Blood and Hemostasis

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  1. Functions of blood
    • Transport O2/CO2
    • transport nutrients, water and waste
    • transports hormones
    • circulates defensive proteins
    • regulate temperature
    • circulate clotting factors
    • maintain pH
  2. blood is made up of
    • Erythrocytes
    • Leukocytes
    • Platelets (thrombocytes)
    • Plasma
  3. Volume of blood and plasma in a dog
    • 80-90 ml/kg of blood
    • 50 ml/kg of plasma
  4. volume of blood and plasma in a cat
    • 55-60ml/kg of blood
    • 44 ml/kg of plasma
  5. pH of arterial and venous blood
    • arterial 7.4
    • venous 7.35
  6. 3 ways that CO2 is transported in blood
    • dissolved (7-10%, in plasma)
    • carbamino compounds (20%, attached to globin)
    • bicarbonate ion (most, HCO3- in plasma)
  7. buffering system
    • stop excess acid or base from causing large changes in pH of body fluids.  
    • can reversibly bind H+ or OH- and tie it up until it can be excreted.  
    • hemoglobin in RBC acts as a blood buffer.  
    • H+ + Hb <--> HHb (reduced hemoglobin)
  8. coupled equations
    • CO2 + H20 <--> H2CO3 <--> H+ + HCO3-
    • Hb-O2 <--> Hb + O2
    • H+ + Hb <--> HHb
  9. HHb
    reduced hemoglobin
  10. Process of gas exchange in blood
    • CO2 comes out of the tissues (concentration gradient), binds with water to form carbonylic acid. 
    • Carbonylic acid disassociates into H+ and HCO3-
    • H+ must be buffered, so it knocks O2 off Hb to form HHb (reduced hemoglobin)
    • O2 flows down its concentration gradient into tissue
    • HHb and HCO3- travel to lungs
    • H+ lets go of HCO3- and is buffered by bicarbonate to form H2CO3, which disassociates to CO2 and H2O
    • CO2 flows down its concentration gradient into the lungs
    • O2 comes out of lungs, binding with Hb to create oxyhemoglobin, which travels in the blood to the tissue
  11. Erythrocyte
    • RBC, gas exchange
    • discoid shape for larger surface area (absorption), minimal diffusion distance, allows greater osmotic swelling
  12. Thrombocyte
    • platelets, clotting factor. 
    • cytoplasmic fragments of megakaryocytes
    • produced in bone marrow
    • granules (alpha and dense) contain many coagulation factors, other proteins, calcium, seratonin, ADP and ATP. 
  13. Neutrophil
    leukocyte, short-term phagocyte (acute response)
  14. Monocyte
    leukocyte associate with chronic illness.  Phagocytosis of larger molecules.  Inflammation mediator, presents antigen to immune system
  15. Basophil
    leukocyte associated with inflammation
  16. Eosinophil
    leukocyte associate with inflammation due to allergy or parasite
  17. Lymphocyte
    leukocyte with two parts.  T cells are the cellular base of immunity.  B cells make antibodies and are in humoral immunity. 
  18. Who has nucleated RBCs?
  19. A hemoglobin molecule has:
    • 1 globin polypeptide chain (where CO2 attaches)
    • 4 heme polypeptide molecules with an ferrous molecule (Fe2+), (2 alpha and 2 beta), where O2 binds at alpha subunit.  H+ bonds in beta subunit. 
    • O2 and CO2 are not competing
  20. methemoglobin (met-Hb)
    • When ferrous iron (Fe2+) oxidizes to ferric iron (Fe3+) and does not bind O2 properly.  Brown blood. 
    • Enzyme in erythrocytes can fix it, but too much can't. 
  21. what was wrong with Betsy?  Bovine, tucked abdomen, frequent urination, diarrhea, colic, dyspnea, tachycardia, brown/chocolate mucous membranes
    • Nitrate poisoning.  Usually death within 1-3 hours.  Treat: methylene blue, but many are stressed and die from hypoxia. 
    • Ate too many nitrates (spoiled feed, some grasses, fertilizer) to cause methemoglobin instead of hemoglobin. 
