Saliva part 2


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Saliva part 2

  1. 1. SALIVADr. Nitika Jain
  2. 2. Contents Saliva - as a diagnostic aid (general and perio)  Stress biomarkers Salivary gland diseases  Infections  Tumours8/12/2012 Saliva 2
  3. 3.  Diagnostic imaging of salivary gland  Sialography  Contrast sialography Conclusion References8/12/2012 Saliva 3
  4. 4. SALIVA - AS A DIAGNOSTIC AID8/12/2012 Saliva 4
  5. 5.  Human saliva performs a wide variety of biological functions that are critical for the maintenance of the oral health. Saliva, a multi constituent oral fluid, has high potential for the surveillance of general health and diseases.8/12/2012 Saliva 5
  6. 6.  Non – invasive  Limited training Why saliva???  No special equipment  Potentially valuable for children and older patients  Cost effective  Eliminates the risk of infection No  Easy, No pain, No needle Pain prick, Fast  Screening of large population8/12/2012 Saliva 6
  7. 7. What is a biomarker???A biomarker is an objective measure that has been evaluated and confirmed either as an indicator of physiologic health, a pathogenic process, or a pharmacologic response to a therapeutic intervention.8/12/2012 Saliva 7
  8. 8.  Biomarkers, whether produced by normal healthy individuals or by individuals affected by specific systemic diseases, are tell - tale molecules that could be used to monitor health status, disease onset, treatment response and outcome.8/12/2012 Saliva 8
  9. 9. Biomarker Detect disease Response Monitor progression Stage to / disease treatment recurrence Treatment efficacy8/12/2012 Saliva 9
  11. 11. Bacteria andLocally produced Genetic ⁄ bacterial proteins of host genomic products, ions, and bacterial biomarkers such steroidorigin (enzymes, as DNA and hormones andimmunoglobulins mRNA of host volatile and cytokines) origin compounds Salivary proteomic, genomic and microbial biomarkers for periodontal diagnosis8/12/2012 Saliva 11
  12. 12. 8/12/2012 Saliva 12
  13. 13. 8/12/2012 Saliva 13
  14. 14. Salivary proteomic approach as biomarkersPeriodontopathic bacteria either cause degradation ofhost tissue directly or activate a host response initiates the release of biological mediators from host cells and when exaggerated in nature, leads to host tissue destruction mediators include proteinases, cytokines and prostaglandins. And bacteria-derived enzymes, such as collagen-degrading enzymes, elastase- like enzymes, trypsin-like proteases, aminopeptidases and dipeptidylpeptidase8/12/2012 Saliva 14
  15. 15. Periodontopathic bacteria8/12/2012 Saliva 15
  16. 16.  Specific salivary proteomic biomarkers have been identified for three key features of the pathogenic processes in periodontal disease – inflammation, collagen degradation and bone turnover8/12/2012 Saliva 16
  17. 17. Innate host defence responses are triggered Neutrophilic polymorphonuclear leukocytes, monocytes and activated macrophages are recruited to the site release numerous cytokines, such as prostaglandin E2, tumour necrosis factor (TNF), interleukins IL-1 and IL-6, which direct further inflammatory processes8/12/2012 Saliva 17
  18. 18. Host-derived MMPs Both MMP-1 (interstitial collagenase) and MMP-8 (polymorphonuclear leukocyte- derived collagenase) gets activated in periodontitis. MMP-8, which is primarily derived from polymorphonuclear leukocytes during active stages of periodontitis, is a major tissue destructive enzyme in periodontal disease8/12/2012 Saliva 18
  19. 19.  An elevated level of MMP-8 was detected in the saliva of subjects affected by periodontitis compared with healthy patients, but the levels of salivary MMP 1 were similar in both groups. Therefore, quantification of the level of MMP-8 is a promising candidate for diagnosing and, more importantly, predicting the progression of this episodic disease.8/12/2012 Saliva 19
