Ch 10, 11, 12 Pathology

Chapter 10
Blood and Circulatory System
Disorders

Review of the Circulatory System
 The circulatory system consists of the
cardiovascular system and lymphatic system
 This chapter will cover the blood vessels, the
blood, and associated disorders.
•Copyright © 2014, 2011, 2006 by Saunders, an imprint of Elsevier, Inc. •2

Blood Vessels
 Arteries—arterioles
 Transport blood away from heart
 Veins—venules
 Return blood back to the heart
 Capillaries
 Microcirculation within tissues
 Systemic circulation
 Exchange of gases, nutrients, and wastes in
tissues
 Pulmonary circulation
 Gas exchange in lungs

Blood Vessels (Cont.)

Histology of Arteries and Veins
 Tunica intima—endothelium (simple
squamous epithelium)
 Tunica media—middle layer, mostly smooth
muscle
 Tunica adventitia (externa)—connective
tissue with fibrocytes, collagen (type I), and
elastic fibers

Blood

Composition of Blood
 Plasma
 Plasma proteins
 Cellular component
 Erythrocytes
 Leukocytes
 Thrombocytes (platelets)

Components of Blood
and Their Functions

Hematopoiesis

Normal Red Blood Cells

Erythrocytes (Red Blood Cells)
 Biconcave flexible discs
 No nucleus in mature state
 Contains hemoglobin
 Globin portion
 Heme group
 Life span—»120 days
 Erythropoietin produced in the kidney
stimulates erythrocyte production.

Normal Blood Cells

Breakdown of Hemoglobin

Blood Clotting—Hemostasis
 Three steps:
 Vasoconstriction or vascular spasm after injury
 Platelet clot
 Coagulation mechanism
 Plasmin will eventually break down the blood
clot.

Hemostasis and Anticoagulant
Drugs

Blood Typing
Blood typing is based on antigens in the plasma
membrane of the erythrocytes.
 ABO system
 Based on the presence or absence of specific
antigens
 Antibodies in the blood plasma
 Rh system
 Antigen D in plasma membrane: Rh+
 Absence of antigen D: Rh-

ABO Blood Groups

Diagnostic Tests
 Complete blood count (CBC)
 Includes total red blood cells (RBCs), white blood
cells (WBCs), and platelets
 Leukocytosis (increased WBCs)
• Associated with inflammation or infection
 Leukopenia (decreased WBCs)
• Associated with some viral infections, radiation,
chemotherapy
 Increased eosinophils
• Common in allergic responses
 Differential count for WBCs

Diagnostic Tests (Cont.)
 Morphology
 Observed with blood smears
 Shows size, shape, uniformity, maturity of cells
• Different types of anemia can be distinguished.
 Hematocrit
 Percent by volume of cellular elements in blood
 Hemoglobin
 Amount of hemoglobin per unit volume of blood
 Mean corpuscular volume (MCV)
• Indicates the oxygen-carrying capacity of blood

Diagnostic Tests (Cont.)
 Reticulocyte count
 Assessment of bone marrow function
 Chemical analysis
 Determines serum levels of components, such as iron,
vitamin B12, folic acid, cholesterol, urea, glucose
 Bleeding time
 Measures platelet function
 Prothrombin time (PT) and partial thromboplastin
time (PTT)
 Measure function of various factors in coagulation process
 International normalized ratio (INR) is a standardized
version.

Blood Therapies
 Whole blood, packed red blood cells, packed
platelets
 For severe anemia or thrombocytopenia
 Plasma or colloid volume-expanding solutions
 To maintain blood volume
 Artificial blood products
 Compatible with all blood types
 None of them can perform all the complex
functions of normal whole blood.

Blood Therapies (Cont.)
 Epoetin alfa
 Artificial form of erythropoietin
• Before certain surgical procedures
• Anemia related to cancer
• Chronic renal failure
 Bone marrow or stem cell transplantation
 Close tissue match necessary
• Treatment of some cancers
• Severe immunodeficiency
• Severe blood cell diseases
 Drug treatment
 Aids in the clotting process

Blood Dyscrasias

The Anemias
 Anemia causes a reduction in oxygen
transport.
 Basic problem is hemoglobin deficit
 Oxygen deficit leads to:
 Less energy production in all cells
• Cell metabolism and reproduction diminished
 Compensation mechanisms
• Tachycardia and peripheral vasoconstriction
 General signs of anemia
• Fatigue, pallor (pale face), dyspnea, tachycardia

The Anemias (Cont.)
 Oxygen deficit leads to:
 Decreased regeneration of epithelial cells
• Digestive tract becomes inflamed and ulcerated, leading
to stomatitis
• Inflamed and cracked lips
• Dysphasia
• Hair and skin may show degenerative changes.
 Severe anemia may lead to angina or congestive
heart failure (CHF).

Iron Deficiency Anemia
 Insufficient iron impairs hemoglobin
synthesis.
 Microcytic, hypochromic RBCs
• Result of low hemoglobin concentration in cells
 Very common
 Ranges from mild to severe
 Occurs in all age groups, but more common in
women of childbearing age
 Estimated that one in five women is affected
• Proportion increases for pregnant women
 Frequently sign of an underlying problem

Iron Deficiency Anemia—Blood
Smear

Iron Deficiency Anemia: Causes
 Dietary intake of iron below minimum
requirement
 Chronic blood loss
 As from bleeding, ulcer, hemorrhoids, cancer
 Impaired duodenal absorption of iron
 In many disorders, malabsorption syndromes
 Severe liver disease
 May affect iron absorption as well as storage

Iron Deficiency Anemia: Signs
and Symptoms
 Pallor of skin and mucous membranes
 Fatigue, lethargy, cold intolerance
 Irritability
 Degenerative changes
 Stomatitis and glossitis
 Menstrual irregularities
 Delayed healing
 Tachycardia, heart palpitations, dyspnea,
syncope

