Blood and Inflammation Flashcards
Erythropoietin
Protein drives RBC differentiation
Erythropoietin released from kidneys in response to hypoxia (e.g. oxygen deficiency secondary to haemorrhage, loss of RBCs, insufficient haemoglobin, reduced oxygen, increased demands)
Erythropoietin → stimulates rapid maturation of committed RBCs, increased circulating reticulocyte count within 2 days (testosterone enhances production -> higher RBC count in males
ERYTHROPOIESIS
(RBC differentiation)
Requires Vitamins B12 & B9
Iron deficient Anaemia;
Most common causes
- Parasites
- Dietary deficiency
- Blood loss
- Malabsorption
- Pregnancy
Signs and symptoms:
- Fatigue
- Pale appearance
- Shortness of breath
- Irritable
- Light headed
- Glossitis/red beefy tongue
- Recurrent mouth ulcers
- Candida infections -> Angular cheilosis
- Poor wound healing
- Burning mouth symptoms
WBCs
= leukocytes, leave blood stream via diapedesis
[Never Let Monkeys Eat Bananas] - (greatest proportion to least)
Haemostasis
= Prevention of blood loss; whenever a vessel is severed or ruptured, haemostasis achieved by several different mechanisms:
- Vessel Injury
- Vascular Spasm
- Platelet plug formation
Platelets adhere to damaged endothelium (platelet plug) and degranulate. Plug activation is regulated by Von Willebrand Factor (found in plasma). Platelets adhere to the collagen fibers in the wound, becoming spiky and sticky. They release chemicals (ADP, serotonin) causing more platelets to stick to the plug and cause further vasoconstriction creating a feedback loop. Clotting factors become activated and begin deposition of fibrin, creating a meshwork. - Coagulation
Coagulation reinforces the clot, which is formed by the transformation of soluble fibrinogen → insoluble fibrin. RBCs and platelets stay trapped in the mesh.
Thrombus
clot that develops and persists in an unbroken blood vessel
- May block circulation, leading to tissue death
Embolus
- Pulmonary emboli impair body’s ability to obtain oxygen
- Cerebral emboli can cause strokes or transient ischaemic attacks (TIA – temporary disruption in blood supply to part of the brain)
- Cardiac emboli can cause MI (myocardial infarction)
Thromboembolism
Deep vein thrombosis
Immobility → high risk .’. put on prophylaxis (measure taken to maintain health and prevent disease/the spread of)
- Aspirin: Antiprostaglandin, inhibits thromboxane A2
- Heparin: Anticoagulant, used clinically for pre and postoperative cardiac care
- Warfarin: used for those prone to atrial fibrillation
- New agents becoming available e.g. Rivaroxaban (Factor Xa inhibitor)
Thrombocytopenia
= too few platelets
- Causes spontaneous bleeding
- Due to suppression or destruction of bone marrow (e.g. malignancy, radiation)
- Platelet count
Impaired liver function
– liver produces vitamin K which produces essential clotting factors
- Impairs ability to produce procoagulants e.g. Vitamin K (necessary for Prothrombin, factor 7, 9, 10)
- Causes are vitamin K deficiency, Hepatitis, cirrhosis, injury
Von Willebrand Disease
- Most common hereditary coagulation disease
- Type 1 (autosomal dominant), Type 2 (autosomal dominant), Type 3 (autosomal recessive), Platelet type (autosomal dominant)
- Deficiency of VWF found in plasma and subendothelial connective tissue; von Willebrand factor mediates the binding of glycoprotein Ib (GPIb) to collagen. This binding helps mediate the activation of platelets and formation of primary hemostasis.
Haemophilias
(group of hereditary genetic bleeding disorders that impair the body’s ability to control blood clotting)
- Symptoms: Prolonged bleeding, especially in joint cavities
- Treated with plasma transfusions and injection of missing factors
- 2 most common deficiencies are factor VIII (A = 1/5000 males) and IX (B 1/30,000 males)
- Both X-linked recessive with occasional spontaneous mutations – affects more males than females
Blood Groups
Based on presence of 2 major antigens in RBC membranes; A and B.
