 6 cmhas a 50:50 chance of rupturing in the next 10years. Treatment often begins with the reduction ofblood pressure by means of vasodilators or beta-blockers (drugs that decrease heart rate and forceof concentration). An aneurysm in an accessiblearea, such as the abdomen, may be surgicallyremoved and the vessel repaired. Figure A-40shows a large aortic aneurysm before and aftersurgical repair with a synthetic patch.

Arteriosclerosis EAP p. 393Arteriosclerosis (ar-t-r-|-skle-R-sis) is a thick-ening and toughening of arterial walls. Althoughthis condition may not sound life-threatening, com-plications related to arteriosclerosis account forroughly one-half of all deaths in the United States.There are many different forms of arteriosclerosis;for example, arteriosclerosis of coronary vessels isresponsible for coronary artery disease (CAD), andarteriosclerosis of arteries supplying the brain canlead to strokes.

There are two major forms of arteriosclerosis:

Focal calcification is the gradual degenerationof smooth muscle in the tunica media and thesubsequent deposition of calcium salts. Thisprocess typically involves arteries of the limbs.Some focal calcification occurs as part of theaging process, and it may develop in associa-tion with atherosclerosis. Rapid and severe cal-cification may occur as a complication ofdiabetes mellitus, an endocrine disorder con-sidered in Chapter 10.

Atherosclerosis (ath-er-|-skle-R-sis) is asso-ciated with damage to the endothelial liningand the formation of lipid deposits in the tuni-ca media. This is the most common form ofarteriosclerosis.

Many factors may be involved in the develop-ment of atherosclerosis. One major factor is lipidlevels in the blood. Atherosclerosis tends to develop


13

Aorta

Clamp

Aneurysm

Left atrium

Intercostalarteries

Intercostalarteries

(sewn up)

Scissors

ClampStep 1

Arteriofemoralbypass

Step 2Step 3

Sutures

Prosthesis

Step 4Step 5

Figure A-40 Repair ofan Aneurysm



13

FIGURE A-41 A Plaque Blocking a Peripheral Artery

(a) A section of a coronary artery narrowed by plaque forma-tion. (b) Sectional view of a large plaque. (LM 18)

Plaque deposit in vessel wall(a) (b)

in persons whose blood contains elevated levels ofplasma lipids, specifically cholesterol. Circulatingcholesterol is transported to peripheral tissues inlipoproteins, protein-lipid complexes. (The varioustypes of lipoproteins and their interrelationshipsare discussed in Chapter 17.) Recent evidenceindicates that many forms of atherosclerosis areassociated with either (1) low levels of apolipopro-tein-E (ApoE), a transport protein whose lipids arequickly removed by peripheral tissues, or (2) highlevels of lipo-protein(a), a low-density lipoprotein(LDL) that is removed at a much slower rate.

When ApoE levels are low, or lipoprotein(a) lev-els are high, cholesterol-rich lipoproteins remain incirculation for an extended period. Circulatingmonocytes then begin removing them from thebloodstream. Eventually the monocytes becomefilled with lipid droplets. Now called foam cells,they attach themselves to the endothelial walls ofblood vessels, where they release growth factors.These cytokines stimulate the divisions of smoothmuscle fibers near the tunica interna, thickeningthe vessel wall.

Other monocytes then invade the area, migrat-ing between the endothelial cells. As these changesoccur, the monocytes, smooth muscle fibers, andendothelial cells begin phagocytizing lipids as well.The result is a plaque, a fatty mass of tissue thatprojects into the lumen of the vessel. At this pointthe plaque has a relatively simple structure, andthere is evidence that the process can be reversedif appropriate dietary adjustments are made.

If the conditions persist, the endothelial cellsbecome swollen with lipids, and gaps appear in theendothelial lining. Platelets now begin sticking tothe exposed collagen fibers, and the combinationof platelet adhesion and aggregation leads to theformation of a localized blood clot that will furtherrestrict blood flow through the artery. The struc-ture of the plaque is now relatively complex.Plaque growth may be halted, but the structuralchanges are usually permanent.