Pernicious Anemia: Vitamin B12
Deficiency
 Basic problem is lack of absorption of vitamin
B12 because of lack of intrinsic factor
 Intrinsic factor secreted by gastric mucosa
 Required for intestinal absorption of vitamin B12
 Characterized by very large, immature,
nucleated erythrocytes
 Carry less hemoglobin
 Shorter life span

Deficiency (Cont.)
 Dietary insufficiency is very rarely a cause.
 Genetic factors have been implicated.
 More common in light-skinned women of northern
European ancestry
 Often accompanies chronic gastritis
 May also be an outcome of gastric surgery

Development of Pernicious
Anemia

Vitamin B12 and Nerve Cells
 Vitamin B12 is needed for the function and
maintenance of neurons.
 Significant deficit of the vitamin will cause
symptoms in the peripheral nerves.
 These may be reversible.

Vitamin B12 Deficiency

Deficiency (Cont.)
 Manifestations in addition to those typical for
anemias
 Tongue is typically enlarged, red, sore, and shiny.
 Digestive discomfort, often with nausea and
diarrhea
 Feeling of pins and needles, tingling in limbs
 Diagnostic tests
 Microscopic examination (erythrocytes)
 Bone marrow examination (hyperactive)
 Vitamin B12 serum levels below normal
 Presence of hypochlorhydria or achlorhydria
• Presence of gastric atrophy

Aplastic Anemia
 Impairment or failure of bone marrow
 May be temporary or permanent
 Often idiopathic but possible causes include:
 Myelotoxins
• Radiation, industrial chemicals, drugs
 Viruses
• Particularly hepatitis C
 Genetic abnormalities
• Myelodysplastic syndrome
• Fanconi’s anemia

Aplastic Anemia (Cont.)
 Blood counts indicate pancytopenia.
 Anemia, leukopenia, thrombocytopenia
 Bone marrow biopsy may be required.
 Erythrocytes often appear normal.
 Identification of cause and prompt treatment
needed for bone marrow recovery
 Removal of any bone marrow suppressants
 Failure to identify cause and treat effectively is
life-threatening!

Hemolytic Anemia
 Results from excessive destruction of RBCs
 Causes
 Genetic defects
 Immune reactions
 Changes in blood chemistry
 Infections such as malaria
 Toxins in the blood
 Antigen-antibody reactions
• Incompatible blood transfusion
• Erythroblastosis fetalis

Sickle Cell Anemia
 Genetic condition
 Autosomal
 Incomplete dominance
 Anemia occurs in homozygous recessive.
 Diagnostic testing is available.
 More common in individuals of African ancestry
• Heterozygous condition is somewhat protective against
malaria.
• One in ten African Americans is heterozygous for the
trait.

Sickle Cell Anemia (Cont.)

 Abnormal hemoglobin (HbS)
 Sickle cell crisis occurs whenever oxygen
levels are lowered.
 Altered hemoglobin is unstable and changes
shape in hypoxemia.
 Sickle-shaped cells are too large to pass
through the microcirculation.
 Obstruction leads to multiple infarctions and
areas of necrosis.

 Multiple infarctions affect brain, bones,
organs
 In addition to basic anemia:
 Hyperbilirubinemia, jaundice, gallstones
• Caused by high rate of hemolysis
 Clinical signs
 Do not usually appear until the child is about 12
months old

Sickle Cell Anemia: Signs and
Symptoms
 Severe pain because of ischemia of tissues and
infarction
 Pallor, weakness, tachycardia, dyspnea
 Hyperbilirubinemia—jaundice
 Splenomegaly
 Vascular occlusions and infarctions
 In lungs
• Acute chest syndrome
 Smaller blood vessels
• Hand-foot syndrome
 Delay of growth and development
 Congestive heart failure

 Blood test
• Hemoglobin electrophoresis
 Prenatal DNA analysis
 Treatment
 Hydroxyurea has reduced the frequency of this
crisis.
 Dietary supplementation with folic acid
 Bone marrow transplantation
 Immunization in children
• Against pneumonia, influenza, meningitis

Comparison of Selected Anemias

Polycythemia
 Primary polycythemia—polycythemia vera
 Increased production of erythrocytes and other
cells in the bone marrow
 Neoplastic disorder
 Serum erythropoietin levels are low.
 Secondary polycythemia—erythrocytosis
 Increase in RBCs in response to prolonged
hypoxia
 Increased erythropoietin secretion
 Compensation mechanism to provide increased
oxygen transport

Polycythemia: Signs and
Symptoms
 Distended blood vessels, sluggish blood flow
 Increased blood pressure
 Hypertrophied heart
 Hepatomegaly
 Splenomegaly
 Dyspnea
 Headaches
 Visual disturbances
 Thromboses and infarctions

Polycythemia (Cont.)
 Increased cell counts
 Increased hemoglobin and hematocrit values
 Hypercellular bone marrow
 Hyperuricemia
 Treatment
 Identify cause
 Drugs or radiation
• Suppression of bone marrow activity
 Periodic phlebotomy

Indications of Blood-Clotting
Disorders
 Persistent bleeding from gums
 Repeated epistaxis
 Petechiae
 Pinpoint, flat, red spots on skin and mucous
membrane
 Frequent purpura and ecchymosis
 More than normal bleeding in trauma
 Bleeding into joint—hemarthroses
 Swollen, red, painful
 Hemoptysis

Blood-Clotting Disorders
 Hematemesis
 Coarse brown particles (coffee ground emesis)
 Blood in feces
 Black or occult
 Anemia
 Feeling faint and anxious
 Low blood pressure
 Rapid pulse

