Lecture 12: The Blood PDF

Lecture 12: The Blood ===================== **Please read pages 696--724 for this lecture.** **Learning Objectives:** - Describe the structure and general functions of blood in the body. - Describe the physical characteristics of blood. - Name the components of blood, including the liquid...

Lecture 12: The Blood ===================== **Please read pages 696--724 for this lecture.** **Learning Objectives:** - Describe the structure and general functions of blood in the body. - Describe the physical characteristics of blood. - Name the components of blood, including the liquid extracellular matrix, solutes, and cellular portions of blood. - Trace the steps of erythropoiesis. - Identify white blood cells by their structure and relate structure to function. - Outline the general steps involved in inflammation. - Describe the structure, function, and origin of platelets. - Define hemostasis and coagulation. - Trace the steps of the: - Intrinsic clotting pathway - Extrinsic clotting pathway - The common pathway - Describe how blood clotting is regulated and what could go wrong if blood clotting is **dysregulated**. - Describe the cellular basis for the ABO and Rh blood groups. - Distinguish between compatible and incompatible blood groups. - Describe the cause and pathogenesis (disease progression) of hemolytic disease of the newborn (HDN). - Explain how the structure and/or function of red blood cells is perturbed in anemia, sickle cell disease, and hemophilia. Introduction to blood --------------------- - Recall the three extracellular fluids of the body: 1. Blood 2. Interstitial fluid 3. Lymph - Nutrients move from blood interstitial fluid cells of tissues - What is **blood**? - **Blood: \_\_\_\_\_formed\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_elements\_\_\_\_\_\_\_\_\_\_** or cells in a liquid ECM - ECM of blood = **blood plasma.** - Blood circulates throughout the body as part of the **cardiovascular system** - Includes blood, blood vessels, and the heart - The scientific study of blood and blood-forming tissues is called **hematology** - Bloody fun facts - Blood accounts for \_\_8\_\_\_% of your total body mass! - The average male has 5--6 L of blood; the average female has 4--5 L of blood. - Blood is more \_\_\_\_\_\_\_viscous (thick)\_\_\_\_\_\_ than water and has a sticky feel to it. - The temperature is kept within a close range around 38ºC and within a pH range of 7.35-7.45. - Three main functions of blood: 1. **\_\_\_\_\_\_\_\_\_transportation\_\_\_\_\_\_\_\_\_\_\_** - Of oxygen, nutrients, hormones, heat, and waste products 2. **\_\_\_\_\_\_\_\_\_\_regulation\_\_\_\_\_\_\_\_\_** - Of pH, body temperature, and osmotic pressure. 3. **Protection** - Against blood loss - Against invasion and disease - What is the composition of blood? - Two components to blood: 1. **Blood plasma** (55%) - Liquid ECM containing \_\_\_\_\_dissolved\_\_\_\_ substances 1. **Formed elements** (45%) - Erythrocytes, leukocytes, and \_\_\_\_platelets\_\_\_\_\_\_\_\_\_\_.  - Blood plasma (55%) - Pale yellow liquid - 91.5% water and 8.5% solutes - Mostly **proteins,** including: - **\_\_\_\_\_\_albumin\_\_\_\_\_\_\_\_\_** (54%) - Maintains osmotic pressure - **Globulins** (38%) - Includes antibodies and transport proteins for ions, lipids, and fat-soluble vitamins - **\_\_\_\_\_\_\_\_\_\_\_fibrinogen\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** (7%) - Functions in blood clotting - Other solutes (1.5%) include: - Electrolytes - Nutrients - \_\_\_\_\_\_\_enzymes\_\_\_\_\_\_\_ - \_\_\_\_\_\_\_hormones\_\_\_\_\_\_\_\_\_\_ - Gases - Metabolic wastes Diagram Description automatically