Typical plaques can be seen in Figure A-41.Elderly individuals, especially elderly men, are

most likely to develop atherosclerotic plaques.There is evidence that estrogens may slow plaqueformation; this may account for the lower inci-dence of coronary artery disease, myocardialinfarctions (MIs), and strokes in younger women.After menopause, when estrogen productiondeclines, the risk of CAD, MIs, and strokes inwomen increases markedly.

In addition to advanced age and male sex, otherimportant risk factors include high blood cholesterollevels, high blood pressure, and cigarette smoking.Roughly 20 percent of middle-aged men have allthree of these risk factors; these individuals are fourtimes more likely to experience an MI or cardiacarrest than are other men in their age group.Although fewer women develop this condition, elder-ly women smokers with high blood cholesterol andhigh blood pressure are at much greater risk thanother women. Other factors that promote develop-ment of atherosclerosis in both men and womeninclude diabetes mellitus, obesity, and stress. Thereis also evidence that at least some forms of athero-sclerosis may be linked to chronic infection withChlamydia pneumoniae, a bacterium responsible forseveral types of respiratory infections, includingsome forms of pneumonia.

Potential treatments for atherosclerotic plaques,such as catheterization, balloon angioplasty and stents, and bypass surgery, were discussed onp. 106. In cases where dietary modifications do notlower circulating LDL levels sufficiently, there aredrug therapies that can bring them under control.Genetic engineering techniques have recently beenused to treat an inherited form of hypercholes-terolemia (high blood cholesterol) linked to exten-sive plaque formation. (The patients were unableto absorb and recycle cholesterol in the liver.) Inthis experimental procedure, circulating choles-terol levels declined after copies of appropriategenes were inserted into some of the individualsliver cells.

Without question, the best approach to athero-sclerosis is to try to avoid it by eliminating orreducing associated risk factors. Suggestionsinclude: (1) reducing the amount of dietary choles-terol and saturated fats by restricting consumptionof fatty meats (such as beef, lamb, and pork), eggyolks, and cream; (2) giving up smoking (or neverstarting to begin with); (3) checking your bloodpressure and taking steps to lower it if necessary;(4) having your blood cholesterol levels checked atannual physical examinations; (5) controlling yourweight; and (6) exercising regularly.

Problems with Venous ValveFunction EAP p. 394

Chapter 4 of the text notes that one of the conse-quences of aging is a loss of elasticity andresilience in connective tissues throughout thebody. Blood vessels are no exception, and with agethe walls of veins begin to sag. This change usually


affects the superficial veins of the legs first,because at these locations gravity opposes bloodflow. The situation is aggravated by a lack of exer-cise or an occupation requiring long hours stand-ing or sitting. Because there is no muscularactivity to help keep the blood moving, venousblood pools on the proximal (heart) side of eachvalve. As the venous walls are distorted, the valvesbecome less effective, and gravity can then pullblood back toward the capillaries. This furtherimpedes normal blood flow, and the veins becomegrossly distended. These sagging, swollen vesselsare called varicose (VAR-i-k|s) veins. Varicoseveins are relatively harmless but unsightly; surgi-cal procedures are sometimes used to remove orconstrict the offending vessels.

Varicose veins are not limited to the extremi-ties, and another common site involves a networkof veins in the walls of the anus. Pressures withinthe abdominopelvic cavity rise dramatically whenthe abdominal muscles are tensed. Straining toforce defecation can force blood into these veins,and repeated incidents leave them permanentlydistended. These distended veins, known as hem-orrhoids (HEM-|-roydz), can be uncomfortable andin severe cases extremely painful.

Hemorrhoids are often associated with preg-nancy, due to changes in circulation and abdomi-nal pressures. Minor cases can be treated by thetopical application of drugs that promote contrac-tion of smooth muscles within the venous walls.More severe cases may require the surgical removalor destruction of the distended veins.

Hypertension and HypotensionEAP p. 395

Elevated blood pressure is considered primaryhypertension, or essential hypertension, if noobvious cause can be determined. Known risk fac-tors include a hereditary history of hypertension,sex (males are at higher risk), high plasma choles-terol, obesity, chronic stresses, and cigarette smok-ing. Secondary hypertension appears as theresult of abnormal hormonal production outsidethe cardiovascular system. For example, a condi-tion resulting in excessive production of antidiuret-ic hormone (ADH), renin, aldosterone, orepinephrine will probably produce hypertension,and many forms of kidney disease will lead tohypertension caused by fluid retention or excessiverenin production.

