Liver disorders

This lecture is a continuation of the last lecture subjects, and we are going to start with liver disorders. To learn about liver disorders we should remember some of its functions, to know the complications that might result. Liver functions: Liver is important in drug metabolism; many drugs are metabolized by the liver, so if any problem occurs in the liver impaired drug detoxification occurs, leading to drug toxicity. most of the drugs are either metabolized in the liver or kidneys Liver is responsible for production of coagulation factors (by means of vitamin k ) , and so problem in liver might result in bleeding. Liver cirrhosis is a major disease affecting the liver; Liver is like a reservoir of viral infections like hepatitis A, B, C and D to live, which is the leading cause of cirrhosis in eastern countries. Alcohol consumption (more than 21 units a week for Males, 14 for Females) is the leading cause of liver disease in western countries. And here the liver is no longer an active organ; it is just a fibrous tissue. If any symptom of liver disease mainly jaundice was confirmed by the patient or if he has one of these diseases or multiple of them combined , referral and proper consultation about his situation is needed , we also should be very cautious in treating the patient i.e. what sort of medication should I give post operatively, many drugs should be avoided: Analgesics like paracetamol for example should not be given for liver disease patients, instead, we give them NSAIDS (because paracetamol is metabolized in the liver ,while NSAIDs are metabolized in kidneys ) ,reduction of drug dose is another option ,but of course always done under proper consultation from a physician or pharmacist .

 Any local anesthetic especially of the amide group we use like lidocaine and mepivacaine. Valium (which is a benzodiazepine like lorazepam and diazepam) Antibiotics like penicillins in general all these categories of drugs should not be given for a patient suffering from liver disease; you have to consult his physician.

If a patient comes with an infectious carious tooth for example and he has got problems in his liver, such patients need comprehensive treatment, they should do full blood test like bleeding profile INR,PT,PTT, which are usually prolonged in liver disease patients, and liver function test which are also usually high and accordingly we give them the proper treatment ,because they have bleeding tendency we should be ready to deal with them not in our service alone but in the hospital environment with some specialists who know how to manage patients with sever bleeding, who tend to use VITAMIN K IV as a main drug in management of such patients . vitamin K is the source of too many factors. More about hepatitis: 2 types, active and chronic hepatitis, active hepatitis is when the patients have the virus in all body fluids and so they are very infectious. Hepatitis B and C are the types we are worried about. As dentists, we all should have the hepatitis vaccination, to maintain our health and jobs because if any dentist was diagnosed with hepatitis he/she would be suspended from their career. They found that hepatitis B is the easiest virus to be transmitted by needle stick injury followed by hepatitis C, then HIV. On the other hand hepatitis B has a vaccine while hepatitis C (fatality of 50%, others have the risk to develop hepatocellular carcinoma) and HIV dont, and they are more fatal.

Endocrine disorders
Diabetes mellitus: *Persistent elevation of blood glucose level. *Normal fasting blood glucose is 100 mg/dl, anything above that is not normal even if it is an elevation of 20 mg/dl. ***Glucose tolerance test is a good test to determine if a patient is diabetic, we first check the fasting blood glucose, and then we give him glucose and we recheck blood glucose after two hours, if it is below 11.1 mmol/liter then this patient is not diabetic, if it is above he is definitely diabetic. Fasting plasma glucose (measured before the OGTT begins) should be below
6.1 mmol/L (110 mg/dL). Fasting levels between 6.1 and 7.0 mmol/L (110 and 125 mg/dL) are borderline, and fasting levels repeatedly at or above 7.0 mmol/L (126 mg/dL) are diagnostic of diabetes reference Wikipedia.

***Diabetes mellitus is a disorder caused by an absolute or relative lack of insulin: there can be a low output of insulin from the pancreas or the peripheral tissues may resist insulin. it is Absolute when the patient has diabetes type 1, they have autoantibodies against the B- cells of Langerhans, occurs in young people, they have deficient insulin, they sustain this disease early, it is insulin dependent from the beginning, no benefit from giving oral hypoglycemic drugs, they need insulin injection .This type is genetically determined (doesnt mean it is inherented, because it is an autoantibody) . Type 2 which is non insulin dependent (there is enough insulin in their bodies), but they have resistance to the receptors of insulin (they wont let glucose get in) and it is inherent. Gestational diabetes: happens in pregnant females usually in their third trimester, they usually recover after delivery but such females are very susceptible to have diabetes in the future.