generated with medium confidence - Formed elements (45%) - Three main components: 1. Erythrocytes or red blood cells (RBCs) - Most abundant cells - Transport \_\_\_O2\_\_\_ and \_\_CO2\_\_\_\_ - Mature cells have no organelles to make room for **\_\_\_\_\_\_\_\_\_\_hemoglobin\_\_\_\_\_\_\_\_\_\_\_** 1. \_\_\_\_\_\_\_\_leukocytes\_\_\_\_\_\_\_\_\_ or white blood cells (WBCs) - Many different types (more later) - Help fight \_\_\_\_\_\_\_infection\_\_\_\_\_ and invasion 2. Platelets - Anucleate cell \_\_\_\_\_\_\_\_\_\_fragments\_\_\_\_\_\_\_\_\_\_\_\_ - **\_\_\_\_\_\_\_\_\_\_\_\_thrombocytes\_\_\_\_\_\_\_\_** are the nucleated blood cells that form clots in lower vertebrates  **Above left**: SEM of an erythrocyte, leukocyte, and platelets. **Above right**: Peripheral blood smear showing the abundance of erythrocytes and relatively large size and low abundance of leukocytes. - What might we want to know about someone's blood? - Percent volume of blood occupied by erythrocytes or **hematocrit** - Adult average is \~47 - Low hematocrit \< 40 - High hematocrit \> 65 - *Why might low or high hematocrit be harmful?* High hematocrit mean less white blood cells to fight off pathogens and low hematocrit means that you have low count of red blood cells called anemia. Also blood clots that can lead to strokes - Summary: Diagram Description automatically generated with medium confidence Blood cell formation -------------------- - Blood cells must be replenished continuously - **Hemopoeisis** is the process of blood cell formation. - Occurs in red bone marrow - *Do you remember where red bone marrow is located in the body?* In the epiphysis of long bones and most of the axial skeleton - Blood cells start as stem cells - Start as **\_\_\_\_\_\_\_pluripotent\_\_\_\_\_\_\_\_\_ stem cells** (develop in to multiple cell types) - Continue development into two lineages: - **\_\_\_\_\_\_myeloid\_\_\_\_\_\_\_\_** stem cells - **Lymphoid** stem cells - Each lineage produces **\_\_\_\_\_\_\_\_precursors\_\_\_\_\_\_\_\_ cells** - Differentiate into formed elements of blood - Only \_\_\_WBCs\_\_\_\_\_ divide after leaving the bone marrow  - What regulates blood cell formation? - **Hematopoeitic growth factors** are **hormones** that affect blood cell formation - **Include:** - **\_\_\_\_\_\_\_\_\_\_Erythropoeitin\_\_\_\_\_\_\_\_\_\_\_ (EPO)** increases the number of erythrocyte precursor increases \# of erythrocytes in blood - Synthesized in the kidneys - **Thrombopoeitin (TPO)** stimulates platelet formation - Synthesized in the liver - **\_\_\_\_\_\_Cytokines\_\_\_\_\_\_\_\_\_\_\_\_\_** are hormones that stimulate increased proliferation of leukocytes and lymphocytes - Synthesized in and acts in the red bone marrow Erythrocytes or red blood cells (RBCs): structure and function -------------------------------------------------------------- - **\_\_\_\_\_\_\_Biconcave\_\_\_\_\_\_\_\_\_ discs** - Large surface area to volume ratio - Strong and flexible shape to pass through narrow capillaries - \_\_\_\_\_\_\_Anucleate\_\_\_\_\_\_\_\_\_ - At maturity, also lack most organelles - Replaced by **hemoglobin (Hb)** 1/3 of RBC weight - Hb transports oxygen - Have no mitochondria - Mitochondria are broken down in a cellular process known as **autophagy** - Makes more space for more Hb - *What* other *advantage do you think lacking mitochondria has for erythrocytes?