Hypertension significantly increases the workload on the heart, and the left ventricle graduallyenlarges. More muscle mass requires a greater oxy-gen demand, and when the coronary circulationcannot keep pace, symptoms of coronary ischemiaappear.

Increased arterial pressures also place a physi-cal stress on the walls of blood vessels throughoutthe body. This stress promotes or accelerates thedevelopment of arteriosclerosis and increases the

risks of aneurysms, heart attacks, and strokes.Vessels supplying the retinas of the eyes are oftenaffected, and hemorrhages and associated circula-tory changes can produce disturbances in vision.Because these vessels are examined in a normalphysical exam, retinal changes may provide thefirst evidence that hypertension is affecting periph-eral circulation.

One of the most difficult aspects of hyperten-sion is that there are usually no obvious symp-toms. As a result, clinical problems do not appearuntil the condition has reached the crisis stage.There is, therefore, considerable interest in earlydetection and prompt treatment of hypertension.

Treatment consists of a combination of life-stylechanges and physiological therapies. Quittingsmoking, getting regular exercise, and restrictingdietary intake of salt, fats, and calories will improveperipheral circulation, prevent increases in bloodvolume and total body weight, and reduce plasmacholesterol levels. These strategies may be sufficientto control hypertension if it has been detectedbefore significant cardiovascular damage hasoccurred. Therapies usually involve antihyperten-sive drugs, such as calcium channel blockers, beta-blockers, diuretics, and vasodilators, singly or incombination. Beta-blockers eliminate the effects ofsympathetic stimulation on the heart, and theunopposed parasympathetic system lowers the rest-ing heart rate and blood pressure. Diuretics pro-mote the loss of water and sodium ions at thekidneys, lowering blood volume, and vasodilatorsfurther reduce blood pressure. A new class of anti-hypertensive drugs lowers blood pressure by pre-venting the production of angiotensin II. Theseangiotensin-converting enzyme (ACE) inhibitors,such as captopril, are being used to treat chronichypertension and congestive heart failure.

In hypotension, blood pressure declines, andperipheral systems begin to suffer from oxygen andnutrient deprivation. One clinically important formof hypotension can develop following the administra-tion of antihypertensive drugs. Problems may appearwhen the individual changes position, going fromlying down to sitting, or sitting to standing. Normallyeach time you sit or stand, blood pressure in thecarotid sinus drops, for the heart must suddenlycounteract gravity to push blood up to the brain.The fall in pressure triggers the carotid reflex, andblood pressure returns to normal. But if the carotidresponse is blunted by beta-blockers or other drugs,blood pressure at the brain may fall so low that theindividual becomes weak, dizzy, disoriented, orunconscious. This condition is known as orthostat-ic hypotension (|r-tho-STAT-ik; orthos, straight +statikos, causing to stand), or simply orthostasis(|r-th|-ST-sis). Most readers will have experiencedbrief episodes of orthostasis when standing up sud-denly after reclining for an extended period. Thecarotid reflex frequently slows with age, and olderpeople learn to sit and stand more carefully to avoidthe effects of orthostatic hypotension.


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Shock EAP p. 404Shock is an acute circulatory crisis marked by lowblood pressure (hypotension) and inadequateperipheral blood flow. Severe and potentially fatalsymptoms develop as vital tissues become starvedfor oxygen and nutrients. Common causes of shockare (1) a fall in cardiac output after hemorrhaging orother fluid losses, (2) damage to the heart, (3) exter-nal pressure on the heart, and (4) extensive periph-eral vasodilation.

CIRCULATORY SHOCK A severe loss of blood vol-ume produces symptoms of circulatory shock.Symptoms of circulatory shock appear after fluidlosses of about 30 percent of the total blood vol-ume. The cause can be hemorrhaging or fluid loss-es to the environment, as in dehydration or aftersevere burns. All cases of circulatory shock sharethe same basic symptoms:

1. Hypotension, with systolic pressures below 90mm Hg.

2. Pale, cool, and moist (clammy) skin. The skinis pale and cool because of peripheral vasocon-striction; the moisture reflects sympatheticactivation of the sweat glands.