  20. 20.  Other MMPs, including MMP-2, MMP-3 and MMP-9, were also reported in the saliva of patients affected by periodontitis8/12/2012 Saliva 20
  21. 21.  Salivary biomarkers have been used to examine the effect of lifestyle factors, including smoking, on periodontal health. Levels of salivary markers including prostaglandin E2, lactoferrin, albumin, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase were significantly lower in current smokers than in non-current smokers.8/12/2012 Saliva 21
  22. 22. 8/12/2012 Saliva 22
  23. 23. Biomarkers of bone resorption or turnover8/12/2012 Saliva 23
  24. 24. Alkaline phosphatase Three main sources:  the actual salivary secretions  the GCF, PMNs and tissue degradation; and  disposed bacterial cells from dental biofilms and mucosal surfaces8/12/2012 Saliva 24
  25. 25. Alkaline phosphatase Significant correlation between ALP and pocket depth and between ALP and inflammation. Higher enzyme activity in individuals with periodontal disease than non diseased individuals. Periodontal destruction by measurement of probing depth, gingival bleeding, and suppuration were related to higher ALP levels in saliva8/12/2012 Saliva 25
  26. 26. Cathepsin B Cysteine proteinases Cathepsin B functions in proteolysis 100% sensitivity and 99.8% specificity for cathepsin B Cathepsin B may have a potential use in distinguishing periodontitis from gingivitis and in planning treatment and monitoring treatment outcomes8/12/2012 Saliva 26
  27. 27. CRP C-reactive protein is a systemic marker released during acute phase of an inflammatory response and is produced by liver. Circulating CRP reaches saliva via GCF or salivary glands. High levels of CRP are associated with chronic and aggressive periodontal diseases.8/12/2012 Saliva 27
  28. 28. Osteopontin (OPN) Noncollagenous calcium binding glycosylated phosphoprotein in bone matrix and is produced by several cells including osteoblasts, osteoclasts and macrophages. Kido et al (2001) demonstrated that OPN level in saliva was increased with progression of periodontal disease. However, no significant difference was observed when OPN level was compared between diseased and healthy sites.8/12/2012 Saliva 28
  29. 29. Osteocalcin Is synthesized mainly by osteoblasts. A number of investigators studied relationship between saliva osteocalcin levels and periodontal diseases.8/12/2012 Saliva 29
  30. 30. Genomic approach as diagnostic markers Reports of genetic polymorphisms associated with periodontal disease are increasing, and strong evidence supports the proposal that genes play a role in the predisposition to and progression of periodontal disease.8/12/2012 Saliva 30
  31. 31. A number of studies have examined links between polymorphisms within host response factors and aggressive periodontitis. Examination of genes encoding inflammatory cytokines such as IL-1 and TNF α, the anti-inflammatory cytokine IL- 10 and the F c- gamma receptors.8/12/2012 Saliva 31
  32. 32.  Reactive oxygen species, participate in the pathogenesis of periodontal tissue destruction. DNA damage, lipid peroxidation, protein disruption and stimulation of inflammatory cytokine release. 8-hydroxy-deoxyguanosine, a product of oxidative DNA damage, is a biomarker for detecting periodontitis in human subjects.8/12/2012 Saliva 32
  33. 33.  Advantages to using genomic and transcriptomic markers to detect disease:  The marker discovery process is high- throughput, involving the use of genome-wide microarray platforms8/12/2012 Saliva 33
  34. 34.  Till now,68 up-regulated and six down- regulated genes was identified, including lactotransferrin, MMP-1, MMP-3, interferon induced-15, keratin 2A and desmocollin-1, and this result was confirmed by real-time polymerase chain reaction.8/12/2012 Saliva 34