* Diagram Description automatically generated - Erythrocytes are abundant! - Per microlitre (μL = 10^-6^ L): - Adult females have \_\_\_4.8\_\_\_\_ million - Adult males have \_\_\_\_5.4\_\_\_ million - Must replace 2 million RBCs *per second* - Erythrocytes transport oxygen and carbon dioxide - Hemoglobin reversibly binds up to **\_\_\_four\_\_\_\_** molecules of oxygen. - \~250 million Hb/erythrocyte - RBCs can also carry up to \_\_\_23\_\_\_% of the body's carbon dioxide - Blood has a special role in carbon dioxide transport - Recall: blood pH *must* be kept within 7.35-7.45 - Erythrocytes contain an enzyme called **\_\_\_\_\_\_\_\_\_carbonic\_\_\_\_\_\_\_ \_\_\_\_\_\_anhydrase\_\_\_\_\_\_\_\_\_\_** - Converts CO~2~ into **carbonic acid** - Dissociates into **bicarbonate** and protons - Important blood **buffering** system!  - Another gas acts as a hormone in blood - Nitric oxide (NO) acts as a \_\_\_\_\_hormone\_\_\_\_\_\_\_ - Released by **endothelial cells** of blood vessels -- *when*? in response to mechanical cardiac muscle stress - NO can bind hemoglobin - Hb releases NO **\_\_\_\_\_\_\_vasodilation (increase of blood vessel diameter)\_\_\_\_\_\_\_\_\_\_** ### The erythrocyte life cycle - Total \~**120** days - Continuous genesis is required because: - Erythrocyte membranes damaged as they squeeze through small blood vessels - Erythrocytes cannot repair damaged organelles -- *why not?* 1. Worn-out or damaged RBCs die - **Macrophages** (type of leukocyte) destroy them in liver, spleen, or red bone marrow( kill ones that are not made properly) 2. The **globin** (\_\_\_\_organic\_\_\_\_\_\_\_\_\_) and **heme** (\_\_\_\_\_inorganic\_\_\_\_\_\_\_\_\_\_\_\_\_) parts or hemoglobin are separated. 3. Globin catabolized into amino acids recycled. 4. **\_\_\_\_\_\_ferric\_\_\_\_\_\_\_ iron (Fe^3+^)** taken from heme and bound to **transferrin** (Fe transport protein in blood plasma)**.** 5. **Fe^3+^** transferred to **\_\_\_\_\_\_\_\_\_ferratin\_\_\_\_\_\_\_\_\_** (Fe storage protein) and shuttled through liver 6. **Fe^3+^** reattached to transferrin in blood. 7. **Fe^3+^** taken to red bone marrow by transferrin - Immature erythrocytes take up Fe^3+^ via **receptor-mediated endocytosis** 8. \_\_\_\_\_\_\_erythropoiesis\_\_\_\_\_\_\_\_\_\_\_\_\_ 9. Meanwhile: - Iron-less heme products are transported to the liver - \_\_\_\_\_\_\_\_yellow\_\_\_\_\_\_\_\_ products are excreted by the kidneys - Other products leave in \_\_\_\_\_\_\_feces\_\_\_\_\_  ### Erythropoiesis - How does **erythropoiesis** work? Diagram Description automatically generated with medium confidence - Erythropoiesis is a tightly controlled process  - Stimulus: **reduction in oxygen transport to tissues** or **\_\_\_\_hypoxia\_\_\_\_\_\_\_\_** - *What kinds of activities/conditions lead to this condition?* - **Sensors**: receptors on **kidney** cells - **Control centre**: Kidney cells - Sends **EPO** - **Effectors**: Proerythroblasts in **red bone marrow** - EPO stimulates proerythroblasts to mature *\_\_\_\_faster\_\_\_\_\_* increased reticulocytes released into circulation - **Net physiological effect**: More erythrocytes in blood = more \_\_\_\_oxygen\_\_\_\_\_\_ delivery to tissues *Practice question on your own*: Is this a **negative** or a **positive** feedback loop? How do you know? It is a negative feedback because it returns back to homeostasis Leukocytes or white blood cells (WBCs): structure and function -------------------------------------------------------------- - All organelles present; no hemoglobin - May be **granular** or **agranular** - **\_\_\_\_\_\_\_\_\_granular\_\_\_\_\_\_\_\_\_\_\_ leukocytes** contain special \_\_\_\_\_vesicles\_\_\_\_\_\_\_ and include: - Neutrophils - Eosinophils - Basophils Graphical user interface, application Description automatically generated ### Granular leukocytes #### Neutrophils - **Neutrophils** are phagocytic cells - Descend from the myeloid stem cell lineage. - Granules do not retain acidic or basic dyes and are therefore \_\_\_\_neutrophilic\_\_\_\_\_\_\_\_\_\_\_\_\_\_ - Nucleus has multiple **lobes** = **\_\_\_\_\_ morphonuclear\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ leukocytes** (PMNs) - Engulf invaders in the blood and destroy them through **phagocytosis**.  #### Eosinophils - **Eosinophils** defend against parasites - **Eosinophils** have granules that stain with \_\_\_\_\_\_acidic\_\_\_\_\_ dyes. - Nucleus usually has two lobes with a thin, tubular \_\_\_\_\_\_\_linker\_\_\_\_\_\_ bridge. - Defend against **parasites**, especially worms. Graphical user interface, application Description automatically generated #### Basophils - **Basophils** have granules that stain with \_\_\_basic\_\_\_\_\_\_ dyes. - Nucleus usually has two lobes. - May be obscured by granules - Release **\_\_\_\_\_\_\_\_\_\_histamine\_\_\_\_\_\_\_**. ### Agranular leukocytes - **Lymphocytes** are agranular - Agranular leukocytes have granules (sorry) - Too small to see with a compound light microscope - **Lymphocytes** are derived from the **\_\_\_\_\_lymphoid\_\_\_\_\_\_\_\_ stem cell lineage**. - Vary in size - Increased number of large lymphocytes sign of disease - **\_\_\_\_\_\_\_Monocytes\_\_\_\_\_\_\_\_\_\_** are derived from the **myeloid** stem cell lineage - Differentiate into macrophages or fuse into **osteoclasts** - Nucleus is kidney-shaped  #### Leukocyte function: inflammation and immunity - White blood cells defend the body from infection and invasion - All WBCs express **major \_\_\_\_\_\_\_\_\_histocompatibility\_\_\_\_\_\_\_\_\_\_\_\_\_ complex (MHC) proteins** - Identify cells as belonging to "\_\_self\_\_\_\_" - Mucous membranes trap invaders - Cilia sweep them away from tissues - If microbial invasion is successful: **leukocytes** accumulate at site of infection - If a tissue is damaged, leukocytes leave the bloodstream = **emigration** - Most never return to blood circulation - **Chemotaxis** permits WBCs to find the site of infection - Invaders and damaged tissues release chemicals that *attract* WBCs - *What is **chemotaxis?*** Chemical stimulus triggers movement towards the place of infection - \_\_\_\_\_\_\_neutrophils\_\_\_\_\_\_\_ are the fastest responders to *bacterial* infection. - Phagocytize pathogens - What do neutrophils do at the site of infection? - Release **lysozyme:** disrupts bacterial membranes - Release oxidizing chemicals (e.g. H~2~O~2~) - **Release \_\_\_\_\_\_defensins\_\_\_\_\_\_\_ =** antimicrobial peptides - Thought to disrupt bacterial membranes - Question: *how does disrupting membranes* kill *cells?* It no longer seperates the cells from the outer environment leading to death - Eosinophils specifically fight \_\_\_\_\_\_parasitic\_\_\_\_\_\_\_ infections. - Secrete **histaminase** - Enzyme that catabolizes **histamine** - Disrupts \_\_\_\_\_signaling\_\_\_\_\_\_\_ that recruits other WBCs to site of infection - Can phagocytize **antigen-antibody** complexes - Basophils participate in \_\_\_\_\_\_\_inflammatory\_\_\_\_\_\_\_\_\_ and \_\_\_\_\_hypersensitivity\_\_\_\_\_\_\_\_\_\_\_\_ reactions (more later) - Release heparin, **histamine(increases leakiness of blood vessels)enlarges gaps)**, and serotonin. - Chemical signals that help body wall off infection, disinfect tissues, and prepare tissue for healing - What do lymphocytes do? - Only 2% of lymphocytes circulate in blood - The rest reside in the organs of the \_\_\_\_lymphatic\_\_\_\_\_\_\_\_ system - **B lymphocytes** differentiate into plasma cells and secrete antibodies - Can also act against bacteria directly - **T lymphocytes and natural killer cells** fight viral-infected and cancerous