Exam 2 Tissue Biology
Statement 1: patient presenting with a platelet count of 75,000 can undergo major and minor surgery in the outpatient dental setting. Statement 2: normal platelet count is 150-450 K/mm3 and platelets are replaced every 14 days. A. Both statements are true B. Both statements are false C. Statement 1 is true, statement 2 is false D. Statement 1 is false, statement 2 is true
Statement 2 is false. Statement 1 is true. Platelets patient Needs (thrombocytopenia lecture) is > 100,000 for Major Surgery in O.R. > 75,000 for ORAL Major surgery; > 50,000 Minor Surgery; > 10,000 to avoid spontaneous bleeding (need platelet replacement therapy here). Normal Platelet count = 150-450 k/mm3 (KNOW THIS). function part of maintaining homeostasis. replaced every seven days.
Fibroblasts
lay down ECM
Sarcolemma
surface membrane of muscle cells. T-tubules are deep invaginations of this.
What are the major differences between HODGKIN LYMPHOMA & NON-""?
HODGKIN: WILL STAY IN LYMPH NODES; WONT SEE IT IN OTHER TISSUES (THO MAY SPREAD TO OTHER LYMPH NODES). NON-HODGKIN: Involve lymph nodes and occur in extranodal sites.
Can you use bacteriostatic antibiotics in immune compromised patients?
NO! Give parenteral bactericidal antibiotics (stop growth of bacteria) when ANC is between 0-500 (start when its below 500 cells, and continue until immunity is above 500 cells), which is when we CLINICALLY consider patient to be TRULY IMMUNE COMPROMIZED. Even though a patient is "said" to be immune compromized if ANC is below 1,500 cells.
1) Activation of prothrombin to thrombin (IIa) [blood coagulation] - what are the functions of thrombin? 2) Conversion of fibrinogen to fibrin 3) Formation of fibrin mesh KNOW ALL THIS FOR EXAM.
(1) - factor II, PROTHROMBIN (MW = 68,700), is a plasma protein produced in the liver and requires vitamin K. - prothrombin activator produced by EITHER the intrinsic or extrinsic pathways plus calcium, converts prothrombin to THROMBIN (MW = 33,700). - thrombin is proteolytic enzyme that splits fibrinogen (factor I) and factor XIII into their activated forms [Ia and XIIIa]. It can also catalyze its own activation and can increase platelet aggregation. (2) thrombin splits two small FIBRINOPEPTIDES from the center of fibrinogen molecule to form a FIBRIN MONOMER (FACTOR Ia). - the monomers spontaneously polymerize into long FIBRIN POLYMER THREADS (PROTOFIBRILS) held loosely together by hydrogen and hydrophobic bonds - forming only weak chains.... (3) However, Factor XIII (FIBRIN STABILIZING FACTOR), which is also activated BY THROMBIN, acts on the fibrin monomers to catalyze the formation of covalent bonds btwn monomers and btwn adjacent fibrin chains to produce branched fibers -> strong 3D fibrous mesh that surrounds the platelet plug to form a permanent clot at the injury site.
1) Describe the steps involved in activation of smooth muscle contraction (cross-bridge activation) 2) Inactivation of cross-bridges (smooth muscle inactivation)
(1) = Cross-bridge activation = controlled by a calcium-activated enzyme that phosphorylates myosin. Steps: 1) stimulation of the cell causes an increase in cytosolic calcium ( the Ca++ can enter the cell via cell surface channels or from the sarcoplasmic reticulum) 2) Ca++ binds to CALMODULIN, a soluble calcium-binding protein in the cytoplasm similar to troponin C 3) The calcium-calmodulin complex binds to the cytoplasmic enzyme, MYOSIN LIGHT-CHAIN KINASE (MLCK) to activate it. 4) active MLCK uses ATP to PHOSPHORYLATE MYOSIN LIGHT CHAINS in the myosin head. (add a phosphate group, PO4 to the protein) 5) phosphorylated myosin is now actively able to bind to actin filaments and develop force. 6_ as long as the myosin remains phosphorylated, cross bridge cycling can continue. (2) To relax the muscle, the myosin must be dephosphorylated by the enzyme MYOSIN LIGHT-CHAIN PHOSPHATASE which is continuously active in smooth muscle. Relaxation can also be promoted by cyclicAMP or cAMP (<- KNOW THESE) which can inhibit the actions of MLCK.
Serum FERRITIN levels are (1) LOW in? (2) NORMAL in ? (3) HIGH in?
(1) Low in IRON DEFICIENCY. (2) Normal in THALASSEMIA (3) High in ANEMIA OF INFLAMMATION. - Serum Ferritin is an indicator of iron storage - Ferritin levels help differentiate between the various causes of microcytosis notes on IRON DEF. ANEMIA(know in caps): - most common nutritional anemia - Once detected, this and other nutritional anemias generally respond to supplementation. - Hemoglobin that fails to show improvement in 4-8 weeks IS ALWAYS FURTHER INVESTIGATION.
What is the purpose of doing a white blood cell count (in complete blood count)?
(A) Check to see if we have sufficient number of: 1) Neutrophils engulf bacteria and cell debris 37-77%, 2) Lymphocytes produce antibodies and regulate immune response 10-44%, 3) Monocytes engulf cellular debris and antigen processing 2-10%, 4) Eosinophils parasitic infections and allergic response 1-7%. 5) Basophils hyeprsensitivity release histamine0-1.6%). (B) Check for WBC disorders normal WBC range = 3.5 to 10 k/mm3. - LEUKOCYTOSIS = inc. WBCs: > 10k/mm3 = Increased production (leukemia) & Reactive (infection, inflammation). - LEUKOPENIA = dec. WBCs: <3.5k/mm3 = Decreased production = some leukemias, drugs (e.g. chemotherapy), radiation; & Immune destruction; & Consumption (infection in patient).
1) After tissue injury, place the following events in the correct order. A) Von Willebrand factor attracts platelets, B) Platelets secrete ADP-attracts more platelets, C) adhesion will activate the platelets, D) The platelets bind to fibrinogen, E) The shape of the platelet changes from biconvex disc to irregular shape: A) C, D, B, A, E B) D, B, C, E, A C) A, C, B, E, D D) B, A, C, E, D
(C) A (platelet adhesion) -> C (platelet activation) -> B (platelet secretion) -> E (platelet change shape) -> D (platelets bind to fibrinogen)
FDA Statement: Clopidogrel (Plavix)
(CLOPIDOGREL is an ADP receptor pathway inhibitor). - Nov. 2009: FDA says Prilosec can block benefits of Plavix: Heartburn medication cuts in half the effectiveness of blood thinning drug - may also increase risk of MI - In March 2010, the U.S. Food and Drug Administration (FDA) added a boxed warning to Plavix alerting that the drug can be less effective in people who cannot metabolize the drug to convert it to its active form (up to 14% of patients). CLOPIDOGREL IS ACTIVATED BY CYP2C19 ,AND GENETIC VARIATION IN EXPRESSION OF THIS ENZYME EXISTS - Nov.2015: FDA says Plavix (clopidogrel) does not increase or decrease overall risk of death in patients with, or at risk for, heart disease, also does not suggest that clopidogrel increases the risk of cancer or death from cancer - AVOID NSAIDS - MAY INCREASE RISK OF BLEEDING. - CLOPIDOGREL SHOULD NOT BE STOPPED FOR DENTAL SURGERY, ESPECIALLY IN THOSE PATIENTS WITH RECENTLY PLACED CARDIAC STENTS [topic -AntiThrombotics Therapy ]
Schwann Cells
(PNS) Wrap around axons of neurons to produce myelin; if not making myelin, still play supporting role.
Anemia - Is RBC count high or low (RBC count includes measurements of what...), and what test do you get this from? COMMON CAUSES? ORAL LESIONS? Types of Anemia? In "CAPS" = must know, medicine red dots.
(RBC disorder) 1) RBC Count LOW [get from complete blood count and differential] - Hemoglobin (Hb) <10 gm/dl [a direct measurement] - Hematocrit < 30% [a percentage of rbcs in a given volume of blood. is LOWER when plasma volume is higher during IV fluids and pregnancy. is HIGHER when plasma volume is contracted w dehydration]. 2) Four Most Common Causes = - Decreased RBC Production in renal disease/failure of bone marrow , or Diet DEFICIENT IRON/B12/Folate {erythropoetin hormone needs them for RBC production} - Excessive Bleed/Loss in MENSTRUAL cycle, - Increased RBC Destruction in Sickle Cell Anemia. - Increased Demand in Pregnancy 3) Other Causes = - INC RBC Destruction either from: Hemolysis/Hemolytic Anemia (immune, membrane defects, congenital enzyme deficiencies), Infections/Malaria, or Hemoglobinopathis (Thalassemia, Sickle Cell is another but more common ^). 4) ORAL ISSUES = Glossitis [pain in tongue] & Angular cheilitis [cracking of lips/corners of mouth; candidiasis fungal infection where ppl keep licking lips bc think they're chapped] 5) Iron Deficiency Anemia (most common cause for anemia) & Hemolytic Anemia (premature destruction RBCS; acquired or inherited; hyperbilirubinemia and jaundice (yellow); includes sickle cell anemia and thelssema). -note: Problem that you need to fix in ur patient because.: Anemia -> Hypoxia -> Organ Damage. && where patient shows signs of= shortness breath, cardiac ischemia, delirium, fatigue, heart failure.
What proteins stabilize the myosin filaments?
(in vivo, a single thick filament contains about 300 molecules of myosin). 1) M protein in center of the filament. 2) Titin which attaches ends of filament to Z disc. 3) Myosin binding protein C, which binds to both myosin tail and S2 (from HMM, makes short segments of tail).
What is the structure of the thick filament? What special properties does it have?
- 2 HEAVY CHAINS and 2 LIGHT CHAINS in asymmetrical structure. Heavy chain contains "TAIL" (16 nm) that form DOUBLE HELIX, and "HEAD" w each about 840 aa's. - Myosin molecules BIND TO THIN FILAMENTS (actin) and have ATPase activity {relevant to muscle contraction}. - If thick filaments are extracted from sarcomeres, they disassemble into individual molecules of myosin w MW ~ 500kDa.
Sickle Cell Anemia - HOW DOES AN INDIVIDUAL GET THIS? WHAT CATEGORY OF ANEMIA? RADIOGRAPHIC FINDINGS? Is found mostly in what population? Sickle cell trait vs sickle cell disease? Oral manifestations?
- AUTOSOMAL RECESSIVE disease - MOST COMMON Type of HEMOLYTIC anemia. - Found predominately in African-Americans - Defective hemoglobin in shape of crescent or sickle - Sickle cell trait = Lowered red blood cell count - Sickle cell disease = Malaise and weakness, Muscle rigidity, AND Wide-spread ischemia leads to death - Oral manifestations? Not specific - RADIOGRAPHIC FINDINGS = "STEPLADDER" TRABECULAE IN POSTERIOR TEETH, "HAIR ON END" APPEARANCE ON SKULL.
Thromboxane A2 Pathway Inhibitors
- Aspirin (acetylsalicylic acid, NSAID group), GIVEN ORALLY = most widely used anti-platelet agent / inhibits platelet aggregation. - PLATELETS CANNOT SYNTHESIZE NEW COX ENZYME (HALTED FOR THE LIFETIME OF THE PLATELET (7-10 DAYS) - Patients will often be taking a reduced dose (81 mg) or baby aspirin on a daily or every other day basis - Used in patients with unstable angina, also as prophylaxis to reduce the risk of MI and stroke in patients with carotid disease - NON-SELECTIVE COX INHIBITOR: COX-1 IN PLATELETS and GUT. COX-2 AT SITE OF INFLAMATION. [topic -AntiThrombotics Therapy]
Thrombocytopenia - Disorder of? PLATELET COUNT (AND PURPOSE OF PLATELETS?)? SCREENING/ASSAYS WOULD SHOW NORMAL ___, BUT ABNORMAL ____? CLINICAL FEATURES? Common hematologic manifestation of what? Causes?
- DEC. # platelets to below 150,000 is Thrombocytopenia (low bc normal is 150,000-450,000). - Thus, DEC. HEMOSTASIS/CLOT FORMATION {<- is what platelets do}. - Normal PT/PTT, but ABNORMAL BLEEDING TIME. - CLIN. FEATURES = SPONTANEOUS GINGIVAL HEMORRHAGE (bleeding), PETECHIAE (red/purple in MOUTH, ECCHYMOSIS (bruising), HEMATOMA. - Common hematologic manifestation of AIDS - 3 main causes = Red. production (Chemotherapy), Inc. destruction (Drugs/HIV/Lupus), Sequestration in spleen (Splenomegaly). - other causes = (a) DEC. PRODUCTION: marrow infiltration w tumor, lymphoma, leukemia; infection (HIV, viral hepatitis, mumps, rubella, parvovirus); nutritional deficiencies (folate, B12 - deficiency of iron, B12, folate; drugs (chemotherapy, radiation, alcohol). (b) INC. DESTRUCTION: - Idiopathic Thrombocytopenic purpura (ITP): antibody against platelet membrane antigens (auto-immune disease, most common one we see). - Thrombotic thrombocytopenic purpura (TTP): caused by protein deficiency/acquired disorder, adams 13 role, life-threatening condition. - Disseminated intravascular Coagulation (DIC): shearing of platelet by fibrin plugs (often patients who r septic). - Vascular problems/trauma. - Drugs: Heparin, Antibiotics, H2 blockers, Quinine. - Alloimmunization (post-transfusion). 4c) SEQUESTRATION of platelets = HYPERSPLENISM seen in patients w Liver Cirrhosis or Chronic Hemolysis /Hemolytic Anemias (platelets being trapped in large spleen)
ERYTHROPOIETIN as a treatment for what? In order for this to be effective, what must body have? know this, medi. red
- For mild to moderate CRF associated anemia (Anemia due to Chronic Renal Failure). - Given as a subcutaneous/SC injection dose of 15-300 IU/kg 1-3 times per week. - Exogenous erythropoietin does NOT suppress endogenous production. This is an advantage over transfusion in the management of anemia. - TO BE EFFECTIVE, THERE MUST BE SUFFICIENT ERYTHROID PRECURSURS IN THE "BONE MARROW." and needs to be ADEQUATE IRON STORES and PROTEIN INTAKE. - Clinically it is common practice to give 3-6 mg/kg/d (KNOW THIS) of supplemental iron concurrently
ADP (Adenosin diphosphate) Receptor Pathway Inhibitors
- Given orally - IRREVERSIBLY INHIBIT THE ADP RECEPTOR (FOR THE LIFE SPAN OF PLATELETS) - They are often prescribed for patients that have an aspirin allergy or are intolerant of aspirin (usually stomach upset). Both agents may be used in patients with atherosclerotic disease to prevent heart attacks, prevent stokes, and prevent coronary artery closure in patient undergoing angioplasty 1) TICLOPIDINE (Ticlid): Twice daily administration, associated with AGRANULOCYTOSIS (Blood counts recommended during first few months) 2) CLOPIDOGREL(Plavix): once daily administration, MORE FAVORABLE TOXICITY PROFILE; preventing expression of GIP __ receptors that bind to strands of fibrinogen resulting in platelet aggregation. = Prodrug ACTIVATED by CYP2C19 -> ACTIVE FORM = anti-platelet agent; INDUCERS OF CYP2C19 will INC. the effect of Plavix; & INHIBITORS "" will DEC. the effect of "". [topic - AntiThrombotics Therapy]
APLASTIC ANEMIA - CAUSED BY (KEY PLAYER)? CLINICAL FEATURES? ORAL FINDINGS? Diagnosis? Treatment? At risk for?