  35. 35. Stress biomarkers in saliva Salivary α-amylase Chromogranin A Salivary cortisol8/12/2012 Saliva 35
  36. 36. Salivary cortisol Itslevel in saliva is lower than that in blood Advantage of salivary over serum cortisol measurement is the minimisation of stress from fear of needles during collection, which may bias the results.8/12/2012 Saliva 36
  37. 37. Salivary – α amylase Chromogranin A biomarkers of acute stress and a-amylase is better Both salivary CgA and a-amylase are considered biomarkers of the stress response by the sympatho–adreno– medullary system, unlike cortisol, which is considered a biomarker of stress response by the Hypothalamic pituitary adrenal system.8/12/2012 Saliva 37
  38. 38. 8/12/2012 Saliva 38
  39. 39. Various other diagnosis Candidiasis – Through the presence of candida spp in saliva The presence of periodontal pathogenic bacteria can also be diagnosed by this method - increasing the risk of cardiovascular and cerebrovascular diseases.8/12/2012 Saliva 39
  40. 40.  Cystic fibrosis  Cystic fibrosis (CF) is a genetically transmitted disease of children and young adults, which is considered a generalized exocrinopathy. CF is the most common lethal autosomal- recessive disorder.  The abnormal secretions present in CF caused clinicians to explore the usefulness of saliva for the diagnosis of the disease.8/12/2012 Saliva 40
  41. 41.  CF patients contains increased calcium levels.  Resulted in a calcium-protein aggregation which caused turbidity of saliva.  Higher occurrence of calculus as compared with healthy controls.  The levels of neutral lipids,phospholipids, and glycolipids are elevated.8/12/2012 Saliva 41
  42. 42.  21-Hydroxylase deficiency  an inherited disorder of steroidogenesis which leads to congenital adrenal hyperplasia. In non-classic 21-hydroxylase deficiency, a partial deficiency of the enzyme is present.(Carlson et al., 1999). In 21- hydroxylase deficiency, a strong correlation has been found between 17- hydroxyprogesterone levels in saliva and serum.8/12/2012 Saliva 42
  43. 43.  Insome malignant diseases, markers can be detected in saliva, such as the presence of protein p53 in patients with oral squamous cell carcinoma. Other biomarkers for OSCC:  M2BP  MRP14  CD59  Profilin  Catalase8/12/2012 Saliva 43
  44. 44.  The presence of the c- erb- 2 tumour marker in the saliva and blood serum of breast cancer patients and its absence in healthy women is a promising tool for the early detection of this disease. In ovarian cancer too, the CA 125 marker can be detected in the saliva with greater specificity and less sensitivity than in serum.8/12/2012 Saliva 44
  45. 45.  PCR detection of H. pylori in the saliva show high sensitivity. The presence of antibodies to other infectious organisms such as Borrelia burdogferi, shigella can also be detected in saliva. Detection of hepatitis A and hepatitis B surface antigen in the saliva has been used in epidemiological studies.8/12/2012 Saliva 45
  46. 46.  In neonates the presence of Ig A is an excellent marker of rota virus infection HIV antibody detection is as precise in saliva as in serum and is both applicable in clinical and epidemiological studies. Salivary and oral fluid test:  Orasure ( available in USA)8/12/2012 Saliva 46
  47. 47. SALIVARY GLAND DISORDERS8/12/2012 Saliva 47
  48. 48. Salivary gland disorders Bacterial infections  Acute bacterial parotitis  Chronic bacterial parotitis  Chronic recurrent juvenile parotitis  Acute suppurative submandibular sialadenitis  Chronic recurrent submandibular sialadenitis  Acute allergic sialadenitis Viral infections  Mumps  HIV/AIDS  Cytomegalovirus8/12/2012 Saliva 48
  49. 49.  Fungal infections Mycobacterial infections  Tuberculosis  Atypical mycobacteria Parasitic infections Autoimmune-related infections  Systemic lupus erythematosus  Sarcoidosis  Sjogren’s syndrome8/12/2012 Saliva 49