Petechiae

Hemophilia A
 Classic hemophilia
 Deficit or abnormality of factor VIII
 Most common inherited clotting disorder
 X-linked recessive trait
 Manifested in men, carried by women
 Varying degrees of severity
 Prolonged bleeding after minor tissue trauma
 Spontaneous bleeding into joints
 Possible hematuria or blood in feces

Hemophilia A (Cont.)
 Bleeding time and PT normal
 PTT, activated PTT (aPTT), coagulation time
prolonged
 Serum levels of factor VIII are low.
 Treatment
 Desmopressin (DDAVP)
 Replacement therapy for factor VIII

Von Willebrand’s Disease
 Most common hereditary clotting disorder
 Three major types
 Signs and symptoms include:
 Skin rashes
 Frequent nosebleeds
 Easy bruising
 Bleeding of gums
 Abnormal menstrual bleeding
 Treatment based on type and severity

Disseminated Intravascular
Coagulation
 Involves both excessive bleeding and clotting
 Excessive clotting in circulation
 Thrombi and infarcts occur.
 Clotting factors are reduced to a dangerous level.
 Widespread, uncontrollable hemorrhage results.
 Very poor prognosis, with high fatality rate
 Complication of many primary problems
 Obstetrical complications, such as abruptio placentae
 Infections
 Carcinomas
 Major trauma

Disseminated Intravascular
Coagulation (Cont.)

Thrombophilia
 Group of inherited or acquired disorders
 Risk of abnormal clots in veins or arteries
 Blood testing for clotting factor levels and
abnormal antibody levels
 Causative condition should be treated.

Myelodysplastic Syndromes
 Diseases that involve inadequate production
of cells by the bone marrow
 Signs and symptoms include anemia;
dependent on type of deficiencies that occur
 May be idiopathic or occur after
chemotherapy or radiation treatment
 Treatment measures depend on deficiency
type.
 Transfusion replacement
 Chelation therapy to reduce iron overload
 Bone marrow transplantation

The Leukemias
 Group of neoplastic disorders involving white blood
cells
 Uncontrolled WBC production in bone or lymph
nodes
 Other hemopoietic tissues are reduced.
 One or more types of leukocytes are undifferentiated,
immature, and nonfunctional.
 Large numbers released into general circulation
 Infiltrate lymph nodes, spleen, liver, brain, other
organs

The Leukemias (Cont.)
 Acute leukemias (ALL and AML)
 High proportion of immature nonfunctional cells in
bone marrow and peripheral circulation
 Onset usually abrupt , marked signs of
complications
• Occurs primarily in children and younger adults
 Chronic leukemias (CLL and CML)
 Higher proportion of mature cells
 Insidious onset
 Mild signs and better prognosis
• Common in older adults

Acute Lymphocytic Leukemia

Signs and Symptoms of
Acute Leukemia
 Usual signs at onset
 Frequent or uncontrolled infections
 Petechiae and purpura
 Signs of anemia
 Severe and steady bone pain
 Weight loss, fatigue, possible fever
 Enlarged lymph nodes, spleen, liver
 Headache, visual disturbances, drowsiness,
vomiting

The Leukemias (Cont.)
 Peripheral blood smears
• Immature leukocytes and altered numbers of WBCs
• Numbers of RBCs and platelets decreased
• Bone marrow biopsy for confirmation
 Treatment
 Chemotherapy
 ALL in young children responds well to drugs
 Biological therapy (interferon)
• May be used to stimulate the immune system

Complications of Leukemia
 Opportunistic infections, including pneumonia
 Sepsis
 Hemorrhage
 Liver failure
 Renal failure
 CNS depression and coma

Multiple Myeloma
 Neoplastic disease that involves increased
production of plasma cells in bone marrow
 Unknown cause
 Occurs in older adults
 Production of other blood cells is impaired
 Multiple tumors in bone
 Loss of bone
 Severe bone pain
 Prognosis poor, with short life expectancy

Multiple Myeloma of the Skull

Chapter 11
Lymphatic System Disorders

Review of the Lymphatic System

Structures
 Lymphatic vessels
 Lymphoid tissue
 Lymphatic nodules
 Tonsils
 Lymph nodes
 Spleen
 Thymus gland
 Red bone marrow

Function
 Return of excess interstitial fluid to the
cardiovascular system
 Vessels empty into the subclavian veins.
 Filter and destroy foreign material
 Initiate the immune response
 Absorb lipids from the GI tract

Lymphatic Vessels
 Originate as capillaries in contact with blood
capillary bed in tissues
 Lymph collected by lymphatic trunks
 Lymphatic trunks empty into ducts
 Ducts empty into the subclavian veins

Lymph
 Clear, watery, isotonic fluid
 Circulates in lymphatic vessels
 Resembles blood plasma, with a lower
protein content
 Returned to the cardiovascular system

Lymphatic Disorders

Lymphomas
 Malignant neoplasms involving lymphocyte
proliferation in lymph nodes
 Specific causes not identified
 Higher risk in adults who received radiation during
childhood
 Two main disorders
 Hodgkin’s lymphoma
 Non-Hodgkin’s lymphoma
• Distinguished by multiple node involvement
• Nonorganized, with widespread metastases

Hodgkin’s Lymphoma
 Initially involves a single lymph node
 Cancer spreads to adjacent nodes
 To organs via lymphatics
 T lymphocytes seem to be defective; lymphocyte
count decreased
 Presence of Reed-Sternberg cells
• Giant cells present in lymph node
 Four subtypes
• Based on cell found at biopsy

Reed-Sternberg Cell

Hodgkin’s Lymphoma (Cont.)
 Symptoms
 First indicator—usually a painless enlarged lymph
node
 Later—splenomegaly and enlarged lymph nodes
 General signs of cancer
• Weight loss, anemia, low-grade fever, night sweats;
fatigue may develop.
 Treatment
 Radiation, chemotherapy, surgery