- HEMATOPOIETIC PRECURSER CELLS DO NOT PRODUCE ADEQUATE NUMBERS OF BLOOD CELLS. - DO NOT UNDERGO NORMAL MATURATION. - CLINICAL FEATURES (dependent on deficiency of blood cells): 1. RBC Defiency => Fatigue, tachycardia, lightheadness 2. Platelet Deficiency => easy bruising/bleeding 3. WBC Deficiency => fungal and bacterial infections - ORAL FINDINGS = HEMORRHAGE, PETECHIAE, PALE ORAL MUCOSA, GINGIVAL HYPERPLASIA {can also be seen in leukemia, DONT CONFUSE}. - Diagnosis (depends on number of cells low) = Pancytopenia-two of following: Less than 500 granulocytes/uL, or Less than 20,000 platelets/uL, or Less than 10,000 reticulocytes/uL - Treatment either = Initial supportive therapy, Bone marrow transport only curable in patients under 40, and/or Steroids. - At risk for acute leukemia
Leukocytosis vs leukopenia and how to treat (medicine review)
- LEUKOCYTOSIS = inc. WBCs - due to: Increased production (leukemia) & Reactive (infection, inflammation) & drugs (prednisone). - LEUKOPENIA = dec. WBCs: Decreased production = some leukemias, drugs (e.g. chemotherapy), radiation; & Immune destruction; & Consumption (infection in patient) - ANC to asses the "gravity" of leukopenia" and calculate it prior to dentistry if patient has leukopenia. - ANC = Total WBC count x (% Neutrophils + % Bands*) If ANC > 1,500/mm3 : Patient CAN fight acute bacterial infections (doesn't need antibiotics).
MULTIPLE MYELOMA - CANCER OF WHAT CELLS? WHAT IS INVOLVED IN HALF OF THEM? Most common in? Ages affected? PRESENTING SYMPTOMS? RADIOGRAPH FINDINGS? Treatment? Prognosis?
- MALIGNANCY OF PLASMA CELLS - BONE INVOLVED IN 50% OF ALL malignancies. - Most common hematologic malignancy in African-Americans - Affects adults ages 60 - 70 - 3 PRESENTING SYMPTOMS = BONE PAIN, FATIGUE, & RENAL FAILURE (due to excess of bence jones proteins). - "PUNCHED OUT" (dark circles) ON RADIOGRAPH. - Treatment either chemotherapy, or bone marrow transplant. - Prognosis is Poor with a five-year survival rate of 25% (eek).
Mean Corpuscular Volume (MCV) indicates what about the RBC? and helps to distinguish between what types of anemias? Dec. MCV due to what (<- know this, red medicine).
- MCV indicates RBC size & helps distinguish between microcytic/macrocytic anemias - Normal MCV: 80-100 fL/RBC - Microcytic cells: MCV is below normal - Macrocytic cells: MCV INC. - Microcytosis or DEC MCV: = DUE TO DEFECTIVE hemoglobin production from ineffective HEME OR GLOBIN synthesis. First leading cause: Iron deficiency anemia, & Second leading cause: Thalassemia .
PERNICIOUS ANEMIA - TYPE OF ANEMIA (SEEN IN WHAT, BUT PATIENT DOES NOT HAVE WHAT)? IS THE RESULT FROM? CLASSIC TRIAD OF SYMPTOMS? Commonly seen in what patient population? Typical symptoms exhibit a problem with what body system? Treatment? At inc. risk for what?
- MEGALOBLASTIC ANEMIA [Also seen in Folate Deficiency (Folic Acid) but that's w/o neuro symptoms]. - Results from POOR ABSORPTION OF VITAMIN B12 (Cobalamin) - CLASSIC TRIAD = GENERAL WEAKNESS, PAIN TONGUE, NUMB OR TINGLES EXTREMITIES. - Vitamin B12 has normal nucleic acid synthesis - elderly and strict vegetarians - Have neurologic symptoms. - Treatment either: IM injections of Vitamin B12, or High dose of oral Vitamin B12. - Increased risk for gastric carcinoma
Burkitt Lymphoma - WHAT ARE THE TWO TYPES AND WHAT TO EACH INVOLVE? Is a malignancy of what cells? Involves EXPRESSION OF WHAT? Clinical findings? Radiographic findings? GENETIC FINDINGS? PATTERN IN HISTO? Prognosis and treatment?
- Malignancy of B-cell lymphocytes (Type of non-Hodgkin lymphoma) - Expression of EPSTEIN BARR VIRUS (EBV). - TWO TYPES: 1) ENDEMIC (African)-Involves posterior maxilla/mandible (50-70%) - DENTAL = Ratio of 2:1 maxillary involvement; in young children 2) SPORADIC (American)-Involves ABDOMINAL region. - Clinical findings: Facial swelling, Proptosis, enlargement of GINGIVA, Destruction of alveolar bone, Deciduous tooth loss - Radiographic findings = Radiolucent, Ill-defined margins, early sign-patchy loss of lamina dura. - TRANSLOCATION t(8;14)(q24;q32) OVER-EXPRESSED MYC ONCOGENE - "STARRY SKY" PATTERN in Histopathology . - Prognosis and Treatment = Aggressive , High doses of cyclophosphamide - If not treated, death in 4-6 months!
HODGKIN LYMPHOMA - AGE OF INCIDENCE? LYMPH NODES AFFECTED? CLASSICAL HISTOLOGICAL? What type of disorder? Linked to what? Gender "bias"? Treatment/curable?
- Malignant lympho-proliferative disorder - Epstein-Barr virus (type of herpes) has been linked - Male predilection - BIMODAL AGE & INCIDENCE: 15 to 35, THEN can occur AFTER AGE 50. - Affects cervical and supraclavicular lymph nodes (initially). - Aka WILL STAY IN LYMPH NODES; WONT SEE IT IN OTHER TISSUES (THO MAY SPREAD TO OTHER LYMPH NODES). - REED-STERNBERG CELL w ("Owl-eye" nucleus) seen microscopically - Treatment depends on staging but IS curable
NON-HODGKIN LYMPHOMA - What is a type of this? Lymph nodes? Involves what cells (majority?)? Clinical presentation? Oral cavity presentation?
- Malignant proliferation of lymphocytes - Involve lymph nodes and occur in extranodal sites - Majority involve B-cell lymphocytes; T-cell lymphomas are rare. - MALT lymphoma (Mucosa Associated Lymphoid Tissue) associated w/ Sjogren syndrome, is a type of it. - Clinical Presentation = Slowly, enlarging non-tender mass of lymph nodes - Oral cavity (Extranodal)- can involve soft tissue or bone; Soft tissue appears erythematous and boggy{(not firm like drying out sponge}. Bony involvement- a vague pain with ill-defined radiolucency (dark) on radiograph
Premedication for sickle cell anemia patient? know this, medi. red
- PREMEDICATION PROPHYLAXIS is a must in sickle cell & splenectomy (surgery remove spleen) patients. - Premed is also needed in SICKLE CELL CRISIS PATIENTS presenting with FEVER & LEUKOCYTOSIS.
Blood Coagulation / Formation of a Clot (hemostasis, 3) - begins (timing) for severe injury vs. minor one? Initiation of coagulation occurs by formation of __________?
- begins within 15-20 seconds in a severe injury, 1-2 minutes in a minor one. - triggered when blood come into contact w collagen from a damaged vessel or other fluids resultnig from tissue trauma. (formation of prothrombin caused by - trauma to tissue, to blood vessles, or contact of blood w collagen). - intitiation of coagulation occurs by formation of PROTHROBIN ACTIVATOR - either of 2 pathways can be involved that involve circulating CLOTTING FACTORS: 1) INTRINSIC PATHWAY - coagulation begins in blood. 2) EXTRINSIC PATHWAY - coagulation begins w trauma to tissues outside blood vessel.
Smooth (visceral) Muscle: MUST KNOW - WHERE DO YOU FIND IT? HOW DOES ITS FUNCTION DIFFER FROM SKELETAL MUSCLE? (1) Regulation of contraction is _________ based in smooth muscle; thin-filament based in skeletal muscle (2) ______________ in smooth muscle is very slow and therefore smooth muscle shortening is slow (3) since the use of ATP is slow, smooth muscle can engage in prolonged periods of __________. (4) some smooth muscles (e.g. sphincters) can maintain tension even if the ATPase rate declines- this is called the_________. In these contractions, Ca2+, cross-bridge phosphorylation, and ATP consumption rates fall. A model for the latch state hypothesizes that cross-bridge phosphorylation is obligatory for cross-bridge attachment, but that dephosphorylation of an attached cross-bridge reduced its detachment rate.
- called smooth muscle because it lacks the banding patterns seen in skeletal and cardiac muscle because it has NO Z-disks and the thick and thin filaments are NOT aligned in parallel. - activated by the autonomic nervous system (NOT under voluntary control). - found in the walls of hollow organs: e.g. bronchi, blood vessels, gastrointestinal tract = VASCULAR (issue w smooth muscle can lead to Hypertension, Vasospasm, Stroke), RESPIRATORY ("" Asthma), URINARY ("" Incontinence), REPRODUCTIVE ("" Preterm Labor), GASTROINTESTINAL ("" Functional Bowel Disease), OCULAR "" Difficulties with near/distant vision; Pupillary constriction/dilation). - like skeletal muscles, they have overlapping thick and thin filaments- thick filaments contain myosin and thin filaments contain actin and tropomyosin but NO TROPONIN. 1) thick-filament based 2) The rate of ATP hydrolysis (energy use). 3) activity without fatigue. 4) latch state ["imp things to remember about (visceral muscle=) smooth muscle contraction"]
What (that patient has, get from med history) would be indicators for ANTI-Coagulation?
1) Atrial Fibrillation 2) Subpopulation of patients w low ejection fraction (inc. risk of thrombus formation causing stroke). 3) Pulmonary Embolus 4) Deep Vein Thrombosis 5) Hypercoagulable states = Lupus anticoagulant; anti-cardiolipin antibodies and Protein C or S deficiency {anti-phospholipid syndrome}; Anti-thrombin III deficiency; Factor V Leiden, prothrombin gene mutation.
Patient A has von willibrand Disease. Patient B has liver cirrosis with platelet count down. 1) Which will have prolonged bleeding time? 2) Which patient will have Thrombocytopenia? 3) What does the bleeding time evaluate? How does aspirin and plavix influence this?
1) Both patients have prolonged bleeding time. 2) Cirrhosis patient will have Thrombocytopenia (prolonged bleeding time, low platelet count). Only Von Willebrand Diseae type 2B has throbocytopenia (all other types have NORMAL platelet count). 3) Bleeding Time = Time for a skin puncture to stop bleeding = measured in MINUTES. Normal is 5-9 minutes. Aspirin use (elongates bleeding time) 9-12 minutes. Plavix use (longer BT than aspirin) >12 minutes w/ mild intra/post-operative bleeding, and significant intra/post-operative bleeding.
Three common characteristics of Muscle Fibers AND Nerve Fibers?
1) Extraordinarily long cells, measured in inches and feet. 2) Excitable plasma membranes capable of conveying action potentials. 3) Well insulated from neighboring cells.
1) All the factors involved in the coagulation process are proteins, except 2) many of the steps in the coagulation cascades involve ______, others involve formation of complexes between factors and cofactors. 3) ____ is involved in many steps of coagulation as a cofactor. 4) both intrinsic and extrinsic pathways share _____. 5) The blood coagulation cascade is an example of ______. 6) Factors, once activated, do what?
1) Factor IV (calcium) and PF3 (a phospholipid. 2) zymogen activation 3) calcium 4) the last four steps 5) biological amplification - each activated factor or complex catalyzes many reactions in the subsequent step. 6) adhere to original site of injury and act locally.
1) Treatment for "Folic Acid (Folate) Deficiency Anemia"? 2) Treatment for "Vitamin B12 deficiency anemia"? know caps
1) Folic acid supplementation = 1 mg/day FOR CHILDREN AND ADULTS. Should help with IMPROVEMENT in anemia. 2) Vitamin B12 deficiency responds to DAILY Cobalamin injections for ONE WEEK. Then, supplemental monthly injections of 250-500 micrograms B12. MCV REDUCTION BY 5 FL OCCURS within TWO WEEKS of treatment.
(a) RBC production has dependency on? What can affect these things? (b) Function of RBCs? Turnover? Imp about their membrane? What is contained within them?
1) Healthy Bone Marrow (can be affected by cancer, fibrosis, meds) - the "factory". 2) Stem Cells (can be affected by genetic thassemia, genetic sickle cell; or acquired leukemias) - the "workers". 3) ERYTHROPOETIN hormone produced in kidneys that drives red cell production (requires iron, vitamin B12, folate, and testosterone). (B) carry oxygen. - they are replaced every 120 days (turnover - note turnover of RBCs more rapid w hemolytic anemia) & have flexible deformable membrane. 1) Hemoglobin is contained with in (Heme = uses iron moiety to transport oxygen; Globin = stabilizes heme).
Erythrocytosis - how do you make differential diagnosis? causes? consequences?
1) Hemoglobin (Hb) > 16gm/dl in woman, and >18 in man [get from red cell count from complete blood count and differential) 2) Causes 2a) Physiologic (secondary) - high altitude, heart and lung diseases (impaired oxygen echange), erythropoetin overproduction (renal cell carcinoma). 2b) Pathologic (Primary) - myeloproliferative disorders (polycythemia vera). 3) Consequence = Hyperviscosity - blood clots: stroke, myocardial infaction, limb loss. - symptoms: fatigue, shortness breath, paresthesias ("pins and needles"), headache, blurred vision, itching.
1) Primary Hemostasis vs. 2) Secondary Hemostasis {involves cascade of what? how can these things be affected?) ? 3) Clot stabilization?
1) Primary Hemostasis = "the formation of platelet plug", occurs w/in seconds to minutes, involves platelets and von Willebrand protein (know him), defects lead to skin and mucous membrane bleeding. 2) Secondary - clot starts to stabilize -> minutes -> hours (<2); coagulation cascade w activity of factors and cofactors; defect lead to soft tissue and joint bleeding. = coagulation cascade = multiple enzymatic reactions involving proteins called "factors" that work toegether to achieve fibrin clot formation. [factors II, VII, IX, X, XI, XII; cofactors V, VIII] = produced in LIVER and constitutively released, - so LIVER DISEASE may result in factor DEFICIENCIES; congenital deficiencies may lead to soft tissue and joint bleeding. - EXCESSIVE FACTOR activity -> pathologic clotting = Thrombosis = TREATED WITH ANTI-COAGULATION. 3) Clot stabilization = balance of fibrin clot formation & plasmin activity; clot breaks down hours after initial clot has formed.
