CHAPTER II
LITERATURE REVIEW OF DIFFERENT
2.1. Etiology Species Corynebacterium Diphteriae is a gram-positive (bacillary aerobic), immobilized, pleomorphic, not-encapsulated, spore-forming bacteria, dead on 60ºC warming, resistant in freezing and dry conditions. With staining, these germs can be seen in the palisade arrangement, L or V form, or a chinese-like formation. Germs are not selective in their growth, their isolation is facilitated by certain media (ie, egg-blooding cysts) that inhibit the growth of rival organisms, and when reduced by C. diphteheriae will make the colony black-gray, or by using loeffler media Medium containing serum that has been coagulated with high concentration phosphate granule occurs that is metachromatically colored with methylene blue, on this medium the colony will be cream colored. In the human mucous membranes C.diphtheriae can live together with the saprophytic diphtheroid germ that has similar morphology, so to distinguish sometimes it takes special inspection by fermentation of glycogen, starch, glucose, maltose or sucrose. (4) It is generally known that 3 main types of C.diphtheriae are the type of garvis, intermedius and mystical, but in terms of antigen, they are heterogeneous and have many serologic types. This may be biased to explain why in an ordinary patient has colonization of more than one type of C.diphtheriae. The characteristic of C.diphtheriae is its ability to produce both in-vivo and in-vitro exotoxins, this toxin may be demonstrated by in vivo toxin neutralization test in guinea pig (mortality test) or demonstrated in vitro by immunoprecipitin agar (Elek test) test reaction Polymerase observations. This exotoxin is a molecular weight 62,000 dalton protein, not heat or light resistant, has 2 fragments of fragment A (amino-terminal) and fragment B (carboxy-terminal). The ability of a strain to form or produce toxins is influenced by the presence of bacteriophages, the only toxin commonly produced by C.diphtheriae infected by bacteriophages containing toxigene. (1)
2.2. Pathogenesis and pathophysiology Germs C. diphtheriae enter through the mucosa / skin, attaches and breeds on the upper airway mucosal surface and begins to produce toxins seeping around and further spread throughout the body through lymph vessels and blood vessels. The effect of toxin on human body tissues is the inhibition of protein formation in cells. The formation of proteins in cells starts from the amalgamation of 2 amino acids that have binding 2 transfer RNAs that find the P and A positions of the ribosome. When this amino acid sequence gets added with other amino acids to form polypeptides according to the blue mold of RNA, a translocation process is required. This translocation is the transfer of a combination of RNA + dipeptide transfer from position A to position P. This translocation process requires active enzyme traslokase (elongation factor-2).
Diphtheria toxin initially attaches to the cell membrane with the help of fragment B and then fragment A enters and causes inactivation of the translocase enzyme through the process of NAD + EF2 (active) toxin ADP-ribosyl-EF2 (inactive) + H2 + Nicotinamide ADP-ribosyl-EF2 This inactive causes the traslocation process is not running so that no polypeptide series is required, with the result that the cell will die. Necrosis is evident in the germ colonization area. In response, localized inflammation, together with necrotic tissue, forms exudate spots that were previously easily removed. Toxic production is increasing, the area of infection is wider and fibrin exudates form. Formed a tightly embedded membrane grayish black, depending on the amount of blood contained. In addition to fibrin, the membrane also consists of inflammatory cells, erythrocytes and epithelium. When forced to release the membrane there will be bleeding. Furthermore, it will be released on its own during the healing period. (1)
In pseudomembranes occasionally secondary infection with bacteria (eg Streptococcus pyogenes) may occur. Membranes and edematous tissues can block the airway. Respiratory disturbance / bias expression occurs with extension of the disease into the larynx or branch of the tracheo-bronchus. Toxins circulated in the body of the bias result in damage to every organ, especially the heart, nerves and kidneys. Diphtheria antithoxin affects only free or absorbed toxins in the cell, but does not neutralize if the toxin penetrates into the cell. After fixed toxin in the cell, there is a varied latent time before the onset of clinical manifestations. Myocarditis usually occurs within 10-14 days, nerve manifestations generally occur after 3-7 weeks. Serious pathological disorders are toxic necrosis and hyaline degeneration of various organs and tissues. At the heart of edema, congestion, mononuclear cell infiltration of muscle fibers and conduction system. If the patient survives muscle regeneration and interstitial fibrosis. On neuritis appears toxic neuritis with fat degeneration in the myelin membrane. Common liver necrosis is accompanied by symptoms of hypoglycemia, sometimes seen as adrenal bleeding and acute tubular necrosis of the kidney. (4)
2.3. Clinical Manifestations Depending on a variety of factors, the manifestations of these diseases may vary from asymptomatic to a hypertensive and fatal condition / disease. The primary factor is host immunity to the diphtheria toxin, virulence and toxigenity of C. diphtheriae (the ability of bacteria to form toxins), and the location of the disease anatomically. Other factors include age, complementary systemic disease and disease in the nasopharyngeal area that has been previously. Difteria has a shoot period of 2 days. Patients are generally dating for treatment after several days of systemic complaints. Fever rarely exceeds 38.9ºC and complaints and other symptoms depend on the localization of diphtheria. (3)
2.3.1. Diphtheria Dysfunction In the classical description of 1400 cases of diphtheria from California published in 1954, the primary infection focus was tonsil or pharynx at 94%, with the most common nose and larynx next place. After about 2-4 days incubation period, there are signs and symptoms of local inflammation. Fever is rarely higher than 39ºC.