 Staging and prognosis dependent on:
 Number of nodes involved
 Location of nodes involved

Non-Hodgkin’s Lymphoma
 Increasing in incidence
 Partially caused by HIV infection
 Similar to Hodgkin’s lymphoma
 Clinical signs and symptoms are similar.
 More difficult to treat when tumors are not
localized
 Initial manifestation—enlarged, painless
lymph node

Multiple Myeloma
 Neoplastic disease that involves increased
production of plasma cells in bone marrow
 Unknown cause
 Occurs in older adults
 Production of other blood cells is impaired
 Multiple tumors in bone
 Loss of bone
 Severe bone pain
 Prognosis poor, with short life expectancy

Multiple Myeloma of the Skull

Signs and Symptoms of Multiple
Myeloma
 Onset usually insidious
 Malignancy well advanced before diagnosis
 Pain caused by bone involvement
 Anemia and bleeding tendency
 Impaired kidney function and eventually
failure
 Chemotherapy to encourage remission
 Median survival, 3 years

Lymphedema
 Obstruction of lymphatic vessels
 Most common form is congenital
 Extremities swell because of lymph
accumulation
 Treatment:
 Diuretics
 Bed rest
 Massage of affected area
 Elevation of affected extremity

Elephantiasis
 Lymphedema
 Caused by blockage because of parasitic infection
 Significant swelling of affected extremity
 Extreme swelling of legs, breast, and/or genitalia
 Thickening of subcutaneous tissue
 Frequent infections
 Skin ulcerations
 Fever
 Treatment—medication regimen to kill
parasite

Castleman’s Disease
 Rare illness
 Involves overgrowth of lymphoid tissue
 Two types
 Unicentric form
• Affects a single lymph node
 Multicentric form
• Affects multiple lymph nodes and tissue—may have
severe effects on the immune system
 Signs, symptoms, and treatment depend on
the type of the disease

Chapter 12
Cardiovascular System Disorders

Review of the Normal
Cardiovascular System

Path of Erythrocyte in the
Circulation

Circulatory System
 The circulatory system is composed of:
 Vessels
 Fluid
 Pump
 Blood flows from systemic to pulmonary to
systemic circulation

Heart: Anatomy
 Located in the mediastinum
 Located in the pericardial sac
 Parietal pericardium
 Epicardium (visceral pericardium)
 Pericardial cavity
 Myocardium
 Endocardium
 Heart valves
 Atrioventricular valves
 Semilunar valves
 Septum

Heart: Conduction System
 Conduction pathway
 Sinoatrial (SA) node
• Pacemaker
• Sinus rhythm
 Atrioventricular (AV) node
 Located in floor of the right atrium
 AV bundle (bundle of His)
 Right and left branches
 Purkinje fibers
 Terminal fibers

Heart: Conduction System (Cont.)
 Electrocardiogram (ECG)
 P wave
• Depolarization of atria
 QRS wave
• Depolarization of ventricles
 T wave
• Repolarization of ventricles

Control of the Heart
 Cardiac control center in medulla oblongata
 Controls rate and force of contraction
 Located in the medulla
 Baroreceptors
 Detect changes in blood pressure
 Located in the aorta and internal carotid arteries
 Sympathetic stimulation (cardiac accelerator nerve)
 Increases heart rate (tachycardia)
 Parasympathetic stimulation (cranial nerve [CN] X;
vagus nerve)
 Decreases heart rate (bradycardia)

Factors that Increase Heart Rate
 Increased thyroid hormones or epinephrine
 Elevated body temperature, infection
 Example: Fever
 Increased environmental temperature
 Especially in high humidity
 Exertion or exercise
 Smoking
 Stress response
 Pregnancy
 Pain

Coronary Circulation
 Right and left coronary arteries
 Branch of aorta immediately distal to the aortic
valve
 Part of the systemic circulation
 Left coronary artery divides into:
 Left anterior descending or interventricular artery
 Left circumflex artery

Coronary Circulation (Cont.)
 Right coronary artery branches
 Right marginal artery
 Posterior interventricular artery
 Many small branches extend from these
arteries to supply the myocardium and
endocardium.
 Collateral circulation is extremely limited.

Major Coronary Arteries

Cardiac Cycle
 Diastole
 Relaxation of myocardium required for filling chambers
 Systole
 Contraction of myocardium provides increase in pressure to
eject blood
 Cycle begins with
 Atria relaxed, filling with blood ® AV valves open ® blood
flows into ventricles ® atria contract, remaining blood
forced into ventricles ® atria relax ® ventricles contract ®
AV valves close ® semilunar valves open ® blood into
aorta and pulmonary artery ® ventricles relax

Cardiac Cycle (Cont.)

Heart Sounds
 “Lubb-dub”
 “Lubb”—closure of AV valves
 “Dub”—closure of semilunar valves
 Murmurs
 Caused by incompetent valves
 Pulse
 Indicates heart rate
 Pulse deficit
 Difference in rate between apical and radial pulses

ECG Strip Chart Recordings

Cardiac Function
 Cardiac output (CO)
 Blood ejected by a ventricle in 1 minute
 CO = SV ´ HR (heart rate)
 Stroke volume (SV)
 Volume of blood pumped out of ventricle—
contraction
 Preload
 Amount of blood delivered to heart by venous
return
 Afterload
 Force required to eject blood from ventricles
• Determined by peripheral resistance in arteries

Cardiac Output

Blood Pressure
 Systolic pressure
 Exerted when blood is ejected from ventricles
(high)
 Diastolic pressure
 Sustained pressure when ventricles relax (lower)
 Blood pressure (BP) is altered by cardiac output,
blood volume, and peripheral resistance to blood
flow.