Rhesus Factor
Rh+ 85% dominant in population
Rh- 15% recessive
Describes presence of Rhesus antigen D
Haemolytic disease of newborn – Rh+ foetus, Rh- mother, can lead to anti-rhesus antibodies from mother attacking the foetal blood cells causing haemolytic anaemia .’. RhoGAM test at 28 weeks
Plasma
Components: 90% Water 8% solutes: PROTEINS: Albumin (60%), Alpha/Beta/Gamma globulins, Fibrinogens GAS ELECTROLYTES =Transport Medium ORGANIC NUTRIENTS: Carbohydrates, amino acids, lipids, vitamins HORMONES METABOLIC WASTE: CO2, Urea etc.
Haemophilia A
Factor VIII deficiency
X-linked recessive
Haemophilia B
Factor IX deficiency
X-linked recessive
Abnormal Bleeding =
when not expected, duration, volume lost, additional treatment required to stop bleeding.
Bleeding associated with dentistry:
o Surgery and trauma – incisions, flaps, lacerations, fractures
o Tooth extraction
o Periodontal therapy (surgical/not surgical and even probing)
o Exposure of vital pulp
o Spontaneous
- Local causes: vascular abnormalities, tumours, disseminated intravascular coagulation (DIC – characterised by widespread activation of clotting cascade, results in blood clot formation in small blood vessels throughout the body. Leads to compromise of tissue blood flow and organ damage. As the coagulation process consumes clotting factors and platelets, normal clotting is disrupted and severe bleeding can occur at various sites)
- Systemic causes: Haemophilia (hereditary genetic disorder that impairs the body’s ability to control blood clotting), Von Willebrand’s disease (inherited bleeding disorder caused by missing/defective Von Willebrand factor; a clotting protein)
- EFFECTS OF BLOOD LOSS **
• Blood in the tissues → bruising, predisposes to infection
• Oesophageal bleed -> blood in stomach → vomiting
• Blood in airway → obstruction (choking, suffocation, death)
• Hypovolaemia (blood loss -> blood volume) → shock
• Reduced oxygen carrying capacity
- Blood loss so less RBCs so less haemoglobin
- Respiratory rate increases to compensate, if can’t meet demand results in death.
• Reduced protein → effects water holding, clotting
• Reduced platelets → less capacity to arrest haemorrhage
Tests of Bleeding Function
INR
APTT
Platelet count
INR
International Normalised Ratio
*Used to assess Warfarin anticoagulation (acts on extrinsic pathway)
= Patient’s Prothrombin Time / Control Prothrombin Time
Blood sample taken into a tube with citrate (prevents coagulation). Calcium added in the lab to reverse citrate then factor III added to activate the extrinsic pathway. Time for sample to clot measured optically, result given in seconds. This time is divided by the result for control group. (uses extrinsic pathway)
INR = ratio .’. INR 1 = normal, 2= bleeding longer than normal
APTT
(Activated Partial Thromboplastin Time)
Used to assess Heparin anticoagulation (acts on intrinsic pathway)
Blood taken into a tube containing citrate (or oxalate) which binds calcium preventing clotting. Sample of plasma extracted and placed in measuring test tube. Excess of calcium added to reverse the anticoagulant effect of citrate. Activator e.g. kaolin added to activate intrinsic pathway. Time measured in seconds (typical range normally 30-50secs).
Warfarin
- Anticoagulation effect reversible with Vitamin K.
- Can’t take when pregnant
Mode of action:
– Prevents action of vitamin K (produced in gut by bacteria)
– Vitamin K required in liver to produce Factors 7 (VII), 9 (IX), 10 (X) and Prothrombin (II)
– Warfarin prevents carboxylation of clotting factor precursors
– Full impact of drug not seen for approx. 7 days (clotting factor half lives vary up to 60hrs). Similar long delay when stopped.
– Many antibiotics enhance effect of warfarin e.g. metronidazole
Patients likely to take Warfarin:
– Atrial fibrillation ( -> turbulence in blood .’. more likely to clot, have heart attacks and strokes)
– Thromboembolic Disease (Deep vein thrombosis and pulmonary embolus)
– Heart valve abnormalities/replacement
– Some other cardiac and vascular abnormalities including some pts with ischaemic (inadequate blood supply) heart disease
INR 4+ = Not suitable for invasive procedures e.g. routine extraction
(NB: no clinical benefit of such a high INR; refer back to warfarin clinic INR too high)
INR 2.5+ = Not suitable for surgical treatment
Heparin
Heparin = shorter acting anticoagulant than warfarin
but CAN NOT be reversed!