1) von Willebrand Factor/Protein - what are the two main FUNCTIONS (KEY PLAYERS)? Is dependent on what? When do levels rise? 2) on Willebrand Disease (primary hemostasis) - IS THE MOST COMMON...? DEFECT IS WHAT? 3) Description of types? 4) What are some indications you should treat a patient with von Willebrand Disease? 5) Treatment of the disease? 6) What are the three tests used to used to SCREEN von Willebrand disease? How can you DECIPHER TYPE 1 VS TYPE 2 ON SCREENING TESTS?
1) Primary hemostasis binds to PLATELETS (help in AGGREGATION) & binds to FACTOR 8 (protects it from proteolysis in circulation and prolongs its half-life (secondary hemostasis). - basic unit (dimer) becomes multimers = large, intermediate (PHYSIOLOGICALLY MOST IMP), and small. - is blood type dependent bc Type O patients have lowest amounts, Type AB patients have highest amounts. - Levels Rise w stress, infection, pregnancy/estrogens bc its an Acute Phase Reactant. 2) von Willebrand's Disease = MOST COMMON INHERITED BLEEDING DISORDER; DEFECT IN PLATELET FORMATION/FUNCTION & COAGULATION = easy bruising & mucocutaneous bleeding= INDICATED BY POST-PARTUM HEMORRAGE (USU.), & SPONTANEOUS BLEEDING FROM MUCOSAL SURFACES (gums, naes, GI, menstural) = defective primary heomostasis 3) Types: 1 = deficiency (quantitative) 3 = absence (quantitative) 2A = not enough intermediate multimers 2B = binds platelets too tightly. Type 2M = can't bind platelets Type 2N = can't bind factor 8 4) ACUTE BLEEDING (give DDAVP if knwn to respond; give factor concentrates if no response to DDAVP); PROPHYLAXIS (prior to surgery or invasive proceure; severe bleeding w frequent spontaneous bleeding episodes; replete to VWF activity of 100%). 5) Tx: prophylaxis before surgery and procedures to prevent bleeding. 5a) DDAVP (DESMOPRESSIN)= Type 1 or 2a ONLY = induces release of VWF from endothelial storage sites = IV, SC, or Nasal Spray. = For a DDAVP trial, measure pre and post dose of VWF. 5b) HUMATE-P (factor replacement strategy) = concentrate of VWF and Factor8 = IV formulation only, dosed every 8-12 hours (half-life); = calculate about of factor needed to replete to 50-100% activity (weight based on RCoF units). 5c) EPSILON AMINOCAPROIC ACID (AMICAR) = Clot Stabilization Strategy = prevents clot lysis = Oral or IV formulations.- IMP FOR DENTIST. - both mild hemophilia and F11 deficiency can be treated with AMICAR which is a drug that prevents the clot from breaking down particularly a the site of active fibrinolyysis such as oral cavity. 6) Three Screening Tests: - Von Willebrand Antigen (vWF) Level - vWF activity (measured by Ristocetin Cofactor method) - Factor 8 Level TYPE 1 = LOW vWF-ag, LOW vWF activity, LOW factor8. Type 2 = NORMAL vWF-ag, LOW vWF activity, NORMAL factor 8. TYPE 2N = NORMAL "", LOW "", LOW "" (Remember: FVIII is bound to vWF in the circulation and relies on this protein for its stabilization. If the D1 domain of vWF has a mutation that compromises binding of FVIII protein, the half-life of FVIII will decrease and the level in the circulation will be low. ). <-- KNOW THESE!!!!
1) Tm and Tn (troponin components) are called "________proteins" bc they make muscle contraction sensitive to calcium. 2) Actin and myosin are the "________ proteins"
1) Regulatory Proteins B) Contractile proteins
1) Sarcoplasmic Reticulum 2) Transvers or T-Tubules - proteins associated with each? how they interact? properties of each. 3) proposed mechanism for release of calcium from the sarcoplasmic reticulum (SR)?
1) SARCOPLASMIC RETICULUM - system of membrane-bound tubules that surround myofibrils and release calcium ions during contraction and retake them up during relaxation}. - RyR - Ryanodine Receptors or calcium release channels = gated channels that do release of calcium from the SR. [Attached to the DHP receptors (of T-tubules) via associated JUNCTIONAL FOOT PROTEINS. Activation of the DHP receptors by an action potential mechanically opens attached RyR channels.] - SERCA (sarcoplasmic-endoplasmic reticulum Calcium = ATPase) active transport pump does RAPID UPTAKE CA2+ from cytoplasm INTO the interior of SR at end of contraction. - Calsequestrin = calcium binding protein within cisternae of the SARCOPLASMIC RETICULUM. Has ability to bind more than 20 Ca++ ions per molecule - helps to keep the INTERNAL (of SR) CALCIUM HIGH. 2) TRANSVERSE OR T-TUBULES are deep invaginations of the surface membrane of muscle cells (SARCOLEMMA) that extend into the interior of myocytes and carry the action potential to the inside. - DHP (dihydropyridine) (proteins associated with T-tubules) voltage gated L-type calcium channels whose structure changes with the T-TUBULE depolarizes. Calcium entry into the myofiber through the DHP receptors is gradual and limited. 3) proposed mechanism for release of calcium from the sarcoplasmic reticulum (SR) = First) Action potential generated in myofiber travels down each transverse tubule. Second) It activates the voltage-gated DHP (know these) receptors in the T-tubule membranes causing them to undergo a structural change. Third) This change "pulls" open the RYR receptors (know this) in the SR, allowing calcium to rapidly diffuse out of the SR into the cytoplasm. Last) The very large calcium concentration gradient btwn SR and the resting cytoplasm causes rapid flux into the cytoplasm.
1) Pseudounipolar Nerve Cell Type - focus on this 2) Bipolar """ 3) Multipolar """
1) Sensory. Has 1 axon that splits into two: 1 split goes to peripheral,1 split goes into CNS. 2) Sensory; sensory organs (e.g. olfactory epithelium). 3) Somatic motor & visceral motor
Types of smooth muscle? - Tonic vs. Phasic; Single unit vs. Multi Unit.
1) TONIC - normally maintain sustained contractions, e.g. vascular smooth muscle- maintains blood pressure, or sphincter muscles in the gastro- intestinal or urinary tract that compartmentalize digestive juices or urine. 2) PHASIC - normally relaxed but can be stimulated to contract e.g. muscular walls of the GI tract 3) A group of smooth muscle cells can behave as: • SINGLE UNITS s with the cells electrically connected by gap junctions and innervated by a single nerve fiber: e.g. gastrointestinal tract. • MULTI UNIT in which each cell has a direct connection with an autonomic motor neuron; e.g. ciliary muscle in the eye
Coagulation Tests (secondary hemostasis): 1) aPTT is for? Prolonged APTT indicates what? 2) PT is for? 3) Factor level measurement? MUST KNOW - what is the normal PT/INR, and what is the therapeutic range of PT/INR?
1) aPTT [activated partial thromboplastin time = 23-31 seconds] = INTRINSIC PATHWAY coagulation aka all factors EXCEPT F7 and TF = secondary hemostasis/coagulation cascade. - Prolonged due to either: Factor deficiencies (11, 8, 9, & 12 if patient not bleeding), or inhibitor of coagulation.. differentiate with mixing study. 2) PT [Prothrombin Time; 8.9 to 11.3 seconds] = EXTRINSIC PATHWAY {time needed for plasma to clot} for F7 (know this), F2 (prothrombin), F5, F10, and fibrinogen = monitored by international normalized ratio (INR) where NORMAL PT/INR = 1.0, and THERAPEUTIC RANGE = 2.0-3.0. 3) Factor Level measurement = expressed as % activity.
Definitions: 1) TERMINAL CISTERNAE, 2) TRIAD
1) enlarged region of Sarcoplasmic Reticulum that associates closely with the T-tubules. 2) Triad = T-tubule + two Cisternae on either side of SR
Thrombocytosis - differential diagnosis? causes? conseuqneces?
1) platelet count (complete blood count and differential) > 450 k mm3 (normal is 150-450). 2) causes: 2a) Reactive = iron deficiency, inflammation, bleeding, splenectomy. 2b) Primary Bone Marrow Disease (myeloproliferative neoplasma e.g. essential thrombocytosis (ET). 3) consequences: 3a) Thrombosis - stroke, heart attack, & DVT. 3b) Paradoxical bleeding = platelets bind to and remove Von Willebrand (know this guy) factor, platelets function impaired.
What do the overlapping thick and thin filaments of the sarcomere give rise to?
1. A band (darker center line) = to length of thick filaments. 2. I band = only thin filaments; bisected by Z discs / Z lines. 3. H zone = central zone = thick filaments, NO overlapping thin filaments. Center of it contains M protein ("M line is in middle"). (phys 11/17)
List of Antithrombin III Enhancers
1. Heparin = parenteral anticoagulant, IV. 2. (LMWH) Enoxaparin (Lovenox), Dalteparin (Fragmin) = parenteral anticoagulant, subcutaneously. acts more selectively than heparin to stop formation of substances that form clots.
In Skeletal muscle electrical excitation/stimulation of myofibers via action potentials, the axon terminates on the _____1_____ of the myofiber. But the two are separated by the ___2____.
1. Motor End Plate 2. Synaptic Cleft (a small space).
What are the components of CBC? What is NOT a component of the CBC? What are CBCs used for (medicine review)
1. RBC 2. Hb 3. Hct 4. MCV (Mean Corpuscular Volume) 5. MCH (Mean Corpuscular Hemoglobin) 6. MCHC (Mean Corpuscular Hemoglobin COncentration). 7. RDW (Red Cell Distribution Width) ^ for Anema, Polycythemia, Hemochromatosis. 8. Total White Blood Cell Count (WBC) - neutrophils, lymphocytes, monocytes, eosinophils, basophils. ^ for Leukocytosis, Leukopenia, ANC Count 9. Platelet Count (PlT) ^ for primary hemostasis & drugs affecting platelet function e.g. Aspirin, Plavix, NSAIDs, etc.
Classification of Muscle: Skeletal vs Visceral vs Cardiac vs Smooth?
1. SKELETAL = STRIATED = voluntary muscles associated w skeletal movement (biceps brachii, trapezius, deltoid, etc.... atypical muscles: lower pharynx, diaphragm, etc.); long UNbranched muscle fibers, continuous external lamina; NO cell-cell gap junctions; rich CT investments {surrounding entire muscle, muscle fascicles, and muscle fibers}; Mutlinucleated (true syncytium). CT Sheaths incl. Epimysium surrounds endomysium w. perimysium separation {these r all continuous w tendons}. 2. VISCERAL = STRIATED = voluntary visceral muscles (upper esophagus, pharynx, tongue, etc. note stuff not attached to bone). 3. CARDIAC = STRIATED = involuntary / autonomic (sympathetic/parasympathetic) control; long branched muscle fibers (formed by end to end cell fusion via specialized cell-cell junctions); DIScontinuous external lamina; many GAP junctions; cells often binucleate (functional syncytium) ; has intrinsic capability to beat (autonomous contractility). 4. SMOOTH = NON-STRIATED = INVOLUNTARY autonomic (sympathetic/parasympathetic) control; unfused spindle shaped cells (20-500 um) with central nucleus; DIScontinuous external lamina; many GAP junctions. wide distribution (hollow/tube organs - gut, bronchioles, blood vessels, ureter, gall bladder, skin arrector pili); NO TRUE SARCOMERES. Peristalsis bc of this typical arrangement in walls of hollow organs.
What is the average life span of the NORMAL RBC? know this - red, medicine.
120 days
Sliding Filament Hypothesis of Muscle Contraction
1954. "contraction occurs when the thick and thin filaments slide past one another to increase their overlap" 1957 showed "actin-myosin linkage (crossbridge) was involved in the sliding.
Is all the premedication just 1 hr prior to the procedure? Or can it be a few days before the procedure as well? Does this change with the different stages of neutropenia?"
: Premedication is a fixed antibiotic dose recommended by the American heart association that when given by mouth is done one hour prior to the treatment and when injected, it is done thirty minutes prior to the procedure.
Heparin - what type of drug? Administered? Actions/ how would it be assayed? Used for what? know this
= Antithrombin III Enhancer [so are: (LMWH) Enoxaparin (Lovenox), Dalteparin (Fragmin)] - PARENTERAL ANTICOAGULANT (INTRAVENOUSLY) - The inhibitory effect of AT3 is very slow, HEPARIN ACTS AS A COFACTOR AND ACCELERATES THE REACTION 1000-FOLD - INHIBITS MOSTLY INTRINSIC PATHWAY FACTORS => PROLONGING PTT ( partial thromboplastin time) - inhibits 9a (conversion F10 to F10a), Xa (F2 to F2a), and 2a (F1 to F1a which is Fibrin). - Used acutely to treat: deep venous thrombosis, pulmonary embolus, unstable angina, acute myocardial infarction, prosthetic heart valves, etc. - Side effects: increased bleeding and thrombocytopenia (reduced platelet count). [topic - AntiThrombotics Therapy]
Types of muscle contraction - Define: Isometric Contraction, Concentric Contraction, Eccentric Contraction
= Isometric, Concentric, Contraction involves the generation of force by activating the cycling of crossbridges. This may or may not cause shortening of the muscle. Isometric = contraction where length doesn't change (velocity of shortening is zero). Concentric = muscle length shortens during contraction. Eccentric = muscle lengthening while maintaining force; all normal muscular function that occur.
Define Thrombocytes and what are they involved in?
= platelets. - Derived from megakaryocytes in the bone marrow. - role in maintenance of endothelial lining of blood vessels, rapidly repairing small breaks e.g. w. vessel injury, they quickly form temporary PLATELET PLUG in the vessel wall to stem the flow of blood until a more permanent repair can be made.
5) Low molecular weight heparins include which of the following: A. Enoxaparin (Lovenox) B. Warfarin C. Coumadin D. Clopidogrel
A. Low molecular weight heparins = Enoxaparin (Lovenox®), Dalteparin (Fragmin)].
LEUKEMIA = CANCER OF WHAT? Occurs where in body? How is it classified? WHAT ARE THE FOUR FORMS? Causes? CLINICAL PRESENTATION? INTRA-ORAL FINDINGS?
