Microbiology Chapter 18: Cardiovascular and Lymphatic System Infections

Composition and Function of the Cardiovascular System

  • The Cardiovascular System

    • Also known as the circulatory system, this is a closed circuit that includes the heart and blood vessels.
    • Blood Vessels: Responsible for transporting blood to and from every region of the body.
    • The Heart: Serves as the central pump for the blood.
    • Primary Functions:
      • Provides tissues with necessary oxygen and nutrients.
      • Transports carbon dioxide and metabolic waste products away from tissues for excretion.

  • The Heart: Anatomy and Layers

    • The heart is a muscular organ roughly the size of a fist.
    • Chambers:
      • Atria: The two upper chambers of the heart (comprising the right atrium and left atrium).
      • Ventricles: The two lower chambers of the heart (comprising the right ventricle and left ventricle).
    • Coverings and Walls:
      • Pericardium: The fibrous outer covering of the heart, which is an occasional site of infection.
      • Epicardium: The outermost layer of the heart wall.
      • Myocardium: The muscular middle layer of the heart wall.
      • Endocardium: The innermost layer that lines the heart chambers and covers the heart valves. It is a frequent target of microbial infection.

  • Blood Vessels: Structure and Classification

    • Arteries: Carry oxygenated blood away from the heart under relatively high pressure. These branch into smaller vessels called arterioles.
    • Veins: Carry deoxygenated blood back toward the heart. These begin as small venules in the periphery of the body.
    • Capillaries: The smallest blood vessels that connect arterioles to venules. They consist of only a single layer of endothelium to facilitate exchange.
    • Vessel Layers:
      • Innermost Layer: Composed of endothelium. This layer provides a smooth surface that encourages the efficient flow of blood cells and platelets.
      • Middle Layer: Composed of muscle fibers and connective tissue.
      • Outer Layer: A thin layer consisting primarily of connective tissue.

The Lymphatic System and Global Surveillance

  • Overview of the Lymphatic System

    • This is a branching network of vessels that extends into most areas of the body. It is closely related to the cardiovascular system but remains a separate entity.
    • Function: It acts as a major source of immune fluids and cells. It collects fluid that has leaked from blood vessels into tissues, filters it for infectious agents and impurities, and returns the fluid to the bloodstream.
    • Directionality: Unlike the cyclic pattern of the blood circulation, the lymphatic system transports fluid in only one direction (toward the heart).
    • Direct Connection: The two systems meet near the heart, where large lymph ducts empty leur fluid into the subclavian veins.

  • Lymphatic Anatomy

    • Lymph Vessels: These roughly parallel the pathways of blood vessels.
    • Lymph Nodes: Clustered at specific sites, including the neck (cervical nodes), armpit (axillary nodes), groin (inguinal nodes), and intestines (abdominal and pelvic nodes).
    • Other Lymphatic Organs: Include the spleen, thymus, tonsils, and Gut-associated lymphoid tissue (GALT).
    • Infection Contact Points: High densities of lymphatic vessels are found in "dead-end" areas such as the hands, feet, and breasts, which are frequent contact points for infections.

  • Immune Surveillance

    • Body compartments are screened by circulating white blood cells (WBCs).
    • The lymphatic system provides a dedicated space for numerous immune defenses to reside and operate.

Defenses and Normal Biota of the Cardiorespiratory and Lymphatic Systems

  • Defenses

    • The cardiovascular system is highly protected because any microbe invading the bloodstream has access to every part of the body, leading to systemic infections.
    • Leukocytes: Blood contains between 5,0005,000 and 10,000 leukocytes/mL10,000\,\text{leukocytes/mL}.
    • Lymphocytes: Provide specific immunity.
    • Phagocytes: Essential for both specific and nonspecific immune responses.

  • Medical Terminology for Blood Conditions

    • The suffix -emia refers to conditions involving the blood.
    • Viremia: The presence of viruses in the blood.
    • Fungemia: The presence of fungi in the blood.
    • Bacteremia: The presence of bacteria in the blood.
    • Septicemia (Sepsis): A condition where bacteria are actively growing and flourishing in the blood.
    • Septic Shock: A cascading immune response to septicemia that results in a dangerous decrease in blood pressure.