Blood Pressure (Cont.)
 Changes in blood pressure
 Sympathetic branch of ANS
• Increased output → vasoconstriction and increased BP
• Decreased output → vasodilation and decreased BP
 BP is directly proportional to blood volume.
 Hormones
• Antidiuretic hormone (↑ BP); aldosterone (↑ blood
volume, ↑ BP); renin-angiotensin-aldosterone
(vasoconstriction; ↑ BP)

Blood Pressure (Cont.)

Heart Disorders

Diagnostic Tests for
Cardiovascular Function
 Electrocardiography
 Useful in the initial diagnosis and monitoring of
dysrhythmias, myocardial infarction, infection, pericarditis
 Auscultation
 Determination of valvular abnormalities or abnormal shunts
of blood that cause murmurs
 Detected by listening through a stethoscope
 Echocardiography
 Used to record heart valve movements, blood flow, and
cardiac output
 Exercise stress tests
 Used to assess general cardiovascular function

Cardiovascular Function (Cont.)
 Chest x-ray films
 Used to show shape and size of the heart
• Nuclear imaging
• Tomographic studies
 Cardiac catheterization
 Measures pressure and assesses valve and heart
function
• Determines central venous pressure and pulmonary
capillary wedge pressure
 Angiography
 Visualization of blood flow in the coronary arteries

Cardiovascular Function (Cont.)
 Doppler studies
 Assess blood flow in peripheral vessels
 Record sounds of blood flow or obstruction
 Blood tests
 Assess levels of serum triglycerides, cholesterol,
sodium, potassium, calcium, other electrolytes
 Arterial blood gas determination
 Checks the current oxygen level and acid-base
balance

General Treatment Measures for
Cardiac Disorders
 Dietary modifications
 To decrease total fat intake
 General weight reduction
 Reduce salt intake
 Regular exercise program
 Increases high-density lipoprotein levels
 Lowers serum lipid levels
 Reduces stress levels
 Cessation of smoking
 Decreases risk of coronary disease

Cardiac Disorders: Drug Therapy
 Vasodilators
 Reduction of peripheral resistance
 Beta blockers
 Treatment of hypertension and dysrhythmias
 Reduction of angina attacks
 Calcium channel blockers
 Decrease cardiac contractility
 Antihypertensives and vasodilators
 Prophylactic against angina

(Cont.)  Digoxin
 Treatment for heart failure
 Antidysrhythmic drug for atrial dysrhythmias
 Antihypertensive drugs
 Used to lower blood pressure
 Adrenergic blocking drugs
 Act on SNS centrally or on the periphery
 Angiotensin-converting enzyme (ACE)
inhibitors
 Block conversion of angiotensin I to angiotensin II

(Cont.)  Diuretics
 Remove excess sodium and/or water.
 Treat high BP and congestive heart failure.
 Anticoagulants
 Reduce risk of blood clot formation
 Cholesterol-lowering drugs
 Reduce low-density lipoprotein and cholesterol
levels

Selected Cardiovascular Drugs

Coronary Artery Disease (CAD) or
Ischemic Heart Disease (IHD) or
Acute Coronary Syndrome

Arteriosclerosis and
Atherosclerosis
 Arteriosclerosis
 General term for all types of arterial changes
• Degenerative changes in small arteries and arterioles
• Loss of elasticity
• Lumen gradually narrows and may become obstructed
• Cause of increased BP
 Atherosclerosis
 Presence of atheromas in large arteries
• Plaques consisting of lipids, calcium, and possible clots
• Related to diet, exercise, and stress

Normal (top) Versus
Atherosclerotic Aorta (bottom)

Lipid Transport
 Lipids are transported in combination with
proteins.
 Low-density lipoprotein (LDL)
 Transports cholesterol from liver to cells
 Major factor contributing to atheroma formation
 High-density lipoprotein (HDL)
 Transports cholesterol away from the peripheral
cells to liver—“good” lipoprotein
 Catabolism in liver and excretion

Possible Consequences of
Atherosclerosis

Development of an Atheroma

Risk Factors for Atherosclerosis
 Nonmodifiable
 Age
 Gender
 Genetic or familial factors
 Modifiable
 Obesity
 Sedentary lifestyle
 Cigarette smoking
 Diabetes mellitus
 Poorly controlled hypertension
 Combination of oral contraceptives and smoking

Atherosclerosis
 Serum lipid levels
 Treatment
 Weight loss
 Increase exercise.
 Lower total serum cholesterol and LDL levels by dietary
modification.
 Reduce sodium intake.
 Control hypertension.
 Cessation of smoking
 Antilipidemic drugs
 Surgical intervention, such as coronary artery bypass
grafting

Coronary Artery Bypass Grafting

Angina Pectoris
 Occurs when there is a deficit of oxygen to
meet myocardial needs
 Chest pain may occur in different patterns.
 Classic or exertional angina
 Variant angina
• Vasospasm occurs at rest.
 Unstable angina
• Prolonged pain at rest—may precede myocardial
infarction

Angina: Imbalance of Oxygen
Supply and Demand

Angina Pectoris (Cont.)
 Recurrent, intermittent brief episodes of
substernal chest pain
 Triggered by physical or emotional stress
 Attacks vary in severity and duration but
become more frequent and longer as disease
progresses.
 Relieved by rest and administration of
coronary vasodilators
 Example: nitroglycerin
• Primarily acts by reducing systemic resistance,
decreasing the demand for oxygen

Emergency Treatment for Angina
 Rest, stop activity
 Patient seated in upright position
 Administration of nitroglycerin—sublingual
 Check pulse and respiration.
 Administer oxygen, if necessary.
 Patient known to have angina
 Second dose of nitroglycerin
 Patient without history of angina
 Emergency medical aid

Myocardial Infarction
 Occurs when coronary artery is totally
obstructed
 Atherosclerosis is most common cause
 Thrombus from atheroma may obstruct artery
 Vasospasm is cause in a small percentage.
 Size and location of the infarct determine the
damage.