P.S infants of diabetic mothers are born overweight because there is too much sugar in blood and sugar can cross the placenta without hormones, so the baby will get bigger .
Because glucose travels across the placenta, in untreated gestational diabetes the fetus is exposed to consistently higher glucose levels. This leads to increased fetal levels of insulin (insulin itself cannot cross the placenta). The growth-stimulating effects of insulin can lead to excessive growth and a large body (macrosomia). After birth, the high glucose environment disappears, leaving these newborns with ongoing high insulin production and susceptibility to low blood glucose levels (hypoglycemia) wikipwdia

Oral manifestation of diabetes mellitus high level of alveolar bone resorption xerostomia delayed or defective wound healing gingivitis pulpitis in non carious teeth impaired sensation in tongue Acetone smell (ketoacidosis): hyperglycemia-body will degrade fat (triglycerides) and supply the organs with some other nutrient---> waste products of such process are ketone bodies. Patients who reach this level are very poorly controlled.

Of course this happens in non controlled diabetic patients, controlled diabetic patients can be treated as normal people. Dental management: *diabetic patients are given early morning appointments, we want them to come after theyve had their breakfast and medicine, and most importantly not to miss a meal, if they do, hypoglycemia is the result. SO (they have their breakfast, come to clinic, get treated, after a couple of hrs they can resume their diet),, they are advised to have small meals with low carbohydrates. *Regarding premedication some would advise certain antibiotics as prophylaxis if the patient come as an emergency. *Make sure appointments are short (about 30 min).

RENAL FAILURE
renal patients are Immunocompromised , so they need antibiotic prophylaxis . If they are having hemodialysis, then they are taking anticoagulants, and this will limit and might prevent you from treating them, so the best day to treat such patients is the day after hemodialysis because the blood will be in its best performance it is fresh and new, and the blood is free of heparin (the blood lost its bleeding tendency). Antibiotics before and after treatment is required for these patients. They are prone to have anemia, because they have deficient erythropoietin which is normally produced from the kidneys. And so only minimal bleeding is allowed. We should check if those patients have any sort of viral diseases,, as they are prone to catch a disease from the hemodialysis machines if they were not very well sterilized . End of part one of the lecture, now we start with another topic which is bleeding disorders. -----------------------------------------------------------------------------------------

Bleeding disorders
Hemostasis consists of three phases; primary, secondary and tertiary. Primary: what vessels do to stop bleeding (vasoconstriction) along with the platelets which aggregate on injured collagen only and they release ADP, thromboxane A2 which will increase the number of blood cells (chemotaxis to start a cascade and initiate the secondary phase). Secondary: the most important phase, which is the coagulation cascade (intrinsic, extrinsic and common pathways). Until it forms the fibrin mesh which will stop the bleeding. Tertiary: fibrinolysis to get the vessel back to its normal state by melting away the fibrin mesh, otherwise thrombosis would result, which actually happens if they have problem in this phase and they develop thrombotic accidents all over the body.

It is very important to take a comprehensive history from the patient, esp. about any previous or current diseases e.g.: liver or kidney diseases. Any medications e.g: heparin, warfarin or aspirin. Family history It is very helpful to ask the pt. about previous tooth extractions or tonsillectomy, and if any complications happened at the time. We would expect that the pt has no diseases like hemophilia A and von willebrand disease. Drugs are also important because there are some medications especially for older people which can lead to bleeding, or the patient will have a tendency for bleeding because of them. Renal diseases, hepatic diseases, infections, hepatitis B and C will cause a problem in the liver in general which will cause bleeding tendency.

 Examination, pts have wide spread purpura or hemarthrosis, it is sign of bleeding problem. Laboratory investigations, of course in the end if you have any suspicion by history if he was taking any medication or if he has any disease or illness or by examination if it revealed some suspicious findings, always the definitive diagnosis would be LABORATORY. Test for homeostasis platelets, now the normal count for platelets is 150-400*10^9/Liter, less than 150*10^9/L then the patient has problems in his platelets, but the range differs sometimes because some people say its from 100-400* 10^9,and its not something constant, for example you might go check your platelet count and find that its 200,then in the next month you might find it 250 so again it is not a constant number all the time but the important thing is that it stays within the normal range. The platelet type is affected by the platelets count and the function in the blood vessels.

