Cardiovascular System Infection:
-Myocarditis.
-Infectious.
-Non-Infectious Autoimmune reaction.
-Pericarditis.
Intravascular system infections:
1-Endocarditis.
2-Bacteremia.
3-Septicemia and Septic shock.
N
Myocarditis:
Definition:
Inflammation of the cardiac muscle, with an immune
cellular infiltrate that results in myocardium destruction
and/or valvular disease , without blockage of coronary
artery that define heart attack (myocardial infarction).
Myocarditis may or may not include death (necrosis) of
heart tissue.
N
Myocarditis may include dilated cardiomyopathy.
Dilated cardiomyopathy or DCM is a condition in which
the heart becomes weakened and enlarged and cannot
pump blood efficiently.
The decreased heart function can affect the lungs, liver, and
other body systems.
N
Dilated Cardiomyopathy:
Gross pathology of idiopathic cardiomyopathy:
Opened left ventricle of heart shows a thickened, dilated left
ventricle with subendocardial fibrosis manifested as increased
whiteness of endocardium (Autopsy).
N
Cellular infiltration and Cardiac necrosis:
Histopathological image of myocarditis ( autopsy); acute congestive
heart failure due to viral infection.
Causes of Myocarditis:
1-Infectious.
2-Non-Infectious Autoimmune rxn.
N
Causes of Infectious Myocarditis:
1-Viral: Coxsackieviruse B, parvovirus B19 (common),
Human Herpes virus 6, HFVs, and others.
2-Bacterial: Treponema palladium (Syphilis) and Borrelia
burgdorferi (Lyme disease),and Rickettsia.
3-Protozoal: Chagas disease (common), Toxoplasmosis.
4-Helminthes: Trichinella spiralis, Ascaris, Echinococcus
granulosus, Schistosoma, Taenia solium, and
Wuchereria bancrofti.
5-Fungal: Blastomycosis, Coccidiomycosis,
Cryptococcosis, and Aspergillosis.
N
Causes of Non-Infectious Myocarditis:
1-Autoimmune rxn due to infection or systemic disorder:
A-Exogenous Antigen:
Post-Streptococcus pyogenes autoimmune reaction.
(Acute rheumatic fever).
B-Endogenous Antigen:
systemic lupus erythematosus , and systemic vasculitis.
2-Cardiotoxins:(Drug-induced Myocarditis):
A-Toxins associated with hypersensitivity reaction:
Toxic shock syndrome toxin, Snake venom, antibiotics.
B-Toxic Myocarditis: Carbon monoxide, Heavy metals,
Ethanol.
Non-infectious Myocarditis:
Autoimmune Rheumatic fever : Group A Streptococcus infection.
-Pharyngitis and tonsillitis caused by Streptococcus
pyogenes (Group A Streptococcus).
-Virulence factors of Streptococcus pyogenes:
1-Streptococcal pyrogenic exotoxin A,B,C:
Superantigen: T-cell activation: STSS.
2-M-protein that cross-reacts Cardiac muscle Myosin,
valves, and synovial myosin:
Autoimmune attack on cardiac muscle valves and
myocardium.
N
Non-Suppurative Complications of Streptococcus
pyogenes Pharyngitis:
1-Acute rheumatic fever:
-Significant cause of valvular heart
disease.
-Appears 1 to 4 weeks following
Streptococcus throat infection.
-Characterized by:
1-Myocarditis (common).
2-Polyarthritis (common).
3-Subcutanous nodules.
4-Erythema marginatum.
N
2-Recurrent Streptococcus infection :
- It causes ongoing inflammation of cardiac muscle.
- Could result in Chronic form:
-Extensive mitral (65-70% of cases) and/or aortic (25%)
valve destruction and Stenosis.
-This manifestation called
rheumatic heart disease:
1-Predisposing for
bacterial endocarditis.
2-Could cause heart
failure and death.
Infectious Myocarditis:(1-Protozoan infection):
N
A-Chagas disease:
In Europe and North America, viruses are common cause of
myocarditis.
Worldwide, however, the most common cause is Chagas'
disease, an illness endemic to Central and South America that
is due to infection by the protozoan Trypanosoma cruzi.
Transmission:
the Winged bug of the genus Triatoma deposits feces on the skin
surface. Bite of skin results in contamination of wound by microbe.
Life Cycle and Pathogenesis:
Infective stage: Metacyclic trypomastigote.
Diagnostic stage: Trypomastigote in blood.
Amastigote in muscle.
Primary infection:
Skin or mucus membranes infection, localized swelling ;
Chagoma, Bloodstream invasion.
Replication of amastigote in cardiac muscle myofibrils;
gradual autoimmune destruction of heart myocardium
lead to cardiac enlargement and arrhythmias, and heart
failure.
Life Cycle and Pathogenesis:
n
Life cycle , and Vector of Chagas’ disease:
Triatoma
Clinical presentation of Chagas’ disease:
1-Acute stage:
-Localized swelling at the site of entry;
(Chagoma in skin, Romana’s sign in Eyelid).