cells directly - **Monocytes** arrive at the site of infection later than neutrophils - Can directly kill bacteria - After tissue has been disinfected, monocytes enlarge - Differentiate into **\_\_\_\_\_wandering\_\_\_\_\_\_\_ macrophages** - **Macrophages** are phagocytic cells that clean up cell \_\_\_\_debris\_\_\_\_ Diagram Description automatically generated - What happens during infection and invasion? - One of first responses: **inflammation** 1. **Tissue damage** from infection/invasion 2. **Emigration and rolling** - **Emigration** is the movement of WBCs from blood to the site of tissue damage - What is **rolling**? leukocytes start to "roll" on the luminal surface of inflamed endothelial cells in order to slow down from the bloodstream 3. **Chemotaxis** - Neutrophils arrive first phagocytize invaders - Other leukocytes + lymphocytes will be recruited -- *how*? chemotaxis 4. **Tissue disinfection** - WBCs perform their functions - Monocytes differentiate into wandering macrophages - Macrophages clean up remaining debris 5. **Tissue healing** ### Platelets - How are platelets formed? - When myeloid stem cells are exposed to **TPO:** - Develop into **\_\_\_\_megakaryoblast\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** - Mature into **\_\_\_\_\_megakaryocytes\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** splinter into 2000--3000 fragments - Each fragment = a **platelet** - Platelets also contain granules containing chemicals required for **blood clotting** - Life span = 5-9 days  Hemostasis ---------- - **Hemostasis** is NOT **homeostasis**. Be careful! - **Hemostasis** is a process that prevents **\_\_\_\_\_\_\_\_hemorrhage\_\_\_\_\_\_\_\_\_\_** (excessive bleeding). - Three general steps: 1. Vascular spasm 2. Platelet plug formation 3. Blood clotting #### Vascular spasm - Blood vessel damage leads to **vascular spasm** - Chemical signals released by \_\_\_\_\_\_damaged\_\_\_\_\_\_\_\_\_\_ smooth muscle and/or activated platelets or - Reflexes initiated by pain receptors... lead to spasm of smooth muscle around blood vessels - Function: \_\_\_\_stems\_\_\_\_\_ bleeding until other mechanisms activated #### Platelet plug formation I. Platelet **adhesion**: platelets stick to the site of vessel injury. II. Platelet **\_\_\_\_\_activation\_\_\_\_\_\_\_\_\_\_\_** - Release granules **vasoconstriction + ADP release** III. ADP release makes platelets sticky - Platelets clump = **platelet \_\_\_\_\_\_\_\_aggregation\_\_\_\_\_\_\_\_\_\_\_\_\_\_** - Forms a **platelet plug** Graphical user interface Description automatically generated with medium confidence #### Blood clot formation - Platelet plugs can stop small bleeds but cannot withstand excessive blood pressure - A **blood clot** is a platelet plug + insoluble \_\_\_\_\_\_\_\_protein\_\_\_\_\_\_\_ \_\_fibres\_\_\_\_\_\_\_\_ that reinforce plug. - **\_\_\_\_\_\_\_\_\_\_coagulation\_\_\_\_\_\_\_\_\_\_\_** is the process of blood clot formation - Requires **clotting factors,** including: - \_\_\_\_\_\_calcium\_\_\_\_\_\_\_\_\_\_\_ ions (Ca^2+^) - Enzymes made in the liver (proenzymes) - Other substances released by platelets + damaged tissues  - Two pathways for blood clotting - Differ by how they are **activated** (how they start) 1. **[Intrinsic pathway]** - Damaged endothelial cells sensed **within** blood vessels - Contact with connective tissue **platelet activation** - Platelets release phospholipids - Contact with **\_\_\_\_\_\_\_collagen\_\_\_\_\_\_\_\_\_\_** factor \_\_\_XII(12)\_\_\_ activation - Phospholipids + factor XII activate **factor X** 2. **[Extrinsic pathway]** - **External** substance called **\_\_\_\_\_tissue\_\_\_\_\_\_ \_\_\_\_\_\_factor\_\_\_\_\_\_\_ (TF)** enters blood through - TF = \_\_\_\_\_\_\_\_\_\_phospholipids\_\_\_\_\_\_\_\_\_\_\_\_ and lipoproteins from damaged blood vessel cells - Activates factor X - Once activated, blood clotting proceeds by the **[common pathway]** *regardless* of how it was activated 1. Activated factor X joins factor V to form **active prothrombinase** 2. Prothrombinase and Ca^2+^ \_\_\_\_\_\_cleave(divide)\_\_\_\_\_ **prothrombin** (inactive) to active **thrombin** 3. Thrombin and Ca^2+^ process inactive **fibrinogen** (soluble) to active **fibrin** (\_\_\_\_\_\_\_\_insoluble\_\_\_\_\_\_\_\_\_\_\_). - Also activates **factor XIII(13):** stabilizes fibrin threads Diagram Description automatically generated - Blood clotting is regulated - Blood clotting tightly controlled because the process is essential for survival of blood vessel damage - If clots *form too easily*, may result in **\_\_\_\_\_\_\_\_\_\_thrombosis\_\_\_\_\_\_\_** - Clots block small vessels **\_\_\_\_\_\_embolism\_\_\_\_\_\_\_\_\_** - If in brain = **stroke**; in lungs = **pulmonary embolism** - If clots *do not form*, may result in **hemorrhage** - Excessive blood loss anemia and shock Diseases and disorders of blood ------------------------------- ### ABO blood groups - There are many different blood groups - Most common = ABO - ABO typing based on **\_\_\_\_\_\_\_\_glycolipid\_\_\_\_\_\_\_\_ antigens** in the plasma membranes of erythrocytes - **\_\_\_\_\_\_\_\_\_\_\_\_agglutinins\_\_\_\_\_\_\_** are antibodies that bind and recognize A and B antigens  - Agglutinins agglutinate erythrocytes! - **Agglutination** is the \_\_\_\_\_\_\_clumping\_\_\_\_\_\_\_\_ of erythrocytes upon contact with agglutinins - Antibodies are **\_\_\_\_\_\_proteins\_\_\_\_\_\_\_\_\_** - Each antibody has **two** antigen-binding domains - Antibodies bind one antigen on one erythrocyte; *same* antigen on another erythrocyte agglutination Diagram Description automatically generated - Individuals make antibodies against **foreign** antigens - E.g. Julia is blood type O - *What antigens decorate the surface of Julia's erythrocytes?* \_\_\_none\_\_\_\_\_\_ - *What **antibodies** or **agglutinins** does Julia make? \_\_\_\_\_a and b\_\_\_\_\_\_\_\_\_\_\_* - Suppose Julia needs major surgery. Blood will be prepared in case of a necessary **transfusion**. *What blood types can **Julia** safely receive?* - Julia also donates blood. *What individual blood types can Julia **donate to?*** All blood types ### Hemolytic Disease of the newborn (HDN) - In addition to ABO antigens, erythrocytes may express a **protein antigen** called the **Rhesus factor (Rh)** - \+ individuals express the Rh antigen; - individuals do not - Julia is O+. *Does she make anti-Rh antibodies?* *\_\_\_\_\_\_\_no\_\_\_\_*  - Imagine: Rh- woman conceives a child with an Rh+ man Rh+ fetus - During pregnancy, maternal and fetal blood NEVER MIX - Substances exchanged through \_\_\_\_\_\_\_\_placenta\_\_\_\_\_\_\_ - During birth, maternal and fetal blood may mix - **After \_\_\_\_\_\_\_exposure\_\_\_\_\_\_\_\_ to Rh antigen**, mother's immune system generates anti-Rh antibodies - First child \_\_\_\_\_\_\_\_\_unaffected\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ - If woman conceives a **second Rh+ child, the *second* child is at risk for HDN** - Maternal and fetal blood **STILL** does not mix - Anti-Rh antibodies can cross the placenta - In the fetal blood, **agglutinate** fetal erythrocytes - *How does this harm the second fetus?* - HDN newborns are swollen and jaundiced - If a woman and her child are at risk, can treat **proactively** with anti-gamma globulins (RhoGam) - Proteins that \_\_\_\_\_\_\_neutralized\_\_\_\_\_\_\_\_ anti-Rh antibodies ### Other homeostatic imbalances of blood #### Anemia - **What is anemia?