Now were going to talk about the platelet tests: Bleeding time, the normal bleeding time is from 2-9 minutes, its a very long span, and if the patients bleeding time is more than 9 minutes, either he has thrombocytopenia (low platelet count) or his platelets arent functioning , there might be a 3rd reason which is a problem in the blood vessels which we will talk about later. Hess test, it is not a reliable test but to perform the test, pressure is applied to the forearm with a blood pressure cuff inflated to between systolic and diastolic blood pressure for 10 minutes. After removing the cuff, the number of petechiae in a 5 cm diameter circle of the area under pressure is counted. Normally less than 15 petechiae are seen, 15 or more petechiae indicate capillary fragility,which occurs due to poor platelet function, bleeding diathesis or thrombocytopenia. Now as for coagulation tests:

 Activated Partial Thromboplastin Time (aPPT): is a performance indicator measuring the efficacy of both the "intrinsic" and the common coagulation pathways. Apart from detecting abnormalities in blood clotting, it is also used to monitor the treatment effects with heparin, a major anticoagulant. It is used in conjunction with the prothrombin time (PT) which measures the extrinsic pathway. The normal time for PPT is 25 seconds, now if a patient came to the clinic to do an extraction and he is on heparin we a PPT test, if its high then that means that the blood is very thin so we cannot perform the procedure because he will keep bleeding. Prothrombin Time : it works on the extrinsic pathways, the normal time is 12 seconds INR (International normalized ratio): its the same as the PT but it is the PT compared to a control, which means the PT of the patient divided by the PT of a normal person multiplied by 100%, but If that patient takes warfarin which works on PT (fights the extrinsic pathway factors) we expect that the PT will be high so as a result the INR will be high as well. Now warfarin is a widely used medication for anyone with heart problems and has a tendency to develop a thrombosis, so to make it easier between all the medical professionals instead of asking about the PT of the patient which could be for example 15, it is easily comprehended to use the INR values which can be 1,2,3 etc The other tests youre not really concerned to about, Fibrinogen degradation product (FDP)> the D dimer is important for deep venous thrombosis, they found that Its very sensitive but not specific which means it could be in many people including the ones who have DVT, for example if we suspect that a certain patient has DVT we do a D dimer test, if its high then there is a very high probability that this patient actually has DVT. Specific factor assays. Now these factors, protein C and protein S and hereditary resistance to activated protein C they are for the coagulation, if someone has a problem in these factors he will develop or tend to have a thrombosis. Tests of physiological inhibitors

Vascular Defects
In addition to increased bleeding time and defective platelets we also have defects in the blood vessels like patients with Hereditary Hemorrhagic Telangiectasia, its an autosomal dominant hereditary disease, patients who have this disease, their skin is very thin to the point that you clearly see the vessels in their faces, they can easily have a nose bleed Its a constant problem for them because even their vessels are very thin. So they develop recurrent bleeding from fragile vessels, iron deficiency anemia They can develop cardiac failure because as we said in the previous lecture patients with severe iron deficiency anemia will develop cardiac failure. Treatment involves cryosurgery or Ar (argon) laser where they burn the area from inside the nose to prevent recurrent bleeding. Dental aspects> they can bleed from any minor trauma, regional anesthesia should be avoided. We mean by regional the ID blocks, and it should be avoided because the needle goes through many layers which can cause bleeding. Problems with GA, because when we insert the tube to give general anesthesia we either put it through the nose or the mouth and that can cause bleeding because of the very fragile vessels. Bleeding disorders They can be divided into two parts, either there is a problem in the production (thrombocytopenia), or there is high destruction which means that the body is producing auto-antibodies which destroy the platelets Or the patient is taking medications like aspirin (anti platelet medication which if the patient took one tablet of, it will destroy the platelets for 8 days) which also leads to the

destruction of the platelets and having them below normal limits. We talked about bleeding time; its a test for patients on aspirin. Hess test we said it is not that reliable or specific. Thrombocytopenia is when the platelet count is less than 100*10^9/L. clinical features include> petechiae, ecchymoses and post operative bleeding. Now we talked about the causes of platelet destruction, which are medications and the other is auto anti-bodies which is like idiopathic thrombocytopenic purpura (ITP) idiopathic thrombocytopenic purpura (ITP) this is a strange disease, it can develop at anytime, for example a patient comes to you and tells you that all of a sudden he woke up with red spots all over his body or he has had these red spots for a week so you check his oral cavity and find that there are red spots in his mouth as well, he has inflamed gum with high tendency to bleed, now these patients have developed all of a sudden an autoimmune disease which is called ITP, where their platelets count can drop really low (<30) to the point where they have spontaneous bleeding. The dental aspects for ITP patients are injections should never be given, especially the block injections (when the platelet count is below 30), minor surgeries should not be performed as well if the platelet count is below 50 *10^9 /L Major surgeries they should be performed when the platelet count is minimum 75*10^9 /L Now the ITP patients if we test their bone marrow we will see that the platelet count is normal and the mother cells are normal, but the problem is in the peripheral blood which contains auto antibodies. The bleeding time is of course high for these patients (20 min for example for a minor cut). As for treatment, in general any autoimmune disease patient is treated by depressing the immune system through high doses of corticosteroids (immuno depressants) and some of these treated patients are fully recovered.