3. Frequent confusion and disorientation, due toa fall in blood pressure at the brain.

4. Rapid, weak pulse.

5. No urination, because the reduced blood flowto the kidneys slows or stops urine production.

6. A drop in blood pH (acidosis), due to lactic acidgeneration in oxygen-deprived tissues.

Circulatory shock is often divided into compen-sated, progressive, and irreversible stages.

THE COMPENSATED STAGE (STAGE I) Duringthe compensated stage homeostatic adjustmentscan cope with the situation; the short-term andlong-term responses detailed in Figure A-42 arepart of the compensation process. During the peri-od of compensation, peripheral blood flow isreduced but remains within tolerable limits.

THE PROGRESSIVE STAGE (STAGE II) Whenblood volume declines by more than 35 percent, theindividual enters the progressive stage of circulatoryshock. Homeostatic mechanisms are now unable tocope with the situation. Despite sustained vasocon-striction and the mobilization of the venous reserve,blood pressure remains abnormally low, venousreturn is reduced, and cardiac output is inadequate.A vicious cycle begins when the low cardiac outputcauses myocardial damage. This damage leads to afurther reduction in cardiac output and subsequentreductions in blood pressure and venous return. Thesequence is diagrammed in Figure A-42a.

When the mean arterial blood pressure falls toabout 50 mm Hg, carotid sinus baroreceptors trigger

a massive activation of the vasomotor centers. Inessence, the goal now is to preserve the circulationto the brain at any cost. Blood flow to cerebral ves-sels is not affected, and the blood pressure in thecarotid arteries remains relatively high (70 mm Hg).But in other organs sympathetic output causes asustained and maximal vasoconstriction. This reflex,called the central ischemic response, reducesperipheral circulation to an absolute minimum.

The central ischemic response is a last-ditcheffort that maintains adequate blood flow to thebrain at the expense of other tissues. Unlessprompt treatment is provided, the condition willsoon prove fatal. Treatment must concentrate on(1) preventing further fluid losses and (2) giving atransfusion of whole blood, plasma expanders, orblood substitutes.

THE IRREVERSIBLE STAGE (STAGE III) In theabsence of treatment, progressive shock will soonturn into irreversible shock (Figure A-42b). At thispoint, conditions in the heart, liver, kidneys, andCNS are rapidly deteriorating to the point thatdeath will occur, even with medical treatment.

Irreversible shock begins when conditions in thetissues become so abnormal that the arteriolarsmooth muscles and precapillary sphinctersbecome unable to contract, despite the commandsof the vasomotor center. The result is a widespreadperipheral vasodilation and an immediate and fataldecline in blood pressure. This event is called circu-latory collapse. The blood pressure in many tis-sues then falls so low that the capillaries collapselike deflating balloons. Blood flow through thesecapillary beds then stops completely, and the cellsin the affected tissues die. The dying cells releasemore abnormal chemicals, and the effect quicklyspreads throughout the body.

Other Types of Shock EAP p. 404

Although the text focuses on circulatory shockcaused by low blood volume, shock can developwhen the blood volume is normal. Cardiogenic(kar-d-|-JEN-ik) shock occurs when the heartbecomes unable to maintain a normal cardiac out-put. The most common cause is failure of the leftventricle as a result of a myocardial infarction.Between 5 and 10 percent of patients surviving aheart attack must be treated for cardiogenic shock.The use of thrombolytic drugs, such as t-PA andstreptokinase, can be very effective in restoringcoronary circulation and ventricular function,thereby relieving the peripheral symptoms.Cardiogenic shock may also be the result ofarrhythmias, valvular heart disease, advancedcoronary artery disease, cardiomyopathy, or ven-tricular arrhythmias (see p. 109).

In obstructive shock, ventricular output isreduced because tissues or fluids are restrictingthe expansion and contraction of the heart. Forexample, fluid buildup in the pericardial cavity


(cardiac tamponade) due to infection or trauma cancompress the heart and limit ventricular filling.

Distributive shock results from a widespread,uncontrolled vasodilation. This produces a dramat-ic fall in blood pressure that leads to a reduction inblood flow and the onset of shock. Three importantexamples are neurogenic shock, septic shock, andanaphylactic shock.

