PBL: Breathing through fish mouth

1. A.Rheumatic fever is an inflammatory disease that can develop as a complication of

inadequately treated strep throat or scarlet fever. Strep throat and scarlet fever are caused by
an infection with group A streptococcus bacteria.Rheumatic fever is most common in 5- to
15-year-old children, though it can develop in younger children and adults. Rheumatic fever
can cause permanent damage to the heart, including damaged heart valves and heart failure.
Treatments can reduce tissue damage from inflammation, lessen pain and other symptoms,
and prevent the recurrence of rheumatic fever.
B. Rheumatic fever can occur after an infection of the throat with a bacterium called
Streptococcus pyogenes, or group A streptococcus. Group A streptococcus infections of the
throat cause strep throat or, less commonly, scarlet fever. Group A streptococcus infections of
the skin or other parts of the body rarely trigger rheumatic fever.
C. Rheumatic fever is a systemic disease affecting the peri-arteriolar connective tissue and can
occur after an untreated Group A Beta hemolytic streptococcal pharyngeal infection. It is
believed to be caused by antibody cross-reactivity. This cross-reactivity is a Type II
hypersensitivity reaction and is termed molecular mimicry. Usually, self reactive B cells
remain anergic in the periphery without T cell co-stimulation. During a Streptococcus
infection, mature antigen presenting cells such as B cells present the bacterial antigen to CD4T cells which differentiate into helper T2 cells. Helper T2 cells subsequently activate the B
cells to become plasma cells and induce the production of antibodies against the cell wall of
Streptococcus. However the antibodies may also react against the myocardium and joints,[11]
producing the symptoms of rheumatic fever.Group A Streptococcus pyogenes has a cell wall
composed of branched polymers which sometimes contain M protein that are highly antigenic.
The antibodies which the immune system generates against the M protein may cross react
with cardiac myofiber protein myosin,[12] heart muscle glycogen and smooth muscle cells of
arteries, inducing cytokine release and tissue destruction. However, the only proven cross
reaction is with perivascular connective tissue.[citation needed] This inflammation occurs through
direct attachment of complement and Fc receptor-mediated recruitment of neutrophils and
macrophages. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen
surrounded by lymphocytes and macrophages can be seen on light microscopy. The larger
macrophages may become Anitschkow cells or Aschoff giant cells. Acute rheumatic valvular
lesions may also involve a cell-mediated immunity reaction as these lesions predominantly
contain T-helper cells and macrophages.[13]In acute rheumatic fever, these lesions can be
found in any layer of the heart and is hence called pancarditis. The inflammation may cause a
serofibrinous pericardial exudate described as "bread-and-butter" pericarditis, which usually
resolves without sequelae. Involvement of the endocardium typically results in fibrinoid
necrosis and verrucae formation along the lines of closure of the left-sided heart valves. Warty

projections arise from the deposition, while subendocardial lesions may induce irregular
thickenings called MacCallum plaques.

D. Inflammation caused by rheumatic fever may last for a few weeks to several months. In some
cases, the inflammation may cause long-term complications.
Rheumatic heart disease is permanent damage to the heart caused by the inflammation of
rheumatic fever. Problems are most common with the valve between the two left chambers of
the heart (mitral valve), but the other valves may be affected. The damage may result in one of
the following conditions:

Valve stenosis. This condition is a narrowing of the valve, which results in decreased blood
flow.
Valve regurgitation. This condition is a leak in the valve, which allows blood to flow in the
wrong direction.
Damage to heart muscle. The inflammation associated with rheumatic fever can weaken the
heart muscle, resulting in poor pumping function.
Damage to the mitral valve, other heart valves or other heart tissues can cause problems with the
heart later in life. Resulting conditions may include:

