Chapter 18: Infectious Diseases Affecting the Cardiovascular and Lymphatic Systems

Learning Outcomes Section 18.1

1. Describe the important anatomical features of the cardiovascular and lymphatic systems.
2. List the natural defenses present in the cardiovascular and lymphatic systems.

The Cardiovascular System

Composition of the Cardiovascular System

• Blood Vessels: These structures carry blood to and from all regions of the body.
• Heart: The muscular organ responsible for pumping blood throughout the body.
• Circulatory System: This is a closed circuit known as the circulatory system.

Functions of the Cardiovascular System

• Oxygen and Nutrient Delivery: The system provides tissues with necessary oxygen and nutrients.
• Waste Removal: It carries away carbon dioxide and metabolic waste products from tissues.

The Lymphatic System

Composition of the Lymphatic System

• Lymph Vessels: These vessels run roughly parallel to the blood vessels.
• Lymph Nodes: Clusters located in body sites such as the groin, neck, armpit, and intestines.
• Spleen: An organ that plays a key role in immune response.

Function of the Lymphatic System

• Immune Cell Source: The lymphatic system serves as a major source of immune cells and lymph fluid.
• Fluid Return: It acts as a one-way passage that returns interstitial fluid from tissues to the cardiovascular system.

Anatomy of the Cardiovascular and Lymphatic Systems

Heart

• Size and Structure: The heart is described as a fist-sized muscular organ that pumps blood throughout the body.
• Chambers: It consists of two upper chambers (atria) and two lower chambers (ventricles).
• Pericardium: A fibrous covering surrounding the heart that can be infected.
• Three Layers of the Heart Wall:
  1. Epicardium: The outermost layer.
  2. Myocardium: The middle layer made of muscle.
  3. Endocardium: The innermost layer that covers the heart valves and is a common target for microbial infections.

Blood Vessels

• Arteries: Carry oxygenated blood away from the heart under relatively high pressure and branch into arterioles.
• Veins: Formed from venules in the periphery of the body; they carry deoxygenated blood back to the heart.
• Capillaries: The smallest blood vessels that connect arterioles to venules and have a one-cell thick layer of endothelium.

Layers of Blood Vessels

• Innermost Layer: Composed of endothelium, providing a smooth surface to promote blood flow.
• Middle Layer: Comprised of connective tissue and muscle fibers.
• Outer Layer: A thin layer of connective tissue.

Defenses of the Cardiovascular and Lymphatic Systems

Infection Protection

• The cardiovascular system has multiple defenses against microbial infections, as microbes invading the system can access all body parts.
• White Blood Cells (WBC): The system contains approximately 5,000 to 10,000 WBC per microliter of blood, with a significant role of lymphocytes in adaptive immunity and phagocytes in innate and adaptive immune responses.

Medical Condition Suffixes

• Conditions involving blood often carry the suffix -emia, indicating their relation to blood, such as:
  • Viremia: Presence of viruses in the blood.
  • Fungemia: Presence of fungi in the blood.
  • Bacteremia: Presence of bacteria in the blood.
  • Septicemia (Sepsis): Condition of bacteria growing and flourishing in the blood.
  • Septic Shock: A cascading immune response to septicemia leading to decreased blood pressure, a life-threatening condition.

Concept Check (1)

Which of the following terms refers to bacteria flourishing and growing in the bloodstream?
A. Fungemia
B. Bacteremia
C. Septicemia
D. Viremia
E. All of the choices are correct.

Learning Outcomes Section 18.2

3. Explain the “what” and the “why” of the normal biota of the cardiovascular and lymphatic systems.

Normal Biota of the Cardiovascular and Lymphatic Systems

• Both systems are classified as “closed” systems with no normal access to the external environment; hence, they are free of microorganisms in a healthy state.
• Recent studies from the Human Microbiome Project suggest that the bloodstream might not be completely sterile, even when the host appears healthy.
• These low-level microbial “infections” could potentially contribute to diseases without identified etiologies, or for conditions previously deemed noninfectious.