Other patients develop splenomegaly because all of the destructed platelets go to the spleen, and in the end they will have to do a splenectomy.

Coagulation defects
Haemophilia A (the most common coagulation disorder) It is not a bleeding problem, Its a coagulation problem, which means its related to the factors, to the secondary part of the haemostasis process. Its an x-linked disease, which means that males are infected whereas females might be infected or carriers of the disease. If the female was a carrier then she can transmit the disease to her offspring but she is not a symptomatic patient. These patients have deficiency in factor VIII and deep bleeding into muscles and joints (haemarthroses) due to the constant pressure on the joints because of movement so it will eventually cause bleeding in these joints. Bleeding from extraction may continue for days or weeks and that is very serious. now in platelet problems the patient takes aspirin and it stops the function of the platelets for almost a 8 days as we said, but this doesnt mean that we tell the patient if you want to do an extraction you should stop the aspirin and come after 8 days so we could to the extraction; because they did a comparison between the importance of aspirin for the patient and the importance of stopping aspirin to do an extraction, and they found that it is much more important for the patient to stay on aspirin because the bleeding will be very minor and can be controlled. Now in haemophilia A, its a coagulation problem so its the opposite, also in patients on warfarin; the bleeding is very serious to the degree they can die from a simple extraction because they lack factor VIII. Now the severity of the bleeding depends on the severity of the trauma, which means if a patient came with haemophilia, haemophilia has types, mild, moderate and severe, if that patient had moderate haemophilia and you did a major surgery for him (extraction of a very deep wisdom tooth), the

possibility that he will develop bleeding is high but if it was a minor surgery he might not have any problem and you wont even notice the bleeding. Level of factor VIII deficiency; now lets say that the normal level of factor VIII is 100%, until 25% a patient with haemophilia can live his life normally without any problems. Patients with 5-25% of factor VIII will have mild haemophilia, patients with 1-5% will have moderate haemophilia, and less than 1% will have severe haemophilia. Diagnosis of haemophilia A comes mainly when taking the history of the patient, and the clinical picture as well because he might have haemarthroses, hell have history of bleeding and elevated aPTT but normal PT and bleeding time. Management of haemophilia A patients: replacement of factor VIII either by Cryoprecipitate, which is a group of factors including factor VIII Human factor concentrate which is given in a less quantity than cryoprecipitate or we could give him human freeze dried factor VIII. The important thing is to replace factor VIII despite of the method. Dental aspects We have to make sure that haemophilia A patients apply preventive dental care, because if they needed extractions it will be a very difficult procedure because they have to take factors and after a while these factors may develop auto antibodies so youll have to give him something else (factor x for example), so its a very complicated procedure. So preventive dentistry is very important for such patients. Always regional anesthesia is never used with patients with coagulation problems unless factor VIII is higher than 30%, and as for the simple extractions factor VIII should be 50-75%. All surgical procedures should be done in one visit following factor VIII replacement. for example if a haemophilia patient came and we gave him a factor replacement, we have to use the time from the minute we gave him the replacement so we perform every surgery needed and that

is to take advantage of the high factor VIII present in the blood at that time. Now after we do the extractions we give him a mouthwash called tranexamic acid, which is either a mouth wash or given as pills, both cases its local, it works to decrease fibrinolysis (which is the 3rd step of hemostasis) because in these patients we try to delay this process to make sure that the fibrin mesh is well established, so we give them something which prevents fibrinolysis (tranexamic acid) and we give him antibiotics of course.

Haemophila B It is just the same as haemophilia A in terms of management but the only difference that the deficiency is in factor IX. Von willebrand disease Its the most common bleeding disorder, and it is one of the most common diseases in our region, the problem here is in von willebrands factor, this factor is a link, as we said before the platelets and the blood forms then the mesh so this factor is the link between them. So it is not really known if this disease is related to the primary hemostasis or the bleeding tendencies like telangiectasia for example, or the coagulation process, but its more close to a bleeding disorder. It is also autosomal dominant so it affects both males and females the patient will develop bruising all over his body and will have prolonged blood oozing from the sockets after extraction, his bleeding time will be prolonged in all types, but the PTT could be high or normal, thats why this disease is closer to the primary type. Warfarin is medication which works against factor VIII,,,,well talk about it in the next lecture The End

Done by Ruby Daoud & Narmeen Ghannam