= MALIGNANCY OF HEMATOPOIETIC STEM CELLS involving Proliferation of abnormal WBCs, and INC. in immature white cells (Leukocytosis). - Occurs in bone marrow and proliferates into peripheral blood. - Classified by clinical behavior and histogenesis: Chronic vs. Acute (Clinical behavior) Myeloid vs. Lymphoid (Histogenesis) - 4 FORMS OF IT = CHRONIC MYELOID LEUKEMIA (CML) with Philadelphia Chromosome-(9,22); CHRONIC LYMPHOCYTIC IS MOST COMMON TYPE IN ELDERLY/ADULTS; ACUTE LYMPHOBLASTIC IN CHILDREN ONLY; && ACUTE MYELOID LEUKEMIA in patients OVER AGE 40. - causes include either: Exposure to pesticides, Benzenes, Ionizing radiation, or Viruses (ex. Retrovirus). - CLIN. PRESENTATION = MYELOPTHISIC ANEMIA WITH CROWDING OUT NORMAL HEMATOPOIETIC STEM CELLS & (white and red blood cells) BY THE MALIGNANT CELLS; FATIGUE; THROMBOCYTOPENIA (SPONTANEOUS GINGIVAL HEMORRHAGE); & FEVER. - INTRAORAL FINDINGS = DIFFUSE/BOGGY GINGIVAL ENLARGEMENT (AML or CML usu.), CANDIDIASIS, DEEP/PUNCHED-OUT NEUTROPENIC ULCERS, HERPETIC INFECTION TO ORAL MUCOSA, & prominent TUMOR-LIKE GROWTH (MYELOID SARCOMA-LEUKEMIC CELLS)
The contractile cycle (BE ABLE TO ANSWER ALL QUESTIONS) - what type of coupling? What happens when muscle is stimulated by CALCIUM? What initiates the power stroke? What does ATP binding to myosin head most immediately result in? What causes the head to become "cocked"? hat is the first step when the muscle is stimulated? When do the filaments actually start moving (name of process / what happens)?
= MECHANO-CHEMICAL coupling. - muscle contraction involves cyclic attachment and detachment of myosin crossbridges (heads) to the actin filaments. (1) First Step in actin-myosin interaction when muscle is stimulated by calcium = HIGH-ENERGY MYOSIN HEAD (cross-bridge) BINDS TO AN ACTIN SUBUNIT IN THE THIN FILAMENT. The hydrolysis products of ATP (ADP + Pi) from a previous cycle remain bound to the head. (2) initial weak binding of the head releases inorganic phosphate (PHOSPHATE RELEASE) and initiates a POWER STROKE = STRONGER BINDING AND RELEASE OF ADP. The actin-activated release of Pi and then ADP is associated w a conformational change of the myosin head - the working stroke - that generates movement. (3) ATP BINDING to myosin 'head' CAUSES DISSOCIATION OF MYOSIN FROM ACTIN. In absence of ATP (as occurs after death), myosin cannot dissociate from actin, and the muscles become stiff. This is known as RIGOR MORTIS. In a living person, rigor corresponds to the short-lived state in which the myosin head is bound to actin in the absence of nucleotide. It represents the lowest potential energy state of the head. (4) ATP HYDROLYSIS CAUSES A SHAPE CHANGE SO THAT THE MYOSIN HEAD IS "COCKED" INTO A HIGH ENERGY CONFORMATION bc they are energized to attach to thin filament and undergo a power stroke - AKA: The products of ATP hydrolysis (ADP and inorganic phosphate) remain bound in this step. The free energy released from ATP hydrolysis is TRANSFERRED to the head (cocking) which now has the potential energy to bind to actin and undergo the power stroke in the next cycle = normal state of the heads in resting muscle.
CYCLIC NEUTROPENIA - REDUCTION IN WHAT? Results from? Occurs how often? How long does it last? These people are more susceptible to what? Clinical features? Oral lesions? Treatment?
= PERIODIC REDUCTION IN NEUTROPHIL POPULATION (every 21 days/3-4 weeks (each month), their neutrophil count drops). - Results from defect in hematopoietic stem cells - Occurs on a 21-day cycle - Noted at lowest point (nadir), lasts for 3-6 days - Infection occurs, resolve as count increases bc These ppl more susceptible to infections until count restores back to normal. - Clinical features = Fever, lymphadenopathy, malaise - ORAL LESIONS = (1) ULCERS on areas exposed to trauma (lips, tongue, buccal mucosa), (2) BONE LOSS and gingival recession - Treatment = Supportive therapy; Good oral hygiene therapy
Nissl Substance - define it (where's it found/what type of neuron)? What is the part of the neuron without any of it?
= RER, Ribosomes ("clumps")- provide power to send signal along. Part of MOTOR Neurons. Axon hillock is area w/o any.
AGRANULOCYTOSIS - TYPE OF DISEASE? RESULTS FROM? IMPORTANT CLINICAL FEATURES (ESP. DENTAL)? Causes? Treatment?
= SEVERE FORM OF LEUKOPENIA / NEUTROPENIA. - Hematologic disorder involving granulocytic cells (neutrophils). - RESULTS FROM DEC. PRODUCTION or INC. DESTRUCTION OF CELLS. - 2 CLIN FEATURES = BACTERIAL INFECTIONS & ORAL LESIONS INVOLVE PALATE, BUCCAL MUCOSA, TONGUE W. NECROTIZING, PUNCHED OUT ULCERATIONS and GINGIVA RESEMBLES NECROTIZING ULCERATIVE GINGIVITIS. - Caused by Exposure to drugs (Anticancer chemotherapeutic). - Tx is to Discontinue drug, which will stimulate neutrophil production by bone marrow, and follow ORAL HYGIENE instructions with chlorhexidine rinse.
Hemophilia - HOW DO YOU GET IT? COMMONLY AFFECTS WHAT PPL? TYPES & WHAT'S DEFICIENT IN EACH (ANOTHER NAME FOR ONE OF THEM)? types? clinical history of? laboratory diagnosis? Whats the difference between mild, moderate, and severe cases? treatments for dif. types of it? DENTAL GUIDELINES for hemophilia? imp know all this.
= X-LINKED RECESSIVE DISORDER (MALES affected more). - often diagnosed in childhood, though mild hemofiliacs may remain undiagnosed until adulthood = patient with CLIN. HISTORY OF: joint hemorrhage with joint deformaties, GINGIVAL hemorrhage, persistant ORAL BLEEDING, bleeding into soft tissues. 1) Types 1a) Hemophilia A = FACTOR 8 DEFICIENCY (reduced activity, and F8 is needed to help activate Factor 10 in intrinsic pathway) => Prolonged aPTT and normal PT; Easy bruising and massive hemorrhage after trauma or operative procedures; NO Petechiae; Treat with Factor 8. 1b) Hemophilia B = CHRISTMAS DISEASE; FACTOR 9 deficiency (which works with factor 8 to activate F10 in intrinsic pathway!) => prolonged aPTT and normal PT (same as type a). 2) Diagnosis in Lab = do a PROLONGED aPTT test {[activated partial thromboplastin time = 23-31 seconds] = interrogates the INTRINSIC PATHWAY of coagulation = screens for all coagulation factors and cofactors EXCEPT FVII and TF} - factor VIII and Factor IX are part of the "intrinsic pathway" = NORMAL PT, NORMAL BLEEDING TIME, NORMAL PLATELET COUNT. 3) MILD, MODERATE, OR SEVERE DEPENDS ON LEVEL OF CLOTTING PROTEIN. Normal Factor Level/Activity is 100%. - Mild Hemophila = 5-25% activity ( - Mild bleeding diaphysis/disorder. Need to pay attention to them bc they bleed when have trauma or when u do procedure on them.). - Moderate 2-5% activity. - Severe < 1% Activity (prob bleed spontaneous all the time) ** moderate and severe hemophiliacs can develop spontaneous bleeds!** 4) Tx [know these!] 4a) Hemophilia A Tx = recombinant factor VIII Replacement protein = first, obtain baseline Factor VII activity; Goal is to correct to desired % factor activity e.g. 100%; 1 unit of FVIII per kg for every 2% inc. desired given every 8-12 hours or by continuous infusion; Then, re-check factor activity level to confirm adequate replacement. 4b) Hemophilia B Tx = Recombinant Factor IX replacement protein = same idea as tx for type A, but give 1 unit of Factor IX per kg for very 1% increase needed every 8-12 hours or by continuous infusion. 5) DENTAL GUIDELINES: - fix this..l listen to audio. 5A) For PREVENTIVE PROCEDURES = e.g. scaling, patients should have replacement therapy. 5b) For RESTORATIVE PROCEDURES = replace factors to 50% activity before anesthetic blocks. 5c) SURGICAL PROCEDURES = replacement therapy w facor concentrates = recombinant factors and/or DDAVP for hemophilia A&B; FFP for Factor XI deficiency; Fibrinolytic inhibitor (e.g AMICAR); continue therapy for at least 7-10 days after the surgical procedure.
What is Fibrinolysis? What is required?
= dissolution of the clot = final step in hemostasis = new fibroblasts migrate to injury site and begin repair process = requires activation of plasma protein plasminogen into PLASMIN, which occurs when clot itself induces release of PLASMINOGEN ACTIVATOR.
Converter Domain (muscle contraction, phys)
= junction of motor and neck domains of S1 is this 70=residue segments of amino acids. It acts as an elastic element in the myosin head. Current evidence that when neck domain tilts relative to motor domain, the elastic element is istorted allowing a strain to develop in teh converter region. Relief of this strain drives the sliding of actin filaments past the myosin filament. [details of the power stroke].
Hemostasis - definition? Four steps?
= maintenance of blood flow & prevention of blood loss in the event of an injury to a vessel. When blood vessel is ruptured, result is (prevention of blood loss via hemostasis) FOUR STEPS: 1. vascular spasm (vasoconstriction) 1a) local myogenic spasm 1b) sympathetic nervous system {injury stimulates SNS to do vasoconstriction over and above that resulting from myogenic reflexes) 1c) local chemical factors {thromboxane A2, kinins, serotonin = powerful vasoconstrictors / vasoactive agents} released from damaged tissue and platelets. 1d) blood loss into a tissue (hematoma formation) can increase local tissue pressure (turgor), slowing blood loss. - note - (The more of the vessel that is traumatized, the more vascular spasm occurs, thus a sharply cut vessel often bleeds more than one ruptured by crushing). 2. FORMATION OF PLATELET PLUG- adhesion, activation, aggregation. 3. BLOOD COAGULATION TO FORM A CLOT. 4. GROWTH OF FIBROUS TISSUE INTO THE CLOT TO CLOSE THE RUPTURE PERMANENTLY (clot retraction and dissolution): clot starts to shrink and retract shortly after its formed. Most of entrapped fluid (SERUM aka plasma w no clotting factors) oozes out of clot. During retraction, the edges of small wounds are pulled together. - retraction result at least in part form the contraction of platelet actomyosin. - FIBRINOLYSIS (dissolution of clot) requires clot to induce release of plasminogen activator, which activates plasmin (from plasminogen plasma protein) => dissolution of clot by new fibroblasts migrating to injury site and begin repair process.
DEFINE ISOMETRIC CONTRACTION. Why is less ATP used in it compared to dynamic contraction? What about isotonic contractions (don't focus as much on isotonic)?
A MUSCLE CONTRACTION IN WHICH VELOCITY OF SHORTENING IS ZERO aka muscle force without a change in length (inc tension, no length change). - less ATP hydrolyzed in this (compared to one in which a similar load is lifted) BECAUSE It oscillates between crossbridge angles without releasing it attachment to the thin fillament - - myosin heads that bind to the actin filament, and oscillate btwn a power stroke that shortens the fiber and an external force (the load) that extends the head to a pre-power stroke position. May also involve the "converter region" of myosin heads (see power stroke fc). = Generation of tension when shortening of contractile components of muscle (thick and thin filaments) causes a stretch in the elastic components (tendon). - Tension or elastic energy is stored in the stretched tendons which are called series elastic components of muscle while the contractile component (the muscle belly) pulls on them. Even in contractions in which the muscle lifts a load, the elastic components of the muscle must stretch until they develop tension equal to the load. The parallel elastic component is related to proteins within the sarcomeres, particularly titin. ISOTONIC CONTRACTION = as load is lifted, length of muscle changes.
THALASSEMIA - is a FORM OF WHAT CATEGORY OF ANEMIA? Is caused by what, which results in what? In what population? RBC's appear as what? Difference between alpha and beta Thalassema? HOW DO YOU (DENTIST) KNOW A PATIENT HAS BETA-THALASSEMIA? Treatment for both types?
A form of HEMOLYTIC ANEMIA. Disorder of hemoglobin synthesis -> Reduced synthesis of alpha/beta globin chains. - Mediterranean, Africa, India, Southeast Asia - RBCs r microcytic and hypochromic. - alpha-Thalessemia (can have up to 4 defects): 1 defect-No disease; 2 defects-Trait, mild anemia; 3 defects is "Hb H disease" with hemolytic anemia and splenomegaly (enlarged spleen); 4 defects is "Hydrops fetalis" is fatal and noted within few hours of birth. - beta-Thalassemia (can have two defects): 1 defect is "Thalassemia minor" or "beta-thalassemia minor" with No clinical manifestations; 2 defects is "Thalessemia major" with "Cooley's anemia aka Severe microcytic, hypochromic anemia after 3-4 months", Bone marrow hyperplasia, and Lymphadenopathy. - 3 SIGNS OF BETA-THALASSEMIA (IMP DENTIST) = "CHIPMUNK FACE" appearance (fuller face); "HAIR ON END" on radiograph; DIE BY AGE ONE bc bacterial infection or cardiac failure. - Treatment for α and β-Thalessemia either: Blood transfusions every 2-3 weeks with iron chelating agent, which prevents the hemochromatosis (Abnormal iron deposit), or Stem cell transplant for curative treatment ("there is a definitive cure")
3) Which of the following is a direct thrombin inhibitor used for DVT prevention in hip replacements? A. Dabigatran (Pradaxa) B. Clopidogrel (Plavix) C. Heparin D. Enoxaparin (Lovenox)
A. Heparin is an enhancer; Copidogrel is anti-platelet has nothing to do with thrombin; Lovenox is anti-thrombin.
2) Which of the following is used in patient allergic to aspirin to prevent stroke? A. Clopidogrel (Plavix) B. Prasugrel (Effient) C. Abciximab D. Tirofiban
A. Clopidogrel (Plavix, ADP pathway inhibitor) is in same class as aspirin but acts in a dif way bc doesnt cause gastric upset.
How is the thin filament formed? What are the two forms of Actin?
ACTIN exists in two forms: GLOBULAR ACTIN (G form, each molecule weighs 42 kDa) and FILAMENTOUS ACTIN (F form, is an actin polymer). In cell-like (cytoplasm) solutions, G-actin (monomeric globular actin) POLYMERIZES into F-actin (filamentous actin) to form actin filament consisting of the two strands of actin subunits wound around each other to form a helix. notes: Lorenz model of F-actin. a single G-actin monomer with inter-actin contact surfaces shown on R in diagram, the entire F-actin on the left. THEN, in sarcomere.... one end of the F-actin is inserted into and forms part of the Z-disc along w alpha-actinin {main protein of Z} and many other proteins. Other end of filament is capped w protein tropomodulin. Thin filament length is about 1um. - 1 tropomyosin (Tm) role: binds seven actin subunits so both actin chains are "decorated" by Tm. - 1 Troponin (Tn) is also bound per seven actins: TnI (inhibitory) binds actin; TnT binds to Tm; TnC binds calcium. - Troponin stabilizes thin filament structure bc has two-pronged attachment: to actin via TnI and to tropomyosin via TnT.