** a condition in which the body does not have enough healthy red blood cells red blood cells don't carry enough oxygen - Many causes, including: - Iron deficiency - Vitamin B12 deficiency - Structural defects of erythrocytes - Destruction of red bone marrow or erythrocytes #### Sickle cell disease - What is **sickle cell disease**? - Aka **sickle cell anemia** - \_\_\_\_genetic\_\_\_\_\_\_\_\_\_ mutation in globin gene - Change in amino acid sequence change in protein \_\_\_\_folding\_\_\_\_\_\_\_ - Cells are elongated instead of disc-shaped A picture containing text Description automatically generated - Sickle cell disease alleles protect against malaria - Gene variants that differ by mutation are called **\_\_\_\_\_\_\_\_alleles\_\_\_\_\_\_** - High frequency of sickle cell alleles in populations where malaria is common  - **Malaria** is caused by a parasitic infection of erythrocytes - Sickled erythrocytes leak **\_\_\_\_\_\_\_\_potassium\_\_\_\_\_\_\_\_\_\_,** an ion essential for the malarial parasite to reproduce - People with at least one sickle cell allele are more **\_\_\_\_\_\_\_\_resistant\_\_\_\_\_\_\_\_** to malaria #### Hemophilia - **Hemophilia** is another inherited disease - Mutation leading to insufficient **clotting factors** - Minor injuries hemorrhage - Commonly affected gene is found on the \_\_x\_\_ chromosome - More common in \_\_\_males\_\_\_\_\_\_\_ because females have 2 and males have 1 - Treatment: Infusions of donated plasma and/or synthetic clotting factors #### Polycythemia - **Polycythemia** is the result of too many erythrocytes in blood - May be caused by genetic mutation, hormonal imbalances, or EPO injection - Leads to **thickened blood** - High risk for strokes, emboli, etc. Summary ------- - Blood is a complex connective tissue consisting of formed elements in blood plasma. - Blood transports oxygen to tissues on hemoglobin and carbon dioxide in red blood cells and plasma. - Carbonic anhydrase catalyzes chemical reactions essential to buffering blood. - Blood protects us from infection through antibodies and white blood cells. - Blood protects us from hemorrhage through blood clotting. - Blood cells possess antigens that form the basis for self- and non-self discrimination by our immune systems. ***Suggested study aid:*** Complete the following chart to organize your knowledge of blood structure/function +-----------------------+-----------------------+-----------------------+ | Component of blood | Description of | Description of | | | structure | function(s) | +=======================+=======================+=======================+ | Erythrocytes | | | +-----------------------+-----------------------+-----------------------+ | Leukocytes: | 1. Granular; | 1. 2. Defends | | | multi-lobed | against parasitic | | 1. Neutrophils | nucleus | invaders; | | | | secretes | | 2. Eosinophils | 2. 3. 4. 5. | **histaminase** | | | | | | 3. Basophils | | 3. 4. 5. | | | | | | 4. Monocytes | | | | macrophages | | | | | | | | 5. Lymphocytes | | | +-----------------------+-----------------------+-----------------------+ | Platelets | Small fragments of | | | | megakaryocytes | | +-----------------------+-----------------------+-----------------------+ | Blood plasma | | Transports nutrients, | | | | hormones, gases, | | | | electrolytes, and | | | | essential blood | | | | proteins required for | | | | hormone transport, | | | | blood clotting, and | | | | other processes. | +-----------------------+-----------------------+-----------------------+