  50. 50. Sialolithiasis• Sialolithiasis is the formation or presence of a calculus or calculi in a salivary gland.• It is most commonly seen in the submandibular gland and duct (about 80% of cases), then the parotid gland and duct .• Sialolithiasis is rare in the sublingual gland.• Most stones are solitary, but multiple stones may be present.• The reason why a stone forms is unknown8/12/2012 Saliva 50
  51. 51. Symptoms:• May be asymptomatic• Dull pain from time to time over the affected gland• Swelling of the gland• Pain with chewing or swallowingComplications• Oral infection8/12/2012 Saliva 51
  52. 52. Sialadenitis• The salivary glands contain a network of ducts. Saliva flows through them into the mouth. If the flow is reduced or stopped for some reason, infection can grow. This infection called sialadenitis .• The most common infection is bacterial.• Sialadenitis is most common in the parotid gland and the submandibular gland.8/12/2012 Saliva 52
  53. 53. Symptoms: • Tender, painful lump in cheek or under chin. • Pus may drain through the gland into the mouth. • If the infection spreads, fever, chills and malaise may occur.Complication • Oral infection. • Upper respiratory tract infection. • Upper GIT infection.8/12/2012 Saliva 53
  54. 54. XEROSTOMIA8/12/2012 Saliva 54
  55. 55. XEROSTOMIA: Epidemiology Factors that Affect Salivary Flow Medication Autoimmune disease (Sjogren’s syndrome, lupus) Systemic diseases (diabetes, asthma, kidney, sarcoidosis, HIV) Stress/anxiety/depression Radiation therapy to the head and neck  30 Gy = glandular fibrosis (gland can still produce some saliva)  60-70 Gy = glandular destruction (gland can no longer produce saliva)8/12/2012 Saliva 55
  56. 56.  Gender (70 % female, usually postmenopausal) Sympathomimetic medications (stimulate the sympathetic nervous system) Parasympatholytic medications (inhibit the parasympathetic nervous system)8/12/2012 Saliva 56
  57. 57. XEROSTOMIA: Epidemiology Factors that Affect Salivary Flow Over 400 Medications Can Produce the Side Effect of Xerostomia Antacid •Cholesterol reducing Antianxiety •Decongestant Anticholinergic •Diet pills Anticonvulsant •Diuretic Antidepressant •Hormonal replacement therapy Antiemetic •Muscle relaxant Antihistamine •Narcotic analgesic Antihypertensive Antiparkinsonian •Sedative Antipsychotic •Bronchodilator Saliva 57
  58. 58. XEROSTOMIA: Epidemiology Factors that Affect Salivary FlowAge o Studies show that among non-institutionalized people not taking medication, neither the quantity or quality of saliva change significantly with age o Studies show a positive correlation between the number of drugs taken and the incidence and severity of xerostomia Saliva 58
  59. 59. XEROSTOMIA: Etiology “Dry Mouth”Xerostomia is the term used for the symptomof oral dryness. While oral dryness is mostcommonly associated with a reduction insalivary gland output (termed salivary glandhypofunction), the symptom may be reportedby patients with apparently normal salivationwho have changes in saliva composition. Saliva 59
  60. 60. XEROSTOMIA: Etiology Prevalence Xerostomia affects 25% of the population and is becoming one of the fastest-growing oral health  Medications are the cause of more than 90% of xerostomia cases  32 million Americans today take three or more medications daily  Xerostomia was not a great problem in the past because people did not take as many medications as they do today8/12/2012 Saliva 60
  61. 61. XEROSTOMIA: Etiology Global Prevalence The reported prevalence of dry mouth varies widely due to the methodological and population differences in various studies. Prevalence has been estimated to range from 10% to 38%, with 20% the most commonly reported figure Xerostomia is becoming increasingly common in developed countries where adults are living longer and poly-pharmacy is very common.8/12/2012 Saliva 61