Warning Signs of Heart Attack
 Feeling of pressure, heaviness, or burning in
chest—especially with increased activity
 Sudden shortness of breath, weakness,
fatigue
 Nausea, indigestion
 Anxiety and fear
 Pain may occur and, if present, is usually
 Substernal
 Crushing
 Radiating

Myocardial Infarction (MI)

Myocardial Infarction (Cont.)
 Changes in ECG
 Serum enzyme and isoenzyme levels
 Serum levels of myosin and cardiac troponin are
elevated.
 Leukocytosis, elevated CRP and ESR common
 Arterial blood gas measurements may be altered
in severe cases.
 Pulmonary artery pressure measurements helpful

Myocardial Infarction:
Complications
 Sudden death
 Cardiogenic shock
 Rupture of necrotic heart tissue/cardiac
tamponade
 Thromboembolism causing cerebrovascular
accident (CVA; with left ventricular MI)

Myocardial Infarction: Treatment
 Reduce cardiac demand.
 Oxygen therapy
 Analgesics
 Anticoagulants
 Thrombolytic agents may be used.
 Tissue plasminogen activator
 Medication to treat:
 Dysrhythmias, hypertension, congestive heart
failure
 Cardiac rehabilitation begins immediately.

Cardiac Dysrhythmias
(Arrhythmias)
 Deviations from normal cardiac rate or rhythm
 Caused by electrolyte abnormalities, fever,
hypoxia, stress, infection, drug toxicity
 Electrocardiography—for monitoring the
conduction system
• Detects abnormalities
 Reduction of the efficiency of the heart’s
pumping cycle
 Many types of abnormal conduction patterns exist.

Sinus Node Abnormalities
 SA node
 Pacemaker of the heart; rate can be altered.
 Bradycardia
 Regular but slow heart rate
 Tachycardia
 Regular rapid heart rate
 Sick sinus syndrome
 Marked by altering bradycardia and tachycardia
• Often requires mechanical pacemaker

Conduction System in the Heart

Atrial Conduction Abnormalities
 Premature atrial contractions or beats (PACs,
PABs)
 Extra contraction or ectopic beats
• Irritable atrial muscle cells outside conduction pathway
 Atrial flutter
 Atrial heart rate of 160 to 350 beats/min
• AV node delays conduction—ventricular rate slower
 Atrial fibrillation
 Rate over 350 beats/min
• Causes pooling of blood in the atria
• Thrombus formation is a risk.

Atrioventricular Node
Abnormalities
 Heart blocks
 Conduction excessively delayed or stopped at AV
node or bundle of His
 First-degree block
 Conduction delay between atrial and ventricular
contractions
 Second-degree block
 Every second to third atrial beat dropped at AV
node
 Third-degree block
 No transmission from atria to ventricles

Ventricular Conduction
Abnormalities
 Bundle branch block
 Interference with conduction in one of the bundle branches
 Ventricular tachycardia
 Likely to reduce cardiac output as reduced diastole occurs
 Ventricular fibrillation
 Muscle fibers contract independently and rapidly
 Cardiac standstill occurs if not treated immediately!
 Premature ventricular contractions (PVCs)
 Additional beats from ventricular muscle cell or ectopic
pacemaker; may lead to ventricular fibrillation

Cardiac Dysrhythmias

Treatment of Cardiac
Dysrhythmias
 Cause needs to be determined and treated.
 Antidysrhythmic drugs are effective in many
cases.
 SA nodal problems or total heart block
require pacemaker
 Defibrillator may be implanted for conversion
of ventricular fibrillation.

Cardiac Arrest
 Cessation of all heart activity
 No conduction of impulses
 Flat ECG
 Many reasons
 Excessive vagal nerve stimulation
 Potassium imbalance
 Cardiogenic shock
 Drug toxicity
 Insufficient oxygen
 Respiratory arrest
 Blow to heart

Congestive Heart Failure
 Heart is unable to pump out sufficient blood
to meet metabolic demands of the body.
 Usually a complication of another
cardiopulmonary condition
 May involve a combination of factors
 Various compensation mechanisms maintain
cardiac output.
 Some of these often aggravate the condition.

Congestive Heart Failure (Cont.)
 When heart cannot maintain pumping
capability
 Cardiac output or stroke volume decreases.
• Less blood reaches the various organs.
• Decreased cell function
• Fatigue and lethargy
• Mild acidosis develops.
 Backup and congestion develop as coronary
demands for oxygen and glucose are not met.
• Output from ventricle is less than the inflow of blood.
• Congestion in venous circulation draining into the
affected side of the heart

Effects of Congestive Heart
Failure
 Left-sided congestive heart failure

Effects of Congestive Heart
Failure (Cont.)
 Right-sided congestive heart failure

Congestive Heart Failure
 Forward effects (similar with failure on either
side)
 Decreased blood supply to tissues, general
hypoxia
 Fatigue and weakness
 Dyspnea and shortness of breath
 Compensation mechanisms
 Tachycardia
 Cutaneous and visceral vasoconstriction
 Daytime oliguria

Signs and Symptoms of Congestive
Heart Failure (Cont.)
 Backup effects of left-sided failure
 Related to pulmonary congestion
 Dyspnea and orthopnea
• Develop as fluid accumulates in the lungs
 Cough
• Associated with fluid irritating the respiratory passages
 Paroxysmal nocturnal dyspnea
• Indicates the presence of acute pulmonary edema
• Usually develops during sleep
• Excess fluid in lungs frequently leads to infections such
as pneumonia.