Defenses of Cardiovascular and Lymphatic Systems

Normal Biota

• Cardiovascular System: Contains blood-borne components of innate and adaptive immunity, including phagocytosis and adaptive immunity mainly found in white blood cells.
• Lymphatic System: Hosts numerous immune defenses, although their specific nature remains unclear.

Concept Check (2)

The cardiovascular and lymphatic systems, being “closed” systems, are always completely sterile.
A. True
B. False

Learning Outcomes Section 18.3 1

4. List the possible causative agents, modes of transmission, virulence factors, diagnostic techniques, and prevention/treatment for the “Highlight Diseases” malaria and HIV.
5. Discuss the epidemiology of malaria.
6. Describe the epidemiology of HIV infection in the developing world.

Learning Outcomes Section 18.3 2

7. Discuss the important features of infectious cardiovascular conditions that have more than one possible cause. These include the two forms of endocarditis, septicemia, hemorrhagic fever diseases, and nonhemorrhagic fever diseases.
8. Identify factors that distinguish hemorrhagic and nonhemorrhagic fever diseases.

Learning Outcomes Section 18.3 3

9. Outline the series of events that may lead to septicemia and how it should be prevented and treated.
10. Discuss the important features of infectious cardiovascular diseases that have only one possible cause, including plague, tularemia, Lyme disease, infectious mononucleosis, Chagas disease, and anthrax.
11. **Describe what makes anthrax a good agent for bioterrorism, and list the important presenting signs to look for in patients.

Note on the Global Fund to Fight AIDS, Tuberculosis, and Malaria

• Established in 2002, it is a unique partnership between governments, private sectors, civil society, and those affected by AIDS, tuberculosis, or malaria.
• Efforts led to a one-third reduction in deaths due to these diseases in countries where the Global Fund operates.
• In response to the COVID-19 pandemic, the Global Fund allocated $1 billion to assist countries in combating COVID-19 while maintaining their fight against HIV, TB, and malaria.

Highlight Disease: Malaria

• Overview: Ranked among the greatest afflictions in human history, alongside bubonic plague, influenza, and tuberculosis, malaria threatens 40% of the world’s population annually.
• Etymology: The name ‘malaria’ derives from the Italian words mal (“bad”) and aria (“air”).

Malaria Signs and Symptoms - Part 1

• Incubation Period: Ranges from 10 to 16 days. The first symptoms include malaise, fatigue, vague aches, nausea with or without diarrhea. Subsequent symptoms include chills, fever, and sweating, occurring at 48- to 72-hour intervals due to synchronous red blood cell ruptures.
• Types of Malaria Symptoms:
  • Falciparum Malaria: Characterized by persistent fever, cough, and weakness lasting for weeks without relief.
• Complications: These can include hemolytic anemia due to lysed red blood cells and organ enlargement or rupture caused by accumulated cellular debris in the spleen, liver, and kidneys.

Malaria Signs and Symptoms - Part 2

• Cerebral Malaria: One severe condition resulting from falciparum malaria, where small blood vessels in the brain become obstructed due to RBC adherence to vessel walls, reducing oxygen supply to the brain, potentially leading to coma or death.
• Overall, malaria is most deadly during the acute phase, particularly affecting children. Infections caused by Plasmodium vivax and P. ovale may relapse due to dormant protozoans in infected liver cells.

Malaria Causative Agent

• Plasmodium species: Protozoans in the sporozoan group. Of over 200 species, five infect humans: P. malariae, P. vivax, P. knowlesi, P. ovale, and P. falciparum, each with variations in disease pattern and severity.
• Life Cycle: The malarial parasite has two phases — the asexual phase in humans and the sexual phase in mosquitoes.