2.3.1.1. Diphtheria Nose diphtheria initially resembles a common cold, with mild cold symptoms without or with mild systemic symptoms. Anterior nares infections (more common in infants) cause erosive, purulent, serosanguine rhinitis with membrane formation. The superficial ulceration of outer nares and inner lips is typical. On examination looks white membrane on the septum rice area. Absorption of toxin is very slow and systemic symptoms are not evident so a slow diagnosis is made. (4)
2.3.1.2 Pharynx Tonsil Diphtheria In tonsill and pharynx diphtheria, sore throat is a common early symptom, but only half suffer from dysphagia, hoarseness, malaise or headache. Within 1-2 days later, a gray-white membrane is attached, a mild pharyngeal injection is accompanied by unilateral or bilateral tonsil membrane formation, which extends differently about the uvula, the palate of the molle, the posterior oropharynx, the hypopharynx and the glottis region. The soft tissue edema underneath and enlarged lymph nodes can lead to a "bull neck" picture. Further symptoms depend on the degree of toxin penetration and membrane area. In severe cases, respiratory or circulatory failure may occur. Paralysis of both the union and bilateral molybasis may be present, with difficulty in swallowing and regurgitation. Stupor, coma, death bias occurs within 1 week to 10 days. In the case of moderate healing occurs gradually and bias accompanied by complications of myocarditis or neuritis. In mild cases the membrane will be released in 7-10 days and usually a complete healing occurs. (6)
Gambar
2.3.1.3. Diphtheria Laryngeal Diphtheria is usually an extension of pharyngeal diphtheria. Patients with diphtheria larynx tend to suffocate due to soft tissue edema and blockage of epithelial respiratory epithelium thickness and necrotic clot. In primary pharyngeal diphtheria toxic symptoms are less pronounced, because the mucosa of the larynx has a lower absorption of toxin than the pharyngeal mucosa so that the upper airway obstruction symptoms are more prominent. Clinical symptoms of laryngeal diphtheria are difficult to distinguish from other types of infectious croups, such as breath sounds, progressive stridor, hoarseness and dry cough. In severe laryngeal obstruction there are suprasternal, intercostal and supraclavicular retractions. If there is a membrane release that closes the normal airway, sudden death occurs. In severe cases, the membrane may extend into the tracheobronchial branches. When laryngeal diphtheria occurs as an extension of pharyngeal diphtheria, the apparent symptom is a mixture of symptoms of obstruction and toxemia.
Gambar
2.3.2. Skin Dysfunction Skin diphtheria is skin ulcers, clear edges and there is basically membrane, chronic deformity. Classic skin dysfunction is a slow, nonprogressive infection characterized by an ulcer that is non-healing, superficial, and abrupt with a grayish brown membrane. Dermal skin infection is not always differentiated from streptococcal or staphylococcal impetigo, and they are usually together. In most cases, underlying dermatoses, scratches, burns or impetigo are contaminated secondary. The limbs are more often affected than the body or head. Pain, pain, erythema, and typical exudates. Local hyperesthesia or hypesthesia is not uncommon. Respiratory colonization or symptomatic infection and toxic complications occur in a small proportion of patients with skin diphtheria.
