Veins have large radii and low resistance. Walls are thin, not elastic Most blood volume is in veins Veins returning blood Veins Valves prevent engorgement and backflow Sympathetic NS constricts veins to increase venous return Skeletal muscles also help return Baroreceptor reflex Baroreceptors detect fluctuations in blood pressure and send info to medulla Signals go to ANS Baroreceptors 1
Response to low pressure Problems with vessels Aneurysm Hemorrhage Why do aneurysms form? Hypertension, inflammation, arteriosclerosis, genetics How are they treated? Blood pressure problems Hypertension Blood pressure over 140/90 Baroreceptors can adjust to higher BP High BP puts stresses on vessels, elasticity (atherosclerosis, strokes) and stresses on heart (heart attacks), kidneys Blood pressure problems Treatments for hypertension: Low salt diet, reduce stress, increase exercise ACE inhibitors (reduce blood volume) Alpha, beta blockers (reduce sympathetic effects) Calcium blockers (reduce cardiac contractions) 2
Blood pressure problems Circulatory shock blood pressure drops too low to serve tissues. From weak heart, blood loss, dilation from allergic response What are long term effects of continual caffeine consumption? Body compensates w/sympathetic signals, fluid shifts Plasma Components of blood Blood cells: erythrocytes leukocytes (WBC), and platelets Hematocrit is the % of blood occupied by RBC. (RBC) What is plasma? Ions: mostly Na+ and Cl-. Gasses, waste, nutrients, hormones Plasma proteins: Albumins establish an osmotic gradient, carry some hormones Globulins (alpha, beta, gamma) transport molecules, serve as antibodies Fibrinogen - blood clotting 3
RBCs RBCs have no nuclei, ribosomes, or organelles Packed with hemoglobin Doughnut-like shape Hemoglobin Heme - contains iron and binds with one molecule of O 2 Globin - 4 protein chains Turns bright red when combined with oxygen CO 2, CO, H + can also bind RBCs replenished every second Spleen removes old RBCs, RBCs last about 4 months RBCs are produced in bone marrow from pluripotent stem cells (2 M/sec) Kidney controls RBC production Kidney is sensitive to anemia and releases erythropoietin 4
Blood doping Banned in competitive sports: Erythropoietin (EPO) can be synthesized and injected to enhance endurance An athlete s own blood can be stored and reinjected to boost RBC s Hematocrit can detect Causes of anemia? Anemia O 2 to tissues is low Due to RBC, erythropoiesis, or hemoglobin Pernicious anemia lack of B 12 results in low RBC production Aplastic anemia bone marrow production Sickle cell anemia Question: How treat the symptoms? Bone marrow transplant (for acute cases) Hydroxyurea activates production of fetal hemoglobin (Hb F) genes, which increases good RBC production (long term effects unknown) Exp tl: gene therapy, nitric oxide (vasodilator) How the body repairs itself Initial response: vascular spasm - reduces blood flow through the vessel platelet plug - Aggregation of platelets. Platelets attach to areas with exposed collagen These processes are stimulated by ADP 5
Platelets Platelets are cell fragments that are functional for 10 days Reduce blood loss (maintain hemostasis) Platelets and a RBC Positive feedback at injury site Initial stimulus is exposed collagen Repair is contained to site of injury Inhibits platelet aggregation ADP 3 Platelets Inhibits platelet aggregation How the body repairs itself Stopping blood loss: Fibrinogen (plasma protein) is converted into fibrin (thread-like protein). This conversion is catalyzed by thrombin Fibrin threads trap RBCs, forming a clot Prostacyclin and nitric oxide 2 4 Prostacyclin and nitric oxide 5 Vessel wall Normal endothelium 1 Plug Normal endothelium Injury site 6
