Microbial Diseases of the Cardiovascular and Lymphoid Systems

Structure & Function of the Cardiovascular and Lymphoid Systems

• Cardiovascular System

  • Consists of heart, arteries, veins, capillaries.

  • Core tasks: deliver O$2$, nutrients, hormones; remove CO$2$, metabolic waste.

  • Closed-loop, high-pressure circulation; intimately linked to lymphoid system for fluid balance.

• Lymphoid System

  • Plasma → interstitial fluid once it exits blood capillaries.

  • Lymph capillaries pick up this fluid and convey it to progressively larger lymph vessels (lymphatics) and lymph nodes.

  • Lymph nodes filter pathogens & present antigens to immune cells.

Sepsis, Septicemia & Septic Shock

• Septicemia: acute illness due to pathogens or their toxins circulating in blood.

• Sepsis: systemic inflammatory response syndrome (SIRS) triggered by infection.

• Septic Shock: sepsis + uncontrollable hypotension → multi-organ failure.

• Lymphangitis: visibly inflamed lymph vessels; often a diagnostic clue.

Gram-Negative (Endotoxic) Sepsis

• Causative agents: Klebsiella spp., Escherichia coli, Pseudomonas aeruginosa.

• Lipid A of LPS → massive cytokine release.

• Paradox: antibiotics lyse cells, releasing more LPS; treatment focuses on LPS neutralization + cytokine suppression.

Gram-Positive Sepsis

• Driven by potent exotoxins (e.g., superantigens) rather than LPS.

• Typical nosocomial culprits:

  • Enterococcus faecium, E. faecalis (vancomycin-resistant strains common).

  • Group B Streptococcus agalactiae → neonatal sepsis.

• Can progress to toxic shock syndrome.

Bacterial Infections of the Heart

• Endocarditis – inflammation of endocardium (valves & inner lining).

• Pericarditis – inflammation of pericardial sac; classically caused by streptococci.

• Myocarditis – inflammation of myocardium (heart muscle) itself.

Puerperal Sepsis (Puerperal Fever)

• Etiology: Streptococcus pyogenes (Group A).

• Virulence factors: M protein, hyaluronic-acid capsule, streptococcal pyrogenic exotoxins (SPEs).

• Transmission: during childbirth → uterine infection → peritonitis.

Rheumatic Fever & Molecular Mimicry

• Autoimmune sequel of untreated S. pyogenes pharyngitis.

• Pathology: antibodies vs. streptococcal M protein cross-react with cardiac tissue (molecular mimicry).

• Clinical facets:

  • Carditis (myocarditis, pericarditis, valvular or mural endocarditis).

  • Subcutaneous nodules, Sydenham’s chorea, erythema marginatum.

  • Long-term risk: chronic rheumatic heart disease.

Select Zoonoses & Environmental Bacterial Diseases

Tularemia (Rabbit Fever)

• Agent: Francisella tularensis (Gram-negative rod).

• Transmission: rabbits, deer flies, ticks; also aerosol & lab exposure.

• Entry ulcer → regional lymphadenopathy; organism multiplies in macrophages.

Brucellosis (Undulant Fever)

• Brucella spp. (aerobic Gram-negative coccobacilli).

• Reservoirs: cattle, goats, sheep, swine; acquired via unpasteurized milk or animal contact.

• Intracellular survival in reticuloendothelial system → periodic («undulant») fever, night sweats, myalgia; rarely fatal.

Anthrax

• Bacillus anthracis (Gram-positive, endospore-forming aerobic rod).

• Spores in soil, ingested by grazing animals.

• Human forms: cutaneous, inhalational, gastrointestinal, injection.

• Virulence factors:

  • Protective antigen (PA) – docks other toxins to host cell.

  • Edema toxin (EF + PA) – cAMP ↑ → local edema; impairs phagocytes.

  • Lethal toxin (LF + PA) – metalloprotease that kills macrophages.

  • Poly-D-glutamic-acid capsule – antiphagocytic, non-immunogenic.

• Therapy: ciprofloxacin or doxycycline; livestock vaccination key.

Gas Gangrene

• Agent: Clostridium perfringens (Gram-positive, endospore-forming anaerobe).

• Grows in ischemic/necrotic tissue → produces exotoxins (e.g., CPA (\alpha\text{-toxin}), CPB (\beta\text{-toxin})) that track along muscle planes.

• Clinical: crepitus, myonecrosis, systemic toxemia.

• Management: aggressive debridement/amputation + hyperbaric O$_2$.

Cat-Scratch Disease

• Bartonella henselae (aerobic Gram-negative) inhabits feline erythrocytes (~50\% of cats).

• Papule at scratch site → localized lymphadenitis; usually self-resolving.

Plague (Black Death)

• Agent: Yersinia pestis (Gram-negative rod).

• Vector: rat flea (Xenopsylla\ cheopis).

• Flea gut blocked → regurgitates infected blood.

• Virulence arsenal: Yops (Yersinia outer proteins) that disable phagocyte signaling; capsule; plasminogen activator.

• Clinical forms:

  • Bubonic – bubo formation; mortality 50–75\% untreated.

  • Septicemic – bacteria & LPS in blood → shock.

  • Pneumonic – inhalation/secondary spread; airborne; mortality ~100\% without prompt therapy.

• Post-exposure prophylaxis: doxycycline or fluoroquinolone.