Gambar
2.3.3. Vulvovaginal Diphtheriae, Conjunctival, and Ear C. diphtheriae sometimes cause mucocutaneous infection in other places, such as the ears (otitis externa), eyes (purulental and ulcerative conjunctivitis), and the genital tract (purulenta and ulcerative vulvovitis). Clinical features, ulceration, membrane formation and submucosal haemorrhage help to distinguish diphtheria from other bacterial and viral causes. (7)
Gambar
2.4. Diagnosis Early diagnosis of diphtheria is important because delay of antitoxin administration greatly affects the patient's prognosis.3 Diagnosis should be established based on clinical symptoms without waiting for microbiological outcomes. Because the smear preparations are less reliable, while for the culture takes several days. A more accurate way is to identify the Flourescent antibody technique, but this requires an expert. The exact diagnosis with isolation of C diphtheriae by culture in loeffler medium is followed by in-vivo (marmot) and in-vitro (Elek test) toxinogenity tests. (1)
The presence of a throat membrane is actually not very specific for diphtheria, because some other diseases can also be found in the presence of membranes. But the membrane in diphtheria is somewhat different from other disease membranes, the color of the membranes in the darker and more gray diphtheria is accompanied by more fibrin and is attached with the underlying mucosa. When raised there is bleeding. It usually starts from the tonsils and spreads to the uvula. (4)
2.5. Differential Diagnosis of Nose Disorders, nasal diphtheria-like illnesses are rhinorrhea (common cold, sinusitis, adenoiditis), foreign bodies in the nose, snuffles (lues congenital). Pharyngeal differsia should be distinguished from acute membranous tonsillitis caused by streptococcus (acute tonsillitis, septic throat afternoon), infectious mononucleosis, non-bacterial membranous tonsillitis, primary herpetic tonsillitis, moniliasis, blood dyscrasia, post tonsillectomy. Diphtheria Larynx, laryngitis-induced laryngitis symptoms, may resemble other infectious croups, spasmodic croup, angioneurotic edema of the larynx, and foreign objects in the larynx. Skin Dysteria, need to be distinguished from impetigo and skin infections caused by streptococci or staphylococci. (1)
2.6. Complications Complications of diphtheria may occur as a result of local inflammation or as a result of exotoxin activity, then the complications of diphtheria can be grouped in other infections by other germs, airway obstruction due to membrane or airway, systemic, Because the effects of exotoxins, especially to the heart muscle, nerves, and kidneys. (3)
Infection in children with diphtheria often affects their clinical symptoms, leading to both diagnostic and treatment problems. These infections can be caused by streptococcal and staphylococcal bacteria. The high heat is mainly found in people with diphtheria with a streptococcal infection. Given this infection infection, we should be more vigilant in diagnosing and treating diphtheria in children. (7)
Airway obstruction, caused by the closing of the airway by the membrane of diphtheria or due to edema of the tonsils, pharynx, submandibular and servical regions. A rare and generally deadly case of septicemia has been described. Cases of sporadic endocarditis occur, and groups of intravenous drug users have been reported in several countries; The skin is a possible entry point, and almost all strains are nontoxigenic. Sporadic pyrogenic arthritis cases are mainly due to nontoxigenic strains, reported in adults and children. Difterioles isolated from sterile body sites should not be considered contaminants without careful clinical consideration. (5).
Toxic myocardiopathy. Occurs in about 10-25% of patients with diphtheria and cause 50-60% of deaths. Subtle signs of myocarditis can be detected in most patients, especially in older children, but the risk of significant complications is directly correlated with the extent and severity of exudative local oropharyngeal disease and delayed administration of antitoxin. Evidence of typical cardiac toxicity occurs in weeks 2 and 3 when the pharyngeal disease improves but may appear acutely as early as 1 week if the likelihood of the end result dies, or is secretly slow until the 6th week of sickness. Tachycardia is beyond the prevalent proportion of fever and may be an effective proof of cardiac toxicity or autonomic nervous system dysfunction. The prolongation of the PR interval and the changes in the ST-T wave on the relative electrocardiogram are common signs. Single cardiac arrhythmias or progressive disarhythmias may occur, such as cardiac blockade I, II and III degrees, atrioventricular dissociation, and ventricular tachycardia. Clinical congestive heart failure may begin to be hidden or acute. The increase in serum aspartate aminotransferase levels is very parallel with the severity of the mionecrosis. Severe dysarhythmias menramalkan death. Postmodern histologic findings may show slight mionecrosis or diffuse with acute inflammatory responses. The survivors of more severe disaritmia may have permanent conductive defects; For others, the cure of toxic myocardiopathy is usually perfect.
Toxic neuropathy, parallel neurologic complications with extent of primary infection and multifacial start. Acute or 2-3 weeks after initiation of inflammation of the oropharynx, frequent hypesthesia and local paralysis of the palate of the molle. Weakness of the pharyngeal, laryngeal, and posterior facial nerves may accompany, leading to nasal quality, difficulty in swallowing, and risk of death from aspiration. Typical cranial neuropathy occurs at week 5 and causes oculomotor paralysis and ciliary paralysis, which appears as strabismus, blurred vision, or accommodation difficulties. Symmetrical polyneuropathy begins 1hari to 3 months after oropharyngeal infection and mainly causes motor deficit with loss of deep tendon reflexes. Proximal leg muscle weakness spreads over and over and over. Clinical signs and cerebrospinal fluid in the second can not be distinguished from clinical signs and cerebrospinal fluids of the Landry-Guillain-Barre syndrome. Diaphragm paralysis may occur. There may be a perfect healing. 2 or 3 weeks after the onset of illness there is seldom dysfunction of vasomotor centers that can cause hypotension or heart failure. (1)