Atrial fibrillation, an irregular and chaotic beating of the upper chambers of the heart (atria)
Heart failure, an inability of the heart to pump enough blood to the body
E. According to revised Jones criteria, the diagnosis of rheumatic fever can be made when two of
the major criteria, or one major criterion plus two minor criteria, are present along with
evidence of streptococcal infection: elevated or rising antistreptolysin O titre or DNAase.[1]
Exceptions are chorea and indolent carditis, each of which by itself can indicate rheumatic
fever.[

Major criteria

Polyarthritis: A temporary migrating inflammation of the large joints, usually starting in the
legs and migrating upwards.
Carditis: Inflammation of the heart muscle (myocarditis) which can manifest as congestive
heart failure with shortness of breath, pericarditis with a rub, or a new heart murmur.
Subcutaneous nodules: Painless, firm collections of collagen fibers over bones or tendons.
They commonly appear on the back of the wrist, the outside elbow, and the front of the knees.

Erythema marginatum: A long-lasting reddish rash that begins on the trunk or arms as
macules, which spread outward and clear in the middle to form rings, which continue to
spread and coalesce with other rings, ultimately taking on a snake-like appearance. This rash
typically spares the face and is made worse with heat.
Sydenham's chorea (St. Vitus' dance): A characteristic series of rapid movements without
purpose of the face and arms. This can occur very late in the disease for at least three months
from onset of infection.

Minor criteria

Fever of 38.238.9 C (100.8102.0 F)

Arthralgia: Joint pain without swelling (Cannot be included if polyarthritis is present as a
major symptom)
Raised erythrocyte sedimentation rate or C reactive protein
Leukocytosis
ECG showing features of heart block, such as a prolonged PR interval[9][10] (Cannot be
included if carditis is present as a major symptom)
Previous episode of rheumatic fever or inactive heart disease

Other signs and symptoms

Abdominal pain
Nose bleeds
Preceding streptococcal infection: recent scarlet fever, raised antistreptolysin O or other
streptococcal antibody titre, or positive throat culture.[10]
2. Chronic rheumatic heart disease (RHD) is characterized by repeated inflammation with
fibrinous repair. The cardinal anatomic changes of the valve include leaflet thickening,
commissural fusion, and shortening and thickening of the tendinous cords.[13] It is caused by
an autoimmune reaction to Group A -hemolytic streptococci (GAS) that results in valvular
damage.[14] Fibrosis and scarring of valve leaflets, commissures and cusps leads to
abnormalities that can result in valve stenosis or regurgitation. The causes is known to involve
molecular mimicry and genetic predisposition that lead to autoimmune reactions.
3.Molecular mimicry occurs when epitopes are shared between host antigens and GAS
antigens.[17] This causes an autoimmune reaction against native tissues in the heart that are
incorrectly recognized as "foreign" due to the cross-reactivity of antibodies generated as a
result of epitope sharing. The valvular endothelium is a prominent site of lymphocyte-induced
damage. CD4+ T cells are the major effectors of heart tissue autoimmune reactions in
RHD.[18] Normally, T cell activation is triggered by the presentation of GAS antigens. In