35 year old male, Mr. BC, patient presents to your clinic today. He has a history of Diabetes. He presents you with his latest CBC with differential that was done last week. The results are as follows: WBC: 2,000 cells/mcl (L) (4,500-12,000) Neutrophils: 30% (50-70%) Bands: 10% (3-5%) Eosinophils: 3% (1-3%) Basophils: 1% (0.4-1%) Lymphocytes: 5% (25-35%) What is the patient's ANC value? A. 1,000 neutrophils/mm3 B. 800 neutrophils/mm3 C. 600 neutrophils/mm3 D. 200 neutrophils/mm3
ANC = Total WBC count x (% Neutrophils + % Bands*) ANC = 2,000 x (30% + 10%) = 800 neutrophils/mm3
Anemia and Hemoglobin levels? What are Normal Hemoglobin values for males and for females? know this - red, medicine.
ANEMIA IS ASSOCIATED W A reduction IN THE HEMOGLOBIN CONTENT, which results in tissue hypoxia and poor wound healing. Normal Hb Levels: Males: 13.5 - 17.5 g/dL Females: 12-16 g/dL
Afferent vs. Efferent
Afferent = dentrites = incoming information synapses on dentrites. Efferent = axons, aka nerve fibers
What is the function of the Node of Ranvier?
Amplifies signal, increase speed of conduction - this is why myelinated nerves are very fast (bc they are junction btwn adjacent myelin sheaths). High concentration SODIUM channels in node causes boost in signal. As you move down axon, signal is decreased; the influx of sodium boosts signal so that it doesn't dissipate over length of axon.
(LMWH) Enoxaparin (Lovenox), Dalteparin (Fragmin) - administration? comparison to drugs of same class? used for what?
Antithrombin III Enhancers (so is heparin, but these r more direct). - PARENTERAL ANTICOAGULANT (SUBCUTANOUSLY) -> ACTS MORE SELECTIVELY THAN HEPARIN BY BLOCKING JUST FACTORS 10A AND 2A (THROMBIN) to stop the formation of substances that cause clots. - prevent blood clots in the leg in patients who are on bedrest or who are having hip replacement, knee replacement, or stomach surgery. - It is used in combination with aspirin to prevent complications from angina (chest pain) and heart attacks. Patient may need a dose adjustment or more frequent monitoring by the doctor to avoid bleeding - It is also used in combination with warfarin to treat blood clots in the leg [topic - AntiThrombotics Therapy]
7) True Syncytium occurs in which of the following a) smooth muscle b) skeletal muscle c) cardiac muscle d) purkinje fibers
B - true syncytium in skeletal muscle = no gap junctions, often multinucleated, giant cells. (cardiac muscle has functional syncytium).
7) Which ONE of the following acts by competitive inhibition of vitamin K epoxide reductase? A. Desirudin (Iparavask) B. Warfarin C. Heparin D. Ezetimibe
B.
Statement 1: Aspirin irreversibly affects platelets and therefore must be stopped 48 hours prior to procedures associated with bleeding risk. Statement 2: Thrombocytosis can lead to paradoxical bleeding in some patients due to the decreased amount of von Willebrand factor. A. Statement 1 is true, statement 2 is false B. Statement 2 is true, statement 1 is false C. Both statements are true D. Both statements are false
B. Aspirin = irreversible inhibition of platelets; Should not use chronic use of aspirin or NSAIDS (for treating anemia) but 2-3 days is typically okay for nutritional anemia. Consequences of Thrombocytosis: 3a) Thrombosis - stroke, heart attack, & DVT. 3b) Paradoxical bleeding bc platelets bind to and remove Von Willebrand (know this guy) factor, platelets function impaired.
Statement 1: Primary hemostasis occurs within hours to days and involves platelets and von willebrand protein Statement 2: Hemophilia is the most common inherited bleeding disorder. A. Both statements are true B. Both statements are false C. Statement 1 is true, statement 2 is false D. Statement 1 is false, statement 2 is true
B. Primary Hemostasis = "the formation of platelet plug", occurs w/in seconds to minutes, involves platelets and von Willebrand protein (know him), defects lead to skin and mucous membrane bleeding. Von Willebrand's Disease = most common inhereted bleeding disorder (incidence 1:00 to 1:000) Hemophilia = x-lined recessive trait that predominantly affects MALES (females often carriers unless both parents cary hemophilia gene); often diagnosed in childhood, though mild hemofiliacs may remain undiagnosed until adulthood = patient with CLIN. HISTORY OF: joint hemorrhage with joint deformaties, GINGIVAL hemorrhage, persistant ORAL BLEEDING, bleeding into soft tissues.
Statement 1: As compared to Warfarin, the novel or new oral anticoagulants are safer to use since they have reversal agents. Statement 2: As compared to Warfarin, patients on novel or new oral anticoagulants do not have any dietary restrictions such as avoiding leafy green vegetables. A. Statement 1 is true, statement 2 is false B. statement 1 is false, statement 2 is true C. both statements are true D. both statements are false
B. Statement 1 is false - New Oral Anticoagulants have LIMITED reversal agents (reverse anti-coagulant effects). Statement 2 is true - Clinical advantages of oral anticoagulants (ex: Dabigatran (Pradaxa)) incl. DOES NOT REQUIRE BLOOD (coagulation) MONITORING, faster onset, fewer DDIs, UNAFFECTED BY FOOD, fixed dosing,
24 year old female patient presents to you today. She has a history of being fatigued and today she's looking rather pale. You reference her latest CBC and see the following lab results: WBC: 8,000 cells/mcl (4-10K/µL) Hemoglobin: 8g/dL (13.2-17.1) How would you classify her anemia? (WHAT ARE Hb LEVELS FOR EACH TYPE OF ANEMIA IN MALES AND FEMALES?) A. Mild anemia B. Moderate anemia C. severe anemia D. None of the above
B. Moderate anemia (Up to 25-50% Hemoglobin drop) - Maximum approx. Hb drop: Males: 7-9g/dL; Females: 6-8g/dL - Normal Hemoglobin: Males: 13.5-17.5g/dL; Females: 12-16g/dL - Mild anemia (Up to 25% Hemoglobin drop); Maximum approx. drop: Males: 10-13g/dL; Females: 9-12g/dL - Severe anemia (Hemoglobin drops by more than 50%): Males: < 7g/dL; Females: < 6g/dL: CHF symptoms & signs invariably occur
Neurokeratin is found in which of the following? a) unmyelinated nerves only b) myelinated nerves only c) both unmyelinated and myelinated nerves d) enteric plexuses e) synapses
B. these are proteins found in the myelin. Enteric Plexuses no - in abdominal viscera, autonomic NS usually un-myelinated. Synapses - axon terminals are un-myelinated.
"STARRY SKY" PATTERN in Histopathology is indicative of what?
BURKITT LYMPHOMA (type of non-hodgkin lymphoma) • Sky = sea of lymphocytes that's taking over (higher turnover rate than macrophages) • Stars (clearer areas) = macrophages trying to get rid of all the lymphocytes.
Difference between bacterial and viral wbc total and diff patterns (medicine review)
Bacterial Infection = Inc. WBC count + Inc Neutrophil Count Pattern (shift left). Viral Infection = Inc. WBC count + Dec. Neutrophils + Inc. Lymphocyte Pattern (shift WBC right).
Perineurial Sheath
Blood Nerve Barrier (BBB)
6. Which step in the contractile cycle is most affected by increasing the load on the muscle. a. ATP hydrolysis b. dissociation of the actomyosin complex c. power stroke d. release of inorganic phosphate
C. fix - why? Power Stroke - step of contractile cycle most affected by increasing the load on the muscle. Power = Work done / unit time = force x velocity Vmax is at zero load.
8) All of the following are characteristics of UNmyelinated nerve fibers EXCEPT: a) Schwann cell investment b) external lamina c) 1:1 relationship between axonal region and Schwann cell d) narrow diameter e) slower conduction rates compared to myelinated fibers
C. Don't need 1:1 relationship btwn axonal region and schwann cell. Unmeylinated Nerves - yes have schwann cell investment; yes have external lamina; yes have narrow diameter; YES SLOWER CONDUCTION RATES than myelinated.
INCREASED MASS OF RED BLOOD CELLS (ERYTHROCYTES) IS SEEN IN WHAT HEMATOLOGIC DISORDER? A. APLASTIC ANEMIA B. AGRANULOCYTOSIS C. POLYCYTHEMIA VERA D. MULTIPLE MYELOMA
C. POLYCYTHEMIA VERA= Inc mass RBCs, Hematologic disorder = Affects older adults (~60 years old) = Non-specific symptoms... Dizziness, Visual disturbances, Sweating, Epigastric pain, Ruddy complexion, 40% generalized pruritus w/o rash, & Erythomelalgia (burning pain in joints). With Treatment and Prognosis = Daily phlebotomy, Long-term therapy, Survival 10-12 years after diagnosis WHY ARE THE OTHER ANSWERS WRONG? Aplastic Anemia = Dec production/increased destruction RBCs. Agranulocytosis = Hematopoietic Precurser cells don't undergo normal maturation and don't make enough blood cells; is hematologic disorder involving neutrophils. Multiple Myeloma = actually not technically a hematologic "disorder" but is a hematologic malignancy (of plasma cells).
1. A muscle is unable to maintain a tetanic contracton indefinitely because. a) it becomes depleted of ATP b) it becomes depleted of Ca++ c) it accumulates metabolic waste products such as lactic acid d) the motor neuron becomes fatigued.
C. Tetanic Contraction = Tetanus = results in inc. lactic acid and fatigue (remember fatigued muscle is NOT out of ATP; without ATP is "Rigor"), so that's why you can't maintain it forever.
What laboratory tests do you use for an anemic (anemia) patient?
CBC, RETICULOCYTE COUNT & BLOOD SMEAR.
Acquired nutritional anemia is due to?
CHRONIC USE OF: Aspirin, NSAIDs, Corticosteroids causing Chronic GI Bleeding.
Neuron Bodies are Clustered in where - CNS vs PNS?
CNS - in nuclei. PNS - in ganglia: Sensory in "Dorsal Root Ganglia" Visceral motor (goes to ANS) in "Autonomic Ganglia"
Vasoconstriction (vascular spasm) involves what two processes?
CONSTRICTION to decrease blood loss and RETRACTION of damaged area into surrounding tissue to protect from exposure to foreign materials, due to contraction of vascular smooth muscle as the immediate reflex response to loss pressure at injury site. = Influenced by neural and humoral factors:
What helps you (dentist) to identify cases of ANEMIA? What are the laboratory tests that assist in diagnosis? Once you figure out it is anemia, what steps do you do (clinical)? What are dental aspects to consider with anemia, esp with anesthetics & analgesics - know what you can vs can't give them? know this - red. medicine.
Careful HISTORY TAKING & SCREENING helps identify cases of anemia. Laboratory testing using CBC, RETICULOCYTE COUNT, & BLOOD SMEAR assists in diagnosis. [IMP -RETICULOCYTE COUNT (RC) IS A SEPARATE TEST, ITS NOT ROUTINE COMPONENT OF CBC ANALYSIS] FIRST determine the cause, NEXT TREAT THE CAUSE, & then plan for dentistry. DENTAL ASPECTS OF ANEMIA (medicine): - can give them Nitris: {Hypoxia, infection or acidosis promotes "crisis" in congenital types of anemias -> use O2 + N2O (stress management)} - Some anemias don't give 4%. - Avoid Benzodiazepines (they depress the respiratory center) & Acidic Drugs (aspirin/NSAIDS) that promote hemolysis/bleeding in patients with Congenital Anemia. - Check with MD if the Sickle Cell or splenectomy patient needs premedication ANEMIA & ANESTHETICS - WHAT DO YOU USE? KNOW THIS. 1) Mild anemia: Use Xylocaine with Epinephrine, maximum 2 carpules 2) Moderate anemia: Use Marcaine with 1:200,000 epinephrine for major procedures or Carbocaine for routine minor procedures 3) Severe cases: Defer treatment till the patient has stabilized * Use Carbocaine ONLY with G6PD anemia ** AVOID CITANEST & ARTICAINE with all anemias ESPECIALLY if the anemia is moderate-severe anemia because of the risk of methemoglobinemia
Connexons
Channels in SMOOTH muscle cells. Allow depolarization of one cell to spread to the next cell.
In order to localize active sites on myosin, the protein was treated with the enzymes __________ to produce WHAT fragments that could be purified and studied separately? What is the "hinge "region? Functions of the fragments produced?
Chymotrypsin (digestive enzyme from pancreas, breaks preferentially tail down) and Papain (enzyme from meat tenderizer)... these both do proteolysis (protein-lysis/splitting). (1) Myosin via Chymotrypsin => HMM (HEAVY MEROMYOSIN) + LMM (no atpase activity, LIGHT MEROMYOSIN). - Site cleaved by chymotrypsin is called "HINGE" region where tail has flexibility bc is a point where there isn't double helix (double helix normally stiff). (2a) HMM portion via Papain enzyme => S1 subfragment 1 {myosin HEAD, binds to actin filaments, is an ATPase, has two domains = MOTOR/CATALYTIC DOMAIN where ATP and actin bind, and NECK/LEVER ARM DOMAIN that's alpha helix where two light chains bind} & S2 subfragment 2 {short segments of the TAIL}. ...think.... 1before2 & HbeforeT.... (2b) LMM is the tail region and can self-assemble into rods (doesn't have ATPase activity).
Domain imp. for the power stroke?
Coverter Doman = ELASTIC element in myosin HEAD, at jxn of the motor neck domains of S1 and a 70-residue segment of aa's. Current evidence suggests Strain develops in coverter region is due to distortion of elastic element when neck domain tilts relative to motor domain. Relief of this strain drives sliding of actin filaments past the myosin filament.
4) What does heparin inhibit? A. The conversion of prothrombin to thrombin. B. The conversion of fibrin to fibrinogen. C. The conversion of factor X to factor Xa D. A and C
D (A and C). Heparin is enhancer of anti-thrombin 3. Anti-thrombin 3 blocks/inhibits three coagulation factors: 9, 10, 2. - F2: prothrombin to thrombin - F10 to active F10 (X to Xa).
All the following are causes of thrombocytopenia EXCEPT? A.Idiopathic thrombocytopenic purpura B.Disseminated Intravascular coagulation C. Heparin D.High altitude
D. Causes of Thrombocytopenia: 4a) DEC. PRODUCTION: - marrow infiltration w tumor, lymphoma, leukemia; - infection (HIV, viral hepatitis, mumps, rubella, parvovirus); - nutritional deficiencies (folate, B12 - deficiency of iron, B12, folate; drugs (chemotherapy, radiation, alcohol). 4b) INC. DESTRUCTION: - Idiopathic Thrombocytopenic purpura (ITP): antibody against platelet membrane antigens (auto-immune disease, most common one we see). - Thrombotic thrombocytopenic purpura (TTP): caused by protein deficiency/acquired disorder, adams 13 role, life-threatening condition. - Disseminated intravascular Coagulation (DIC): shearing of platelet by fibrin plugs (often patients who r septic). - Vascular problems/trauma. - Drugs: Heparin, Antibiotics, H2 blockers, Quinine. - Alloimmunization (post-transfusion). 4c) SEQUESTRATION of platelets = HYPERSPLENISM seen in patients w Liver Cirrhosis or Chronic Hemolysis /Hemolytic Anemias (platelets being trapped in large spleen)
DDAVP can be used to treat which type of von Willebrand's disease? A. Type I only B. Type 2A only C. Type 2B D. Type 1 and 2A
D. Treatments for VWD's: 3a) DDAVP (DESMOPRESSIN) = releases VwF from storage = type 1 or 2A only = IV, SC, or Nasal Spray. 3b) Factor replacement strategy: HUMATE-P = concentrate of VWF + = calculate amt of factor needed to replete to 50-100% activity (weight based on RCoF units) = IV only, dose every 8-12 hours (half-life). 3c) Clot Stabilization Strategy: EPSILON AMINOCAPROIC ACID (AMICAR)= prevents clot lysis = Oral or IV formulations.