  • Normal Biota

    • The cardiovascular and lymphatic systems are considered "closed" systems with no natural access to the external environment.
    • Healthy State: Traditionally, it was believed that no microorganisms colonize either system in health.
    • Human Microbiome Project (HMP) Findings: Recent studies suggest the bloodstream is not completely sterile even in healthy individuals. Low-level microbial "infections" may contribute to diseases previously thought to be noninfectious or of unknown etiology.

Highlight Disease: Malaria

  • Background and Significance

    • Malaria is a dominant protozoan disease and one of the greatest historical human afflictions, comparable to tuberculosis or the bubonic plague.
    • It threatens 40%40\% of the world’s population annually.
    • The name comes from the Italian words "mal" (bad) and "aria" (air).

  • Signs and Symptoms

    • Incubation Period: Typically 10 days10\,\text{days}.
    • Initial Symptoms: Malaise, vague aches, fatigue, and nausea, often accompanied by diarrhea, fever, chills, and sweating.
    • Cyclic Pattern: Symptoms recur at intervals of 4848 or 72 hours72\,\text{hours} due to the synchronous rupture of red blood cells (RBCs).
    • Falciparum Malaria: Characterized by persistent fever, weakness, and cough lasting for weeks without relief.
    • Complications:
      • Hemolytic Anemia: Results from the lysis of red blood cells.
      • Organ Damage: Cellular debris accumulates in the liver, spleen, and kidneys, leading to enlargement or rupture.
      • Cerebral Malaria: A serious complication of P.falciparumP. falciparum where RBCs adhere to blood vessel walls in the brain, obstructing flow and potentially causing coma or death.
    • Relapses: Malaria caused by PlasmodiumvivaxPlasmodium vivax and PlasmodiumovalePlasmodium ovale can relapse as dormant protozoans can remain in liver cells for up to 5 years5\,\text{years}.

  • Causative Agents

    • Members of the genus Plasmodium, which are protozoans in the sporozoan group.
    • Species: P.malariaeP. malariae, P.vivaxP. vivax, P.falciparumP. falciparum, and P.ovaleP. ovale.
    • Hosts: Humans are the primary vertebrate hosts.

  • Life Cycle of the Malarial Parasite

    1. Inoculation: An infected female Anopheles mosquito injects saliva containing anticoagulant and motile, spindle-shaped sporozoites into a human capillary.
    2. Liver Phase (Asexual Phase - Schizogony): Sporozoites migrate to the liver, where they undergo asexual division to generate merozoites. This pre-erythrocytic stage lasts 55 to 16 days16\,\text{days}. At the end, liver cells erupt, releasing between 2,0002,000 and 40,00040,000 merozoites.
    3. Erythrocytic Phase (Asexual Phase): Merozoites invade RBCs and become ring-shaped trophozoites. They feed on hemoglobin and divide to produce a schizont filled with more merozoites. RBCs burst, releasing merozoites to infect more cells. Some merozoites differentiate into gametocytes (macrogametocytes and microgametocytes).
    4. Sexual Phase (Sporogony): A mosquito draws infected RBCs into its stomach. Microgametocytes release gametes that fertilize macrogametocytes to form a diploid ookinete. This implants in the stomach wall as an oocyst, which eventually releases sporozoites that migrate to the mosquito's salivary glands.

  • Pathogenesis and Virulence

    • Merozoite invasion of RBCs triggers the release of fever-inducing chemicals.
    • High rates of glucose metabolism by the parasite lead to host hypoglycemia.
    • Immune stimulation results in the enlargement of the spleen and liver.

  • Epidemiology and Transmission

    • Primarily spread by the female Anopheles mosquito.
    • Global Burden: 300300 to 500 million500\,\text{million} new cases annually; 90%90\% occur in Africa.
    • Mortality: Approximately 2 million2\,\text{million} deaths per year, mostly among children and young adults.
    • USA Cases: 1,0001,000 to 2,0002,000 cases per year, mostly in travelers/immigrants.

  • Diagnosis and Prevention

    • Diagnosis: Discovery of Plasmodium stages in stained blood smears; serological tests.
    • Prevention: Mosquito abatement (screens, netting, repellants), human chemoprophylaxis, and remaining indoors at night.
    • Treatment: Quinine (mainstay), Chloroquine (nonresistant forms), Mefloquine, or Artemisinin (highly effective plant compound, recommended in combination therapy by the WHO).