Life Cycle of Malarial Parasite

• Stages:

  1. Sporozoite Stage
  2. Merozoite Stage

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Malaria Pathogenesis and Virulence Factors

• The invasion of merozoites into RBCs leads to the release of fever-inducing chemicals into the bloodstream, resulting in a cyclic occurrence of chills and fevers.
• Plasmodium’s high glucose metabolism leads to host hypoglycemia.
• Damage to RBCs causes anemia, while the accumulation of malarial byproducts in the liver and immune stimulation in the spleen may result in organ enlargement.
• Individual protozoa can express various surface antigens, complicating the host immune response.

Malaria Transmission and Epidemiology

• Transmission: Primarily via the female Anopheles mosquito, with malaria once distributed globally, now restricted to areas near the equator due to mosquito control in temperate regions.
• Statistics: Approximately 200 million new cases reported annually, predominantly affecting children and young adults in Africa, who account for around 500,000 deaths yearly.
• In the U.S., about 1,000 to 2,000 cases typically occur each year, primarily among immigrants or travelers to endemic regions.

Malaria Culture and Diagnosis

• Diagnosis: The definitive method involves discovering a typical stage of Plasmodium in stained blood smears, still regarded as the gold standard, despite newer antigen-specific tests.
• Indicators also include understanding patient residence or travel history to endemic areas alongside symptoms of recurring chills, fever, and sweating.

Malaria Prevention - Part 1

• Methods: Prevention efforts focus on long-term mosquito control and chemoprophylaxis for humans, including the use of protective netting, screens, repellents, avoiding outdoor activity at night, and regular antimalarial medication.

Malaria Prevention - Part 2

• Vaccine Development: A significant breakthrough in vaccine research occurred in 2019 with trials of RTS,S, effective against P. falciparum. It is highly effective in children and was set for pilot vaccination programs in African countries beginning in 2021.

Malaria Treatment

• Quinine has traditionally been used for malaria treatment, with chloroquine being the least toxic for non-resistant forms of the disease.
• Resistance has developed against nearly every drug used, making artemisinin, a plant compound, the most effective treatment, especially when combined with other drugs to prevent resistance development.

Highlight Disease: HIV Infection and AIDS

Signs and Symptoms

• A spectrum of clinical signs and symptoms associated with human immunodeficiency virus (HIV) relates closely to both the virus level and T cell count in the blood.
• Initial Symptoms: Include fatigue, diarrhea, weight loss, and neurological changes; opportunistic infections or neoplasms (cancer) may also arise.
• Severe immune deregulation accompanies other disease-related symptoms like pronounced wasting, hormone imbalances, and metabolic disturbances resulting in body mass loss.
• Neurological Complications: Notable neurological involvement may occur with lesions in the brain, meninges, and peripheral nerves, causing withdrawal, memory loss, spasticity, sensory loss, and progressive AIDS dementia.

AIDS-Defining Illnesses

• Common opportunistic infections and malignancies include:
  • Skin and Mucous Membrane Issues: Cytomegalovirus retinitis leading to vision loss, herpes simplex chronic ulcers, Kaposi’s sarcoma.
  • Nervous System: HIV encephalopathy, Progressive multifocal leukoencephalopathy, toxoplasmosis of the brain.
  • Multiple Organ Systems: Lymphoma, disseminated coccidioidomycosis, and other infections.

HIV Infection and AIDS Causative Agent

• HIV: A retrovirus classified under the genus Lentivirus; capable of causing severe diseases, alters host DNA, and possesses reverse transcriptase (RT) which catalyzes the replication of double-stranded DNA from single-stranded RNA.
• Retroviruses can integrate their genes into the host genome, enabling transmission to progeny cells.

Enveloped RNA Virus

• Characterized by an outer lipid envelope, with membrane glycoprotein spikes facilitating viral adsorption to host cells.
• HIV requires a unique combination receptor consisting of the CD4 marker along with coreceptor CCR-5 for cell entry, allowing infection of various leukocytes and tissue cells.