6) What is NOT true about Rivaroxaban (Xeralto): A. First oral anticoagulant B. selective inhibitor of factor Xa C. Prophylaxis of DVT in patients undergoing knee or hip replacement surgery D. Antifungals decrease the anticoagulant effect of Xeralto
D. Antifungals INCREASE Xeralto is metabolized to INACTIVE METABOLITES by CYP3A4. - INDUCERS of CYP3A4 will DEC. the effect of Xeralto. - INHIBITORS will INC. the effect "" = ANTIFUNGALS.
6) Which of the following pairs is IMPROPERLY matched? a) ganglion cells - satellite cells b) reticular fibers - endoneurium c) perineurium - blood-nerve barrier d) axon - rough endoplasmic reticulum e) nerve fibers - Schwann cells
D. Rough ER is contained within cell body (not axon). Nissl body found in cell body. A. Ganglion cells = cell body, satelite cells. B. Reticular Fibers - endoneurium: yes component of connective tissue (endoneurium). C. Perineurium - blood-nerve barrier: produces separation between blood and nervous system (axons/schwann cells are invested by perineurium -> forming the BNB). E. Nerve fibers - schwann cells; yes, always with schwann cells.
What is neutropenia? Equation for ANC (what does that stand for)? Differentiate between mild, moderate, severe neutropenia (ANC value - know!)?
DECREASE IN ABSOLUTE NEUTROPHIL COUNT (ANC). MILD NEUTROPENIA: ANC 1,000 -1,500 neutrophils. MODERATE: ANC: 500-1,000 (note 0.9k = 900). SEVERE: ANC: 0-500 ANC = WBC x (% neutrophils + % bands). - ANC predicts risk for serious (fatal infection) - if ANC drops as low as 500 (ANC<500), must be AWARE of this in clinic bc it dramatically inc. of infection and these patients will need ANTIMICROBIAL PROPHYLAXIS (or else become bactoremic / bacteria in blood; and septic, which is life-threatening). - Chemotherapy most common cause of decreased ANC & these patients will prob need antimicrobial prophylaxis.
Direct Thrombin Inhibitors
Dabigatran (Pradaxa). - ORAL ANTICOAGULANT (CAME OUT WITH ONE DOSE ). - BIND TO THE ACTIVE SITES ON THE THROMBIN MOLECULE aka Factor2a {which does activation of clotting factors & cleaving fibrinogen/F1 to fibrin/F1a} - Prodrug is rapidly hydrolyzed by ESTERASES, (DABIGATRAN IS NOT A SUBSTRATE, INHIBITOR, OR INDUCER OF CYPS ) = Pradaxa is NOT a substrate of CYP enzymes. - indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Has also shown benefit for prevention of venous thromboembolism after orthopedic surgery and in the treatment of acute venous thromboembolism. - Clinical advantages: DOES NOT REQUIRE BLOOD MONITORING, faster onset, fewer DDIs, UNAFFECTED BY FOOD - Reversal agent (Praxbind) recently approved, October, 2015 - human monoclonal antibody that binds to dabigatran - FDA is currently reviewing the safety of Pradaxa [topic - AntiThrombotics Therapy]
When would you perform a mixing study (what does it tell you)? What is a similar assay you could do?
Do it AFTER find out that APTT prolonged (intrinsic path) which can indicate either: Deficient factors. 8, 9, 11, or 12 if non-bleeding patient), or an Inhibitor of that pathway. Thus, doing it bc need to repeat assay of PTT to figure out which caused the inc. APTT. Results of mixing with PTT still prolonged (w mix study) = INHIBITOR of INTRINSIC (APTT) PATHWAY coagulation. ~vs~ if PTT normalizes, patient has factor deficiency of intrinsic (APTT) pathway (e.g. hemophilia). "Fresh Frozen Plasma" = similar to it.
Thrombosis (secondary hemostasis)
EXCESSIVE FACTOR (proteins of coagulation cascade) activity -> pathologic clotting (e.g. DVT). Treated with ANTI-COAGULATION.
Describe the steps involved in the extrinsic method of blood clotting & intrinsic pathway - TWO INITIATORS FOR EXTRINSIC PATHWAY?
EXTRINSIC Pathway: when liquid extract of any tissue is added to plasma, there is rapid clotting. 1) TISSUE THROMBOPLASTIN (factor III) and TISSUE PHOSPHOLIPIDS {=two initiators of clotting} released by damaged cells. 2) FACTOR X ACTIVATION - bc tissue thromboplastin along with calcium (factor IV) form complex with factor VII - this complex in presence of tissue phospholipids activates factor X. 3) Activated Factor X forms complex with tissue or platelet phospholipids also with Factor V to form complex =PROTHROMBIN ACTIVATOR. INTRINSIC pathway: less common, usu occurs with atherosclerosis. (Begins with trauma to blood itself, usu. When it comes in contact w damaged vessels.) 1) Blood trauma causes activation of factor XIII and release of platelet phospholipids (containing platelet factor 3) 2) Activated factor XII (XIIa) enzymatically activates factor XI (XIa), which needs kinsinogen (cofactor) and is accelerated by prekallikrein. 3) Factor XIa enzymatically activates factor IX to IXa. 4) Factor IXa plus Factor VIIIa plus platelet phospholipids and factor 3 activates Factor X to Xa. 5) Factor Xa plus Factor V plus platelet or tissue phospholipid form the complex called PROTHROMBIN ACTIVATOR (this step is the same in both intrinsic and extrinsic pathways!!). 6) the Prothrombin activator in turn initiates within seconds the cleavage of PROTHROMBIN to form THROMBIN.
Patient presents with "mild bleeding diaphysis", DELAYED pattern of bleeding, and is an Ashkenazi jew... what factor do you suspect is deficient?
Factor 11 deficiency - delayed pattern of bleeding.
If assay shows "Normal Factor 8" but "Low for all other factors", what can you conclude?
Factor 8 NOT made in liver. all others are. => IF ASSAY SHOWS "NORMAL FACTOR 8 LEVELS" & ALL OTHERS LOW -> CAN CONCLUDE: "A PROBLEM OF MULTIPLE COAGULATION FACTORS THAT IS LOCALIZED TO THE LIVER."
Formation of a platelet plug (primary hemostasis, 2) - KNOW THE STUFF INVOLVED IN EACH STEP FOR EXAM! ESP WHERE FIBRINOGEN IS INVOLVED.
Form a platelet plug because vessel injury so need to fix blood flow until more permanent repair can be made. (1) ADHESION: - Positive charged COLLAGEN fibers (in BM of endothelium and underlying CT) exposed at break spot in vessel wall. - GbIb/Ix/V (GLYCOPROTEIN complex) on platelet surface. - VON Willebrand FACTOR (vWF) protein is secreted by both endothelial cells and platelets -> binds to Ib subunit of complex, and also exposed to collagen fibers. => platelets "linked" to injury site. (2) PLATELET ACTIVATION AND AGGGREGATION: - "adherent platelets" swell and extend processes w neighbors. - they release THROMBOXANE A2 & SEROTONIN (vasoconstrictors, dec. blood flow) & ADP (causes addnl platelets to attach to site). - GpIIb/IIIa COMPLEX on platelets surfaces Reacts with FIBRINOGEN => to form platelet plug over injury site. - platelets secrete other substances incl: growth factors, platelet factors (PF3) needed for plasma coagulation, calcium, kinins, etc. (these are stored in granules).
Patient has inhibitor of coagulation pathway, can you operate on them?
From history, figure out if the inhibitor is one that promotes bleed (history says "bleed), or clot ("history says no bleed"). Only operate on patient who is NOT bleeding / does NOT have a bleeding disorder. note: figure out inhibitor of intrinsic pathway from a mixing study showing PTT still prolonged.
Pathology when your body absorbs too much iron from your diet?
Hemochromatosis (don't need to know that much detail) hereditary - most common genetic disease in Caucasians. occurs more in men and post menopausal women (more serious in men). - Initial Signs & Symptoms are often from organ damage & include: • Fatigue • Weakness • Joint pain • Diabetes • Loss of libido • Impotence • Heart failure - Why does the body absorb more iron than it needs? Hepcidin hormone action disrupted - this is secreted by liver, which controls iron absorption by the gut, iron utilization & iron storage in various organs => Excess iron is stored in the tissues of major organs, especially the liver This excess iron is toxic to the body - With time excess iron damages many organs leading to organ failure & chronic diseases -> Cirrhosis, DM, Heart failure, Kidney disease & increased Skin pigmentation often occurs - Diagnosis is made by 2 key Tests that detect Iron overload: 1) Serum Transferrin Saturation Test: Test measures the amount of iron bound to Transferrin that carries iron in the blood: = Transferrin sat, > 45% is too high 2) Serum Ferritin Test: Test measures amount of iron stored in the liver. Ferritin level is checked when serum Transferrin saturation test are higher than normal - Management: 1) Phlebotomy is the primary Rx of choice for all non anemic and non cardiac failure patients (these get chelation Rx) 2) Chelation with Deferoxamine-induced iron depletion is used for all anemic & HF patients 3) Deferoxamine is given PO/IV to expel iron via urine or stool
Force -velocity relationship (muscle mechanics, 6) - type of curve? At what LOAD does Maximim Shortening velocity occur? Vmax decreases with _______, then at zero velocity we reach what? The maximum force a muscle is capable of generating is when the load equals?
Hyperbolic curve of "initial velocity of shortening of a series of isotonic twitches" versus "load on the muscle." Vmax (maximum shortening velocity, y-int) = at zero load. Vmax decreases with increasing load. Maximal isometric load/tension (x-int, Po) = at zero velocity; - At loads greater the the maximum isometric tension, the fiber will lengthen with a velocity that increases with the load (eccentric contractions). All lifts at loads less than Po, the muscle is contracting isotonically which implies that as long as the muscle can lift a load, it hasn't yet reached its maximum attainable tension. Thus the maximum force a muscle is capable of generating is an isometric contraction carried out at Lo (load zero) - work carried out in each contraction = force x distance shortened = zero when load is zero, or when shortening is zero. - power = work done / unit time = force x distance shortened/ time = force X velocity = greatest when product of force x velocity is maximum. - Although at Po there is no work done according to the laws of physics, there is considerable metabolic work in the form of ATP hydrolysis. - In some exercises when activated muscles are forcibly stretched during eccentric phases of the exercise, kinetic and/or gravitational energy can be stored in the elastic components of the muscle for utilization in the energy yield if stretching is immediately followed by a shortening. Such a recoil of tense elastic elements, like a stretched spring, can i) increase the mechanical efficiency and ii) enhance the peak force and power of the contraction so the the mass affected by the muscles can be subjected to a greater acceleration. These effects are noted particularly in "rebound" exercises such as running and jumping.
IMPORTANT! DIFFERENTIATE ANEMIA PATTERNS 1. Hemoglobin levels in: Microcytic Hypochromic Anemia, Macrocytic Normochromic Anemia, Normochromic Normocytic anemia 2. Hematocrit "" 3. MCV "" 4. MCHC "" 5. Causes and associated disease states ""
IMPORTANT! DIFFERENTIATE ANEMIA PATTERNS 1. Hemoglobin levels in: Microcytic Hypochromic Anemia, Macrocytic Normochromic Anemia, Normochromic Normocytic anemia 2. Hematocrit "" 3. MCV "" 4. MCHC "" 5. Causes and associated disease states ""
Red Cell Distribution Width (RDW) INC RDW indicates what and would be seen in what pathology? Low/normal to low RDW seen in what pathology? Normal RDW? ... THUS, RDW IS USEFUL TO DIFFERENTIATE WHAT PATHOLOGIES? know this, medi. red
INC RDW = inc ANISOCYTOSIS aka RBCs of unequal size = means greater number of IMMATURE RBCs in circulation that DO NOT CARRY OXYGEN & are larger in size = IRON DEFICIENCY ANEMIA has high RDW. LOW NORMAL TO LOW in Thalassemia bc same sized RBCs, NO RBC SIZE VARIATION!). Normal RDW = 11.5%-14.5%. Differentiate types of Microcytic Hypochromic Anemia that have Problems with Hb Synthesis (i.e. Iron Deficiency, & Thalassemia).
You figure out patient has a "factor deficiency" involving intrinsic pathway (how?), but need to be careful because which factor is NOT deficient if patient's history/current illness includes "abnormal bleeding /bruising"?
If patient is bleeding, factor 12 is NOT deficient (deficiency in F12 results in patient NOT bleeding). Factor Deficiency of intrinsic pathway = APTT prolonged & THEN, blood mix APTT normalizes (know its not inhibitor).
Polycythemia Vera - inc or dec number of what cells and what does this result in? Can present as what? Is what type of disorder and characterized as what? How do you diagnose it? What are the levels of Red Cell Mass, MCV, and MCH? What is the WBC count? Platelet count?
Increased number of RBCs resulting in compensatory SUPPRESSION of ERYTHROPOIETIN/EPO levels. Present as Primary Polycythemia Vera or Secondary (SPV) - secondary occurs from an APPROPRIATE (CHRONIC HYPOXIA, EPO INCREASED) or INAPPROPRIATE (tumors, brain secrete EPO so EPO INCREASED) increase in Red Cell Mass. NEOPLASTIC bone marrow disorder w. INC. production of Hematopoietic cells. Diagnosis: either ALL 3 MAJOR CRITERIA, OR FIRST 2 MAJOR PLUS MINOR. 1) FIRST MAJOR CRITERIA: Hb >16.5 men, >16 women, or Hct >49% men, 48% women, or Red Cell Mass >25% above mean normal: 7-12million/>15 million - know this. 2) SECOND MAJOR CRITERIA: BM biopsy showing HYPER CELLULARITY of all 3 cell lines esp. RBC mass. 3) 3RD MAJOR CRITERIA: presence of JAK2 gene MUTATION. 4) Minor Criteria: ERYTHROPOIETIN/EPO = LOW.
How does diabetes affect ANC count? Know - how many people in the WORLD suffer from diabetes? (medicine review)
Leading cause of reduced immunity in patients. 1 in 3 people in the WORLD suffer from diabetes.
Patients with Siogren syndrome are susceptible for getting? know this
MALT lymphoma (special type of non-hodgkin lymphoma).
(1) Mean Corpuscular Hemoglobin (MCH) - measures what? high MCH indicates what? Normal MCH? (2) Mean Corpuscular Hemoglobin Concentration (MCHC) - measures what? high amounts indicate what? low amounts what? normal levels? know this, medi red.