-Lasts for the first few weeks or months of infection.
-Mild symptoms can include fever, fatigue , headache,
rash, diarrhea, and vomiting.
-Other sign on physical examination include mild
enlargement of the liver or spleen.
-The acute form usually goes unnoticed; so the microbial
colonization of tissue results in chronic stage.
Clinical presentation of acute stage of Chagas’ disease
Chagoma in skin
Romaña's sign: swelling of
eyelid in acute Chagas disease
due to bug feces being
accidentally rubbed into the
eye, or because the bite wound
was on the same side of the
face.
N
2-Chronic Stage:
-It appears 10 to 20 years after primary infection.
-The parasite invades the myofibrils of the heart;
colonization of muscle; causing myocytolysis; myocarditis.
-The gradual autoimmune destruction of heart
myocardium (T-cell delayed hypersensitivity) lead to:
A-Dilated Cardiomyopathy (In 2/3 of Patients); Cardiac
arrhythmias.
B-Cardiac enlargement, heart failure, and Sudden death.
C-Other body systems (Digestive, CNS) are involved.
Autoantibodies produced: Anti-actin, myosin,& laminin.
Chronic stage and diagnosis of Chagas’s disease:
Amastigote in muscle tissue.
Dilated Cardiomyopathy
and Cardiac muscle
Myocardium destruction
(Chronic stage; Chagas’disease)
Trypomastigote in Blood (Giemsa).
Infectious Myocarditis:(1-Protozoan infection)
B-Toxoplasmosis:
-Usually minor and self-limiting but can have serious or
fatal effects on a fetus whose mother first contracts the
disease during pregnancy or on an immunocompromised
Patients.
-Caused by Toxoplasma gondii ; which is Protozoa.
-Cats are definitive host, that produce fecal oocyst; the
infective stage for man and other warm-blooded animals
(mice, birds, cattle , pigs).
-Man could be infected due to ingestion of tissue cyst (in
skeletal muscles of warm-blooded animals).
Life cycle of Toxoplasma gondii :
n
2-Viral Myocarditis:
A- Group B Coxsackievirus infection:
-Group B Coxsackievirus are the main viral causes of acute
myocarditis , and pericarditis.
-The virus invades the pharynx or gut wall to the lymphatics
and then to the blood.
-Invasion of striated muscle, heart or pericardium takes place
across small blood vessels and results in acute inflammation
of the myofibrils (Lymphocytic infiltrates).
n
Mechanism of Myocardium destruction:
1-Direct Myocyte damage due to viral invasion.
2-Cellular immune response against virusassociated antigen on cell surface; NK cell, Tc
cell.
TH and B-cell activation; Autoantibodies:
1-Anti-Myocyte ion transporter.
2- Anti-signal transduction protein antibodies.
Autoimmune reaction against self-Ag of infected cells:
Chronic myocarditis, and DCM.
N
Group B tend to infect the heart, pleura and pancreas,
causing Pleurodynia, Myocarditis and Pericarditis.
Group A tend to infect skin and mucous membranes,
causing herpangina, acute hemorrhagic conjunctivitis, and
hand, foot, and mouth disease.
Both group A and B can cause upper respiratory tract
disease, and aseptic meningitis.
N
Virology:
Coxsackievirus group A and B:
Family: Picornaviridae
Genus: Enterovirus
: Non enveloped, linear, positive-sense ss RNA viruses.
-Two groups: A &B
-It is mainly transmitted by Fecal-Oral route.
Coxs. Virus as
illustrated by
electron microscopy.
2-Viral Myocarditis:
B- Parvovirus B19 infection:
Parvovirus B19: OR Erythrovirus B19:
-Erythroviruses belong to the Parvoviridae family.
-Small DNA viruses.
-It is a non-enveloped, icosahedral virus
that contains a single-stranded linear DNA genome.
-It is classified as Erythrovirus because of its capability to
invade Red blood cell precursors in the bone marrow.
Transmission:
-The virus is primarily spread by
infected respiratory droplets; and blood- transfusion.
Fifth disease: (Manifestation of Parvovirus infection).
-Fifth disease or erythema infectiosum
(fifth pink-red infectious rash) or slapped cheeks
disease.
-Incubation period: four to fourteen days
-Symptoms:
fever, runny nose, headache then a red rash appear in
the face and may spread to other parts.
-In adults, parvovirus B19 may lead to autoimmune
arthritis due to formation of circulating virionantibodies complexes.
Fifth disease:
N
N
Parvovirus B19 infection in inherited blood diseased
patients:
Most patients have normal erythropoiesis (production
of red blood cells) during the infection.
In sickle cell anemia and hereditary spherocytosis;
patients develop dangerous reticulocytopenia;
(aplastic crisis).