RHD, molecular mimicry results in incorrect T cell activation, and these T lymphocytes can
go on to activate B cells, which will begin to produce self-antigen-specific antibodies. This
leads to an immune response attack mounted against tissues in the heart that have been
misidentified as pathogens. Rheumatic valves display increased expression of VCAM-1, a
protein that mediates the adhesion of lymphocytes.[19] Self-antigen-specific antibodies
generated via molecular mimicry between human proteins and GAS antigens up-regulate
VCAM-1 after binding to the valvular endothelium. This leads to the inflammation and valve
scarring observed in rheumatic valvulitis, mainly due to CD4+ T cell infiltration.[19]
While the mechanisms of genetic predisposition remain unclear, a few genetic factors have been
found to increase susceptibility to autoimmune reactions in RHD. The dominant contributors
are a component of MHC class II molecules, found on lymphocytes and antigen-presenting
cells, specifically the DR and DQ alleles on human chromosome 6.[20] Certain allele
combinations appear to increase RHD autoimmune susceptibility. Human leukocyte antigen
(HLA) class II allele DR7 (HLA-DR7) is most often associated with RHD, and its
combination with certain DQ alleles is seemingly associated with the development of valvular
lesions.[20] The mechanism by which MHC class II molecules increase a host's susceptibility
to autoimmune reactions in RHD is unknown, but it is likely related to the role HLA
molecules play in presenting antigens to T cell receptors, thus triggering an immune response.
Also found on human chromosome 6 is the cytokine TNF- which is also associated with
RHD.[20] High expression levels of TNF- may exacerbate valvular tissue inflammation,
contributing to RHD pathogenesis. Mannose-binding lectin (MBL) is an inflammatory protein
involved in pathogen recognition. Different variants of MBL2 gene regions are associated in
RHD. RHD-induced mitral valve stenosis has been associated with MBL2 alleles encoding for
high production of MBL.[21] Aortic valve regurgitation in RHD patients has been associated
with different MBL2 alleles that encode for low production of MBL.[22] Other genes are also
being investigated to better understand the complexity of autoimmune reactions that occur in
RHD.
4. Heart valve damage is the hallmark of this disease, which can lead to congestive heart failure
and death. Carditis, skin lesions, chorea and mitral stenosis are all complications associated
with rheumatic heart disease.

Carditis
Carditis is the most serious complication of rheumatic heart disease. Carditis results in damage
and disease of the heart valve. The term carditis is used to describe inflammation of the entire
heart, including the pericardium or the heart outer layer, myocardium or heart muscle, and
endocardium or the inner lining of the heart. Subsequently, the heart valves enlarge and
become diseased with vegetation called verrucae. Upon examination, the disease is confirmed

by the presence of pericardial friction created by the heart outside layer rubbing against the
chest cavity, elevated heart rate, heart murmurs and valve regurgitation.

Skin Lesions
Two types of skin lesions occur in those with rheumatic heart disease. Lumps underneath the
skin, referred to by physicians as subcutaneous nodules, appear for periods of 2 weeks over
bony surfaces or near tendons. The lumps range in size from several millimeters to 2
centimeters.. These lumps are typically described as hard and painless.
The second type of lesion, erythema marginatum, is a skin rash that occurs early in the
development of rheumatic heart disease. It has a pink to red appearance and often occurs on
the torso and upper arm and leg areas.

Chorea
Chorea, less formally referred to as St. Vitus dance, is a neurological movement disorder
resulting in abrupt and involuntary motions of the face, torso, arms and legs. Muscle weakness
and behavioral disorders, such as obsessive-compulsive disorder, have also been associated
with the disease. The onset of chorea develops slowly, and symptoms progressively getting
worse over a 1 to 2 month period and then go away gradually after 3 to 6 months. However,
the symptoms may come and go in cycles over a 2 year period.

Mitral Stenosis
Mitral stenosis is another serious complication associated with rheumatic heart disease. It
involves the thickening of the mitral or left heart valve and progressive calcification of its
surface, leading to reduced blood flow from the heart and subsequent heart failure.

5. Treatment
Treatment is not necessary in asymptomatic patients.[2]
The treatment options for mitral stenosis include medical management, mitral valve replacement
by surgery, and percutaneous mitral valvuloplasty by balloon catheter.
The indication for invasive treatment with either a mitral valve replacement or valvuloplasty is
NYHA functional class III or IV symptoms.
Another option is balloon dilatation. To determine which patients would benefit from
percutaneous balloon mitral valvuloplasty, a scoring system has been developed. Scoring is

based on 4 echocardiographic criteria: leaflet mobility, leaflet thickening, subvalvar

thickening, and calcification. Individuals with a score of 8 tended to have suboptimal
results. Superb results with valvotomy are seen in individuals with a crisp opening snap, score
< 8, and no calcium in the commissures.
Treatment also focuses on concomitant conditions often seen in mitral stenosis:
Any angina is treated with short-acting nitrovasodilators, beta-blockers and/or calcium blockers
[9]
Any hypertension is treated aggressively, but caution must be taken in administering beta-blockers
Any heart failure is treated with digoxin, diuretics, nitrovasodilators and, if not contraindicated,

cautious inpatient administration of ACE inhibitors[9]