CAN take when pregnant
Platelet Count
(normal 200-400*〖10〗^9/L)
- bleeding problem if lower than 50*〖10〗^9/L
New generation anticoagulants
- Dabigatran – targets thrombin
- Rivaroxaban – targets Factor Xa
- Unlike warfarin do not need routine monitoring of anticoagulation
- INR not very meaningful in assessing anticoagulant effect
- IRREVERSIBLE
- Dental procedures (including uncomplicated extractions) okay
- Local measures (also used for warfarin pts) - e.g. place in extraction socket oxidised regenerated cellulose (SurgicelTM ,CuracelTM); promotes clotting. Then use of sutures post-op are advised
- For more invasive surgery, discontinuation of drug pre-operatively
Antiplatelet Drugs
Aspirin
- IRREVERSIBLY binds platelets
- Reduces risk of strokes, atherosclerosis
- Inactivates platelet COX (cyclooxygenase) required for thromboxane A2 mediated aggregation
Clopidogrel
- Binds P2Y12 receptor IRREVERSIBLY; prevents ADP mediated aggregation
Platelets renewed over approx. 10 days
(Ibuprofen binds platelets REVERSIBLY)
(Packing and suturing socket after extractions is to be considered but not mandatory)
Patients likely to be taking Clopidogrel or Aspirin:
• Vascular disease
• Ischaemic heart disease
• Thromboembolic disease
• Stoke
• Peripheral vascular disease (build-up of fatty deposits in the arteries restricts blood supply to leg muscles.)
• In whom thrombi (platelet aggregations) likely to form within vascular system
Antifibrinolytic Drugs
e.g. Tranexamic acid
Widely used in haemophiliacs to back up factor VIII replacement
Demonstrated to be effective as a mouthwash in stopping bleeding in warfarin anticoagulated patients having extractions.
Effectiveness strongly suggests fibrinolysis is an important factor in prolonged bleeding.
Blood Borne Viruses
HIV
Hepatitis A/B/C
Hepatitis A
Infection with hepatitis A is usually mild, but occasionally causes severe inflammation of the liver, requiring admission to hospital.
There is little likelihood of chronic liver damage and no chronic carrier state (where a person remains chronically infected).
Immunisation
For hepatitis A you are given a single injection in the arm which gives you protection for a year. A second booster injection at 6 to 12 months gives you protection for up to 10 years.
Hepatitis B
VERY INFECTIOUS
HBV – Vaccine and immunoglobulin
Most adults infected with the hepatitis B virus fully recover and develop life-long immunity. Between 2% and 10% of individuals infected as adults will become chronic carriers, which means they will be infectious to others and can develop chronic liver damage. Infected children, especially new-born babies, are much more likely to become chronic carriers.
–>
• chronic hepatitis
• liver cirrhosis
• liver cancer.
Immunisation
Three injections are given over a period of 3-6 months. A blood test is taken once the course of injections is completed to check that they have worked. Immunity should last for at least 5 years.
Hepatitis C
Single stranded RNA virus which replicates in hepatocytes.
HCV – no vaccine available
Human Immunodeficiency Virus
=Retrovirus
- Uses RNA to store genetic information, then uses reverse transcription to produce DNA which is incorporated into host cell genome
Main transmission routes…
Blood to blood contact
Sexual transmission
Vertically (mother to baby)
HIV – no vaccine available, but PEP
HIV and AIDS
HIV depletes CD4+ T cells
- If enough CD4+ cells are depleted, progression to full blown immunodeficiency happens (AIDS)
- Leads to opportunistic infections, increased risk of certain cancer. Also systemic and neurological issues.
ATHEROSCLEROSIS
Degeneration of arterial walls characterised by fibrosis, lipid deposition and inflammation which limits blood circulation and predisposes to thrombosis
- Intimal fibrofatty plaques with lipid rich core
- Fatty streaks, atheromatous plaques
- Complicated plaques – calcification, ulceration, thrombosis, haemorrhage
- Risk factors: age, M>F, familial, hyperlipidaemia, raised BP, smoking, diabetes
- Can affect any artery; cerebral, coronary, aorta
- Accounts for >50% deaths in western world
- Normal blood vessel
- Fatty Streaks
- Fibrolipid plaques
- Complicated plaques