Highlight Disease: HIV Infection and AIDS

  • Signs and Symptoms

    • Symptoms are directly correlated with blood levels of the virus and levels of T cells.
    • Initial Infection: Vague, mononucleosis-like symptoms (fatigue, diarrhea, weight loss, neurological changes) that disappear as the immune system responds.
    • Asymptomatic Period: Can last 22 to 15 years15\,\text{years}. Lymphadenopathy may be the only prominent symptom while T-cell levels steadily decline.
    • Wasting Syndrome: Pronounced loss of body mass due to diarrhea and poor nutrient absorption (the virus is particularly hard on the GI tract).
    • Neurological Complications: Lesions in the brain, spinal column, and nerves; symptoms include memory loss, spasticity, and progressive AIDS dementia.

  • AIDS-Defining Illnesses (ADIs)

    • Skin/Mucous Membranes: Kaposi's sarcoma, chronic Herpes simplex ulcers (>1 month>1\,\text{month}), Cytomegalovirus retinitis.
    • Nervous System: Cryptococcosis (extrapulmonary), Toxoplasmosis of the brain, HIV encephalopathy.
    • Respiratory: Pneumocystis jiroveci pneumonia, Pulmonary tuberculosis (Mycobacterium tuberculosis), Candidiasis of the trachea/bronchi/lungs.
    • GI Tract: Esophageal candidiasis, chronic Cryptosporidiosis.
    • Genitourinary: Invasive cervical carcinoma (linked to HPV).

  • Causative Agent and Pathogenesis

    • Virus: HIV is a retrovirus in the genus Lentivirus.
    • Reverse Transcriptase (RT): Catalyzes the replication of double-stranded DNA from single-stranded RNA.
    • Genome Integration: Viral genes can be permanently integrated into the host genome.
    • Infection Pathway: Virus enters skin or mucous membranes $\rightarrow$ dendritic cells beneath the epithelium $\rightarrow$ amplified by macrophages $\rightarrow$ infects/destroys helper T4 (CD4) lymphocytes, B lymphocytes, and monocytes.
    • Syncytia: The virus causes host cells to fuse together.

  • Transmission and Epidemiology

    • Primary Routes: Sexual intercourse, transfer of blood/blood products, and vertical transmission (before/during birth or via breast milk).
    • Sensitive Nature: HIV does not survive long outside the host and is sensitive to disinfectants; it is not transmitted through saliva.
    • Health Care Exposure: Potential for transmission via amniotic fluid, spinal fluid, and synovial fluid.

  • Diagnosis of AIDS (CDC Criteria)

    1. Test positive for HIV.
    2. Check for one of the following:
      • CD4 count below 200\,\text{cells/\mu L}.
      • CD4 cells account for less than 14%14\% of total lymphocytes.
      • Presence of one or more AIDS-defining illnesses.

  • Treatment

    • There is no cure; however, drugs like Triumeq (containing one integrase inhibitor and two reverse transcriptase inhibitors) improve quality of life.
    • Treatment should begin immediately following diagnosis.

Endocarditis

  • Overview

    • Inflammation of the endocardium, typically involving infection of the heart valves (often the mitral or aortic valve).
    • Prosthetic Valve Hazard: Surgical innovation introduces sites for bacterial colonization and biofilm formation.

  • Acute Endocarditis

    • Result of sudden, overwhelming bloodstream challenges.
    • Causative Agents: Staphylococcus aureus (most common), Streptococcus pyogenes, Streptococcus pneumoniae, and Neisseria gonorrhoeae.
    • Pathology: "Vegetations" (bacterial accumulations) hamper valve function, potentially causing cardiac malfunction, death, or emboli.
    • Transmission: Parenteral route (direct entry via IV drug use, surgery, or traumatic injury).

  • Subacute Endocarditis

    • Almost always preceded by heart valve damage (e.g., from rheumatic fever) or congenital malformations.
    • Causative Agents: Low pathogenicity bacteria from the oral cavity, such as Alpha-hemolytic streptococci (Streptococcus sanguis, S. oralis, S. mutans).
    • Transmission: Minor disruptions like rigorous tooth brushing, dental procedures, or minor cuts.
    • Prevention: Prophylactic antibiotic therapy before dental or surgical procedures.

