Blood and Hemostasis

• Transport O2/CO2
• transport nutrients, water and waste
• transports hormones
• circulates defensive proteins
• regulate temperature
• circulate clotting factors
• maintain pH

• Erythrocytes
• Leukocytes
• Platelets (thrombocytes)
• Plasma

• 80-90 ml/kg of blood
• 50 ml/kg of plasma

• 55-60ml/kg of blood
• 44 ml/kg of plasma

• arterial 7.4
• venous 7.35

• dissolved (7-10%, in plasma)
• carbamino compounds (20%, attached to globin)
• bicarbonate ion (most, HCO3- in plasma)

• 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)

• CO2 + H20 <--> H2CO3 <--> H+ + HCO3-
• Hb-O2 <--> Hb + O2
• H+ + Hb <--> HHb

reduced hemoglobin

• 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

• RBC, gas exchange
• discoid shape for larger surface area (absorption), minimal diffusion distance, allows greater osmotic swelling

• 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. 

leukocyte, short-term phagocyte (acute response)

leukocyte associate with chronic illness.  Phagocytosis of larger molecules.  Inflammation mediator, presents antigen to immune system

leukocyte associated with inflammation

leukocyte associate with inflammation due to allergy or parasite

leukocyte with two parts.  T cells are the cellular base of immunity.  B cells make antibodies and are in humoral immunity. 

birds

• 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

• 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. 

• 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. 

Hb combines with CO.  Attaches at same spot as O₂ with greater affinity.  To treat, give O₂

differs by species

goat

sheep

pig

• 10-20% intravascular hemolysis (in vessel)
• 80-90% extravascular (intracellular) hemolysis (Mononuclear Phagocytic System (MPS))

• Reticuloendothelial System (RES)
• macrophages in liver, spleen, bone marrow, lungs and lymph nodes
• Phagocytose aged RBCs

• 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

feces as urobilin or stercobilin

the ileum

• jaundice.  body/tissues/mucous membranes turn yellow due to buildup of bilirubin.  Separated into 3 sections
• prehepatic
• hepatic
• posthepatic

goes wrong before the liver.  Increased hemolysis (immune-mediated hemolytic anemia, tick-borne ehrlichia, adverse drug reactions, transfusion reaction, hemolytic disease in newborns)

disease of liver causes jaundice.  Impedes ability of hepatocytes to take up bilirubin and conjugate it.  Any liver disease can cause it. 

problem occurs beyond liver.  Inflammation of pancreas around bile duct, stone in the bile system, duodenal disease

smaller, rounder, darker RBCs caused by marcophages eating part of membrane.  Indication of IMHA

• 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

• a series of responses that stop bleeding
• components: proteins, vascular endothelium, platelets

• 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. 

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. 

• Y cascade (older, easier to understand but wrong)
• Cell-based model (physiological, in vivo model.  Right but more complicated). 

• 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)

both hyper and hypo coagulation at the same time.  Makes microclots that are ineffective, so still bleeds.

• 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

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)

breakdown of RBC inside a macrophage. 

• 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) 

injury, cells bearing Tissue Factor exposed, generate small amount of thrombin.

(small amount of) thrombin activates platelet, cleaves  von Willebrand factor from Factor VIII leading to platelet aggregation and adhesion to exposed subendothelial collagen

coagulation propagated on activated platelet surface, LARGE amount of thrombin formed.

• 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

• Prothrombin (Factor II)
• plasma protein
• proenzyme continuously form in liver
• requires vitamin K for synthesis
• makes thrombin (factor IIa)

• Plasma protein formed in liver
• thrombin converts to fibrin, held together by hydrogen bonds

• FVa + FXa = prothrombin complex
• Prothrombin (II) + prothrombin complex = thrombin (IIa)
• Fibrinogen + thrombin = Fibrin
• FXIII + thrombin = FXIIIa
• Fibrin + FXIIIa = crosslinked fibrin clot

makes platelets stick together (platelet aggregation) and stick to subendothelial collagen.

a dense network of fibrin fibers that enmesh platelets, blood cells and plasma

• 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

• 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

Plasminogen is activated into plasmin (clot-buster), digests fibrin fibers into fibrin degredation products (covalent bonds break to create D dimers)

• 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)

• 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. 

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)

returns oxidized vitamin K to useable vitamin K.  Rodent poison (warfarin) inhibits. 

abnormal clot that develops in a blood vessel and STAYS at the site of its formation. 

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.