3-Bacterial Myocarditis:
-Bacterial Myocarditis is rare in patients with normal
immunity.
-It is associated mainly with immunodeficiency patients.
-It could be established due to formation of septic emboli
secondary to bacterial endocarditis.
-Causative agents of Bacterial Myocarditis in patients with
normal immunity:
1-Borrelia burgdorferi: Lyme disease; (Plasma cell infiltrate).
2-Leptospirosis.
3-Rickettsial disease(RMSF): Lymphocytic infiltrate.
4-Cardiovascular Syphilis.
3-Bacterial Myocarditis:
A-Lyme disease: Borrelia burgdorferi infection.
Borrelia burgdorferi is a species of Gram negative bacteria of
the spirochete class of the genus Borrelia.
Lyme disease is a zoonotic, vector-borne disease transmitted
by ticks of the genus Ixodes from Rodent and Deer.
The microbe is transmitted from lymph nodes, lymphatic
vessels, and blood stream to cardiac muscle and CNS.
Weeks to months after the primary infection, the second stage
begins with Myocarditis, cardiomyopathy, meningitis, and
neuropathies.
Life Cycle, Vector, and Clinical pres. of Lyme disease:
N
B-Cardiovascular Syphilis: (Bacterial Myocarditis):
-Caused by the Spirochete Treponema pallidium infection.
-Accounts for 10% of cases of tertiary syphilis.
-It could appear after 10-30 years of primary infection.
-It is associated with Syphilitic aortitis
that could be complicated by
aortic aneurysm.
-Mechanism of tissue destruction:
1-T-cell delayed type hypersensitivity.
2-Humoral response due to Anti-Cardiolipin Antibodies.
N
-Transmission of Treponema pallidium:
-Sexually, transplacental, vertical, blood transfusion.
-Microbial characteristics:
-Thin spirochete; Basically it has Gram’s negative cell
envelope.
-Axial filaments present (endoflagella).
-Can not be cultivated in vitro; Sero-diagnosis(TPHA).
-Myocarditis could
be established in late syphilis
due to autoimmune
reactions
against myocardium.
N
Other causative agents for Bacterial Myocarditis:
-Brucella
-Corynebacterium diphtheriae
-Neisseria gonorrhoeae
-Haemophilus influenzae
-Actinomyces
-Staphylococcus aureus (Endocarditis origin)
-Streptococcus species (Endocarditis origin)
-Streptococcus pyogenes (Rheumatic fever).
4-Fungal Myocarditis: Example: Aspergillosis:
Aspergillosis develops mainly in individuals who
are immunocompromised. The most common forms
are allergic broncho-pulmonary aspergillosis,
pulmonary aspergilloma and invasive aspergillosis.
5-Parasitic Myocarditis: Trichinella spiralis (Helminthes):
-Is a nematode , infect rats, pigs, bears and humans, and is
responsible for the disease trichinosis.
-Humans typically become infected when they eat
improperly cooked pork
contains Trichinella encystic
larvae (infective stage).
-Female Trichinella worms live for about six weeks, and in
that time can produce up to 1,500 larvae
-Larvae may migrate with blood to cardiac muscle causing
myocarditis.
Trichinella spiralis Life cycle:
N
Diagnosis of Myocarditis:
Myocardial inflammation can be suspected on the basis
of electrocardiographic results (ECG), elevated C-reactive
protein (CRP) and/or Erythrocyte sedimentation rate (ESR) and
increased IgM (serology) against viruses known to affect
the myocardium.
Markers of myocardial damage ( Troponin or creatine
kinase cardiac isoenzymes) are elevated.
A small tissue sample (Endomyocardium biopsy) is taken, and
examined microscopically. Immunochemistry and special staining
methods could be used to confirm the results.
Pericarditis:
Pericardium: is a fibroelastic sac surrounding the heart
that consists of visceral and parietal pericardium.
-Visceral pericardium:
Simple layer of mesothelial
cells; serous layer.
-Parietal pericardium:
Innervated fibrous and
Elastic tissues (2 mm thick).
N
Pericarditis: is the inflammation of pericardium due to
infectious or non-infectious etiology.
-90% of cases of acute form are caused by idiopathic or
viral etiology.
Infectious pericarditis:
1-Acute:
A-Viral: Enteroviruses: Cox virus A and B, and echovirus.
B-Bacterial: (high mortality rate):
-Most common causes:
H.influenzae, Meningococci, Pneumococci,
Staphylococcus aureus, Streptococcus group A.
-Caused by Bacteremia or Contiguous (Pneumonia).
N
2-Chronic :
A-Tuberculous pericarditis:
-Accounts for fewer than 5% of cases in developed
world.
-Accounts for 50% to 70% of cases in Sub-Saharan
Africa.
-More common in HIV-Patients.
-Presence of caseating granulomas and positive AFB
staining reaction.
B-Fungal pericarditis: Immunocompromised patients:
-Histoplasmosis, and Coccidioides infection.