HIV Infection and AIDS Pathogenesis and Virulence Factors

• The infection begins when HIV enters through mucous membranes or skin, traveling to dendritic cells and replicating without immediate destruction.
• Amplification occurs within macrophages in skin and lymphatic organs, eventually targeting and destroying helper T4 and CD4 lymphocytes, monocytes, macrophages, and B lymphocytes.
• Virus interaction with host receptors induces cell fusion, resulting in large multinucleated cells (syncytia).

Multiplication Cycle of HIV

• The viral replication process includes adsorption to host cell receptors, endocytosis, uncoating, reverse transcription of viral RNA to DNA, and integration into the host genome, leading to a latent phase.
• Upon activation, the provirus expels viral mRNA, which the host machinery translates into virus components followed by assembly and budding from the host cell.

HIV Infection and AIDS Transmission

• Transmission occurs predominantly via sexual contact or through blood/blood product transfer.
• Modes: Infected mothers can transmit the virus pre-birth, durably through nursing, while the virus shows limited survival outside of the host body.
• HIV is not transmitted through saliva, and healthcare workers must be cautious with various bodily fluids potentially transmitting the virus, including amniotic and synovial fluids.

HIV Infection and AIDS Epidemiology

• Since the start of the AIDS epidemic in the early 1980s, about 35 million deaths have occurred globally.
• An estimated 37.9 million individuals are infected, with over 1.2 million in the U.S.
• There has been a significant decrease in new cases in the U.S. from 2005 to 2016 due to global health initiatives, allowing developing regions to access lifesaving treatments.

Maternal-to-Infant Transmission of HIV Infection and AIDS

• Anti-HIV drug treatments for expecting HIV-infected mothers have successfully reduced maternal-to-infant transmission rates during pregnancy from 33% (untreated) to as low as 1% in some studies with protease inhibitors.
• Cuba notably became the first country to eliminate mother-to-child transmission through testing and treatment.

HIV Infection and AIDS Culture and Diagnosis

• Diagnosis is made with a positive test for HIV, distinct from a diagnosis of AIDS.
• Common tests detect antibodies to the virus in serum; newer tests can detect both antibodies and antigens.
• Negative results can occur early in infection; retesting is advised after 3 to 6 months if exposure is suspected.

HIV Infection and AIDS Prevention

• Strategies: Avoidance of sexual contact with infected individuals, use of barrier protection, and pre-exposure prophylaxis (PrEP) for high-risk groups.
• Testing and treatment for other STDs is also essential for overall health and reducing transmission risk.

HIV Infection and AIDS Treatment

• Treatment: There is currently no cure for HIV, yet treatment options greatly enhance the quality of life.
• Guidelines for the treatment of individuals testing positive for HIV typically involve a combination of three drugs from two different classes to manage complications and improve health outcomes.
• Urgent efforts lie in making treatments accessible globally to address the persistent disparities in treatment availability.

Highlight Disease: Endocarditis

Overview

• Endocarditis is inflammation of the endocardium, primarily referencing infections of the heart valves such as mitral and aortic valves.
• Variations: Acute and subacute endocarditis, each defined by different causative agents.
• Risk increases with procedures involving prosthetic valves, leading to potential introduction of bacteria and subsequent infections.

Endocarditis Signs and Symptoms

• Common signs include fever, fatigue, joint pain, edema in extremities, weakness, anemia, and abnormal heartbeat.
• Acute endocarditis symptoms arise swiftly and can be severe; subacute symptoms develop more gradually and typically are less pronounced.
• Specific indicators such as Janeway lesions (painless red spots on palms/soles) and Osler’s nodes (painful skin nodules on fingers/toes) may be observed, with subacute cases possibly leading to splenic enlargement or clubbing of fingers/toes.