Tick-Borne Bacterial Diseases

Lyme Disease (Lyme Borreliosis)

• Agent: Borrelia burgdorferi (spirochete).

• Vector: Ixodes ticks; reservoir: white-footed field mice; deer amplify ticks but are not infected.

• Tick life cycle: 2 yrs, 3 blood meals (larva → nymph → adult). Infection acquired at first (mouse) meal → transmitted at second (nymph) meal.

• Clinical stages:

  1. Early localized – expanding bull’s-eye (erythema migrans), flu-like symptoms.

  2. Early disseminated – heart block, facial palsy, meningitis, memory deficits.

  3. Late – migrating arthritis due to immune complexes, months–years later.

• Diagnosis: ELISA → confirm with Western blot/IFA.

• Tx: doxycycline or amoxicillin; IV ceftriaxone for neurologic/cardiac forms.

Rocky Mountain Spotted Fever (RMSF)

• Agent: Rickettsia rickettsii (obligate intracellular).

• Vectors: wood tick (Dermacentor\ andersoni) & dog tick (D. variabilis).

• Pathogenesis: invades endothelial cells → escapes phagosome → replicates cytosolically → cell lysis → vascular leak → petechiae, hypotension.

• Clinical: fever, severe headache, maculopapular rash incl. palms/soles.

• Mortality \approx20\% untreated; doxycycline highly effective if early.

Viral Hemorrhagic & Febrile Illnesses

Dengue / Severe Dengue (DHF • DSS)

• Agent: Dengue virus (DENV 1-4), a Flavivirus.

• Vector: Aedes aegypti.

• Epidemiology: Caribbean, SE Asia, Latin America, Africa.

• Spectrum: asymptomatic → classic dengue (break-bone fever) → DHF/DSS with plasma leakage, hemorrhage, organ failure.

• Antibody-dependent enhancement (ADE): heterotypic non-neutralizing Abs from a prior serotype bind FcyR on monocytes → ↑ viral load, ↑ severe disease risk.

• No specific antivirals; Dengvaxia licensed for 9–16 y olds with documented previous infection.

Protozoan & Helminthic Cardiovascular/Lymphatic Diseases

Chagas Disease (American Trypanosomiasis)

• Agent: Trypanosoma cruzi (flagellate).

• Vector: reduviid (kissing) bug; parasite deposited in feces, rubbed into bite/eye/conjunctiva.

• Acute: fever, lymphadenopathy, Romaña’s sign (eyelid swelling).

• Chronic (~20–30\%): cardiomyopathy, megacolon, megaesophagus; death from heart failure/arrhythmia.

Toxoplasmosis

• Agent: Toxoplasma gondii (obligate intracellular).

• Life cycle:

  1. Felines shed oocysts (sporulate in 1–5\text{ d}).

  2. Intermediate hosts (rodents, livestock, humans) ingest oocysts → tachyzoites disseminate → bradyzoite cysts in tissues.

• Human acquisition: cat litter, gardening, consumption of tissue cysts in undercooked meat.

• Major concern: congenital toxoplasmosis if primary maternal infection during pregnancy → stillbirth, hydrocephalus, chorioretinitis.

Malaria

• Agents: Plasmodium spp. — P. vivax (dormant hypnozoites in liver), P. falciparum (cerebral malaria, severe anemia).

• Vector: female Anopheles mosquito.

• Life cycle highlights:

  • Sporozoite inoculation → hepatocyte schizogony → merozoites released → cyclic RBC invasion & lysis (36–48 h) producing paroxysms of chills/fever.

  • Some merozoites → gametocytes → taken up by mosquito to complete cycle.

• Global burden: \approx250\text{ million} cases & \approx6\times10^{5} deaths annually.

• Key pathology: hemolysis, microvascular sequestration (falciparum), immune activation.

Schistosomiasis

• Agents: Schistosoma mansoni, S. haematobium, S. japonicum (blood flukes).

• Life cycle: eggs in feces/urine → hatch miracidia → infect snail (intermediate host) → produce fork-tailed cercariae → penetrate human skin → mature in portal circulation → adult pairs reside in mesenteric or vesical veins, laying eggs.

• Eggs trapped in tissues → granulomas → intestinal / urinary / hepatic fibrosis.

• Distribution: Africa, Middle East, South America, Caribbean.

Cross-Cutting Themes & Exam Tips

• Endotoxins vs. Exotoxins: Gram-negatives rely on LPS (heat-stable, macrophage cytokine storm); Gram-positives on protein exotoxins (often superantigens).

• Vector-borne diseases: Remember arthropod & reservoir pairings (e.g., Ixodes–mice for Lyme, Aedes–human for dengue, Dermacentor–dogs/rodents for RMSF).

• Immune-mediated pathology: rheumatic fever (molecular mimicry), dengue (ADE), Lyme arthritis (immune complexes).

• Lifecycle questions: be able to sketch Plasmodium, Schistosoma, Toxoplasma, Ixodes tick.

• Therapeutic pearls:

  • Doxycycline covers RMSF, Lyme early, anthrax alternative.

  • Hyperbaric O$_2$ for gas gangrene; antitoxin not yet widely available.

  • No antivirals for dengue; vaccine restricted to seropositive children.

• Public health: pasteurization (Brucella), livestock vaccination (anthrax), vector control (dengue, malaria), obstetric screening (GBS).

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