  62. 62. XEROSTOMIA: Diagnosis Symptoms Viscous saliva Sticky saliva Difficulty speaking Difficulty swallowing Halitosis Altered taste Complaint of dryness Complaint of burning mouth, lips, or tongue Altered sense of smell Saliva 62
  63. 63. XEROSTOMIA: Diagnosis Signs Increased caries Food sticking to the oral structures Frothy saliva Gingivitis Absence of saliva Cracking and fissuring of the tongue Ulceration of oral mucosa No pooling of saliva in the floor of the mouth Recurrent candidal infections A toothbrush, mouth mirror, or instrument that sticks to the soft tissues Poorly fitting prostheses Saliva 63
  64. 64. XEROSTOMIA: Diagnosis Simple Management Strategies for Patients  Perform oral hygiene at least 4 times daily, after each meal and before bedtimes  Use fluoride toothpaste  Rinse with a salt and baking soda solution 4 to 6 times daily  Avoid citrus juices (oranges, grapefruit, tomatoes)  Rinse and wipe oral cavity immediately after meals  Keep water handy to moisten the mouth at all times  Avoid liquids and foods with high sugar content  Avoid rinses containing alcohol and salty foods  Brush and rinse dentures after meals  Apply prescription-strength fluoride get at bedtime as prescribed  Use moisturizers regularly on the lips  Try salivary substitutes or artificial saliva preparations8/12/2012 Saliva 64
  65. 65. Saliva substitutes - contents Xanthan gum Sodium carboxymethylcellulose Potassium chloride Sodium chloride Magnesium chloride Calcium chloride Di-potassium hydrogen orthophosphate Potassium di-hydrogen orthophosphate Sodium fluoride Sorbitol Methyl p-hydroxybenzoate Spirit of lemon8/12/2012 Saliva 65
  66. 66.  Commercially available:  Orabalance  XERO – Lube  Salivart  Optimoist8/12/2012 Saliva 66
  67. 67. XEROSTOMIA: ManagementSome patients are predisposed to candidiasis because of the lack of salivary histatins Recommendation: o Antifungal medication can be recommended to control fungal growth 8/12/2012 Saliva 67
  68. 68. XEROSTOMIA: Management Treatment of Xerostomia-Associated Problems8/12/2012 Saliva 68
  69. 69. XEROSTOMIA: Management Treatment of Xerostomia-Associated Problems8/12/2012 Saliva 69
  70. 70. XEROSTOMIA GETTING INVOLVED IN DIAGNOSING XEROSTOMIA CAN BE A WINDOW TO PATIENTS’ OVERALL HEALTH Diagnosing xerostomia is an important diagnostic tool for othersystemic diseases. The signs and symptoms of xerostomia are often associated with and/or result from other conditions. Saliva 70
  71. 71. Salivary gland Neoplasia Tumors of the salivary glands are uncommon and represent 2-4% of head and neck neoplasms. 80 % of tumors occur within the parotid glands & most of the others in the submandibular glands. Males and females are affected equally. 70% to 80% of these tumors are benign.8/12/2012 Saliva 71
  72. 72. Salivary gland neoplasia Benign  Warthins tumor (benign papillary cystadenoma)  Benign mixed tumors  Monomorphic adenoma  Benign lymphoepithelial lesions Malignant  Mucoepidermoid carcinoma  Adenoid cystic carcinoma  Adenocarcinoma  Malignant mixed tumor8/12/2012 Saliva 72
  73. 73. Benign tumors Benign mixed tumors  Is the most common tumor of the major salivary glands. Pathologically, it is characterized by slow growth and few symptoms. Warthins tumor (benign papillary cystadenoma)  A slow-growing, cystic tumor that almost always occurs in older men.8/12/2012 Saliva 73
  74. 74. Benign tumors Monomorphic adenoma  Are a group of benign lesions with a variety of growth patterns. These lesions usually are found in the parotid glands. Benign lymphoepithelial lesions  Include a wide range of cystic changes that share the common denominator in atypical lymphoid hyperplasia. These changes are found often in patients infected with HIV.8/12/2012 Saliva 74