  22. Carboxyhemoglobin
    Hb combines with CO.  Attaches at same spot as O2 with greater affinity.  To treat, give O2
  23. RBC lifespan
    differs by species
  24. caprine
  25. ovine
  26. porcine
  27. Erythrocyte destruction
    • 10-20% intravascular hemolysis (in vessel)
    • 80-90% extravascular (intracellular) hemolysis (Mononuclear Phagocytic System (MPS))
  28. Mononuclear phagocytic system (MPS)
    • Reticuloendothelial System (RES)
    • macrophages in liver, spleen, bone marrow, lungs and lymph nodes
    • Phagocytose aged RBCs
  29. Breakdown of RBC within MPS (beast)
    • RBC
    • Hemoglobin
    • Globin (amino acids, recycled),  Heme
    • Fe2+ (recycled or stored in plasma), biliverdin (green)
    • Reduced/unconjugated bilirubin
    • Mixes with albumin in plasma, goes into liver
    • bilirubin + glucuronic acid (conjugated, water-soluble).  Goes into bile, gallbladder, intestines
    • Bilirubin glucuronide (out in feces or bacteria breaks down to Bilirubin, reduced to urobilinogen
    • out in feces (urobilin or stercobilin) or back into liver
    • reuptake or bypasses into systemic blood
    • caught by kidneys, Oxidized to urobilin
    • out in urine
  30. Where does most urobiligen go?
    feces as urobilin or stercobilin
  31. bile is absorbed in
    the ileum
  32. Icterus
    • jaundice.  body/tissues/mucous membranes turn yellow due to buildup of bilirubin.  Separated into 3 sections
    • prehepatic
    • hepatic
    • posthepatic
  33. prehepatic
    goes wrong before the liver.  Increased hemolysis (immune-mediated hemolytic anemia, tick-borne ehrlichia, adverse drug reactions, transfusion reaction, hemolytic disease in newborns)
  34. hepatic
    disease of liver causes jaundice.  Impedes ability of hepatocytes to take up bilirubin and conjugate it.  Any liver disease can cause it. 
  35. post-hepatic
    problem occurs beyond liver.  Inflammation of pancreas around bile duct, stone in the bile system, duodenal disease
  36. Spherocytes
    smaller, rounder, darker RBCs caused by marcophages eating part of membrane.  Indication of IMHA
  37. What was wrong with Sandy?  Lethargy, weakness, pale/jaundiced mucous membranes, low RBCs
    • IMHA--autoimmune disease.  Primary (caused directly) or secondary (another problem causes it).  Coombs test, autoagglutinate (clumpy blood).  Spherocytes. 
    • Adult and middle-aged animals.  Secondary in any breed or cats, primary usually in cocker, poodle, etc. 
    • Prehepatic bilirubinemia.  Hemolytic jaundice.  Caused by antibodies attacking own RBCs. 
    • Severe anemia, tachypnea, tachycardia, pale membranes, icteric, symptoms of hypoxia
  38. hemostasis
    • a series of responses that stop bleeding
    • components: proteins, vascular endothelium, platelets
  39. clotting factors
    • proteins.  Circulate in blood as proenzymes (zymogens)  (roman numerals, inactivated enzymes that must be activated to function). 
    • An a is added to the roman numeral if activated. 
    • #s 1-13, not 4 or 6. 
  40. vascular endothelium and anticoagulants
    when squamous endothelium in vessels is damaged, platelets and factor 8 attach to basement membrane (collagen and fibronectin) to form clot.  Only if broken or activated. 
  41. Models of hemostasis
    • Y cascade (older, easier to understand but wrong)
    • Cell-based model (physiological, in vivo model.  Right but more complicated). 
  42. Sequence of events in vascular injury
    • vascular constriction
    • primary hemostasis (unstable platelet plug)
    • secondary hemostasis (stable platelet plug.  Activation of coagulation factors, mesh of fibrin)
    • anticoagulent events (keeps clots localized)
    • fibrinolysis (repair of damage, dissolution of clot)
  43. DIC
    both hyper and hypo coagulation at the same time.  Makes microclots that are ineffective, so still bleeds.
  44. Difference between extrinsic and intrinsic traditional model of hemostasis
    • Extrinsic is started by a damaged tissue, simple process, tissue factor, Calcium to common pathway
    • Intrinsic is started with damaged vessel, MANY STEPS and factors but get to common pathway.  Then same
  45. Common pathway in traditional model of hemostasis
    Factor X to activated X, Factor V, Ca2+, Prothrombinase, Prothrombin to thrombin, thrombin activates XIII and fibrinogen.  Fibrinogen plus Ca2+ to loose fibrin plus activated XIII to strenghtened fibrin (strengthened clot)
  46. Extravascular hemolysis
    breakdown of RBC inside a macrophage. 