Acute Endocarditis

• Often results from an overwhelming bacterial presence in the bloodstream, with bacteria capable of colonizing normal heart valves.
• Causative Agents: Commonly caused by Staphylococcus aureus and others like Streptococcus pyogenes, pneumoniae, Enterococcus, and Pseudomonas aeruginosa.
• Increasing risk groups include intravenous drug users and those with traumatic injuries.

Subacute Endocarditis

• Typically arises after heart valve damage or congenital malformations that encourage bacterial attachment, leading to biofilm formation and further infections.
• Causative Agents: Low pathogenicity bacteria predominant, often from normal oral biota like alpha-hemolytic streptococci.
• Transmission: Introduced into the bloodstream via minor skin disruptions such as dental procedures or cut lacerations.
• Prophylactic antibiotics may be prescribed before surgical interventions to mitigate infection risk.

Septicemia

• Defined by active organism multiplication in the blood, caused by various bacteria and some fungi. Patients may be described as “septic.”

Septicemia Signs and Symptoms

• Characterized by fever and severe illness, including altered mental states, shaking, gastrointestinal symptoms, and an increased breathing rate.
• A hallmark of septicemia is low blood pressure, stemming from the inflammatory response leading to vascular fluid loss and potential death due to resultant shock.

Septicemia Causative Agents

• Primarily bacterial, comprising both gram-positive and gram-negative; MRSA is a common culprit.
• Fungal infections account for 10% of causes, with an increase in identification of polymicrobial infections.

Septicemia Pathogenesis and Virulence Factors

• Gram-negative bacteria release endotoxins that stimulate inflammatory cascades, inducing pronounced blood pressure drops (endotoxic shock).
• Gram-positive bacteria elicit similar responses through cell wall fragments released into circulation.

Septicemia Transmission and Epidemiology

• Transmission can occur via parenteral introduction through IV lines or surgical procedures, as well as secondary infections from severe urinary, renal, pancreatic, or gallbladder infections.
• At-risk populations include those with underlying spleen dysfunction or conditions such as meningitis and pneumonia.

Septicemia Culture and Diagnosis

• Diagnosis typically involves blood cultures and may be complemented by newer deep sequencing techniques for quicker treatment initiation.
• Empiric therapy with broad-spectrum antibiotics begins immediately prior to confirmation of the infectious agent.

Highlight Disease: Plague

Overview

• Plague, historically significant, includes variations such as pneumonic, bubonic, and septicemic plague, with the first recorded epidemic resulting in approximately 100 million deaths.

Bubonic Plague Signs and Symptoms

• Transmission occurs through flea bites, leading to inflammation and necrosis of lymph nodes, resulting in a bubo (swollen lesion).
• Symptoms include fever, chills, headache, nausea, weakness, and tenderness of the bubo.

Septicemic Plague Signs and Symptoms

• Often progresses from bubonic or pneumonic forms, leading to massive bacterial growth in the blood, causing disseminated intravascular coagulation, subcutaneous hemorrhaging, and purpura (100% mortality without treatment).
• The appearance of darkening skin in septicemic cases has historically led to the term “Black Death.”

Plague Causative Agent

• Yersinia pestis: A small, gram-negative rod marked by bipolar staining resembling a safety pin.
• A very small infective dose of 3-50 cells can initiate an infection.

Plague Transmission and Epidemiology

• Fleas act as the primary transmission agents after ingesting blood from infected animals and subsequently becoming blocked, leading to regurgitation of infectious material into new hosts.
• Historically widespread, prevalence in the developed world has decreased, while the disease is increasing in Africa and certain other regions.
• Regional endemics exist in the western and southwestern U.S., with at-risk individuals including veterinarians and those in proximity to infected animal habitats.

Highlight Disease: Tularemia

Overview

• Causative Agent: Francisella tularensis, a facultative intracellular gram-negative bacterium, often referred to as “rabbit fever.”
• Listed as a Category A bioterrorism agent.