Congestive Heart Failure (Cont.)
 Signs of right-sided failure and systemic
backup
 Dependent edema in feet, legs, or buttocks
 Increased pressure in jugular veins leads to
distention.
 Hepatomegaly and splenomegaly
• Digestive disturbances
 Ascites
• Complication when fluid accumulates in peritoneal cavity
• Marked abdominal distention
 Acute right-sided failure
• Flushed face, distended neck veins, headache, visual
disturbances

Congestive Heart Failure (CHF)

Young Children with CHF
 Often secondary to congenital heart disease
 Feeding difficulties often first sign
 Failure to gain weight or meet developmental
guidelines
 Short sleep periods
 Tripod position to play
 Cough, rapid grunting respirations, flared
nostrils, wheezing
 Radiographs show cardiomegaly.
 Arterial blood gases used to measure hypoxia

Congenital Heart Defects
 Cardiac anomalies
 Structural defects in the heart that develop during
the first 8 weeks of embryonic life
 Congenital heart disease
 Valvular defects
 Septal defects
 Detected by the presence of heart murmurs
 If untreated, child may develop heart failure.
 May be cyanotic or acyanotic, depending on
direction of shunting

Congenital Heart Defects (Cont.)
 Signs and symptoms of large defects
 Pallor
 Tachycardia
• Occurs with very rapid sleeping pulse and frequent pulse
deficit
 Dyspnea on exertion
 Squatting position—toddlers and older children
• Appears to modify blood flow, more comfortable
 Clubbed fingers
 Intolerance for exercise and exposure to cold
weather
 Delayed growth and development

Congenital Heart Defects (Cont.)
 Severe defects are often diagnosed at birth.
 Others may not be detected for some time.
 Examination techniques
 Radiography
 Diagnostic imaging
 Cardiac catheterization
 Echocardiography
 Electrocardiography
 Surgical repair

Ventricular Septal Defect
 VSD is the most common congenital heart
defect.
 Opening in the interventricular septum
 May vary in size and location
 Untreated VSD
 Pressure usually higher in left ventricle.
 Shunt from left → right
 Acyanotic condition unless respiratory condition
increases pressure in right ventricle

Valvular Defects
 Usually affect aortic and pulmonary valves
 May be classified as stenosis or valvular
incompetence
 Failure of valve to close completely
 Blood regurgitates or leaks backward
 Mitral valve prolapse
 Abnormally enlarged and floppy valve leaflets
 Surgical replacement
 Mechanical or animal (porcine) tissue

Effects of Heart Valve Defects

Tetralogy of Fallot
 Most common cyanotic (R → L shunt) congenital
heart condition
 Cyanosis occurs because shunt bypasses the
pulmonary circulation.
 Alters pressures in heart and alters blood flow
 Includes four abnormalities
 Involves heart as well as joints
 VSD
 Dextroposition of the aorta
 Right ventricular hypertrophy

Inflammation and Infection in the
Heart

Rheumatic Fever and Rheumatic
Heart Disease
 Rheumatic fever
 Acute systemic inflammatory condition
• May result from an abnormal immune reaction
• Can occur a few weeks after an untreated infection
(usually group A b-hemolytic Streptococcus)
 Involves heart as well as joints
 Usually occurs in children ages 5 to 15 years
 Long-term effects
• Rheumatic heart disease
• May be complicated by infective endocarditis and heart
failure in older adults

Heart Disease (Cont.)
 Acute stage—inflammation of the heart
 Pericarditis
 Myocarditis
 Endocarditis and incompetent heart valves
 Other sites of inflammation
 Large joints
 Erythema marginatum
 Nontender subcutaneous nodules
 Involuntary jerky movement of the face, arms, legs

Heart Disease (Cont.)
 Signs and symptoms
 Low-grade fever, leukocytosis, malaise, anorexia,
fatigue, tachycardia
 Heart function test
 Electrocardiography
 ASO titer
 Treatment
 Prophylactic antibacterial agents
 Anti-inflammatory agents

Development of Rheumatic Fever
and Rheumatic Heart Disease

Infective Endocarditis
 Subacute
 Streptococcus viridans
 Acute
 Staphylococcus aureus
 Basic effects
 Same regardless of organism
 Factors that predispose to infection
 Presence of abnormal valves in heart
 Bacteremia
 Reduced host defenses

Infective Endocarditis (Cont.)
 Low-grade fever or fatigue
 Anorexia, splenomegaly, congestive heart
failure in severe cases
 Acute endocarditis
 Sudden, marked onset—spiking fever, chills,
drowsiness
 Subacute endocarditis
 Insidious onset—increasing fatigue, anorexia,
cough, and dyspnea
 Blood culture to identify causative agent
 Antimicrobial drugs for several weeks, often IV

Pericarditis
 Usually secondary to another condition
 Classified by cause or type of exudate
 Acute pericarditis
 May involve simple inflammation of the
pericardium
 May be secondary to:
• Open heart surgery, myocardial infarction, rheumatic
fever, systemic lupus erythematosus, cancer, renal
failure, trauma, viral infection
 Effusion may develop.
• Large volume of fluid accumulates in pericardial sac
• Leads to distended neck veins, faint heart sounds,
pulsus paradoxus

Effects of Pericardial Effusion

Pericarditis (Cont.)
 Chronic pericarditis
 Results in formation of adhesions between the
pericardial membranes
 Fibrous tissue often results from tuberculosis or
radiation to the mediastinum.
 Limiting movement of the heart during diastole
and systole → reduced cardiac output
 Inflammation or infection may develop from
adjacent structures.
 Causes fatigue, weakness, abdominal discomfort
• Caused by systemic venous congestion

Vascular Disorders

Arterial Diseases—Hypertension
 High blood pressure
 Common
 May occur in any age group
 More common in individuals of African ancestry
 Sometimes classified as systolic or diastolic

(Cont.)
 Primary
 Essential hypertension
 Blood pressure consistently above 140/90 mm Hg
• May be adjusted for age
 Increase in arteriolar vasoconstriction
 Over long period of time—damage to arterial walls
• Blood supply to involved area is reduced.
• Ischemia and necrosis of tissues, with loss of function

(Cont.)
 Secondary hypertension
 Results from renal or endocrine disease,
pheochromocytoma (benign tumor of the adrenal
medulla)
 Underlying problem must be treated to reduce
blood pressure.
 Malignant or resistant hypertension
 Uncontrollable, severe, and rapidly progressive
form with many complications
 Diastolic pressure is extremely high.