  • Signs and Symptoms

    • Fever, fatigue, joint pain, edema (feet, legs, abdomen), and abnormal heartbeat.
    • Janeway Lesions: Painless red spots on palms and soles.
    • Osler’s Nodes: Small, painful nodes on finger and toe pads.
    • Petechiae: Small hemorrhages over the upper body and under fingernails.
    • Long-term cases can result in clubbed fingers/toes due to chronic oxygen deficiency.

Septicemia and Plague

  • Septicemia (Sepsis)

    • Occurs when organisms actively multiply in the blood.
    • Symptoms: Fever (prominent), respiratory alkalosis (due to increased breathing rate), and low blood pressure (hallmark caused by fluid loss from the vasculature).
    • Causative Agents: 90%90\% bacterial (evenly split between Gram-positive and Gram-negative; MRSA is common), 10%10\% fungal.
    • Endotoxic Shock: In Gram-negative sepsis, the release of endotoxin stimulates a massive cytokine-mediated inflammatory response, leading to a drastic drop in blood pressure.
    • Epidemiology: Approximately 500,000500,000 cases resulting in 100,000100,000 deaths annually in the U.S.

  • Plague

    • Causative Agent: Yersinia pestis, a tiny, Gram-negative rod with bipolar "safety pin" staining. Infectious dose is only 33 to 5050 cells.
    • Pneumonic Plague: Respiratory form of the disease.
    • Bubonic Plague: Flea bite $\rightarrow$ lymph $\rightarrow$ lymph node inflammation $\rightarrow$ bubo (swollen lesion in groin or axilla). Mortality >15%>15\%.
    • Septicemic Plague: Bacterial growth in the blood $\rightarrow$ disseminated intravascular coagulation $\rightarrow$ necrosis/gangrene ("The Black Death"). Mortality 3030 to 50%50\% with treatment; 100%100\% without.
    • Transmission: Fleas ingest blood from infected animals; bacteria block the flea's esophagus; the hungry flea bites repeatedly, regurgitating bacteria into wounds. Endemic in western U.S. states.

Lyme Disease and Infectious Mononucleosis

  • Lyme Disease

    • Causative Agent: Borrelia burgdorferi, a large spirochete (0.20.2 to 0.5 μm0.5\,\mu m wide, 1010 to 20 μm20\,\mu m long) with 33 to 1010 loose coils.
    • Signs and Symptoms:
      1. Stage 1: Erythema migrans (bull's-eye rash with a raised red ring and pale center) in 70%70\% of cases; fever, headache, stiff neck.
      2. Stage 2: Cardiac and neurological symptoms (e.g., facial palsy).
      3. Stage 3: Crippling arthritis and chronic neurological complications.
    • Pathogenesis: Immune evasion via antigenic shifting. The immune response may contribute to pathology.
    • Transmission: Two-year life cycle involving mice (larvae infection), deer, and humans (accidental host via nymph/adult bites).
    • Prevention/Treatment: Tick avoidance, protective clothing; early treatment with doxycycline or amoxicillin for 33 to 4 weeks4\,\text{weeks}.

  • Infectious Mononucleosis ("Mono")

    • Causative Agent: Primarily Epstein-Barr virus (EBV), a herpesvirus.
    • Incubation: 3030 to 50 days50\,\text{days}.
    • Symptoms: Sore throat (with gray-white exudate), high fever, cervical lymphadenopathy, fatigue, and sudden leukocytosis (infected B cells then T cells).
    • Epidemiology: Over 90%90\% of the world population is infected. Infection during teen years usually results in disease, while earlier/later infections are often asymptomatic.
    • Transmission: Direct oral contact and saliva contamination ("The Kissing Disease").

Questions & Discussion

  • Concept Check 1: Which of the following terms refers to bacteria flourishing and growing in the bloodstream?
    • Answer: Septicemia.
  • Concept Check 2: The cardiovascular and lymphatic systems, being “closed” systems, are always completely sterile.
    • Answer: False (based on HMP evidence of low-level microbes in healthy blood).
  • Concept Check 3: HIV is primarily transmitted through:
    • Answer: Homosexual and heterosexual intercourse, nonsterile needles, blood products, and mother-to-infant transmission.