Tularemia Signs and Symptoms

• Incubation period lasts from a few days up to 3 weeks, with acute symptoms of headache, fever, chills, weakness, and coughing.
• Further clinical manifestations depend on the entry portal:
  • Ulcerative skin lesions or conjunctival inflammation, sore throat, and pulmonary involvement are common.
  • The serious forms of tularemia can lead to death rates around 30%, but conventional treatment with gentamicin or streptomycin can drastically reduce mortality risk.

Tularemia Transmission and Epidemiology

• Transmission pathways include contact with infected animals, specifically rabbits/rodents, and through tick bites.
• Ticks, biting flies, mites, and mosquitoes serve as arthropod vectors; aerosol transmission is possible.

Tularemia Prevention

• With the potential for intracellular persistence leading to relapses, completion of antimicrobial therapy is crucial.
• Post-exposure prophylaxis using doxycycline or ciprofloxacin is recommended for those exposed in laboratory or high-risks environments.

Highlight Disease: Lyme Disease

Signs and Symptoms

• A slow-progressing condition mimicking neuromuscular and rheumatoid arthritis, marked by erythema migrans, presenting as a bull's-eye rash.
• Early symptoms like fever, headaches, and stiff neck can progress to cardiac and neurological issues if untreated, leading to crippling arthritis.

Lyme Disease Causative Agent

• Borrelia burgdorferi: A large spirochete with a capacity for immune evasion achieved through antigenic switching.
• The immune response is ineffective due to the bacterium's ability to change its surface markers.

Lyme Disease Transmission and Epidemiology

• Transmitted by hard ticks of the genus Ixodes, particularly during their two-year life cycle that involves multiple hosts.
• The highest concentrations of cases correspond with regions that support abundant tick populations, primarily found in Northeast and California.

Lyme Disease Culture and Diagnosis

• Culture methods are ineffective; diagnosis is typically based on symptoms and tick exposure history.
• In later stages, serological tests such as ELISAs and Western blots are utilized to detect antibodies.
• Consideration of potential co-infections like Anaplasma or Babesia, also tick-transmitted, is vital in lingering cases.

Lyme Disease Prevention and Treatment

• Individuals engaging in outdoor activities should wear appropriate protective clothing and insect repellents.
• Early intervention with doxycycline or amoxicillin is effective in treatment; ticking removal should be handled carefully to prevent infection.

Highlight Disease: Infectious Mononucleosis

Overview

• Often titled “mono” or “the kissing disease,” it is primarily caused by the Epstein-Barr virus (EBV), a member of the herpesvirus family.

Signs and Symptoms

• Symptoms develop after an incubation period of 30-50 days and include sore throat, high fever, cervical lymphadenopathy, and fatigue.
• Other notable features include gray-white exudate in the throat and the potential for splenic and liver enlargement.

Transmission and Epidemiology

• EBV is prevalent globally, with over 90% of people infected, often asymptomatic.
• First-time infections during teenage years significantly increase disease risk, while earlier or later infections might be asymptomatic.

Prevention and Treatment

• Treatment focuses on managing symptoms, and hospitalization is rare unless complications like splenic rupture occur.

Highlight Disease: Hemorrhagic Fever Diseases

Overview

• Caused by various agents that infect blood and lymphatics, leading to extreme fevers and sometimes internal hemorrhaging.
• All viruses responsible for hemorrhagic fevers are RNA enveloped viruses.

Notable Diseases

• Ebola, yellow fever, and dengue fever, spread primarily by the Aedes mosquito.
• Diseases exhibit various geographical distributions, with notable cases rising recently in the Americas.

Prevention and Treatment

• Effective control measures include vaccination (where applicable) and vector management strategies to minimize disease spread.

Conclusion

These detailed notes comprehensively cover crucial aspects of the cardiovascular and lymphatic systems, emphasizing both the anatomy and the infectious diseases that significantly impact these vital systems. They serve as a foundation for understanding disease mechanisms, symptoms, epidemiology, transmission, prevention, and treatment strategies relevant to various infectious diseases.