Neurogenic (noo-r|-JEN-ik) shock can becaused by general or spinal anesthesia and bytrauma or inflammation of the brain stem. Theunderlying problem is damage to the vasomotorcenter or to the sympathetic tracts or nerves, lead-ing to a loss of vasomotor tone.

Septic shock results from the massive releaseof endotoxins, poisons derived from the cell wallsof bacteria during a systemic infection. These com-pounds cause a vasodilation of precapillarysphincters throughout the body, resulting in a

drop in peripheral resistance and a decline inblood pressure. Symptoms of septic shock general-ly resemble those of other types of shock, but theskin is flushed and the individual may have a highfever. For this reason septic shock is also knownas warm shock. One interesting example of sep-tic shock, called toxic shock syndrome (TSS),results from an infection by the bacteriumStaphylococcus aureus. This disease was unrecog-nized before 1978, when it appeared in a group ofchildren. Since that time there have been morecases in the United States, most (95 percent)affecting women. Although other sources of infec-tion are possible, infection most often appears tooccur during menstruation, and the chances ofinfection are increased with the use of superab-sorbent tampons. (The brands involved have beentaken off the market, and the incidence hasdeclined steadily since 1980.)


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Severe reductionof blood volume

Decreasedcardiacoutput

Decreasedarterial

pressure

Decreasedperipheralblood flow

Tissueoxygen

starvation

Increased lacticacid

Decreased pHIncreased PCO2

Clottingwithin

vessels

Decreasedvenousreturn Decreased

cardiacblood flow

Damageto heartmuscle

POSITIVE FEEDBACKLOOP 2

POSITIVEFEEDBACK

LOOP 3

POSITIVEFEEDBACK

LOOP 1

HOMEOSTATICFAILURES

Increasedcapillary

permeability

Sympatheticactivation and

central ischemicresponse

If BP falls below50 mm Hg

If damage reachescritical levels

(a) Progessive shock

FIGURE A-42 Shock

(a) The progressive stage is characterized by a gradualdecline in systemic blood pressure, tissue blood flow,and cardiac output. (b) The irreversible stage involvesa series of integrated chain reactions leading to arapid decline in cardiac output, a dramatic and irre-versible fall in blood pressure,circulatory collapse, and even-tual death.



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tricular muscle (see the discussion of myocardialinfarctions on p. 107) or high arterial pressures(hypertension, p. 112). In effect, the left ventriclecan no longer keep pace with the right ventricle,and blood backs up into the pulmonary circuit.This venous congestion is responsible for the termcongestive heart failure. The right ventricle nowneeds to works harder, elevating pulmonary arteri-al pressures and forcing blood through the lungsand into the weakened left ventricle.

At the capillaries of the lungs, arterial andvenous pressures are now elevated. This elevatedpressure pushes additional fluid out of the capillariesand into the interstitial fluids. The fluid buildup andcompression of the airways reduces the effectivenessof gas exchange, leading to shortness of breath, oftenthe first obvious sign of congestive failure. This fluidbuildup begins at a postcapillary pressure of around25 mm Hg. At a capillary pressure of around 30 mmHg, fluid not only enters the tissues of the lungs butcrosses the alveolar walls and begins filling the air-spaces. This condition is called pulmonary edema.

Over time, the less muscular right ventriclemay become unable to generate enough pressure toforce blood through the pulmonary circuit. Venouscongestion now occurs in the systemic circuit, andcardiac output declines further. When the reduc-tion in systemic pressures lowers blood flow to thekidneys, renin and erythropoietin are released.This in turn elevates blood volume, due toincreased salt and water retention at the kidneys,and accelerated red blood cell production. This risein blood volume actually complicates the situation,as it tends to increase venous congestion andcause widespread edema.

The increased volume of blood in the venoussystem leads to a distension of the veins, makingsuperficial veins more prominent. When the heartcontracts, the rise in pressure at the right atriumproduces a pressure pulse in the large veins. Thisvenous pulse can be seen and palpated most easilyover the right external jugular vein.

Treatment of congestive heart failure oftenincludes:

Restriction of salt intake. The expression waterfollows salt applies here, because when sodi-um and chloride ions are absorbed acros

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