  47. Major steps of cell-based hemolysis
    • Initiation (injury, tissue factor exposed, small thrombin)
    • Amplification (thrombin activates platelets, cleaves von Willebrand factor from VIII, platelet aggregation and adhesion)
    • Propagation (Coagulation propagated on activated platelet, LOTS OF THROMBIN) 
  48. Initiation of cell-based model of hemostasis
    injury, cells bearing Tissue Factor exposed, generate small amount of thrombin.
  49. Amplification of cell-based model of hemostasis
    (small amount of) thrombin activates platelet, cleaves  von Willebrand factor from Factor VIII leading to platelet aggregation and adhesion to exposed subendothelial collagen
  50. Propagation of cell-based model of hemostasis
    coagulation propagated on activated platelet surface, LARGE amount of thrombin formed.
  51. Cell-based model steps
    • Vascular injury (collagen exposed, release of molecules from endothelium and nocioceptors)
    • Vascular constriction (to prevent blood loss)
    • initiation
    • Amplification
    • Platelet adhesion and aggregation (swell, get sticky and develop pseudopods)
    • formation of platelet plug (release granules, recruitment of more platelets)
    • propagation
  52. Thrombin formation in clotting
    • Prothrombin (Factor II)
    • plasma protein
    • proenzyme continuously form in liver
    • requires vitamin K for synthesis
    • makes thrombin (factor IIa)
  53. Fibrinogen
    • Plasma protein formed in liver
    • thrombin converts to fibrin, held together by hydrogen bonds
  54. Fibrin formation
    • FVa + FXa = prothrombin complex
    • Prothrombin (II) + prothrombin complex = thrombin (IIa)
    • Fibrinogen + thrombin = Fibrin
    • FXIII + thrombin = FXIIIa
    • Fibrin + FXIIIa = crosslinked fibrin clot
  55. Von willebrand factor
    makes platelets stick together (platelet aggregation) and stick to subendothelial collagen.
  56. Blood clot
    a dense network of fibrin fibers that enmesh platelets, blood cells and plasma
  57. Why doesn't the whole body coagulate? 
    • constant blood flow (active factors float away, need activated platelet and damaged endothelium)
    • removal of activated factors by hepatocytes
    • removal of particulate matter by mononuclear cells
    • Restriction of the clotting process to activated membrane
  58. Clot retraction
    • within minutes of formation, expresses serum, pulls edges of broken blood vessels together
    • Platelet-derived growth factor is released to stimulate smooth muscle and fibroblast to divide and repair
    • Vascular endothelial growth factor causes endothelial cells to multiply and restore BV lining
  59. Clot degredation
    Plasminogen is activated into plasmin (clot-buster), digests fibrin fibers into fibrin degredation products (covalent bonds break to create D dimers)
  60. Anticoagulants
    • Lower Calcium levels: sodium or potassium citrate
    • EDTA
    • Heparin: inactivates FIIa, IXa, Xa and XIa
    • Dicoumarol: Found in mouldy sweet clover and rodenticide.  Inhibits vitamin K clotting factors (II, VII, IX and X)
  61. What was wrong with Butch?  Blood in urine, dark stool, pale gums, weak, cold, epistaxis.  Outside dog on farm. 
    • ate rodenticide or poisoned rat.  Blocks epoxide reductase, vitamin K can't be reused, inhibits clotting factors. 
    • Induce vomiting if just ate
    • Give vitamin K and transfusion if bleeding. 
  62. Vitamin K and coagulation factors
    Vitamin K (quinon).  Vitamin K reductase makes reduce vitK, gamma carboxylase (activates II, VII, IX, X, proteins C, S, Z), Oxidized vitamin K, Epoxide reductase (warfarin inhibits)
  63. Epoxide reductase
    returns oxidized vitamin K to useable vitamin K.  Rodent poison (warfarin) inhibits. 
  64. Thrombus
    abnormal clot that develops in a blood vessel and STAYS at the site of its formation. 
  65. Embolus
    abnormal clot that has broken away from its attachment and flowed away with current.  MOVES.  Can obstuct a blood vessel.  Could be a plug of other material too. 
Card Set:
Blood and Hemostasis
2013-03-05 17:57:59
Physiology t2

Test 2 blood and hemostasis
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