  75. 75. Malignant tumors Mucoepidermoid carcinoma • Is unique in that the tumors it produces can vary in aggressiveness from low-grade and slow growing to high-grade and rapidly growing. • It occurs more frequently than any other malignancy of the major salivary glands.8/12/2012 Saliva 75
  76. 76. Malignant tumours Adenoid cystic carcinoma • Account for 25% of malignant salivary gland tumors and 15% of all parotid gland tumors. • Occur most often in the minor, rather than major, salivary glands. • The disease is unique in that its tumors grow slowly, but metastasize readily.8/12/2012 Saliva 76
  77. 77. Malignant tumours Adenocarcinoma • Are most frequently found in the minor salivary glands of the nose and paranasal sinuses. • Account for 15% of malignancies of the parotid and 10% of malignancies of the submandibular glands. Malignant mixed tumor • Make up approximately 15% and 12% of parotid and submandibular neoplasms respectively. • The disease typically is characterized by slow,8/12/2012protracted growth. Saliva 77
  78. 78. Drug monitoring in saliva molecular size, lipid solubility, and the degree of ionization of the drug molecule, as well as the effect of salivary pH and the degree of protein binding of the drug8/12/2012 Saliva 78
  79. 79. Therapeutic Drugs Antipyrine  Irinotecan Caffeine  Lithium Carbamazepine  Methadone Cisplatin  Metoprolol Cyclosporine Diazepam  Oxprenolol Digoxin  Paracetamol Ethosuximide  Phenytoin  Primidone8/12/2012 Saliva 79
  80. 80. Saliva and age With age, a generalized loss of salivary gland parenchymal tissue loss. Salivary acini are replaced by adipose tissue. Decreased production of saliva8/12/2012 Saliva 80
  82. 82. Diagnostic imaging for salivary gland To differentiate inflammatory from neoplastic diseases Differentiate diffuse from focal suppurative disease Identify and localize sialoliths Demonstrate ductal morphology8/12/2012 Saliva 82
  83. 83. Methods Plain film radiography Intra oral radiography Extra oral radiography Conventional sialography Computed tomography ( CT) Magnetic resonance imaging Scintigraphy Ultrasonography8/12/2012 Saliva 83
  84. 84. Conventional SialographyA radiographic technique wherein a radiopaque contrast agent is infused into the ductal system of a salivary gland before imaging. Imaging is done with plain films, fluoroscopy, panoramic radiography, CT. Mainly submandibular and parotid8/12/2012 Saliva 84
  85. 85. TechniqueA lacrimal or periodontal probe is used to dilate the sphincter at the ductal orifice before the passage of a cannula, blunt needle or catheter, which is connected to a syringe containing contrast agent.8/12/2012 Saliva 85
  86. 86.  Indications Contraindications8/12/2012 Saliva 86
  87. 87.  Phases of sialography  Ductal phase  Acinar phase  Post – evacuation phase8/12/2012 Saliva 87
  88. 88. Contrast sialography Lipid soluble agents  37% iodine e.g.: ethiadol Water soluble agents  28 to 38 % iodine e.g.: hypaque 50%, hypaque M 75%, renografin 60, isopaque, triosol, dionosil.8/12/2012 Saliva 88
  89. 89. Computed tomography8/12/2012 Saliva 89
  90. 90. Magnetic resonance imaging8/12/2012 Saliva 90
  91. 91. Sialoendoscopy Specialized procedure that uses a small video camera at the end of a flexible cannula, which is introduced into the ductal orifice. Both diagnostically and therapeutic Can demonstrate the strictures and kinks in the ductal system, as well as mucous plugs.8/12/2012 Saliva 91
  92. 92. Conclusion Biomarkers of disease in succession play an important role in life sciences and have begun to assume a greater role in diagnosis, monitoring and therapy outcomes and drug discovery. The challenge for biomarkers is to allow earlier detection of disease evolution and more robust therapy efficacy measurements.8/12/2012 Saliva 92
  93. 93. References8/12/2012 Saliva 93