How the body repairs itself Stopping blood loss: Fibrinogen (plasma protein) is converted into fibrin (thread-like protein). This conversion is catalyzed by thrombin Fibrin threads trap RBCs, forming a clot The clotting cascade...! Clotting cascade is a series of reactions activating enzymes in a series... final conversion is fibrinogen into fibrin Thrombin is formed from inactive prothrombin in plasma Platelet aggregation Vessel damage Exposed collagen PF3 Hageman factor Activation of next thrombin Activation of thrombin Cascade is initiated when a platelet plug is present or from exposed collagen. Clotting cascade Clots are temporary Fibroblasts form scar tissue for vessel repair. The clot is dissolved slowly by the enzyme plasmin (breaks down fibrin). Plasmin is activated by the clotting cascade Phagocytic WBC remove the products of clot breakdown Formation of fibrin meshwork Damaged vessel is sealed 7
Ok, but what is pus? Well, pus comes from infected wounds and consists of phagocytes, dead tissue and bacteria. End of exam 3 material White blood cells There are five kinds of WBCs WBCs defend against pathogens, cancer and clean up debris Introduction to the WBCs Granulocytes Eosinophils - attack parasitic worms Basophils - make and store histamine and heparin Neutrophils - phagocytes, 1 st to respond to infection Monocytes - settle in tissue and become macrophages Lymphocytes - Neutrophil B and T cells of specific immune response Monocyte Eosinophil Lymphocyte Basophil 8
Production of WBCs Produced from pluripotent stem cells in bone marrow Lymphocytes made in lymph tissue during adulthood Two-thirds of the leukocytes in the blood are granulocytes, mainly neutrophils Immune system Body must resist disease in order to function Defends against pathogens, identifies and destroys abnormal cells. The primary pathogens are bacteria and viruses. Nonspecific immunity vs. Adaptive immunity Nonspecific responses work immediately - 1st line of defense. Neutrophils, macrophages, inflammation, MAC attack Adaptive immunity specifically targets certain pathogens to which the body has been exposed B and T lymphocytes, antibodies Nonspecific response: inflammation Redness and warmth Blood flow due to vasodilation Swelling Increased capillary permeability Pain inflamed knee Nociceptors stimulated by fluid pressure 9
Inflammation : the beginning How do phagocytes know what to eat? First response involves cells already in nearby tissue: macrophages and mast cells Macrophages eat bacteria Triggered by infection, mast cells secrete histamine, causing vasodilation Mast cells in tissue Bacteria get labeled for destruction by opsonins Opsonins are made from complement cascade, helper T cells, antibodies Fibrin walls off infection Guided by chemotaxins, neutrophils and monocytes go to the area Bacteria acquire opsonins, getting labeled for macrophage to engulf it Phagocytes also send signals They present antigens to helper T-cells to induce a specific response They wear what they eat histamine plasma proteins (including opsonins and chemotaxins) Phagocytes: stimulate histamine release, trigger clotting cascade, release pyrogen which causes fever, induce more WBC 10
Review What do those plasma proteins do? Some are clotting proteins..clotting cascade! Some are antibodies! (discussed later) Some are part of the complement system! (discussed now ) Nonspecific response : Complement system Complement = cascade of plasma proteins Cascade activated by molecules on surface of bacteria or antibodies Complement proteins are opsonins, chemotaxins or form MAC attack MAC Complement has the potential to be very damaging to host tissues Bacterial wall has holes from membrane attack complex 11
Nonspecific response: What about viral infections? Infected cells release interferon Cause neighboring cells to produce virusfighting enzymes Attracts natural killer cells Nasty virus Host Interferon Adaptive immune response Also fights viral and bacterial infections but uses B and T lymphocytes found in lymph Pathogens have particular antigens, which induce a specific response from B and T cells. B cell response B lymphocytes respond to bacteria and toxins An antigen stimulates some specific B cells to become plasma cells and produce antibodies Contact with antigen can occur via macrophages Only cells with the antigen are attacked. 12
B cell response How antibodies work antigen bacteria binding site for this specific antigen Once labeled, bacteria killed by: MAC attack Phagocytosis Killer cells Labels cell to be killed Result of labeling 13