Illustration of mitral valvuloplasty

Mitral valvuloplasty
Mitral valvuloplasty is a minimally invasive therapeutic procedure to correct an uncomplicated
mitral stenosis by dilating the valve using a balloon. Under local anaesthetic, a catheter with a
special balloon is passed from the right femoral vein, up the inferior vena cava and into the
right atrium. The interatrial septum is punctured and the catheter passed into the left atrium
using a "trans-septal technique." The balloon is sub-divided into 3 segments and is dilated in 3
stages. First, the distal portion (lying in the left ventricle) is inflated and pulled against the
valve cusps. Second, the proximal portion is dilated, in order to fix the centre segment at the
valve orifice. Finally, the central section is inflated, this should take no longer than 30
seconds, since full inflation obstructs the valve and causes congestion, leading to circulatory
arrest and flash pulmonary edema.[citation needed]
With careful patient pre-selection, percutaneous balloon mitral valvuloplasty (PBMV) is
associated with good success rates and a low rate of complications. By far the most serious
adverse event is the occurrence of acute severe mitral regurgitation. Severe mitral
regurgitation usually results from a tear in one of the valve leaflets or the subvalvular

apparatus. It can lead to pulmonary oedema and hemodynamic compromise, necessitating

urgent surgical mitral valve replacement.
Other serious complications with PBMV usually relate to the technique of trans-septal puncture
(TSP). The ideal site for TSP is the region of the fossa ovalis in the inter-atrial septum.
Occasionally, however, the sharp needle used for TSP may inadvertently traumatize other
cardiac structures, leading to cardiac tamponade or serious blood loss]
Although the immediate results of PBMV are often quite gratifying, the procedure does not
provide permanent relief from mitral stenosis. Regular follow-up is mandatory, to detect
restenosis. Long-term follow-up data from patients undergoing PBMV indicates that up to 7075% individuals can be free of restenosis 10 years following the procedure. The number falls
to about 40% 15 years post-PBMV.
8. Almost all cases of mitral stenosis are due to disease in the heart secondary to rheumatic fever
and the consequent rheumatic heart disease.[2][3] Uncommon causes of mitral stenosis are
calcification[4][5] of the mitral valve leaflets, and as a form of congenital heart disease.
However, there are primary causes of mitral stenosis that emanate from a cleft mitral
valve.[citation needed] It is the most common valvular heart disease in pregnancy.[6]
Other causes include infective endocarditis where the vegetations may favor increase risk of
stenosis. Other rare causes are include mitral annular calcification, endomyocardial
fibroelastosis, malignant carcinoid syndrome, systemic lupus erythematosus, whipple disease,
fabry disease, and rheumatoid arthritis
9. Rheumatic fever is characterized pathologically by exudative and proliferative inflammatory
lesions of the connective tissue in the heart, joints, blood vessels, and subcutaneous tissue.
In the early stage, fragmentation of collagen fibers, cellular infiltration that is predominantly
lymphocytic, and fibrinoid deposition followed by the appearance of a myocardial Aschoff
nodule (a perivascular focus of inflammation that has an area of central necrosis surrounded
by a rosette of large mononuclear and giant multinuclear cells) occur. The nuclei of these cells
resemble owl eyes and are called Anichkov cells.
Subcutaneous nodules histologically resemble Aschoff nodules. The brain may show scattered
areas of arteritis and petechial hemorrhages, which have an uncertain relationship to
Sydenham chorea.