MCH - measures the AVERAGE AMOUNT OF HEMOGLOBIN in each mature RBC. - MICROcytic ANEMIA = low MCH. - MACROCYTIC ANEMIA = "RELATIVELY" INC. MCH bc an increase in red cell size. - NORMAL MCH = 26-34. MCHC - measures HB concentration in a given volume of packed RBC (is normal). - "HYPOCHROMIC" MICROCYTIC ANEMIA = DEC. MCHC. - "NORMOCHROMIC" MACROCYTIC ANEMIA = MCHC NORMAL. - NORMAL MCHC = 31-37.
Do a mixing study and results show APTT still prolonged - what does this tell you? ....Also, why would you be doing this mixing study in the first place? KNOW THIS
MIXING STUDY = mix one part patient plasma w one part normal plasma and repeat PTT. Mixture incubated at 37deg.C for at least 1 hour (imp bc inhibition is time and temp. dependent). - Doing this because need to repeat assay of PTT since results showed PROLONGED APTTT which can indicate EITHER factor deficiency (intrinsic pathway) or inhibitor. If PTT still prolonged (w mix study), patient has INHIBITOR of INTRINSIC (APTT) PATHWAY coagulation. ~vs~ if PTT normalizes, patient has factor deficiency of intrinsic (APTT) pathway (e.g. hemophilia). Some inhibitors make you bleed and some make you clot -> if history says "no bleed" you know its inhibitor that promotes clotting. You can OPERATE on patient if don't bleed / if don't have bleeding disorder.
Muscle Tissue Components versus Non-Muscle Contractile Tissue
MUSCLE TISSUE = Muscle Cells (myocytes, myofibers); Stem Cells (satellite cells); Nerve supply - Somatic motor for voluntary muscle, visceral motor for involuntary muscle, sensory. Excitable Plasma Membranes (capable of action potentials) Connective Tissue. Blood Vessels, Lymphatics. NON-MUSCLE CONTRACTILE TISSUES = Myoepithelial cells (glandular tissues), Myofibroblasts (wound healing).
What is the normal RBC count for male patients and for female patients? know this - red, medicine.
Males: 4.5 - 5.9 million/uL. Females: 4 - 5.2 million/uL.
What happens with the sliding filaments during muscle contraction?
Muscle contraction = sarcomere shortens (Z-discs move together); neither thin (actin) nor thick (myosin) filaments shorten; A band width does NOT change; I band and H band narrows.
These are "residual protein elements in myelin sheath following lipid extraction"
Neurokeratin
Test to check for F7 levels?
PT = Prothrombin Time (not aPTT).= Extrinsic Coagulation.
Neutropenia - what are prescriptions for acute dental problems? Other dental related things to do?
Palliative Rx (prescription) for acute dental problems: 1) I&D abscess 2) Pain medications 3) Antibiotics: Cidal drugs given IV/IM - Handle patient with FREQ. HAND WASHINGS and strict infection control - Use a NON ALCOHOLIC MOUTH RINSE prior to attending to the oral cavity. - Provide PREMEDICATION with SYSTEMIC BACTERICIDAL (IV/IM), 30 minutes prior to the handling of the oral tissues - Use systemic antibiotics for FIVE OR SEVEN OR TEN DAYS following PALLIATIVE dentistry - Duration for which antibiotics are given will depend on extent of under lying infection - Give SYSTEMIC PAIN MEDICATIONS & provide NUTRITIONAL SUPPORT for adequate T cell function.
PLUMMER-VINSON SYNDROME - IS KNOWN AS? ASSOCIATED WITH (IS A ____ CONDITION)? CLINICAL SYMPTOMS? Affects what population? Treatment?
Paterson-Kelly Syndrome. Type of Iron-deficiency anemia with Hyperchromic (pale colored cells) micrositic (smaller cells than normal anemia) cells. - PREMALIGNANT condition - Associated with both ORAL and ESOPHAGEAL squamous cell CARCINOMA (head and neck exam imp dentist). - 5 Symptoms 1. BURNING sensation of ORAL mucosa, tongue 2. Angular cheilitis 3. BALD TONGUE (smooth, loss of papillae). 4. Esophageal WEBBING 5. SPOON-shaped and BRITTLE NAILS. - Affects women between ages of 30-50, of Scandinavian or Northern European descent - Treatment either: Dietary iron, or Evaluate for cancer (bc 5-50% chance for malignancy.
Innervation of smooth muscle?
Peripheral endings of autonomic nerves contain varicosities or swellings along the ends of axons that release neuro-transmitters such as acetyl choline or norepinephrine.
You have a patient on Plavix. Should you tell them to stop taking it for surgery?
Plavix should NOT be stopped for any surgery. However, if a patient were on both aspirin and Plavix, the MD could stop Plavix and keep aspirin going just so both drugs won't be stopped. Key point: If either Aspiring or Plavix is approved for stoppage (before surgery), then either drug needs 7 days to clear after the last dose.
If you have a prolonged PT time AND APTT, what can you conclude?
Problem with Intrinsic Pathway (factor 7, PT assay) AND Extrinsic Pathway (8, 9, 11, & 12 only deficient if patient is NOT bleeding). Conclude 2 possibilities: - Deficiency in "Common Pathway" (10). - Deficiency in "Multiple Factors in both pathways" = 7, and 11 or 9 or 8 or possibly 12 (see above).
How do we limit the platelet response to the site of injury (rel. to platelet plug formation)?
Prostacyclin and Nitric Oxide (NO) = potent inhibitors of platelet adhesion, activation, and aggregation - secreted by undamaged endothelial cells adjacent to the injury site.
Reticulocyte count measures what? What is the normal reticulocyte count? What does a high RC indicate? and a low RC? know this medicine
RATE at which reticulocytes (immature RBCs that mature in 48 hours once in the blood from BM) are made AND THEN RELEASED into the blood. - It establishes the erythropoietic activity and associated Bone Marrow function/response of BM to anemia. - Normal Reticulocyte count = KNOW THIS = 0.5% to 2.5% IN ADULTS. - HIGH RC = more NUCLEATED IMMATURE RBCs ABOUND in the circulation => POOR OXYGEN CARRYING CAPACITY, ACTIVE BONE MARROW (not depressed, imp for cancer patients) = premature release of immature RBCs into circulation. - LOW RC = ANEMIA => DEC. RBC PRODUCTION by the bone marrow bc of either: Bone Marrow Failure, Chronic Renal Failure (CRF) associated w dec. Erythropoietin production, or Anemia of CHRONIC DISEASE or CHRONIC INFLAMMATION associated anemia.
In resting muscle, cytoplasmic [Ca++] is _____. When muscle is stimulated, cytoplasmic [Ca++] ______.
Resting = less than 10^-6. Stimulated = Rises
Selective Factor Xa Inhibitors
Rivaroxaban (Xarelto®), Apixaban (Eliquis) - FIRST ORAL, ONCE-DAILY, SELECTIVE INHIBITOR OF FACTOR XA. - Prophylaxis of DVT in patients undergoing knee or hip replacement surgery. - Atrial fibrillation to reduce the risk of stroke and systemic embolism. - ANTIDOTE IN DEVELOPMENT: recombinant genetic technology used to produce mutated factor Xa molecule with no procoagulant activity but the ability to bind factor Xa inhibitors and neutralize their anticoagulant activity. - DDI: XARELTO IS A SUBSTRATE FOR CYP3A4 = avoid 3A4 inhibitors (LIKE ANTIFUNGALS), especially in renally compromised patients, as anticoagulation effect will increase. [topic - AntiThrombotics Therapy]
SKELETAL MUSCLE excitation-contraction coupling is regulated how? How does this compare to CARDIAC MUSCLE excitation-conTraction coupling? What happens in SMOOTH MUSCLE?
SKELETAL = Two T-tubules / sarcomere; continuous, enlarged SER cisterna; propagate depolarization into cell; stimulate calcium release from SR. CARDIAC = one T-tubule/sarcomere; discontinuous, anastomosing cisterna; T-tubules situated at Z-bands; SER does not encircle myofibrils. LESS EFFICIENT than skeeltal muscle, BUT COMPENSATED BC cell-AUTONOMOUS contractility and a functional SYNCYTIUM (GAP JUNCTIONS). SMOOTH = CAVEOLAE replace T tubule system; gap junctions propagate signals; note proximity to SER (Sarcoplasmic reticulum)= 3 mechanisms: 1) ELECTRICAL, via gated calcium channels: atypical neuromuscular junction: slow excitation (neurotransmitter released 10-200u from muscle). 2) MECHANICAL: stretching stimulates mechano-sensitive ion channels ("myogenic" response) e.g. stretch vascular smooth muscle -> opens calcium channels in membrane causing muscle to contract. 3) HORMONAL: e.g. ocytocin stimulates uterine smooth muscle contractions. 4) FLUCTUATIONS IN THE LOCAL CHEMICAL COMPOSITION - chemical compounds such as acid (lactic), oxygen, carbon dioxide, various ion, adenosine can increase calcium influx into vascular smooth muscle cells causing them to contract. 5) SLOW WAVES (Gastric Motility)- rhythmic fluctuations in the membrane charge that occur in the smooth muscle lining of the the gastro intestinal tract. They are initiated by pacemakers within the gut lining and propagate through the stomach and small intestine. If slow waves reach a given threshold voltage, they can cause the opening of calcium channels in the smooth muscle cells and the activation of contraction. Slow waves are key regulators of gastric motility.
Sacromeres in series vs. Parallel? Fusiform vs Pennate Skeletal Muscles? What about muscles in lower extremities?
Sarcomeres arranged in series, the higher velocity of shortening; the more arranged in parallel, the greater force production. FUSIFORM muscle = long fibers parallel to long axis of muscle, allows maximal velocity; max force is proportional to cross-sectional area. PENNATE muscle = shorter fibers angled relative to tendon, allows for maximum force development; force developed is cosine function of pennation angle; velocity is LESS THAN FUSIFORM bc fibers r shorter; Total force generated by muscle is GREATER bc large number of fibers can be packed into the pennate muscle (greater than fusiform). Muscles in Lower Extremities - Long fiber lengths & low pennate angles (e.g. in knee flexor and hip extensor / hamstrings) -> higher velocity. - Short fibers and large pennate angles (more fibers) in quadriceps and gastroextremities give increased force development [advantage].
Most common type of hemolytic anemia?
Sickle Cell Anemia (autosomal recessive disease, xray w "Stepladder" trabeculae in posterior region, and "Hair-on-end" appearance on skull) = CONGENITAL anemia.
Motor Units (muscle mechanics, 2) - definition? associated with what type of muscle?
Skeletal Muscle activated in MOTOR UNITS (rather than single myofibers). MOTOR UNIT consists of a somatic motor neuron plus all the muscle fibers it stimulates/innervates [know this]. Groups of motor units often work together to coordinate the contraction of a single muscle; all of the motor units within a single muscle are considered a motor pool. Only a few motor units may be activated in activities that do not require great strength.
Somatic Motor Neurons innervate what type of muscle fibers? Where do they originate and where do they extend?
Skeletal muscle fibers r innervated by SOMATIC MOTOR NEURONS (efferent neurons) that originate in spinal cord and extend their axons into periphery of body to form MYONEURAL or NEUROMUSCULAR junctions w myofibers.
In the model of muscle regulation that we studied, myosin heads are prevented from interacting with actin in the RESTING state by what? How are they able to interact?
TROPOMYOSIN (NOT troponin) bound to actin covering myosin head binding site (where cross-bridges form). Thus, the myosin heads although they are energized, cannot bind to the actin to initiate contraction. Binding of calcium to TnC (troponin component) at low affinity sites [note high affinity sites occupied by magnesium, if calcium binds here prob role in prolonged contraction] results in change in structure to TnC thats transmitted to TnI and TnT (other troponin components). Causes CHANGE in STRUCTURE of entire thin filament & UNCOVERS (tropomyosin moves into grooves btwn two actin chains) binding site for myosin heads, or the "heptameric unit of the thin filament."
Twitches-tetanus (muscle mechanics, 4)
TWITCH = response to single stimulus with transient rise and fall in tension; has latent period immediately following action potential where muscle stiffens but doesn't develop a force yet. Stimuli separated by suitable intervals produce identical force records. SUMMATION & FUSION OF TWITCHES / TETANUS: - twitches add together with increased force/tension rises when there is an increase in the stimulus frequency. They fuse forming tetanus AKA the max. isometric force attainable. - This causes inc. lactic acid and fatigue (reason why muscle can't maintain Tetanic Contraction forever). - Tetanus = Tetanic Contraction = occurs at a stimulus frequency of 150-200 Hz for fast muscle, 80-100Hz for slow. Is maximal force development that requires ATP obtained from both aerobic and anaerobc metabolism (reason why lactic acid accumulates) = a sustained muscle contraction evoked when the motor nerve that innervates a skeletal muscle emits action potentials at a very high rate. KEY POINTS: - More tension when sum twitches together. - Maximum = fuse twitches toegether resulting in sustained contraction called Tetanus. This is a small contraction from high frequency stimulation. Doesn't last forever bc even though you stimulate it, will become fatigued {lactic acid associated w fatigue}. - Remember - fatigued muscle is not out of ATP (without ATP it Is in "rigor).
Careful on exam - Xray with "Hair on End" apperance could either be?
Thalassemia or Sickle Cell Anemia {also stepladder trabeculae in posterior teeth}.
In the contractile cycle, energy is TRANSFERRED where? and energy is EXPENDED during the ____?
The free energy released from the hydrolysis of ATP is in a sense TRANSFERRED to the head (cocking) but is EXPENDED in the power stoke {part of contractile cycle}.
1) UFH (Unfractionated heparin) 2) Warfarin 3) LMWH (Low Molecular Weight Heparin) 4) Arixtra what do each do (in coagulation pathway)? How are each administered? Monitored? Cost?
These are anticoagulants (medicine lecture). 1) inc. effect of Antithrombin 3; inhibits factor Xa. Continuous IV drip. Monitor w PTT 6 hours after rate change. Cost = ++(+) 2) inhibits synthesis of vitamin K dependent factors. Given Oral/Daily. Monitor w PT/INR, 48-72 hour lag after dose change. Cost = + (cheapest). 3) Inhibits factor Xa and IIa. Given SQ 1/2x daily. No monitoring. Cost = ++++ (second most exp). 4) Inhibits factor Xa and IIa also. Given SQ daily. No monitoring. Cost = +++++ (most expensive).
What is Methemoglobinemia? What can you give these patients / what can't you?
This is a clinical condition with >1% level of methemoglobin CAUSING OXYGEN NOT TO BE DELIVERED efficiently to the tissues. - at risk of getting this if you give moderate-severe Anemic patient Citanest and Articane Anesthetics (dental).
Fiber Types (muscle mechanics, 1) - Type one vs. type 2 ? Impact of exercise on muscle types?