Development of Hypertension

(Cont.)
 Areas most frequently damaged by hypertension
 Kidneys
 Heart
 Brain
 Retina
 Predisposing factors
 Incidence increases with age.
 Men affected more frequently and more severely
 Incidence in women increases after middle age.
 Genetic factors
 Sodium intake, excessive alcohol intake, obesity, smoking,
prolonged or recurrent stress

Effects of Uncontrolled
Hypertension

(Cont.)
 Frequently asymptomatic in early stages
 Initial signs vague and nonspecific
• Fatigue, malaise, sometimes morning occipital headache
 Essential hypertension treated in steps
 Lifestyle changes
 Reduction of sodium intake
 Weight reduction
 Reduction of stress
 Drugs
• Diuretics, ACE inhibitors, drug combinations

Peripheral Vascular Disease:
Atherosclerosis
 Disease in arteries outside the heart
 Increased incidence with diabetes
 Most common sites
 Abdominal aorta
 Carotid arteries
 Femoral and iliac arteries
 Blood flow assessed by Doppler studies and
arteriography
 Plethysmography measures the size of limbs and
blood volume in organs or tissues.

Atherosclerosis (Cont.)
 Increasing fatigue and weakness in the legs
 Intermittent claudication (leg pain)
• Associated with exercise caused by muscle ischemia
 Sensory impairment
• Tingling, burning, numbness
 Peripheral pulses distal to occlusion become
weak.
 Appearance of the skin of the feet and legs
changes.
• Marked pallor or cyanosis
• Skin dry and hairless
• Toenails thick and hard

Atherosclerosis (Cont.)
 Treatment
 Maintain control of blood glucose level.
 Reduce body mass index.
 Reduce serum cholesterol level.
 Platelet inhibitors or anticoagulant medication
 Cessation of smoking
 Increase activity and exercise
 Maintain dependent position for legs—improves
arterial perfusion
 Peripheral vasodilators
 Observe skin for breakdown and treat promptly.
 If gangrene develops, amputation is required.

Aortic Aneurysm
 Localized dilation and weakening of arterial
wall
 Develops from a defect in the medial layer
 Different shapes
 Saccular
• Bulging wall on the side
 Fusiform
• Circumferential dilation along a section of artery
 Dissecting aneurysm
• Develops when there is a tear in the intima of the wall
and blood continues to dissect or separate tissues

Types of Aortic Aneurysms

Aortic Aneurysm (Cont.)
 Causes
 Atherosclerosis
 Trauma
 Syphilis and other infections
 Congenital defects
 Bruit may be heard on auscultation.
 Pulse may be felt on palpation of abdomen.
 Frequently asymptomatic until they become large
or rupture
• Rupture may lead to moderate bleeding but usually
causes severe hemorrhage and death.

Aortic Aneurysm (Cont.)
 Radiography
 Ultrasound
 CT scanning
 MRI
 Treatment
 Maintain blood pressure at normal level.
 Prevent sudden elevations caused by exertion.
 Prevent stress, coughing, constipation
 Surgical repair

Venous Disorders

Varicose Veins
 Irregular, dilated, tortuous areas of superficial
veins
 Familial tendency
 Increased body mass index, parity, and
weight lifting are risks.
 In the legs
 May develop from defect or weakness in vein
walls or valves
 Appear as irregular, purplish, bulging structures
 Treatment
 Keep legs elevated, support stockings
 Restricted clothing, crossing legs to be avoided

Varicose Veins (Cont.)

Thrombophlebitis and
Phlebothrombosis
 Thrombophlebitis
 Thrombus development in inflamed vein (e.g., IV
site)
 Phlebothrombosis
 Thrombus forms spontaneously without prior
inflammation; attached loosely
 Factors for thrombus development
 Stasis of blood or sluggish blood flow
 Endothelial injury
 Increased blood coagulability

Thrombophlebitis and
Phlebothrombosis (Cont.)
 Often unnoticed
 Aching, burning, tenderness in affected legs
 Systemic signs—fever, malaise, leukocytosis
 Complication—pulmonary embolism
 Treatment
 Preventive measures
• Exercise, elevating legs
 Anticoagulant therapy
 Surgical intervention

Shock
 Hypovolemic shock
 Loss of circulating blood volume
 Cardiogenic shock
 Inability of heart to maintain cardiac output to
circulation
 Distributive, vasogenic, neurogenic, septic,
anaphylactic shock
 Changes in peripheral resistance leading to
pooling of blood in the periphery

Types of Shock

Shock: Early Manifestations
 Anxiety
 Tachycardia
 Pallor
 Light-headedness
 Syncope
 Sweating
 Oliguria

Shock (Cont.)
 Compensation mechanisms
 SNS and adrenal medulla stimulated—increase
heart rate, force of contraction, systemic
vasoconstriction
 Renin secretion increases.
 Increased ADH secretion
 Secretion of glucocorticoids
 Acidosis stimulates increased respiration.
• With prolonged shock, cell metabolism is diminished,
waste not removed—leads to lower pH

Shock (Cont.)
 Complications of shock
 Acute renal failure
 Shock lung, or adult respiratory distress syndrome
 Hepatic failure
 Paralytic ileus, stress or hemorrhagic ulcers
 Infection or septicemia
 Disseminated intravascular coagulation
 Depression of cardiac function

Manifestations of Shock

General Effects of Circulatory
Shock

Ch 10, 11, 12 Pathology

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