Three types of myofibers exist in humans, Type 1 Fibers = SLOW twitch = slow-oxidative fibers, contain lots mitochondria and oxidative enzymes, are surrounded by more capillaries than other fiber types; have higher concentrations myoglobin ["red muscle"] -> large capacity for aerobic metabolism & high resistance to FATIGUE. Compare Type 1/2 - type 1 have slower rate of force development and lower tension. 2b develop higher tension and have higher speed of contraction than Type 1. Type 2 Fibers = fast twitch = two subtyples: 2a & 2b. - Type 2b = fast twitch fibers = fast-glycolytic fibers = smaller number mitochondria, not well vascularized -> less resistant to fatigue. But rich in glycolytic enzymes -> lots aNaerobic capacity. - Type 2a = fast oxidative/glycolytic or intermediate fibers - develop force rapidly and have increased aerobic capacity; respond readily to training. Exercise: - can improve the performance of all muscle types which respond to speciifc training regimens. 1) Endurance training can increase the endurance qualities of Type 1, and increase mitochondrial number and vascularity of both type II fibers (2a esp.) 2) Strength training increase radius of all muscle types and increase synthesis of myofibrillar proteins.
Platelet count BELOW 150,000 means your patient (probably) has what? Versus, platelet counts GREATER than 450,000 means your patient (probably) has what? MUST KNOW
Thrombocytopenia is platelet count BELOW 150,000. (normal is 150,000-450,000). Thrombocytosis is associated with platelet counts greater than 450,000.
What is the result of using NSAIDs with anti-coagulants? (imp dental considerations, know this). on AntiCoagulant medications (KNOW THIS)?
Use of NSAID with anticoagulants (Dabigatran/pradaxa, Warfarin/coumadin, Heparin, Clopidogrel/Plavix & Ticlopidine/Ticlid, Aspirin, Rivaroxaban/Xeralto & Apixaban/Eliquis), increases the RISK OF BLEEDING (gastric erosion and GI bleeding, that may bleed more profusely in the anti-coagulated patient). - If surgery is anticipated, decisions must be made regarding whether or not to reduce or discontinue anticoagulant therapy prior to procedure. - Consider prophylactic antibiotics, but be aware Antibiotics plus Warfarin -> over-coagulation (can inc. bleeding, dec. platelet count) since antibiotics inhibit CYP2C9 (which inactivates warfarin).
Vitamin K Antagonists - name of drug? interaction with coagulation pathway? enzyme related and associations with that enzyme? Why is it involved in so many drug-drug interactions and what affect would such have on the assay measurement? know this.
WARFARIN (COUMADIN®), COMPETITIVE INHIBITOR OF VITAMIN K EPOXIDE REDUCTASE. - Oral anticoagulant ** INTERFERES W VITAMIN K DEPENDENT FACTORS (2, 7, 9, 10 - KNOW THESE!) => PROLONGS PT time (extrinsic F7) bc onset of action is delayed. - Has NO effect on the active clotting factors already present - The intensity of therapy is measured by the International Normalized Ratio INR - WARFARIN IS METABOLIZED TO INACTIVE METABOLITES BY CYP2C9 - get interaction with warfarin due to INHIBITORS AND INDUCERS OF CYP2C9. - DRUG-DRUG INTERACTIONS bc is very PLASMA PROTEIN BOUND (NARROW THERAPEUTIC WINDOW) ** PT/INR will INC. INC. if Warfarin NOT BEING METABOLIZED BC OF E.G. COMPETITIVE INHIBITION OF A CYP450 ENZYME OF LIVER. - STUFF THAT ENHANCES ANTI-COAGULANT EFFECT (OVER-ANTICOAGULATION) = 1) CYP2C9 INHIBITORS = METRONIDAZOLE, MACROLIDE ANTIBIOTICS AND AZOLE ANTIFUNGALS = INHIBIT METABOLIC BREAKDOWN OF WARFARIN (to inactive). 2. TETRACYCLINES (broad spectrum ANTIBIOTICS**) DIMINISH GUT FLORA needed for VITAMIN K SYNTHESIS, AND THIS REDUCTION MAY FURTHER ENHANCE THE ANTICOAGULANT EFFECT OF WARFARIN. [topic - AntiThrombotics Therapy]
Myofibrils are packed with ______, which consist of repeating ________.
[Muscle cells are packed with myofibrils]. Myofibrils are packed with MYOFILAMENTS; myofilaments (thick and thin myofilaments) consist of repeating SARCOMERES (lay between z-lines). know this image.
Tropomyosin - one molecule of this binds to what?
[part of thin filament = 7 (actin): 1(tropomyosin): 1(troponin)] = Long, thin molecule that extends the length of 7 F-actin subunits consisting of two chains of aa's coiled around each other to form a double helix {aka tropomyosin lies alongside and binds to each of seven consecutive actin subunits in each of the F-actin chains; it follows the helical contours of the F-actin helix and binds to identical sites on each subunit}. = Tropomyosin chains can bind to each other end-to-end to form a long, continuous "ribbon" of protein.
The THIN filament is comprised of what three proteins in what molecular ratio?
actin, tropomyosin, and troponin = 7:1:1 respectively (9 total - know this ratio).
All crossbridges on a thick filament are cycling simultaneously ________________ as long as the muscle is active.
all crossbridges on a thick filament are cycling simultaneously at THE AME RATE BUT ASYNCHRONOUSLY (NOT AT SAME TIME) as long as the muscle is active. Crosbridges occur every 14 nm along filament axis and in six directions radially, corresponding to the positions of the surrounding actin filaments. Only one of the two heads of each myosin molecule is active in a given cycle - it is not clear if the inactive head is affected by the active head. One molecule of ATP is hydrolyzed for each cycle of a myosin molecule.
How does the body prevent coagulation in your healthy vessels?
anticoagulants circulate in normal plasma or are expressed on endothelial surface e.g. 1) FIBRIN - absorbs most of the thrombin that is formed, keeping it from spreading. 2) ANTITHROMBIN II - an alpha-globulin that binds excess thrombin. 3) THROMBOMODULIN - reacts w thrombin: resulting complex activates proteins C and S which inhibit the action of factors VIIIa and Va. 4) TFPI (TISSUE FACTOR PATHWAY INHIBITOR) - inhibits activation of factor X via the extrinsic pathway. 5) HEPARIN - a polysaccharide produced by many cell types that interferes w activation of factor X. 6) Prostacyclin and NO - inhibition of platelet activation.
Junctional Foot Proteins
attatch RyR Ryanodine Receptors or calcium release channels of SR to DHP receptors of T-tubules. Thus, activation of DHP receptors by an AP mechanically opens the attached RyR (gated channels) channels.
Thin Filament Structure fix this maybe on dif fc.
coiled-coil actin polymer w every seven actins covered by a tropomyosin molecule anchored by the two-pronged attachment of troponin to actin via TnI and TnT, both of which also bind to TnC [this structure = actin filament in resting muscle]}.
Actin-myosin interaction requires
displacement of TROPOMYOSIN from ACTIN (to REVEAL MYOSIN BINDING SITES); this is dependent on Calcium released from sarcoplasmic reticulum {"skeletal muscle excitation-contraction coupling regulated by... Two T-tubules / sarcomere; continuous, enlarged SER cisterna; propagate depolarization into cell; stimulate calcium release from SR"}.
Leverage (muscle mechanics, 7) - example given? If distance btwn elbow and biceps muscle insertion into forearm is 5cm, and distance btwn elbow and center of mass being lifted is 35 cm, then how much force must the biceps develop to lift a 10kg weight? What are advantages and disadvantages of this arrangement?
e.g. Contraction of the bicpes brachii pulls the bones of the forearm towards the humerus of the upper arm = a type 3 lever = 1 Fulcrum (moving point, e.g. elbow) + 2 levers/force arms {distance btwn elbow and biceps muscle insertion into forearm (e.g. 5cm); and between elbow and center of mass being lifted (e.g 35cm)}. Given numbers above, how much force must the biceps develop to lift the 10kg weight? force x length 1 = weight x length 2. force x 5 cm = 10kg x 35 cm; or force = 10kg x (35cm/5cm) = 70 kg. Thus, one must develop force approximately 7 times the weight being lifted, a mechanical disadvantage. However, as the figure below indicates, we gain advantages from this arrangement that include i) amplification of the range of movement- a 1 cm change in the length of the biceps allows a 7 cm movement of the hand. ii) amplification of the velocity - if the velocity of shortening is Vm, the velocity at the hand is 7 x Vm.
Generation of Action Potential at Myoneural Junction (EC coupling): (1) APs propagate down motor neurons to the expanded axon terminal. (2) Terminal contains many vesicles, EACH VESICLE CONTAINING _________ (3,000-5,000 molecules) of the neurotransmitter, ________________. (3) Arrival of AP at terminal results in calcium-dependent release of Ach into the cleft btwn the neuron and the __________ of the myofiber. (4) The released Ach binds to __________ on the motor end plate which are _______________. (5) ACh induced opening of the channels allows Na" to diffuse into the myofiber, generating an ____________________, which generates an action potential that is conducted bi-directionally to each end of the myofiber.
each vesicle contains QUANTUM of ACETYLCHOLINE, ACh. calcium-dependent Ach release into cleft between neuron and MOTOR END PLATE of myofiber. Released Ach binds to ACH RECEPTORS = LIGAND-GATED ION CHANNELS. Channels opening (bc Ach induces it) and Na" diffuse into myofiber results in END PLATE POTENTIAL.
Action Potentials (skeletal muscle) are what type of signals?
electrical signals. they propagate from neuron to myofiber at the myoneural junctions.
Gap Junctions
electrically link together Smooth Muscle adjacent cells. Are areas where the cell membranes of the two cells share channels that allow Na+ and Ca++ to flow btwn.
Complete Blood Count (CBC) and Differential - what can be measured?
evaluate fidelity of hematopoeisis process 1) White Blood Cells (WBCS) number of dif. types of white cells. 2a) Hematocrit (red cell) 2b) Hemoglobin (red cell) 3) Platelet Count
Hematocrit (Hct) reflects what? Clinically, can be estimated by what? A DROP IN NORMAL AMOUNT REFLECTS WHAT? know this - red, medicine.
expressed as a percentage. It reflects the RED CELL MASS divided by THE TOTAL BODY VOLUME. CLINICALLY, Hct can also be ESTIMATED by multiplying the Hb by 3. Anemia is associated with decreased hematocrit (<- helps establish the extend/severity of anemia). A drop in normal amount reflects BLEED IN PATIENT need to identify it.
Length-tension relationship (muscle mechanics, 5) - how is it determined?
key point - Maximum tension that a muscle can develop occurs when you hold it at its rest length plus/minus a few percent - at that length, you optimize cross bridge of thick-thin filaments - more cross bridges you can form, the greater force you develop. The amount of force a muscle fiber can develop is related to its initial length relative to its optimal length. The optimal length is the rest length of the fiber in which thick and thin filament overlap allows for optimal formation of crossbridges. How is the length-tension relationship is determined = A muscle is suspended between two supports at a fixed length. A force transducer measures the isometric tension developed at various lengths greater or less than Lo, the in situ rest length. At each length, the passive tension is determined then the muscle is stimulated and the total tension determined. The active tension at each length is the total minus the passive. - At lengths shorter that 60% of Lo no tension is developed when the muscle is stimulated. - As the length is increased from this point the isometric tension increases to a maximum at Lo ± 5% then decreases beyond that point to 0 at about 1.75 Lo. - Sarcomere lengths corresponding to Lo ± 5% allows for optimal crossbridge formation. At shorter lengths, thin filaments from opposite ends of the sarcomere begin to overlap in the center interfering with crossbrigdge formation and the thick filament ends abut the Z disks. At longer lengths, the ovelap between thick and thin filaments is pulled apart.
Rigor Mortis
lack of ATP (happens after death) makes it so myosin head cannot dissociate from actin, and muscle becomes stiff. [bc normally, ATP attaches to myosin, resulting in myosin head detaching from actin - first step of contractile cycle]
Troponin composition and functions (what binds to what)? What is its role in the assembly of thin filament?
made up of three protein subunits: C, I, T. 1) TnC = troponin C - has four calcium binding sites. 2) TnI = troponin I - inhibitory subunit, binds to actin. 3) TnT = troponin t - binds to tropomyosin Function in assembly of thin filament: one Troponin (Tn) is also bound per seven actins: TnI (inhibitory) binds actin; TnT binds to Tm; TnC binds calcium. Troponin stabilizes thin filament structure bc has two-pronged attachment: to actin via TnI and to tropomyosin via TnT.
Platelets - normal range/ platelet count? function? turnover? inhibited by what (know reversible vs non - medicine review?
normal 150-450 k/mm3 (KNOW THIS). function part of maintaining homeostasis. replaced every seven days. Inhibited by: 1) Aspirin (irreversible inhibition) = permanent. 2) NonSteroidal Anti-inflammatory Drugs (reversible "") = temporary effect of platelet count. 3) Glycoprotein 2b/3a receptor antagonists.
How do myosin molecules self-assemble into filaments?
placed in low ionic strength solution similar to cytoplasm. - tails align themselves in parallel and bind together to form => thick filament rod. - pairs of heads extend outward from the rod at regular intervals of 14 nanometeres = same spacing as the crossbridges. - myosin molecules are oriented in two directions (bi-polar molecule bc tails come together central area and heads on outside) so that the central part of the filament has no cross bridges {= bare zone}. - note that the crossbridges extend radially (like the spokes of a wheel) out from the rod. They point in six directions corresponding to the six surrounding thin filaments. - Result = in vivo, a single thick filament contains about 300 molecules of myosin.
The contractile properties of platelets are due to?
platelets contain actin and myosin in amounts comparable to skeletal muscle. These proteins play role in shape changes during platelet activation - these changes compress the platelet and may strengthen the platelet plug and play a role in clot retraction (see below). - platelet plug is usu. strong enough to stop blood loss until you need a more permanent seal than the plug {need for this is bc - blood coagulation process causes more alteration to the platelets so they bind tightly together with fibrin and to firmly anchor them to the vessel wall}. - w small injuries, the platelet plug alone can stop the blood loss completely. w/ larger injury, blood coagulation is also needed. - platelet plug formation closes MINUTE RUPTURES in the vessel walls that may occur many times daily - lack of platelets can lead to formation of multiple small hemorrhages under the skin called petechiae.
What is the main clinical setback due to anemia?
poor wound healing from decreased tissue oxygen.
AMICAR Drug
prevents clot breakdown at oral cavity (site of active fibrinolysis) aka controls bleeding during/after surgery, or TX for conditions w excessive bleeding = Von Willebrand Disease, Mild Hemophilia, and F11 deficiency.
Increased bleeding time indicates a problem with?
primary hemostasis - key players include: platelets, vw-antigen, collagen.
Hematopoietic Stem Cell (medicine 1) - resides where? two imp. properties?
resides mostly in bone marrow, esp. pelvis and long bones. Two imp properties = self renewal (regeneration throughout lifetime so we can continue to form blood) & cell differentiation (-> white blood cells, red blood cells, platelets).
Dense Areas vs. Dense Bodies vs Intermediate Filaments
thin filaments of SMOOTH muscle cell are attached either to DENSE AREAS in the plasma membrane or to DENSE BODIES in the cytoplasm . Other dense bodies are linked to each other by INTERMEDIATE FILAMENTS.
Impact of calcium channel blockers on smooth muscle cells?
α1-calcium channel blockers prevent the influx of calcium into smooth muscle cells (so they relax) - used to treat hypertension